From Medscape Medical News
AAD Develops Guidelines for Psoriasis and Psoriatic Arthritis
Emma Hitt, PhD
February 22, 2011 — Therapeutic recommendations for the treatment of mild, moderate, and severe psoriasis, with and without psoriatic arthritis, have been issued by the American Academy of Dermatology (AAD) and published in the Journal of the American Academy of Dermatology in a 6-part series.
The AAD workgroup obtained evidence through a search of the PubMed/MEDLINE database, spanning from 1960 to 2010. In the first 5 parts of the 6-section guidelines, the authors presented evidence supporting the use of topical treatments, phototherapy, traditional systemic agents, and biological therapies for patients with psoriasis and psoriatic arthritis. In the sixth and final section, reported by Alan Menter, MD, from the Baylor University Medical Center in Dallas, Texas, and colleagues and published online February 7, cases were used to illustrate how to apply the guidelines in clinical practice.
According to the authors, treatment options for psoriasis must be tailored to the individual patient, taking into account "efficacy, side effects, availability, ease of administration, comorbidities, family history, and coexisting diseases."
Treating Limited Psoriasis
Topical corticosteroids of varying strengths are a first-line treatment for limited psoriasis (ie, <5% body surface area). The vitamin D analogs calcipotriene, calcipotriol, and calcitriol may also be used as first-line in certain settings. Other topical approaches include retinoids, tacrolimus, and ultraviolet-based therapy, such as the 308-nm monochromatic xenonchloride (excimer) laser.
Evidence is limited to support the efficacy of emollients and ointments, although they may be able to restore normal hydration and water barrier function to the epidermal layer of the psoriatic plaque, the authors state, adding that such moisturizers are an important aspect of routine skin care for patients with psoriasis.
Patients with limited disease (representing at least 80% of patients with psoriasis) should still be assessed for psoriatic arthritis. If present, or if there is psoriasis in vulnerable areas such as the face, genitals, hands or feet (palmoplantar), scalp, or intertriginous areas that is either unresponsive to topical therapy or interferes with quality of life, more intensive therapy — rather than just topical or ultraviolet-based therapies — should be used.
Other topics on limited disease covered by the guidelines include the topical treatment of inverse/intertriginous, genital, and scalp psoriasis, as well as clinical trials comparing topical agents. Adherence to topical treatment and short-term use of systemic agents in patients with limited disease are also addressed.
"For the majority of patients with limited disease, topical treatments are safe, effective, and convenient provided patients are fully counseled and educated on the multiple nuances of this form of therapy," the authors conclude.
Clinical Care for Moderate to Severe Psoriasis
In patients with moderate to severe psoriasis without psoriatic arthritis, ultraviolet therapy remains an important therapeutic option. Systemic agents, such as methotrexate, cyclosporin, and acitretin, may also be used. In addition, biologic agents are used in the event that traditional systemic agents fail or are not tolerated. Biologic agents approved for the treatment of either psoriasis or psoriatic arthritis include alefacept (psoriasis only), infliximab, etanercept, adalimumab, golimumab (psoriatic arthritis only), and ustekinumab (psoriasis only).
Agents in phase 2/3 clinical trials for moderate to severe psoriasis include an anti-interleukin (IL)-12/23 antibody, briakinumab, anti-IL-17 antibodies, IL-17 receptor blockers, p-selectin inhibitors, and Janus kinase inhibitors.
Psoriatic Arthritis
Psoriatic arthritis develops in 25% to 30% of patients with psoriasis, usually 5 to 12 years after the start of skin involvement. According to the guidelines, in general, it is appropriate to initiate methotrexate treatment for patients with moderate to severe psoriatic arthritis without contraindications. After 12 to 16 weeks without improvement, the patient may be switched to any tumor necrosis factor alpha inhibitor, or a tumor necrosis factor alpha inhibitor may be added to the methotrexate therapy.
Future Research
The authors also identified several gaps in knowledge requiring further study. Topics include, but are not limited to, the comparative efficacy of treatment for various forms of psoriasis; how treatment relates to reduced risk of comorbidities, such as cardiovascular risk; and the genetics underlying the pathology of psoriatic disease.
The report was not commercially funded. The authors' disclosure information is extensive and is listed at the end of the guidelines.
J Am Acad Dermatol. Published online February 7, 2011.
Monday, February 28, 2011
Glycosylated Hemoglobin Associated With Diabetes Risk
From Medscape Medical News
Emma Hitt, PhD
February 23, 2011 — A glycosylated hemoglobin (HbA1c) level equal to or more than 5.0% is associated with a progressively and significantly increased risk for diabetes, with greatest risk for those with an HbA1c level of 6.0% to 6.4%, according to the findings of an historical cohort study.
Levels of HbA1c were also found to be an independent risk factor for type 2 diabetes, according to the findings of a second study.
Peiyao Cheng, MS, with the Department of Veterans Affairs Medical Center, in Tampa, Florida, and colleagues reported their findings online February 2 in Diabetes Care. A second study by Enzo Bonoro, MD, with the Section of Endocrinology and Metabolism, at the University of Verona, in Verona, Italy, and colleagues was reported online February 9 in Diabetes Care.
The American Diabetes Association indicates that HbA1c level can be used to diagnose diabetes, but its value in the prediction of type 2 diabetes is poorly understood. Two studies investigated HbA1c as a predictor of diabetes. Cheng and colleagues' study was designed to determine the ability of HbA1c to predict the incidence of a diabetic diagnosis. The second study, by Bonoro and colleagues, evaluated how high-to-normal HbA1c levels predict type 2 diabetes.
Cheng and Colleagues
Cheng and colleagues identified more than 12,000 nondiabetic patients with a baseline HbA1c level of 6.5% using electronic medical record data. These patients were tracked for 8 years for a subsequent diagnosis of diabetes.
During an average follow-up of 4.4 years, diabetes developed in 26.9% of patients. When compared with the reference group (HbA1c level < 4.5%), participants with an HbA1c level of 4.5% to 4.9% were at no significant increased risk for incident diabetes.
However, the incidence of diabetes progressively and significantly increased among patients with an HbA1c level above or equal to 5.0%, and a significantly increased risk was evident for those with an HbA1c level of 6.0% to 6.4% (P = .0001).
The respective multivariable-adjusted odds ratios for patients with HbA1c values from 5.0% to 5.4%, 5.5% to 5.9%, and 6.0% to 6.4% were 1.70 (95% CI, 1.21 - 2.36), 4.87 (95% CI, 3.49 - 6.79), and 16.06 (95% CI, 11.40 - 22.65).
"These data show a progressive risk for developing diabetes when HbA1c is ≥5.0%, with nominal risk below that level," Dr. Cheng and colleagues conclude. The researchers developed a risk calculator to estimate the 5-year risk for diabetes based on these and other clinical data.
Bonoro and Colleagues
The second study also found that high-to-normal levels of HbA1c were a risk factor for diabetes. "To the best of our knowledge, this study is the first to examine how baseline HbA1c predicts HbA1c-diagnosed diabetes," Dr. Bonoro and colleagues note.
The researchers measured HbA1c level in 919 Caucasian participants, aged 40 to 79 years. New cases of type 2 diabetes were recorded during a 15-year follow-up period.
"The findings of the current study confirm a progressively increased risk of type 2 diabetes across categories of HbA1c and clearly document that subjects with high-normal HbA1c have a strong risk of developing type 2 diabetes..., "Dr. Bonoro and colleagues conclude.
According to the researchers, their findings support the American Diabetes Association recommendations of using HbA1c level for diabetes risk stratification and targeting participants with high-normal levels with preventive strategies.
Diabetes Care. Published online February 2, 2011. Abstract
Emma Hitt, PhD
February 23, 2011 — A glycosylated hemoglobin (HbA1c) level equal to or more than 5.0% is associated with a progressively and significantly increased risk for diabetes, with greatest risk for those with an HbA1c level of 6.0% to 6.4%, according to the findings of an historical cohort study.
Levels of HbA1c were also found to be an independent risk factor for type 2 diabetes, according to the findings of a second study.
Peiyao Cheng, MS, with the Department of Veterans Affairs Medical Center, in Tampa, Florida, and colleagues reported their findings online February 2 in Diabetes Care. A second study by Enzo Bonoro, MD, with the Section of Endocrinology and Metabolism, at the University of Verona, in Verona, Italy, and colleagues was reported online February 9 in Diabetes Care.
The American Diabetes Association indicates that HbA1c level can be used to diagnose diabetes, but its value in the prediction of type 2 diabetes is poorly understood. Two studies investigated HbA1c as a predictor of diabetes. Cheng and colleagues' study was designed to determine the ability of HbA1c to predict the incidence of a diabetic diagnosis. The second study, by Bonoro and colleagues, evaluated how high-to-normal HbA1c levels predict type 2 diabetes.
Cheng and Colleagues
Cheng and colleagues identified more than 12,000 nondiabetic patients with a baseline HbA1c level of 6.5% using electronic medical record data. These patients were tracked for 8 years for a subsequent diagnosis of diabetes.
During an average follow-up of 4.4 years, diabetes developed in 26.9% of patients. When compared with the reference group (HbA1c level < 4.5%), participants with an HbA1c level of 4.5% to 4.9% were at no significant increased risk for incident diabetes.
However, the incidence of diabetes progressively and significantly increased among patients with an HbA1c level above or equal to 5.0%, and a significantly increased risk was evident for those with an HbA1c level of 6.0% to 6.4% (P = .0001).
The respective multivariable-adjusted odds ratios for patients with HbA1c values from 5.0% to 5.4%, 5.5% to 5.9%, and 6.0% to 6.4% were 1.70 (95% CI, 1.21 - 2.36), 4.87 (95% CI, 3.49 - 6.79), and 16.06 (95% CI, 11.40 - 22.65).
"These data show a progressive risk for developing diabetes when HbA1c is ≥5.0%, with nominal risk below that level," Dr. Cheng and colleagues conclude. The researchers developed a risk calculator to estimate the 5-year risk for diabetes based on these and other clinical data.
Bonoro and Colleagues
The second study also found that high-to-normal levels of HbA1c were a risk factor for diabetes. "To the best of our knowledge, this study is the first to examine how baseline HbA1c predicts HbA1c-diagnosed diabetes," Dr. Bonoro and colleagues note.
The researchers measured HbA1c level in 919 Caucasian participants, aged 40 to 79 years. New cases of type 2 diabetes were recorded during a 15-year follow-up period.
"The findings of the current study confirm a progressively increased risk of type 2 diabetes across categories of HbA1c and clearly document that subjects with high-normal HbA1c have a strong risk of developing type 2 diabetes..., "Dr. Bonoro and colleagues conclude.
According to the researchers, their findings support the American Diabetes Association recommendations of using HbA1c level for diabetes risk stratification and targeting participants with high-normal levels with preventive strategies.
Diabetes Care. Published online February 2, 2011. Abstract
Long-term Outcomes of Two Different Decompressive Techniques for Lumbar Spinal Stenosis
From Spine
Yi-Shan Fu, MD; Bing-Fang Zeng, MD; Jian-Guang Xu, MD
Abstract and Introduction
Introduction
Study Design: A prospective study to evaluate the outcomes of 2 different decompressive techniques for lumbar spinal stenosis.
Objective: To explore a more effective and less invasive decompression technique without instrument and fusion for lumbar spinal stenosis.
Summary of Background Data: The traditional surgical decompression of spinal stenosis involves laminectomy or unilateral laminotomy. Even in unilateral laminotomy cases, 85.3% had an excellent-to-fair operative result, and the incidence of complications was 9.8%. Although the addition of instrumentation does not increase the complication rate, but compared to the efficiency, the higher costs was controversial. Minimal invasion and destabilization are recommended.
Methods: This prospective study included 152 consecutive patients, sequentially divided into 2 groups, underwent Windows technique (group A) and decompressive laminectomy (group B) by 2 groups of surgeons.
Results: The evaluation of the back pain, leg pain, walking tolerance, and neurologic recovery were performed before surgery and after surgery. In group A, at the final evaluation, the overall results were good to excellent in 89% (68/76) of the patients, fair 11% (8/76), and poor 0%. In group B, at the final evaluation, the overall results were good to excellent in 63% (48/76) of the patients, fair 30% (23/76), and poor 7% (5/76).
Conclusion: Degenerative spinal stenosis can be decompressed adequately with preserving the posterior elements. The Windows technique laminoforaminotomy, which obtained satisfactory long-term outcomes with few complications and low cost, can be a standard procedure for the surgical treatment of the degenerative spinal stenosis even with slight congenital spinal stenosis.
Introduction
Acquired spinal stenosis is the most common condition leading to spine surgery in the geriatric population. Degenerative changes lead to central stenosis from ligamentum flavum hypertrophy, disc bulging, and osteophytes. Lateral recess or foraminal compression can result from facet hypertrophy and settling. Several studies on nonoperative treatment of patients with between 1 and 5 years of follow-up suggest that variably 15% to 43% of patients will have continued improvement after nonoperative treatment.[1] On the other side, for most patients, surgical procedures are preferred.
Traditionally, laminectomy is the most popular surgical decompression of spinal stenosis involved extensive removal of the posterior elements including the lamina, spinous processes, interspinous ligaments, and even facet joints.
Although, the short-term outcome of the laminectomy is good enough but the long-term outcome is not so satisfactory.
Seven to 10 years after decompressive surgery for spinal stenosis, 23% of patients had undergone reoperation and 33% of respondents had severe back pain. Even in unilateral laminotomy cases, 85.3% had an excellent-to-fair operative result, and the incidence of complications was 9.8%.[3]
A minimal removal decompressive procedure was prospectively evaluated for the treatment of lumbar spinal stenosis compared to traditional laminectomy. From 2002 to 2004 in our hospital, a total of 152 consecutive patients were divided into 2 groups and operated by different spine surgeons. No instruments and fusions were performed. At an average follow-up assessment of 40 months, the outcomes in 2 groups were evaluated prospectively.
http://www.medscape.com/viewarticle/573223
Yi-Shan Fu, MD; Bing-Fang Zeng, MD; Jian-Guang Xu, MD
Abstract and Introduction
Introduction
Study Design: A prospective study to evaluate the outcomes of 2 different decompressive techniques for lumbar spinal stenosis.
Objective: To explore a more effective and less invasive decompression technique without instrument and fusion for lumbar spinal stenosis.
Summary of Background Data: The traditional surgical decompression of spinal stenosis involves laminectomy or unilateral laminotomy. Even in unilateral laminotomy cases, 85.3% had an excellent-to-fair operative result, and the incidence of complications was 9.8%. Although the addition of instrumentation does not increase the complication rate, but compared to the efficiency, the higher costs was controversial. Minimal invasion and destabilization are recommended.
Methods: This prospective study included 152 consecutive patients, sequentially divided into 2 groups, underwent Windows technique (group A) and decompressive laminectomy (group B) by 2 groups of surgeons.
Results: The evaluation of the back pain, leg pain, walking tolerance, and neurologic recovery were performed before surgery and after surgery. In group A, at the final evaluation, the overall results were good to excellent in 89% (68/76) of the patients, fair 11% (8/76), and poor 0%. In group B, at the final evaluation, the overall results were good to excellent in 63% (48/76) of the patients, fair 30% (23/76), and poor 7% (5/76).
Conclusion: Degenerative spinal stenosis can be decompressed adequately with preserving the posterior elements. The Windows technique laminoforaminotomy, which obtained satisfactory long-term outcomes with few complications and low cost, can be a standard procedure for the surgical treatment of the degenerative spinal stenosis even with slight congenital spinal stenosis.
Introduction
Acquired spinal stenosis is the most common condition leading to spine surgery in the geriatric population. Degenerative changes lead to central stenosis from ligamentum flavum hypertrophy, disc bulging, and osteophytes. Lateral recess or foraminal compression can result from facet hypertrophy and settling. Several studies on nonoperative treatment of patients with between 1 and 5 years of follow-up suggest that variably 15% to 43% of patients will have continued improvement after nonoperative treatment.[1] On the other side, for most patients, surgical procedures are preferred.
Traditionally, laminectomy is the most popular surgical decompression of spinal stenosis involved extensive removal of the posterior elements including the lamina, spinous processes, interspinous ligaments, and even facet joints.
Although, the short-term outcome of the laminectomy is good enough but the long-term outcome is not so satisfactory.
Seven to 10 years after decompressive surgery for spinal stenosis, 23% of patients had undergone reoperation and 33% of respondents had severe back pain. Even in unilateral laminotomy cases, 85.3% had an excellent-to-fair operative result, and the incidence of complications was 9.8%.[3]
A minimal removal decompressive procedure was prospectively evaluated for the treatment of lumbar spinal stenosis compared to traditional laminectomy. From 2002 to 2004 in our hospital, a total of 152 consecutive patients were divided into 2 groups and operated by different spine surgeons. No instruments and fusions were performed. At an average follow-up assessment of 40 months, the outcomes in 2 groups were evaluated prospectively.
http://www.medscape.com/viewarticle/573223
Cannabis Enhances Appetite in Cancer Patients
From Medscape Medical News > Oncology
Roxanne Nelson
February 25, 2011 — The active ingredient in cannabis appears to help stimulate the appetite of patients with advanced cancer, according to the results of a pilot study. Canadian researchers also found that delta-9-tetrahydrocannabinol (THC) can improve the sense of taste in this population.
The findings come from a randomized study of nearly 50 patients published online February 22 in the Annals of Oncology.
In this study, the authors used a synthetic form of delta-9-THC, which is marketed as dronabinol (Marinol, Solvay). Dronabinol was first licensed and approved in 1986 for the treatment of nausea and vomiting associated with chemotherapy; the indication was expanded in 1992 for the treatment of anorexia associated with weight loss in patients with AIDS.
In the THC (dronabinol) group, 64% experienced an increase in appetite and 27% experienced no change. In the placebo group, 50% experienced a decrease in appetite and 20% experienced no change.
In the THC goup, 73% reported "an increased overall appreciation of food," compared with 30% in the placebo group. Those in the THC group were also more likely to say that it "made food taste better" than those in the placebo group (P = .04).
In addition, patients who received THC consumed more protein, even though total caloric intake was similar for the 2 study groups (P = .008). Participants in the THC group also reported improvements in their quality of sleep (P = .025) and relaxation (P = .045).
"Based on the results of our study, doctors could consider THC to improve both appetite and food enjoyment for advanced cancer patients," lead author Wendy Wismer, PhD, told Medscape Medical News.
"When approved for use in the cancer setting, it could be integrated into therapy. When researching the topic, we did not find anything to suggest that long-term use should not be considered," added Dr. Wismer, associate professor at the University of Alberta in Edmonton, Canada.
Cannabis Known to Stimulate Appetite
Dr. Donald Abrams
However, in an independent comment, Donald I. Abrams, MD, professor of clinical medicine at the University of California, San Francisco, pointed out that these data really aren't all that new.
"I don't think there's anything startling about the fact that cannabis or cannabinoids increases the appetite," he said in an interview. "That's been well known for years."
In this study, Dr. Abrams noted, the authors suggest that THC improved the sensory aspects of food, such as taste and smell. "Other research that we're more familiar with suggests that cannabinoid receptors in the brain that are involved with the reward aspect of eating are stimulated when they complex with either the plant cannabinoids or endocannabinoids," he said.
"We've always known that cannabinoids are involved in the regulation of appetite, the interesting point in this study is that it enhanced the sensory aspect of eating via taste and smell," added Dr. Abrams, who is also director of the Integrative Oncology Research Program at the Osher Center for Integrative Medicine.
One explanation for the findings might be that the authors only looked at delta-9-THC, which is just 1 of 400 components of cannabis. "There are probably about 70 other cannabinoids in the plant, so to show that this single most psychoactive component led to these findings might be noteworthy," Dr. Abrams explained.
Grow Your Own?
Cannabis in its natural form is still considered illegal by the US federal government, although several states — including California — have passed laws that allow it for medicinal use.
However, Dr. Abrams noted that dronabinol is unlikely to be approved for the palliation of chemosensory alterations or to improve food enjoyment among cancer patients. "I don't think that any insurance companies are going to pay for this indication — to improve chemosensory perception. It is very expensive to use [dronabinol]," he said.
"I think it's cheaper to grow your own; then you get a benefit from the many other compounds in the cannabis," Dr. Abrams added.
