National Institute For Health Research Research Articles

Transmission dynamics and effect of control measures on the 2022 outbreak of mpox among gay, bisexual, and other men who have sex with men in England: a mathematical modelling study

The 2022 global outbreak of mpox (formerly known as monkeypox) spread primarily among gay, bisexual, and other men who have sex with men (GBMSM), with the initial cluster being identified in England in May, 2022. Understanding its epidemiological characteristics and the reasons for its downturn in July, 2022, will help to control future outbreaks. We collated data for all diagnosed mpox cases (3621) from England from May 1, 2022, to Nov 16, 2022. Data from 75 individuals with mpox allowed estimation of the incubation period, while data from 121 case-contact pairs were used to estimate the serial interval. Six methods, including a structured dynamic compartmental transmission model, were used to estimate the basic reproduction number (R0). The structured model assumed all male individuals with mpox were GBMSM, who were then stratified into subgroups for those at low risk and high risk for mpox. This best fitting model was used to estimate the reduction in transmissibility, and the effective infectious period (before isolating), that resulted in the outbreak downturn, and the effect of vaccination initiated from June 27, 2022. Bayesian methods were used for parameter estimation and model calibration. Most cases occurred in men (3544 of 3621, 97·9%). The median incubation period for mpox was 6·90 days (95% credible interval [CrI] 4·08-20·21), and the serial interval was 8·82 days (5·22-25·81). R0 estimates ranged from 1·41 to 2·17. The structured transmission model estimated that 83·8% of infections (95% CrI 83·5-85·3) resulted from sexual partnerships with GBMSM individuals at high risk of mpox. The outbreak downturn probably resulted from a 44·5% reduction in the sexual partner rate among all GBMSM (24·9-55·8) and 20·0% reduction in the effective infectious period (4·1-33·9), preventing 165 896 infections (115 584-217 730). Vaccination marginally increased the number of infections prevented (166 081, 115 745-217 947), but minimised a resurgence in cases from January, 2023, and could have averted four times more infections if initiated earlier. Our findings were sensitive to assumptions regarding the vaccine's effectiveness and the GBMSM subgroup at high risk of mpox. The mpox outbreak in England probably resulted from high sexual partner rates among some GBMSM, with reductions in partner rates reversing the outbreak, and with vaccination minimising future outbreaks. National Institute for Health Research (UK).

Academic productivity and NIH funding for anesthesiology departmental chairs: A 15-year comparison

Study objectiveThis study evaluated whether there were improvements in the number of departmental National Institutes of Health (NIH) training grants and the academic productivity of departmental chairs in terms of NIH research funding and PubMed-cited publications when compared to chairs of the same departments in 2006. DesignEach chair was identified from the Society of Academic Associations of Academic Anesthesiology & Perioperative Medicine's Association of Academic Anesthesiology Chairs and entered into the NIH Research Portfolio Online Reporting Tools (RePORTER), PubMed, SCOPUS, and the National Provider Identifier Registry. MeasurementsThe number and funding amounts of training grants awarded to the department in 2010, 2015, and 2020 were obtained as well as the department's national ranking and total dollar amount for NIH funding in 2020. For the current chair cohort, total publications and m-quotient (h-index corrected for active research years) were recorded along with each chair's history of NIH grant funding. These data were compared to a previous study of anesthesiology chairs that reviewed funding and publications through 2006. Main resultsWe analyzed data from 100 academic departments of anesthesiology and compared their scholarly activity relative to data gathered in 2006. In 2020, 52 of 100 departments of anesthesiology had evidence of NIH funding. There were not statistically significant (P > 0.05) differences in grants funding obtained by chairs between 2006 and 2020 with the exception that more chairs in 2006 had program or center grants. Median publications for chairs significantly increased from 35 in 2006 to 55 in 2021 (IRR = 1.5, 95% CI = 1.2–2.0, P = 0.003). Nineteen percent of chairs were female, which did not significantly differ from the proportion of women in the 2006 paper (15%, χ2 = 0.57, df = 1, P = 0.452). Of the male chairs, 90% were professors whereas 63% of female chairs were professors (χ2 = 8.8, df = 1, P = 0.003). Female chairs had fewer publications than male chairs (IRR = 1.8, 95% CI = 1.2–1.8, P = 0.002); however, m-quotients were not significantly different between men and women (P = 0.602). ConclusionsWhen compared to 2006, department of anesthesiology chairs had more publications in 2021; however, NIH funding rates remained unchanged. The specialty had 19% female chairs, and those chairs had fewer publications than their male counterparts, though sex differences were attenuated using metrics that account for disparities in career length.

Codesigning a systemic discharge intervention for inpatient mental health settings (MINDS): a protocol for integrating realist evaluation and an engineering-based systems approach

IntroductionTransition following discharge from mental health hospital is high risk in terms of relapse, readmission and suicide. Discharge planning supports transition and reduces risk. It is a complex activity involving...

