Mapping changes in housing in sub-Saharan Africa from 2000 to 2015.

Access to adequate housing is a fundamental human right, essential to human security, nutrition and health, and a core objective of the United Nations Sustainable Development Goals1,2. Globally, the housing need is most acute in Africa, where the population will more than double by 2050. However, existing data on housing quality across Africa are limited primarily to urban areas and are mostly recorded at the national level. Here we quantify changes in housing in sub-Saharan Africa from 2000 to 2015 by combining national survey data within a geostatistical framework. We show a marked transformation of housing in urban and rural sub-Saharan Africa between 2000 and 2015, with the prevalence of improved housing (with improved water and sanitation, sufficient living area and durable construction) doubling from 11% (95% confidence interval, 10-12%) to 23% (21-25%). However, 53 (50-57) million urban Africans (47% (44-50%) of the urban population analysed) were living in unimproved housing in 2015. We provide high-resolution, standardized estimates of housing conditions across sub-Saharan Africa. Our maps provide a baseline for measuring change and a mechanism to guide interventions during the era of the Sustainable Development Goals.

GLP-1 metabolite GLP-1(9-36) is a systemic inhibitor of mouse and human pancreatic islet glucagon secretion.

AIMS/HYPOTHESIS: Diabetes mellitus is associated with impaired insulin secretion, often aggravated by oversecretion of glucagon. Therapeutic interventions should ideally correct both defects. Glucagon-like peptide 1 (GLP-1) has this capability but exactly how it exerts its glucagonostatic effect remains obscure. Following its release GLP-1 is rapidly degraded from GLP-1(7-36) to GLP-1(9-36). We hypothesised that the metabolite GLP-1(9-36) (previously believed to be biologically inactive) exerts a direct inhibitory effect on glucagon secretion and that this mechanism becomes impaired in diabetes. METHODS: We used a combination of glucagon secretion measurements in mouse and human islets (including islets from donors with type 2 diabetes), total internal reflection fluorescence microscopy imaging of secretory granule dynamics, recordings of cytoplasmic Ca2+ and measurements of protein kinase A activity, immunocytochemistry, in vivo physiology and GTP-binding protein dissociation studies to explore how GLP-1 exerts its inhibitory effect on glucagon secretion and the role of the metabolite GLP-1(9-36). RESULTS: GLP-1(7-36) inhibited glucagon secretion in isolated islets with an IC50 of 2.5 pmol/l. The effect was particularly strong at low glucose concentrations. The degradation product GLP-1(9-36) shared this capacity. GLP-1(9-36) retained its glucagonostatic effects after genetic/pharmacological inactivation of the GLP-1 receptor. GLP-1(9-36) also potently inhibited glucagon secretion evoked by ß-adrenergic stimulation, amino acids and membrane depolarisation. In islet alpha cells, GLP-1(9-36) led to inhibition of Ca2+ entry via voltage-gated Ca2+ channels sensitive to ω-agatoxin, with consequential pertussis-toxin-sensitive depletion of the docked pool of secretory granules, effects that were prevented by the glucagon receptor antagonists REMD2.59 and L-168049. The capacity of GLP-1(9-36) to inhibit glucagon secretion and reduce the number of docked granules was lost in alpha cells from human donors with type 2 diabetes. In vivo, high exogenous concentrations of GLP-1(9-36) (>100 pmol/l) resulted in a small (30%) lowering of circulating glucagon during insulin-induced hypoglycaemia. This effect was abolished by REMD2.59, which promptly increased circulating glucagon by >225% (adjusted for the change in plasma glucose) without affecting pancreatic glucagon content. CONCLUSIONS/INTERPRETATION: We conclude that the GLP-1 metabolite GLP-1(9-36) is a systemic inhibitor of glucagon secretion. We propose that the increase in circulating glucagon observed following genetic/pharmacological inactivation of glucagon signalling in mice and in people with type 2 diabetes reflects the removal of GLP-1(9-36)'s glucagonostatic action.

Identification of high-performing antibodies for the reliable detection of Tau proteoforms by Western blotting and immunohistochemistry.

Antibodies are essential research tools whose performance directly impacts research conclusions and reproducibility. Owing to its central role in Alzheimer's disease and other dementias, hundreds of distinct antibody clones have been developed against the microtubule-associated protein Tau and its multiple proteoforms. Despite this breadth of offer, limited understanding of their performance and poor antibody selectivity have hindered research progress. Here, we validate a large panel of Tau antibodies by Western blot (79 reagents) and immunohistochemistry (35 reagents). We address the reagents' ability to detect the target proteoform, selectivity, the impact of protein phosphorylation on antibody binding and performance in human brain samples. While most antibodies detected Tau at high levels, many failed to detect it at lower, endogenous levels. By WB, non-selective binding to other proteins affected over half of the antibodies tested, with several cross-reacting with the related MAP2 protein, whereas the "oligomeric Tau" T22 antibody reacted with monomeric Tau by WB, thus calling into question its specificity to Tau oligomers. Despite the presumption that "total" Tau antibodies are agnostic to post-translational modifications, we found that phosphorylation partially inhibits binding for many such antibodies, including the popular Tau-5 clone. We further combine high-sensitivity reagents, mass-spectrometry proteomics and cDNA sequencing to demonstrate that presumptive Tau "knockout" human cells continue to express residual protein arising through exon skipping, providing evidence of previously unappreciated gene plasticity. Finally, probing of human brain samples with a large panel of antibodies revealed the presence of C-term-truncated versions of all main Tau brain isoforms in both control and tauopathy donors. Ultimately, we identify a validated panel of Tau antibodies that can be employed in Western blotting and/or immunohistochemistry to reliably detect even low levels of Tau expression with high selectivity. This work represents an extensive resource that will enable the re-interpretation of published data, improve reproducibility in Tau research, and overall accelerate scientific progress.

