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The use of primary care databases has been integral in pharmacoepidemiological studies and pharmacovigilance. Primary care databases derive from electronic health records and offer a comprehensive description of aggregate patient data, from demography to medication history, and good sample sizes. Studies using these databases improve our understanding of prescribing characteristics and associated risk factors to facilitate better patient care, but there are limitations. We describe eight key scenarios where study data outcomes can be affected by absent prescriptions in UK primary care databases: (1) out-of-hours, urgent care and acute care prescriptions; (2) specialist-only prescriptions; (3) alternative community prescribing, such as pharmacy, family planning clinic or sexual health clinic medication prescriptions; (4) newly licensed medication prescriptions; (5) medications that do not require prescriptions; (6) hospital inpatient and outpatient prescriptions; (7) handwritten prescriptions; and (8) private pharmacy and private doctor prescriptions. The significance of each scenario is dependent on the type of medication under investigation, nature of the study and expected outcome measures. We recommend that all researchers using primary care databases be aware of the potential for missing prescribing data and be sensitive to how this can vary substantially between items, drug classes, patient groups and over time. Close liaison with practising primary care clinicians in the UK is often essential to ensure awareness of nuances in clinical practice. [ABSTRACT FROM AUTHOR]

Electronic healthcare record data have been used to study risk factors of disease, treatment effectiveness and safety, and to inform healthcare service planning. There has been increasing interest in utilizing these data for new purposes such as for machine learning to develop predictive algorithms to aid diagnostic and treatment decisions. Synthetic data could potentially be an alternative to real‐world data for these purposes as well as reveal any biases in the data used for algorithm development. This article discusses the key requirements of synthetic data for multiple purposes and proposes an approach to generate and evaluate synthetic data focused on, but not limited to, cross‐sectional healthcare data. To our knowledge, this is the first article to propose a framework to generate and evaluate synthetic healthcare data with the aim of simultaneously preserving the complexities of ground truth data in the synthetic data while also ensuring privacy. We include findings and new insights from synthetic datasets modeled on both the Indian liver patient dataset and UK primary care dataset to demonstrate the application of this framework under different scenarios. [ABSTRACT FROM AUTHOR]

Background: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear.Methods: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded.Results: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78-.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS.Conclusions: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment. [ABSTRACT FROM AUTHOR]

The importance of evaluation to demonstrate the effectiveness of policies, programmes and interventions is widely recognised. Evaluation in the context of public health and healthcare is viewed as a complicated exercise, particularly when dealing with complex interventions involving multiple partners, multiple components and multiple outcomes. Eliciting the programme theory is an important starting point of an evaluation process to enable the link between theory and action to be articulated. This article gives a pragmatic account of the practicalities of working with stakeholders as they embark on a formative evaluation of a complex public health initiative, using a using a theory-based approach. Drawing on the principles of Leeuw's strategic assessment, we planned a workshop to reflect the four stages of this approach–group formation, assumption surfacing, dialectical debate and synthesis. Stakeholders took part in four activities–Free Listing, Sphere of Influence, Beattie's Theoretical Framework and Programme Concept Mapping. We found that our elicitation approach was particularly suited to reconstructing the programme theory in a non-threatening and playful environment, bringing about an alignment of programme theories by consensus and reducing anxiety. [ABSTRACT FROM AUTHOR]

Background. While evidence exists to support the effectiveness of neuraminidase inhibitors (NAIs) in reducing mortality when given to hospitalized patients with A(H1N1)pdm09 virus infection, the impact of outpatient treatment on hospitalization has not been clearly established. We investigated the impact of outpatient NAI treatment on subsequent hospitalization in patients with A(H1N1)pdm09 virus infection. Methods. We assembled general community and outpatient data from 9 clinical centers in different countries collected between January 2009 and December 2010. We standardized data from each study center to create a pooled dataset and then used mixed-effects logistic regression modeling to determine the effect of NAI treatment on hospitalization. We adjusted for NAI treatment propensity and preadmission antibiotic use, including "study center" as a random intercept to account for differences in baseline hospitalization rate between centers. Results. We included 3376 patients with influenza A(H1N1)pdm09, of whom 3085 (91.4%) had laboratory-confirmed infection. Eight hundred seventy-three patients (25.8%) received outpatient or community-based NAI treatment, 928 of 2395 (38.8%) with available data had dyspnea or respiratory distress, and hospitalizations occurred in 1705 (50.5%). After adjustment for preadmission antibiotics and NAI treatment propensity, preadmission NAI treatment was associated with decreased odds of hospital admission compared to no NAI treatment (adjusted odds ratio, 0.24; 95% confidence interval, 0.20-0.30). Conclusions. In a population with confirmed or suspected A(H1N1)pdm09 and at high risk of hospitalization, outpatient or community-based NAI treatment significantly reduced the likelihood of requiring hospital admission. These data suggest that community patients with severe influenza should receive NAI treatment. [ABSTRACT FROM AUTHOR]

Background: In India, chronic diseases are the leading cause of death and their prevalence has constantly increased over the last decade. Objective: This study aimed to identify risk factors associated with common chronic diseases among people aged 50 years and over in India. Materials and Methods: Data from Wave 1 of the 2007/2008 Indian Study on Global Ageing and Adult Health (SAGE) was used to investigate the association between lifestyle choices and chronic diseases using logistic regression. Result: The fully adjusted model showed that significant independent risk factors for angina included area of residence, being diagnosed with diabetes, chronic lung disease (CLD) [highest odds ratio (OR) 4.77, 95% confidence interval (CI): 2.95-7.70] and arthritis. For arthritis, risk factors included having underlying diabetes, CLD diagnosis, or angina (highest OR 2.32, 95% CI: 1.63-3.31). Risk factors associated with CLD included arthritis, angina (highest OR 4.76, 95% CI: 2.94-7.72), alcohol use, and tobacco use. Risk factors associated with diabetes included level of education, area of residence, socioeconomic status, angina (highest OR 3.59, 95% CI: 2.44-5.29), CLD, arthritis, stroke, and vegetable consumption. Finally, risk factors associated with stroke included diabetes and angina (highest OR 3.34, 95% CI: 1.72-6.50). The presence of any other comorbidity was significantly associated with all five chronic diseases studied. Conclusion: The results show that within the older population, the contribution of lifestyle risk factors to the common chronic diseases investigated in this study was limited. Our findings showed that the major health issue within the study population was multimorbidity. [ABSTRACT FROM AUTHOR]

