Factors associated with infection after operative vaginal birth-a secondary analysis of a randomized controlled trial of prophylactic antibiotics for the prevention of infection following operative vaginal birth.

BACKGROUND: A recent randomized controlled trial of prophylactic antibiotics for the prevention of infection following operative vaginal birth showed that women allocated prophylactic intravenous amoxicillin and clavulanic acid had a significantly lower risk of developing confirmed or suspected infection within 6 weeks after operative vaginal birth (risk ratio [RR], 0.58; 95% confidence interval [CI], 0.49-0.69; P < .001). Some international and national guidelines have subsequently been updated to include prophylactic antibiotics after operative vaginal birth. However, the generalizability of the trial results may be limited in settings where the episiotomy rate is lower (89% of women in the trial had an episiotomy). In addition, there was a high burden of infection in the prophylactic antibiotics group despite the administration of prophylactic antibiotics. It is essential to identify modifiable risk factors for infection after operative vaginal birth, including the timing of antibiotic administration. OBJECTIVE: This study aimed to evaluate if the effectiveness of the prophylactic antibiotic in reducing confirmed or suspected infection was independent of perineal trauma, identify risk factors for infection after operative vaginal birth, and investigate variation in efficacy with the timing of antibiotic administration. STUDY DESIGN: This study was a secondary analysis of 3225 women with primary outcome data from the prophylactic antibiotics for the prevention of infection following operative vaginal birth randomized controlled trial. Women were divided into subgroups according to the perineal trauma experienced (episiotomy and/or perineal tear). The consistency of the prophylactic antibiotics in preventing infection across the subgroups was assessed using log-binomial regression and the likelihood ratio test. Multivariable log-binomial regression was used to investigate factors associated with infection. The multivariable risk factor model was subsequently fitted to the group of women who received amoxicillin and clavulanic acid to investigate the timing of antibiotic administration. RESULTS: Of the 3225 women included in the secondary analysis, 2144 (66.5%) had an episiotomy alone, 726 (22.5%) had an episiotomy and a tear, 277 (8.6%) had a tear alone, and 78 (2.4%) had neither episiotomy nor tear. Among women who experienced perineal trauma, amoxicillin and clavulanic acid administration was protective against infection in all subgroups compared with placebo with no significant interaction between subgroup and trial allocation (P=.17). Moreover, 2925 women were included in the multivariable risk factor analysis. The following were associated with adjusted risk ratios of infection: episiotomy, 2.94 (95% confidence interval, 1.62-5.31); forceps, 1.37 (95% confidence interval, 1.12-1.69) compared to vacuum extraction; primiparity, 1.34 (95% confidence interval, 1.05-1.70); amoxicillin and clavulanic acid administration, 0.60 (95% confidence interval, 0.51-0.72); body mass index of 25.0 to 29.9 kg/m2, 1.21 (95% confidence interval, 1.00-1.47), and body mass index of ≥30 kg/m2, 1.22 (95% confidence interval, 0.98-1.52) compared to body mass index of <25 kg/m2. Each 15-minute increment between birth and antibiotic administration was associated with a 3% higher risk of infection (adjusted risk ratio, 1.03; 95% confidence interval, 1.01-1.06). CONCLUSION: Timely prophylactic antibiotics should be administered to all women after operative vaginal birth, irrespective of the type of perineal trauma. The use of episiotomy, forceps birth, primiparity, and overweight were associated with an increased risk of confirmed or suspected infection after operative vaginal birth.

What can we do when the smoke rolls in? An exploratory qualitative analysis of the impacts of rural wildfire smoke on mental health and wellbeing, and opportunities for adaptation.

BACKGROUND: Extreme, prolonged wildfire smoke (WFS) events are becoming increasingly frequent phenomena across the Western United States. Rural communities, dependent on contributions of nature to people's quality of life, are particularly hard hit. While prior research has explored the physical health impacts of WFS exposure, little work has been done to assess WFS impacts on mental health and wellbeing, or potential adaptation solutions. METHODS: Using qualitative methods, we explore the mental health and wellbeing impacts experienced by community members in a rural Washington State community that has been particularly hard hit by WFS in recent years, as well as individual, family, and community adaptation solutions. We conducted focus groups with residents and key informant interviews with local health and social service providers. RESULTS: Participants identified a variety of negative mental health and wellbeing impacts of WFS events, including heightened anxiety, depression, isolation, and a lack of motivation, as well as physical health impacts (e.g., respiratory issues and lack of exercise). Both positive and negative economic and social impacts, as well as temporary or permanent relocation impacts, were also described. The impacts were not equitably distributed; differential experiences based on income level, outdoor occupations, age (child or elderly), preexisting health conditions, housing status, and social isolation were described as making some residents more vulnerable to WFS-induced physical and mental health and wellbeing challenges than others. Proposed solutions included stress reduction (e.g., meditation and relaxation lessons), increased distribution of air filters, development of community clean air spaces, enhancing community response capacity, hosting social gatherings, increasing education, expanding and coordination risk communications, and identifying opportunities for volunteering. Findings were incorporated into a pamphlet for community distribution. We present a template version herein for adaptation and use in other communities. CONCLUSIONS: Wildfire smoke events present significant mental health and wellbeing impacts for rural communities. Community-led solutions that promote stress reduction, physical protection, and community cohesion have the opportunity to bolster resilience amid this growing public health crisis.

Metabolic Changes and Diabetes Microvascular Complications 5 Years After Obesity Surgery.

