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Background Typically, the fitness of UK firefighters is assessed via submaximal estimate methods due to the low demands on time, money, expertise and equipment. However, the firefighter-specific validity of such testing in relation to maximum aerobic capacity (⁠ V ˙ O 2 max ⁠) and particularly muscular strength is not well established. Aims To examine the validity of submaximal methods to estimate V ˙ O 2 max and maximal strength in operational firefighters. Methods Twenty-two full-time operational firefighters (3 female) completed same-day submaximal (Chester Step Test; CST) and maximal (treadmill) assessments of V ˙ O 2 max ⁠ , with a sub-sample of 10 firefighters (1 female) also completing submaximal and maximal back-squat (i.e. one repetition maximum; 1RM) assessments. All participants then completed the Firefighter Simulation Test (FFST) within 2–4 days. Results CST underestimated actual V ˙ O 2 max by 1.4 ml·kg–1·min–1 (~3%), although V ˙ O 2 max values were positively correlated (r  = 0.61, P  < 0.01) and not significantly different. Estimated V ˙ O 2 max values negatively correlated with FFST performance (r  = –0.42). Predicted 1RM underestimated actual 1RM by ~2%, although these values were significantly correlated (r  = 0.99, P  < 0.001) and did not significantly differ. The strongest predictive model of FFST performance included age, body mass index, and direct maximal measures of 1RM and V ˙ O 2 max ⁠. Conclusions Submaximal back-squat testing offers good validity in estimating maximum firefighter strength without exposure to the fatigue associated with maximal methods. The CST provides a reasonably valid and cost-effective V ˙ O 2 max estimate which translates to firefighting task performance, although the error observed means it should be used cautiously when making operational decisions related to V ˙ O 2 max benchmarks. [ABSTRACT FROM AUTHOR]

Background: Within the United Kingdom's National Health System (NHS), patients suffering from obesity may be provided with bariatric surgery. After receiving surgery many of these patients require further support to continue to lose more weight or to maintain a healthy weight. Remotely monitoring such patients' physical activity and other health-related variables could provide healthworkers with a more 'ecologically valid' picture of these patients' behaviours to then provide more personalised support. The current study assesses the feasibility of two smartphone apps to do so. In addition, the study looks at the barriers and facilitators patients experience to using these apps effectively.Methods: Participants with a BMI > 35 kg/m2 being considered for and who had previously undergone bariatric surgery were recruited. Participants were asked to install two mobile phone apps. The 'Moves' app automatically tracked participants' physical activity and the 'WLCompanion' app prompted participants to set goals and input other health-related information. Then, to learn about participants' facilitators and barriers to using the apps, some participants were asked to complete a survey informed by the Theoretical Domains Framework. The data were analysed using regressions and descriptive statistics.Results: Of the 494 participants originally enrolled, 274 participants data were included in the analyses about their activity pre- and/or post-bariatric surgery (ages 18-65, M = 44.02, SD ± 11.29). Further analyses were performed on those 36 participants whose activity was tracked both pre- and post-surgery. Participants' activity levels pre- and post-surgery did not differ. In addition, 54 participants' survey responses suggested that the main facilitator to their continued use of the Moves app was its automatic nature, and the main barrier was its battery drain.Conclusions: The current study tracked physical activity in patients considered for and who had previously undergone bariatric surgery. The results should be interpreted with caution because of the small number of participants whose data meet the inclusion criteria and the barriers participants encountered to using the apps. Future studies should take note of the barriers to develop more user-friendly apps.Trial Registration: ClinicalTrials.gov- NCT01365416 on the 3rd of June 2011. [ABSTRACT FROM AUTHOR]

The provision of healthcare is being challenged by a 'perfect storm' of forces including an increasing population with multiple comorbidities, high expectations and resource limitations, and in the background, the pre-eminence of the 'curative medical model'. Non-beneficial (futile) treatments are wasteful and costly. They have a negative impact on quality of life especially in the last year of life. Among professionals, frequent encounters with futility cause moral distress and demoralisation. The factors that drive non-beneficial treatments include personal biases, patient-related pressures and institutional imperatives. Breaking loose from the perceived necessity to deliver non-beneficial treatment is a major challenge. Curative intent should give way to appropriateness such that curative and palliative interventions are valued equally. Goals of treatment should be shaped by illness trajectory, the risk of harms as well as potential benefits and patient preferences. This strategy should be reflected in professional training and the design of acute services. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate reported ingested dose of paracetamol as a risk assessment tool in acute paracetamol overdose. Methods: Data was retrospectively obtained from a clinical toxicology database linked to one Australian and two United Kingdom hospitals. Plasma paracetamol concentrations (PPCs) of adult patients presenting with acute single ingestion, non-staggered paracetamol deliberate self-poisoning between 2006 and 2012 were recorded and plotted on a treatment nomogram to determine accuracy of reported dose ingested as an indicator for antidotal treatment. PPC plotted on a treatment nomogram with a line intersecting a 4-h concentration of 100 mg/L [667 μmol/L] was considered an indication for antidotal treatment in the UK; the corresponding Australasian population utilised a line intersecting 150 mg/L [1000 μmol/L]. Results: Of 1246 patients, 65.7 % were female and 88 % were from the UK. Fifty-two percent of patients reporting ingestion of ≥8 g paracetamol had a PPC above the 100 mg/L treatment line; PPV 52 % [95 % confidence interval (CI) 49 %, 55 %], sensitivity 81 % [95 %CI 78 %, 85 %]. Forty-four of patients reporting percent ingestion of ≥10 g had a PPC above the 150 mg/L treatment line; PPV 44 % [95 % CI 41 %, 49 %], sensitivity 85 % [95 % CI 78 %, 89 %], 72 % of patients reporting ingestion of ≥16 g had a PPC above the 100 mg/L treatment line; PPV 72 % [95% CI 67 %, 77 %], sensitivity 50 % [95 % CI 45 %, 54 %]. Overall, there was moderate correlation ( R = 0.58) between reported paracetamol dose ingested and extrapolated 4-h PPC. Conclusions: There is a positive correlation between reported ingested dose of paracetamol and subsequent chance of a PPC being above a defined treatment line; however, ingested dose of paracetamol alone is a poor risk assessment tool in accurately determining need for treatment with an antidote. [ABSTRACT FROM AUTHOR]

