New Research Consortium on Quest to Improve Male Infertility Treatment

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Changed
Wed, 10/02/2024 - 11:34

A study by researchers at two academic medical centers determined which infertile men may benefit from treatment with anastrozole. They found that those with azoospermia (no sperm in their ejaculate) rarely respond to the drug while those with baseline nonazoospermia, lower levels of luteinizing hormone and follicle-stimulating hormone, and higher levels of testosterone are more likely to obtain improvement in semen parameters.

The retrospective cohort study of 90 infertile men, published in the October 2023 issue of Fertility and Sterility, was conducted by researchers at Cleveland Clinic and the University of California Los Angeles. It is the first project of Male Organ Biology Yielding United Science (MOBYUS), a new, multi-institutional research consortium seeking to better understand male infertility and expand treatment options. 

Launched last year, MOBYUS now includes investigators from 14 large US-based academic medical centers. They select research topics and search their patient population for eligible participants and share resulting deidentified data for analysis and publication. 

Members of the consortium conducted another study which found that combination therapy with clomiphene citrate and anastrozole was associated with modest benefits on semen parameters, including volume, concentration, and motility after treatment, compared with anastrozole monotherapy. That retrospective cohort analysis of 21 men was published online in Translational Andrology and Urology in February. 

“We know that if we treat the right men with these medications, about 40% will improve their fertility, but only if we choose the right population. These studies identified those groups,” Scott Lundy, MD, PhD, section head of male infertility at Cleveland Clinic’s Glickman Urological and Kidney Institute in Cleveland, and director of the clinic’s andrology lab, told Medscape Medical News. 

Dr. Lundy, a coauthor of both papers, conceived MOBYUS to overcome constraints in research into male infertility. Many studies in the field are limited by small numbers of patients and retrospective designs, he said. “I sought to develop a collaborative network of reproductive urologists and hospitals like ours, so that we can combine our data and generate large series of data, even for rare patient groups, so that we can improve their patient outcomes,” he said.

“Our treatments are in the stone age in many ways. We are far behind other types of treatment for other conditions, including female infertility,” Dr. Lundy added. “And so, our goal is to identify new and data-driven ways to help these men become fathers, whether those are medications or surgeries or combinations of treatments.”
 

Moving the Field Forward

The name of the consortium is a cheeky play on Moby Dick, the most famous sperm whale. MOBYUS investigators conveyed the challenges that patients, doctors, and researchers experience in an article published last December in the Journal of Urology

They noted that 1 in 6 couples will have difficulty conceiving a child, with male-factor infertility contributing to at least half of such cases. The lead author, Catherine Nam, MD, a principal investigator for MOBYUS at the University of Michigan, in Ann Arbor, said the paper is unusual for a medical journal, as it provides personal accounts of the psychological and emotional aspects of infertility as well as factors that have led to a global decline in sperm counts among men and the financial costs of treatment.

Dr. Nam said infertility is a sensitive topic for couples and families to talk about and there is less conversation about male infertility than female infertility. “I think the only way that we can be able to make headway, both in terms of protocol and policy outcomes, is to really start to raise awareness,” said Dr. Nam, who is doing a fellowship in clinical andrology at Northwestern University, in Chicago.

Dr. Nam said the collaborative environment of MOBYUS has enabled her to learn about different practice patterns across different institutions. “For someone like me just starting off my professional career in male infertility, an opportunity like this is incredibly exciting and makes me very hopeful about the kinds of collaboration and scientific discovery that we’re able to do together as a group,” she said.

Robert E. Brannigan, MD, vice chair of clinical urology at Northwestern University Feinberg School of Medicine, Chicago, said the consortium is drawing on the strength of many individual centers and allowing them to study critical issues in the field. The group’s outstanding clinicians and scientists “are looking to move the field forward, and I applaud them and I’m eager to watch things unfold,” said Dr. Brannigan, who is not a member of the group.

Dr. Brannigan noted that for a large percentage of patients, clinicians cannot identify the root cause of their impaired reproductive potential. Some people may have a recognizable decline in semen parameters over time without clear lifestyle issues or clear hormonal imbalances or anatomical problems. 

“And the question is, what’s causing that? Is there some as yet unrecognized environmental exposure? Is there some underlying genetic issue that’s predisposing to decline in semen parameters over time? We see this, and we don’t have answers,” Dr. Brannigan said. 

“This is where I think the potential power of a large group like MOBYUS comes into play,” he added. “When you’ve got large datasets and very granular information about your patients, sometimes that can provide the opportunity for insights that can then answer the question, ‘What is the root cause of my patient’s challenges?’ ”

Dr. Brannigan was part of a previous group, the Andrology Research Consortium, which collected data on patient history and treatment through a standardized questionnaire. The consortium was founded in 2013 by the Society for the Study of Male Reproduction, a specialty section of the American Urological Association, to obtain data on the demographics, clinical characteristics, and fertility histories and therapies of men referred for a male infertility investigation at clinics across North America. 

Clinicians analyzed data from the questionnaires, which a team in Toronto collected and stored, in a series of studies, including a comparison of fertility characteristics between men in the United States and Canada. Dr. Brannigan said MOBYUS is poised to produce a large dataset that can address retrospective questions and potentially prospectively collect data to answer prospective questions.
 

 

 

Clinical Implications

Dr. Lundy said between 100 and 200 practicing reproductive urologists across the country regularly communicate with each other. He first raised the idea of creating a consortium with friends and colleagues and then discussed it at scientific meetings. The network steadily gained traction and is continuing to add institutions. “There’s a great deal of excitement in our community about this,” Dr. Lundy said.

MOBYUS, which is IRB approved, has a database with data from more than 4000 patients. The consortium has not received any industry funding but plans to pursue grant applications in the future. 

The MOBYUS website includes a list of its member institutions and leading investigators and its three proof-of-principle manuscripts published to date. The team identifies new research projects at monthly virtual meetings.

Dr. Lundy said MOBYUS’ main goal is to identify a treatment that will change the avenue available for a couple to get pregnant. For example, he said, if a man has zero sperm in his semen, he often requires surgery to find and remove sperm from the testicle. If medications can produce low sperm counts, sperm found in the ejaculate can be frozen and surgery can be avoided. 

Dr. Lundy said MOBYUS’ two publications on medical therapies have changed clinical practice, as he and many others have begun to provide the treatments on more carefully selected patients with good outcomes. 

Dr. Nam said patients want to know what they can expect from therapies and these research findings will have “a lot of clinical implications” in counseling them. 

The MOBYUS team will be describing the consortium and its goals in an abstract presentation at the American Society for Reproductive Medicine Scientific Congress & Expo, to be held October 19-23 in Denver, Colorado, and in an oral presentation at the Sexual Medicine Society of North America’s annual fall scientific meeting, to be held October 17-20 in Scottsdale, Arizona.

The sources in this story reported no relevant financial conflicts of interest.
 

A version of this article first appeared on Medscape.com.

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A study by researchers at two academic medical centers determined which infertile men may benefit from treatment with anastrozole. They found that those with azoospermia (no sperm in their ejaculate) rarely respond to the drug while those with baseline nonazoospermia, lower levels of luteinizing hormone and follicle-stimulating hormone, and higher levels of testosterone are more likely to obtain improvement in semen parameters.

The retrospective cohort study of 90 infertile men, published in the October 2023 issue of Fertility and Sterility, was conducted by researchers at Cleveland Clinic and the University of California Los Angeles. It is the first project of Male Organ Biology Yielding United Science (MOBYUS), a new, multi-institutional research consortium seeking to better understand male infertility and expand treatment options. 

Launched last year, MOBYUS now includes investigators from 14 large US-based academic medical centers. They select research topics and search their patient population for eligible participants and share resulting deidentified data for analysis and publication. 

Members of the consortium conducted another study which found that combination therapy with clomiphene citrate and anastrozole was associated with modest benefits on semen parameters, including volume, concentration, and motility after treatment, compared with anastrozole monotherapy. That retrospective cohort analysis of 21 men was published online in Translational Andrology and Urology in February. 

“We know that if we treat the right men with these medications, about 40% will improve their fertility, but only if we choose the right population. These studies identified those groups,” Scott Lundy, MD, PhD, section head of male infertility at Cleveland Clinic’s Glickman Urological and Kidney Institute in Cleveland, and director of the clinic’s andrology lab, told Medscape Medical News. 

Dr. Lundy, a coauthor of both papers, conceived MOBYUS to overcome constraints in research into male infertility. Many studies in the field are limited by small numbers of patients and retrospective designs, he said. “I sought to develop a collaborative network of reproductive urologists and hospitals like ours, so that we can combine our data and generate large series of data, even for rare patient groups, so that we can improve their patient outcomes,” he said.

