Belimumab treatment of adult idiopathic inflammatory myopathy.

OBJECTIVE: To evaluate belimumab addition to the standard of care in patents with refractory idiopathic inflammatory myopathy (IIM). METHODS: We conducted a 40-week multicentre, randomized, double-blind, placebo-controlled trial with 1:1 IV belimumab 10 mg/kg or placebo randomization and a 24-week open-label extension. Clinical responses were measured by the definition of improvement (DOI) and total improvement score (TIS). Flow cytometry analyses were performed on available samples before randomization, at 24 and 60-64 weeks. Descriptive statistics, t-test, Fisher's exact test and analysis of variance tests were used. RESULTS: A total of 17 patients were randomized, 15 received five or more doses of belimumab or placebo and were included in the intention-to-treat analysis. More belimumab patients vs placebo attained a TIS ≥40 [55.5% vs 33.3%; P = non-significant (NS)] and achieved the DOI (33.3% vs 16.7%; P = NS) at weeks 40 and 64; the mean TIS was similar among groups. Two patients achieved major responses (TIS = 72.5) after week 40 in the belimumab arm and none in the placebo arm. No improvement in the placebo arm after switching to the open-label phase was observed. There was no steroid-sparing effect. No new safety signals were detected. Although total B cells were not reduced, belimumab induced naïve B cell depletion while enhancing the number and frequency memory B cells. CONCLUSION: The study did not meet the primary endpoint and no statistically significant differences were observed in clinical responses between arms. More patients achieved sustained TIS ≥40 and reached the DOI. Most patients who received belimumab for >40 weeks had clinical improvement. Phenotypic changes in B cell populations were not associated with clinical responses. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov (https://clinicaltrials.gov/), NCT02347891.

Investigation of intradetrusor onabotulinum toxin A efficacy and safety in older adults with urge urinary incontinence.

PURPOSE: Intradetrusor onabotulinum toxin A (BTX-A) has been demonstrated to be an effective treatment option for overactive bladder (OAB). However, concerns about frailty and frequent injections may deter its use in the elderly. This study aims to assess the safety, efficacy, and treatment duration of BTX-A in managing OAB in elderly women. METHODS: We retrospectively reviewed female patients aged 70 and above who were diagnosed with OAB with predominant urge urinary incontinence and underwent intravesical BTX-A treatment. We collected demographic and clinical data, with repeat BTX-A injections re-administered upon patient-reported symptom recurrence. RESULTS: Twenty-one female patients, median age 77 (range 71-92), were included. The median time between the first and second injection was 185 (84-448) days, 186 (105-959) days between the second and third injection, and increased to 206.5 (84-256) days between the third and fourth injection. However, the median interval trended downward after the fourth injection (Fig. 1). Patients with four or more injections had a shorter median interval between injections, 154 days, compared to those with fewer injections, 210 days. Two patients (6.9%) experienced urinary retention after the initial treatment, with 1 (2.2%) among a total of 46 subsequent treatments (Table 3). There were ten (13.3%) episodes of UTIs within 2 weeks of treatment. Patients reported improvement in symptoms following 93.3% of the injections. CONCLUSION: This real-world study demonstrates that BTX-A effectively controls OAB symptoms in elderly women, with just two injections annually. BTX-A appears safe and efficacious for treating OAB in elderly females.

Implementing Workplace-Based Assessments at Scale: The SIMPL Approach.

Over the past decade, medical education has shifted from a time-based approach to a competency-based approach for surgical training. This transition presents many new systemic challenges. The Society for Improving Medical Professional Learning (SIMPL) was created to respond to these challenges through coordinated collaboration across an international network of medical educators. The primary goal of the SIMPL network was to implement a workplace-based assessment and feedback platform. To date, SIMPL has developed, implemented, and sustained a platform that represents the earliest and largest effort to support workplace-based assessment at scale. The SIMPL model for collaborative improvement demonstrates a potential approach to addressing other complex systemic problems in medical education.

A case report of an adolescent with ligase-4 deficiency and the potential dangers of ionizing radiation in this rare patient population.

DNA ligase IV deficiency is a rare disorder characterized by mutations in the LIG4 gene. Mutations in this gene cause a wide array of phenotypes, many of which are fatal early in life. We present an adolescent patient with heterozygous LIG4 mutations and the T-B-NK+ DNA ligase IV phenotype. Pelvic ultrasound and magnetic resonance imaging was completed to assess the patient's amenorrhea and delayed puberty, which demonstrated an atrophic cervix, distal vagina, and uterus without direct visualization of the ovaries. Early diagnosis of DNA ligase IV deficiency is important to minimize exposure to ionizing radiation from radiologic studies and preferentially utilize imaging studies that do not require ionizing radiation, such as ultrasonography and magnetic resonance imaging.