Am Fam Physician. 2009;80:841-846. Abstract
Clinical Context
Skeletal development, bone health, and neuromuscular function all require vitamin D. There are 2 forms of vitamin D: vitamin D2 (ergocalciferol), produced by irradiating ergosterol found in yeast and plants; and vitamin D3 (cholecalciferol), found in oily fish and synthesized in the skin in response to sunlight.
Because few foods contain vitamin D2, it is difficult to maintain adequate levels of vitamin D from dietary sources alone, and humans typically obtain 90% of vitamin D from sunlight. Because milk and other foods have been fortified with vitamin D, the rickets epidemic has subsided, but vitamin D deficiency and insufficiency are still linked to other pathologic conditions affecting persons of all ages.
Study Highlights
Signs and symptoms of vitamin D deficiency develop slowly or are nonspecific.
These may include symmetric low back pain in women, proximal muscle weakness, muscle aches, and throbbing bone pain.
Vitamin D deficiency is defined as a 25-hydroxyvitamin D level of less than 20 ng/mL (50 nmol/L).
Vitamin D insufficiency is defined as a serum 25-hydroxyvitamin D level of 20 to 30 ng/mL (50 - 75 nmol/L).
To prevent vitamin D deficiency, infants and children should have vitamin D intake of at least 400 IU/day from diet and supplements.
Unless infants are ingesting at least 1 L/day (33.8 fl oz) of vitamin D-fortified formula or milk, they should receive supplementation of 400 IU/day.
Vitamin D supplementation, 400 IU/day, is recommended for all children and adolescents who do not get regular sunlight exposure, who do not consume 1 L/day or more of vitamin D-fortified formula or milk, or who do not take a daily multivitamin supplement containing at least 400 IU of vitamin D.
In adults, vitamin D supplementation of 700 to 800 IU or more per day may reduce rates of falls and fractures.
Contraindications to vitamin D supplementation include tuberculosis or other granulomatous diseases, metastatic bone disease, sarcoidosis, or Williams syndrome.
Patients with vitamin D deficiency should receive oral ergocalciferol (vitamin D2), 50,000 IU per week for 8 weeks.
Serum 25-hydroxyvitamin D levels should be checked when this 8-week course is completed, and if these levels are not at least 30 ng/mL, the most likely cause is nonadherence to therapy or malabsorption.
A second 8-week course of ergocalciferol should be given if the level is not at least 30 ng/mL. Patients with suspected malabsorption may need gastroenterologic consultation.
Once vitamin D levels normalize in patients who were deficient, patients should receive maintenance dosages of cholecalciferol (vitamin D3), 800 to 1000 IU per day from dietary sources and/or supplements.
Because vitamin D is fat soluble, toxicity may result from excessive supplementation.
Signs and symptoms of vitamin D toxicity may include headache, metallic taste, nephrocalcinosis or vascular calcinosis, pancreatitis, nausea, and/or vomiting.
Clinical Implications
The diagnosis of vitamin D deficiency is often missed because the signs and symptoms develop slowly or are nonspecific, such as symmetric low back pain, proximal muscle weakness, muscle aches, and throbbing bone pain. Diagnosis of suspected vitamin D deficiency or insufficiency is confirmed with measurement of 25-hydroxyvitamin D levels.
In older adults, vitamin D supplementation of 700 to 800 IU per day is associated with a lower risk for falls and fractures. Suggested treatment in patients with vitamin D deficiency is oral ergocalciferol, 50,000 IU per week for 8 weeks. Adults with vitamin D deficiency, except for those with malabsorption syndromes, should receive maintenance dosages of 800 to 1000 IU of vitamin D per day.
Sunday, November 22, 2009
Thursday, November 19, 2009
Folate Supplementation Linked to Increased Cancer Incidence and Mortality
From Medscape Medical News
Zosia Chustecka
November 18, 2009 — Folic acid and vitamin B supplementation was associated with an increase in cancer incidence, cancer mortality, and all-cause mortality in a new analysis with long-term follow-up of data from 2 trials conducted in Norway, where there is no folic acid fortification of foods.
The results are reported in the November 18 issue of the Journal of the American Medical Association.
The authors, led by Marta Ebbing, MD, from Haukeland University Hospital in Bergen, Norway, say that these results, although in need of confirmation, suggest that there is a need for "safety monitoring" because there is now widespread folic acid fortification of foods and increasing use of folic acid in dietary supplements.
However, the authors of an accompanying editorial points out that data from the United States, where there has been mandatory folic acid fortification of flour and other foods since 1998, have been showing a significant decrease in cancer incidence. "These national incidence rates do not support a substantial population-wide adverse effect of the magnitude suggested in the study," write the editorialists, Bettina F. Drake, PhD, MPH, and Graham Colditz, MD, DrPH, both from the Washington University School of Medicine in St Louis, Missouri.
"The population data from the United States do not suggest that there is a problem," Dr. Drake said in an interview with Medscape Oncology. She pointed out that folate supplementation used in the study resulted in much higher blood levels than would be seen after eating foods fortified with folic acid. In addition, the study was conducted in individuals with heart disease and was of limited duration.