Serovars and bacteriophage (phage) types were determined for 442 isolates of Salmonella enterica from dogs in the UK submitted to the Scottish Salmonella Reference Laboratory from 1954 to 2012. The most frequent serovars were Salmonella Typhimurium (196 isolates; 44.3 per cent), Dublin (40 isolates; 9.0 per cent), Enteritidis (28 isolates; 6.3 per cent), Montevideo (19 isolates; 4.3 per cent), Virchow (10 isolates; 2.3 per cent), Heidelberg (8 isolates; 1.8 per cent) and Derby (8 isolates; 1.8 per cent), along with 55 other recognised serovars among 127 other isolates, and six incompletely classified isolates. Serovars were frequently represented by strains commonly associated with poultry, cattle or pigs and their products. Among 196 Salmonella Typhimurium isolates from dogs, the most frequent phage types (definitive types) were the multiple antimicrobial-resistant strains DT104 (62 isolates), DT204c (18 isolates) and DT193 (8 isolates), along with antimicrobial sensitive wild finch strains DT40 (13 isolates) and DT56 variant (8 isolates). Eleven of 28 isolates of Salmonella Enteritidis were phage type 4. S enterica was frequently recovered from faecal or intestinal samples of dogs with diarrhoea, although many dogs had concurrent infection with other enteric pathogens. Salmonella Dublin was recovered from the brain and/or cerebrospinal fluid of two dogs with meningoencephalitis. Salmonella Kedougou was isolated from the joint fluid of a dog with septic arthritis. Salmonella Typhimurium and Salmonella Dublin were each recovered from the vaginas of bitches that had aborted. Isolates of Salmonella Enteritidis phage types 1, 4 and 8, Salmonella Typhimurium DT104, Salmonella Dublin and Salmonella Indiana were isolated from clinically healthy dogs in households where the same strains were recovered from human beings with diarrhoea. The pattern ampicillinchloramphenicol- spectinomycin-streptomycin-sulfamethoxazole-tetracycline (ACSpSSuT) was the most frequent resistance phenotype and was observed in 44 (13.3 per cent) of 330 isolates. Dogs in the UK are exposed to a wide variety of serovars of S enterica, sometimes associated with clinical disease, and represent a zoonotic risk. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Kenyon S, Pike K, Jones D, Brocklehurst P, Marlow N, Salt A, Taylor D. Has publication of the results of the ORACLE Children Study changed practice in the UK? BJOG 2010;117:1344–1349. Objective To investigate whether publication of the results of the ORACLE Children’s Study, a 7-year follow-up of the ORACLE trial, changed practice with regard to the routine prescription of antibiotics to women with preterm rupture of membranes or spontaneous preterm labour (intact membranes). Design A comparative questionnaire survey of clinical practice in November 2007 (before publication) and March 2009 (after publication). Population Lead obstetricians for labour wards of all maternity units in the UK. Methods Self-administered questionnaires requested information about the routine prescription of antibiotics to women with either preterm rupture of membranes or spontaneous preterm labour (intact membranes). Main outcome measures Change in practice for prescription of antibiotics. Results The response rate was 166/214 (78%) in 2007 and 158/209 (76%) in 2009. In total, 120 maternity units responded on both occasions. For women with preterm rupture of membranes, 162/214 (98%) in 2007 and 151/158 (96%) in 2009 maternity units reported that they prescribed antibiotics, with the majority using erythromycin (98%). For women with spontaneous preterm labour (intact membranes), 35/166 (21%) in 2007 and 25/158 (16%) in 2009 maternity units reported that they routinely prescribed antibiotics. The findings from units who responded on both occasions are similar. Conclusions There has been little change in the reported prescription of antibiotics to women with either preterm rupture of membranes or spontaneous preterm labour following publication of the ORACLE Children’s Study. This suggests that current practice may require updated guidance. [ABSTRACT FROM AUTHOR]

Aripiprazole has recently received approval for the treatment of moderate to severe manic episodes in bipolar I disorder and prevention of new manic episodes in aripiprazole-responsive patients. Aripiprazole differs from other antipsychotics in its pharmacology, and the need for prescribing guidance in the UK was recently identified. A UK multidisciplinary panel was convened in November 2007. This report describes the consensus agreed during the meeting on the optimal approach to prescribing aripiprazole: how best to approach initiation of, and switching to, treatment with aripiprazole and management strategies for side effects. A literature review of the randomised controlled clinical trials of aripiprazole in mania supports these recommendations. Aripiprazole should be initiated at 15 mg/day (range 5-20 mg/day). If necessary, adjunctive medication should be used in early treatment to manage side effects or assist in management of symptoms such as agitation. When switching to aripiprazole, the therapeutic dose of current treatment should be maintained while adding aripiprazole 15 (5-20) mg/day. Only once an effective dose of aripiprazole is reached should previous medication be reduced. Nausea, insomnia and agitation typically resolve within days. Some principles for dosing and switching are provided to assist with a successful treatment outcome with aripiprazole in mania. [ABSTRACT FROM AUTHOR]

