69832 research outputs found
Sort by
Distribution of Anopheles gambiae s.l siblings, insecticide resistance and prevalence of markers of resistance (Kdr & Ace-1) in Edea and Buea: forest region of Cameroon.
Get PDFBACKGROUND: The complexity and heterogeneity of malaria transmission in Cameroon is enhanced by the different eco-systems and topology which enhance the proliferation of Anopheline mosquitoes. Though long-lasting insecticide-treated nets have been massively distributed across the country, malaria still remains a significant public health concern, with innate and adaptive resistance mechanisms exploited by malaria vectors against different insecticides; the micro-ecological variations in Cameroon could be playing a viral role in the expression of essential insecticide resistance genes in malaria vectors. Thus, this study sought to assess and compare phenotypic resistance to commonly used insecticides and the prevalence of markers of insecticide resistance to Anopheles gambiae s.l from two localities within the forest ecological zone of Cameroon. MATERIAL AND METHODS: Three to five days mosquitoes obtained from larva collected at eight breeding sites in Buea and Edea were morphologically identified and phenotypic resistance to pyrethroid, organophosphate and carbamate insecticides assessed using the WHO bioassay protocol. Molecular speciation of An. gambiae s.l and the prevalence of L1014F and Ace-1R G119S mutations was assessed using PCR. RESULTS: Anopheles coluzzii and An. gambiae were the only siblings species identified in both communities, with An. coluzzii being the dominant sibling in Edea and the latter in Buea. Anopheles gambiae s.l was resistance to diagnostic concentrations of all insecticides in Buea but susceptible to 1X bendiocarb and 1X pirimiphosmethyl in Edea. In both communities, mortality increased with increasing concentration of alphacypermethrin, permethrin, pirimiphosmethyl and bendiocarb while PBO had a synergistic effect on all pyrethroid insecticides tested. There was a significant difference in the mortality to 1X permethrin (p = 0.014),1X permethrin + PBO (p = 0.001), 5X permethrin (p < 0.001), 1X alphacypermethrin + PBO (p < 0.001), 1X pirimiphosmethyl (p < 0.001) and 1X bendiocarb (p < 0.001) in Buea compared to Edea. CONCLUSION: Anopheles gambiae and An. coluzzii were the major malaria vectors in both communities.Though these vectors were resistant to the diagnostic dose of all insecticides in Buea, they were susceptible to 1X bendiocarb and 1X pirimiphosmethyl in Edea
Kidney Function Measures and Mortality: A Mendelian Randomization Study.
Get PDFRationale & Objective: Individuals with a low estimated glomerular filtration rate (eGFR) are at a high risk of death. However, the causes underpinning this association are largely uncertain. This study aimed to assess the causal relationship of low eGFR with all-cause and cause-specific mortality.
Study Design: Retrospective cohort study incorporating Mendelian randomization (MR).
Setting & Participants: Individual-level data from 436,214 White participants (54.3% female; aged 56.8 ± 8.0 years) included in the UK Biobank.
Exposures: eGFR estimated using cystatin C (eGFRcyst).
Outcomes: The outcomes of interest included all-cause mortality, cardiovascular mortality, cancer mortality, infection mortality, and other-cause mortality.
Analytical Approach
Cox proportional hazards analysis for the conventional observational analyses; linear and nonlinear MR analyses implemented using genetic allele scores as instrumental variables representing kidney function to estimate the effect of kidney function on the survival outcomes.
Results: During a median follow-up of 12.1 years, there were 30,489 deaths, 6,098 of which were attributed to cardiovascular events, 15,538 to cancer, 1,516 to infection, and 7,227 to other events. In the conventional observational analysis, eGFRcyst exhibited a nonlinear association with all the outcomes. MR analysis suggested that a genetically predicted lower eGFRcyst was linearly associated with a higher rate of cardiovascular mortality (HR, 1.43; 95% CI, 1.18-1.75) across the entire measurement range (every 10–mL/min/1.73 m2 decrement). Nonetheless, no causal associations between eGFRcyst and all-cause mortality (HR, 1.07; 95% CI, 0.98-1.17) or any types of noncardiovascular mortality were detected.
Limitations: Potential misclassification of the actual cause of death, a nonrepresentative sample, and potential error in the interpretation of the magnitude of associations generated in MR analyses.
Conclusions: These findings suggest a potential causal association between low eGFR and cardiovascular mortality in the general population, but no causal relationship with all-cause mortality or noncardiovascular mortality was observed. Further studies in other populations are warranted to confirm these findings.
