The impact of the COVID-19 pandemic on non-COVID-associated mortality: A descriptive longitudinal study of UK data.

Background: It has been previously reported in the literature that the COVID-19 pandemic resulted in overall excess deaths and an increase in non-COVID deaths during the pandemic period.Specifically, our research elucidates the impact of the COVID-19 pandemic on non-COVID associated mortality. Study aim: To compare mortality rates in non-COVID conditions before and after the onset of the COVID-19 pandemic in England and Wales. Study design: Annual mortality data for the years 2011-2019 (pre-pandemic) and 2020 (pandemic) in England and Wales were retrieved from the Office for National Statistics (ONS). These data were filtered by ICD-10 codes for nine conditions with high associated mortality. We calculated mortality numbers - overall and age stratified (20-64 and 65+ years) and rates per 100 000, using annual mid-year population estimates. Methods: Interrupted time series analyses were conducted using segmented quasi-Poisson regression to identify whether there was a statistically significant change (p < 0.05) in condition-specific death rates following the pandemic onset. Results: Eight of the nine conditions investigated in this study had significant changes in mortality rate during the pandemic period (2020). All-age mortality rate was significantly increased in: 'Symptoms Signs and Ill-defined conditions', 'Cirrhosis and Other Diseases of the Liver', and 'Malignant Neoplasm of the Breast', whereas 'Chronic Lower Respiratory Disorders' saw a significant decrease. Age-stratified analyses also revealed significant increases in the 20-64 age-group in: 'Cerebrovascular Disorders', 'Dementia and Alzheimer's Disease', and 'Ischaemic Heart Diseases'. Conclusion: Trends in non-COVID condition-specific mortality rates from 2011 to 2020 revealed that some non-COVID conditions were disproportionately affected during the pandemic. This may be due to the direct impact COVID-19 had on these conditions or the effect the public health response had on non-COVID risk factor development and condition-related management. Further work is required to understand the reasons behind these disproportionate changes.

Pertussis immunisation strategies to optimise infant pertussis control: A narrative systematic review.

OBJECTIVE: Countries routinely offering acellular pertussis vaccine, where long-term protection is not sustained, have the challenge of selecting an optimal schedule to minimise disease among young infants. We conducted a narrative systematic review and synthesis of information to evaluate different pertussis immunisation strategies at controlling pertussis disease, hospitalisation, deaths, and vaccine effectiveness among young infants. METHODS: We conducted a review of the literature on studies about the primary, booster, and/or maternal vaccination series and synthesised findings narratively. Countries offering the first three doses of vaccine within six-months of life and a booster on or before the second year or life were defined as accelerated primary and booster schedules, respectively. Countries offering primary and booster doses later were defined as extended primary and booster schedules. All search results were screened, and articles reviewed and reconciled, by two authors. The Risk of Bias in Non-randomised Studies of Intervention tool was used to evaluate the risk of bias. FINDINGS: A total of 98 studies were included in the analyses and the following recurring themes were described: timing of vaccination, vaccine coverage, waning immunity/vaccine effectiveness, direct and indirect effectiveness, switching from an accelerated to extended schedule, impact of changes in testing. The risk of bias was generally low to moderate for most studies. CONCLUSION: Comparing schedules is challenging and there was insufficient evidence to that one schedule was superior to another. Countries must select a schedule that maintains high vaccine coverage and reduced the risk of delaying the delivery vaccines to protect infants.

The relationship between Quality and Outcomes Framework scores and socioeconomic deprivation: a longitudinal study.

BACKGROUND: The Quality Outcomes Framework (QOF) is a pay incentive scheme in England designed to improve and standardise general practice. QOF attainment has been used as a proxy for primary care quality in previous research. AIM: To investigate whether there is a relationship between socioeconomic deprivation and QOF attainment in primary care in England. DESIGN & SETTING: Retrospective longitudinal study of primary care providers in England. METHOD: QOF scores were obtained for individual general practices in England from between 2007-2019 and linked to practice-level Indices of Multiple Deprivation (IMD) scores derived from census data. Beta regression analyses were used to analyse the relationship with either percentage of total QOF attainment or of domain-specific attainment with multivariate analyses, adjusting for additional practice-level demographics. QOF attainment in the most affluent quintile was used as the reference group. RESULTS: General practices in less deprived areas have consistently outperformed those in more deprived areas in terms of QOF achievement. Initially, the gap between least and most deprived practices decreased, however since 2015 there has been relatively little change in comparative performance. The magnitude of inequality was reduced after adjusting for demographic factors. Of the independent variables analysed, the proportion of patients aged >65 years ('over 65s') had the strongest relationship with QOF attainment. CONCLUSION: There remains an inequality in primary care quality by socioeconomic deprivation in England, even after accounting for demographic differences.