The findings from this study "do not nullify the potential long-term benefits that folic acid fortification may have on population health," Dr. Drake explained. The measure was introduced to reduce neural tube defects in newborns (which arise from folate deficiency during pregnancy). A reduction was seen within a "few years," the editorialists note.
Concerns about a link between cancer and folic acid supplementation have been raised previously, most recently with regard to colorectal cancer, as reported by Medscape Oncology. At that time, leading expert on nutrition and cancer Walter Willet MD, DrPH, from the Harvard School of Public Health in Boston, Massachusetts, said: "I am certain that we are not causing an epidemic of colorectal cancer with folic acid fortification of flour." He added that there was a small increase in the incidence of this cancer soon after fortification was introduced, but this coincided with an increase in colonoscopy, and he pointed out that mortality rates from this cancer have been declining steadily.
Latest Results from Norway
The latest results come from 2 trials conducted in 6837 patients with ischemic heart disease, in which half the participants took supplements of vitamin B (including folic acid) to lower homocysteine levels to see if this would reduce cardiovascular outcomes. It did not, and these results are in line with other large trials.
At the same time, both trials showed — independently — an increase in cancer in the supplementation group, compared with the placebo group, but this was not statistically significant.
In these 2 trials, participants took supplements containing folic acid (0.8 mg/d), vitamin B12 (0.4 mg/d), and B6 (40 mg/d), or various combinations of these. This dose of folic acid is 4 to 6 times higher than the average dose delivered by the mandatory fortification in the United States, and is twice the recommended daily allowance, the authors note, although they add that it is below the tolerable upper intake level of 1 mg/d set by the US Institute of Medicine.
The current analysis pooled results from the 2 trials, which had a median participation of 39 months, and added data from an observational posttrial follow-up of 38 months, giving a total duration of around 5.5 years. The authors note that pooling the data from the 2 trials is "justified" because they were nearly identical.
This pooled analysis found a statistically significant increase in cancer incidence, cancer mortality, and all-cause mortality.
These results for cancer outcomes are not supported by other studies of homocysteine-lowering vitamin B trials, the authors note.
Cancer Decreasing Significantly
In their editorial, Drs. Drake and Colditz write that these results indicate an excess of approximately 3.5 new cases of cancer per 1000 people per year, and 1 excess case of lung cancer per 1000 people per year. The excess deaths correspond to 1.7 cancer deaths per 1000 people per year.
"These numbers, if generalizable to the United States, would be substantial at the overall levels of total cancer incidence and mortality," they write. In addition, an increase in lung cancer incidence would be expected.
"However, the rates of total cancer incidence decreased significantly from 2001 to 2005, and the lung cancer incidence has also declined significantly," they point out.
Although the study suggests there is an association between folic acid supplementation and an increase in cancer, the US population data suggest that there isn't a problem with folic acid fortification of foods and cancer, Dr. Drake told Medscape Oncology. Folic acid fortification has been mandatory in the United States for more than 10 years and, given the results of this study, we would have expected a significant increase in the incidence of cancer by now, she suggested.
One of the issues with clinical trials is that observations are reported with a short time frame after the implementation of an intervention, the editorialists note. This can often lead to "looking for effects that fit the time frame," they add. "By analogy, when keys are missing it is common to look for them under the lamppost where the light is, rather than in the murky location where the keys were more likely to have been dropped."
One of the coauthors on the paper, Klaus Meyer, PhD, is employed at the laboratory of Bevital AS. The other authors and both editorialists have disclosed no relevant financial relationships.
JAMA. 2009;302:2119-2126, 2152-2153.
Zosia Chustecka
November 18, 2009 — Folic acid and vitamin B supplementation was associated with an increase in cancer incidence, cancer mortality, and all-cause mortality in a new analysis with long-term follow-up of data from 2 trials conducted in Norway, where there is no folic acid fortification of foods.
The results are reported in the November 18 issue of the Journal of the American Medical Association.
The authors, led by Marta Ebbing, MD, from Haukeland University Hospital in Bergen, Norway, say that these results, although in need of confirmation, suggest that there is a need for "safety monitoring" because there is now widespread folic acid fortification of foods and increasing use of folic acid in dietary supplements.
However, the authors of an accompanying editorial points out that data from the United States, where there has been mandatory folic acid fortification of flour and other foods since 1998, have been showing a significant decrease in cancer incidence. "These national incidence rates do not support a substantial population-wide adverse effect of the magnitude suggested in the study," write the editorialists, Bettina F. Drake, PhD, MPH, and Graham Colditz, MD, DrPH, both from the Washington University School of Medicine in St Louis, Missouri.
"The population data from the United States do not suggest that there is a problem," Dr. Drake said in an interview with Medscape Oncology. She pointed out that folate supplementation used in the study resulted in much higher blood levels than would be seen after eating foods fortified with folic acid. In addition, the study was conducted in individuals with heart disease and was of limited duration.
The findings from this study "do not nullify the potential long-term benefits that folic acid fortification may have on population health," Dr. Drake explained. The measure was introduced to reduce neural tube defects in newborns (which arise from folate deficiency during pregnancy). A reduction was seen within a "few years," the editorialists note.
