Underdiagnosis of internal anal sphincter trauma following vaginal delivery.

OBJECTIVE: Damage to the anal sphincter during childbirth remains the leading cause of fecal incontinence in women. Defects in the internal (IAS) or external anal sphincter, alongside symptoms and sphincter tone, will generally dictate the suggested mode of delivery in any successive pregnancy. This study aimed to examine using endoanal ultrasonography the prevalence of IAS damage in women referred with Grade-3a or -3b obstetric anal sphincter injury (OASI) in a tertiary-referral perineal clinic. METHODS: This was a retrospective observational study of all women referred to a tertiary-referral perineal clinic after primary repair of OASI (Grade 3a-c, 4) diagnosed for the first time following vaginal delivery between January 2016 and December 2019, inclusive. Women were assessed using the Wexner bowel continence questionnaire, digital examination of sphincter tone and endoanal ultrasound. Injuries in each sphincter were classified as a scar (≤ 30°) or defect (> 30-90° or > 90°) on endoanal imaging in the axial plane. RESULTS: In total, 615 women were referred following primary repair of OASI. Sonographic evidence of damage to the IAS was seen in 9.1% (46/506) of women diagnosed with a Grade-3a/3b injury. In women referred with a Grade-3a/3b tear, symptom scores were statistically higher (P = 0.025) in those with an IAS defect > 30° compared to those with an intact or scarred IAS, although the median score was zero in both groups. The proportion of women in each group with severe symptoms (score > 9) was similar (2.6% vs 6.5%; P = 0.148). Among women referred with a Grade-3a/3b tear, sphincter tone was reduced more frequently in those with a defect of the IAS than in those with an intact or scarred IAS (52.2% vs 11.7%; odds ratio, 8.14 (95% CI, 4.26-15.67); P < 0.001). Regardless of the reason for referral, women with reduced sphincter tone on rectal examination were four times as likely to have had an IAS defect > 30° than were those with normal resting tone (risk ratio, 4.58 (95% CI, 3.25-6.45); P < 0.001). CONCLUSIONS: One in 11 women diagnosed with a Grade-3a or -3b tear have evidence of damage to their IAS on endoanal ultrasound. Damage to this muscle is linked to fecal incontinence in women and can have a significant impact on the planning of any future deliveries. This study highlights the importance of established perineal clinics with access to ultrasound. Nonetheless, if reduced sphincter tone is felt on rectal examination, a clinician should have a high index of suspicion for an occult IAS injury. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The acquisition of clinical experience during GP training - how can we mitigate for the impact of COVID-19?

The COVID-19 pandemic has profoundly impacted the way general practice is run and this is expected to have had a knock-on effect upon GP training. A questionnaire-based study was designed to investigate what was happening to GP trainees 16 months into the pandemic in terms of opportunities to develop clinical experience and clinical decision-making. We also asked trainers and trainees for ideas on how we might mitigate for the effects of COVID-19. In particular, there has been decreased exposure to clinical examination during the pandemic and there appear to be gaps in opportunities to learn from urgent and unscheduled care settings and to develop skills in rapid clinical decision-making. It is interesting to consider what general practice will look like when the pandemic is over and how this will this affect the GP training curriculum going forwards. Although response rates were low, we were able to determine some emerging themes for national, local and educational review going forwards to help shape and improve GP training for the future.

Treatment of cutaneous basal cell carcinoma with combined laser extirpation and methyl aminolevulinic acid: five-year success rates.

INTRODUCTION: Basal cell carcinoma is the most common cancer. Excisional surgery is associated with a high clearance rate, at the expense of significant functional and aesthetic morbidity, especially within the T-zone or for extensive lesions. We report five-year follow-up outcomes for carbon dioxide laser extirpation of cutaneous basal cell carcinoma, assisted by immediate methyl aminolevulinate photodynamic therapy and cost-benefit considerations. MATERIALS AND METHODS: Retrospective cohort database analysis of adult patients with biopsy-proven primary cutaneous basal cell carcinoma, completing five years of follow-up. Direct per-lesion cost was compared with conventional wide local excision. Patients with morphoeic basal cell carcinoma were excluded. RESULTS: Treated lesions were up to 1% total body surface area and up to 3.8mm (1.38 ± 0.695cm, mean ± standard deviation) in biopsy-proven depth. At the five-year follow-up mark, 93.6% of treated areas remained free of recurrence. Nodular basal cell carcinoma was the most common subtype (41.5%). A mean tumour depth greater than 2 ± 0.872mm was significantly associated with recurrence (Mann-Whitney, p = 0.0487). For a service delivered through the NHS at 2015 prices, we report a 43% saving, equating to a saving of £235 per basal cell carcinoma or a national annualised saving of £70 million by 2025 for the NHS. CONCLUSION: Our results suggest that CO2-assisted photodynamic therapy is non-inferior to excision but may offer better functional and cosmetic preservation at a fraction of the direct like for like cost of operative surgery. Investigation of this method by randomised controlled methodology is warranted.