The objective of the study was to assess the long-term efficacy of fluoroscopically-guided cervical nerve root block as a non-surgical treatment for cervical radicular pain. This was a retrospective study of 19 consecutive patients who had undergone cervical nerve root blocks over a period of 18 months, at a regional neurosurgery referral centre in the UK. Two of these patients underwent a second procedure; therefore, the number of total nerve root blocks was 21. Data regarding age, sex and diagnosis were obtained from medical records. MR reports formed the basis for imaging findings. Patients were contacted by telephone and post in order to obtain information about their 'pain relief. This was measured by using a 100-point Visual Analogue Scale (VAS). Four points in time were chosen in order to determine the time course of pain relief, i.e. before procedure, at 2 weeks, at 2 months and at 6 months following the procedure. Mean VAS scores at 6 month follow-up were broken up into 3 categories to indicate the level of pain relief. These categories were: VAS decrease of less than 20 points indicating no relief (12 procedures, 57.1%); VAS decrease 20 - 40 points, i.e. moderate relief (three procedures, 14.3%); VAS decrease of greater than 40 points, i.e. significant relief (six procedures, 28.6%). CNRB has limited efficacy for definitive treatment of nerve root pain, but may lead to significant short term relief, in a subgroup of such patients. [ABSTRACT FROM AUTHOR]

This paper presents the findings of research into real-world emission levels of a typical EURO-IV passenger car in the United Kingdom (UK). Four real-world drive cycles representing typical urban driving in the UK were used for the experiments. The work identified that the real-world emission levels of a EURO-IV vehicle in the UK are significantly higher than the certified legislative emission levels. The present work also identified that tailpipe-out carbon monoxide is the most affectedemission specie in a gasoline-powered vehicle for real-world driving conditions. [ABSTRACT FROM AUTHOR]

This paper seeks to summarise BNFL's experience with regard to recent developments in reactor decommissioning and demonstrate how commercial projects in crucial areas of strategy development, project implementation and site restoration are beginning to reduce the risks and uncertainties associated with this important aspect of the nuclear power generation industry. Although the reactor decommissioning market cannot yet be regarded as mature, the key elements of strategy development, waste treatment, dismantling and delicensing have been separately demonstrated as achievable. Together with the implementation of the right organisation, and the developing technology, the risks are being reduced. As more decommissioning projects are delivered, the risks will be reduced further and the confidence of the regulator in the process will improve. This paper sets out to demonstrate this viewpoint. [ABSTRACT FROM AUTHOR]

A prospective collection and analysis of examination marks for three consecutive academic years was undertaken to determine the correlation between the objective structured clinical examination (OSCE) and various other components of medical students' examination, and also to examine how discriminatory the OSCE examination is in the assessment of clinical competence. Out of 388 students, 96·3% passed the examination at the first attempt. Of those who passed, 15·5% had merit while 1·0% had a distinction. When the OSCE component was excluded from the analysis, 11·6% and 2·8% had merits and distinctions, respectively, but when the clinical examination was excluded, there were 17·8% and 6·2% merits and distinctions, respectively. Correlations between the various components of the examination were significant except for that between the clinical examination and the project. Although the OSCE and clinical components of examinations for clinical students are complementary, the OSCE component awards more merit and distinction categories. Although there were statistically significant correlations between the various components of the examination, only 11% of the variability in clinical examination scores could be explained by the performance in OSCE suggesting that the different components are testing different aspects of the student's clinical competence. Completely replacing clinicals with an OSCE may not necessarily be the best way of assessing medical students' clinical competence. [ABSTRACT FROM AUTHOR]

The article presents a case of a degenerative brain disorder Korsakov's syndrome which is caused by craniopharyngioma. The case presented emphasizes the need to undertake full investigation of any amnestic syndrome that is without a history of alcoholism. The case involves a 52-year-old British woman admitted at Guy's Maudsley Neurosurgical Unit in England, who demonstrated an amnestic behavior. She came from a family remarkable for the extreme frequency of neoplastic disease in its members. In analyzing the patient's case, the authors diagnosed the patient with Korsakov's syndrome due to the clinical features she demonstrated, which is caused by the rapid development and early presentation of amnestic state in the history of tumor.

The article examines the hypertensive interactions between monoamine oxidase inhibitors and foodstuffs during treatment in Great Britain. The study is aimed at defining the characterisitcs of the reaction and the factors in patients or treatment which influence susceptibility. It uses animals when it conducted the pharmacological tests, where they found an increase in heart beat accompanied by throbbing of the blood vessels in the neck and followed within minutes by a severe pulsating headache of sudden onset after the drug was administered. This article offers an overview of the results as well as the methods used in the study.

The article examines the causes of Salmonella in cats in Great Britain. It states that the Salmonella Typhimurium have been associated with enteric disease in cats. It suggests that the known sources of infection with Salmonella species for cats include ingestion of raw meat and some processed foods, hunting rodents, and exposure to reptiles. Such species were characterised from 100 cats from 1955 to 2007.

The article discusses the isolation of avian strains of Salmonella enterica serovar Typhimurium from nine cats with enteric disease in Great Britain. S. typhimurium phage types DT40 or DT56V were isolated from fecal samples or intestinal contents of the cats. All cats have a history of hunting small birds. The affected cats were dull, pyrexic, anorexic and often developed diarrhea. [ABSTRACT FROM AUTHOR]

Presents congenital cataract as a cause of preventable blindness in children in Great Britain. Recommended age for surgical treatment; Description of Amblyopia; Clinical diagnoses of the disease.

Bovine spongiform encephalopathy (BSE) clearly originated in the UK, where there have now been more than 180 000 cases. However, through the exportation of cattle and cattle-feed additives from the UK, BSE also became established to a lesser extent in other European countries. There is current concern that BSE might have been distributed more widely as a result of the exportation of cattle or BSE-infected feed or foodstuff not only from the UK but also from other European countries that later became affected. It is now recognized that the transmissible agent that causes BSE also causes a new variant form of Creutzfeldt–Jakob disease (vCJD) in humans, and the evidence for this is presented. This probably resulted from dietary exposure to the bovine agent, and the potential role of mechanically recovered meat is discussed. There is a brief discussion on the controversial issue of the nature of the causal agents of diseases like BSE and vCJD. Whether or not sheep or goats could have become infected with BSE, and whether they represent a human health hazard, is also debated. Finally, the question of the control of BSE, and consequently vCJD, is discussed with regard to the rigorous application of the relevant regulations. [ABSTRACT FROM AUTHOR]

While clozapine has risks, relative risk of fatality is overestimated. The UK pharmacovigilance programme is efficient, but comparisons with other drugs can mislead because of reporting variations. Clozapine actually lowers mortality, partly by reducing schizophrenia-related suicides, but preventable deaths still occur. Clozapine should be used earlier and more widely, but there should be better monitoring and better management of toxicity.

Background and Aim: There is increasing evidence linking antipsychotic use with pneumonia, but limited evidence of an effect on pneumonia-related outcomes such as mortality. In this study, we aimed to examine the association of pneumonia-related death with specific antipsychotic exposure., Method: Deaths analysed were those reported to a UK-based drug-related deaths database, the National Programme on Substance Abuse Deaths (NPSAD), between 1997 and September 2020. We conducted a case-control study with cases defined as pneumonia-related deaths and controls as cases with alternative causes of death. Cases were analysed by considering drugs detected at post-mortem (PM) and by drugs prescribed to the deceased at the time of their death with calculated odds ratios (ORs) adjusted to account for confounders., Results: There were 2467 PM cases and 40,128 controls; 1818 prescribed cases and 28,018 controls. Second generation antipsychotics (SGAs) were robustly associated with an increased risk of pneumonia-related death compared with those not prescribed or taking antipsychotics (PM detection adjusted OR [AOR] 1·34 [95% CI 1·15-1·55]; prescribed AOR 1·28 [95% CI 1·11-1·49]). First generation antipsychotics had no clear association with death from pneumonia (PM detection AOR 1·06 [95% CI 0·77-1·47]; prescribed AOR 0·91 [95% CI 0·71-1·17]). Amongst SGAs, olanzapine was associated with an increased risk of death due to pneumonia (PM detection AOR 1·49 [95% CI 1·22-1·82]; prescribed AOR 1·44 [95% CI 1·18-1·76]) as was quetiapine (PM detection AOR 1·34 [95% CI 1·07-1·66]; prescribed AOR 1·28 [95% CI 1·01-1·64])., Conclusion: Olanzapine and quetiapine were found to increase the risk of pneumonia-related death in this NPSAD sample to a clinically important extent., (© 2023 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Background: Clozapine is uniquely effective in treatment-resistant psychosis. In the UK, patients must discontinue clozapine indefinitely if they are placed on the Central Non-Rechallenge Database (CNRD) after their haematological parameters fall below particular thresholds. Under exceptional circumstances, patients can be rechallenged on clozapine under an off-licence agreement. In the USA in 2015, restrictive practice was discontinued to allow greater flexibility for clozapine maintenance. The absolute neutrophil count leading to treatment interruption was lowered from less than 1·5 × 10 9 /L to less than 1·0 × 10 9 /L and platelet and white cell count monitoring were ceased. We aimed to investigate the implications of a similar policy change on clozapine use in the UK., Methods: This was a modelling study of all patients registered on the UK CNRD. First, we determined the proportion of patients placed on the database in the UK who would have had to discontinue clozapine treatment under the US Food and Drug Administration (FDA) criteria. Second, we compared the haematological characteristics of patients who did or did not meet FDA criteria for discontinuing clozapine, including the time to registration from clozapine initiation and the proportion of cases of severe neutropenia at registration. Third, we investigated the success rates of clozapine re-challenge for patients that had been placed on the CNRD. Successful rechallenge was defined as no recurrence of CNRD registration., Findings: Between May 2, 2002 and March 1, 2021, 3731 patients were placed on the CNRD, with a mean age of 47 years (SD 15), including 1420 (38%) women and 2311 (62%) men, of whom 3089 (83%) were White, 360 (10%) were Black, 190 (5%) were Asian, and 92 (2%) were classified as other. 566 (15%) of 3731 patients met the equivalent criteria for clozapine discontinuation under the FDA guidelines. The median time to CNRD registration from clozapine initiation was 1·6 years (IQR 0·2-4·9). Data for 519 rechallenged patients were examined; 419 (81%) were successful. Clozapine rechallenge success rates were broadly similar between individuals who did not meet the US CNRD registration criteria (36 [78%] of 46) and those who did meet the criteria (383 [81%] of 473)., Interpretation: Implementing the revised FDA monitoring criteria in the UK would substantially reduce clozapine discontinuation for haematological reasons, which would greatly improve the mental health outcomes of these patients without having a major effect on their physical health., Funding: None., Competing Interests: Declaration of interests DT has received speaker honoraria and research funding from Janssen, Recordati, and Sunovion, and has stock in Psychiatric Genetic Testing outside the submitted work. JHM has received research funding from Lundbeck outside the submitted work. All other authors declare no competing interests. EO is part funded by the Maudsley Charity. JHM, FG, and PM are part funded by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. FG is part supported by the Maudsley Charity and the NIHR Applied Research Collaboration South London at King's College Hospital NHS Foundation Trust., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

