Comparison of gene targets and sampling regimes for SARS-CoV-2 quantification for wastewater epidemiology in UK prisons.

Prisons are high-risk settings for infectious disease transmission, due to their enclosed and semi-enclosed environments. The proximity between prisoners and staff, and the diversity of prisons reduces the effectiveness of non-pharmaceutical interventions, such as social distancing. Therefore, alternative health monitoring methods, such as wastewater-based epidemiology (WBE), are needed to track pathogens, including SARS-CoV-2. This pilot study assessed WBE to quantify SARS-CoV-2 prevalence in prison wastewater to determine its utility within a health protection system for residents. The study analysed 266 samples from six prisons in England over a 12-week period for nucleoprotein 1 (N1 gene) and envelope protein (E gene) using quantitative reverse transcriptase-polymerase chain reaction. Both gene assays successfully detected SARS-CoV-2 fragments in wastewater samples, with both genes significantly correlating with COVID-19 case numbers across the prisons (p < 0.01). However, in 25% of the SARS-positive samples, only one gene target was detected, suggesting that both genes be used to reduce false-negative results. No significant differences were observed between 14- and 2-h composite samples, although 2-h samples showed greater signal variance. Population normalisation did not improve correlations between the N1 and E genes and COVID-19 case data. Overall, WBE shows considerable promise for health protection in prison settings.

The knowledge and attitudes regarding pressure ulcer prevention among healthcare support workers in the UK: A cross-sectional study.

BACKGROUND: Pressure ulcers cause significant, detrimental effects on personal wellbeing. They represent a serious health and social care burden. Nurses and those working in support roles are primarily accountable for preventing pressure ulcers. Healthcare support workers are an expanding group of key workers in the UK. OBJECTIVE: To examine healthcare support workers' knowledge and attitudes regarding pressure ulcer prevention. METHODS: A cross-sectional study was conducted from December 2020 to June 2021, using Knowledge and Attitudes toward Pressure Ulcer Prevention Assessment Tool. RESULTS: A total of 164 participants completed the questionnaire fully. A low mean knowledge score of 0.42 ± 0.14, but a positive attitude score of 0.76 ± 0.10 per item were reported. The weakest areas of knowledge include aetiology, risk assessment and addressing pressure-reducing interventions for patients at risk. Higher mean scores per item in knowledge of pressure ulcer prevention were reported in participants working in acute hospital wards and nursing homes (0.468 ± 0.15, 0.47 ± 0.08 respectively) than those in other settings (p < 0.05). Participants working in primary care scored lowest (0.33 ± 0.12). The scores of participants with more positive attitudes towards pressure ulcer prevention significantly correlated with higher score of knowledge (p < 0.005). CONCLUSION: While positive attitudes towards pressure ulcer prevention exist among healthcare support workers, this is overshadowed by significant knowledge deficits. Findings highlight the importance of continuing structured education for support workers across both acute and community settings. A future national survey and interventional study are needed to examine support workers' pressure ulcer knowledge and to inform a national continuous education strategy.

The epidemiological burden of obesity in childhood: a worldwide epidemic requiring urgent action.

BACKGROUND: In recent decades, the prevalence of obesity in children has increased dramatically. This worldwide epidemic has important consequences, including psychiatric, psychological and psychosocial disorders in childhood and increased risk of developing non-communicable diseases (NCDs) later in life. Treatment of obesity is difficult and children with excess weight are likely to become adults with obesity. These trends have led member states of the World Health Organization (WHO) to endorse a target of no increase in obesity in childhood by 2025. MAIN BODY: Estimates of overweight in children aged under 5 years are available jointly from the United Nations Children's Fund (UNICEF), WHO and the World Bank. The Institute for Health Metrics and Evaluation (IHME) has published country-level estimates of obesity in children aged 2-4 years. For children aged 5-19 years, obesity estimates are available from the NCD Risk Factor Collaboration. The global prevalence of overweight in children aged 5 years or under has increased modestly, but with heterogeneous trends in low and middle-income regions, while the prevalence of obesity in children aged 2-4 years has increased moderately. In 1975, obesity in children aged 5-19 years was relatively rare, but was much more common in 2016. CONCLUSIONS: It is recognised that the key drivers of this epidemic form an obesogenic environment, which includes changing food systems and reduced physical activity. Although cost-effective interventions such as WHO 'best buys' have been identified, political will and implementation have so far been limited. There is therefore a need to implement effective programmes and policies in multiple sectors to address overnutrition, undernutrition, mobility and physical activity. To be successful, the obesity epidemic must be a political priority, with these issues addressed both locally and globally. Work by governments, civil society, private corporations and other key stakeholders must be coordinated.