“Our treatments are in the stone age in many ways. We are far behind other types of treatment for other conditions, including female infertility,” Dr. Lundy added. “And so, our goal is to identify new and data-driven ways to help these men become fathers, whether those are medications or surgeries or combinations of treatments.”
 

Moving the Field Forward

The name of the consortium is a cheeky play on Moby Dick, the most famous sperm whale. MOBYUS investigators conveyed the challenges that patients, doctors, and researchers experience in an article published last December in the Journal of Urology

They noted that 1 in 6 couples will have difficulty conceiving a child, with male-factor infertility contributing to at least half of such cases. The lead author, Catherine Nam, MD, a principal investigator for MOBYUS at the University of Michigan, in Ann Arbor, said the paper is unusual for a medical journal, as it provides personal accounts of the psychological and emotional aspects of infertility as well as factors that have led to a global decline in sperm counts among men and the financial costs of treatment.

Dr. Nam said infertility is a sensitive topic for couples and families to talk about and there is less conversation about male infertility than female infertility. “I think the only way that we can be able to make headway, both in terms of protocol and policy outcomes, is to really start to raise awareness,” said Dr. Nam, who is doing a fellowship in clinical andrology at Northwestern University, in Chicago.

Dr. Nam said the collaborative environment of MOBYUS has enabled her to learn about different practice patterns across different institutions. “For someone like me just starting off my professional career in male infertility, an opportunity like this is incredibly exciting and makes me very hopeful about the kinds of collaboration and scientific discovery that we’re able to do together as a group,” she said.

Robert E. Brannigan, MD, vice chair of clinical urology at Northwestern University Feinberg School of Medicine, Chicago, said the consortium is drawing on the strength of many individual centers and allowing them to study critical issues in the field. The group’s outstanding clinicians and scientists “are looking to move the field forward, and I applaud them and I’m eager to watch things unfold,” said Dr. Brannigan, who is not a member of the group.

Dr. Brannigan noted that for a large percentage of patients, clinicians cannot identify the root cause of their impaired reproductive potential. Some people may have a recognizable decline in semen parameters over time without clear lifestyle issues or clear hormonal imbalances or anatomical problems. 

“And the question is, what’s causing that? Is there some as yet unrecognized environmental exposure? Is there some underlying genetic issue that’s predisposing to decline in semen parameters over time? We see this, and we don’t have answers,” Dr. Brannigan said. 

“This is where I think the potential power of a large group like MOBYUS comes into play,” he added. “When you’ve got large datasets and very granular information about your patients, sometimes that can provide the opportunity for insights that can then answer the question, ‘What is the root cause of my patient’s challenges?’ ”

Dr. Brannigan was part of a previous group, the Andrology Research Consortium, which collected data on patient history and treatment through a standardized questionnaire. The consortium was founded in 2013 by the Society for the Study of Male Reproduction, a specialty section of the American Urological Association, to obtain data on the demographics, clinical characteristics, and fertility histories and therapies of men referred for a male infertility investigation at clinics across North America. 

Clinicians analyzed data from the questionnaires, which a team in Toronto collected and stored, in a series of studies, including a comparison of fertility characteristics between men in the United States and Canada. Dr. Brannigan said MOBYUS is poised to produce a large dataset that can address retrospective questions and potentially prospectively collect data to answer prospective questions.
 

 

 

Clinical Implications

Dr. Lundy said between 100 and 200 practicing reproductive urologists across the country regularly communicate with each other. He first raised the idea of creating a consortium with friends and colleagues and then discussed it at scientific meetings. The network steadily gained traction and is continuing to add institutions. “There’s a great deal of excitement in our community about this,” Dr. Lundy said.

MOBYUS, which is IRB approved, has a database with data from more than 4000 patients. The consortium has not received any industry funding but plans to pursue grant applications in the future. 

The MOBYUS website includes a list of its member institutions and leading investigators and its three proof-of-principle manuscripts published to date. The team identifies new research projects at monthly virtual meetings.

Dr. Lundy said MOBYUS’ main goal is to identify a treatment that will change the avenue available for a couple to get pregnant. For example, he said, if a man has zero sperm in his semen, he often requires surgery to find and remove sperm from the testicle. If medications can produce low sperm counts, sperm found in the ejaculate can be frozen and surgery can be avoided. 

Dr. Lundy said MOBYUS’ two publications on medical therapies have changed clinical practice, as he and many others have begun to provide the treatments on more carefully selected patients with good outcomes. 

Dr. Nam said patients want to know what they can expect from therapies and these research findings will have “a lot of clinical implications” in counseling them. 

The MOBYUS team will be describing the consortium and its goals in an abstract presentation at the American Society for Reproductive Medicine Scientific Congress & Expo, to be held October 19-23 in Denver, Colorado, and in an oral presentation at the Sexual Medicine Society of North America’s annual fall scientific meeting, to be held October 17-20 in Scottsdale, Arizona.

The sources in this story reported no relevant financial conflicts of interest.
 

A version of this article first appeared on Medscape.com.

A study by researchers at two academic medical centers determined which infertile men may benefit from treatment with anastrozole. They found that those with azoospermia (no sperm in their ejaculate) rarely respond to the drug while those with baseline nonazoospermia, lower levels of luteinizing hormone and follicle-stimulating hormone, and higher levels of testosterone are more likely to obtain improvement in semen parameters.

The retrospective cohort study of 90 infertile men, published in the October 2023 issue of Fertility and Sterility, was conducted by researchers at Cleveland Clinic and the University of California Los Angeles. It is the first project of Male Organ Biology Yielding United Science (MOBYUS), a new, multi-institutional research consortium seeking to better understand male infertility and expand treatment options. 

Launched last year, MOBYUS now includes investigators from 14 large US-based academic medical centers. They select research topics and search their patient population for eligible participants and share resulting deidentified data for analysis and publication. 

Members of the consortium conducted another study which found that combination therapy with clomiphene citrate and anastrozole was associated with modest benefits on semen parameters, including volume, concentration, and motility after treatment, compared with anastrozole monotherapy. That retrospective cohort analysis of 21 men was published online in Translational Andrology and Urology in February. 

“We know that if we treat the right men with these medications, about 40% will improve their fertility, but only if we choose the right population. These studies identified those groups,” Scott Lundy, MD, PhD, section head of male infertility at Cleveland Clinic’s Glickman Urological and Kidney Institute in Cleveland, and director of the clinic’s andrology lab, told Medscape Medical News. 

Dr. Lundy, a coauthor of both papers, conceived MOBYUS to overcome constraints in research into male infertility. Many studies in the field are limited by small numbers of patients and retrospective designs, he said. “I sought to develop a collaborative network of reproductive urologists and hospitals like ours, so that we can combine our data and generate large series of data, even for rare patient groups, so that we can improve their patient outcomes,” he said.

“Our treatments are in the stone age in many ways. We are far behind other types of treatment for other conditions, including female infertility,” Dr. Lundy added. “And so, our goal is to identify new and data-driven ways to help these men become fathers, whether those are medications or surgeries or combinations of treatments.”
 

Moving the Field Forward

The name of the consortium is a cheeky play on Moby Dick, the most famous sperm whale. MOBYUS investigators conveyed the challenges that patients, doctors, and researchers experience in an article published last December in the Journal of Urology

They noted that 1 in 6 couples will have difficulty conceiving a child, with male-factor infertility contributing to at least half of such cases. The lead author, Catherine Nam, MD, a principal investigator for MOBYUS at the University of Michigan, in Ann Arbor, said the paper is unusual for a medical journal, as it provides personal accounts of the psychological and emotional aspects of infertility as well as factors that have led to a global decline in sperm counts among men and the financial costs of treatment.

Dr. Nam said infertility is a sensitive topic for couples and families to talk about and there is less conversation about male infertility than female infertility. “I think the only way that we can be able to make headway, both in terms of protocol and policy outcomes, is to really start to raise awareness,” said Dr. Nam, who is doing a fellowship in clinical andrology at Northwestern University, in Chicago.

Dr. Nam said the collaborative environment of MOBYUS has enabled her to learn about different practice patterns across different institutions. “For someone like me just starting off my professional career in male infertility, an opportunity like this is incredibly exciting and makes me very hopeful about the kinds of collaboration and scientific discovery that we’re able to do together as a group,” she said.

Robert E. Brannigan, MD, vice chair of clinical urology at Northwestern University Feinberg School of Medicine, Chicago, said the consortium is drawing on the strength of many individual centers and allowing them to study critical issues in the field. The group’s outstanding clinicians and scientists “are looking to move the field forward, and I applaud them and I’m eager to watch things unfold,” said Dr. Brannigan, who is not a member of the group.

Dr. Brannigan noted that for a large percentage of patients, clinicians cannot identify the root cause of their impaired reproductive potential. Some people may have a recognizable decline in semen parameters over time without clear lifestyle issues or clear hormonal imbalances or anatomical problems. 

