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Muscle spasms, twitches in arm upon throwing • Dx?
THE CASE
A 31-year-old right-handed college baseball coach presented to his family physician (FP) with concerns about the “yips” in his right arm. His ability to throw a baseball had been gradually deteriorating. Involuntary upper right arm muscle contractions and spasms, which began intermittently when he was a teenager, were now a real problem for him as an adult. (See the video below.) The patient was having difficulty rolling a baseball underhand to players as part of infield practice and he was experiencing muscle spasms when lifting his right arm over his head. “Twitches” in the patient’s upper arm were making drinking difficult, but he had no problems feeding himself, writing, or performing other basic activities of daily living.
The patient experienced the same symptoms whether it was baseball season or not. He hadn’t noticed a change in symptoms with caffeine and denied use of any other stimulants in the last 4 years. His symptoms didn’t improve or worsen with greater or lesser quantity or quality of sleep or when he concentrated on stifling the involuntary movements. He had attempted to learn to throw left-handed to overcome the impairment, but was concerned that the same problem would occur in his left arm.
The patient had previously worked with a sports psychologist and hypnotherapist to overcome any potential subconscious performance anxiety, but this hadn’t helped. Stretching and strengthening with a physical therapist and numerous sessions with an acupuncturist hadn’t helped either. Despite this, he believed the problem to be primarily psychological.
The patient’s history included mild attention deficit disorder and exercise-induced asthma; his family history was negative for any movement or psychiatric disorders. He had 2 dislocation repairs on his left, non-throwing shoulder in his early twenties. His medications included fluticasone-salmeterol twice daily and albuterol, as needed.
The patient denied myalgia or arthralgia, decreased passive range of motion, shoulder or arm weakness, swelling, or muscle atrophy. He also didn’t have paresthesias in his right arm or hand, a resting tremor, difficulty moving (other than drinking from a cup), difficulty moving other extremities, dizziness, imbalance, or seizures.
The patient’s vital signs were normal. He had full range of motion and 5 out of 5 strength without pain during right shoulder abduction, external and internal rotation, an empty can test, a lower back lift off (Gerber’s) test, and a test of bicep and tricep strength, along with negative Neer and Hawkins tests.
There was no evidence of muscle wasting or asymmetry in the bilateral upper extremities. The patient’s deep tendon reflex grade was 2+ out of 4 in both of his arms. He didn’t have a sensory deficit to light touch in areas of C5 to T1 and he had normal cranial nerves II to XII. He had normal rapid alternating movements, heel-to-shin testing, and finger-to-nose testing, as well as a normal gait and Romberg test.
The patient provided a video showing the abnormal involuntary flexion of his shoulder when attempting to throw a baseball.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
THE DIAGNOSIS
The patient’s FP was aware of the “yips,” a condition that is commonly viewed as psychological or related to performance anxiety. (The “yips” are colloquially known as “Steve Blass Disease”—named after a Pittsburgh Pirates pitcher who suddenly lost the ability to control his pitches.1) But based on the patient’s clinical presentation and history of seeing a number of mental health care providers—in addition to his worsening symptoms—the FP ordered magnetic resonance imaging (MRI) of the brain. The MRI turned out to be unremarkable, so the patient was referred to Neurology.
In the general neurology clinic, a diagnosis of Wilson’s disease (a condition that leads to excess copper deposition in multiple organ systems, including the nervous system) was considered, as it can cause symptoms similar to those our patient was experiencing. However, a complete blood count, complete metabolic panel, antinuclear antibody test, ceruloplasmin test, and copper level were all normal, effectively ruling it out. An MRI of the cervical spine showed mild to moderate right foraminal stenosis at C3-4 and C5-6, but this did not explain the patient’s symptoms.
A diagnosis of paroxysmal exercise-induced dystonia was also considered at the time of the initial work-up, as our patient’s symptoms were most pronounced during physical activity. But this condition usually responds to antiepileptics, and carbamazepine and phenytoin were each tried for multiple months early in his evaluation without benefit.
3 factors led to a diagnosis of focal limb dystonia: Only our patient’s right arm was affected, his laboratory and imaging work-ups were negative, and he didn’t respond to antiepileptic treatment. Characterization of a movement disorder is based upon phenomenology. In this case, the patient had sustained abnormal posturing at the shoulder during right upper limb activation, which was only triggered with specific voluntary actions. This was consistent with dystonia, a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal movements and/or postures—often initiated or worsened by voluntary action.2
DISCUSSION
The “yips,” or intermittent, transient tremors, jerks, or spasms3 that are seen in athletes, are well-documented in the lay press, but haven’t been significantly addressed in the medical literature.4 Stigma surrounding the condition among athletes likely leads to under-reporting. Athletes typically experience yips with fine motor movements, such as short putts in golf and pitching in baseball. In fact, while the majority of the medical literature on yips revolves around golfers, many talented baseball players have had their careers altered by the condition. The yips may also affect movements in sports like darts, cricket, table tennis, and billiards.
In 1984, dystonia was defined as a disorder of sensorimotor integration that results in co-contraction of agonist/antagonist muscles, and may be characterized by state dependence (exacerbation with specific activities) or sensory tricks (amelioration with specific types of sensory input).5 In 2013, the definition was revised to remove “co-contraction” from the definition because phenomenology alone is sufficient to make the diagnosis.1
Many athletes and sports fans believe the yips are caused by performance anxiety or related phobias, but evidence suggests that many athletes with the movement disorder may actually have focal limb dystonia.6,7 The yips can, however, lead to performance anxiety,3 but there has been no difference noted between the anxiety level of golfers with or without the yips.7 Psychological treatment approaches are commonly employed, but surface electromyograms have shown abnormal co-contraction of wrist flexor and extensor muscles in 5 out of 10 golfers with the yips (but 0 of those without) while putting—which is consistent with focal limb dystonia.8
Botulinum toxin injections are Tx of choice, but can cause weakness
Muscle relaxers, such as baclofen and benzodiazepines, as well as dopamine antagonists, can ameliorate dystonia.9 Focal limb dystonia may also respond to the antispasmodic trihexyphenidyl, but the dose must often be limited due to adverse effects such as nausea, dizziness, and anxiety.10
Botulinum toxin injections have proven effective for focal limb dystonia11 and are considered the treatment of choice. However, there are few reports on their use in athletes, where the adverse effect of weakness could affect performance. One case report also showed improvement of yips with acupuncture, although this has not been extensively studied.12
Our patient didn’t respond to low-dose (2 mg twice a day) trihexyphenidyl. Tetrabenazine, a dopamine depletor frequently used for hyperkinetic disorders, was not effective at 25 mg taken prior to coaching sessions. Higher doses of an anticholinergic could have been effective, but the patient declined our recommendation to pursue this (or botulinum toxin injections). He decided instead to train himself to use his left arm while coaching.
THE TAKEAWAY
Athletes who play sports that require precision movements commonly develop the yips. While the prevailing theory among athletes is that this is a psychological phenomenon, evidence shows that this may in fact be a neurologic focal dystonia caused by repetitive use. Greater awareness of yips as a possible organic, treatable neurologic condition is needed in order to stimulate more research on this topic.
1. Baseball’s head cases often prove baffling. USA Today Baseball Weekly. 2001. Available at: http://usatoday30.usatoday.com/sports/bbw/2001-02-07/2001-02-07-head.htm. Accessed March 15, 2017.
2. Albanese A, Bhatia K, Bressman SB, et al. Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013;28:863-873.
3. Dhungana S, Jankovic J. Yips and other movement disorders in golfers. Mov Disord. 2013;28:576-581.
4. Stacy MA, ed. Handbook of dystonia. New York, NY: Informa Healthcare USA, Inc; 2007.
5. Fahn S, Marsden CD, Calne DB. Classification and investigation of dystonia. In: Marsden CD, Fahn S, eds. Movement disorders 2. London: Butterworths; 1987:332-358.
6. Smith AM, Adler CH, Crews D, et al. The ‘yips’ in golf: a continuum between a focal dystonia and choking. Sports Med. 2003;33:13-31.
7. Sachdev P. Golfers’ cramp: clinical characteristics and evidence against it being an anxiety disorder. Mov Disord. 1992;7:326-332.
8. Adler CH, Crews D, Hentz JG, et al. Abnormal co-contraction in yips-affected but not unaffected golfers: evidence for focal dystonia. Neurology. 2005;64:1813-1814.
9. Jankovic J. Treatment of hyperkinetic movement disorders. Lancet Neurol. 2009;8:844-856.
10. Jankovic J. Treatment of dystonia. Lancet Neurol. 2006;5:864-872.
11. Lungu C, Karp BI, Alter K, et al. Long-term follow-up of botulinum toxin therapy for focal hand dystonia: outcome at 10 years or more. Mov Disord. 2011;26:750-753.
12. Rosted P. Acupuncture for treatment of the yips?—a case report. Acupunct Med. 2005;23:188-189.
THE CASE
A 31-year-old right-handed college baseball coach presented to his family physician (FP) with concerns about the “yips” in his right arm. His ability to throw a baseball had been gradually deteriorating. Involuntary upper right arm muscle contractions and spasms, which began intermittently when he was a teenager, were now a real problem for him as an adult. (See the video below.) The patient was having difficulty rolling a baseball underhand to players as part of infield practice and he was experiencing muscle spasms when lifting his right arm over his head. “Twitches” in the patient’s upper arm were making drinking difficult, but he had no problems feeding himself, writing, or performing other basic activities of daily living.
The patient experienced the same symptoms whether it was baseball season or not. He hadn’t noticed a change in symptoms with caffeine and denied use of any other stimulants in the last 4 years. His symptoms didn’t improve or worsen with greater or lesser quantity or quality of sleep or when he concentrated on stifling the involuntary movements. He had attempted to learn to throw left-handed to overcome the impairment, but was concerned that the same problem would occur in his left arm.
The patient had previously worked with a sports psychologist and hypnotherapist to overcome any potential subconscious performance anxiety, but this hadn’t helped. Stretching and strengthening with a physical therapist and numerous sessions with an acupuncturist hadn’t helped either. Despite this, he believed the problem to be primarily psychological.
The patient’s history included mild attention deficit disorder and exercise-induced asthma; his family history was negative for any movement or psychiatric disorders. He had 2 dislocation repairs on his left, non-throwing shoulder in his early twenties. His medications included fluticasone-salmeterol twice daily and albuterol, as needed.
The patient denied myalgia or arthralgia, decreased passive range of motion, shoulder or arm weakness, swelling, or muscle atrophy. He also didn’t have paresthesias in his right arm or hand, a resting tremor, difficulty moving (other than drinking from a cup), difficulty moving other extremities, dizziness, imbalance, or seizures.
The patient’s vital signs were normal. He had full range of motion and 5 out of 5 strength without pain during right shoulder abduction, external and internal rotation, an empty can test, a lower back lift off (Gerber’s) test, and a test of bicep and tricep strength, along with negative Neer and Hawkins tests.
There was no evidence of muscle wasting or asymmetry in the bilateral upper extremities. The patient’s deep tendon reflex grade was 2+ out of 4 in both of his arms. He didn’t have a sensory deficit to light touch in areas of C5 to T1 and he had normal cranial nerves II to XII. He had normal rapid alternating movements, heel-to-shin testing, and finger-to-nose testing, as well as a normal gait and Romberg test.
The patient provided a video showing the abnormal involuntary flexion of his shoulder when attempting to throw a baseball.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
THE DIAGNOSIS
The patient’s FP was aware of the “yips,” a condition that is commonly viewed as psychological or related to performance anxiety. (The “yips” are colloquially known as “Steve Blass Disease”—named after a Pittsburgh Pirates pitcher who suddenly lost the ability to control his pitches.1) But based on the patient’s clinical presentation and history of seeing a number of mental health care providers—in addition to his worsening symptoms—the FP ordered magnetic resonance imaging (MRI) of the brain. The MRI turned out to be unremarkable, so the patient was referred to Neurology.
In the general neurology clinic, a diagnosis of Wilson’s disease (a condition that leads to excess copper deposition in multiple organ systems, including the nervous system) was considered, as it can cause symptoms similar to those our patient was experiencing. However, a complete blood count, complete metabolic panel, antinuclear antibody test, ceruloplasmin test, and copper level were all normal, effectively ruling it out. An MRI of the cervical spine showed mild to moderate right foraminal stenosis at C3-4 and C5-6, but this did not explain the patient’s symptoms.
