Mary Ann Moon

Elderly patients who took potassium-sparing diuretics had a 70% lower rate of developing Alzheimer's disease than those who did not take antihypertensive drugs in a population-based study of dementing illnesses, reported Ara S. Khachaturian, Ph.D., and his colleagues.

Antihypertensive agents in general reduced the risk for Alzheimer's disease (AD), but the potassium-sparing diuretics were particularly beneficial, said Dr. Khachaturian of Potomac, Md., and his colleagues.

To assess whether protection against AD might be specific to individual classes of antihypertensive drugs, the investigators analyzed data from the Cache County study, an ongoing investigation of dementias in the elderly population of Cache County, Utah (Arch. Neurol. 2006 March 13 [Epub doi:10.1001/archneur.63.5.noc60013).

They studied medication usage in 3,227 patients who were aged 65 years or older when they enrolled in the study in 1995, including 104 who developed AD during follow-up. Of the 3,217 patients who provided drug information, nearly half of the patients (45.3%) took antihypertensive drugs, including ACE inhibitors (13.0%); β-blockers (11.5%); calcium channel blockers (14.9%); diuretics (26.5%); or some combination of these (18.2%).

The risk of developing AD was significantly smaller in those who took antihypertensive medications than in those who did not (adjusted hazard ratio [aHR] 0.64). When the results were broken down by drug class, diuretics showed the greatest protective effect against AD (aHR 0.61), whereas β-blockers showed a statistical trend toward a significant protective effect (aHR, 0.53); ACE inhibitors (aHR, 1.13) and calcium channel blockers (aHR, 0.86) showed no effect. Closer analysis showed the potassium-sparing diuretics accounted for all the risk reduction attributed to their drug class (aHR, 0.26); thiazide diuretics and loop diuretics were not protective (aHR, 0.72 and 1.45, respectively). Analysis also showed that the dihydropyridine subclass of calcium channel blockers cut the risk of AD (aHR, 0.53), but other subclasses did not, said the researchers.

The finding that antihypertensive agents that protect against AD seem to do so independently of controlling blood pressure was of particular interest. It's not known why the diuretics cut the AD risk. Other diuretics reduce potassium concentrations, and low potassium levels have been tied to oxidative stress, inflammation, platelet aggregation, and vasoconstriction, possible contributors to AD pathogenesis, they said.

Elderly patients who took potassium-sparing diuretics had a 70% lower rate of developing Alzheimer's disease than those who did not take antihypertensive drugs in a population-based study of dementing illnesses, reported Ara S. Khachaturian, Ph.D., and his colleagues.

Antihypertensive agents in general reduced the risk for Alzheimer's disease (AD), but the potassium-sparing diuretics were particularly beneficial, said Dr. Khachaturian of Potomac, Md., and his colleagues.

To assess whether protection against AD might be specific to individual classes of antihypertensive drugs, the investigators analyzed data from the Cache County study, an ongoing investigation of dementias in the elderly population of Cache County, Utah (Arch. Neurol. 2006 March 13 [Epub doi:10.1001/archneur.63.5.noc60013).

They studied medication usage in 3,227 patients who were aged 65 years or older when they enrolled in the study in 1995, including 104 who developed AD during follow-up. Of the 3,217 patients who provided drug information, nearly half of the patients (45.3%) took antihypertensive drugs, including ACE inhibitors (13.0%); β-blockers (11.5%); calcium channel blockers (14.9%); diuretics (26.5%); or some combination of these (18.2%).

The risk of developing AD was significantly smaller in those who took antihypertensive medications than in those who did not (adjusted hazard ratio [aHR] 0.64). When the results were broken down by drug class, diuretics showed the greatest protective effect against AD (aHR 0.61), whereas β-blockers showed a statistical trend toward a significant protective effect (aHR, 0.53); ACE inhibitors (aHR, 1.13) and calcium channel blockers (aHR, 0.86) showed no effect. Closer analysis showed the potassium-sparing diuretics accounted for all the risk reduction attributed to their drug class (aHR, 0.26); thiazide diuretics and loop diuretics were not protective (aHR, 0.72 and 1.45, respectively). Analysis also showed that the dihydropyridine subclass of calcium channel blockers cut the risk of AD (aHR, 0.53), but other subclasses did not, said the researchers.

The finding that antihypertensive agents that protect against AD seem to do so independently of controlling blood pressure was of particular interest. It's not known why the diuretics cut the AD risk. Other diuretics reduce potassium concentrations, and low potassium levels have been tied to oxidative stress, inflammation, platelet aggregation, and vasoconstriction, possible contributors to AD pathogenesis, they said.

Elderly patients who took potassium-sparing diuretics had a 70% lower rate of developing Alzheimer's disease than those who did not take antihypertensive drugs in a population-based study of dementing illnesses, reported Ara S. Khachaturian, Ph.D., and his colleagues.

Antihypertensive agents in general reduced the risk for Alzheimer's disease (AD), but the potassium-sparing diuretics were particularly beneficial, said Dr. Khachaturian of Potomac, Md., and his colleagues.

To assess whether protection against AD might be specific to individual classes of antihypertensive drugs, the investigators analyzed data from the Cache County study, an ongoing investigation of dementias in the elderly population of Cache County, Utah (Arch. Neurol. 2006 March 13 [Epub doi:10.1001/archneur.63.5.noc60013).

They studied medication usage in 3,227 patients who were aged 65 years or older when they enrolled in the study in 1995, including 104 who developed AD during follow-up. Of the 3,217 patients who provided drug information, nearly half of the patients (45.3%) took antihypertensive drugs, including ACE inhibitors (13.0%); β-blockers (11.5%); calcium channel blockers (14.9%); diuretics (26.5%); or some combination of these (18.2%).

The risk of developing AD was significantly smaller in those who took antihypertensive medications than in those who did not (adjusted hazard ratio [aHR] 0.64). When the results were broken down by drug class, diuretics showed the greatest protective effect against AD (aHR 0.61), whereas β-blockers showed a statistical trend toward a significant protective effect (aHR, 0.53); ACE inhibitors (aHR, 1.13) and calcium channel blockers (aHR, 0.86) showed no effect. Closer analysis showed the potassium-sparing diuretics accounted for all the risk reduction attributed to their drug class (aHR, 0.26); thiazide diuretics and loop diuretics were not protective (aHR, 0.72 and 1.45, respectively). Analysis also showed that the dihydropyridine subclass of calcium channel blockers cut the risk of AD (aHR, 0.53), but other subclasses did not, said the researchers.

The finding that antihypertensive agents that protect against AD seem to do so independently of controlling blood pressure was of particular interest. It's not known why the diuretics cut the AD risk. Other diuretics reduce potassium concentrations, and low potassium levels have been tied to oxidative stress, inflammation, platelet aggregation, and vasoconstriction, possible contributors to AD pathogenesis, they said.

Antidepressants modestly heighten the risk of suicide in pediatric patients, according to Dr. Tarek A. Hammad and his associates at the Food and Drug Administration's Center for Drug Evaluation and Research in Rockville, Md.

Noting the longstanding concern that these drugs may induce rather than avert suicidality in children and adolescents, the FDA did a metaanalysis of 23 placebo-controlled clinical trials run by the drug manufacturers and 1 placebo-controlled multicenter trial performed by the National Institute of Mental Health. Among the 4,582 subjects, there were 109 suicide-related events in the manufacturers' trials and 11 in the NIMH trial.

Data on fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, bupropion, extended-release venlafaxine, nefazodone, and mirtazapine were pooled and assessed. Most of the studies were done in the late 1990s and ran from 4 to 16 weeks. Thus, this analysis focused on short-term risks and did not address possible suicidality beyond 16 weeks of treatment (Arch. Gen. Psychiatry 2006;63:332–9).

The antidepressants were used to treat major depressive disorder in only 16 of the trials. Other indications included obsessive-compulsive disorder (four trials), generalized anxiety disorder (two trials), social anxiety disorder (one trial), and ADHD (one trial).

The overall relative risk of suicidal ideation or behavior was 1.95, and it was consistent across the studies. The investigators characterized this rise in risk as statistically robust but modest. Its implications for clinical practice remain unclear, Dr. Hammad and his associates noted.

“It is important to be clear that the FDA has not contraindicated any of the antidepressant drugs for pediatric use. Instead, the new labeling warns of the risk of suicidality and encourages prescribers to balance this risk with clinical need. The FDA recognizes that depression and other psychiatric disorders in pediatric patients can have significant consequences if not appropriately treated,” the investigators said.

Although there were no completed suicides among the subjects, that finding “does not provide much reassurance regarding a small increase in the risk of suicide because this sample is not large enough to detect such an effect,” they said.

It is possible that treatment increased the reporting of suicidality rather than suicidality itself, since the drugs often are given in the hope of increasing pediatric patients' verbalization and communication with others. It is also possible that patients assigned to active drug therapy experienced other adverse events that were not induced by the placebo and which drew clinical attention to them and resulted in better assessment for suicidality, the FDA investigators noted.

Some evidence from other sources seems to belie their findings, they added. The rate of adolescent suicide has declined in recent years, and some data suggest that this decrease correlates with an increasing number of prescriptions for antidepressants. Moreover, autopsy studies have failed to find evidence of antidepressant use in most adolescent suicide victims, even those who had been prescribed the drugs.

In an editorial comment accompanying this report, Dr. Ross J. Baldessarini and his associates at McLean Hospital in Belmont, Mass., noted that, when adverse effects do occur in pediatric patients treated with antidepressants, “they are often detectable with close clinical follow-up and psychological support, especially early in treatment, as recommended in recent Food and Drug Administration clinical advisories.

“Moreover, they may be reversed with appropriately modified treatment, including removal of antidepressant drugs and adding agents likely to reduce agitation and aggression (antipsychotic, antimanic, anxiolytic drugs), as well as close follow-up” (Arch. Gen. Psychiatry 2006;63:246–8).

Adverse effects 'are often detectable with close clinical follow-up and' support. DR. BALDESSARINI

Antidepressants modestly heighten the risk of suicide in pediatric patients, according to Dr. Tarek A. Hammad and his associates at the Food and Drug Administration's Center for Drug Evaluation and Research in Rockville, Md.