A systematic review of the burden of, access to services for and perceptions of patients with overweight and obesity, in humanitarian crisis settings.

INTRODUCTION: Excess body weight causes 4 million deaths annually across the world. The number of people affected by humanitarian crises stands at a record high level with 1 in 95 people being forcibly displaced. These epidemics overlap. Addressing obesity is a post-acute phase activity in non-communicable disease management in humanitarian settings. Information is needed to inform guidelines and timing of interventions. The objective of this review was to explore the prevalence of overweight and obesity in populations directly affected by humanitarian crises; the cascade of care in these populations and perceptions of patients with overweight and obesity. METHODS: Literature searches were carried out in five databases. Grey literature was identified. The population of interest was non-pregnant, civilian adults who had experience of humanitarian crises (armed conflict, complex emergencies and natural disasters). All study types published from January 1st, 2011, were included. Screening, data extraction and quality appraisal were carried out in duplicate. A narrative synthesis is presented. RESULTS: Fifty-six reports from forty-five studies were included. Prevalence estimates varied widely across the studies and by subgroups. Estimates of overweight and obesity combined ranged from 6.4% to 82.8%. Studies were heterogenous. Global distribution was skewed. Increasing adiposity was seen over time, in older adults and in women. Only six studies were at low risk of bias. Body mass index was the predominant measure used. There were no studies reporting cascade of care. No qualitative studies were identified. CONCLUSION: Overweight and obesity varied in crisis affected populations but were rarely absent. Improved reporting of existing data could provide more accurate estimates. Worsening obesity may be prevented by acting earlier in long-term crises and targeting risk groups. The use of waist circumference would provide useful additional information. Gaps remain in understanding the existing cascade of care. Cultural norms around diet and ideal body size vary.

Impact of national COVID-19 restrictions on incidence of notifiable communicable diseases in England: an interrupted time series analysis.

BACKGROUND: Non-pharmaceutical interventions (NPIs), such as travel restrictions, social distancing and isolation policies, aimed at controlling the spread of COVID-19 may have reduced transmission of other endemic communicable diseases, such as measles, mumps and meningitis in England. METHODS: An interrupted time series analysis was conducted to examine whether NPIs was associated with trends in endemic communicable diseases, using weekly reported cases of seven notifiable communicable diseases (food poisoning, measles, meningitis, mumps, scarlet fever and pertussis) between 02/01/2017 to 02/01/2021 for England. RESULTS: Following the introduction of COVID-19 restrictions, there was an 81.1% (95% CI; 77.2-84.4) adjusted percentage reduction in the total number of notifiable diseases recorded per week in England. The greatest decrease was observed for measles, with a 90.5% percentage reduction (95% CI; 86.8-93.1) from 42 to 5 cases per week. The smallest decrease was observed for food poisoning, with a 56.4% (95%CI; 42.5-54.2) decrease from 191 to 83 cases per week. CONCLUSIONS: A total reduction in the incidence of endemic notifiable diseases was observed in England following the implementation of public health measures aimed at reducing transmission of SARS-COV-2 on March 23, 2020. The greatest reductions were observed in diseases most frequently observed during childhood that are transmitted via close human-to-human contact, such as measles and pertussis. A less substantive reduction was observed in reported cases of food poisoning, likely due to dining services (i.e., home deliveries and takeaways) remaining open and providing a potential route of transmission. This study provides further evidence of the effectiveness of non-pharmaceutical public health interventions in reducing the transmission of both respiratory and food-borne communicable diseases.

Associations between socioeconomic deprivation and pharmaceutical prescribing in primary care in England.