A diagnosis of paroxysmal exercise-induced dystonia was also considered at the time of the initial work-up, as our patient’s symptoms were most pronounced during physical activity. But this condition usually responds to antiepileptics, and carbamazepine and phenytoin were each tried for multiple months early in his evaluation without benefit.
3 factors led to a diagnosis of focal limb dystonia: Only our patient’s right arm was affected, his laboratory and imaging work-ups were negative, and he didn’t respond to antiepileptic treatment. Characterization of a movement disorder is based upon phenomenology. In this case, the patient had sustained abnormal posturing at the shoulder during right upper limb activation, which was only triggered with specific voluntary actions. This was consistent with dystonia, a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal movements and/or postures—often initiated or worsened by voluntary action.2
DISCUSSION
The “yips,” or intermittent, transient tremors, jerks, or spasms3 that are seen in athletes, are well-documented in the lay press, but haven’t been significantly addressed in the medical literature.4 Stigma surrounding the condition among athletes likely leads to under-reporting. Athletes typically experience yips with fine motor movements, such as short putts in golf and pitching in baseball. In fact, while the majority of the medical literature on yips revolves around golfers, many talented baseball players have had their careers altered by the condition. The yips may also affect movements in sports like darts, cricket, table tennis, and billiards.
In 1984, dystonia was defined as a disorder of sensorimotor integration that results in co-contraction of agonist/antagonist muscles, and may be characterized by state dependence (exacerbation with specific activities) or sensory tricks (amelioration with specific types of sensory input).5 In 2013, the definition was revised to remove “co-contraction” from the definition because phenomenology alone is sufficient to make the diagnosis.1
Many athletes and sports fans believe the yips are caused by performance anxiety or related phobias, but evidence suggests that many athletes with the movement disorder may actually have focal limb dystonia.6,7 The yips can, however, lead to performance anxiety,3 but there has been no difference noted between the anxiety level of golfers with or without the yips.7 Psychological treatment approaches are commonly employed, but surface electromyograms have shown abnormal co-contraction of wrist flexor and extensor muscles in 5 out of 10 golfers with the yips (but 0 of those without) while putting—which is consistent with focal limb dystonia.8
Botulinum toxin injections are Tx of choice, but can cause weakness
Muscle relaxers, such as baclofen and benzodiazepines, as well as dopamine antagonists, can ameliorate dystonia.9 Focal limb dystonia may also respond to the antispasmodic trihexyphenidyl, but the dose must often be limited due to adverse effects such as nausea, dizziness, and anxiety.10
Botulinum toxin injections have proven effective for focal limb dystonia11 and are considered the treatment of choice. However, there are few reports on their use in athletes, where the adverse effect of weakness could affect performance. One case report also showed improvement of yips with acupuncture, although this has not been extensively studied.12
Our patient didn’t respond to low-dose (2 mg twice a day) trihexyphenidyl. Tetrabenazine, a dopamine depletor frequently used for hyperkinetic disorders, was not effective at 25 mg taken prior to coaching sessions. Higher doses of an anticholinergic could have been effective, but the patient declined our recommendation to pursue this (or botulinum toxin injections). He decided instead to train himself to use his left arm while coaching.
THE TAKEAWAY
Athletes who play sports that require precision movements commonly develop the yips. While the prevailing theory among athletes is that this is a psychological phenomenon, evidence shows that this may in fact be a neurologic focal dystonia caused by repetitive use. Greater awareness of yips as a possible organic, treatable neurologic condition is needed in order to stimulate more research on this topic.
THE CASE
A 31-year-old right-handed college baseball coach presented to his family physician (FP) with concerns about the “yips” in his right arm. His ability to throw a baseball had been gradually deteriorating. Involuntary upper right arm muscle contractions and spasms, which began intermittently when he was a teenager, were now a real problem for him as an adult. (See the video below.) The patient was having difficulty rolling a baseball underhand to players as part of infield practice and he was experiencing muscle spasms when lifting his right arm over his head. “Twitches” in the patient’s upper arm were making drinking difficult, but he had no problems feeding himself, writing, or performing other basic activities of daily living.
The patient experienced the same symptoms whether it was baseball season or not. He hadn’t noticed a change in symptoms with caffeine and denied use of any other stimulants in the last 4 years. His symptoms didn’t improve or worsen with greater or lesser quantity or quality of sleep or when he concentrated on stifling the involuntary movements. He had attempted to learn to throw left-handed to overcome the impairment, but was concerned that the same problem would occur in his left arm.
The patient had previously worked with a sports psychologist and hypnotherapist to overcome any potential subconscious performance anxiety, but this hadn’t helped. Stretching and strengthening with a physical therapist and numerous sessions with an acupuncturist hadn’t helped either. Despite this, he believed the problem to be primarily psychological.
The patient’s history included mild attention deficit disorder and exercise-induced asthma; his family history was negative for any movement or psychiatric disorders. He had 2 dislocation repairs on his left, non-throwing shoulder in his early twenties. His medications included fluticasone-salmeterol twice daily and albuterol, as needed.
The patient denied myalgia or arthralgia, decreased passive range of motion, shoulder or arm weakness, swelling, or muscle atrophy. He also didn’t have paresthesias in his right arm or hand, a resting tremor, difficulty moving (other than drinking from a cup), difficulty moving other extremities, dizziness, imbalance, or seizures.
The patient’s vital signs were normal. He had full range of motion and 5 out of 5 strength without pain during right shoulder abduction, external and internal rotation, an empty can test, a lower back lift off (Gerber’s) test, and a test of bicep and tricep strength, along with negative Neer and Hawkins tests.
There was no evidence of muscle wasting or asymmetry in the bilateral upper extremities. The patient’s deep tendon reflex grade was 2+ out of 4 in both of his arms. He didn’t have a sensory deficit to light touch in areas of C5 to T1 and he had normal cranial nerves II to XII. He had normal rapid alternating movements, heel-to-shin testing, and finger-to-nose testing, as well as a normal gait and Romberg test.
The patient provided a video showing the abnormal involuntary flexion of his shoulder when attempting to throw a baseball.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
THE DIAGNOSIS
The patient’s FP was aware of the “yips,” a condition that is commonly viewed as psychological or related to performance anxiety. (The “yips” are colloquially known as “Steve Blass Disease”—named after a Pittsburgh Pirates pitcher who suddenly lost the ability to control his pitches.1) But based on the patient’s clinical presentation and history of seeing a number of mental health care providers—in addition to his worsening symptoms—the FP ordered magnetic resonance imaging (MRI) of the brain. The MRI turned out to be unremarkable, so the patient was referred to Neurology.
In the general neurology clinic, a diagnosis of Wilson’s disease (a condition that leads to excess copper deposition in multiple organ systems, including the nervous system) was considered, as it can cause symptoms similar to those our patient was experiencing. However, a complete blood count, complete metabolic panel, antinuclear antibody test, ceruloplasmin test, and copper level were all normal, effectively ruling it out. An MRI of the cervical spine showed mild to moderate right foraminal stenosis at C3-4 and C5-6, but this did not explain the patient’s symptoms.
A diagnosis of paroxysmal exercise-induced dystonia was also considered at the time of the initial work-up, as our patient’s symptoms were most pronounced during physical activity. But this condition usually responds to antiepileptics, and carbamazepine and phenytoin were each tried for multiple months early in his evaluation without benefit.
3 factors led to a diagnosis of focal limb dystonia: Only our patient’s right arm was affected, his laboratory and imaging work-ups were negative, and he didn’t respond to antiepileptic treatment. Characterization of a movement disorder is based upon phenomenology. In this case, the patient had sustained abnormal posturing at the shoulder during right upper limb activation, which was only triggered with specific voluntary actions. This was consistent with dystonia, a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal movements and/or postures—often initiated or worsened by voluntary action.2
DISCUSSION
The “yips,” or intermittent, transient tremors, jerks, or spasms3 that are seen in athletes, are well-documented in the lay press, but haven’t been significantly addressed in the medical literature.4 Stigma surrounding the condition among athletes likely leads to under-reporting. Athletes typically experience yips with fine motor movements, such as short putts in golf and pitching in baseball. In fact, while the majority of the medical literature on yips revolves around golfers, many talented baseball players have had their careers altered by the condition. The yips may also affect movements in sports like darts, cricket, table tennis, and billiards.
In 1984, dystonia was defined as a disorder of sensorimotor integration that results in co-contraction of agonist/antagonist muscles, and may be characterized by state dependence (exacerbation with specific activities) or sensory tricks (amelioration with specific types of sensory input).5 In 2013, the definition was revised to remove “co-contraction” from the definition because phenomenology alone is sufficient to make the diagnosis.1
Many athletes and sports fans believe the yips are caused by performance anxiety or related phobias, but evidence suggests that many athletes with the movement disorder may actually have focal limb dystonia.6,7 The yips can, however, lead to performance anxiety,3 but there has been no difference noted between the anxiety level of golfers with or without the yips.7 Psychological treatment approaches are commonly employed, but surface electromyograms have shown abnormal co-contraction of wrist flexor and extensor muscles in 5 out of 10 golfers with the yips (but 0 of those without) while putting—which is consistent with focal limb dystonia.8
Botulinum toxin injections are Tx of choice, but can cause weakness
Muscle relaxers, such as baclofen and benzodiazepines, as well as dopamine antagonists, can ameliorate dystonia.9 Focal limb dystonia may also respond to the antispasmodic trihexyphenidyl, but the dose must often be limited due to adverse effects such as nausea, dizziness, and anxiety.10
Botulinum toxin injections have proven effective for focal limb dystonia11 and are considered the treatment of choice. However, there are few reports on their use in athletes, where the adverse effect of weakness could affect performance. One case report also showed improvement of yips with acupuncture, although this has not been extensively studied.12
Our patient didn’t respond to low-dose (2 mg twice a day) trihexyphenidyl. Tetrabenazine, a dopamine depletor frequently used for hyperkinetic disorders, was not effective at 25 mg taken prior to coaching sessions. Higher doses of an anticholinergic could have been effective, but the patient declined our recommendation to pursue this (or botulinum toxin injections). He decided instead to train himself to use his left arm while coaching.
THE TAKEAWAY
Athletes who play sports that require precision movements commonly develop the yips. While the prevailing theory among athletes is that this is a psychological phenomenon, evidence shows that this may in fact be a neurologic focal dystonia caused by repetitive use. Greater awareness of yips as a possible organic, treatable neurologic condition is needed in order to stimulate more research on this topic.
1. Baseball’s head cases often prove baffling. USA Today Baseball Weekly. 2001. Available at: http://usatoday30.usatoday.com/sports/bbw/2001-02-07/2001-02-07-head.htm. Accessed March 15, 2017.
2. Albanese A, Bhatia K, Bressman SB, et al. Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013;28:863-873.
3. Dhungana S, Jankovic J. Yips and other movement disorders in golfers. Mov Disord. 2013;28:576-581.
4. Stacy MA, ed. Handbook of dystonia. New York, NY: Informa Healthcare USA, Inc; 2007.
5. Fahn S, Marsden CD, Calne DB. Classification and investigation of dystonia. In: Marsden CD, Fahn S, eds. Movement disorders 2. London: Butterworths; 1987:332-358.
6. Smith AM, Adler CH, Crews D, et al. The ‘yips’ in golf: a continuum between a focal dystonia and choking. Sports Med. 2003;33:13-31.
7. Sachdev P. Golfers’ cramp: clinical characteristics and evidence against it being an anxiety disorder. Mov Disord. 1992;7:326-332.
8. Adler CH, Crews D, Hentz JG, et al. Abnormal co-contraction in yips-affected but not unaffected golfers: evidence for focal dystonia. Neurology. 2005;64:1813-1814.
9. Jankovic J. Treatment of hyperkinetic movement disorders. Lancet Neurol. 2009;8:844-856.
10. Jankovic J. Treatment of dystonia. Lancet Neurol. 2006;5:864-872.
11. Lungu C, Karp BI, Alter K, et al. Long-term follow-up of botulinum toxin therapy for focal hand dystonia: outcome at 10 years or more. Mov Disord. 2011;26:750-753.
