A large multi-ethnic genome-wide association study identifies novel genetic loci for intraocular pressure.

Elevated intraocular pressure (IOP) is a major risk factor for glaucoma, a leading cause of blindness. IOP heritability has been estimated to up to 67%, and to date only 11 IOP loci have been reported, accounting for 1.5% of IOP variability. Here, we conduct a genome-wide association study of IOP in 69,756 untreated individuals of European, Latino, Asian, and African ancestry. Multiple longitudinal IOP measurements were collected through electronic health records and, in total, 356,987 measurements were included. We identify 47 genome-wide significant IOP-associated loci (P < 5 × 10-8); of the 40 novel loci, 14 replicate at Bonferroni significance in an external genome-wide association study analysis of 37,930 individuals of European and Asian descent. We further examine their effect on the risk of glaucoma within our discovery sample. Using longitudinal IOP measurements from electronic health records improves our power to identify new variants, which together explain 3.7% of IOP variation

Mortality and its risk factors in Malawian children admitted to hospital with clinical pneumonia, 2001–12: a retrospective observational study

Background Few studies have reported long-term data on mortality rates for children admitted to hospital with pneumonia in Africa. We examined trends in case fatality rates for all-cause clinical pneumonia and its risk factors in Malawian children between 2001 and 2012. Methods Individual patient data for children (<5 years) with clinical pneumonia who were admitted to hospitals participating in Malawi’s Child Lung Health Programme between 2001 and 2012 were recorded prospectively on a standardised medical form. We analysed trends in pneumonia mortality and children’s clinical characteristics, and we estimated the association of risk factors with case fatality for children younger than 2 months, 2–11 months of age, and 12–59 months of age using separate multivariable mixed eff ects logistic regression models. Findings Between November, 2012, and May, 2013, we retrospectively collected all available hard copies of yellow forms from 40 of 41 participating hospitals. We examined 113 154 pneumonia cases, 104 932 (92∧7%) of whom had mortality data and 6903 of whom died, and calculated an overall case fatality rate of 6·6% (95% CI 6·4–6·7). The case fatality rate signifi cantly decreased between 2001 (15·2% [13·4–17·1]) and 2012 (4·5% [4·1–4·9]; ptrend<0·0001). Univariable analyses indicated that the decrease in case fatality rate was consistent across most subgroups. In multivariable analyses, the risk factors signifi cantly associated with increased odds of mortality were female sex, young age, very severe pneumonia, clinically suspected Pneumocystis jirovecii infection, moderate or severe underweight, severe acute malnutrition, disease duration of more than 21 days, and referral from a health centre. Increasing year between 2001 and 2012 and increasing age (in months) were associated with reduced odds of mortality. Fast breathing was associated with reduced odds of mortality in children 2–11 months of age. However, case fatality rate in 2012 remained high for children with very severe pneumonia (11·8%), severe undernutrition (15·4%), severe acute malnutrition (34·8%), and symptom duration of more than 21 days (9·0%). Interpretation Pneumonia mortality and its risk factors have steadily improved in the past decade in Malawi; however, mortality remains high in specifi c subgroups. Improvements in hospital care may have reduced case fatality rates though a lack of suffi cient data on quality of care indicators and the potential of socioeconomic and other improvements outside the hospital precludes adequate assessment of why case-fatality rates fell. Results from this study emphasise the importance of eff ective national systems for data collection. Further work combining this with data on trends in the incidence of pneumonia in the community are needed to estimate trends in the overall risk of mortality from pneumonia in children in Malawi

Strengthening health human resources and improving clinical outcomes through an integrated guideline and educational outreach in resource-poor settings: a cluster-randomized trial