Inequalities in non-communicable diseases and effective responses.

In most countries, people who have a low socioeconomic status and those who live in poor or marginalised communities have a higher risk of dying from non-communicable diseases (NCDs) than do more advantaged groups and communities. Smoking rates, blood pressure, and several other NCD risk factors are often higher in groups with low socioeconomic status than in those with high socioeconomic status; the social gradient also depends on the country's stage of economic development, cultural factors, and social and health policies. Social inequalities in risk factors account for more than half of inequalities in major NCDs, especially for cardiovascular diseases and lung cancer. People in low-income countries and those with low socioeconomic status also have worse access to health care for timely diagnosis and treatment of NCDs than do those in high-income countries or those with higher socioeconomic status. Reduction of NCDs in disadvantaged groups is necessary to achieve substantial decreases in the total NCD burden, making them mutually reinforcing priorities. Effective actions to reduce NCD inequalities include equitable early childhood development programmes and education; removal of barriers to secure employment in disadvantaged groups; comprehensive strategies for tobacco and alcohol control and for dietary salt reduction that target low socioeconomic status groups; universal, financially and physically accessible, high-quality primary care for delivery of preventive interventions and for early detection and treatment of NCDs; and universal insurance and other mechanisms to remove financial barriers to health care.

The Heart of the World.

Cardiovascular diseases (CVDs) are the leading cause of mortality globally. Of the 20.5 million CVD-related deaths in 2021, approximately 80% occurred in low- and middle-income countries. Using data from the Global Burden of Disease Study, NCD Risk Factor Collaboration, NCD Countdown initiative, WHO Global Health Observatory, and WHO Global Health Expenditure database, we present the burden of CVDs, associated risk factors, their association with national health expenditures, and an index of critical policy implementation. The Central Europe, Eastern Europe, and Central Asia region face the highest levels of CVD mortality globally. Although CVD mortality levels are generally lower in women than men, this is not true in almost 30% of countries in the North Africa and Middle East and Sub-Saharan regions. Raised blood pressure remains the leading global CVD risk factor, contributing to 10.8 million deaths in 2019. The regions with the highest proportion of countries achieving the maximum score for the WHF Policy Index were South Asia, Central Europe, Eastern Europe, and Central Asia, and the High-Income regions. The Sub-Saharan Africa region had the highest proportion of countries scoring two or less. Policymakers must assess their country's risk factor profile to craft effective strategies for CVD prevention and management. Fundamental strategies such as the implementation of National Tobacco Control Programmes, ensuring the availability of CVD medications, and establishing specialised units within health ministries to tackle non-communicable diseases should be embraced in all countries. Adequate healthcare system funding is equally vital, ensuring reasonable access to care for all communities.

Wastewater monitoring for detection of public health markers during the COVID-19 pandemic: Near-source monitoring of schools in England over an academic year.