12. Rosted P. Acupuncture for treatment of the yips?—a case report. Acupunct Med. 2005;23:188-189.
1. Baseball’s head cases often prove baffling. USA Today Baseball Weekly. 2001. Available at: http://usatoday30.usatoday.com/sports/bbw/2001-02-07/2001-02-07-head.htm. Accessed March 15, 2017.
2. Albanese A, Bhatia K, Bressman SB, et al. Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013;28:863-873.
3. Dhungana S, Jankovic J. Yips and other movement disorders in golfers. Mov Disord. 2013;28:576-581.
4. Stacy MA, ed. Handbook of dystonia. New York, NY: Informa Healthcare USA, Inc; 2007.
5. Fahn S, Marsden CD, Calne DB. Classification and investigation of dystonia. In: Marsden CD, Fahn S, eds. Movement disorders 2. London: Butterworths; 1987:332-358.
6. Smith AM, Adler CH, Crews D, et al. The ‘yips’ in golf: a continuum between a focal dystonia and choking. Sports Med. 2003;33:13-31.
7. Sachdev P. Golfers’ cramp: clinical characteristics and evidence against it being an anxiety disorder. Mov Disord. 1992;7:326-332.
8. Adler CH, Crews D, Hentz JG, et al. Abnormal co-contraction in yips-affected but not unaffected golfers: evidence for focal dystonia. Neurology. 2005;64:1813-1814.
9. Jankovic J. Treatment of hyperkinetic movement disorders. Lancet Neurol. 2009;8:844-856.
10. Jankovic J. Treatment of dystonia. Lancet Neurol. 2006;5:864-872.
11. Lungu C, Karp BI, Alter K, et al. Long-term follow-up of botulinum toxin therapy for focal hand dystonia: outcome at 10 years or more. Mov Disord. 2011;26:750-753.
12. Rosted P. Acupuncture for treatment of the yips?—a case report. Acupunct Med. 2005;23:188-189.
Choice of protease inhibitor may impact CVD risk in HIV+ patients
SEATTLE – A study of newer generation protease inhibitors (PIs) suggests that ritonavir-boosted atazanavir (ATV/r) has a better cardiovascular safety profile than ritonavir-boosted darunavir (DRV/r). After adjustment for age and other factors, patients taking DRV/r had a higher incidence rate ratio of cardiovascular disease during a 5-year follow-up compared to pre-exposure, while no such increase was seen in patients taking ATV/r.
Older protease inhibitors had been shown to be associated with increased CVD risk, but the newer generation of drugs had not been similarly examined. A previous analysis of the D:A:D (Data collection on Adverse events of Anti-HIV Drugs) study had shown no effect of ATV/r with cardiovascular risk, but the follow-up time was short.
The data suggest that ATV/r may be the best choice for patients at heightened risk of cardiovascular disease. “This is just the results from the first five years, and we need to reassess at some point, but according to what we know now, it does really look like a quite real effect,” Dr Ryom added.
The researchers examined longer-term results from 35,711 (47.8% white, 73.6% men, median age 44) participants in the D:A:D study, who were followed beginning January 1, 2009 through the earliest CVD diagnosis, last visit plus 6 months, or February 1, 2016.
After adjustment for baseline variables potentially on the causal pathway between PI use and cardiovascular disease, the researchers found that, compared to baseline pre-exposure levels, patients taking ATV/r had a 5-year incidence rate ratio (IRR) of CVD of 1.03 (95% confidence interval 0.90-1.18), while those taking DRV/r had an IRR 1.59 (95% CI, 1.33-1.91).
Time-updated adjustment analyses for factors potentially on the causal pathway made no meaningful difference in the calculation of incidence risk ratios. “This suggests that the association we say for boosted darunavir is not moderated by dyslipidemia, which is interesting and in contrast to what we saw in first-generation protease inhibitors,” Dr Ryom said during her talk.
Adjusting for bilirubin levels had no impact on the associations.
There was no data on drug dose, and due to the observational nature of the study, the researchers could not prove a causal association between CVD risk and use of either drug, but the results were convincing enough for Dr Ryom to consider a drug that appears friendlier to the cardiovascular system, particularly in high risk patients, though she also noted that there is evidence that ATV/r could lead to kidney stones and chronic kidney disease. “So it’s very difficult to balance the different risks. You really need to tailor your choice according to the patient that is in front of you,” Dr Ryom said.
The study was funded by The Oversight Committee for the Evaluation of Metabolic Complications of HAART, which included both academic and industry sources, and the Danish National Research Foundation. Dr Ryom reported having no financial disclosures.
SEATTLE – A study of newer generation protease inhibitors (PIs) suggests that ritonavir-boosted atazanavir (ATV/r) has a better cardiovascular safety profile than ritonavir-boosted darunavir (DRV/r). After adjustment for age and other factors, patients taking DRV/r had a higher incidence rate ratio of cardiovascular disease during a 5-year follow-up compared to pre-exposure, while no such increase was seen in patients taking ATV/r.
Older protease inhibitors had been shown to be associated with increased CVD risk, but the newer generation of drugs had not been similarly examined. A previous analysis of the D:A:D (Data collection on Adverse events of Anti-HIV Drugs) study had shown no effect of ATV/r with cardiovascular risk, but the follow-up time was short.
The data suggest that ATV/r may be the best choice for patients at heightened risk of cardiovascular disease. “This is just the results from the first five years, and we need to reassess at some point, but according to what we know now, it does really look like a quite real effect,” Dr Ryom added.
The researchers examined longer-term results from 35,711 (47.8% white, 73.6% men, median age 44) participants in the D:A:D study, who were followed beginning January 1, 2009 through the earliest CVD diagnosis, last visit plus 6 months, or February 1, 2016.
After adjustment for baseline variables potentially on the causal pathway between PI use and cardiovascular disease, the researchers found that, compared to baseline pre-exposure levels, patients taking ATV/r had a 5-year incidence rate ratio (IRR) of CVD of 1.03 (95% confidence interval 0.90-1.18), while those taking DRV/r had an IRR 1.59 (95% CI, 1.33-1.91).
Time-updated adjustment analyses for factors potentially on the causal pathway made no meaningful difference in the calculation of incidence risk ratios. “This suggests that the association we say for boosted darunavir is not moderated by dyslipidemia, which is interesting and in contrast to what we saw in first-generation protease inhibitors,” Dr Ryom said during her talk.
Adjusting for bilirubin levels had no impact on the associations.
There was no data on drug dose, and due to the observational nature of the study, the researchers could not prove a causal association between CVD risk and use of either drug, but the results were convincing enough for Dr Ryom to consider a drug that appears friendlier to the cardiovascular system, particularly in high risk patients, though she also noted that there is evidence that ATV/r could lead to kidney stones and chronic kidney disease. “So it’s very difficult to balance the different risks. You really need to tailor your choice according to the patient that is in front of you,” Dr Ryom said.
The study was funded by The Oversight Committee for the Evaluation of Metabolic Complications of HAART, which included both academic and industry sources, and the Danish National Research Foundation. Dr Ryom reported having no financial disclosures.
SEATTLE – A study of newer generation protease inhibitors (PIs) suggests that ritonavir-boosted atazanavir (ATV/r) has a better cardiovascular safety profile than ritonavir-boosted darunavir (DRV/r). After adjustment for age and other factors, patients taking DRV/r had a higher incidence rate ratio of cardiovascular disease during a 5-year follow-up compared to pre-exposure, while no such increase was seen in patients taking ATV/r.
Older protease inhibitors had been shown to be associated with increased CVD risk, but the newer generation of drugs had not been similarly examined. A previous analysis of the D:A:D (Data collection on Adverse events of Anti-HIV Drugs) study had shown no effect of ATV/r with cardiovascular risk, but the follow-up time was short.
The data suggest that ATV/r may be the best choice for patients at heightened risk of cardiovascular disease. “This is just the results from the first five years, and we need to reassess at some point, but according to what we know now, it does really look like a quite real effect,” Dr Ryom added.
The researchers examined longer-term results from 35,711 (47.8% white, 73.6% men, median age 44) participants in the D:A:D study, who were followed beginning January 1, 2009 through the earliest CVD diagnosis, last visit plus 6 months, or February 1, 2016.
After adjustment for baseline variables potentially on the causal pathway between PI use and cardiovascular disease, the researchers found that, compared to baseline pre-exposure levels, patients taking ATV/r had a 5-year incidence rate ratio (IRR) of CVD of 1.03 (95% confidence interval 0.90-1.18), while those taking DRV/r had an IRR 1.59 (95% CI, 1.33-1.91).
Time-updated adjustment analyses for factors potentially on the causal pathway made no meaningful difference in the calculation of incidence risk ratios. “This suggests that the association we say for boosted darunavir is not moderated by dyslipidemia, which is interesting and in contrast to what we saw in first-generation protease inhibitors,” Dr Ryom said during her talk.
Adjusting for bilirubin levels had no impact on the associations.
There was no data on drug dose, and due to the observational nature of the study, the researchers could not prove a causal association between CVD risk and use of either drug, but the results were convincing enough for Dr Ryom to consider a drug that appears friendlier to the cardiovascular system, particularly in high risk patients, though she also noted that there is evidence that ATV/r could lead to kidney stones and chronic kidney disease. “So it’s very difficult to balance the different risks. You really need to tailor your choice according to the patient that is in front of you,” Dr Ryom said.
The study was funded by The Oversight Committee for the Evaluation of Metabolic Complications of HAART, which included both academic and industry sources, and the Danish National Research Foundation. Dr Ryom reported having no financial disclosures.
AT CROI 2017
Key clinical point: Atazanavir may be safer for HIV-positive patients at high CVD risk.
Major finding: Patients taking darunavir had a 59% higher incidence of cardiovascular disease than those taking atazanavir.
Data source: Retrospective analysis of 35,711 patients.
Disclosures: The study was funded by The Oversight Committee for the Evaluation of Metabolic Complications of HAART, which included both academic and industry sources, and the Danish National Research Foundation. Dr Ryom reported having no financial disclosures.
In type 2 diabetes, chronotype may affect depressive symptoms
ORLANDO – For patients with type 2 diabetes, larks may have an edge on owls when it comes to mood, according to a new study. Significantly more depressive symptoms were seen in owls – individuals whose sleep time preference, or chronotype, was later-to-bed and later-to-rise – in a cohort of 476 patients with type 2 diabetes.
In work that accounted for regional differences in chronotype by drawing from two different geographic regions, a later chronotype was associated with a higher score on the Center for Epidemiologic Studies Depression scale (CES-D), after controlling for potentially confounding factors (P = .045 for each cohort).
The study’s senior author, Sirimon Reutrakul, MD, of the faculty of medicine at Mahidol University, Bangkok, Thailand, said that previous work had also shown that when depression in patients with diabetes is untreated, self-care and blood glucose control can suffer, and more complications of diabetes are seen.
Dr. Reutrakul’s facility teamed with Rush University School of Medicine in Chicago, administering questionnaires designed to assess where patients fell along the morningness-eveningness scale. For the Chicago cohort (n = 194, 70% female), the Morningness-Eveningness Questionnaire (MEQ) was administered, while the Thailand cohort (n = 282, 57% female) completed the Composite Score of Morningness (CSM). Both groups completed the CES-D to assess depressive symptoms and the Pittsburgh Sleep Quality Index (PSQI); hemoglobin A1c values for both groups were ascertained by medical record review.
The mean age for the two cohorts was similar (Chicago, 58.3 plus or minus 13.0 years; Thailand, 55.7 plus or minus 11.6 years). The Chicago patients who scored higher on the CES-D, indicating that they had more depressive symptoms, were more likely to have a later chronotype on unadjusted analysis (P = .001). They were also likely to be younger (P = .005) and to have poorer sleep quality (P less than .001). Patients with more depressive symptoms were significantly more likely to be female, non-white, to use insulin, and to have poor glycemic control.
For the patients in Thailand, more depressive symptoms were also associated with a later chronotype on unadjusted analysis (P less than .001); younger age (P = .019), and poor sleep quality (P less than .001) were also associated with more depressive symptoms. Correction for a number of potentially confounding variables yielded modest statistical significance (P = .045) of the depressive symptoms-later chronotype relationship in both cohorts.
