Variation in opioid prescribing patterns after abdominal transplant surgery.

BACKGROUND: Opioids are associated with negative transplant outcomes. We sought to identify patient and center effects on over-prescribing of opioids (> 200 OME (oral morphine equivalents)). STUDY DESIGN: Clinical and opioid prescription data (2014-2017) were collected from three academic transplant centers for kidney (KT), liver (LT), and simultaneous liver-kidney transplant (SLK) patients. Multivariable models were used to identify predictors of opioid over-prescribing at discharge and the occurrence of refill prescriptions at 90 days. RESULTS: Three-thousand seven-hundred and two patients underwent transplant in the cohort (KT: n = 2358, LT: n = 1221, SLK: n = 123). More than 80% of recipients were over-prescribed opioids at discharge (Median OME (mOME) = 300 (IQR 225-375). LT and SLK had the largest prescription size (LT mOME 338 (IQR 300-450); SLK mOME 338 (IQR 225-450) and refill rate (LT: 64%, SLK 59%) (all, P < .001). Multivariable analysis indicated that transplant center was a significant predictor of opioid over-prescription after KT and LT (all, P < .001); older age (in KT) and length of stay (LOS) (in LT) were protective factors (both, P < .05). Refill occurrence was associated with initial prescription size and was reduced by older age and initial LOS (all, P < .05). CONCLUSIONS: The wide variation in opioid prescribing patterns has implications for transplant practice innovation, guideline development, and further study.

Genome-Wide Association Study of Late-Onset Myasthenia Gravis: Confirmation of TNFRSF11A and Identification of ZBTB10 and Three Distinct HLA Associations.

To investigate the genetics of late-onset myasthenia gravis (LOMG), we conducted a genome-wide association study imputation of>6 million single nucleotide polymorphisms (SNPs) in 532 LOMG cases (anti-acetylcholine receptor [AChR] antibody positive; onset age≥50 years) and 2,128 controls matched for sex and population substructure. The data confirm reported TNFRSF11A associations (rs4574025, P = 3.9 × 10-7, odds ratio [OR] 1.42) and identify a novel candidate gene, ZBTB10, achieving genome-wide significance (rs6998967, P = 8.9 × 10-10, OR 0.53). Several other SNPs showed suggestive significance including rs2476601 (P = 6.5 × 10-6, OR 1.62) encoding the PTPN22 R620W variant noted in early-onset myasthenia gravis (EOMG) and other autoimmune diseases. In contrast, EOMG-associated SNPs in TNIP1 showed no association in LOMG, nor did other loci suggested for EOMG. Many SNPs within the major histocompatibility complex (MHC) region showed strong associations in LOMG, but with smaller effect sizes than in EOMG (highest OR ~2 versus ~6 in EOMG). Moreover, the strongest associations were in opposite directions from EOMG, including an OR of 0.54 for DQA1*05:01 in LOMG (P = 5.9 × 10-12) versus 2.82 in EOMG (P = 3.86 × 10-45). Association and conditioning studies for the MHC region showed three distinct and largely independent association peaks for LOMG corresponding to (a) MHC class II (highest attenuation when conditioning on DQA1), (b) HLA-A and (c) MHC class III SNPs. Conditioning studies of human leukocyte antigen (HLA) amino acid residues also suggest potential functional correlates. Together, these findings emphasize the value of subgrouping myasthenia gravis patients for clinical and basic investigations and imply distinct predisposing mechanisms in LOMG.

Musician's dystonia.

Musician's dystonia is a task-specific dystonia that usually affects the embouchure or the most active digits of the most active hand, and therefore differs between instruments. Since it is usually painless and intermittent, the diagnosis is often delayed and it is commonly misdiagnosed as being an overuse disorder or tendon pathology. It arises from pathological brain plasticity: physiological studies suggest that it is an exaggeration of brain changes that are required to achieve advanced musical skills. Its treatment often has limited success; however, musical retraining, botulinum toxin or rehabilitation based on modifying the aberrant plasticity may help.

