The impact of scaling up cervical cancer screening and treatment services among women living with HIV in Kenya: a modelling study

Introduction: We aimed to quantify health outcomes and programmatic implications of scaling up cervical cancer (CC) screening and treatment options for women living with HIV in care aged 18–65 in Kenya. Methods: Mathematical model comparing from 2020 to 2040: (1) visual inspection with acetic acid (VIA) and cryotherapy (Cryo); (2) VIA and Cryo or loop excision electrical procedure (LEEP), as indicated; (3) human papillomavirus (HPV)-DNA testing and Cryo or LEEP; and (4) enhanced screening technologies (either same-day HPV-DNA testing or digitally enhanced VIA) and Cryo or LEEP. Outcomes measured were annual number of CC cases, deaths, screening and treatment interventions, and engaged in care (numbers screened, treated and cured) and five yearly age-standardised incidence. Results: All options will reduce CC cases and deaths compared with no scale-up. Options 1–3 will perform similarly, averting approximately 28 000 (33%) CC cases and 7700 (27%) deaths. That is, VIA screening would yield minimal losses to follow-up (LTFU). Conversely, LTFU associated with HPV-DNA testing will yield a lower care engagement, despite better diagnostic performance. In contrast, option 4 would maximise health outcomes, averting 43 200 (50%) CC cases and 11 800 (40%) deaths, given greater care engagement. Yearly rescreening with either option will impose a substantial burden on the health system, which could be reduced by spacing out frequency to three yearly without undermining health gains. Conclusions: Beyond the specific choice of technologies to scale up, efficiently using available options will drive programmatic success. Addressing practical constraints around diagnostics’ performance and LTFU will be key to effectively avert CC cases and deaths

Report 29: The impact of the COVID-19 epidemic on all-cause attendances to emergency departments in two large London hospitals: an observational study

The health care system in England has been highly affected by the surge in demand due to patients afflicted by COVID-19. Yet the impact of the pandemic on the care seeking behaviour of patients and thus on Emergency department (ED) services is unknown, especially for non-COVID-19 related emergencies. In this report, we aimed to assess how the reorganisation of hospital care and admission policies to respond to the COVID-19 epidemic affected ED attendances and emergency hospital admissions. We performed time-series analyses of present year vs historic (2015-2019) trends of ED attendances between March 12 and May 31 at two large central London hospitals part of Imperial College Healthcare NHS Trust (ICHNT) and compared these to regional and national trends. Historic attendances data to ICHNT and publicly available NHS situation reports were used to calibrate time series auto-regressive integrated moving average (ARIMA) forecasting models. We thus predicted the (conterfactual) expected number of ED attendances between March 12 (when the first public health measure leading to lock-down started in England) to May 31, 2020 (when the analysis was censored) at ICHNT, at all acute London Trusts and nationally. The forecasted trends were compared to observed data for the same periods of time. Lastly, we analysed the trends at ICHNT disaggregating by mode of arrival, distance from postcode of patient residence to hospital and primary diagnosis amongst those that were subsequently admitted to hospital and compared these data to an average for the same period of time in the years 2015 to 2019. During the study period (January 1 to May 31, 2020) there was an overall decrease in ED attendances of 35% at ICHNT, of 50% across all London NHS Trusts and 53% nationally. For ICHNT, the decrease in attendances was mainly amongst those aged younger than 65 and those arriving by their own means (e.g. personal or public transport). Increasing distance (km) from postcode of residence to hospital was a significant predictor of reduced attendances, which could not be explained by weighted (for population numbers) mean index of multiple deprivation. Non-COVID emergency admissions to hospital after March 12 fell by 48% at ICHNT compared to previous years. This was seen across all disease areas, including acute coronary syndromes, stroke and cancer-related emergencies. The overall non-COVID-19 hospitalisation mortality risk did not differ (RR 1.13, 95%CI 0.94-1.37, p=0.19), also in comparison to previous years. Our findings suggest emergency healthcare seeking to hospitals drastically changed amongst the population within the catchment area of ICHNT. This trend was echoed regionally and nationally, suggesting those suffering a medical emergency may not have attended other (i.e. closer-to-home) hospitals. Furthermore, our time-series analyses showed that, even after COVID-19 cases and deaths decreased (i.e. from early April), non-COVID-19 ED attendances did not increase. The impact of emergency triaging systems (e.g. 111 calls) and alternative (e.g. private hospital, chemist) health services on these trends remains unknown. However, another recent report found increased non-COVID excess deaths in the community, which may be partially explained by people experiencing an emergency and not attending health services at all. Whether those that attended ED services have done so with longer delays from the moment of emergency onset also remains unknown. National analyses into the factors causing reduced attendances to ED services and strategies to revert these negative trends are urgently needed