BACKGROUND: Schools are high-risk settings for infectious disease transmission. Wastewater monitoring for infectious diseases has been used to identify and mitigate outbreaks in many near-source settings during the COVID-19 pandemic, including universities and hospitals but less is known about the technology when applied for school health protection. This study aimed to implement a wastewater surveillance system to detect SARS-CoV-2 and other public health markers from wastewater in schools in England. METHODS: A total of 855 wastewater samples were collected from 16 schools (10 primary, 5 secondary and 1 post-16 and further education) over 10 months of school term time. Wastewater was analysed for SARS-CoV-2 genomic copies of N1 and E genes by RT-qPCR. A subset of wastewater samples was sent for genomic sequencing, enabling determination of the presence of SARS-CoV-2 and emergence of variant(s) contributing to COVID-19 infections within schools. In total, >280 microbial pathogens and >1200 AMR genes were screened using RT-qPCR and metagenomics to consider the utility of these additional targets to further inform on health threats within the schools. RESULTS: We report on wastewater-based surveillance for COVID-19 within English primary, secondary and further education schools over a full academic year (October 2020 to July 2021). The highest positivity rate (80.4%) was observed in the week commencing 30th November 2020 during the emergence of the Alpha variant, indicating most schools contained people who were shedding the virus. There was high SARS-CoV-2 amplicon concentration (up to 9.2x106 GC/L) detected over the summer term (8th June - 6th July 2021) during Delta variant prevalence. The summer increase of SARS-CoV-2 in school wastewater was reflected in age-specific clinical COVID-19 cases. Alpha variant and Delta variant were identified in the wastewater by sequencing of samples collected from December to March and June to July, respectively. Lead/lag analysis between SARS-CoV-2 concentrations in school and WWTP data sets show a maximum correlation between the two-time series when school data are lagged by two weeks. Furthermore, wastewater sample enrichment coupled with metagenomic sequencing and rapid informatics enabled the detection of other clinically relevant viral and bacterial pathogens and AMR. CONCLUSIONS: Passive wastewater monitoring surveillance in schools can identify cases of COVID-19. Samples can be sequenced to monitor for emerging and current variants of concern at the resolution of school catchments. Wastewater based monitoring for SARS-CoV-2 is a useful tool for SARS-CoV-2 passive surveillance and could be applied for case identification and containment, and mitigation in schools and other congregate settings with high risks of transmission. Wastewater monitoring enables public health authorities to develop targeted prevention and education programmes for hygiene measures within undertested communities across a broad range of use cases.

Use of an age-period-cohort model to reveal the impact of cigarette smoking on trends in twentieth-century adult cohort mortality in England and Wales.

We use an age-period-cohort (APC) model to estimate the contribution of smoking-related mortality to cohort changes in adult mortality in Britain since 1950. We show that lung cancer and overall mortality can be satisfactorily modelled using cohort relative risk and a fixed age pattern. The results of the model suggest that smoking by itself can account for a substantial fraction of change in cohort mortality for those born around the first half of the twentieth century. In particular, smoking provides an explanation for the higher-than-average improvement in the mortality of both males and females born around 1930. Our confidence in the correctness of the results of the models is strengthened by the fact that they are very similar to those of the Peto-Lopez and Preston-Glei-Wilmoth models that estimate the contribution of smoking-related to overall mortality.

Monitoring occurrence of SARS-CoV-2 in school populations: A wastewater-based approach.

Clinical testing of children in schools is challenging, with economic implications limiting its frequent use as a monitoring tool of the risks assumed by children and staff during the COVID-19 pandemic. Here, a wastewater-based epidemiology approach has been used to monitor 16 schools (10 primary, 5 secondary and 1 post-16 and further education) in England. A total of 296 samples over 9 weeks have been analysed for N1 and E genes using qPCR methods. Of the samples returned, 47.3% were positive for one or both genes with a detection frequency in line with the respective local community. WBE offers a low cost, non-invasive approach for supplementing clinical testing and can provide longitudinal insights that are impractical with traditional clinical testing.

Patellar shape can be a predisposing factor in patellar instability.

