Robot-assisted prostatectomy providing better outcomes

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Robot-assisted radical prostatectomy shows better early postoperative outcomes than does laparoscopic radical prostatectomy, but the differences between the two surgical approaches disappeared by the 6-month follow-up.

Dr. Hiroyuki Koike and his colleagues at Wakayama (Japan) Medical University Hospital conducted a study of two groups of patients treated for localized prostate cancer. One group of 229 patients underwent laparoscopic radical prostatectomy (LRP) between July 2007 and July 2013. The other group of 115 patients had robot-assisted radical prostatectomy (RARP) between December 2012 and August 2014 (J Robot Surg. 2017;11[3]:325-31).

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The patients were given health-related quality of life self-assessment surveys prior to surgery and at 3, 6, and 12 months post surgery. In addition, a generic questionnaire, the eight-item Short-Form Health Survey, was used to assess a physical component summary (PCS) and a mental component summary (MCS). The Expanded Prostate Cancer Index of Prostate, which covers four domains – urinary, sexual, bowel, and hormonal – was used as a disease-specific measure, and the response rates for both LRP and RARP at each follow-up interval were over 80%.
 

 

“The RARP group showed significantly better scores in urinary summary and all urinary subscales at postoperative 3-month follow-up. However, these differences disappeared at postoperative 6 and 12-month follow-up,” the investigators wrote. For the urinary summary score, LRP significantly underperformed, compared with RARP, with scores of 63.3 vs. 75.8, respectively, after 3 months. In addition, the bowel function score was superior for RARP, compared with LRP, at 96.9 vs. 92.9, respectively. Sexual function results were similar, with RARP and LRP scores of 2.8 vs. 0.

The general measures of the PCS and MCS also favored RARP. At the 3-month follow-up, PCS (51.3 vs. 48.1) and MCS (50 vs. 47.8) scores were higher for RARP, compared with LRP.

“It is unclear why our superiority of urinary function in RARP was observed only in early period. However, we can speculate several reasons for better urinary function in RARP group. First, we were able to treat the apex area more delicately with RARP. Second, some of the new techniques which we employed after the introduction of RARP could influence the urinary continence recovery,” the investigators wrote.

The authors had no relevant financial disclosures.

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Robot-assisted radical prostatectomy shows better early postoperative outcomes than does laparoscopic radical prostatectomy, but the differences between the two surgical approaches disappeared by the 6-month follow-up.

Dr. Hiroyuki Koike and his colleagues at Wakayama (Japan) Medical University Hospital conducted a study of two groups of patients treated for localized prostate cancer. One group of 229 patients underwent laparoscopic radical prostatectomy (LRP) between July 2007 and July 2013. The other group of 115 patients had robot-assisted radical prostatectomy (RARP) between December 2012 and August 2014 (J Robot Surg. 2017;11[3]:325-31).

Master Video/Shutterstock


The patients were given health-related quality of life self-assessment surveys prior to surgery and at 3, 6, and 12 months post surgery. In addition, a generic questionnaire, the eight-item Short-Form Health Survey, was used to assess a physical component summary (PCS) and a mental component summary (MCS). The Expanded Prostate Cancer Index of Prostate, which covers four domains – urinary, sexual, bowel, and hormonal – was used as a disease-specific measure, and the response rates for both LRP and RARP at each follow-up interval were over 80%.
 

 

“The RARP group showed significantly better scores in urinary summary and all urinary subscales at postoperative 3-month follow-up. However, these differences disappeared at postoperative 6 and 12-month follow-up,” the investigators wrote. For the urinary summary score, LRP significantly underperformed, compared with RARP, with scores of 63.3 vs. 75.8, respectively, after 3 months. In addition, the bowel function score was superior for RARP, compared with LRP, at 96.9 vs. 92.9, respectively. Sexual function results were similar, with RARP and LRP scores of 2.8 vs. 0.

The general measures of the PCS and MCS also favored RARP. At the 3-month follow-up, PCS (51.3 vs. 48.1) and MCS (50 vs. 47.8) scores were higher for RARP, compared with LRP.

“It is unclear why our superiority of urinary function in RARP was observed only in early period. However, we can speculate several reasons for better urinary function in RARP group. First, we were able to treat the apex area more delicately with RARP. Second, some of the new techniques which we employed after the introduction of RARP could influence the urinary continence recovery,” the investigators wrote.

The authors had no relevant financial disclosures.

 

Robot-assisted radical prostatectomy shows better early postoperative outcomes than does laparoscopic radical prostatectomy, but the differences between the two surgical approaches disappeared by the 6-month follow-up.

Dr. Hiroyuki Koike and his colleagues at Wakayama (Japan) Medical University Hospital conducted a study of two groups of patients treated for localized prostate cancer. One group of 229 patients underwent laparoscopic radical prostatectomy (LRP) between July 2007 and July 2013. The other group of 115 patients had robot-assisted radical prostatectomy (RARP) between December 2012 and August 2014 (J Robot Surg. 2017;11[3]:325-31).

Master Video/Shutterstock


The patients were given health-related quality of life self-assessment surveys prior to surgery and at 3, 6, and 12 months post surgery. In addition, a generic questionnaire, the eight-item Short-Form Health Survey, was used to assess a physical component summary (PCS) and a mental component summary (MCS). The Expanded Prostate Cancer Index of Prostate, which covers four domains – urinary, sexual, bowel, and hormonal – was used as a disease-specific measure, and the response rates for both LRP and RARP at each follow-up interval were over 80%.
 

 

“The RARP group showed significantly better scores in urinary summary and all urinary subscales at postoperative 3-month follow-up. However, these differences disappeared at postoperative 6 and 12-month follow-up,” the investigators wrote. For the urinary summary score, LRP significantly underperformed, compared with RARP, with scores of 63.3 vs. 75.8, respectively, after 3 months. In addition, the bowel function score was superior for RARP, compared with LRP, at 96.9 vs. 92.9, respectively. Sexual function results were similar, with RARP and LRP scores of 2.8 vs. 0.

The general measures of the PCS and MCS also favored RARP. At the 3-month follow-up, PCS (51.3 vs. 48.1) and MCS (50 vs. 47.8) scores were higher for RARP, compared with LRP.

“It is unclear why our superiority of urinary function in RARP was observed only in early period. However, we can speculate several reasons for better urinary function in RARP group. First, we were able to treat the apex area more delicately with RARP. Second, some of the new techniques which we employed after the introduction of RARP could influence the urinary continence recovery,” the investigators wrote.

The authors had no relevant financial disclosures.

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FROM JOURNAL OF ROBOTIC SURGERY

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Key clinical point: Robotic-assisted radical prostatectomy provides better outcomes than laparoscopic procedures.

Major finding: Quality-of-life score for robotic-assisted radical prostatectomy was higher in all urinary categories after 3 months.

Data source: Postop survey results from patients with localized prostate cancer who underwent laparoscopic radical prostatectomy (n = 229) or robot-assisted radical prostatectomy (n = 115).

Disclosures: The investigators had no financial disclosures to report.

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FDA approves pembrolizumab for gastric and GEJ adenocarcinoma

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The Food and Drug Administration has approved pembrolizumab (Keytruda) for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, in cases where tests confirm that the tumors contain programmed death–ligand 1 and where the disease is progressing on or after two or more prior lines of therapy.

 

Pembrolizumab has been approved in the United States since 2014 for the treatment of melanoma, with subsequent approvals for treatment of non–small-cell lung cancer, head and neck squamous cell carcinoma, Hodgkin lymphoma, and several other advanced cancers.

The drug, now approved under the FDA’s accelerated approval regulations for the current indication in a 50-mg and 100-mg injection, blocks the interaction between the PD-1 protein and its ligands.

The approval comes on the basis of the nonrandomized, open label KEYNOTE-059 trial, which enrolled 259 patients with gastric or GEJ adenocarcinoma that progressed on at least two prior systemic treatments for advanced disease. Of the enrollees, 143 patients had tumors with a PD-L1 Combined Positive Score of 1 or greater. The primary trial outcome, the objective response rate for these 143 patients, was 13.3% (95% confidence interval; 8.2-20), with a complete response rate of 1.4% and a partial response rate of 11.9%. The duration of response ranged from at least 2.8 months to at least 19.4 months.

