69832 research outputs found
Sort by
ERK activation waves coordinate mechanical cell competition leading to collective elimination via extrusion of bacterially infected cells.
Get PDFEpithelial cells respond to infection with the intracellular bacterial pathogen Listeria monocytogenes by altering their mechanics to promote collective infected cell extrusion (CICE) and limit infection spread across cell monolayers. However, the underlying biochemical pathways remain elusive. Here, using in vitro (epithelial monolayers) and in vivo (zebrafish larvae) models of infection with L. monocytogenes or Shigella flexneri, we explored the role of extracellular-signal-regulated kinase (ERK) activity waves in coordinating the mechanical battle between infected and surrounder uninfected cells that leads to CICE. We discovered that when ERK waves are suppressed, cells fail to exhibit alterations in cell shape and kinematics associated with CICE and behave more like quiescent uninfected monolayers. In particular, uninfected cells surrounding infection foci are unable to polarize, reinforce their monolayer stresses, and promote CICE. Our findings reveal that crosstalk between ERK waves and cell mechanics is key to collective elimination of large domains of infected cells
Assessing the reliability and validity of pictorial-assisted 24-h recall for measuring hand hygiene and child faeces disposal: A cross-sectional study in Malawi.
Get PDFWhilst improving hygiene and sanitation behaviours is key to cost-effective and sustainable water, sanitation and hygiene interventions, measuring behaviour change remains a challenge. This study assessed the validity and reliability of pictorial 24-h recall (P24 hR), a novel method using unprompted recall of past activities through pictures, compared to structured observation for measuring handwashing with soap (HWWS) and safe child faeces disposal in rural Malawi. Data were collected from 88 individuals across 74 households in Chiradzulu district using both methods over a two-day period, with the recall period of the P24 hR corresponding to the period of structured observation completed the previous day. Results showed poor agreement between P24 hR and observations in detection of hygiene opportunities and behaviours. P24 hR under-reported handwashing opportunities when frequency was high and over-reported them when frequency was low. The 95% limits of agreement for handwashing opportunities estimated through Bland-Altman analysis (-7.62 to 4.89) were unacceptably wide given median 5 opportunities observed per participant. P24 hR also over-reported HWWS and safe child faeces disposal, and kappa statistics indicated agreement no better than by chance. Structured observation remains the better method for measuring hygiene behaviours as compared to the P24 hR method despite its known limitations, including potential reactivity bias
Sex differences in survival from melanoma of the skin: The role of age, anatomic location and stage at diagnosis: A CONCORD-3 study in 59 countries.
Get PDFBACKGROUND: CONCORD-3 highlighted wide disparities in population-based 5-year net survival for cutaneous melanoma during 2000-2014. Studies showed a survival advantage in women, but the reasons are not completely understood. We aim to estimate trends in age-standardised 5-year net survival by sex and to examine the role of age, anatomic location and stage on the survival advantage for women worldwide. METHODS: Patients were grouped into five anatomic locations (head and neck, trunk, limbs, genital organs and not otherwise specified locations), into five age groups (15-29, 30-44, 45-59, 60-74 and 75-99 years) and into binary stage (non-metastatic vs. metastatic). We estimated net survival with the non-parametric Pohar Perme estimator, correcting for background mortality by single-year of age, sex, race/ethnicity where possible and calendar year in each country. All-ages estimates were standardised with the International Cancer Survival Standard weights. RESULTS: Men were generally older and with higher proportion of metastatic melanomas than women. Overall, the trunk was the most common location in men (range 31 %-58 %) and the lower limbs and hips in women (26 %-40 %). Age-standardised 5-year net survival was lower in men (43 %-92 %) than in women (54 %-95 %) in all countries during 2010-2014 and it was lower at older ages for both sexes. A survival advantage for women was observed for all anatomic sites and for localised disease. CONCLUSIONS: Women had a more favourable distribution of main prognostic factors, and showed highest survival for any prognostic factor. Public health efforts should focus on raising awareness of early signs of melanoma, especially among elderly in South-East Europe and to increase awareness in East-Asia, where survival was poorest
Evaluation of a peer support group programme for vulnerable host population and refugees living with diabetes and/or hypertension in Lebanon: a before-after study.