BACKGROUND: Obesity surgery has pronounced effects on metabolic profile of patients with type 2 diabetes mellitus (T2DM); however, reports on long-term remission rates based on the standardised and holistic criteria by the International Diabetes Federation (IDF) and effects on T2DM microvascular complications are scarce in the literature. In this retrospective clinical trial, our objectives were to assess these variables 5 years after surgery. METHODS: Clinical data and direct measurements of renal and retinal damage were collected prospectively and analysed retrospectively for 82 patients with T2DM who underwent obesity surgery and were followed up for 5 years. RESULTS: The cohort of 82 patients with T2DM that were followed up 5 years after obesity surgery was predominantly female (71%) with a median age of 51 years, weight of 133.5 kg, BMI of 46.8 kg/m2 and pre-operative duration of T2DM of 8 years; 6% of patients had diet-controlled T2DM, 57% were on non-insulin treatment and 37% were on insulin treatment pre-operatively. Of the total 82 patients, 59 patients underwent Roux-en-Y gastric bypass, 15 sleeve gastrectomy and 8 patients underwent gastric band operations. At 5 years, 5% and 15% patients achieved optimisation and improvement of the metabolic state based on the IDF criteria respectively. Surgery was associated with almost halving of the albumin-creatinine ratio in 22 patients with pre-existing albuminuria (follow-up data available for 64 patients) and an overall stabilisation of retinopathy in 24 patients with retinal images available at 5 years. CONCLUSION: Whilst the findings on microvascular complications are encouraging, the rates of metabolic remission were lower than expected and raise the need for validated protocols to assist clinicians in managing these patients more aggressively post-operatively to achieve optimum cardio-metabolic risk factor control and hopefully further reduction in microvascular and macrovascular complications.

Individual and diabetes presentation characteristics associated with partial remission status in children and adults evaluated up to 12 months following diagnosis of type 1 diabetes: An ADDRESS-2 (After Diagnosis Diabetes Research Support System-2) study analysis.

AIMS: People with recently-diagnosed type 1 diabetes mellitus (T1D) may undergo a transient period of glycaemic control with less exogenous insulin. Identification of predictors of this 'remission' could inform a better understanding of glycaemic control. METHODS: Participants in the ADDRESS-2 study were included who had 1 or 2 assessments of remission status (coincident insulin dose and HbA1c measurement, with remission defined by ≤0.4 units insulin/kg-body-weight/day with HbA1c < 53 mmol/mol). Demographic and clinical presentation characteristics were compared according to remission status and predictors of remission were explored by logistic regression analysis. RESULTS: 1470 first and 469 second assessments of remission status were recorded within 12 months of diagnosis of T1D. Step increases in the probability of remission were identified at age-at-diagnosis 20 years and 3 months after diagnosis (both p < 0.001). Among those aged < 20 years, remission was associated with male gender (p = 0.02), no ketoacidosis (p = 0.02) and fewer than 2 symptoms at presentation (p = 0.004). None of these characteristics predicted remission in those aged ≥ 20 years. In the subgroup with two assessments, transition to remission was independently associated with first remission assessment in months 1-2 post-diagnosis (p = 0.01), with age-at-diagnosis ≥ 20 years (p = 0.01) and, in those aged < 20 years, with an early HbA1c of <57 mmol/mol. Adiposity, ethnicity, autoantibody status and other autoimmune disease were unrelated to remission. CONCLUSIONS: For those diagnosed before 20 years of age, males, ketoacidosis-free, with fewer symptoms and low early HbA1c were more likely to experience remission, but remission was most likely in anyone aged ≥ 20 at diagnosis.

Screening contacts of patients with extrapulmonary TB for latent TB infection.

2016 TB National Institute for Health and Care Excellence (NICE) guidelines imply that contacts of extrapulmonary TB do not require screening for latent TB infection. At our high TB prevalence site, we identified 189 active cases of TB for whom there were 698 close contacts. 29.1% of the contacts of pulmonary TB and 10.7% of the contacts of extrapulmonary TB had active or latent TB infection. This supports screening contacts of extrapulmonary TB at our site and presents a way to access high-risk individuals. We propose to continue to screen the contacts of our patients with extrapulmonary TB and recommend other TB units audit their local results.

A letrozole-based dual aromatase-sulphatase inhibitor with in vivo activity.

The role of aromatase inhibitors in the treatment of hormone-dependent breast cancer is well established. However, it is now recognised that steroid sulphatase (STS) inhibitors represent a new form of endocrine therapy. To explore the potential advantage of dual inhibition by a single agent, we recently developed a series of dual aromatase-sulphatase inhibitors (DASIs) based on the aromatase inhibitor YM511. We report here a new structural class of DASI obtained by obtained introducing the pharmacophore for STS inhibition, i.e. a phenol sulphamate ester into another established aromatase inhibitor letrozole. Hence, the bis-sulphamate 9 was synthesised which exhibited IC(50) values of 3044 nM for aromatase and >10 microM for STS in JEG-3 cells. However, at a single oral dose of 10mg/kg, 9 inhibited aromatase and rat liver STS by 60% and 88%, respectively, 24h after administration. A proposed metabolite of 9, carbinol 10, was synthesised. Despite also showing weak STS inhibition in JEG-3 cells, 10 inhibited rat liver STS activity to the same extent as 9 at a single oral dose of 10mg/kg. Thus, the concept of a letrozole-based DASI has been validated and could be further developed and modified for therapeutic exploitation.