COVID-19 Pandemic in the United Kingdom

Objectives To describe epidemiological data on cases of COVID-19 and the spread of Severe Acute Respiratory Syndrome Coronavirus 2 in the United Kingdom (UK), and the subsequent policy and technological response to the pandemic, including impact on healthcare, business and the economy. Methods Epidemiological, business and economic data were extracted from official government sources covering the period 31st January to 13th August 2020; healthcare system data up to end of June 2019. Results UK-wide COVID-19 cases and deaths were 313,798 and 46,706 respectively (472 cases and 70 deaths per 100,000 population) by 12th August. There were regional variations in England, with London and North West (756 and 666 cases per 100,000 population respectively) disproportionately affected compared with other regions. As of 11th August, 13,618,470 tests had been conducted in the UK. Increased risk of mortality was associated with age (≥60 years), gender (male) and BAME groups. Since onset of the pandemic, emergency department attendance, primary care utilisation and cancer referrals and inpatient/outpatient referrals have declined; emergency ambulance and NHS111 calls increased. Business sectors most impacted are the arts, entertainment and recreation, followed by accommodation and food services. Government interventions aimed at curtailing the business and economic impact have been implemented, but applications for state benefits have increased. Conclusions The impact of COVID-19 on the UK population, health system and economy has been profound. More data are needed to implement the optimal policy and technological responses to preventing further spikes in COVID-19 cases, and to inform strategic planning to manage future pandemics

Functional Investigation of Iron-Responsive Microsomal Proteins, including MirC, in Aspergillus fumigatus

The functionality of many microsome-associated proteins which exhibit altered abundance in response to iron limitation in Aspergillus fumigatus is unknown. Here, we generate and characterize eight gene deletion strains, and of most significance reveal that MirC (AFUA_2G05730) contributes to the maintenance of intracellular siderophore [ferricrocin (FC)] levels, augments conidiation, confers protection against oxidative stress, exhibits an intracellular localization and contributes to fungal virulence in the Galleria mellonella animal model system. FC levels were unaffected following deletion of all other genes encoding microsome-associated proteins. MirC does not appear to play a role in either siderophore export from, or uptake into, A. fumigatus. Label-free quantitative proteomic analysis unexpectedly revealed increased abundance of siderophore biosynthetic enzymes. In addition, increased expression of hapX (7.2 and 13.8-fold at 48 and 72 h, respectively; p < 0.001) was observed in ΔmirC compared to wild-type under iron-replete conditions by qRT-PCR. This was complemented by significantly elevated extracellular triacetylfusarinine C (TAFC; p < 0.01) and fusarinine C (FSC; p < 0.05) siderophore secretion. We conclude that MirC plays an important role in FC biosynthesis and contributes to the maintenance of iron homeostasis in A. fumigatus

Systematic Review of Economic Models Used to Compare Techniques for Detecting Peripheral Arterial Disease

Background and objective Peripheral arterial disease (PAD) is a common condition, in which atherosclerotic narrowing in the arteries restricts blood supply to the leg muscles. In order to support future model-based economic evaluations comparing methods of diagnosis in this area, a systematic review of economic modelling studies was conducted. Methods A systematic literature review was performed in June 2017 to identify model-based economic evaluations of diagnostic tests to detect PAD, with six individual databases searched. The review was conducted in accordance with the methods outlined in the Centre for Reviews and Dissemination’s guidance for undertaking reviews in healthcare, and appropriate inclusion criteria were applied. Relevant data were extracted, and studies were quality assessed. Results Seven studies were included in the final review, all of which were published between 1995 and 2014. There was wide variation in the types of diagnostic test compared. The majority of the studies (six of seven) referenced the sources used to develop their model, and all studies stated and justified the structural assumptions. Reporting of the data within the included studies could have been improved. Only one identified study focused on the cost-effectiveness of a test typically used in primary care. Conclusions This review brings together all applied modelling methods for tests used in the diagnosis of PAD, which could be used to support future model-based economic evaluations in this field. The limited modelling work available on tests typically used for the detection of PAD in primary care, in particular, highlights the importance of future work in this area

Surgical treatments for women with stress urinary incontinence : a systematic review of economic evidence

Acknowledgements We would like to acknowledge all those involved in the wider study exploring the effectiveness and cost-effectiveness of surgical treatments for women with stress urinary incontinence. Funding This research was commissioned by the NIHR HTA Programme as project number 15/09/06. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care, UK. The funders were not actively involved in the research process at any stage. The study design, collection, analysis and interpretation of data, the writing of the manuscript and the decision to submit it for publication were all performed independent of the funders.Peer reviewedPublisher PD

Economic evaluation of surgical treatments for women with stress urinary incontinence : a cost-utility and value of information analysis