Get PDFBACKGROUND: Non-communicable diseases (NCDs) are the leading cause of death globally, and many humanitarian crises occur in countries with high NCD burdens. Peer support is a promising approach to improve NCD care in these settings. However, evidence on peer support for people living with NCDs in humanitarian settings is limited. We evaluated the implementation of peer support groups (PSGs) for people with diabetes and/or hypertension as part of an integrated NCD care model in four primary care centers in Lebanon. METHODS: Our objectives were to: (1) evaluate the reach of the PSGs; (2) evaluate the association of PSGs with patient-reported outcomes; and (3) evaluate the association of PSGs with clinical outcomes (blood pressure, HbA1c, and BMI). We used a before-after study design and included a control group for clinical outcomes. The PSG intervention began in December 2022 and was carried out in two waves. The first wave was implemented from December 2022 to July 2023, and the second wave from July 2023 to January 2024. For the control group on clinical outcomes, we used data collected from January 2023 to January 2024. We used routinely collected programmatic and administrative data. The patient reported outcomes (PROMs) were collected at baseline and at six months by trained volunteers for all PSG participants. We performed a before-after analysis of PROMs for all patients who completed the PSG sessions. T-tests were used to analyze the differences in PROMs from baseline. Change in PROMs, together with 95% confidence intervals (CIs), and p-values for the changes were reported. To assess the association between the implementation of the PSG strategy and changes in clinical outcomes, including systolic blood pressure (SBP), glycated hemoglobin A1c (HbA1c), and body mass index (BMI), analysis of covariance (ANCOVA) models were used, adjusting for age, sex, and the baseline values of the outcome being analyzed (baseline SBP and baseline HbA1c, respectively). RESULTS: A total of 445 patients were approached for enrolment in wave 1, 259 (58%) consented, of whom 81 were enrolled. In wave 2, 169 patients were approached, 92 (54%) consented of whom 91 were enrolled. We found some statistical evidence that PSG improved certain PROMs, including potentially clinical meaningful improvements in overall quality of life (wave 1), physical quality of life (wave 1), social quality of life (wave 2), environmental quality of life (wave 1), adherence (wave 2), patient centeredness (wave 1), and exercise (wave 1). However, we did not find strong statistical evidence of an improvement in clinical outcomes (SBP, HbA1c, or BMI) in participants of the PSGs compared to the control group. We found differences in the association of PSGs and outcomes between the two waves. CONCLUSION: Our study showed mixed results. In terms of reach, over 50% of those approached consented to participate. Regarding the impact on PROMs, we observed improvements in most outcomes; however we found some statistical evidence only for some. We did not find strong statistical evidence of improvement in clinical outcomes compared to the control group. Differences between the two waves may be due to differences in the populations, the way the intervention was delivered, or the individuals implementing it. Additionally, as multiple outcomes were measured, some observed differences may be due to chance. We demonstrated that it is feasible to implement PSGs in humanitarian settings and found some statistical evidence of improvement in quality of life. Further studies should assess the implementation and impact of PSGs in ways that are well accepted by local stakeholders (including humanitarian actors and people living with NCDs) and are potentially amenable to scale-up
Quantitative profiling of the vaginal microbiota improves resolution of the microbiota-immune axis.
Get PDFBACKGROUND: The composition of the vaginal microbiota is closely linked to adverse sexual and reproductive health outcomes, due in part to effects on genital immunology. Compositional approaches such as metagenomic sequencing provide a snapshot of all bacteria in a sample and have become the standard for characterizing the vaginal microbiota, but only provide microbial relative abundances. We hypothesized that the addition of absolute abundance data would provide a more complete picture of host-microbe interactions in the female genital tract. RESULTS: We analyzed cervicovaginal secretions from 196 female sex workers in Kenya and found that bacterial load was elevated among women with diverse, bacterial vaginosis (BV)-type microbiota and lower among women with Lactobacillus predominance. Bacterial load was also positively associated with proinflammatory cytokines, such as IL-1α, and negatively associated with chemokines, such as IP-10. The associations between bacterial load and immune factors differed across bacterial community states, but L. crispatus predominance was the only microbial community where higher bacterial load was not associated with higher proinflammatory cytokines. Total vaginal bacterial load was also a stronger predictor of the genital immune environment than BV by Nugent score, the current clinical standard, in the Kenya-based cohort and in a Uganda-based confirmatory cohort. CONCLUSIONS: Our results suggest that total vaginal bacterial load is at least as strong a predictor of the genital immune milieu as current BV clinical diagnostic tools, supporting exploration of the vaginal bacterial load as a predictor of adverse reproductive and sexual health outcomes. Video Abstract
Weight gain among children under five with severe malnutrition in therapeutic feeding programmes: a systematic review and meta-analysis.