Continued approval for the new indication will depend upon further demonstration of a clinical benefit in confirmatory trials.

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The Food and Drug Administration has approved pembrolizumab (Keytruda) for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, in cases where tests confirm that the tumors contain programmed death–ligand 1 and where the disease is progressing on or after two or more prior lines of therapy.

 

Pembrolizumab has been approved in the United States since 2014 for the treatment of melanoma, with subsequent approvals for treatment of non–small-cell lung cancer, head and neck squamous cell carcinoma, Hodgkin lymphoma, and several other advanced cancers.

The drug, now approved under the FDA’s accelerated approval regulations for the current indication in a 50-mg and 100-mg injection, blocks the interaction between the PD-1 protein and its ligands.

The approval comes on the basis of the nonrandomized, open label KEYNOTE-059 trial, which enrolled 259 patients with gastric or GEJ adenocarcinoma that progressed on at least two prior systemic treatments for advanced disease. Of the enrollees, 143 patients had tumors with a PD-L1 Combined Positive Score of 1 or greater. The primary trial outcome, the objective response rate for these 143 patients, was 13.3% (95% confidence interval; 8.2-20), with a complete response rate of 1.4% and a partial response rate of 11.9%. The duration of response ranged from at least 2.8 months to at least 19.4 months.

Continued approval for the new indication will depend upon further demonstration of a clinical benefit in confirmatory trials.

The Food and Drug Administration has approved pembrolizumab (Keytruda) for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, in cases where tests confirm that the tumors contain programmed death–ligand 1 and where the disease is progressing on or after two or more prior lines of therapy.

 

Pembrolizumab has been approved in the United States since 2014 for the treatment of melanoma, with subsequent approvals for treatment of non–small-cell lung cancer, head and neck squamous cell carcinoma, Hodgkin lymphoma, and several other advanced cancers.

The drug, now approved under the FDA’s accelerated approval regulations for the current indication in a 50-mg and 100-mg injection, blocks the interaction between the PD-1 protein and its ligands.

The approval comes on the basis of the nonrandomized, open label KEYNOTE-059 trial, which enrolled 259 patients with gastric or GEJ adenocarcinoma that progressed on at least two prior systemic treatments for advanced disease. Of the enrollees, 143 patients had tumors with a PD-L1 Combined Positive Score of 1 or greater. The primary trial outcome, the objective response rate for these 143 patients, was 13.3% (95% confidence interval; 8.2-20), with a complete response rate of 1.4% and a partial response rate of 11.9%. The duration of response ranged from at least 2.8 months to at least 19.4 months.

Continued approval for the new indication will depend upon further demonstration of a clinical benefit in confirmatory trials.

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Commentary—A Credible Case for Neuroprotection

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To date, efforts to translate exciting laboratory findings into clinical trials for Parkinson’s disease have not met with much success. However, the latest exenatide study results offer another chance for improving this situation. This randomized, placebo-controlled trial also highlights how a medication already in human use might be repurposed for a novel application.

Peter A. LeWitt, MD

Whether this study actually proved its concept will require confirmation by further clinical investigation. The biggest challenge presented by this study has to do with studying patients with Parkinson’s disease who already are receiving symptomatic therapy with dopaminergic drugs. The study plan was to eliminate this effect by an overnight washout of Parkinson’s disease drugs. But waiting for a day or two after stopping medication, even for a short-acting drug like levodopa, does not necessarily abolish all of its symptomatic effects. If exenatide acted by enhancing the temporary relief of parkinsonism offered by medications rather than by protecting against further neurodegeneration, study ratings would not be able to discern this difference. Similarly, if exenatide exerts a trophic effect on striatal dopamine transporters, the observed reduction of decline in dopamine transporter (DAT) scan readings would not necessarily reflect sparing of further dopaminergic neuron loss.

Another potentially confounding factor was that during the course of the trial, the exenatide group increased its concomitant dopaminergic therapy more than the placebo-treated controls did. In a study of only 62 subjects who were already advanced in the course of Parkinson’s disease and experiencing motor fluctuations, any imbalance between treatment and placebo groups might impart uncertainties for which it may be difficult to correct.

Despite all the reasonable objections that might detract from a definitive interpretation of this study, its results make a credible argument for a neuroprotection outcome. The happenstance of two seemingly independent indicators of disease modification—in this case, the washout ratings of parkinsonian features and the DAT scan results—provides grounds for optimism. In the quest for halting the advance of Parkinson’s disease, the perfect study has yet to emerge. The exenatide investigators’ careful attention to detail and collection of other study information and biomarker specimens will serve well the next researchers who explore the potential for glucagon-like peptide-1 treatments.

Peter A. LeWitt, MD
Professor of Neurology
Wayne State University School of Medicine
Director, Parkinson's Disease and Movement Disorders Program
Henry Ford Hospital West Bloomfield
West Bloomfield, Michigan

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To date, efforts to translate exciting laboratory findings into clinical trials for Parkinson’s disease have not met with much success. However, the latest exenatide study results offer another chance for improving this situation. This randomized, placebo-controlled trial also highlights how a medication already in human use might be repurposed for a novel application.

Peter A. LeWitt, MD

Whether this study actually proved its concept will require confirmation by further clinical investigation. The biggest challenge presented by this study has to do with studying patients with Parkinson’s disease who already are receiving symptomatic therapy with dopaminergic drugs. The study plan was to eliminate this effect by an overnight washout of Parkinson’s disease drugs. But waiting for a day or two after stopping medication, even for a short-acting drug like levodopa, does not necessarily abolish all of its symptomatic effects. If exenatide acted by enhancing the temporary relief of parkinsonism offered by medications rather than by protecting against further neurodegeneration, study ratings would not be able to discern this difference. Similarly, if exenatide exerts a trophic effect on striatal dopamine transporters, the observed reduction of decline in dopamine transporter (DAT) scan readings would not necessarily reflect sparing of further dopaminergic neuron loss.

Another potentially confounding factor was that during the course of the trial, the exenatide group increased its concomitant dopaminergic therapy more than the placebo-treated controls did. In a study of only 62 subjects who were already advanced in the course of Parkinson’s disease and experiencing motor fluctuations, any imbalance between treatment and placebo groups might impart uncertainties for which it may be difficult to correct.

Despite all the reasonable objections that might detract from a definitive interpretation of this study, its results make a credible argument for a neuroprotection outcome. The happenstance of two seemingly independent indicators of disease modification—in this case, the washout ratings of parkinsonian features and the DAT scan results—provides grounds for optimism. In the quest for halting the advance of Parkinson’s disease, the perfect study has yet to emerge. The exenatide investigators’ careful attention to detail and collection of other study information and biomarker specimens will serve well the next researchers who explore the potential for glucagon-like peptide-1 treatments.

Peter A. LeWitt, MD
Professor of Neurology
Wayne State University School of Medicine
Director, Parkinson's Disease and Movement Disorders Program
Henry Ford Hospital West Bloomfield
West Bloomfield, Michigan

To date, efforts to translate exciting laboratory findings into clinical trials for Parkinson’s disease have not met with much success. However, the latest exenatide study results offer another chance for improving this situation. This randomized, placebo-controlled trial also highlights how a medication already in human use might be repurposed for a novel application.

Peter A. LeWitt, MD

Whether this study actually proved its concept will require confirmation by further clinical investigation. The biggest challenge presented by this study has to do with studying patients with Parkinson’s disease who already are receiving symptomatic therapy with dopaminergic drugs. The study plan was to eliminate this effect by an overnight washout of Parkinson’s disease drugs. But waiting for a day or two after stopping medication, even for a short-acting drug like levodopa, does not necessarily abolish all of its symptomatic effects. If exenatide acted by enhancing the temporary relief of parkinsonism offered by medications rather than by protecting against further neurodegeneration, study ratings would not be able to discern this difference. Similarly, if exenatide exerts a trophic effect on striatal dopamine transporters, the observed reduction of decline in dopamine transporter (DAT) scan readings would not necessarily reflect sparing of further dopaminergic neuron loss.

