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Reconciling founder variant multiplicity of HIV-1 infection with the rate of CD4+ decline.
Get PDFHIV-1 transmission precipitates a stringent genetic bottleneck, with 75% of new infections initiated by a single genetic variant. Where multiple variants initiate infection, recipient set point viral load (SpVL) and the rate of CD4+ T cell decline may be elevated, but these findings remain inconsistent. Here, we summarised the evidence for this phenomenon, then tested whether previous studies possessed sufficient statistical power to reliably identify a true effect of multiple variant infection leading to higher SpVL. Next, we combined models of HIV-1 transmission, heritability and disease progression to understand whether available data suggest a faster CD4+ T cell decline would be expected to associated with multiple variant infection, without an explicit dependency between the two. First, we found that most studies had insufficient power to identify a true significant difference, prompting an explanation for previous inconsistencies. Next, our model framework revealed we would not expect to observe a positive association between multiple variant infections and faster CD4+ T cell decline, in the absence of an explicit dependency. Consequently, while empirical evidence may be consistent with a positive association between multiple variant infection and faster CD4+ T cell decline, further investigation is required to establish a causal basis
NHS national data opt-outs: trends and potential consequences for health data research.
Get PDFBACKGROUND: The English NHS data opt-out allows people to prevent use of their health data for purposes other than direct care. In 2021, the number of opt-outs increased in response to government-led proposals to create a centralised pseudonymised primary care record database. AIM: To describe the potential impact of NHS national data opt-outs in 2021 on health data research. DESIGN & SETTING: We conducted a descriptive analysis of opt-outs using publicly available data and the potential consequences on research are discussed. METHOD: Trends in opt-outs in England were described by age, sex, and region. Using a hypothetical study, we explored statistical and epidemiological implications of opt-outs. RESULTS: During the lead up to a key government-led deadline for registering opt-outs (from 31 May 2021-30 June 2021), 1 339 862 national data opt-outs were recorded; increasing the percentage of opt-outs in England from 2.77% to 4.97% of the population. Among females, percentage opt-outs increased by 83% (from 3.02% to 5.53%) compared with 76% in males (from 2.51% to 4.41%). Across age groups, the highest relative increase was among people aged 40-49 years, which rose from 2.89% to 6.04%. Considerable geographical variation was not clearly related to deprivation. Key research consequences of opt-outs include reductions in sample size and unpredictable distortion of observed measures of the frequency of health events or associations between these events. CONCLUSION: Opt-out rates varied by age, sex, and place. The impact of this and variation by other characteristics on research is not quantifiable. Potential effects of opt-outs on research and consequences for health policies based on this research must be considered when creating future opt-out solutions
XEN®-45 implantation for refractory uveitic glaucoma.
Get PDFPURPOSE: To evaluate the efficacy of XEN®-45 gel stent ab interno implantation for medically uncontrolled uveitic glaucoma. METHODS: Retrospective analysis of 25 eyes receiving XEN® gel stent for medically uncontrolled uveitic glaucoma from February 2019 to February 2023 with recording of intraocular pressure (IOP) values, ocular hypotensive medication, requirement for revision or secondary surgery and complications. Prerequisites for XEN® implantation were a clear cornea, an open iridocorneal angle and an unscarred, mobile conjunctiva at the implantation site. Minimum follow-up required for inclusion was 3 months. The primary outcome measure was IOP compared to baseline. Complete and qualified success were defined as final IOP of ≤ 18 mmHg without or with topical antiglaucomatous treatment, respectively. Failure was defined as IOP > 18 mmHg on two consecutive visits, IOP reduction < 20%, persisting complications from hypotony and open conjunctival bleb revision. Further glaucoma surgical intervention was defined as complete failure. RESULTS: Mean preoperative IOP was 35.3 ± 10.9 mmHg on 2.9 ± 0.9 topical antiglaucomatous agents. 19 of 25 patients (76%) received additional oral acetazolamide. 19 eyes were pseudophakic, 5 eyes phakic and 1 aphakic. Early postoperatively, mean IOP reduced to 7.7 ± 3.0 mmHg (75.8% reduction). At final follow-up (mean 17.7 months) mean IOP was 12.0 ± 3.8 mmHg (62.5% reduction) on 0.2 ± 0.6 medications. Six eyes (24%) required bleb revision at mean 28 weeks and therefore were categorized as failure. One eye failed despite bleb revision and restart of topical ocular hypotensive medication. Three other eyes (12%) had IOP spikes with uveitis flare-ups. Transient hypotony complications occurred in 32%. At final follow-up, 18 eyes (72%) achieved complete success and one eye (4%) qualified success. CONCLUSION: The XEN® gel stent effectively reduced IOP in uncontrolled uveitic glaucoma, with 72% complete success. Bleb revision was required in 24%. IOP spikes occurred in 12% despite functioning blebs. Further follow-up is needed to determine long-term outcomes
Dimensions of vulnerability. Case 8.3: Studying the Impact of COVID-19 on Vulnerable Populations
Get PDFLocating Medical Television: The Televisual Spaces of Medicine and Health in the Twentieth Century
Get PDFMedical television programmes, across their history, have had specific relationships to places and spaces. On one level, they have represented medical and health places, such as, consulting rooms, hospitals, the home, community spaces, public health infrastructures, etc. Television producers have represented these places, in line with the capabilities of television technologies and grammars. Moreover, producers have borrowed their images of medical and health places from other media (film, photographs, museum displays, etc.) and integrated, adjusted and reformulated them into their work. But medical television has also worked spatially in the political sense of being broadcast internationally, nationally, and locally; therein interacting with differing regimes and polities. This facet includes regional and local broadcasting, as well as public-private divides, including pay television, advertisement and audience measurement. On both levels, medical television programmes have served to represent familiar and unfamiliar locations and medical modes to patients and medical or health practitioners. This issue of Media History on medical television follows the conference of the same title, Locating Medical Television, organised in the framework of the ERC funded BodyCapital project and the Science Museum London. It intends to locate medical television more precisely; to engage (medical) TV history with recent questions concerning the relevance of space within and beyond national borders
Genome Sequences of Extended-Spectrum Beta-Lactamase-Producing Escherichia coli Recovered from Mid-Stream Urine Samples in Accra, Ghana.
