Effect of pessary cleaning and optimal time interval for follow-up: a prospective cohort study

Introduction and hypothesis: The objective of this study was to determine the efficacy of routine follow-up visits for pessary cleaning, the effect of extended time intervals between visits and the proportion of patients being able to self-manage their pessary for pelvic organ prolapse (POP). Methods: We conducted a prospective cohort study in patients with a stage ≥II POP without previous POP surgery. All patients received a pessary as primary treatment. Our main outcome measure was a difference ≥2 in median visual analogue scale (VAS) scores (for pain, discharge, irritation) 1 week before and 1 week after cleaning. Measurements were performed after 3- and 9-month cleaning intervals. For the evaluation of the effect of cleaning, 132 patients (3 months’ follow-up) and 87 patients (12 months’ follow-up) were available for analysis. For the evaluation of the effect of the lengthening interval, 123 patients were available. Results: Self-management was performed in 45.2% of patients at 1 year. In 93.1% of patients, no differences were observed in pre-and post-cleaning VAS scores (effect of cleaning) on vaginal pain. Nor was there a difference in discharge (72.4%) or irritation 85.1% (p = 0.00). No differences were observed in pre-cleaning VAS scores for vaginal pain, discharge and irritation when the interval was lengthened from 3 to 9 months. No serious adverse events occurred. Conclusions: There is no proven benefit of regular follow-up visits to clean a pessary. Also, the length of the cleaning interval does not seem to matter

A comparison of long-term outcome between Manchester Fothergill and vaginal hysterectomy as treatment for uterine descent

Introduction and hypothesis The objective of this study was to compare the Manchester Fothergill (MF) procedure with vaginal hysterectomy (VH) as surgical treatment of uterine descent. Methods Consecutive patients who underwent MF were matched for prolapse grade, age and parity to consecutive patients treated with VH. Evaluated outcomes included functional outcome, morbidity, recurrence of pelvic organ prolapse (POP) and sexual function. Follow-up was performed using validated questionnaires. Results We included 196 patients (98 patients per group). The response rate after a follow-up of 4-9 years was 80%. We found no differences in functional outcome and recurrence rates of POP between groups. Blood loss was significantly less and operating time was significantly shorter in the MF group. However, incomplete emptying of the bladder was more common in the MF group. Conclusions The MF procedure is equally effective to the VH and should be considered as a surgical option that allows preservation of the uteru

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease