Rufus Cartwright

Objective: Comorbidity between urinary incontinence (UI) and affective disorders, including anxiety and depression, is well established in cross-sectional studies and prospective bidirectional associations have also been reported. It is, however, unclear whether these associations are causal. We applied two-sample Mendelian randomization (MR) analysis to examine if there are causal bidirectional relationships between UI and anxiety, depression, and neuroticism in women. Materials and methods: We used summary level data from independent genome-wide association studies (GWAS) to estimate the bidirectional causal effects of UI and its subtypes (stress urinary incontinence (SUI), urgency urinary incontinence (UUI), and mixed urinary incontinence (MUI), n=10,931) on anxiety (n=83,566), depression (n=1,035,760), broad depression phenotype (n=500,199) and neuroticism (n=329,821). Results: We found little evidence of causal effects in either direction, except for weak evidence suggesting that UUI may reduce the risk of depression (causal odds ratio (OR) for depression: 0.99, 95% confidence interval (95%CI) 0.98-1.00; OR for broad depression 0.98, 95%CI 0.96-1.00). However, the direction of effect estimates did not consistently align across sensitivity analysis methods and the magnitude of this effect could be considered negligible. Conclusion: Our study provided little evidence for causal bidirectional relationships between UI and anxiety, depression and neuroticism. This study highlights the need for further GWAS of UI (including different subtypes) with larger sample sizes. Highlights: There was little evidence for causal bidirectional relationships between urinary incontinence (UI) and anxiety, depression, and neuroticism. Study limitations, including low statistical power, UI phenotype definition, and genetic instrument strength, need to be considered when interpreting the findings. Larger and more comprehensive GWAS of UI (including subtypes) are needed before ruling out causal relationships between UI and mental health.

Objective: To evaluate the effectiveness of various de-implementation interventions in primary care, targeting care (treatments or tests) that provides no or limited value for patients (low value care). Design: Systematic review and meta-analysis. Data sources: Medline and Scopus databases, from inception to 10 July 2024. Eligibility criteria for selecting studies: Randomised trials comparing de-implementation interventions with placebo or sham intervention, no intervention, or other de-implementation intervention strategies in primary care. Eligible trials provided information on the use of low value care, total volume of care, appropriate care, and health outcomes. Data extraction and synthesis: Titles, abstracts, and full texts were screened, data were extracted, and risk of bias was assessed independently and in duplicate. Random effects meta-analyses were conducted, and the certainty of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: 13 008 abstracts were screened and 140 were eligible for inclusion in the study. Median follow-up was 287 days (interquartile range 180-365). In 75 (54%) trials the aim was to reduce the use of antibiotics, in 42 (30%) to reduce other drug treatments, in 17 (12%) to reduce imaging, and in 15 (11%) to reduce laboratory testing. The certainty of the evidence was moderate that provider education combined with audit and feedback reduced the use of targeted low value care (odds ratio 0.73, 95% confidence interval (95% CI) 0.63 to 0.84). Provider education (0.86, 95% CI 0.72 to 1.03), audit and feedback (0.82, 0.67 to 1.00), and patient education (0.70, 0.30 to 1.66), and a combination of these strategies (point estimates for odds ratios ranging from 0.57 to 0.64) may reduce the use of targeted low value care (low certainty of evidence for all). Conclusions: The results suggested with moderate certainty of evidence that provider education combined with audit and feedback reduced the use of targeted low value care. Individual strategies may slightly reduce the use of targeted low value care, but achieving a meaningful impact on low value care may require the use of multiple strategies. The results may be useful for patients, clinicians, policy makers, and guideline developers when deciding on future de-implementation strategies and research priorities. Systematic review registration: PROSPERO CRD42023411768.

Introduction: Treatment decisions for stress urinary incontinence (SUI) are preference sensitive, because the disease is non-lethal and there are multiple reasonable treatment options. However, little is known about patients’ and physicians’ preferred decision-making styles for SUI. To aid physicians in their counselling and decision-making in consultations for SUI, we studied patients’ and physicians’ preferred and perceived decision-making in medical specialist consultations for SUI. Methods: This mixed-methods study combined the validated control preference scale (CPS) and the CPS perception version, and semi-structured, in-depth interviews with both patients and physicians. This study took place in Canada, the United Kingdom and the Netherlands. Sixteen physicians from all three countries and seventeen women from the Netherlands and Canada were interviewed. Results: All women expressed a preference for being involved in the decision-making process, either by informative or shared decision-making (SDM) in the CPS, because they valued the autonomy to make their own choice regarding treatment for SUI and appreciated receiving information and advice from their doctor. Physicians also preferred an involved patient, but used medical expertise to steer towards their preferred treatment option. Physicians found SDM difficult to understand, expressing different interpretations. Conclusions: SDM is not a precise concept either for patients or physicians, with multiple interpretations. All patients with SUI want to be involved in the decision-making process, either by informative or by shared decision-making. Physicians both express the desire to involve patients in their decision making, but conversely to steer patients towards the decision that they feel suits them best.