BACKGROUND: Socioeconomic deprivation is associated with health inequality. Previous studies have described associations between primary care prescribing rates and deprivation for individual drugs or drug classes. We explore the correlation between socioeconomic deprivation and the rate of prescribing of individual pharmaceutical drugs, and drug classes, in primary care in England, to identify prescribing inequalities that would require further investigation. METHODS: In this cross-sectional study, national primary care prescribing data, by primary care practice, were retrieved for the calendar year 2019 in England. Socioeconomic deprivation was quantified using the Index of Multiple Deprivation (IMD) score. Correlations were calculated using Spearman's rank correlation coefficient (ρ), adjusting for practice list size and demographics, with a Bonferroni-corrected p value threshold of 5×10-5. RESULTS: We included 1.05 billion prescription items dispensed from 6896 England practices. 142/206 (69%) drug classes and 505/774 (65%) drugs were significantly correlated with IMD score (p<5×10-5). Of the 774 included drugs, 31 (4%) were moderately positively associated with IMD score (ρ>0.4). Only one was moderately negatively correlated with IMD score (ρ<-0.4), suggesting higher prescribing rates in more affluent areas. The drug classes most strongly associated with IMD score included opioid and non-opioid analgesics, antipsychotics and reflux medications. Drug classes most strongly associated with affluence included epinephrine, combined oral contraceptives and hormone replacement therapy. CONCLUSION: We identify novel associations of prescribing with deprivation. Further work is required to identify the underlying reasons for these associations so that appropriate interventions can be formulated to address drivers of inequality.

A scoping review of studies on the health impact of electronic nicotine delivery systems.

We conducted a scoping review of studies on health outcomes from electronic nicotine delivery systems (ENDS). The objective was to identify, narratively synthesize, assess the strength and quality of evidence and critically appraise studies that have reported disease end points associated with the use of ENDS. We included published literature on the health impact of ENDS from 01/01/2015 until 01/02/2020 following the PRISMA guidelines using PubMed, Embase, Scopus and Google Scholar. The database search identified 755 studies, and other sources 265; 37 studies met final eligibility criteria. Levels of evidence included 24(65%) cross-sectional, one (2.7%) case-control and six (16%) case studies, four (11%) cohort studies, one (2.7%) randomized controlled trial (RCT) and one (2.7%) meta-analysis; 27(73%) studies reported only on harms, eight (22%) reported on benefits, two (2%) on benefits and harms. Quality ratings were poor in 20 (54%), fair in 9(24%) and good in 8(22%) of studies. In our review, ENDS was not shown to be causative for harmful cardiovascular disease (CVD) outcomes and shown to be beneficial for hypertensive patients. Switching from cigarettes to e-cigarettes resulted in reduced exacerbations of chronic obstructive pulmonary disease (COPD), with no evidence of long-term deterioration in lung function. Mental Health, cancer and mortality were not adequately studied to form any consensus. Our review has not demonstrated ENDS to be causative of harmful CVD outcomes; furthermore switching from cigarettes to e-cigarettes was associated with improved hypertensive control and reduced exacerbations of COPD, with no evidence of increased asthma risk or long-term respiratory harm. Mental health, cancer and mortality outcomes have not been adequately studied to form a conclusion. Overall, the findings of our review did not provide evidence to counter the consensus held by many that ENDS use is safer than the risks posed from smoking cigarettes.

The impact of disasters on contraception in OECD member countries: a scoping review.

OBJECTIVES: Review evidence is lacking about how contraception is affected by severe social disruption, such as that caused by the COVID-19 pandemic. The purpose of this scoping review was to explore the impact of natural and man-made disasters on contraception in OECD member countries. METHODS: Manual searches and systematic searches in six electronic databases were conducted with no language restrictions. All articles were screened by at least two researchers. The data were analysed thematically. RESULTS: 108 articles were included. Most focussed on the Zika virus outbreak (n = 50) and the COVID-19 pandemic (n = 28). Four key themes were identified: importance of contraception during disasters, impact of disasters on contraceptive behaviour, barriers to contraception during disasters and ways of improving use of contraception during disasters. Despite efforts to increase access to contraception including by transforming ways of delivery, barriers to use meant that unmet need persisted. CONCLUSIONS: To prevent adverse health outcomes and reduce health costs as a result of failure to have access to contraception during disasters, there is a need to intensify efforts to remove barriers to use. This should include increasing access and information on methods of contraception and their side effects (e.g., menstrual suppression) and making contraception freely available.

