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Evaluating clinical decision rules and rapid diagnostic tests for the diagnosis of Streptococcus pyogenes pharyngitis in Gambian children: A diagnostic accuracy study.
OBJECTIVES: Accurate diagnosis of Streptococcus pyogenes (S. pyogenes) pharyngitis is imperative in high rheumatic heart disease-burden countries. We aimed to assess the diagnostic accuracy of two rapid diagnostic tests and five clinical decision rules (CDRs) in The Gambia. METHODS: Children under 16 years presenting with signs and symptoms of pharyngitis were recruited at Sukuta Health Centre, The Gambia. A rapid antigen detection test (SD Bioline; LFT) and a rapid gene-amplification test (ID NOW™ STREP A2) were assessed for diagnostic accuracy alongside five CDRs against culture and qPCR for S. pyogenes. Logistic regression was used to determine risk factors for S. pyogenes pharyngitis. RESULTS: Among 376 participants, S. pyogenes positivity was 9·8% (37/376) by culture, 32·4% (122/376) by PCR, 31·6% (119/376) by LFT, and 33·3% (122/366) by ID NOW. The ID NOW had sensitivities and specificities of 94·6% and 73·6% against culture, and 93·5% and 87·6% against PCR. The LFT had sensitivities and specificities of 83·8% and 74·0% against culture and 55·7% and 80·0% against PCR. The Smeesters CDR performed best with an area under the curve (AUC) of 0·694 against culture. S. pyogenes pharyngitis risk increased with age. Recent chest infection/cough (aOR 1·89, 1·08-3·28) and concurrent skin infection (aOR 2·11, 1·21-3·69) were associated with increased S. pyogenes pharyngitis. CONCLUSIONS: The LFT and the CDRs had poor performance in detecting S. pyogenes pharyngitis compared to PCR and culture. Molecular methods detected a higher proportion of S. pyogenes than culture. Affordable and sensitive diagnostics are urgently needed to improve S. pyogenes management in resource-limited settings
Evaluation of primary healthcare worker training to screen children under 5 years of age with a low-cost alternative to the direct ophthalmoscope, the 'Arclight', as part of the Integrated Management of Newborn and Childhood Illness (IMNCI) programme in Tanzania.
OBJECTIVE: To evaluate the integration of childhood eye screening with the Arclight direct ophthalmoscope into an already existing WHO/UNICEF Integrated Management of Newborn and Childhood Illness (IMNCI) programme in Tanzania. DESIGN: Prospective interventional study. SETTING: Primary healthcare facilities in a semirural district, central Tanzania. PARTICIPANTS: Two IMNCI (Integrated Management of Newborn and Childhood Illness) facilitators received training enhanced with four newly developed videos on using the Arclight. These facilitators then trained 378 primary healthcare workers (PHCWs) who were already familiar with the IMNCI 'Eye Module'. The training covered how to perform red reflex testing with the Arclight device, interpret the results and appropriately refer children who failed the screening. INTERVENTION: 'Arclight' direct ophthalmoscope and training of primary healthcare workers. MAIN OUTCOME MEASURES: Number of children screened and diagnosed with eye conditions. RESULTS: Over 4 months, 2 trained IMNCI facilitators trained 378 PHCWs on how to use the Arclight direct ophthalmoscope to screen children's eyes. Over a 6-month period, 36 000 children were screened in primary care settings with 136 seen at district level facilities and 105 referred to regional and tertiary facilities. The most common diagnoses of children referred were allergic conjunctivitis (37.4%), bacterial conjunctivitis (31.2%) and cataract (7.1%). There were six cases of ophthalmia neonatorum (3.9%) and two cases of retinoblastoma (1.3%). The incidence rate per 10 000 children of cataract was 3.05, ophthalmia neonatorum 1.67 and retinoblastoma 0.55. CONCLUSION: Primary healthcare workers in Tanzania can be trained to screen for eye disease in babies and children using the Arclight direct ophthalmoscope as part of an ongoing child health programme leading to the detection of treatable and serious eye diseases. Training all PHCWs would allow every child under 5 years old to be screened for eye disease, detecting serious eye conditions such as cataract and retinoblastoma earlier preventing avoidable childhood blindness and mortality
Health outcomes of patients in the Complex Chronic Diseases Program
Background: Complex chronic diseases affect almost 3% of Canadians and lead to persistent, debilitating symptoms. The BC Ministry of Health funded the Complex Chronic Diseases Program to address service gaps for affected individuals. We evaluated health outcomes of the program’s patients. Methods: Analysis of data from the Complex Chronic Diseases Program Data Registry (June 2017–September 2022) focused on patientreported outcomes and clinical measures at baseline, 6-month follow-up, and discharge, and on changes in symptoms across these time points. Results: Among the 668 participants included in the study, slight improvements in overall physical and mental health were observed between baseline and discharge. However, symptoms such as sleep dysfunction, fatigue, and pain showed no significant changes. Conclusions: While participation in the Complex Chronic Diseases Program yielded some health benefits, further research and interventions are required to address symptoms and optimize patient outcomes. The further development and use of objective outcome markers are needed for improved program evaluation