This paper describes the evaluation of a pilot e-supervision programme, with a focus on feasibility. The findings suggest that e-supervision in mental health using the World Health Organization (WHO) Mental Health Gap Action Programme (mhGAP) Intervention Guide and case-based discussions is valued by participants and can improve the knowledge, confidence and beliefs of primary care doctors in low- and middle-income countries. [ABSTRACT FROM AUTHOR]

During severe influenza pandemics healthcare demand can exceed clinical capacity to provide normal standards of care. Community Assessment Tools (CATs) could provide a framework for triage decisions for hospital referral and admission. CATs have been developed based on evidence that supports the recognition of severe influenza and pneumonia in the community (including resource limited settings) for adults, children and infants, and serious feverish illness in children. CATs use six objective criteria and one subjective criterion, any one or more of which should prompt urgent referral and admission to hospital. A retrospective evaluation of the ability of CATs to predict use of hospital-based interventions and patient outcomes in a pandemic was made using the first recorded routine clinical assessment on or shortly after admission from 1520 unselected patients (800 female, 480 children <16 years) admitted with PCR confirmed A(H1N1)pdm09 infection (the FLU-CIN cohort). Outcome measures included: any use of supplemental oxygen; mechanical ventilation; intravenous antibiotics; length of stay; intensive or high dependency care; death; and “severe outcome” (combined: use of intensive or high dependency care or death during admission). Unadjusted and multivariable analyses were conducted for children (age <16 years) and adults. Each CATs criterion independently identified both use of clinical interventions that would in normal circumstances only be provided in hospital and patient outcome measures. “Peripheral oxygen saturation ≤92% breathing air, or being on oxygen” performed well in predicting use of resources and outcomes for both adults and children; supporting routine measurement of peripheral oxygen saturation when assessing severity of disease. In multivariable analyses the single subjective criterion in CATs “other cause for clinical concern” independently predicted death in children and in adults predicted length of stay, mechanical ventilation and “severe outcome”; supporting the role of clinical acumen as an important independent predictor of serious illness. [ABSTRACT FROM AUTHOR]

Background. The impact of neuraminidase inhibitor (NAI) treatment on clinical outcomes of public health importance during the 2009–2010 pandemic has not been firmly established.Methods. We conducted a systematic review and meta-analysis, searching 11 databases (2009 through April 2012) for relevant studies. We used standard methods conforming to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random effects models.Results. Regarding mortality we observed a nonsignificant reduction associated with NAI treatment (at any time) versus none (OR, 0.72 [95% CI, .51–1.01]). However we observed significant reductions for early treatment (≤48 hours after symptom onset) versus late (OR, 0.38 [95% CI, .27–.53]) and for early treatment versus none (OR, 0.35 [95% CI, .18–.71]). NAI treatment (at any time) versus none was associated with an elevated risk of severe outcome (OR, 1.76 [95% CI, 1.22–2.54]), but early versus late treatment reduced the likelihood (OR, 0.41 [95% CI, .30–.56]).Conclusions. During the 2009–2010 influenza A(H1N1) pandemic, early initiation of NAI treatment reduced the likelihood of severe outcomes compared with late or no treatment.PROSPERO Registration. CRD42011001273. [ABSTRACT FROM AUTHOR]

Introduction: The Influenza Clinical Information Network (FLU-CIN) was established to gather detailed clinical and epidemiological information about patients with laboratory confirmed A(H1 N1)pdm09 infection in UK hospitals. This report focuses on the clinical course and outcomes of infection in pregnancy. Methods: A standardised data extraction form was used to obtain detailed clinical information from hospital case notes and electronic records, for patients with PCR-confirmed A(H1N1)pdm09 infection admitted to 13 sentinel hospitals in five clinical 'hubs' and a further 62 non-sentinel hospitals, between 11th May 2009 and 31st January 2010.Outcomes were compared for pregnant and non-pregnant women aged 15-44 years, using univariate and multivariable techniques. Results: Of the 395 women aged 15-44 years, 82 (21%) were pregnant; 73 (89%) in the second or third trimester. Pregnant women were significantly less likely to exhibit severe respiratory distress at initial assessment (OR = 0.49 (95% CI: 0.30-0.82)), require supplemental oxygen on admission (OR = 0.40 (95% CI: 0.20-0.80)), or have underlying co-morbidities (p-trend <0.001). However, they were equally likely to be admitted to high dependency (Level 2) or intensive care (Level 3) and/or to die, after adjustment for potential confounders (adj. OR = 0.93 (95% CI: 0.46-1.92). Of 11 pregnant women needing Level 2/3 care, 10 required mechanical ventilation and three died. Conclusions: Since the expected prevalence of pregnancy in the source population was 6%, our data suggest that pregnancy greatly increased the likelihood of hospital admission with A(H1N1)pdm09. Pregnant women were less likely than non-pregnant women to have respiratory distress on admission, but severe outcomes were equally likely in both groups. [ABSTRACT FROM AUTHOR]