COVID-19 (SARS-CoV-2) in Non-Airborne body fluids: A systematic review & Meta-analysis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been predominantly respiratory. This study aimed to evaluate the presence of virus in non-airborne body fluids as transmission vehicles. Medline, EMBASE, and Cochrane Library databases were searched from December 01, 2019, to July 01, 2020, using terms relating to SARS-CoV-2 and non-airborne clinical sample sources (feces, urine, blood, serum, serum, and peritoneum). Studies in humans, of any design, were included. Risk of bias assessment was performed using the Quality Assessment of Diagnostic Accuracy 2 tool. Preferred Reporting Items for Systematic Reviews & Meta-Analyses) guidelines were used for abstracting data. If ≥5 studies reported proportions for the same non-respiratory site, a meta-analysis was conducted using either a fixed or random-effects model, depending on the presence of heterogeneity. A total of 22 studies with 648 patients were included. Most were cross-sectional and cohort studies. The SARS-CoV-2 RNA was most frequently detected in feces. Detectable RNA was reported in 17% of the blood samples, 8% of the serum, 16% in the semen, but rarely in urine. Prevalence of SARS-CoV-2 in non-airborne sites varies widely with a third of non-airborne fluids. Patients with bowel and non-specific symptoms have persistence of virus in feces for upto 2 weeks after symptom resolution. Although there was a very low detection rate in urine, given the more frequent prevalence in blood samples, the presence of SARS-CoV-2 in patients with disrupted urothelium or undergoing urinary tract procedures, is likely to be higher. Healthcare providers need to consider non-airborne transmission and persistence of SARS-CoV-2 in body fluids to enable appropriate precautions to protect healthcare workers and carers.

Guidance impact on primary care prescribing rates of simple analgesia: an interrupted time series analysis in England.

BACKGROUND: In March 2018, NHS England published guidance for clinical commissioning groups (CCGs) to encourage implementation of policy to reduce primary care prescriptions of over-the-counter medications, including simple analgesia. AIM: To investigate the impact of guidance publication on prescribing rates of simple analgesia (oral paracetamol, oral ibuprofen, and topical non-steroidal anti-inflammatory drugs) in primary care; CCG guidance implementation intentions; and whether the guidance has created health inequality based on socioeconomic status. DESIGN AND SETTING: Interrupted time series analysis of primary care prescribing data in England. METHOD: Practice-level prescribing data from January 2015 to March 2019 were obtained from NHS Digital. Interrupted time series analyses were used to assess the association of guidance publication with prescribing rates. The association between practice-level prescribing rates and Index of Multiple Deprivation scores before and after publication was quantified using multivariable Poisson regression. Freedom of information requests were submitted to all CCGs. RESULTS: There was a statistically significant 4.4% reduction in prescribing of simple analgesia following guidance publication (adjusted incidence rate ratio 0.96, 95% CI = 0.92 to 0.99, P = 0.027), adjusting for underlying time trend and seasonality. There was considerable diversity across CCGs in whether or how they chose to implement the guidance. Practice-level prescribing rates were greater in more deprived areas. CONCLUSION: Guidance publication was associated with a small reduction in the prescribing rates of simple analgesia across England, without evidence of creating additional health inequality. Careful implementation by CCGs would be required to optimise cost saving to the NHS.

A systematic review of the burden of hypertension, access to services and patient views of hypertension in humanitarian crisis settings.

INTRODUCTION: Globally, a record number of people are affected by humanitarian crises caused by conflict and natural disasters. Many such populations live in settings where epidemiological transition is underway. Following the United Nations high level meeting on non-communicable diseases, the global commitment to Universal Health Coverage and needs expressed by humanitarian agencies, there is increasing effort to develop guidelines for the management of hypertension in humanitarian settings. The objective was to investigate the prevalence and incidence of hypertension in populations directly affected by humanitarian crises; the cascade of care in these populations and patient knowledge of and attitude to hypertension. METHODS: A literature search was carried out in five databases. Grey literature was searched. The population of interest was adult, non-pregnant, civilians living in any country who were directly exposed to a crisis since 1999. Eligibility assessment, data extraction and quality appraisal were carried out in duplicate. RESULTS: Sixty-one studies were included in the narrative synthesis. They reported on a range of crises including the wars in Syria and Iraq, the Great East Japan Earthquake, Hurricane Katrina and Palestinian refugees. There were few studies from Africa or Asia (excluding Japan). The studies predominantly assessed prevalence of hypertension. This varied with geography and age of the population. Access to care, patient understanding and patient views on hypertension were poorly examined. Most of the studies had a high risk of bias due to methods used in the diagnosis of hypertension and in the selection of study populations. CONCLUSION: Hypertension is seen in a range of humanitarian settings and the burden can be considerable. Further studies are needed to accurately estimate prevalence of hypertension in crisis-affected populations throughout the world. An appreciation of patient knowledge and understanding of hypertension as well as the cascade of care would be invaluable in informing service provision.