Tumour stage, treatment, and survival of women with high-grade serous tubo-ovarian cancer in UKCTOCS: an exploratory analysis of a randomised controlled trial

In UKCTOCS, there was a decrease in the diagnosis of advanced stage tubo-ovarian cancer but no reduction in deaths in the multimodal screening group compared with the no screening group. Therefore, we did exploratory analyses of patients with high-grade serous ovarian cancer to understand the reason for the discrepancy. UKCTOCS was a 13-centre randomised controlled trial of screening postmenopausal women from the general population, aged 50-74 years, with intact ovaries. The trial management system randomly allocated (2:1:1) eligible participants (recruited from April 17, 2001, to Sept 29, 2005) in blocks of 32 using computer generated random numbers to no screening or annual screening (multimodal screening or ultrasound screening) until Dec 31, 2011. Follow-up was through national registries until June 30, 2020. An outcome review committee, masked to randomisation group, adjudicated on ovarian cancer diagnosis, histotype, stage, and cause of death. In this study, analyses were intention-to-screen comparisons of women with high-grade serous cancer at censorship (Dec 31, 2014) in multimodal screening versus no screening, using descriptive statistics for stage and treatment endpoints, and the Versatile test for survival from randomisation. This trial is registered with the ISRCTN Registry, 22488978, and ClinicalTrials.gov, NCT00058032. 202 562 eligible women were recruited (50 625 multimodal screening; 50 623 ultrasound screening; 101 314 no screening). 259 (0·5%) of 50 625 participants in the multimodal screening group and 520 (0·5%) of 101 314 in the no screening group were diagnosed with high-grade serous cancer. In the multimodal screening group compared with the no screening group, fewer were diagnosed with advanced stage disease (195 [75%] of 259 vs 446 [86%] of 520; p=0·0003), more had primary surgery (158 [61%] vs 219 [42%]; p<0·0001), more had zero residual disease following debulking surgery (119 [46%] vs 157 [30%]; p<0·0001), and more received treatment including both surgery and chemotherapy (192 [74%] vs 331 [64%]; p=0·0032). There was no difference in the first-line combination chemotherapy rate (142 [55%] vs 293 [56%]; p=0·69). Median follow-up from randomisation of 779 women with high-grade serous cancer in the multimodal and no screening groups was 9·51 years (IQR 6·04-13·00). At censorship (June 30, 2020), survival from randomisation was longer in women with high-grade serous cancer in the multimodal screening group than in the no screening group with absolute difference in survival of 6·9% (95% CI 0·4-13·0; p=0·042) at 18 years (21% [95% CI 15·6-26·2] vs 14% [95% CI 10·5-17·4]). To our knowledge, this is the first evidence that screening can detect high-grade serous cancer earlier and lead to improved short-term treatment outcomes compared with no screening. The potential survival benefit for women with high-grade serous cancer was small, most likely due to only modest gains in early detection and treatment improvement, and tumour biology. The cumulative results of the trial suggest that surrogate endpoints for disease-specific mortality should not currently be used in screening trials for ovarian cancer. National Institute for Health Research, Medical Research Council, Cancer Research UK, The Eve Appeal.

Gender Differences in Academic Rank, Leadership, and Awards Among NIH Grant Recipients in Diagnostic Radiology.

Objective: Females have been traditionally underrepresented in academia across multiple medical specialties, including radiology. The present study investigated primary investigators (PIs) who received National Institutes of Health (NIH) radiology funding between 2016 and 2019 to establish if there was a correlation between NIH grants, gender, academic rank, first and second tier leadership positions, geographic location, and professional awards. Materials and Methods: Funding information was obtained from the NIH Research Portfolio Online Reporting Tools Expenditure and Results (RePORTER) website for 2016-2019. Information for each PI was obtained from academic institutional websites, LinkedIn, and Doximity. Mann-Whitney U tests and chi-square analyses were performed to compare and determine associations between gender and the stated variables of interest. Results: Of the 805 radiology PIs included in this study, 78% were male. There was a significant association of gender with the attainment of the highest academic rank (p = 0.026), with females occupied more of the assistant professor ranks (M:F = 1:1.5) and less of the professor ranks (F:M = 1:1.2). Between genders, there was no significant difference in first and second tier leadership positions (p = 0.497, p = 0.116), and postgraduate honors and awards (p = 0.149). The greatest proportion of grants was awarded in the setting of sole male PIs (55%) and the least proportion of grants were awarded when the contact PI and other project leader were female (1%). Conclusion: Despite having similar academic credentials, including number of leadership positions and postgraduate honors and awards, female radiology PIs who have received NIH grants continue to be underrepresented in higher academic ranks.