Noting the longstanding concern that these drugs may induce rather than avert suicidality in children and adolescents, the FDA did a metaanalysis of 23 placebo-controlled clinical trials run by the drug manufacturers and 1 placebo-controlled multicenter trial performed by the National Institute of Mental Health. Among the 4,582 subjects, there were 109 suicide-related events in the manufacturers' trials and 11 in the NIMH trial.

Data on fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, bupropion, extended-release venlafaxine, nefazodone, and mirtazapine were pooled and assessed. Most of the studies were done in the late 1990s and ran from 4 to 16 weeks. Thus, this analysis focused on short-term risks and did not address possible suicidality beyond 16 weeks of treatment (Arch. Gen. Psychiatry 2006;63:332–9).

The antidepressants were used to treat major depressive disorder in only 16 of the trials. Other indications included obsessive-compulsive disorder (four trials), generalized anxiety disorder (two trials), social anxiety disorder (one trial), and ADHD (one trial).

The overall relative risk of suicidal ideation or behavior was 1.95, and it was consistent across the studies. The investigators characterized this rise in risk as statistically robust but modest. Its implications for clinical practice remain unclear, Dr. Hammad and his associates noted.

“It is important to be clear that the FDA has not contraindicated any of the antidepressant drugs for pediatric use. Instead, the new labeling warns of the risk of suicidality and encourages prescribers to balance this risk with clinical need. The FDA recognizes that depression and other psychiatric disorders in pediatric patients can have significant consequences if not appropriately treated,” the investigators said.

Although there were no completed suicides among the subjects, that finding “does not provide much reassurance regarding a small increase in the risk of suicide because this sample is not large enough to detect such an effect,” they said.

It is possible that treatment increased the reporting of suicidality rather than suicidality itself, since the drugs often are given in the hope of increasing pediatric patients' verbalization and communication with others. It is also possible that patients assigned to active drug therapy experienced other adverse events that were not induced by the placebo and which drew clinical attention to them and resulted in better assessment for suicidality, the FDA investigators noted.

Some evidence from other sources seems to belie their findings, they added. The rate of adolescent suicide has declined in recent years, and some data suggest that this decrease correlates with an increasing number of prescriptions for antidepressants. Moreover, autopsy studies have failed to find evidence of antidepressant use in most adolescent suicide victims, even those who had been prescribed the drugs.

In an editorial comment accompanying this report, Dr. Ross J. Baldessarini and his associates at McLean Hospital in Belmont, Mass., noted that, when adverse effects do occur in pediatric patients treated with antidepressants, “they are often detectable with close clinical follow-up and psychological support, especially early in treatment, as recommended in recent Food and Drug Administration clinical advisories.

“Moreover, they may be reversed with appropriately modified treatment, including removal of antidepressant drugs and adding agents likely to reduce agitation and aggression (antipsychotic, antimanic, anxiolytic drugs), as well as close follow-up” (Arch. Gen. Psychiatry 2006;63:246–8).

Adverse effects 'are often detectable with close clinical follow-up and' support. DR. BALDESSARINI

Antidepressants modestly heighten the risk of suicide in pediatric patients, according to Dr. Tarek A. Hammad and his associates at the Food and Drug Administration's Center for Drug Evaluation and Research in Rockville, Md.

Noting the longstanding concern that these drugs may induce rather than avert suicidality in children and adolescents, the FDA did a metaanalysis of 23 placebo-controlled clinical trials run by the drug manufacturers and 1 placebo-controlled multicenter trial performed by the National Institute of Mental Health. Among the 4,582 subjects, there were 109 suicide-related events in the manufacturers' trials and 11 in the NIMH trial.

Data on fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, bupropion, extended-release venlafaxine, nefazodone, and mirtazapine were pooled and assessed. Most of the studies were done in the late 1990s and ran from 4 to 16 weeks. Thus, this analysis focused on short-term risks and did not address possible suicidality beyond 16 weeks of treatment (Arch. Gen. Psychiatry 2006;63:332–9).

The antidepressants were used to treat major depressive disorder in only 16 of the trials. Other indications included obsessive-compulsive disorder (four trials), generalized anxiety disorder (two trials), social anxiety disorder (one trial), and ADHD (one trial).

The overall relative risk of suicidal ideation or behavior was 1.95, and it was consistent across the studies. The investigators characterized this rise in risk as statistically robust but modest. Its implications for clinical practice remain unclear, Dr. Hammad and his associates noted.

“It is important to be clear that the FDA has not contraindicated any of the antidepressant drugs for pediatric use. Instead, the new labeling warns of the risk of suicidality and encourages prescribers to balance this risk with clinical need. The FDA recognizes that depression and other psychiatric disorders in pediatric patients can have significant consequences if not appropriately treated,” the investigators said.

Although there were no completed suicides among the subjects, that finding “does not provide much reassurance regarding a small increase in the risk of suicide because this sample is not large enough to detect such an effect,” they said.

It is possible that treatment increased the reporting of suicidality rather than suicidality itself, since the drugs often are given in the hope of increasing pediatric patients' verbalization and communication with others. It is also possible that patients assigned to active drug therapy experienced other adverse events that were not induced by the placebo and which drew clinical attention to them and resulted in better assessment for suicidality, the FDA investigators noted.

Some evidence from other sources seems to belie their findings, they added. The rate of adolescent suicide has declined in recent years, and some data suggest that this decrease correlates with an increasing number of prescriptions for antidepressants. Moreover, autopsy studies have failed to find evidence of antidepressant use in most adolescent suicide victims, even those who had been prescribed the drugs.

In an editorial comment accompanying this report, Dr. Ross J. Baldessarini and his associates at McLean Hospital in Belmont, Mass., noted that, when adverse effects do occur in pediatric patients treated with antidepressants, “they are often detectable with close clinical follow-up and psychological support, especially early in treatment, as recommended in recent Food and Drug Administration clinical advisories.

“Moreover, they may be reversed with appropriately modified treatment, including removal of antidepressant drugs and adding agents likely to reduce agitation and aggression (antipsychotic, antimanic, anxiolytic drugs), as well as close follow-up” (Arch. Gen. Psychiatry 2006;63:246–8).

Adverse effects 'are often detectable with close clinical follow-up and' support. DR. BALDESSARINI

Tracking FSH levels each year from premenopause on can help predict bone loss during menopause, reported MaryFran R. Sowers, Ph.D., of the University of Michigan, Ann Arbor, and her associates.

They conducted what they called the first study to longitudinally characterize bone mineral density (BMD) loss at the spine and hip in conjunction with changes in reproductive hormone concentrations. The interaction between baseline FSH level before menopause and serial FSH levels measured every year thereafter predicted bone loss. However, this interaction “is complex, requires at least two FSH values, and may be challenging to apply in a busy clinical setting,” they cautioned.

The study comprised 2,311 women aged 42–52 at baseline who were assessed at several medical centers across the United States for 5 years. Half the women were white, 28% were African American, and 22% were Asian American.

The women underwent annual spine, femoral neck, and total hip BMD assessments with densitometers. Blood samples obtained annually in the early follicular phase of the menstrual cycle were analyzed for estradiol, FSH, testosterone, sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS) content.

At baseline, 53% were classified as premenopausal due to no reported drop in menstrual regularity in the preceding year; 47% were grouped in the “early perimenopausal” period, having reported less menstrual regularity in the last 3 months (J. Clin. Endocrin. Metab. doi:10.1210/jc.2005–1836; Jan. 10, 2006).

The interaction between baseline FSH levels and subsequent levels predicted bone loss. Estradiol levels measured throughout this transitional period “were poor predictors of incremental BMD change.”

Tracking FSH levels each year from premenopause on can help predict bone loss during menopause, reported MaryFran R. Sowers, Ph.D., of the University of Michigan, Ann Arbor, and her associates.

They conducted what they called the first study to longitudinally characterize bone mineral density (BMD) loss at the spine and hip in conjunction with changes in reproductive hormone concentrations. The interaction between baseline FSH level before menopause and serial FSH levels measured every year thereafter predicted bone loss. However, this interaction “is complex, requires at least two FSH values, and may be challenging to apply in a busy clinical setting,” they cautioned.

The study comprised 2,311 women aged 42–52 at baseline who were assessed at several medical centers across the United States for 5 years. Half the women were white, 28% were African American, and 22% were Asian American.

The women underwent annual spine, femoral neck, and total hip BMD assessments with densitometers. Blood samples obtained annually in the early follicular phase of the menstrual cycle were analyzed for estradiol, FSH, testosterone, sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS) content.

At baseline, 53% were classified as premenopausal due to no reported drop in menstrual regularity in the preceding year; 47% were grouped in the “early perimenopausal” period, having reported less menstrual regularity in the last 3 months (J. Clin. Endocrin. Metab. doi:10.1210/jc.2005–1836; Jan. 10, 2006).

The interaction between baseline FSH levels and subsequent levels predicted bone loss. Estradiol levels measured throughout this transitional period “were poor predictors of incremental BMD change.”

Tracking FSH levels each year from premenopause on can help predict bone loss during menopause, reported MaryFran R. Sowers, Ph.D., of the University of Michigan, Ann Arbor, and her associates.

They conducted what they called the first study to longitudinally characterize bone mineral density (BMD) loss at the spine and hip in conjunction with changes in reproductive hormone concentrations. The interaction between baseline FSH level before menopause and serial FSH levels measured every year thereafter predicted bone loss. However, this interaction “is complex, requires at least two FSH values, and may be challenging to apply in a busy clinical setting,” they cautioned.

The study comprised 2,311 women aged 42–52 at baseline who were assessed at several medical centers across the United States for 5 years. Half the women were white, 28% were African American, and 22% were Asian American.

The women underwent annual spine, femoral neck, and total hip BMD assessments with densitometers. Blood samples obtained annually in the early follicular phase of the menstrual cycle were analyzed for estradiol, FSH, testosterone, sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS) content.

At baseline, 53% were classified as premenopausal due to no reported drop in menstrual regularity in the preceding year; 47% were grouped in the “early perimenopausal” period, having reported less menstrual regularity in the last 3 months (J. Clin. Endocrin. Metab. doi:10.1210/jc.2005–1836; Jan. 10, 2006).

The interaction between baseline FSH levels and subsequent levels predicted bone loss. Estradiol levels measured throughout this transitional period “were poor predictors of incremental BMD change.”