“And the question is, what’s causing that? Is there some as yet unrecognized environmental exposure? Is there some underlying genetic issue that’s predisposing to decline in semen parameters over time? We see this, and we don’t have answers,” Dr. Brannigan said. 

“This is where I think the potential power of a large group like MOBYUS comes into play,” he added. “When you’ve got large datasets and very granular information about your patients, sometimes that can provide the opportunity for insights that can then answer the question, ‘What is the root cause of my patient’s challenges?’ ”

Dr. Brannigan was part of a previous group, the Andrology Research Consortium, which collected data on patient history and treatment through a standardized questionnaire. The consortium was founded in 2013 by the Society for the Study of Male Reproduction, a specialty section of the American Urological Association, to obtain data on the demographics, clinical characteristics, and fertility histories and therapies of men referred for a male infertility investigation at clinics across North America. 

Clinicians analyzed data from the questionnaires, which a team in Toronto collected and stored, in a series of studies, including a comparison of fertility characteristics between men in the United States and Canada. Dr. Brannigan said MOBYUS is poised to produce a large dataset that can address retrospective questions and potentially prospectively collect data to answer prospective questions.
 

 

 

Clinical Implications

Dr. Lundy said between 100 and 200 practicing reproductive urologists across the country regularly communicate with each other. He first raised the idea of creating a consortium with friends and colleagues and then discussed it at scientific meetings. The network steadily gained traction and is continuing to add institutions. “There’s a great deal of excitement in our community about this,” Dr. Lundy said.

MOBYUS, which is IRB approved, has a database with data from more than 4000 patients. The consortium has not received any industry funding but plans to pursue grant applications in the future. 

The MOBYUS website includes a list of its member institutions and leading investigators and its three proof-of-principle manuscripts published to date. The team identifies new research projects at monthly virtual meetings.

Dr. Lundy said MOBYUS’ main goal is to identify a treatment that will change the avenue available for a couple to get pregnant. For example, he said, if a man has zero sperm in his semen, he often requires surgery to find and remove sperm from the testicle. If medications can produce low sperm counts, sperm found in the ejaculate can be frozen and surgery can be avoided. 

Dr. Lundy said MOBYUS’ two publications on medical therapies have changed clinical practice, as he and many others have begun to provide the treatments on more carefully selected patients with good outcomes. 

Dr. Nam said patients want to know what they can expect from therapies and these research findings will have “a lot of clinical implications” in counseling them. 

The MOBYUS team will be describing the consortium and its goals in an abstract presentation at the American Society for Reproductive Medicine Scientific Congress & Expo, to be held October 19-23 in Denver, Colorado, and in an oral presentation at the Sexual Medicine Society of North America’s annual fall scientific meeting, to be held October 17-20 in Scottsdale, Arizona.

The sources in this story reported no relevant financial conflicts of interest.
 

A version of this article first appeared on Medscape.com.

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To Live Longer, Get to Know Your Toes

Article Type
Changed
Wed, 08/21/2024 - 13:23

The more flexible you are as you age, the longer you’re likely to live. That’s the conclusion of a new study that associated increased flexibility in middle age with lower odds of mortality over the next dozen or so years.

The prospective cohort study, which evaluated the flexibility of more than 3100 men and women in Brazil, found body flexibility was strongly and inversely associated with mortality risk over a 13-year follow-up period.

Claudio Gil Araújo, MD, PhD, the research director of the Exercise Medicine Clinic-CLINIMEX in Rio de Janeiro, who led the study, said his group was not surprised by the results. “We found what we expected. Reduced flexibility was related to poor survival,” he said.

The findings, published in the Scandinavian Journal of Medicine & Science in Sports, used data from 2087 men and 1052 women who underwent a medical-functional evaluation at CLINIMEX. They received a body flexibility score, called the Flexindex, based on range of motion in 20 movements in seven joints, with a minimum score of 0 and a maximum score of 80.

Among the 3139 participants, there were 302 deaths (9.6%) during a mean follow-up of 12.9 years, with cardiovascular diseases and cancer the most common underlying causes in men and women, respectively.

“The probability of death during nearly 13 years of follow-up was close to 1% when Flexindex scores exceed 49 for men and 56 for women,” Dr. Araújo told this news organization. “On the other hand, for men and women placed in the lower 10 percent of Flexindex scores, death rates were, respectively, 26.9% and 18.2%.”

Barry Franklin, PhD, director of preventive cardiology and cardiac rehabilitation at Corewell Health William Beaumont University Hospital in Royal Oak, Michigan, and a co-author of the new study, said men with the poorest flexibility were nearly twice as likely to die over the follow-up period than men with high flexibility. Women with the poorest flexibility were almost five times more likely to die than those with high flexibility.
 

Flexibility Assessment and Training

Dr. Araújo opened CLINIMEX in 1994, and since then, its staff of five physicians have evaluated more than 10,000 individuals using the Flexitest. Dr. Araújo has published two previous studies on flexibility. The first showed that the ability to rise from a sitting position on the floor is a strong predictor of longevity, and the second demonstrated that the inability to stand on one leg for at least 10 seconds is linked to an increased risk for death over 7 years.

Dr. Araújo and his colleagues believe the current study is the first to assess the association between levels of body flexibility and mortality. But the observational analysis was unable to establish causality, and therefore, they could not show a definitive mechanism to explain the association between low levels of flexibility and premature mortality.

The authors noted several limitations of their study. The participants were primarily affluent White people, and the researchers did not control for the time of day flexibility was measured or for variables such as diet and physical activity. They also acknowledged reduced flexibility may be a consequence of poor lifestyle habits rather than a causal risk factor for mortality.

Jonathan Bonnet, MD, MPH, an exercise expert at the Stanford Center on Longevity Lifestyle Medicine in California, said the researchers used a more robust evaluation of flexibility than a traditional sit-and-reach test. However, he expressed concern that the primary comparisons were of the upper and lower 10% of performers and that the average differences in Flexindex scores between people who died and those who survived were only a handful of points in an 80-point test.

“People who are not flexible probably have other health-related issues that limit their mobility and those who are very flexible are either genetically different from inflexible individuals or are doing something to maintain or increase their flexibility to a high level,” Dr. Bonnet said. “Not knowing how active or inactive people are at baseline when flexibility was assessed or over the duration of the study limits how confident we can be that flexibility is the cause of mortality.”

Dr. Bonnet, a member of the American College of Lifestyle Medicine, noted that the latest guidelines on physical activity from the US Department of Health and Human Services do not include recommendations on stretching, given the lack of data demonstrating its specific health benefits. While maintaining mobility and range of motion in joints is important for long-term health, he said the new study does not provide sufficient evidence to recommend stretching as a way to reduce mortality.

“Until there are more data that can show a cause-and-effect relationship with stretching and health outcomes, time is better spent doing aerobic and muscle-strengthening activities,” Dr. Bonnet said.

Dr. Franklin said future studies could better account for missing potential confounders like physical activity and whether individuals were taking protective medications, such as aspirin, cholesterol-lowering drugs, or beta-blockers. Studies also are needed to assess whether training-induced gains in flexibility are specifically related to increases in survival and whether their findings apply to people over the age of 65, he said.

The current findings “give us some additional ammo to say, ‘Wow, being more flexible may, in fact, improve long-term survival or outcomes’,” Dr. Franklin said. Regardless, flexibility still “improves quality of life, it improves balance and reduces the potential for falls, and all those things make it worthy of better recognition or appreciation by the general public and clinicians,” he added.

Dr. Araújo said he would like his research to influence people’s health. “While to exercise regularly is advisable, what really matters is to be physically fit and not only in aerobic or strength fitness but also in flexibility,” he said. “The study is adding a new and, I believe, important ‘relevant for survival’ label on flexibility assessment and training.”
 

 

 

Recommended Stretches for Increased Mobility and Flexibility

By Matthew Accetta, MS, exercise physiologist at Hospital for Special Surgery in New York City

Hip Hug Stretch

This stretch effectively targets the gluteal muscles, piriformis, and other deep hip rotators, which can become tight from prolonged sitting or lack of movement. Tight hips can contribute to lower back pain. By stretching the hip muscles, you can reduce tension and pressure on the lower back. Regularly performing this stretch helps to improve hip joint mobility, which is essential for maintaining functional movement and preventing stiffness as you age.

  • Start by sitting and crossing one leg over the other.
  • Hug your knee to your chest.
  • Focus on keeping your chest up to feel the stretch in the glute.
  • Hold for 20-30 seconds.
  • Repeat on the opposite side.