Potentially modifiable dementia risk factors in all Australians and within population groups: an analysis using cross-sectional survey data

Dementia is the second leading cause of disease burden in Australia. We aimed to calculate the population attributable fractions (PAFs) of dementia attributable to 11 of 12 previously identified potentially modifiable health and social risk factors (less education, hearing loss, hypertension, obesity, smoking, depression, social isolation, physical inactivity, diabetes, alcohol excess, air pollution, and traumatic brain injury), for Australians overall and three population groups (First Nations, and those of European and Asian ancestry). We calculated the prevalence of dementia risk factors (excluding traumatic brain injury) and PAFs, adjusted for communality, from the cross-sectional National Aboriginal and Torres Strait Islander Health Survey (2018-19), National Aboriginal and Torres Strait Islander Social Survey (2014-15), National Health Survey (2017-18), and General Social Survey (2014) conducted by the Australian Bureau of Statistics. We conducted sensitivity analyses using proxy estimates for traumatic brain injury (12th known risk factor) for which national data were not available. A large proportion (38·2%, 95% CI 37·2-39·2) of dementia in Australia was theoretically attributable to the 11 risk factors; 44·9% (43·1-46·7) for First Nations Australians, 36·4% (34·8-38·1) for European ancestry, and 33·6% (30·1-37·2) for Asian ancestry. Including traumatic brain injury increased the PAF to 40·6% (39·6-41·6) for all Australians. Physical inactivity (8·3%, 7·5-9·2), hearing loss (7·0%, 6·4-7·6), and obesity (6·6%, 6·0-7·3) accounted for approximately half of the total PAF estimates across Australia, and for all three population groups. Our PAF estimates indicate a substantial proportion of dementia in Australia is potentially preventable, which is broadly consistent with global trends and results from other countries. The highest potential for dementia prevention was among First Nations Australians, reflecting the enduring effect of upstream social, political, environmental, and economic disadvantage, leading to greater life-course exposure to dementia risk factors. Although there were common dementia risk factors across different population groups, prevention strategies should be informed by community consultation and be culturally and linguistically appropriate. Australian National Health and Medical Research Council and University College London Hospitals' National Institute for Health Research (NIHR) Biomedical Research Centre, and North Thames NIHR Applied Research Collaboration.

Obstetric and neonatal outcomes in pregnant women with and without a history of specialist mental health care: a national population-based cohort study using linked routinely collected data in England

Pregnant women with pre-existing mental illnesses have increased risks of adverse obstetric and neonatal outcomes compared with pregnant women without pre-existing mental illnesses. We aimed to estimate these differences in risks according to the highest level of pre-pregnancy specialist mental health care, defined as psychiatric hospital admission, crisis resolution team (CRT) contact, or specialist community care only, and the timing of the most recent care episode in the 7 years before pregnancy. Hospital and birth registration records of women with singleton births between April 1, 2014, and March 31, 2018 in England were linked to records of babies and records from specialist mental health services provided by the England National Health Service, a publicly funded health-care system. We compared the risks of adverse pregnancy outcomes, including fetal and neonatal death, preterm birth, and babies being born small for gestational age (SGA; birthweight <10th percentile), and composite indicators for neonatal adverse outcomes and maternal morbidity, between women with and without a history of contact with specialist mental health care. We calculated odds ratios adjusted for maternal characteristics (aORs), using logistic regression. Of 2 081 043 included women (mean age 30·0 years; range 18-55 years; 77·7% White, 11·4% South Asian, 4·7% Black, and 6·2% mixed or other ethnic background), 151 770 (7·3%) had at least one pre-pregnancy specialist mental health-care contact. 7247 (0·3%) had been admitted to a psychiatric hospital, 29 770 (1·4%) had CRT contact, and 114 753 (5·5%) had community care only. With a pre-pregnancy mental health-care contact, risk of stillbirth or neonatal death within 7 days of birth was not significantly increased (0·45-0·49%; aOR 1·11, 95% CI 0·99-1·24): risk of preterm birth (<37 weeks) increased (6·5-9·8%; aOR 1·53, 1·35-1·73), as did risk of SGA (6·2- 7·5%; aOR 1·34, 1·30-1·37) and neonatal adverse outcomes (6·4-8·4%; aOR 1·37, 1·21-1·55). With a pre-pregnancy mental health-care contact, risk of maternal morbidity increased slightly from 0·9% to 1·0% (aOR 1·18, 1·12-1·25). Overall, risks were highest for women who had a psychiatric hospital admission any time or a mental health-care contact in the year before pregnancy. Information about the level and timing of pre-pregnancy specialist mental health-care contacts helps to identify women at increased risk of adverse obstetric and neonatal outcomes. These women are most likely to benefit from dedicated community perinatal mental health teams working closely with maternity services to provide integrated care. National Institute for Health Research.

ENRICH Scotland: a research network enabling research in care homes in Scotland

There is a need to understand the lives of people who live in care homes and how care should be delivered in this setting. Enabling Research in Care Homes (ENRICH) was funded by National Institute for Health Research in 2012 in England to increase research awareness and participation for people who live and work in care homes. A similar model was developed for Scotland, but without funding this proved difficult. In 2021, the Chief Scientist Office funded an expansion of the existing model for Scottish care homes. This article describes the components of enabling research in care homes in Scotland and the research infrastructure the team are developing to enable more research, including clinical trials, to be carried out in Scottish care homes, and how this will benefit the residents, families and staff.