The relationship between physicians and the makers of pharmaceuticals and medical devices now is so fraught with conflicts of interest that broad reforms regulating their interactions are essential, according to a group of medical ethics experts.

Industry-sponsored events, the dispensing of free samples and other “gifts” by detail people and drug reps, and lucrative “consultation” agreements are unmistakable ploys by drug and device makers to promote the use of their products. These practices have intensified in recent years to the point that they pose a “serious threat” to both physician integrity and patient welfare, Dr. Troyen A. Brennan of Harvard Medical School, Boston, and his 10 coauthors noted.

Existing guidelines of such groups as the American Medical Association, the American College of Physicians, and the Accreditation Council for Continuing Medical Education “are not sufficiently stringent” and allow both professionalism and patient care to be undermined. “The profession itself must exert much tighter control over the relationships between manufacturers and physicians,” Dr. Brennan and his associates said (JAMA 2006;295:429–33).

The group, whose work was sponsored by the American Board of Internal Medicine Foundation and the Institute on Medicine as a Profession, called for academic medical centers to take the lead in:

▸ Prohibiting all gifts to physicians including free samples, meals, payment for travel, and payment for time spent at meetings.

▸ Strictly regulating industry support of continuing medical education and prohibiting direct funding of CME meetings.

▸ Strictly regulating industry support of research.

▸ Strictly regulating hospital purchases of drugs and medical devices.

▸ Prohibiting faculty from serving on manufacturers' speakers bureaus and from publishing material ghostwritten by industry employees.

Of these proposed reforms, the prohibition of gifts such as drug and device samples may have the greatest effect on physicians in private practice, if it is enacted.

Most physicians believe that detailers' gifts don't influence their prescribing behavior. But pharmaceutical companies would hardly spend some 90% of their $21 billion marketing budget on these and other practices if the strategies weren't successful in promoting their products, Dr. Brennan and his associates said.

“An overwhelming majority of interactions [with drug and device makers] had negative results on clinical care” in a recent review of the literature, the authors wrote. Prohibiting detailers' visits to physicians' offices will deprive manufacturers of “foot in the door” access that unduly influences physicians' choices of treatment, they added. But regardless of whether sampling should be eliminated, what goes on in a private practice is beyond the control of academic medical centers and the AMA, commented Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco, and chief of the cardiology section at the Veterans Affairs Medical Center in Fresno. And the practice simply doesn't exist in many academic institutions, such as UCSF, which neither accepts samples nor allows pharmaceutical representatives in the offices, he added.

Regarding pay for physicians' travel expenses to medical meetings, the editorial writers are ignoring the fact that trainees don't get financial support from their institutions as they once did, and that those institutions don't have the money to send them, Dr. Deedwania said.

Also unrealistic is the notion that CME can survive without industry support, said Dr. John Flack, professor and interim chair of the department of medicine and chief of the division of clinical epidemiology and translational research at Wayne State University, Detroit.

“Without industry support, CME will become a thing of the past, because few entities can afford to pay for it,” Dr. Flack said.

Nonetheless, many in the academic community have had a more positive response to the proposals, said Dr. Jordan J. Cohen, one of the JAMA report's coauthors and president of the Association of American Medical Colleges, Washington. The reforms will, of course, meet with resistance because they “represent a big change in practices that have been very widely accepted over a significant time, and frankly there's a significant amount of money in play here. I won't suggest that it would be at all easy to implement these changes, but it is looking possible,” he said.

The proposals “will at least inspire a good deal more conversation about, and examination of, current policies and their unintended consequences, which are not in the best interests of the public. It will allow the medical community to find other ways of supporting activities that are now dependent on the health care industry,” he said.

Dr. David L. Coleman, interim chair of internal medicine at Yale University, New Haven, Conn., applauded Dr. Brennan's group for “stepping forward with a very bold set of recommendations.” Yale has already implemented strict guidelines prohibiting any gifts from industry representatives, any meals funded by industry, and any payment for attending CME meetings. The Yale guidelines are detailed in a report published in February (Acad. Med. 2006;81:154–60).

“I think banning food and gifts makes things a lot easier, frankly,” he said. “It's so nice to walk into a conference and not have to have that awkward conversation with a drug rep, and not have to feel squeamish about possible conflicts of interest.”

He acknowledged that the proposed reform central to most physicians in private practice—banning free samples and other gifts from detail people—is not likely to be adopted any time soon. At Yale, “we considered banning free samples for patients, because it clearly encourages the use of more expensive medications. Even worse, it is a poorly regulated process, so these drugs can end up in the hands of patients who are not followed adequately. But it was finally decided that free samples could not be prohibited until some other system for delivering free samples to needy patients is in place.”

Yale did ban the use of free samples by physicians and their families, a measure that has had an unexpectedly large effect. “There has been some grumbling,” but the response to the strict guidelines from Yale physicians as well as outsiders has been overwhelmingly positive, Dr. Coleman said.

Another dissenting note was sounded by Ken Johnson, senior vice president of Pharmaceutical Research and Manufacturers of America, Washington, who noted that sales representatives are technically well trained and provide crucial information to doctors about the way drugs work and their side effects. Most detailers already follow PhRMA's voluntary guidelines and focus on ensuring that medicines are used correctly, he said.

Most physicians interviewed agreed heartily with one proposed reform: ghostwriting. This should be controlled or eliminated, because some companies do influence the wording in research manuscripts, and busy investigators may go along with it, Dr. Deedwania said.

The relationship between physicians and the makers of pharmaceuticals and medical devices now is so fraught with conflicts of interest that broad reforms regulating their interactions are essential, according to a group of medical ethics experts.

Industry-sponsored events, the dispensing of free samples and other “gifts” by detail people and drug reps, and lucrative “consultation” agreements are unmistakable ploys by drug and device makers to promote the use of their products. These practices have intensified in recent years to the point that they pose a “serious threat” to both physician integrity and patient welfare, Dr. Troyen A. Brennan of Harvard Medical School, Boston, and his 10 coauthors noted.

Existing guidelines of such groups as the American Medical Association, the American College of Physicians, and the Accreditation Council for Continuing Medical Education “are not sufficiently stringent” and allow both professionalism and patient care to be undermined. “The profession itself must exert much tighter control over the relationships between manufacturers and physicians,” Dr. Brennan and his associates said (JAMA 2006;295:429–33).

The group, whose work was sponsored by the American Board of Internal Medicine Foundation and the Institute on Medicine as a Profession, called for academic medical centers to take the lead in:

▸ Prohibiting all gifts to physicians including free samples, meals, payment for travel, and payment for time spent at meetings.

▸ Strictly regulating industry support of continuing medical education and prohibiting direct funding of CME meetings.

▸ Strictly regulating industry support of research.

▸ Strictly regulating hospital purchases of drugs and medical devices.

▸ Prohibiting faculty from serving on manufacturers' speakers bureaus and from publishing material ghostwritten by industry employees.

Of these proposed reforms, the prohibition of gifts such as drug and device samples may have the greatest effect on physicians in private practice, if it is enacted.

Most physicians believe that detailers' gifts don't influence their prescribing behavior. But pharmaceutical companies would hardly spend some 90% of their $21 billion marketing budget on these and other practices if the strategies weren't successful in promoting their products, Dr. Brennan and his associates said.

“An overwhelming majority of interactions [with drug and device makers] had negative results on clinical care” in a recent review of the literature, the authors wrote. Prohibiting detailers' visits to physicians' offices will deprive manufacturers of “foot in the door” access that unduly influences physicians' choices of treatment, they added. But regardless of whether sampling should be eliminated, what goes on in a private practice is beyond the control of academic medical centers and the AMA, commented Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco, and chief of the cardiology section at the Veterans Affairs Medical Center in Fresno. And the practice simply doesn't exist in many academic institutions, such as UCSF, which neither accepts samples nor allows pharmaceutical representatives in the offices, he added.

Regarding pay for physicians' travel expenses to medical meetings, the editorial writers are ignoring the fact that trainees don't get financial support from their institutions as they once did, and that those institutions don't have the money to send them, Dr. Deedwania said.

Also unrealistic is the notion that CME can survive without industry support, said Dr. John Flack, professor and interim chair of the department of medicine and chief of the division of clinical epidemiology and translational research at Wayne State University, Detroit.

“Without industry support, CME will become a thing of the past, because few entities can afford to pay for it,” Dr. Flack said.

Nonetheless, many in the academic community have had a more positive response to the proposals, said Dr. Jordan J. Cohen, one of the JAMA report's coauthors and president of the Association of American Medical Colleges, Washington. The reforms will, of course, meet with resistance because they “represent a big change in practices that have been very widely accepted over a significant time, and frankly there's a significant amount of money in play here. I won't suggest that it would be at all easy to implement these changes, but it is looking possible,” he said.

The proposals “will at least inspire a good deal more conversation about, and examination of, current policies and their unintended consequences, which are not in the best interests of the public. It will allow the medical community to find other ways of supporting activities that are now dependent on the health care industry,” he said.

Dr. David L. Coleman, interim chair of internal medicine at Yale University, New Haven, Conn., applauded Dr. Brennan's group for “stepping forward with a very bold set of recommendations.” Yale has already implemented strict guidelines prohibiting any gifts from industry representatives, any meals funded by industry, and any payment for attending CME meetings. The Yale guidelines are detailed in a report published in February (Acad. Med. 2006;81:154–60).

“I think banning food and gifts makes things a lot easier, frankly,” he said. “It's so nice to walk into a conference and not have to have that awkward conversation with a drug rep, and not have to feel squeamish about possible conflicts of interest.”

He acknowledged that the proposed reform central to most physicians in private practice—banning free samples and other gifts from detail people—is not likely to be adopted any time soon. At Yale, “we considered banning free samples for patients, because it clearly encourages the use of more expensive medications. Even worse, it is a poorly regulated process, so these drugs can end up in the hands of patients who are not followed adequately. But it was finally decided that free samples could not be prohibited until some other system for delivering free samples to needy patients is in place.”

Yale did ban the use of free samples by physicians and their families, a measure that has had an unexpectedly large effect. “There has been some grumbling,” but the response to the strict guidelines from Yale physicians as well as outsiders has been overwhelmingly positive, Dr. Coleman said.