Triage tools have an important role in pandemics to identify those most likely to benefit from higher levels of care. We compared Community Assessment Tools (CATs), the CURB-65 score, and the Pandemic Medical Early Warning Score (PMEWS); to predict higher levels of care (high dependency - Level 2 or intensive care - Level 3) and/or death in patients at or shortly after admission to hospital with A/H1N1 2009 pandemic influenza. This was a case-control analysis using retrospectively collected data from the FLU-CIN cohort (1040 adults, 480 children) with PCR-confirmed A/H1N1 2009 influenza. Area under receiver operator curves (AUROC), sensitivity, specificity, positive predictive values and negative predictive values were calculated. CATs best predicted Level 2/3 admissions in both adults [AUROC (95% CI): CATs 0.77 (0.73, 0.80); CURB-65 0.68 (0.64, 0.72); PMEWS 0.68 (0.64, 0.73), p<0.001] and children [AUROC: CATs 0.74 (0.68, 0.80); CURB-65 0.52 (0.46, 0.59); PMEWS 0.69 (0.62, 0.75), p<0.001]. CURB-65 and CATs were similar in predicting death in adults with both performing better than PMEWS; and CATs best predicted death in children. CATs were the best predictor of Level 2/3 care and/or death for both adults and children. CATs are potentially useful triage tools for predicting need for higher levels of care and/or mortality in patients of all ages. [ABSTRACT FROM AUTHOR]

Background: Statins are drugs that are used to lower plasma cholesterol levels. Recently, contradictory claims have been made about possible additional effects of statins on progression of a variety of inflammatory disorders, including infections. We therefore examined the clinical course of patients admitted to hospital with 2009 pandemic influenza A(H1N1), who were or weren't taking statins at time of admission. Methods: A retrospective case-control study was performed using the United Kingdom Influenza Clinical Information Network (FLU-CIN) database, containing detailed information on 1,520 patients admitted to participating hospitals with confirmed 2009 pandemic influenza A(H1N1) infection between April 2009 and January 2010. We confined our analysis to those aged over 34 years. Univariate analysis was used to calculate unadjusted odds ratios (OR) and 95 percent confidence intervals (95%CI) for factors affecting progression to severe outcome (high dependency or intensive care unit level support) or death (cases); two multivariable logistic regression models were then established for age and sex, and for age, sex, obesity and ''indication for statin'' (e.g., heart disease or hypercholesterolaemia). Results: We found no statistically significant association between pre-admission statin use and severity of outcome after adjustment for age and sex [adjusted OR: 0.81 (95% CI: 0.46-1.38); n = 571]. After adjustment for age, sex, obesity and indication for statin, the association between pre-admission statin use and severe outcome was not statistically significant; point estimates are compatible with a small but clinically significant protective effect of statin use [adjusted OR: 0.72 (95% CI: 0.38-1.33)]. Conclusions: In this group of patients hospitalized with pandemic influenza, a significant beneficial effect of pre-admission statin use on the in-hospital course of illness was not identified. Although the database from which these observations are derived represents the largest available suitable UK hospital cohort, a larger study would be needed to confirm whether there is any benefit in this setting. [ABSTRACT FROM AUTHOR]

To determine clinical characteristics of patients hospitalized in the United Kingdom with pandemic (H1N1) 2009, we studied 1,520 patients in 75 National Health Service hospitals. We characterized patients who acquired influenza nosocomially during the pandemic (H1N1) 2009 outbreak. Of 30 patients, 12 (80%) of 15 adults and 14 (93%) of 15 children had serious underlying illnesses. Only 12 (57%) of 21 patients who received antiviral therapy did so within 48 hours after symptom onset, but 53% needed escalated care or mechanical ventilation; 8 (27%) of 30 died. Despite national guidelines and standardized infection control procedures, nosocomial transmission remains a problem when influenza is prevalent. Health care workers should be routinely offered influenza vaccine, and vaccination should be prioritized for all patients at high risk. Staff should remain alert to the possibility of influenza in patients with complex clinical problems and be ready to institute antiviral therapy while awaiting diagnosis during influenza outbreaks. [ABSTRACT FROM AUTHOR]

Background: The relationship between public transport use and acquisition of acute respiratory infection (ARI) is not well understood but potentially important during epidemics and pandemics. Methods: A case-control study performed during the 2008/09 influenza season. Cases (n = 72) consulted a General Practitioner with ARI, and controls with another non-respiratory acute condition (n = 66). Data were obtained on bus or tram usage in the five days preceding illness onset (cases) or the five days before consultation (controls) alongside demographic details. Multiple logistic regression modelling was used to investigate the association between bus or tram use and ARI, adjusting for potential confounders. Results: Recent bus or tram use within five days of symptom onset was associated with an almost six-fold increased risk of consulting for ARI (adjusted OR = 5.94 95% CI 1.33-26.5). The risk of ARI appeared to be modified according to the degree of habitual bus and tram use, but this was not statistically significant (1-3 times/week: adjusted OR = 0.54 (95% CI 0.15-1.95; >3 times/week: 0.37 (95% CI 0.13-1.06). Conclusions: We found a statistically significant association between ARI and bus or tram use in the five days before symptom onset. The risk appeared greatest among occasional bus or tram users, but this trend was not statistically significant. However, these data are plausible in relation to the greater likelihood of developing protective antibodies to common respiratory viruses if repeatedly exposed. The findings have differing implications for the control of seasonal acute respiratory infections and for pandemic influenza. [ABSTRACT FROM AUTHOR]