In addition, he noted that because it is ingested orally, dronabinol has a slower onset of action and lower rate of absorption. In comparison, smoked or inhaled cannabis has a rapid onset of action — peak plasma levels are reached very quickly — and patients are better able to control dosing.
Previous studies have shown that both smoked cannabis and synthetic THC can offer medical benefits. For example, smoking cannabis appears to reduce posttraumatic or postsurgical neuropathic pain and improve sleep, as previously reported by Medscape Medical News.
It also appears to be effective for the treatment of HIV-related sensory neuropathy, and for delayed and acute chemotherapy-induced nausea and vomiting.
Improved Taste and Smell
The current study was conducted in adult patients with any advanced cancer (defined as locally recurrent, locally advanced, or metastatic) of any site except the brain. Patients were randomized to receive either THC 2.5 mg (n = 24) or oral placebo capsules (n = 22) twice daily for 18 days. The authors explain that because this was an exploratory study, the nature of treatment effects and potential effects were unknown. For that reason, 10 participants from each group were assessed at the end of the 18-day study period. Overall, 21 patients completed the trial.
At baseline and following treatment, all patients were interviewed and completed a panel of patient-reported outcomes: the Taste and Smell Survey, a 3-day food record, appetite and macronutrient preference assessments, and a quality-of-life questionnaire.
Half of the patients in the THC group who reported food odors to be unpleasant at baseline did not find them offensive after treatment (P = .083), and nearly three quarters reported a "renewed ability" to discriminate tastes, flavors, and food odors. In comparison, 80% of those in the placebo group found that their taste and smell function had not changed or had worsened.
Quality-of-life and nausea scores were similar for both groups. Overall, THC was well tolerated and there were no differences in adverse events between the 2 groups during the trial period or within the 30-day follow-up period.
"Our findings are important, as there is no accepted treatment for chemosensory alterations experienced by cancer patients," write the authors. They suggest that THC treatment might have multiple clinical benefits for cancer patients, "beyond its indication as a treatment for nausea and its effects on appetite."
This work was supported by the Canadian Institutes of Health Research, the Alberta Cancer Board, the Alberta Heritage Foundation for Medical Research, and the Natural Sciences and Engineering Research Council of Canada.
Ann Oncol. Published online February 22, 2011. Abstract
Roxanne Nelson
February 25, 2011 — The active ingredient in cannabis appears to help stimulate the appetite of patients with advanced cancer, according to the results of a pilot study. Canadian researchers also found that delta-9-tetrahydrocannabinol (THC) can improve the sense of taste in this population.
The findings come from a randomized study of nearly 50 patients published online February 22 in the Annals of Oncology.
In this study, the authors used a synthetic form of delta-9-THC, which is marketed as dronabinol (Marinol, Solvay). Dronabinol was first licensed and approved in 1986 for the treatment of nausea and vomiting associated with chemotherapy; the indication was expanded in 1992 for the treatment of anorexia associated with weight loss in patients with AIDS.
In the THC (dronabinol) group, 64% experienced an increase in appetite and 27% experienced no change. In the placebo group, 50% experienced a decrease in appetite and 20% experienced no change.
In the THC goup, 73% reported "an increased overall appreciation of food," compared with 30% in the placebo group. Those in the THC group were also more likely to say that it "made food taste better" than those in the placebo group (P = .04).
In addition, patients who received THC consumed more protein, even though total caloric intake was similar for the 2 study groups (P = .008). Participants in the THC group also reported improvements in their quality of sleep (P = .025) and relaxation (P = .045).
"Based on the results of our study, doctors could consider THC to improve both appetite and food enjoyment for advanced cancer patients," lead author Wendy Wismer, PhD, told Medscape Medical News.
"When approved for use in the cancer setting, it could be integrated into therapy. When researching the topic, we did not find anything to suggest that long-term use should not be considered," added Dr. Wismer, associate professor at the University of Alberta in Edmonton, Canada.
Cannabis Known to Stimulate Appetite
Dr. Donald Abrams
However, in an independent comment, Donald I. Abrams, MD, professor of clinical medicine at the University of California, San Francisco, pointed out that these data really aren't all that new.
"I don't think there's anything startling about the fact that cannabis or cannabinoids increases the appetite," he said in an interview. "That's been well known for years."
In this study, Dr. Abrams noted, the authors suggest that THC improved the sensory aspects of food, such as taste and smell. "Other research that we're more familiar with suggests that cannabinoid receptors in the brain that are involved with the reward aspect of eating are stimulated when they complex with either the plant cannabinoids or endocannabinoids," he said.
"We've always known that cannabinoids are involved in the regulation of appetite, the interesting point in this study is that it enhanced the sensory aspect of eating via taste and smell," added Dr. Abrams, who is also director of the Integrative Oncology Research Program at the Osher Center for Integrative Medicine.
One explanation for the findings might be that the authors only looked at delta-9-THC, which is just 1 of 400 components of cannabis. "There are probably about 70 other cannabinoids in the plant, so to show that this single most psychoactive component led to these findings might be noteworthy," Dr. Abrams explained.
Grow Your Own?
Cannabis in its natural form is still considered illegal by the US federal government, although several states — including California — have passed laws that allow it for medicinal use.
However, Dr. Abrams noted that dronabinol is unlikely to be approved for the palliation of chemosensory alterations or to improve food enjoyment among cancer patients. "I don't think that any insurance companies are going to pay for this indication — to improve chemosensory perception. It is very expensive to use [dronabinol]," he said.
"I think it's cheaper to grow your own; then you get a benefit from the many other compounds in the cannabis," Dr. Abrams added.
In addition, he noted that because it is ingested orally, dronabinol has a slower onset of action and lower rate of absorption. In comparison, smoked or inhaled cannabis has a rapid onset of action — peak plasma levels are reached very quickly — and patients are better able to control dosing.
Previous studies have shown that both smoked cannabis and synthetic THC can offer medical benefits. For example, smoking cannabis appears to reduce posttraumatic or postsurgical neuropathic pain and improve sleep, as previously reported by Medscape Medical News.
It also appears to be effective for the treatment of HIV-related sensory neuropathy, and for delayed and acute chemotherapy-induced nausea and vomiting.
Improved Taste and Smell
The current study was conducted in adult patients with any advanced cancer (defined as locally recurrent, locally advanced, or metastatic) of any site except the brain. Patients were randomized to receive either THC 2.5 mg (n = 24) or oral placebo capsules (n = 22) twice daily for 18 days. The authors explain that because this was an exploratory study, the nature of treatment effects and potential effects were unknown. For that reason, 10 participants from each group were assessed at the end of the 18-day study period. Overall, 21 patients completed the trial.
At baseline and following treatment, all patients were interviewed and completed a panel of patient-reported outcomes: the Taste and Smell Survey, a 3-day food record, appetite and macronutrient preference assessments, and a quality-of-life questionnaire.
Half of the patients in the THC group who reported food odors to be unpleasant at baseline did not find them offensive after treatment (P = .083), and nearly three quarters reported a "renewed ability" to discriminate tastes, flavors, and food odors. In comparison, 80% of those in the placebo group found that their taste and smell function had not changed or had worsened.
Quality-of-life and nausea scores were similar for both groups. Overall, THC was well tolerated and there were no differences in adverse events between the 2 groups during the trial period or within the 30-day follow-up period.
"Our findings are important, as there is no accepted treatment for chemosensory alterations experienced by cancer patients," write the authors. They suggest that THC treatment might have multiple clinical benefits for cancer patients, "beyond its indication as a treatment for nausea and its effects on appetite."
This work was supported by the Canadian Institutes of Health Research, the Alberta Cancer Board, the Alberta Heritage Foundation for Medical Research, and the Natural Sciences and Engineering Research Council of Canada.
Ann Oncol. Published online February 22, 2011. Abstract
Light to Moderate Drinking: Likely Cardioprotective, But Recommended?
From Heartwire
Steve Stiles
February 28, 2011 (Calgary, Alberta) — It's time to acknowledge the pile of evidence that light to moderate alcohol consumption is not only good for cardiovascular health, it could potentially be recommended for CV risk reduction, according to authors of two meta-analyses published online February 22, 2011 in BMJ
An analysis of prospective cohort studies showing alcohol effects on cardiovascular end points, with first author Dr Paul E Ronksley (University of Calgary, AB), suggested that most any level of alcohol intake is protective against CV mortality, incident CHD, and CHD mortality, while intake of up to one drink per day is protective against incident stroke and stroke mortality. The findings are consistent with a vast evidence base linking light to moderate alcohol intake with reduced CV risk.
The other report focused on clinical intervention studies of alcohol effects on biomarkers associated with CV disease and concluded that moderate intake raises levels of HDL cholesterol, apolipoprotein A1, and adiponectin and reduces fibrinogen levels. In their analysis, Dr Susan E Brien (University of Calgary) et al defined moderate alcohol intake as up to a drink per day for women and two drinks per day for men.
Although observational studies can't establish cause and effect, the group observes, together the two reports make a compelling case for alcohol as an actual cause of the reduced CV risk long associated with light to moderate drinking.
But What Do You Do With the Information?
"Then the question becomes, what do you do with that [information]? There are two levels at which it needs to be considered. One is: what does a doctor say to a patient in a clinical setting? And the second is: what do public-health officials tell the public?" Dr William A Ghali (University of Calgary), senior author of both reports, said for heartwire .
"With respect to public-health messages," he and his coauthors write, "there may now be an impetus to better communicate to the public that alcohol, in moderation, may have overall health benefits that outweigh the risks in selected subsets of patients."
In clinical practice, they contend, the evidence base supporting CV benefits from alcohol intake could be the basis for "counseling for selected patients to incorporate moderate amounts of alcohol into their diets to improve their coronary heart disease risk."
But before that could happen, the strategy would have to be evaluated "in pragmatic clinical trials that assess the questions of optimal patient selection, compliance, risks, and benefits."
I just don't think we should close our eyes and ears to this evidence.
Such trials wouldn't focus as much on links between alcohol intake and clinical outcomes, but more on "the receptivity of both physicians and patients to the recommended consumption of alcohol for therapeutic purposes and the extent to which it can be successfully and safely implemented."
Ghali recognizes that he and his colleagues are extending the public debate about alcohol and CV health beyond its comfort zone, in which people who already partake are assured their moderate drinking may improve cardiovascular health. Teetotalers are not currently advised that if they start drinking, it will be good for their hearts.
On the other hand, public-health messages advocating "consumption of alcohol for therapeutic purposes" would likely be offensive to "people who view, and people who have good reason to view, alcohol as a very dangerous substance," Ghali acknowledged.
"I think we should undertake a process of dialog and debate around what should be said and then evaluate whatever we come up with in terms of public-health messages to see what impact that has on behaviors," he said. "I just don't think we should close our eyes and ears to this evidence."
Outcomes and Biomarker Studies: Consistent Message
The group's outcomes meta-analysis included 84 prospective cohort studies of adults without preexisting CV disease, both drinkers and nondrinkers. Follow-up ranged from 2.5 to 35 years (mean 11 years); 85% of the studies followed participants for more than five years.
Adjusted Relative Risk (RR) for Outcomes, Drinkers Compared With Nondrinkers
End point Number of studies RR (95% CI)
CV mortality 21 0.75 (0.70–0.80)
Incident CHD 29 0.71 (0.66–0.77)
CHD mortality 31 0.75 (0.68–0.81)
Incident stroke 17 0.98 (0.91–1.06)
Stroke mortality 10 1.06 (0.91–1.23)
The adjusted RR for death from any cause was 0.87 (95% CI 0.83–0.92) for drinkers compared with nondrinkers, an analysis that accounted for the opposing effects of potentially fatal alcohol-related risk (as from car accidents or liver cirrhosis) and any protective effect on CV health, Ghali observed.
A look at end points by level of alcohol intake showed that the CV-event risk was lowest at one to two drinks per day (figuring that one drink contains 2.5 g to <15 g alcohol). Reductions in stroke risk or stroke mortality weren't seen at greater than one drink per day.
Adjusted Relative Risk (RR) for Outcomes by Daily Alcohol Intake, Drinkers vs Nondrinkers
End point <2.5 g/d, RR (95% CI) 2.5–14.9 g/d* RR (95% CI) 15–29.9 g/d RR (95% CI)
CV mortality 0.71 (0.57–0.89) 0.77 (0.71–0.83) 0.75 (0.70–0.80)
Incident CHD 0.96 (0.86–1.06) 0.75 (0.65–0.88) 0.66 (0.59–0.75)
CHD mortality 0.92 (0.80–1.06) 0.79 (0.73–0.86) 0.79 (0.71–0.88)
Incident stroke 0.81 (0.74–0.89) 0.80 (0.74–0.87) 0.92 (0.82–1.04)
Stroke mortality 1.00 (0.75–1.34) 0.86 (0.75–0.99) 1.15 (0.86–1.54)
*About one drink per day
The adjusted risk of incident stroke was significantly increased at a daily intake exceeding 60 g: RR 1.62 (95% CI 1.32–1.98).
The group's "companion review" included 44 studies that "evaluated the circulating blood levels of [prespecified] biomarkers during a period of intentional, prescribed alcohol feeding vs a period of no alcohol use."
No significant effect of alcohol use was seen on total cholesterol levels or levels of LDL cholesterol, triglycerides, or Lp(a). However, "significant changes in levels of high-density lipoprotein cholesterol, fibrinogen, and adiponectin after alcohol consumption were well within a pharmacologically relevant magnitude."
The effects were independent of whether alcohol was consumed in beer, wine, or liquor.
Pooled Mean Differences in Biomarker Levels During Periods of Alcohol Use vs Periods of Nonuse
Biomarker Number of studies Mean difference (95% CI)
HDL cholesterol (mmol/L) 33 0.094 (0.064–0.123)
Apolipoprotein A1 (g/L) 16 0.101 (0.073–0.129)
Fibrinogen (g/L) 7 −0.20 (−0.29 to −0.11)
Adiponectin (mg/L) 4 0.56 (0.39–0.72)
All changes alcohol use vs nonuse p<0.01
The effect on HDL cholesterol went up with alcohol-intake level, increasing by 0.072 mmol/L at one to two drinks per day up to 0.14 mmol/L at more than four drinks per day (p=0.013 for the trend), the group reports.
"This degree of increase is greater than any currently available single pharmacological therapy, including fibrates (approved by the Food and Drug Administration for people with low levels of high-density lipoprotein cholesterol)."
"I don't want to come across as a proponent of widespread consumption of alcohol," Ghali said; concern that promoting light to moderate alcohol consumption could cause harm is appropriate. "But there isn't proof that recommending it would lead to harm, and that's worth just keeping in the back of our minds."
Ghali said the authors have no conflicts of interest. The analyses were supported by the Robert Wood Johnson Foundation, Substance Abuse and Mental Health Services, and Administration Center for Substance Abuse Treatment. Individual coauthors were supported by the Alberta Heritage Foundation for Medical Research and the Canadian Institutes of Health Research.
References
Steve Stiles
February 28, 2011 (Calgary, Alberta) — It's time to acknowledge the pile of evidence that light to moderate alcohol consumption is not only good for cardiovascular health, it could potentially be recommended for CV risk reduction, according to authors of two meta-analyses published online February 22, 2011 in BMJ
An analysis of prospective cohort studies showing alcohol effects on cardiovascular end points, with first author Dr Paul E Ronksley (University of Calgary, AB), suggested that most any level of alcohol intake is protective against CV mortality, incident CHD, and CHD mortality, while intake of up to one drink per day is protective against incident stroke and stroke mortality. The findings are consistent with a vast evidence base linking light to moderate alcohol intake with reduced CV risk.
The other report focused on clinical intervention studies of alcohol effects on biomarkers associated with CV disease and concluded that moderate intake raises levels of HDL cholesterol, apolipoprotein A1, and adiponectin and reduces fibrinogen levels. In their analysis, Dr Susan E Brien (University of Calgary) et al defined moderate alcohol intake as up to a drink per day for women and two drinks per day for men.
Although observational studies can't establish cause and effect, the group observes, together the two reports make a compelling case for alcohol as an actual cause of the reduced CV risk long associated with light to moderate drinking.
But What Do You Do With the Information?
"Then the question becomes, what do you do with that [information]? There are two levels at which it needs to be considered. One is: what does a doctor say to a patient in a clinical setting? And the second is: what do public-health officials tell the public?" Dr William A Ghali (University of Calgary), senior author of both reports, said for heartwire .
"With respect to public-health messages," he and his coauthors write, "there may now be an impetus to better communicate to the public that alcohol, in moderation, may have overall health benefits that outweigh the risks in selected subsets of patients."
In clinical practice, they contend, the evidence base supporting CV benefits from alcohol intake could be the basis for "counseling for selected patients to incorporate moderate amounts of alcohol into their diets to improve their coronary heart disease risk."
But before that could happen, the strategy would have to be evaluated "in pragmatic clinical trials that assess the questions of optimal patient selection, compliance, risks, and benefits."
I just don't think we should close our eyes and ears to this evidence.
Such trials wouldn't focus as much on links between alcohol intake and clinical outcomes, but more on "the receptivity of both physicians and patients to the recommended consumption of alcohol for therapeutic purposes and the extent to which it can be successfully and safely implemented."
Ghali recognizes that he and his colleagues are extending the public debate about alcohol and CV health beyond its comfort zone, in which people who already partake are assured their moderate drinking may improve cardiovascular health. Teetotalers are not currently advised that if they start drinking, it will be good for their hearts.
On the other hand, public-health messages advocating "consumption of alcohol for therapeutic purposes" would likely be offensive to "people who view, and people who have good reason to view, alcohol as a very dangerous substance," Ghali acknowledged.
"I think we should undertake a process of dialog and debate around what should be said and then evaluate whatever we come up with in terms of public-health messages to see what impact that has on behaviors," he said. "I just don't think we should close our eyes and ears to this evidence."
Outcomes and Biomarker Studies: Consistent Message
The group's outcomes meta-analysis included 84 prospective cohort studies of adults without preexisting CV disease, both drinkers and nondrinkers. Follow-up ranged from 2.5 to 35 years (mean 11 years); 85% of the studies followed participants for more than five years.
Adjusted Relative Risk (RR) for Outcomes, Drinkers Compared With Nondrinkers
End point Number of studies RR (95% CI)
CV mortality 21 0.75 (0.70–0.80)
Incident CHD 29 0.71 (0.66–0.77)
CHD mortality 31 0.75 (0.68–0.81)
Incident stroke 17 0.98 (0.91–1.06)
Stroke mortality 10 1.06 (0.91–1.23)
The adjusted RR for death from any cause was 0.87 (95% CI 0.83–0.92) for drinkers compared with nondrinkers, an analysis that accounted for the opposing effects of potentially fatal alcohol-related risk (as from car accidents or liver cirrhosis) and any protective effect on CV health, Ghali observed.
A look at end points by level of alcohol intake showed that the CV-event risk was lowest at one to two drinks per day (figuring that one drink contains 2.5 g to <15 g alcohol). Reductions in stroke risk or stroke mortality weren't seen at greater than one drink per day.
Adjusted Relative Risk (RR) for Outcomes by Daily Alcohol Intake, Drinkers vs Nondrinkers
End point <2.5 g/d, RR (95% CI) 2.5–14.9 g/d* RR (95% CI) 15–29.9 g/d RR (95% CI)
CV mortality 0.71 (0.57–0.89) 0.77 (0.71–0.83) 0.75 (0.70–0.80)
Incident CHD 0.96 (0.86–1.06) 0.75 (0.65–0.88) 0.66 (0.59–0.75)
CHD mortality 0.92 (0.80–1.06) 0.79 (0.73–0.86) 0.79 (0.71–0.88)
Incident stroke 0.81 (0.74–0.89) 0.80 (0.74–0.87) 0.92 (0.82–1.04)
Stroke mortality 1.00 (0.75–1.34) 0.86 (0.75–0.99) 1.15 (0.86–1.54)
*About one drink per day
The adjusted risk of incident stroke was significantly increased at a daily intake exceeding 60 g: RR 1.62 (95% CI 1.32–1.98).
The group's "companion review" included 44 studies that "evaluated the circulating blood levels of [prespecified] biomarkers during a period of intentional, prescribed alcohol feeding vs a period of no alcohol use."