Another dissenting note was sounded by Ken Johnson, senior vice president of Pharmaceutical Research and Manufacturers of America, Washington, who noted that sales representatives are technically well trained and provide crucial information to doctors about the way drugs work and their side effects. Most detailers already follow PhRMA's voluntary guidelines and focus on ensuring that medicines are used correctly, he said.

Most physicians interviewed agreed heartily with one proposed reform: ghostwriting. This should be controlled or eliminated, because some companies do influence the wording in research manuscripts, and busy investigators may go along with it, Dr. Deedwania said.

The relationship between physicians and the makers of pharmaceuticals and medical devices now is so fraught with conflicts of interest that broad reforms regulating their interactions are essential, according to a group of medical ethics experts.

Industry-sponsored events, the dispensing of free samples and other “gifts” by detail people and drug reps, and lucrative “consultation” agreements are unmistakable ploys by drug and device makers to promote the use of their products. These practices have intensified in recent years to the point that they pose a “serious threat” to both physician integrity and patient welfare, Dr. Troyen A. Brennan of Harvard Medical School, Boston, and his 10 coauthors noted.

Existing guidelines of such groups as the American Medical Association, the American College of Physicians, and the Accreditation Council for Continuing Medical Education “are not sufficiently stringent” and allow both professionalism and patient care to be undermined. “The profession itself must exert much tighter control over the relationships between manufacturers and physicians,” Dr. Brennan and his associates said (JAMA 2006;295:429–33).

The group, whose work was sponsored by the American Board of Internal Medicine Foundation and the Institute on Medicine as a Profession, called for academic medical centers to take the lead in:

▸ Prohibiting all gifts to physicians including free samples, meals, payment for travel, and payment for time spent at meetings.

▸ Strictly regulating industry support of continuing medical education and prohibiting direct funding of CME meetings.

▸ Strictly regulating industry support of research.

▸ Strictly regulating hospital purchases of drugs and medical devices.

▸ Prohibiting faculty from serving on manufacturers' speakers bureaus and from publishing material ghostwritten by industry employees.

Of these proposed reforms, the prohibition of gifts such as drug and device samples may have the greatest effect on physicians in private practice, if it is enacted.

Most physicians believe that detailers' gifts don't influence their prescribing behavior. But pharmaceutical companies would hardly spend some 90% of their $21 billion marketing budget on these and other practices if the strategies weren't successful in promoting their products, Dr. Brennan and his associates said.

“An overwhelming majority of interactions [with drug and device makers] had negative results on clinical care” in a recent review of the literature, the authors wrote. Prohibiting detailers' visits to physicians' offices will deprive manufacturers of “foot in the door” access that unduly influences physicians' choices of treatment, they added. But regardless of whether sampling should be eliminated, what goes on in a private practice is beyond the control of academic medical centers and the AMA, commented Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco, and chief of the cardiology section at the Veterans Affairs Medical Center in Fresno. And the practice simply doesn't exist in many academic institutions, such as UCSF, which neither accepts samples nor allows pharmaceutical representatives in the offices, he added.

Regarding pay for physicians' travel expenses to medical meetings, the editorial writers are ignoring the fact that trainees don't get financial support from their institutions as they once did, and that those institutions don't have the money to send them, Dr. Deedwania said.

Also unrealistic is the notion that CME can survive without industry support, said Dr. John Flack, professor and interim chair of the department of medicine and chief of the division of clinical epidemiology and translational research at Wayne State University, Detroit.

“Without industry support, CME will become a thing of the past, because few entities can afford to pay for it,” Dr. Flack said.

Nonetheless, many in the academic community have had a more positive response to the proposals, said Dr. Jordan J. Cohen, one of the JAMA report's coauthors and president of the Association of American Medical Colleges, Washington. The reforms will, of course, meet with resistance because they “represent a big change in practices that have been very widely accepted over a significant time, and frankly there's a significant amount of money in play here. I won't suggest that it would be at all easy to implement these changes, but it is looking possible,” he said.

The proposals “will at least inspire a good deal more conversation about, and examination of, current policies and their unintended consequences, which are not in the best interests of the public. It will allow the medical community to find other ways of supporting activities that are now dependent on the health care industry,” he said.

Dr. David L. Coleman, interim chair of internal medicine at Yale University, New Haven, Conn., applauded Dr. Brennan's group for “stepping forward with a very bold set of recommendations.” Yale has already implemented strict guidelines prohibiting any gifts from industry representatives, any meals funded by industry, and any payment for attending CME meetings. The Yale guidelines are detailed in a report published in February (Acad. Med. 2006;81:154–60).

“I think banning food and gifts makes things a lot easier, frankly,” he said. “It's so nice to walk into a conference and not have to have that awkward conversation with a drug rep, and not have to feel squeamish about possible conflicts of interest.”

He acknowledged that the proposed reform central to most physicians in private practice—banning free samples and other gifts from detail people—is not likely to be adopted any time soon. At Yale, “we considered banning free samples for patients, because it clearly encourages the use of more expensive medications. Even worse, it is a poorly regulated process, so these drugs can end up in the hands of patients who are not followed adequately. But it was finally decided that free samples could not be prohibited until some other system for delivering free samples to needy patients is in place.”

Yale did ban the use of free samples by physicians and their families, a measure that has had an unexpectedly large effect. “There has been some grumbling,” but the response to the strict guidelines from Yale physicians as well as outsiders has been overwhelmingly positive, Dr. Coleman said.

Another dissenting note was sounded by Ken Johnson, senior vice president of Pharmaceutical Research and Manufacturers of America, Washington, who noted that sales representatives are technically well trained and provide crucial information to doctors about the way drugs work and their side effects. Most detailers already follow PhRMA's voluntary guidelines and focus on ensuring that medicines are used correctly, he said.

Most physicians interviewed agreed heartily with one proposed reform: ghostwriting. This should be controlled or eliminated, because some companies do influence the wording in research manuscripts, and busy investigators may go along with it, Dr. Deedwania said.

Aspirin therapy for the primary prevention of cardiovascular disease may reduce the risk of ischemic stroke in women and the risk of myocardial infarction in men, according to a metaanalysis specifically designed to tease out gender-based differences in response to aspirin therapy.

But the results should be interpreted cautiously, because aspirin dose, treatment duration, and length of follow-up varied among the six trials in the metaanalysis. Moreover, the populations studied were healthy and at low risk for cardiovascular events, and the number of events was low.

Few data are available on aspirin for primary CVD prevention in women, and the single large, randomized trial to examine the issue showed different effects in women from those found in studies that enrolled men predominantly or exclusively, said Dr. Jeffrey S. Berger of Duke University, Durham, N.C., and his associates.

To clarify any possible differences in the benefits for men and women, the investigators performed a metaanalysis of six prospective, randomized, controlled trials that included data on cardiovascular death, MI, and stroke. Three trials studied only men, one only women, and two had both.

Together the studies yielded data on 51,342 women and 44,144 men followed for a mean of 6.4 years after they began aspirin therapy or a placebo/control treatment.

Major cardiovascular events occurred in 1,285 women and 2,047 men. Pooled results showed a statistically significant 12% decrease in the risk of cardiovascular events in women taking aspirin and a significant 14% reduction in men taking aspirin, the investigators said (JAMA 2006;295:306–13).

The absolute risk reduction for cardiovascular events was 0.30% for women and 0.37% for men, and the number needed to treat to prevent one cardiovascular event over the mean follow-up of 6.4 years was 333 for women and 270 for men.

“In other words, aspirin therapy for an average of 6.4 years results in an average absolute benefit of approximately 3 CV events prevented per 1,000 women and 4 CV events prevented per 1,000 men,” Dr. Berger and his associates explained.

However, aspirin's effects differed between the sexes when specific cardiovascular events were examined.

A total of 469 women developed MI (0.9%), and this rate was similar between those taking aspirin and those taking a placebo/control treatment. In contrast, 1,023 men developed MI (2.3%), and the rate was 32% lower in those taking aspirin.

Strokes occurred in 625 women (1.2%), and the rate was 17% lower in those taking aspirin—a significant difference. For women, aspirin cut ischemic stroke by 24% but did not appear to affect hemorrhagic stroke. In contrast, strokes occurred in 597 men (1.3%), and the rate was nonsignificantly increased in those taking aspirin. For men, aspirin had no effect on ischemic stroke but raised the risk for hemorrhagic stroke by a significant 69%.

Aspirin therapy did not affect the rate of death from cardiovascular causes or all-cause mortality in either men or women. It raised the risk for major bleeding events, usually gastrointestinal bleeding, for both sexes.

The reason for these apparent gender-related differences in response to aspirin therapy remains unclear. It may be related to the fact that overall risk for MI is lower in women than in men, while overall risk for stroke is higher in women than in men. There also may be differences between men and women in aspirin metabolism and aspirin resistance, the investigators reported.

The relatively small number of MIs in women and of ischemic strokes in men “suggest that further studies are needed before we can [definitively] conclude that men and women differ in their cardiovascular response to aspirin,” they said.

Aspirin therapy for the primary prevention of cardiovascular disease may reduce the risk of ischemic stroke in women and the risk of myocardial infarction in men, according to a metaanalysis specifically designed to tease out gender-based differences in response to aspirin therapy.

But the results should be interpreted cautiously, because aspirin dose, treatment duration, and length of follow-up varied among the six trials in the metaanalysis. Moreover, the populations studied were healthy and at low risk for cardiovascular events, and the number of events was low.

Few data are available on aspirin for primary CVD prevention in women, and the single large, randomized trial to examine the issue showed different effects in women from those found in studies that enrolled men predominantly or exclusively, said Dr. Jeffrey S. Berger of Duke University, Durham, N.C., and his associates.

To clarify any possible differences in the benefits for men and women, the investigators performed a metaanalysis of six prospective, randomized, controlled trials that included data on cardiovascular death, MI, and stroke. Three trials studied only men, one only women, and two had both.

Together the studies yielded data on 51,342 women and 44,144 men followed for a mean of 6.4 years after they began aspirin therapy or a placebo/control treatment.