Background: Pneumonia is a common diagnosis in general practice in the United Kingdom and yet there is little known about the short- and long-term prognosis of people with a diagnosis of pneumonia in general practice. We investigated the short- and long-term survival of people with pneumonia diagnosed in general practice as compared to the general population for all ages. Methods: This was a general population-based cohort study. Data was obtained from a comprehensive general practice database called The Health Improvement Network (THIN) database which has computerized medical records from 300 general practice surgeries in the United Kingdom. We used Cox regression for our analyses. Results: For pneumonia cases the 30-day mortality was 18.5% and the 3-year mortality was 30.8%. The equivalent figures for the general population controls were 0.4% and 10.3% respectively. The adjusted hazard ratio (HR) for all-cause mortality (for total follow-up time) in pneumonia cases vs. general population was 4.64 (95% CI 4.35–4.95). For the first 30 days the risk of mortality in cases was 46 times more (adj. HR 45.90, 95% CI 36.80–55.20). Even in the period of follow-up 91 days after diagnosis cases were almost 20% more likely to die compared to general population (adj. HR 1.19, 95% CI 1.08–1.31). Conclusion: People in general practice who have a diagnosis of pneumonia have a markedly increased mortality in the short-term but some increase in mortality persists during longer-term follow-up. [ABSTRACT FROM PUBLISHER]

Background Contributing to a mission to build Public Health capacity in developing countries, two online epidemiology courses are offered: a tutor facilitated Master's level module 'Introduction to Epidemiology', and a free self-study 'Basic Epidemiology' Open Online Course (OOC). We report differences between these two. Methods Student demographics on enrolled students were abstracted. A follow-up online survey of former students was performed in January 2020. Results Among 772 students on the Master's and 619 students on the OOC courses: respectively 29% and 39% were female; 36% and 38% were medical practitioners; 80% and 43% were from Africa. For 64% of OOC students this was their first time learning online; 17% completed the course. 82% of students formally enrolled on a Master's programme passed the module. The majority of survey respondents reported that the courses had helped with reading articles critically (81% Master's; 67% OOC) and improving professional practice (75% Master's; 67% OOC); though fewer felt that the courses helped them perform their own research (67% Master's; 51% OOC). The majority (87% Masters; 79% OOC) would recommend the course to others. Conclusions Online epidemiology courses have the ability to reach a wide audience in the developing world and contribute to capacity building. While both Master's facilitated and self-study online courses were evaluated positively by students, the completion and potential impact was higher for the former. Key messages Online courses reaching wide audiences can help build global capacity in epidemiology [ABSTRACT FROM AUTHOR]

Background: Quality improvement (QI) initiatives are increasingly used to improve the quality of care and reduce prescribing errors. The Royal College of General Practitioners (RCGP) and Clinical Practice Research Datalink (CPRD) QI initiative uses routinely collected electronic primary care data to provide bespoke practice-level reports on prescribing safety. The aim of this study was to explore how the QI reports were used, barriers and facilitators to use, long-term culture change and perceived impact on patient care and practices systems as a result of receiving the reports.Methods: A qualitative study using purposive sampling of practices contributing to the CPRD, semi-structured interviews and inductive thematic analysis. We interviewed general practitioners, pharmacists, practice managers and research nurses.Results: We conducted 18 interviews, and organised themes summarising the use of QI reports in practice: receiving the report, facilitators and barriers to acting upon the reports, acting upon the report, and how the reports contribute to a quality culture. Effective dissemination of reports, and a positive attitude to audit and the perceived relevance of the clinical topic facilitated use. Lack of time and failure to see or act upon the reports meant they were not used. Factors influencing use of the reports included the structure of the report, ease of identifying cases, and perceptions about coding accuracy. GPs and pharmacists used the reports to conduct case reviews and directly contact patients to discuss unsafe prescribing and patient medication preferences. Finally, the reports contributed to the development of a quality culture within practices through promoting audit activity and acting as a reminder of good prescribing behaviours, promoting future patient safety initiatives, contributing to continuing professional development and improving local networks.Conclusions: This study found the reports facilitated individual case review leading to an enhanced sense of quality culture in practices where they were utilised. Our findings demonstrate that the reports were generally considered useful and have been used to support patient safety and clinical practice in specific cases. [ABSTRACT FROM AUTHOR]

Background: Quality improvement (QI) initiatives are increasingly used to improve the quality of care and reduce prescribing errors. The Royal College of General Practitioners (RCGP) and Clinical Practice Research Datalink (CPRD) QI initiative uses routinely collected electronic primary care data to provide bespoke practice-level reports on prescribing safety. The aim of this study was to explore how the QI reports were used, barriers and facilitators to use, long-term culture change and perceived impact on patient care and practices systems as a result of receiving the reports. Methods: A qualitative study using purposive sampling of practices contributing to the CPRD, semi-structured interviews and inductive thematic analysis. We interviewed general practitioners, pharmacists, practice managers and research nurses. Results: We conducted 18 interviews, and organised themes summarising the use of QI reports in practice: receiving the report, facilitators and barriers to acting upon the reports, acting upon the report, and how the reports contribute to a quality culture. Effective dissemination of reports, and a positive attitude to audit and the perceived relevance of the clinical topic facilitated use. Lack of time and failure to see or act upon the reports meant they were not used. Factors influencing use of the reports included the structure of the report, ease of identifying cases, and perceptions about coding accuracy. GPs and pharmacists used the reports to conduct case reviews and directly contact patients to discuss unsafe prescribing and patient medication preferences. Finally, the reports contributed to the development of a quality culture within practices through promoting audit activity and acting as a reminder of good prescribing behaviours, promoting future patient safety initiatives, contributing to continuing professional development and improving local networks. Conclusions: This study found the reports facilitated individual case review leading to an enhanced sense of quality culture in practices where they were utilised. Our findings demonstrate that the reports were generally considered useful and have been used to support patient safety and clinical practice in specific cases. [ABSTRACT FROM AUTHOR]