Half Kneeling Hip Flexor Stretch

As people age, they often spend more time sitting, which can lead to tight hip flexors. This stretch specifically targets these muscles, helping to alleviate tightness and improve mobility. Tight hip flexors can contribute to poor posture by pulling the pelvis into an anterior tilt, which can lead to lower back pain and other postural issues. Stretching these muscles helps to counteract this effect and promote better posture.

  • Kneel on a pad (the side you kneel on is the side being stretched); position the front leg far enough away so the front knee stays behind the toes.
  • With a tall posture, engage your abdominals and tuck your tailbone by engaging your glutes until a stretch is felt in the front of the thigh on the kneeling leg.
  • Hold for 20-30 seconds.
  • Repeat on the opposite side.

Calf Stretch at a Wall

Tight calf muscles can lead to discomfort and limit the range of motion in the ankles. Stretching the calves helps to maintain and improve flexibility in these muscles. Flexible calf muscles contribute to better mobility in the ankles and feet, making daily activities like walking, climbing stairs, and running more comfortable. Tight calves can increase the risk for strains, Achilles tendinitis, and other injuries. Stand facing a wall with your hands on the wall at about eye level. Put the leg you want to stretch about a step behind your other leg.

  • Stand in a staggered stance in front of a wall with your arms stretched out.
  • Keeping your back heel on the floor, bend your front knee until you feel a stretch in the back leg.
  • Hold the stretch for 15-30 seconds.
  • Repeat on the opposite side.

Standing Quad Stretch

Regularly stretching the quadriceps helps maintain and improve flexibility in these muscles, which is crucial for overall lower body mobility. Flexible quadriceps are less prone to strains and injuries. Tight quadriceps can contribute to knee pain and discomfort by exerting excessive pressure on the knee joint. Stretching these muscles helps alleviate this pressure and reduce knee pain.

  • While standing, hold onto a countertop or chair back to assist in balance.
  • Bend your knee by grasping your ankle with one hand and moving your foot toward your buttocks.
  • Gently pull on your ankle to bend your knee as far as possible.
  • Maintain the position for 30 seconds.
  • Repeat on the opposite side.

Seated Hamstring Stretch

Regularly stretching the hamstrings helps maintain and improve their flexibility, which is crucial for the overall mobility of the lower body. Tight hamstrings can contribute to lower back pain by pulling on the pelvis and causing an anterior pelvic tilt. Stretching these muscles can help alleviate tension and reduce back pain. Hamstring flexibility helps to contribute to a better range of motion in the hip and knee joints, making daily activities such as walking, bending, and reaching easier.

  • Sit on the front half of a firm chair with your back straight.
  • Extend one leg out in front of you with your heel on the floor and your toes pointed up.
  • Bend the opposite knee so that your foot is flat on the floor.
  • Center your chest over your straight leg.
  • Slowly lean forward at the hips until you feel a stretch in the back of your thigh.
  • Hold the stretch for 30 seconds.
  • Slowly return to your original position and repeat on the opposite side.

The sources in this story reported no relevant financial conflicts of interest.

A version of this article appeared on Medscape.com.

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The more flexible you are as you age, the longer you’re likely to live. That’s the conclusion of a new study that associated increased flexibility in middle age with lower odds of mortality over the next dozen or so years.

The prospective cohort study, which evaluated the flexibility of more than 3100 men and women in Brazil, found body flexibility was strongly and inversely associated with mortality risk over a 13-year follow-up period.

Claudio Gil Araújo, MD, PhD, the research director of the Exercise Medicine Clinic-CLINIMEX in Rio de Janeiro, who led the study, said his group was not surprised by the results. “We found what we expected. Reduced flexibility was related to poor survival,” he said.

The findings, published in the Scandinavian Journal of Medicine & Science in Sports, used data from 2087 men and 1052 women who underwent a medical-functional evaluation at CLINIMEX. They received a body flexibility score, called the Flexindex, based on range of motion in 20 movements in seven joints, with a minimum score of 0 and a maximum score of 80.

Among the 3139 participants, there were 302 deaths (9.6%) during a mean follow-up of 12.9 years, with cardiovascular diseases and cancer the most common underlying causes in men and women, respectively.

“The probability of death during nearly 13 years of follow-up was close to 1% when Flexindex scores exceed 49 for men and 56 for women,” Dr. Araújo told this news organization. “On the other hand, for men and women placed in the lower 10 percent of Flexindex scores, death rates were, respectively, 26.9% and 18.2%.”

Barry Franklin, PhD, director of preventive cardiology and cardiac rehabilitation at Corewell Health William Beaumont University Hospital in Royal Oak, Michigan, and a co-author of the new study, said men with the poorest flexibility were nearly twice as likely to die over the follow-up period than men with high flexibility. Women with the poorest flexibility were almost five times more likely to die than those with high flexibility.
 

Flexibility Assessment and Training

Dr. Araújo opened CLINIMEX in 1994, and since then, its staff of five physicians have evaluated more than 10,000 individuals using the Flexitest. Dr. Araújo has published two previous studies on flexibility. The first showed that the ability to rise from a sitting position on the floor is a strong predictor of longevity, and the second demonstrated that the inability to stand on one leg for at least 10 seconds is linked to an increased risk for death over 7 years.

Dr. Araújo and his colleagues believe the current study is the first to assess the association between levels of body flexibility and mortality. But the observational analysis was unable to establish causality, and therefore, they could not show a definitive mechanism to explain the association between low levels of flexibility and premature mortality.

The authors noted several limitations of their study. The participants were primarily affluent White people, and the researchers did not control for the time of day flexibility was measured or for variables such as diet and physical activity. They also acknowledged reduced flexibility may be a consequence of poor lifestyle habits rather than a causal risk factor for mortality.

Jonathan Bonnet, MD, MPH, an exercise expert at the Stanford Center on Longevity Lifestyle Medicine in California, said the researchers used a more robust evaluation of flexibility than a traditional sit-and-reach test. However, he expressed concern that the primary comparisons were of the upper and lower 10% of performers and that the average differences in Flexindex scores between people who died and those who survived were only a handful of points in an 80-point test.

“People who are not flexible probably have other health-related issues that limit their mobility and those who are very flexible are either genetically different from inflexible individuals or are doing something to maintain or increase their flexibility to a high level,” Dr. Bonnet said. “Not knowing how active or inactive people are at baseline when flexibility was assessed or over the duration of the study limits how confident we can be that flexibility is the cause of mortality.”

Dr. Bonnet, a member of the American College of Lifestyle Medicine, noted that the latest guidelines on physical activity from the US Department of Health and Human Services do not include recommendations on stretching, given the lack of data demonstrating its specific health benefits. While maintaining mobility and range of motion in joints is important for long-term health, he said the new study does not provide sufficient evidence to recommend stretching as a way to reduce mortality.

“Until there are more data that can show a cause-and-effect relationship with stretching and health outcomes, time is better spent doing aerobic and muscle-strengthening activities,” Dr. Bonnet said.

Dr. Franklin said future studies could better account for missing potential confounders like physical activity and whether individuals were taking protective medications, such as aspirin, cholesterol-lowering drugs, or beta-blockers. Studies also are needed to assess whether training-induced gains in flexibility are specifically related to increases in survival and whether their findings apply to people over the age of 65, he said.

The current findings “give us some additional ammo to say, ‘Wow, being more flexible may, in fact, improve long-term survival or outcomes’,” Dr. Franklin said. Regardless, flexibility still “improves quality of life, it improves balance and reduces the potential for falls, and all those things make it worthy of better recognition or appreciation by the general public and clinicians,” he added.

Dr. Araújo said he would like his research to influence people’s health. “While to exercise regularly is advisable, what really matters is to be physically fit and not only in aerobic or strength fitness but also in flexibility,” he said. “The study is adding a new and, I believe, important ‘relevant for survival’ label on flexibility assessment and training.”
 

 

 

Recommended Stretches for Increased Mobility and Flexibility

By Matthew Accetta, MS, exercise physiologist at Hospital for Special Surgery in New York City

Hip Hug Stretch

This stretch effectively targets the gluteal muscles, piriformis, and other deep hip rotators, which can become tight from prolonged sitting or lack of movement. Tight hips can contribute to lower back pain. By stretching the hip muscles, you can reduce tension and pressure on the lower back. Regularly performing this stretch helps to improve hip joint mobility, which is essential for maintaining functional movement and preventing stiffness as you age.

  • Start by sitting and crossing one leg over the other.
  • Hug your knee to your chest.
  • Focus on keeping your chest up to feel the stretch in the glute.
  • Hold for 20-30 seconds.
  • Repeat on the opposite side.

Half Kneeling Hip Flexor Stretch

As people age, they often spend more time sitting, which can lead to tight hip flexors. This stretch specifically targets these muscles, helping to alleviate tightness and improve mobility. Tight hip flexors can contribute to poor posture by pulling the pelvis into an anterior tilt, which can lead to lower back pain and other postural issues. Stretching these muscles helps to counteract this effect and promote better posture.