Validation of algorithms identifying diagnosed obstructive sleep apnoea and narcolepsy in coded primary care and linked hospital activity data in England
Purpose: To assist sleep epidemiology research, we created and tested the accuracy of five algorithms identifying diagnosed Obstructive Sleep Apnoea (OSA) and narcolepsy in routinely collected data from England (01/01/1998–29/03/2021). Methods: The primary algorithm identified the first coded record in Clinical Practice Research Datalink (CPRD) primary care or linked hospital admissions data as an incident diagnosis of OSA (n = 92,222) or narcolepsy (n = 1072). Alternative algorithms required codes in CPRD, both datasets, or an additional proximate possible-sleep-related outpatient visit or excessive daytime sleepiness drug prescription (narcolepsy only). Staff in 73/1574 CPRD practices completed online questionnaires for a convenience sample of 144 OSA and 101 narcolepsy cases. We estimated Positive Predictive Values (PPVs) describing the proportion of cases confirmed by a gold standard hospital specialist diagnosis, the percentage of gold standard cases from the primary algorithm retained with alternative algorithms, and time between specialist and recorded diagnosis dates. Results: Using the primary algorithm, the PPV (95 % CI) was 75.3 % (69.2–81.3) and 65.2 % (57.0–73.4) for OSA and narcolepsy, respectively: 80.6 % and 62.7 % of confirmed cases were recorded within 6 months of the specialist diagnosis. The CPRD-only algorithm increased the PPV to 85.3 (77.3–91.4, OSA) and 71.0 (58.8–81.3, narcolepsy) and retained high proportions of gold standard cases. Requiring additional outpatient or prescribing data increased PPVs, and for OSA improved diagnostic date accuracy, but omitted a high proportion of gold standard cases. Conclusion: Highly accurate OSA diagnoses can be identified in routinely collected data. Recorded cases of narcolepsy are moderately accurate, but diagnosis dates are not
Understanding the impact of covariates for trachoma prevalence prediction using geostatistical methods.
BACKGROUND: Model-based geostatistics (MBG) is increasingly used for estimating the prevalence of neglected tropical diseases, including trachoma, in low- and middle-income countries. We sought to investigate the impact of spatially referenced covariates to improve spatial predictions for trachomatous inflammation-follicular (TF) prevalence generated by MBG. To this end, we assessed the ability of spatial covariates to explain the spatial variation of TF prevalence and to reduce uncertainty in the assessment of TF elimination for pre-defined evaluation units (EUs). METHODS: We used data from Tropical Data-supported population-based trachoma prevalence surveys conducted in EUs in Ethiopia, Malawi, Niger, and Nigeria between 2016 and 2023. We then compared two models: a model that used only age, a variable required for the standardization of prevalence as used in the routine, standard prevalence estimation, and a model that included spatial covariates in addition to age. For each fitted model, we reported estimates of the parameters that quantify the strength of residual spatial correlation and 95% prediction intervals as the measure of uncertainty. RESULTS: The strength of the association between covariates and TF prevalence varied within and across countries. For some EUs, spatially referenced covariates explained most of the spatial variation and thus allowed us to generate predictive inferences for TF prevalence with a substantially reduced uncertainty, compared with models without the spatial covariates. For example, the prediction interval for TF prevalence in the areas with the lowest TF prevalence in Nigeria narrowed substantially, from a width of 2.9 to 0.7. This reduction occurred as the inclusion of spatial covariates significantly decreased the variance of the spatial Gaussian process in the geostatistical model. In other cases, spatial covariates only led to minor gains, with slightly smaller prediction intervals for the EU-level TF prevalence or even a wider prediction interval. CONCLUSIONS: Although spatially referenced covariates could help reduce prediction uncertainty in some cases, the gain could be very minor, or uncertainty could even increase. When considering the routine, standardized use of MBG methods to support national trachoma programs worldwide, we recommend that spatial covariate use be avoided
Evaluating the performance of common reference laboratory tests for acute dengue diagnosis: a systematic review and meta-analysis of RT-PCR, NS1 ELISA, and IgM ELISA.
