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Aims: Assess long-term quality of life (QoL), bowel and voiding function in anorectal malformation (ARM) paediatric patients. Method: Retrospective review of ARM patients between 2007 and 2020 was performed. QoL (all patients), bowel and voiding function (> 5 yo) were assessed using the paediatric quality of life inventory (PedsQL), paediatric incontinence and constipation score (PICS) and dysfunctional voiding scoring system (DVSS), respectively. Results: There were 122 patients (49% female, 85 > 5 yo) with ARM. Two had died, four refused, twenty-two were non-contactable, leaving ninety-four patients (65 > 5 yo) included. Mean age was 89 months (19–183), and follow-up was 86 months (13–183). Patients had significantly poorer scores for QoL, bowel and voiding function compared to published healthy controls. 57% had poor bowel function, 32% had poor voiding function and 38% required 'ancillary aids' to facilitate function. Patients using 'ancillary aids' for voiding function had a significantly lower QoL (parent: 62 vs 77; p = 0.01, patient: 66 vs 79; p = 0.05). Bowel continence was worse in those with high vs low ARM (13 vs 20, p = 0.004) and timely vs delayed diagnosis (17 vs 24, p = 0.04). Conclusion: Patients with ARM have significantly worse QoL, bowel and voiding function than normal healthy controls. There is a need for long-term monitoring of function and further support for these children. Level of evidence: III. [ABSTRACT FROM AUTHOR]

Clozapine, an antipsychotic, is associated with increased susceptibility to infection with COVID-19, compared to other antipsychotics. Here, we investigate associations between clozapine treatment and increased risk of adverse outcomes of COVID-19, namely COVID-related hospitalisation, intensive care treatment, and death, amongst patients taking antipsychotics with schizophrenia-spectrum disorders. Using the clinical records of South London and Maudsley NHS Foundation Trust, we identified 157 individuals who had an ICD-10 diagnosis of schizophrenia-spectrum disorders, were taking antipsychotics (clozapine or other antipsychotics) at the time of COVID-19 pandemic in the UK and had a laboratory-confirmed COVID-19 infection. The following health outcomes were measured: COVID-related hospitalisation, COVID-related intensive care treatment and death. We tested associations between clozapine treatment and each outcome using logistic regression models, adjusting for gender, age, ethnicity, neighbourhood deprivation, obesity, smoking status, diabetes, asthma, bronchitis and hypertension using propensity scores. Of the 157 individuals who developed COVID-19 while on antipsychotics (clozapine or other antipsychotics), there were 28% COVID-related hospitalisations, 8% COVID-related intensive care treatments and 8% deaths of any cause during the 28 days follow-up period. amongst those taking clozapine, there were 25% COVID-related hospitalisations, 7% COVID-related intensive care treatments and 7% deaths. In both unadjusted and adjusted analyses, we found no significant association between clozapine and any of the outcomes. Thus, we found no evidence that patients with clozapine treatment at time of COVID-19 infection had increased risk of hospitalisation, intensive care treatment or death, compared to non-clozapine antipsychotic-treated patients. However, further research should be considered in larger samples to confirm this. [ABSTRACT FROM AUTHOR]

Introduction: The immunogenicity of BCG vaccination in infants differs between populations. We hypothesized that prenatal exposure to mycobacterial antigens might explain the differences in immune responses to BCG seen in other studies of infants in Africa and the United Kingdom (UK) and we explored this in birth cohorts in Uganda and the UK. Materials and Methods: Blood samples were obtained from BCG-immunized infants of mothers with (n = 110) and without (n = 121) latent Mycobacterium tuberculosis infection (LTBI) in Uganda and BCG-immunized infants of mothers without LTBI (n = 25) in the UK at 10 and 52 weeks after birth. Cytokine and chemokine responses to PPD were measured to assess responses to BCG immunization, and to ESAT6/CFP10 to assess exposure to or infection with M. tuberculosis or non-tuberculous mycobacteria (NTM) in 6-day whole blood culture supernatants by a 17-plex Luminex assay. Median responses were compared between Ugandan infants (together, and separated by maternal LTBI status) and UK infants. Results: The IFN-γ response to BCG vaccination was similar between Ugandan and UK infants at 10 and 52 weeks. At week 52, TNF production was marginally higher in Ugandan infants, but after adjusting for multiple comparisons this difference was not significant. At weeks 10 and 52, stimulation of blood with ESAT6/CFP10 produced significantly higher IFN-γ, TNF, IL-12p40, IL-1α, IL-1β, IL-1Ra, IP-10, MIP-1α, MIP-1β, and GM-CSF in Ugandan compared to UK infants. Stimulation of blood with ESAT6/CFP10 produced significantly higher amounts of IL-8 (p = 0.0001), IL-10 (p = 0.0022), and IL-13 (p = 0.0020) in the UK than in Ugandan infants of mothers without LTBI at week 10, but not at week 52. Conclusions: Immune responses to mycobacterial antigens following BCG immunization are similar for PPD, but differ for ESAT6/CFP10, between infants in Uganda and the UK. Neither maternal LTBI nor infant exposure to or infection with mycobacteria impacts the response to BCG. The observed global differences in immune response to BCG immunization are likely to be due to other causes. [ABSTRACT FROM AUTHOR]