Concerns about a link between cancer and folic acid supplementation have been raised previously, most recently with regard to colorectal cancer, as reported by Medscape Oncology. At that time, leading expert on nutrition and cancer Walter Willet MD, DrPH, from the Harvard School of Public Health in Boston, Massachusetts, said: "I am certain that we are not causing an epidemic of colorectal cancer with folic acid fortification of flour." He added that there was a small increase in the incidence of this cancer soon after fortification was introduced, but this coincided with an increase in colonoscopy, and he pointed out that mortality rates from this cancer have been declining steadily.
Latest Results from Norway
The latest results come from 2 trials conducted in 6837 patients with ischemic heart disease, in which half the participants took supplements of vitamin B (including folic acid) to lower homocysteine levels to see if this would reduce cardiovascular outcomes. It did not, and these results are in line with other large trials.
At the same time, both trials showed — independently — an increase in cancer in the supplementation group, compared with the placebo group, but this was not statistically significant.
In these 2 trials, participants took supplements containing folic acid (0.8 mg/d), vitamin B12 (0.4 mg/d), and B6 (40 mg/d), or various combinations of these. This dose of folic acid is 4 to 6 times higher than the average dose delivered by the mandatory fortification in the United States, and is twice the recommended daily allowance, the authors note, although they add that it is below the tolerable upper intake level of 1 mg/d set by the US Institute of Medicine.
The current analysis pooled results from the 2 trials, which had a median participation of 39 months, and added data from an observational posttrial follow-up of 38 months, giving a total duration of around 5.5 years. The authors note that pooling the data from the 2 trials is "justified" because they were nearly identical.
This pooled analysis found a statistically significant increase in cancer incidence, cancer mortality, and all-cause mortality.
These results for cancer outcomes are not supported by other studies of homocysteine-lowering vitamin B trials, the authors note.
Cancer Decreasing Significantly
In their editorial, Drs. Drake and Colditz write that these results indicate an excess of approximately 3.5 new cases of cancer per 1000 people per year, and 1 excess case of lung cancer per 1000 people per year. The excess deaths correspond to 1.7 cancer deaths per 1000 people per year.
"These numbers, if generalizable to the United States, would be substantial at the overall levels of total cancer incidence and mortality," they write. In addition, an increase in lung cancer incidence would be expected.
"However, the rates of total cancer incidence decreased significantly from 2001 to 2005, and the lung cancer incidence has also declined significantly," they point out.
Although the study suggests there is an association between folic acid supplementation and an increase in cancer, the US population data suggest that there isn't a problem with folic acid fortification of foods and cancer, Dr. Drake told Medscape Oncology. Folic acid fortification has been mandatory in the United States for more than 10 years and, given the results of this study, we would have expected a significant increase in the incidence of cancer by now, she suggested.
One of the issues with clinical trials is that observations are reported with a short time frame after the implementation of an intervention, the editorialists note. This can often lead to "looking for effects that fit the time frame," they add. "By analogy, when keys are missing it is common to look for them under the lamppost where the light is, rather than in the murky location where the keys were more likely to have been dropped."
One of the coauthors on the paper, Klaus Meyer, PhD, is employed at the laboratory of Bevital AS. The other authors and both editorialists have disclosed no relevant financial relationships.
JAMA. 2009;302:2119-2126, 2152-2153.
Friday, October 30, 2009
Oral contraceptives and adverse birth outcomes
It has been suggested that the use of oral contraceptives near to the time of conception may be associated with an increased risk of some congenital anomalies. Now a study using Canadian data has indicated that oral contraceptive use at this time may increase the risk of low birthweight and pre-term birth.
The study included 1,540 pregnant women who had used oral contraceptives within 3 months of their last menstrual period and 6,108 controls unexposed to oral contraceptives. Oral contraceptive use within 30 days before the last menstrual period significantly increased the risk of very low birthweight (<1,500 g) 3.2-fold, of low birthweight (<2,500 g) by 93% and of preterm birth (<37 weeks) by 61%. Oral contraceptive use during the period 31–90 days before the last menstrual period did not increase these risks.
Use of oral contraceptives in the month before the last menstrual period increases the risks of low birthweight and preterm birth.
Chen X-K, et al. Recent oral contraceptive use and adverse birth outcomes. Eur J Obstet Gynecol Reprod Biol 2009;144:40–43.
http://www.mims.com/Page.aspx?menuid=RecentHL&RecentHeaderID=351
The study included 1,540 pregnant women who had used oral contraceptives within 3 months of their last menstrual period and 6,108 controls unexposed to oral contraceptives. Oral contraceptive use within 30 days before the last menstrual period significantly increased the risk of very low birthweight (<1,500 g) 3.2-fold, of low birthweight (<2,500 g) by 93% and of preterm birth (<37 weeks) by 61%. Oral contraceptive use during the period 31–90 days before the last menstrual period did not increase these risks.
Use of oral contraceptives in the month before the last menstrual period increases the risks of low birthweight and preterm birth.
Chen X-K, et al. Recent oral contraceptive use and adverse birth outcomes. Eur J Obstet Gynecol Reprod Biol 2009;144:40–43.
http://www.mims.com/Page.aspx?menuid=RecentHL&RecentHeaderID=351
Wednesday, October 28, 2009
Contrary to Common Belief, Women Feel Same Heart-Attack Symptoms as Men
From Heartwire
Reed Miller
October 27, 2009 (Edmonton, Alberta) — Women are as likely as men to feel chest pain or other typical heart-attack symptoms, a study presented October 26, 2009 here at the Canadian Cardiovascular Congress shows [1].
