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Several studies suggest that physical activity improves cognitive functions and reduces cognitive decline, whereas others did not find any evidence of a neuroprotective effect. Furthermore, few cohort studies have analyzed the different physical activity types and particularly household activities. Our objective was to assess the association of two physical activity types with the decline in different cognitive domains in a large prospective cohort of community-dwelling older adults from the Three-city study. Physical activity (domestic/transportation activities and leisure/sport activities) was assessed with the Voorrips questionnaire, specific for older adults. Baseline sociodemographic and health history variables as well as cognitive performance data at baseline and during the 8-year follow-up (Mini-Mental State Examination, Benton Visual Retention Test, Trail Making Tests A and B, Isaac's Set Test and Free and Cued Selective Reminding Test) were also available. Associations between physical activity scores and cognitive decline in different domains were tested using minimally- and multi-adjusted linear mixed models. The analysis included 1697 participants without dementia at baseline and with at least one follow-up visit. At baseline, participants with higher sub-scores for the two physical activity types had better cognitive performances. Interaction with time showed that decline in some cognitive scores (Trail Making Test B and Isaac's Set Test) was significantly less pronounced in participants with higher household/transportation activity sub-scores. No significant effect over time was found for leisure/sport activities. This study shows that during an 8-year follow-up, executive functions and verbal fluency were better preserved in older adults who performed household/transportation activities at moderate to high level. Participation in domestic activities and using adapted transport means could allow older adults to maintain specific cognitive abilities.

BACKGROUND:In sub-Saharan Africa there is an increasing need to leverage available health care workers to provide care for non-communicable diseases (NCDs). This study was conducted to evaluate adherence to Médecins Sans Frontières clinical protocols when the care of five stable NCDs (hypertension, diabetes mellitus type 2, epilepsy, asthma, and sickle cell) was shifted from clinical officers to nurses. METHODS:Descriptive, retrospective review of routinely collected clinic data from two integrated primary health care facilities within an urban informal settlement, Kibera, Nairobi, Kenya (May to August 2014). RESULTS:There were 3,554 consultations (2025 patients); 733 (21%) were by nurses out of which 725 met the inclusion criteria among 616 patients. Hypertension (64%, 397/616) was the most frequent NCD followed by asthma (17%, 106/616) and diabetes mellitus (15%, 95/616). Adherence to screening questions ranged from 65% to 86%, with an average of 69%. Weight and blood pressure measurements were completed in 89% and 96% of those required. Laboratory results were reviewed in 91% of indicated visits. Laboratory testing per NCD protocols was higher in those with hypertension (88%) than diabetes mellitus (67%) upon review. Only 17 (2%) consultations were referred back to clinical officers. CONCLUSION:Nurses are able to adhere to protocols for managing stable NCD patients based on clear and standardized protocols and guidelines, thus paving the way towards task shifting of NCD care to nurses to help relieve the significant healthcare gap in developing countries.

Objective: The objective of this study is twofold. First, we seek to understand the characteristics of the multimorbid population that needs hospital care by using all diagnoses information (ICD-10 codes) and two aggregated multimorbidity and frailty scores. Second, we use machine learning prediction models on these multimorbid patients characteristics to predict rehospitalization within 30 and 365 days and their length of stay., Methods: This study was conducted on 8 882 anonymized patients hospitalized at the University Hospital of Saint-Étienne. A descriptive statistical analysis was performed to better understand the characteristics of the patient population. Multimorbidity was measured using raw diagnoses information and two specific scores based on clusters of diagnoses: the Hospital Frailty Risk Score and the Calderon-Larrañaga index. Based on these variables different machine learning models (Decision Tree, Random forest and k-nearest Neighbors) were used to predict near future rehospitalization and length of stay (LoS)., Results: The use of random forest algorithms yielded better performance to predict both 365 and 30 days rehospitalization and using the diagnoses ICD-10 codes directly was significantly more efficient. However, using the Calderon-Larrañaga's clusters of diagnoses can be used as an efficient substitute for diagnoses information for predicting readmission. The predictive power of the algorithms is quite low on length of stay indicator., Conclusion: Using machine learning techniques using patients' diagnoses information and Calderon-Larrañaga's score yielded efficient results to predict hospital readmission of multimorbid patients. These methods could help improve the management of care of multimorbid patients in hospitals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Le Lay et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: We aimed to investigate whether anakinra, an interleukin-1receptor inhibitor, could improve outcome in moderate COVID-19 patients., Methods: In this controlled, open-label trial, we enrolled adults with COVID-19 requiring oxygen. We randomly assigned patients to receive intravenous anakinra plus optimized standard of care (oSOC) vs. oSOC alone. The primary outcome was treatment success at day 14 defined as patient alive and not requiring mechanical ventilation or extracorporeal membrane oxygenation., Results: Between 27th April and 6th October 2020, we enrolled 71 patients (240 patients planned to been enrolled): 37 were assigned to the anakinra group and 34 to oSOC group. The study ended prematurely by recommendation of the data and safety monitoring board due to safety concerns. On day 14, the proportion of treatment success was significantly lower in the anakinra group 70% (n = 26) vs. 91% (n = 31) in the oSOC group: risk difference-21 percentage points (95% CI, -39 to -2), odds ratio 0.23 (95% CI, 0.06 to 0.91), p = 0.027. After a 28-day follow-up, 9 patients in the anakinra group and 3 in the oSOC group had died. Overall survival at day 28 was 75% (95% CI, 62% to 91%) in the anakinra group versus 91% (95% CI, 82% to 100%) (p = 0.06) in the oSOC group. Serious adverse events occurred in 19 (51%) patients in the anakinra group and 18 (53%) in the oSOC group (p = 0·89)., Conclusion: This trial did not show efficacy of anakinra in patients with COVID-19. Furthermore, contrary to our hypothesis, we found that anakinra was inferior to oSOC in patients with moderate COVID-19 pneumonia., Competing Interests: The authors have declared that no competing interests exist.