  • Kneel on a pad (the side you kneel on is the side being stretched); position the front leg far enough away so the front knee stays behind the toes.
  • With a tall posture, engage your abdominals and tuck your tailbone by engaging your glutes until a stretch is felt in the front of the thigh on the kneeling leg.
  • Hold for 20-30 seconds.
  • Repeat on the opposite side.

Calf Stretch at a Wall

Tight calf muscles can lead to discomfort and limit the range of motion in the ankles. Stretching the calves helps to maintain and improve flexibility in these muscles. Flexible calf muscles contribute to better mobility in the ankles and feet, making daily activities like walking, climbing stairs, and running more comfortable. Tight calves can increase the risk for strains, Achilles tendinitis, and other injuries. Stand facing a wall with your hands on the wall at about eye level. Put the leg you want to stretch about a step behind your other leg.

  • Stand in a staggered stance in front of a wall with your arms stretched out.
  • Keeping your back heel on the floor, bend your front knee until you feel a stretch in the back leg.
  • Hold the stretch for 15-30 seconds.
  • Repeat on the opposite side.

Standing Quad Stretch

Regularly stretching the quadriceps helps maintain and improve flexibility in these muscles, which is crucial for overall lower body mobility. Flexible quadriceps are less prone to strains and injuries. Tight quadriceps can contribute to knee pain and discomfort by exerting excessive pressure on the knee joint. Stretching these muscles helps alleviate this pressure and reduce knee pain.

  • While standing, hold onto a countertop or chair back to assist in balance.
  • Bend your knee by grasping your ankle with one hand and moving your foot toward your buttocks.
  • Gently pull on your ankle to bend your knee as far as possible.
  • Maintain the position for 30 seconds.
  • Repeat on the opposite side.

Seated Hamstring Stretch

Regularly stretching the hamstrings helps maintain and improve their flexibility, which is crucial for the overall mobility of the lower body. Tight hamstrings can contribute to lower back pain by pulling on the pelvis and causing an anterior pelvic tilt. Stretching these muscles can help alleviate tension and reduce back pain. Hamstring flexibility helps to contribute to a better range of motion in the hip and knee joints, making daily activities such as walking, bending, and reaching easier.

  • Sit on the front half of a firm chair with your back straight.
  • Extend one leg out in front of you with your heel on the floor and your toes pointed up.
  • Bend the opposite knee so that your foot is flat on the floor.
  • Center your chest over your straight leg.
  • Slowly lean forward at the hips until you feel a stretch in the back of your thigh.
  • Hold the stretch for 30 seconds.
  • Slowly return to your original position and repeat on the opposite side.

The sources in this story reported no relevant financial conflicts of interest.

A version of this article appeared on Medscape.com.

The more flexible you are as you age, the longer you’re likely to live. That’s the conclusion of a new study that associated increased flexibility in middle age with lower odds of mortality over the next dozen or so years.

The prospective cohort study, which evaluated the flexibility of more than 3100 men and women in Brazil, found body flexibility was strongly and inversely associated with mortality risk over a 13-year follow-up period.

Claudio Gil Araújo, MD, PhD, the research director of the Exercise Medicine Clinic-CLINIMEX in Rio de Janeiro, who led the study, said his group was not surprised by the results. “We found what we expected. Reduced flexibility was related to poor survival,” he said.

The findings, published in the Scandinavian Journal of Medicine & Science in Sports, used data from 2087 men and 1052 women who underwent a medical-functional evaluation at CLINIMEX. They received a body flexibility score, called the Flexindex, based on range of motion in 20 movements in seven joints, with a minimum score of 0 and a maximum score of 80.

Among the 3139 participants, there were 302 deaths (9.6%) during a mean follow-up of 12.9 years, with cardiovascular diseases and cancer the most common underlying causes in men and women, respectively.

“The probability of death during nearly 13 years of follow-up was close to 1% when Flexindex scores exceed 49 for men and 56 for women,” Dr. Araújo told this news organization. “On the other hand, for men and women placed in the lower 10 percent of Flexindex scores, death rates were, respectively, 26.9% and 18.2%.”

Barry Franklin, PhD, director of preventive cardiology and cardiac rehabilitation at Corewell Health William Beaumont University Hospital in Royal Oak, Michigan, and a co-author of the new study, said men with the poorest flexibility were nearly twice as likely to die over the follow-up period than men with high flexibility. Women with the poorest flexibility were almost five times more likely to die than those with high flexibility.
 

Flexibility Assessment and Training

Dr. Araújo opened CLINIMEX in 1994, and since then, its staff of five physicians have evaluated more than 10,000 individuals using the Flexitest. Dr. Araújo has published two previous studies on flexibility. The first showed that the ability to rise from a sitting position on the floor is a strong predictor of longevity, and the second demonstrated that the inability to stand on one leg for at least 10 seconds is linked to an increased risk for death over 7 years.

Dr. Araújo and his colleagues believe the current study is the first to assess the association between levels of body flexibility and mortality. But the observational analysis was unable to establish causality, and therefore, they could not show a definitive mechanism to explain the association between low levels of flexibility and premature mortality.

The authors noted several limitations of their study. The participants were primarily affluent White people, and the researchers did not control for the time of day flexibility was measured or for variables such as diet and physical activity. They also acknowledged reduced flexibility may be a consequence of poor lifestyle habits rather than a causal risk factor for mortality.

Jonathan Bonnet, MD, MPH, an exercise expert at the Stanford Center on Longevity Lifestyle Medicine in California, said the researchers used a more robust evaluation of flexibility than a traditional sit-and-reach test. However, he expressed concern that the primary comparisons were of the upper and lower 10% of performers and that the average differences in Flexindex scores between people who died and those who survived were only a handful of points in an 80-point test.

“People who are not flexible probably have other health-related issues that limit their mobility and those who are very flexible are either genetically different from inflexible individuals or are doing something to maintain or increase their flexibility to a high level,” Dr. Bonnet said. “Not knowing how active or inactive people are at baseline when flexibility was assessed or over the duration of the study limits how confident we can be that flexibility is the cause of mortality.”

Dr. Bonnet, a member of the American College of Lifestyle Medicine, noted that the latest guidelines on physical activity from the US Department of Health and Human Services do not include recommendations on stretching, given the lack of data demonstrating its specific health benefits. While maintaining mobility and range of motion in joints is important for long-term health, he said the new study does not provide sufficient evidence to recommend stretching as a way to reduce mortality.

“Until there are more data that can show a cause-and-effect relationship with stretching and health outcomes, time is better spent doing aerobic and muscle-strengthening activities,” Dr. Bonnet said.

Dr. Franklin said future studies could better account for missing potential confounders like physical activity and whether individuals were taking protective medications, such as aspirin, cholesterol-lowering drugs, or beta-blockers. Studies also are needed to assess whether training-induced gains in flexibility are specifically related to increases in survival and whether their findings apply to people over the age of 65, he said.

The current findings “give us some additional ammo to say, ‘Wow, being more flexible may, in fact, improve long-term survival or outcomes’,” Dr. Franklin said. Regardless, flexibility still “improves quality of life, it improves balance and reduces the potential for falls, and all those things make it worthy of better recognition or appreciation by the general public and clinicians,” he added.

Dr. Araújo said he would like his research to influence people’s health. “While to exercise regularly is advisable, what really matters is to be physically fit and not only in aerobic or strength fitness but also in flexibility,” he said. “The study is adding a new and, I believe, important ‘relevant for survival’ label on flexibility assessment and training.”
 

 

 

Recommended Stretches for Increased Mobility and Flexibility

By Matthew Accetta, MS, exercise physiologist at Hospital for Special Surgery in New York City

Hip Hug Stretch

This stretch effectively targets the gluteal muscles, piriformis, and other deep hip rotators, which can become tight from prolonged sitting or lack of movement. Tight hips can contribute to lower back pain. By stretching the hip muscles, you can reduce tension and pressure on the lower back. Regularly performing this stretch helps to improve hip joint mobility, which is essential for maintaining functional movement and preventing stiffness as you age.

  • Start by sitting and crossing one leg over the other.
  • Hug your knee to your chest.
  • Focus on keeping your chest up to feel the stretch in the glute.
  • Hold for 20-30 seconds.
  • Repeat on the opposite side.

Half Kneeling Hip Flexor Stretch

As people age, they often spend more time sitting, which can lead to tight hip flexors. This stretch specifically targets these muscles, helping to alleviate tightness and improve mobility. Tight hip flexors can contribute to poor posture by pulling the pelvis into an anterior tilt, which can lead to lower back pain and other postural issues. Stretching these muscles helps to counteract this effect and promote better posture.