In the study, presented by critical-care nurse Martha Mackay (University of British Columbia School of Nursing, Vancouver), 305 patients (39.7% women, average age 64) undergoing a nonemergent PCI were asked a series of open-ended questions about their sensations and experience while the angioplasty balloon was creating an ECG-evident ischemia.
Women and men were equally likely to report chest discomfort or other "typical" symptoms of acute coronary syndrome, regardless of ischemic status. However, women were significantly more likely to report nonchest discomfort such as pain in the neck, jaw, and throat. Older patients were more likely to report chest or throat discomfort. Patients who had undergone a PCI before were more likely to report jaw pain, and prior MI and older age increased the likelihood of neck pain.
Countering Common Misperceptions
Even as professional organizations such as the American Heart Association (AHA) have made a major push to make women aware of their risk for cardiovascular disease, the perception that women's heart-attack symptoms are different from men's persists. Recent retrospective research--subject to recall bias and the usual problems associated with reliance on written medical records--has suggested that this perception is misguided, so Mackay and her colleagues chose to conduct this study because the question "hadn't really been settled."
To rectify the methodological issues of the previous research, Mackay's group developed their questions for the study subjects carefully to ensure they weren't influencing them to report a particular symptom. For example, they did not tell the patients they were studying ACS symptoms but instead told them they were researching patients' overall experience during PCI.
The study underlines the importance of public-education campaigns aimed at women such as the AHA's Go Red for Women campaign or the Heart Truth campaign run by the Heart and Stroke Foundation in Canada, Mackay said.
The study also suggests a need for new protocols and tools that will help health providers get a better understanding of patients' symptoms. Patients may not say they are feeling chest pain if another pain is more dominant. So providers must ask questions that elicit a more complete description of the patient's symptoms in order to make an accurate diagnosis, she explained.
Reed Miller
October 27, 2009 (Edmonton, Alberta) — Women are as likely as men to feel chest pain or other typical heart-attack symptoms, a study presented October 26, 2009 here at the Canadian Cardiovascular Congress shows [1].
In the study, presented by critical-care nurse Martha Mackay (University of British Columbia School of Nursing, Vancouver), 305 patients (39.7% women, average age 64) undergoing a nonemergent PCI were asked a series of open-ended questions about their sensations and experience while the angioplasty balloon was creating an ECG-evident ischemia.
Women and men were equally likely to report chest discomfort or other "typical" symptoms of acute coronary syndrome, regardless of ischemic status. However, women were significantly more likely to report nonchest discomfort such as pain in the neck, jaw, and throat. Older patients were more likely to report chest or throat discomfort. Patients who had undergone a PCI before were more likely to report jaw pain, and prior MI and older age increased the likelihood of neck pain.
Countering Common Misperceptions
Even as professional organizations such as the American Heart Association (AHA) have made a major push to make women aware of their risk for cardiovascular disease, the perception that women's heart-attack symptoms are different from men's persists. Recent retrospective research--subject to recall bias and the usual problems associated with reliance on written medical records--has suggested that this perception is misguided, so Mackay and her colleagues chose to conduct this study because the question "hadn't really been settled."
To rectify the methodological issues of the previous research, Mackay's group developed their questions for the study subjects carefully to ensure they weren't influencing them to report a particular symptom. For example, they did not tell the patients they were studying ACS symptoms but instead told them they were researching patients' overall experience during PCI.
The study underlines the importance of public-education campaigns aimed at women such as the AHA's Go Red for Women campaign or the Heart Truth campaign run by the Heart and Stroke Foundation in Canada, Mackay said.
The study also suggests a need for new protocols and tools that will help health providers get a better understanding of patients' symptoms. Patients may not say they are feeling chest pain if another pain is more dominant. So providers must ask questions that elicit a more complete description of the patient's symptoms in order to make an accurate diagnosis, she explained.
Monday, October 26, 2009
Exercise Improves Fatigue in Cancer Patients on Chemotherapy
From Medscape Medical News
News Author: Zosia Chustecka
CME Author: Désirée Lie, MD, MSEd
October 21, 2009 — A supervised exercise program significantly improved fatigue in cancer patients undergoing chemotherapy, according to a study published online October 13 in the British Medical Journal.
The study also found significant improvements in vitality, aerobic capacity, muscular strength, physical and functional activity, and emotional well-being. However, there was no improvement in quality of life.
"The effect size of the improvement in fatigue (0.33) suggests a small to medium clinically important change," say the researchers, headed by Lis Adamsen, PhD, professor of clinical nursing at the Copenhagen University Hospital in Denmark. This is in contrast to some previous studies that found only a small or no effect.
The researchers suggest that the larger effect on fatigue seen in their study was due to several elements of their exercise program, including the high-intensity training.
"Doctors may encourage patients to exercise, but the exercise must be supervised," Dr. Adamsen told Medscape Oncology. In addition, for patients who are undergoing chemotherapy, there must be "specific inclusion criteria and screening procedures" in place to prevent adverse reactions, she added.