Another potentially confounding factor was that during the course of the trial, the exenatide group increased its concomitant dopaminergic therapy more than the placebo-treated controls did. In a study of only 62 subjects who were already advanced in the course of Parkinson’s disease and experiencing motor fluctuations, any imbalance between treatment and placebo groups might impart uncertainties for which it may be difficult to correct.

Despite all the reasonable objections that might detract from a definitive interpretation of this study, its results make a credible argument for a neuroprotection outcome. The happenstance of two seemingly independent indicators of disease modification—in this case, the washout ratings of parkinsonian features and the DAT scan results—provides grounds for optimism. In the quest for halting the advance of Parkinson’s disease, the perfect study has yet to emerge. The exenatide investigators’ careful attention to detail and collection of other study information and biomarker specimens will serve well the next researchers who explore the potential for glucagon-like peptide-1 treatments.

Peter A. LeWitt, MD
Professor of Neurology
Wayne State University School of Medicine
Director, Parkinson's Disease and Movement Disorders Program
Henry Ford Hospital West Bloomfield
West Bloomfield, Michigan

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Exenatide Aids Motor Function in Parkinson’s Disease

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Compared with conventional dopaminergic drugs, exenatide may have a more persistent effect on disease severity.

Exenatide improves motor function in patients with Parkinson’s disease, according to research published online ahead of print August 3 in Lancet. The improvements may persist for months after treatment exposure.

Exenatide, an analogue of glucagon-like peptide-1, is used to treat type 2 diabetes. In rodent models of Parkinson’s disease, exenatide had neuroprotective effects and improved motor performance, behavior, learning, and memory. The drug also provided motor and cognitive benefits in a proof-of-concept study including patients with Parkinson’s disease.

Active Group Was Slightly Older

Dilan Athauda, MBBS, Senior Clinical Research Associate at University College London, and colleagues conducted a double-blind study to assess exenatide’s potential disease-modifying effects. At screening for study entry, patients with idiopathic Parkinson’s disease underwent physical and neurologic examinations, assessments of mood and cognition, and blood sampling. The investigators randomized eligible participants to subcutaneous injections of exenatide (2 mg) or placebo once weekly for 48 weeks. Participants continued to take their regular medications. Investigators examined patients in an off-medication state and collected blood and urine at baseline and weeks 12, 24, 36, and 48. Study drugs were withdrawn after 48 weeks, and the final follow-up visit was at week 60.

The primary outcome was change in Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part 3 score at 60 weeks. Secondary outcomes included differences between exenatide and placebo in each subsection of the MDS-UPDRS in the on-medication state, and the Mattis Dementia Rating Scale at weeks 48 and 60.

In all, 62 participants were randomized. Patients assigned to exenatide were slightly older, had higher baseline MDS-UPDRS part 3 scores, and had lower levodopa equivalent dose than did controls. Average age was about 62 in the exenatide group and about 58 among controls. About 26% of the population was female, and the mean disease duration at baseline was 6.4 years. Approximately 97% of the population were between Hoehn and Yahr stage 1 and 2 at baseline.

Exenatide Yielded Motor Improvement

At week 60, off-medication MDS-UPDRS part 3 scores had worsened by 2.1 points in the placebo group and improved by 1.0 point in the exenatide group, yielding a significant adjusted difference of 3.5 points. At week 48, scores among controls had deteriorated by 1.7 points, and those in the exenatide group had improved by 2.3 points, resulting in a significant adjusted between-group difference of 4.3 points.

On-medication scores on MDS-UPDRS parts 1 through 4 did not differ significantly between groups at weeks 48 or 60. The researchers also did not observe a significant difference between groups in Mattis Dementia Rating Scale score at those time points. The frequency of adverse events was similar between groups.

“Exenatide could have a longer-lasting effect on disease severity beyond conventional drug effects on dopaminergic receptors,” said the researchers. “Whether exenatide affects the underlying disease pathophysiology or simply induces long-lasting symptomatic effects is uncertain. Exenatide represents a major new avenue for investigation in Parkinson’s disease, and effects on everyday symptoms should be examined in longer-term trials.”

Erik Greb

Suggested Reading

Athauda D, Maclagan K, Skene SS, et al. Exenatide once weekly versus placebo in Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. Lancet. 2017 Aug 3 [Epub ahead of print].

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Compared with conventional dopaminergic drugs, exenatide may have a more persistent effect on disease severity.
Compared with conventional dopaminergic drugs, exenatide may have a more persistent effect on disease severity.

Exenatide improves motor function in patients with Parkinson’s disease, according to research published online ahead of print August 3 in Lancet. The improvements may persist for months after treatment exposure.

Exenatide, an analogue of glucagon-like peptide-1, is used to treat type 2 diabetes. In rodent models of Parkinson’s disease, exenatide had neuroprotective effects and improved motor performance, behavior, learning, and memory. The drug also provided motor and cognitive benefits in a proof-of-concept study including patients with Parkinson’s disease.

Active Group Was Slightly Older

Dilan Athauda, MBBS, Senior Clinical Research Associate at University College London, and colleagues conducted a double-blind study to assess exenatide’s potential disease-modifying effects. At screening for study entry, patients with idiopathic Parkinson’s disease underwent physical and neurologic examinations, assessments of mood and cognition, and blood sampling. The investigators randomized eligible participants to subcutaneous injections of exenatide (2 mg) or placebo once weekly for 48 weeks. Participants continued to take their regular medications. Investigators examined patients in an off-medication state and collected blood and urine at baseline and weeks 12, 24, 36, and 48. Study drugs were withdrawn after 48 weeks, and the final follow-up visit was at week 60.

The primary outcome was change in Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part 3 score at 60 weeks. Secondary outcomes included differences between exenatide and placebo in each subsection of the MDS-UPDRS in the on-medication state, and the Mattis Dementia Rating Scale at weeks 48 and 60.

In all, 62 participants were randomized. Patients assigned to exenatide were slightly older, had higher baseline MDS-UPDRS part 3 scores, and had lower levodopa equivalent dose than did controls. Average age was about 62 in the exenatide group and about 58 among controls. About 26% of the population was female, and the mean disease duration at baseline was 6.4 years. Approximately 97% of the population were between Hoehn and Yahr stage 1 and 2 at baseline.

Exenatide Yielded Motor Improvement

At week 60, off-medication MDS-UPDRS part 3 scores had worsened by 2.1 points in the placebo group and improved by 1.0 point in the exenatide group, yielding a significant adjusted difference of 3.5 points. At week 48, scores among controls had deteriorated by 1.7 points, and those in the exenatide group had improved by 2.3 points, resulting in a significant adjusted between-group difference of 4.3 points.

On-medication scores on MDS-UPDRS parts 1 through 4 did not differ significantly between groups at weeks 48 or 60. The researchers also did not observe a significant difference between groups in Mattis Dementia Rating Scale score at those time points. The frequency of adverse events was similar between groups.

“Exenatide could have a longer-lasting effect on disease severity beyond conventional drug effects on dopaminergic receptors,” said the researchers. “Whether exenatide affects the underlying disease pathophysiology or simply induces long-lasting symptomatic effects is uncertain. Exenatide represents a major new avenue for investigation in Parkinson’s disease, and effects on everyday symptoms should be examined in longer-term trials.”

Erik Greb

Suggested Reading

Athauda D, Maclagan K, Skene SS, et al. Exenatide once weekly versus placebo in Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. Lancet. 2017 Aug 3 [Epub ahead of print].

Exenatide improves motor function in patients with Parkinson’s disease, according to research published online ahead of print August 3 in Lancet. The improvements may persist for months after treatment exposure.

Exenatide, an analogue of glucagon-like peptide-1, is used to treat type 2 diabetes. In rodent models of Parkinson’s disease, exenatide had neuroprotective effects and improved motor performance, behavior, learning, and memory. The drug also provided motor and cognitive benefits in a proof-of-concept study including patients with Parkinson’s disease.