Plain-Language Summary: This study investigated the existence of a causal relationship between lower kidney function and death of different causes. Using data from 436,214 people in the United Kingdom, we applied conventional statistical analyses and those incorporating genetic data to implement Mendelian randomization, an approach that estimates causal associations. The observational analysis showed a nonlinear association between kidney function and various types of mortality outcomes. However, Mendelian randomization analysis suggested a linear increase in the risk of cardiovascular mortality with lower kidney function, but no causal link between the level of kidney function and all-cause or noncardiovascular mortality was identified. Managing kidney health may help reduce cardiovascular mortality, but caution is needed in interpreting the magnitudes of these results. Further validation in other populations and in those with advanced kidney failure is needed
Exhaled nitric oxide is associated with inflammatory biomarkers and risk of acute respiratory exacerbations in children with HIV-associated chronic lung disease.
Get PDFOBJECTIVES: Chronic lung disease is a recognized complication in children with HIV. Acute respiratory exacerbations (ARE) are common among this group and cause significant morbidity. Exhaled nitric oxide (eNO) is a known marker of local airway inflammation. We investigated the association between eNO and ARE, biomarkers of systemic inflammation, and the effect of azithromycin on eNO levels.
METHODS: Individuals aged 6-19 years with HIV-associated chronic lung disease in Harare, Zimbabwe, were enrolled in a placebo-controlled randomized trial investigating the effect of 48-week azithromycin treatment on lung function and ARE. eNO levels and biomarkers were measured at inclusion and after treatment in a consecutively enrolled subset of participants. Linear regression and generalized linear models were used to study associations between eNO and ARE, biomarkers, and the effect of azithromycin on eNO levels.
RESULTS: In total, 172 participants were included in this sub-study, 86 from the placebo group and 86 from the azithromycin group. Participants experiencing at least one ARE during follow-up had significantly higher eNO levels at baseline than participants who did not (geometric mean ratio 1.13, 95% confidence interval [CI] 1.03-1.24, p = 0.015), adjusted for trial arm, age, sex and history of tuberculosis. Matrix metalloproteinase (MMP)-3, -7, and -10 were significantly associated with higher baseline eNO levels. At 48 weeks, azithromycin treatment did not affect eNO levels (geometric mean ratio 0.86, 95% CI 0.72-1.03, p = 0.103).
CONCLUSION: Higher baseline eNO levels were a risk factor for ARE. eNO was associated with proinflammatory biomarkers previously found to contribute to the development of chronic lung disease. The potential use of eNO as a marker of inflammation and risk factor for ARE in HIV-associated chronic lung disease needs further investigation
Susceptibility of Anopheles gambiae to Natural Plasmodium falciparum Infection: A Comparison between the Well-Established Anopheles gambiae s.s Line and a Newly Established Ugandan Anopheles gambiae s.s. Line.
Get PDFMuch of our understanding of malaria transmission comes from mosquito feeding assays using Anopheles mosquitoes from colonies that are well adapted to membrane feeding. This raises the question whether results from colony mosquitoes lead to overestimates of outcomes in wild Anopheles mosquitoes. We successfully established an Anopheles colony using progeny of wild Anopheles gambiae s.s. mosquitoes (Busia mosquitoes) and directly compared their susceptibility to infection with Plasmodium falciparum with the widely used An. gambiae s.s. mosquitoes (Kisumu mosquitoes) using gametocyte-infected Ugandan donor blood. The proportion of infectious feeds did not differ between Busia (71.8%, 23/32) and Kisumu (68.8%, 22/32, P = 1.00) mosquitoes. When correcting for random effects of donor blood, we observed a 23% higher proportion of infected Busia mosquitoes than infected Kisumu mosquitoes (RR, 1.23; 95% CI, 1.10-1.38, P < 0.001). This study suggests that feeding assays with Kisumu mosquitoes do not overestimate outcomes in wild An. gambiae s.s. mosquitoes, the mosquito species most relevant to malaria transmission in Uganda
A Delphi study to assess the effect of changes in language between the first and second editions of the WHO's Joint External Evaluation.