Implementation of a Delayed Prescribing Model to Reduce Antibiotic Prescribing for Suspected Upper Respiratory Tract Infections in a Hospital Outpatient Department, Ghana.

Background: High levels of antimicrobial resistance (AMR) in Ghana require the exploration of new approaches to optimise antimicrobial prescribing. This study aims to establish the feasibility of implementation of different delayed/back-up prescribing models on antimicrobial prescribing for upper respiratory tract infections (URTIs). Methods: This study was part of a quality improvement project at LEKMA Hospital, Ghana, (Dec 2019-Feb 2020). Patients meeting inclusion criteria were assigned to one of four groups (Group 0: No prescription given; Group 1; Patient received post-dated antibiotic prescription; Group 2: Offer of a rapid reassessment of patient by a nurse practitioner after 3 days; and Group 3: Post-dated prescription forwarded to hospital pharmacy). Patients were contacted 10 days afterwards to ascertain wellbeing and actions taken, and patients were asked rate the service on a Likert scale. Post-study informal discussions were conducted with hospital staff. Results: In total, 142 patients met inclusion criteria. Groups 0, 1, 2 and 3 had 61, 16, 44 and 21 patients, respectively. Common diagnosis was sore throat (73%). Only one patient took antibiotics after 3 days. Nearly all (141/142) patients were successfully contacted on day 10, and of these, 102 (72%) rated their experiences as good or very good. Informal discussions with staff revealed improved knowledge of AMR. Conclusions: Delayed/back-up prescribing can reduce antibiotic consumption amongst outpatient department patients with suspected URTIs. Delayed/back-up prescribing can be implemented safely in low and middle-income countries (LMICs).

Socioeconomic status and HRT prescribing: a study of practice-level data in England.

BACKGROUND: Concerns have been raised that women from deprived backgrounds are less likely to be receiving hormone replacement therapy (HRT) treatment and its benefits, although evidence in support of this is lacking. AIM: To investigate general practice HRT prescription trends and their association with markers of socioeconomic deprivation. DESIGN AND SETTING: Cross-sectional study of primary care prescribing data in England in 2018. METHOD: Practice-level prescribing rate was defined as the number of items of HRT prescribed per 1000 registered female patients aged ≥40 years. The association between Index of Multiple Deprivation (IMD) score and HRT prescribing rate was tested using multivariate Poisson regression, adjusting for practice proportions of obesity, smoking, hypertension, diabetes, coronary heart disease and cerebrovascular disease, and practice list size. RESULTS: The overall prescribing rate of HRT was 29% lower in practices from the most deprived quintile compared with the most affluent (incidence rate ratio [IRR] = 0.71; 95% confidence interval [CI] = 0.68 to 0.73). After adjusting for all cardiovascular disease outcomes and risk factors, the prescribing rate in the most deprived quintile was still 18% lower than in the least deprived quintile (adjusted IRR = 0.82; 95% CI = 0.77 to 0.86). In more deprived practices, there was a significantly higher tendency to prescribe oral HRT than transdermal preparations (P<0.001). CONCLUSION: This study highlights inequalities associated with HRT prescription. This may reflect a large unmet need in terms of menopause care in areas of deprivation. Further research is needed to identify the factors from patient and GP perspectives that may explain this.

Outbreak of Clostridium perfringens food poisoning linked to leeks in cheese sauce: an unusual source.