Patient satisfaction with joint colorectal-urogynaecology pelvic floor surgery

Introduction Pelvic floor dysfunction is a global term used to describe conditions such as pelvic organ prolapse, and faecal or urinary incontinence. The Pelvic Floor Centre is a multi-disciplinary clinic for pelvic floor dysfunction. The aim of this study was to assess patient satisfaction following joint colorectal-urogynaecology surgery in the Pelvic Floor Centre. Methods All patients who underwent a joint procedure in the Pelvic Floor Centre from 1st October 2015 to 31st October 2016 were contacted via telephone. Patient satisfaction was assessed using the Surgical Satisfaction Questionnaire (SSQ-8). Results Fifteen patients underwent joint surgeries between 1st October 2015 and 31st October 2016. All patients consented to the questionnaire. Patients underwent a variety of combined procedures including vaginal repairs, anal sphincter repairs, mid-urethral slings, perineal injections, and stapled trans-rectal resection of the rectum. Discussion Thirteen (86.7%) patients were satisfied with their surgery, and would recommend it to other patients with a similar condition. All patients were satisfied that their pain was well controlled after discharge. Eleven (73.3%) patients were satisfied with the time taken to return to daily activities, work, and their usual exercise routine. There is a high level of satisfaction amongst patients undergoing joint colorectal-urogynaecology surgery at the Pelvic Floor Centre. Further investigation into patient satisfaction with the clinic itself and international comparison is warranted.

Circulating tumour DNA is a potential biomarker for disease progression and response to targeted therapy in advanced thyroid cancer.

BACKGROUND: Conventional biomarkers in thyroid cancer are not disease specific and fluctuate in advanced disease, making interpretation difficult. Circulating tumour DNA (ctDNA) has been shown to be a useful biomarker in other solid tumours. This is a multimutational study of ctDNA over multiple timepoints, designed to test the hypothesis that ctDNA is a potential biomarker in patients with advanced thyroid cancer. METHODS: Mutational analysis of archival tumour tissue was performed using NGS with a targeted gene panel. Custom TaqMan assays were designed for plasma ctDNA testing using digital droplet polymerase chain reaction. Concentrations of detected ctDNA were correlated with the conventional biomarker concentration and axial imaging status defined by the Response Evaluation Criteria in Solid Tumours criteria. RESULTS: Tumour tissue from 51 patients was obtained, with the following histologies: 32 differentiated (differentiated thyroid cancer [DTC]), 15 medullary (medullary thyroid cancer [MTC]), three poorly differentiated and one anaplastic. NGS analysis detected variants in 42 (82%) of cases. Plasma was assayed for these patients in 190 samples, and ctDNA was detected in 67% of patients. Earlier detection of disease progression was noted in three patients with MTC. In two cases (PTC and ATC), where conventional biomarkers were not detectable, ctDNA was detected before disease progression. Changes in ctDNA concentration occurred earlier than conventional markers in response to disease progression in multiple patients with DTC receiving targeted therapies. CONCLUSION: The majority of patients with advanced thyroid cancer had detectable ctDNA. ctDNA measurement may offer superiority over conventional markers in several scenarios: earlier detection of progression in MTC; as an alternative biomarker when conventional markers are not available; more rapid assessment of the disease status in response to targeted therapies, thereby potentially allowing prompter discontinuation of futile therapies. These early results support the hypothesis that ctDNA may be a clinically useful biomarker in thyroid cancer.

Tracking evolution of aromatase inhibitor resistance with circulating tumour DNA analysis in metastatic breast cancer.