Community Psychiatric Mental Health Nursing: Practice and Challenges

Due to the rising incidence of social risk incidents, the Mental Health Act was amended to provide community treatment and community support for patients with mental illness. Community mental health centers have added a public sector function to follow-up with the care of mentally ill patients using case management as an integrated service model. Under this amendment, the unique role and task of community psychiatric mental healthcare should be framed and developed. The National Health Research Institutes have advocated recovery-oriented case management as a mental health policy. Thus, in line with this policy, the authors developed a need-tailored recovery program led by nurses that has demonstrated significant effectiveness with regard to the recovery of mentally ill patients. Also, a mobile-care platform was subsequently developed to assess the care needs of community-dwelling patients with mental illness, implement recovery-oriented care, and evaluate its effectiveness, which may be incorporated into evidence-based community psychiatric mental healthcare guidelines. To improve the practice of community psychiatric mental health nursing, this article addresses key community nursing contexts, including: psychiatric home treatment and care, community mental health centers, the needs-tailored recovery-oriented case management model, and the roles and certification of community psychiatric mental health nurses promoted by the psychiatric mental health nurses association. Finally, future challenges and strategies are proposed to improve the quality of community psychiatric mental healthcare and to assist patients move from mental disorder to recovery.

Mechanical transmission of dengue virus by Aedes aegypti may influence disease transmission dynamics during outbreaks.

Dengue virus outbreaks are increasing in number and severity worldwide. Viral transmission is assumed to require a minimum time period of viral replication within the mosquito midgut. It is unknown if alternative transmission periods not requiring replication are possible. We used a mouse model of dengue virus transmission to investigate the potential of mechanical transmission of dengue virus. We investigated minimal viral titres necessary for development of symptoms in bitten mice and used resulting parameters to inform a new model of dengue virus transmission within a susceptible population. Naïve mice bitten by mosquitoes immediately after they took partial blood meals from dengue infected mice showed symptoms of dengue virus, followed by mortality. Incorporation of mechanical transmission into mathematical models of dengue virus transmission suggest that this supplemental transmission route could result in larger outbreaks which peak sooner. The potential of dengue transmission routes independent of midgut viral replication has implications for vector control strategies that target mosquito lifespan and suggest the possibility of similar mechanical transmission routes in other disease-carrying mosquitoes. This study was funded by grants from the National Health Research Institutes, Taiwan (04D2-MMMOST02), the Human Frontier Science Program (RGP0033/2021), the National Institutes of Health (1R01AI143698-01A1, R01AI151004 and DP2AI152071) and the Ministry of Science and Technology, Taiwan (MOST104-2321-B-400-016).

Factors associated with the diagnosis and treatment of obstructive sleep apnoea in chronic heart failure: a mixed methods study

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): This study was co-funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care East Midlands (CLAHRC EM), now recommissioned as NIHR Applied Research Collaboration East Midlands (ARC EM) and Leicestershire Partnership NHS Trust - Raising Health Charitable Funds Award and supported by the NIHR Leicester Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Background Heart Failure (HF) is associated with a considerable burden of disability that includes frequent hospitalisation and high risk of mortality. Despite advances in HF treatment, many patients continue to experience symptoms and will die from progressive HF, often exacerbated by the presence of co-morbidities, such as obstructive sleep apnea (OSA). Despite the high prevalence of OSA in chronic HF and the association with the development and progression of chronic HF, OSA remains largely under diagnosed and under treated. Purpose To explore factors associated with the diagnosis and treatment of OSA in CHF. Methods A convergent parallel mixed methods research design was utilised. Quantitative methods included a systematic review and meta-analysis, diagnostic validation study and a survey study, whilst semi-structured interviews and reflexive thematic analysis was utilised for the qualitative component. Data collection and data analysis were conducted simultaneously with the integration of the findings in the discussion. Results The systematic review and meta-analysis showed that the STOP-Bang screening questionnaire had a high sensitivity to detect OSA in the sleep clinic and surgical populations but lacked adequate specificity. The diagnostic validation study indicated a high sensitivity of the STOP-Bang questionnaire, but due to differences in prevalence, risk of selection bias and spectrum effect, validation in a sleep clinic population is unlikely to reflect the true performance of the STOP-Bang questionnaire in a stable CHF population. The survey study demonstrated a knowledge deficit in the diagnosis and treatment of OSA, and variable practice among HF clinicians in the UK. Findings from the qualitative component identified several key barriers and enablers across the OSA diagnostic pathway from both patients’ and clinicians’ accounts. Conclusion Due to a lack of typical OSA symptoms, there is currently no real evidence of cardiovascular hospitalisation and mortality benefit for OSA treatment in CHF. This contributed to a paucity of guidance on the management of OSA in CHF clinical guidelines. Due to a lack of typical OSA symptoms, screening questionnaires that rely on patient symptoms may be less effective. Although clinicians felt that OSA was an important clinical condition, findings demonstrated a disconnect between the stated level of clinical importance and clinicians’ actual level of knowledge. The current absence of evidence to support the treatment of OSA in CHF and paucity of CHF guidelines to inform the management of OSA in CHF, are likely to contribute to clinicians not prioritising the recognition and treatment of OSA in CHF.