Get PDFINTRODUCTION: Countries use the WHO Joint External Evaluation (JEE) tool-part of the WHO International Health Regulations (2005) Monitoring and Evaluation Framework-for voluntary evaluation of global health security (GHS) capacities. After releasing the JEE first edition (E1) in 2016, WHO released the JEE second edition (E2) in 2018 with language changes to multiple indicators and associated capacity levels. To understand the effect of language changes on countries' ability to meet requirements in each edition, we conducted a Delphi study-a method where a panel of experts reach consensus on a topic through iterative, anonymous surveys-to solicit feedback from 40+ GHS experts with expertise in one or more of the 19 JEE technical areas. METHODS: We asked experts first to compare the language changes for each capacity level within each indicator and identify how these changes affected the indicator overall; then to assess the ability of a country to achieve the same capacity level using E2 as compared with E1 using a Likert-style score (1-5), where '1' was 'significantly easier' and '5' was 'significantly harder'; and last to provide a qualitative justification for score selections. We analysed the medians and IQR of responses to determine where experts reached consensus. RESULTS: Results demonstrate that 14 indicators and 49 capacity levels would be harder to achieve in E2. CONCLUSION: Findings underscore the importance of considering how language alterations impact how the JEE measures GHS capacity and the feasibility of using the JEE to monitor changes in capacity over time
Expression of the MSPDBL2 antigen in a discrete subset of Plasmodium falciparum schizonts is regulated by GDV1 but may not be linked to sexual commitment.
Get PDFThe Plasmodium falciparum merozoite surface protein MSPDBL2 is a polymorphic antigen targeted by acquired immune responses, and normally expressed in only a minority of mature schizonts. The potential relationship of MSPDBL2 to sexual commitment is examined, as variable mspdbl2 transcript levels and proportions of MSPDBL2-positive mature schizonts in clinical isolates have previously correlated with levels of many sexual stage parasite gene transcripts, although not with the master regulator ap2-g. It is demonstrated that conditional overexpression of the gametocyte development protein GDV1, which promotes sexual commitment, also substantially increases the proportion of MSPDBL2-positive schizonts in culture. Conversely, truncation of the gdv1 gene is shown to prevent any expression of MSPDBL2. However, across diverse P. falciparum cultured lines, the variable proportions of MSPDBL2 positivity in schizonts do not correlate significantly with variable gametocyte conversion rates, indicating it is not involved in sexual commitment. Confirming this, examining a line with endogenous hemagglutinin-tagged AP2-G showed that the individual schizonts expressing MSPDBL2 are mostly different from those expressing AP2-G. Using a selection-linked integration system, modified P. falciparum lines were engineered to express an intact or disrupted version of MSPDBL2, showing the protein is not required for sexual commitment or early gametocyte development. Asexual parasite multiplication rates were also not affected by expression of either intact or disrupted MSPDBL2 in a majority of schizonts. Occurring alongside sexual commitment, the role of the discrete MSPDBL2-positive schizont subpopulation requires further investigation in natural infections where it is under immune selection. IMPORTANCE: Malaria parasites in the blood are remarkably variable, able to switch antigenic targets so they may survive within humans who have already developed specific immune responses. This is one of the challenges in developing vaccines against malaria. MSPDBL2 is a target of naturally acquired immunity expressed in minority proportions of schizonts, the end stages of each 2-day replication cycle in red blood cells which contain merozoites prepared to invade new red blood cells. Results show that the proportion of schizonts expressing MSPDBL2 is positively controlled by the expression of the regulatory gametocyte development protein GDV1. It was previously known that expression of GDV1 leads to increased expression of AP2-G which causes parasites to switch to sexual development, so a surprising finding here is that MSPDBL2-positive parasites are mostly distinct from those that express AP2-G. This discrete antigenic subpopulation of mostly asexual parasites is regulated alongside sexually committed parasites, potentially enabling survival under stress conditions
Evaluating the clinical and cost-effectiveness of a conservative approach to oxygen therapy for invasively ventilated adults in intensive care: Protocol for the UK-ROX trial.
Get PDFBACKGROUND: In the United Kingdom, around 184,000 adults are admitted to an intensive care unit (ICU) each year with over 30% receiving mechanical ventilation. Oxygen is the commonest therapeutic intervention provided to these patients but it is unclear how much oxygen should be administered for the best clinical outcomes.
METHODS: The UK-ROX trial will evaluate the clinical and cost-effectiveness of conservative oxygen therapy (the minimum oxygen concentration required to maintain an oxygen saturation of 90% ± 2%) versus usual oxygen therapy in critically ill adults receiving supplemental oxygen when invasively mechanically ventilated in ICUs in England, Wales and Northern Ireland. The trial will recruit 16,500 patients from approximately 100 UK adult ICUs. Using a deferred consent model, enrolled participants will be randomly allocated (1:1) to conservative or usual oxygen therapy until ICU discharge or 90 days after randomisation.