The Chicago patients were at approximately latitude 42N, while the patients in Thailand were at about latitude 13N, much closer to the equator. Populations that live closer to the equator, where days and nights are of approximately equal length year-round, tend to have more larks than owls, wrote Dr. Reutrakul and her colleagues.
In these two cohorts, which differed both by ethnic composition and geographic distance from the equator, “later chronotype was found to be independently associated with depressive symptoms” for patients with type 2 diabetes, wrote Dr. Reutrakul and her coauthors in the abstract accompanying the presentation. “In addition, sleep disturbances, more prevalent in evening types, have been associated with depression,” which is common in type 2 diabetes, the investigators wrote.
Dr. Reutrakul acknowledged that the work found an “only modest,” though consistent, association between eveningness and depressive symptoms. “We need further research to explore a combination of interventions that help with circadian timing, such as light therapy and melatonin,” she said in a press statement preceding her presentation. “Learning more about the relationship between depression and circadian functioning might help us figure out strategies to improve physical and mental health for patients with diabetes…We need further research to explore a combination of interventions that help with circadian timing, such as light therapy and melatonin,” Dr. Reutrakul said.
Dr. Reutrakul reported financial relationships with Medtronic Minimed, Novo Nordisk, Merck, and Sanofi.
[email protected]
On Twitter @karioakes
ORLANDO – For patients with type 2 diabetes, larks may have an edge on owls when it comes to mood, according to a new study. Significantly more depressive symptoms were seen in owls – individuals whose sleep time preference, or chronotype, was later-to-bed and later-to-rise – in a cohort of 476 patients with type 2 diabetes.
In work that accounted for regional differences in chronotype by drawing from two different geographic regions, a later chronotype was associated with a higher score on the Center for Epidemiologic Studies Depression scale (CES-D), after controlling for potentially confounding factors (P = .045 for each cohort).
The study’s senior author, Sirimon Reutrakul, MD, of the faculty of medicine at Mahidol University, Bangkok, Thailand, said that previous work had also shown that when depression in patients with diabetes is untreated, self-care and blood glucose control can suffer, and more complications of diabetes are seen.
Dr. Reutrakul’s facility teamed with Rush University School of Medicine in Chicago, administering questionnaires designed to assess where patients fell along the morningness-eveningness scale. For the Chicago cohort (n = 194, 70% female), the Morningness-Eveningness Questionnaire (MEQ) was administered, while the Thailand cohort (n = 282, 57% female) completed the Composite Score of Morningness (CSM). Both groups completed the CES-D to assess depressive symptoms and the Pittsburgh Sleep Quality Index (PSQI); hemoglobin A1c values for both groups were ascertained by medical record review.
The mean age for the two cohorts was similar (Chicago, 58.3 plus or minus 13.0 years; Thailand, 55.7 plus or minus 11.6 years). The Chicago patients who scored higher on the CES-D, indicating that they had more depressive symptoms, were more likely to have a later chronotype on unadjusted analysis (P = .001). They were also likely to be younger (P = .005) and to have poorer sleep quality (P less than .001). Patients with more depressive symptoms were significantly more likely to be female, non-white, to use insulin, and to have poor glycemic control.
For the patients in Thailand, more depressive symptoms were also associated with a later chronotype on unadjusted analysis (P less than .001); younger age (P = .019), and poor sleep quality (P less than .001) were also associated with more depressive symptoms. Correction for a number of potentially confounding variables yielded modest statistical significance (P = .045) of the depressive symptoms-later chronotype relationship in both cohorts.
The Chicago patients were at approximately latitude 42N, while the patients in Thailand were at about latitude 13N, much closer to the equator. Populations that live closer to the equator, where days and nights are of approximately equal length year-round, tend to have more larks than owls, wrote Dr. Reutrakul and her colleagues.
In these two cohorts, which differed both by ethnic composition and geographic distance from the equator, “later chronotype was found to be independently associated with depressive symptoms” for patients with type 2 diabetes, wrote Dr. Reutrakul and her coauthors in the abstract accompanying the presentation. “In addition, sleep disturbances, more prevalent in evening types, have been associated with depression,” which is common in type 2 diabetes, the investigators wrote.
Dr. Reutrakul acknowledged that the work found an “only modest,” though consistent, association between eveningness and depressive symptoms. “We need further research to explore a combination of interventions that help with circadian timing, such as light therapy and melatonin,” she said in a press statement preceding her presentation. “Learning more about the relationship between depression and circadian functioning might help us figure out strategies to improve physical and mental health for patients with diabetes…We need further research to explore a combination of interventions that help with circadian timing, such as light therapy and melatonin,” Dr. Reutrakul said.
Dr. Reutrakul reported financial relationships with Medtronic Minimed, Novo Nordisk, Merck, and Sanofi.
[email protected]
On Twitter @karioakes
ORLANDO – For patients with type 2 diabetes, larks may have an edge on owls when it comes to mood, according to a new study. Significantly more depressive symptoms were seen in owls – individuals whose sleep time preference, or chronotype, was later-to-bed and later-to-rise – in a cohort of 476 patients with type 2 diabetes.
In work that accounted for regional differences in chronotype by drawing from two different geographic regions, a later chronotype was associated with a higher score on the Center for Epidemiologic Studies Depression scale (CES-D), after controlling for potentially confounding factors (P = .045 for each cohort).
The study’s senior author, Sirimon Reutrakul, MD, of the faculty of medicine at Mahidol University, Bangkok, Thailand, said that previous work had also shown that when depression in patients with diabetes is untreated, self-care and blood glucose control can suffer, and more complications of diabetes are seen.
Dr. Reutrakul’s facility teamed with Rush University School of Medicine in Chicago, administering questionnaires designed to assess where patients fell along the morningness-eveningness scale. For the Chicago cohort (n = 194, 70% female), the Morningness-Eveningness Questionnaire (MEQ) was administered, while the Thailand cohort (n = 282, 57% female) completed the Composite Score of Morningness (CSM). Both groups completed the CES-D to assess depressive symptoms and the Pittsburgh Sleep Quality Index (PSQI); hemoglobin A1c values for both groups were ascertained by medical record review.
The mean age for the two cohorts was similar (Chicago, 58.3 plus or minus 13.0 years; Thailand, 55.7 plus or minus 11.6 years). The Chicago patients who scored higher on the CES-D, indicating that they had more depressive symptoms, were more likely to have a later chronotype on unadjusted analysis (P = .001). They were also likely to be younger (P = .005) and to have poorer sleep quality (P less than .001). Patients with more depressive symptoms were significantly more likely to be female, non-white, to use insulin, and to have poor glycemic control.
For the patients in Thailand, more depressive symptoms were also associated with a later chronotype on unadjusted analysis (P less than .001); younger age (P = .019), and poor sleep quality (P less than .001) were also associated with more depressive symptoms. Correction for a number of potentially confounding variables yielded modest statistical significance (P = .045) of the depressive symptoms-later chronotype relationship in both cohorts.
The Chicago patients were at approximately latitude 42N, while the patients in Thailand were at about latitude 13N, much closer to the equator. Populations that live closer to the equator, where days and nights are of approximately equal length year-round, tend to have more larks than owls, wrote Dr. Reutrakul and her colleagues.
In these two cohorts, which differed both by ethnic composition and geographic distance from the equator, “later chronotype was found to be independently associated with depressive symptoms” for patients with type 2 diabetes, wrote Dr. Reutrakul and her coauthors in the abstract accompanying the presentation. “In addition, sleep disturbances, more prevalent in evening types, have been associated with depression,” which is common in type 2 diabetes, the investigators wrote.
Dr. Reutrakul acknowledged that the work found an “only modest,” though consistent, association between eveningness and depressive symptoms. “We need further research to explore a combination of interventions that help with circadian timing, such as light therapy and melatonin,” she said in a press statement preceding her presentation. “Learning more about the relationship between depression and circadian functioning might help us figure out strategies to improve physical and mental health for patients with diabetes…We need further research to explore a combination of interventions that help with circadian timing, such as light therapy and melatonin,” Dr. Reutrakul said.
Dr. Reutrakul reported financial relationships with Medtronic Minimed, Novo Nordisk, Merck, and Sanofi.
[email protected]
On Twitter @karioakes
AT ENDO 2017
Key clinical point:
Major finding: Later chronotype was associated with more depressive symptoms in 2 cohorts with type 2 diabetes (P = .045)
Data source: Cross-sectional study of 476 patients with type 2 diabetes in Chicago and Thailand..
Disclosures: Dr. Reutrakul reported financial relationships with Medtronic Minimed, Merck, Novo Nordisk, and Sanofi.
What do doctors want from health reform?
With the demise of Republican repeal and replace legislation, analysts say the landscape is ripe for repairs to the Affordable Care Act or for additional legislation that both political parties could support. So what do physicians want from health reform?
The first step should be stabilizing the health insurance marketplaces by strengthening and perhaps extending risk mitigation measures such as the risk adjustment, risk corridors, and reinsurance provisions of the law, said Patricia Salber, MD, an internist and health care consultant who blogs at TheDoctorWeighsIn.com. Those three ACA provisions were intended to promote insurer competition on the basis of quality and value and promote insurance market stability.
Keeping premiums at manageable levels for patients should also be addressed, said William J. Burke, DO, dean of Ohio University Heritage College of Osteopathic Medicine.
That was echoed in a poll taken by this news organization. Of 390 respondents, fully half (50%) said they would repair the ACA by stabilizing premiums and out-of-pocket costs for patients as of April 2. About 11% stated they would increase payment rates for care provided to Medicaid patients, and 10% said they would return the primary care incentive payment. About 9% of those surveyed would address workforce issues exacerbated by more patients in the system.
Improving reimbursement for Medicaid services is a necessary health reform change, agreed Diane J. Horvath-Cosper MD, an obstetrician-gynecologist and reproductive health advocacy fellow for Physicians for Reproductive Health, a reproductive rights advocacy organization.
“Reimbursement rates are so low that sometimes [physicians] have to limit the number of Medicaid patients to be able to pay staff,” Dr. Horvath said in an interview. “That’s a terrible position to put physicians in because we want to be able to see as many people who want to see us.”
Speaking of Medicaid, Dr. Salber adds that governors should be encouraged to continue expanding Medicaid to eliminate the coverage gap for the “near poor” that exists in states that did not participate in the expansion.
“Now that the [American Health Care Act] has failed, I think we will see some expansion take place organically even in states that were deeply opposed before,” she said.
“The volume of prior authorizations that all physicians face, but especially primary care physicians, is huge,” Dr. Munger said in an interview. “In many cases, we’re having to hire extra staff just to handle all of the prior authorizations. Every patient may not just have one prior authorization, but they may require two or three or four prior authorizations each month or quarterly. It really detracts from meaningful time you can spend with the patient.”
For starters, doctors should provide care to patients based on mutually agreed terms and without the interference of insurers, Dr. Orient said in an interview. In such a private medicine system, patients would pay doctors for services, and patients would then file claims with their insurer for reimbursement. Similarly, physicians should not be at the mercy of Medicare for payment, Dr. Orient said.
“Doctors can sign away their rights if they want in a Medicare participation agreement,” she said. “Doctors who do not sign the agreement to take assignment in all cases doctors should be freed of price controls and coding demands. Their patients should be allowed to file their own simple claims to Medicare with an itemized bill as they did before the 1990s law that requires physicians to submit the claims. Non-participating doctors should be exempted from MACRA [the Medicare Access and CHIP Reauthorization Act], and without the price controls, there is no need for [Recovery Audit Contractors] and other auditors.”
While contraceptive care was strengthened by the ACA, Dr. Horvath said further efforts should be made to improve coverage and level the playing field for reproductive medicine. In addition, she said that abortion should be treated a valid medical procedure, rather than parsed out, and both public and private insurers should be required to pay for the procedure, she said.
“I would love to see strengthened provisions for contraception coverage,” Dr. Horvath said. “[We need to] make sure that doesn’t get bargained away. The other thing is to expand coverage and make sure every method is covered, not just one method in each category.”
However, Robert Doherty, ACP senior vice president of governmental affairs and public policy, said the college is concerned that the current administration may fail to maintain the ACA now that its proposed repeal law has fallen through.
