Analysis and applications of respiratory surface EMG: report of a round table meeting.

Surface electromyography (sEMG) can be used to measure the electrical activity of the respiratory muscles. The possible applications of sEMG span from patients suffering from acute respiratory failure to patients receiving chronic home mechanical ventilation, to evaluate muscle function, titrate ventilatory support and guide treatment. However, sEMG is mainly used as a monitoring tool for research and its use in clinical practice is still limited-in part due to a lack of standardization and transparent reporting. During this round table meeting, recommendations on data acquisition, processing, interpretation, and potential clinical applications of respiratory sEMG were discussed. This paper informs the clinical researcher interested in respiratory muscle monitoring about the current state of the art on sEMG, knowledge gaps and potential future applications for patients with respiratory failure.

Systematic Review of Genomic Associations with Blood Pressure and Hypertension in Populations with African-Ancestry.

Background: Despite hypertension being highly prevalent in individuals with African-ancestry, they are under-represented in large genome-wide association studies. Inclusion of African participants is essential to better understand genetic associations with blood pressure-related traits in Africans. This systematic review critically evaluates existing studies with African-ancestry participants and identifies knowledge gaps. Methods: We followed the PRISMA protocol, HuGE Review handbook to identify literature on original research, in English, on genetic association studies for blood pressure-related traits (systolic and diastolic blood pressure, pulse and mean-arterial pressure, and hypertension) in populations with African-ancestry (January 2007 to April 2020). A narrative synthesis of the evidence was conducted. Results: Twelve studies with African-ancestry participants met the eligibility criteria, within which 10 studies met the additional genetic association data criteria (i.e., reporting only on African-ancestry participants). Across the five blood pressure-related traits, 26 genome-wide significantly associated SNPs were identified, with six SNPs linked to more than one trait, illustrating pleiotropic effects. Among the SNP associations, 12 had not previously been described in non-African studies. Discussion: The limited number of relevant studies highlights the dearth of genomic association studies on participants with African-ancestry, especially those located within Africa. Variations in study methodology, participant inclusion, adjustment for covariates (e.g., antihypertensive medication) and relatively small sample sizes make comparisons challenging, and have resulted in fewer significant associations, compared to large European studies. Regional variation in the prevalence and associated risk factors of hypertension across Africa makes a compelling argument to develop African cohorts to facilitate large genomic studies, using African-centric arrays. Data harmonisation and comparable study designs, such as described in the H3Africa CHAIR initiative, provide a good example toward achieving this goal. Other relevant information: SS and J-TB were funded by the South African National Research Foundation. MR is a South African Research Chair in Genomics and Bioinformatics of African populations hosted by the University of the Witwatersrand, funded by the Department of Science and Innovation, and administered by the NRF. This review was registered at PROSPERO (registration number: CRD42020179221) and OSF (registration DOI: 10.17605/OSF.IO/QT2HA).

Impact analysis of rotavirus vaccination in various geographic regions in Western Europe.

BACKGROUND: Universal mass vaccination (UMV) against rotavirus has been implemented in many but not all European countries. This study investigated the impact of UMV on rotavirus incidence trends by comparing European countries with UMV: Belgium, England/Wales and Germany versus countries without UMV: Denmark and the Netherlands. METHODS: For this observational retrospective cohort study, time series data (2001-2016) on rotavirus detections, meteorological factors and population demographics were collected. For each country, several meteorological and population factors were investigated as possible predictors of rotavirus incidence. The final set of predictors were incorporated in negative binomial models accounting for seasonality and serial autocorrelation, and time-varying incidence rate ratios (IRR) were calculated for each age group and country separately. The overall vaccination impact two years after vaccine implementation was estimated by pooling the results using a random effects meta-analyses. Independent t-tests were used to compare annual epidemics in the pre-vaccination and post-vaccination era to explore any changes in the timing of rotavirus epidemics. RESULTS: The population size and several meteorological factors were predictors for the rotavirus epidemiology. Overall, we estimated a 42% (95%-CI 23;56%) reduction in rotavirus incidence attributable to UMV. Strongest reductions were observed for age-groups 0-, 1- and 2-years (IRR 0.47, 0.48 and 0.63, respectively). No herd effect induced by UMV in neighbouring countries was observed. In all UMV countries, the start and/or stop and corresponding peak of the rotavirus season was delayed by 4-7 weeks. CONCLUSIONS: The introduction of rotavirus UMV resulted in an overall reduction of 42% in rotavirus incidence in Western European countries two years after vaccine introduction and caused a change in seasonal pattern. No herd effect induced by UMV neighbouring countries was observed for Denmark and the Netherlands.

