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Urine high-risk human papillomavirus testing as an alternative to routine cervical screening: A comparative diagnostic accuracy study of two urine collection devices using a randomised study design trial.
Get PDFOBJECTIVE: To evaluate the sensitivity of human papillomavirus (HPV) tested urine to detect high-grade cervical precancer (cervical intraepithelial neoplasia grade 2+ [CIN2+]) using two urine collection devices. DESIGN: Randomised controlled trial. SETTING: St Mary's Hospital, Manchester, UK. POPULATION: Colposcopy attendees with abnormal cervical screening; a total of 480 participants were randomised. Matched urine and cervical samples were available for 235 and 230 participants using a first-void urine (FVU)-collection device and standard pot, respectively. METHODS: Urine was self-collected and mixed with preservative - randomised 1:1 to FVU-collection device (Novosanis Colli-pee® 10 mL with urine conservation medium [UCM]) or standard pot. Matched clinician-collected cervical samples were taken before colposcopy. HPV testing used Roche cobas® 8800. A questionnaire evaluated urine self-sampling acceptability. MAIN OUTCOME MEASURES: The primary outcome measured sensitivity of HPV-tested urine (FVU-collection device and standard pot) for CIN2+ detection. Secondary outcomes compared HPV-tested cervical and urine samples for CIN2+ and evaluated the acceptability of urine self-sampling. RESULTS: Urine HPV test sensitivity for CIN2+ was higher with the FVU-collection device (90.3%, 95% CI 83.7%-94.9%, 112/124) than the standard pot (73.4%, 95% CI 64.7%-80.9%, 91/124, p = 0.0005). The relative sensitivity of FVU-device-collected urine was 0.92 (95% CI 0.87-0.97, pMcN = 0.004) compared with cervical, considering that all women were referred after a positive cervical HPV test. Urine-based sampling was acceptable to colposcopy attendees. CONCLUSIONS: Testing of FVU-device-collected urine for HPV was superior to standard-pot-collected urine in colposcopy attendees and has promising sensitivity for CIN2+ detection. General population HPV testing of FVU-device-collected urine will establish its clinical performance and acceptability as an alternative to routine cervical screening
Immortal time bias in the analysis of time-varying environmental exposures in the UK Biobank.
No full textAddressing water, sanitation and hygiene inequalities: A review of evidence, gaps, and recommendations for disability-inclusive WASH by 2030
Get PDFOne in six people worldwide experiences significant disability. Many of these people living in low-and middle-income countries (LMICs) are disproportionately affected by inadequate access to water, sanitation and hygiene (WASH) services, a fundamental necessity for health and well-being. This review aimed to examine the existing evidence on disability and WASH in LMICs, identify gaps and make recommendations to strengthen disability-inclusive WASH research, policies and practices to make significant progress by 2030. While evidence of WASH challenges faced by people with disabilities has grown in the last decade, revealing significant inequalities, there is a lack of controlled studies to assess the impact of disability-inclusive WASH interventions. This research gap makes it difficult to prioritise investments for scalable solutions. This review proposes three key recommendations: 1) Further expand research on WASH challenges faced by people with disabilities, prioritising climate risks, health impacts, and educational inequalities. 2) Design and test evidence-based disability-inclusive WASH interventions. 3) Rigorously evaluate these interventions to determine what successfully reduces WASH disparities for people with disabilities and their caregivers cost-effectively. This review is the first to synthesise available evidence across disability and WASH and offer a roadmap for future efforts to drive improvements in disability-inclusive WASH by 2030
Uncovering the genetic diversity in Aedes aegypti insecticide resistance genes through global comparative genomics.
Get PDFAedes aegypti is vector of many arboviruses including Zika, dengue, yellow fever, West Nile, and Chikungunya. Its control efforts are hampered by widespread insecticide resistance reported in the Americas and Asia, while data from Africa is more limited. Here we use publicly available 729 Ae. aegypti whole-genome sequencing samples from 15 countries, including nine in Africa, to investigate the genetic diversity in four insecticide resistance linked genes: ace-1, GSTe2, rdl and vgsc. Apart from vgsc, the other genes have been less investigated in Ae. aegypti, and almost no genetic diversity information is available. Among the four genes, we identified 1,829 genetic variants including 474 non-synonymous substitutions, some of which have been previously documented, as well as putative copy number variations in GSTe2 and vgsc. Global insecticide resistance phenotypic data demonstrated variable resistance in geographic areas with resistant genotypes. Overall, our work provides the first global catalogue and geographic distribution of known and new amino-acid mutations and duplications that can be used to guide the identification of resistance drivers in Ae. aegypti and thereby support monitoring efforts and strategies for vector control
Synthesis and Anti-Chagas Activity Profile of a Redox-Active Lead 3-Benzylmenadione Revealed by High-Content Imaging.