Acknowledgements: We would like to acknowledge all those involved in the wider study exploring the effectiveness and cost-effectiveness of surgical treatments for women with stress urinary incontinence. Funding: This research was commissioned by the NIHR HTA Programme as project number 15/09/06. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care, UK. The funders were not actively involved in the research process at any stage. The study design, collection, analysis and interpretation of data, the writing of the manuscript and the decision to submit it for publication were all performed independent of the funders.Peer reviewedPublisher PD

Treatments for hyperemesis gravidarum and nausea and vomiting in pregnancy:A systematic review and economic assessment

Background: Nausea and vomiting in pregnancy (NVP) affects up to 85% of all women during pregnancy, but for the majority self-management suffices. For the remainder, symptoms are more severe and the most severe form of NVP – hyperemesis gravidarum (HG) – affects 0.3–1.0% of pregnant women. There is no widely accepted point at which NVP becomes HG. Objectives: This study aimed to determine the relative clinical effectiveness and cost-effectiveness of treatments for NVP and HG. Data sources: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, PsycINFO, Commonwealth Agricultural Bureaux (CAB) Abstracts, Latin American and Caribbean Health Sciences Literature, Allied and Complementary Medicine Database, British Nursing Index, Science Citation Index, Social Sciences Citation Index, Scopus, Conference Proceedings Index, NHS Economic Evaluation Database, Health Economic Evaluations Database, China National Knowledge Infrastructure, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects were searched from inception to September 2014. References from studies and literature reviews identified were also examined. Obstetric Medicine was hand-searched, as were websites of relevant organisations. Costs came from NHS sources. Review methods: A systematic review of randomised and non-randomised controlled trials (RCTs) for effectiveness, and population-based case series for adverse events and fetal outcomes. Treatments: vitamins B6 and B12, ginger, acupressure/acupuncture, hypnotherapy, antiemetics, dopamine antagonists, 5-hydroxytryptamine receptor antagonists, intravenous (i.v.) fluids, corticosteroids, enteral and parenteral feeding or other novel treatment. Two reviewers extracted data and quality assessed studies. Results were narratively synthesised; planned meta-analysis was not possible due to heterogeneity and incomplete reporting. A simple economic evaluation considered the implied values of treatments. Results: Seventy-three studies (75 reports) met the inclusion criteria. For RCTs, 33 and 11 studies had a low and high risk of bias respectively. For the remainder (n = 20) it was unclear. The non-randomised studies (n = 9) were low quality. There were 33 separate comparators. The most common were acupressure versus placebo (n = 12); steroid versus usual treatment (n = 7); ginger versus placebo (n = 6); ginger versus vitamin B6 (n = 6); and vitamin B6 versus placebo (n = 4). There was evidence that ginger, antihistamines, metoclopramide (mild disease) and vitamin B6 (mild to severe disease) are better than placebo. Diclectin® [Duchesnay Inc.; doxylamine succinate (10 mg) plus pyridoxine hydrochloride (10 mg) slow release tablet] is more effective than placebo and ondansetron is more effective at reducing nausea than pyridoxine plus doxylamine. Diclectin before symptoms of NVP begin for women at high risk of severe NVP recurrence reduces risk of moderate/severe NVP compared with taking Diclectin once symptoms begin. Promethazine is as, and ondansetron is more, effective than metoclopramide for severe NVP/HG. I.v. fluids help correct dehydration and improve symptoms. Dextrose saline may be more effective at reducing nausea than normal saline. Transdermal clonidine patches may be effective for severe HG. Enteral feeding is effective but extreme method treatment for very severe symptoms. Day case management for moderate/severe symptoms is feasible, acceptable and as effective as inpatient care. For all other interventions and comparisons, evidence is unclear. The economic analysis was limited by lack of effectiveness data, but comparison of costs between treatments highlights the implications of different choices. Limitations: The main limitations were the quantity and quality of the data available. Conclusion: There was evidence of some improvement in symptoms for some treatments, but these data may not be transferable across disease severities. Methodologically sound and larger trials of the main therapies considered within the UK NHS are needed. Study registration: This study is registered as PROSPERO CRD42013006642. Funding: The National Institute for Health Research Health Technology Assessment programme

Evaluation of a complex healthcare intervention to increase smoking cessation in pregnant women: interrupted time series analysis with economic evaluation

