ObjectiveTo estimate the regression, persistence, and progression of untreated cervical intraepithelial neoplasia grade 2 (CIN2) lesions managed conservatively as well as compliance with follow-up protocols.DesignSystematic review and meta-analysis.Data sourcesMedline, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from 1 January 1973 to 20 August 2016.Eligibility criteriaStudies reporting on outcomes of histologically confirmed CIN2 in non-pregnant women, managed conservatively for three or more months.Data synthesisTwo reviewers extracted data and assessed risk of bias. Random effects model was used to calculate pooled proportions for each outcome, and heterogeneity was assessed using I2 statistics.Main outcome measuresRates of regression, persistence, or progression of CIN2 and default rates at different follow-up time points (3, 6, 12, 24, 36, and 60 months).Results36 studies that included 3160 women were identified (seven randomised trials, 16 prospective cohorts, and 13 retrospective cohorts; 50% of the studies were at low risk of bias). At 24 months, the pooled rates were 50% (11 studies, 819/1470 women, 95% confidence interval 43% to 57%; I2=77%) for regression, 32% (eight studies, 334/1257 women, 23% to 42%; I2=82%) for persistence, and 18% (nine studies, 282/1445 women, 11% to 27%; I2=90%) for progression. In a subgroup analysis including 1069 women aged less than 30 years, the rates were 60% (four studies, 638/1069 women, 57% to 63%; I2=0%), 23% (two studies, 226/938 women, 20% to 26%; I2=97%), and 11% (three studies, 163/1033 women, 5% to 19%; I2=67%), respectively. The rate of non-compliance (at six to 24 months of follow-up) in prospective studies was around 10%.ConclusionsMost CIN2 lesions, particularly in young women (<30 years), regress spontaneously. Active surveillance, rather than immediate intervention, is therefore justified, especially among young women who are likely to adhere to monitoring.Systematic review registrationPROSPERO 2014: CRD42014014406.

ContextStress urinary incontinence (SUI) and urgency urinary incontinence (UUI) are associated with physical and psychological morbidity, and large societal costs. The long-term effects of delivery modes on each kind of incontinence remain uncertain.ObjectiveTo investigate the long-term impact of delivery mode on SUI and UUI.Evidence acquisitionWe searched Medline, Scopus, CINAHL, and relevant major conference abstracts up to October 31, 2014, including any observational study with adjusted analyses or any randomized trial addressing the association between delivery mode and SUI or UUI ≥1 yr after delivery. Two reviewers extracted data, including incidence/prevalence of SUI and UUI by delivery modes, and assessed risk of bias.Evidence synthesisPooled estimates from 15 eligible studies demonstrated an increased risk of SUI after vaginal delivery versus cesarean section (adjusted odds ratio [aOR]: 1.85; 95% confidence interval [CI], 1.56–2.19; I2 = 57%; risk difference: 8.2%). Metaregression demonstrated a larger effect of vaginal delivery among younger women (p = 0.005). Four studies suggested no difference in the risk of SUI between spontaneous vaginal and instrumental delivery (aOR: 1.11; 95% CI, 0.84–1.45; I2 = 50%). Eight studies suggested an elevated risk of UUI after vaginal delivery versus cesarean section (aOR: 1.30; 95% CI, 1.02–1.65; I2 = 37%; risk difference: 2.6%).ConclusionsCompared with cesarean section, vaginal delivery is associated with an almost twofold increase in the risk of long-term SUI, with an absolute increase of 8%, and an effect that is largest in younger women. There is also an increased risk of UUI, with an absolute increase of approximately 3%.Patient summaryIn this systematic review we looked for the long-term effects of childbirth on urinary leakage. We found that vaginal delivery is associated with an almost twofold increase in the risk of developing leakage with exertion, compared with cesarean section, with a smaller effect on leakage in association with urgency.

Objective. Several recent studies have demonstrated that cathepsin K, a proteolytic enzyme capable of degrading native fibrillar collagen, is overexpressed in osteoarthritic cartilage and inflamed synovial tissue. However, it is not known whether increased cathepsin K production is a primary or a secondary event in these diseases. The availability of transgenic UTU17 mice, which exhibit constitutive overexpression of the cathepsin K gene, prompted us to study possible arthritic changes in their knee joints.Methods. Progression of synovitis and articular cartilage degeneration in the knee joints of UTU17 mice and their nontransgenic littermates was monitored by histologic analyses at 7 and 12 months of age. Distribution of cathepsin K in the knee joints was studied by immunohistochemistry.Results. At the age of 7 months, UTU17 mice exhibited clear signs of synovitis, with strong immunostaining for cathepsin K in the synovial lining and the stroma, while control knee joints appeared normal. At 12 months, marked synovial thickening and fibrosis and severe degradation of cartilage and subchondral bone were observed in UTU17 mouse knee joints. In areas of cartilage degeneration, both chondrocytes and cells of hypertrophic synovia were positive for cathepsin K. At 12 months, synovia of control mice revealed only a few isolated cathepsin K-positive cells and mild changes in articular cartilage.Conclusion. Our findings demonstrate that overexpression of the cathepsin K gene under its own promoter in transgenic mice makes them susceptible to progressive synovitis, which, upon aging, results in synovial hyperplasia and fibrosis and subsequent destruction of articular cartilage and bone.