Get PDFChagas disease, or American trypanosomiasis, is a neglected tropical disease which is a top priority target of the World Health Organization. The disease, endemic mainly in Latin America, is caused by the protozoan Trypanosoma cruzi and has spread around the globe due to human migration. There are multiple transmission routes, including vectorial, congenital, oral, and iatrogenic. Less than 1% of patients have access to treatment, relying on two old redox-active drugs that show poor pharmacokinetics and severe adverse effects. Hence, the priorities for the next steps of R&D include (i) the discovery of novel drugs/chemical classes, (ii) filling the pipeline with drug candidates that have new mechanisms of action, and (iii) the pressing need for more research and access to new chemical entities. In the present work, we first identified a hit (4a) with a potent anti-T. cruzi activity from a library of 3-benzylmenadiones. We then designed a synthetic strategy to build a library of 49 3-(4-monoamino)benzylmenadione derivatives via reductive amination to obtain diazacyclic benz(o)ylmenadiones. Among them, we identified by high content imaging an anti-amastigote "early lead" 11b (henceforth called cruzidione) revealing optimized pharmacokinetic properties and enhanced specificity. Studies in a yeast model revealed that a cruzidione metabolite, the 3-benzoylmenadione (cruzidione oxide), enters redox cycling with the NADH-dehydrogenase, generating reactive oxygen species, as hypothesized for the early hit (4a)
Retinoblastoma survival and enucleation outcomes in 41 countries from the African continent.
Get PDFBACKGROUND: Retinoblastoma is the most common intraocular malignancy in childhood. Despite one-third of cases occurring in Africa, little is known of the outcomes on the continent. This study aims to explore survival and globe salvage outcomes and identify their risk factors across a large cohort of patients from the African continent. METHODS: A 3-year prospective, observational study was conducted. Kaplan-Meier survival analysis was used to investigate the risk of globe loss and death from retinoblastoma in Africa. Cox regression was used to identify risk factors associated with these outcomes. RESULTS: A total of 958 patients from 41 African countries and 66 participating centres were enrolled in the study. The survival rate was 78.2% at 1 year and 66.2% at 3 years after diagnosis. Cox regression showed a higher risk of death with the most advanced clinical stage (cT4, HR=6.29 vs cT2, p<0.001). The risk of losing at least one eye after diagnosis was 50% within 4 months and 72.6% within 3 years. Higher risk of enucleation was associated with a higher clinical stage compared with cT1 (cT3, HR=4.11, p=0.001; cT4, HR=3.77, p=0.005). CONCLUSION: Nearly one in every four children diagnosed with retinoblastoma in African participating centres succumb to retinoblastoma within 1 year. There is also high morbidity associated with the diagnosis as a large majority of patients require eye removal surgery. The outcome of disease in children with retinoblastoma in Africa is poor compared with other continents and requires prompt intervention by increasing efforts to improve survival and eye salvage outcomes
Temporal change in minimum mortality temperature under changing climate: A multicountry multicommunity observational study spanning 1986-2015.
Get PDFBACKGROUND: The minimum mortality temperature (MMT) or MMT percentile (MMTP) is an indicator of population susceptibility to nonoptimum temperatures. MMT and MMTP change over time; however, the changing directions show region-wide heterogeneity. We examined the heterogeneity of temporal changes in MMT and MMTP across multiple communities and in multiple countries. METHODS: Daily time-series data for mortality and ambient mean temperature for 699 communities in 34 countries spanning 1986-2015 were analyzed using a two-stage meta-analysis. First, a quasi-Poisson regression was employed to estimate MMT and MMTP for each community during the designated subperiods. Second, we pooled the community-specific temporally varying estimates using mixed-effects meta-regressions to examine temporal changes in MMT and MMTP in the entire study population, as well as by climate zone, geographical region, and country. RESULTS: Temporal increases in MMT and MMTP from 19.5 °C (17.9, 21.1) to 20.3 °C (18.5, 22.0) and from the 74.5 (68.3, 80.6) to 75.0 (71.0, 78.9) percentiles in the entire population were found, respectively. Temporal change was significantly heterogeneous across geographical regions (P < 0.001). Temporal increases in MMT were observed in East Asia (linear slope [LS] = 0.91, P = 0.02) and South-East Asia (LS = 0.62, P = 0.05), whereas a temporal decrease in MMT was observed in South Europe (LS = -0.46, P = 0.05). MMTP decreased temporally in North Europe (LS = -3.45, P = 0.02) and South Europe (LS = -2.86, P = 0.05). CONCLUSIONS: The temporal change in MMT or MMTP was largely heterogeneous. Population susceptibility in terms of optimum temperature may have changed under a warming climate, albeit with large region-dependent variations
Vitamin B12 deficiency presenting as progressive blindness in a 33-year-old HIV-positive female patient on Efavirenz-based regimen: case report.