Myasthenia gravis: Association of British Neurologists' management guidelines.

Myasthenia gravis is an autoimmune disease of the neuromuscular junction for which many therapies were developed before the era of evidence based medicine. The basic principles of treatment are well known, however, patients continue to receive suboptimal treatment as a result of which a myasthenia gravis guidelines group was established under the aegis of The Association of British Neurologists. These guidelines attempt to steer a path between evidence-based practice where available, and established best practice where evidence is unavailable. Where there is insufficient evidence or a choice of options, the guidelines invite the clinician to seek the opinion of a myasthenia expert. The guidelines support clinicians not just in using the right treatments in the right order, but in optimising the use of well-known therapeutic agents. Clinical practice can be audited against these guidelines.

Mycophenolate and methotrexate are better tolerated than azathioprine in myasthenia gravis.

Azathioprine is recommended as the first-line steroid-sparing immunosuppressive agent for myasthenia gravis. Mycophenolate and methotrexate are often considered as second-line choices despite widespread consensus on their efficacy. We aimed to gather real-world data comparing the tolerability and reasons for discontinuation for these agents, by performing a national United Kingdom survey of side effects and reasons for discontinuation of immunosuppressants in myasthenia gravis. Of 235 patients, 166 had taken azathioprine, 102 mycophenolate, and 40 methotrexate. The most common side effects for each agent were liver dysfunction for azathioprine (23 %), diarrhoea for mycophenolate (14 %), and fatigue for methotrexate (18 %). Women were generally more likely to experience side effects of immunosuppressants. Azathioprine was significantly more likely to be discontinued than mycophenolate and methotrexate due to side effects. There was no significant difference in treatment cessation due to lack of efficacy. This study highlights the significant side-effect burden of treatment for myasthenia gravis. Mechanisms to reduce azathioprine toxicity should be utilised, however mycophenolate and methotrexate appear to be good treatment choices if teratogenicity is not a concern. Women are disadvantaged due to higher frequency of side effects and considerations around pregnancy and breastfeeding. Treatments with improved tolerability are needed.

Risk for myasthenia gravis maps to a (151) Pro→Ala change in TNIP1 and to human leukocyte antigen-B*08.

OBJECTIVE: The objective of this study is to comprehensively define the genetic basis of early onset myasthenia gravis (EOMG). METHODS: We have carried out a 2-stage genome-wide association study on a total of 649 North European EOMG patients. Cases were matched 1:4 with controls of European ancestry. We performed imputation and conditional analyses across the major histocompatibility complex, as well as in the top regions of association outside the human leukocyte antigen (HLA) region. RESULTS: We observed the strongest association in the HLA class I region at rs7750641 (p = 1.2 × 10(-92) ; odds ratio [OR], 6.25). By imputation and conditional analyses, HLA-B*08 proves to be the major associated allele (p = 2.87 × 10(-113) ; OR, 6.41). In addition to the expected association with PTPN22 (rs2476601; OR, 1.71; p = 8.2 × 10(-10) ), an imputed coding variant (rs2233290) at position 151 (Pro→Ala) in the TNFAIP3-interacting protein 1, TNIP1, confers even stronger risk than PTPN22 (OR, 1.91; p = 3.2 × 10(-10) ). INTERPRETATION: The association at TNIP1 in EOMG implies disease mechanisms involving ubiquitin-dependent dysregulation of NF-κB signaling. The localization of the major HLA signal to the HLA-B*08 allele suggests that CD8(+) T cells may play a key role in disease initiation or pathogenesis.

A successful antenatal outcome in a patient with refractory Takayasu's arteritis treated with tocilizumab throughout pregnancy-a case report.