Active Group Was Slightly Older

Dilan Athauda, MBBS, Senior Clinical Research Associate at University College London, and colleagues conducted a double-blind study to assess exenatide’s potential disease-modifying effects. At screening for study entry, patients with idiopathic Parkinson’s disease underwent physical and neurologic examinations, assessments of mood and cognition, and blood sampling. The investigators randomized eligible participants to subcutaneous injections of exenatide (2 mg) or placebo once weekly for 48 weeks. Participants continued to take their regular medications. Investigators examined patients in an off-medication state and collected blood and urine at baseline and weeks 12, 24, 36, and 48. Study drugs were withdrawn after 48 weeks, and the final follow-up visit was at week 60.

The primary outcome was change in Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part 3 score at 60 weeks. Secondary outcomes included differences between exenatide and placebo in each subsection of the MDS-UPDRS in the on-medication state, and the Mattis Dementia Rating Scale at weeks 48 and 60.

In all, 62 participants were randomized. Patients assigned to exenatide were slightly older, had higher baseline MDS-UPDRS part 3 scores, and had lower levodopa equivalent dose than did controls. Average age was about 62 in the exenatide group and about 58 among controls. About 26% of the population was female, and the mean disease duration at baseline was 6.4 years. Approximately 97% of the population were between Hoehn and Yahr stage 1 and 2 at baseline.

Exenatide Yielded Motor Improvement

At week 60, off-medication MDS-UPDRS part 3 scores had worsened by 2.1 points in the placebo group and improved by 1.0 point in the exenatide group, yielding a significant adjusted difference of 3.5 points. At week 48, scores among controls had deteriorated by 1.7 points, and those in the exenatide group had improved by 2.3 points, resulting in a significant adjusted between-group difference of 4.3 points.

On-medication scores on MDS-UPDRS parts 1 through 4 did not differ significantly between groups at weeks 48 or 60. The researchers also did not observe a significant difference between groups in Mattis Dementia Rating Scale score at those time points. The frequency of adverse events was similar between groups.

“Exenatide could have a longer-lasting effect on disease severity beyond conventional drug effects on dopaminergic receptors,” said the researchers. “Whether exenatide affects the underlying disease pathophysiology or simply induces long-lasting symptomatic effects is uncertain. Exenatide represents a major new avenue for investigation in Parkinson’s disease, and effects on everyday symptoms should be examined in longer-term trials.”

Erik Greb

Suggested Reading

Athauda D, Maclagan K, Skene SS, et al. Exenatide once weekly versus placebo in Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. Lancet. 2017 Aug 3 [Epub ahead of print].

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Peer-to-peer learning about robotic surgery is happening on social media

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Social media is now being used by surgeons for interaction among peers, informal learning, exchange of technical information, and diffusion of ideas.

A study has examined posting and membership data from a closed Facebook page, the “Robotic Surgery Collaboration,” created by surgeons who practice robotic-assisted procedures. Overall, the findings show exponential growth in membership in January 2015 through August 2016, some signs of stagnating engagement, and use of the platform for peer-to-peer learning and discussion.

audioundwerbung/iStockphoto
The investigators used the Grytics program to analyze membership numbers, frequency of posting, and the engagement in different times of postings. These robotic surgery clinicians “appear to post on the platform more often during the middle of the week, and text posts receive more active engagement (comments) than multimedia posts, while multimedia posts receive more passive responses (likes) than text posts,” said Christopher Myers, PhD, and his associates.

“The growth in this group over time suggests that surgeons found it useful for engaging in informal interactions and learning vicariously from one another, but also reveals that not all users were actively engaged in these interactions each month and that growth in active membership differed from growth in overall group membership (as evident in the stagnating growth of active members, despite continued growth in total members),” the investigators concluded. Read the full study at Ann Surg. 2017 Aug 29. doi: 10.1097/SLA.0000000000002479. (Epub ahead of print).

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Social media is now being used by surgeons for interaction among peers, informal learning, exchange of technical information, and diffusion of ideas.

A study has examined posting and membership data from a closed Facebook page, the “Robotic Surgery Collaboration,” created by surgeons who practice robotic-assisted procedures. Overall, the findings show exponential growth in membership in January 2015 through August 2016, some signs of stagnating engagement, and use of the platform for peer-to-peer learning and discussion.

audioundwerbung/iStockphoto
The investigators used the Grytics program to analyze membership numbers, frequency of posting, and the engagement in different times of postings. These robotic surgery clinicians “appear to post on the platform more often during the middle of the week, and text posts receive more active engagement (comments) than multimedia posts, while multimedia posts receive more passive responses (likes) than text posts,” said Christopher Myers, PhD, and his associates.

“The growth in this group over time suggests that surgeons found it useful for engaging in informal interactions and learning vicariously from one another, but also reveals that not all users were actively engaged in these interactions each month and that growth in active membership differed from growth in overall group membership (as evident in the stagnating growth of active members, despite continued growth in total members),” the investigators concluded. Read the full study at Ann Surg. 2017 Aug 29. doi: 10.1097/SLA.0000000000002479. (Epub ahead of print).

 

Social media is now being used by surgeons for interaction among peers, informal learning, exchange of technical information, and diffusion of ideas.

A study has examined posting and membership data from a closed Facebook page, the “Robotic Surgery Collaboration,” created by surgeons who practice robotic-assisted procedures. Overall, the findings show exponential growth in membership in January 2015 through August 2016, some signs of stagnating engagement, and use of the platform for peer-to-peer learning and discussion.

audioundwerbung/iStockphoto
The investigators used the Grytics program to analyze membership numbers, frequency of posting, and the engagement in different times of postings. These robotic surgery clinicians “appear to post on the platform more often during the middle of the week, and text posts receive more active engagement (comments) than multimedia posts, while multimedia posts receive more passive responses (likes) than text posts,” said Christopher Myers, PhD, and his associates.

“The growth in this group over time suggests that surgeons found it useful for engaging in informal interactions and learning vicariously from one another, but also reveals that not all users were actively engaged in these interactions each month and that growth in active membership differed from growth in overall group membership (as evident in the stagnating growth of active members, despite continued growth in total members),” the investigators concluded. Read the full study at Ann Surg. 2017 Aug 29. doi: 10.1097/SLA.0000000000002479. (Epub ahead of print).

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Immunogenicity concerns for biosimilars so far don’t go beyond originator biologics

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A key factor that impacts the efficacy and the toxicity of biologics used for rheumatic diseases is their immunogenicity, and this factor doesn’t appear to be any different for biosimilars in studies conducted so far.

In a meta-analysis of 63 studies of tumor necrosis factor (TNF) inhibitors, investigators including Daniel E. Furst, MD, professor of rheumatology at the University of Washington, Seattle, who also is affiliated with the University of California, Los Angeles, and the University of Florence, Italy, found that antidrug antibodies developed in 17% of patients (BioDrugs 2015;29:241-58).

“That doesn’t sound too bad, but does it differ by medication?” asked Dr. Furst, who spoke at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “For infliximab, 30% of the time, there are antidrug antibodies. So if that has a clinical effect, that’s a big deal. For certolizumab ... it’s only 6%, so there is a huge difference within the TNF inhibitors.” At the same time, antidrug antibodies developed in patients on adalimumab 23% of the time, followed by certolizumab (6%), golimumab (4%), and etanercept (2%).

Dr. Daniel E. Furst
The same meta-analysis found that the frequency of having immunogenicity differed among diseases as well. For example, antidrug antibodies developed in about 14% of patients with rheumatoid arthritis (RA), in 25% of patients with inflammatory bowel disease, and in 7% among patients with ankylosing spondylitis. “There are huge differences in the relative risk of having an antidrug antibody,” said Dr. Furst, director of research for Arthritis Associates of Southern California in Los Angeles. He also noted that the rate of drug response among patients who develop antidrug antibodies is decreased by about 50%. “So if you have the antibodies, it really makes a difference,” he said. “That differs by drug, and it differs by disease.”