Report 17: Clinical characteristics and predictors of outcomes of hospitalised patients with COVID-19 in a London NHS Trust: a retrospective cohort study

Clinical characteristics and determinants of outcomes for hospitalised COVID-19 patients in the UK remain largely undescribed and emerging evidence suggests ethnic minorities might be disproportionately affected. We describe the characteristics and outcomes of patients hospitalised for COVID-19 in three large London hospitals with a multi-ethnic catchment population. We performed a retrospective cohort study on all patients hospitalised with laboratory-confirmed SARS-CoV-2 infection at Imperial College Healthcare NHS Trust between February 25 and April 5, 2020. Outcomes were recorded as of April 19, 2020. Logistic regression models, survival analyses and cumulative competing risk analyses were performed to evaluate factors associated with COVID-19 hospital mortality. Of 520 patients in this cohort (median age 67 years, (IQR 26) and 62% male), 302 (68%) had been discharged alive, 144 (32%) died and 74 (14%) were still hospitalised at the time of censoring. Increasing age (adjusted odds ratio [aOR] 2·16, 95%CI 1·50-3·12), severe hypoxia (aOR 3·75, 95%CI 1·80-7·80), low platelets (aOR 0·65, 95%CI 0.49·0·85), reduced estimated glomerular filtration rate (aOR 4·11, 95%CI 1·58-10·69), bilirubin >21mmol/L (aOR 2·32, 95%CI 1·05-5·14) and low albumin (aOR 0·77, 9%%CI 0·59-1·01) were associated with increased risk of in-hospital mortality. Individual comorbidities were not independently associated with risk of death. Regarding ethnicity, 209 (40%) were from a black and Asian minority, for 115 (22%) ethnicity was unknown and 196 (38%) patients were white. Compared to the latter, black patients were significantly younger and had less comorbidities. Whilst the crude OR of death of black compared to white patients was not significant (1·14, 95%CI 0·69-1·88, p=0.62), adjusting for age and comorbidity showed a trend towards significance (aOR 1·72, 95%CI 0·98-3·02, p=0.06) and further accounting for admission severity (Early Warning Score) showed a significant difference (aOR 1·83 95% CI 1·02-3·30, p=0.04). In the first study to describe the characteristics and predictors of outcome for hospitalised COVID-19 patients in the UK, we find that older age, male sex and admission hypoxia, thrombocytopenia, renal failure, hypoalbuminaemia and raised bilirubin are associated with increased odds of death. Ethnic minority groups were over-represented in our cohort and, compared to whites, people of black ethnicity may be at increased odds of mortality. Further research is urgently needed to investigate these associations on a larger scale

Key epidemiological drivers and impact of interventions in the 2020 SARS-CoV-2 epidemic in England