Major cardiovascular events occurred in 1,285 women and 2,047 men. Pooled results showed a statistically significant 12% decrease in the risk of cardiovascular events in women taking aspirin and a significant 14% reduction in men taking aspirin, the investigators said (JAMA 2006;295:306–13).

The absolute risk reduction for cardiovascular events was 0.30% for women and 0.37% for men, and the number needed to treat to prevent one cardiovascular event over the mean follow-up of 6.4 years was 333 for women and 270 for men.

“In other words, aspirin therapy for an average of 6.4 years results in an average absolute benefit of approximately 3 CV events prevented per 1,000 women and 4 CV events prevented per 1,000 men,” Dr. Berger and his associates explained.

However, aspirin's effects differed between the sexes when specific cardiovascular events were examined.

A total of 469 women developed MI (0.9%), and this rate was similar between those taking aspirin and those taking a placebo/control treatment. In contrast, 1,023 men developed MI (2.3%), and the rate was 32% lower in those taking aspirin.

Strokes occurred in 625 women (1.2%), and the rate was 17% lower in those taking aspirin—a significant difference. For women, aspirin cut ischemic stroke by 24% but did not appear to affect hemorrhagic stroke. In contrast, strokes occurred in 597 men (1.3%), and the rate was nonsignificantly increased in those taking aspirin. For men, aspirin had no effect on ischemic stroke but raised the risk for hemorrhagic stroke by a significant 69%.

Aspirin therapy did not affect the rate of death from cardiovascular causes or all-cause mortality in either men or women. It raised the risk for major bleeding events, usually gastrointestinal bleeding, for both sexes.

The reason for these apparent gender-related differences in response to aspirin therapy remains unclear. It may be related to the fact that overall risk for MI is lower in women than in men, while overall risk for stroke is higher in women than in men. There also may be differences between men and women in aspirin metabolism and aspirin resistance, the investigators reported.

The relatively small number of MIs in women and of ischemic strokes in men “suggest that further studies are needed before we can [definitively] conclude that men and women differ in their cardiovascular response to aspirin,” they said.

Aspirin therapy for the primary prevention of cardiovascular disease may reduce the risk of ischemic stroke in women and the risk of myocardial infarction in men, according to a metaanalysis specifically designed to tease out gender-based differences in response to aspirin therapy.

But the results should be interpreted cautiously, because aspirin dose, treatment duration, and length of follow-up varied among the six trials in the metaanalysis. Moreover, the populations studied were healthy and at low risk for cardiovascular events, and the number of events was low.

Few data are available on aspirin for primary CVD prevention in women, and the single large, randomized trial to examine the issue showed different effects in women from those found in studies that enrolled men predominantly or exclusively, said Dr. Jeffrey S. Berger of Duke University, Durham, N.C., and his associates.

To clarify any possible differences in the benefits for men and women, the investigators performed a metaanalysis of six prospective, randomized, controlled trials that included data on cardiovascular death, MI, and stroke. Three trials studied only men, one only women, and two had both.

Together the studies yielded data on 51,342 women and 44,144 men followed for a mean of 6.4 years after they began aspirin therapy or a placebo/control treatment.

Major cardiovascular events occurred in 1,285 women and 2,047 men. Pooled results showed a statistically significant 12% decrease in the risk of cardiovascular events in women taking aspirin and a significant 14% reduction in men taking aspirin, the investigators said (JAMA 2006;295:306–13).

The absolute risk reduction for cardiovascular events was 0.30% for women and 0.37% for men, and the number needed to treat to prevent one cardiovascular event over the mean follow-up of 6.4 years was 333 for women and 270 for men.

“In other words, aspirin therapy for an average of 6.4 years results in an average absolute benefit of approximately 3 CV events prevented per 1,000 women and 4 CV events prevented per 1,000 men,” Dr. Berger and his associates explained.

However, aspirin's effects differed between the sexes when specific cardiovascular events were examined.

A total of 469 women developed MI (0.9%), and this rate was similar between those taking aspirin and those taking a placebo/control treatment. In contrast, 1,023 men developed MI (2.3%), and the rate was 32% lower in those taking aspirin.

Strokes occurred in 625 women (1.2%), and the rate was 17% lower in those taking aspirin—a significant difference. For women, aspirin cut ischemic stroke by 24% but did not appear to affect hemorrhagic stroke. In contrast, strokes occurred in 597 men (1.3%), and the rate was nonsignificantly increased in those taking aspirin. For men, aspirin had no effect on ischemic stroke but raised the risk for hemorrhagic stroke by a significant 69%.

Aspirin therapy did not affect the rate of death from cardiovascular causes or all-cause mortality in either men or women. It raised the risk for major bleeding events, usually gastrointestinal bleeding, for both sexes.

The reason for these apparent gender-related differences in response to aspirin therapy remains unclear. It may be related to the fact that overall risk for MI is lower in women than in men, while overall risk for stroke is higher in women than in men. There also may be differences between men and women in aspirin metabolism and aspirin resistance, the investigators reported.

The relatively small number of MIs in women and of ischemic strokes in men “suggest that further studies are needed before we can [definitively] conclude that men and women differ in their cardiovascular response to aspirin,” they said.

Tracking follicle-stimulating hormone levels every year from premenopause onward can help predict bone loss during the menopausal transition, reported MaryFran R. Sowers, Ph.D., of the University of Michigan, Ann Arbor, and her associates.

The researchers conducted what they described as the first study to longitudinally characterize bone mineral density (BMD) loss at the spine and hip in conjunction with changes in reproductive hormone concentrations. They found that the interaction between the baseline FSH level obtained before menopause and serial FSH levels taken every year thereafter predicted bone loss. However, this interaction “is complex, requires at least two FSH values, and may be challenging to apply in a busy clinical setting,” they cautioned.

The study population comprised 2,311 women aged 42–52 at baseline who were assessed at several medical centers across the United States for 5 years. Half of the women were white, 28% were African American, 11% were Japanese, and 11% were Chinese.

The women underwent annual spine, femoral neck, and total hip BMD assessments with densitometers. Blood samples obtained annually during the early follicular phase of the menstrual cycle were analyzed for estradiol, FSH, testosterone, sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS) content.

At baseline, 53% of the women were classified as premenopausal because they reported no decrease in menstrual regularity during the preceding year, and 47% were classified as being in the “early perimenopausal” period because they reported decreased menstrual regularity in the preceding 3 months (J. Clin. Endocrinol. Metab. doi:10.1210/jc.2005/1836, published Jan. 10, 2006).

The interaction between baseline FSH levels and subsequent levels predicted bone loss. “If baseline FSH was lower (<25 mIU/mL), then statistical modeling indicated that more lumbar spine change occurred only when the follow-up FSH concentrations were higher (40–70 mIU/mL), and the greatest amount of spine BMD loss (−0.05 g/cm

“However, if the baseline FSH was higher (35–45 mIU/mL), then modeling indicated that lower levels of follow-up FSH (40–50 mIU/mL)” predicted a decrease in spine BMD, the investigators said. They devised charts to show predicted bone loss for various levels of baseline and subsequent FSH.

Estradiol levels measured throughout this transitional period “were poor predictors of incremental BMD change,” Dr. Sowers and her associates noted.

Similarly, there was no correlation between BMD changes and levels of testosterone, DHEAS, or SHBG.

Tracking follicle-stimulating hormone levels every year from premenopause onward can help predict bone loss during the menopausal transition, reported MaryFran R. Sowers, Ph.D., of the University of Michigan, Ann Arbor, and her associates.

The researchers conducted what they described as the first study to longitudinally characterize bone mineral density (BMD) loss at the spine and hip in conjunction with changes in reproductive hormone concentrations. They found that the interaction between the baseline FSH level obtained before menopause and serial FSH levels taken every year thereafter predicted bone loss. However, this interaction “is complex, requires at least two FSH values, and may be challenging to apply in a busy clinical setting,” they cautioned.

The study population comprised 2,311 women aged 42–52 at baseline who were assessed at several medical centers across the United States for 5 years. Half of the women were white, 28% were African American, 11% were Japanese, and 11% were Chinese.

The women underwent annual spine, femoral neck, and total hip BMD assessments with densitometers. Blood samples obtained annually during the early follicular phase of the menstrual cycle were analyzed for estradiol, FSH, testosterone, sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS) content.

At baseline, 53% of the women were classified as premenopausal because they reported no decrease in menstrual regularity during the preceding year, and 47% were classified as being in the “early perimenopausal” period because they reported decreased menstrual regularity in the preceding 3 months (J. Clin. Endocrinol. Metab. doi:10.1210/jc.2005/1836, published Jan. 10, 2006).

The interaction between baseline FSH levels and subsequent levels predicted bone loss. “If baseline FSH was lower (<25 mIU/mL), then statistical modeling indicated that more lumbar spine change occurred only when the follow-up FSH concentrations were higher (40–70 mIU/mL), and the greatest amount of spine BMD loss (−0.05 g/cm

“However, if the baseline FSH was higher (35–45 mIU/mL), then modeling indicated that lower levels of follow-up FSH (40–50 mIU/mL)” predicted a decrease in spine BMD, the investigators said. They devised charts to show predicted bone loss for various levels of baseline and subsequent FSH.

Estradiol levels measured throughout this transitional period “were poor predictors of incremental BMD change,” Dr. Sowers and her associates noted.

Similarly, there was no correlation between BMD changes and levels of testosterone, DHEAS, or SHBG.

Tracking follicle-stimulating hormone levels every year from premenopause onward can help predict bone loss during the menopausal transition, reported MaryFran R. Sowers, Ph.D., of the University of Michigan, Ann Arbor, and her associates.

The researchers conducted what they described as the first study to longitudinally characterize bone mineral density (BMD) loss at the spine and hip in conjunction with changes in reproductive hormone concentrations. They found that the interaction between the baseline FSH level obtained before menopause and serial FSH levels taken every year thereafter predicted bone loss. However, this interaction “is complex, requires at least two FSH values, and may be challenging to apply in a busy clinical setting,” they cautioned.

The study population comprised 2,311 women aged 42–52 at baseline who were assessed at several medical centers across the United States for 5 years. Half of the women were white, 28% were African American, 11% were Japanese, and 11% were Chinese.

The women underwent annual spine, femoral neck, and total hip BMD assessments with densitometers. Blood samples obtained annually during the early follicular phase of the menstrual cycle were analyzed for estradiol, FSH, testosterone, sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS) content.