The effect of physical barriers under a raised house on mosquito entry: an experimental study in rural Gambia.

BACKGROUND: Anopheles gambiae, the major malaria mosquito in sub-Saharan Africa, feed largely indoors at night. Raising a house off the ground with no barriers underneath reduces mosquito-house entry. This experiment tested whether walling off the space under an elevated hut affects mosquito-hut entry. METHODS: Four inhabited experimental huts, each of which could be moved up and down, were used in rural Gambia. Nightly collections of mosquitoes were made using light traps and temperature and carbon dioxide levels monitored indoors and outdoors using loggers. Each night, a reference hut was kept at ground level and three huts raised 2 m above the ground; with the space under the hut left open, walled with air-permeable walls or solid walls. Treatments were rotated every four nights using a randomized block design. The experiment was conducted for 32 nights. Primary measurements were mosquito numbers and indoor temperature in each hut. RESULTS: A total of 1,259 female Anopheles gambiae sensu lato were collected in the hut at ground level, 655 in the hut with an open ground floor, 981 in the hut with air-permeable walls underneath and 873 in the hut with solid walls underneath. Multivariate analysis, adjusting for confounders, showed that a raised hut open underneath had 53% fewer mosquitoes (95% CI 47-58%), those with air-permeable walls underneath 24% fewer (95% CI 9-36%) and huts with solid walls underneath 31% fewer (95% CI 24-37%) compared with a hut on the ground. Similar results were found for Mansonia spp. and total number of female mosquitoes, but not for Culex mosquitoes where hut entry was unaffected by height or barriers. Indoor temperature and carbon dioxide levels were similar in all huts. CONCLUSION: Raising a house 2 m from the ground reduces the entry of An. gambiae and Mansonia mosquitoes, but not Culex species. The protective effect of height is reduced if the space underneath the hut is walled off.

Acute urinary retention in men: 21-year trends in incidence, subsequent benign prostatic hyperplasia-related treatment and mortality: A Danish population-based cohort study.

OBJECTIVE: To examine trends in incidence of acute urinary retention, subsequent benign prostatic hyperplasia-related treatment and mortality in the era of medical therapy for benign prostatic hyperplasia. Additionally, to compare mortality with the general population. MATERIALS AND METHODS: We conducted a Danish nationwide registry-based study including 70,775 men aged 45 years or older with a first hospitalization for acute urinary retention during 1997-2017. We computed annual standardized incidence rates, subsequent 1-year cumulative incidence of benign prostatic hyperplasia-related surgical and medical treatment, and standardized 3-month and 1-year mortality rates. Finally, we compared standardized all-cause and cause-specific mortality ratios with the general population. RESULTS: The standardized incidence rate of acute urinary retention per 1000 person-years increased transiently from 2.34 to 3.42 during 1997-2004, but gradually declined to 2.95 in 2017. The 1-year cumulative incidence of benign prostatic hyperplasia-related surgery declined from 31.2% to 19.8% and 20.5% to 7.7% after spontaneous and precipitated acute urinary retention, respectively. During 1997-2017, the standardized 1-year mortality declined from 22.2% to 17.2%. Compared with the general population, mortality was 4-5 times higher after 3 months and 2-3 times higher after 1 year of acute urinary retention. The cause-specific standardized mortality ratios were particularly high for deaths attributable to malignancies, urogenital disease, certain infections, chronic pulmonary disease, and diabetes. CONCLUSION: During 1997-2017, we observed a transient increase in the incidence of acute urinary retention. The subsequent use of benign prostatic hyperplasia-related surgery declined considerably and mortality continued to be high, mainly because of deaths from malignancies, urogenital disease, infections, and preexisting comorbidity.

Loss of tetraspanin-7 expression reduces pancreatic ß-cell exocytosis Ca2+ sensitivity but has limited effect on systemic metabolism.