Strengthening HPV vaccination delivery: findings from a qualitative service evaluation of the adolescent girls' HPV vaccination programme in England.

BACKGROUND: In 2014, the number of HPV vaccine doses given to adolescent girls as part of the English school-based immunization programme was reduced from three to two. This was based on evidence that a two-dose schedule provides long-lasting protection against HPV infection. In 2015/16 a small decline in HPV vaccination coverage in adolescent girls was noted; from 86.7% for the three-dose schedule in 2013/14 to 85.1% for the two-dose schedule. This evaluation examined whether service-related factors contributed to this decline. METHODS: In May-August 2017, we conducted semi-structured qualitative interviews with 39 participants responsible for commissioning or delivering immunization programmes in six local authorities in the South West, North Central Midlands and South Central Midlands, England. RESULTS: Effective planning and data management were key for successful service provision of HPV vaccination, as well as close collaboration between commissioners, service providers and data system managers, a team skill mix with experienced staff, pro-active engagement with schools and service providers equipped to respond to parental concerns. CONCLUSIONS: To maintain and improve the high HPV adolescent girls' vaccine coverage rates achieved in England, in the context of an expanding school-based immunization programme, it is essential to strengthen the organizational capacity of the delivery system.

Preparations for a European R&D roadmap for an inertial fusion demo reactor.

A European consortium of 15 laboratories across nine nations have worked together under the EUROFusion Enabling Research grants for the past decade with three principle objectives. These are: (a) investigating obstacles to ignition on megaJoule-class laser facilities; (b) investigating novel alternative approaches to ignition, including basic studies for fast ignition (both electron and ion-driven), auxiliary heating, shock ignition, etc.; and (c) developing technologies that will be required in the future for a fusion reactor. A brief overview of these activities, presented here, along with new calculations relates the concept of auxiliary heating of inertial fusion targets, and provides possible future directions of research and development for the updated European Roadmap that is due at the end of 2020. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 2)'.

Whole-beam self-focusing in fusion-relevant plasma.

Fast ignition inertial confinement fusion requires the production of a low-density channel in plasma with density scale-lengths of several hundred microns. The channel assists in the propagation of an ultra-intense laser pulse used to generate fast electrons which form a hot spot on the side of pre-compressed fusion fuel. We present a systematic characterization of an expanding laser-produced plasma using optical interferometry, benchmarked against three-dimensional hydrodynamic simulations. Magnetic fields associated with channel formation are probed using proton radiography, and compared to magnetic field structures generated in full-scale particle-in-cell simulations. We present observations of long-lived, straight channels produced by the Habara-Kodama-Tanaka whole-beam self-focusing mechanism, overcoming a critical barrier on the path to realizing fast ignition. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 2)'.

Privacy rights of human research participants in South Africa must be taken seriously.

Letter by Thaldar and Townsend, following an article by the same authors (Thaldar D, Townsend B. Genomic research and privacy: A response to Staunton et al. S Afr Med J 2020;110(3):172-174. https://doi.org/10.7196/SAMJ.2020.v110i3.14431) and both commenting on an article by Staunton et al. (Staunton C, Adams R, Botes M, et al. Safeguarding the future of genomic research in South Africa: Broad consent and the Protection of Personal Information Act No. 4 of 2013. S Afr Med J 2019;109(7):468-470. https://doi.org/10.7196/SAMJ.2019.v109i7.14148); and response to article and letter by Staunton et al.

Surveillance optimisation to detect poliovirus in the pre-eradication era: a modelling study of England and Wales.