Without aggressively pushing ACA enrollment for younger patients and continued support for the individual mandate, more insurers may pull out of the marketplaces, and the ACA could implode, Mr. Doherty said.
“There are a number of ways that Republicans could either make things better or worse with action or inaction,” Mr. Doherty said during the press conference. “The insurance [companies] have gone to this administration with a wish list of things that will help keep them in the market. What remains to be seen is whether this administration is going to be receptive. If they don’t aggressively enforce the requirement that people buy coverage, more younger people will opt out and stay out until they get sick. That would make the problem of adverse selection even worse and could create the death cycle for insurance.”
Dr. Price consistently answered that Americans should be able to select the kinds of coverage they want. What “we believe is that individuals ought to be able to have access to the kind of coverage that they select for themselves and for their families and not what the government forces them to buy,” Dr. Price testified, echoing the message from his confirmation hearings.
He was also pressed on issues such as the individual mandate, and while noting that it is his duty to uphold the law of the land, he also remained noncommittal in answering questions about whether he would direct the agency to enforce the individual mandate. The first executive order from President Trump beginning his administration gave the agency discretion to not enforce mandates if they caused harm.
[email protected]
On Twitter @legal_med
Gregory Twachtman contributed to this report.
With the demise of Republican repeal and replace legislation, analysts say the landscape is ripe for repairs to the Affordable Care Act or for additional legislation that both political parties could support. So what do physicians want from health reform?
The first step should be stabilizing the health insurance marketplaces by strengthening and perhaps extending risk mitigation measures such as the risk adjustment, risk corridors, and reinsurance provisions of the law, said Patricia Salber, MD, an internist and health care consultant who blogs at TheDoctorWeighsIn.com. Those three ACA provisions were intended to promote insurer competition on the basis of quality and value and promote insurance market stability.
Keeping premiums at manageable levels for patients should also be addressed, said William J. Burke, DO, dean of Ohio University Heritage College of Osteopathic Medicine.
That was echoed in a poll taken by this news organization. Of 390 respondents, fully half (50%) said they would repair the ACA by stabilizing premiums and out-of-pocket costs for patients as of April 2. About 11% stated they would increase payment rates for care provided to Medicaid patients, and 10% said they would return the primary care incentive payment. About 9% of those surveyed would address workforce issues exacerbated by more patients in the system.
Improving reimbursement for Medicaid services is a necessary health reform change, agreed Diane J. Horvath-Cosper MD, an obstetrician-gynecologist and reproductive health advocacy fellow for Physicians for Reproductive Health, a reproductive rights advocacy organization.
“Reimbursement rates are so low that sometimes [physicians] have to limit the number of Medicaid patients to be able to pay staff,” Dr. Horvath said in an interview. “That’s a terrible position to put physicians in because we want to be able to see as many people who want to see us.”
Speaking of Medicaid, Dr. Salber adds that governors should be encouraged to continue expanding Medicaid to eliminate the coverage gap for the “near poor” that exists in states that did not participate in the expansion.
“Now that the [American Health Care Act] has failed, I think we will see some expansion take place organically even in states that were deeply opposed before,” she said.
“The volume of prior authorizations that all physicians face, but especially primary care physicians, is huge,” Dr. Munger said in an interview. “In many cases, we’re having to hire extra staff just to handle all of the prior authorizations. Every patient may not just have one prior authorization, but they may require two or three or four prior authorizations each month or quarterly. It really detracts from meaningful time you can spend with the patient.”
For starters, doctors should provide care to patients based on mutually agreed terms and without the interference of insurers, Dr. Orient said in an interview. In such a private medicine system, patients would pay doctors for services, and patients would then file claims with their insurer for reimbursement. Similarly, physicians should not be at the mercy of Medicare for payment, Dr. Orient said.
“Doctors can sign away their rights if they want in a Medicare participation agreement,” she said. “Doctors who do not sign the agreement to take assignment in all cases doctors should be freed of price controls and coding demands. Their patients should be allowed to file their own simple claims to Medicare with an itemized bill as they did before the 1990s law that requires physicians to submit the claims. Non-participating doctors should be exempted from MACRA [the Medicare Access and CHIP Reauthorization Act], and without the price controls, there is no need for [Recovery Audit Contractors] and other auditors.”
While contraceptive care was strengthened by the ACA, Dr. Horvath said further efforts should be made to improve coverage and level the playing field for reproductive medicine. In addition, she said that abortion should be treated a valid medical procedure, rather than parsed out, and both public and private insurers should be required to pay for the procedure, she said.
“I would love to see strengthened provisions for contraception coverage,” Dr. Horvath said. “[We need to] make sure that doesn’t get bargained away. The other thing is to expand coverage and make sure every method is covered, not just one method in each category.”
However, Robert Doherty, ACP senior vice president of governmental affairs and public policy, said the college is concerned that the current administration may fail to maintain the ACA now that its proposed repeal law has fallen through.
Without aggressively pushing ACA enrollment for younger patients and continued support for the individual mandate, more insurers may pull out of the marketplaces, and the ACA could implode, Mr. Doherty said.
“There are a number of ways that Republicans could either make things better or worse with action or inaction,” Mr. Doherty said during the press conference. “The insurance [companies] have gone to this administration with a wish list of things that will help keep them in the market. What remains to be seen is whether this administration is going to be receptive. If they don’t aggressively enforce the requirement that people buy coverage, more younger people will opt out and stay out until they get sick. That would make the problem of adverse selection even worse and could create the death cycle for insurance.”
Dr. Price consistently answered that Americans should be able to select the kinds of coverage they want. What “we believe is that individuals ought to be able to have access to the kind of coverage that they select for themselves and for their families and not what the government forces them to buy,” Dr. Price testified, echoing the message from his confirmation hearings.
He was also pressed on issues such as the individual mandate, and while noting that it is his duty to uphold the law of the land, he also remained noncommittal in answering questions about whether he would direct the agency to enforce the individual mandate. The first executive order from President Trump beginning his administration gave the agency discretion to not enforce mandates if they caused harm.
[email protected]
On Twitter @legal_med
Gregory Twachtman contributed to this report.
With the demise of Republican repeal and replace legislation, analysts say the landscape is ripe for repairs to the Affordable Care Act or for additional legislation that both political parties could support. So what do physicians want from health reform?
The first step should be stabilizing the health insurance marketplaces by strengthening and perhaps extending risk mitigation measures such as the risk adjustment, risk corridors, and reinsurance provisions of the law, said Patricia Salber, MD, an internist and health care consultant who blogs at TheDoctorWeighsIn.com. Those three ACA provisions were intended to promote insurer competition on the basis of quality and value and promote insurance market stability.
Keeping premiums at manageable levels for patients should also be addressed, said William J. Burke, DO, dean of Ohio University Heritage College of Osteopathic Medicine.
That was echoed in a poll taken by this news organization. Of 390 respondents, fully half (50%) said they would repair the ACA by stabilizing premiums and out-of-pocket costs for patients as of April 2. About 11% stated they would increase payment rates for care provided to Medicaid patients, and 10% said they would return the primary care incentive payment. About 9% of those surveyed would address workforce issues exacerbated by more patients in the system.
Improving reimbursement for Medicaid services is a necessary health reform change, agreed Diane J. Horvath-Cosper MD, an obstetrician-gynecologist and reproductive health advocacy fellow for Physicians for Reproductive Health, a reproductive rights advocacy organization.
“Reimbursement rates are so low that sometimes [physicians] have to limit the number of Medicaid patients to be able to pay staff,” Dr. Horvath said in an interview. “That’s a terrible position to put physicians in because we want to be able to see as many people who want to see us.”
Speaking of Medicaid, Dr. Salber adds that governors should be encouraged to continue expanding Medicaid to eliminate the coverage gap for the “near poor” that exists in states that did not participate in the expansion.
“Now that the [American Health Care Act] has failed, I think we will see some expansion take place organically even in states that were deeply opposed before,” she said.
“The volume of prior authorizations that all physicians face, but especially primary care physicians, is huge,” Dr. Munger said in an interview. “In many cases, we’re having to hire extra staff just to handle all of the prior authorizations. Every patient may not just have one prior authorization, but they may require two or three or four prior authorizations each month or quarterly. It really detracts from meaningful time you can spend with the patient.”
For starters, doctors should provide care to patients based on mutually agreed terms and without the interference of insurers, Dr. Orient said in an interview. In such a private medicine system, patients would pay doctors for services, and patients would then file claims with their insurer for reimbursement. Similarly, physicians should not be at the mercy of Medicare for payment, Dr. Orient said.
“Doctors can sign away their rights if they want in a Medicare participation agreement,” she said. “Doctors who do not sign the agreement to take assignment in all cases doctors should be freed of price controls and coding demands. Their patients should be allowed to file their own simple claims to Medicare with an itemized bill as they did before the 1990s law that requires physicians to submit the claims. Non-participating doctors should be exempted from MACRA [the Medicare Access and CHIP Reauthorization Act], and without the price controls, there is no need for [Recovery Audit Contractors] and other auditors.”
While contraceptive care was strengthened by the ACA, Dr. Horvath said further efforts should be made to improve coverage and level the playing field for reproductive medicine. In addition, she said that abortion should be treated a valid medical procedure, rather than parsed out, and both public and private insurers should be required to pay for the procedure, she said.
“I would love to see strengthened provisions for contraception coverage,” Dr. Horvath said. “[We need to] make sure that doesn’t get bargained away. The other thing is to expand coverage and make sure every method is covered, not just one method in each category.”
However, Robert Doherty, ACP senior vice president of governmental affairs and public policy, said the college is concerned that the current administration may fail to maintain the ACA now that its proposed repeal law has fallen through.
Without aggressively pushing ACA enrollment for younger patients and continued support for the individual mandate, more insurers may pull out of the marketplaces, and the ACA could implode, Mr. Doherty said.
“There are a number of ways that Republicans could either make things better or worse with action or inaction,” Mr. Doherty said during the press conference. “The insurance [companies] have gone to this administration with a wish list of things that will help keep them in the market. What remains to be seen is whether this administration is going to be receptive. If they don’t aggressively enforce the requirement that people buy coverage, more younger people will opt out and stay out until they get sick. That would make the problem of adverse selection even worse and could create the death cycle for insurance.”
Dr. Price consistently answered that Americans should be able to select the kinds of coverage they want. What “we believe is that individuals ought to be able to have access to the kind of coverage that they select for themselves and for their families and not what the government forces them to buy,” Dr. Price testified, echoing the message from his confirmation hearings.
He was also pressed on issues such as the individual mandate, and while noting that it is his duty to uphold the law of the land, he also remained noncommittal in answering questions about whether he would direct the agency to enforce the individual mandate. The first executive order from President Trump beginning his administration gave the agency discretion to not enforce mandates if they caused harm.
[email protected]
On Twitter @legal_med
Gregory Twachtman contributed to this report.
Statins may protect against HIV rebound
SEATTLE – Statins appeared to reduce the risk of viral rebound in HIV patients on antiretroviral therapy, suggesting modest antiviral activity, according to a review of 19,324 HIV-positive veterans who started combination ART from 1995-2011.
It’s been shown before that statins are active against HIV in vitro; the new study is likely the first to show an effect in actual patients, and it was only found in those who used statins consistently, perhaps because of the drugs’ short half-life. “In addition to their cardiovascular benefits, statins could increase the durability of successful antiretroviral therapy. Whether this effect is direct or mediated by [statins’] anti-inflammatory properties merits further evaluation,” concluded investigators led by Henning Drechsler, MD, an infectious disease specialist at the Dallas Veterans Affairs Medical Center.
After adjusting for a range of confounders, including demographics, substance use, and ART adherence assessed by pharmacy fill records, the team found that statins use within 7 days of testing was associated with almost a 20% drop in the risk of decreased risk of VF (adjusted HR 0.81, 95% 0.75-0.88), with a similar benefit for use within 3 months. There was no protective effect for blood pressure drugs, and a slight increase for patients on cardioprotective aspirin.
About a third of the patients – almost all men, around 48 years old – had at least tried statins, generally after their viral loads were suppressed and most often pravastatin or simvastatin. Statins’ protection against VF was present over the whole study period and among all types of ART and levels, but became less pronounced after 2005 in patients with optimal ART adherence, and in those taking newer options. The median observation time was 5.9 years.