BACKGROUND: Tetraspanin-7 (Tspan7) is an islet autoantigen involved in autoimmune type 1 diabetes and known to regulate ß-cell L-type Ca2+ channel activity. However, the role of Tspan7 in pancreatic ß-cell function is not yet fully understood. METHODS: Histological analyses were conducted using immunostaining. Whole-body metabolism was tested using glucose tolerance test. Islet hormone secretion was quantified using static batch incubation or dynamic perifusion. ß-cell transmembrane currents, electrical activity and exocytosis were measured using whole-cell patch-clamping and capacitance measurements. Gene expression was studied using mRNA-sequencing and quantitative PCR. RESULTS: Tspan7 is expressed in insulin-containing granules of pancreatic ß-cells and glucagon-producing α-cells. Tspan7 knockout mice (Tspan7y/- mouse) exhibit reduced body weight and ad libitum plasma glucose but normal glucose tolerance. Tspan7y/- islets have normal insulin content and glucose- or tolbutamide-stimulated insulin secretion. Depolarisation-triggered Ca2+ current was enhanced in Tspan7y/- ß-cells, but ß-cell electrical activity and depolarisation-evoked exocytosis were unchanged suggesting that exocytosis was less sensitive to Ca2+ . TSPAN7 knockdown (KD) in human pseudo-islets led to a significant reduction in insulin secretion stimulated by 20 mM K+ . Transcriptomic analyses show that TSPAN7 KD in human pseudo-islets correlated with changes in genes involved in hormone secretion, apoptosis and ER stress. Consistent with rodent ß-cells, exocytotic Ca2+ sensitivity was reduced in a human ß-cell line (EndoC-ßH1) following Tspan7 KD. CONCLUSION: Tspan7 is involved in the regulation of Ca2+ -dependent exocytosis in ß-cells. Its function is more significant in human ß-cells than their rodent counterparts.

House screening for malaria control: views and experiences of participants in the RooPfs trial.

BACKGROUND: The housing stock of rural sub-Saharan Africa is changing rapidly. With millions of new homes required over the coming decades, there is an opportunity to protect residents by screening homes from malaria mosquitoes. This study, undertaken in the Upper River Region of The Gambia, explores local perceptions of what a good house should provide for its inhabitants and responses to living in a house that has been modified as part of a randomized control trial designed to assess whether improved housing provided additional protection against clinical malaria in children (the RooPfs trial). METHODS: This descriptive, exploratory study was undertaken over 22 months using mixed-methods (informal conversations, observations, focus group discussions, photovoice, and a questionnaire survey) in a parallel convergent design. Analysis was conducted across the data sets using a framework approach. Following coding, the textual data were charted by a priori and emerging themes. These themes were compared with the quantitative survey results. The nature and range of views about housing and the RooPfs study modifications and the relationships among them were identified and described. RESULTS: The data were derived from a total of 35 sets of observations and informal conversations in 10 villages, 12 discussions with the photovoice photographers, 26 focus group discussions (across 13 villages) and 391 completed questionnaires. The study participants described a 'good house' as one with a corrugate-metal roof, cement walls (preferably cement block, but mud block covered with cement plaster was also an acceptable and cheaper substitute) and well-fitting doors. These features align with local perceptions of a modern house that provides social status and protection from physical harms. The RooPfs modifications were largely appreciated, although poor workmanship caused concerns that houses had become insecure. However, the long-term trusting relationship with the implementing institution and the actions taken to rectify problems provided reassurance and enhanced acceptability. CONCLUSION: In developing housing to address population needs in Africa, attention should be paid to local perceptions of what is required to make a house secure for its inhabitants, as well as providing a healthy environment.

The durability, functionality and acceptability of novel screened doors and windows after 4 years of use in a Gambian village: a cross-sectional survey.

BACKGROUND: The World Health Organization recommends house screening as a tool for malaria control, yet evidence of the long-term durability, functionality and acceptability of this intervention is lacking. In this study, the sustainability and use of novel types of screened doors and windows was examined 4 years after installation in a Gambian village. METHODS: A survey of 31 houses, each with two screened doors and two screened windows, was conducted in the rainy season. There were four types of screened door and two types of screened window. Trained staff carried out the survey and interviews of room owners were conducted in the local language before translation into English. RESULTS: Structurally, the manufactured doors and windows were highly durable and in excellent condition. Most doors shut smoothly 50/61 (82%), although only 25/61 (41%) shut fully automatically with the latch slotting into the hole on the frame and holding fast. Door locks were less robust, with only (24/61) 39% present and working. Blinds proved especially flimsy, with only 4/109 (4%) of door blinds and 10/56 (18%) of window blinds present and in working order. Householders hung curtains inside most doors 50/61 (82%) and in 26/61 (43%) of the windows. Front doors were commonly found propped open 21/31 (68%) and 23/27 (85%) of those with a front door curtain, put their curtains down at night. Doors and windows were well liked, 19/31 (61%) of respondents were happy with them because they kept mosquitoes out 14/31 (45%) and provided security 12/31 (39%). The main reason given for the use of curtains was to provide privacy 26/28 (93% of those with curtains), especially while the door was open or had 'see-through' panels. CONCLUSIONS: Overall, the screened doors and windows were in full-working order and undamaged after 4 years of use. The doors and windows were well liked, especially for their ability to reduce the entry of mosquitoes and for the security they afforded. Improvements to the lock design are needed before scale-up. Most householders hung curtains behind their doors for privacy. Installation of screening in buildings should be accompanied with recommendations that at night, when doors and windows are closed, curtains be lifted or drawn to one side-to improve ventilation and keep the house cool.

The effect of light and ventilation on house entry by Anopheles arabiensis sampled using light traps in Tanzania: an experimental hut study.