PURPOSE: Predisposing factors to objective patellar instability include trochlear dysplasia, patella alta, patellar tilt and elevated tibial tuberosity-femoral groove distance. The shape of the patella is classically not considered a predisposing factor. Anomalies of dynamic and static factors, including excessive patellar height, tibial tubercle lateralisation or trochlear dysplasia, may influence the development of the patella. METHODS: One hundred and five patients (140 knees) with objective patellar instability were retrospectively reviewed to identify a possible association between the above-mentioned predisposing factors and patellar shape. All patients were evaluated with static and dynamic CT scans, and plain lateral and antero-posterior radiographs, and skyline patellar views. RESULTS: Evidence of a significant association emerged between patellar shape and patellar tilt in static (r(s) = 0.20, P = 0.019) or dynamic conditions (r(s) = 0.18, P = 0.031) and a significant association between Wiberg patellar shape type C and trochlear dysplasia grade 3 (χ(2) = 4.5, P = 0.035). Also, we found a significant association between trochlear dysplasia stage 3 and tibial tuberosity-trochlear groove (TT-TG) and patellar tilt relaxed (P < 0.01 and P < 0.05, respectively). There is an association between patellar shape and patellar tilt. CONCLUSION: Increased lateral stresses may produce a Wiberg type C patella, with a hypoplastic medial facet and a more developed lateral facet. Unbalance between dynamic medial and lateral stabilisers may act as an additional factor. A rehabilitation program aiming to reduce this unbalance may decrease the incidence of type C patella in young patients.

Localized hyperthermia induced by microwave diathermy in osteoarthritis of the knee: a randomized placebo-controlled double-blind clinical trial.

PURPOSE: To investigate the effects of hyperthermia on knee osteoarthritis (OA) in a randomized placebo-controlled double-blind clinical trial. METHODS: Sixty-three patients with clinical evidence and radiographic confirmation of knee OA (Kellgren and Lawrence grades II and III) were randomized to either three 30-min sessions of hyperthermia per week for 4 weeks were administered using a 433.92 MHZ microwave generator or receive placebo treatment (machine not turned on) for same number of sessions. The Western Ontario McMaster Universities (WOMAC) questionnaire and the Timed Up and Go test (TUGT), a performance-based measure of function, were obtained at baseline (week 0), at the end of treatment (week 4), and at final follow-up (week 16). RESULTS: The treatment group showed a significant decrease in the overall WOMAC score and each of its components, and in the TGUG test between the beginning (week 0) and the end of treatment (week 4), as well as at final follow-up (week 16). In the placebo group, a significant fall was only visible in the pain subscore at week 4. However, the mean improvement was only 1 point and was lost at final follow-up (P=0.332). There was a significant difference in pain -7.4 pre-post (P<0.01), -8.1 pre-follow-up (P<0.01); stiffness -4.6 pre-post (P<0.01), -5.1 pre-follow-up (P<0.01); activities daily living (ADL) -30.9 pre-post (P<0.01), -33.2 pre-follow-up (P<0.01); and WOMAC total score -43 pre-post (P<0.01), -46.4 pre-follow-up (P<0.01); and in TGUG test -2.4 pre-post (P<0.01), -2.9 pre-follow-up (P<0.01) between the treatment and placebo group over the whole length of the trial. CONCLUSIONS: A 433.92 MHz microwave hyperthermia regimen showed beneficial effects in patients with moderate knee OA to reduce pain and to improve their physical function. LEVEL OF EVIDENCE: I.

Evaluating equality in prescribing Novel Oral Anticoagulants (NOACs) in England: The protocol of a Bayesian small area analysis.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting about 1.6% of the population in England. Novel oral anticoagulants (NOACs) are approved AF treatments that reduce stroke risk. In this study, we estimate the equality in individual NOAC prescriptions with high spatial resolution in Clinical Commissioning Groups (CCGs) across England from 2014 to 2019. METHODS: A Bayesian spatio-temporal model will be used to estimate and predict the individual NOAC prescription trend on 'prescription data' as an indicator of health services utilisation, using a small area analysis methodology. The main dataset in this study is the "Practice Level Prescribing in England," which contains four individual NOACs prescribed by all registered GP practices in England. We will use the defined daily dose (DDD) equivalent methodology, as recommended by the World Health Organization (WHO), to compare across space and time. Four licensed NOACs datasets will be summed per 1,000 patients at the CCG-level over time. We will also adjust for CCG-level covariates, such as demographic data, Multiple Deprivation Index, and rural-urban classification. We aim to employ the extended BYM2 model (space-time model) using the RStan package. DISCUSSION: This study suggests a new statistical modelling approach to link prescription and socioeconomic data to model pharmacoepidemiologic data. Quantifying space and time differences will allow for the evaluation of inequalities in the prescription of NOACs. The methodology will help develop geographically targeted public health interventions, campaigns, audits, or guidelines to improve areas of low prescription. This approach can be used for other medications, especially those used for chronic diseases that must be monitored over time.