Background: The economic impact of managing long COVID in primary care is unknown. We estimated the costs of primary care consultations associated with long COVID and explored the relationship between risk factors and costs. Methods: Data were obtained on non-hospitalised adults from the Clinical Practice Research Datalink Aurum primary care database. We used propensity score matching with an incremental cost method to estimate additional primary care consultation costs associated with long COVID (12 weeks after COVID-19) at an individual and UK national level. We applied multivariable regression models to estimate the association between risk factors and consultations costs beyond 12 weeks from acute COVID-19. Results: Based on an analysis of 472,173 patients with COVID-19 and 472,173 unexposed individuals, the annual incremental cost of primary care consultations associated with long COVID was £2.44 per patient and £23,382,452 at the national level. Among patients with COVID-19, a long COVID diagnosis and reporting of longer-term symptoms were associated with a 43% and 44% increase in primary care consultation costs respectively, compared to patients without long COVID symptoms. Older age, female sex, obesity, being from a white ethnic group, comorbidities and prior consultation frequency were all associated with increased primary care consultation costs. Conclusions: The costs of primary care consultations associated with long COVID in non-hospitalised adults are substantial. Costs are significantly higher among those diagnosed with long COVID, those with long COVID symptoms, older adults, females, and those with obesity and comorbidities. [ABSTRACT FROM AUTHOR]

Objectives The effectiveness of inactivated influenza vaccine in people with autoimmune rheumatic disease (AIRDs) is not known. We investigated whether the influenza vaccine is effective in preventing respiratory morbidity, mortality and all-cause mortality in AIRD patients. Methods Adults with AIRDs treated with DMARDs prior to 1 September of each year between 2006 and 2009, and 2010 and 2015 were identified from the Clinical Practice Research Datalink. Exposure and outcome data were extracted. Data from multiple seasons were pooled. Propensity score (PS) for vaccination was calculated. Cox-proportional hazard ratios (HRs) and 95% CIs were calculated, and were (i) adjusted, (ii) matched for PS for vaccination. Results Data for 30 788 AIRD patients (65.7% female, 75.5% with RA, 61.1% prescribed MTX) contributing 125 034 influenza cycles were included. Vaccination reduced risk of influenza-like illness [adjusted HR (aHR) 0.70], hospitalization for pneumonia (aHR 0.61) and chronic obstructive pulmonary disease exacerbations (aHR 0.67), and death due to pneumonia (aHR 0.56) on PS-adjusted analysis in the influenza active periods (IAPs). The associations were of similar magnitude and remained statistically significant on PS-matched analysis except for protection from influenza-like illness, which became non-significant. Sub-analysis restricted to pre-IAP, IAP and post-IAP did not yield evidence of residual confounding on influenza-like illness and death due to pneumonia. Vaccination reduced risk of all-cause mortality, although IAP-restricted analysis demonstrated residual confounding for this outcome. Conclusion Influenza vaccine associates with reduced risk of respiratory morbidity and mortality in people with AIRDs. These findings call for active promotion of seasonal influenza vaccination in immunosuppressed people with AIRDs by healthcare professionals. [ABSTRACT FROM AUTHOR]

Background: Limited healthcare facility (HCF) resources and capacity to implement multi-stranded cholera interventions (water, sanitation, and hygiene (WASH), surveillance, case management, and community engagement) can hinder the actualisation of the global strategic roadmap goals for cholera control, especially in settings made fragile by armed conflicts, such as the north-east region of Nigeria. Therefore, we aimed to assess HCF resource availability and capacity to implement these cholera interventions in Adamawa and Bauchi States in Nigeria as well as assess their coordination in both states and Abuja where national coordination of cholera is based. Methods: We conducted a cross-sectional survey using a face-to-face structured questionnaire to collect data on multi-stranded cholera interventions and their respective indicators in HCFs. We generated scores to describe the resource availability of each cholera intervention and categorised them as follows: 0–50 (low), 51–70 (moderate), 71–90 (high), and over 90 (excellent). Further, we defined an HCF with a high capacity to implement a cholera intervention as one with a score equal to or above the average intervention score. Results: One hundred and twenty HCFs (55 in Adamawa and 65 in Bauchi) were surveyed in March 2021, most of which were primary healthcare centres (83%; 99/120). In both states, resource availability for WASH indicators had high to excellent median scores; surveillance and community engagement indicators had low median scores. Median resource availability scores for case management indicators ranged from low to moderate. Coordination of cholera interventions in Adamawa State and Abuja was high but low in Bauchi State. Overall, HCF capacity to implement multi-stranded cholera interventions was high, though higher in Adamawa State than in Bauchi State. Conclusions: The study found a marked variation in HCF resource availability and capacity within locations and by cholera interventions and identified cholera interventions that should be prioritised for strengthening as surveillance and laboratory, case management, and community engagement. The findings support adopting a differential approach to strengthening cholera interventions for better preparedness and response to cholera outbreaks. [ABSTRACT FROM AUTHOR]

Objectives To examine temporal trend in uptake of seasonal influenza vaccine (SIV) in the UK and explore disease and demographic factors associated with vaccination. Methods From the Clinical Practice Research Datalink, 32 751 people with auto-immune rheumatic diseases prescribed DMARDs between 2006 and 2016 were identified. The proportion vaccinated between 1 September of one year and 31 March of the next year was calculated and stratified by age, other indications for vaccination, auto-immune rheumatic diseases type and number of DMARDs prescribed. Stata and Joinpoint regression programs were used. Results SIV uptake was high in those aged ⩾65 years (82.3 and 80.7% in 2006–07 and 2015–16, respectively). It was significantly lower in other age groups, but improved over time with 51.9 and 61.9% in the 45–64 year age group, and 32.3 and 50.1% in the <45 year age group being vaccinated in 2006–07 and 2015–16, respectively. While 64.9% of the vaccinations in those ⩾65 years old occurred by 3 November, in time to mount a protective immune response before the influenza activity becomes substantial in the UK, only 38.9% in the 45–64 year and 26.2% in the <45 year age group without any other reason for vaccination received SIV by this date. Women, those with additional indications for vaccination, on multiple DMARDs and with SLE were more likely to be vaccinated. Conclusion SIV uptake is low in the under 65s, and the majority of them are not vaccinated in time. Additional effort is required to promote timely uptake of SIV in this population. [ABSTRACT FROM AUTHOR]