One approach to circumventing the impact of antidrug antibodies on clinical response is by using immunosuppression, which in the meta-analysis had a 70% probability for decreasing antidrug antibodies. But this approach comes with a hitch, Dr. Furst said. The effect of immunosuppression on antidrug antibody positivity differs by disease. Immunosuppression had a 78% probability for decreasing antidrug antibody positivity in RA, 63% probability in inflammatory bowel disease, and 32% probability in ankylosing spondylitis. “That’s a wild mix of immunogenicity and the possibility that it’s going to affect the underlying response,” he said. The best studies in this area are of infliximab and adalimumab, which showed that antidrug antibodies in patients on infliximab reduced the probability of a clinical response by 54% and for adalimumab by 65%.

The same meta-analysis found that there were more antibodies to adalimumab than to certolizumab, golimumab, or etanercept, and also more antibodies to infliximab than to certolizumab, golimumab, or etanercept, but no difference between adalimumab and infliximab. “You’d think that maybe there is a difference between adalimumab and infliximab, but that’s not true,” Dr. Furst said. The apparent effect on the percentage of antidrug antibodies depends on what type of assay is used. For example, radioimmunoassay measures about 11% more antidrug antibodies, compared with enzyme-linked immunosorbent assay. Disease duration also matters. Each year of disease duration increases the antidrug antibodies by 1%.

What about the non-TNF inhibitors? A meta-analysis of five core trials of tocilizumab for RA found that the antidrug antibodies ranged from 1.7% at baseline to 2.3% during the respective trials (Clin Ther. 2010;32:1597-1609). “Anywhere along the way, the percentage of antidrug antibodies was about 1.5%,” said Dr. Furst, who was not involved with the study. “So as opposed to the TNF inhibitors, when you look at tocilizumab, this whole immunity question is probably a non-issue. The same is true for abatacept. With rituximab, the question is a little bit different. In one randomized, controlled trial, immunogenicity was 2.9%, while in the next it was 7.9%. In an open-label trial, it was 11.5%. So I think for rituximab we have to assume that you have some potentially important antidrug antibodies that might affect response.”

Studies have shown that antidrug antibodies do affect the pharmacokinetics of a biologic (and thereby clinical response) by producing lower trough levels of the biologic through an increase in its clearance. However, studies of infliximab and its biosimilars have not yielded any significant differences in clinical responses rates despite small differences in rates of antidrug antibodies or in rates of treatment-emergent adverse events, he said.

There has also been no difference in disease worsening in the only reported double-blind, randomized, switching study for infliximab and an infliximab biosimilar, the NOR-SWITCH study. However, the small numbers of patients in the study with certain diseases for which infliximab is indicated do not allow for conclusions to be drawn for specific diseases, Dr. Furst said.

Dr. Furst disclosed that he has received grant/research support from AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Corbus, the National Institutes of Health, Novartis, and Roche/Genentech. He is also a consultant for AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Cytori, Novartis, Pfizer, and Roche/Genentech. Global Academy for Medical Education and this news organization are owned by the same parent company.
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A key factor that impacts the efficacy and the toxicity of biologics used for rheumatic diseases is their immunogenicity, and this factor doesn’t appear to be any different for biosimilars in studies conducted so far.

In a meta-analysis of 63 studies of tumor necrosis factor (TNF) inhibitors, investigators including Daniel E. Furst, MD, professor of rheumatology at the University of Washington, Seattle, who also is affiliated with the University of California, Los Angeles, and the University of Florence, Italy, found that antidrug antibodies developed in 17% of patients (BioDrugs 2015;29:241-58).

“That doesn’t sound too bad, but does it differ by medication?” asked Dr. Furst, who spoke at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “For infliximab, 30% of the time, there are antidrug antibodies. So if that has a clinical effect, that’s a big deal. For certolizumab ... it’s only 6%, so there is a huge difference within the TNF inhibitors.” At the same time, antidrug antibodies developed in patients on adalimumab 23% of the time, followed by certolizumab (6%), golimumab (4%), and etanercept (2%).

Dr. Daniel E. Furst
The same meta-analysis found that the frequency of having immunogenicity differed among diseases as well. For example, antidrug antibodies developed in about 14% of patients with rheumatoid arthritis (RA), in 25% of patients with inflammatory bowel disease, and in 7% among patients with ankylosing spondylitis. “There are huge differences in the relative risk of having an antidrug antibody,” said Dr. Furst, director of research for Arthritis Associates of Southern California in Los Angeles. He also noted that the rate of drug response among patients who develop antidrug antibodies is decreased by about 50%. “So if you have the antibodies, it really makes a difference,” he said. “That differs by drug, and it differs by disease.”

One approach to circumventing the impact of antidrug antibodies on clinical response is by using immunosuppression, which in the meta-analysis had a 70% probability for decreasing antidrug antibodies. But this approach comes with a hitch, Dr. Furst said. The effect of immunosuppression on antidrug antibody positivity differs by disease. Immunosuppression had a 78% probability for decreasing antidrug antibody positivity in RA, 63% probability in inflammatory bowel disease, and 32% probability in ankylosing spondylitis. “That’s a wild mix of immunogenicity and the possibility that it’s going to affect the underlying response,” he said. The best studies in this area are of infliximab and adalimumab, which showed that antidrug antibodies in patients on infliximab reduced the probability of a clinical response by 54% and for adalimumab by 65%.

The same meta-analysis found that there were more antibodies to adalimumab than to certolizumab, golimumab, or etanercept, and also more antibodies to infliximab than to certolizumab, golimumab, or etanercept, but no difference between adalimumab and infliximab. “You’d think that maybe there is a difference between adalimumab and infliximab, but that’s not true,” Dr. Furst said. The apparent effect on the percentage of antidrug antibodies depends on what type of assay is used. For example, radioimmunoassay measures about 11% more antidrug antibodies, compared with enzyme-linked immunosorbent assay. Disease duration also matters. Each year of disease duration increases the antidrug antibodies by 1%.

What about the non-TNF inhibitors? A meta-analysis of five core trials of tocilizumab for RA found that the antidrug antibodies ranged from 1.7% at baseline to 2.3% during the respective trials (Clin Ther. 2010;32:1597-1609). “Anywhere along the way, the percentage of antidrug antibodies was about 1.5%,” said Dr. Furst, who was not involved with the study. “So as opposed to the TNF inhibitors, when you look at tocilizumab, this whole immunity question is probably a non-issue. The same is true for abatacept. With rituximab, the question is a little bit different. In one randomized, controlled trial, immunogenicity was 2.9%, while in the next it was 7.9%. In an open-label trial, it was 11.5%. So I think for rituximab we have to assume that you have some potentially important antidrug antibodies that might affect response.”

Studies have shown that antidrug antibodies do affect the pharmacokinetics of a biologic (and thereby clinical response) by producing lower trough levels of the biologic through an increase in its clearance. However, studies of infliximab and its biosimilars have not yielded any significant differences in clinical responses rates despite small differences in rates of antidrug antibodies or in rates of treatment-emergent adverse events, he said.

There has also been no difference in disease worsening in the only reported double-blind, randomized, switching study for infliximab and an infliximab biosimilar, the NOR-SWITCH study. However, the small numbers of patients in the study with certain diseases for which infliximab is indicated do not allow for conclusions to be drawn for specific diseases, Dr. Furst said.

Dr. Furst disclosed that he has received grant/research support from AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Corbus, the National Institutes of Health, Novartis, and Roche/Genentech. He is also a consultant for AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Cytori, Novartis, Pfizer, and Roche/Genentech. Global Academy for Medical Education and this news organization are owned by the same parent company.

 

A key factor that impacts the efficacy and the toxicity of biologics used for rheumatic diseases is their immunogenicity, and this factor doesn’t appear to be any different for biosimilars in studies conducted so far.

In a meta-analysis of 63 studies of tumor necrosis factor (TNF) inhibitors, investigators including Daniel E. Furst, MD, professor of rheumatology at the University of Washington, Seattle, who also is affiliated with the University of California, Los Angeles, and the University of Florence, Italy, found that antidrug antibodies developed in 17% of patients (BioDrugs 2015;29:241-58).