New technologies, including pharmaceuticals and medical devices, can improve treatment options in healthcare but also bring concerns about rising healthcare costs. We undertake a narrative review of the United Kingdom's (UK) approach to appraising new health technologies. We find that the National Institute for Health and Care Excellence (NICE), Scottish Medicines Consortium (SMC) and All Wales Medicines Strategy Group (AWMSG) have contributed to the UK's robust and transparent approach towards the evaluation of new health technologies using the cost per QALY approach. However, there are limitations to this approach including several external benefits not captured, bias against less treatable diseases, and deciding the appropriate level of the threshold. NICE, SMC, and AWMSG have attempted to overcome some of these limitations by considering additional factors such as end-of-life criteria, highly specialised treatments, and populations that experience unmet need. Looking to the future, the advent of 'personalised' and 'genomic' medicine, will likely mean the UK has to accommodate an increasing number of 'step-change' and 'highly specialised' technologies as well as respond to changes in pharmaceutical licensing and increasing use of real-world evidence., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this manuscript to declare., (Copyright © 2022. Published by Elsevier B.V.)

Background: To examine the risk of infection in patients prescribed clozapine compared with patients prescribed paliperidone palmitate long-acting injection (PPLAI)., Method: A retrospective, 1-year, cohort study conducted on events occurring in eligible patients beginning treatment for the first time with clozapine or PPLAI between June 2017 and June 2019 in a UK mental health trust providing in-patient and out-patient services., Results: The study included 64 patients starting clozapine and 120 patients starting PPLAI. Incidence of infection was greater in clozapine starters than in PPLAI starters (28% vs 6%; p  = 0.001; adjusted odds ratio 5.82 (95% confidence interval (CI) = 2.15-15.76, p  = 0.001). Infectious episodes in clozapine patients were not related to changes in neutrophil counts. Incident infection in the clozapine group was highest in the first 3 months of treatment. The most commonly reported infection in the clozapine group was chest infection; however, the majority of infections were non-chest-related., Conclusion: Patients starting clozapine showed a substantially increased likelihood of infection compared with patients starting PPLAI.

Importance: People with psychotic disorders have an increased risk of vitamin D deficiency, which is evident during first-episode psychosis (FEP) and associated with unfavorable mental and physical health outcomes., Objective: To examine whether vitamin D supplementation contributes to improved clinical outcomes in FEP., Design, Setting, and Participants: This multisite, double-blind, placebo-controlled, parallel-group randomized clinical trial from the UK examined adults 18 to 65 years of age within 3 years of a first presentation with a functional psychotic disorder who had no contraindication to vitamin D supplementation. A total of 2136 patients were assessed for eligibility, 835 were approached, 686 declined participation or were excluded, 149 were randomized, and 104 were followed up at 6 months. The study recruited participants from January 19, 2016, to June 14, 2019, with the final follow-up (after the last dose) completed on December 20, 2019., Interventions: Monthly augmentation with 120 000 IU of cholecalciferol or placebo., Main Outcomes and Measures: The primary outcome measure was total Positive and Negative Syndrome Scale (PANSS) score at 6 months. Secondary outcomes included total PANSS score at 3 months; PANSS positive, negative, and general psychopathology subscale scores at 3 and 6 months; Global Assessment of Function scores (for symptoms and disability); Calgary Depression Scale score, waist circumference, body mass index, and glycated hemoglobin, total cholesterol, C-reactive protein, and vitamin D concentrations at 6 months; and a planned sensitivity analysis in those with insufficient vitamin D levels at baseline., Results: A total of 149 participants (mean [SD] age, 28.1 (8.5) years; 89 [59.7%] male; 65 [43.6%] Black or of other minoritized racial and ethnic group; 84 [56.4%] White [British, Irish, or of other White ethnicity]) were randomized. No differences were observed in the intention-to-treat analysis in the primary outcome, total PANSS score at 6 months (mean difference, 3.57; 95% CI, -1.11 to 8.25; P = .13), or the secondary outcomes at 3 and 6 months (PANSS positive subscore: mean difference, -0.98; 95% CI, -2.23 to 0.27 at 3 months; mean difference, 0.68; 95% CI, -0.69 to 1.99 at 6 months; PANSS negative subscore: mean difference, 0.68; 95% CI, -1.39 to 2.76 at 3 months; mean difference, 1.56; 95% CI, -0.31 to 3.44 at 6 months; and general psychopathology subscore: mean difference, -2.09; 95% CI, -4.36 to 0.18 at 3 months; mean difference, 1.31; 95% CI, -1.42 to 4.05 at 6 months). There also were no significant differences in the Global Assessment of Function symptom score (mean difference, 0.02; 95% CI, -4.60 to 4.94); Global Assessment of Function disability score (mean difference, -0.01; 95% CI, -5.25 to 5.23), or Calgary Depression Scale score (mean difference, -0.39; 95% CI, -2.05 to 1.26) at 6 months. Vitamin D levels were very low in the study group, especially in Black participants and those who identified as another minoritized racial and ethnic group, 57 of 61 (93.4%) of whom had insufficient vitamin D. The treatment was safe and led to a significant increase in 25-hydroxyvitamin D concentrations., Conclusions and Relevance: In this randomized clinical trial, no association was found between vitamin D supplementation and mental health or metabolic outcomes at 6 months. Because so few patients with FEP were vitamin D replete, the results of this study suggest that this group would benefit from active consideration in future population health strategies., Trial Registration: isrctn.org Identifier: ISRCTN12424842.