“I am very confident that this is not a data fluke,” Dr. Drechsler said at the 2017 Conference on Retroviruses and Opportunistic Infections. He noted that there may even be role for statin use in HIV patients without dyslipidemia, but with the current study, “it’s hard to say. You really do need a prospect study.”
He plans to keep looking into the issue. Meanwhile, a large trial of statin use in HIV is underway.
Dr. Drechsler said he had no disclosures.
SEATTLE – Statins appeared to reduce the risk of viral rebound in HIV patients on antiretroviral therapy, suggesting modest antiviral activity, according to a review of 19,324 HIV-positive veterans who started combination ART from 1995-2011.
It’s been shown before that statins are active against HIV in vitro; the new study is likely the first to show an effect in actual patients, and it was only found in those who used statins consistently, perhaps because of the drugs’ short half-life. “In addition to their cardiovascular benefits, statins could increase the durability of successful antiretroviral therapy. Whether this effect is direct or mediated by [statins’] anti-inflammatory properties merits further evaluation,” concluded investigators led by Henning Drechsler, MD, an infectious disease specialist at the Dallas Veterans Affairs Medical Center.
After adjusting for a range of confounders, including demographics, substance use, and ART adherence assessed by pharmacy fill records, the team found that statins use within 7 days of testing was associated with almost a 20% drop in the risk of decreased risk of VF (adjusted HR 0.81, 95% 0.75-0.88), with a similar benefit for use within 3 months. There was no protective effect for blood pressure drugs, and a slight increase for patients on cardioprotective aspirin.
About a third of the patients – almost all men, around 48 years old – had at least tried statins, generally after their viral loads were suppressed and most often pravastatin or simvastatin. Statins’ protection against VF was present over the whole study period and among all types of ART and levels, but became less pronounced after 2005 in patients with optimal ART adherence, and in those taking newer options. The median observation time was 5.9 years.
“I am very confident that this is not a data fluke,” Dr. Drechsler said at the 2017 Conference on Retroviruses and Opportunistic Infections. He noted that there may even be role for statin use in HIV patients without dyslipidemia, but with the current study, “it’s hard to say. You really do need a prospect study.”
He plans to keep looking into the issue. Meanwhile, a large trial of statin use in HIV is underway.
Dr. Drechsler said he had no disclosures.
SEATTLE – Statins appeared to reduce the risk of viral rebound in HIV patients on antiretroviral therapy, suggesting modest antiviral activity, according to a review of 19,324 HIV-positive veterans who started combination ART from 1995-2011.
It’s been shown before that statins are active against HIV in vitro; the new study is likely the first to show an effect in actual patients, and it was only found in those who used statins consistently, perhaps because of the drugs’ short half-life. “In addition to their cardiovascular benefits, statins could increase the durability of successful antiretroviral therapy. Whether this effect is direct or mediated by [statins’] anti-inflammatory properties merits further evaluation,” concluded investigators led by Henning Drechsler, MD, an infectious disease specialist at the Dallas Veterans Affairs Medical Center.
After adjusting for a range of confounders, including demographics, substance use, and ART adherence assessed by pharmacy fill records, the team found that statins use within 7 days of testing was associated with almost a 20% drop in the risk of decreased risk of VF (adjusted HR 0.81, 95% 0.75-0.88), with a similar benefit for use within 3 months. There was no protective effect for blood pressure drugs, and a slight increase for patients on cardioprotective aspirin.
About a third of the patients – almost all men, around 48 years old – had at least tried statins, generally after their viral loads were suppressed and most often pravastatin or simvastatin. Statins’ protection against VF was present over the whole study period and among all types of ART and levels, but became less pronounced after 2005 in patients with optimal ART adherence, and in those taking newer options. The median observation time was 5.9 years.
“I am very confident that this is not a data fluke,” Dr. Drechsler said at the 2017 Conference on Retroviruses and Opportunistic Infections. He noted that there may even be role for statin use in HIV patients without dyslipidemia, but with the current study, “it’s hard to say. You really do need a prospect study.”
He plans to keep looking into the issue. Meanwhile, a large trial of statin use in HIV is underway.
Dr. Drechsler said he had no disclosures.
AT CROI 2017
Ebola vaccine maintains immune response after 1 year
People who received an Ebola virus vaccine maintained immune response one year after vaccination, according to a research letter from Rebecca L.Winslow, MRCGP, of the University of Oxford (UK) and her associates.
The immune response of 64 vaccine recipients of European descent 360 days after receiving either adenovirus type 26 vector vaccine encoding Ebolavirus glycoprotein (Ad26.ZEBOV) followed by modified vaccinia virus Ankara vector vaccine (MVA-BN-Filo), or MVA-BN-Filo followed by Ad26.ZEBOV. The 360 day follow-up occurred 120 days after the previous follow-up, during which time no significant adverse events were reported.
“Immune responses may differ in a sub-Saharan African population; these vaccine candidates are being assessed in this region. Additional research is also warranted to explore the persistence of immunity beyond 1 year following immunization and response to booster doses of vaccine,” the investigators concluded.
Find the full research letter in JAMA (doi: 10.1001/jama.2016.20644)
People who received an Ebola virus vaccine maintained immune response one year after vaccination, according to a research letter from Rebecca L.Winslow, MRCGP, of the University of Oxford (UK) and her associates.
The immune response of 64 vaccine recipients of European descent 360 days after receiving either adenovirus type 26 vector vaccine encoding Ebolavirus glycoprotein (Ad26.ZEBOV) followed by modified vaccinia virus Ankara vector vaccine (MVA-BN-Filo), or MVA-BN-Filo followed by Ad26.ZEBOV. The 360 day follow-up occurred 120 days after the previous follow-up, during which time no significant adverse events were reported.
“Immune responses may differ in a sub-Saharan African population; these vaccine candidates are being assessed in this region. Additional research is also warranted to explore the persistence of immunity beyond 1 year following immunization and response to booster doses of vaccine,” the investigators concluded.
Find the full research letter in JAMA (doi: 10.1001/jama.2016.20644)
People who received an Ebola virus vaccine maintained immune response one year after vaccination, according to a research letter from Rebecca L.Winslow, MRCGP, of the University of Oxford (UK) and her associates.
The immune response of 64 vaccine recipients of European descent 360 days after receiving either adenovirus type 26 vector vaccine encoding Ebolavirus glycoprotein (Ad26.ZEBOV) followed by modified vaccinia virus Ankara vector vaccine (MVA-BN-Filo), or MVA-BN-Filo followed by Ad26.ZEBOV. The 360 day follow-up occurred 120 days after the previous follow-up, during which time no significant adverse events were reported.
“Immune responses may differ in a sub-Saharan African population; these vaccine candidates are being assessed in this region. Additional research is also warranted to explore the persistence of immunity beyond 1 year following immunization and response to booster doses of vaccine,” the investigators concluded.
Find the full research letter in JAMA (doi: 10.1001/jama.2016.20644)
FROM JAMA
Temozolomide may help half of patients with aggressive pituitary tumors
ORLANDO – Temozolomide, an alkylating agent approved for glioblastoma, improved long-term survival in about half of patients who took it for aggressive pituitary tumors, a retrospective study has determined.
The study, conducted by members of the French Society of Endocrinology, comprised 43 patients. Of the 51% who responded to the treatment, the median overall survival time was 44 months, compared to just 16 months for patients who didn’t respond, Gérald Raverot, MD, said at the annual meeting of the Endocrine Society.
“Despite the very good response we saw in some patients, we also saw a high risk of recurrence, with a median of about 30 months,” for relapse, he noted. “And a second course of temozolomide always failed.”
When used for aggressive pituitary tumors, temozolomide is usually given in a conventional scheme of up to 12 cycles. It’s typically reserved for tumors that have responded poorly to other treatment regimens, Dr. Raverot said.
The drug has not been widely studied in patients with aggressive pituitary tumors, although there have been a number of case reports suggesting that can be beneficial. Data on about 90 patients have been published. The largest series to date appeared in 2015 and comprised 24 patients. It found about a 50% response rate to the drug. Two patients had a complete regression and seven patients had a partial regression of tumor mass. Tumor mass shrunk to less than 30% in three patients, less than 50% in three, and less than 75% in one.
Because of both the promise temozolomide shows in these very tough cases, and the paucity of descriptive and clinical data, Dr. Raverot and his colleagues conducted a multi-center study that spanned 21 facilities in France and comprised 43 patients who were treated from 2006-2016. The intent was to evaluate efficacy at the end of treatment, or at last follow-up in the case of those who were still being treated. Tumor response was defined as a decrease of more than 30% in the largest tumor diameter; hormonal response was more than a 50% decrease in baseline hormone levels. The endpoint was overall survival and relapse-free survival.
Of the 43 patients, 29 were men. The group’s mean age at diagnosis was 43 years, and the mean age at temozolomide treatment, 53 years. Fourteen of the tumors were carcinomas and 12 were silent or initially silent.
About half of the tumors (23) were adrenocorticotropic hormone-producing. Other tumor types were prolactin-secreting (13) and growth hormone-secreting (3); an additional three tumors secreted both prolactin and growth hormone.
Most patients (36) underwent a typical temozolomide protocol. This consisted of at least one 5-day cycle of 150 mg/m2/day every 28 days, followed by 250 mg/m2/day thereafter. The median number of cycles was 6.5, but this ranged from 1-24 cycles.
Six patients were treated according to the Stupp protocol for temozolomide in glioblastoma. This consists of daily temozolomide 75 mg/m2 with concomitant radiotherapy for 6 weeks, followed by a standard temozolomide protocol. Four patients underwent 6 cycles; one patient 12 cycles, and one patient, 17 cycles.
An additional four patients had concomitant radiotherapy within 4 months of their temozolomide treatment.
The overall response rate was 51% (22 patients). Dr. Raverot attempted to identify clinical characteristics predictive of response. There was no association with gender, age at diagnosis or age at temozolomide treatment, tumor type, whether or not the tumor was a carcinoma, or what type of hormone it secreted. Nor was there a response associated with hypermethylation of the O6-methylguanine-DNA-methyltransferase (MGMT) gene.
Dr. Raverot found only one positive association with response. Tumors that were silent or initially silent (12) were much less likely to respond than secreting tumors. Of the 21 nonresponsive tumors, 10 were silent (45%). Of the 22 responsive tumors, only 2 were silent (9%).
Dr. Raverot also analyzed response by protocol and found intriguing results. Of the 10 patients who had concomitant radiotherapy, seven responded and three did not. Patients who underwent the Stupp protocol also tended to do better, he said. “Of the six who had this, five responded, so this is interesting.”
However, he cautioned, both of these positive associations are based on such small numbers that it’s impossible to draw firm conclusions.
Dr. Raverot had survival data on 38 patients with a median follow-up of 16 months after the end of treatment. Of these, 20 were responders and 18 were non-responders. Death had occurred in 13 of the nonresponders and five responders.
Of the 20 responders, 10 were still controlled at the time of last follow-up, and 10 had relapsed at a median of 5 months after treatment cessation. Five of these patients had a second course of temozolomide, but none of them responded to it, Dr. Raverot said. Three of these patients have died and two are still living.
“We looked at other salvage treatments for them, but none of these therapies could control the disease. Unfortunately, we just don’t have good treatment options for these patients. And even among those with good treatment response, there is a risk of early recurrence, with a median time of 30 months to relapse. The second course of temozolomide always fails. So we have now some questions about who we should maintain on treatment. We don’t have this answered yet, and we need to.”
Dr. Raverot had no financial disclosures.
[email protected]
On Twitter @Alz_gal
ORLANDO – Temozolomide, an alkylating agent approved for glioblastoma, improved long-term survival in about half of patients who took it for aggressive pituitary tumors, a retrospective study has determined.
The study, conducted by members of the French Society of Endocrinology, comprised 43 patients. Of the 51% who responded to the treatment, the median overall survival time was 44 months, compared to just 16 months for patients who didn’t respond, Gérald Raverot, MD, said at the annual meeting of the Endocrine Society.