BACKGROUND: In sub-Saharan Africa, house design and ventilation affects the number of malaria mosquito vectors entering houses. This study hypothesized that indoor light from a CDC-light trap, visible from outside a hut, would increase entry of Anopheles arabiensis, an important malaria vector, and examined whether ventilation modifies this effect. METHODS: Four inhabited experimental huts, each situated within a large chamber, were used to assess how light and ventilation affect the number of hut-entering mosquitoes in Tanzania. Each night, 300 female laboratory-reared An. arabiensis were released inside each chamber for 72 nights. Nightly mosquito collections were made using light traps placed indoors. Temperature and carbon dioxide concentrations were measured using data loggers. Treatments and sleepers were rotated between huts using a randomized block design. RESULTS: When indoor light was visible outside the huts, there was an 84% increase in the odds of collecting mosquitoes indoors (Odds ratio, OR = 1.84, 95% confidence intervals, 95% CI 1.74-1.95, p < 0.001) compared with when it was not. Although the odds of collecting mosquitoes in huts with closed eaves (OR = 0.54, 95% CI 0.41-0.72, p < 0.001) was less than those with open eaves, few mosquitoes entered either type of well-ventilated hut. The odds of collecting mosquitoes was 99% less in well-ventilated huts, compared with poorly-ventilated traditional huts (OR = 0.01, 95% CI 0.01-0.03, p < 0.001). In well-ventilated huts, indoor temperatures were 1.3 °C (95% CI 0.9-1.7, p < 0.001) cooler, with lower carbon dioxide (CO2) levels (mean difference = 97 ppm, 77.8-116.2, p < 0.001) than in poorly-ventilated huts. CONCLUSION: Although light visible from outside a hut increased mosquito house entry, good natural ventilation reduces indoor carbon dioxide concentrations, a major mosquito attractant, thereby reducing mosquito-hut entry.

Development and validation of a model for predicting mortality in patients with hip fracture.

OBJECTIVE: to develop a user-friendly prediction tool of 1-year mortality for patients with hip fracture, in order to guide clinicians and patients on appropriate targeted preventive measures. DESIGN: population-based cohort study from 2011 to 2017 using nationwide data from the Danish Hip Fracture Registry. SUBJECTS: a total of 28,791 patients age 65 and above undergoing surgery for a first-time hip fracture. METHODS: patient-related prognostic factors at the time of admission were assessed as potential predictors: Nursing home residency, comorbidity (Charlson Comorbidity Index [CCI] Score), frailty (Hospital Frailty Risk Score), basic mobility (Cumulated Ambulation Score), atrial fibrillation, fracture type, body mass index (BMI), age and sex. Association with 1-year mortality examined by determining the cumulative incidence, applying univariable logistic regression and assessing discrimination (area under the receiver operating characteristics curve [AUROC]). The final model (logistic regression) was utilised on a development cohort (70% of patients). Discrimination and calibration were assessed on the validation cohort (remaining 30% of patients). RESULTS: all predictors showed an association with 1-year mortality, but discrimination was moderate. The final model included nursing home residency, CCI Score, Cumulated Ambulation Score, BMI and age. It had an acceptable discrimination (AUROC 0.74) and calibration, and predicted 1-year mortality risk spanning from 5 to 91% depending on the combination of predictors in the individual patient. CONCLUSIONS: using information obtainable at the time of admission, 1-year mortality among patients with hip fracture can be predicted. We present a user-friendly chart for daily clinical practice and provide new insight regarding the interplay between prognostic factors.

Beta2 -agonist increases skeletal muscle interleukin 6 production and release in response to resistance exercise in men.

OBJECTIVE: Several tissues produce and release interleukin-6 (IL-6) in response to beta2 -adrenergic stimulation with selective agonists (beta2 -agonists). Moreover, exercise stimulates muscle IL-6 production, but whether beta2 -agonists regulate skeletal muscle production and release of IL-6 in humans in association with exercise remains to be clarified. Thus, we investigated leg IL-6 release in response to beta2 -agonist salbutamol in lean young men at rest and in recovery from resistance exercise. DESIGN: The study employed a randomized controlled crossover design, where 12 men ingested either salbutamol (16 mg) or placebo for 4 days, followed by the last dose (24 mg) administered 1½ h before exercise. Arterial and femoral venous plasma IL-6 as well as femoral artery blood flow was measured before and ½-5 h in recovery from quadriceps muscle resistance exercise. Furthermore, vastus lateralis muscle biopsies were collected ½ and 5 h after exercise for determination of mRNA levels of IL-6 and Tumor Necrosis Factor (TNF)-α. RESULTS: Average leg IL-6 release was 1.7-fold higher (p = 0.01) for salbutamol than placebo, being 138 ± 76 and 79 ± 66 pg min-1 (mean ± SD) for salbutamol and placebo, respectively, but IL-6 release was not significantly different between treatments within specific sampling points at rest and after exercise. Muscle IL-6 mRNA was 1.5- and 1.7-fold higher (p = 0.001) for salbutamol than placebo ½ and 5 h after exercise, respectively, whereas no significant treatment differences were observed for TNF-α mRNA. CONCLUSIONS: Beta2 -adrenergic stimulation with high doses of the selective beta2 -agonist salbutamol, preceeded by 4 consecutive daily doses, induces transcription of IL-6 in skeletal muscle in response to resistance exercise, and increases muscle IL-6 release in lean individuals.