At baseline, 53% of the women were classified as premenopausal because they reported no decrease in menstrual regularity during the preceding year, and 47% were classified as being in the “early perimenopausal” period because they reported decreased menstrual regularity in the preceding 3 months (J. Clin. Endocrinol. Metab. doi:10.1210/jc.2005/1836, published Jan. 10, 2006).

The interaction between baseline FSH levels and subsequent levels predicted bone loss. “If baseline FSH was lower (<25 mIU/mL), then statistical modeling indicated that more lumbar spine change occurred only when the follow-up FSH concentrations were higher (40–70 mIU/mL), and the greatest amount of spine BMD loss (−0.05 g/cm

“However, if the baseline FSH was higher (35–45 mIU/mL), then modeling indicated that lower levels of follow-up FSH (40–50 mIU/mL)” predicted a decrease in spine BMD, the investigators said. They devised charts to show predicted bone loss for various levels of baseline and subsequent FSH.

Estradiol levels measured throughout this transitional period “were poor predictors of incremental BMD change,” Dr. Sowers and her associates noted.

Similarly, there was no correlation between BMD changes and levels of testosterone, DHEAS, or SHBG.

Transsternal thymectomy is safe and effective for patients with myasthenia gravis at any stage of the disease, according to Dr. Hassan Kattach of Radcliffe Infirmary, Oxford, England, and associates.

Dr. Kattach and his associates assessed outcomes in 85 consecutive patients who underwent transsternal thymectomy at their institution between 1987 and 1998.

Most of the patients chose surgery because their symptoms were refractory to all other treatment. The mean age at surgery was 31 years (range, 11–74 years), and mean follow-up was 5 years.

Transsternal thymectomy was performed through a full sternotomy. The resection borders were the thyroid gland above, the diaphragm below, and the phrenic nerves laterally. This resection is more extensive than that with standard transsternal thymectomy but less extensive than that with aggressive, extended transsternal thymectomy advocated by some clinicians, the investigators said (Ann. Thorac. Surg. 2006;81:305–8).

There were no patient deaths perioperatively or during follow-up. Of the patients, 67 reported clinical improvement, and 63 became asymptomatic or achieved clinical stage I disease with no or minimal treatment required. This included 15 patients who achieved complete stable remission. After the surgery, 13 patients reported no symptom improvement.

Patients who had more advanced disease preoperatively showed the greatest improvement after the surgery.

Complications developed in 13 patients, including 8 patients with major operative complications. These were related to advanced thymomas that required extensive dissection and included two cases of phrenic nerve palsy in patients whose thymomas involved the phrenic nerves.

Neither improvement nor clinical remission were predicted by patient age, gender, duration of disease, or thymic pathology. As such, these factors should not be considered as indications or contraindications to the procedure, Dr. Kattach and associates wrote. Some clinicians have questioned the role of thymectomy in patients who show no evidence of thymoma on chest imaging, but these results show that the presence or absence of thymoma should not influence the decision to do the surgery.

Transsternal thymectomy is safe and effective for patients with myasthenia gravis at any stage of the disease, according to Dr. Hassan Kattach of Radcliffe Infirmary, Oxford, England, and associates.

Dr. Kattach and his associates assessed outcomes in 85 consecutive patients who underwent transsternal thymectomy at their institution between 1987 and 1998.

Most of the patients chose surgery because their symptoms were refractory to all other treatment. The mean age at surgery was 31 years (range, 11–74 years), and mean follow-up was 5 years.

Transsternal thymectomy was performed through a full sternotomy. The resection borders were the thyroid gland above, the diaphragm below, and the phrenic nerves laterally. This resection is more extensive than that with standard transsternal thymectomy but less extensive than that with aggressive, extended transsternal thymectomy advocated by some clinicians, the investigators said (Ann. Thorac. Surg. 2006;81:305–8).

There were no patient deaths perioperatively or during follow-up. Of the patients, 67 reported clinical improvement, and 63 became asymptomatic or achieved clinical stage I disease with no or minimal treatment required. This included 15 patients who achieved complete stable remission. After the surgery, 13 patients reported no symptom improvement.

Patients who had more advanced disease preoperatively showed the greatest improvement after the surgery.

Complications developed in 13 patients, including 8 patients with major operative complications. These were related to advanced thymomas that required extensive dissection and included two cases of phrenic nerve palsy in patients whose thymomas involved the phrenic nerves.

Neither improvement nor clinical remission were predicted by patient age, gender, duration of disease, or thymic pathology. As such, these factors should not be considered as indications or contraindications to the procedure, Dr. Kattach and associates wrote. Some clinicians have questioned the role of thymectomy in patients who show no evidence of thymoma on chest imaging, but these results show that the presence or absence of thymoma should not influence the decision to do the surgery.

Transsternal thymectomy is safe and effective for patients with myasthenia gravis at any stage of the disease, according to Dr. Hassan Kattach of Radcliffe Infirmary, Oxford, England, and associates.

Dr. Kattach and his associates assessed outcomes in 85 consecutive patients who underwent transsternal thymectomy at their institution between 1987 and 1998.

Most of the patients chose surgery because their symptoms were refractory to all other treatment. The mean age at surgery was 31 years (range, 11–74 years), and mean follow-up was 5 years.

Transsternal thymectomy was performed through a full sternotomy. The resection borders were the thyroid gland above, the diaphragm below, and the phrenic nerves laterally. This resection is more extensive than that with standard transsternal thymectomy but less extensive than that with aggressive, extended transsternal thymectomy advocated by some clinicians, the investigators said (Ann. Thorac. Surg. 2006;81:305–8).

There were no patient deaths perioperatively or during follow-up. Of the patients, 67 reported clinical improvement, and 63 became asymptomatic or achieved clinical stage I disease with no or minimal treatment required. This included 15 patients who achieved complete stable remission. After the surgery, 13 patients reported no symptom improvement.

Patients who had more advanced disease preoperatively showed the greatest improvement after the surgery.

Complications developed in 13 patients, including 8 patients with major operative complications. These were related to advanced thymomas that required extensive dissection and included two cases of phrenic nerve palsy in patients whose thymomas involved the phrenic nerves.

Neither improvement nor clinical remission were predicted by patient age, gender, duration of disease, or thymic pathology. As such, these factors should not be considered as indications or contraindications to the procedure, Dr. Kattach and associates wrote. Some clinicians have questioned the role of thymectomy in patients who show no evidence of thymoma on chest imaging, but these results show that the presence or absence of thymoma should not influence the decision to do the surgery.

An autologous hematopoietic stem cell transplantation technique that achieves lymphoablation without myeloablation proved effective against severe refractory systemic lupus erythematosus in a preliminary study.

Serology, complement, immunomediated hemolysis and thrombocytopenia, thrombotic events, and pulmonary function all improved while preserving renal function in a single-center study of 48 patients. This nonmyeloablative hematopoietic stem cell transplantation (HSCT) significantly improved SLE symptoms and gave patients a 50% probability of 5-year remission, reported Dr. Richard K. Burt of Northwestern University, Chicago, and associates.

These results justify a randomized clinical trial comparing autologous HSCT with standard care, Dr. Burt and his associates said (JAMA 2006;295:527–35).

Fifty “very ill” patients underwent the two-step procedure involving a lupus-specific conditioning regimen to eliminate self-reactive lymphocytes followed by stem cell infusion. All patients had glomerulonephritis, lung involvement, CNS involvement, vasculitis, myositis, cytopenias, serositis, ulcerative mucocutaneous disease, and/or antiphospholipid syndrome refractory to optimal treatment.

One patient died from pulmonary and cerebral mucormycosis after stem cell mobilization commenced but before transplantation, for treatment-related mortality of 2%. A second patient died from active SLE after postponing transplantation.

The remaining 48 patients were followed for a mean of 29 months. Scores on measures of serology, complement, and disease activity all improved and remained so throughout follow-up. Pulmonary function also improved.

Eighteen of 22 patients were able to discontinue anticoagulation subsequent thrombotic events. Renal function remained stable or improved; 16 patients who had nephritis before HSCT were able to discontinue dialysis afterward. Idiopathic thrombocytopenic purpura cleared in five of seven patients, and autoimmune hemolytic anemia cleared in three of five patients.

An autologous hematopoietic stem cell transplantation technique that achieves lymphoablation without myeloablation proved effective against severe refractory systemic lupus erythematosus in a preliminary study.

Serology, complement, immunomediated hemolysis and thrombocytopenia, thrombotic events, and pulmonary function all improved while preserving renal function in a single-center study of 48 patients. This nonmyeloablative hematopoietic stem cell transplantation (HSCT) significantly improved SLE symptoms and gave patients a 50% probability of 5-year remission, reported Dr. Richard K. Burt of Northwestern University, Chicago, and associates.

These results justify a randomized clinical trial comparing autologous HSCT with standard care, Dr. Burt and his associates said (JAMA 2006;295:527–35).

Fifty “very ill” patients underwent the two-step procedure involving a lupus-specific conditioning regimen to eliminate self-reactive lymphocytes followed by stem cell infusion. All patients had glomerulonephritis, lung involvement, CNS involvement, vasculitis, myositis, cytopenias, serositis, ulcerative mucocutaneous disease, and/or antiphospholipid syndrome refractory to optimal treatment.

One patient died from pulmonary and cerebral mucormycosis after stem cell mobilization commenced but before transplantation, for treatment-related mortality of 2%. A second patient died from active SLE after postponing transplantation.

The remaining 48 patients were followed for a mean of 29 months. Scores on measures of serology, complement, and disease activity all improved and remained so throughout follow-up. Pulmonary function also improved.

Eighteen of 22 patients were able to discontinue anticoagulation subsequent thrombotic events. Renal function remained stable or improved; 16 patients who had nephritis before HSCT were able to discontinue dialysis afterward. Idiopathic thrombocytopenic purpura cleared in five of seven patients, and autoimmune hemolytic anemia cleared in three of five patients.

An autologous hematopoietic stem cell transplantation technique that achieves lymphoablation without myeloablation proved effective against severe refractory systemic lupus erythematosus in a preliminary study.