Background: This descriptive study assessed the completeness, agreement, and representativeness of ethnicity recording in the United Kingdom (UK) Clinical Practice Research Datalink (CPRD) primary care databases alone and, for those patients registered with a GP in England, when linked to secondary care data from Hospital Episode Statistics (HES). Methods: Ethnicity records were assessed for all patients in the May 2021 builds of the CPRD GOLD and CPRD Aurum databases for all UK patients. In analyses of the UK, English data was from combined CPRD-HES, whereas data from Northern Ireland, Scotland, and Wales drew from CPRD only. The agreement of ethnicity records per patient was assessed within each dataset (CPRD GOLD, CPRD Aurum, and HES datasets) and between datasets at the highest level ethnicity categorisation ('Asian', 'black', 'mixed', 'white', 'other'). Representativeness was assessed by comparing the ethnic distributions at the highest-level categorisation of CPRD-HES to those from the Census 2011 across the UK's devolved administrations. Additionally, CPRD-HES was compared to the experimental ethnic distributions for England and Wales from the Office for National Statistics in 2019 (ONS2019) and the English ethnic distribution from May 2021 from NHS Digital's General Practice Extraction Service Data for Pandemic Planning and Research with HES data linkage (GDPPR-HES). Results: In CPRD-HES, 81.7% of currently registered patients in the UK had ethnicity recorded in primary care. For patients with multiple ethnicity records, mismatched ethnicity within individual primary and secondary care datasets was < 10%. Of English patients with ethnicity recorded in both CPRD and HES, 93.3% of records matched at the highest-level categorisation; however, the level of agreement was markedly lower in the 'mixed' and 'other' ethnic groups. CPRD-HES was less proportionately 'white' compared to the UK Census 2011 (80.3% vs. 87.2%) and experimental ONS2019 data (80.4% vs. 84.3%). CPRD-HES was aligned with the ethnic distribution from GDPPR-HES ('white' 80.4% vs. 80.7%); however, with a smaller proportion classified as 'other' (1.1% vs. 2.8%). Conclusions: CPRD-HES has suitable representation of all ethnic categories with some overrepresentation of minority ethnic groups and a smaller proportion classified as 'other' compared to the UK general population from other data sources. CPRD-HES data is useful for studying health risks and outcomes in typically underrepresented groups. [ABSTRACT FROM AUTHOR]

Background: Healthcare workers' (HCWs) knowledge of multi-stranded cholera interventions (including case management, water, sanitation, and hygiene (WASH), surveillance/laboratory methods, coordination, and vaccination) is crucial to the implementation of these interventions in healthcare facilities, especially in conflict-affected settings where cholera burden is particularly high. We aimed to assess Nigerian HCWs' knowledge of cholera interventions and identify the associated factors. Methods: We conducted a cross-sectional study using a structured interviewer-administered questionnaire with HCWs from 120 healthcare facilities in Adamawa and Bauchi States, North-East Nigeria. A knowledge score was created by assigning a point for each correct response. HCWs' knowledge of cholera interventions, calculated as a score, was recoded for ease of interpretation as follows: 0–50 (low); 51–70 (moderate); ≥ 71 (high). Additionally, we defined the inadequacy of HCWs' knowledge of cholera interventions based on a policy-relevant threshold of equal or lesser than 75 scores for an intervention. Multivariable logistic regression was used to identify the factors associated with the adequacy of knowledge score. Results: Overall, 490 HCWs participated in the study (254 in Adamawa and 236 in Bauchi), with a mean age of 35.5 years. HCWs' knowledge score was high for surveillance/laboratory methods, moderate for case management, WASH, and vaccination, and low for coordination. HCWs' knowledge of coordination improved with higher cadre, working in urban- or peri-urban-based healthcare facilities, and secondary education; cholera case management and vaccination knowledge improved with post-secondary education, working in Bauchi State and urban areas, previous training in cholera case management and response to a cholera outbreak—working in peri-urban areas had a negative effect. HCWs' knowledge of surveillance/laboratory methods improved with a higher cadre, 1-year duration in current position, secondary or post-secondary education, previous training in cholera case management and response to a cholera outbreak. However, HCWs' current position had both positive and negative impacts on their WASH knowledge. Conclusions: HCWs in both study locations recorded a considerable knowledge of multi-stranded cholera interventions. While HCWs' demographic characteristics appeared irrelevant in determining their knowledge of cholera interventions, geographic location and experiences from the current position, training and involvement in cholera outbreak response played a significant role. [ABSTRACT FROM AUTHOR]

Background Early identification of patients with H1N1 influenza-related pneumonia is desirable for the early instigation of antiviral agents. A study was undertaken to investigate whether adults admitted to hospital with H1N1 influenza-related pneumonia could be distinguished clinically from patients with non-H1N1 community-acquired pneumonia (CAP). Methods Between May 2009 and January 2010, clinical and epidemiological data of patients with confirmed H1N1 influenza infection admitted to 75 hospitals in the UK were collected by the Influenza Clinical Information Network (FLU-CIN). Adults with H1N1 influenza-related pneumonia were identified and compared with a prospective study cohort of adults with CAP hospitalised between September 2008 and June 2010, excluding those admitted during the period of the pandemic. Results Of 1046 adults with confirmed H1N1 influenza infection in the FLU-CIN cohort, 254 (25%) had H1N1 influenza-related pneumonia on admission to hospital. In-hospital mortality of these patients was 11.4% compared with 14.0% in patients with inter-pandemic CAP (n=648). A multivariate logistic regression model was generated by assigning one point for each of five clinical criteria: age ≤65⇔…years, mental orientation, temperature ≥38°C, leucocyte count ≤12⇔-109/l and bilateral radiographic consolidation. A score of 4 or 5 predicted H1N1 influenza-related pneumonia with a positive likelihood ratio of 9.0. A score of 0 or 1 had a positive likelihood ratio of 75.7 for excluding it. Conclusion There are substantial clinical differences between H1N1 influenza-related pneumonia and inter-pandemic CAP. A model based on five simple clinical criteria enables the early identification of adults admitted with H1N1 influenza-related pneumonia. [ABSTRACT FROM AUTHOR]

