IMPORTANCE Severe impulse control disorders involving pathological gambling, hypersexuality, and compulsive shopping have been reported in association with the use of dopamine receptor agonist drugs in case series and retrospective patient surveys. These agents are used to treat Parkinson disease, restless leg syndrome, and hyperprolactinemia. OBJECTIVES To analyze serious adverse drug event reports about these impulse control disorders received by the US Food and Drug Administration (FDA) and to assess the relationship of these case reports with the 6 FDA-approved dopamine receptor agonist drugs. DESIGN, SETTING, AND PARTICIPANTS We conducted a retrospective disproportionality analysis based on the 2.7 million serious domestic and foreign adverse drug event reports from 2003 to 2012 extracted from the FDA Adverse Event Reporting System. MAIN OUTCOMES AND MEASURES Cases were selected if they contained any of 10 preferred terms in the Medical Dictionary for Regulatory Activities (MedDRA) that described the abnormal behaviors. We used the proportional reporting ratio (PRR) to compare the proportion of target events to all serious events for the study drugs with a similar proportion for all other drugs. RESULTS We identified 1580 events indicating impulse control disorders from the United States and 21 other countries: 710 for dopamine receptor agonist drugs and 870 for other drugs. The dopamine receptor agonist drugs had a strong signal associated with these impulse control disorders (n = 710; PRR = 277.6, P < .001). The association was strongest for the dopamine agonists pramipexole (n = 410; PRR = 455.9, P < .001) and ropinirole (n = 188; PRR = 152.5, P < .001), with preferential affinity for the dopamine D 3 receptor. A signal was also seen for aripiprazole, an antipsychotic classified as a partial agonist of the D 3 receptor (n = 37; PRR = 8.6, P < .001). CONCLUSIONS AND RELEVANCE Our findings confirm and extend the evidence that dopamine receptor agonist drugs are associated with these specific impulse control disorders. At present, none of the dopamine receptor agonist drugs approved by the FDA have boxed warnings as part of their prescribing information. Our data, and data from prior studies, show the need for more prominent warnings.

findings should be confirmed by future studies involving diverse groups of older adults.

And his daughter‐in‐law, the wife of Phinehas, was pregnant near to giving birth, and got to hear the report that the ark of the true God was captured and that her father‐in‐law and her husband had died. At that she bowed herself and began giving birth, because her pangs came unexpectedly upon her.

BackgroundElderly adults should avoid medications with anticholinergic effects since they may increase the risk of adverse events, including falls, delirium, and cognitive impairment. However, data on anticholinergic burden are limited in subpopulations, such as individuals with Parkinson disease (PD). The objective of this study was to determine whether anticholinergic burden was associated with adverse outcomes in a PD inpatient population.MethodsUsing the Cerner Health Facts® database, we retrospectively examined anticholinergic medication use, diagnoses, and hospital revisits within a cohort of 16,302 PD inpatients admitted to a Cerner hospital between 2000 and 2011. Anticholinergic burden was computed using the Anticholinergic Risk Scale (ARS). Primary outcomes were associations between ARS score and diagnosis of fracture and delirium. Secondary outcomes included associations between ARS score and 30-day hospital revisits.ResultsMany individuals (57.8%) were prescribed non-PD medications with moderate to very strong anticholinergic potential. Individuals with the greatest ARS score (≥4) were more likely to be diagnosed with fractures (adjusted odds ratio (AOR): 1.56, 95% CI: 1.29–1.88) and delirium (AOR: 1.61, 95% CI: 1.08–2.40) relative to those with no anticholinergic burden. Similarly, inpatients with the greatest ARS score were more likely to visit the emergency department (adjusted hazard ratio (AHR): 1.32, 95% CI: 1.10–1.58) and be readmitted (AHR: 1.16, 95% CI: 1.01–1.33) within 30-days of discharge.ConclusionsWe found a positive association between increased anticholinergic burden and adverse outcomes among individuals with PD. Additional pharmacovigilance studies are needed to better understand risks associated with anticholinergic medication use in PD.

PurposeAlthough therapeutic options and clinical guidelines for Parkinson’s disease (PD) have changed significantly in the past 15 years, prescribing trends in the USA remain unknown. The purpose of this population-based cohort study was to examine patterns of inpatient antiparkinson drug use between January 2001 and December 2012 in relation to clinical guideline publication, drug introduction/withdrawal, and emerging safety concerns.MethodsA total of 16,785 inpatients receiving pharmacological treatment for PD were identified in the Cerner Health Facts database. Our primary outcome was standardized (age, sex, race, and census region) annual prevalence of antiparkinson drug use. We also examined antiparkinson medication trends and polypharmacy by age and sex.ResultsThe most frequently prescribed antiparkinson drugs between 2001 and 2012 were levodopa (85 %) and dopamine agonists (28 %). Dopamine agonist use began declining in 2007, from 34 to 27 % in 2012. The decline followed publication of the American Academy of Neurology’s practice parameter refuting levodopa toxicity, pergolide withdrawal, and pramipexole label revisions. Despite safety concerns for cognitive impairment and falls, individuals ≥80 years of age demonstrated stable rates of dopamine agonist use from 2001 to 2012. Polypharmacy was most common in younger patients.ConclusionsDopamine agonist use declined from 2007 to 2012, suggesting that increased awareness of safety issues and practice guidelines influenced prescribing. These events appear to have minimally influenced treatment provided to older PD patients. Antiparkinson prescribing trends indicate that safety and best practice information may be communicated effectively.Electronic supplementary materialThe online version of this article (doi:10.1007/s00228-015-1881-4) contains supplementary material, which is available to authorized users.

Thiazolidinedione (TZD) drugs used in the treatment of type 2 diabetes mellitus (T2DM) have proven effective in improving insulin sensitivity, hyperglycemia, and lipid metabolism. Though well tolerated by some patients, their mechanism of action as ligands of peroxisome proliferator-activated receptors (PPARs) results in the activation of several pathways in addition to those responsible for glycemic control and lipid homeostasis. These pathways, which include those related to inflammation, bone formation, and cell proliferation, may lead to adverse health outcomes. As treatment with TZDs has been associated with adverse hepatic, cardiovascular, osteological, and carcinogenic events in some studies, the role of TZDs in the treatment of T2DM continues to be debated. At the same time, new therapeutic roles for TZDs are being investigated, with new forms and isoforms currently in the pre-clinical phase for use in the prevention and treatment of some cancers, inflammatory diseases, and other conditions. The aims of this review are to provide an overview of the mechanism(s) of action of TZDs, a review of their safety for use in the treatment of T2DM, and a perspective on their current and future therapeutic roles.

Premature menopause, ovarian failure younger than 40 years of age, is relatively rare but may preclude childbearing for some women who delay attempts at fertility. We present five kindreds in which a genetic association for premature ovarian failure is strongly suggested. Transmission is either autosomal or (less likely) X-linked dominant in these examples. Chromosomal abnormalities, history of diseases, and toxic chemical or viral exposures previously associated with premature ovarian failure could not be demonstrated in these women. This suggests that these kindreds all represent familial idiopathic premature ovarian failure. These data support the need for menopausal histories on both sides of the family for women seeking to postpone reproduction, as well as for patients with ovarian failure.

Propylthiouracil (PTU) was introduced for clinical use in July 1947 for Graves' disease (GD) treatment. Over the 60 years that this medication has been used, reports of PTU-related liver failure and death have accumulated. On October 28, 2008, an expert panel evaluated PTU drug safety in children at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) It is estimated that about 4000 pediatric patients per year with GD are being treated with antithyroid drugs (ATDs) in the United States, and up to 30% of pediatric patients with GD are being treated with PTU. The risk of severe PTU-induced liver failure is estimated as 1 in 2000–4000 children. The number of children developing reversible PTU-induced liver injury is estimated to be at least 1 in 200. Routine biochemical surveillance of liver function and hepatocellular integrity is not useful in identifying children who will develop liver failure. Children appear to be at higher risk for PTU-induced liver injury than adults. PTU should not be used as first line therapy for the treatment of GD in children. Current PTU use in children taking this medication should be stopped in favor of alternate therapies.