The impact of hospital-diagnosed depression or use of antidepressants on treatment initiation, adherence and HbA1c/LDL target achievement in newly diagnosed type 2 diabetes.

AIMS/HYPOTHESIS: We aimed to assess whether current antidepressant therapy or a history of hospital-diagnosed depression affects diabetes treatment initiation, adherence, and HbA1c and LDL-cholesterol target achievement. METHODS: In this register-based study, we included all individuals from Central and Northern Denmark with newly diagnosed type 2 diabetes, defined as a first-ever HbA1c measurement of ≥48 mmol/mol (6.5%), between 2000 and 2016. Individuals either diagnosed with depression at a psychiatric hospital in the 2 years prior to their diabetes diagnosis or currently receiving treatment with an antidepressant were compared with individuals with type 2 diabetes, but without depression treatment or previous history of depression. Outcome measures included initiation of glucose-lowering drugs and lipid-modifying agents, adherence to these medications (medication possession ratio >80%), and HbA1c (<53 mmol/mol [7%]) and LDL-cholesterol (<2.6 mmol/l) target achievement. The assessment of association between depression or antidepressant treatment and these outcomes was conducted using regression analyses with adjustment for potential confounders. RESULTS: We included a total of 87,650 individuals with first-ever HbA1c-diagnosed type 2 diabetes, of whom 0.9% (n = 784) had hospital-diagnosed depression and 11.4% (n = 9963) currently received antidepressant treatment. Compared with those without depression treatment, treatment with an antidepressant was associated with increased likelihood of glucose-lowering drug initiation (HR 1.39 [95% CI 1.34, 1.44]) and adherence (OR 1.27 [95% CI 1.18, 1.36]), lipid-modifying agent initiation (HR 1.17 [95% CI 1.11, 1.23]) and adherence (OR 1.25 [95% CI 1.09, 1.43]), and achievement of LDL (OR 1.08 [95% CI 1.03, 1.14]) but not HbA1c target (OR 0.99 [95% CI 0.93, 1.06]). The findings were similar for individuals who had hospital-diagnosed depression. CONCLUSIONS/INTERPRETATION: In individuals with newly diagnosed type 2 diabetes, antidepressant treatment and depression were associated with improved diabetes treatment quality. Graphical abstract.

Systemic lupus erythematosus during pregnancy is not associated with school performance in offspring - A Danish population-based study.

INTRODUCTION: Systemic lupus erythematosus (SLE) in pregnancy is considered a risk factor for a range of adverse outcomes in the offspring. Studies have indicated increased risk of neurodevelopmental disorders such as autism spectrum disorders, dyslexia and ADHD. However, the overall long-term cognitive development of children born to women with SLE has scarcely been examined. In this study, we compare test scores from the Danish National School Tests of children born to women SLE with children of the background population. METHODS: We included all singleton children born in Denmark between 1995 and 2008, who were listed in the Danish National School Test Register (n=738,862). Children born to women with SLE were identified through linkage of national healthcare registers. We assessed the children's performance in the national school tests between 2nd and 8th grade, in reading and mathematics. Information on the mothers' redeemed prescriptions in pregnancy was included in stratified analyses. Differences of mean test scores were derived from linear regressions and compared according to maternal SLE status, and predefined categories of medication exposures. RESULTS: In total, 312 (0.04%) children were born to mothers with SLE. There were no differences in performance in neither reading nor mathematics tests between those born to mothers with SLE and children born to mothers without SLE. When stratifying on medication exposures among children whose mothers had SLE, there was a non-significant tendency towards poorer results among those exposed to hydroxychloroquine and/or immunosuppressants (n=31), compared to those not exposed to these medications. A similar tendency was not observed among children whose mothers received hydroxychloroquine for non-SLE reasons (n=1,235). CONCLUSION: This study indicates no major harmful effect on the child's neurocognitive development from exposure in utero to SLE, hydroxychloroquine and/or immunosuppressants, as measured by school performance.

Effect of roof colour on indoor temperature and human comfort levels, with implications for malaria control: a pilot study using experimental houses in rural Gambia.