See-saws: the delicate balance of burden of treatment in chronic heart failure

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): This work was supported as a part of a fully funded Clinical Academic Doctoral Fellowship at the University of Southampton, Portsmouth Hospitals University NHS Trust, and the National Institute for Health Research (NIHR) Applied Research Collaboration (ARC) Wessex. This article is independent research supported in part by the NIHR ARC Wessex. Carl May’s contribution was supported by NIHR ARC North Thames and Alison Richardson’s by NIHR ARC Wessex. Rosalynn Austin is funded by an NIHR ARC Wessex Internship. Background Burden of Treatment (BoT) is often described as a delicate balance between a patient’s capacity (capabilities and resources) to do the work of illness management and the workload (self-care, treatment and illness burden). Chronic heart failure (CHF) is regarded as a burdensome disease for both patients and healthcare services with the burden expected to rise. While research in BoT in CHF is increasing, the factors influencing the balance between capacity and workload has yet to be fully elucidated. Purpose To identify factors which may influence BoT in CHF. Methods Secondary analysis of 32 semi-structured interviews of participants with CHF who participated in the SYMPACT trial. All participants were asked to describe the balance between capabilities and workload of manging CHF using the metaphor of a see-saw. Responses to that question were examined for factors patients reported as altering the balance between capacity and workload. Results Most participants (n=31) described the seesaw as dynamic, where capacity and workload were balanced or unbalanced. If capacity &amp;gt; workload this was viewed as positive, "I would stay down because the things that you mentioned are very easy" (T137). When instead the balance reversed and capacity &amp;lt; workload it was viewed as negative, "The heavier you know with the work and the abilities less, you kind of think […] I’m good for nothing" (B001). Factors reported by patients, to alter their capacity included: ability to self-care, support from social networks, symptoms, illness identity, and quality of life. Workload was reported to be altered by nature of healthcare interactions, effectiveness of treatments, comorbidities and the feeling of overwhelming treatment burden (Figure 1). One participant described overwhelming burden with a different metaphor: "A huge weight around my neck. Pulling me down into a pit of despair" (S110), was reported as more accurate than a seesaw when thinking about treatment burden. Conclusions BoT is an important factor to consider in the clinical management of CHF. Modifiable factors such as symptoms, quality of life, and the nature of healthcare interactions are reported as altering the balance between a patient’s capacity and the workload associated with self-care.Factors balancing burden of treatment

Insights from linking police domestic abuse data and health data in South Wales, UK: a linked routine data analysis using decision tree classification

Exposure to domestic abuse can lead to long-term negative impacts on the victim's physical and psychological wellbeing. The 1998 Crime and Disorder Act requires agencies to collaborate on crime reduction strategies, including data sharing. Although data sharing is feasible for individuals, rarely are whole-agency data linked. This study aimed to examine the knowledge obtained by integrating information from police and health-care datasets through data linkage and analyse associated risk factor clusters. This retrospective cohort study analyses data from residents of South Wales who were victims of domestic abuse resulting in a Public Protection Notification (PPN) submission between Aug 12, 2015 and March 31, 2020. The study links these data with the victims' health records, collated within the Secure Anonymised Information Linkage databank, to examine factors associated with the outcome of an Emergency Department attendance, emergency hospital admission, or death within 12 months of the PPN submission. To assess the time to outcome for domestic abuse victims after the index PPN submission, we used Kaplan-Meier survival analysis. We used multivariable Cox regression models to identify which factors contributed the highest risk of experiencing an outcome after the index PPN submission. Finally, we created decision trees to describe specific groups of individuals who are at risk of experiencing a domestic abuse incident and subsequent outcome. After excluding individuals with multiple PPN records, duplicates, and records with a poor matching score or missing fields, the resulting clean dataset consisted of 8709 domestic abuse victims, of whom 6257 (71·8%) were female. Within a year of a domestic abuse incident, 3650 (41·9%) individuals had an outcome. Factors associated with experiencing an outcome within 12 months of the PPN included younger victim age (hazard ratio 1·183 [95% CI 1·053-1·329], p=0·0048), further PPN submissions after the initial referral (1·383 [1·295-1·476]; p<0·0001), injury at the scene (1·484 [1·368-1·609]; p<0·0001), assessed high risk (1·600 [1·444-1·773]; p<0·0001), referral to other agencies (1·518 [1·358-1·697]; p<0·0001), history of violence (1·229 [1·134-1·333]; p<0·0001), attempted strangulation (1·311 [1·148-1·497]; p<0·0001), and pregnancy (1·372 [1·142-1·648]; p=0·0007). Health-care data before the index PPN established that previous Emergency Department and hospital admissions, smoking, smoking cessation advice, obstetric codes, and prescription of antidepressants and antibiotics were associated with having a future outcome following a domestic abuse incident. The results indicate that vulnerable individuals are detectable in multiple datasets before and after involvement of the police. Operationalising these findings could reduce police callouts and future Emergency Department or hospital admissions, and improve outcomes for those who are vulnerable. Strategies include querying previous Emergency Department and hospital admissions, giving a high-risk assessment for a pregnant victim, and facilitating data linkage to identify vulnerable individuals. National Institute for Health Research.