Get PDFOptic neuritis is a rare presentation of vitamin B12 deficiency. We describe a 33-year-old female patient living with HIV presenting with progressive loss of vision for 1 week. She had a history of severe peripheral neuropathy that was managed with vitamin B12-containing tablets approximately three years before presenting with progressive loss of vision. On examination, she had no perception of light in the left eye and no perception of hand motion in the right eye. The fundus in her left eye had mild blurring of disc margins. Results from tests done showed a haemoglobin of 12.9g/dl, MCV 101fl, a serum vitamin B12 of 78pmol/l, and cytomegalovirus (CMV) test showed no active disease. She was diagnosed with optic neuritis and started on 30 mg tablets of prednisolone for 1 week with slight improvement. She was then started on vitamin B12 injections 1 mg daily for 10 days and thereafter, monthly for 6 months. She reported gradual improvement and regained her sight after 5 months treatment of with Vitamin B12 injections. Ophthalmic manifestations of vitamin B12 deficiency are not common and may present without haematological signs therefore, a high index of suspicion is required for early diagnosis and management of vitamin B12 deficiency
Applying two approaches to detect unmeasured confounding due to time-varying variables in a self-controlled risk interval design evaluating COVID-19 vaccine safety signals, using myocarditis as a case example.
Get PDFWe test the robustness of the self-controlled risk interval (SCRI) design in a setting where time between doses may introduce time-varying confounding, using both negative control outcomes (NCOs) and quantitative bias analysis (QBA). All vaccinated cases identified from 5 European databases between September 1, 2020, and end of data availability were included. Exposures were doses 1-3 of the Pfizer, Moderna, AstraZeneca, and Janssen COVID-19 vaccines; outcomes were myocarditis and, as the NCO, otitis externa. The SCRI used a 60-day control window and dose-specific 28-day risk windows, stratified by vaccine brand and adjusted for calendar time. The QBA included two scenarios: (1) baseline probability of the confounder was higher in the control window and (2) vice versa. The NCO was not associated with any of the COVID-19 vaccine types or doses except Moderna dose 1 (IRR = 1.09; 95% CI 1.01-1.09). The QBA suggested that even the strongest literature-reported confounder (COVID-19; RR for myocarditis = 18.3) could only explain away part of the observed effect, from IRR = 3 to IRR = 1.40. The SCRI seems robust to unmeasured confounding in the COVID-19 setting, although a strong unmeasured confounder could bias the observed effect upward. Replication of our findings for other safety signals would strengthen this conclusion. This article is part of a Special Collection on Pharmacoepidemiology
Patient and health professional attitudes towards the use of telemedicine for abortion care in Britain: Findings from the SACHA study.
Get PDFINTRODUCTION: Use of telemedicine in abortion care is safe and effective. Patient satisfaction with telemedically supported abortion is high, but as use expands in Britain, little is known about patients' or health professionals' views on how it is best used. We sought the views of both groups on telemedicine's role in abortion provision and how its use might be optimised. METHODS: We administered a structured survey with an additional free-text response option to a range of health professionals from services identified via clustered random sampling. We conducted semi-structured interviews with patients with recent experience of abortion, purposively sampled from abortion services. Participants were recruited from England, Scotland and Wales. We analysed qualitative data using thematic analysis alongside framework analysis. RESULTS: Support for telemedicine was high among participants, which included 771 health professionals from a range of services and 48 patients. Among health professionals, 23% opposed the use of telemedicine in abortion provision. Opposition was highest among those uninvolved, or who did not feel skilled, in remote provision. Reported benefits included patient convenience and comfort. Patient concerns centred on adequate provision of emotional support. Participants made suggestions for augmenting and extending the use of telemedicine to meet some patients' needs, including combining telemedical consultation with in-person care and providing information and follow-up via digital methods. CONCLUSIONS: Acceptability of telemedically supported abortion, which offers logistical and emotional benefits to patients, is high in Britain. Novel ways of providing telemedical support should be explored to enhance remote abortion provision. In-person care should remain an option for patients