“Despite the very good response we saw in some patients, we also saw a high risk of recurrence, with a median of about 30 months,” for relapse, he noted. “And a second course of temozolomide always failed.”
When used for aggressive pituitary tumors, temozolomide is usually given in a conventional scheme of up to 12 cycles. It’s typically reserved for tumors that have responded poorly to other treatment regimens, Dr. Raverot said.
The drug has not been widely studied in patients with aggressive pituitary tumors, although there have been a number of case reports suggesting that can be beneficial. Data on about 90 patients have been published. The largest series to date appeared in 2015 and comprised 24 patients. It found about a 50% response rate to the drug. Two patients had a complete regression and seven patients had a partial regression of tumor mass. Tumor mass shrunk to less than 30% in three patients, less than 50% in three, and less than 75% in one.
Because of both the promise temozolomide shows in these very tough cases, and the paucity of descriptive and clinical data, Dr. Raverot and his colleagues conducted a multi-center study that spanned 21 facilities in France and comprised 43 patients who were treated from 2006-2016. The intent was to evaluate efficacy at the end of treatment, or at last follow-up in the case of those who were still being treated. Tumor response was defined as a decrease of more than 30% in the largest tumor diameter; hormonal response was more than a 50% decrease in baseline hormone levels. The endpoint was overall survival and relapse-free survival.
Of the 43 patients, 29 were men. The group’s mean age at diagnosis was 43 years, and the mean age at temozolomide treatment, 53 years. Fourteen of the tumors were carcinomas and 12 were silent or initially silent.
About half of the tumors (23) were adrenocorticotropic hormone-producing. Other tumor types were prolactin-secreting (13) and growth hormone-secreting (3); an additional three tumors secreted both prolactin and growth hormone.
Most patients (36) underwent a typical temozolomide protocol. This consisted of at least one 5-day cycle of 150 mg/m2/day every 28 days, followed by 250 mg/m2/day thereafter. The median number of cycles was 6.5, but this ranged from 1-24 cycles.
Six patients were treated according to the Stupp protocol for temozolomide in glioblastoma. This consists of daily temozolomide 75 mg/m2 with concomitant radiotherapy for 6 weeks, followed by a standard temozolomide protocol. Four patients underwent 6 cycles; one patient 12 cycles, and one patient, 17 cycles.
An additional four patients had concomitant radiotherapy within 4 months of their temozolomide treatment.
The overall response rate was 51% (22 patients). Dr. Raverot attempted to identify clinical characteristics predictive of response. There was no association with gender, age at diagnosis or age at temozolomide treatment, tumor type, whether or not the tumor was a carcinoma, or what type of hormone it secreted. Nor was there a response associated with hypermethylation of the O6-methylguanine-DNA-methyltransferase (MGMT) gene.
Dr. Raverot found only one positive association with response. Tumors that were silent or initially silent (12) were much less likely to respond than secreting tumors. Of the 21 nonresponsive tumors, 10 were silent (45%). Of the 22 responsive tumors, only 2 were silent (9%).
Dr. Raverot also analyzed response by protocol and found intriguing results. Of the 10 patients who had concomitant radiotherapy, seven responded and three did not. Patients who underwent the Stupp protocol also tended to do better, he said. “Of the six who had this, five responded, so this is interesting.”
However, he cautioned, both of these positive associations are based on such small numbers that it’s impossible to draw firm conclusions.
Dr. Raverot had survival data on 38 patients with a median follow-up of 16 months after the end of treatment. Of these, 20 were responders and 18 were non-responders. Death had occurred in 13 of the nonresponders and five responders.
Of the 20 responders, 10 were still controlled at the time of last follow-up, and 10 had relapsed at a median of 5 months after treatment cessation. Five of these patients had a second course of temozolomide, but none of them responded to it, Dr. Raverot said. Three of these patients have died and two are still living.
“We looked at other salvage treatments for them, but none of these therapies could control the disease. Unfortunately, we just don’t have good treatment options for these patients. And even among those with good treatment response, there is a risk of early recurrence, with a median time of 30 months to relapse. The second course of temozolomide always fails. So we have now some questions about who we should maintain on treatment. We don’t have this answered yet, and we need to.”
Dr. Raverot had no financial disclosures.
[email protected]
On Twitter @Alz_gal
ORLANDO – Temozolomide, an alkylating agent approved for glioblastoma, improved long-term survival in about half of patients who took it for aggressive pituitary tumors, a retrospective study has determined.
The study, conducted by members of the French Society of Endocrinology, comprised 43 patients. Of the 51% who responded to the treatment, the median overall survival time was 44 months, compared to just 16 months for patients who didn’t respond, Gérald Raverot, MD, said at the annual meeting of the Endocrine Society.
“Despite the very good response we saw in some patients, we also saw a high risk of recurrence, with a median of about 30 months,” for relapse, he noted. “And a second course of temozolomide always failed.”
When used for aggressive pituitary tumors, temozolomide is usually given in a conventional scheme of up to 12 cycles. It’s typically reserved for tumors that have responded poorly to other treatment regimens, Dr. Raverot said.
The drug has not been widely studied in patients with aggressive pituitary tumors, although there have been a number of case reports suggesting that can be beneficial. Data on about 90 patients have been published. The largest series to date appeared in 2015 and comprised 24 patients. It found about a 50% response rate to the drug. Two patients had a complete regression and seven patients had a partial regression of tumor mass. Tumor mass shrunk to less than 30% in three patients, less than 50% in three, and less than 75% in one.
Because of both the promise temozolomide shows in these very tough cases, and the paucity of descriptive and clinical data, Dr. Raverot and his colleagues conducted a multi-center study that spanned 21 facilities in France and comprised 43 patients who were treated from 2006-2016. The intent was to evaluate efficacy at the end of treatment, or at last follow-up in the case of those who were still being treated. Tumor response was defined as a decrease of more than 30% in the largest tumor diameter; hormonal response was more than a 50% decrease in baseline hormone levels. The endpoint was overall survival and relapse-free survival.
Of the 43 patients, 29 were men. The group’s mean age at diagnosis was 43 years, and the mean age at temozolomide treatment, 53 years. Fourteen of the tumors were carcinomas and 12 were silent or initially silent.
About half of the tumors (23) were adrenocorticotropic hormone-producing. Other tumor types were prolactin-secreting (13) and growth hormone-secreting (3); an additional three tumors secreted both prolactin and growth hormone.
Most patients (36) underwent a typical temozolomide protocol. This consisted of at least one 5-day cycle of 150 mg/m2/day every 28 days, followed by 250 mg/m2/day thereafter. The median number of cycles was 6.5, but this ranged from 1-24 cycles.
Six patients were treated according to the Stupp protocol for temozolomide in glioblastoma. This consists of daily temozolomide 75 mg/m2 with concomitant radiotherapy for 6 weeks, followed by a standard temozolomide protocol. Four patients underwent 6 cycles; one patient 12 cycles, and one patient, 17 cycles.
An additional four patients had concomitant radiotherapy within 4 months of their temozolomide treatment.
The overall response rate was 51% (22 patients). Dr. Raverot attempted to identify clinical characteristics predictive of response. There was no association with gender, age at diagnosis or age at temozolomide treatment, tumor type, whether or not the tumor was a carcinoma, or what type of hormone it secreted. Nor was there a response associated with hypermethylation of the O6-methylguanine-DNA-methyltransferase (MGMT) gene.
Dr. Raverot found only one positive association with response. Tumors that were silent or initially silent (12) were much less likely to respond than secreting tumors. Of the 21 nonresponsive tumors, 10 were silent (45%). Of the 22 responsive tumors, only 2 were silent (9%).
Dr. Raverot also analyzed response by protocol and found intriguing results. Of the 10 patients who had concomitant radiotherapy, seven responded and three did not. Patients who underwent the Stupp protocol also tended to do better, he said. “Of the six who had this, five responded, so this is interesting.”
However, he cautioned, both of these positive associations are based on such small numbers that it’s impossible to draw firm conclusions.
Dr. Raverot had survival data on 38 patients with a median follow-up of 16 months after the end of treatment. Of these, 20 were responders and 18 were non-responders. Death had occurred in 13 of the nonresponders and five responders.
Of the 20 responders, 10 were still controlled at the time of last follow-up, and 10 had relapsed at a median of 5 months after treatment cessation. Five of these patients had a second course of temozolomide, but none of them responded to it, Dr. Raverot said. Three of these patients have died and two are still living.
“We looked at other salvage treatments for them, but none of these therapies could control the disease. Unfortunately, we just don’t have good treatment options for these patients. And even among those with good treatment response, there is a risk of early recurrence, with a median time of 30 months to relapse. The second course of temozolomide always fails. So we have now some questions about who we should maintain on treatment. We don’t have this answered yet, and we need to.”
Dr. Raverot had no financial disclosures.
[email protected]
On Twitter @Alz_gal
AT ENDO 2017
Key clinical point:
Major finding: Of the 51% who responded to the treatment, the median overall survival time was 44 months, compared to just 16 months for patients who didn’t respond.
Data source: The retrospective study comprised 43 patients treated in France.
Disclosures: Dr. Raverot had no financial disclosures.
Thyroid cancer incidence: It’s not all good news
ORLANDO – The incidence of thyroid cancer in the United States between 2000-2013 has dropped in whites while increasing in blacks and Hispanics, Anupam Kotwal, MBBS, said during a press briefing at the annual meeting of the Endocrine Society.
Other recently reported data have shown a steady gradual incidence in thyroid cancer between 1974-2013 (JAMA. 2017 Mar 31. doi:10.1001/jama.2017.2719).
From 2000 to 2013, the incidence of thyroid cancer as a whole increased from 7.4 to 14.5 cases per 100,000 population with an annual percent increase of 6.7% from 2000-2009 (P less than .05) and 2.4% from 2010 to 2013 (P less than .05). In Hispanics and African-Americans, thyroid cancer incidence has continuously increased, with an annual percent increase of 4.7% (P less than .05) and 5.1% (P less than .05) respectively, whereas for non-Hispanic whites, the annual percent increase decelerated from 7.1% (P less than .05) before 2009 to 2.2% after 2009.
Looking at changes to incidence by age, non-Hispanic white women over the age of 75 are the only ones to see a decrease, from 6.5 cases per 100,000 in 2010 to 2.4 cases per 100,000 population in 2014. The investigations reported the same acceleration of incidence among everyone under the age of 20 years.
These findings are consistent with recent reports demonstrating that thyroid cancer is the 2nd most common cancer among Hispanic females, female adolescents and young adults.
Dr. Kotwal reported that he had no relevant conflicts of interest.
ORLANDO – The incidence of thyroid cancer in the United States between 2000-2013 has dropped in whites while increasing in blacks and Hispanics, Anupam Kotwal, MBBS, said during a press briefing at the annual meeting of the Endocrine Society.
Other recently reported data have shown a steady gradual incidence in thyroid cancer between 1974-2013 (JAMA. 2017 Mar 31. doi:10.1001/jama.2017.2719).
From 2000 to 2013, the incidence of thyroid cancer as a whole increased from 7.4 to 14.5 cases per 100,000 population with an annual percent increase of 6.7% from 2000-2009 (P less than .05) and 2.4% from 2010 to 2013 (P less than .05). In Hispanics and African-Americans, thyroid cancer incidence has continuously increased, with an annual percent increase of 4.7% (P less than .05) and 5.1% (P less than .05) respectively, whereas for non-Hispanic whites, the annual percent increase decelerated from 7.1% (P less than .05) before 2009 to 2.2% after 2009.
Looking at changes to incidence by age, non-Hispanic white women over the age of 75 are the only ones to see a decrease, from 6.5 cases per 100,000 in 2010 to 2.4 cases per 100,000 population in 2014. The investigations reported the same acceleration of incidence among everyone under the age of 20 years.
These findings are consistent with recent reports demonstrating that thyroid cancer is the 2nd most common cancer among Hispanic females, female adolescents and young adults.
Dr. Kotwal reported that he had no relevant conflicts of interest.
ORLANDO – The incidence of thyroid cancer in the United States between 2000-2013 has dropped in whites while increasing in blacks and Hispanics, Anupam Kotwal, MBBS, said during a press briefing at the annual meeting of the Endocrine Society.