No significant effect of alcohol use was seen on total cholesterol levels or levels of LDL cholesterol, triglycerides, or Lp(a). However, "significant changes in levels of high-density lipoprotein cholesterol, fibrinogen, and adiponectin after alcohol consumption were well within a pharmacologically relevant magnitude."
The effects were independent of whether alcohol was consumed in beer, wine, or liquor.
Pooled Mean Differences in Biomarker Levels During Periods of Alcohol Use vs Periods of Nonuse
Biomarker Number of studies Mean difference (95% CI)
HDL cholesterol (mmol/L) 33 0.094 (0.064–0.123)
Apolipoprotein A1 (g/L) 16 0.101 (0.073–0.129)
Fibrinogen (g/L) 7 −0.20 (−0.29 to −0.11)
Adiponectin (mg/L) 4 0.56 (0.39–0.72)
All changes alcohol use vs nonuse p<0.01
The effect on HDL cholesterol went up with alcohol-intake level, increasing by 0.072 mmol/L at one to two drinks per day up to 0.14 mmol/L at more than four drinks per day (p=0.013 for the trend), the group reports.
"This degree of increase is greater than any currently available single pharmacological therapy, including fibrates (approved by the Food and Drug Administration for people with low levels of high-density lipoprotein cholesterol)."
"I don't want to come across as a proponent of widespread consumption of alcohol," Ghali said; concern that promoting light to moderate alcohol consumption could cause harm is appropriate. "But there isn't proof that recommending it would lead to harm, and that's worth just keeping in the back of our minds."
Ghali said the authors have no conflicts of interest. The analyses were supported by the Robert Wood Johnson Foundation, Substance Abuse and Mental Health Services, and Administration Center for Substance Abuse Treatment. Individual coauthors were supported by the Alberta Heritage Foundation for Medical Research and the Canadian Institutes of Health Research.
References
Thursday, February 24, 2011
ACIP Revises Language for Tdap Vaccination of Healthcare Workers
From Medscape Medical News
Emma Hitt, PhD
February 23, 2011 — Revised language on the use of tetanus, diphtheria, and pertussis (Tdap) vaccination in healthcare personnel was voted on and approved by the Centers for Disease Control and Prevention's (CDC's) Advisory Committee in Immunization Practices (ACIP) yesterday.
The wording states that healthcare personnel, regardless of age, should receive a single dose of Tdap as soon as feasible if they have not previously received Tdap, and regardless of time since their last dose of tetanus and diphtheria toxoids (Td) vaccine.
In addition, after the receipt of Tdap, healthcare personnel should receive routine booster immunization against tetanus and diphtheria, according to previously published guidelines. Hospitals and ambulatory care facilities should provide Tdap for healthcare personnel and use approaches that maximize vaccination rates, such as providing Tdap at no charge.
In 2005, ACIP voted to recommend routine use of a single dose of Tdap for adults aged 19 to 64 years to replace the next booster dose Td vaccine. ACIP also recommended Tdap for adults who have close contact with infants younger than 12 months.
At the last meeting, in October 2010, ACIP recommended a booster vaccination with Tdap vaccine in people between aged 11 and 64 years and in those older than 65 years if they come in close contact with infants.
Today, proposed modified language on the use of Tdap in healthcare personnel was voted on by 15 members, with 14 votes in favor that the new language should be adopted and 1 abstention.
Antimicrobial Prophylaxis in Healthcare Personnel
The committee also voted on whether the use of postexposure antimicrobial prophylaxis in healthcare personnel should be expressly stated in the guidelines.
Jennifer L. Liang, DVM, from the ACIP Pertussis Working Group, described findings from a study conducted at Vanderbilt University, Nashville, Tennessee, supporting the idea that Tdap-vaccinated healthcare personnel should receive postexposure prophylaxis.
The study included 116 exposures that occurred among 94 healthcare personnel and found that pertussis infection occurred in 10% of exposed healthcare personnel who did not receive postexposure prophylaxis, whereas it occurred in 2% of exposed healthcare personnel who did receive postexposure prophylaxis.
"There may be a benefit for postexposure prophylaxis in vaccinated healthcare personnel," said Dr. Liang. "The low risk of infection in both groups suggests that both strategies may be acceptable," she added.
The new ACIP guidelines state that Tdap vaccination may not preclude the need for postexposure antimicrobial prophylaxis, which is recommended for all healthcare personnel who have unprotected exposure to pertussis and are likely to be exposed to a patient at risk for severe pertussis; for example, hospitalized neonates and pregnant women.
According to the new guidelines, healthcare personnel should receive postexposure antimicrobial prophylaxis or should be monitored daily for 21 days after pertussis exposure for signs and symptoms of pertussis. The vote carried unanimously in favor of incorporating the new language.
The CDC is not obligated to follow the ACIP's suggestions, but the agency usually does.
Use of Tdap in Pregnant Women
The committee also discussed, but did not vote on, the use of Tdap in pregnant women — a group that has been excluded from randomized trials, making data unavailable in this setting. Tdap is not currently licensed for use during pregnancy, but 2 large clinical trials are ongoing, said presenter Tejpratap Tiwari, MD, from the CDC's National Center for Immunization and Respiratory Diseases.
The new ACIP wording recommends Td vaccination for booster protection against tetanus and diphtheria in pregnant women, although healthcare providers may choose to administer Tdap instead of Td during pregnancy to add protection against pertussis in special situations. In this case, "pregnant women should be informed of the lack of data confirming the safety and immunogenicity of Tdap in pregnant women," said Dr. Tiwari.
"The working group felt current strategies to prevent infant deaths were insufficient," Dr. Liang concluded. "All but one working group member felt that safety data were supportive of maternal vaccination on maternal and infant outcomes," she said. "In addition, the majority of the working group wanted to modify current recommendations, but the working group was split on the issue since the data are not conclusive."
Emma Hitt, PhD
February 23, 2011 — Revised language on the use of tetanus, diphtheria, and pertussis (Tdap) vaccination in healthcare personnel was voted on and approved by the Centers for Disease Control and Prevention's (CDC's) Advisory Committee in Immunization Practices (ACIP) yesterday.
The wording states that healthcare personnel, regardless of age, should receive a single dose of Tdap as soon as feasible if they have not previously received Tdap, and regardless of time since their last dose of tetanus and diphtheria toxoids (Td) vaccine.
In addition, after the receipt of Tdap, healthcare personnel should receive routine booster immunization against tetanus and diphtheria, according to previously published guidelines. Hospitals and ambulatory care facilities should provide Tdap for healthcare personnel and use approaches that maximize vaccination rates, such as providing Tdap at no charge.
In 2005, ACIP voted to recommend routine use of a single dose of Tdap for adults aged 19 to 64 years to replace the next booster dose Td vaccine. ACIP also recommended Tdap for adults who have close contact with infants younger than 12 months.
At the last meeting, in October 2010, ACIP recommended a booster vaccination with Tdap vaccine in people between aged 11 and 64 years and in those older than 65 years if they come in close contact with infants.
Today, proposed modified language on the use of Tdap in healthcare personnel was voted on by 15 members, with 14 votes in favor that the new language should be adopted and 1 abstention.
Antimicrobial Prophylaxis in Healthcare Personnel
The committee also voted on whether the use of postexposure antimicrobial prophylaxis in healthcare personnel should be expressly stated in the guidelines.
Jennifer L. Liang, DVM, from the ACIP Pertussis Working Group, described findings from a study conducted at Vanderbilt University, Nashville, Tennessee, supporting the idea that Tdap-vaccinated healthcare personnel should receive postexposure prophylaxis.
The study included 116 exposures that occurred among 94 healthcare personnel and found that pertussis infection occurred in 10% of exposed healthcare personnel who did not receive postexposure prophylaxis, whereas it occurred in 2% of exposed healthcare personnel who did receive postexposure prophylaxis.
"There may be a benefit for postexposure prophylaxis in vaccinated healthcare personnel," said Dr. Liang. "The low risk of infection in both groups suggests that both strategies may be acceptable," she added.
The new ACIP guidelines state that Tdap vaccination may not preclude the need for postexposure antimicrobial prophylaxis, which is recommended for all healthcare personnel who have unprotected exposure to pertussis and are likely to be exposed to a patient at risk for severe pertussis; for example, hospitalized neonates and pregnant women.
According to the new guidelines, healthcare personnel should receive postexposure antimicrobial prophylaxis or should be monitored daily for 21 days after pertussis exposure for signs and symptoms of pertussis. The vote carried unanimously in favor of incorporating the new language.
The CDC is not obligated to follow the ACIP's suggestions, but the agency usually does.
Use of Tdap in Pregnant Women
The committee also discussed, but did not vote on, the use of Tdap in pregnant women — a group that has been excluded from randomized trials, making data unavailable in this setting. Tdap is not currently licensed for use during pregnancy, but 2 large clinical trials are ongoing, said presenter Tejpratap Tiwari, MD, from the CDC's National Center for Immunization and Respiratory Diseases.
The new ACIP wording recommends Td vaccination for booster protection against tetanus and diphtheria in pregnant women, although healthcare providers may choose to administer Tdap instead of Td during pregnancy to add protection against pertussis in special situations. In this case, "pregnant women should be informed of the lack of data confirming the safety and immunogenicity of Tdap in pregnant women," said Dr. Tiwari.
"The working group felt current strategies to prevent infant deaths were insufficient," Dr. Liang concluded. "All but one working group member felt that safety data were supportive of maternal vaccination on maternal and infant outcomes," she said. "In addition, the majority of the working group wanted to modify current recommendations, but the working group was split on the issue since the data are not conclusive."
Tuesday, February 15, 2011
Old Influenza Vaccines Can Boost New Ones
From Medscape Medical News
Jim Kling
February 14, 2011 — An H5 influenza vaccine that is antigenically out of date can be effectively used as a primer for a second dose of a contemporary antigen.
The strategy could help public health officials respond quickly to a pandemic, because they could give the first dose immediately, without having to wait for the delivery of a novel vaccine, according to a study published in the March issue of the Journal of Infectious Diseases.
Avian influenza viruses of the H5N1 subtype have caused severe disease in humans, prompting concerns that an H5N1 virus could develop into a pandemic form. Effective immunization would likely require 2 doses, but inactivated H5N1 vaccines have generated low frequencies of immune response, which could pose difficulties for an immunization program.
The United States has stockpiled 20 million doses of A/Vietnam/04 vaccine. The researchers wanted to determine the effect of priming with this older strain on a later dose of the more contemporary H5 antigen (A/Indonesia/05). They also determined the effect of dose timing on induced immunity.
The study included 505 healthy adults aged 18 to 49 years (41% men, 59% women) who received 2 vaccine doses. The participants were divided into various groups, with some given only A/Vietnam/04 vaccine, some only given A/Indonesia/05, and others given a combination of the 2 doses.
For each participant, the researchers determined the geometric mean titer (GMT) of serum hemagglutinating inhibiting (HI) antibody and microneutralizing antibody. Neither group showed any cross-reactivity; that is, if they were vaccinated with A/Vietnam/04, they produced no antibodies to A/Indonesia/05.
When a dose of A/Vietnam/04 vaccine was used to prime a later booster with A/Indonesia/05, participants developed antibodies to both virus types (HI GMT 13.6 to A/Vietnam/04 vaccine and 10.1 to A/Indonesia/05 vaccine at day 56). These levels were lower than the levels achieved when 2 doses of homologous vaccines were given to another group of participants, although it was not statistically significant for A/Vietnam/04 antigen (A/Vietnam/04 antigen HI GMT on day 56, 22.9 vs 13.6 [P = .372]; A/Indonesia/05 vaccine HI GMT on day 56, 27.6 vs 10.1 [P = .001]). Similar trends were seen in the measurement of microneutralizing antibody (P = .05 for each comparison).
A regimen of both antigens combined in half doses also produced responses to both viruses. At days 0 and 28, the researchers observed no significant difference between HI antibody to A/Indonesia/05 antigen after A/Indonesia/05 vaccine alone or after a combination vaccine consisting of 45 μg A/Vietnam/04 vaccine and 45 μg A/Indonesia/05 vaccine.
The researchers found that doses on days 0 and 7 created some immunity. Dosing regimens of days 0 and 14 and 0 and 28 produced a stronger response. The best response came at the longest interval, between 0 and 180 days. In a pandemic, this time period is likely to be too long for effective countermeasures. The authors suggest further research to determine whether the same patterns hold with adjuvanted vaccines.
Inducement of titers high enough to confer protection against novel hemagglutinin antigens will require 2 doses. The immune responses measured in the study were modest, but the results hint at potential strategies for vaccinating against an avian influenza outbreak The results suggest that at-risk individuals could be preimmunized with a dose of antigenically distantly related H5 to conserve new vaccine.
The results echo immunization experience with the 2009 H1 vaccine, when a single dose of 2009 H1 HA subunit vaccine produced a response in persons aged 10 years and older. The authors believe that previous H1 infection had primed them to respond to the vaccine, even though the antigen of the previous infection was probably distantly related.
J Infect Dis. 2011;203:666-673. Abstract
Jim Kling
February 14, 2011 — An H5 influenza vaccine that is antigenically out of date can be effectively used as a primer for a second dose of a contemporary antigen.
The strategy could help public health officials respond quickly to a pandemic, because they could give the first dose immediately, without having to wait for the delivery of a novel vaccine, according to a study published in the March issue of the Journal of Infectious Diseases.
Avian influenza viruses of the H5N1 subtype have caused severe disease in humans, prompting concerns that an H5N1 virus could develop into a pandemic form. Effective immunization would likely require 2 doses, but inactivated H5N1 vaccines have generated low frequencies of immune response, which could pose difficulties for an immunization program.
The United States has stockpiled 20 million doses of A/Vietnam/04 vaccine. The researchers wanted to determine the effect of priming with this older strain on a later dose of the more contemporary H5 antigen (A/Indonesia/05). They also determined the effect of dose timing on induced immunity.
The study included 505 healthy adults aged 18 to 49 years (41% men, 59% women) who received 2 vaccine doses. The participants were divided into various groups, with some given only A/Vietnam/04 vaccine, some only given A/Indonesia/05, and others given a combination of the 2 doses.
For each participant, the researchers determined the geometric mean titer (GMT) of serum hemagglutinating inhibiting (HI) antibody and microneutralizing antibody. Neither group showed any cross-reactivity; that is, if they were vaccinated with A/Vietnam/04, they produced no antibodies to A/Indonesia/05.
When a dose of A/Vietnam/04 vaccine was used to prime a later booster with A/Indonesia/05, participants developed antibodies to both virus types (HI GMT 13.6 to A/Vietnam/04 vaccine and 10.1 to A/Indonesia/05 vaccine at day 56). These levels were lower than the levels achieved when 2 doses of homologous vaccines were given to another group of participants, although it was not statistically significant for A/Vietnam/04 antigen (A/Vietnam/04 antigen HI GMT on day 56, 22.9 vs 13.6 [P = .372]; A/Indonesia/05 vaccine HI GMT on day 56, 27.6 vs 10.1 [P = .001]). Similar trends were seen in the measurement of microneutralizing antibody (P = .05 for each comparison).
A regimen of both antigens combined in half doses also produced responses to both viruses. At days 0 and 28, the researchers observed no significant difference between HI antibody to A/Indonesia/05 antigen after A/Indonesia/05 vaccine alone or after a combination vaccine consisting of 45 μg A/Vietnam/04 vaccine and 45 μg A/Indonesia/05 vaccine.
The researchers found that doses on days 0 and 7 created some immunity. Dosing regimens of days 0 and 14 and 0 and 28 produced a stronger response. The best response came at the longest interval, between 0 and 180 days. In a pandemic, this time period is likely to be too long for effective countermeasures. The authors suggest further research to determine whether the same patterns hold with adjuvanted vaccines.
Inducement of titers high enough to confer protection against novel hemagglutinin antigens will require 2 doses. The immune responses measured in the study were modest, but the results hint at potential strategies for vaccinating against an avian influenza outbreak The results suggest that at-risk individuals could be preimmunized with a dose of antigenically distantly related H5 to conserve new vaccine.
The results echo immunization experience with the 2009 H1 vaccine, when a single dose of 2009 H1 HA subunit vaccine produced a response in persons aged 10 years and older. The authors believe that previous H1 infection had primed them to respond to the vaccine, even though the antigen of the previous infection was probably distantly related.
J Infect Dis. 2011;203:666-673. Abstract
Friday, February 11, 2011
U-Shaped Curve for Sleep Duration and Cardiovascular Disease
From Heartwire
Sue Hughes
February 10, 2011 (Warwick, United Kingdom) — Both short and long duration of sleep are predictors or markers of cardiovascular outcomes, a new review suggests [1].
The review, published online February 7, 2011 in the European Heart Journal, included 15 prospective studies in a total of 474 684 participants and shows an increased risk of developing or dying of CHD and stroke on either end of the distribution of sleep duration. But results for total cardiovascular events showed no detectable effect in short sleepers and a significant increased risk in long sleepers.
In the studies, sleep duration was assessed by questionnaire and incident cases through certification and event registers. Follow-up ranged from 6.9 to 25 years, and there were a total of 16 067 events.
Normal sleep time was defined as seven to eight hours per night.
Short sleepers were designated as those with less than five to sixhours per night, and long sleepers as those with more than eight to nine hours per night.
The researchers, led by Dr Francesco Cappuccio (Warwick Medical School, Coventry, UK), say that the mechanisms behind these associations are not fully understood. They list causative mechanisms relating short duration of sleep to adverse health outcomes as including changes in circulating levels of leptin and ghrelin, which in turn would increase appetite, caloric intake, reduce energy expenditure, and facilitate the development of obesity and impaired glycemic control, with increased cardiovascular risk. Increased cortisol secretion and altered growth hormone metabolism have also been implicated. Low-grade inflammation is also activated during short sleep, with possible implications not only for cardiovascular disease but also for other chronic conditions, including cancer.
Long Sleep: Just a Marker of Comorbidity
However, they note that there have been no postulated mechanisms to explain long duration of sleep as a cause of cardiovascular disease, and this association may just be a result of residual confounding and comorbidities. In particular, depressive symptoms, low socioeconomic status, unemployment, low level of physical activity, and undiagnosed health conditions have all been shown to be associated with long duration of sleep and to confound the association with morbidity and mortality. They add that a recent intervention study of weight reduction, healthy diet, and increased physical activity showed, compared with a control group, a significant reduction in the seven-year incidence of type 2 diabetes among long sleepers, supporting the view that long sleep may be an indicator of risk, reversible upon changes in the risk factors.
They conclude that people reporting consistently sleeping five hours or less per night should be regarded as a higher-risk group for cardiovascular morbidity and mortality. And that sleeping nine hours or more per night may represent a useful diagnostic tool for detecting subclinical or undiagnosed comorbidity.
References
Sue Hughes
February 10, 2011 (Warwick, United Kingdom) — Both short and long duration of sleep are predictors or markers of cardiovascular outcomes, a new review suggests [1].
The review, published online February 7, 2011 in the European Heart Journal, included 15 prospective studies in a total of 474 684 participants and shows an increased risk of developing or dying of CHD and stroke on either end of the distribution of sleep duration. But results for total cardiovascular events showed no detectable effect in short sleepers and a significant increased risk in long sleepers.
In the studies, sleep duration was assessed by questionnaire and incident cases through certification and event registers. Follow-up ranged from 6.9 to 25 years, and there were a total of 16 067 events.
Normal sleep time was defined as seven to eight hours per night.
Short sleepers were designated as those with less than five to sixhours per night, and long sleepers as those with more than eight to nine hours per night.
The researchers, led by Dr Francesco Cappuccio (Warwick Medical School, Coventry, UK), say that the mechanisms behind these associations are not fully understood. They list causative mechanisms relating short duration of sleep to adverse health outcomes as including changes in circulating levels of leptin and ghrelin, which in turn would increase appetite, caloric intake, reduce energy expenditure, and facilitate the development of obesity and impaired glycemic control, with increased cardiovascular risk. Increased cortisol secretion and altered growth hormone metabolism have also been implicated. Low-grade inflammation is also activated during short sleep, with possible implications not only for cardiovascular disease but also for other chronic conditions, including cancer.