Background and Aims: In the United Kingdom, patients on clozapine whose hematological parameters fall below certain thresholds are placed on the Central Non-Rechallenge Database (CNRD), meaning that they cannot be prescribed clozapine again except under exceptional circumstances. This practice was discontinued in the United States in 2015 by expanding the hematological monitoring guidelines, allowing more patients to receive clozapine. Our objective was to investigate the implications this policy change would have on clozapine utilization in the United Kingdom., Methods: This was an observational, retrospective analysis of patients registered on the CNRD in a large mental health trust. The first objective was to compare the number of patients placed on the CNRD under the United Kingdom and the US Food and Drug Administration (FDA) criteria. The second objective was to explore the hematological and clinical outcomes of CNRD patients. The third objective was to investigate the hematological outcomes of patients rechallenged on clozapine after nonrechallengeable status., Results: One hundred and fifteen patients were placed on CNRD from 2002 to 2019, of whom 7 (6%) met the equivalent criteria for clozapine discontinuation under the FDA guidelines. Clinical outcomes, as measured by the Clinical Global Impression-Severity scale, were worse 3 months after clozapine cessation than on clozapine (t = -7.4862; P < .001). Sixty-two (54%) patients placed on CNRD were rechallenged. Fifty-nine of those (95%) were successfully rechallenged; 3 patients were placed back on CNRD, only one of which would have had to stop clozapine again under FDA criteria., Conclusion: Implementation of the updated FDA's monitoring criteria in the United Kingdom would significantly reduce clozapine discontinuation due to hematological reasons. The evidence suggests an urgent need for revising the UK clozapine monitoring guidelines to improve outcomes in treatment-resistant schizophrenia., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Health information technology can support the development of national learning health and care systems, which can be defined as health and care systems that continuously use data-enabled infrastructure to support policy and planning, public health, and personalisation of care. The COVID-19 pandemic has offered an opportunity to assess how well equipped the UK is to leverage health information technology and apply the principles of a national learning health and care system in response to a major public health shock. With the experience acquired during the pandemic, each country within the UK should now re-evaluate their digital health and care strategies. After leaving the EU, UK countries now need to decide to what extent they wish to engage with European efforts to promote interoperability between electronic health records. Major priorities for strengthening health information technology in the UK include achieving the optimal balance between top-down and bottom-up implementation, improving usability and interoperability, developing capacity for handling, processing, and analysing data, addressing privacy and security concerns, and encouraging digital inclusivity. Current and future opportunities include integrating electronic health records across health and care providers, investing in health data science research, generating real-world data, developing artificial intelligence and robotics, and facilitating public-private partnerships. Many ethical challenges and unintended consequences of implementation of health information technology exist. To address these, there is a need to develop regulatory frameworks for the development, management, and procurement of artificial intelligence and health information technology systems, create public-private partnerships, and ethically and safely apply artificial intelligence in the National Health Service., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The demographics of the UK population are changing and so is the need for health care. In this Health Policy, we explore the current health of the population, the changing health needs, and future threats to health. Relative to other high-income countries, the UK is lagging on many health outcomes, such as life expectancy and infant mortality, and there is a growing burden of mental illness. Successes exist, such as the striking improvements in oral health, but inequalities in health persist as well. The growth of the ageing population relative to the working-age population, the rise of multimorbidity, and persistent health inequalities, particularly for preventable illness, are all issues that the National Health Service (NHS) will face in the years to come. Meeting the challenges of the future will require an increased focus on health promotion and disease prevention, involving a more concerted effort to understand and tackle the multiple social, environmental, and economic factors that lie at the heart of health inequalities. The immediate priority of the NHS will be to mitigate the wider and long-term health consequences of the COVID-19 pandemic, but it must also strengthen its resilience to reduce the impact of other threats to health, such as the UK leaving the EU, climate change, and antimicrobial resistance., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Competing Interests: Declaration of interests AzS reports grants from Health Data Research UK BREATHE Hub, outside the submitted work. BC reports in-kind contributions to research projects from Roche Diagnostics and iRhythm, outside the submitted work. BDF reports grants from Cerner and personal fees from Pfizer, outside the submitted work. JNN is employed by Public Health England. MF is the chair of NHS Wales Shared Services Partnership Committee. ML is the chair of the Cwm Taf Morgannwg University Health Board. MoW was a non-executive director of NHS Lothian between February, 2015, and February, 2021. RH is a member of the Health Inequality Advisory Board of Public Health England, governor of the Health Foundation, interim chair at the Food Standards Agency, and Advisory Board member of National Institute for Health Research School of Public Health Research. RR is supported by National Institute for Health Research Applied Research Collaboration North Thames. The views expressed in this publication are those of the author and not necessarily those of the National Institute for Health Research or the Department of Health and Social Care. All other authors declare no competing interests.