  • Kneel on a pad (the side you kneel on is the side being stretched); position the front leg far enough away so the front knee stays behind the toes.
  • With a tall posture, engage your abdominals and tuck your tailbone by engaging your glutes until a stretch is felt in the front of the thigh on the kneeling leg.
  • Hold for 20-30 seconds.
  • Repeat on the opposite side.

Calf Stretch at a Wall

Tight calf muscles can lead to discomfort and limit the range of motion in the ankles. Stretching the calves helps to maintain and improve flexibility in these muscles. Flexible calf muscles contribute to better mobility in the ankles and feet, making daily activities like walking, climbing stairs, and running more comfortable. Tight calves can increase the risk for strains, Achilles tendinitis, and other injuries. Stand facing a wall with your hands on the wall at about eye level. Put the leg you want to stretch about a step behind your other leg.

  • Stand in a staggered stance in front of a wall with your arms stretched out.
  • Keeping your back heel on the floor, bend your front knee until you feel a stretch in the back leg.
  • Hold the stretch for 15-30 seconds.
  • Repeat on the opposite side.

Standing Quad Stretch

Regularly stretching the quadriceps helps maintain and improve flexibility in these muscles, which is crucial for overall lower body mobility. Flexible quadriceps are less prone to strains and injuries. Tight quadriceps can contribute to knee pain and discomfort by exerting excessive pressure on the knee joint. Stretching these muscles helps alleviate this pressure and reduce knee pain.

  • While standing, hold onto a countertop or chair back to assist in balance.
  • Bend your knee by grasping your ankle with one hand and moving your foot toward your buttocks.
  • Gently pull on your ankle to bend your knee as far as possible.
  • Maintain the position for 30 seconds.
  • Repeat on the opposite side.

Seated Hamstring Stretch

Regularly stretching the hamstrings helps maintain and improve their flexibility, which is crucial for the overall mobility of the lower body. Tight hamstrings can contribute to lower back pain by pulling on the pelvis and causing an anterior pelvic tilt. Stretching these muscles can help alleviate tension and reduce back pain. Hamstring flexibility helps to contribute to a better range of motion in the hip and knee joints, making daily activities such as walking, bending, and reaching easier.

  • Sit on the front half of a firm chair with your back straight.
  • Extend one leg out in front of you with your heel on the floor and your toes pointed up.
  • Bend the opposite knee so that your foot is flat on the floor.
  • Center your chest over your straight leg.
  • Slowly lean forward at the hips until you feel a stretch in the back of your thigh.
  • Hold the stretch for 30 seconds.
  • Slowly return to your original position and repeat on the opposite side.

The sources in this story reported no relevant financial conflicts of interest.

A version of this article appeared on Medscape.com.

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DOJ Bars Generic Drug Maker Ranbaxy, Citing Fraud

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DOJ Bars Generic Drug Maker Ranbaxy, Citing Fraud

Generic drug manufacturer Ranbaxy Laboratories Ltd. will have to withdraw all drug applications that contain data generated at one of its facilities in India and relinquish 180-day marketing exclusivity for three pending abbreviated New Drug Applications under a consent decree for permanent injunction filed the U.S. Department of Justice.

The decree follows a lengthy investigation by the DOJ and the Food and Drug Administration that found numerous problems at three Ranbaxy facilities in India and one facility in Gloversville, N.Y.

According to the DOJ, the problems with Ranbaxy's drug manufacturing and testing include failure to keep records showing that drugs had been manufactured properly; failure to investigate evidence indicating that drugs did not meet their specifications; failure to adequately separate the manufacture of penicillin drugs from nonpenicillin drugs in order to prevent cross-contamination; lack of adequate procedures to prevent contamination of sterile drugs; and inadequate testing of drug to ensure that they maintained strength and effectiveness until their expiration date.

The government also said that Ranbaxy submitted false data in drug applications, including backdating tests and submitting test data for which no test samples existed.

The consent decree is unprecedented in its scope, according to DOJ officials.

“This action … is groundbreaking in its international reach – it requires the company to make fundamental changes to its plants in both the United States and India,” Assistant Attorney General Tony West said in a statement. “Submitting false data to the FDA in drug applications will not be tolerated.”

Ranbaxy said in a statement that the consent decree would not affect the company's recently launched generic atorvastatin, because it is not manufactured in the facilities cited in the decree.

“Today's announcement is the next step in the process of finalizing our agreement with the FDA to resolve this legacy issue,” according to Arun Sawhney, managing director of Ranbaxy Laboratories. “We are pleased with the progress we have made in upgrading and enhancing the quality of our business and manufacturing processes and remain committed to ensuring that all of our facilities and products meet the high standards that patients, prescribers, and the public have come to expect from Ranbaxy.”

Ranbaxy announced earlier that it had entered into the consent decree with the FDA and had set aside $500 million to settle the related DOJ investigation. The consent decree itself does not mention the size of the settlement.

Brenda Sandburg is a reporter for “The Pink Sheet.” This news organization and “The Pink Sheet” are owned by Elsevier.

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Generic drug manufacturer Ranbaxy Laboratories Ltd. will have to withdraw all drug applications that contain data generated at one of its facilities in India and relinquish 180-day marketing exclusivity for three pending abbreviated New Drug Applications under a consent decree for permanent injunction filed the U.S. Department of Justice.

The decree follows a lengthy investigation by the DOJ and the Food and Drug Administration that found numerous problems at three Ranbaxy facilities in India and one facility in Gloversville, N.Y.

According to the DOJ, the problems with Ranbaxy's drug manufacturing and testing include failure to keep records showing that drugs had been manufactured properly; failure to investigate evidence indicating that drugs did not meet their specifications; failure to adequately separate the manufacture of penicillin drugs from nonpenicillin drugs in order to prevent cross-contamination; lack of adequate procedures to prevent contamination of sterile drugs; and inadequate testing of drug to ensure that they maintained strength and effectiveness until their expiration date.

The government also said that Ranbaxy submitted false data in drug applications, including backdating tests and submitting test data for which no test samples existed.

The consent decree is unprecedented in its scope, according to DOJ officials.

“This action … is groundbreaking in its international reach – it requires the company to make fundamental changes to its plants in both the United States and India,” Assistant Attorney General Tony West said in a statement. “Submitting false data to the FDA in drug applications will not be tolerated.”

Ranbaxy said in a statement that the consent decree would not affect the company's recently launched generic atorvastatin, because it is not manufactured in the facilities cited in the decree.

“Today's announcement is the next step in the process of finalizing our agreement with the FDA to resolve this legacy issue,” according to Arun Sawhney, managing director of Ranbaxy Laboratories. “We are pleased with the progress we have made in upgrading and enhancing the quality of our business and manufacturing processes and remain committed to ensuring that all of our facilities and products meet the high standards that patients, prescribers, and the public have come to expect from Ranbaxy.”

Ranbaxy announced earlier that it had entered into the consent decree with the FDA and had set aside $500 million to settle the related DOJ investigation. The consent decree itself does not mention the size of the settlement.

Brenda Sandburg is a reporter for “The Pink Sheet.” This news organization and “The Pink Sheet” are owned by Elsevier.

Generic drug manufacturer Ranbaxy Laboratories Ltd. will have to withdraw all drug applications that contain data generated at one of its facilities in India and relinquish 180-day marketing exclusivity for three pending abbreviated New Drug Applications under a consent decree for permanent injunction filed the U.S. Department of Justice.

The decree follows a lengthy investigation by the DOJ and the Food and Drug Administration that found numerous problems at three Ranbaxy facilities in India and one facility in Gloversville, N.Y.

According to the DOJ, the problems with Ranbaxy's drug manufacturing and testing include failure to keep records showing that drugs had been manufactured properly; failure to investigate evidence indicating that drugs did not meet their specifications; failure to adequately separate the manufacture of penicillin drugs from nonpenicillin drugs in order to prevent cross-contamination; lack of adequate procedures to prevent contamination of sterile drugs; and inadequate testing of drug to ensure that they maintained strength and effectiveness until their expiration date.

The government also said that Ranbaxy submitted false data in drug applications, including backdating tests and submitting test data for which no test samples existed.

The consent decree is unprecedented in its scope, according to DOJ officials.

“This action … is groundbreaking in its international reach – it requires the company to make fundamental changes to its plants in both the United States and India,” Assistant Attorney General Tony West said in a statement. “Submitting false data to the FDA in drug applications will not be tolerated.”

Ranbaxy said in a statement that the consent decree would not affect the company's recently launched generic atorvastatin, because it is not manufactured in the facilities cited in the decree.