Get PDFEscherichia coli, a member of the commensal intestinal microbiota, is a significant aetiology of urinary tract infections (UTIs) and has a propensity for acquiring multidrug resistance characteristics, such as extended-spectrum beta-lactamases (ESBLs). Despite the increase in the incidence of ESBL-producing E. coli infections in sub-Saharan Africa, routine ESBL detection in Ghana is often absent, and molecular data on ESBL genotypes is scarce. Eleven ESBL-producing E. coli recovered from mid-stream urine samples were subjected to antimicrobial susceptibility testing and whole-genome sequence analyses. All isolates exhibited multidrug resistance, demonstrating phenotypic resistance to third-generation cephalosporins, such as cefotaxime, ceftazidime, and cefpodoxime. Three isolates demonstrated resistance to norfloxacin (a fluoroquinolone), and one isolate demonstrated intermediate resistance to ertapenem (a carbapenem). Analysis of the draft genomes identified multiple antimicrobial resistance genes including ESBL genotypes blaTEM-1B/TEM-190 (6/11 and 1/11, respectively), blaCTX-M-15/CTX-M-3 (7/11 and 1/11) and blaOXA-1/OXA-181 (3/11 and 1/11). The strains belong to 10 different serotypes and 10 different multilocus sequence types. This study provides information on phenotypic resistance in 11 ESBL E. coli from Ghana and AMR genotypes within their genomes
Cycles of antibiotic use and emergent antimicrobial resistance in the South African tuberculosis programme (1950-2021): A scoping review and critical reflections on stewardship.
Get PDFThe emergent threat of antimicrobial resistance (AMR) has resulted in debates around the use and preservation of effective antimicrobials. Concerns around AMR reflect a history of increasing dependence on antibiotics to address disease epidemics rooted in profound structural and systemic challenges. In the context of global health, this process, often referred to as pharmaceuticalisation, has commonly occurred within disease programmes, of which lessons are vital for adding nuance to conversations around antimicrobial stewardship. Tuberculosis (TB) is a notable example. A disease which accounts for one-third of AMR globally and remains the leading cause of death from a single infectious agent in many low - and middle-income countries, including South Africa. In this scoping review, we chart TB science in South Africa over 70 years of programming. We reviewed published manuscripts about the programme and critically reflected on the implications of our findings for stewardship. We identified cycles of programmatic responses to new drug availability and the emergence of drug resistance, which intersected with cycles of pharmaceuticalisation. These cycles reflect the political, economic, and social factors influencing programmatic decision-making. Our analysis offers a starting point for research exploring these cycles and drawing out implications for stewardship across the TB and AMR communities
Immunity against measles, mumps, rubella, and varicella among homeless individuals in Germany - A nationwide multi-center cross-sectional study.
Get PDFINTRODUCTION: Homeless individuals suffer a high burden of vaccine-preventable infectious diseases. Moreover, they are particularly susceptible to adverse infection outcomes with limited access to the health care system. Data on the seroprevalence of measles, mumps, rubella, and varicella within this cohort are missing. METHODS: The seroprevalence of measles, mumps, rubella, and varicella was determined within the homeless population in Germany. Predictors of lacking immune protection were determined using multivariable logistic regression analysis. RESULTS: Homeless individuals in Germany (n = 611) showed a seroprevalence of 88.5% (95% CI: 85.8-91.0) for measles, 83.8% (95% CI: 80.6-86.6) for mumps, 86.1% (95% CI: 83.1-88.7) for rubella, and 95.7% (95% CI 93.8-97.2) for varicella. Measles seroprevalences declined from individuals born in 1965 to individuals born in 1993, with seroprevalences not compatible with a 95% threshold in individuals born after 1980. For mumps, seroprevalences declined from individuals born in 1950 to individuals born in 1984. Here, seroprevalences were not compatible with a 92% threshold for individuals born after 1975. Seronegativity for measles, mumps and rubella was associated with age but not with gender or country of origin. DISCUSSION: Herd immunity for measles and mumps is not achieved in this homeless cohort, while there was sufficient immune protection for rubella and varicella. Declining immune protection rates in younger individuals warrant immunization campaigns also targeting marginalized groups such as homeless individuals. Given that herd immunity thresholds are not reached for individuals born after 1980 for measles, and after 1975 for mumps, vaccination campaigns should prioritize individuals within these age groups
Study of How Adiposity in Pregnancy has an Effect on outcomeS (SHAPES): protocol for a prospective cohort study.