Between 11-13 December 2018, local public health authorities in the West Midlands, England were alerted to 34 reports of diarrhoea with abdominal cramps. Symptom onset was ~10 h after diners ate Christmas meals at a restaurant between 7-9 December 2018. A retrospective case-control study, environmental and microbiological investigations were undertaken to determine the source and control the outbreak. An analytical study was undertaken with odds ratios (OR) and 95% confidence intervals (CI). Forty persons were recruited to the analytical study (28/40 cases). Multivariable analysis found that leeks in cheese sauce was the only item associated with illness (aOR 51.1; 95% CI 4.13-2492.1). Environmental investigations identified significant lapses in food safety, including lapses in temperature control during cooking and hot holding, likely cross-contamination between raw and cooked foods and the reuse of leftover cheese sauce for the next day's service. No food samples were taken during the exposure period. Two faecal samples were positive for Clostridium perfringens with one confirming the enterotoxigenic gene. Cheese sauce is an unusual vehicle for the organism and the first time this has been reported in England.

Socioeconomic status and benzodiazepine and Z-drug prescribing: a cross-sectional study of practice-level data in England.

BACKGROUND: Benzodiazepines and Z-drugs (such as zopiclone) are widely prescribed in primary care. Given their association with addiction and dependence, understanding where and for whom these medications are being prescribed is a necessary step in addressing potentially harmful prescribing. OBJECTIVE: To determine whether there is an association between primary care practice benzodiazepine and Z-drug prescribing and practice population socioeconomic status in England. METHODS: This was a cross-sectional study. An aggregated data set was created to include primary care prescribing data for 2017, practice age and sex profiles and practice Index of Multiple Deprivation (IMD) scores-a marker of socioeconomic status. Drug doses were converted to their milligram-equivalent of diazepam to allow comparison. Multiple linear regression was used to examine the association between IMD and prescribing (for all benzodiazepines and Z-drugs in total, and individually), adjusting for practice sex (% male) and older age (>65 years) distribution (%). RESULTS: Benzodiazepine and Z-drug prescribing overall was positively associated with practice-level IMD score, with more prescribing in practices with more underserved patients, after adjusting for age and sex (P < 0.001), although the strength of the association varied by individual drug. Overall, however, IMD score, age and sex only explained a small proportion of the overall variation in prescribing across GP practices. CONCLUSION: Our findings may, in part, be a reflection of an underlying association between the indications for benzodiazepine and Z-drug prescribing and socioeconomic status. Further work is required to more accurately define the major contributors of prescribing variation.

Knowledge about E-Cigarettes and Tobacco Harm Reduction among Public Health Residents in Europe.

INTRODUCTION: Although electronic cigarettes (e-cigarettes) and other tobacco-related products are becoming widely popular as alternatives to tobacco, little has been published on the knowledge of healthcare workers about their use. Thus, the aim of this study was to elicit the current knowledge and perceptions about e-cigarettes and tobacco harm reduction (THR) among medical residents in public health (MRPH). MATERIAL AND METHODS: A Europe-wide cross-sectional study was carried out amongst MRPH from the countries associated with the European Network of MRPH from April to October 2018 using an online questionnaire. RESULTS: 256 MRPHs agreed to participate in the survey. Approximately half the participants were women (57.4%), with a median age of 30 years, and were mainly Italian (26.7%), Spanish (16.9%) and Portuguese (16.5%). Smoking prevalence was 12.9%. Overall, risk scores significantly differed for each investigated smoking product when compared with e-cigarettes; with tobacco cigarettes and snus perceived as more risky, and nicotine replacement therapy (NRT) and non-NRT oral medications seen as less risky (p < 0.01 for all). Regarding the effects of nicotine on health, the vast majority of MRPHs associated nicotine with all smoking-related diseases. Knowledge of THR was low throughout the whole sample. CONCLUSIONS: European MRPH showed a suboptimal level of knowledge about e-cigarettes and THR. Training programs for public health and preventive medicine trainees should address this gap.

miR-15a/-16 Inhibit Angiogenesis by Targeting the Tie2 Coding Sequence: Therapeutic Potential of a miR-15a/16 Decoy System in Limb Ischemia.