Takayasu's arteritis (TA) is a rare form of large-vessel vasculitis for which tocilizumab (TCZ) may be administered in resistant or refractory disease. Current British Society of Rheumatology advice is to stop TCZ 3-months pre-conception. We report the case of a 33-year-old woman with extensive TA treated with TCZ, azathioprine and glucocorticoids in pregnancy. She was closely monitored with MDT input and TCZ was continued throughout pregnancy as the benefits were thought to outweigh the risks. Our case also highlights the importance of accurate blood pressure monitoring in an appropriate anatomical location, given the extent of her disease. Our patient's disease remained stable throughout the antenatal and post-partum period with a successful pregnancy outcome and no maternal or foetal complications. TCZ is suitable for select cases of refractory TA during pregnancy.

Transgender Health Care Curriculum Development: A Dual-Site Medical School Campus Pilot.

Purpose: Lack of physician training contributes to health care disparities for transgender people. The limited generalizability and feasibility of published training approaches lessen their utility in lowering barriers for other institutions to adopt similar training. Methods: All first-year medical students at the Mayo Clinic Alix School of Medicine (MCASOM) in Minnesota and Arizona received a 1-h lecture introducing key concepts related to transgender people and their health disparities. Students completed a 21-question survey before and after the lecture, and 1 year later. Chi-square likelihood coefficients were used to compare responses between the three time points. Results: Eighty-six of 100 students answered the prelecture survey (86% response rate); 70 the postlecture survey; and 44 the 1-year follow-up survey. Twenty-five (29%) students had prior education in any lesbian, gay, bisexual, and transgender (LGBT+) health disparities, but this did not correlate with more favorable attitudes or knowledge. LGBT+ students and those with close LGBT+ friends had the most favorable attitudes and knowledge. The proportion of students comfortable with caring for transgender people changed significantly (76% self-reported very comfortable prelecture vs. 91% postlecture, p=0.0073) and remained at 89% 1 year later. The proportion of students comfortable with a transgender patient scenario significantly increased (67% self-reported very comfortable prelecture vs. 87% postlecture, p=0.032) even when surveyed 1 year later (95% very comfortable, p<0.0001). Conclusion: This study demonstrates that a 1-h lecture can increase the proportion of medical students who demonstrate positive attitudes and correct knowledge on transgender patient care for at least a year, and how a survey can gather essential information on student learning needs to guide training development.

Minimal manifestation status and prednisone withdrawal in the MGTX trial.

OBJECTIVE: To examine whether sustained minimal manifestation status (MMS) with complete withdrawal of prednisone is better achieved in thymectomized patients with myasthenia gravis (MG). METHODS: This study is a post hoc analysis of data from a randomized trial of thymectomy in MG (Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy [MGTX]). MGTX was a multicenter, randomized, rater-blinded 3-year trial that was followed by a voluntary 2-year extension for patients with acetylcholine receptor (AChR) antibody-positive MG without thymoma. Patients were randomized 1:1 to thymectomy plus prednisone vs prednisone alone. Participants were age 18-65 years at enrollment with disease duration less than 5 years. All patients received oral prednisone titrated up to 100 mg on alternate days until they achieved MMS, which prompted a standardized prednisone taper as long as MMS was maintained. The achievement rate of sustained MMS (no symptoms of MG for 6 months) with complete withdrawal of prednisone was compared between the thymectomy plus prednisone and prednisone alone groups. RESULTS: Patients with MG in the thymectomy plus prednisone group achieved sustained MMS with complete withdrawal of prednisone more frequently (64% vs 38%) and quickly compared to the prednisone alone group (median time 30 months vs no median time achieved, p < 0.001) over the 5-year study period. Prednisone-associated adverse symptoms were more frequent in the prednisone alone group and distress level increased with higher doses of prednisone. CONCLUSIONS: Thymectomy benefits patients with MG by increasing the likelihood of achieving sustained MMS with complete withdrawal of prednisone. CLINICALTRIALSGOV IDENTIFIER: NCT00294658. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with generalized MG with AChR antibody, those receiving thymectomy plus prednisone are more likely to attain sustained MMS and complete prednisone withdrawal than those on prednisone alone.