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
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