Introduction: Different decision-making styles can be used to provide counselling for the multiple reasonable treatment options for patients with stress urinary incontinence (SUI). Shared decision-making (SDM) is currently advocated as the preferred style for preference sensitive decisions, as SDM takes patient preferences into account. This study aimed to map the current decision-making process for SUI in three Western countries. Methods: We included 124 patients and 18 physicians in a multicentre, prospective study in five hospitals in Canada, the United Kingdom and the Netherlands. We used patient and physician versions of the Control Preference Scale (CPS) questionnaires and examined audio-recordings of consultations with the OPTION-5 instrument to assess the degree of SDM. Results: Most patients (63%) perceived the decision-making as informative, some (29%) as shared and only a few (8%) as paternalistic. Dutch patients more often perceived the decision-making as informative than UK or Canadian patients. Patients’ preferred and perceived decision-making styles matched in 70% of consultations. Patients’ and physicians’ perceptions of decision-making were the same in 60% of consultations, but their perceptions of SDM use did not match. This also did not match the OPTION-5 scores reflecting the use of SDM. Almost all patients were satisfied with the decision-making they perceived. Conclusion: Most patients and physicians prefer and perceive the current decision-making process as informative decision-making. However, patients and physicians have different perceptions of their mutual consultation. This highlights the imprecise concept of SDM for both patients and physicians.

Introduction and hypothesis: Urinary tract infection (UTI) is one of the most common human infections. Evidence suggests that there might be a genetic predisposition to UTI. Previous small candidate gene studies have suggested that common variants in genes involved in the immune response to UTI could increase susceptibility to the development of recurrent UTI (rUTI). The objective was to conduct a gene association study to replicate previous gene association studies identifying single nucleotide polymorphisms (SNPs) putatively associated with rUTI in adult women. Methods: Women with a history of rUTI and healthy controls were recruited (n = 1,008) from gynaecology outpatient clinics. Participants completed a signed consent form and questionnaire for phenotyping. DNA was extracted from blood or saliva samples for each participant. Putative associated SNPs were identified from a comprehensive systematic review of prior gene association studies. Primers for each selected SNP were designed, and genotyping was conducted using a competitive polymerase chain reaction (PCR) method. The Chi-squared test was used to assess the association between each variant and rUTI. Genotyping quality was assessed by checking for deviation from Hardy–Weinberg equilibrium. Results: We found no association between SNPs tested in the VDR (p = 0.16, p = 0.09, p = 0.36), CXCR1 (p = 0.09), CXCR2 (p = 0.39), PSCA (p = 0.74) genes, and rUTI in adult women. Conclusions: To our knowledge, this is the largest study to date, finding no significant associations. Previously reported positive associations may have been due to type 1 error, or genotyping errors. Future studies should adjust for confounders and employ adequate sample sizes. A greater understanding of the genetic components associated with rUTI may influence future treatment guidelines and screening for susceptible patients.

Purpose: Stress urinary incontinence (SUI) represents a major health burden in women, but a thorough understanding of the underlying molecular mechanisms is lacking. Our aim was to further elucidate these mechanisms to ultimately find new treatments. Materials and Methods: This study integrated the most significant genes from 4 genome-wide association studies (GWASs) of SUI in women with other genetic, expression, and/or functional evidence from the literature into a molecular landscape. A network enrichment analysis of the top SUI GWAS genes was conducted, followed by an extensive literature search to identify interactions between the proteins encoded by the GWAS genes and proteins/molecules implicated in SUI through other evidence. Results: In total, 188 GWAS genes were used for network enrichment analysis that yielded 12 networks, of which 8 were overlapping, with beta-catenin as the central protein. Based on this finding and our literature search, we built a molecular landscape of female SUI that centers on beta-catenin signaling. Other important functional landscape themes are epithelial-mesenchymal transition, NANOG signaling, and female sex hormone signaling. Conclusions: The molecular landscape of female SUI that we built based on genetic data provides novel molecular insights that may be instrumental for better understanding the etiology of SUI and developing novel SUI treatments.