Background: Selection of resistance mutations may play a major role in the development of endocrine resistance. ESR1 mutations are rare in primary breast cancer but have high prevalence in patients treated with aromatase inhibitors (AI) for advanced breast cancer. We investigated the evolution of genetic resistance to the first-line AI therapy using sequential ctDNA sampling in patients with advanced breast cancer. Patients and methods: Eighty-three patients on the first-line AI therapy for metastatic breast cancer were enrolled in a prospective study. Plasma samples were collected every 3 months to disease progression and ctDNA analysed by digital droplet PCR and enhanced tagged-amplicon sequencing (eTAm-Seq). Mutations identified in progression samples by sequencing were tracked back through samples before progression to study the evolution of mutations on therapy. The frequency of novel mutations was validated in an independent cohort of available baseline plasma samples in the Study of Faslodex versus Exemestane with or without Arimidex (SoFEA) trial, which enrolled patients with prior sensitivity to AI. Results: Of the 39 patients who progressed on the first-line AI, 56.4% (22/39) had ESR1 mutations detectable at progression, which were polyclonal in 40.9% (9/22) patients. In serial tracking, ESR1 mutations were detectable median 6.7 months (95% confidence interval 3.7-NA) before clinical progression. Utilising eTAm-Seq ctDNA sequencing of progression plasma, ESR1 mutations were demonstrated to be sub-clonal in 72.2% (13/18) patients. Mutations in RAS genes were identified in 15.4% (6/39) of progressing patients (4 KRAS, 1 HRAS, 1 NRAS). In SoFEA, KRAS mutations were detected in 21.2% (24/113) patients although there was no evidence that KRAS mutation status was prognostic for progression free or overall survival. Conclusions: Cancers progressing on the first-line AI show high levels of genetic heterogeneity, with frequent sub-clonal mutations. Sub-clonal KRAS mutations are found at high frequency. The genetic diversity of AI resistant cancers may limit subsequent targeted therapy approaches.

Early Pregnancy Ultrasound and Management: Effect of a Multifaceted Training on Physician Knowledge.

Vaginal bleeding is a common event in early pregnancy, with 20-40% of pregnancies affected. Prompt diagnosis and management of bleeding is important, both to reduce morbidity and to avoid excessive emotional distress. This was a prospective study of an educational programme aimed at Obstetrics and Gynaecology BST trainees in the National Maternity Hospital, Dublin. The educational programme consisted of didactic lectures, and simulation and practical sessions. A questionnaire reviewing early pregnancy complications was used to assess participant knowledge. Six trainees participated in the programme, with five (83%) answering the questionnaire. The pre-education questionnaire showed a generally poor level of knowledge of early pregnancy complications with 8/50 (16%) questions answered correctly. Following the educational intervention there was a statistically significant increase in participant knowledge with 45/50 (90%) questions answered correctly. A significant increase in participant knowledge of early pregnancy complications followed our multifaceted educational programme. Study limitations exist, however we have shown the potential value of our educational programme.

Study profile: the Durban Diabetes Study (DDS): a platform for chronic disease research.

The Durban Diabetes Study (DDS) is a population-based cross-sectional survey of an urban black population in the eThekwini Municipality (city of Durban) in South Africa. The survey combines health, lifestyle and socioeconomic questionnaire data with standardised biophysical measurements, biomarkers for non-communicable and infectious diseases, and genetic data. Data collection for the study is currently underway and the target sample size is 10 000 participants. The DDS has an established infrastructure for survey fieldwork, data collection and management, sample processing and storage, managed data sharing and consent for re-approaching participants, which can be utilised for further research studies. As such, the DDS represents a rich platform for investigating the distribution, interrelation and aetiology of chronic diseases and their risk factors, which is critical for developing health care policies for disease management and prevention. For data access enquiries please contact the African Partnership for Chronic Disease Research (APCDR) at data@apcdr.org or the corresponding author.

Order of magnitude smaller limit on the electric dipole moment of the electron.

The Standard Model of particle physics is known to be incomplete. Extensions to the Standard Model, such as weak-scale supersymmetry, posit the existence of new particles and interactions that are asymmetric under time reversal (T) and nearly always predict a small yet potentially measurable electron electric dipole moment (EDM), d(e), in the range of 10(-27) to 10(-30) e·cm. The EDM is an asymmetric charge distribution along the electron spin (S(→)) that is also asymmetric under T. Using the polar molecule thorium monoxide, we measured d(e) = (-2.1 ± 3.7stat ± 2.5syst) × 10(-29) e·cm. This corresponds to an upper limit of |d(e)| < 8.7 × 10(-29) e·cm with 90% confidence, an order of magnitude improvement in sensitivity relative to the previous best limit. Our result constrains T-violating physics at the TeV energy scale.