Long Sleep: Just a Marker of Comorbidity
However, they note that there have been no postulated mechanisms to explain long duration of sleep as a cause of cardiovascular disease, and this association may just be a result of residual confounding and comorbidities. In particular, depressive symptoms, low socioeconomic status, unemployment, low level of physical activity, and undiagnosed health conditions have all been shown to be associated with long duration of sleep and to confound the association with morbidity and mortality. They add that a recent intervention study of weight reduction, healthy diet, and increased physical activity showed, compared with a control group, a significant reduction in the seven-year incidence of type 2 diabetes among long sleepers, supporting the view that long sleep may be an indicator of risk, reversible upon changes in the risk factors.
They conclude that people reporting consistently sleeping five hours or less per night should be regarded as a higher-risk group for cardiovascular morbidity and mortality. And that sleeping nine hours or more per night may represent a useful diagnostic tool for detecting subclinical or undiagnosed comorbidity.
References
Wednesday, February 9, 2011
Vitamin D and Cancer Mortality: Not to be Taken Lightly
Craig A. Elmets, MD
Introduction
Ultraviolet radiation has various deleterious effects but a positive influence on vitamin D metabolism.
Dermatologists typically recommend that patients use sunscreen and take other precautions to prevent sunburn, nonmelanoma skin cancer, melanoma, and cutaneous photoaging.
This practice is increasingly being scrutinized because much of the population is vitamin D deficient and because several healthful effects have been attributed to vitamin D, including a potential cancer-protection effect.
To assess the association between baseline serum 25-hydroxyvitamin D levels (25[OH]D) and cancer mortality, researchers prospectively examined data on 16,819 participants in the Third National Health and Nutritional Examination Survey (NHANES III). Levels of 25(OH)D were measured once, in spring or summer in higher latitudes and in fall or winter in lower latitudes.
During a mean follow-up of 13.4 years, 884 participants died of cancer.
Cancer mortality did not correlate with serum 25(OH)D in the total population or in men and women analyzed separately.
However, men with 25(OH)D levels >80 nmol/L had a significantly higher cancer mortality rate than those with levels <50 nmol/L.
Among women in the summer/higher-latitude group, the overall cancer risk trended significantly lower with higher 25(OH)D level.
Serum 25(OH)D levels were not associated with cancer mortality among non-Hispanic white, non-Hispanic black, and Mexican-American subgroups.
Colon cancer deaths trended nonsignificantly lower with higher 25(OH)D levels.
In men, but not women, elevated baseline serum 25(OH)D was associated with increased deaths from lung cancer and from digestive tract cancers other than colorectal cancer. No clear trend was apparent for female breast cancer, prostate cancer, or combined deaths from non-Hodgkin lymphoma or leukemia.
Comment
The large NHANES III database provides a unique opportunity to evaluate in detail the relation between vitamin D and diseases in the U.S. Study limitations include the measurement of vitamin D levels only at baseline. The findings suggest that we don't yet have the final word on the relationship between vitamin D and human health and that claims that vitamin D protects against specific cancers are not necessarily supported by the facts. Dermatologists can use this information to counter people's presumption that sun exposure or tanning bed use will protect against cancer mortality; in fact, such exposure may actually increase deaths from some cancers.
Introduction
Ultraviolet radiation has various deleterious effects but a positive influence on vitamin D metabolism.
Dermatologists typically recommend that patients use sunscreen and take other precautions to prevent sunburn, nonmelanoma skin cancer, melanoma, and cutaneous photoaging.
This practice is increasingly being scrutinized because much of the population is vitamin D deficient and because several healthful effects have been attributed to vitamin D, including a potential cancer-protection effect.
To assess the association between baseline serum 25-hydroxyvitamin D levels (25[OH]D) and cancer mortality, researchers prospectively examined data on 16,819 participants in the Third National Health and Nutritional Examination Survey (NHANES III). Levels of 25(OH)D were measured once, in spring or summer in higher latitudes and in fall or winter in lower latitudes.
During a mean follow-up of 13.4 years, 884 participants died of cancer.
Cancer mortality did not correlate with serum 25(OH)D in the total population or in men and women analyzed separately.
However, men with 25(OH)D levels >80 nmol/L had a significantly higher cancer mortality rate than those with levels <50 nmol/L.
Among women in the summer/higher-latitude group, the overall cancer risk trended significantly lower with higher 25(OH)D level.
Serum 25(OH)D levels were not associated with cancer mortality among non-Hispanic white, non-Hispanic black, and Mexican-American subgroups.
Colon cancer deaths trended nonsignificantly lower with higher 25(OH)D levels.
In men, but not women, elevated baseline serum 25(OH)D was associated with increased deaths from lung cancer and from digestive tract cancers other than colorectal cancer. No clear trend was apparent for female breast cancer, prostate cancer, or combined deaths from non-Hodgkin lymphoma or leukemia.
Comment
The large NHANES III database provides a unique opportunity to evaluate in detail the relation between vitamin D and diseases in the U.S. Study limitations include the measurement of vitamin D levels only at baseline. The findings suggest that we don't yet have the final word on the relationship between vitamin D and human health and that claims that vitamin D protects against specific cancers are not necessarily supported by the facts. Dermatologists can use this information to counter people's presumption that sun exposure or tanning bed use will protect against cancer mortality; in fact, such exposure may actually increase deaths from some cancers.
Chocolate May Exacerbate Acne in Men
From Medscape Medical News
Fran Lowry
February 8, 2011 (New Orleans, Louisiana) — Bad news for chocolate lovers who are prone to acne — researchers report that the consumption of pure chocolate can exacerbate facial acne vulgaris within days in people who have a history of the skin disorder.
The finding runs counter to the results of earlier studies that reported no connection between chocolate and acne breakouts, said Samantha Block, a medical student at the University of Miami Miller School of Medicine, in Florida, who spoke here at the American Academy of Dermatology 69th Annual Meeting.
The studies that were fundamental to the notion that diet and acne are not related looked at acne outbreaks after the consumption of chocolate candy, which contains added ingredients such as milk, sugar, and nuts, Ms Block said.
"No studies were found in the literature assessing the effects of pure chocolate, made of 100% cocoa, on acne, so we set out to see what effect pure chocolate might have on acne exacerbation," she said.
The study involved 10 healthy male subjects between 18 and 35 years of age with a history of facial acne vulgaris. The subjects had at least 1 but no more than 4 total facial acneiform lesions (comedones and papules without pustules, nodules, or cysts) at study entry, and were not allowed to use any over-the-counter or prescribed medications.
"We limited our study to males because we didn't want any confounding influences of hormones that women might have around their menstrual cycle affecting our study," Ms. Block explained.
The subjects consumed 6 ounces of 100% Ghirardelli chocolate, which they washed down with a glass of water. They were instructed to maintain their usual diet for 1 week.
Lesion counts were assessed at baseline and on days 4 and 7.
The researchers found a statistically significant increase in the mean number of total acneiform lesions (comedones, papules, and pustules) on day 4 (P = .031) and on day 7 (P = .050), compared with baseline. There was also a trend toward increases in the mean number of noninflammatory comedones on days 4 (P = .058) and 7 (P = .067). There were no significant differences in the number of inflammatory lesions (papules and pustules) at any time point.
The study found a strong correlation between the amount of chocolate that was consumed and the amount of acneiform lesions that developed (r = 0.510 on day 4 and 0.608 on day 7).
Subjects also reported headache, nausea, gastrointestinal distress, vomiting, and diarrhea, Ms. Block noted.
"I think these results show that 100% chocolate does exacerbate acne in individuals who are acne prone," she told Medscape Medical News. "We are planning to continue this work and are recruiting patients for a randomized placebo-controlled trial."
She explained the reasons for choosing Ghirardelli chocolate. "We felt that if our subjects were going to eat chocolate, why don't we give them the best? Also, Ghirardelli makes a chocolate bar that is made with 100% pure cocoa. Not all the manufacturers have 100% chocolate."
"There is a possible mechanism here," F.W. (Bill) Danby, MD, a dermatologist in private practice in Manchester, New Hampshire, told Medscape Medical News after the presentation. "There are theobromines in chocolate. I have no idea whether Ghirardelli chocolate has more theobromines than other chocolate, but I get more headaches from Ghirardelli chocolate than I do from Hershey's, so I wonder about that as a mechanism. That should be quantitated and investigated further."
He added that the earlier work that found no link between chocolate consumption and acne was "fuzzy," but everyday evidence would indicate otherwise. "We all have patients who swear that their acne breakout was due to eating chocolate, so this may be a reason," he said.
Jonette Keri, MD, from the University of Miami Miller School of Medicine, told Medscape Medical News that this study adds another piece to the puzzle of what causes acne to flare up.
"We're getting closer and closer to figuring out how diet affects acne. I love this study because it's adding a piece to that puzzle, so I think it's important. I'm pleased that they are going to continue with a randomized trial," Dr. Keri, who moderated the session, said. She was not part of the study.
Ms. Block, Dr. Danby, and Dr. Keri have disclosed no relevant financial relationships.
American Academy of Dermatology (AAD) 69th Annual Meeting: Abstract 305. Presented February 6, 2011.
Fran Lowry
February 8, 2011 (New Orleans, Louisiana) — Bad news for chocolate lovers who are prone to acne — researchers report that the consumption of pure chocolate can exacerbate facial acne vulgaris within days in people who have a history of the skin disorder.
The finding runs counter to the results of earlier studies that reported no connection between chocolate and acne breakouts, said Samantha Block, a medical student at the University of Miami Miller School of Medicine, in Florida, who spoke here at the American Academy of Dermatology 69th Annual Meeting.
The studies that were fundamental to the notion that diet and acne are not related looked at acne outbreaks after the consumption of chocolate candy, which contains added ingredients such as milk, sugar, and nuts, Ms Block said.
"No studies were found in the literature assessing the effects of pure chocolate, made of 100% cocoa, on acne, so we set out to see what effect pure chocolate might have on acne exacerbation," she said.
The study involved 10 healthy male subjects between 18 and 35 years of age with a history of facial acne vulgaris. The subjects had at least 1 but no more than 4 total facial acneiform lesions (comedones and papules without pustules, nodules, or cysts) at study entry, and were not allowed to use any over-the-counter or prescribed medications.
"We limited our study to males because we didn't want any confounding influences of hormones that women might have around their menstrual cycle affecting our study," Ms. Block explained.
The subjects consumed 6 ounces of 100% Ghirardelli chocolate, which they washed down with a glass of water. They were instructed to maintain their usual diet for 1 week.
Lesion counts were assessed at baseline and on days 4 and 7.
The researchers found a statistically significant increase in the mean number of total acneiform lesions (comedones, papules, and pustules) on day 4 (P = .031) and on day 7 (P = .050), compared with baseline. There was also a trend toward increases in the mean number of noninflammatory comedones on days 4 (P = .058) and 7 (P = .067). There were no significant differences in the number of inflammatory lesions (papules and pustules) at any time point.
The study found a strong correlation between the amount of chocolate that was consumed and the amount of acneiform lesions that developed (r = 0.510 on day 4 and 0.608 on day 7).
Subjects also reported headache, nausea, gastrointestinal distress, vomiting, and diarrhea, Ms. Block noted.
"I think these results show that 100% chocolate does exacerbate acne in individuals who are acne prone," she told Medscape Medical News. "We are planning to continue this work and are recruiting patients for a randomized placebo-controlled trial."
She explained the reasons for choosing Ghirardelli chocolate. "We felt that if our subjects were going to eat chocolate, why don't we give them the best? Also, Ghirardelli makes a chocolate bar that is made with 100% pure cocoa. Not all the manufacturers have 100% chocolate."
"There is a possible mechanism here," F.W. (Bill) Danby, MD, a dermatologist in private practice in Manchester, New Hampshire, told Medscape Medical News after the presentation. "There are theobromines in chocolate. I have no idea whether Ghirardelli chocolate has more theobromines than other chocolate, but I get more headaches from Ghirardelli chocolate than I do from Hershey's, so I wonder about that as a mechanism. That should be quantitated and investigated further."
He added that the earlier work that found no link between chocolate consumption and acne was "fuzzy," but everyday evidence would indicate otherwise. "We all have patients who swear that their acne breakout was due to eating chocolate, so this may be a reason," he said.
Jonette Keri, MD, from the University of Miami Miller School of Medicine, told Medscape Medical News that this study adds another piece to the puzzle of what causes acne to flare up.
"We're getting closer and closer to figuring out how diet affects acne. I love this study because it's adding a piece to that puzzle, so I think it's important. I'm pleased that they are going to continue with a randomized trial," Dr. Keri, who moderated the session, said. She was not part of the study.
Ms. Block, Dr. Danby, and Dr. Keri have disclosed no relevant financial relationships.
American Academy of Dermatology (AAD) 69th Annual Meeting: Abstract 305. Presented February 6, 2011.
Simple Steps to Prevent Common Cancers
From WebMD Health News
Bill Hendrick
February 4, 2011 — About a third of some of the most common forms of cancer could be prevented through healthy diet, physical fitness, and limiting alcohol intake, the American Institute for Cancer Research and the World Cancer Research Fund say in a new report.
About 7.6 million people die from cancer every year worldwide, and 12.7 million new cases are diagnosed. According to the Union for International Cancer Control, a third of cancer cases could be cured through early diagnosis and treatment and 30% to 40% could be prevented.
About 340,000 cases of cancer could be prevented annually in the U.S. if more people started eating a varied and healthy diet, started a regimen of physical activity, limited alcohol intake, and maintained a healthy weight, the new report says.
Exercise Reduces Cancer Risk
“Physical activity is recommended for people of all ages as a means to reduce risks for certain types of cancers and other non-communicable diseases,” says Tim Armstrong, MD, of the World Health Organization, says in a news release.
“In order to improve their health and prevent several diseases, adults should do at least 150 minutes moderate physical activity throughout the week. This can be achieved by simply walking 30 minutes fives times per week or by cycling to work daily.”
To reduce cancer risk, people also should quit smoking, avoid excessive sun exposure, and protect themselves against cancer-causing infections.
Tim Byers, MD, MPH, of the Colorado School of Public Health, says scientists urge Americans “to make the simple lifestyle changes of eating healthy food, getting regular physical activity, and maintaining a healthy weight to reduce cancer risk.”
The World Cancer Declaration outlines 11 targets it says could be achieved by 2020 to fight cancer. These goals include: significant drops in global tobacco use, obesity, and alcohol intake; universal vaccination programs for hepatitis B and human papilloma virus (HPV); universal availability of effective pain medication; and efforts to dispel misconceptions about cancer.
The health organizations say in a detailed report that the most common cancers in the U.S. and Britain are of the breast, colon/rectum, lung, and prostate.
Cancer Prevention Steps
The American Institute for Cancer Research recommends the following cancer-prevention steps.
* Limit consumption of calorie-dense foods, particularly processed foods high in added sugar, low in fiber, or high in fat.
* Avoid sugary drinks.
* Eat more of a variety of vegetables, fruits, whole grains, and beans.
* Limit consumption of red meats such as beef, pork, and lamb, and avoid processed meats.
* Limit consumption of salty foods and foods processed with sodium.
* Dietary supplements for lowering cancer risk are not recommended.
* Be as lean as possible without becoming underweight.
* Be physically active for 30 minutes or more every day.
SOURCE:
News release, Union for International Cancer Control.
Bill Hendrick
February 4, 2011 — About a third of some of the most common forms of cancer could be prevented through healthy diet, physical fitness, and limiting alcohol intake, the American Institute for Cancer Research and the World Cancer Research Fund say in a new report.
About 7.6 million people die from cancer every year worldwide, and 12.7 million new cases are diagnosed. According to the Union for International Cancer Control, a third of cancer cases could be cured through early diagnosis and treatment and 30% to 40% could be prevented.
About 340,000 cases of cancer could be prevented annually in the U.S. if more people started eating a varied and healthy diet, started a regimen of physical activity, limited alcohol intake, and maintained a healthy weight, the new report says.
Exercise Reduces Cancer Risk
“Physical activity is recommended for people of all ages as a means to reduce risks for certain types of cancers and other non-communicable diseases,” says Tim Armstrong, MD, of the World Health Organization, says in a news release.
“In order to improve their health and prevent several diseases, adults should do at least 150 minutes moderate physical activity throughout the week. This can be achieved by simply walking 30 minutes fives times per week or by cycling to work daily.”
To reduce cancer risk, people also should quit smoking, avoid excessive sun exposure, and protect themselves against cancer-causing infections.
Tim Byers, MD, MPH, of the Colorado School of Public Health, says scientists urge Americans “to make the simple lifestyle changes of eating healthy food, getting regular physical activity, and maintaining a healthy weight to reduce cancer risk.”
The World Cancer Declaration outlines 11 targets it says could be achieved by 2020 to fight cancer. These goals include: significant drops in global tobacco use, obesity, and alcohol intake; universal vaccination programs for hepatitis B and human papilloma virus (HPV); universal availability of effective pain medication; and efforts to dispel misconceptions about cancer.
The health organizations say in a detailed report that the most common cancers in the U.S. and Britain are of the breast, colon/rectum, lung, and prostate.
Cancer Prevention Steps
The American Institute for Cancer Research recommends the following cancer-prevention steps.
* Limit consumption of calorie-dense foods, particularly processed foods high in added sugar, low in fiber, or high in fat.
* Avoid sugary drinks.
* Eat more of a variety of vegetables, fruits, whole grains, and beans.
* Limit consumption of red meats such as beef, pork, and lamb, and avoid processed meats.
* Limit consumption of salty foods and foods processed with sodium.
* Dietary supplements for lowering cancer risk are not recommended.
* Be as lean as possible without becoming underweight.
* Be physically active for 30 minutes or more every day.
SOURCE:
News release, Union for International Cancer Control.
Tuesday, February 8, 2011
Calcium and Vitamin D May Reduce Melanoma Risk in High-Risk Women
From Medscape Medical News
Fran Lowry
February 7, 2011 (New Orleans, Louisiana) — A new analysis of the Women's Health Initiative (WHI) study suggests that calcium and vitamin D supplementation reduce the risk for melanoma in women at high risk for the disease because of a history of nonmelanoma skin cancer.
The finding was presented in a late-breaking abstract session here at the American Academy of Dermatology 69th Annual Meeting by Teresa Fu, a medical student at Stanford University School of Medicine in Palo Alto, California.
"There is a lot of interest in vitamin D and whether it can affect your risk for cancer," Ms. Fu told Medscape Medical News. "Researchers here at Stanford and others have shown that mice lacking vitamin D receptors have more skin cancer, and in vitro studies have shown that adding vitamin D to skin cancer cells sometimes reduces their growth. We wanted to see whether people taking vitamin D and calcium supplements might have a lower risk of skin cancer."
Ms. Fu and her team did a retrospective analysis of one part of the WHI trial that had randomized 36,282 postmenopausal women to vitamin D and calcium supplements or placebo and then followed them for 7 years to see if the supplements would ward off hip fracture and colon cancer.
The women, who ranged in age from 50 to 79 years, received 1000 mg of calcium and 400 IU of vitamin D3 or placebo daily and self-reported their health outcomes every year.
The Stanford researchers searched the data for the incidence of nonmelanoma and melanoma skin cancers in the 2 groups of women. Nonmelanoma skin cancers were ascertained by annual self report, and melanoma cases were adjudicated by physicians.
Overall, there were no differences in the rates of nonmelanoma skin cancers, which included basal cell and squamous cell carcinoma, and melanoma in the 2 groups. The hazard ratio (HR) was 1.02 (P = .59) for the treatment group and 0.86 (P = .32) for the placebo group.
However, when the researchers looked at outcomes in different subgroups, an important difference emerged. In women with a history of nonmelanoma skin cancer, calcium and vitamin D supplementation reduced the risk for melanoma by almost 55% (HR = 0.43; P = .038).
In women without a history of nonmelanoma skin cancer, there was no reduction in risk with calcium and vitamin D supplementation (HR = 1.02), Ms. Fu reported.
A separate analysis of the WHI data also revealed that women who had lower serum 25-hydroxyvitamin D levels at study entry had a higher risk for melanoma.
"These findings suggest a possible role for calcium, vitamin D, or both in reducing melanoma risk in women who are at high risk for melanoma because of history of nonmelanoma skin cancer," she said.
Coauthor Jean Y. Tang, MD, also from Stanford School of Medicine, pointed out that this is the first time that the WHI trial of calcium and vitamin D supplementation has shown a difference in the efficacy of anything.