BACKGROUND:In low-income countries, only about a third of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) patients eligible for anti-retroviral treatment currently receive it. Providing decentralized treatment close to where patients live is crucial to a faster scale up, however, a key obstacle is limited health system capacity due to a shortage of trained health-care workers and challenges of integrating HIV/AIDS care with other primary care services (e.g. tuberculosis, malaria, respiratory conditions). This study will test an adapted primary care health care worker training and guideline intervention, Practical Approach to Lung Health and HIV/AIDS Malawi (PALM PLUS), on staff retention and satisfaction, and quality of patient care.METHODS/DESIGN:A cluster-randomized trial design is being used to compare usual care with a standardized clinical guideline and training intervention, PALM PLUS. The intervention targets middle-cadre health care workers (nurses, clinical officers, medical assistants) in 30 rural primary care health centres in a single district in Malawi. PALM PLUS is an integrated, symptom-based and user-friendly guideline consistent with Malawian national treatment protocols. Training is standardized and based on an educational outreach approach. Trainers will be front-line peer healthcare workers trained to provide outreach training and support to their fellow front-line healthcare workers during focused (1-2 hours), intermittent, interactive sessions on-site in health centers. Primary outcomes are health care worker retention and satisfaction. Secondary outcomes are clinical outcomes measured at the health centre level for HIV/AIDS, tuberculosis, prevention-of-mother-to-child-transmission of HIV and other primary care conditions. Effect sizes and 95% confidence intervals for outcomes will be presented. Assessment of outcomes will occur at 1 year post- implementation.DISCUSSION:The PALM PLUS trial aims to address a key problem: strengthening middle-cadre health care workers to support the broader scale up of HIV/AIDS services and their integration into primary care. The trial will test whether the PALM PLUS intervention improves staff satisfaction and retention, as well as the quality of patient care, when compared to usual practice.TRIAL REGISTRATION:Current controlled Trials: ISRCTN4780523

Mortality and its risk factors in Malawian children admitted to hospital with clinical pneumonia, 2001-12: a retrospective observational study.

BACKGROUND: Few studies have reported long-term data on mortality rates for children admitted to hospital with pneumonia in Africa. We examined trends in case fatality rates for all-cause clinical pneumonia and its risk factors in Malawian children between 2001 and 2012. METHODS: Individual patient data for children (<5 years) with clinical pneumonia who were admitted to hospitals participating in Malawi's Child Lung Health Programme between 2001 and 2012 were recorded prospectively on a standardised medical form. We analysed trends in pneumonia mortality and children's clinical characteristics, and we estimated the association of risk factors with case fatality for children younger than 2 months, 2-11 months of age, and 12-59 months of age using separate multivariable mixed effects logistic regression models. FINDINGS: Between November, 2012, and May, 2013, we retrospectively collected all available hard copies of yellow forms from 40 of 41 participating hospitals. We examined 113 154 pneumonia cases, 104 932 (92·7%) of whom had mortality data and 6903 of whom died, and calculated an overall case fatality rate of 6·6% (95% CI 6·4-6·7). The case fatality rate significantly decreased between 2001 (15·2% [13·4-17·1]) and 2012 (4·5% [4·1-4·9]; ptrend<0·0001). Univariable analyses indicated that the decrease in case fatality rate was consistent across most subgroups. In multivariable analyses, the risk factors significantly associated with increased odds of mortality were female sex, young age, very severe pneumonia, clinically suspected Pneumocystis jirovecii infection, moderate or severe underweight, severe acute malnutrition, disease duration of more than 21 days, and referral from a health centre. Increasing year between 2001 and 2012 and increasing age (in months) were associated with reduced odds of mortality. Fast breathing was associated with reduced odds of mortality in children 2-11 months of age. However, case fatality rate in 2012 remained high for children with very severe pneumonia (11·8%), severe undernutrition (15·4%), severe acute malnutrition (34·8%), and symptom duration of more than 21 days (9·0%). INTERPRETATION: Pneumonia mortality and its risk factors have steadily improved in the past decade in Malawi; however, mortality remains high in specific subgroups. Improvements in hospital care may have reduced case fatality rates though a lack of sufficient data on quality of care indicators and the potential of socioeconomic and other improvements outside the hospital precludes adequate assessment of why case-fatality rates fell. Results from this study emphasise the importance of effective national systems for data collection. Further work combining this with data on trends in the incidence of pneumonia in the community are needed to estimate trends in the overall risk of mortality from pneumonia in children in Malawi. FUNDING: Bill & Melinda Gates Foundation

Evaluating a streamlined clinical tool and educational outreach intervention for health care workers in Malawi: the PALM PLUS case study