Surveillance for acute flaccid paralysis (AFP) cases are essential for polio eradication. However, as most poliovirus infections are asymptomatic and some regions of the world are inaccessible, additional surveillance tools require development. Within England and Wales, we demonstrate how inclusion of environmental sampling (ENV) improves the sensitivity of detecting both wild and vaccine-derived polioviruses (VDPVs) when compared to current surveillance. Statistical modelling was used to estimate the spatial risk of wild and VDPV importation and circulation in England and Wales. We estimate the sensitivity of each surveillance mode to detect poliovirus and the probability of being free from poliovirus, defined as being below a pre-specified prevalence of infection. Poliovirus risk was higher within local authorities in Manchester, Birmingham, Bradford and London. The sensitivity of detecting wild poliovirus within a given month using AFP and enterovirus surveillance was estimated to be 0.096 (95% CI 0.055-0.134). Inclusion of ENV in the three highest risk local authorities and a site in London increased surveillance sensitivity to 0.192 (95% CI 0.191-0.193). The sensitivity of ENV strategies can be compared using the framework by varying sites and the frequency of sampling. The probability of being free from poliovirus slowly increased from the date of the last case in 1993. ENV within areas thought to have the highest risk improves detection of poliovirus, and has the potential to improve confidence in the polio-free status of England and Wales and detect VDPVs.

School-based vaccination programmes: An evaluation of school immunisation delivery models in England in 2015/16.

Schools are increasingly being used to deliver vaccines. In 2015/16 three school-based vaccination programmes were delivered to adolescents in England: human papillomavirus (HPV), meningococcal groups A, C, W and Y disease (MenACWY) and tetanus, diphtheria and polio (Td/IPV). We assessed how school delivery models impact vaccine coverage and how a delivery model for one programme may impact another. Routinely collected national data were analysed to ascertain the school grade achieving highest coverage within each one-dose programme and to compare two-dose delivery models (within year vs across years) for the HPV vaccine. We also assessed whether the HPV delivery model was associated with coverage in other programmes. MenACWY and Td/IPV coverage was highest in younger school grades. Overall similar HPV coverage was achieved with both models (86.7% two doses within one year, 85.8% two doses across two years, p = 0.20). High two-dose HPV coverage in 2015/16 was reported in areas that achieved high HPV coverage in 2013/14 when three doses were required. Areas with high three-dose coverage in 2013/14 achieved higher coverage with a within-one-year approach (92.0% vs 85.2%, p < 0.001), whilst areas reporting low coverage in 2013/14 achieved lower but similar coverage in 2015/16 with both models (79.2% vs 80.9% p = 0.29). MenACWY and Td/IPV coverage were higher in areas with high HPV coverage in 2013/14. Among high HPV coverage areas, MenACWY coverage was higher when HPV doses were delivered within year. School-based programmes should be offered as early as feasible and acceptable to optimise coverage. The choice of delivery model for HPV should take into account local performance and provider experience. Single providers may delivery multiple vaccines and the delivery for one programme may affect the performance of other programmes. Providers should consider local circumstances including past and current vaccine coverage and factors influencing coverage when deciding what delivery model to adopt.

Monitoring liver transplant rates in persons diagnosed with hepatitis C: a data linkage study, England 2008 to 2017.

IntroductionLiver transplantation is an important measure of burden from hepatitis C virus (HCV)-associated liver disease.AimsTo describe transplant rates and survival in individuals with HCV infection from 2008 to 2017 in England through data linkage.MethodsThis is a retrospective observational cohort study. Laboratory reports of HCV infection were linked to the Liver Transplant Registry for individuals aged 15 years and over, first diagnosed between 1998 and 2017. We estimated age-sex standardised incidence rates and used Poisson regression to investigate predictors of liver transplantation and test for a change in incidence after introduction of direct-acting antivirals (DAAs) in 2014. Kaplan-Meier survival analysis was used to calculate post-transplant survival rates.ResultsOf 124,238 individuals diagnosed with HCV infection, 1,480 were registered and 1,217 received a liver transplant. Of individuals registered, 1,395 had post-HCV cirrhosis and 636 had hepatocellular carcinoma (618 also had post-HCV cirrhosis). Median time from HCV diagnosis to transplant was 3.4 years (interquartile range: 1.3-6.8 years). Liver transplant rates were lower 2014-17 compared with 2011-13 (incidence rate ratio: 0.64; 95% confidence interval: 0.55-0.76). Survival rates were 93.4%, 79.9% and 67.9% at 1, 5 and 10 years, respectively. Data linkage showed minimal under-reporting of HCV in the transplant registry.ConclusionIn the post-DAA era, liver transplant rates have fallen in individuals with HCV infection, showing early impact of HCV treatment scale-up; but the short time from HCV diagnosis to liver transplant suggests late diagnosis is a problem.

