Introduction Increased mortality has been demonstrated in older adults with COVID-19, but the effect of frailty has been unclear. Methods This multi-centre cohort study involved patients aged 18 years and older hospitalised with COVID-19, using routinely collected data. We used Cox regression analysis to assess the impact of age, frailty, and delirium on the risk of inpatient mortality, adjusting for sex, illness severity, inflammation, and co-morbidities. We used ordinal logistic regression analysis to assess the impact of age, Clinical Frailty Scale (CFS), and delirium on risk of increased care requirements on discharge, adjusting for the same variables. Results Data from 5,711 patients from 55 hospitals in 12 countries were included (median age 74, IQR 54–83; 55.2% male). The risk of death increased independently with increasing age (>80 vs 18–49: HR 3.57, CI 2.54–5.02), frailty (CFS 8 vs 1–3: HR 3.03, CI 2.29–4.00) inflammation, renal disease, cardiovascular disease, and cancer, but not delirium. Age, frailty (CFS 7 vs 1–3: OR 7.00, CI 5.27–9.32), delirium, dementia, and mental health diagnoses were all associated with increased risk of higher care needs on discharge. The likelihood of adverse outcomes increased across all grades of CFS from 4 to 9. Conclusions Age and frailty are independently associated with adverse outcomes in COVID-19. Risk of increased care needs was also increased in survivors of COVID-19 with frailty or older age.

For patients with PUJ obstruction, our meta-analyses show that RAP is advantageous concerning operating time, length of hospital stay, complication rate and success rate. Our conclusions, however, are weakened by poor quality of evidence and significant study heterogeneity. In addition, whether the statistical significance observed in the present meta-analysis translates into clinical significance is an important question. Further high-quality studies, particularly randomized controlled trials, are necessary to strengthen conclusions.

Objective: Pelvic fracture can be complicated by posterior urethral injury (PUI) in up to 25% of cases. PUI can produce considerable morbidity, including urethral stricture, erectile dysfunction (ED), and urinary incontinence. Optimal management of PUI is unclear, however, the current gold standard is placement of a suprapubic cystostomy with delayed urethroplasty (SCDU) performed several months later. Another option is early primary realignment (PR) with urethral catheter, performed either open or endoscopically. Through a systematic review and meta-analysis, we aimed to compare PR and SCDU regarding stricture, ED, and urinary incontinence rates. In light of advancing endoscopic techniques, we also aimed to compare early endoscopic realignment (EER) alone with SCDU. Methods: PubMed, Medline, and Embase were searched for eligible studies comparing PR, including EER, and suprapubic cystostomy plus delayed urethroplasty from database inception until July 17th, 2018. We also reviewed reference lists from relevant articles. Study quality assessment was conducted using a modified Newcastle-Ottawa (mNOS) scale (maximum score 9). Results: From 461 identified articles, 13 studies encompassing 414 PR and 308 SCDU patients met our eligibility criteria. Twelve studies were retrospective non-randomized case studies, with 1 prospective randomized case study. Included studies were of moderately low quality (mNOS mean score: 6.0 ± 0.6). Meta-analysis demonstrated that PR and SCDU had similar stricture rates [odds ratio (OR): 2.14; 95% confidence interval (CI): 0.67-6.85; p = 0.20], similar rates of ED (OR: 1.06; 95% CI: 0.62-1.81; p = 0.84), and similar rates of urinary incontinence (OR: 0.94; 95% CI: 0.49-1.79; p = 0.86). Six studies compared EER alone (229 patients) versus SCDU (195 patients). Meta-analysis demonstrated that these modalities also had similar stricture rates (OR: 4.14; 95% CI: 0.76-22.45; p = 0.10), similar rates of ED (OR: 0.79; 95% CI: 0.41-1.54; p = 0.49), and similar rates of urinary incontinence (OR: 1.10; 95% CI: 0.48-2.53; p = 0.82). Conclusion: For PUI patients, neither PR nor EER produces superior outcomes compared to SCDU regarding stricture, ED, and urinary incontinence rates. The quality of studies in the literature, however, is very poor, with the majority of studies being non-randomized retrospective case studies with potentially high bias. Additional high-quality research, particularly prospective studies and randomized controlled trials, are needed to strengthen the evidence base.

Background Immune mechanisms are indicated in schizophrenia (SCZ). Recent genome-wide association studies (GWAS) have identified genetic variants associated with SCZ and immune-related phenotypes. Here, we use cutting edge statistical tools to identify shared genetic variants between SCZ and white blood cell (WBC) counts and further understand the role of the immune system in SCZ. Study Design GWAS results from SCZ (patients, n = 53 386; controls, n = 77 258) and WBC counts (n = 56 3085) were analyzed. We applied linkage disequilibrium score regression, the conditional false discovery rate method and the bivariate causal mixture model for analyses of genetic associations and overlap, and 2 sample Mendelian randomization to estimate causal effects. Study Results The polygenicity for SCZ was 7.5 times higher than for WBC count and constituted 32%–59% of WBC count genetic loci. While there was a significant but weak positive genetic correlation between SCZ and lymphocytes (rg = 0.05), the conditional false discovery rate method identified 383 shared genetic loci (53% concordant effect directions), with shared variants encompassing all investigated WBC subtypes: lymphocytes, n = 215 (56% concordant); neutrophils, n = 158 (49% concordant); monocytes, n = 146 (47% concordant); eosinophils, n = 135 (56% concordant); and basophils, n = 64 (53% concordant). A few causal effects were suggested, but consensus was lacking across different Mendelian randomization methods. Functional analyses indicated cellular functioning and regulation of translation as overlapping mechanisms. Conclusions Our results suggest that genetic factors involved in WBC counts are associated with the risk of SCZ, indicating a role of immune mechanisms in subgroups of SCZ with potential for stratification of patients for immune targeted treatment.