<p>Abstract</p> <p>Background</p> <p>Nearly 3 million people in resource-poor countries receive antiretrovirals for the treatment of HIV/AIDS, yet millions more require treatment. Key barriers to treatment scale up are shortages of trained health care workers, and challenges integrating HIV/AIDS care with primary care.</p> <p>The research</p> <p>PALM PLUS (Practical Approach to Lung Health and HIV/AIDS in Malawi) is an intervention designed to simplify and integrate existing Malawian national guidelines into a single, simple, user-friendly guideline for mid-level health care workers. Training utilizes a peer-to-peer educational outreach approach. Research is being undertaken to evaluate this intervention to generate evidence that will guide future decision-making for consideration of roll out in Malawi. The research consists of a cluster randomized trial in 30 public health centres in Zomba District that measures the effect of the intervention on staff satisfaction and retention, quality of patient care, and costs through quantitative, qualitative and health economics methods.</p> <p>Results and outcomes</p> <p>In the first phase of qualitative inquiry respondents from intervention sites demonstrated in-depth knowledge of PALM PLUS compared to those from control sites. Participants in intervention sites felt that the PALM PLUS tool empowered them to provide better health services to patients. Interim staff retention data shows that there were, on average, 3 to 4 staff departing from the control and intervention sites per month. Additional qualitative, quantitative and economic analyses are planned.</p> <p>The partnership</p> <p>Dignitas International and the Knowledge Translation Unit at the University of Cape Town Lung Institute have led the adaptation and development of the PALM PLUS intervention, using experience gained through the implementation of the South African precursor, PALSA PLUS. The Malawian partners, REACH Trust and the Research Unit at the Ministry of Health, have led the qualitative and economic evaluations. Dignitas and Ministry of Health have facilitated interaction with implementers and policy-makers.</p> <p>Challenges and successes</p> <p>This initiative is an example of South-South knowledge translation between South Africa and Malawi, mediated by a Canadian academic-NGO hybrid. Our success in developing and rolling out PALM PLUS in Malawi suggests that it is possible to adapt and implement this intervention for use in other resource-limited settings.</p

Adaptación de inteligencia artificial por el modelo de regresión múltiple estocástica para determinar la calidad de la fibra de alpaca (Lama pacos)

The application of artificial intelligence based on the multiple linear regression model with stochastic descending gradient is described in order to determine the quality of the white Huacaya alpaca fibre. In total, 1200 fibres corresponding to six alpaca samples were analysed. The fibres were characterized by optical microscopy and with the optical fibre diameter analyser (OFDA 100) equipment. Fibre diameter, medulla diameter, percentage of medullation by volume, comfort factor, and objectionable fibres were considered as independent variables, and the “Soft” factor was considered as a response variable. This last variable resulting from the difference in the comfort factor and objectionable fibres served to give a logical order to the data matrix and obtain an accurate prediction model. The average values were 26.80 ± 6.95 for the fibre diameter, 14.10 ± 5.92 for the medulla diameter, 24.75 ± 13.20 µm for the percentage of medullation by volume and 71.56 ± 13.04% for the comfort factor. The machine learning multiple linear regression modelling fitted a small sample size with high precision, showing minimal errors, and optimized with the stochastic gradient descent algorithm predicted a Soft factor very close to the observed Soft factor. It is concluded that the multiple linear regression technique with the stochastic approach satisfies the prediction of the new factor called "soft" and that it represents the appropriate modelling for the prediction of fibre quality in the textile industry.Se describe la aplicación de inteligencia artificial basada en el modelo de regresión lineal múltiple con gradiente descendiente estocástica con la finalidad de determinar la calidad de la fibra de alpaca Huacaya de color blanco. Se analizaron 1200 fibras correspondientes a seis muestras de alpaca. Las fibras se caracterizaron mediante microscopía óptica y con el equipo analizador óptico de diámetro de fibra (OFDA 100). Se consideraron como variables independientes al diámetro de fibra, diámetro de médula, porcentaje de medulación por volumen, factor de confort, fibras objetables y como variable de respuesta al factor “Soft”. Esta última variable resultante de la diferencia del factor de confort y fibras objetables sirvió para darle un ordenamiento lógico a la matriz de datos y obtener un modelo de predicción preciso. Los valores promedio fueron 26.80±6.95 para el diámetro de fibra, 14.10±5.92 en diámetro de medula, 24.75±13.20 μm para el porcentaje de medulación por volumen y 71.56± 13.04% para el factor de confort. El modelamiento de regresión lineal múltiple de machine learning se adaptó con gran precisión a un tamaño muestral pequeño, mostrando errores mínimos, y optimizado con el algoritmo de gradiente descendiente estocástico predijo un factor Soft muy cercano al factor Soft observado. Se concluye que la técnica de regresión lineal múltiple con el enfoque estocástico satisface la predicción del nuevo factor denominado “soft” y que representa el modelamiento adecuado para la predicción de calidad de fibras en la industria textil