Background The impact of neuraminidase inhibitors ( NAIs) on influenza-related pneumonia ( IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. Methods A worldwide meta-analysis of individual participant data from 20 634 hospitalised patients with laboratory-confirmed A(H1N1)pdm09 ( n = 20 021) or clinically diagnosed ( n = 613) 'pandemic influenza'. The primary outcome was radiologically confirmed IRP. Odds ratios ( OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. Results Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64-1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44-1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71-1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55-0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54-0·85; P = 0·001)]. Conclusions Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support. [ABSTRACT FROM AUTHOR]

Use of prescribing safety quality improvement reports in UK general practices: a qualitative assessment. The incorrect author name is: Nick Thomas The correct author name is: Nicholas PB Thomas The author group has been updated above, and the original publication has been corrected. [Extracted from the article]

Background: Recent data suggest that beta blockers are associated with increased perioperative risk in hypertensive patients. We investigated whether beta blockers were associated with an increased risk in elderly patients with raised preoperative arterial blood pressure.Methods: We conducted a propensity-score-matched cohort study of primary care data from the UK Clinical Practice Research Datalink (2004-13), including 84 633 patients aged 65 yr or over. Conditional logistic regression models, including factors that were significantly associated with the outcome, were constructed for 30-day mortality after elective noncardiac surgery. The effects of beta blockers (primary outcome), renin-angiotensin system (RAS) inhibitors, calcium-channel blockers, thiazides, loop diuretics, and statins were investigated at systolic and diastolic arterial pressure thresholds.Results: Beta blockers were associated with increased odds of postoperative 30-day mortality in patients with systolic hypertension (defined as systolic BP >140 mm Hg; adjusted odds ratio [aOR]: 1.92; 95% confidence interval [CI]: 1.05-3.51). After excluding patients for whom prior data suggest benefit from perioperative beta blockade (patients with prior myocardial infarction or heart failure), rather than adjusting for them, the point estimate shifted slightly (aOR: 2.06; 95% CI: 1.09-3.89). Compared with no use, statins (aOR: 0.35; 95% CI: 0.17-0.75) and thiazides (aOR: 0.28; 95% CI: 0.10-0.78) were associated with lower mortality in patients with systolic hypertension.Conclusions: These data suggest that the safety of perioperative beta blockers may be influenced by preoperative blood pressure thresholds. A randomised controlled trial of beta-blocker withdrawal, in select populations, is required to identify a causal relationship. [ABSTRACT FROM AUTHOR]

Background: Standardised clinical outcome measures are urgently needed for the surveillance of influenza and influenza‐like illness (ILI) based on individual patient data (IPD). Objectives: We report a multicentre prospective cohort using a predefined disease severity score in routine care. Patients/Methods: The Vienna Vaccine Safety initiative (ViVI) Disease Severity Score ("ViVI Score") was made available as an android‐based mobile application to three paediatric hospitals in Berlin and Athens between 2013 and 2016. Healthcare professionals assessed ILI patients at the point of care including severity, risk factors and use of antibiotics/antivirals/vaccines. RT‐PCR for influenza A/B viruses was performed at the Hellenic Pasteur Institute and the Robert Koch Institute. PCR testing was blinded to severity scoring and vice versa. Results: A total of 1615 children aged 0‐5 years (54.4% males) were assessed at the three sites. The mean age was 1.7 years (SD 1.5; range 0‐5.9). The success rate (completion of the scoring without disruption to the ER workflow) was 100%. ViVI Disease Severity Scores ranged from 0 to 35 (mean 13.72). Disease severity in the Berlin Cohort was slightly higher (mean 15.26) compared to the Athens Cohorts (mean 10.86 and 11.13). The administration of antibiotics was most prevalent in the Berlin Cohort, with 41.2% on antibiotics (predominantly cefuroxime) as opposed to only 0.5% on neuraminidase inhibitors. Overall, Risk‐adjusted ViVI Scores were significantly linked to the prescription of both, antibiotics and antivirals. Conclusions: The Risk‐adjusted ViVI Score enables a precision medicine approach to managing ILI in multicentre settings. Using mobile applications, severity data will be obtained in real time with important implications for the evaluation of antiviral/vaccine use. [ABSTRACT FROM AUTHOR]

Background: The impact of neuraminidase inhibitor (NAI) treatment on clinical outcomes of public health importance during the 2009-2010 pandemic has not been firmly established.Methods: We conducted a systematic review and meta-analysis, searching 11 databases (2009 through April 2012) for relevant studies. We used standard methods conforming to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random effects models.Results: Regarding mortality we observed a nonsignificant reduction associated with NAI treatment (at any time) versus none (OR, 0.72 [95% CI, .51-1.01]). However we observed significant reductions for early treatment (≤48 hours after symptom onset) versus late (OR, 0.38 [95% CI, .27-.53]) and for early treatment versus none (OR, 0.35 [95% CI, .18-.71]). NAI treatment (at any time) versus none was associated with an elevated risk of severe outcome (OR, 1.76 [95% CI, 1.22-2.54]), but early versus late treatment reduced the likelihood (OR, 0.41 [95% CI, .30-.56]).Conclusions: During the 2009-2010 influenza A(H1N1) pandemic, early initiation of NAI treatment reduced the likelihood of severe outcomes compared with late or no treatment.Prospero Registration: CRD42011001273. [ABSTRACT FROM AUTHOR]