"It didn't show a reduction in breast cancer or colon cancer, and it only showed a mild reduction in hip fractures with supplementation, so it is amazing that we are seeing some signal that it may actually be reducing melanoma, although just in women with a history of skin cancer," she said. "As a dermatologist, this is exciting for me because these are the patients I worry about. I also want to be able to tailor my prevention methods."
Ms. Fu added that "so many people have had basal cell and squamous cell cancer and they are known to have higher risks of melanoma, so it may be that a vitamin D and calcium supplement may be useful for that subgroup to prevent much deadlier melanoma."
"The beauty of this study is that it really looked at the Women's Health Initiative population," said Richard L. Gallo, MD, PhD, professor and chair of the Department of Dermatology at the University of California at San Diego. "There was a large population base and there were some trends to suggest a potential for benefit."
But, he continued, "there are a number of potential confounders in the study. It supports the need for other studies to be done specifically to answer this question, so it is supportive but not conclusive."
Ms. Fu and Dr. Tang have disclosed no relevant financial relationships. Dr. Gallo reports financial relationships with Allergan, Ceregenex, Galderma, Inimex, Intendis, Johnson and Johnson, Novartis, and Skin Epibiotics.
American Academy of Dermatology (AAD) 69th Annual Meeting. Presented February 5, 2011.
Fran Lowry
February 7, 2011 (New Orleans, Louisiana) — A new analysis of the Women's Health Initiative (WHI) study suggests that calcium and vitamin D supplementation reduce the risk for melanoma in women at high risk for the disease because of a history of nonmelanoma skin cancer.
The finding was presented in a late-breaking abstract session here at the American Academy of Dermatology 69th Annual Meeting by Teresa Fu, a medical student at Stanford University School of Medicine in Palo Alto, California.
"There is a lot of interest in vitamin D and whether it can affect your risk for cancer," Ms. Fu told Medscape Medical News. "Researchers here at Stanford and others have shown that mice lacking vitamin D receptors have more skin cancer, and in vitro studies have shown that adding vitamin D to skin cancer cells sometimes reduces their growth. We wanted to see whether people taking vitamin D and calcium supplements might have a lower risk of skin cancer."
Ms. Fu and her team did a retrospective analysis of one part of the WHI trial that had randomized 36,282 postmenopausal women to vitamin D and calcium supplements or placebo and then followed them for 7 years to see if the supplements would ward off hip fracture and colon cancer.
The women, who ranged in age from 50 to 79 years, received 1000 mg of calcium and 400 IU of vitamin D3 or placebo daily and self-reported their health outcomes every year.
The Stanford researchers searched the data for the incidence of nonmelanoma and melanoma skin cancers in the 2 groups of women. Nonmelanoma skin cancers were ascertained by annual self report, and melanoma cases were adjudicated by physicians.
Overall, there were no differences in the rates of nonmelanoma skin cancers, which included basal cell and squamous cell carcinoma, and melanoma in the 2 groups. The hazard ratio (HR) was 1.02 (P = .59) for the treatment group and 0.86 (P = .32) for the placebo group.
However, when the researchers looked at outcomes in different subgroups, an important difference emerged. In women with a history of nonmelanoma skin cancer, calcium and vitamin D supplementation reduced the risk for melanoma by almost 55% (HR = 0.43; P = .038).
In women without a history of nonmelanoma skin cancer, there was no reduction in risk with calcium and vitamin D supplementation (HR = 1.02), Ms. Fu reported.
A separate analysis of the WHI data also revealed that women who had lower serum 25-hydroxyvitamin D levels at study entry had a higher risk for melanoma.
"These findings suggest a possible role for calcium, vitamin D, or both in reducing melanoma risk in women who are at high risk for melanoma because of history of nonmelanoma skin cancer," she said.
Coauthor Jean Y. Tang, MD, also from Stanford School of Medicine, pointed out that this is the first time that the WHI trial of calcium and vitamin D supplementation has shown a difference in the efficacy of anything.
"It didn't show a reduction in breast cancer or colon cancer, and it only showed a mild reduction in hip fractures with supplementation, so it is amazing that we are seeing some signal that it may actually be reducing melanoma, although just in women with a history of skin cancer," she said. "As a dermatologist, this is exciting for me because these are the patients I worry about. I also want to be able to tailor my prevention methods."
Ms. Fu added that "so many people have had basal cell and squamous cell cancer and they are known to have higher risks of melanoma, so it may be that a vitamin D and calcium supplement may be useful for that subgroup to prevent much deadlier melanoma."
"The beauty of this study is that it really looked at the Women's Health Initiative population," said Richard L. Gallo, MD, PhD, professor and chair of the Department of Dermatology at the University of California at San Diego. "There was a large population base and there were some trends to suggest a potential for benefit."
But, he continued, "there are a number of potential confounders in the study. It supports the need for other studies to be done specifically to answer this question, so it is supportive but not conclusive."
Ms. Fu and Dr. Tang have disclosed no relevant financial relationships. Dr. Gallo reports financial relationships with Allergan, Ceregenex, Galderma, Inimex, Intendis, Johnson and Johnson, Novartis, and Skin Epibiotics.
American Academy of Dermatology (AAD) 69th Annual Meeting. Presented February 5, 2011.
Diagnosis and Treatment of Gout Reviewed
From Medscape Medical News
Laurie Barclay, MD
February 7, 2011 — The diagnosis and treatment of gout are reviewed in an article published in the February 3 issue of the New England Journal of Medicine.
"Gout is a type of inflammatory arthritis induced by the deposition of monosodium urate crystals in synovial fluid and other tissues," writes Tuhina Neogi, MD, PhD, from the Section of Clinical Epidemiology Research and Training Unit, Boston University School of Medicine; and the Department of Epidemiology, Boston University School of Public Health, in Massachusetts.
"It is associated with hyperuricemia, which is defined as a serum urate level of 6.8 mg per deciliter (404 μmol per liter) or more, the limit of urate solubility at physiologic temperature and pH. Humans lack uricase and thus cannot convert urate to soluble allantoin as the end product of purine metabolism. Hyperuricemia that is caused by the overproduction of urate or, more commonly, by renal urate underexcretion is necessary but not sufficient to cause gout."
Definitive diagnosis of gout requires synovial fluid or tophus aspiration to identify negatively birefringent monosodium urate crystals under polarizing microscopy, but crystal evaluation is not routinely performed in clinical practice. Hyperuricemia may not be present during acute gout attacks and therefore may not be useful for diagnosis.
Diagnosis of acute gout is largely clinical based on a characteristic presentation with rapid (within 24 hours) development of severe pain, erythema, and swelling in the first metatarsophalangeal joint (podagra) or other typical distribution. Differential diagnosis of acute gout includes calcium pyrophosphate dehydrate or other crystal-induced arthritides and a septic joint. If a septic joint is suspected, joint aspiration with Gram staining and culture must be performed.
"The main aim of therapy for acute gout is rapid relief of pain and disability caused by intense inflammation," Dr. Neogi writes. "Options for managing acute attacks include the use of nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, glucocorticoids, and possibly corticotropin. The choice of agent, dose, and duration of therapy is guided by consideration of coexisting illnesses that preclude the safe use of a particular regimen, as well as the severity of the gout."
First-line agents for acute attacks are NSAIDs and colchicines, and adjunctive measures include applying ice to and resting the affected joint.
NSAIDs should be avoided in patients with renal or hepatic impairment, bleeding disorder, congestive heart failure, or allergy and may increase the risk for adverse thrombotic and gastrointestinal tract events.
Naproxen may be used at a dose of 375 to 500 mg orally twice daily for 3 days, then 250 to 375 mg orally twice daily for 4 to 7 days or until the attack resolves. Indomethacin may be given 50 mg orally 3 times daily for 3 days, then 25 mg orally 3 times daily for 4 to 7 days or until the attack resolves.
Oral colchicine has a long history of use but was only approved in 2009 by the Food and Drug Administration (FDA) for use in patients with acute gout. Based on a randomized trial, colchicine 1.2 mg at the onset of a flare, followed by 0.6 mg 1 hour later, was significantly more likely than placebo to be associated with pain reduction of 50% or more 24 hours later (rates, 37.8% vs 15.5%, respectively). Colchicine should be avoided in older adults and in patients with renal or hepatic impairment or known gastrointestinal tract symptoms, and there are numerous drug-drug interactions.
When the use of NSAIDs or colchicine is poorly tolerated or contraindicated, glucocorticoids such as prednisolone or prednisone or corticotropin may be prescribed for acute gout, although evidence from randomized controlled trials is lacking for the use of intraarticular and intramuscular glucocorticoids and corticotropin.
To help prevent acute flares and development of tophi in the patient with gout, urate-lowering therapy may be helpful, but not without risk. Urate-lowering therapy should be considered in patients with hyperuricemia who have 2 or more gout attacks per year or tophi, as determined either clinically or radiographically. Additional considerations are the severity and frequency of flares, the presence of kidney stones and other coexisting illnesses, and patient preference.
Xanthine oxidase inhibitors, uricosuric agents, and uricase agents are 3 classes of drugs approved for lowering urate levels.
Allopurinol is the most commonly prescribed xanthine oxidase inhibitor, with an acceptable adverse effect profile in most patients. Approximately 2% of patients experience a mild rash, with potentially life-threatening severe hypersensitivity to allopurinol much less common.
Most patients receive 300 mg of allopurinol daily, but this dose may not achieve target urate levels, and daily doses up to 800 mg may be used in patients with normal renal function. Patients with renal impairment are typically given a lower dose.
Febuxostat, another xanthine oxidase inhibitor approved by the FDA in 2009 for treatment of hyperuricemia in patients with gout, is second-line therapy. Starting dose is 40 mg orally daily, increasing to 80 mg daily after 2 to 4 weeks if needed to achieve a target serum urate level. It is contraindicated for use with theophylline. No dose adjustments are needed for patients with mild to moderate renal or hepatic impairment, but data are insufficient regarding patients with severe impairment.
Probenecid, sulfinpyrazone, benzbromarone, and other uricosuric drugs block renal tubular urate reabsorption, but they are contraindicated in patients with a history of nephrolithiasis.
"Because rapid lowering of urate levels is associated with gout flares, with an increased risk associated with therapies that more effectively lower urate levels, prophylaxis against acute flares is advised during the initiation of urate-lowering therapy," Dr. Neogi concludes. "...[T]he general recommendation for flare prophylaxis is to use colchicine at a dose of 0.6 mg once or twice daily, with dose adjustments as needed for renal impairment, potential drug interactions, or intolerance. Although NSAIDs are also used for prophylaxis, there are few studies that support their use."
Dr. Neogi has served as a core expert panel leader for the American College of Rheumatology Gout Treatment Guidelines and has disclosed no other relevant financial relationships.
N Engl J Med. 2011;364:443-452. Abstract
Laurie Barclay, MD
February 7, 2011 — The diagnosis and treatment of gout are reviewed in an article published in the February 3 issue of the New England Journal of Medicine.
"Gout is a type of inflammatory arthritis induced by the deposition of monosodium urate crystals in synovial fluid and other tissues," writes Tuhina Neogi, MD, PhD, from the Section of Clinical Epidemiology Research and Training Unit, Boston University School of Medicine; and the Department of Epidemiology, Boston University School of Public Health, in Massachusetts.
"It is associated with hyperuricemia, which is defined as a serum urate level of 6.8 mg per deciliter (404 μmol per liter) or more, the limit of urate solubility at physiologic temperature and pH. Humans lack uricase and thus cannot convert urate to soluble allantoin as the end product of purine metabolism. Hyperuricemia that is caused by the overproduction of urate or, more commonly, by renal urate underexcretion is necessary but not sufficient to cause gout."
Definitive diagnosis of gout requires synovial fluid or tophus aspiration to identify negatively birefringent monosodium urate crystals under polarizing microscopy, but crystal evaluation is not routinely performed in clinical practice. Hyperuricemia may not be present during acute gout attacks and therefore may not be useful for diagnosis.
Diagnosis of acute gout is largely clinical based on a characteristic presentation with rapid (within 24 hours) development of severe pain, erythema, and swelling in the first metatarsophalangeal joint (podagra) or other typical distribution. Differential diagnosis of acute gout includes calcium pyrophosphate dehydrate or other crystal-induced arthritides and a septic joint. If a septic joint is suspected, joint aspiration with Gram staining and culture must be performed.
"The main aim of therapy for acute gout is rapid relief of pain and disability caused by intense inflammation," Dr. Neogi writes. "Options for managing acute attacks include the use of nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, glucocorticoids, and possibly corticotropin. The choice of agent, dose, and duration of therapy is guided by consideration of coexisting illnesses that preclude the safe use of a particular regimen, as well as the severity of the gout."
First-line agents for acute attacks are NSAIDs and colchicines, and adjunctive measures include applying ice to and resting the affected joint.
NSAIDs should be avoided in patients with renal or hepatic impairment, bleeding disorder, congestive heart failure, or allergy and may increase the risk for adverse thrombotic and gastrointestinal tract events.
Naproxen may be used at a dose of 375 to 500 mg orally twice daily for 3 days, then 250 to 375 mg orally twice daily for 4 to 7 days or until the attack resolves. Indomethacin may be given 50 mg orally 3 times daily for 3 days, then 25 mg orally 3 times daily for 4 to 7 days or until the attack resolves.
Oral colchicine has a long history of use but was only approved in 2009 by the Food and Drug Administration (FDA) for use in patients with acute gout. Based on a randomized trial, colchicine 1.2 mg at the onset of a flare, followed by 0.6 mg 1 hour later, was significantly more likely than placebo to be associated with pain reduction of 50% or more 24 hours later (rates, 37.8% vs 15.5%, respectively). Colchicine should be avoided in older adults and in patients with renal or hepatic impairment or known gastrointestinal tract symptoms, and there are numerous drug-drug interactions.
When the use of NSAIDs or colchicine is poorly tolerated or contraindicated, glucocorticoids such as prednisolone or prednisone or corticotropin may be prescribed for acute gout, although evidence from randomized controlled trials is lacking for the use of intraarticular and intramuscular glucocorticoids and corticotropin.
To help prevent acute flares and development of tophi in the patient with gout, urate-lowering therapy may be helpful, but not without risk. Urate-lowering therapy should be considered in patients with hyperuricemia who have 2 or more gout attacks per year or tophi, as determined either clinically or radiographically. Additional considerations are the severity and frequency of flares, the presence of kidney stones and other coexisting illnesses, and patient preference.
Xanthine oxidase inhibitors, uricosuric agents, and uricase agents are 3 classes of drugs approved for lowering urate levels.
Allopurinol is the most commonly prescribed xanthine oxidase inhibitor, with an acceptable adverse effect profile in most patients. Approximately 2% of patients experience a mild rash, with potentially life-threatening severe hypersensitivity to allopurinol much less common.
Most patients receive 300 mg of allopurinol daily, but this dose may not achieve target urate levels, and daily doses up to 800 mg may be used in patients with normal renal function. Patients with renal impairment are typically given a lower dose.
Febuxostat, another xanthine oxidase inhibitor approved by the FDA in 2009 for treatment of hyperuricemia in patients with gout, is second-line therapy. Starting dose is 40 mg orally daily, increasing to 80 mg daily after 2 to 4 weeks if needed to achieve a target serum urate level. It is contraindicated for use with theophylline. No dose adjustments are needed for patients with mild to moderate renal or hepatic impairment, but data are insufficient regarding patients with severe impairment.
Probenecid, sulfinpyrazone, benzbromarone, and other uricosuric drugs block renal tubular urate reabsorption, but they are contraindicated in patients with a history of nephrolithiasis.
"Because rapid lowering of urate levels is associated with gout flares, with an increased risk associated with therapies that more effectively lower urate levels, prophylaxis against acute flares is advised during the initiation of urate-lowering therapy," Dr. Neogi concludes. "...[T]he general recommendation for flare prophylaxis is to use colchicine at a dose of 0.6 mg once or twice daily, with dose adjustments as needed for renal impairment, potential drug interactions, or intolerance. Although NSAIDs are also used for prophylaxis, there are few studies that support their use."
Dr. Neogi has served as a core expert panel leader for the American College of Rheumatology Gout Treatment Guidelines and has disclosed no other relevant financial relationships.
N Engl J Med. 2011;364:443-452. Abstract
Updated BPH Treatment Guideline Released
From Medscape Medical News
Emma Hitt, PhD
February 7, 2011 — The American Urological Association (AUA) has issued updated guidance on the treatment of benign prostatic hyperplasia (BPH).
The newly released guidelines update current recommendations, first published in 2003, for diagnosing and treating this disorder. The guidelines were released online February 3 and will be published in an upcoming print issue of the Journal of Urology.
The updated guidelines include a detailed diagnostic algorithm to guide physicians in diagnosing and treating lower urinary tract symptoms (LUTS) that result from BPH. They also provide in-depth information on BPH management strategies in general and on complicated cases in particular.
"Physicians treating men with suspected cases of LUTS should obtain a relevant medical history, assess symptoms using the AUA Symptom Index and conduct a full physical examination (including a digital rectal exam)," states a written release from the AUA. "Laboratory tests should include a prostate-specific antigen...test and a urinalysis to exclude infection or other causes for LUTS," and "frequency and volume charts may also be useful in providing a diagnosis."
The guidelines maintain that some patients may benefit using a combination of all 3 modalities. "Should improvement be insufficient and symptoms severe, then newer modalities of treatment such as botulinum toxin and sacral neuromodulation can be considered," the report states.
According to the AUA, the 2003 update provided key information on the use of surgical and medical approaches, whereas the 2010 updated version contains added recommendations for the use of anticholinergic drugs and the use of laser therapies. In addition, the index patient age has been lowered from 50 years to 45 years to improve guidance for the treatment of younger men with LUTS.
The guidelines also advise clinicians to remain vigilant about intraoperative floppy iris syndrome in patients with cataract who are taking alpha-blockers to treat BPH. Patients should be asked about any planned cataract surgery before starting an alpha-blocker regimen, and if surgery is planned, alpha-blockers should be avoided until after the procedure.
The panel also recommends against the routine measurement of serum creatinine levels in the initial evaluation of men with LUTS secondary to BPH.
The clinical guideline was developed after panelists had conducted a systematic review and had synthesized the clinical literature on current and emerging therapies for the treatment of BPH.
The panelists asked 3 questions regarding current therapy for BPH: "(1) What is the comparative efficacy...and effectiveness...of currently available and emerging treatments for BPH? What are the predictors of beneficial effects from treatments? (2) What are the adverse events associated with each of the included treatments, and how do the adverse events compare across treatments? (3) Are there subpopulations in which the efficacy, effectiveness, and adverse event rates vary from those in general populations?"
"The methodology followed the same process used in the development of the 2003 Guideline and, as such, did not include an evaluation of the strength of the body of evidence as will be instituted in future Guidelines produced by the AUA," the report states.
In a news release, chair of the guideline's panel Kevin T. McVary, MD, noted, "The increasing life expectancy and growth of our elderly population will increase the number of men who suffer from LUTS.
"This will place increased demands for treatment services, and necessitate the incorporation of evidence-based medicine" and "provides much-needed guidance to doctors who are already treating LUTS."
The report was compiled without commercial support.
AUA. Published online February 3, 2011.
Emma Hitt, PhD
February 7, 2011 — The American Urological Association (AUA) has issued updated guidance on the treatment of benign prostatic hyperplasia (BPH).
The newly released guidelines update current recommendations, first published in 2003, for diagnosing and treating this disorder. The guidelines were released online February 3 and will be published in an upcoming print issue of the Journal of Urology.
The updated guidelines include a detailed diagnostic algorithm to guide physicians in diagnosing and treating lower urinary tract symptoms (LUTS) that result from BPH. They also provide in-depth information on BPH management strategies in general and on complicated cases in particular.
"Physicians treating men with suspected cases of LUTS should obtain a relevant medical history, assess symptoms using the AUA Symptom Index and conduct a full physical examination (including a digital rectal exam)," states a written release from the AUA. "Laboratory tests should include a prostate-specific antigen...test and a urinalysis to exclude infection or other causes for LUTS," and "frequency and volume charts may also be useful in providing a diagnosis."
The guidelines maintain that some patients may benefit using a combination of all 3 modalities. "Should improvement be insufficient and symptoms severe, then newer modalities of treatment such as botulinum toxin and sacral neuromodulation can be considered," the report states.