Objective: Mining the data contained within Electronic Health Records (EHRs) can potentially generate a greater understanding of medication effects in the real world, complementing what we know from Randomised control trials (RCTs). We Propose a text mining approach to detect adverse events and medication episodes from the clinical text to enhance our understanding of adverse effects related to Clozapine, the most effective antipsychotic drug for the management of treatment-resistant schizophrenia, but underutilised due to concerns over its side effects. Material and methods: We used data from de-identified EHRs of three mental health trusts in the UK (>50 million documents, over 500,000 patients, 2835 of which were prescribed Clozapine). We explored the prevalence of 33 adverse effects by age, gender, ethnicity, smoking status and admission type three months before and after the patients started Clozapine treatment. Where possible, we compared the prevalence of adverse effects with those reported in the Side Effects Resource (SIDER). Results: Sedation, fatigue, agitation, dizziness, hypersalivation, weight gain, tachycardia, headache, constipation and confusion were amongst the highest recorded Clozapine adverse effect in the three months following the start of treatment. Higher percentages of all adverse effects were found in the first month of Clozapine therapy. Using a significance level of (p< 0.05) our chi-square tests show a significant association between most of the ADRs and smoking status and hospital admission, and some in gender, ethnicity and age groups in all trusts hospitals. Later we combined the data from the three trusts hospitals to estimate the average effect of ADRs in each monthly interval. In gender and ethnicity, the results show significant association in 7 out of 33 ADRs, smoking status shows significant association in 21 out of 33 ADRs and hospital admission shows the significant association in 30 out of 33 ADRs. Conclusion: A better understanding of how drugs work in the real world can complement clinical trials. [ABSTRACT FROM AUTHOR]

The Affordable Care Act ("ACA") made health insurance accessible to many. Yet unaffordable insurance still abounds. This Article proposes a strategy for improving affordability that enables health insurance purchasers to choose, within reasonable limits, which treatments their insurance covers. After critiquing recently proposed strategies for improving affordability and reviewing past legal scholarship on content choice in health insurance, this Article introduces the "Affordable Choices" framework. This framework regulates choice in four ways. First, health plans should only exclude treatments whose merits are subject to reasonable disagreement among patients and physicians. Second, plans should appeal to purchasers' health-related values--values about the sort of life they want to live--rather than predictions about their health status. Third, plans should include interventions like vaccines that protect others from harm. Fourth, excluded interventions should be those costly enough that exclusion meaningfully shifts affordability. This Article will then discuss potential plan offerings, such as "international reference coverage" based on national plans in other developed countries like Canada or the United Kingdom, and discuss what legal reforms--if any--would be needed in order to offer Affordable Choices plans as part of ACA exchanges, employer-provided insurance, Medicare, or Medicaid. This Article then considers legal and ethical objections that ill people, plan purchasers, society, or providers might advance. It first addresses the objection that Affordable Choices plans will unfairly raise health insurance costs for less healthy people and argues that requiring plans to appeal to healthrelated values rather than health status expectations will help to avoid this problem. It then explains how the Affordable Choices framework can be structured to protect purchasers from misprediction or choice overload. Turning to objections from society, this Article explains how choice about the content of insurance is compatible with solidarity among insured patients, albeit liberal solidarity (focused on the framework that enables choice for all) rather than communitarian solidarity (focused on the substantive content of individuals' choices). It also explains how Affordable Choices plans can be compatible with state requirements regarding specific benefits and with anti-discrimination law. Last, it explains why participation in Affordable Choices plans accords, rather than conflicts, with providers' legal obligations and ethical duties, and argues that providers are not only permitted but ethically encouraged to protect patients from financial hardship. [ABSTRACT FROM AUTHOR]

This article argues that in the mid to late eighteenth century, political economy, through writers such as Francois Quesnay, David Hume and Adam Smith, saw a discussion of ‘despotism’, which stood for thinking through the political arrangement within which economic productivity was formulated; even as the distinction between the two was not always self-evident. This theoretical function of despotism disappears in the ‘mature’ phase of political economy (David Ricardo), precisely when it was taking shape—in institutional and conceptual-lexical terms—in the subcontinent through Britain’s conquest of India via the East India Company. We argue that the disappearance of despotism at the conceptual level in this phase in Britain is not only questionable from a theoretical standpoint but also played its historical role as a decoy in occluding attention toward imperialism in India wherein the distinction between the political and the economic was becoming more and more difficult to make. Through such an investigation we thus hope to examine the emergence of the economy (and by implication the state-political) as an independent analytic site as well as evaluate its categories and historical significance. We base our argument on a reading of the canonical texts of figures such as Adam Smith, William Blackstone and David Ricardo, Land Revenue Settlement sources in India and the hitherto neglected economic writings of W.H. Sleeman. [ABSTRACT FROM PUBLISHER]