Other recently reported data have shown a steady gradual incidence in thyroid cancer between 1974-2013 (JAMA. 2017 Mar 31. doi:10.1001/jama.2017.2719).
From 2000 to 2013, the incidence of thyroid cancer as a whole increased from 7.4 to 14.5 cases per 100,000 population with an annual percent increase of 6.7% from 2000-2009 (P less than .05) and 2.4% from 2010 to 2013 (P less than .05). In Hispanics and African-Americans, thyroid cancer incidence has continuously increased, with an annual percent increase of 4.7% (P less than .05) and 5.1% (P less than .05) respectively, whereas for non-Hispanic whites, the annual percent increase decelerated from 7.1% (P less than .05) before 2009 to 2.2% after 2009.
Looking at changes to incidence by age, non-Hispanic white women over the age of 75 are the only ones to see a decrease, from 6.5 cases per 100,000 in 2010 to 2.4 cases per 100,000 population in 2014. The investigations reported the same acceleration of incidence among everyone under the age of 20 years.
These findings are consistent with recent reports demonstrating that thyroid cancer is the 2nd most common cancer among Hispanic females, female adolescents and young adults.
Dr. Kotwal reported that he had no relevant conflicts of interest.
AT ENDO 2017
Key clinical point:
Major finding: The incidence of thyroid cancer has dropped from 7 cases per 100,000 in 2000 to 2.2 cases per 100,000 in 2013 among whites. Among blacks it has increased from 5 cases to 7 cases per 100,000 over that time frame and in Hispanics from 7 cases to 12 cases per 100,000.
Data source: Data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results data base.
Disclosures: The study received no external funding. Dr. Kotwal reported he had no relevant financial conflicts of interest.
Rotterdam Study: High T4 levels increased the risk for atherosclerotic events, death
ORLANDO – Elevated serum levels of free T4 are associated with a greater risk of atherosclerotic events and, in some cases, death, among adults in their 60s, Arjola Bano, MD, said at a press briefing at the annual meeting of the Endocrine Society.
Earlier research has shown that high FT4 levels are associated with a greater likelihood of development of atherosclerosis. But no one has looked beyond that to see if an excess of FT4 can change the course of the disease.
The investigators used electron beam computed tomography to measure coronary artery calcification. Confounders such as age, sex, smoking, alcohol intake, body mass index, total cholesterol, triglycerides, systolic blood pressure, diabetes, and use of anti-hypertension or lipid lowering medications were controlled for using multivariable-adjusted Cox proportional and logistic regression models.
Dr. Bano reported that during a median follow-up of 8.8 years (range, 4.5-11.8 years), there were 580 ASCV deaths and 1,130 first-time hard ASCV events. The risk of ASCV mortality increased with higher FT4 levels (hazard ratio, 2.35; 95% confidence interval, 1.61-3.41 per 1 ng/dL) and lower TSH levels (HR, 0.92; 95% CI, 0.84-1.00/1 logTSH), predominantly among participants with prevalent ASCV disease (HR, 5.76; 95% CI, 2.79-11.89 for FT4; HR, 0.81; 95% CI, 0.69-0.95 for TSH).
In addition, higher FT4 levels were associated with higher risk of first-time hard ASCV event (HR, 1.87; 95% CI, 1.34-2.59). Also, FT4 levels were positively associated with having a high CAC score (OR, 2.34; 95% CI, 1.36-4.04).
It is noteworthy that results remained similar after restricting the analyses to participants with thyroid function within reference ranges, she stressed.
How to explain these findings? These data suggest that the link between thyroid function and atherosclerosis is mediated through yet unexplored cardiovascular risk factors or via alternative pathways.
Dr. Bano and her associates all report that they have no relevant financial conflicts of interest.
ORLANDO – Elevated serum levels of free T4 are associated with a greater risk of atherosclerotic events and, in some cases, death, among adults in their 60s, Arjola Bano, MD, said at a press briefing at the annual meeting of the Endocrine Society.
Earlier research has shown that high FT4 levels are associated with a greater likelihood of development of atherosclerosis. But no one has looked beyond that to see if an excess of FT4 can change the course of the disease.
The investigators used electron beam computed tomography to measure coronary artery calcification. Confounders such as age, sex, smoking, alcohol intake, body mass index, total cholesterol, triglycerides, systolic blood pressure, diabetes, and use of anti-hypertension or lipid lowering medications were controlled for using multivariable-adjusted Cox proportional and logistic regression models.
Dr. Bano reported that during a median follow-up of 8.8 years (range, 4.5-11.8 years), there were 580 ASCV deaths and 1,130 first-time hard ASCV events. The risk of ASCV mortality increased with higher FT4 levels (hazard ratio, 2.35; 95% confidence interval, 1.61-3.41 per 1 ng/dL) and lower TSH levels (HR, 0.92; 95% CI, 0.84-1.00/1 logTSH), predominantly among participants with prevalent ASCV disease (HR, 5.76; 95% CI, 2.79-11.89 for FT4; HR, 0.81; 95% CI, 0.69-0.95 for TSH).
In addition, higher FT4 levels were associated with higher risk of first-time hard ASCV event (HR, 1.87; 95% CI, 1.34-2.59). Also, FT4 levels were positively associated with having a high CAC score (OR, 2.34; 95% CI, 1.36-4.04).
It is noteworthy that results remained similar after restricting the analyses to participants with thyroid function within reference ranges, she stressed.
How to explain these findings? These data suggest that the link between thyroid function and atherosclerosis is mediated through yet unexplored cardiovascular risk factors or via alternative pathways.
Dr. Bano and her associates all report that they have no relevant financial conflicts of interest.
ORLANDO – Elevated serum levels of free T4 are associated with a greater risk of atherosclerotic events and, in some cases, death, among adults in their 60s, Arjola Bano, MD, said at a press briefing at the annual meeting of the Endocrine Society.
Earlier research has shown that high FT4 levels are associated with a greater likelihood of development of atherosclerosis. But no one has looked beyond that to see if an excess of FT4 can change the course of the disease.
The investigators used electron beam computed tomography to measure coronary artery calcification. Confounders such as age, sex, smoking, alcohol intake, body mass index, total cholesterol, triglycerides, systolic blood pressure, diabetes, and use of anti-hypertension or lipid lowering medications were controlled for using multivariable-adjusted Cox proportional and logistic regression models.
Dr. Bano reported that during a median follow-up of 8.8 years (range, 4.5-11.8 years), there were 580 ASCV deaths and 1,130 first-time hard ASCV events. The risk of ASCV mortality increased with higher FT4 levels (hazard ratio, 2.35; 95% confidence interval, 1.61-3.41 per 1 ng/dL) and lower TSH levels (HR, 0.92; 95% CI, 0.84-1.00/1 logTSH), predominantly among participants with prevalent ASCV disease (HR, 5.76; 95% CI, 2.79-11.89 for FT4; HR, 0.81; 95% CI, 0.69-0.95 for TSH).
In addition, higher FT4 levels were associated with higher risk of first-time hard ASCV event (HR, 1.87; 95% CI, 1.34-2.59). Also, FT4 levels were positively associated with having a high CAC score (OR, 2.34; 95% CI, 1.36-4.04).
It is noteworthy that results remained similar after restricting the analyses to participants with thyroid function within reference ranges, she stressed.
How to explain these findings? These data suggest that the link between thyroid function and atherosclerosis is mediated through yet unexplored cardiovascular risk factors or via alternative pathways.
Dr. Bano and her associates all report that they have no relevant financial conflicts of interest.
AT ENDO 2017
Key clinical point: Major finding: The odds of an atherosclerotic event were 2.28 times higher in adults with elevated FT4 levels than those with high TSH, even when the high levels were still within the normal range.
Data source: Prospective study of 9,231 adults followed over 8.8 years.
Disclosures: Dr. Bano and her associates all report that they have no relevant financial conflicts of interest.
Assay intended to aid PV diagnosis cleared for use in US
The US Food and Drug Administration has granted 510(k) clearance for QIAGEN’s ipsogen® JAK2 RGQ PCR Kit (ipsogen JAK2 assay), and the company has launched the assay in the US.
The ipsogen JAK2 assay is designed to detect the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood.
The assay is intended for use in conjunction with other clinicopathological factors to aid the diagnosis of polycythemia vera (PV).
The test does not detect less common mutations associated with PV, including mutations in exon 12, and is not intended for stand-alone diagnosis of PV.
The ipsogen JAK2 assay is a real-time polymerase chain reaction test performed on the QIAGEN Rotor-Gene Q MDx instrument.
Researchers evaluated the utility of the ipsogen JAK2 assay for PV diagnosis in a prospective trial enrolling more than 200 subjects.
Data from this trial have not been published. However, according to QIAGEN, the assay provided 94.6% sensitivity and 98.1% specificity, together with a 100% positive percentage agreement and a 99.4% negative percentage agreement to bi-directional sequencing.
QIAGEN said these results suggest the ipsogen JAK2 assay enables detection of PV in the majority of subjects with the disease and helps rule out PV in the majority of individuals without it.
“We are pleased to be able to offer our ipsogen JAK2 assay, which is already available in Europe and other markets, for use in the United States and make it easier for hematologists and oncologists to follow recommended diagnostic testing algorithms and international guidelines for suspected PV patients,” said Thierry Bernard, senior vice president and head of QIAGEN’s Molecular Diagnostics Business Area. 
The US Food and Drug Administration has granted 510(k) clearance for QIAGEN’s ipsogen® JAK2 RGQ PCR Kit (ipsogen JAK2 assay), and the company has launched the assay in the US.
The ipsogen JAK2 assay is designed to detect the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood.
The assay is intended for use in conjunction with other clinicopathological factors to aid the diagnosis of polycythemia vera (PV).
The test does not detect less common mutations associated with PV, including mutations in exon 12, and is not intended for stand-alone diagnosis of PV.
The ipsogen JAK2 assay is a real-time polymerase chain reaction test performed on the QIAGEN Rotor-Gene Q MDx instrument.
Researchers evaluated the utility of the ipsogen JAK2 assay for PV diagnosis in a prospective trial enrolling more than 200 subjects.
Data from this trial have not been published. However, according to QIAGEN, the assay provided 94.6% sensitivity and 98.1% specificity, together with a 100% positive percentage agreement and a 99.4% negative percentage agreement to bi-directional sequencing.
QIAGEN said these results suggest the ipsogen JAK2 assay enables detection of PV in the majority of subjects with the disease and helps rule out PV in the majority of individuals without it.
“We are pleased to be able to offer our ipsogen JAK2 assay, which is already available in Europe and other markets, for use in the United States and make it easier for hematologists and oncologists to follow recommended diagnostic testing algorithms and international guidelines for suspected PV patients,” said Thierry Bernard, senior vice president and head of QIAGEN’s Molecular Diagnostics Business Area.
The US Food and Drug Administration has granted 510(k) clearance for QIAGEN’s ipsogen® JAK2 RGQ PCR Kit (ipsogen JAK2 assay), and the company has launched the assay in the US.
The ipsogen JAK2 assay is designed to detect the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood.
The assay is intended for use in conjunction with other clinicopathological factors to aid the diagnosis of polycythemia vera (PV).
The test does not detect less common mutations associated with PV, including mutations in exon 12, and is not intended for stand-alone diagnosis of PV.
The ipsogen JAK2 assay is a real-time polymerase chain reaction test performed on the QIAGEN Rotor-Gene Q MDx instrument.
Researchers evaluated the utility of the ipsogen JAK2 assay for PV diagnosis in a prospective trial enrolling more than 200 subjects.
Data from this trial have not been published. However, according to QIAGEN, the assay provided 94.6% sensitivity and 98.1% specificity, together with a 100% positive percentage agreement and a 99.4% negative percentage agreement to bi-directional sequencing.
QIAGEN said these results suggest the ipsogen JAK2 assay enables detection of PV in the majority of subjects with the disease and helps rule out PV in the majority of individuals without it.
“We are pleased to be able to offer our ipsogen JAK2 assay, which is already available in Europe and other markets, for use in the United States and make it easier for hematologists and oncologists to follow recommended diagnostic testing algorithms and international guidelines for suspected PV patients,” said Thierry Bernard, senior vice president and head of QIAGEN’s Molecular Diagnostics Business Area.