We fitted a model of SARS-CoV-2 transmission in care homes and the community to regional surveillance data for England. Compared with other approaches, our model provides a synthesis of multiple surveillance data streams into a single coherent modelling framework allowing transmission and severity to be disentangled from features of the surveillance system. Of the control measures implemented, only national lockdown brought the reproduction number (Rteff ) below 1 consistently; if introduced one week earlier it could have reduced deaths in the first wave from an estimated 48,600 to 25,600 (95% credible interval [95%CrI]: 15,900-38,400). The infection fatality ratio decreased from 1.00% (95%CrI: 0.85%-1.21%) to 0.79% (95%CrI: 0.63%-0.99%), suggesting improved clinical care. The infection fatality ratio was higher in the elderly residing in care homes (23.3%, 95%CrI: 14.7%-35.2%) than those residing in the community (7.9%, 95%CrI: 5.9%-10.3%). On 2nd December 2020 England was still far from herd immunity, with regional cumulative infection incidence between 7.6% (95%CrI: 5.4%-10.2%) and 22.3% (95%CrI: 19.4%-25.4%) of the population. Therefore, any vaccination campaign will need to achieve high coverage and a high degree of protection in vaccinated individuals to allow non-pharmaceutical interventions to be lifted without a resurgence of transmission

Key epidemiological drivers and impact of interventions in the 2020 SARS-CoV-2 epidemic in England

We fitted a model of SARS-CoV-2 transmission in care homes and the community to regional surveillance data for England. Compared with other approaches, our model provides a synthesis of multiple surveillance data streams into a single coherent modelling framework allowing transmission and severity to be disentangled from features of the surveillance system. Of the control measures implemented, only national lockdown brought the reproduction number (Rteff ) below 1 consistently; if introduced one week earlier it could have reduced deaths in the first wave from an estimated 48,600 to 25,600 (95% credible interval [95%CrI]: 15,900-38,400). The infection fatality ratio decreased from 1.00% (95%CrI: 0.85%-1.21%) to 0.79% (95%CrI: 0.63%-0.99%), suggesting improved clinical care. The infection fatality ratio was higher in the elderly residing in care homes (23.3%, 95%CrI: 14.7%-35.2%) than those residing in the community (7.9%, 95%CrI: 5.9%-10.3%). On 2nd December 2020 England was still far from herd immunity, with regional cumulative infection incidence between 7.6% (95%CrI: 5.4%-10.2%) and 22.3% (95%CrI: 19.4%-25.4%) of the population. Therefore, any vaccination campaign will need to achieve high coverage and a high degree of protection in vaccinated individuals to allow non-pharmaceutical interventions to be lifted without a resurgence of transmission

Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015:a systematic analysis for the Global Burden of Disease Study 2015