Investigates the behavior of audit firms during the period of mergers among large audit firms in Great Britain in the late 1980s. Testing of the extant audit fee model; Consistency of findings with those of the National Economic Research Associates that competition in the audit market would remain as long as there are no further mergers among the Big 6 companies.

The article discusses two cases of a retained fetal bone which was mistaken for intrauterine contraceptive device (IUCD) on ultrasound scan in Great Britain. Ultrasound scanning is the first-line investigation for missing IUCD. It is difficult to differentiate a fetal bone from IUCD because they both present a linear calcified image.

Objective: How do numbers of oocytes retrieved per In vitro fertilisation (IVF) cycle impact on the live birth rate (LBR) and multiple gestation pregnancy (MGP) rates?, Design: Retrospective observational longitudinal study., Setting: UK IVF clinics., Population: Non-donor IVF patients., Main Outcome Measures: LBR per IVF cycle and MGP levels against number of oocytes retrieved into subgroups: 0, 1-5, 6-15, 16-25, 26-49 oocytes and 50+ oocytes. Relative risk (RR) and 95% CIs were calculated for each group against the intermediate responder with '6-15 oocytes collected'., Results: From 172 341 attempted fresh oocyte retrieval cycles, the oocyte retrieved was: 0 in 10 148 (5.9%) cycles from 9439 patients; 1-5 oocytes in 42 574 cycles (24.7%); 6-15 oocytes in 91 797 cycles (53.3%); 16-25 oocytes in 23 794 cycles (13.8%); 26-49 oocytes in 3970 cycles (2.3%); ≥50 oocytes in 58 cycles (0.033%). The LBRs for the 1-5, 6-15, 16-25 and 26-49 subgroups of oocytes retrieved were 17.2%, 32.4%, 35.3% and 18.7%, respectively. The RR (95% CI) of live birth in comparison to the intermediate group (6-15) for 1-5, 16-25 and 26-49 groups was 0.53 (0.52 to 0.54), 1.09 (1.07 to 1.11) and 0.58 (0.54 to 0.62), respectively. The corresponding MGP rates and RR were 9.2%, 11.0%, 11.4% and 11.3%, respectively and 0.83 (0.77 to 0.90), 1.04 (0.97 to 1.11) and 1.03 (0.84 to 1.26), respectively., Conclusion: There was only limited benefit in LBR beyond the 6-15 oocyte group going to the 16-25 oocytes group, after which there was significant decline in LBR. The MGP risk was lower in 1-5 group., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Patients who decline blood products because of their religious beliefs pose a unique challenge in the context of obstetric haemorrhage. Four large series assessing maternal outcomes in Jehovah's Witnesses from USA, UK, Netherlands and Japan estimate that maternal mortality is increased by between 44 and 160-fold. A review of maternal deaths from obstetric haemorrhage was undertaken in mothers who decline blood transfusion, using UK Confidential Enquiries into Maternal Deaths reports (1967-2019) in order to identify common trends and lessons learnt., Design: Retrospective review using 18 triennial Confidential Enquiries in Maternal Deaths reports between 1967 and 2019., Results: Fifteen maternal deaths from haemorrhage were reported in patients who declined blood products for religious beliefs in the 52 years reviewed. Common themes noted included delay in senior escalation, hesitation to perform life-saving hysterectomy and loss of situational awareness. Placental abruptions (3/15) and curettage for secondary postpartum haemorrhage (2/15) especially warrant senior input and cooperation with Jehovah's Witness Hospital Liaison Committees is recommended., Conclusions: Guidelines from the UK's Royal College of Obstetricians and Gynaecologists and Royal College of Surgeons highlight the need for collaborative, Montgomery-competent discussions during the antenatal period, as well as the engagement of local Jehovah's Witness Hospital Liaison committees. Consultant-led care, antenatal optimisation of haemoglobin and techniques to mitigate blood loss at delivery are paramount. We advocate using a lower threshold for hysterectomy than was used in the cases analysed, for example when the haemoglobin level drops below 8-9 g/l in the context of ongoing bleeding. As patients increasingly begin to decline blood products for non-religious reasons, the lessons learnt in the management of Jehovah's Witnesses are becoming ever more relevant., (Copyright © 2022 Elsevier B.V. All rights reserved.)