Reflections of maternity service users and midwives' on the co-creation of interventions to support midwives addressing alcohol during antenatal care

BackgroundThere are divergent perspectives between midwives and pregnant women on how alcohol consumption during pregnancy could be addressed. Co-creation is an approach where lay people and professionals work together as equal partners, offering the opportunity to bridge the gap. ObjectivesOur aim was to evaluate how well we carried out authentic co-creation of an intervention to support midwives have a dialogue about alcohol consumption with pregnant women. Patient involvementRecent maternity service users including women with experience of harm due to alcohol during pregnancy provided feedback on the design, conduct and dissemination of the study. MethodsAn iterative co-creation approach rooted in participatory research methods was used. Five online workshops were carried out with thirteen midwives and six maternity service users via Zoom July-August 2021. Data were analysed using the core values of co-create as a framework: equality, inclusivity, holistic, resource, positivity, transparency, iterative, and sustainability. ResultsThe co-creation process was productive and rewarding to midwives and maternity service users. There were positive experiences across the co-creation framework with some unintended positive consequences for maternity-service users. DiscussionThis evaluation provides new knowledge on how well the co-creation process worked in relation to research involving a sensitive topic that can invite stigma. Co-creation projects require generous time and financial resources to ensure a high-quality process and robust outcome for all. Practical valueCo-creation of strategies involving both service providers and service users have potential to facilitate evidence-based practice. FundingThis research is funded by the National Institute for Health Research (Reference: NIHR201128)

Metformin for the prevention of diabetes among people with HIV and either impaired fasting glucose or impaired glucose tolerance (prediabetes) in Tanzania: a Phase II randomised placebo-controlled trial

Aims/hypothesisIn sub-Saharan Africa (SSA), 5% of adults are living with type 2 diabetes and this is rising sharply, with a greater increase among people with HIV. Evidence on the efficacy of prevention strategies in this cohort is scarce. We conducted a Phase II double-blind placebo-controlled trial that aimed to determine the impact of metformin on blood glucose levels among people with prediabetes (defined as impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT]) and HIV in SSA.MethodsAdults (≥18 years old) who were stable in HIV care and found to have prediabetes (IFG and/or IGT) and who were attending hospitals in Dar es Salaam, Tanzania, were randomised to receive sustained-release metformin, 2000 mg daily, or matching placebo between 4 November 2019 and 21 July 2020. Randomisation used permuted blocks. Allocation was concealed in the trial database and made visible only to the Chief Pharmacist after consent was taken. All participants, research and clinical staff remained blinded to the allocation. Participants were provided with information on diet and lifestyle and had access to various health information following the start of the coronavirus disease 2019 (COVID-19) pandemic. Participants were followed up for 12 months. The primary outcome measure was capillary blood glucose measured 2 h following a 75 g glucose load. Analyses were by intention-to-treat.ResultsIn total, 364 participants (182 in each arm) were randomised to the metformin or placebo group. At enrolment, in the metformin and placebo arms, mean fasting glucose was 6.37 mmol/l (95% CI 6.23, 6.50) and 6.26 mmol/l (95% CI 6.15, 6.36), respectively, and mean 2 h glucose levels following a 75 g oral glucose load were 8.39 mmol/l (95% CI 8.22, 8.56) and 8.24 mmol/l (95% CI 8.07, 8.41), respectively. At the final assessment at 12 months, 145/182 (79.7%) individuals randomised to metformin compared with 158/182 (86.8%) randomised to placebo indicated that they had taken >95% of their medicines in the previous 28 days (p=0.068). At this visit, in the metformin and placebo arms, mean fasting glucose levels were 6.17 mmol/l (95% CI 6.03, 6.30) and 6.30 mmol/l (95% CI 6.18, 6.42), respectively, and mean 2 h glucose levels following a 75 g oral glucose load were 7.88 mmol/l (95% CI 7.65, 8.12) and 7.71 mmol/l (95% CI 7.49, 7.94), respectively. Using a linear mixed model controlling for respective baseline values, the mean difference between the metformin and placebo group (metformin–placebo) was −0.08 mmol/l (95% CI −0.37, 0.20) for fasting glucose and 0.20 mmol/l (95% CI −0.17, 0.58) for glucose levels 2 h post a 75 g glucose load. Weight was significantly lower in the metformin arm than in the placebo arm: using the linear mixed model adjusting for baseline values, the mean difference in weight was −1.47 kg (95% CI −2.58, −0.35). In total, 16/182 (8.8%) individuals had a serious adverse event (Grade 3 or Grade 4 in the Division of Acquired Immunodeficiency Syndrome [DAIDS] adverse event grading table) or died in the metformin arm compared with 18/182 (9.9%) in the placebo arm; these events were either unrelated to or unlikely to be related to the study drugs.Conclusions/interpretationBlood glucose decreased over time in both the metformin and placebo arms during the trial but did not differ significantly between the arms at 12 months of follow up. Metformin therapy was found to be safe for use in individuals with HIV and prediabetes. A larger trial with longer follow up is needed to establish if metformin can be safely used for the prevention of diabetes in people who have HIV.Trial registrationThe trial is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry (www.isrctn.com/), registration number: ISCRTN76157257.FundingThis research was funded by the National Institute for Health Research using UK aid from the UK Government to support global health research.Graphical

Bromelain-based enzymatic burn debridement: A systematic review of clinical studies on patient safety, efficacy and long-term outcomes.

