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We lead multidisciplinary applied research and training to rethink the way health care is delivered in general practice and across the community.
Adrenaline to improve survival in out-of-hospital cardiac arrest: the PARAMEDIC2 RCT
<jats:sec id="abs1-1"> <jats:title>Background</jats:title> <jats:p>Adrenaline has been used as a treatment for cardiac arrest for many years, despite uncertainty about its effects on long-term outcomes and concerns that it may cause worse neurological outcomes.</jats:p> </jats:sec> <jats:sec id="abs1-2"> <jats:title>Objectives</jats:title> <jats:p>The objectives were to evaluate the effects of adrenaline on survival and neurological outcomes, and to assess the cost-effectiveness of adrenaline use.</jats:p> </jats:sec> <jats:sec id="abs1-3"> <jats:title>Design</jats:title> <jats:p>This was a pragmatic, randomised, allocation-concealed, placebo-controlled, parallel-group superiority trial and economic evaluation. Costs are expressed in Great British pounds and reported in 2016/17 prices.</jats:p> </jats:sec> <jats:sec id="abs1-4"> <jats:title>Setting</jats:title> <jats:p>This trial was set in five NHS ambulance services in England and Wales.</jats:p> </jats:sec> <jats:sec id="abs1-5"> <jats:title>Participants</jats:title> <jats:p>Adults treated for an out-of-hospital cardiac arrest were included. Patients were ineligible if they were pregnant, if they were aged < 16 years, if the cardiac arrest had been caused by anaphylaxis or life-threatening asthma, or if adrenaline had already been given.</jats:p> </jats:sec> <jats:sec id="abs1-6"> <jats:title>Interventions</jats:title> <jats:p>Participants were randomised to either adrenaline (1 mg) or placebo in a 1 : 1 allocation ratio by the opening of allocation-concealed treatment packs.</jats:p> </jats:sec> <jats:sec id="abs1-7"> <jats:title>Main outcome measures</jats:title> <jats:p>The primary outcome was survival to 30 days. The secondary outcomes were survival to hospital admission, survival to hospital discharge, survival at 3, 6 and 12 months, neurological outcomes and health-related quality of life through to 6 months. The economic evaluation assessed the incremental cost per quality-adjusted life-year gained from the perspective of the NHS and Personal Social Services. Participants, clinical teams and those assessing patient outcomes were masked to the treatment allocation.</jats:p> </jats:sec> <jats:sec id="abs1-8"> <jats:title>Results</jats:title> <jats:p>From December 2014 to October 2017, 8014 participants were assigned to the adrenaline (<jats:italic>n</jats:italic> = 4015) or to the placebo (<jats:italic>n</jats:italic> = 3999) arm. At 30 days, 130 out of 4012 participants (3.2%) in the adrenaline arm and 94 out of 3995 (2.4%) in the placebo arm were alive (adjusted odds ratio for survival 1.47, 95% confidence interval 1.09 to 1.97). For secondary outcomes, survival to hospital admission was higher for those receiving adrenaline than for those receiving placebo (23.6% vs. 8.0%; adjusted odds ratio 3.83, 95% confidence interval 3.30 to 4.43). The rate of favourable neurological outcome at hospital discharge was not significantly different between the arms (2.2% vs. 1.9%; adjusted odds ratio 1.19, 95% confidence interval 0.85 to 1.68). The pattern of improved survival but no significant improvement in neurological outcomes continued through to 6 months. By 12 months, survival in the adrenaline arm was 2.7%, compared with 2.0% in the placebo arm (adjusted odds ratio 1.38, 95% confidence interval 1.00 to 1.92). An adjusted subgroup analysis did not identify significant interactions. The incremental cost-effectiveness ratio for adrenaline was estimated at £1,693,003 per quality-adjusted life-year gained over the first 6 months after the cardiac arrest event and £81,070 per quality-adjusted life-year gained over the lifetime of survivors. Additional economic analyses estimated incremental cost-effectiveness ratios for adrenaline at £982,880 per percentage point increase in overall survival and £377,232 per percentage point increase in neurological outcomes over the first 6 months after the cardiac arrest.</jats:p> </jats:sec> <jats:sec id="abs1-9"> <jats:title>Limitations</jats:title> <jats:p>The estimate for survival with a favourable neurological outcome is imprecise because of the small numbers of patients surviving with a good outcome.