Evaluation of GPT-3.5 and GPT-4 for supporting real-world information needs in healthcare delivery

Despite growing interest in using large language models (LLMs) in healthcare, current explorations do not assess the real-world utility and safety of LLMs in clinical settings. Our objective was to determine whether two LLMs can serve information needs submitted by physicians as questions to an informatics consultation service in a safe and concordant manner. Sixty six questions from an informatics consult service were submitted to GPT-3.5 and GPT-4 via simple prompts. 12 physicians assessed the LLM responses' possibility of patient harm and concordance with existing reports from an informatics consultation service. Physician assessments were summarized based on majority vote. For no questions did a majority of physicians deem either LLM response as harmful. For GPT-3.5, responses to 8 questions were concordant with the informatics consult report, 20 discordant, and 9 were unable to be assessed. There were 29 responses with no majority on "Agree", "Disagree", and "Unable to assess". For GPT-4, responses to 13 questions were concordant, 15 discordant, and 3 were unable to be assessed. There were 35 responses with no majority. Responses from both LLMs were largely devoid of overt harm, but less than 20% of the responses agreed with an answer from an informatics consultation service, responses contained hallucinated references, and physicians were divided on what constitutes harm. These results suggest that while general purpose LLMs are able to provide safe and credible responses, they often do not meet the specific information need of a given question. A definitive evaluation of the usefulness of LLMs in healthcare settings will likely require additional research on prompt engineering, calibration, and custom-tailoring of general purpose models.Comment: 27 pages including supplemental informatio

Prospective cohort study of referred Malawian children and their survival by hypoxaemia and hypoglycaemia status

Objective To investigate survival in children referred from primary care in Malawi, with a focus on hypoglycaemia and hypoxaemia progression. Methods The study involved a prospective cohort of children aged 12 years or under referred from primary health-care facilities in Mchinji district, Malawi in 2019 and 2020. Peripheral blood oxygen saturation (SpO2) and blood glucose were measured at recruitment and on arrival at a subsequent health-care facility (i.e. four hospitals and 14 primary health-care facilities). Children were followed up 2 weeks after discharge or their last clinical visit. The primary study outcome was the case fatality ratio at 2 weeks. Associations between SpO2 and blood glucose levels and death were evaluated using Cox proportional hazards models and the treatment effect of hospitalization was assessed using propensity score matching. Findings Of 826 children recruited, 784 (94.9%) completed follow-up. At presentation, hypoxaemia was moderate (SpO2: 90–93%) in 13.1% (108/826) and severe (SpO2: < 90%) in 8.6% (71/826) and hypoglycaemia was moderate (blood glucose: 2.5–4.0 mmol/L) in 9.0% (74/826) and severe (blood glucose: < 2.5 mmol/L) in 2.3% (19/826). The case fatality ratio was 3.7% (29/784) overall but 26.3% (5/19) in severely hypoglycaemic children and 12.7% (9/71) in severely hypoxaemic children. Neither moderate hypoglycaemia nor moderate hypoxaemia was associated with mortality. Conclusion Presumptive pre-referral glucose treatment and better management of hypoglycaemia could reduce the high case fatality ratio observed in children with severe hypoglycaemia. The morbidity and mortality burden of severe hypoxaemia was high; ways of improving hypoxaemia identification and management are needed