Get PDFBACKGROUND: Globally, some 45 million children under five years of age are wasted (low weight-for-height). Although 2023 World Health Organisation guidelines on their care did not aim to identify optimal weight gain, they did mention 5-10 g/kg/day as a target, which is a change from prior guidelines that recommended 10-15 g/kg/day, when inpatient-only care was the norm. We aimed to inform future policy/programming on weight gain targets. METHODS: For this systematic review and meta-analysis, we searched Embase, Global Health and Medline. The final search was on 23/02/2024. Papers were included if they reported weight gain of children aged 6-59 months with severe malnutrition during inpatient (facility-based), outpatient (home-based), and hybrid treatment (initially inpatient and progressing to outpatient treatment). Summary data were extracted, and quality was assessed using a NICE Quality Appraisal Checklist. Our primary outcome was mean rate of weight gain (g/kg/day) during treatment. We conducted random-effects meta-analysis to describe pooled mean weight gain by programme type. Meta-regression investigated potential associations of weight gain with length of stay and programme outcomes. We registered the study on PROSPERO (CRD42023266472). FINDINGS: Our search yielded 3173 papers. We reviewed 321 full texts, identifying 126 eligible papers. Of these, 104 papers, including some 240,650 participants, reported weight gain as g/kg/day and were eligible for meta-analysis. Mean rate of weight gain was 8.8 g/kg/day (95% CI: 7.6, 9.9; I2 = 97.8%) across 18 inpatient programmes, 3.4 g/kg/day (95% CI: 2.0, 4.7; I2 = 99.4%) across 12 hybrid programmes, and 3.9 g/kg/day (95% CI: 3.4, 4.4; I2 = 99.7%) across 60 outpatient programmes. We found inconsistent evidence of an association between slower weight gain and higher mortality: there was weak evidence of association after adjusting for programme type (coefficient = -0.4; 95% CI: -0.7, -0.02; p = 0.04; n = 118 programmes). There was high heterogeneity between studies. Details of weight gain calculation methods varied. We found no evidence for publication bias when accounting for programme type (Egger's test p-value = 0.2). INTERPRETATION: Weight gain in outpatient programmes was markedly slower than in inpatient treatment. Clearer reporting of weight gain and a better understanding of the sequelae of faster/slower recovery is important to set future weight gain targets. Our results set an important baseline for current programmes to benchmark against. FUNDING: Medical Research Council/Global Challenges Research Fund, grant number: MR/V000802/1
Towards the Development of a Conceptual Framework of the Determinants of Pre-Eclampsia: A Hierarchical Systematic Review of Social Determinants.
Get PDFBACKGROUND: Existing reviews of pre-eclampsia determinants have focused on clinical and genetic risk factors. OBJECTIVE: To evaluate social determinants for pre-eclampsia prevention. SEARCH STRATEGY: Systematic searches were conducted from relevant electronic databases from inception of each database to 30th December 2024. SELECTION CRITERIA: Reviews and large cohort studies (≥ 1000 participants), published between 2013 and 2024, reporting quantitative associations between social determinant exposures and pre-eclampsia outcomes. DATA COLLECTION AND ANALYSIS: Titles and abstracts, then relevant full-texts were reviewed by two reviewers, independently. Strength of association was evaluated as 'definite' (odds ratios [OR] or relative risk [RR] ≥ 3.00 or < 0.33), 'probable' (OR or RR 1.50-2.99 or 0.33-0.67), 'possible' (OR or RR 1.10-1.49 or 0.68-0.89), or 'unlikely' (OR or RR 0.90-1.09). Quality of the evidence was high, moderate, low, or very-low, using GRADE. MAIN RESULTS: Twenty-seven publications found 24 associations of pre-eclampsia with socioeconomic status, social support/exclusion, healthcare access, and occupational and physical environmental factors. One association (polygamy) was definite (low-quality evidence). Probable associations included: work stress, lack of antenatal care and heat exposure in early pregnancy (high-quality evidence); prolonged occupational exposure to whole body vibrations or bending, distance to health facility, and UV-B radiation exposure (protective factor), all based on moderate-quality evidence; and neighbourhood deprivation, rotating work shifts, and Asian/Oceanian origins (protective factor), all based on low-quality evidence. There were 13 possible associations, which did not include education. CONCLUSION: Our findings support recommendations to address climate change, strengthen occupational protection, and promote early antenatal attendance. Social determinants may be indicative of upstream factors (e.g., obesity) that increase likelihood of clinical risk factors for pre-eclampsia incidence and severity
Piloting Multiple Micronutrient Supplementation Within the Routine Antenatal Care System in Ethiopia: Insights From Stakeholders.