For example, 1 participant in this study who had a brain tumor experienced a grade 3 seizure after cardiovascular training. "We must therefore advise patients with brain tumors or brain metastases not to participate in high-intensity exercise interventions," the researchers note.
Nine Hours of Training Each Week
The study involved 269 patients with a variety of different cancers being treated at 2 Copenhagen university hospitals. There was a broad range of diagnoses and disease statuses, the researchers note. There were 27 patients with ovarian cancer, 28 with hematological malignancies, and 15 with testicular cancer; the remainder had cancer affecting the esophagus, brain, cervix, pharynx, pancreas, or stomach.
All of the patients were receiving chemotherapy, either as treatment for advanced disease or as adjuvant therapy, and there was a wide range of regimens in use.
Half of the patients were randomly assigned to the exercise program, which was supervised by trained nurse specialists and physiotherapists. It lasted for 6 weeks and involved 9 hours of training each week. The patients had to follow the program exactly; they could not pick and choose the activities they preferred, the researchers note. "The intervention was offered as a package and must be viewed as an entity [in which] each component has a role in the outcomes," they explain.
On Mondays, Wednesdays, and Fridays, there was a high-intensity physical training session lasting 90 minutes, followed by 30 minutes of relaxation training. The high-intensity session involved resistance training on machines, such as leg and chest presses, and cardiovascular training on a stationary exercise bike. On Tuesdays, there was a body awareness training session (which included stretching and exercises based on yoga and Pilates) lasting 90 minutes, followed by 30 minutes of relaxation training. On Mondays and Fridays, patients had 30 minutes of massage, which could include scar tissue massage and venous pump massage.
Larger Effect on Fatigue Than Seen in Previous Studies
Fatigue was the primary outcome, and was measured on a scale of 0 to 100. In this study, it was the most frequently reported symptom and, at baseline, 65% of study participants reported a fatigue level greater than that of the general population (mean score, 21), and 29% of participants reported severe fatigue (mean score, >60).
After 6 weeks on the exercise program, the patients who participated reported a significant improvement in fatigue, with ratings falling by an average of 6.6 points (P = .02; size effect, 0.33). The researchers note that this size effect could be clinically important. Although the intervention reduced fatigue, the mean score for these patients was 34.6, which is still higher than that for the general population.
This reduction in fatigue is greater than has been seen in previous studies, the researchers note. A meta-analysis of several studies (Cancer Epidemiol Biomarkers Prev. 2005;14:1588-1595) found an effect size of only 0.13, which may be "too small to be clinically meaningful," they write. In addition, 2 recent studies of moderate exercise in women with breast cancer who were receiving adjuvant therapy found no significant improvement in fatigue (BMJ. 2007;334:517-520; J Clin Oncol. 2007;25:4396-4404).
When asked about the differences between the results from the latest study and those from previous studies, Dr. Adamsen suggested that her team found a larger effect on fatigue because the exercise program they used involved high-volume training (9 hours per week) and because it involved a combination of high- and low-intensity elements.
The researchers believe that this is the first study to incorporate a high-intensity design; none of those mentioned in a review of 26 studies of exercise in cancer patients did (J Clin Oncol. 2005:23:899-909).
We found a reduction in fatigue that we consider to be of importance to the patients' daily lives.
"We found a reduction in fatigue that we consider to be of importance to the patients' daily lives, even though no change was seen in the global health status/quality of life," the researchers conclude.
"Being diagnosed with cancer and exposed to chemotherapy disrupts the patient's life, affecting physiological and psychological functioning and contributing to negative effects on global health status/quality of life," they point out. "Improvements in this measure may have been too ambitious a goal in this short-term clinical trial."
The researchers have disclosed no relevant financial relationships.
BMJ. 2009;339:b3410. Abstract
News Author: Zosia Chustecka
CME Author: Désirée Lie, MD, MSEd
October 21, 2009 — A supervised exercise program significantly improved fatigue in cancer patients undergoing chemotherapy, according to a study published online October 13 in the British Medical Journal.
The study also found significant improvements in vitality, aerobic capacity, muscular strength, physical and functional activity, and emotional well-being. However, there was no improvement in quality of life.
"The effect size of the improvement in fatigue (0.33) suggests a small to medium clinically important change," say the researchers, headed by Lis Adamsen, PhD, professor of clinical nursing at the Copenhagen University Hospital in Denmark. This is in contrast to some previous studies that found only a small or no effect.
The researchers suggest that the larger effect on fatigue seen in their study was due to several elements of their exercise program, including the high-intensity training.
"Doctors may encourage patients to exercise, but the exercise must be supervised," Dr. Adamsen told Medscape Oncology. In addition, for patients who are undergoing chemotherapy, there must be "specific inclusion criteria and screening procedures" in place to prevent adverse reactions, she added.
For example, 1 participant in this study who had a brain tumor experienced a grade 3 seizure after cardiovascular training. "We must therefore advise patients with brain tumors or brain metastases not to participate in high-intensity exercise interventions," the researchers note.