According to the AUA, the 2003 update provided key information on the use of surgical and medical approaches, whereas the 2010 updated version contains added recommendations for the use of anticholinergic drugs and the use of laser therapies. In addition, the index patient age has been lowered from 50 years to 45 years to improve guidance for the treatment of younger men with LUTS.
The guidelines also advise clinicians to remain vigilant about intraoperative floppy iris syndrome in patients with cataract who are taking alpha-blockers to treat BPH. Patients should be asked about any planned cataract surgery before starting an alpha-blocker regimen, and if surgery is planned, alpha-blockers should be avoided until after the procedure.
The panel also recommends against the routine measurement of serum creatinine levels in the initial evaluation of men with LUTS secondary to BPH.
The clinical guideline was developed after panelists had conducted a systematic review and had synthesized the clinical literature on current and emerging therapies for the treatment of BPH.
The panelists asked 3 questions regarding current therapy for BPH: "(1) What is the comparative efficacy...and effectiveness...of currently available and emerging treatments for BPH? What are the predictors of beneficial effects from treatments? (2) What are the adverse events associated with each of the included treatments, and how do the adverse events compare across treatments? (3) Are there subpopulations in which the efficacy, effectiveness, and adverse event rates vary from those in general populations?"
"The methodology followed the same process used in the development of the 2003 Guideline and, as such, did not include an evaluation of the strength of the body of evidence as will be instituted in future Guidelines produced by the AUA," the report states.
In a news release, chair of the guideline's panel Kevin T. McVary, MD, noted, "The increasing life expectancy and growth of our elderly population will increase the number of men who suffer from LUTS.
"This will place increased demands for treatment services, and necessitate the incorporation of evidence-based medicine" and "provides much-needed guidance to doctors who are already treating LUTS."
The report was compiled without commercial support.
AUA. Published online February 3, 2011.
Monday, February 7, 2011
Cochrane Review Stirs Controversy Over Statins in Primary Prevention
From Heartwire CME
News Author: Sue Hughes
CME Author: Hien T. Nghiem, MD
January 25, 2011 — A new Cochrane review has provoked controversy by concluding that there is not enough evidence to recommend the widespread use of statins in the primary prevention of heart disease.
The authors of the new Cochrane meta-analysis, led by Dr Fiona Taylor (London School of Hygiene and Tropical Medicine, UK), issued a press release questioning the benefit of statins in primary prevention and suggesting that the previous data showing benefit may have been biased by industry-funded studies.
This has led to headlines in many UK newspapers saying that the drugs are being overused and that millions of people are needlessly exposing themselves to potential side effects.
This has angered researchers who have conducted other large statin meta-analyses, who say the drugs are beneficial, even in the lowest-risk individuals, and their risk of side effects is negligible.
They maintain that the Cochrane reviewers have misrepresented the data, which they say could have serious negative consequences for many patients currently taking these agents.
The Cochrane authors reviewed data from 14 trials involving 34 272 patients. Outcomes in patients given statins were compared with outcomes in patients given placebos or usual care. Although results suggested that deaths were reduced on statins, the researchers say the effect is not large enough to justify the cost/effort and risk of adverse effects.
Senior author Dr Shah Ebrahim (South Asia Network for Chronic Disease, New Delhi, India) told heartwire that their review differed from others done in primary prevention in that it looked at just those at low risk, limiting the studies included to just those with populations where <10% had a previous history of cardiovascular disease (CVD). It is probably a real effect but it means a lot of people have to be treated to gain this small benefit. Ebrahim commented to heartwire : "If you look at the hard end points of all deaths and coronary deaths, the effects are consistent with both benefit and with the play of chance. But importantly, the absolute benefits are really rather small--1000 people have to be treated for one year to prevent one death. It is probably a real effect, but it means a lot of people have to be treated to gain this small benefit. As we don't know the harms, it seems wrong-minded to me to treat everyone with a statin. In these circumstances, lifestyle changes and stopping smoking would be far preferable." I object to the conclusions they have drawn from their review. But Dr Colin Baigent (Clinical Trials Service Unit, Oxford, UK) commented to heartwire : "I object to the conclusions they have drawn from their review. They say there is not good evidence of benefit, but their own data show significant reductions in deaths and cardiac events." And Baigent further objects to the Cochrane authors' suggestion that harms are not known with statins. "They didn't show any increase in adverse events in their review, but they then say the benefit is not worth the risk. That doesn't make sense." Cochrane Results The Cochrane review showed that in the eight trials that reported on total mortality, none of the individual trials showed strong evidence of a reduction in total mortality, but when the data were pooled, a relative risk reduction of 17% was observed with statin treatment. On combined fatal and nonfatal coronary heart disease (CHD) events, nine trials reported on this end point, with four trials showing evidence of a reduction in this combined outcome, which was maintained in the pooled analysis, with a 28% relative reduction. Seven trials reported on fatal and nonfatal stroke, and on pooled analysis, statin treatment was associated with a 22% relative reduction. Cochrane Review: Risk Ratio of Major Events With Statins in Lower-Risk Primary-Prevention Patients No excess in combined adverse events, cancers, or specific biochemical markers were found. The authors conclude: "This current systematic review highlights the shortcomings in the published trials of statins for primary prevention. Selective reporting and inclusion of people with cardiovascular disease in many of the trials . . . in previous reviews of [statins'] role in primary prevention make the evidence impossible to disentangle without individual patient data." They say that in people at high risk of cardiovascular events (>20% 10-year risk), "it is likely that the benefits of statins are greater than potential short-term harms, although long-term effects (over decades) remain unknown." They conclude: "Any decision to use statins for primary prevention should be made cautiously and in the light of an assessment of the patient's overall cardiovascular risk profile. Widespread use of statins in people at low risk of cardiovascular events--below a 1% annual all-cause mortality risk or an annual CVD event rate of below 2% observed in the control groups in the trials considered here--is not supported by the existing evidence."
Latest Oxford Meta-Analysis Not Included
The Cochrane review did not include the recent meta-analysis from the Oxford group, published late last year, which showed a clear reduction in events with statin therapy in primary-prevention patients.
Baigent noted that this meta-analysis was more reliable than the Cochrane review, as the Oxford researchers used individual patient data from all the trials. "Our 2010 meta-analysis in primary prevention is substantially more complete than the Cochrane review and provides direct and overwhelmingly statistically convincing evidence of a clear reduction in events in all patient groups, right down to those at the lowest risk."
On the possible hazards of taking these drugs, Baigent says: "Statin therapy is very safe. The most serious hazard, rhabdomyolysis, is very rare, and most often seen at high doses. There is a possibility that reducing low-density lipoprotein cholesterol might increase the risk of hemorrhagic stroke, but even in primary prevention these hazards would be much smaller than the benefits, and there is no reliable evidence for other hazards mentioned by the Cochrane authors, such as depression and cognitive impairment."
It All Comes Down to Economics
Baigent says the only argument against using statins in low-risk people is economic. "The absolute benefits of statin therapy become very small when used among people at low absolute risk, so it is important that the costs of such treatment are considered when weighing how widely statins should be used. That is a government decision."
In the UK, the National Institute for Clinical Excellence [NICE] currently recommends that statins not be used for people with a CHD risk below 20% over 10 years. Ebrahim says the Cochrane conclusions are in line with this.
But Baigent argues that the benefits of statins are clear at levels far below this threshold. "Whether or not it is economic to use them in the lowest-risk individuals is not for me to say, but generic statins are now very cheap, and there is clear evidence of benefit and safety based on substantial numbers of individuals studied in large-scale trials. So, when all the relevant randomized evidence is considered, there does not seem to me to be any justification at all for the Cochrane authors' claim that the evidence is unclear on this issue."
Educational Programs Also of Little Benefit
In a separate Cochrane review [2], the same group looked at the use of "healthy heart programs" that use counseling and educational methods to encourage people to reduce their risks for developing heart disease. These risk factors include high cholesterol, excessive salt intake, high blood pressure, excess weight, a high-fat diet, smoking, diabetes, and a sedentary lifestyle. They reviewed 55 trials that aimed to reduce more than one risk factor in people without evidence of cardiovascular disease. Results showed that after a median duration of 12 months of follow-up, multiple risk-factor intervention was associated with small reductions in risk factors, including blood pressure, cholesterol, and smoking, but had little or no impact on the risk of coronary heart disease mortality or morbidity. They conclude: "The methods of attempting behavior change in the general population are limited and do not appear to be effective. Different approaches to behavior change are needed and should be tested empirically before being widely promoted, particularly in developing countries where cardiovascular disease rates are rising."
In an accompanying editorial [3], Dr Carl Heneghan (University of Oxford, UK) suggests an alternative approach for policy is to focus on populationwide prevention. He reports that "legislating for smoke-free public spaces, redesigning public spaces to improve exercise, or reducing daily dietary salt intake prove generally effective and can be cost-saving interventions. Given the scale of the worldwide CVD problem, large-scale commissioned studies of multiple risk-factor interventions are urgently required."
References
1. Taylor F, Ward K, Moore THM, et al. Statins for the primary prevention of cardiovascular disease - Available here.Cochrane Database Syst Rev 2011; 1 (CD004816).
2. Ebrahim S, Taylor F, Ward K et al. Multiple risk factor interventions for primary prevention of coronary heart disease - Available here. Cochrane Database Syst Rev 2011; 1 (CD001561).
3. Heneghan C. Considerable uncertainty remains in the evidence for primary prevention of cardiovascular disease [editorial].Cochrane Libr2011 (January 19, 2011). Available here.
Clinical Context
CVD is mutifactorial in its causation, and lifestyle changes are the basis of any treatment strategy. Treatment usually includes eating a healthy diet, ceasing tobacco use, and increasing physical activity. Reducing high blood cholesterol, a risk factor for CVD events in people with and without a history of CHD, is an important goal of pharmacotherapy. Typically, statins are the first-line agents. Studies have demonstrated the effects of statins and its benefits in people with coronary artery disease; however, the case for primary prevention is less clear.
The aim of this study was to assess the effects, both harms and benefits, of statins in people with no history of CVD.
Study Highlights
* The investigators conducted a search within the Cochrane Central Register of Controlled Trials (Issue 1, 2007), MEDLINE (2001 to March 2007), and EMBASE (2003 to March 2007) for trials comparing statins vs usual care or placebo. There were no language restrictions.
* Randomized controlled trials of statins with minimum duration of 1 year and follow-up of 6 months, trials of adults with no restrictions on their total low-density lipoprotein or high-density lipoprotein cholesterol levels, and trials in which 10% or less of participants had a history of CVD were included.
* Drug treatments and other interventions were accepted, provided they were given to both groups of the intervention groups.
* 2 authors independently selected studies for inclusion and extracted data.
* Outcomes included all-cause mortality, fatal and nonfatal CHD, CVD, stroke events, combined endpoints (fatal and nonfatal CHD, CVD, and stroke events), change in blood total cholesterol concentration, revascularization, adverse events, quality of life, and costs.
* Relative risk was calculated for dichotomous data, and for continuous data, pooled weighted mean differences (with 95% confidence intervals) were calculated.
* 14 randomized control trials (16 trial groups; 34,272 participants) were included.
* 11 trials recruited patients with specific conditions (increased lipid levels, diabetes, hypertension, and microalbuminuria).
* All tested the effectiveness of a statin vs placebo, 9 studies tested pravastatin (10 - 40 mg/day) and atorvastatin (10 mg/day), 2 studies tested fluvastatin (40 - 80 mg/day) and lovastatin (20 - 40 mg/day), and the remaining studies tested simvastatin (40 mg/day).
* 2 trials — the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) 1998 and the Collaborative AtoRvastatin Diabetes Study (CARDS) 2004 — were stopped prematurely because of significant reductions in primary composite outcomes between the intervention and placebo groups.
* Results demonstrated that all-cause mortality risk was reduced by statins (relative risk, 0.83; 95% CI, 0.73 - 0.95), as were combined fatal and nonfatal CVD endpoints (relative risk, 0.70; 95% CI, 0.61 - 0.79).
* No significant risk reduction was observed in fatal CHD events and fatal and nonfatal stroke events.
* Benefits were also seen in the reduction of revascularization rates (relative risk, 0.66; 95% CI, 0.53 - 0.83).
* Total cholesterol and low-density lipoprotein cholesterol levels were reduced in all trials; however, there was evidence of heterogeneity of effects, possibly because of differences in the statin and dosage used as well as reporting biases.
* There was no clear evidence of any significant harm caused by statin prescription or of effects on patient quality of life.
* No statistical differences in outcomes were observed in age and sex.
* There was limited evidence to suggest that the use of statins for primary prevention may be cost effective and improve patient-perceived quality of life.
Clinical Implications
* According to the World Health Organization in 2008, the major causes of CVD are unhealthy diet, tobacco use, and physical inactivity.
* Although reductions in all-cause mortality risk, composite endpoints, and revascularizations were found with no excess of adverse events, there was evidence of selective reporting of outcomes, failure to report adverse events, and inclusion of people with cardiovascular disease. Therefore, caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.
News Author: Sue Hughes
CME Author: Hien T. Nghiem, MD
January 25, 2011 — A new Cochrane review has provoked controversy by concluding that there is not enough evidence to recommend the widespread use of statins in the primary prevention of heart disease.
The authors of the new Cochrane meta-analysis, led by Dr Fiona Taylor (London School of Hygiene and Tropical Medicine, UK), issued a press release questioning the benefit of statins in primary prevention and suggesting that the previous data showing benefit may have been biased by industry-funded studies.
This has led to headlines in many UK newspapers saying that the drugs are being overused and that millions of people are needlessly exposing themselves to potential side effects.
This has angered researchers who have conducted other large statin meta-analyses, who say the drugs are beneficial, even in the lowest-risk individuals, and their risk of side effects is negligible.
They maintain that the Cochrane reviewers have misrepresented the data, which they say could have serious negative consequences for many patients currently taking these agents.
The Cochrane authors reviewed data from 14 trials involving 34 272 patients. Outcomes in patients given statins were compared with outcomes in patients given placebos or usual care. Although results suggested that deaths were reduced on statins, the researchers say the effect is not large enough to justify the cost/effort and risk of adverse effects.
Senior author Dr Shah Ebrahim (South Asia Network for Chronic Disease, New Delhi, India) told heartwire that their review differed from others done in primary prevention in that it looked at just those at low risk, limiting the studies included to just those with populations where <10% had a previous history of cardiovascular disease (CVD). It is probably a real effect but it means a lot of people have to be treated to gain this small benefit. Ebrahim commented to heartwire : "If you look at the hard end points of all deaths and coronary deaths, the effects are consistent with both benefit and with the play of chance. But importantly, the absolute benefits are really rather small--1000 people have to be treated for one year to prevent one death. It is probably a real effect, but it means a lot of people have to be treated to gain this small benefit. As we don't know the harms, it seems wrong-minded to me to treat everyone with a statin. In these circumstances, lifestyle changes and stopping smoking would be far preferable." I object to the conclusions they have drawn from their review. But Dr Colin Baigent (Clinical Trials Service Unit, Oxford, UK) commented to heartwire : "I object to the conclusions they have drawn from their review. They say there is not good evidence of benefit, but their own data show significant reductions in deaths and cardiac events." And Baigent further objects to the Cochrane authors' suggestion that harms are not known with statins. "They didn't show any increase in adverse events in their review, but they then say the benefit is not worth the risk. That doesn't make sense." Cochrane Results The Cochrane review showed that in the eight trials that reported on total mortality, none of the individual trials showed strong evidence of a reduction in total mortality, but when the data were pooled, a relative risk reduction of 17% was observed with statin treatment. On combined fatal and nonfatal coronary heart disease (CHD) events, nine trials reported on this end point, with four trials showing evidence of a reduction in this combined outcome, which was maintained in the pooled analysis, with a 28% relative reduction. Seven trials reported on fatal and nonfatal stroke, and on pooled analysis, statin treatment was associated with a 22% relative reduction. Cochrane Review: Risk Ratio of Major Events With Statins in Lower-Risk Primary-Prevention Patients No excess in combined adverse events, cancers, or specific biochemical markers were found. The authors conclude: "This current systematic review highlights the shortcomings in the published trials of statins for primary prevention. Selective reporting and inclusion of people with cardiovascular disease in many of the trials . . . in previous reviews of [statins'] role in primary prevention make the evidence impossible to disentangle without individual patient data." They say that in people at high risk of cardiovascular events (>20% 10-year risk), "it is likely that the benefits of statins are greater than potential short-term harms, although long-term effects (over decades) remain unknown." They conclude: "Any decision to use statins for primary prevention should be made cautiously and in the light of an assessment of the patient's overall cardiovascular risk profile. Widespread use of statins in people at low risk of cardiovascular events--below a 1% annual all-cause mortality risk or an annual CVD event rate of below 2% observed in the control groups in the trials considered here--is not supported by the existing evidence."
Latest Oxford Meta-Analysis Not Included
The Cochrane review did not include the recent meta-analysis from the Oxford group, published late last year, which showed a clear reduction in events with statin therapy in primary-prevention patients.
Baigent noted that this meta-analysis was more reliable than the Cochrane review, as the Oxford researchers used individual patient data from all the trials. "Our 2010 meta-analysis in primary prevention is substantially more complete than the Cochrane review and provides direct and overwhelmingly statistically convincing evidence of a clear reduction in events in all patient groups, right down to those at the lowest risk."
On the possible hazards of taking these drugs, Baigent says: "Statin therapy is very safe. The most serious hazard, rhabdomyolysis, is very rare, and most often seen at high doses. There is a possibility that reducing low-density lipoprotein cholesterol might increase the risk of hemorrhagic stroke, but even in primary prevention these hazards would be much smaller than the benefits, and there is no reliable evidence for other hazards mentioned by the Cochrane authors, such as depression and cognitive impairment."
It All Comes Down to Economics
Baigent says the only argument against using statins in low-risk people is economic. "The absolute benefits of statin therapy become very small when used among people at low absolute risk, so it is important that the costs of such treatment are considered when weighing how widely statins should be used. That is a government decision."
In the UK, the National Institute for Clinical Excellence [NICE] currently recommends that statins not be used for people with a CHD risk below 20% over 10 years. Ebrahim says the Cochrane conclusions are in line with this.
But Baigent argues that the benefits of statins are clear at levels far below this threshold. "Whether or not it is economic to use them in the lowest-risk individuals is not for me to say, but generic statins are now very cheap, and there is clear evidence of benefit and safety based on substantial numbers of individuals studied in large-scale trials. So, when all the relevant randomized evidence is considered, there does not seem to me to be any justification at all for the Cochrane authors' claim that the evidence is unclear on this issue."
Educational Programs Also of Little Benefit
In a separate Cochrane review [2], the same group looked at the use of "healthy heart programs" that use counseling and educational methods to encourage people to reduce their risks for developing heart disease. These risk factors include high cholesterol, excessive salt intake, high blood pressure, excess weight, a high-fat diet, smoking, diabetes, and a sedentary lifestyle. They reviewed 55 trials that aimed to reduce more than one risk factor in people without evidence of cardiovascular disease. Results showed that after a median duration of 12 months of follow-up, multiple risk-factor intervention was associated with small reductions in risk factors, including blood pressure, cholesterol, and smoking, but had little or no impact on the risk of coronary heart disease mortality or morbidity. They conclude: "The methods of attempting behavior change in the general population are limited and do not appear to be effective. Different approaches to behavior change are needed and should be tested empirically before being widely promoted, particularly in developing countries where cardiovascular disease rates are rising."
In an accompanying editorial [3], Dr Carl Heneghan (University of Oxford, UK) suggests an alternative approach for policy is to focus on populationwide prevention. He reports that "legislating for smoke-free public spaces, redesigning public spaces to improve exercise, or reducing daily dietary salt intake prove generally effective and can be cost-saving interventions. Given the scale of the worldwide CVD problem, large-scale commissioned studies of multiple risk-factor interventions are urgently required."
References
1. Taylor F, Ward K, Moore THM, et al. Statins for the primary prevention of cardiovascular disease - Available here.Cochrane Database Syst Rev 2011; 1 (CD004816).