Safeguarding the future of genomic research in South Africa: Broad consent and the Protection of Personal Information Act No. 4 of 2013.

Genomic research has been identified in South Africa (SA) as important in developing a strong bio-economy that has the potential to improve human health, drive job creation and offer potential solutions to the disease burden harboured by low- and middle-income countries. Central to the success of genomic research is the wide sharing of biological samples and data, but the true value of data can only be unlocked if there are laws and policies in place that foster the legal and ethical sharing of genomic data. The introduction and entry into force of SA's Protection of Personal Information Act (POPIA) No. 4 of 2013 is to be welcomed, but the wording of POPIA as it pertains to consent for the processing of personal information for research purposes has sparked a debate about the legal status of broad consent. We argue that a purposive interpretation of the legislation would permit broad consent for the processing of personal information for research. Although there are ongoing debates surrounding the ethical use of broad consent in Africa, the objective of this article is not to engage with the ethics of broad consent itself, but rather to focus on the legal status of broad consent for genomic data sharing under POPIA.

Mapping the hepatitis C cascade of care in people attending drug treatment services in England: A data linkage study.

INTRODUCTION: Hepatitis C (HCV) infection in England primarily affects people who inject drugs (PWID). We describe persons HCV tested, estimate incidence and establish the cascade of care (CoC) for people engaging with drug services. METHODS: Persons testing for HCV in drug services in Sentinel Surveillance of Blood Borne Virus Testing (SSBBV) between 2008 and 2016 were linked with people attending drug services in the National Drug and Treatment Monitoring System (NDTMS). We describe risk characteristics, establish the CoC, and estimate HCV incidence in PWID diagnosed in drug services. RESULTS: Of 46,721 persons tested for anti-HCV in SSBBV in drug services, 29,773 (63.7%) linked to NDTMS. Of these, 9100 (30.6%) were antiV positive and anti-HCV positivity was 45.0% in persons reporting urgent housing problems and 43.8% in persons reporting ever injecting. Among persons anti-HCV positive, half had ≥1 positive anti-HCV test. For persons' first anti-HCV positive between 2008 and 2013 (n = 3123), 74.9% were HCV RNA tested, of whom 71.2% were RNA positive, and of these, 14.0% had evidence of interferon-based treatment, with 52.8% achieving cure. Among PWID, HCV incidence was 8.7 per 100 person-years (95% CI: 8.1-9.2). CONCLUSION: Through record linkage of surveillance datasets, we estimated the HCV CoC for people attending drug services, providing a benchmark from which to monitor the impact of strategies to scale-up prevention, testing, and curative treatment with direct acting antivirals. Our study highlights wasteful repeated testing and poor linkage to care for this high risk population which need to be addressed.

Lower risk of invasive meningococcal disease during pregnancy: national prospective surveillance in England, 2011-2014.

OBJECTIVE: To describe cases of invasive meningococcal disease (IMD) in women of childbearing age and to estimate the disease incidence and relative risk of IMD in pregnant compared with non-pregnant women. DESIGN: Prospective enhanced national surveillance for IMD. SETTING: England. POPULATION: Women of reproductive age (15-44 years) with laboratory-confirmed IMD. METHODS: Public Health England conducts enhanced national surveillance for IMD in England. Laboratory-confirmed cases are followed up with postal questionnaires to general practitioners. All cases confirmed in women of reproductive age from 1 January 2011 to 31 December 2014 were included. MAIN OUTCOME MEASURES: Annual IMD incidence and relative risk of IMD in pregnant compared with non-pregnant women of reproductive age. RESULTS: During the 4-year surveillance period, there were 1502 cases of IMD in females across England; of these, 310 (20.6%) cases were in women of reproductive age, including four women who were pregnant at the time of IMD confirmation (1.3%). Serogroup distribution of IMD cases in women of childbearing age was similar to the overall distribution. The four cases in otherwise healthy pregnant women were confirmed across all trimesters and all survived; one case in the first trimester had a septic miscarriage. The incidence of IMD was lower in pregnant than in non-pregnant women (0.16 compared with 0.76 per 100 000 pregnant and non-pregnant years, respectively), giving a lower risk of IMD in pregnant women (incidence rate ratio, IRR, 0.21; 95% confidence interval, 0.06-0.54). CONCLUSIONS: Pregnant women are nearly five times less likely to develop IMD compared with non-pregnant women, but the infection can be severe. TWEETABLE ABSTRACT: The risk of meningococcal disease is lower in pregnant women compared with non-pregnant women; the infection can occur across all trimesters and can be severe.