BACKGROUND: In rural sub-Saharan Africa, thatch roofs are being replaced by metal roofs. Metal roofing, however, increases indoor temperatures above human comfort levels, and thus makes it more likely that residents will not use an insecticide-treated bed net (ITN) at night. Whether the colour of a metal roof affects indoor temperature and human comfort was assessed. METHODS: Two identical, experimental houses were constructed with metal roofs in rural Gambia. Roof types were: (1) original bare-metal, (2) painted with red oxide primer or (3) white gloss, to reflect solar radiation. Pairwise comparisons were run in six, five-night blocks during the malaria season 2018. Indoor climate was measured in each house and multivariate analysis used to compare indoor temperatures during the day and night. RESULTS: From 21.00 to 23.59 h, when most residents decide whether to use an ITN or not, the indoor temperature of a house with a bare metal roof was 31.5 °C (95% CI 31.2-31.8 °C), a red roof, 30.3 °C (95% CI 30.0-30.6) and a white roof, 29.8 °C (95% CI 29.4-30.1). During the same period, red-roofed houses were 1.23 °C cooler (95% CI 1.22-1.23) and white roofs 1.74 °C cooler (95% CI 1.70-1.79) than bare-metal roofed houses (p < 0.001). Similar results were found from 00.00 to 06.00 h. Maximum daily temperatures were 0.93 °C lower in a white-roofed house (95% CI 0.10-0.30, p < 0.001), but not a red roof (mean maximum temperature difference = 0.44 °C warmer, 95% CI 0.43-0.45, p = 0.081), compared with the bare-metal roofed houses. Human comfort analysis showed that from 21.00 to 23.59 h houses with white roofs (comfortable for 87% time) were more comfortable than bare-metal roofed houses (comfortable for 13% time; odds ratio = 43.7, 95% CI 27.5-69.5, p < 0.001). The cost of painting a metal roof white is approximately 31-68 USD. CONCLUSIONS: Houses with a white roof were consistently cooler and more comfortable than those with a bare metal roof. Painting the roofs of houses white is a cheap way of making a dwelling more comfortable for the occupants and could potentially increase bed net use in hot humid countries.

Real-world use of cardioprotective glucose-lowering drugs in patients with type 2 diabetes and cardiovascular disease: A Danish nationwide cohort study, 2012 to 2019.

AIMS: To investigate temporal trends in time to initiation of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide 1 analogues (cardioprotective glucose-lowering drugs [GLDs]) in patients with a new dual diagnosis of type 2 diabetes (T2DM) and cardiovascular disease (CVD). MATERIALS AND METHODS: In a cohort study, we identified patients with a new dual diagnosis of T2DM and CVD using linked healthcare data from nationwide registries on drug prescriptions and diagnosis codes. For each calendar year between 2012 and 2018, we examined time to initiation and cumulative user proportions (CUPs) for cardioprotective GLD use 1 and 2 years after the dual diagnosis. RESULTS: Among all individuals living in Denmark in the period 2012 to 2018, 41 733 patients with a new dual diagnosis of T2DM and CVD were identified (median [interquartile range] age 71 [64-79] years, 61% male, and 57% with CVD as the latest diagnosis). Incidence curve slopes and 1- and 2-year CUPs for cardioprotective GLDs increased during the study period (1-year CUP 4.0%, 95% confidence interval [CI] 3.6-4.5) in 2012 to 14.7, 95% CI 13.7-15.7, in 2018; 2-year CUP 5.5, 95% CI 5.0-6.1, in 2012 to 16.7, 95% CI 15.8-17.7, in 2017). T2DM patients with CVD as the second (latest) diagnosis had higher 1-year CUPs than CVD patients with T2DM as the latest diagnosis: 2012: 7.0 (95% CI 6.2-8.0) versus 1.4 (95% CI 1.0-1.8); 2018: 18.1 (95% CI 16.8-19.6) versus 10.0 (95% CI 8.8-11.3). CONCLUSIONS: In patients with T2DM and CVD, the incidence of cardioprotective GLD initiation increased between 2012 and 2018, however, within 2 years of dual diagnosis, it remained low.

A large remaining potential in lipid-lowering drug treatment in the type 2 diabetes population: A Danish nationwide cohort study.

AIM: To assess lipid-lowering drug (LLD) use patterns during 1996-2017 and examine lipid levels in relation to the use of LLDs and prevalent atherosclerotic cardiovascular disease (ASCVD). METHODS: Using a nationwide diabetes register, 404 389 individuals with type 2 diabetes living in Denmark during 1996-2017 were identified. Individuals were followed from 1 January 1996 or date of type 2 diabetes diagnosis until date of emigration, death or 1 January 2017. Redemptions of prescribed LLDs were ascertained from the nationwide Register of Medicinal Products Statistics. Data on lipid levels were sourced from the National Laboratory Database since 2010. LLD coverage was calculated at any given time based on the redeemed amount and dose. Trends in lipid levels were estimated using an additive mixed-effect model. Low-density lipoprotein cholesterol (LDL-C) goal attainment was assessed based on recommended targets by the 2011, 2016 and 2019 guidelines for management of dyslipidaemias. RESULTS: LLD use has decreased since 2012 and only 55% of those with type 2 diabetes were LLD users in 2017. A decline in levels of total cholesterol and LDL-C, and an increase in triglycerides, was observed during 2010-2017. Annual mean levels of LDL-C were lower among LLD users compared with non-users (in 2017: 1.84 vs. 2.57 mmol/L). A greater fraction of LLD users achieved the LDL-C goal of less than 1.8 mmol/L compared with non-users (in 2017: 51.7% and 19%, respectively). Among LLD users with prevalent ASCVD, 26.9% and 55% had, as recommended by current 2019 European guidelines, an LDL-C level of less than 1.4 mmol/L and less than 1.8 mmol/L, respectively, in 2017. CONCLUSIONS: LLD use and LDL-C levels are far from optimal in the Danish type 2 diabetes population and improvement in LLD use could reduce ASCVD events.

Crowding has consequences: Prevention and management of COVID-19 in informal urban settlements.

