Sleep and cognition in South African patients with non-functioning pituitary adenomas.

Strong lines of evidence in the neuroscience literature indicate that (a) healthy sleep facilitates cognitive processing, and (b) sleep disruption is associated with cognitive dysfunction. Despite the fact that patients with pituitary disease often display both disrupted sleep and cognitive dysfunction, few previous studies investigate whether these clinical characteristics in these patients might be related. Hence, we explored whether sleep disruption in patients with pituitary disease mediates their cognitive dysfunction. We recruited 18 patients with non-functioning pituitary adenomas (NFPA) and 19 sociodemographically matched healthy controls. They completed the Global Sleep Assessment Questionnaire (thus providing self-report data regarding sleep disruption) and were administered the Brief Test of Adult Cognition by Telephone, which assesses cognitive functioning in the domains of processing speed, working memory, episodic memory, inhibition, and reasoning. We found no significant differences in cognition between patients and controls. Furthermore, spectra of sleep disturbance did not differ significantly between patients and controls. Our data suggest that NFPA patients' cognition and sleep quality is relatively intact, and that sleep disruption does not mediate cognitive dysfunction. Larger studies should characterize sleep and cognition in patients with NFPA (and other pituitary diseases) to confirm whether disruption of the former mediates impairment in the latter.

Determinants of Willingness to Pay for Fecal Sludge Management Services and Knowledge Gaps: A Scoping Review.

Achieving universal access to safely managed sanitation services is one of the Sustainable Development Goal 6 targets (SDG6.2). The cost and availability of services to ensure the safe management of on-site sanitation, such as pit latrines and septic tanks, can be major barriers for poor households. Particularly, fecal sludge emptying services have become increasingly important due to the growing urban population. This review aims to scope the literature on stated and revealed willingness to pay (WTP) for emptying on-site sanitation systems and to identify determinants of WTP and gaps in knowledge. We performed electronic searches of six databases. After deduplication, 1846 records were identified, of which 14 were included in the review. In these studies, we identified 26 distinct scenarios that reported mean or median WTP values for emptying services and their market price (i.e., price at which the services were provided). Among the 26 scenarios, 77% (n = 20) reported that WTP was lower than the market price. We identified 20 statistically significant determinants of WTP, which can be leveraged when developing or improving manual and mechanical emptying services to attract more customers. Future research should consider services that adopt flexible pricing or mobile money payment and optimize their emptying operations to increase WTP. Validating the effectiveness of such services in solving the WTP-market price imbalance is a significant knowledge gap.

Microalgae: potential novel protein for sustainable human nutrition.

To support a global population of ~10 billion people in 2050, dietary protein demand is forecast to increase 32-78% compared to 2017, requiring significantly higher planetary resources. Microalgae are an attractive sustainable protein source compared with current plant and animal sources. Benefits include mass scalability, low CO2 emissions, and significantly reduced land and freshwater use per unit protein. Microalgae are already used as food products and numerous species exhibit high total protein contents and well-balanced essential amino acid (EAA) compositions for human dietary requirements. Microalgae proteins are also bioavailable for human digestion, and downstream processing steps are likely to further enhance protein digestibility. Species, cultivation, and process/product optimisation are actively being developed to enhance their nutritional, social, and environmental benefits.

Serial KinderMiner (SKiM) discovers and annotates biomedical knowledge using co-occurrence and transformer models.

BACKGROUND: The PubMed archive contains more than 34 million articles; consequently, it is becoming increasingly difficult for a biomedical researcher to keep up-to-date with different knowledge domains. Computationally efficient and interpretable tools are needed to help researchers find and understand associations between biomedical concepts. The goal of literature-based discovery (LBD) is to connect concepts in isolated literature domains that would normally go undiscovered. This usually takes the form of an A-B-C relationship, where A and C terms are linked through a B term intermediate. Here we describe Serial KinderMiner (SKiM), an LBD algorithm for finding statistically significant links between an A term and one or more C terms through some B term intermediate(s). The development of SKiM is motivated by the observation that there are only a few LBD tools that provide a functional web interface, and that the available tools are limited in one or more of the following ways: (1) they identify a relationship but not the type of relationship, (2) they do not allow the user to provide their own lists of B or C terms, hindering flexibility, (3) they do not allow for querying thousands of C terms (which is crucial if, for instance, the user wants to query connections between a disease and the thousands of available drugs), or (4) they are specific for a particular biomedical domain (such as cancer). We provide an open-source tool and web interface that improves on all of these issues. RESULTS: We demonstrate SKiM's ability to discover useful A-B-C linkages in three control experiments: classic LBD discoveries, drug repurposing, and finding associations related to cancer. Furthermore, we supplement SKiM with a knowledge graph built with transformer machine-learning models to aid in interpreting the relationships between terms found by SKiM. Finally, we provide a simple and intuitive open-source web interface ( https://skim.morgridge.org ) with comprehensive lists of drugs, diseases, phenotypes, and symptoms so that anyone can easily perform SKiM searches. CONCLUSIONS: SKiM is a simple algorithm that can perform LBD searches to discover relationships between arbitrary user-defined concepts. SKiM is generalized for any domain, can perform searches with many thousands of C term concepts, and moves beyond the simple identification of an existence of a relationship; many relationships are given relationship type labels from our knowledge graph.

Management of Type 2 Diabetes Mellitus and Kidney Failure in People with HIV-Infection in Africa: Current Status and a Call to Action.

There is an increasing global burden of diabetes mellitus (DM) and chronic kidney disease (CKD), coupled with a high burden of people with HIV (PWH). Due to an increased lifespan on ART, PWH are now at risk of developing non-communicable diseases, including DM. Africa has the greatest burden of HIV infection and will experience the greatest increase in prevalence of DM over the next two decades. In addition, there is a rising number of people with CKD and progression to kidney failure. Therefore, there is an urgent need for the early identification and management of all 3 diseases to prevent disease progression and complications. This is particularly important in Africa for people with CKD where there is restricted or no access to dialysis and/or transplantation. This review focuses on the epidemiology and pathophysiology of the interaction between HIV infection and DM and the impact that these diseases have on the development and progression of CKD. Finally, it also aims to review the data on the management, which stems from the growing burden of all three diseases.

Serial KinderMiner (SKiM) Discovers and Annotates Biomedical Knowledge Using Co-Occurrence and Transformer Models.

Background: The PubMed database contains more than 34 million articles; consequently, it is becoming increasingly difficult for a biomedical researcher to keep up-to-date with different knowledge domains. Computationally efficient and interpretable tools are needed to help researchers find and understand associations between biomedical concepts. The goal of literature-based discovery (LBD) is to connect concepts in isolated literature domains that would normally go undiscovered. This usually takes the form of an A-B-C relationship, where A and C terms are linked through a B term intermediate. Here we describe Serial KinderMiner (SKiM), an LBD algorithm for finding statistically significant links between an A term and one or more C terms through some B term intermediate(s). The development of SKiM is motivated by the the observation that there are only a few LBD tools that provide a functional web interface, and that the available tools are limited in one or more of the following ways: 1) they identify a relationship but not the type of relationship, 2) they do not allow the user to provide their own lists of B or C terms, hindering flexibility, 3) they do not allow for querying thousands of C terms (which is crucial if, for instance, the user wants to query connections between a disease and the thousands of available drugs), or 4) they are specific for a particular biomedical domain (such as cancer). We provide an open-source tool and web interface that improves on all of these issues. Results: We demonstrate SKiM's ability to discover useful A-B-C linkages in three control experiments: classic LBD discoveries, drug repurposing, and finding associations related to cancer. Furthermore, we supplement SKiM with a knowledge graph built with transformer machine-learning models to aid in interpreting the relationships between terms found by SKiM. Finally, we provide a simple and intuitive open-source web interface ( https://skim.morgridge.org ) with comprehensive lists of drugs, diseases, phenotypes, and symptoms so that anyone can easily perform SKiM searches. Conclusions: SKiM is a simple algorithm that can perform LBD searches to discover relationships between arbitrary user-defined concepts. SKiM is generalized for any domain, can perform searches with many thousands of C term concepts, and moves beyond the simple identification of an existence of a relationship; many relationships are given relationship type labels from our knowledge graph.

A fuzzy inference-based index for piped water supply service quality in a complex, low-income urban setting.

Sustainable Development Goal (SDG) 6 calls for universal access to safely managed drinking water services. We studied the evolution of the water supply service between January 2017 and December 2021 in the town of Uvira (South Kivu, Democratic Republic of the Congo) where large investments were made to improve the water supply infrastructure during this period, including a new 2,000-m3 tank, 56 community taps and 1,191 private taps. Across 16 geographic clusters in the town, we assessed water service accessibility, water quantity, continuity, and affordability, based on data provided by the construction team and the utility. We combined these dimensions into a single index ranging 0-100% according to rules defined using the fuzzy inference Mamdani method. Our results show that despite substantial increases in accessibility (i.e. proportion of households with a private tap or within 200 m of a community tap), overall service quality remained unsatisfactory, with a maximum index value of 38.1%, and worsened in many parts of the town due to limitations of the water production capacity after major flooding events and persistent electricity supply issues. The estimated amount of water supplied per user per day remained under 20 L during >95% of the observation period, with a decreasing trend. Pumps operated 58% of the time on average and the frequency of days without electricity supply increased over time. Our study highlights the important gap between upgrades in water supply infrastructure and improvements in the quality of service. The analysis of potential future scenarios for Uvira indicates that increasing production capacity is priority to improve overall service quality. Our results demonstrate that meeting SDG6 will be challenging in complex urban settings and will not only require sustained investments in water supply infrastructure but also in systems management and in energy supply.

A description of the elevation of pericardial cortisol: cortisone ratio in patients with tuberculous pericarditis.

Pulmonary tuberculosis is an inflammatory disease associated with an elevated cortisol/cortisone ratio at the site of infection and an array of cytokine changes. Tuberculous pericarditis is a less common but more lethal form of tuberculosis and has a similar inflammatory process in the pericardium. As the pericardium is largely inaccessible, the effect of tuberculous pericarditis on pericardial glucocorticoids is largely unknown. We wished to describe pericardial cortisolcortisone ratio in relation to plasma and saliva cortisol/cortisone ratios and the associated changes in cytokine concentrations. The median (interquartile range) of plasma, pericardial, and saliva cortisol concentration was 443 (379-532), 303 (257-384), and 20 (10-32) nmol/L, respectively, whereas the median (interquartile range) of plasma, pericardial, and saliva cortisone concentrations was 49 (35-57), 15.0 (0.0-21.7), and 37 (25-55) nmol/L, respectively. The cortisol/cortisone ratio was highest in pericardium with median (interquartile range) of 20 (13-445), followed by plasma of 9.1 (7.4-12.1) and saliva of 0.4 (0.3-0.8). The elevated cortisol/cortisone ratio was associated with elevated pericardial, interferon gamma, tumor necrosis factor-alpha, interleukin-6, interleukin-8, and induced protein 10. Administration of a single dose of 120 mg of prednisolone was associated with the suppression of pericardial cortisol and cortisone within 24 h of administration. The cortisol/cortisone ratio was highest at the site of infection, in this case, the pericardium. The elevated ratio was associated with a differential cytokine response. The observed pericardial cortisol suppression suggests that 120 mg of prednisolone was sufficient to evoke an immunomodulatory effect in the pericardium.

Effectiveness of handwashing with soap for preventing acute respiratory infections in low-income and middle-income countries: a systematic review and meta-analysis.

BACKGROUND: Acute respiratory infection (ARI) is a leading cause of morbidity and mortality globally, with 83% of ARI mortality occurring in low-income and middle-income countries (LMICs) before the COVID-19 pandemic. We aimed to estimate the effect of interventions promoting handwashing with soap on ARI in LMICs. METHODS: In our systematic review and meta-analysis, we searched MEDLINE, Embase, Web of Science, Scopus, Cochrane Library, Global Health, and Global Index Medicus for studies of handwashing with soap interventions in LMICs from inception to May 25, 2021. We included randomised and non-randomised controlled studies of interventions conducted in domestic, school, or childcare settings. Interventions promoting hand hygiene methods other than handwashing with soap were excluded, as were interventions in health-care facilities or the workplace. The primary outcome was ARI morbidity arising from any pathogen for participants of any age. Secondary outcomes were lower respiratory infection, upper respiratory infection, influenza confirmed by diagnostic test, COVID-19 confirmed by diagnostic test, and all-cause mortality. We extracted relative risks (RRs), using random-effects meta-analysis to analyse study results, and metaregression to evaluate heterogeneity. We assessed risk of bias in individual studies using an adapted Newcastle-Ottawa scale, and assessed the overall body of evidence using a Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The study is registered with PROSPERO, CRD42021231414. FINDINGS: 26 studies with 161 659 participants met inclusion criteria, providing 27 comparisons (21 randomised). Interventions promoting handwashing with soap reduced any ARI compared with no handwashing intervention (RR 0·83 [95% CI 0·76-0·90], I2 88%; 27 comparisons). Interventions also reduced lower respiratory infections (0·78 [0·64-0·94], I2 64%; 12 comparisons) and upper respiratory infections (0·74 [0·59-0·93], I2 91%; seven comparisons), but not test-confirmed influenza (0·94 [0·42-2·11], I2 90%; three comparisons), test-confirmed COVID-19 (no comparisons), or all-cause mortality (prevalence ratio 0·95 [95% CI 0·71-1·27]; one comparison). For ARI, no heterogeneity covariates were significant at p<0·1 and the GRADE rating was moderate certainty evidence. INTERPRETATION: Interventions promoting handwashing with soap can reduce ARI in LMICs, and could help to prevent the large burden of respiratory disease. FUNDING: Bill & Melinda Gates Foundation, Reckitt Global Hygiene Institute, and UK FCDO.

Validating lactate dehydrogenase (LDH) as a component of the PLASMIC predictive tool (PLASMIC-LDH).

Background: The PLASMIC score is a convenient tool for predicting ADAMTS13 activity of <10%. Lactate dehydrogenase (LDH) is widely used as a marker of haemolysis in thrombotic thrombocytopenic purpura (TTP) monitoring, and could be used as a replacement marker for lysis. We aimed to validate the PLASMIC score in a multi-centre Asia Pacific region, and to explore whether LDH could be used as a replacement marker for lysis. Methods: Records of patients with thrombotic microangiopathy (TMA) were reviewed. Patients' ADAMTS13 activity levels were obtained, along with clinical/laboratory findings relevant to the PLASMIC score. Both PLASMIC scores and PLASMIC-LDH scores, in which LDH replaced traditional lysis markers, were calculated. We generated a receiver operator characteristics (ROC) curve and compared the area under the curve values (AUC) to determine the predictive ability of each score. Results: 46 patients fulfilled the inclusion criteria, of which 34 had ADAMTS13 activity levels of <10%. When the patients were divided into intermediate-to-high risk (scores 5‒7) and low risk (scores 0‒4), the PLASMIC score showed a sensitivity of 97.1% and specificity of 58.3%, with a positive predictive value (PPV) of 86.8% and negative predictive value (NPV) of 87.5%. The PLASMIC-LDH score had a sensitivity of 97.1% and specificity of 33.3%, with a PPV of 80.5% and NPV of 80.0%. Conclusion: Our study validated the utility of the PLASMIC score, and demonstrated PLASMIC-LDH as a reasonable alternative in the absence of traditional lysis markers, to help identify high-risk patients for treatment via plasma exchange.

Outcome of COVID-19 infections in patients with adrenal insufficiency and excess.