OBJECTIVES: The primary clinical outcome is all cause mortality at 90 days following randomisation.
DISCUSSION: The UK-ROX trial has received ethical approval from the South Central - Oxford C Research Ethics Committee (Reference: 20/SC/0423) and the Confidentiality Advisory Group (Reference: 22/CAG/0154). The trial commenced in May 2021 and, at the time of publication, 95 sites had opened to recruitment
Physicians' inclination towards standard guidelines and regulations on incentive based prescribing practices in Karachi. A mixed methods study design.
Get PDFOBJECTIVE: To investigate private General Practitioners' (GPs) interest in continuous professional development (CPD), with a focus on ethical practices.
METHOD: A mixed method study design conducted a cross-sectional survey of registered private GPs (n=419) in Karachi was conducted in the year 2022 on their professional and ethical practices with perspectives on engagement in training in the year 2022. Qualitative interviews were conducted with 28 GPs to get a deeper understanding of their views on professional development.
RESULTS: The median age of participants was 55 years (IQR 48-63 years) and 361 (86.2%) were males. The median number of years of professional experience was 31.0 years (IQR 24-37 years). It was observed that 116 (27.6%) of GPs saw more than 50 patients per day, and 377 (90%) met with pharmaceutical sales representative (PSR) regularly. Reported awareness of guidelines on ethical practices was 325 (77.6.0%), and willingness to sign a pledge committing to a code of ethics and to be part of a professional network of ethical doctors was high, 389 (~93.0%). However, both qualitative and quantitative data indicated that GPs had limited time for training, despite the interest in filling gaps in knowledge about ethical practice.
CONCLUSIONS: Most GPs were willing to engage in CPD activities with a focus on ethics. Many GPs met regularly with PSRs, and CPD may reduce the pharmaceutical industry influence on their prescribing practices
Perceptions about respiratory syncytial virus (RSV) and attitudes toward the RSV vaccine among the general public in China: A cross-sectional survey.
Get PDFOur study aims to assess the public's perceptions of respiratory syncytial virus (RSV) and attitudes toward the RSV vaccine and to identify associated factors in China. A nationwide cross-sectional survey conducted using an online platform between August 16 and September 14, 2023. Questions related to socio-demographics, awareness, knowledge, perceptions of susceptibility and severity of RSV, and attitudes toward the RSV vaccine were included in the questionnaire. We used the chi-square test and logistic regression model to explore the associated factors. Overall, 2133 individuals were included in this study. Nearly a quarter of participants (24.3%) indicated that they had never heard of RSV. The proportion of individuals aged over 50 years reporting never having heard of RSV (36.5%) and having a low knowledge level of RSV (55.3%) was significantly higher that of other younger age groups. More than half of individuals (55.7%) exhibited low level of perceptions of susceptibility concerning RSV infection. A total of 68.4% of the participants expressed willingness to receive the RSV vaccine. Younger age was positively associated with a higher willingness to be vaccinated. The most frequent reason for declining the vaccine was "Concern about vaccine's safety or side effects." About 60% of individuals considered a price of RSV vaccine below 200 CNY (28 USD) as acceptable. The awareness and perceived susceptibility to RSV infection were limited to the Chinese public. It is necessary to take measures to address the low awareness and knowledge of RSV and acceptability of the RSV vaccine among older adults
Investigating inflation, living costs and mental health service utilization in post-COVID-19 England
Get PDFThis study investigates the association between price inflation and mental health conditions in the general population during the post-coronavirus disease 2019 (COVID-19) era in England, beginning from April 2022. Here, utilizing data from the Office for National Statistics and the National Health Service, we examined the association between price inflation, reflected by an official index ‘Consumer Prices Index including owner occupiers’ housing costs’ and the number of people in contact with mental health services across different age groups. Our findings revealed that, compared with the pre-COVID-19 period (August 2016 to February 2020), significant associations emerged between specific living costs (including costs for ‘food and non-alcoholic beverages’, ‘housing, water and fuels’ and ‘miscellaneous goods and services’) and mental health service utilization during the post-COVID-19 era. This association was particularly noted for adults aged 19–64 years and the elderly population aged 65 years and over. The results highlight the importance of addressing the potential causes of mental health issues in the context of rising living costs and can inform targeted social and economic policies, such as financial subsidies for food and non-alcoholic beverages and the need to scale up mental health services