Objectives To evaluate the effectiveness of a complex intervention to improve referral and treatment of pregnant smokers in routine practice, and to assess the incremental costs to the National Health Service (NHS) per additional woman quitting smoking. Design Interrupted time series analysis of routine data before and after introducing the intervention, within-study economic evaluation. Setting Eight acute NHS hospital trusts and 12 local authority areas in North East England. Participants 37 726 records of singleton delivery including 10 594 to mothers classified as smoking during pregnancy. Interventions A package of measures implemented in trusts and smoking cessation services, aimed at increasing the proportion of pregnant smokers quitting during pregnancy, comprising skills training for healthcare and smoking cessation staff; universal carbon monoxide monitoring with routine opt-out referral for smoking cessation support; provision of carbon monoxide monitors and supporting materials; and an explicit referral pathway and follow-up protocol. Main outcome measures Referrals to smoking cessation services; probability of quitting smoking during pregnancy; additional costs to health services; incremental cost per additional woman quitting. Results After introduction of the intervention, the referral rate increased more than twofold (incidence rate ratio=2.47, 95% CI 2.16 to 2.81) and the probability of quitting by delivery increased (adjusted OR=1.81, 95% CI 1.54 to 2.12). The additional cost per delivery was £31 and the incremental cost per additional quit was £952; 31 pregnant women needed to be treated for each additional quitter. Conclusions The implementation of a system-wide complex healthcare intervention was associated with significant increase in rates of quitting by delivery

Surgical treatments for women with stress urinary incontinence : the ESTER systematic review and economic evaluation

Funded by The National Institute for Health Research Health Technology Assessment programme.Peer reviewedPublisher PD

Treatments for Hyperemesis Gravidarum and Nausea and Vomiting in Pregnancy

Importance Nausea and vomiting affects approximately 85% of pregnant women. The most severe form, hyperemesis gravidarum, affects up to 3% of women and can have significant adverse physical and psychological sequelae.Objective To summarize current evidence on effective treatments for nausea and vomiting in pregnancy and hyperemesis gravidarum.Evidence Review Databases were searched to June 8, 2016. Relevant websites and bibliographies were also searched. Titles and abstracts were assessed independently by 2 reviewers. Results were narratively synthesized; planned meta-analysis was not possible because of heterogeneity and incomplete reporting of findings.Findings Seventy-eight studies (n  = 8930 participants) were included: 67 randomized clinical trials (RCTs) and 11 nonrandomized studies. Evidence from 35 RCTs at low risk of bias indicated that ginger, vitamin B6, antihistamines, metoclopramide (for mild symptoms), pyridoxine-doxylamine, and ondansetron (for moderate symptoms) were associated with improved symptoms compared with placebo. One RCT (n = 86) reported greater improvements in moderate symptoms following psychotherapy (change in Rhodes score [range, 0 {no symptoms} to 40 {worst possible symptoms}], 18.76 [SD, 5.48] to 7.06 [SD, 5.79] for intervention vs 19.18 [SD, 5.63] to 12.81 [SD, 6.88] for comparator [P < .001]). For moderate-severe symptoms, 1 RCT (n = 60) suggested that pyridoxine-doxylamine combination taken preemptively reduced risk of recurrence of moderate-severe symptoms compared with treatment once symptoms begin (15.4% vs 39.1% [P < .04]). One RCT (n = 83) found that ondansetron was associated with lower nausea scores on day 4 than metoclopramide (mean visual analog scale [VAS] score, 4.1 [SD, 2.9] for ondansetron vs 5.7 [SD, 2.3] for metoclopramide [P = .023]) but not episodes of emesis (5.0 [SD, 3.1] vs 3.3 [SD, 3], respectively [P = .013]). Although there was no difference in trend in nausea scores over the 14-day study period, trend in vomiting scores was better in the ondansetron group (P = .042). One RCT (n = 159) found no difference between metoclopramide and promethazine after 24 hours (episodes of vomiting, 1 [IQR, 0-5] for metoclopramide vs 2 [IQR, 0-3] for promethazine [P = .81], VAS [0-10 scale] for nausea, 2 [IQR, 1-5] vs 2 [IQR, 1-4], respectively [P = .99]). Three RCTs compared corticosteroids with placebo or promethazine or metoclopramide in women with severe symptoms. Improvements were seen in all corticosteroid groups, but only a significant difference between corticosteroids vs metoclopramide was reported (emesis reduction, 40.9% vs 16.5% at day 2; 71.6% vs 51.2% at day 3; 95.8% vs 76.6% at day 7 [n = 40, P < .001]). For other interventions, evidence was limited.Conclusions and Relevance For mild symptoms of nausea and emesis of pregnancy, ginger, pyridoxine, antihistamines, and metoclopramide were associated with greater benefit than placebo. For moderate symptoms, pyridoxine-doxylamine, promethazine, and metoclopramide were associated with greater benefit than placebo. Ondansetron was associated with improvement for a range of symptom severity. Corticosteroids may be associated with benefit in severe cases. Overall the quality of evidence was low

Surgical interventions for women with stress urinary incontinence : systematic review and network meta-analysis of randomised controlled trials

Funding: This project was funded by the NIHR HTA programme (project No 15/09/06). The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health and Social Care, UK. The funders were not actively involved in the research process at any stage. The study design; collection, analysis, and interpretation of data; writing of the manuscript; and decision to submit it for publication were performed independent of the funders.Peer reviewedPublisher PD