Serology, complement, immunomediated hemolysis and thrombocytopenia, thrombotic events, and pulmonary function all improved while preserving renal function in a single-center study of 48 patients. This nonmyeloablative hematopoietic stem cell transplantation (HSCT) significantly improved SLE symptoms and gave patients a 50% probability of 5-year remission, reported Dr. Richard K. Burt of Northwestern University, Chicago, and associates.

These results justify a randomized clinical trial comparing autologous HSCT with standard care, Dr. Burt and his associates said (JAMA 2006;295:527–35).

Fifty “very ill” patients underwent the two-step procedure involving a lupus-specific conditioning regimen to eliminate self-reactive lymphocytes followed by stem cell infusion. All patients had glomerulonephritis, lung involvement, CNS involvement, vasculitis, myositis, cytopenias, serositis, ulcerative mucocutaneous disease, and/or antiphospholipid syndrome refractory to optimal treatment.

One patient died from pulmonary and cerebral mucormycosis after stem cell mobilization commenced but before transplantation, for treatment-related mortality of 2%. A second patient died from active SLE after postponing transplantation.

The remaining 48 patients were followed for a mean of 29 months. Scores on measures of serology, complement, and disease activity all improved and remained so throughout follow-up. Pulmonary function also improved.

Eighteen of 22 patients were able to discontinue anticoagulation subsequent thrombotic events. Renal function remained stable or improved; 16 patients who had nephritis before HSCT were able to discontinue dialysis afterward. Idiopathic thrombocytopenic purpura cleared in five of seven patients, and autoimmune hemolytic anemia cleared in three of five patients.

Limiting Tunnel Widening in ACL Repair

A novel hamstring anterior cruciate ligament reconstruction technique that uses a shorter, more rigidly fixed graft prevents the tunnel widening that can lead to a bungee-cord effect following ACL repair.

Dr. Peter Fauno of Randers (Denmark) Central Hospital and colleagues randomly assigned 100 patients to undergo either the new technique using a transfemoral fixation implant with an interference screw in the tibial tunnel, or extracortical fixation in the femur with a bicortical screw and washer distal to the tibial tunnel. A total of 87 patients were available for assessment at 1-year follow-up.

Patients who underwent the new technique had a lower incidence of tunnel widening, compared with those in the conventional technique group (Arthroscopy 2005;21:1337–41.)

A total of 7 of 41 patients (17%) undergoing transfemoral fixation implantation with an interference screw in the tibial tunnel experienced femoral tunnel widening; 5 patients (12%) in that group experienced tibial tunnel widening.

By comparison, 20 of 46 patients (44%) who received extracortical fixation had femoral tunnel widening; 16 patients (35%) in that group had tibial tunnel widening.

Despite the similarity in clinical outcome at 1 year and assuming tunnel widening has no clinical implications, Dr. Fauno believes the risk of tunnel widening should be kept as low as possible.

Vitamin D Beats Calcium for Bones

Vitamin D sufficiency appears to be more important for bone health than is high calcium intake, according to Laufey Steingrimsdottir, Ph.D., of the Public Health Institute of Iceland, Reykjavik, and associates.

Both nutrients are known to influence calcium homeostasis, but the relative contributions of each haven't been studied before, they said (JAMA 2005:294:2336–41).

Vitamin D supplements should be recommended “when sun exposure and dietary sources are insufficient,” Dr. Steingrimsdottir and associates said.

The researchers assessed the relative importance of calcium intake and serum levels of 25-hydroxyvitamin D for maintaining calcium homeostasis in a study of 944 healthy white adult residents of Iceland. The 491 women and 453 men were aged 30–85 years.

Most Icelanders take vitamin supplements or cod liver oil to supply vitamin D because there isn't sufficient sunshine there throughout the year for adequate biosynthesis of vitamin D. Most also have a relatively high calcium intake, chiefly through the consumption of dairy products. In this study, the mean intake of both vitamin D and calcium were well above recommended levels in all age groups, although there was great variation.

Vitamin D status was found to ensure ideal values for serum parathyroid hormone, a marker of bone health, even when calcium intake was not sufficient to maintain those PTH levels. In contrast, high calcium intake did not make up for decreased vitamin D.

In addition, mean serum ionized calcium levels, a more precise marker of calcium homeostasis and thus of bone health, were found to be dependent on serum 25-hydroxyvitamin D levels, but not on calcium intake.

“Our study indicates that as long as vitamin D status is secured by vitamin D, supplements or sufficient sunshine calcium intake levels of more than 800 mg [per day] may be unnecessary,” the investigators noted.

Botox Effective for Tennis Elbow Pain

Botulinum toxin injections may provide short-term pain relief for patients with lateral epicondylitis, Chinese researchers have reported.

A randomized, placebo-controlled trial of botulinum toxin in 60 patients with lateral epicondylitis was conducted at Prince of Wales Hospital in Hong Kong. Dr. Shiu Man Wong and colleagues administered either a single 60-unit injection of botulinum toxin type A or an equivalent volume of normal saline to patients.

Baseline pain scores, using a 100-mm visual analog scale (VAS) of 65.5 mm at baseline, improved to a score of 25.4 mm at 4 weeks in patients receiving botulinum toxin. In controls, the VAS score was 66 mm at baseline and 51 mm at 4 weeks (Ann. Intern. Med. 2005;143:793–7).

Twelve weeks after injection, VAS scores were 23.5 mm for the study group and 43.5 mm for controls.

Mild paresis of the fingers was found at the 4-week check in four patients in the study group, with symptoms persisting in one patient through 12 weeks of follow-up. No patient in the placebo group developed finger paresis. Weak finger extension in the affected limb was noted in 10 patients who received botulinum toxin and in 6 patients in the placebo group.

There was no significant difference in grip strength between the two groups during the study period.

Limiting Tunnel Widening in ACL Repair

A novel hamstring anterior cruciate ligament reconstruction technique that uses a shorter, more rigidly fixed graft prevents the tunnel widening that can lead to a bungee-cord effect following ACL repair.

Dr. Peter Fauno of Randers (Denmark) Central Hospital and colleagues randomly assigned 100 patients to undergo either the new technique using a transfemoral fixation implant with an interference screw in the tibial tunnel, or extracortical fixation in the femur with a bicortical screw and washer distal to the tibial tunnel. A total of 87 patients were available for assessment at 1-year follow-up.

Patients who underwent the new technique had a lower incidence of tunnel widening, compared with those in the conventional technique group (Arthroscopy 2005;21:1337–41.)

A total of 7 of 41 patients (17%) undergoing transfemoral fixation implantation with an interference screw in the tibial tunnel experienced femoral tunnel widening; 5 patients (12%) in that group experienced tibial tunnel widening.

By comparison, 20 of 46 patients (44%) who received extracortical fixation had femoral tunnel widening; 16 patients (35%) in that group had tibial tunnel widening.

Despite the similarity in clinical outcome at 1 year and assuming tunnel widening has no clinical implications, Dr. Fauno believes the risk of tunnel widening should be kept as low as possible.

Vitamin D Beats Calcium for Bones

Vitamin D sufficiency appears to be more important for bone health than is high calcium intake, according to Laufey Steingrimsdottir, Ph.D., of the Public Health Institute of Iceland, Reykjavik, and associates.

Both nutrients are known to influence calcium homeostasis, but the relative contributions of each haven't been studied before, they said (JAMA 2005:294:2336–41).

Vitamin D supplements should be recommended “when sun exposure and dietary sources are insufficient,” Dr. Steingrimsdottir and associates said.

The researchers assessed the relative importance of calcium intake and serum levels of 25-hydroxyvitamin D for maintaining calcium homeostasis in a study of 944 healthy white adult residents of Iceland. The 491 women and 453 men were aged 30–85 years.

Most Icelanders take vitamin supplements or cod liver oil to supply vitamin D because there isn't sufficient sunshine there throughout the year for adequate biosynthesis of vitamin D. Most also have a relatively high calcium intake, chiefly through the consumption of dairy products. In this study, the mean intake of both vitamin D and calcium were well above recommended levels in all age groups, although there was great variation.

Vitamin D status was found to ensure ideal values for serum parathyroid hormone, a marker of bone health, even when calcium intake was not sufficient to maintain those PTH levels. In contrast, high calcium intake did not make up for decreased vitamin D.

In addition, mean serum ionized calcium levels, a more precise marker of calcium homeostasis and thus of bone health, were found to be dependent on serum 25-hydroxyvitamin D levels, but not on calcium intake.

“Our study indicates that as long as vitamin D status is secured by vitamin D, supplements or sufficient sunshine calcium intake levels of more than 800 mg [per day] may be unnecessary,” the investigators noted.

Botox Effective for Tennis Elbow Pain

Botulinum toxin injections may provide short-term pain relief for patients with lateral epicondylitis, Chinese researchers have reported.

A randomized, placebo-controlled trial of botulinum toxin in 60 patients with lateral epicondylitis was conducted at Prince of Wales Hospital in Hong Kong. Dr. Shiu Man Wong and colleagues administered either a single 60-unit injection of botulinum toxin type A or an equivalent volume of normal saline to patients.

Baseline pain scores, using a 100-mm visual analog scale (VAS) of 65.5 mm at baseline, improved to a score of 25.4 mm at 4 weeks in patients receiving botulinum toxin. In controls, the VAS score was 66 mm at baseline and 51 mm at 4 weeks (Ann. Intern. Med. 2005;143:793–7).

Twelve weeks after injection, VAS scores were 23.5 mm for the study group and 43.5 mm for controls.

Mild paresis of the fingers was found at the 4-week check in four patients in the study group, with symptoms persisting in one patient through 12 weeks of follow-up. No patient in the placebo group developed finger paresis. Weak finger extension in the affected limb was noted in 10 patients who received botulinum toxin and in 6 patients in the placebo group.

There was no significant difference in grip strength between the two groups during the study period.

Limiting Tunnel Widening in ACL Repair

A novel hamstring anterior cruciate ligament reconstruction technique that uses a shorter, more rigidly fixed graft prevents the tunnel widening that can lead to a bungee-cord effect following ACL repair.

Dr. Peter Fauno of Randers (Denmark) Central Hospital and colleagues randomly assigned 100 patients to undergo either the new technique using a transfemoral fixation implant with an interference screw in the tibial tunnel, or extracortical fixation in the femur with a bicortical screw and washer distal to the tibial tunnel. A total of 87 patients were available for assessment at 1-year follow-up.