“That doesn’t sound too bad, but does it differ by medication?” asked Dr. Furst, who spoke at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “For infliximab, 30% of the time, there are antidrug antibodies. So if that has a clinical effect, that’s a big deal. For certolizumab ... it’s only 6%, so there is a huge difference within the TNF inhibitors.” At the same time, antidrug antibodies developed in patients on adalimumab 23% of the time, followed by certolizumab (6%), golimumab (4%), and etanercept (2%).

Dr. Daniel E. Furst
The same meta-analysis found that the frequency of having immunogenicity differed among diseases as well. For example, antidrug antibodies developed in about 14% of patients with rheumatoid arthritis (RA), in 25% of patients with inflammatory bowel disease, and in 7% among patients with ankylosing spondylitis. “There are huge differences in the relative risk of having an antidrug antibody,” said Dr. Furst, director of research for Arthritis Associates of Southern California in Los Angeles. He also noted that the rate of drug response among patients who develop antidrug antibodies is decreased by about 50%. “So if you have the antibodies, it really makes a difference,” he said. “That differs by drug, and it differs by disease.”

One approach to circumventing the impact of antidrug antibodies on clinical response is by using immunosuppression, which in the meta-analysis had a 70% probability for decreasing antidrug antibodies. But this approach comes with a hitch, Dr. Furst said. The effect of immunosuppression on antidrug antibody positivity differs by disease. Immunosuppression had a 78% probability for decreasing antidrug antibody positivity in RA, 63% probability in inflammatory bowel disease, and 32% probability in ankylosing spondylitis. “That’s a wild mix of immunogenicity and the possibility that it’s going to affect the underlying response,” he said. The best studies in this area are of infliximab and adalimumab, which showed that antidrug antibodies in patients on infliximab reduced the probability of a clinical response by 54% and for adalimumab by 65%.

The same meta-analysis found that there were more antibodies to adalimumab than to certolizumab, golimumab, or etanercept, and also more antibodies to infliximab than to certolizumab, golimumab, or etanercept, but no difference between adalimumab and infliximab. “You’d think that maybe there is a difference between adalimumab and infliximab, but that’s not true,” Dr. Furst said. The apparent effect on the percentage of antidrug antibodies depends on what type of assay is used. For example, radioimmunoassay measures about 11% more antidrug antibodies, compared with enzyme-linked immunosorbent assay. Disease duration also matters. Each year of disease duration increases the antidrug antibodies by 1%.

What about the non-TNF inhibitors? A meta-analysis of five core trials of tocilizumab for RA found that the antidrug antibodies ranged from 1.7% at baseline to 2.3% during the respective trials (Clin Ther. 2010;32:1597-1609). “Anywhere along the way, the percentage of antidrug antibodies was about 1.5%,” said Dr. Furst, who was not involved with the study. “So as opposed to the TNF inhibitors, when you look at tocilizumab, this whole immunity question is probably a non-issue. The same is true for abatacept. With rituximab, the question is a little bit different. In one randomized, controlled trial, immunogenicity was 2.9%, while in the next it was 7.9%. In an open-label trial, it was 11.5%. So I think for rituximab we have to assume that you have some potentially important antidrug antibodies that might affect response.”

Studies have shown that antidrug antibodies do affect the pharmacokinetics of a biologic (and thereby clinical response) by producing lower trough levels of the biologic through an increase in its clearance. However, studies of infliximab and its biosimilars have not yielded any significant differences in clinical responses rates despite small differences in rates of antidrug antibodies or in rates of treatment-emergent adverse events, he said.

There has also been no difference in disease worsening in the only reported double-blind, randomized, switching study for infliximab and an infliximab biosimilar, the NOR-SWITCH study. However, the small numbers of patients in the study with certain diseases for which infliximab is indicated do not allow for conclusions to be drawn for specific diseases, Dr. Furst said.

Dr. Furst disclosed that he has received grant/research support from AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Corbus, the National Institutes of Health, Novartis, and Roche/Genentech. He is also a consultant for AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Cytori, Novartis, Pfizer, and Roche/Genentech. Global Academy for Medical Education and this news organization are owned by the same parent company.
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EXPERT ANALYSIS FROM THE ANNUAL PERSPECTIVES IN RHEUMATIC DISEASES

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In hypoparathyroidism, phosphate, calcium levels may matter

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– Most patients maintained time-weighted serum levels in the normal range in a case-control study of hypoparathyroidism, but serum levels of phosphate and calcium phosphate above median values were associated with a higher mortality and risk of complications.

The findings cannot prove causation, but they nevertheless suggest that physicians treating hypoparathyroidism should consider aiming to keep serum calcium and phosphate levels in the lower range of the reference interval, although all treatment decisions should be patient specific, according to Line Underbjerg, MD, of Aarhus (Denmark) University Hospital, who presented the study in a poster session at the annual meeting of the American Society for Bone and Mineral Research.

Denmark has a well-established cohort of patients with hypoparathyroidism, and previous epidemiologic studies have shown that those patients have increased risks of cardiovascular disease, renal diseases, and infections.

“From our epidemiologic study, we did not see increased mortality when we compared patients with hypoparathyroidism to [the] Danish population. So, we were actually a bit surprised that the phosphate and the calcium phosphate product had an influence on mortality,” said Dr. Underbjerg.

To find out if there were any associations between the biochemical findings and complications, the researchers collected biochemical data on 431 patients with hypoparathyroidism (81% of whom were women, with an average age of 41 years and a median disease duration of 12 years); 88% of the patients had the condition as a result of surgery, and 95% of patients received daily calcium and/or activated vitamin D supplements.

The researchers looked at four complications: mortality, cardiovascular disease, renal disease, and any infection. For each complication, they compared patients who had experienced the complication to hypoparathyroidism patients who did not experience the complication.

The subjects had a median time-weighted serum level of ionized calcium of 1.17 mmol/L (interquartile range [IQR], 1.14-1.21), a median of value of 1.21 mmol/L of phosphate (IQR, 1.11-1.32), and a median value of 2.80 mmol2/L2 of the calcium-phosphate product (IQR, 2.51-3.03).

Patients in the lowest tertile of ionized calcium (less than or equal to 1.16) had a greater risk of developing cardiovascular diseases than patients in the midtertile (1.16-1.19; odds ratio [OR], 2.96; 95% confidence interval [CI], 1.02-8.59).

Compared with patients in the midquartile, patients with serum phosphate levels above the median value of 1.21 were at a higher risk of mortality (OR, 2.76; 95% CI, 1.32-5.80) and infections (OR, 1.77; 95% CI, 1.04-3.01).

Calcium-phosphate product levels above the median value of 2.80 were associated with heightened mortality (OR, 2.67; 95% CI, 1.27-5.63) and renal diseases (OR, 1.71; 95% CI, 1.03-2.86).

Hypercalcemia occurred in 41% of patients and was also tied to increased mortality (OR, 1.76; 95% CI, 1.02-3.05) and risk of infections (OR, 1.86; 95% CI, 1.18-2.93).

The results suggest that those values have the potential to be clinically important. “I think you have to be aware that phosphate and calcium phosphate levels have an influence on a patient’s well-being,” said Dr. Underbjerg.

Shire funded the study. Dr. Underbjerg reported having no relevant financial disclosures.

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– Most patients maintained time-weighted serum levels in the normal range in a case-control study of hypoparathyroidism, but serum levels of phosphate and calcium phosphate above median values were associated with a higher mortality and risk of complications.

The findings cannot prove causation, but they nevertheless suggest that physicians treating hypoparathyroidism should consider aiming to keep serum calcium and phosphate levels in the lower range of the reference interval, although all treatment decisions should be patient specific, according to Line Underbjerg, MD, of Aarhus (Denmark) University Hospital, who presented the study in a poster session at the annual meeting of the American Society for Bone and Mineral Research.

Denmark has a well-established cohort of patients with hypoparathyroidism, and previous epidemiologic studies have shown that those patients have increased risks of cardiovascular disease, renal diseases, and infections.

