654 Fragility of functional/symptomatic endpoints to assess the efficacy of drugs for pulmonary arterial hypertension

Aims Drugs for pulmonary arterial hypertension (PAH) have historically been evaluated for their efficacy in improving functional capacity and decreasing symptoms. However, these measures of treatment effect are approximate and subject to substantial variability, and therapeutic choices based on them may be aleatory. Methods and results We reviewed the articles reporting the results of phase 3 PAH randomized controlled trials (RCTs) and calculated the fragility index (FI) for the outcomes exploring functional capacity and symptoms. The FI corresponds to the number of events that need to be added to the arm with the smallest number of events to make a significant result non-significant: the lower the FI, the fragile the trial with respect to the endpoint examined. For RCTs with non-significant results, we calculated the FI as the number of events that need to be removed from the investigational drug (ID) group to reach a P-value <0.05. When possible, we also computed the FI for PAH hospitalization. Data about the rate of functional/symptomatic improvement were available for 22 (63%) of 35 RCTs (Table). The ID was superior to placebo or comparator with P < 0.05 in 10 (45%) of these 22 studies. The median FI was 2 [interquartile range (IQR): 6.5], with 4 RCTs having a FI = 1 and only 2 > 10 (Table). For the 12 RCTs in which the effect of the ID was neutral (P > 0.05), the median FI was 6 (IQR 4.25) (Table). The hospitalization FI was determined for 17 (77%) of the 22 RCTs and was overall higher than the one for the functional/symptomatic outcome (median 6, IQR 8). Conclusions Accessible information about the effects of PAH drugs on functional capacity and/or symptoms is published for 6 in 10 RCTs, in which very few events in one arm could have flipped the results from non-significant to significant or, more remarkably, from significant to non-significant. The evidence supporting the reduction of PAH hospitalizations as a treatment goal appears to be more robust.

Ambulatory Urodynamic Findings Change Patient Outcomes

Objectives Whilst ambulatory urodynamics (aUDS) may be used as a second-stage test for patients with refractory lower urinary tract symptoms (LUTS) having non-diagnostic conventional urodynamics (UDS), the evidence for their use is limited. We have assessed the diagnostic utility and consequent symptomatic outcome of aUDS in patients with refractory LUTS. Methods A retrospective review of a prospectively acquired urodynamics database was made of 84 consecutive patients (23 male) with a median age 50.5 years (range 18 to 79) having aUDS following non-diagnostic or contradictory baseline UDS over a 12-month period. Patient demographics and urodynamic and clinical diagnosis before and after aUDS were recorded. Forty-six patients (55%) had formal urinary symptom assessment recorded before and a minimum of 6 months following aUDS-related change in management. Results Eighty-two patients (98%) had a urodynamic diagnosis made following aUDS, 57(68%) of whom had detrusor overactivity (DO); the final 2 patients had no abnormalities detected on aUDS. Change in primary UDS diagnosis occurred in 66 patients (79%). Of these 66 patients, 59 (89%) also had their clinical diagnosis changed, and 55 (83%) had their management pathway changed. There was a significant improvement in urinary symptoms 6 months following aUDS. Conclusion Change in primary diagnosis following aUDS led to a significant change in treatment care pathway and resulted in significant improvement in urinary symptoms.

Gender differences in symptomatology in people with psychotic spectrum disorders: protocol for a systematic review and pairwise meta-analysis of observational studies

Gender differences in symptomatology in people with psychosis have been studied extensively in last decades. Previous narrative reviews have shown some evidence of gender differences in depressive, negative and paranoid symptoms, but yielding inconclusive findings. These reviews are limited by not doing systematic searches nor performing quantitative synthesis of the evidence. Therefore, we aimed to systematically investigate if there are gender differences in symptoms in people with psychosis. We describe the protocol for a systematic review and pairwise meta-analysis comparing a range of symptomatic outcome measures between men and women diagnosed with a psychotic spectrum disorder at different stages of the disorder (ultra-high risk for psychosis, early psychosis and established psychosis) in observational studies.

Revision of total knee replacement (TKR) secondary to raised cobalt levels: should this be considered in the painful TKR patient?

A 63-year-old woman was referred to the specialised knee revision clinic with ongoing knee pain after total knee replacement. She incidentally had cobalt and chromium levels measured. These were seen to be elevated. Comprehensive assessment and investigation did not identify any other source of cobalt or chromium. Aseptic loosening of the knee was diagnosed, and the knee was revised. At the time of surgery, the tissue was seen to be darkened consistent with metallosis. Multiple samples excluded infection on extended cultures. Aspirated fluid showed that periprosthetic fluid had elevated cobalt levels. The knee was successfully revised with good symptomatic outcome and significantly, over the course of several months post-revision, the cobalt and chromium levels returned to normal.