Objectives Benzodiazepines have been associated with an increased incidence of infections, and mortality from sepsis, in the critically ill. Here, we determined the effect of community use of benzodiazepines on the occurrence of, and mortality following, pneumonia. Methods A nested case-control study using 29 697 controls and 4964 cases of community-acquired pneumonia (CAP) from The Health Improvement Network, a UK primary care patient database (2001-2002), investigated the association between benzodiazepines and pneumonia occurrence using conditional logistic regression. Cox regression was then used to determine the impact of benzodiazepines on mortality in the 4964 cases of CAP. Results are presented as adjusted OR, adjusted HR and 95% CI. Results Exposure to benzodiazepines was associated with an increased risk of pneumonia (OR 1.54, 95% CI 1.42 to 1.67). Individually diazepam, lorazepam and temazepam, but not chlordiazepoxide, were associated with an increased incidence of CAP. As a class, benzodiazepines were associated with increased 30-day (HR 1.22 (95% CI 1.06 to 1.39)) and long-term mortality (HR 1.32 (95% CI 1.19 to 1.47)) in patients with a prior diagnosis of CAP. Individually diazepam, chlordiazepoxide, lorazepam and temazepam affected long-term mortality in these patients. Conclusions Benzodiazepines were associated with an increased risk of, and mortality from, CAP. These hypothesis generating data suggest further research is required into the immune safety profile of benzodiazepines. [ABSTRACT FROM AUTHOR]

Introduction: Illness and death from influenza increase during pregnancy. In the United Kingdom pregnant women were targeted in a national programme for vaccination during the H1N1 2009-10 pandemic. Methods: In this study, pregnant women were recruited in labour from November 9, 2009 to March 10, 2010. Pandemic vaccination status was determined. Venous cord blood collected at delivery was evaluated for transplacental transfer of antibodies by measurement of haemagglutination inhibition and microneutralization titres. Results: Samples were collected from 77 vaccinated and 27 unvaccinated women. Seroprotection (HI titre ≥1:40) was detected in 58 (75.3%, 95% CI 64.2-84.4) cord blood samples from vaccinated women and 5 (18.5%, 95% CI 6.3-38.1) from unvaccinated women (P<0.0001). There was evidence of transplacental seroprotection 8 days after maternal immunization (77.9%, 95 CI 66.2-87.1), maintained in most cases for at least 16 weeks. Discussion: Immunization of pregnant women with AS03A-adjuvanted vaccine is followed by transplacental transfer of passive immunity at titres consistent with clinical protection in three-quarters of new-born infants. The findings support national and international pandemic H1N1 2009 recommendations for immunization during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Although generally mild, the 2009-2010 influenza A/H1N1 pandemic caused two major surges in hospital admissions in the UK. The characteristics of patients admitted during successive waves are described.Methods: Data were systematically obtained on 1520 patients admitted to 75 UK hospitals between May 2009 and January 2010. Multivariable analyses identified factors predictive of severe outcome.Results: Patients aged 5-54 years were over-represented compared with winter seasonal admissions for acute respiratory infection, as were non-white ethnic groups (first wave only). In the second wave patients were less likely to be school age than in the first wave, but their condition was more likely to be severe on presentation to hospital and they were more likely to have delayed admission. Overall, 45% had comorbid conditions, 16.5% required high dependency (level 2) or critical (level 3) care and 5.3% died. As in 1918-1919, the likelihood of severe outcome by age followed a W-shaped distribution. Pre-admission antiviral drug use decreased from 13.3% to 10% between the first and second waves (p=0.048), while antibiotic prescribing increased from 13.6% to 21.6% (p<0.001). Independent predictors of severe outcome were age 55-64 years, chronic lung disease (non-asthma, non-chronic obstructive pulmonary disease), neurological disease, recorded obesity, delayed admission (≥5 days after illness onset), pneumonia, C-reactive protein ≥100 mg/litre, and the need for supplemental oxygen or intravenous fluid replacement on admission.Conclusions: There were demographic, ethnic and clinical differences between patients admitted with pandemic H1N1 infection and those hospitalised during seasonal influenza activity. Despite national policies favouring use of antiviral drugs, few patients received these before admission and many were given antibiotics. [ABSTRACT FROM AUTHOR]

A response by Wei Shen Lim and colleagues to a letter to the editor about their study of H1N1 pneumonia cohort.

A letter to the editor is presented in response to the article which discusses the leadership in the public health sector in the September 17, 2011 issue.

Background: Peoples-uni (People's Open Access Education Initiative) was established to help build Public Health capacity in low- and middle-income countries (LMICs) through postgraduate level online courses. Graduates are invited to join a virtual alumni group. We report the results of efforts to meet the need for health research capacity building by exploring how the course alumni could be mobilised to perform collaborative research into the health problems of their populations.Methods: Two online surveys of Peoples-uni graduates were conducted with graduates from the first two and first four cohorts in 2013 and 2014, respectively, to explore the formation of an alumni group that would collaborate to further the research and development agenda in LMICs. This was followed by feedback on research-related activity and outcomes via the online alumni and tutors' forum to estimate early indicators of alumni success in relation to capacity building in both the conduct and utilisation of research.Results: Responses were received from 26 (87% response rate) graduates of the first survey and 42 (60% response rate) of the second survey. Overall, 92% of the respondents to the first survey supported the creation of an alumni group, especially if it helped to develop their own research skills and improve the health of their populations. Findings from the second survey showed that study with Peoples-uni was felt to have had a major or potential impact on the careers of the respondents, with 19% of graduates having progressed to a PhD programme to further their research skills, and a further 48% being in the process of applying or intending to apply for doctoral studies. Further feedback shows that at least one collaborative study has been completed and published by alumni members with other collaborative studies planned. Ongoing support has been provided to graduates to help them publish their work and apply for individual or collaborative research grants.Conclusions: Harnessing the alumni of a Masters level course to perform collaborative research has considerable potential to build research capacity in LMICs. [ABSTRACT FROM AUTHOR]