Background: The timing at which venous thromboembolism (VTE) occurs after major surgery has major implications for the optimal duration of thromboprophylaxis. The aim of this study was to perform a systematic review and meta-analysis of the timing of postoperative VTE up to 4 weeks after surgery. Methods: A systematic search of MEDLINE, Scopus, and CINAHL databases was performed between 1 January 2009 and 1 April 2022. Prospective studies that recruited patients who underwent a surgical procedure and reported at least 20 symptomatic, postoperative VTE events by time were included. Two reviewers independently selected studies according to the eligibility criteria, extracted data, and evaluated risk of bias. Data were analysed with a Poisson regression model, and the GRADE approach was used to rate the certainty of evidence. Results: Some 6258 studies were evaluated, of which 22 (11 general, 5 urological, 4 mixed, and 2 orthopaedic postoperative surgical populations; total 1 864 875 patients and 24 927 VTE events) were eligible. Pooled evidence of moderate certainty showed that 47.1 per cent of the VTE events occurred during the first, 26.9 per cent during the second, 15.8 per cent during the third, and 10.1 per cent during the fourth week after surgery. The timing of VTE was consistent between individual studies. Conclusion: Although nearly half of symptomatic VTE events in first 4 weeks occur during the first postoperative week, a substantial number of events occur several weeks after surgery. These data will inform clinicians and guideline developers about the duration of postoperative thromboprophylaxis.

Dear Editor

Background: Healthcare costs are rising, and a substantial proportion of medical care is of little value. De-implementation of low-value practices is important for improving overall health outcomes and reducing costs. We aimed to identify and synthesize randomized controlled trials (RCTs) on de-implementation interventions and to provide guidance to improve future research. Methods: MEDLINE and Scopus up to May 24, 2021, for individual and cluster RCTs comparing de-implementation interventions to usual care, another intervention, or placebo. We applied independent duplicate assessment of eligibility, study characteristics, outcomes, intervention categories, implementation theories, and risk of bias. Results: Of the 227 eligible trials, 145 (64%) were cluster randomized trials (median 24 clusters; median follow-up time 305 days), and 82 (36%) were individually randomized trials (median follow-up time 274 days). Of the trials, 118 (52%) were published after 2010, 149 (66%) were conducted in a primary care setting, 163 (72%) aimed to reduce the use of drug treatment, 194 (85%) measured the total volume of care, and 64 (28%) low-value care use as outcomes. Of the trials, 48 (21%) described a theoretical basis for the intervention, and 40 (18%) had the study tailored by context-specific factors. Of the de-implementation interventions, 193 (85%) were targeted at physicians, 115 (51%) tested educational sessions, and 152 (67%) multicomponent interventions. Missing data led to high risk of bias in 137 (60%) trials, followed by baseline imbalances in 99 (44%), and deficiencies in allocation concealment in 56 (25%). Conclusions: De-implementation trials were mainly conducted in primary care and typically aimed to reduce low-value drug treatments. Limitations of current de-implementation research may have led to unreliable effect estimates and decreased clinical applicability of studied de-implementation strategies. We identified potential research gaps, including de-implementation in secondary and tertiary care settings, and interventions targeted at other than physicians. Future trials could be improved by favoring simpler intervention designs, better control of potential confounders, larger number of clusters in cluster trials, considering context-specific factors when planning the intervention (tailoring), and using a theoretical basis in intervention design. Registration: OSF Open Science Framework hk4b2

Introduction and hypothesis This manuscript is the International Urogynecology Consultation (IUC) on pelvic organ prolapse (POP) chapter one, committee three, on the Pathophysiology of Pelvic Organ Prolapse assessing genetics, pregnancy, labor and delivery, age and menopause and animal models. Materials and methods An international group of urogynecologists and basic scientists performed comprehensive literature searches using pre-specified terms in selected biomedical databases to summarize the current knowledge on the pathophysiology of the development of POP, exploring specifically factors including (1) genetics, (2) pregnancy, labor and delivery, (3) age and menopause and (4) non-genetic animal models. This manuscript represents the summary of three systematic reviews with meta-analyses and one narrative review, to which a basic scientific comment on the current understanding of pathophysiologic mechanisms was added. Results The original searches revealed over 15,000 manuscripts and abstracts which were screened, resulting in 202 manuscripts that were ultimately used. In the area of genetics the DNA polymorphisms rs2228480 at the ESR1 gene, rs12589592 at the FBLN5 gene, rs1036819 at the PGR gene and rs1800215 at the COL1A1 gene are significantly associated to POP. In the area of pregnancy, labor and delivery, the analysis confirmed a strong etiologic link between vaginal birth and symptoms of POP, with the first vaginal delivery (OR: 2.65; 95% CI: 1.81–3.88) and forceps delivery (OR: 2.51; 95% CI: 1.24–3.83) being the main determinants. Regarding age and menopause, only age was identified as a risk factor (OR : 1.102; 95% CI: 1.02–1.19) but current data do not identify postmenopausal status as being statistically associated with POP. In several animal models, there are measurable effects of pregnancy, delivery and iatrogenic menopause on the structure/function of vaginal support components, though not on the development of POP. Conclusions Genetics, vaginal birth and age all have a strong etiologic link to the development of POP, to which other factors may add or protect against the risk.