Background: Information on clinical outcomes of coronavirus disease 19 (COVID-19) infection in patients with adrenal disorders is scarce. Methods: A collaboration between the European Society of Endocrinology (ESE) Rare Disease Committee and European Reference Network on Rare Endocrine Conditions via the European Registries for Rare Endocrine Conditions allowed the collection of data on 64 cases (57 adrenal insufficiency (AI), 7 Cushing's syndrome) that had been reported by 12 centres in 8 European countries between January 2020 and December 2021. Results: Of all 64 patients, 23 were males and 41 females (13 of those children) with a median age of 37 and 51 years. In 45/57 (95%) AI cases, COVID-19 infection was confirmed by testing. Primary insufficiency was present in 45/57 patients; 19 were affected by Addison's disease, 19 by congenital adrenal hyperplasia and 7 by primary AI (PAI) due to other causes. The most relevant comorbidities were hypertension (12%), obesity (n = 14%) and diabetes mellitus (9%). An increase by a median of 2.0 (IQR 1.4) times the daily replacement dose was reported in 42 (74%) patients. Two patients were administered i.m. injection of 100 mg hydrocortisone, and 11/64 were admitted to the hospital. Two patients had to be transferred to the intensive care unit, one with a fatal outcome. Four patients reported persistent SARS-CoV-2 infection, all others complete remission. Conclusion: This European multicentre questionnaire is the first to collect data on the outcome of COVID-19 infection in patients with adrenal gland disorders. It suggests good clinical outcomes in case of duly dose adjustments and emphasizes the importance of patient education on sick day rules.

Sustainable Production of Pigments from Cyanobacteria.

Pigments are intensely coloured compounds used in many industries to colour other materials. The demand for naturally synthesised pigments is increasing and their production can be incorporated into circular bioeconomy approaches. Natural pigments are produced by bacteria, cyanobacteria, microalgae, macroalgae, plants and animals. There is a huge unexplored biodiversity of prokaryotic cyanobacteria which are microscopic phototrophic microorganisms that have the ability to capture solar energy and CO2 and use it to synthesise a diverse range of sugars, lipids, amino acids and biochemicals including pigments. This makes them attractive for the sustainable production of a wide range of high-value products including industrial chemicals, pharmaceuticals, nutraceuticals and animal-feed supplements. The advantages of cyanobacteria production platforms include comparatively high growth rates, their ability to use freshwater, seawater or brackish water and the ability to cultivate them on non-arable land. The pigments derived from cyanobacteria and microalgae include chlorophylls, carotenoids and phycobiliproteins that have useful properties for advanced technical and commercial products. Development and optimisation of strain-specific pigment-based cultivation strategies support the development of economically feasible pigment biorefinery scenarios with enhanced pigment yields, quality and price. Thus, this chapter discusses the origin, properties, strain selection, production techniques and market opportunities of cyanobacterial pigments.

Gynaecological care of women with chronic pelvic pain: Patient perspectives and care preferences.

OBJECTIVE: To explore the experiences and care preferences of women with chronic pelvic pain, with or without a history of sexual trauma, seeking gynaecological care. DESIGN: Qualitative study. SETTING: Ambulatory endometriosis centre. POPULATION OR SAMPLE: Women aged 18-55 years with chronic pelvic pain. METHODS: Baseline demographics and sexual trauma history were obtained, and participants were assigned to focus groups according to a positive (four groups, 13 participants) or negative (two groups, nine participants) screen for a history of sexual trauma. The focus groups were led by a clinical psychologist and a gynaecological surgeon and consisted of semi-structured interviews. The interviews were audio-recorded and transcribed, and the transcripts were coded in NVivo 12. MAIN OUTCOME MEASURES: Content analysis was used to derive themes according to the participants' own words. RESULTS: Participants with chronic pelvic pain, with or without a history of sexual trauma, experienced delay in diagnosis and repetitive dismissals by clinicians. Participants' experiences of dismissals included: clinicians not listening, insufficient allocation of time to appointments and perceived redundant medical testing (i.e. sexually transmitted infection testing, urine cultures, ultrasounds). Participants identified clinician interactions as pivotal in coping with both pelvic pain and sexual abuse. Participants also provided feedback regarding trauma-informed practices and care delivery specific to patients with chronic pelvic pain. CONCLUSION: Patients with chronic pelvic pain, with or without a history of sexual trauma, report negative experiences when interacting with the healthcare system. They have clear needs and preferences regarding gynaecological care and provide feasible suggestions for improving care delivery.