Get PDFINTRODUCTION: Maternal obesity increases the risk of multiple maternal and infant pregnancy complications, such as gestational diabetes and pre-eclampsia. Current UK guidelines use body mass index (BMI) to identify which women require additional care due to increased risk of complications. However, BMI may not accurately predict which women will develop complications during pregnancy as it does not determine amount and distribution of adipose tissue. Some adiposity measures (eg, waist circumference, ultrasound measures of abdominal visceral fat) can better identify where body fat is stored, which may be useful in predicting those women who need additional care. METHODS AND ANALYSIS: This prospective cohort study (SHAPES, Study of How Adiposity in Pregnancy has an Effect on outcomeS) aims to evaluate the prognostic performance of adiposity measures (either alone or in combination with other adiposity, sociodemographic or clinical measures) to estimate risk of adverse pregnancy outcomes. Pregnant women (n=1400) will be recruited at their first trimester ultrasound scan (11+2-14+1 weeks') at Newcastle upon Tyne National Health Service Foundation Trust, UK. Early pregnancy adiposity measures and clinical and sociodemographic data will be collected. Routine data on maternal and infant pregnancy outcomes will be collected from routine hospital records. Regression methods will be used to compare the different adiposity measures with BMI in terms of their ability to predict pregnancy complications. If no individual measure performs better than BMI, multivariable models will be developed and evaluated to identify the most parsimonious model. The apparent performance of the developed model will be summarised using calibration, discrimination and internal validation analyses. ETHICS AND DISSEMINATION: Ethical favourable opinion has been obtained from the North East: Newcastle & North Tyneside 1 Research Ethics Committee (REC reference: 22/NE/0035). All participants provide informed consent to take part in SHAPES. Planned dissemination includes peer-reviewed publications and additional dissemination appropriate to target audiences, including policy briefs for policymakers, media/social-media coverage for public and conferences for research TRIAL REGISTRATION NUMBER: ISRCTN82185177
Assessing COVID-19 vaccine roll-out in Uganda: a case study of uptake and associated factors among health care workers and older people
Get PDFIntroduction We conducted a survey to investigate the uptake of COVID-19 vaccination among healthcare workers (HCWs) and older persons (≥ 50 years) in Uganda, groups at particular risk of infection and severe disease outcomes respectively. Methods The survey was conducted between May and August 2021, during the early phase of COVID-19 vaccine roll-out. All HCWs at Entebbe and Kisubi hospitals, Wakiso district (urban/peri-urban) and Villa Maria hospital, Kalungu district (rural), and non-healthcare worker (non-HCW) individuals enrolled in an ongoing older persons’ cohort study in Wakiso district, completed an interviewer-administered questionnaire on socio-demographics, pre-existing medical conditions, attitudes regarding COVID-19 vaccines, and vaccination uptake. Logistic regression was performed to investigate factors associated with uptake. Findings A total of 746 individuals, 597 HCWs and 149 non-HCW older persons, participated. Majority were aged ≤50 years (71.6%), female (63.1%), and had secondary school/other higher-level education (77.8%). COVID-19 uptake was 63.7%, overall; 95.2%, Entebbe Hospital; 75.4%, Kisubi Hospital; 49.5%, Villa Maria Hospital; and 20.8%, non-HCW. Among HCWs, health facility [Entebbe hospital (aOR 18.9, 95% CI 8.9-40.2), Kisubi hospital (aOR 5.2, 95% CI 3.0-9.0) all compared with Villa Maria], age >50 years (aOR 3.1, 95% CI 1.2-8.4) and positive attitude towards COVID-19 vaccines (aOR 5.0, 95% CI 2.1-11.8) were associated with high uptake, while female sex (aOR 0.5, 95% CI 0.3-0.9) was associated with low uptake. Among non-HCW older persons, absence of chronic infectious disease (aOR 4.3, 95% CI 1.1-16.3) good attitude towards COVID-19 vaccines (aOR 29.2, 95% CI 4.1-208.8) were associated with high uptake, while advanced age 70-79 years (aOR 0.1, 95% CI 0.01-0.97) was associated with low uptake. Conclusion COVID-19 vaccine uptake was lowest among rural-based HCWs and non-HCW older persons. Vaccination campaigns during a pandemic need to foster positive attitudes towards vaccines and employ strategies specifically designed to improve vaccine uptake among disadvantaged populations.</ns3:p