Nine Hours of Training Each Week
The study involved 269 patients with a variety of different cancers being treated at 2 Copenhagen university hospitals. There was a broad range of diagnoses and disease statuses, the researchers note. There were 27 patients with ovarian cancer, 28 with hematological malignancies, and 15 with testicular cancer; the remainder had cancer affecting the esophagus, brain, cervix, pharynx, pancreas, or stomach.
All of the patients were receiving chemotherapy, either as treatment for advanced disease or as adjuvant therapy, and there was a wide range of regimens in use.
Half of the patients were randomly assigned to the exercise program, which was supervised by trained nurse specialists and physiotherapists. It lasted for 6 weeks and involved 9 hours of training each week. The patients had to follow the program exactly; they could not pick and choose the activities they preferred, the researchers note. "The intervention was offered as a package and must be viewed as an entity [in which] each component has a role in the outcomes," they explain.
On Mondays, Wednesdays, and Fridays, there was a high-intensity physical training session lasting 90 minutes, followed by 30 minutes of relaxation training. The high-intensity session involved resistance training on machines, such as leg and chest presses, and cardiovascular training on a stationary exercise bike. On Tuesdays, there was a body awareness training session (which included stretching and exercises based on yoga and Pilates) lasting 90 minutes, followed by 30 minutes of relaxation training. On Mondays and Fridays, patients had 30 minutes of massage, which could include scar tissue massage and venous pump massage.
Larger Effect on Fatigue Than Seen in Previous Studies
Fatigue was the primary outcome, and was measured on a scale of 0 to 100. In this study, it was the most frequently reported symptom and, at baseline, 65% of study participants reported a fatigue level greater than that of the general population (mean score, 21), and 29% of participants reported severe fatigue (mean score, >60).
After 6 weeks on the exercise program, the patients who participated reported a significant improvement in fatigue, with ratings falling by an average of 6.6 points (P = .02; size effect, 0.33). The researchers note that this size effect could be clinically important. Although the intervention reduced fatigue, the mean score for these patients was 34.6, which is still higher than that for the general population.
This reduction in fatigue is greater than has been seen in previous studies, the researchers note. A meta-analysis of several studies (Cancer Epidemiol Biomarkers Prev. 2005;14:1588-1595) found an effect size of only 0.13, which may be "too small to be clinically meaningful," they write. In addition, 2 recent studies of moderate exercise in women with breast cancer who were receiving adjuvant therapy found no significant improvement in fatigue (BMJ. 2007;334:517-520; J Clin Oncol. 2007;25:4396-4404).
When asked about the differences between the results from the latest study and those from previous studies, Dr. Adamsen suggested that her team found a larger effect on fatigue because the exercise program they used involved high-volume training (9 hours per week) and because it involved a combination of high- and low-intensity elements.
The researchers believe that this is the first study to incorporate a high-intensity design; none of those mentioned in a review of 26 studies of exercise in cancer patients did (J Clin Oncol. 2005:23:899-909).
We found a reduction in fatigue that we consider to be of importance to the patients' daily lives.
"We found a reduction in fatigue that we consider to be of importance to the patients' daily lives, even though no change was seen in the global health status/quality of life," the researchers conclude.
"Being diagnosed with cancer and exposed to chemotherapy disrupts the patient's life, affecting physiological and psychological functioning and contributing to negative effects on global health status/quality of life," they point out. "Improvements in this measure may have been too ambitious a goal in this short-term clinical trial."
The researchers have disclosed no relevant financial relationships.
BMJ. 2009;339:b3410. Abstract
Thursday, October 22, 2009
Herpes Zoster Attacks Increase Stroke Risk By 30%
From Medscape Medical News CME
News Author: Susan Jeffrey
CME Author: Désirée Lie, MD, MSEd
October 20, 2009 — A new epidemiological study suggests that the risk for stroke, both ischemic and hemorrhagic, is increased by 30% after a herpes zoster attack. The risk is even higher, about 4-fold, if the attack involves the eye (herpes zoster ophthalmicus).
Herpes zoster infection, also known as shingles, has been shown in other studies to be associated with an increased risk for stroke, the researchers, with lead author Jiunn-Horng Kang, MD, from the Department of Physical Medicine and Rehabilitation and chair of the Sleep Physiological Lab at Taipei Medical University Hospital in Taiwan, point out. Their study is the first attempt to their knowledge to look at the exact risk and frequency of stroke after herpes zoster attacks.
There is still no established therapy to prevent herpes zoster vasculopathy and associated stroke, Dr. Kang told Medscape Neurology. Early antiviral medication could have an important role, he noted, but this role still needs to be studied.
"From the practical view, physicians should be aware of the potential elevated risk of stroke when they care [for] patients with acute herpes zoster attack," he said. "Furthermore, [careful] monitoring and management of the preexisting risk factors for stroke such as hypertension, hyperlipidemia, and diabetic mellitus could be helpful to reduce the risk for stroke."
The report was published online October 8 and will appear in the November issue of Stroke.
Large- and Small-Vessel VZV Vasculopathy
Primary varicella zoster virus (VZV) infection usually affects children and causes varicella or chicken pox, the researchers note. Although some children can have serious complications, varicella is usually benign and transient. The VZV then becomes inactive, sequestered in the sensory and autonomic ganglia. By mechanisms that are not entirely clear, the researchers note, spontaneous reactivation of VZV causes lesions with painful vesicles known as herpes zoster or shingles.