2. Ebrahim S, Taylor F, Ward K et al. Multiple risk factor interventions for primary prevention of coronary heart disease - Available here. Cochrane Database Syst Rev 2011; 1 (CD001561).
3. Heneghan C. Considerable uncertainty remains in the evidence for primary prevention of cardiovascular disease [editorial].Cochrane Libr2011 (January 19, 2011). Available here.
Clinical Context
CVD is mutifactorial in its causation, and lifestyle changes are the basis of any treatment strategy. Treatment usually includes eating a healthy diet, ceasing tobacco use, and increasing physical activity. Reducing high blood cholesterol, a risk factor for CVD events in people with and without a history of CHD, is an important goal of pharmacotherapy. Typically, statins are the first-line agents. Studies have demonstrated the effects of statins and its benefits in people with coronary artery disease; however, the case for primary prevention is less clear.
The aim of this study was to assess the effects, both harms and benefits, of statins in people with no history of CVD.
Study Highlights
* The investigators conducted a search within the Cochrane Central Register of Controlled Trials (Issue 1, 2007), MEDLINE (2001 to March 2007), and EMBASE (2003 to March 2007) for trials comparing statins vs usual care or placebo. There were no language restrictions.
* Randomized controlled trials of statins with minimum duration of 1 year and follow-up of 6 months, trials of adults with no restrictions on their total low-density lipoprotein or high-density lipoprotein cholesterol levels, and trials in which 10% or less of participants had a history of CVD were included.
* Drug treatments and other interventions were accepted, provided they were given to both groups of the intervention groups.
* 2 authors independently selected studies for inclusion and extracted data.
* Outcomes included all-cause mortality, fatal and nonfatal CHD, CVD, stroke events, combined endpoints (fatal and nonfatal CHD, CVD, and stroke events), change in blood total cholesterol concentration, revascularization, adverse events, quality of life, and costs.
* Relative risk was calculated for dichotomous data, and for continuous data, pooled weighted mean differences (with 95% confidence intervals) were calculated.
* 14 randomized control trials (16 trial groups; 34,272 participants) were included.
* 11 trials recruited patients with specific conditions (increased lipid levels, diabetes, hypertension, and microalbuminuria).
* All tested the effectiveness of a statin vs placebo, 9 studies tested pravastatin (10 - 40 mg/day) and atorvastatin (10 mg/day), 2 studies tested fluvastatin (40 - 80 mg/day) and lovastatin (20 - 40 mg/day), and the remaining studies tested simvastatin (40 mg/day).
* 2 trials — the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) 1998 and the Collaborative AtoRvastatin Diabetes Study (CARDS) 2004 — were stopped prematurely because of significant reductions in primary composite outcomes between the intervention and placebo groups.
* Results demonstrated that all-cause mortality risk was reduced by statins (relative risk, 0.83; 95% CI, 0.73 - 0.95), as were combined fatal and nonfatal CVD endpoints (relative risk, 0.70; 95% CI, 0.61 - 0.79).
* No significant risk reduction was observed in fatal CHD events and fatal and nonfatal stroke events.
* Benefits were also seen in the reduction of revascularization rates (relative risk, 0.66; 95% CI, 0.53 - 0.83).
* Total cholesterol and low-density lipoprotein cholesterol levels were reduced in all trials; however, there was evidence of heterogeneity of effects, possibly because of differences in the statin and dosage used as well as reporting biases.
* There was no clear evidence of any significant harm caused by statin prescription or of effects on patient quality of life.
* No statistical differences in outcomes were observed in age and sex.
* There was limited evidence to suggest that the use of statins for primary prevention may be cost effective and improve patient-perceived quality of life.
Clinical Implications
* According to the World Health Organization in 2008, the major causes of CVD are unhealthy diet, tobacco use, and physical inactivity.
* Although reductions in all-cause mortality risk, composite endpoints, and revascularizations were found with no excess of adverse events, there was evidence of selective reporting of outcomes, failure to report adverse events, and inclusion of people with cardiovascular disease. Therefore, caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.
Sunday, February 6, 2011
In Cancer Survival, 'Mind Matters,' Says Expert
From Medscape Medical News > Oncology
Nick Mulcahy
February 2, 2011 — Social support and psychologic/psychiatric interventions can improve survival in cancer but are "overlooked" in the treatment of the disease, argues a psychiatrist in an essay published in the February 2 issue of the Journal of the American Medical Association.
"A patient's personal mental management of the stresses associated with cancer" is a "natural ally" in the battle with this disease, writes David Spiegel, MD, from the Department of Psychiatry and Behavioral Sciences at Stanford University School of Medicine in Palo Alto, California.
"It is plausible that interventions providing emotional and social support at the end of life have a positive influence on physiological stress-response systems that affect survival," he writes, suggesting a mechanism of action.
But another expert in the field of behavioral medicine noted that there is very little evidence of such survival benefit.
"Social support almost certainly makes people feel better, which is hugely important, and I wouldn't be surprised if it did improve survival," said Richard Sloan, PhD, from the Division of Behavioral Medicine at the Columbia University Medical Center in New York City. But, he added, there is no strong body of evidence that treatments and services addressing social or emotional issues improve survival in the field of cancer.
For instance, "I know of no study in cancer patients that shows that reducing depression improves survival," he said. "We should treat depression because it makes patients miserable, not because we think it may improve survival," he added.
Dr. Sloan's great concern about the discussion of the evidence regarding psychosocial support and cancer survival is how the information is received by the public, most importantly cancer patients.
"We have to be really careful not to oversell the interventions we have," he told Medscape Medical News. The reason? "People can feel at fault if they don't respond to a program," he said. In a recent editorial in the New York Times, Dr. Sloan discusses some of the history of "mind cure" movements in the United States. The editorial touches on the lack of scientific validity in the belief that personality or "a way of thinking" can influence disease outcomes. As he notes, a recent large study dismissed the idea that any personality type is associated with the risk of getting or surviving cancer.
Dr. Spiegel does not say that cancer can be cured by psychosocial interventions and makes no claims about the power of positive thinking. Instead, he argues that psychosocial support, which includes the discussion of death and learning how to manage pain and anxiety, might extend survival, particularly at the end of life. He summarizes: "It is not simply mind over matter — but mind matters."
Follows Palliative Care Study
Dr. Spiegel's essay comes about 6 months after a study on palliative care in cancer was published in the New England Journal of Medicine (2010;363:733-742). In that study, the introduction of palliative care — a program designed to minimize pain and improve quality of life — at diagnosis, in parallel with standard oncologic care, was associated with a significant improvement in survival in patients with metastatic nonsmall-cell lung cancer (NSCLS).
After discussing the palliative care study in his essay, Dr. Spiegel states that "there is increasing evidence that social support affects survival [in cancer]." He cites 2 studies in particular: a study in women with early-stage breast cancer, which was led by Barbara Andersen, PhD, from Ohio State University in Columbus (Cancer. 2008;113:3450-3458); and a study by Dr. Spiegel himself in women with metastatic breast cancer (Lancet. 1989;2:888-891).
To Medscape Medical News, he mentioned 3 other randomized trials and 1 matched-cohort trial that "have found that psychosocial treatment for patients with a variety of cancers produced both psychological and survival benefits." The cancers in these types of studies tend to be those with the poorest prognosis, including malignant melanoma, NSCLC, leukemia, and gastrointestinal tract cancers, Dr. Spiegel points out in his essay.
"For breast and other cancers, when aggressive antitumor treatments are less effective, supportive approaches appear to become more useful," observed Dr. Spiegel.
Dr. Andersen said that the quantity of cancer research that indicates a survival benefit of psychosocial interventions is not abundant. "There is not all that much data on social support in particular," she told Medscape Medical News.
Nonetheless, Dr. Andersen suggested that the palliative care study represents a pivotal moment in this area of research. The fact that the New England Journal of Medicine published it was "quite amazing," she said. The journal has a "history of considerable skepticism with regard to the importance of psychological and behavioral factors in cancer," she explained.
Dr. Andersen also pointed out that "there's a whole lot more going on in psychosocial interventions than just social support." For instance, in her breast cancer study, she and her colleagues note that the intervention was psychologist led, conducted in small groups, and included strategies to reduce stress, improve mood, alter health behaviors, and maintain adherence to cancer treatment and care.
Therein lies a problem, said Dr. Sloan. "It's hard to know which is the active agent" in such multifactorial studies. For instance, he wondered whether treatment adherence was the element of the Ohio State program that tipped the scale toward a survival benefit.
Dr. Andersen responded that adherence was not a factor in the differential survival.
Dr. Andersen would like the discussion about the benefits of psychosocial interventions and drug therapies and other treatments to not be a matter of "either/or." The various interventions should work together, she said.
The authors have disclosed no relevant financial relationships.
JAMA. 2011;305:502-503.
Nick Mulcahy
February 2, 2011 — Social support and psychologic/psychiatric interventions can improve survival in cancer but are "overlooked" in the treatment of the disease, argues a psychiatrist in an essay published in the February 2 issue of the Journal of the American Medical Association.
"A patient's personal mental management of the stresses associated with cancer" is a "natural ally" in the battle with this disease, writes David Spiegel, MD, from the Department of Psychiatry and Behavioral Sciences at Stanford University School of Medicine in Palo Alto, California.
"It is plausible that interventions providing emotional and social support at the end of life have a positive influence on physiological stress-response systems that affect survival," he writes, suggesting a mechanism of action.
But another expert in the field of behavioral medicine noted that there is very little evidence of such survival benefit.
"Social support almost certainly makes people feel better, which is hugely important, and I wouldn't be surprised if it did improve survival," said Richard Sloan, PhD, from the Division of Behavioral Medicine at the Columbia University Medical Center in New York City. But, he added, there is no strong body of evidence that treatments and services addressing social or emotional issues improve survival in the field of cancer.
For instance, "I know of no study in cancer patients that shows that reducing depression improves survival," he said. "We should treat depression because it makes patients miserable, not because we think it may improve survival," he added.
Dr. Sloan's great concern about the discussion of the evidence regarding psychosocial support and cancer survival is how the information is received by the public, most importantly cancer patients.
"We have to be really careful not to oversell the interventions we have," he told Medscape Medical News. The reason? "People can feel at fault if they don't respond to a program," he said. In a recent editorial in the New York Times, Dr. Sloan discusses some of the history of "mind cure" movements in the United States. The editorial touches on the lack of scientific validity in the belief that personality or "a way of thinking" can influence disease outcomes. As he notes, a recent large study dismissed the idea that any personality type is associated with the risk of getting or surviving cancer.
Dr. Spiegel does not say that cancer can be cured by psychosocial interventions and makes no claims about the power of positive thinking. Instead, he argues that psychosocial support, which includes the discussion of death and learning how to manage pain and anxiety, might extend survival, particularly at the end of life. He summarizes: "It is not simply mind over matter — but mind matters."
Follows Palliative Care Study
Dr. Spiegel's essay comes about 6 months after a study on palliative care in cancer was published in the New England Journal of Medicine (2010;363:733-742). In that study, the introduction of palliative care — a program designed to minimize pain and improve quality of life — at diagnosis, in parallel with standard oncologic care, was associated with a significant improvement in survival in patients with metastatic nonsmall-cell lung cancer (NSCLS).
After discussing the palliative care study in his essay, Dr. Spiegel states that "there is increasing evidence that social support affects survival [in cancer]." He cites 2 studies in particular: a study in women with early-stage breast cancer, which was led by Barbara Andersen, PhD, from Ohio State University in Columbus (Cancer. 2008;113:3450-3458); and a study by Dr. Spiegel himself in women with metastatic breast cancer (Lancet. 1989;2:888-891).
To Medscape Medical News, he mentioned 3 other randomized trials and 1 matched-cohort trial that "have found that psychosocial treatment for patients with a variety of cancers produced both psychological and survival benefits." The cancers in these types of studies tend to be those with the poorest prognosis, including malignant melanoma, NSCLC, leukemia, and gastrointestinal tract cancers, Dr. Spiegel points out in his essay.
"For breast and other cancers, when aggressive antitumor treatments are less effective, supportive approaches appear to become more useful," observed Dr. Spiegel.
Dr. Andersen said that the quantity of cancer research that indicates a survival benefit of psychosocial interventions is not abundant. "There is not all that much data on social support in particular," she told Medscape Medical News.
Nonetheless, Dr. Andersen suggested that the palliative care study represents a pivotal moment in this area of research. The fact that the New England Journal of Medicine published it was "quite amazing," she said. The journal has a "history of considerable skepticism with regard to the importance of psychological and behavioral factors in cancer," she explained.
Dr. Andersen also pointed out that "there's a whole lot more going on in psychosocial interventions than just social support." For instance, in her breast cancer study, she and her colleagues note that the intervention was psychologist led, conducted in small groups, and included strategies to reduce stress, improve mood, alter health behaviors, and maintain adherence to cancer treatment and care.
Therein lies a problem, said Dr. Sloan. "It's hard to know which is the active agent" in such multifactorial studies. For instance, he wondered whether treatment adherence was the element of the Ohio State program that tipped the scale toward a survival benefit.
Dr. Andersen responded that adherence was not a factor in the differential survival.
Dr. Andersen would like the discussion about the benefits of psychosocial interventions and drug therapies and other treatments to not be a matter of "either/or." The various interventions should work together, she said.
The authors have disclosed no relevant financial relationships.
JAMA. 2011;305:502-503.
Friday, February 4, 2011
Using ANA Patterns to Diagnose Autoimmune Disorders
From Medscape Rheumatology > Viewpoints
Kevin Deane, MD
Pattern on the Antinuclear Antibody-HEp-2 Test Is a Critical Parameter for Discriminating Antinuclear Antibody-Positive Healthy Individuals and Patients With Autoimmune Rheumatic Diseases
Mariz HA, Sato EI, Barbosa SH, Rodrigues SH, Dellavance A, Andrade LE
Arthritis Rheum. 2011;63:191-200.
Introduction
Testing for antinuclear antibodies (ANAs) is an important aspect of the clinical evaluation of patients with autoimmune rheumatic diseases (ARDs). Understanding how ANA patterns, titers, and extractable nuclear antigen (ENA) profiles are associated with disease or healthy states can help rheumatologists, as well as other healthcare providers, better utilize ANA testing to accurately identify disease. In this study, the authors evaluated the features of ANA testing that discriminated between healthy individuals and those with ARDs.
Study Summary
In Brazilian patients with a variety of known ARDs (N=138; 87 with systemic lupus erythematosus, 45 with systemic sclerosis, 11 with Sjögren syndrome, and 10 with inflammatory myopathy) and healthy controls (N=118), the authors evaluated ANA titers and patterns using indirect immunofluorescence (IIF) with HEp-2 cells as antigen. Additionally, in these groups, the authors tested for autoantibodies to the ENAs Sm, U1 RNP, SSA, and SSB using Ouchterlony methodology, and for antibodies to double-stranded DNA using the Crithidia luciliae assay.
The authors found that an ANA titer of 1:80 was 90.2% sensitive and 87.1% specific for an ARD; a titer of 1:1280 was 65.4% sensitive and 97.9% specific for an ARD. Also, the ANA patterns of nuclear homogeneous, coarse speckled, and centromeric were highly specific for patients with ARDs, while the nuclear dense fine speckled pattern only appeared in healthy individuals (this latter pattern was associated with a 75kd antigen on Western blot). Antibodies to ENAs were highly specific to patients with ARDs; anti-SSA positivity was present in only 1 healthy individual. Additionally, a subset (N=41) of the healthy individuals who were initially positive for ANA (> 1:80) with an IIF appearance of a dense fine speckled pattern were evaluated 4 years after initial testing, and none had developed an ARD.
The authors concluded that on ANA testing with IIF, the titer and pattern were helpful in discriminating between disease and healthy states.
Viewpoint
In the United States and elsewhere, there is increasing popularity of ANA testing by high-throughput methodologies such as ELISA or array-based assays that do not identify ANA patterns, even though there are concerns that these newer methodologies may lack the diagnostic accuracy for ARDs of IIF testing.[1] Although there are some flaws with this paper, the findings presented support that providing ANA testing by IIF may yield valuable clinical information, and, therefore, healthcare providers who evaluate patients with suspected ARDs may lose valuable clinical information if IIF testing is completely abandoned. As an editorial that accompanies this article points out,[2] the authors of this paper could have provided valuable data to inform the ongoing debate about which methodology for ANA testing is optimal for the identification of ARDs if comparison testing between ANA methodologies were performed. Going forward, such direct comparisons are crucial to allow providers to make the best decisions regarding which type of ANA testing methodology to use in clinical practice.
abstract
OBJECTIVE: To identify features of antinuclear antibody (ANA)-HEp-2 test results that discriminate ANA-positive healthy individuals and patients with autoimmune rheumatic diseases (ARDs).
METHODS: We sequentially retrieved data on 918 healthy individuals and 153 patients with ARDs after clinical assessment. ANA-positive healthy individuals for whom data were available were reevaluated after 3.6-5.0 years. An ANA-HEp-2 test result was considered positive when a clear ANA pattern was observed at 1:80 dilution in 2 distinct commercial HEp-2 slides by 2 blinded independent observers.
RESULTS: ANAs were present in 118 healthy individuals (12.9%) and 138 patients with ARDs (90.2%). The ANA titer was higher in patients with ARDs than in healthy individuals (P<0.001). The ANA pattern profile was distinct in the 2 groups. Nuclear homogeneous, nuclear coarse speckled, and nuclear centromeric patterns appeared exclusively in patients with ARDs. The nuclear dense fine speckled pattern occurred only in healthy individuals. The most frequent ANA pattern in both groups was the nuclear fine speckled pattern, which occurred at lower titer in healthy individuals than in patients with ARDs (P<0.001). Anti-extractable nuclear antigen was present in 1 healthy individual (anti-SSA/Ro) and in 52 patients with ARDs (37.7%). None of the 40 reevaluated healthy individuals developed ARDs, and 29 (72.5%) remained ANA positive. All healthy individuals who became ANA negative had an ANA titer of 1:80 at baseline.
CONCLUSION: Our findings suggest that the titer, and especially the pattern, on the ANA-HEp-2 test strongly enhances our ability to discriminate ANA-positive healthy individuals and patients with ARDs.
Kevin Deane, MD
Pattern on the Antinuclear Antibody-HEp-2 Test Is a Critical Parameter for Discriminating Antinuclear Antibody-Positive Healthy Individuals and Patients With Autoimmune Rheumatic Diseases
Mariz HA, Sato EI, Barbosa SH, Rodrigues SH, Dellavance A, Andrade LE
Arthritis Rheum. 2011;63:191-200.
Introduction
Testing for antinuclear antibodies (ANAs) is an important aspect of the clinical evaluation of patients with autoimmune rheumatic diseases (ARDs). Understanding how ANA patterns, titers, and extractable nuclear antigen (ENA) profiles are associated with disease or healthy states can help rheumatologists, as well as other healthcare providers, better utilize ANA testing to accurately identify disease. In this study, the authors evaluated the features of ANA testing that discriminated between healthy individuals and those with ARDs.
Study Summary
In Brazilian patients with a variety of known ARDs (N=138; 87 with systemic lupus erythematosus, 45 with systemic sclerosis, 11 with Sjögren syndrome, and 10 with inflammatory myopathy) and healthy controls (N=118), the authors evaluated ANA titers and patterns using indirect immunofluorescence (IIF) with HEp-2 cells as antigen. Additionally, in these groups, the authors tested for autoantibodies to the ENAs Sm, U1 RNP, SSA, and SSB using Ouchterlony methodology, and for antibodies to double-stranded DNA using the Crithidia luciliae assay.
The authors found that an ANA titer of 1:80 was 90.2% sensitive and 87.1% specific for an ARD; a titer of 1:1280 was 65.4% sensitive and 97.9% specific for an ARD. Also, the ANA patterns of nuclear homogeneous, coarse speckled, and centromeric were highly specific for patients with ARDs, while the nuclear dense fine speckled pattern only appeared in healthy individuals (this latter pattern was associated with a 75kd antigen on Western blot). Antibodies to ENAs were highly specific to patients with ARDs; anti-SSA positivity was present in only 1 healthy individual. Additionally, a subset (N=41) of the healthy individuals who were initially positive for ANA (> 1:80) with an IIF appearance of a dense fine speckled pattern were evaluated 4 years after initial testing, and none had developed an ARD.
