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Screening with cardiac non-invasive stress studies (NISS) prior to listing for kidney transplantation can help in identifying treatable coronary disease and is considered an integral part of pre-kidney transplant evaluation. However, few studies assessed their effectiveness in all patients evaluated for transplantation in clinical practice. To evaluate the role of NISS in pre-kidney transplant evaluation we analyzed their impact prior to waitlisting in 1053 adult CKD-5 patients consecutively evaluated in Greater Manchester, UK during a 6-year period. 918 waitlisted patients were grouped based on presence or absence of Diabetes or Cardio-Vascular Disease (CVD): Group-1 (255 DM-/CVD-/NISS-), Group-2 (368 DM-/CVD-/NISS+) and Group-3 (295 with DM or CVD). Group-2 patients had longer 'time-to-listing' (5.5months in Group-1 vs 6.9months in 'Normal-NISS' vs 9.9months in 'Abnormal-NISS', p<0.01) but none with 'Abnormal-NISS' needed coronary revascularization before listing. NISS was followed by revascularization in 8 Group-3 patients (3%). In multi-variate analyses, there was no association of NISS on death or MACE in listed patients. During follow up, Transplantation was the most significant factor associated with improved outcomes in all subgroups (HR:0.97, p<0.001). 135 patients were considered unsuitable for waitlisting, with NISS influencing management in 11 of these patients (8%). Pre-kidney transplant evaluation with NISS influenced clinical management in 19 of 1053 (2%) patients. Screening with NISS added limited benefit but contributes to significant delays in listing and adding resource implications. Further studies are needed to assess clinical and cost effectiveness of NISS in pretransplant evaluation to optimize outcomes and resources.

IntroductionIvacaftor was the first therapy licensed to address the underlying defect in cystic fibrosis (CF). The improvements in lung function, nutritional status and pulmonary exacerbations in patients carrying a Gly551Asp mutation were greater than previously seen in clinical trials for other therapies. Limited data are available regarding long-term outcomes and adherence to ivacaftor outside clinical trials.MethodsWe conducted a 5-year single-centre retrospective study of people with CF carrying the Gly551Asp mutation who received ivacaftor. Clinical outcome data were extracted from medical notes and databases. Drug delivery data were used to assess medicine possession ratio (MPR).Results35 people were included. After commencing ivacaftor, FEV1 improved by 9.6% (SE±1.59%) predicted by 6 months. Thereafter, FEV1 declined, and at 5 years had returned to pre-ivacaftor baseline. Ivacaftor did not alter annual rate of FEV1 decline (1.57% pre vs 1.82% post, p=0.74). Body mass index (BMI) increased for 4 years. There was a significant reduction in inpatient and total intravenous antibiotic days sustained over 5 years. MPR remained high but declined over time (−2.5±0.9% per year, p=0.007). FEV1 was better maintained in patients with higher MPRs.ConclusionThe addition of ivacaftor provides acute benefits for people with the Gly551Asp mutation and established lung disease. We report a sustained reduction in intravenous antibiotic use but following acute improvement in lung function, decline continues, and patients will continue to require medical observation and optimisation. Strategies to maintain high adherence should be a priority to prolong the benefits of ivacaftor.

BackgroundConcern remains about how occupational SARS-CoV-2 risk has evolved during the COVID-19 pandemic. We aimed to ascertain occupations with the greatest risk of SARS-CoV-2 infection and explore how relative differences varied over the pandemic.MethodsAnalysis of cohort data from the UK Office of National Statistics COVID-19 Infection Survey from April 2020 to November 2021. This survey is designed to be representative of the UK population and uses regular PCR testing. Cox and multilevel logistic regression were used to compare SARS-CoV-2 infection between occupational/sector groups, overall and by four time periods with interactions, adjusted for age, sex, ethnicity, deprivation, region, household size, urban/rural neighbourhood and current health conditions.ResultsBased on 3 910 311 observations (visits) from 312 304 working age adults, elevated risks of infection can be seen overall for social care (HR 1.14; 95% CI 1.04 to 1.24), education (HR 1.31; 95% CI 1.23 to 1.39), bus and coach drivers (1.43; 95% CI 1.03 to 1.97) and police and protective services (HR 1.45; 95% CI 1.29 to 1.62) when compared with non-essential workers. By time period, relative differences were more pronounced early in the pandemic. For healthcare elevated odds in the early waves switched to a reduction in the later stages. Education saw raises after the initial lockdown and this has persisted. Adjustment for covariates made very little difference to effect estimates.ConclusionsElevated risks among healthcare workers have diminished over time but education workers have had persistently higher risks. Long-term mitigation measures in certain workplaces may be warranted.

To identify strategies used in recent randomized controlled trials (RCTs) and their associated Cochrane Reviews where patients with the same gynecological condition present with different symptoms but would plausibly benefit from a common intervention. We searched the Cochrane library (February 2022) for reviews in polycystic ovarian syndrome (PCOS) and endometriosis. Reviews were included if the intervention was intended to treat all condition-specific symptoms. For each trial we recorded the strategy used and the number of potentially eligible participants excluded as a direct result of the chosen strategy. For each review we recorded the numbers of RCTs and participants excluded on the basis of symptoms experienced. There were 89 distinct PCOS trials in 13 reviews, and 13 Endometriosis trials in 11 reviews. Most trials restricted their eligibility to participants with specific symptoms (55% PCOS, 46% endometriosis). The second most common strategy was to measure and analyze clinical outcomes that were not relevant to all participants (38% PCOS, 31% endometriosis). Reviews excluded 27% of trials in participants evaluating the same intervention in participants experiencing the same condition based on the outcomes measured in the trials. Most gynecological trials exclude patients who could benefit from treatment or measure outcomes not relevant to all participants. We introduce a taxonomy to describe trial design strategies for conditions with heterogeneous symptoms.

Introduction and hypothesisObstructive defecation syndrome (ODS) is a common urogynaecology presentation. This study compares two questionnaires, the electronic Personal Assessment Questionnaire (e-PAQ), used in urogynaecology clinics, with the ODS-Score (ODS-S), a simple validated scoring system used in colorectal clinics for diagnosing ODS, to identify patients with an ODS-S cut-off ≥9.MethodsA total of 221 paired ODS-S and e-PAQ questionnaires were completed; 80 during the second trimester of pregnancy, 73 during the third and 68 post-natally, including women sustaining obstetric anal sphincter injury (OASI). e-PAQ score and ODS-S were compared and Pearson’s correlation coefficient calculated. Areas under the curve assessed the diagnostic ability of e-PAQ scores to identify patients with ODS-S of ≥9.ResultsThe e-PAQ and ODS-S scores showed a positive correlation in the second and third trimesters of pregnancy, post-natally and following OASI. Pearson’s correlation coefficient was calculated (0.77; p < 0.001, 0.79; p < 0.001, 0.66; p = 0.001 and 0.79; p < 0.001 respectively). An e-PAQ evacuatory domain score of ≥33 identified women with an ODS score of ≥9 with a sensitivity and specificity of 71% and 94% in the second trimester, 86% and 95% third trimester and 78% and 97% in the OASI group respectively. Area under the curve was >0.90 for all groups.ConclusionsComparison of e-PAQ evacuatory domain scores and ODS-S show a strong correlation, with an e-PAQ score of ≥33 promising for identifying women with an ODS score of ≥9, indicating ODS. This study will enable us to identify women during pregnancy and post-natally with ODS for whom early recognition and intervention may be beneficial.

PurposeWhile it is known that histologically involved margins lead to a higher local recurrence rate, re-excision of anterior margins is less common than that of radial margins. However, there are minimal long-term data on the oncological safety of non-surgical management of anterior margins.Patients and methodsA retrospective study was performed of all patients who underwent breast conserving surgery for breast cancer between 2000 and 2008 at two tertiary referral centres. A close margin was defined as disease within two mm of the resection margin (including disease at the margin).Results6922 patients underwent surgery for invasive or in situ breast cancer of whom 277 patients had a close anterior margin alone after breast conserving surgery. Two hundred and twenty patients had non-surgical management of their margins, while 57 had re-excision surgery. Overall, there were 4/57 local recurrences in the surgical management group and 12/220 in the non-surgical management group. The local recurrence-free survival rate at 5 years was 98.2% (1 recurrence, 95% CI 87.8–99.7) in the surgical management group and 97.2% (6 recurrences, 95% CI 93.8–98.7) in the non-surgical management group. At 10 years, the rates were 92.2% (4 recurrences, 95% CI 80.3–97.0) in the surgical management group and 93.9% (12 recurrences, 95% CI 89.4–96.5) in the non-surgical management group. There was no significant difference found in the local recurrence rate between management groups (HR 1.24, 95% CI 0.40, 3.85; p = 0.71).ConclusionsLocal recurrence rates are acceptable and similar in both the surgically and non-surgically managed groups. Non-surgical management of close anterior margins appears oncologically safe when combined with appropriate adjuvant therapy.

The levonorgestrel-releasing intrauterine system (LNG-IUS) is a conservative management option for atypical hyperplasia (AH) and low grade early stage endometrial cancer (EEC), but around 1 in 3 patients fail to respond to treatment. The aim of this study was to investigate if serum and/or tissue HE4 expression could predict response to LNG-IUS therapy. Patients with AH or presumed Stage I EEC had serum and endometrial samples taken at baseline and at 3-month intervals over 12 months post-insertion of LNG-IUS. 74 patients were recruited and baseline demographics recorded. Of 57 patients for whom response was histologically determinable, 39 (68%) were responders and 18 (32%) non-responders. Mean baseline serum HE4 was significantly lower in responders (62.1 ± 1.1 pM, 95% confidence interval (CI) 52.7–73.2), compared to non-responders (125.6 ± 1.3 pM, 95% CI 74.5–211.7, p = 0.014), including when considering age, BMI, menopausal status, smoking status, and histological grade as covariables (p = 0.005). Baseline tissue HE4 expression was not significantly different in responders compared to non-responders (p = 0.999). Responders showed a significant mean reduction (−9.8 ± 3.4%, 95% CI −16.7 to −2.8%, p = 0.008) in serum HE4 between baseline and 3 months (p = 0.008), whereas non-responders showed no significant change (p = 0.676). Neither responders nor non-responders showed a significant percentage change in serum HE4 from baseline beyond 3 months (p > 0.05). Change in serum HE4 between baseline and 3 and 6 months and tissue HE4 tissue expression between baseline and 3, 6, and 12 months was not significantly different in responders compared to non-responders (p > 0.05). This study suggests that baseline serum HE4, but not baseline tissue HE4 expression, is independently predictive of response to the LNG-IUS and could be used to guide management decisions.

A barrier to Lynch syndrome testing is the need for prior genetic counselling, a resource demanding process for both patients and healthcare services. We explored the impact of gynaecologist led Lynch syndrome testing in women with endometrial cancer. Women were approached before surgery, on the day of surgery or during routine follow up. Lynch syndrome testing was offered irrespective of age, family history or tumour characteristics. Women’s reasons for being tested were explored using the Motivations and Concerns for GeNEtic Testing (MACGNET) instrument. The short form State-Trait Anxiety Inventory (STAI-6) was used to measure anxiety levels. Only 3/305 women declined Lynch syndrome testing. In total, 175/220 completed MACGNET and STAI-6 psychological instruments. The consent process took an average of 7 min 36 s (SD 5 min 16 s) to complete. The point of care at which consent was taken (before, day of surgery, during follow up) did not influence motivation for Lynch syndrome testing. Anxiety levels were significantly lower when women were consented during follow up (mean reversed STAI-6 score 32 vs. 42, p = 0.001). Anxiety levels were not affected by familial cancer history (p = 0.41). Gynaecologist led Lynch syndrome testing is feasible and may even be desirable in endometrial cancer, especially when offered during routine follow up.