</jats:p> </jats:sec> <jats:sec id="abs1-10"> <jats:title>Conclusions</jats:title> <jats:p>Adrenaline improved long-term survival, but there was no evidence that it significantly improved neurological outcomes. The incremental cost-effectiveness ratio per quality-adjusted life-year exceeds the threshold of £20,000–30,000 per quality-adjusted life-year usually supported by the NHS.</jats:p> </jats:sec> <jats:sec id="abs1-11"> <jats:title>Future work</jats:title> <jats:p>Further research is required to better understand patients’ preferences in relation to survival and neurological outcomes after out-of-hospital cardiac arrest and to aid interpretation of the trial findings from a patient and public perspective.</jats:p> </jats:sec> <jats:sec id="abs1-12"> <jats:title>Trial registration</jats:title> <jats:p>Current Controlled Trials ISRCTN73485024 and EudraCT 2014-000792-11.</jats:p> </jats:sec> <jats:sec id="abs1-13"> <jats:title>Funding</jats:title> <jats:p>This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in <jats:italic>Health Technology Assessment</jats:italic>; Vol. 25, No. 25. See the NIHR Journals Library website for further project information.</jats:p> </jats:sec>
Using Point of Care Testing to estimate influenza vaccine effectiveness in the English primary care sentinel surveillance network
Introduction Rapid Point of Care Testing (POCT) for influenza could be used to provide information on influenza vaccine effectiveness (IVE) as well as influencing clinical decision-making in primary care. Methods We undertook a test negative case control study to estimate the overall and age-specific (6 months-17 years, 18–64 years, ≥65 years old) IVE against medically attended POCT-confirmed influenza. The study took place over the winter of 2019–2020 and was nested within twelve general practices that are part of the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC), the English sentinel surveillance network. Results 648 POCT were conducted. 193 (29.7%) of those who were swabbed had received the seasonal influenza vaccine. The crude unadjusted overall IVE was 46.1% (95% CI: 13.9–66.3). After adjusting for confounders the overall IVE was 26.0% (95% CI: 0–65.5). In total 211 patients were prescribed an antimicrobial after swab testing. Given a positive influenza POCT result, the odds ratio (OR) of receiving an antiviral was 21.1 (95%CI: 2.4–182.2, p = <0.01) and the OR of being prescribed an antibiotic was 0.6 (95%CI: 0.4–0.9, p = <0.01). Discussion Using influenza POCT in a primary care sentinel surveillance network to estimate IVE is feasible and provides comparable results to published IVE estimates. A further advantage is that near patient testing of influenza is associated with improvements in appropriate antiviral and antibiotic use. Larger, randomised studies are needed in primary care to see if these trends are still present and to explore their impact on outcomes.
Disseminated tuberculosis following liver transplant presenting with an axillary abscess
Four years after an orthoptic liver transplant for hepatocellular carcinoma secondary to alcoholic liver disease, the patient presented in a crescendo manner with skin infections and finally a septic right arm wound. The abscess was drained and cultures grew Mycobacterium tuberculosis. The patient reported previous episode of 'pneumonia' and subsequent hospitalisations for recurrent chest infections, and following further investigation, he was diagnosed with disseminated tuberculosis. The infection responded to triple therapy, but primary closure of the arm wound was unsuccessful and it was treated conservatively with negative pressure wound therapy. The patient remains an inpatient 3 months after his presentation, responding well to therapy and anticipating imminent discharge. The patient's case serves as a reminder that infections are common in solid organ transplant recipients andclinicians should be aware of unusual or recurrent presentations in these patients, to allow for early diagnosis and timely management. Copyright 2014 BMJ Publishing Group. All rights reserved. © 2014 BMJ Publishing Group.
NHS Health Checks: Equity and outcomes 2009-17: An observational study.