“From our epidemiologic study, we did not see increased mortality when we compared patients with hypoparathyroidism to [the] Danish population. So, we were actually a bit surprised that the phosphate and the calcium phosphate product had an influence on mortality,” said Dr. Underbjerg.

To find out if there were any associations between the biochemical findings and complications, the researchers collected biochemical data on 431 patients with hypoparathyroidism (81% of whom were women, with an average age of 41 years and a median disease duration of 12 years); 88% of the patients had the condition as a result of surgery, and 95% of patients received daily calcium and/or activated vitamin D supplements.

The researchers looked at four complications: mortality, cardiovascular disease, renal disease, and any infection. For each complication, they compared patients who had experienced the complication to hypoparathyroidism patients who did not experience the complication.

The subjects had a median time-weighted serum level of ionized calcium of 1.17 mmol/L (interquartile range [IQR], 1.14-1.21), a median of value of 1.21 mmol/L of phosphate (IQR, 1.11-1.32), and a median value of 2.80 mmol2/L2 of the calcium-phosphate product (IQR, 2.51-3.03).

Patients in the lowest tertile of ionized calcium (less than or equal to 1.16) had a greater risk of developing cardiovascular diseases than patients in the midtertile (1.16-1.19; odds ratio [OR], 2.96; 95% confidence interval [CI], 1.02-8.59).

Compared with patients in the midquartile, patients with serum phosphate levels above the median value of 1.21 were at a higher risk of mortality (OR, 2.76; 95% CI, 1.32-5.80) and infections (OR, 1.77; 95% CI, 1.04-3.01).

Calcium-phosphate product levels above the median value of 2.80 were associated with heightened mortality (OR, 2.67; 95% CI, 1.27-5.63) and renal diseases (OR, 1.71; 95% CI, 1.03-2.86).

Hypercalcemia occurred in 41% of patients and was also tied to increased mortality (OR, 1.76; 95% CI, 1.02-3.05) and risk of infections (OR, 1.86; 95% CI, 1.18-2.93).

The results suggest that those values have the potential to be clinically important. “I think you have to be aware that phosphate and calcium phosphate levels have an influence on a patient’s well-being,” said Dr. Underbjerg.

Shire funded the study. Dr. Underbjerg reported having no relevant financial disclosures.

 

– Most patients maintained time-weighted serum levels in the normal range in a case-control study of hypoparathyroidism, but serum levels of phosphate and calcium phosphate above median values were associated with a higher mortality and risk of complications.

The findings cannot prove causation, but they nevertheless suggest that physicians treating hypoparathyroidism should consider aiming to keep serum calcium and phosphate levels in the lower range of the reference interval, although all treatment decisions should be patient specific, according to Line Underbjerg, MD, of Aarhus (Denmark) University Hospital, who presented the study in a poster session at the annual meeting of the American Society for Bone and Mineral Research.

Denmark has a well-established cohort of patients with hypoparathyroidism, and previous epidemiologic studies have shown that those patients have increased risks of cardiovascular disease, renal diseases, and infections.

“From our epidemiologic study, we did not see increased mortality when we compared patients with hypoparathyroidism to [the] Danish population. So, we were actually a bit surprised that the phosphate and the calcium phosphate product had an influence on mortality,” said Dr. Underbjerg.

To find out if there were any associations between the biochemical findings and complications, the researchers collected biochemical data on 431 patients with hypoparathyroidism (81% of whom were women, with an average age of 41 years and a median disease duration of 12 years); 88% of the patients had the condition as a result of surgery, and 95% of patients received daily calcium and/or activated vitamin D supplements.

The researchers looked at four complications: mortality, cardiovascular disease, renal disease, and any infection. For each complication, they compared patients who had experienced the complication to hypoparathyroidism patients who did not experience the complication.

The subjects had a median time-weighted serum level of ionized calcium of 1.17 mmol/L (interquartile range [IQR], 1.14-1.21), a median of value of 1.21 mmol/L of phosphate (IQR, 1.11-1.32), and a median value of 2.80 mmol2/L2 of the calcium-phosphate product (IQR, 2.51-3.03).

Patients in the lowest tertile of ionized calcium (less than or equal to 1.16) had a greater risk of developing cardiovascular diseases than patients in the midtertile (1.16-1.19; odds ratio [OR], 2.96; 95% confidence interval [CI], 1.02-8.59).

Compared with patients in the midquartile, patients with serum phosphate levels above the median value of 1.21 were at a higher risk of mortality (OR, 2.76; 95% CI, 1.32-5.80) and infections (OR, 1.77; 95% CI, 1.04-3.01).

Calcium-phosphate product levels above the median value of 2.80 were associated with heightened mortality (OR, 2.67; 95% CI, 1.27-5.63) and renal diseases (OR, 1.71; 95% CI, 1.03-2.86).

Hypercalcemia occurred in 41% of patients and was also tied to increased mortality (OR, 1.76; 95% CI, 1.02-3.05) and risk of infections (OR, 1.86; 95% CI, 1.18-2.93).

The results suggest that those values have the potential to be clinically important. “I think you have to be aware that phosphate and calcium phosphate levels have an influence on a patient’s well-being,” said Dr. Underbjerg.

Shire funded the study. Dr. Underbjerg reported having no relevant financial disclosures.

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Key clinical point: Serum phosphate and calcium-phosphate levels may influence patient outcomes in hypoparathyroidism.

Major finding: Higher phosphate levels are tied to an increased risk of mortality (OR, 2.76) and infections (OR, 1.77).

Data source: A case-control study of 431 patients with hypoparathyroidism.

Disclosures: Shire funded the study. Dr. Underbjerg reported having no relevant financial disclosures.

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Laser Interstitial Thermal Ablation: A Promising Approach to TLE

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Epilepsy Res ePub 2017 Jul 25; Kang et al.

Laser interstitial thermal ablation (LiTT) appears to benefit patients with temporal lobe epilepsy (TLE) according to a recent article published in Epilepsy Research.

  • According to the author, LiTT has been found to eliminate seizures in about half of patients with mesial temporal lobe epilepsy who undergo the procedure.
  • Neuropsychological side effects of the procedure seem to be less severe, when compared to surgeries that require large resections.
  • LiTT involves inserting a probe into the area of the brain responsible for the seizures, including the mesial temporal lobe and hypothalamic hamartoma, and heating the tip of the probe by means of laser energy.
  • Advantages include the fact that LiTT is less invasive than open surgery and allows patients to leave the hospital sooner and experience less pain.
  • The minimally invasive surgery typically requires a single day of hospitalization and allows patients to return to work in 3 days.
  • It remains uncertain whether LiTT is as efficacious as more invasive procedures but appears to be about as efficacious as anterior temporal lobectomy.

Kang JY, Sperling MR. Epileptologist’s view: Laser interstitial thermal ablation for treatment of temporal lobe epilepsy.  [Published online ahead of print July 25, 2017] Epilepsy Res. https://doi.org/10.1016/j.eplepsyres.2017.07.007

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Epilepsy Res ePub 2017 Jul 25; Kang et al.
Epilepsy Res ePub 2017 Jul 25; Kang et al.

Laser interstitial thermal ablation (LiTT) appears to benefit patients with temporal lobe epilepsy (TLE) according to a recent article published in Epilepsy Research.

  • According to the author, LiTT has been found to eliminate seizures in about half of patients with mesial temporal lobe epilepsy who undergo the procedure.
  • Neuropsychological side effects of the procedure seem to be less severe, when compared to surgeries that require large resections.
  • LiTT involves inserting a probe into the area of the brain responsible for the seizures, including the mesial temporal lobe and hypothalamic hamartoma, and heating the tip of the probe by means of laser energy.
  • Advantages include the fact that LiTT is less invasive than open surgery and allows patients to leave the hospital sooner and experience less pain.
  • The minimally invasive surgery typically requires a single day of hospitalization and allows patients to return to work in 3 days.
  • It remains uncertain whether LiTT is as efficacious as more invasive procedures but appears to be about as efficacious as anterior temporal lobectomy.