Objectives: To determine the differences in information between prescribing guidelines and drug labeling, as well as to compare the approval of psychotropic medicines for major depression in pediatric patients ("pediatric depression") across countries. Methods: The recommendations of The Maudsley Prescribing Guidelines in Psychiatry (MPGP) for the treatment of pediatric depression (<18 years) were compared against the regulatory-approved drug-labeling documents from the United Kingdom, Australia, New Zealand, Canada, and the United States. The use of medicines outside of their regulatory approval is defined as off-label use, so differences between the drug labeling and MPGP were characterized according to unapproved age, indication, dosage, or route of administration. Information in the drug labeling was also compared across countries. Results: MPGP provides recommendations for 6 medicines for the treatment of pediatric depression, for which, 30 drug labeling were retrieved. Three of 30 drug labeling were consistent with MPGP recommendations (fluoxetine in the United Kingdom, fluoxetine and escitalopram in the United States). Differences in information between MPGP and the drug labeling were identified in 26 of 30 drug labeling analyzed, most often due to age (24/26) followed by indication (2/26). No differences pertaining to dosage or route of administration information were identified. The number of approved psychotropic medicines varied across the studied countries and we found cross-country discrepancies in information in the drug labeling. Conclusion: Significant differences in information exists between MPGP and the drug labeling for psychotropic medicines for pediatric depression, due to unapproved ages or indications. Additionally, approval information in the drug labeling are not consistent across countries. Further research into reasons for variability and impact on practice may be warranted.

Objectives: The Medicines and Healthcare Products Regulatory Agency in the United Kingdom (UK) formally reclassified sildenafil citrate 50 mg tablets as a pharmacy medicine (sildenafil-P) in 2017 for adult men with erectile dysfunction (ED). A 1-year prospective real-world observational study was conducted to track men's health behaviour, particularly their healthcare resource utilisation (HCRU) and quality of life (QoL) before and after the availability of sildenafil-P., Methods: Adult men with ED aged ≥18 years provided data at baseline (prior to launch of sildenafil-P) and every 3 months after the launch. Demographics, health characteristics, treatments at baseline and HCRU, including number of pharmacist and physician/nurse practitioner visits over time are reported. QoL-related outcomes were assessed via the Self-Esteem and Relationship Questionnaire (SEAR), 2-Item Patient Health Questionnaire and ratings of sexual satisfaction. Generalised linear models were used to assess the association of sildenafil-P use with total physician/nurse practitioner and pharmacist visits and QoL-related outcomes at 12 months., Results: Overall, 1162 men completed the survey at all 5 time points. The mean ± SD age was 59.02 ± 12.06 years; 55.42% reported having a moderate-to-severe ED. Hypertension (37.52%) and hypercholesterolaemia (31.50%) were the most common risk factors for ED. At baseline, 62.99% were not using any ED treatment. After adjusting for baseline visits/other covariates, mean physician/nurse practitioner (3.68 vs 2.87; P = .003) and pharmacist visits for any reason (2.10 vs 1.34; P < .001) at 12 months were significantly higher among sildenafil-P users than those who never used sildenafil-P. Sildenafil-P users also had significantly higher SEAR total and domain (sexual relationship and self-esteem) scores at 12 months., Conclusion: Following the reclassification to a pharmacy medicine in the UK, sildenafil-P was associated with a higher number of physician/nurse practitioner and pharmacist visits for any reason. Sildenafil-P use was also associated with better QoL, although group differences were small in magnitude., (© 2020 The Authors. International Journal of Clinical Practice published by John Wiley & Sons Ltd.)

Introduction: Major depressive disorder (MDD) is a globally prevalent chronic psychiatric illness with a significant disease impact. As many as 30% of patients with MDD do not adequately respond to two therapies and are considered to be treatment resistant. This study aimed to quantify healthcare costs associated with treatment resistant depression (TRD) in the UK., Methods: A retrospective chart review of patients with TRD was conducted in primary and secondary care settings over a 2 year period. Data abstracted from medical records of patients included demographics, clinical characteristics and healthcare resource utilization (HCRU; number of consultations, use of Crisis Resolution and Home Treatment Teams [CRHTTs], non-drug and drug interventions, and hospitalizations). HCRU per patient per month (28 days) was calculated for three health states: major depressive episode (MDE), remission and recovery. Unit costs were from the British National Formulary (BNF) and the Personal Social Services Research Unit (PSSRU)., Results: A total of 295 patients with TRD were recruited between January 2016 and May 2018. The mean age of the total sample was 43.3 years; 60.3% were female. Costs per patient, per 28 days, were highest in the MDE state, with the average cost (£992) mainly driven by consultations, non-drug treatment, hospitalizations and CRHTT, with a considerable fall in costs as patients moved into remission and subsequent recovery., Conclusion: The results suggest that antidepressant treatments for TRD that are more effective in reducing the time spent in an MDE health state, and helping patients achieve remission and recovery, are essential for reducing the overall HCRU and costs in patients with TRD. Cost of TRD in the UK Strengths and limitations of this study This observational study of TRD is the first to assess the HCRU impact associated with different predefined health states. Using retrospective data from both primary and secondary care physicians from regions across the UK ensures a representative real-world patient population. One limitation is that the selection of patients is based on criteria that define TRD that rely on physician judgement. Although the study captures direct HCRU costs, the indirect costs of lost productivity and care are not included in the overall burden. This study has defined the current clinical management of patients with TRD in the UK and provides an estimate of the associated HCRU and associated costs.