There have been numerous reports linking VZV vasculopathy and stroke syndrome after zoster attacks since the 1970s, the authors write, and VZV is the only recognized human virus able to replicate in cerebral arteries. "It is hypothesized to spread along the nerve fibers to the blood vessels, where it induces further inflammatory and thrombotic responses," Dr. Kang and colleagues note.
VZV vasculopathy can affect both the large and small vessels. In large-vessel VZV vasculopathy, vessels are damaged by inflammation induced by the virus, which can result in stroke. Small-vessel VZV vasculopathy, in contrast, can manifest as nonspecific symptoms including fever, headache, seizures, weakness, consciousness disturbances, and cognitive impairments, known as small-vessel encephalitis.
"To our knowledge, despite many case reports of conditions associated with VZV vasculopathy, large sample data regarding the exact frequency and risk of stroke occurring postherpes zoster attack are still lacking," the authors write.
In this study, the researchers used a data set released by the Taiwan National Health Research Institute in 2006, a representative sample of enrollees in Taiwan's National Health Insurance program. For this analysis, they identified a total of 7760 patients who received treatment for herpes zoster between 1997 and 2001 and matched them with 23,280 randomly selected subjects. The researchers then calculated the 1-year stroke-free survival for patients who received treatment for herpes zoster and for control subjects.
During the 1-year follow up, a total of 439 strokes occurred, 133 among those treated for herpes zoster (1.71%) and 306 from the control group (1.31%). The log rank test showed that those treated for herpes zoster had a significantly lower stroke-free survival rate (P < .001).
The risk for stroke after herpes zoster was increased by 31% compared with that for control patients and increased more than 4-fold for herpes zoster ophthalmicus.
http://cme.medscape.com/viewarticle/710960?sssdmh=dm1.546207&src=nldne&uac=71630FV
NOTES: Protect your child from chickenpox with the vaccine to be given at 15months and 4 1/2 year of age. If the unvaccinated child is known to have contact with a case of chickenpox or zoster, he should be vaccinated within 24 hours for maximal protection.
News Author: Susan Jeffrey
CME Author: Désirée Lie, MD, MSEd
October 20, 2009 — A new epidemiological study suggests that the risk for stroke, both ischemic and hemorrhagic, is increased by 30% after a herpes zoster attack. The risk is even higher, about 4-fold, if the attack involves the eye (herpes zoster ophthalmicus).
Herpes zoster infection, also known as shingles, has been shown in other studies to be associated with an increased risk for stroke, the researchers, with lead author Jiunn-Horng Kang, MD, from the Department of Physical Medicine and Rehabilitation and chair of the Sleep Physiological Lab at Taipei Medical University Hospital in Taiwan, point out. Their study is the first attempt to their knowledge to look at the exact risk and frequency of stroke after herpes zoster attacks.
There is still no established therapy to prevent herpes zoster vasculopathy and associated stroke, Dr. Kang told Medscape Neurology. Early antiviral medication could have an important role, he noted, but this role still needs to be studied.
"From the practical view, physicians should be aware of the potential elevated risk of stroke when they care [for] patients with acute herpes zoster attack," he said. "Furthermore, [careful] monitoring and management of the preexisting risk factors for stroke such as hypertension, hyperlipidemia, and diabetic mellitus could be helpful to reduce the risk for stroke."
The report was published online October 8 and will appear in the November issue of Stroke.
Large- and Small-Vessel VZV Vasculopathy
Primary varicella zoster virus (VZV) infection usually affects children and causes varicella or chicken pox, the researchers note. Although some children can have serious complications, varicella is usually benign and transient. The VZV then becomes inactive, sequestered in the sensory and autonomic ganglia. By mechanisms that are not entirely clear, the researchers note, spontaneous reactivation of VZV causes lesions with painful vesicles known as herpes zoster or shingles.
There have been numerous reports linking VZV vasculopathy and stroke syndrome after zoster attacks since the 1970s, the authors write, and VZV is the only recognized human virus able to replicate in cerebral arteries. "It is hypothesized to spread along the nerve fibers to the blood vessels, where it induces further inflammatory and thrombotic responses," Dr. Kang and colleagues note.
VZV vasculopathy can affect both the large and small vessels. In large-vessel VZV vasculopathy, vessels are damaged by inflammation induced by the virus, which can result in stroke. Small-vessel VZV vasculopathy, in contrast, can manifest as nonspecific symptoms including fever, headache, seizures, weakness, consciousness disturbances, and cognitive impairments, known as small-vessel encephalitis.
"To our knowledge, despite many case reports of conditions associated with VZV vasculopathy, large sample data regarding the exact frequency and risk of stroke occurring postherpes zoster attack are still lacking," the authors write.
In this study, the researchers used a data set released by the Taiwan National Health Research Institute in 2006, a representative sample of enrollees in Taiwan's National Health Insurance program. For this analysis, they identified a total of 7760 patients who received treatment for herpes zoster between 1997 and 2001 and matched them with 23,280 randomly selected subjects. The researchers then calculated the 1-year stroke-free survival for patients who received treatment for herpes zoster and for control subjects.