Validating lactate dehydrogenase (LDH) as a component of the PLASMIC predictive tool (PLASMIC-LDH)

Background@#The PLASMIC score is a convenient tool for predicting ADAMTS13 activity of ＜10%.Lactate dehydrogenase (LDH) is widely used as a marker of haemolysis in thrombotic thrombocytopenic purpura (TTP) monitoring, and could be used as a replacement marker for lysis. We aimed to validate the PLASMIC score in a multi-centre Asia Pacific region, and to explore whether LDH could be used as a replacement marker for lysis. @*Methods@#Records of patients with thrombotic microangiopathy (TMA) were reviewed. Patients’ ADAMTS13 activity levels were obtained, along with clinical/laboratory findings relevant to the PLASMIC score. Both PLASMIC scores and PLASMIC-LDH scores, in which LDH replaced traditional lysis markers, were calculated. We generated a receiver operator characteristics (ROC) curve and compared the area under the curve values (AUC) to determine the predictive ability of each score. @*Results@#46 patients fulfilled the inclusion criteria, of which 34 had ADAMTS13 activity levels of ＜10%. When the patients were divided into intermediate-to-high risk (scores 5‒7) and low risk (scores 0‒4), the PLASMIC score showed a sensitivity of 97.1% and specificity of 58.3%, with a positive predictive value (PPV) of 86.8% and negative predictive value (NPV) of 87.5%. The PLASMIC-LDH score had a sensitivity of 97.1% and specificity of 33.3%, with a PPV of 80.5% and NPV of 80.0%. @*Conclusion@#Our study validated the utility of the PLASMIC score, and demonstrated PLASMIC-LDH as a reasonable alternative in the absence of traditional lysis markers, to help identify high-risk patients for treatment via plasma exchange.

Significant risk of COVID-19 and related-hospitalization among patients with adrenal insufficiency: A large multinational survey.

Objective: To determine self-reported incidence and potential risk factors for COVID-19 in patients with adrenal insufficiency (AI). Methods: A 27-item AI survey was developed for AI and COVID-19 status, vetted by specialists and patients, and distributed via social media, websites, and advocacy groups. Participation was voluntary and anonymous. Data were collected from September 20th, 2020 until December 31st, 2020. Results: Respondents (n=1291) with self-reported glucocorticoid treatment for AI, completed the survey, with 456 who reported having symptoms and were screened for COVID-19 during 2020; 40 tested positive (+ve), representing an 8.8% incidence. Of the COVID-19+ve, 31 were female (78%), with mean age of 39.9 years. COVID-19 among AI patients occurred most commonly in those aged 40-59 years (n=17; 42.5%); mean time since AI diagnosis was 13.5 years (range 0.2-42.0 years). Pulmonary disease, congenital adrenal hyperplasia, and higher maintenance doses of glucocorticoids were significantly associated with +ve COVID-19 (p=0.04, p=0.01, and p=0.001, respectively. In respondents the cumulative incidence of COVID-19+ve during 2020 was 3.1%; greater than the 1.03% worldwide-incidence reported by WHO, by December 31st, 2020. There was a 3-fold (95% CI 2.16-3.98) greater relative risk (RR) of COVID-19 infection and a 23.8- fold (95% CI 20.7-31.2) RR of hospitalization in patients with AI, compared with the global population. Conclusion: A markedly raised RR of COVID-19 and hospitalization in respondents reporting chronic AI was detected. We found that a diagnosis of congenital adrenal hyperplasia, age>40 years, male gender, pulmonary disease, and higher maintenance doses of glucocorticoids were associated with greatest risk.