Geographical and socioeconomic inequalities in female breast cancer incidence and mortality in Iran: A Bayesian spatial analysis of registry data.

BACKGROUND: In Iran, trends in breast cancer incidence and mortality have generally been monitored at national level. The purpose of this study is to examine province-level disparities in age-standardised breast cancer incidence versus mortality from 2000 to 2010 and their association with socioeconomic status. METHODS: In this study, data from Iran's national cancer and death registry systems, and covariates from census and household expenditure surveys were used. We estimated the age-standardised incidence and mortality rates in women aged more than 30 years for all 31 provinces in the consecutive time intervals 2000-2003, 2004-2007 and 2008-2010 using a Bayesian spatial model. RESULTS: Mean age-standardised breast cancer incidence across provinces increased over time from 15.0 per 100,000 people (95% credible interval 12.0,18.3) in 2000-2003 to 39.6 (34.5,45.1) in 2008-2010. The mean breast cancer mortality rate declined from 10.9 (8.3,13.8) to 9.9 (7.5,12.5) deaths per 100,000 people in the same period. When grouped by wealth index quintiles, provinces in the highest quintile had higher levels of incidence and mortality. In the wealthiest quintile, reductions in mortality over time were larger than those observed among provinces in the poorest quintile. Relative breast cancer mortality decreased by 16.7% in the highest quintile compared to 10.8% in the lowest quintile. CONCLUSIONS: Breast cancer incidence has increased over time, with lower incidence in the poorest provinces likely driven by underdiagnoses or late-stage diagnosis. Although the reported mortality rate is still higher in wealthier provinces, the larger decline over time in these provinces indicates a possible future reversal, with the most deprived provinces having higher mortality rates. Ongoing analysis of incidence and mortality at sub-national level is crucial in addressing inequalities in healthcare systems and public health both in Iran and elsewhere.

The contribution of specific non-communicable diseases to the achievement of the Sustainable Development Goal 3.4 in Peru.

BACKGROUND: Non-communicable diseases (NCDs) have received political attention and commitment, yet surveillance is needed to measure progress and set priorities. Building on global estimates suggesting that Peru is not on target to meet the Sustainable Development Goal 3.4, we estimated the contribution of various NCDs to the change in unconditional probability of dying from NCDs in 25 regions in Peru. METHODS: Using national death registries and census data, we estimated the unconditional probability of dying between ages 30 and 69 from any and from each of the following NCDs: cardiovascular, cancer, diabetes, chronic respiratory diseases and chronic kidney disease. We estimated the contribution of each NCD to the change in the unconditional probability of dying from any of these NCDs between 2006 and 2016. RESULTS: The overall unconditional probability of dying improved for men (21.4%) and women (23.3%). Cancer accounted for 10.9% in men and 13.7% in women of the overall reduction; cardiovascular diseases also contributed substantially: 11.3% in men) and 9.8% in women. Consistently in men and women and across regions, diabetes moved in the opposite direction of the overall reduction in the unconditional probability of dying from any selected NCD. Diabetes contributed a rise in the unconditional probability of 3.6% in men and 2.1% in women. CONCLUSIONS: Although the unconditional probability of dying from any selected NCD has decreased, diabetes would prevent Peru from meeting international targets. Policies are needed to prevent diabetes and to strengthen healthcare to avoid diabetes-related complications and delay mortality.

NOACs Added to WHO's Essential Medicines List: Recommendations for Future Policy Actions.