During the 1-year follow up, a total of 439 strokes occurred, 133 among those treated for herpes zoster (1.71%) and 306 from the control group (1.31%). The log rank test showed that those treated for herpes zoster had a significantly lower stroke-free survival rate (P < .001).
The risk for stroke after herpes zoster was increased by 31% compared with that for control patients and increased more than 4-fold for herpes zoster ophthalmicus.
http://cme.medscape.com/viewarticle/710960?sssdmh=dm1.546207&src=nldne&uac=71630FV
NOTES: Protect your child from chickenpox with the vaccine to be given at 15months and 4 1/2 year of age. If the unvaccinated child is known to have contact with a case of chickenpox or zoster, he should be vaccinated within 24 hours for maximal protection.
Wednesday, October 7, 2009
Oxygen Therapy Relieves Headache Pain in the ED, Cuts Length of Stay, Drug Use
From Reuters Health Information
By Marilyn Larkin
NEW YORK (Reuters Health) Oct 05 - Giving high-flow oxygen therapy for 15 minutes to emergency department patients with headaches provides rapid relief and reduces hospital stays, use of CT scans, and headache pharmacotherapy, according to a pilot study.
Dr. Boris Veysman of the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School reported the results on Monday at the annual meeting of the American College of Emergency Physicians in Boston.
"Very often, when a patient comes to the emergency department with one complaint being headache, they're uncomfortable and symptomatic and they have to wait for a workup before anyone can determine the cause. A diagnosis may not even be made in the emergency department," Dr. Veysman told Reuters Health. "So we approached it from a different perspective and asked, 'What if therapy were the first thing you did (for a headache) before attempting to find a cause?' And so we tried giving oxygen therapy, because it's so widespread and safe."
In the placebo-controlled study, 17 patients were randomized to 100% oxygen at 15 L/min for 15 minutes; 14 received high flow air for 15 minutes; and 17 received no intervention prior to standard treatment. Headache intensity was assessed using a 10-point visual analog scale.
Median times to relief were significantly shorter for patients treated with oxygen (40 minutes) compared with those treated with high flow air (110 minutes) or nothing (120 minutes). Median length of stay was also significantly shorter for patients treated with oxygen (57.5 minutes) than for those treated with air (210 minutes) or nothing (180 minutes).
In addition, CT scans were ordered less frequently: for four of 17 patients (24%) who received oxygen; 11 of 14 (79%) who received air; and eight of 17 (47%) who got nothing.
Medication was given to 29% of those who received oxygen, 86% of those who received air, and 82% of those who received no treatment.
Headache intensity was significantly reduced at both 15 minutes and 30 minutes after initiation of treatment, with patients treated with oxygen realizing the greatest reductions.
"It was a small study, and our results are preliminary," Dr. Veysman stressed. "But the medical community is starting to recognize that it's important to treat discomfort even when you don't know what's causing it, as long as you feel confident the treatment won't make the patient worse. In this case, we found more relief with oxygen than with placebo, although the fact that the headache goes away doesn't necessarily mean the patient can go home."
By Marilyn Larkin
NEW YORK (Reuters Health) Oct 05 - Giving high-flow oxygen therapy for 15 minutes to emergency department patients with headaches provides rapid relief and reduces hospital stays, use of CT scans, and headache pharmacotherapy, according to a pilot study.
Dr. Boris Veysman of the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School reported the results on Monday at the annual meeting of the American College of Emergency Physicians in Boston.
"Very often, when a patient comes to the emergency department with one complaint being headache, they're uncomfortable and symptomatic and they have to wait for a workup before anyone can determine the cause. A diagnosis may not even be made in the emergency department," Dr. Veysman told Reuters Health. "So we approached it from a different perspective and asked, 'What if therapy were the first thing you did (for a headache) before attempting to find a cause?' And so we tried giving oxygen therapy, because it's so widespread and safe."
In the placebo-controlled study, 17 patients were randomized to 100% oxygen at 15 L/min for 15 minutes; 14 received high flow air for 15 minutes; and 17 received no intervention prior to standard treatment. Headache intensity was assessed using a 10-point visual analog scale.
Median times to relief were significantly shorter for patients treated with oxygen (40 minutes) compared with those treated with high flow air (110 minutes) or nothing (120 minutes). Median length of stay was also significantly shorter for patients treated with oxygen (57.5 minutes) than for those treated with air (210 minutes) or nothing (180 minutes).
In addition, CT scans were ordered less frequently: for four of 17 patients (24%) who received oxygen; 11 of 14 (79%) who received air; and eight of 17 (47%) who got nothing.
Medication was given to 29% of those who received oxygen, 86% of those who received air, and 82% of those who received no treatment.
Headache intensity was significantly reduced at both 15 minutes and 30 minutes after initiation of treatment, with patients treated with oxygen realizing the greatest reductions.
"It was a small study, and our results are preliminary," Dr. Veysman stressed. "But the medical community is starting to recognize that it's important to treat discomfort even when you don't know what's causing it, as long as you feel confident the treatment won't make the patient worse. In this case, we found more relief with oxygen than with placebo, although the fact that the headache goes away doesn't necessarily mean the patient can go home."
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