Background Non-fatal outcomes of disease and injury increasingly detract from the ability of the world's population to live in full health, a trend largely attributable to an epidemiological transition in many countries from causes affecting children, to non-communicable diseases (NCDs) more common in adults. For the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015), we estimated the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.Methods We estimated incidence and prevalence by age, sex, cause, year, and geography with a wide range of updated and standardised analytical procedures. Improvements from GBD 2013 included the addition of new data sources, updates to literature reviews for 85 causes, and the identification and inclusion of additional studies published up to November, 2015, to expand the database used for estimation of non-fatal outcomes to 60 900 unique data sources. Prevalence and incidence by cause and sequelae were determined with DisMod-MR 2.1, an improved version of the DisMod-MR Bayesian meta-regression tool first developed for GBD 2010 and GBD 2013. For some causes, we used alternative modelling strategies where the complexity of the disease was not suited to DisMod-MR 2.1 or where incidence and prevalence needed to be determined from other data. For GBD 2015 we created a summary indicator that combines measures of income per capita, educational attainment, and fertility (the Socio-demographic Index [SDI]) and used it to compare observed patterns of health loss to the expected pattern for countries or locations with similar SDI scores.Findings We generated 9.3 billion estimates from the various combinations of prevalence, incidence, and YLDs for causes, sequelae, and impairments by age, sex, geography, and year. In 2015, two causes had acute incidences in excess of 1 billion: upper respiratory infections (17.2 billion, 95% uncertainty interval [UI] 15.4-19.2 billion) and diarrhoeal diseases (2.39 billion, 2.30-2.50 billion). Eight causes of chronic disease and injury each affected more than 10% of the world's population in 2015: permanent caries, tension-type headache, iron-deficiency anaemia, age-related and other hearing loss, migraine, genital herpes, refraction and accommodation disorders, and ascariasis. The impairment that affected the greatest number of people in 2015 was anaemia, with 2.36 billion (2.35-2.37 billion) individuals affected. The second and third leading impairments by number of individuals affected were hearing loss and vision loss, respectively. Between 2005 and 2015, there was little change in the leading causes of years lived with disability (YLDs) on a global basis. NCDs accounted for 18 of the leading 20 causes of age-standardised YLDs on a global scale. Where rates were decreasing, the rate of decrease for YLDs was slower than that of years of life lost (YLLs) for nearly every cause included in our analysis. For low SDI geographies, Group 1 causes typically accounted for 20-30% of total disability, largely attributable to nutritional deficiencies, malaria, neglected tropical diseases, HIV/AIDS, and tuberculosis. Lower back and neck pain was the leading global cause of disability in 2015 in most countries. The leading cause was sense organ disorders in 22 countries in Asia and Africa and one in central Latin America; diabetes in four countries in Oceania; HIV/AIDS in three southern sub-Saharan African countries; collective violence and legal intervention in two north African and Middle Eastern countries; iron-deficiency anaemia in Somalia and Venezuela; depression in Uganda; onchoceriasis in Liberia; and other neglected tropical diseases in the Democratic Republic of the Congo.Interpretation Ageing of the world's population is increasing the number of people living with sequelae of diseases and injuries. Shifts in the epidemiological profile driven by socioeconomic change also contribute to the continued increase in years lived with disability (YLDs) as well as the rate of increase in YLDs. Despite limitations imposed by gaps in data availability and the variable quality of the data available, the standardised and comprehensive approach of the GBD study provides opportunities to examine broad trends, compare those trends between countries or subnational geographies, benchmark against locations at similar stages of development, and gauge the strength or weakness of the estimates available. Copyright (C) The Author(s). Published by Elsevier Ltd.</p

Combined Tevatron upper limit on gg->H->W+W- and constraints on the Higgs boson mass in fourth-generation fermion models

Report number: FERMILAB-PUB-10-125-EWe combine results from searches by the CDF and D0 collaborations for a standard model Higgs boson (H) in the process gg->H->W+W- in p=pbar collisions at the Fermilab Tevatron Collider at sqrt{s}=1.96 TeV. With 4.8 fb-1 of integrated luminosity analyzed at CDF and 5.4 fb-1 at D0, the 95% Confidence Level upper limit on \sigma(gg->H) x B(H->W+W-) is 1.75 pb at m_H=120 GeV, 0.38 pb at m_H=165 GeV, and 0.83 pb at m_H=200 GeV. Assuming the presence of a fourth sequential generation of fermions with large masses, we exclude at the 95% Confidence Level a standard-model-like Higgs boson with a mass between 131 and 204 GeV.We combine results from searches by the CDF and D0 collaborations for a standard model Higgs boson (H) in the process gg→H→W+W- in pp̅ collisions at the Fermilab Tevatron Collider at √s=1.96  TeV. With 4.8  fb-1 of integrated luminosity analyzed at CDF and 5.4  fb-1 at D0, the 95% confidence level upper limit on σ(gg→H)×B(H→W+W-) is 1.75 pb at mH=120  GeV, 0.38 pb at mH=165  GeV, and 0.83 pb at mH=200  GeV. Assuming the presence of a fourth sequential generation of fermions with large masses, we exclude at the 95% confidence level a standard-model-like Higgs boson with a mass between 131 and 204 GeV.Peer reviewe

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis