Is methotrexate safe for men with an immune-mediated inflammatory disease and an active desire to become a father? Results of a prospective cohort study (iFAME-MTX).

INTRODUCTION: Current scientific evidence guiding the decision whether men with an active desire to become a father should be treated with methotrexate (MTX) remains controversial. We aimed to prospectively evaluate the testicular toxicity profile of MTX focusing on several markers of male fertility, including semen parameters and sperm DNA fragmentation index (sDFI). As a secondary outcome, we aimed to evaluate whether MTX-polyglutamates can be detected in spermatozoa and seminal plasma and to evaluate the enzymatic activity in spermatozoa of folylpolyglutamate synthetase (FPGS). METHODS: In a prospective cohort study, men ≥18 years who started therapy with MTX were invited to participate (MTX-starters). Participants were instructed to produce two semen samples (a pre-exposure and a post-exposure sample after 13 weeks). Healthy men ≥18 years were invited to participate as controls. Conventional semen analyses, male reproductive endocrine axis and sDFI were compared between groups. FPGS enzymatic activity and MTX-PG1-5 concentrations were determined by mass spectrometry analytical methods. RESULTS: In total, 20 MTX-starters and 25 controls were included. The pre-exposure and postexposure semen parameters of MTX-starters were not statistically significant different. Compared with healthy controls, the conventional semen parameters and the sDFI of MTX-starters were not statistically significant different. These data were corroborated by the marginal accumulation of MTX-PGs in spermatozoa, consistent with the very low FPGS enzymatic activity associated with the expression of an alternative FPGS splice-variant. DISCUSSION: Treatment with MTX is not associated with testicular toxicity, consistent with the very low concentration of intracellular MTX-PG. Therefore, therapy with MTX can be safely started or continued in men and with a wish to become a father.

Effect of Default Order Standardization on Opioid Prescribing Patterns.

BACKGROUND: Opioid misuse, overprescribing, dependency, and overdose remains a significant concern in the United States. A quality improvement study was conducted at the University of Illinois Hospital & Health Sciences System to determine the effect of standardizing the default orders for hydrocodone-acetaminophen products implemented on June 22, 2016. METHODS: Prior to the intervention, default orders had variable dose tablet numbers (1 or 2) and dosing frequencies (every 4 or 6 hours), and no default dispense quantity. Defaults were modified to 1 tablet every 6 hours as needed for pain and dispense quantities of 3 and 5 days' supply were added. Number of tablets per order, dosing frequency, and days' supply prescribed between January 1, 2016, and June 21, 2016, were compared to those placed between June 22, 2016, and December 31, 2016. Opioid doses were converted into morphine milligram equivalents (MME). Analyses were performed to determine the effect of the intervention on daily opioid dose and number of days' supply prescribed. RESULTS: 22,052 orders were included in this study. Following the intervention, the number of tablets prescribed was reduced by an average of 19,832 tablets per month. Every 6 hours dosing (as opposed to every 4 hours) increased by 21.52 percentage points. Prescriptions with ≥ 50 MME/day dropped by 5.8 percentage points, and > 3 days' supply decreased by 2.54 percentage points. Linear regression demonstrated an increase in opioid prescriptions with daily < 50 MME (odds ratio [OR] = 1.72, p < 0.001) and ≤ 3 days' supply (OR = 1.27, p < 0.001). CONCLUSION: Default electronic health record settings strongly influence prescribing patterns.

Modern treatment approach results in low disease activity in 90% of pregnant rheumatoid arthritis patients: the PreCARA study.

OBJECTIVES: In patients with rheumatoid arthritis (RA), high disease activity impairs fertility outcomes and increases the risk of adverse pregnancy outcomes. The aim of this study was to determine the feasibility of a modern treatment approach, including treat-to-target (T2T) and the prescription of tumour necrosis factor (TNF) inhibitors, in patients with RA with a wish to conceive or who are pregnant. METHODS: Patients were derived from the Preconception Counseling in Active RA (PreCARA) cohort. Patients with a wish to conceive or who are pregnant were treated according to a modified T2T approach, in which the obvious restrictions of pregnancy were taken into account. Results of the PreCARA study were compared with results of the Pregnancy-induced Amelioration of Rheumatoid Arthritis (PARA) study, a historic reference cohort on RA during pregnancy. Patients in the PARA cohort were treated according to the standards of that time (2002-2010). Differences in disease activity over time between the two cohorts were tested using a linear mixed model. RESULTS: 309 patients with RA were included in the PreCARA study, 188 children were born. 47.3% of the patients used a TNF inhibitor at any time during pregnancy. Mean disease activity over time in the PreCARA cohort was lower than in the reference cohort (p<0.001). In the PreCARA cohort, 75.4% of the patients were in low disease activity (LDA) or remission before pregnancy increasing to 90.4% in the third trimester, whereas in the PARA cohort, these percentages were 33.2% and 47.3%, respectively. CONCLUSIONS: This first study on a modern treatment approach in pregnant patients with RA shows that LDA and remission are an attainable goal during pregnancy, with 90.4% of patients achieving this in the third trimester.

Dentists' prescribing of antibiotics and opioids to Medicare Part D beneficiaries: Medications of high impact to public health.

BACKGROUND: Gaining a better understanding of dental prescribing can help identify opportunities for intervention regarding optimal medication use. The purpose of this study is to characterize opioid and antibiotic prescribing patterns of dentists in the United States for Medicare Part D beneficiaries. METHODS: The authors conducted a retrospective cross-sectional analysis of national 2014 Medicare Part D Prescriber Public Use File data. Providers in the data set with dental-related disciplines were included (n = 99,797). Outcomes of interest were mean days' supply and mean number of claims reported per claim, beneficiary, and prescriber discipline. RESULTS: Of the 6,724,372 dental prescription claims submitted, 3,947,848 (58.7%) and 1,312,796 (19.5%) were for antibiotics and opioids, respectively. Sixty-nine percent of dentists in the highest quartile of opioid prescribers were also in the highest quartile of antibiotic prescribers (r2 = 0.7778; P < .01). The mean (standard deviation) days' supply per claim was 6.9 (5.3) days (range, 1-90 days) for antibiotics and 3.6 (2.0) days (range, 1-44.5 days) for opioids. Of the 33,348 dental providers who prescribed opioids, 18,971 (56.9%) prescribed a mean opioid days per claim greater than the recommended duration of 3 days for acute pain. CONCLUSION: Opioids and antibiotics are the medications most prescribed by dentists. On the basis of national recommendations and results of studies from other countries, the length of therapy prescribed may be excessive. Further studies should be conducted to assess appropriateness of dental prescriptions. PRACTICAL IMPLICATIONS: Dentistry should be considered for antibiotic and opioid stewardship interventions along with medicine.

Efficacy of Berberine Alone and in Combination for the Treatment of Hyperlipidemia: A Systematic Review.

The objective of this review is to identify, summarize, and evaluate clinical trials of berberine for the treatment of hyperlipidemia and other dyslipidemias. A literature search for randomized, controlled trials of berberine that assessed at least 2 lipid values as endpoints resulted in identification of 12 articles that met criteria. The majority of evaluated articles consistently suggest that berberine has a beneficial effect on low-density lipoprotein (reductions ranging from approximately 20 to 50 mg/dL) and triglycerides (reductions ranging from approximately 25 to 55 mg/dL). Common study limitations included lack of reporting of precision in their endpoints, description of blinding, transparency in flow of patients, and reporting of baseline concomitant medications. Berberine could serve as an alternative for patients who are intolerant to statins, patients resistant to starting statin therapy but who are open to alternative treatments, and for low-risk patients not indicated for statin therapy.

Analysis of reference sources used in drug-related Wikipedia articles.

OBJECTIVE: References from drug-related Wikipedia articles and a drug information database were compared. METHODS: Drugs in Food and Drug Administration (FDA) MedWatch alerts from January-July 2013 were searched in Wikipedia and Lexicomp to compare reference types and to assess the time for drug safety information to be incorporated into Wikipedia articles. RESULTS: Wikipedia most commonly cited peer-reviewed journal articles (49.2%) and news articles (12.0%). MedWatch citations were incorporated into Wikipedia on average in 5.9 days. CONCLUSIONS: Wikipedia cited various sources but may not be a reliable, up-to-date resource for drug safety information.

Global application of disorders of sex development-related electronic resources: e-learning, e-consultation and e-information sharing.

The past 20 years have seen proliferation of electronic (e) resources that promote improved understanding of disorders of sex development (DSD): e-learning for physicians and trainees, e-consultation between clinicians, and e-information for families and affected individuals. Recent e-learning advances have emerged from the European Society for Pediatric Endocrinology's online learning portal for current physicians and trainees. Developed with attention to developing clinical competencies incorporating learning theory, and presenting material that represents international best practice, this e-learning portal offers advances in training, making information more accessible for clinicians and trainees. Multiple levels of instruction, authentic case examples, collaborative forums for physicians and trainees, individualized feedback and user-friendly tools represent advances in trainee and physician learning that can take place in any location. e-consultation is an emerging tool that aims to connect physicians with specialists experienced in DSD care. Although it faces logistical challenges, e-consultation carries the potential to improve DSD care, especially in remote areas with limited access to DSD specialists. e-information for families and patients of all ages is widely accessible online, often with focus on DSD biology, medical care, and psychological and social support. e-information tools aid self-management and support of those affected by DSD. Efforts to improve these resources should aim to map information to individual users, incorporate optimally clear nomenclature, and continue as a 'shared enterprise' of clinicians, affected individuals, families and researchers. Improving the quality of DSD-related e-learning and e-information and developing e-consultation carries the potential to transform DSD care and support for patients, families and physicians worldwide.

Ergonomics in thoracoscopic surgery: results of a survey among thoracic surgeons.

OBJECTIVES: The frequent and prolonged use of thoracoscopic equipment raises ergonomic risks which may cause physical distress. We aimed to determine the relationship between ergonomic problems encountered in thoracoscopic surgery and physical distress among thoracic surgeons. METHODS: An online questionnaire which investigated personal factors, product factors, interaction factors and physical discomfort was sent to all members of the European Society of Thoracic Surgeons (ESTS). RESULTS: Of the respondents, 2.4% indicated that a one arm's length should be the optimal distance between the surgeon and the monitor. Only 2.4% indicated that the monitor should be positioned below the eye level of the surgeon. Most of the respondents agreed, partially to fully, that they experienced neck discomfort because of inappropriate monitor height, bad monitor position and bad table height. Most respondents experienced numb fingers and shoulder discomfort due to instrument manipulation. Most of the respondents (77.1%) experienced muscle fatigue to some extent due to a static posture during thoracoscopic surgery. The majority of respondents (81.9, 76.3 and 83.2% respectively) indicated that they had varying degrees of discomfort mainly in the neck, shoulder and back. Some 94.4% of respondents were unaware of any guidelines concerning table height, monitor and instrument placement for endoscopic surgery. CONCLUSIONS: Most thoracic surgeons in Europe are unaware of ergonomic guidelines and do not practise them, hence they suffer varying degrees of physical discomfort arising from ergonomic issues.