In 2012 the European Medicines Agency approved a pineapple stem-derived Bromelain-based debridement concentrate of proteolytic enzymes (NexoBrid®, MediWound Ltd, Yavne, Israel) for adult deep burns. Over 10 000 patients have been successfully treated with NexoBrid® globally, including in the US. The aim of our study is to perform a systematic review of the current literature on Nexobrid® outcomes. We conducted a literature search in PubMed, Google Scholar, Embase, and other search engines (2013-2023). The online screening process was performed by two independent reviewers with the Covidence tool. The protocol was reported using the Preferred Reporting Items for Systematic Review and Meta-Analyses, and it was registered at the International Prospective Register of Systematic Reviews of the National Institute for Health Research. We identified 103 relevant studies of which 34 were found eligible. The included studies report the positive effects of Nexobrid® on burn debridement, functional and cosmetic outcomes, scarring, and quality of life. Also, they validate the high patient satisfaction thanks to enhanced protocols of analgosedation and/or locoregional anaesthesia during Bromelain-based debridement. Two studies investigate potential risks (coagulopathy, burn wound infection) which concluded there is no strong evidence of these adverse events. NexoBrid® is a safe, selective, non-surgical eschar removal treatment modality. The benefits of Bromelain-based debridement are faster debridement and healing times, reduced operations, length of stay, cases of sepsis, blood transfusions, and prevention of compartment syndrome. Existing evidence suggests that the indications and the role of Bromelain-based debridement are expanding to cover "off-label" cases with significant benefits to the global healthcare economy.

Spending on Phased Clinical Development of Approved Drugs by the US National Institutes of Health Compared With Industry

The launch of the Advanced Research Projects Agency for Health to advance new cures and address public concern regarding drug prices has raised questions about the roles of government and industry in drug development. To compare National Institutes of Health (NIH) spending on phased clinical development of approved drugs with that by industry. This cross-sectional study examined NIH funding for published research reporting the results of phased clinical trials of drugs approved between 2010 and 2019 and compared the findings with reported industry spending estimates. Data analysis was performed between May 2021 and August 2022 using PubMed data from January 1999 through October 2021 and NIH Research Portfolio Online Reporting Tools Expenditures and Results data from January 1999 through December 2020. Drugs approved between 2010 and 2019. National Institutes of Health funding for published research describing applied research on approved drugs, basic research on their biological targets, and phased clinical trials related to drugs approved between 2010 and 2019 were evaluated using Mann-Whitney U tests. All costs were inflation adjusted to 2018. National Institutes of Health funding for basic or applied research related to 386 of 387 drugs approved between 2010 and 2019 totaled $247.3 billion. Of this amount, $8.1 billion (3.3%) was related to phased clinical development. This funding contributed to 12 340 publications on phased clinical trial results involving 240 of 387 (62.0%) drugs. Average NIH spending was $33.8 million per drug, including $13.9 million per drug for phase 1, $22.2 million per drug for phase 2, and $12.9 million per drug for phase 3 trials. Spending by NIH on phased development represented 9.8% to 10.7% of estimated industry spending, including 24.6% to 25.3% of estimated phase 1, 21.4% to 23.2% of phase 2, and 3.7% to 4.3% of phase 3 costs. Considering 60 products for which estimated industry costs were publicly available, NIH spending on clinical trials was significantly lower than estimated industry spending (sum of averages, $54.9 million per drug; mean difference, $326.0 million; 95% CI, $235.6-$416.4 million; 2-tailed paired t test P < .001). More than 90% of NIH funding came through cooperative agreements or program projects and centers, while 3.3% of NIH funding came through investigator-initiated research projects. In this cross-sectional study, NIH funding for phased clinical development of drugs approved between 2010 and 2019 represented a small fraction of NIH spending on pharmaceutical innovation. This spending focused primarily on early-phase clinical trials and research capacity and was significantly less than estimated industry spending on clinical development. These results may inform the efficient allocation of government funding to advance pharmaceutical innovation.

Limited number of spine surgeons among recipients of National Institutes of Health grants awarded for degenerative spine disease research.