Using water-adjusted person years to quantify the value of being water secure for an individual's quality of life.

Domestic water insecurity harms quality of life outcomes beyond health, for example in worry about water availability or anger at disrupted plans. However, these outcomes are excluded from cost-benefit analyses of water supply interventions, which typically measure and value only prevented disease and time savings. In this paper, I propose a means of quantifying the value of being water secure for an individual's quality of life, the water-adjusted person year (WAPY). One WAPY represents a year lived in complete water security. It is inspired by the quality-adjusted life year in health economics, which combines time with a health-related quality of life index. The WAPY combines time using water services with a water-related quality of life (WaterQoL) index, where 0 = completely water insecure and 1 = completely water secure. The index could be derived from an existing four-attribute Water Insecurity Experiences scale, which includes questions such as "how often did you worry that you would not have enough water for all of your needs?". Other questions concern drinking water, disrupted plans, and handwashing. Responses can be combined in a weighted index based on the relative importance of the four attributes to people. If someone has a WaterQoL index of 0.6, over a 10 year period they would have 6 WAPYs. If a water supply intervention raised WaterQoL to 0.8, they would gain 2 WAPYs over 10 years. The monetary value of WAPYs gained (e.g. in US$) could be estimated by willingness to pay and included in a cost-benefit analysis. Some interventions might result in greater WaterQoL gains than others, or longer-lasting services. Incorporating WAPYs in cost-benefit analyses, alongside prevented disease and time savings, could help identify interventions which provide better water services to more people within a given budget.

Impact of a sanitation intervention on quality of life and mental well-being in low-income urban neighbourhoods of Maputo, Mozambique: an observational study.

OBJECTIVES: Toilet users often report valuing outcomes such as privacy and safety more highly than reduced disease, but effects of urban sanitation interventions on such outcomes have never been assessed quantitatively. In this study, we evaluate the impact of a shared sanitation intervention on quality of life (QoL) and mental well-being. DESIGN: We surveyed individuals living in intervention and control clusters of a recent non-randomised controlled trial, and used generalised linear mixed regression models to make an observational comparison of outcomes between arms. SETTING: Low-income unsewered areas of Maputo City, Mozambique. PARTICIPANTS: We interviewed 424 participants, 222 from the prior trial's intervention group and 202 from the control group. INTERVENTIONS: The control group used low-quality pit latrines. The intervention group received high-quality shared toilets, with users contributing 10%-15% of capital cost. OUTCOMES: Our primary outcome was the Sanitation-related QoL (SanQoL) index, which applies respondent-derived weights to combine perceptions of sanitation-related disgust, privacy, safety, health and shame. Secondary outcomes were the WHO-5 mental well-being index and a sanitation Visual Analogue Scale. RESULTS: The intervention group experienced a 1.6 SD gain in SanQoL compared with the control group. This adjusted SanQoL gain was 0.34 (95% CI 0.29 to 0.38) on a 0-1 scale with control mean 0.49. Effect sizes were largest for safety and privacy attributes. Intervention respondents also experienced a 0.2 SD gain in mental well-being. The adjusted gain was 6.2 (95% CI 0.3 to 12.2) on a 0-100 scale with control mean 54.4. CONCLUSIONS: QoL outcomes are highly valued by toilet users and can be improved by sanitation interventions. Such outcomes should be measured in future sanitation trials, to help identify interventions which most improve people's lives. Since SanQoL weights are derived from respondent valuation, our primary result can be used in economic evaluation.

Characteristics and Challenges of Primary Adrenal Insufficiency in Africa: A Review of the Literature.