“Today's announcement is the next step in the process of finalizing our agreement with the FDA to resolve this legacy issue,” according to Arun Sawhney, managing director of Ranbaxy Laboratories. “We are pleased with the progress we have made in upgrading and enhancing the quality of our business and manufacturing processes and remain committed to ensuring that all of our facilities and products meet the high standards that patients, prescribers, and the public have come to expect from Ranbaxy.”

Ranbaxy announced earlier that it had entered into the consent decree with the FDA and had set aside $500 million to settle the related DOJ investigation. The consent decree itself does not mention the size of the settlement.

Brenda Sandburg is a reporter for “The Pink Sheet.” This news organization and “The Pink Sheet” are owned by Elsevier.

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Feds Bar Generic Drug Maker Ranbaxy

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Generic drug manufacturer Ranbaxy Laboratories Ltd. will have to withdraw all drug applications that contain data generated at one of its facilities in India and relinquish 180-day marketing exclusivity for three pending abbreviated New Drug Applications under a consent decree for permanent injunction filed Jan. 25 by the U.S. Department of Justice.

The decree follows a lengthy investigation by the DOJ and the U.S. Food and Drug Administration that found numerous problems at three Ranbaxy facilities in India and one facility in Gloversville, N.Y.

According to the DOJ, the problems with Ranbaxy’s drug manufacturing and testing include failure to keep records showing that drugs had been manufactured properly; failure to investigate evidence indicating that drugs did not meet their specifications; failure to adequately separate the manufacture of penicillin drugs from nonpenicillin drugs in order to prevent cross-contamination; lack of adequate procedures to prevent contamination of sterile drugs; and inadequate testing of drug to ensure that they maintained strength and effectiveness until their expiration date.

The government also said that Ranbaxy submitted false data in drug applications, including backdating tests and submitting test data for which no test samples existed.

The consent decree is unprecedented in its scope, according to DOJ officials.

"This action against Ranbaxy is groundbreaking in its international reach – it requires the company to make fundamental changes to its plants in both the United States and India," Assistant Attorney General Tony West said in a statement. "Submitting false data to the FDA in drug applications will not be tolerated."

Ranbaxy said in a statement that the consent decree would not affect the company’s recently launched generic atorvastatin, because it is not manufactured in the facilities cited in the decree.

"Today’s announcement is the next step in the process of finalizing our agreement with the FDA to resolve this legacy issue," according to Arun Sawhney, managing director of Ranbaxy Laboratories. "We are pleased with the progress we have made in upgrading and enhancing the quality of our business and manufacturing processes and remain committed to ensuring that all of our facilities and products meet the high standards that patients, prescribers and the public have come to expect from Ranbaxy."

Ranbaxy announced earlier that it had entered into the consent decree with the FDA and had set aside $500 million to settle the related DOJ investigation. The consent decree itself does not mention the size of the settlement, although it does note that "if defendants fail to comply with any provision of the law or this decree at any covered facility and/or with respect to any affected application, then [they] ... shall pay to the United States of America $15,000 in liquidated damages for each day such violation continues."

The company also agreed to relinquish the 180-day marketing exclusivity that it might have for three pending generic applications, but did not specify which drugs would be affected. The company also agreed to relinquish any 180-day marketing exclusivity that it may have for several additional generic applications if it fails to meet certain decree requirements by specified dates.

The manufacturing plants cited in the consent decree are the Paonta Sahib, Batamandi, and Dewas facilities, all in India, and the now-closed facility of Ranbaxy’s Ohm Laboratories subsidiary in Gloversville, N.Y. Import alerts for more than 30 products manufactured at the Paonta Sahib and Dewas sites have been in place since September 2008.

The consent decree also prevents Ranbaxy from manufacturing drugs for introduction to the U.S. market and for the President’s Emergency Plan for AIDS Relief Program at the four facilities.

Brenda Sandburg is a reporter for "The Pink Sheet." This news organization and "The Pink Sheet" are owned by Elsevier.

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Generic drug manufacturer Ranbaxy Laboratories Ltd. will have to withdraw all drug applications that contain data generated at one of its facilities in India and relinquish 180-day marketing exclusivity for three pending abbreviated New Drug Applications under a consent decree for permanent injunction filed Jan. 25 by the U.S. Department of Justice.

The decree follows a lengthy investigation by the DOJ and the U.S. Food and Drug Administration that found numerous problems at three Ranbaxy facilities in India and one facility in Gloversville, N.Y.

According to the DOJ, the problems with Ranbaxy’s drug manufacturing and testing include failure to keep records showing that drugs had been manufactured properly; failure to investigate evidence indicating that drugs did not meet their specifications; failure to adequately separate the manufacture of penicillin drugs from nonpenicillin drugs in order to prevent cross-contamination; lack of adequate procedures to prevent contamination of sterile drugs; and inadequate testing of drug to ensure that they maintained strength and effectiveness until their expiration date.

The government also said that Ranbaxy submitted false data in drug applications, including backdating tests and submitting test data for which no test samples existed.

The consent decree is unprecedented in its scope, according to DOJ officials.

"This action against Ranbaxy is groundbreaking in its international reach – it requires the company to make fundamental changes to its plants in both the United States and India," Assistant Attorney General Tony West said in a statement. "Submitting false data to the FDA in drug applications will not be tolerated."

Ranbaxy said in a statement that the consent decree would not affect the company’s recently launched generic atorvastatin, because it is not manufactured in the facilities cited in the decree.

"Today’s announcement is the next step in the process of finalizing our agreement with the FDA to resolve this legacy issue," according to Arun Sawhney, managing director of Ranbaxy Laboratories. "We are pleased with the progress we have made in upgrading and enhancing the quality of our business and manufacturing processes and remain committed to ensuring that all of our facilities and products meet the high standards that patients, prescribers and the public have come to expect from Ranbaxy."

Ranbaxy announced earlier that it had entered into the consent decree with the FDA and had set aside $500 million to settle the related DOJ investigation. The consent decree itself does not mention the size of the settlement, although it does note that "if defendants fail to comply with any provision of the law or this decree at any covered facility and/or with respect to any affected application, then [they] ... shall pay to the United States of America $15,000 in liquidated damages for each day such violation continues."

The company also agreed to relinquish the 180-day marketing exclusivity that it might have for three pending generic applications, but did not specify which drugs would be affected. The company also agreed to relinquish any 180-day marketing exclusivity that it may have for several additional generic applications if it fails to meet certain decree requirements by specified dates.

The manufacturing plants cited in the consent decree are the Paonta Sahib, Batamandi, and Dewas facilities, all in India, and the now-closed facility of Ranbaxy’s Ohm Laboratories subsidiary in Gloversville, N.Y. Import alerts for more than 30 products manufactured at the Paonta Sahib and Dewas sites have been in place since September 2008.

The consent decree also prevents Ranbaxy from manufacturing drugs for introduction to the U.S. market and for the President’s Emergency Plan for AIDS Relief Program at the four facilities.

Brenda Sandburg is a reporter for "The Pink Sheet." This news organization and "The Pink Sheet" are owned by Elsevier.

Generic drug manufacturer Ranbaxy Laboratories Ltd. will have to withdraw all drug applications that contain data generated at one of its facilities in India and relinquish 180-day marketing exclusivity for three pending abbreviated New Drug Applications under a consent decree for permanent injunction filed Jan. 25 by the U.S. Department of Justice.

The decree follows a lengthy investigation by the DOJ and the U.S. Food and Drug Administration that found numerous problems at three Ranbaxy facilities in India and one facility in Gloversville, N.Y.

According to the DOJ, the problems with Ranbaxy’s drug manufacturing and testing include failure to keep records showing that drugs had been manufactured properly; failure to investigate evidence indicating that drugs did not meet their specifications; failure to adequately separate the manufacture of penicillin drugs from nonpenicillin drugs in order to prevent cross-contamination; lack of adequate procedures to prevent contamination of sterile drugs; and inadequate testing of drug to ensure that they maintained strength and effectiveness until their expiration date.

The government also said that Ranbaxy submitted false data in drug applications, including backdating tests and submitting test data for which no test samples existed.

The consent decree is unprecedented in its scope, according to DOJ officials.

"This action against Ranbaxy is groundbreaking in its international reach – it requires the company to make fundamental changes to its plants in both the United States and India," Assistant Attorney General Tony West said in a statement. "Submitting false data to the FDA in drug applications will not be tolerated."

Ranbaxy said in a statement that the consent decree would not affect the company’s recently launched generic atorvastatin, because it is not manufactured in the facilities cited in the decree.

"Today’s announcement is the next step in the process of finalizing our agreement with the FDA to resolve this legacy issue," according to Arun Sawhney, managing director of Ranbaxy Laboratories. "We are pleased with the progress we have made in upgrading and enhancing the quality of our business and manufacturing processes and remain committed to ensuring that all of our facilities and products meet the high standards that patients, prescribers and the public have come to expect from Ranbaxy."