BACKGROUND: Dengue fever is listed among the top ten global health threats by WHO. Prompt identification of dengue virus can guide clinical management and outbreak response, yet laboratory diagnosis is complex, costly, and lacks consensus on performance evaluation. This systematic review aims to provide reliable diagnostic accuracy estimates in order to inform global guidance and evaluate novel rapid diagnostic tests. METHODS: In this systematic review and meta-analysis, we searched nine literature databases on Feb 16, 2021, for reports on five common reference tests for dengue infection: NS1 ELISA, IgM ELISA, IgG ELISA, RT-PCR, and viral neutralisation test. Articles were included if they reported primary data from more than five participants to complete 2×2 tables comparing one of these tests (on human serum) with any comparator. Diagnostic accuracy was estimated using Bayesian random-effect meta-analysis, which does not require a gold-standard comparator. Risk of bias was assessed using QUADAS-2. This review is registered with PROSPERO (CRD42022341552). FINDINGS: Data were extracted from 161 articles, allowing analysis of multiple timeframes for three tests of interest. Pooled sensitivities of RT-PCR (0-4 days after symptom onset), NS1 ELISA (0-4 days), and IgM ELISA (1-7 days) were 95% (95% credible interval 77-99), 90% (68-98), and 71% (57-84), respectively. The corresponding pooled estimates of specificity were 89% (60-98), 93% (71-99), and 91% (82-95). A subanalysis of only studies at low risk of bias demonstrated similar estimates. INTERPRETATION: IgM ELISA shows poor diagnostic accuracy early in the symptom course. NS1 ELISA shows similar diagnostic accuracy to RT-PCR, which has important implications for global public health policy, given its relatively low cost and accessibility. FUNDING: None
The potential global health impact and cost-effectiveness of next-generation influenza vaccines: A modelling analysis.
BACKGROUND: Next-generation influenza vaccines (NGIVs) are in development and have the potential to achieve substantial reductions in influenza burden, with resulting widespread health and economic benefits. The prices at which their market can be sustained and which vaccination strategies may maximise health impact and cost-effectiveness, particularly in low- and middle-income countries, are unknown, yet such an understanding could provide a valuable tool for vaccine development and investment decision-making at a national and global level. To address this evidence gap, we projected the health and economic impact of NGIVs in 186 countries and territories. METHODS AND FINDINGS: We inferred current influenza transmission parameters from World Health Organization (WHO) FluNet data in regions defined by their seasonal influenza timing and positivity, and projected 30 years of influenza epidemics, accounting for demographic changes. We considered vaccines including current seasonal vaccines, vaccines with increased efficacy, duration, and breadth of protection, and universal vaccines, defined in line with WHO Preferred Product Characteristics. We estimated cost-effectiveness of different vaccination scenarios using novel estimates of key health outcomes and costs. NGIVs have the potential to substantially reduce influenza burden: compared to no vaccination, vaccinating 50% of children aged under 18 annually prevented 1.3 (95% uncertainty range (UR): 1.2-1.5) billion infections using current vaccines, 2.6 (95% UR: 2.4-2.9) billion infections using vaccines with improved efficacy or breadth, and 3.0 (95% UR: 2.7-3.3) billion infections using universal vaccines. In many countries, NGIVs were cost-effective at higher prices than typically paid for existing seasonal vaccines. However, tiered prices may be necessary for improved vaccines to be cost-effective in lower income countries. This study is limited by the availability of accurate data on influenza incidence and influenza-associated health outcomes and costs. Furthermore, the model involves simplifying assumptions around vaccination coverage and administration, and does not account for societal costs or budget impact of NGIVs. How NGIVs will compare to the vaccine types considered in this model when developed is unknown. We conducted sensitivity analyses to investigate key model parameters. CONCLUSIONS: This study highlights the considerable potential health and economic benefits of NGIVs, but also the variation in cost-effectiveness between high-income and low- and middle-income countries. This work provides a framework for long-term global cost-effectiveness evaluations, and the findings can inform a pathway to developing NGIVs and rolling them out globally
The Effectiveness of Partnerships With Commercial Actors to Improve Food Environments: A Systematic Review.