Patients who underwent the new technique had a lower incidence of tunnel widening, compared with those in the conventional technique group (Arthroscopy 2005;21:1337–41.)

A total of 7 of 41 patients (17%) undergoing transfemoral fixation implantation with an interference screw in the tibial tunnel experienced femoral tunnel widening; 5 patients (12%) in that group experienced tibial tunnel widening.

By comparison, 20 of 46 patients (44%) who received extracortical fixation had femoral tunnel widening; 16 patients (35%) in that group had tibial tunnel widening.

Despite the similarity in clinical outcome at 1 year and assuming tunnel widening has no clinical implications, Dr. Fauno believes the risk of tunnel widening should be kept as low as possible.

Vitamin D Beats Calcium for Bones

Vitamin D sufficiency appears to be more important for bone health than is high calcium intake, according to Laufey Steingrimsdottir, Ph.D., of the Public Health Institute of Iceland, Reykjavik, and associates.

Both nutrients are known to influence calcium homeostasis, but the relative contributions of each haven't been studied before, they said (JAMA 2005:294:2336–41).

Vitamin D supplements should be recommended “when sun exposure and dietary sources are insufficient,” Dr. Steingrimsdottir and associates said.

The researchers assessed the relative importance of calcium intake and serum levels of 25-hydroxyvitamin D for maintaining calcium homeostasis in a study of 944 healthy white adult residents of Iceland. The 491 women and 453 men were aged 30–85 years.

Most Icelanders take vitamin supplements or cod liver oil to supply vitamin D because there isn't sufficient sunshine there throughout the year for adequate biosynthesis of vitamin D. Most also have a relatively high calcium intake, chiefly through the consumption of dairy products. In this study, the mean intake of both vitamin D and calcium were well above recommended levels in all age groups, although there was great variation.

Vitamin D status was found to ensure ideal values for serum parathyroid hormone, a marker of bone health, even when calcium intake was not sufficient to maintain those PTH levels. In contrast, high calcium intake did not make up for decreased vitamin D.

In addition, mean serum ionized calcium levels, a more precise marker of calcium homeostasis and thus of bone health, were found to be dependent on serum 25-hydroxyvitamin D levels, but not on calcium intake.

“Our study indicates that as long as vitamin D status is secured by vitamin D, supplements or sufficient sunshine calcium intake levels of more than 800 mg [per day] may be unnecessary,” the investigators noted.

Botox Effective for Tennis Elbow Pain

Botulinum toxin injections may provide short-term pain relief for patients with lateral epicondylitis, Chinese researchers have reported.

A randomized, placebo-controlled trial of botulinum toxin in 60 patients with lateral epicondylitis was conducted at Prince of Wales Hospital in Hong Kong. Dr. Shiu Man Wong and colleagues administered either a single 60-unit injection of botulinum toxin type A or an equivalent volume of normal saline to patients.

Baseline pain scores, using a 100-mm visual analog scale (VAS) of 65.5 mm at baseline, improved to a score of 25.4 mm at 4 weeks in patients receiving botulinum toxin. In controls, the VAS score was 66 mm at baseline and 51 mm at 4 weeks (Ann. Intern. Med. 2005;143:793–7).

Twelve weeks after injection, VAS scores were 23.5 mm for the study group and 43.5 mm for controls.

Mild paresis of the fingers was found at the 4-week check in four patients in the study group, with symptoms persisting in one patient through 12 weeks of follow-up. No patient in the placebo group developed finger paresis. Weak finger extension in the affected limb was noted in 10 patients who received botulinum toxin and in 6 patients in the placebo group.

There was no significant difference in grip strength between the two groups during the study period.

Vapotherm respiratory gas administration devices are being voluntarily recalled, following federal government reports that twenty-nine hospitals in 16 states found Ralstonia organisms colonizing the devices, and cultures from approximately 40 pediatric patients also yielded the bacteria.

The Centers for Disease Control and Prevention and the Food and Drug Administration late last year had advised clinicians to use alternative devices to provide humidified oxygen therapy until the source of contamination has been identified and removed. They also recommended that any patients who have been exposed to the Vapotherm system be monitored for signs and symptoms suggesting infection, including fever, poor feeding, irritability, and changes in hematologic indices.

In addition, “clinicians may want to consider Ralstonia species infection in the differential diagnosis of symptomatic patients even if the organism has not been isolated,” the FDA said in a public health notification (www.fda.gov/cdrh/safety/122005-vapotherm.html

In response, the device manufacturer, Vapotherm, announced last month that it would recall and disinfect Vapotherm 2000i and 2000h devices. Units will then be returned to the owners with updated disinfection and usage recommendations.

Contamination of the Vapotherm system was first reported by the CDC and the FDA in October 2005, after a Pennsylvania hospital isolated Ralstonia in several patients who had used the device. The Vapotherm system is used “to add moisture to and to warm breathing gases for administration to patients,” according to its manufacturer, Vapotherm Inc. (Stevensville, Md.).

Since the October reports, the CDC and FDA have found additional cases of Ralstonia contamination. Cultures of unused Vapotherm cartridges at two hospitals yielded Ralstonia, but cultures of other unused cartridges from the same lot did not grow the organism.

After the procedures for disinfecting the device that were listed in its original instructions were found to be inadequate, the manufacturer issued new instructions for chloride dioxide disinfection. However this method also “may not achieve sustained bacterial control,” according to the FDA.

“Infections caused by Ralstonia should be treated on the basis of results of susceptibility testing of the patient's isolate,” according to the CDC (MMWR 2005;54:1–2).

“Clinicians who elect to use Vapotherm are encouraged to weigh the risk of potential bacterial contamination of the device against the benefits Vapotherm might provide patients who require humidified oxygen therapy,” the CDC said.

For more information, visit www.vtherm.com/recallwww.fda.gov/Medwatch

Vapotherm respiratory gas administration devices are being voluntarily recalled, following federal government reports that twenty-nine hospitals in 16 states found Ralstonia organisms colonizing the devices, and cultures from approximately 40 pediatric patients also yielded the bacteria.

The Centers for Disease Control and Prevention and the Food and Drug Administration late last year had advised clinicians to use alternative devices to provide humidified oxygen therapy until the source of contamination has been identified and removed. They also recommended that any patients who have been exposed to the Vapotherm system be monitored for signs and symptoms suggesting infection, including fever, poor feeding, irritability, and changes in hematologic indices.

In addition, “clinicians may want to consider Ralstonia species infection in the differential diagnosis of symptomatic patients even if the organism has not been isolated,” the FDA said in a public health notification (www.fda.gov/cdrh/safety/122005-vapotherm.html

In response, the device manufacturer, Vapotherm, announced last month that it would recall and disinfect Vapotherm 2000i and 2000h devices. Units will then be returned to the owners with updated disinfection and usage recommendations.

Contamination of the Vapotherm system was first reported by the CDC and the FDA in October 2005, after a Pennsylvania hospital isolated Ralstonia in several patients who had used the device. The Vapotherm system is used “to add moisture to and to warm breathing gases for administration to patients,” according to its manufacturer, Vapotherm Inc. (Stevensville, Md.).

Since the October reports, the CDC and FDA have found additional cases of Ralstonia contamination. Cultures of unused Vapotherm cartridges at two hospitals yielded Ralstonia, but cultures of other unused cartridges from the same lot did not grow the organism.

After the procedures for disinfecting the device that were listed in its original instructions were found to be inadequate, the manufacturer issued new instructions for chloride dioxide disinfection. However this method also “may not achieve sustained bacterial control,” according to the FDA.

“Infections caused by Ralstonia should be treated on the basis of results of susceptibility testing of the patient's isolate,” according to the CDC (MMWR 2005;54:1–2).

“Clinicians who elect to use Vapotherm are encouraged to weigh the risk of potential bacterial contamination of the device against the benefits Vapotherm might provide patients who require humidified oxygen therapy,” the CDC said.

For more information, visit www.vtherm.com/recallwww.fda.gov/Medwatch

Vapotherm respiratory gas administration devices are being voluntarily recalled, following federal government reports that twenty-nine hospitals in 16 states found Ralstonia organisms colonizing the devices, and cultures from approximately 40 pediatric patients also yielded the bacteria.

The Centers for Disease Control and Prevention and the Food and Drug Administration late last year had advised clinicians to use alternative devices to provide humidified oxygen therapy until the source of contamination has been identified and removed. They also recommended that any patients who have been exposed to the Vapotherm system be monitored for signs and symptoms suggesting infection, including fever, poor feeding, irritability, and changes in hematologic indices.

In addition, “clinicians may want to consider Ralstonia species infection in the differential diagnosis of symptomatic patients even if the organism has not been isolated,” the FDA said in a public health notification (www.fda.gov/cdrh/safety/122005-vapotherm.html

In response, the device manufacturer, Vapotherm, announced last month that it would recall and disinfect Vapotherm 2000i and 2000h devices. Units will then be returned to the owners with updated disinfection and usage recommendations.

Contamination of the Vapotherm system was first reported by the CDC and the FDA in October 2005, after a Pennsylvania hospital isolated Ralstonia in several patients who had used the device. The Vapotherm system is used “to add moisture to and to warm breathing gases for administration to patients,” according to its manufacturer, Vapotherm Inc. (Stevensville, Md.).

Since the October reports, the CDC and FDA have found additional cases of Ralstonia contamination. Cultures of unused Vapotherm cartridges at two hospitals yielded Ralstonia, but cultures of other unused cartridges from the same lot did not grow the organism.

After the procedures for disinfecting the device that were listed in its original instructions were found to be inadequate, the manufacturer issued new instructions for chloride dioxide disinfection. However this method also “may not achieve sustained bacterial control,” according to the FDA.

“Infections caused by Ralstonia should be treated on the basis of results of susceptibility testing of the patient's isolate,” according to the CDC (MMWR 2005;54:1–2).

“Clinicians who elect to use Vapotherm are encouraged to weigh the risk of potential bacterial contamination of the device against the benefits Vapotherm might provide patients who require humidified oxygen therapy,” the CDC said.

For more information, visit www.vtherm.com/recallwww.fda.gov/Medwatch