HIV coinfection among persons diagnosed with hepatitis B in England in 2008-2014.

OBJECTIVES: The aim of the study was to estimate HIV prevalence among persons with hepatitis B virus (HBV) infection in England and to examine associated risk factors. METHODS: Persons aged ≥ 15 years with an HBV surface antigen (HBsAg) test reported to Public Health England (PHE) sentinel surveillance during 2008-2014 were linked to the PHE national HIV/AIDS database. Coinfection was defined as an HIV diagnosis prior to, or within 6 months following, a positive HBsAg test. RESULTS: During 2008-2014, 2 149 933 persons were tested for HBsAg and 3.9% (1129 of 28 789) of HBsAg-positive persons were HIV positive. The probable route of HIV infection was heterosexual exposure for 95.3% of female patients and 32.3% of male patients, with 61.5% of male patients reporting sex between men. Among African-born coinfected persons, 84% probably acquired HIV there. Predictors of HIV positivity included older age [adjusted odds ratio (aOR) 1.1] and being of black ethnicity (aOR 15.5 for males; aOR 16.4 for females) or being male and of white ethnicity (aOR 8.2) compared with being female and of white ethnicity. HIV coinfection was more likely when HBV was diagnosed in sexual health (aOR 55.0), specialist liver (aOR 6.7), emergency department (aOR 5.3) and renal services (aOR 2.8) compared with general practice. Most (60.4%; 682 of 1129) coinfected persons were diagnosed with HIV infection > 6 months before HBV diagnosis. CONCLUSIONS: Persons testing positive for HBsAg had a low HIV infection rate and fell largely into two groups: those of black ethnicity with probable Africa-acquired infections and white men who have sex with men (MSM) with probable UK-acquired infections. Findings reinforce existing recommendations to sustain and improve both HBV testing of migrants from HBV-prevalent countries and vaccination among HIV-positive MSM. Findings also support blood-borne virus testing in sexual health services and emergency departments.

Establishing the cascade of care for hepatitis C in England-benchmarking to monitor impact of direct acting antivirals.

Little is known about engagement and retention in care of people diagnosed with chronic hepatitis C (HCV) in England. Establishing a cascade of care informs targeted interventions for improving case finding, referral, treatment uptake and retention in care. Using data from the sentinel surveillance of blood-borne virus (SSBBV) testing between 2005 and 2014, we investigate the continuum of care of those tested for HCV in England. Persons ≥1 year old with an anti-HCV test and subsequent RNA tests between 2005 and 2014 reported to SSBBV were collated. We describe the cascade of care, as the patient pathway from a diagnostic test, referral into care, treatment and patient outcomes. Between 2005 and 2014, 2 390 507 samples were tested for anti-HCV, corresponding to 1 766 515 persons. A total of 53 038 persons (35 190 men and 17 165 women) with anti-HCV positive were newly reported to SSBBV. An RNA test was conducted on 77.0% persons who were anti-HCV positive, 72.3% of whom were viraemic (RNA positive) during this time period, 21.4% had evidence of treatment and 3130 49.5% had evidence of a sustained virological response (SVR). In multivariable models, confirmation of viraemia by RNA test varied by age and region/test setting; evidence of treatment varied by age, year of test and region/test setting; and SVR varied by age, year of test and region/setting of test. In conclusion, our findings provide HCV cascade of care estimates prior to the introduction of direct acting antivirals. These findings provide important baseline cascade estimates to benchmark progress towards elimination of HCV as a major public health threat.