BACKGROUND: The NHS Health Check cardiovascular prevention programme is now 10 years old. AIM: We describe NHS Heath Check attendance, new diagnoses and treatment in relation to equity indicators. DESIGN AND SETTING: Using a national general practice database 2009-17, we compared NHS Health Check attendance and new diagnoses and treatments, by age, gender, ethnic group and deprivation. RESULTS: In 2013-17, 590,218 eligible people age 40-74 years attended an NHS Health Check (16.9%) and 2,902,598 (83.1%) did not attend. South Asian ethnic groups were most likely to attend and women more than men. New diagnoses were more likely in attendees than non-attendees; hypertension 25/1000 attendees vs 9/1000 in non-attendees; type 2 diabetes 8/1000 vs 3/1000; chronic kidney disease 7/1000 vs 4/1000. In people aged 65 or older, new atrial fibrillation was diagnosed in 5/1000 attendees and 3/1000 non-attendees and for dementia 2/1000 versus 1/1000 respectively. Type 2 diabetes, hypertension and CKD were more likely in more deprived groups, South Asian and black African/Caribbean ethnic groups. Attendees were more likely to be prescribed statins, 26/1000, than non-attendees 8/1000; and anti-hypertensive medicines, 25/1000 vs 13/1000 non-attendees. However, of the 117,963 people with 10% or greater CVD risk eligible for statins only 9,785 (8.3%) were prescribed them. CONCLUSIONS: NHS Health Checks uptake remains low. Attendees were more likely than non-attendees to be diagnosed with type 2 diabetes, hypertension and CKD and receive treatment with statins and antihypertensives. Most attendees received neither treatment nor referral. Of those eligible for statins, fewer than 10% were treated.
Hormone replacement therapy in women with cancer and risk of cancer-specific mortality and cardiovascular disease: a protocol for a cohort study from Scotland and Wales
Background: Hormone replacement therapy (HRT) is widely used and has proven benefits for women with menopausal symptoms. An increasing number of women with cancer experience menopausal symptoms but the safety of HRT use in women with cancer is unclear. There are particular concerns that HRT could accelerate cancer progression in women with cancer, and also that HRT could increase the risk of cardiovascular disease in such women. Therefore, our primary aim is to determine whether HRT use alters the risk of cancer-specific mortality in women with a range of common cancers. Our secondary objectives are to investigate whether HRT alters the risk of second cancers, cardiovascular disease, venous thromboembolism and all-cause mortality. Methods: The study will utilise independent population-based data from Wales using the SAIL databank and Scotland based upon the national Prescribing Information System. The study will include women newly diagnosed with common cancers from 2000 to 2016, identified from cancer registries. Women with breast cancers will be excluded. HRT will be ascertained using electronic prescribing in Wales or dispensing records in Scotland. The primary outcome will be time to cancer-specific mortality from national mortality records. Time-dependent cox regression models will be used to calculate hazard ratios (HR) and 95% confidence intervals (95% CIs) for cancer specific death in HRT users compared with non-users after cancer diagnosis after adjusting for relevant confounders, stratified by cancer site. Analysis will be repeated investigating the impact of HRT use immediately before cancer diagnosis. Secondary analyses will be conducted on the risk of second cancers, cardiovascular disease, venous thromboembolism and all-cause mortality. Analyses will be conducted within each cohort and pooled across cohorts. Discussion: Our study will provide evidence to inform guidance given to women diagnosed with cancer on the safety of HRT use and/or guide modifications to clinical practice.
Predictors for sexual dysfunction in the first year postpartum: a systematic review and meta-analysis
<h4>Background: </h4> Pregnancy and childbirth increase the risk for pelvic floor dysfunction, including sexual dysfunction. So far, the mechanisms and the extent to which certain risk factors play a role, remain unclear. Objectives In this systematic review of literature, we aimed to determine the risk factors for sexual dysfunction in the first year after delivery. Search Strategy We searched MEDLINE, Embase and CENTRAL using the search strategy: Sexual dysfunction AND Obstetric events. Selection Criteria We included original English, comparative studies that used validated questionnaires and the ICS/IUGA terminology for sexual dysfunction, dyspareunia and vaginal dryness. Data Collection and Analysis We assessed the quality and the risk of bias of the included studies with the Newcastle Ottawa Scale. We extracted the reported data and we performed random-effects meta-analysis to obtain the summary Odds Ratios (OR) with 95% Confidence Intervals. Heterogeneity across studies was assessed using the I2 statistic. Main Results We found no significant difference in the odds for both sexual dysfunction and dyspareunia between cesarean section and spontaneous delivery (OR:1.17[0.88-1.57] and OR:0.75[0.53-1.07]) and between operative delivery and spontaneous delivery (OR:1.56[0.87-2.79] and OR:1.35[0.75-2.42]). Anal sphincter injury was associated with increased odds for both sexual dysfunction (OR:3.00[1.28-7.03]) and dyspareunia (OR:1.71[1.09-2.67]). Episiotomy was associated with dyspareunia (OR:1.65[1.20-2.29]) but not with sexual dysfunction (OR:1.90[0.94-3.84]). We retrieved one study of low quality which reported on vaginal dryness and found no significant association with obstetric events.