Get PDFIn low and middle-income countries, addressing maternal and child nutrition needs is crucial. Prenatal multiple micronutrient supplementation (MMS) holds promise in reducing low birthweight and preterm births. Ethiopia is considering a transition from the provision of iron-folate supplementation to the provision of MMS in antenatal care, guided by WHO guidelines. This paper explores stakeholders' early perceptions and experiences in piloting that transition in five Ethiopian regions, informing decision making about future policy and scale-up. We used a qualitative study involving interviews and document reviews to assess the MMS pilot, analyzing themes with Nvivo 12 software. Key informant interviews revealed challenges such as supply chain issues and funding constraints, along with proposed improvement strategies such as closer coordination within existing structures. The importance of engaging with communities to create demand was emphasized, as was the need for capacity-building efforts utilizing existing staff in the health system with a clear plan for ongoing refresher training. Finally, enhancing the monitoring and evaluation framework, including a dedicated regional team for supportive supervision, was vital for accountability. In conclusion, prioritizing supply chain strengthening, community engagement through demand creation, coordination, and continuous capacity building for healthcare workers were thought to be crucial for the MMS program's success. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05708183 Registered 01 February 2023-Retrospectively registered, https://classic.clinicaltrials.gov/ct2/show/NCT05708183
Cerebral Malaria in Adults: A Retrospective Descriptive Analysis of 80 Cases in a Tertiary Hospital in The Gambia, 2020-2023.
Get PDFBACKGROUND AND AIM: Cerebral malaria in Gambian children has been studied but there is limited information on CM in adults. The study assesses the clinical features and outcome of CM in adult patients admitted at the Edward Francis Small Teaching Hospital. METHOD: This was a retrospective review of all adult patients with malaria admitted to the internal medicine department from October 18, 2020 to February 2, 2022. RESULTS: A total number of 319 adults were admitted with malaria. Eighty (25%) patients met the criteria for CM. The median age of the CM patients was 19 years. CM patients were younger (p < 0.001), more likely to be of the adolescent age group (p < 0.001), more likely to be referred from a lower-level health facility (p < 0.001), and more likely to be admitted in intensive care p < 0.001) as compared to NSCM or UM patients. The total in-hospital mortality of CM patients was 23.8%. Ten (52.6%) out of the 19 patients died within the first 24 h of admission. In multivariate analysis, CM patients with acute kidney injury at presentation was an independent predictor of mortality in this study. CONCLUSION: CM seems to affect the adolescent age group more than the older adults in The Gambia. The clinicians should be able to identify these high-risk patient group and institute prompt critical care interventions and/or treatment. The findings in this study also identify the need to expand access of critical care interventions and hemodialysis to help improve the prognosis of adult CM patients in The Gambia
Age- and sex-specific incidence rates and future projections for hip fractures in Zimbabwe.
Get PDFINTRODUCTION: Population ageing in Africa is increasing healthcare demands. Hip fractures require multidisciplinary care and are considered an indicator condition for age-related health services. We aimed to estimate current hip fracture incidence in Zimbabwe, compare rates against other regional estimates and estimate future fracture numbers. METHODS: All hip fracture cases in adults aged ≥40 years, presenting to any hospital in Harare over 2 years, were identified. From this, age- and sex-specific hip fracture incidence rates per 100 000 person-years were estimated using 2022 Zimbabwean Census data and compared with South African and Botswanan estimates. Furthermore, using the United Nations population projections, future hip fracture numbers were estimated to 2052 for Zimbabwe. RESULTS: In 2022, 1 83 312 women and 1 79 212 men aged ≥40 years were living in Harare (14.9% of the city's population). Over 2 years 243 hip fracture cases, 133 (54.7%) female, mean (SD) age 71.2 (15.9) years, were identified. Most presented to public hospitals (202 [83.1%]) and were fragility hip fractures (211 [86.8%]); high-impact trauma (eg, traffic accidents) was more common in younger men. Presentation delays of >2 weeks were common (37.4%). Incidence rates for adults aged ≥40 years in Harare (observed) and Zimbabwe (estimated) were 33.5 and 53.8/100 000 person-years, respectively. Over age 50, rates increased with age, with the highest rates seen in women aged ≥85 years (704/100 000 person-years). Age-standardised hip fracture incidence rates are broadly comparable between Zimbabwe, Botswana and Black South Africans in those aged 40-69 years; thereafter, rates in Zimbabwean women and men exceed those in Botswana and South Africa. Across Zimbabwe, the number of hip fractures occurring annually is expected to increase more than 2.5-fold from 1709 in 2022 to 4414 by 2052. CONCLUSION: In Zimbabwe, most hip fractures in adults ≥50 years are fragility fractures, consistent with age-associated osteoporosis; incidence rates exceed those previously reported regionally. Demands on already challenged healthcare systems will increase