MicroRNA-15a (miR-15a) and miR-16, which are transcribed from the miR-15a/miR-16-1 cluster, inhibit post-ischemic angiogenesis. MicroRNA (miRNA) binding to mRNA coding sequences (CDSs) is a newly emerging mechanism of gene expression regulation. We aimed to (1) identify new mediators of the anti-angiogenic action of miR-15a and -16, (2) develop an adenovirus (Ad)-based miR-15a/16 decoy system carrying a luciferase reporter (Luc) to both sense and inhibit miR-15a/16 activity, and (3) investigate Ad.Luc-Decoy-15a/16 therapeutic potential in a mouse limb ischemia (LI) model. LI increased miR-15a and -16 expression in mouse muscular endothelial cells (ECs). The miRNAs also increased in cultured human umbilical vein ECs (HUVECs) exposed to serum starvation, but not hypoxia. Using bioinformatic tools and luciferase activity assays, we characterized miR-15a and -16 binding to Tie2 CDS. In HUVECs, miR-15a or -16 overexpression reduced Tie2 at the protein, but not the mRNA, level. Conversely, miR-15a or -16 inhibition improved angiogenesis in a Tie2-dependent manner. Local Ad.Luc-Decoy-15a/16 delivery increased Tie2 levels in ischemic skeletal muscle and improved post-LI angiogenesis and perfusion recovery, with reduced toe necrosis. Bioluminescent imaging (in vivo imaging system [IVIS]) provided evidence that the Ad.Luc-Decoy-15a/16 system responds to miR-15a/16 increases. In conclusion, we have provided novel mechanistic evidence of the therapeutic potential of local miR-15a/16 inhibition in LI.

Does a bursary scheme for students in low- to middle-income countries influence outcomes in a master's programme in Public Health?

This article was migrated. The article was marked as recommended. Introduction The People's Open Access Education Initiative (Peoples-uni) provides online education for health professionals in Public Health at the master's level. Although fees are low due to the use of volunteers and Open Educational Resources, a bursary scheme is provided to waive all or some of the fees. This study tests the hypothesis that student outcomes of completing and passing modules are higher among those given a bursary than others. Methods Data were retrieved for all students enrolling between 2009-2017, including demographics and module outcomes, where available. Multivariable logistic regression was used to identify factors associated with a successful bursary application, as well as to elicit whether a successful bursary application was associated with ever completing, or ever passing, a module. Results Data were obtained from 1499 students. Of these, 624 (42%) had ever completed a module, and 513 (34%) had ever passed a module. 503 students (34%) had applied for a bursary, of whom 285 (57%) were successful. After adjusting for demographic variables, employment status and education level, students who were given a bursary were more likely to ever pass a module (adjusted odds ratio [aOR] 2.3, 95% CI 1.7,3.3), as were those who applied for a bursary but were unsuccessful (aOR 1.9, 95% CI 1.3,2.8), compared with students who had not applied for a bursary. Similar results were obtained for the outcome of completing a module. Conclusions Students who were successful in gaining a bursary, as well as those who were not but still able to enroll, were more likely to complete or pass a module than those who did not apply. These results point to the success of the bursary scheme and give us confidence to continue to offer bursaries, in order to sustain the mission of improving population health through capacity building in low resource settings.

Cardiovascular disease risk factors in chronic kidney disease: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Chronic kidney disease (CKD) is a global health burden and is independently associated with increased cardiovascular disease risk. Assessment of cardiovascular risk in the general population using prognostic models based on routinely collected risk factors is embedded in clinical practice. In CKD, prognostic models may misrepresent risk due to the interplay of traditional atherosclerotic and non-traditional risk factors. This systematic review's aim was to identify routinely collected risk factors for inclusion in a CKD-specific cardiovascular prognostic model. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: Systematic review and meta-analysis of observational cohort studies and randomized controlled trials. Studies identified from MEDLINE and Embase searches using a pre-defined and registered protocol (PROSPERO ID-2016:CRD42016036187). The main inclusion criteria were individuals ≥18 years of age with non-endstage CKD. Routinely collected risk factors where multi-variable adjustment for established cardiovascular risk factors had occurred were extracted. The primary outcome was fatal and non-fatal cardiovascular events. RESULTS: The review of 3,232, abstracts identified 29 routinely collected risk factors of which 20 were presented in more than 1 cohort. 21 cohorts were identified in relation to 27,465 individuals and 100,838 person-years. In addition to established traditional general population cardiovascular risk factors, left ventricular hypertrophy, serum albumin, phosphate, urate and hemoglobin were all found to be statistically significant in their association with future cardiovascular events. CONCLUSIONS: These non-traditional risk factors should be assessed in the development of future cardiovascular prognostic models for use in individuals with CKD.