Partnerships with commercial actors have been proposed as a policy approach to create healthier food environments. We conducted a systematic review to assess their effectiveness for improving food environments and population health at state, national, or international levels. We searched in 14 databases and two websites for real-world evaluations published between 2010 and 2020. Study quality was appraised using a modified Newcastle-Ottawa Scale. Data were synthesized narratively by outcome (human, food environment, policy content, and implementation progress), considering their effect direction. Seventeen studies reporting on seven PPPs in four countries were included. Most studies (n = 14) involved food reformulation, especially salt reduction. Three focused on specific settings (the eating out-of-home sector, schools, and convenience stores). There was mixed evidence that partnerships make people buy fewer calories or more school meals (n = 3 studies) or reduce product sodium content (n = 6). Some positive effects were described in one uncontrolled study each for decreasing trans-fatty acid intake and for making healthier options more available in school cafeterias, but these studies had important limitations. Five document analyses highlighted shortcomings in the partnerships, including their limited scope, failure to add value to ongoing actions, varying participation levels, and lack of implementation, monitoring, and reporting. Alternative policy approaches should be considered. This systematic review is registered on PROSPERO as CRD42020170963
Examining the effect of nearby armed conflict on access to maternal and child health services in Burkina Faso's primary healthcare facilities.
BACKGROUND: Armed conflict is increasing in sub-Saharan Africa, impacting access to vital health services. However, scant evidence exists on the effects of the recently escalated conflict in Burkina Faso, a country severely affected by rising violence. METHODS: We conducted a longitudinal study, aligning conflict event data from the Uppsala Conflict Data Program with Burkina Faso's Health Management Information System data spanning from 2013 to 2021. Applying negative binomial regression models with health facility fixed effects, we assessed the impact of nearby armed conflict events (within 25 km of primary healthcare centres) on access to six essential maternal and child health services. We investigated effect heterogeneity by varying conflict intensity and duration, and facility characteristics. RESULTS: Any nearby armed conflict significantly reduced the incidence of all examined health services, except for non-significant caesarean section declines. Specifically, antenatal care 4 visits decreased by 3.9%, facility-based deliveries by 7.2%, caesarean sections by 9.4%, postnatal care 1 visits by 4.3% and outpatient care visits for children under 5 and aged 5-14 by 7.2% and 12.0%, respectively. High-intensity conflict events significantly amplified the negative effects across all health services. We observed less pronounced effects on children under 5 compared with those aged 5-14 not encompassed by existing fee removal policies. Prolonged conflicts did not adversely affect outpatient care visits for children. Rural facilities bore a more pronounced effect than urban facilities. CONCLUSIONS: Our findings show a significant disruption of health services due to contemporaneous conflict in Burkina Faso. However, child curative care services seem to exhibit a stabilisation trend in prolonged conflicts, and the mitigating effects of existing fee removal policies were evident. This underscores the need for nuanced policy interventions that consider varying conflict intensities, service types and financing schemes and highlights the importance of detailed, fine-scale analyses during conflict scenarios
Integrated community-based HIV and sexual and reproductive health services for youth: a cluster-randomized trial.
Human immunodeficiency virus (HIV) viral suppression rates are disproportionately worse in youth compared to other age groups, and improving this will require addressing the whole HIV cascade, including HIV testing, linkage to care and support to maintain viral suppression. We conducted a cluster-randomized trial of community-based services incorporating HIV testing, treatment and adherence support integrated with sexual and reproductive health (SRH) services for youth (16-24 years) in Zimbabwe. Our hypothesis was that integrated services in community-based settings would increase demand and access. In total, 24 clusters (geographically demarcated areas) were randomized 1:1 to intervention or control (existing services). Primary outcome was virological suppression (defined as HIV viral load <1,000 copies per ml) among youth with HIV (YWH), ascertained through a population-level outcome survey of 17,682 youth (18-24 years). Secondary outcomes, corresponding to UNAIDS 90-90-90 targets, were the proportion of YWH who knew their HIV status, the proportion of YWH who knew their HIV status who were taking antiretroviral therapy (ART) and the proportion of YWH taking ART who achieved viral suppression (HIV viral load <1,000 copies per ml). There was no difference by arm in primary outcome (mean cluster prevalence-41.3% (intervention) versus 38.3% (control); risk ratio (RR)-1.07 (95% confidence interval (CI), 0.88-1.30)) or in proportion of YWH who were diagnosed. In the intervention arm, a lower proportion of diagnosed YWH were taking treatment (RR = 0.91 (95% CI, 0.83-0.99)), but a higher proportion of those on ART had viral suppression (RR = 1.18 (95% CI, 1.02-1.37)). The intervention did not impact the proportion of youth with undiagnosed HIV, which explains the lack of effect on the primary outcome. Among those taking treatment, the intervention improved viral suppression. Delivery of integrated HIV and SRH services was feasible and facilitated uptake by youth of essential services beyond HIV, addressing an important programmatic gap. Trial registration number: NCT03719521