Ranbaxy announced earlier that it had entered into the consent decree with the FDA and had set aside $500 million to settle the related DOJ investigation. The consent decree itself does not mention the size of the settlement, although it does note that "if defendants fail to comply with any provision of the law or this decree at any covered facility and/or with respect to any affected application, then [they] ... shall pay to the United States of America $15,000 in liquidated damages for each day such violation continues."

The company also agreed to relinquish the 180-day marketing exclusivity that it might have for three pending generic applications, but did not specify which drugs would be affected. The company also agreed to relinquish any 180-day marketing exclusivity that it may have for several additional generic applications if it fails to meet certain decree requirements by specified dates.

The manufacturing plants cited in the consent decree are the Paonta Sahib, Batamandi, and Dewas facilities, all in India, and the now-closed facility of Ranbaxy’s Ohm Laboratories subsidiary in Gloversville, N.Y. Import alerts for more than 30 products manufactured at the Paonta Sahib and Dewas sites have been in place since September 2008.

The consent decree also prevents Ranbaxy from manufacturing drugs for introduction to the U.S. market and for the President’s Emergency Plan for AIDS Relief Program at the four facilities.

Brenda Sandburg is a reporter for "The Pink Sheet." This news organization and "The Pink Sheet" are owned by Elsevier.

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Megace Lawsuit Claims Right to Talk to Off-Label Prescribers

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Par Pharmaceutical has filed suit against the Food and Drug Administration, claiming that FDA regulations violate its First Amendment right to provide physicians with information about the on-label use of its appetite stimulant Megace ES.

The FDA approved megestrol acetate, marketed as Megace ES, in 2005 for the treatment of anorexia, cachexia, or an unexplained significant weight loss in AIDS patients. Par noted that physicians frequently prescribe the drug off label to treat wasting in non-AIDS, cancer, and geriatric patients.

"Certain FDA regulations nevertheless purport to ban Par from speaking about the approved use of Megace ES to physicians who may prescribe the drug for unapproved uses," the firm said in its announcement of the suit.

In an Oct. 14 news release, Par said it "hopes to elicit tailored and constitutionally permissible regulatory guidance to ensure that physicians may be kept abreast of valuable, on-label information about prescription drugs to aid in their provision of quality and informed patient care."

The complaint, filed in the U.S. District Court for the District of Columbia, seeks a declaratory judgment and preliminary injunction.

The concern presumably centers on Par promoting or detailing the product to physicians that do not primarily treat HIV patients, although the firm did not specify.

"Par’s preliminary injunction motion argues that those FDA regulations are contrary to both the First Amendment to the U.S. Constitution and the Federal Food, Drug, and Cosmetic Act."

"Par contends that the government’s effort to minimize off-label use by means of banning Par’s truthful speech is unjustified since off-label use is lawful, widespread, medically necessary, and reimbursed by the federal government under the Medicare and Medicaid programs," the company said.

Allergan made similar claims in a suit it filed against the FDA in October 2009. It challenged the FDA’s prohibitions on what it could tell physicians about unapproved uses of Botox (onabotulinumtoxinA). Allergan dropped the complaint last year as part of its settlement with the Department of Justice over its off-label marketing of the drug.

There is a chance Par’s suit could be similarly derailed. The Department of Justice is investigating Par’s promotional practices in sales and marketing of Megace ES. The company received a subpoena from the government for documents relating to Megace ES marketing in 2009. Any settlement is likely to require Par to drop its complaint against the FDA.

Allergan had proposed prohibiting promotion of uses for which a company was not seeking approval or having companies disclose that a use is unapproved. But, in a court filing, the FDA said it would not be possible to narrowly define promotion as companies are constantly developing new ways to convey messages about their products, in part to avoid detection by the agency.

This coverage is provided courtesy of "The Pink Sheet." This news organization and "The Pink Sheet" are owned by Elsevier.

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Par Pharmaceutical has filed suit against the Food and Drug Administration, claiming that FDA regulations violate its First Amendment right to provide physicians with information about the on-label use of its appetite stimulant Megace ES.

The FDA approved megestrol acetate, marketed as Megace ES, in 2005 for the treatment of anorexia, cachexia, or an unexplained significant weight loss in AIDS patients. Par noted that physicians frequently prescribe the drug off label to treat wasting in non-AIDS, cancer, and geriatric patients.

"Certain FDA regulations nevertheless purport to ban Par from speaking about the approved use of Megace ES to physicians who may prescribe the drug for unapproved uses," the firm said in its announcement of the suit.

In an Oct. 14 news release, Par said it "hopes to elicit tailored and constitutionally permissible regulatory guidance to ensure that physicians may be kept abreast of valuable, on-label information about prescription drugs to aid in their provision of quality and informed patient care."

The complaint, filed in the U.S. District Court for the District of Columbia, seeks a declaratory judgment and preliminary injunction.

The concern presumably centers on Par promoting or detailing the product to physicians that do not primarily treat HIV patients, although the firm did not specify.

"Par’s preliminary injunction motion argues that those FDA regulations are contrary to both the First Amendment to the U.S. Constitution and the Federal Food, Drug, and Cosmetic Act."

"Par contends that the government’s effort to minimize off-label use by means of banning Par’s truthful speech is unjustified since off-label use is lawful, widespread, medically necessary, and reimbursed by the federal government under the Medicare and Medicaid programs," the company said.

Allergan made similar claims in a suit it filed against the FDA in October 2009. It challenged the FDA’s prohibitions on what it could tell physicians about unapproved uses of Botox (onabotulinumtoxinA). Allergan dropped the complaint last year as part of its settlement with the Department of Justice over its off-label marketing of the drug.

There is a chance Par’s suit could be similarly derailed. The Department of Justice is investigating Par’s promotional practices in sales and marketing of Megace ES. The company received a subpoena from the government for documents relating to Megace ES marketing in 2009. Any settlement is likely to require Par to drop its complaint against the FDA.

Allergan had proposed prohibiting promotion of uses for which a company was not seeking approval or having companies disclose that a use is unapproved. But, in a court filing, the FDA said it would not be possible to narrowly define promotion as companies are constantly developing new ways to convey messages about their products, in part to avoid detection by the agency.

This coverage is provided courtesy of "The Pink Sheet." This news organization and "The Pink Sheet" are owned by Elsevier.

Par Pharmaceutical has filed suit against the Food and Drug Administration, claiming that FDA regulations violate its First Amendment right to provide physicians with information about the on-label use of its appetite stimulant Megace ES.

The FDA approved megestrol acetate, marketed as Megace ES, in 2005 for the treatment of anorexia, cachexia, or an unexplained significant weight loss in AIDS patients. Par noted that physicians frequently prescribe the drug off label to treat wasting in non-AIDS, cancer, and geriatric patients.

"Certain FDA regulations nevertheless purport to ban Par from speaking about the approved use of Megace ES to physicians who may prescribe the drug for unapproved uses," the firm said in its announcement of the suit.

In an Oct. 14 news release, Par said it "hopes to elicit tailored and constitutionally permissible regulatory guidance to ensure that physicians may be kept abreast of valuable, on-label information about prescription drugs to aid in their provision of quality and informed patient care."

The complaint, filed in the U.S. District Court for the District of Columbia, seeks a declaratory judgment and preliminary injunction.

The concern presumably centers on Par promoting or detailing the product to physicians that do not primarily treat HIV patients, although the firm did not specify.

"Par’s preliminary injunction motion argues that those FDA regulations are contrary to both the First Amendment to the U.S. Constitution and the Federal Food, Drug, and Cosmetic Act."

"Par contends that the government’s effort to minimize off-label use by means of banning Par’s truthful speech is unjustified since off-label use is lawful, widespread, medically necessary, and reimbursed by the federal government under the Medicare and Medicaid programs," the company said.

Allergan made similar claims in a suit it filed against the FDA in October 2009. It challenged the FDA’s prohibitions on what it could tell physicians about unapproved uses of Botox (onabotulinumtoxinA). Allergan dropped the complaint last year as part of its settlement with the Department of Justice over its off-label marketing of the drug.

There is a chance Par’s suit could be similarly derailed. The Department of Justice is investigating Par’s promotional practices in sales and marketing of Megace ES. The company received a subpoena from the government for documents relating to Megace ES marketing in 2009. Any settlement is likely to require Par to drop its complaint against the FDA.

Allergan had proposed prohibiting promotion of uses for which a company was not seeking approval or having companies disclose that a use is unapproved. But, in a court filing, the FDA said it would not be possible to narrowly define promotion as companies are constantly developing new ways to convey messages about their products, in part to avoid detection by the agency.

This coverage is provided courtesy of "The Pink Sheet." This news organization and "The Pink Sheet" are owned by Elsevier.

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