COVID-19 spreads via aerosols, droplets, fomites and faeces. The built environment that facilitates crowding increases exposure and hence transmission of COVID-19 as evidenced by outbreaks in both cool-dry and hot-humid climates, such as in the US prison system and dormitories in Singapore, respectively. This paper explores how the built environment influences crowding and COVID-19 transmission, focusing on informal urban settlements (slums). We propose policy and practice changes that could reduce COVID-19 transmission. There are several issues on how COVID-19 affects informal urban settlements. Slum populations tend to be younger than the overall population. Lower numbers of older people lessen the morbidity and mortality of the pandemic in slum areas. Second, many slum populations are highly mobile. By returning to their ancestral villages residents can avoid the risks of overcrowding and reduce the population density in a given area but may spread COVID-19 to other areas. Third, detection and registration of COVID-19 cases depends on patients presenting to health care providers. If the risk of visiting a health care centre outweighs the potential benefits patients may prefer not to seek treatment. The control and prevention of COVID-19 in informal urban settlements starts with organizing community infrastructure for diagnosis and treatment and assuring that basic needs (food, water, sanitation, health care and public transport) are met during quarantine. Next, community members at highest risk need to be identified and protected. Low-income, informal settlements need to be recognized as a reservoir and source for persistent transmission. Solutions to overcrowding must be developed for this and future pandemics. In view of the constant risk that slums present to the entire population decisive steps need to be taken to rehabilitate and improve informal settlements, while avoiding stigmatization.

Housing and child health in sub-Saharan Africa: A cross-sectional analysis.

BACKGROUND: Housing is essential to human well-being but neglected in global health. Today, housing in Africa is rapidly improving alongside economic development, creating an urgent need to understand how these changes can benefit health. We hypothesised that improved housing is associated with better health in children living in sub-Saharan Africa (SSA). We conducted a cross-sectional analysis of housing conditions relative to a range of child health outcomes in SSA. METHODS AND FINDINGS: Cross-sectional data were analysed for 824,694 children surveyed in 54 Demographic and Health Surveys, 21 Malaria Indicator Surveys, and two AIDS Indicator Surveys conducted in 33 countries between 2001 and 2017 that measured malaria infection by microscopy or rapid diagnostic test (RDT), diarrhoea, acute respiratory infections (ARIs), stunting, wasting, underweight, or anaemia in children aged 0-5 years. The mean age of children was 2.5 years, and 49.7% were female. Housing was categorised into a binary variable based on a United Nations definition comparing improved housing (with improved drinking water, improved sanitation, sufficient living area, and finished building materials) versus unimproved housing (all other houses). Associations between house type and child health outcomes were determined using conditional logistic regression within surveys, adjusting for prespecified covariables including age, sex, household wealth, insecticide-treated bed net use, and vaccination status. Individual survey odds ratios (ORs) were pooled using random-effects meta-analysis. Across surveys, improved housing was associated with 8%-18% lower odds of all outcomes except ARI (malaria infection by microscopy: adjusted OR [aOR] 0.88, 95% confidence intervals [CIs] 0.80-0.97, p = 0.01; malaria infection by RDT: aOR 0.82, 95% CI 0.77-0.88, p < 0.001; diarrhoea: aOR 0.92, 95% CI 0.88-0.97, p = 0.001; ARI: aOR 0.96, 95% CI 0.87-1.07, p = 0.49; stunting: aOR 0.83, 95% CI 0.77-0.88, p < 0.001; wasting: aOR 0.90, 95% CI 0.83-0.99, p = 0.03; underweight: aOR 0.85, 95% CI 0.80-0.90, p < 0.001; any anaemia: aOR 0.87, 95% CI 0.82-0.92, p < 0.001; severe anaemia: aOR 0.89, 95% CI 0.84-0.95, p < 0.001). In comparison, insecticide-treated net use was associated with 16%-17% lower odds of malaria infection (microscopy: aOR 0.83, 95% CI 0.78-0.88, p < 0.001; RDT: aOR 0.84, 95% CI 0.79-0.88, p < 0.001). Drinking water source and sanitation facility alone were not associated with diarrhoea. The main study limitations are the use of self-reported diarrhoea and ARI, as well as potential residual confounding by socioeconomic position, despite adjustments for household wealth and education. CONCLUSIONS: In this study, we observed that poor housing, which includes inadequate drinking water and sanitation facility, is associated with health outcomes known to increase child mortality in SSA. Improvements to housing may be protective against a number of important childhood infectious diseases as well as poor growth outcomes, with major potential to improve children's health and survival across SSA.

Acute pancreatitis: 31-Year trends in incidence and mortality - A Danish population-based cohort study.