The introduction of non-vitamin K antagonists oral anticoagulants, a class of medicines which includes dabigatran, apixaban, edoxaban and rivaroxaban, has resulted in improvements in the safety and efficacy of non valvular atrial fibrillation treatment for stroke prevention, with significant reductions in stroke, intracranial haemorrhage, and mortality. For these reasons, a team of World Heart Federation Emerging Leaders led efforts to add non-vitamin K antagonists oral anticoagulants to the World Health Organization's Model List of Essential Medicines in 2019. Following the inclusion of this class of medicines in the Essential Medicines List, this editorial proposes several recommendations to improve the accessibility, affordability and acceptability of non-vitamin K oral anticoagulants, especially in low- and middle-income settings, in order to successfully manage non-valvular atrial fibrillation and to lower the risk of stroke.

Magnitude, demographics and dynamics of the effect of the first wave of the COVID-19 pandemic on all-cause mortality in 21 industrialized countries.

The Coronavirus Disease 2019 (COVID-19) pandemic has changed many social, economic, environmental and healthcare determinants of health. We applied an ensemble of 16 Bayesian models to vital statistics data to estimate the all-cause mortality effect of the pandemic for 21 industrialized countries. From mid-February through May 2020, 206,000 (95% credible interval, 178,100-231,000) more people died in these countries than would have had the pandemic not occurred. The number of excess deaths, excess deaths per 100,000 people and relative increase in deaths were similar between men and women in most countries. England and Wales and Spain experienced the largest effect: ~100 excess deaths per 100,000 people, equivalent to a 37% (30-44%) relative increase in England and Wales and 38% (31-45%) in Spain. Bulgaria, New Zealand, Slovakia, Australia, Czechia, Hungary, Poland, Norway, Denmark and Finland experienced mortality changes that ranged from possible small declines to increases of 5% or less in either sex. The heterogeneous mortality effects of the COVID-19 pandemic reflect differences in how well countries have managed the pandemic and the resilience and preparedness of the health and social care system.

Laboratory-based and office-based risk scores and charts to predict 10-year risk of cardiovascular disease in 182 countries: a pooled analysis of prospective cohorts and health surveys.

BACKGROUND: Worldwide implementation of risk-based cardiovascular disease (CVD) prevention requires risk prediction tools that are contemporarily recalibrated for the target country and can be used where laboratory measurements are unavailable. We present two cardiovascular risk scores, with and without laboratory-based measurements, and the corresponding risk charts for 182 countries to predict 10-year risk of fatal and non-fatal CVD in adults aged 40-74 years. METHODS: Based on our previous laboratory-based prediction model (Globorisk), we used data from eight prospective studies to estimate coefficients of the risk equations using proportional hazard regressions. The laboratory-based risk score included age, sex, smoking, blood pressure, diabetes, and total cholesterol; in the non-laboratory (office-based) risk score, we replaced diabetes and total cholesterol with BMI. We recalibrated risk scores for each sex and age group in each country using country-specific mean risk factor levels and CVD rates. We used recalibrated risk scores and data from national surveys (using data from adults aged 40-64 years) to estimate the proportion of the population at different levels of CVD risk for ten countries from different world regions as examples of the information the risk scores provide; we applied a risk threshold for high risk of at least 10% for high-income countries (HICs) and at least 20% for low-income and middle-income countries (LMICs) on the basis of national and international guidelines for CVD prevention. We estimated the proportion of men and women who were similarly categorised as high risk or low risk by the two risk scores. FINDINGS: Predicted risks for the same risk factor profile were generally lower in HICs than in LMICs, with the highest risks in countries in central and southeast Asia and eastern Europe, including China and Russia. In HICs, the proportion of people aged 40-64 years at high risk of CVD ranged from 1% for South Korean women to 42% for Czech men (using a ≥10% risk threshold), and in low-income countries ranged from 2% in Uganda (men and women) to 13% in Iranian men (using a ≥20% risk threshold). More than 80% of adults were similarly classified as low or high risk by the laboratory-based and office-based risk scores. However, the office-based model substantially underestimated the risk among patients with diabetes. INTERPRETATION: Our risk charts provide risk assessment tools that are recalibrated for each country and make the estimation of CVD risk possible without using laboratory-based measurements. FUNDING: National Institutes of Health.