Backgrounds: Africa comprises 54 countries with varying degrees of economic development. As with other healthcare systems, rare diseases such as adrenal insufficiency are neglected and poorly documented. Objectives: We wished to explore primary adrenal insufficiency (PAI) in Africa, its prevalence, aetiology, genetics, presentation, diagnosis, and treatment and to determine the unmet needs in clinical care, education, and research. Materials and Methods: A narrative nonsystematic review of the literature was undertaken. We searched two online databases (PubMed and Google scholar) using the search terms "Addison's disease/PAI, primary adrenal insufficiency coupled with "Africa," "country names," and "genetic disorders." A total of 184 PAI records were reviewed. The exclusion of abstracts, conference proceedings, single case reports, and duplicate studies covering the same subject matter yielded 124 articles, of which 97 informed the final manuscript. Results: A wide range of aetiology of PAI was encountered, but their true prevalence is unknown. Aetiology varied with region and age of presentation as reflected by predominantly TB, HIV, and infective causes occurring in sub-Saharan Africa and more congenital forms described in North Africa associated with consanguinity. In Africa, the diagnostic criteria for PAI do not universally accord with conventional criteria, and there is a heavy reliance on clinical suspicion and biochemistry, including random cortisol of <400 nmol/L, rather than the tetracosactide test where stimulated cortisol <500-550 nmol/L confirms the diagnosis. Conclusions: A high index of suspicion is warranted to diagnose PAI in resource-limited settings, especially where tetracosactide tests are not universally available.

Effectiveness of interventions to improve drinking water, sanitation, and handwashing with soap on risk of diarrhoeal disease in children in low-income and middle-income settings: a systematic review and meta-analysis.

BACKGROUND: Estimates of the effectiveness of water, sanitation, and hygiene (WASH) interventions that provide high levels of service on childhood diarrhoea are scarce. We aimed to provide up-to-date estimates on the burden of disease attributable to WASH and on the effects of different types of WASH interventions on childhood diarrhoea in low-income and middle-income countries (LMICs). METHODS: In this systematic review and meta-analysis, we updated previous reviews following their search strategy by searching MEDLINE, Embase, Scopus, Cochrane Library, and BIOSIS Citation Index for studies of basic WASH interventions and of WASH interventions providing a high level of service, published between Jan 1, 2016, and May 25, 2021. We included randomised and non-randomised controlled trials conducted at household or community level that matched exposure categories of the so-called service ladder approach of the Sustainable Development Goal (SDG) for WASH. Two reviewers independently extracted study-level data and assessed risk of bias using a modified Newcastle-Ottawa Scale and certainty of evidence using a modified Grading of Recommendations, Assessment, Development, and Evaluation approach. We analysed extracted relative risks (RRs) and 95% CIs using random-effects meta-analyses and meta-regression models. This study is registered with PROSPERO, CRD42016043164. FINDINGS: 19 837 records were identified from the search, of which 124 studies were included, providing 83 water (62 616 children), 20 sanitation (40 799 children), and 41 hygiene (98 416 children) comparisons. Compared with untreated water from an unimproved source, risk of diarrhoea was reduced by up to 50% with water treated at point of use (POU): filtration (n=23 studies; RR 0·50 [95% CI 0·41-0·60]), solar treatment (n=13; 0·63 [0·50-0·80]), and chlorination (n=25; 0·66 [0·56-0·77]). Compared with an unimproved source, provision of an improved drinking water supply on premises with higher water quality reduced diarrhoea risk by 52% (n=2; 0·48 [0·26-0·87]). Overall, sanitation interventions reduced diarrhoea risk by 24% (0·76 [0·61-0·94]). Compared with unimproved sanitation, providing sewer connection reduced diarrhoea risk by 47% (n=5; 0·53 [0·30-0·93]). Promotion of handwashing with soap reduced diarrhoea risk by 30% (0·70 [0·64-0·76]). INTERPRETATION: WASH interventions reduced risk of diarrhoea in children in LMICs. Interventions supplying either water filtered at POU, higher water quality from an improved source on premises, or basic sanitation services with sewer connection were associated with increased reductions. Our results support higher service levels called for under SDG 6. Notably, no studies evaluated interventions that delivered access to safely managed WASH services, the level of service to which universal coverage by 2030 is committed under the SDG. FUNDING: WHO, Foreign, Commonwealth & Development Office, and National Institute of Environmental Health Sciences.