Aims: Co-design implies genuine partnership in the generation of knowledge between service users and researchers. Service user involvement in research has been encouraged in government policy, but it is rarely achieved, especially at trial initial stages. Co-designed with service users, we adapted existing manualised social cognition intervention for people with a first episode of psychosis to a virtual world environment., Methods: We invited a group of young people who have used mental health services to co-design a virtual environment to deliver an accessible social cognition intervention to a hard to engage service user group. We used an iterative process with young service users and the design team that included developing initial ideas, creating a prototype and testing the virtual world., Results: Twenty young service users of local mental healthcare services provided feedback on the design and delivery of the intervention. Reflecting the demographic of the sample, young people felt the virtual environment should be familiar, urban spaces, akin to therapy rooms or classrooms they have used in real-life situations rather than non-traditional therapy spaces that were initially proposed., Conclusion: The co-design process led to the development of a specific design, approach and protocol to be tested in a proof-of-concept trial. Young service users were integral to an agile and iterative design. Technological innovations should be routinely co-designed and co-produced if they are to realise their potential to deliver acceptable and affordable mental health interventions., (© 2019 John Wiley & Sons Australia, Ltd.)

Background: The first episode of psychosis is a critical period in the emergence of cardiometabolic risk., Aims: We set out to explore the influence of individual and lifestyle factors on cardiometabolic outcomes in early psychosis., Method: This was a prospective cohort study of 293 UK adults presenting with first-episode psychosis investigating the influence of sociodemographics, lifestyle (physical activity, sedentary behaviour, nutrition, smoking, alcohol, substance use) and medication on cardiometabolic outcomes over the following 12 months., Results: Rates of obesity and glucose dysregulation rose from 17.8% and 12%, respectively, at baseline to 23.7% and 23.7% at 1 year. Little change was seen over time in the 76.8% tobacco smoking rate or the quarter who were sedentary for over 10 h daily. We found no association between lifestyle at baseline or type of antipsychotic medication prescribed with either baseline or 1-year cardiometabolic outcomes. Median haemoglobin A1c (HbA1c) rose by 3.3 mmol/mol in participants from Black and minority ethnic (BME) groups, with little change observed in their White counterparts. At 12 months, one-third of those with BME heritage exceeded the threshold for prediabetes (HbA1c >39 mmol/mol)., Conclusions: Unhealthy lifestyle choices are prevalent in early psychosis and cardiometabolic risk worsens over the next year, creating an important window for prevention. We found no evidence, however, that preventative strategies should be preferentially directed based on lifestyle habits. Further work is needed to determine whether clinical strategies should allow for differential patterns of emergence of cardiometabolic risk in people of different ethnicities.

Background: Antimicrobial treatment is common at end of life. A treatment escalation/limitation plan (TELP) offers the opportunity to avoid non-beneficial treatment in critically ill patients. Our aim was to evaluate antimicrobial prescribing in terminally ill patients, and assess whether it was modified using a TELP., Methods: Appropriateness of antimicrobial treatment was audited using a priori criteria in 94 consecutive hospital deaths. Prescribing in patients whose death was expected/unexpected, and who had a TELP with/without a 'ceiling' for antimicrobials, were compared., Results: Twenty three of 94 patients (24.5%) were receiving antimicrobials at time of death. This was not influenced by evidence of infection or whether death was expected. The use of a TELP (n = 81) with an antimicrobial 'ceiling' (28 with, 53 without) was associated with a significant reduction in antimicrobials administered (28.6% vs 81.1%; p < 0.0005)., Conclusions: Many complex factors contribute to antimicrobial misuse at end of life. An appropriately constructed TELP reduces inappropriate prescribing., Competing Interests: No conflict of interests declared

Background Opioid substitution therapy involves prescribing of medical substitutes like methadone and buprenorphine to patients who are addicted to opioids. The majority of opioid substitution therapy dispensing in the UK is done by community pharmacists and they often see the patients on daily basis. It is unknown to what extent community pharmacists implement the policy to prevent overdose in patients receiving such treatment. Objective To explore what UK community pharmacists think about their role in preventing opium substitution-related deaths, their understanding of the risks associated with this substitution therapy and their views on what else community pharmacists could do to reduce such deaths. Setting Twenty four community pharmacists from two areas in UK (Worcestershire and Bath and North East Somerset). Method  Between January and March 2013, community pharmacists providing opoin substitution therapy were interviewed in their pharmacy, using semi-structured interviews. Interpretative Phenomenology Analysis was used to analyse the data. Main outcome measure Thematically organised description of professional practice as reported by the participants against the clinical/practice guidance for opioid substitution therapy in UK. Results While participants felt their role to be essential in providing the service, they did not feel part of an integrated system. Participants' ability to act in risk situations was affected by their knowledge, confidence in intervening in such situation, as well as the support they receive in providing the service. Conclusion Participants reported large differences in how 'opioid substitution therapy' services are provided in community pharmacy. Lack of knowledge among some pharmacists and lack of support in providing the service resulted in some patients at high risk not having their risks acted upon.

Background: Minocycline has neurological anti-inflammatory properties and has been hypothesised to have antipsychotic effects., Aim: The aim of this study was to investigate, using routinely collected United Kingdom primary health care data, whether adolescent men and women are more or less likely to receive an urgent psychiatric referral during treatment for acne with minocycline compared with periods of non-treatment., Method: A self-controlled case series using United Kingdom Clinical Practice Research Datalink to calculate the incidence rate ratio of urgent psychiatric referrals for individuals, comparing periods during which minocycline was prescribed with unexposed periods, adjusted for age., Results: We found 167 individuals who were at the time exposed to minocycline for a mean of 99 days and who received an urgent psychiatric referral. There was no difference in psychiatric referral risk during periods of exposure compared with periods of non-exposure: incidence rate ratio first 6 weeks of exposure 1.96, 95% confidence interval 0.82-4.71, p=0.132; incidence rate ratio remaining exposure period=1.97, 95% confidence interval 0.86-4.47, p=0.107., Conclusions: We found no evidence in support of a protective effect of minocycline against severe psychiatric symptoms in adolescence.