Surgeon scientists remain underrepresented among recipients of National Institutes of Health (NIH) grants despite their unique ability to perform translational research. This study elucidates the portfolio of NIH grants awarded for degenerative spine diseases and the role of spine surgeons in this portfolio. The most common diagnoses and surgical procedures for degenerative spine diseases were queried on the NIH Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER) database (2011-2021). Total NIH funding was extracted for 20 additional clinical areas and compound annual growth rates (CAGRs) were calculated. A retrospective cohort study of principal investigators (PIs) was conducted. NIH grants and funding totals were extracted and compared to those from other clinical areas. The total NIH research budget increased from $31 to $43 billion over the 10-year period (CAGR 3.4%). A total of 273 unique grants equaling $91 million (CAGR 0%) were awarded for degenerative spine diseases. Diabetes ($11.8 billion, CAGR 0%), obesity ($10.6 billion, CAGR 3%), and chronic pain ($5.6 billion, CAGR 7%) received the most funding. Most NIH funding for degenerative spine disease research was awarded through the R01 (66%) and R44 (8%) grant mechanisms. The National Institute of Arthritis and Musculoskeletal and Skin Diseases awarded the most NIH funding (64%). Departments of orthopedic surgery were awarded the most funding (32%). NIH funding supported clinical (28%), translational (37%), and basic science (35%) research. Disease mechanisms (58%), imaging modalities (20%), and emerging technologies (16%) received the most funding. Nineteen spine surgeons were identified as PIs (16%). There were no significant differences in NIH funding totals by PI demographic and academic characteristics (p > 0.05)-except for full professors, who had the most NIH funding (p = 0.007) and highest h-index values (p < 0.001). Few spine surgeons receive NIH grants for degenerative spine disease research. Future opportunities may exist for spine surgeons to collaborate in identified areas of clinical interest. Additional strategies are needed to increase NIH funding in spine surgery.

Impact of COVID-19 on broad-spectrum antibiotic prescribing for common infections in primary care in England: a time-series analyses using OpenSAFELY and effects of predictors including deprivation.

The COVID-19 pandemic impacted the healthcare systems, adding extra pressure to reduce antimicrobial resistance. Therefore, we aimed to evaluate changes in antibiotic prescription patterns after COVID-19 started. With the approval of NHS England, we used the OpenSAFELY platform to access the TPP SystmOne electronic health record (EHR) system in primary care and selected patients prescribed antibiotics from 2019 to 2021. To evaluate the impact of COVID-19 on broad-spectrum antibiotic prescribing, we evaluated prescribing rates and its predictors and used interrupted time series analysis by fitting binomial logistic regression models. Over 32 million antibiotic prescriptions were extracted over the study period; 8.7% were broad-spectrum. The study showed increases in broad-spectrum antibiotic prescribing (odds ratio [OR] 1.37; 95% confidence interval [CI] 1.36-1.38) as an immediate impact of the pandemic, followed by a gradual recovery with a 1.1-1.2% decrease in odds of broad-spectrum prescription per month. The same pattern was found within subgroups defined by age, sex, region, ethnicity, and socioeconomic deprivation quintiles. More deprived patients were more likely to receive broad-spectrum antibiotics, which differences remained stable over time. The most significant increase in broad-spectrum prescribing was observed for lower respiratory tract infection (OR 2.33; 95% CI 2.1-2.50) and otitis media (OR 1.96; 95% CI 1.80-2.13). An immediate reduction in antibiotic prescribing and an increase in the proportion of broad-spectrum antibiotic prescribing in primary care was observed. The trends recovered to pre-pandemic levels, but the consequence of the COVID-19 pandemic on AMR needs further investigation. This work was supported by Health Data Research UK and by National Institute for Health Research.

Managing the cancer backlog: a national population-based study of patient mobility, waiting times and 'spare capacity' for cancer surgery.

Waiting times for cancer treatments continue to increase in many countries. In this study we estimated potential 'spare surgical capacity' in the English NHS and identified regions more likely to have spare capacity based on patterns of patient mobility (the extent to which patients receive surgery at hospitals other than their nearest). We identified patients who had an elective breast or colorectal cancer surgical resection between January 2016 and December 2018. We estimated each hospital's 'maximum surgical capacity' as the maximum 6-month moving average of its surgical volume. 'Spare surgical capacity' was estimated as the difference between maximum surgical capacity and observed surgical volume. We assessed the association between spare surgical capacity and whether a hospital performed more or fewer procedures than expected due to patient mobility as well as the association between spare surgical capacity and whether or not waiting times targets for treatment were likely to be met. 100,585 and 49,445 patients underwent breast and colorectal cancer surgery respectively. 67 of 166 hospitals (40.4%) providing breast cancer surgery and 82 of 163 hospitals (50.3%) providing colorectal cancer surgery used less than 80% of their maximum surgical capacity. Hospitals with a 'net loss' of patients to hospitals further away had more potential spare capacity than hospitals with a 'net gain' of patients (p<0.001 for breast and p=0.01 for colorectal cancer). At the national level, we projected an annual potential spare capacity of 8389 breast cancer and 4262 colorectal cancer surgical procedures, approximately 25% of the volumes actually performed. Spare surgical capacity potentially exists in the present configuration of hospitals providing cancer surgery and requires regional allocation for efficient utilisation. National Institute for Health Research.