BACKGROUND: Objectives: Increasing incidence rates and declining mortality rates have made acute pancreatitis a common cause of hospitalization. We aimed to examine 31-year trends in first-time hospitalization for acute pancreatitis, the subsequent short-term and long-term mortality, and the prognostic impacts of age, sex, and comorbidity. METHODS: In this nationwide Danish population-based cohort study of 47,711 incident cases, we computed the annual sex-specific age-standardized incidence rates of acute pancreatitis for 1988-2018. Among patients with incident hospitalization for acute pancreatitis, we computed sex-specific 30-day and 31-365-day mortality rates, stratified them, and performed proportional-hazards regression to estimate mortality rate ratios adjusted for sex, age, and comorbidity, measured by Charlson Comorbidity Index categories. RESULTS: From 1988 to 2018, the standardized incidence rate of acute pancreatitis per 100,000 person-years increased by 29% for men (28.8-37.0%) and by 148% for women (15.7-38.9%). Among patients with pancreatitis, the 30-day mortality declined from 10.0% in those diagnosed in 1988-1992 to 6.3% for those diagnosed in 2013-2017. The corresponding 31-365 day mortality increased from 5.5% to 6.0%. In comparing periods 1988-1992 and 2013-17, the adjusted 30-day mortality rate ratio was 0.36 (95% confidence interval: 0.32-0.41) and the adjusted 31-365 day mortality rate ratio was 0.64 (95% confidence interval: 0.56-0.74). Comorbidity was a strong predictor of mortality among patients with pancreatitis. CONCLUSIONS: Over the 31 years of observations, annual rates of acute pancreatitis more than doubled among women, converging with those among men. The comorbidity burden was a strong prognostic factor for short and long-term mortality. Treatments for acute pancreatitis should focus on existing comorbidities.

Old age is associated with decreased wealth in rural villages in Mtwara, Tanzania: findings from a cross-sectional survey.

OBJECTIVE: In many countries, housing is used for wealth accumulation and provides financial security in old age. We tested the hypothesis that household wealth, measured by housing quality and ownership of durable assets, would increase with age of the household head. METHODS: We conducted a survey of household heads in 68 villages surrounding Mtwara town, Tanzania and recorded relevant demographic, housing and social characteristics for each household. The primary analysis assessed the relationship between age of the household head, quality of the house structure and socio-economic score (SES) using multivariate analysis. Principal Components Analysis (PCA) was used as a data reduction tool to estimate the social-economic status of subjects based on relevant variables that are considered as proxy for SES. RESULTS: Of 13 250 household heads were surveyed of whom 49% were male. Those at least 50 years old were more likely to live in homes with an earth floor (86%) compared to younger household heads (80%; P < 0.0001), wattle and daub walls (94% vs. 90%; P < 0.0001) and corrugated iron roofs (56% vs. 52%; P < 0.0001). Wealth accumulation in the villages included in the study tends to be an inverted V-relationship with age. Housing quality and SES rose to a peak by 50 years and then rapidly decreased. Households with a large number of members were more likely to have better housing than smaller households. CONCLUSIONS: Housing plays a critical role in wealth accumulation and socio-economic status of a household in rural villages in Tanzania. Households with a head under 50 years were more likely to live in improved housing and enjoyed a higher SES, than households with older heads. Larger families may provide protection against old age poverty in rural areas. Assuring financial security in old age, specifically robust and appropriate housing would have wide-ranging benefits.

OBJECTIF: Dans de nombreux pays, le logement est utilisé pour l'accumulation de richesse et offre une sécurité financière à un âge avancé. Nous avons testé l'hypothèse selon laquelle la richesse des ménages, mesurée par la qualité du logement et la possession d'actifs durables, augmenterait avec l'âge du chef de ménage. MÉTHODES: Nous avons mené une enquête auprès des chefs de ménage dans 68 villages entourant la ville de Mtwara, en Tanzanie et enregistré les caractéristiques démographiques, de logement et sociales pertinentes pour chaque ménage. L'analyse primaire a évalué la relation entre l'âge du chef de ménage, la qualité de la structure du logement et le score socioéconomique (SES) à l'aide d'une analyse multivariée. L'analyse en composantes principales (ACP) a été utilisée comme outil de réduction des données pour estimer le statut socioéconomique des sujets sur la base de variables pertinentes qui sont considérées comme une approximation du SSE. RÉSULTATS: 13.250 chefs de ménage ont été interrogés, dont 49% de sexe masculin. Les personnes âgées d'au moins 50 ans étaient plus susceptibles de vivre dans des maisons avec un sol en terre (86%) que les chefs de ménage plus jeunes (80%; P < 0,0001), des murs en clayonnage enduit de torchis (94% contre 90%; P < 0,0001) et des toitures en tôle ondulée (56% contre 52%; P < 0,0001). L'accumulation de richesse dans les villages inclus dans l'étude a tendance à être une relation en V inversée avec l'âge. La qualité du logement et le SSE ont atteint un sommet de 50 ans, puis ont rapidement diminué. Les ménages comptant un grand nombre de membres étaient plus susceptibles d'avoir un meilleur logement que les ménages plus petits. CONCLUSIONS: Le logement joue un rôle essentiel dans l'accumulation de richesse et le statut socioéconomique d'un ménage dans les villages ruraux de Tanzanie. Les ménages dont le chef avait moins de 50 ans étaient plus susceptibles de vivre dans un logement amélioré et jouissaient d'un SSE plus élevé que les ménages dont le chef était plus âgé. Les familles plus nombreuses pourraient offrir une protection contre la pauvreté aux personnes âgées dans les zones rurales. Assurer la sécurité financière dans la vieillesse, en particulier un logement solide et approprié, aurait des avantages considérables.