Strengthening human genetics research in Africa: report of the 9th meeting of the African Society of Human Genetics in Dakar in May 2016.

The 9th meeting of the African Society of Human Genetics, in partnership with the Senegalese Cancer Research and Study Group and the Human Heredity and Health in Africa (H3Africa) Consortium, was held in Dakar, Senegal. The theme was Strengthening Human Genetics Research in Africa. The 210 delegates came from 21 African countries and from France, Switzerland, UK, UAE, Canada and the USA. The goal was to highlight genetic and genomic science across the African continent with the ultimate goal of improving the health of Africans and those across the globe, and to promote the careers of young African scientists in the field. A session on the sustainability of genomic research in Africa brought to light innovative and practical approaches to supporting research in resource-limited settings and the importance of promoting genetics in academic, research funding, governmental and private sectors. This meeting led to the formation of the Senegalese Society for Human Genetics.

Le 9ème congrès de la Société Africaine de Génétique Humaine, en partenariat avec le Groupe d'Etude et de Recherche sur le Cancer (GERC) et le Consortium H3Africa, s'est tenu à Dakar, au Sénégal. Le thème était «Renforcer la recherche en Génétique Humaine en Afrique¼. Les 210 participants sont venus de 21 pays africains et de six non africains. L'objectif était de valoriser la génétique et la génomique à travers l'Afrique avec comme but ultime d'améliorer la santé des populations, et de promouvoir les carrières des jeunes chercheurs Africains. Une session sur la pérennité de la recherche génomique a révélé des approches innovantes et pratiques supportant la recherche dans des contextes de ressources limitées et l'importance de promouvoir la formation universitaire en génétique, le financement de la recherche par les gouvernements et le privé. Ce congrès conduisit à la création de la Société Sénégalaise de Génétique Humaine.

Estimating true hospital morbidity of complications associated with mumps outbreak, England, 2004/05.

Mumps outbreaks in highly vaccinated populations continue to be reported globally. Therefore, quantifying the burden of mumps morbidity accurately will be necessary to better assess the impact of mumps vaccination programmes. We aim to estimate the true morbidity resulting from mumps complications in terms of hospitalised orchitis, meningitis, oophoritis and pancreatitis in England during the outbreak in 2004/05. This outbreak in England led to a clear increase in hospitalisations coded to mumps for complications of orchitis in those born in the 1970s and 1980s and possibly for meningitis in those born in the 1980s. A simple statistical model, based on analysing time trends for diagnosed complications in hospital databases with routine laboratory surveillance data, found that the actual morbidity was much higher. There were 2.5 times (166 cases) more mumps orchitis cases in the 1970s cohort and 2.0 times (708 cases) more mumps orchitis cases in the 1980s cohort than complications coded to mumps in hospital databases. Our study demonstrated that the mumps outbreak in England 2004/05 resulted in a substantial increase in hospitalised mumps complications, and the model we used can improve the ascertainment of morbidity from a mumps outbreak.

Current epidemiology of tetanus in England, 2001-2014.

Public Health England conducts enhanced national surveillance of tetanus, a potentially life-threatening vaccine-preventable disease. A standardized questionnaire was used to ascertain clinical and demographic details of individuals reported with clinically suspected tetanus. The 96 cases identified between 2001 and 2014 were analysed. The average annual incidence was 0·13/million (95% confidence interval 0·10-0·16) of which 50·0% were male. Where reported, 70·3% of injuries occurred in the home/garden (45/64). Overall, 40·3% (31/77) cases were in people who inject drugs (PWID), including a cluster of 22 cases during 2003-2004. Where known (n = 68), only 8·8% were age-appropriately immunized. The overall case-fatality rate was 11·0% (9/82). All tetanus-associated deaths occurred in adults aged >45 years, none of whom were fully immunized. Due to the success of the childhood immunization programme, tetanus remains a rare disease in England with the majority of cases occurring in older unimmunized or partially immunized adults. Minor injuries in the home/garden were the most commonly reported likely sources of infection, although cases in PWID increased during this period. It is essential that high routine vaccine coverage is maintained and that susceptible individuals, particularly older adults, are protected through vaccination and are offered timely post-exposure management following a tetanus-prone wound.