Abdominal sacrohysteropexy versus vaginal hysterectomy for pelvic organ prolapse in young women

Background: Pelvic organ prolapse (POP) is the descent of the pelvic organs beyond their anatomical confines. The definitive treatment of symptomatic prolapse is surgery but its management in young is unique due to various considerations. Aim of this study was to evaluate anatomical and functional outcome after abdominal sacrohysteropexy and vaginal hysterectomy for pelvic organ prolapse in young women.Methods: A total 27 women less than 35 years of age with pelvic organ prolapse underwent either abdominal sacrohysteropexy or vaginal hysterectomy with repair. In all women, pre-op and post-op POP-Q was done for evaluation of anatomical defect and a validated questionnaire was given for subjective outcome.Results: Anatomical outcome was significant in both groups as per POP-Q grading but the symptomatic outcome was better for sacrohysteropexy with regard to surgical time, bleeding, ovarian conservation, urinary symptoms, sexual function.Conclusions: Sacrohysteropexy is a better option.

Redo Surgery after Failure of Antireflux Surgery

Surgery for refractory gastroesophageal reflux disease (GERD) has a satisfactory outcome for most patients; however, sometimes redo surgery is required. The Outcome and morbidity of a redo are suggested to be less successful than those of primary surgery. The aim of this study was to describe our experience, long-term results, and complications in redo surgery. From 2000 to 2016, 765 patients were operated on for GERD at our hospital. A retrospective analysis of 56 patients (7.3%) who underwent redo surgery was conducted. Large symptomatic recurrent hiatal hernia (50%) and dysphagia (28.6%) were the most frequent indications for redo. An open approach was chosen in 64.5 per cent of patients. Intraoperative and postoperative complication rates were 18 per cent and 14.3 per cent, respectively. Mortality rate was 1.8 per cent. Symptomatic outcome was successful in 71.3 per cent. Patients reoperated because of dysphagia and large recurrent hiatal hernia had a significantly higher failure rate (32.3% and 31.2%, respectively; P = 0.001). Complication rate was significantly lower in the laparoscopic group (0% vs 22.2%; P = 0.04). There were no statistical differences between expert and nonexpert surgeons. Laparoscopic approach has increased to 83.3 per cent in the last five years. Symptomatic outcome after redo surgery was less satisfactory than that after primary surgery. Complications were lower if a minimally invasive surgical approach was used.

Effect of impaired cardiac conduction after alcohol septal ablation on clinical outcomes: insights from the Euro-ASA registry

Aims We analysed the impact of bundle branch block (BBB) and pacemaker (PM) implantation on symptoms and survival after alcohol septal ablation (ASA) in patients with hypertrophic cardiomyopathy (HCM). Methods and results Among 1416 HCM patients from the Euro-ASA registry, 58 (4%) patients had a PM and 64 (5%) patients had an implantable cardioverter-defibrillator (ICD) before ASA. At latest follow-up (5.0 ± 4.0 years) after ASA, 118 (8%) patients had an ICD and 229 (16%) patients had a PM. In patients without an implantable device prior to ASA 13% had a PM and 5% had an ICD implanted following ASA. New onset BBB was present in 44% (right BBB in 31%) of patients without previous BBB. At latest follow-up, we found no associations between BBB and New York Heart Association (NYHA) Class 3–4 [odds ratio (OR) 0.98, 95% confidence interval (CI) 0.63–1.51; P = 0.91] or Canadian Cardiovascular Society (CCS) Class 3–4 (OR 1.5, CI 0.32–6.7; P = 0.62), respectively, and no associations between PM and NYHA Class 3–4 (OR 1.2, CI 0.70–2.0; P = 0.52) or CCS 3–4 (OR 1.3, CI 0.24–6.6; P = 0.79), respectively. The survival after ASA was not reduced in patients with BBB [hazard ratio (HR) 0.73, CI 0.53–1.01; P = 0.06] or PM (HR 0.78, CI 0.52–1.17; P = 0.24). Conclusions Development of BBB or need for a PM after ASA in patients with obstructive HCM was not associated with inferior symptomatic outcome or reduced survival, thus concerns for the negative impact of impaired cardiac conduction on the clinical outcome after ASA were not confirmed.