Kang JY, Sperling MR. Epileptologist’s view: Laser interstitial thermal ablation for treatment of temporal lobe epilepsy.  [Published online ahead of print July 25, 2017] Epilepsy Res. https://doi.org/10.1016/j.eplepsyres.2017.07.007

Laser interstitial thermal ablation (LiTT) appears to benefit patients with temporal lobe epilepsy (TLE) according to a recent article published in Epilepsy Research.

  • According to the author, LiTT has been found to eliminate seizures in about half of patients with mesial temporal lobe epilepsy who undergo the procedure.
  • Neuropsychological side effects of the procedure seem to be less severe, when compared to surgeries that require large resections.
  • LiTT involves inserting a probe into the area of the brain responsible for the seizures, including the mesial temporal lobe and hypothalamic hamartoma, and heating the tip of the probe by means of laser energy.
  • Advantages include the fact that LiTT is less invasive than open surgery and allows patients to leave the hospital sooner and experience less pain.
  • The minimally invasive surgery typically requires a single day of hospitalization and allows patients to return to work in 3 days.
  • It remains uncertain whether LiTT is as efficacious as more invasive procedures but appears to be about as efficacious as anterior temporal lobectomy.

Kang JY, Sperling MR. Epileptologist’s view: Laser interstitial thermal ablation for treatment of temporal lobe epilepsy.  [Published online ahead of print July 25, 2017] Epilepsy Res. https://doi.org/10.1016/j.eplepsyres.2017.07.007

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The Link Between Ischemic Stroke and Seizures

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Neurology 2017 Sep 19; Wang et al.

The threat of seizures and epilepsy is a significant concern for patients who have had a stroke, according to a review of 41 studies published in Neurology.  

  • Investigators found 35 studies that reported stroke-related seizures and 6 studies that found details on the effects of antiepileptic drugs.
  • Seizures occurred early on in 3.3% of patients who had experienced a stroke.
  • Late-onset seizures or epilepsy was reported in 18/1000 person-years.
  • Researchers were unable to find any evidence to suggest that a specific drug was more effective among patients who had seizures after a stroke.
  • Newer drugs caused fewer side effects than older medications.
  • The systematic review and meta-analysis included measurement of I2 statistic to evaluate heterogeneity and sensitivity analyses were also performed.
  • Early onset and late onset seizures generated I2 statistics of 92.8% and 94.1%, respectively.
  • Sensitivity analyses was unable to explain the high degree of heterogeneity.

Wang JZ, Vyas MV, Saposnik G, Burneo JG. Incidence and management of seizures after ischemic stroke. Neurology. 2017;89:1220-1228.  

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Neurology 2017 Sep 19; Wang et al.
Neurology 2017 Sep 19; Wang et al.

The threat of seizures and epilepsy is a significant concern for patients who have had a stroke, according to a review of 41 studies published in Neurology.  

  • Investigators found 35 studies that reported stroke-related seizures and 6 studies that found details on the effects of antiepileptic drugs.
  • Seizures occurred early on in 3.3% of patients who had experienced a stroke.
  • Late-onset seizures or epilepsy was reported in 18/1000 person-years.
  • Researchers were unable to find any evidence to suggest that a specific drug was more effective among patients who had seizures after a stroke.
  • Newer drugs caused fewer side effects than older medications.
  • The systematic review and meta-analysis included measurement of I2 statistic to evaluate heterogeneity and sensitivity analyses were also performed.
  • Early onset and late onset seizures generated I2 statistics of 92.8% and 94.1%, respectively.
  • Sensitivity analyses was unable to explain the high degree of heterogeneity.

Wang JZ, Vyas MV, Saposnik G, Burneo JG. Incidence and management of seizures after ischemic stroke. Neurology. 2017;89:1220-1228.  

The threat of seizures and epilepsy is a significant concern for patients who have had a stroke, according to a review of 41 studies published in Neurology.  

  • Investigators found 35 studies that reported stroke-related seizures and 6 studies that found details on the effects of antiepileptic drugs.
  • Seizures occurred early on in 3.3% of patients who had experienced a stroke.
  • Late-onset seizures or epilepsy was reported in 18/1000 person-years.
  • Researchers were unable to find any evidence to suggest that a specific drug was more effective among patients who had seizures after a stroke.
  • Newer drugs caused fewer side effects than older medications.
  • The systematic review and meta-analysis included measurement of I2 statistic to evaluate heterogeneity and sensitivity analyses were also performed.
  • Early onset and late onset seizures generated I2 statistics of 92.8% and 94.1%, respectively.
  • Sensitivity analyses was unable to explain the high degree of heterogeneity.

Wang JZ, Vyas MV, Saposnik G, Burneo JG. Incidence and management of seizures after ischemic stroke. Neurology. 2017;89:1220-1228.  

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Sleep, Age, and Prone Position Linked to SUDEP

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Sleep, Age, and Prone Position Linked to SUDEP
Epilepsy Behav. ePub 2017 Sep 17, Ali et al.

Patients are more likely to die of sudden unexpected death in epilepsy (SUDEP) while they are asleep, according to a review of over 1000 SUDEP cases gleaned from 67 studies.

  • Among 1025 patients with SUDEP, 880 cases had a circadian pattern.
  • Of the 880 cases with a circadian pattern, 69.3% of the deaths occurred during sleep and 30.7% while patients were awake (P<0.001).
  • Subgroup analysis found 272 patients in which both circadian pattern and age could be established.
  • In this subgroup, patients aged 40 years and younger were more likely to die while asleep, when compared with older patients (odds ratio, 2.0).
  • Among patients whose body position could also be verified, prone position was more often associated with death, when compared with those in prone position who were awake (87.6% vs 52.9%).

Ali A, Wu S, Issa NP, et al. Association of sleep with sudden unexpected death in epilepsy. [Published online ahead of print September 13, 2017] Epilepsy Behav. https://doi.org/10.1016/j.yebeh.2017.08.021

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Epilepsy Behav. ePub 2017 Sep 17, Ali et al.
Epilepsy Behav. ePub 2017 Sep 17, Ali et al.

Patients are more likely to die of sudden unexpected death in epilepsy (SUDEP) while they are asleep, according to a review of over 1000 SUDEP cases gleaned from 67 studies.

  • Among 1025 patients with SUDEP, 880 cases had a circadian pattern.
  • Of the 880 cases with a circadian pattern, 69.3% of the deaths occurred during sleep and 30.7% while patients were awake (P<0.001).
  • Subgroup analysis found 272 patients in which both circadian pattern and age could be established.
  • In this subgroup, patients aged 40 years and younger were more likely to die while asleep, when compared with older patients (odds ratio, 2.0).
  • Among patients whose body position could also be verified, prone position was more often associated with death, when compared with those in prone position who were awake (87.6% vs 52.9%).

Ali A, Wu S, Issa NP, et al. Association of sleep with sudden unexpected death in epilepsy. [Published online ahead of print September 13, 2017] Epilepsy Behav. https://doi.org/10.1016/j.yebeh.2017.08.021

Patients are more likely to die of sudden unexpected death in epilepsy (SUDEP) while they are asleep, according to a review of over 1000 SUDEP cases gleaned from 67 studies.

  • Among 1025 patients with SUDEP, 880 cases had a circadian pattern.
  • Of the 880 cases with a circadian pattern, 69.3% of the deaths occurred during sleep and 30.7% while patients were awake (P<0.001).
  • Subgroup analysis found 272 patients in which both circadian pattern and age could be established.
  • In this subgroup, patients aged 40 years and younger were more likely to die while asleep, when compared with older patients (odds ratio, 2.0).
  • Among patients whose body position could also be verified, prone position was more often associated with death, when compared with those in prone position who were awake (87.6% vs 52.9%).

Ali A, Wu S, Issa NP, et al. Association of sleep with sudden unexpected death in epilepsy. [Published online ahead of print September 13, 2017] Epilepsy Behav. https://doi.org/10.1016/j.yebeh.2017.08.021

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Sleep, Age, and Prone Position Linked to SUDEP
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