The authors concluded that on ANA testing with IIF, the titer and pattern were helpful in discriminating between disease and healthy states.
Viewpoint
In the United States and elsewhere, there is increasing popularity of ANA testing by high-throughput methodologies such as ELISA or array-based assays that do not identify ANA patterns, even though there are concerns that these newer methodologies may lack the diagnostic accuracy for ARDs of IIF testing.[1] Although there are some flaws with this paper, the findings presented support that providing ANA testing by IIF may yield valuable clinical information, and, therefore, healthcare providers who evaluate patients with suspected ARDs may lose valuable clinical information if IIF testing is completely abandoned. As an editorial that accompanies this article points out,[2] the authors of this paper could have provided valuable data to inform the ongoing debate about which methodology for ANA testing is optimal for the identification of ARDs if comparison testing between ANA methodologies were performed. Going forward, such direct comparisons are crucial to allow providers to make the best decisions regarding which type of ANA testing methodology to use in clinical practice.
abstract
OBJECTIVE: To identify features of antinuclear antibody (ANA)-HEp-2 test results that discriminate ANA-positive healthy individuals and patients with autoimmune rheumatic diseases (ARDs).
METHODS: We sequentially retrieved data on 918 healthy individuals and 153 patients with ARDs after clinical assessment. ANA-positive healthy individuals for whom data were available were reevaluated after 3.6-5.0 years. An ANA-HEp-2 test result was considered positive when a clear ANA pattern was observed at 1:80 dilution in 2 distinct commercial HEp-2 slides by 2 blinded independent observers.
RESULTS: ANAs were present in 118 healthy individuals (12.9%) and 138 patients with ARDs (90.2%). The ANA titer was higher in patients with ARDs than in healthy individuals (P<0.001). The ANA pattern profile was distinct in the 2 groups. Nuclear homogeneous, nuclear coarse speckled, and nuclear centromeric patterns appeared exclusively in patients with ARDs. The nuclear dense fine speckled pattern occurred only in healthy individuals. The most frequent ANA pattern in both groups was the nuclear fine speckled pattern, which occurred at lower titer in healthy individuals than in patients with ARDs (P<0.001). Anti-extractable nuclear antigen was present in 1 healthy individual (anti-SSA/Ro) and in 52 patients with ARDs (37.7%). None of the 40 reevaluated healthy individuals developed ARDs, and 29 (72.5%) remained ANA positive. All healthy individuals who became ANA negative had an ANA titer of 1:80 at baseline.
CONCLUSION: Our findings suggest that the titer, and especially the pattern, on the ANA-HEp-2 test strongly enhances our ability to discriminate ANA-positive healthy individuals and patients with ARDs.
Analysis Suggests Back Disease May Run in Families
From Medscape Medical News
Norra MacReady
February 4, 2011 — In an analysis of a database of more than 2 million people, first-degree and third-degree relatives of people with lumbar disc disease had a significantly increased relative risk of developing the back condition themselves compared with expected rates for the general population. "The results of this study support a heritable predisposition to lumbar disc disease," lead author Alpesh A. Patel, MD, and colleagues from the departments of Orthopaedics and Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, report in the February 2 issue of the Journal of Bone and Joint Surgery.
Low back pain is common and costly — its estimated lifetime risk in the United States is 84%, with an annual cost that exceeds $100 billion — yet its etiology remains incompletely understood, the authors write. Several earlier studies have hinted at a familial predisposition, but "we are aware of no study that has evaluated the familial clustering of lumbar disc disease on a population-based, multigenerational level."
To test the hypothesis that lumbar disc disease may be inherited, the authors analyzed data from both the Utah Population Database, which permits the tracking of medical information on the founding pioneers of Utah and their descendents, and the University of Utah Health Sciences Center data warehouse, which has diagnosis and procedure data on all patients treated at the University Hospital. Together, the databases contain information on more than 2.4 million patients. Only patients and control participants with at least 3 generations of genealogical data were included in the study.
Of those individuals, 1254 people had at least 1 diagnosis of lumbar disc disease or lumbar disc herniation, along with the requisite genealogical data. The authors tested for heritability in 2 ways: by estimating the relative risk for lumbar disease in relatives and by determining a genealogical index of familiality (GIF). They compared their findings in affected families with the expected results for the general population of Utah.
First-degree relatives of people with lumbar disc disease had a relative risk of 4.15 of having the disease themselves (95% confidence interval [CI], 2.82 - 6.10; P < .001). In third-degree relatives, the relative risk was 1.46 (95% CI, 1.06 - 2.01; P = .027). Relative risk was slightly elevated in second-degree relatives, at 1.15, but this was not significant (95% CI, .71 - 1.87; P = .60), perhaps because of limitations in the data.
The GIF tests the hypothesis that there is no excess familial clustering, or relatedness, of the phenotype of interest by measuring excess relationships between pairs of patients compared with pairs of control participants. "It is not the absolute value of the GIF statistic that reveals excess relatedness of disease, but the relative value of the case-GIF to the control-GIF," the authors explain. In this analysis, the case overall GIF was 3.05 compared with a mean control GIF of 2.51 (P < .001 for overall GIF), suggesting "a significant excess of relationships among patients compared with controls."
The investigators relied on International Classification of Diseases, Ninth Revision, codes to identify patients, so diagnostic accuracy may have varied, depending on physician specialty and experience, they noted. Also, they were unable to determine disease severity and response to treatment. Genetically, the population of Utah is similar to the US population and to the northern European population from which the founders of Utah came, so the findings may be generalized to those groups.
Now that a genetic predisposition to lumbar disc disease has been identified, the authors conclude, "identification of the specific genetic products responsible for lumbar disc disease may help in the development of potential biologic interventions to prevent and/or treat lumbar disc disease in the population at large."
In an accompanying editorial published online, David A. Wong, MD, from the Denver Spine Center, Greenwood Village, Colorado, commends Dr. Patel and colleagues for their study design and conclusion. Dr. Wong remarks on the future possibilities that may lead researchers to identify specific genes responsible for spine and other musculoskeletal disorders, akin to what is currently known about breast cancer. He states: "We can look forward to more genetic research in the area of the spine. Inevitably better treatments are likely to be found. Perhaps the treatment for so-called black disc disease is lurking on the horizon."
J Bone Joint Surg Am. 2011;93:225-229. Abstract
Norra MacReady
February 4, 2011 — In an analysis of a database of more than 2 million people, first-degree and third-degree relatives of people with lumbar disc disease had a significantly increased relative risk of developing the back condition themselves compared with expected rates for the general population. "The results of this study support a heritable predisposition to lumbar disc disease," lead author Alpesh A. Patel, MD, and colleagues from the departments of Orthopaedics and Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, report in the February 2 issue of the Journal of Bone and Joint Surgery.
Low back pain is common and costly — its estimated lifetime risk in the United States is 84%, with an annual cost that exceeds $100 billion — yet its etiology remains incompletely understood, the authors write. Several earlier studies have hinted at a familial predisposition, but "we are aware of no study that has evaluated the familial clustering of lumbar disc disease on a population-based, multigenerational level."
To test the hypothesis that lumbar disc disease may be inherited, the authors analyzed data from both the Utah Population Database, which permits the tracking of medical information on the founding pioneers of Utah and their descendents, and the University of Utah Health Sciences Center data warehouse, which has diagnosis and procedure data on all patients treated at the University Hospital. Together, the databases contain information on more than 2.4 million patients. Only patients and control participants with at least 3 generations of genealogical data were included in the study.
Of those individuals, 1254 people had at least 1 diagnosis of lumbar disc disease or lumbar disc herniation, along with the requisite genealogical data. The authors tested for heritability in 2 ways: by estimating the relative risk for lumbar disease in relatives and by determining a genealogical index of familiality (GIF). They compared their findings in affected families with the expected results for the general population of Utah.
First-degree relatives of people with lumbar disc disease had a relative risk of 4.15 of having the disease themselves (95% confidence interval [CI], 2.82 - 6.10; P < .001). In third-degree relatives, the relative risk was 1.46 (95% CI, 1.06 - 2.01; P = .027). Relative risk was slightly elevated in second-degree relatives, at 1.15, but this was not significant (95% CI, .71 - 1.87; P = .60), perhaps because of limitations in the data.
The GIF tests the hypothesis that there is no excess familial clustering, or relatedness, of the phenotype of interest by measuring excess relationships between pairs of patients compared with pairs of control participants. "It is not the absolute value of the GIF statistic that reveals excess relatedness of disease, but the relative value of the case-GIF to the control-GIF," the authors explain. In this analysis, the case overall GIF was 3.05 compared with a mean control GIF of 2.51 (P < .001 for overall GIF), suggesting "a significant excess of relationships among patients compared with controls."
The investigators relied on International Classification of Diseases, Ninth Revision, codes to identify patients, so diagnostic accuracy may have varied, depending on physician specialty and experience, they noted. Also, they were unable to determine disease severity and response to treatment. Genetically, the population of Utah is similar to the US population and to the northern European population from which the founders of Utah came, so the findings may be generalized to those groups.
Now that a genetic predisposition to lumbar disc disease has been identified, the authors conclude, "identification of the specific genetic products responsible for lumbar disc disease may help in the development of potential biologic interventions to prevent and/or treat lumbar disc disease in the population at large."
In an accompanying editorial published online, David A. Wong, MD, from the Denver Spine Center, Greenwood Village, Colorado, commends Dr. Patel and colleagues for their study design and conclusion. Dr. Wong remarks on the future possibilities that may lead researchers to identify specific genes responsible for spine and other musculoskeletal disorders, akin to what is currently known about breast cancer. He states: "We can look forward to more genetic research in the area of the spine. Inevitably better treatments are likely to be found. Perhaps the treatment for so-called black disc disease is lurking on the horizon."
J Bone Joint Surg Am. 2011;93:225-229. Abstract
Tuesday, February 1, 2011
USA Adult Immunization Schedule for 2011 Released
From Medscape Medical News
Laurie Barclay, MD
January 31, 2011 — In October 2010, the Advisory Committee on Immunization Practices (ACIP) approved the Adult Immunization Schedule for 2011, which includes several changes.
An adult woman receives a vaccine at her primary care provider's office.
The 2011 schedule, which reflects current recommendations for the licensed vaccines, is published in the February 1 issue of the Annals of Internal Medicine. The 2011 schedule was also approved by the American Academy of Family Physicians, American College of Obstetricians and Gynecologists, and the American College of Physicians.
"The notation for seasonal influenza vaccine in the figure and footnotes was changed to reflect the expanded recommendation for annual influenza vaccination for everyone 6 months of age or older, which was approved by ACIP in February 2010," write Abigail Shefer, MD, Immunization Services Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, and colleagues.
"In October 2010, ACIP issued a permissive recommendation for use of the tetanus, diphtheria, pertussis (Tdap) vaccine in adults aged 65 years or older; approved the recommendation that Tdap can be administered regardless of how much time has elapsed since the last tetanus and diphtheria (Td)–containing vaccine;
and approved a recommendation for a 2-dose series of meningococcal vaccine in adults with certain high-risk medical conditions. The vaccines listed in the Figure have been reordered to keep all universally recommended vaccines together (for example, influenza, Td/Tdap, varicella, human papillomavirus [HPV], and zoster)."
Other changes include clarifications to the footnotes for the measles, mumps, rubella; HPV; and Haemophilus influenza type B (Hib) vaccines and for revaccination with pneumococcal polysaccharide (PPSV). A vaccine series does not need to be restarted, regardless of the time elapsed between doses.
Specific Updated Changes
Specific changes in the schedule for 2011 include the following:
* All persons at least 6 months old, including all adults, should be vaccinated against seasonal influenza. Adults at least 65 years old may receive the high-dose influenza vaccine (Fluzone; sanofi-pasteur, Swiftwater, Pennsylvania), licensed in 2010 for use in this age group, as an option.
* Persons at least 65 years old in close contact with an infant younger than 12 months should receive Tdap vaccine, and all persons at least 65 years old may receive Tdap vaccine. Tdap should be administered regardless of time elapsed since receiving the last Td-containing vaccine.
* Either quadrivalent human papillomavirus (HPV4) vaccine or bivalent (HPV2) vaccine is recommended for girls and women.
* For revaccination with PPSV, 1-time revaccination after 5 years applies only to persons 19 through 64 years old with indicated chronic conditions, namely chronic renal failure or the nephrotic syndrome, functional or anatomic asplenia, or immunocompromising conditions.
* For adults with anatomic or functional asplenia or persistent complement component deficiencies and adults with HIV infection who are vaccinated with meningococcal conjugate vaccine (MCV4), a 2-dose series of meningococcal vaccine is recommended, with the 2 doses given 2 months apart.
For those with other indications, a single dose of meningococcal vaccine is still recommended.
Information in the new schedule clarifies that MCV4 is a quadrivalent vaccine.
* Information regarding the Hib vaccine clarifies which high-risk persons may receive 1 dose of Hib vaccine, namely persons who have sickle cell disease, leukemia, or HIV infection, or those who have had a splenectomy, if they have not previously received Hib vaccine.
Additional Schedule Highlights
Additional highlights of the Adult Immunization Schedule include the following:
* Adults younger than 65 years whose previous Td status is unknown should receive 1 dose of Tdap. Tdap should be administered immediately to postpartum women, close contacts of infants younger than 12 months, and healthcare workers.
* Girls 11 to 12 years old should receive HPV4 or HPV2. Catch-up vaccination in girls may be given until age 26 years. Boys and men 9 to 26 years old may be given HPV4 to lower their risk of acquiring genital warts.
* All persons at least 60 years old should receive a single dose of vaccine against herpes zoster, regardless of whether personal history is positive for herpes zoster.
* Recommendations for varicella vaccination are unchanged. Two vaccine doses at least 4 weeks apart should be given to all adults born during or after 1980 who have no evidence of immunity to varicella.
Healthcare workers should not be considered to have immunity against varicella simply because of their age.
Pregnant women should be evaluated for evidence of varicella immunity, and those lacking such evidence should receive the first dose of varicella vaccine on completion or termination of pregnancy and before discharge from the healthcare facility.
The second dose should be given 4 to 8 weeks after the first dose.
* Hepatitis A vaccination should be given to anyone seeking protection from hepatitis A virus (HAV) infection, men who have sex with men, users of injection drugs, persons working with HAV-infected primates or with HAV in a research laboratory setting, persons with chronic liver disease and persons who receive clotting factor concentrates, and persons traveling to or working in countries with high or intermediate endemicity of hepatitis A.
* Hepatitis B vaccination should be given to anyone seeking protection from hepatitis B virus (HBV) infection, persons with more than 1 sex partner during the previous 6 months, persons seeking evaluation or treatment of a sexually transmitted disease, current or recent injection-drug users, men who have sex with men, healthcare personnel and public safety workers exposed to blood or other potentially infectious body fluids, persons with end-stage renal disease, persons with HIV infection, persons with chronic liver disease, household contacts and sex partners of persons with chronic HBV infection, clients and staff members of institutions for persons with developmental disabilities, and international travelers to countries with a high or intermediate prevalence of chronic HBV infection.
Ann Intern Med. 2011:154:168-173. Full text
Laurie Barclay, MD
January 31, 2011 — In October 2010, the Advisory Committee on Immunization Practices (ACIP) approved the Adult Immunization Schedule for 2011, which includes several changes.
An adult woman receives a vaccine at her primary care provider's office.
The 2011 schedule, which reflects current recommendations for the licensed vaccines, is published in the February 1 issue of the Annals of Internal Medicine. The 2011 schedule was also approved by the American Academy of Family Physicians, American College of Obstetricians and Gynecologists, and the American College of Physicians.
"The notation for seasonal influenza vaccine in the figure and footnotes was changed to reflect the expanded recommendation for annual influenza vaccination for everyone 6 months of age or older, which was approved by ACIP in February 2010," write Abigail Shefer, MD, Immunization Services Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, and colleagues.
"In October 2010, ACIP issued a permissive recommendation for use of the tetanus, diphtheria, pertussis (Tdap) vaccine in adults aged 65 years or older; approved the recommendation that Tdap can be administered regardless of how much time has elapsed since the last tetanus and diphtheria (Td)–containing vaccine;
and approved a recommendation for a 2-dose series of meningococcal vaccine in adults with certain high-risk medical conditions. The vaccines listed in the Figure have been reordered to keep all universally recommended vaccines together (for example, influenza, Td/Tdap, varicella, human papillomavirus [HPV], and zoster)."
Other changes include clarifications to the footnotes for the measles, mumps, rubella; HPV; and Haemophilus influenza type B (Hib) vaccines and for revaccination with pneumococcal polysaccharide (PPSV). A vaccine series does not need to be restarted, regardless of the time elapsed between doses.
Specific Updated Changes
Specific changes in the schedule for 2011 include the following:
* All persons at least 6 months old, including all adults, should be vaccinated against seasonal influenza. Adults at least 65 years old may receive the high-dose influenza vaccine (Fluzone; sanofi-pasteur, Swiftwater, Pennsylvania), licensed in 2010 for use in this age group, as an option.
* Persons at least 65 years old in close contact with an infant younger than 12 months should receive Tdap vaccine, and all persons at least 65 years old may receive Tdap vaccine. Tdap should be administered regardless of time elapsed since receiving the last Td-containing vaccine.
* Either quadrivalent human papillomavirus (HPV4) vaccine or bivalent (HPV2) vaccine is recommended for girls and women.
* For revaccination with PPSV, 1-time revaccination after 5 years applies only to persons 19 through 64 years old with indicated chronic conditions, namely chronic renal failure or the nephrotic syndrome, functional or anatomic asplenia, or immunocompromising conditions.
* For adults with anatomic or functional asplenia or persistent complement component deficiencies and adults with HIV infection who are vaccinated with meningococcal conjugate vaccine (MCV4), a 2-dose series of meningococcal vaccine is recommended, with the 2 doses given 2 months apart.
For those with other indications, a single dose of meningococcal vaccine is still recommended.
Information in the new schedule clarifies that MCV4 is a quadrivalent vaccine.
* Information regarding the Hib vaccine clarifies which high-risk persons may receive 1 dose of Hib vaccine, namely persons who have sickle cell disease, leukemia, or HIV infection, or those who have had a splenectomy, if they have not previously received Hib vaccine.
Additional Schedule Highlights
Additional highlights of the Adult Immunization Schedule include the following:
* Adults younger than 65 years whose previous Td status is unknown should receive 1 dose of Tdap. Tdap should be administered immediately to postpartum women, close contacts of infants younger than 12 months, and healthcare workers.
* Girls 11 to 12 years old should receive HPV4 or HPV2. Catch-up vaccination in girls may be given until age 26 years. Boys and men 9 to 26 years old may be given HPV4 to lower their risk of acquiring genital warts.
* All persons at least 60 years old should receive a single dose of vaccine against herpes zoster, regardless of whether personal history is positive for herpes zoster.
* Recommendations for varicella vaccination are unchanged. Two vaccine doses at least 4 weeks apart should be given to all adults born during or after 1980 who have no evidence of immunity to varicella.
Healthcare workers should not be considered to have immunity against varicella simply because of their age.
Pregnant women should be evaluated for evidence of varicella immunity, and those lacking such evidence should receive the first dose of varicella vaccine on completion or termination of pregnancy and before discharge from the healthcare facility.
The second dose should be given 4 to 8 weeks after the first dose.
* Hepatitis A vaccination should be given to anyone seeking protection from hepatitis A virus (HAV) infection, men who have sex with men, users of injection drugs, persons working with HAV-infected primates or with HAV in a research laboratory setting, persons with chronic liver disease and persons who receive clotting factor concentrates, and persons traveling to or working in countries with high or intermediate endemicity of hepatitis A.
* Hepatitis B vaccination should be given to anyone seeking protection from hepatitis B virus (HBV) infection, persons with more than 1 sex partner during the previous 6 months, persons seeking evaluation or treatment of a sexually transmitted disease, current or recent injection-drug users, men who have sex with men, healthcare personnel and public safety workers exposed to blood or other potentially infectious body fluids, persons with end-stage renal disease, persons with HIV infection, persons with chronic liver disease, household contacts and sex partners of persons with chronic HBV infection, clients and staff members of institutions for persons with developmental disabilities, and international travelers to countries with a high or intermediate prevalence of chronic HBV infection.
Ann Intern Med. 2011:154:168-173. Full text
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