Introduction: To sustainably provide good quality care to increasing numbers of people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in resource-limited settings, care delivery must shift from a "one-size-fits-all" approach to differentiated service delivery models. Such models should reallocate resources from PLHIV who are doing well to groups of PLHIV who may need more attention, such as those with treatment failure. The VIral load Triggered ART care Lesotho (VITAL) trial assesses a viral load (VL)-, participant's preference-informed, electronic health (eHealth)-supported, automated differentiated service delivery model (VITAL model). With VITAL, we aim to assess if the VITAL model is at least non-inferior to the standard of care in the proportion of participants engaged in care with viral suppression at 24 months follow-up and if it is cost-saving., Methods: The VITAL trial is a pragmatic, multicenter, cluster-randomized, non-blinded, non-inferiority trial with 1:1 allocation conducted at 18 nurse-led, rural health facilities in two districts of northern Lesotho, enrolling adult PLHIV taking ART. In intervention clinics, providers are trained to implement the VITAL model and are guided by a clinical decision support tool, the VITALapp. VITAL differentiates care according to VL results, clinical characteristics, sub-population and participants' and health care providers' preferences., Expected Outcomes: Evidence on the effect of differentiated service delivery for PLHIV on treatment outcomes is still limited. This pragmatic cluster-randomized trial will assess if the VITAL model is at least non-inferior to the standard of care and if it is cost saving., Trial Registration: The study has been registered with clinicaltrials.gov (Registration number NCT04527874; August 27, 2020)., Competing Interests: The authors have declared that no competing interests exist.

Several studies suggest that physical activity improves cognitive functions and reduces cognitive decline, whereas others did not find any evidence of a neuroprotective effect. Furthermore, few cohort studies have analyzed the different physical activity types and particularly household activities. Our objective was to assess the association of two physical activity types with the decline in different cognitive domains in a large prospective cohort of community-dwelling older adults from the Three-city study. Physical activity (domestic/transportation activities and leisure/sport activities) was assessed with the Voorrips questionnaire, specific for older adults. Baseline sociodemographic and health history variables as well as cognitive performance data at baseline and during the 8-year follow-up (Mini-Mental State Examination, Benton Visual Retention Test, Trail Making Tests A and B, Isaac's Set Test and Free and Cued Selective Reminding Test) were also available. Associations between physical activity scores and cognitive decline in different domains were tested using minimally- and multi-adjusted linear mixed models. The analysis included 1697 participants without dementia at baseline and with at least one follow-up visit. At baseline, participants with higher sub-scores for the two physical activity types had better cognitive performances. Interaction with time showed that decline in some cognitive scores (Trail Making Test B and Isaac's Set Test) was significantly less pronounced in participants with higher household/transportation activity sub-scores. No significant effect over time was found for leisure/sport activities. This study shows that during an 8-year follow-up, executive functions and verbal fluency were better preserved in older adults who performed household/transportation activities at moderate to high level. Participation in domestic activities and using adapted transport means could allow older adults to maintain specific cognitive abilities., Competing Interests: The authors have declared that no competing interests exist.

Main Objective: To prospectively assess the cost-consequence of a standardized diagnostic strategy as to compared to an open one for the etiological diagnosis of uveitis., Design: This was a prospective, non-inferiority, multicentre, randomized controlled trial., Methods: We included all consecutive patients with uveitis who had visited at least one of the Departments of Ophthalmology. In the standardized group, patients had a minimal work-up regardless of the type of uveitis (including evaluation of the CBC, ESR, C-reactive protein, tuberculin skin test, syphilis serology and chest X-ray). Depending on ophthalmological findings, further investigations could be performed. In the open strategy, ophthalmologists were free to order any kind of investigation. The main outcome was the mean cost per patient of each strategy., Results: 903 uveitis patients were included from January, 2010 to May, 2013. The mean cost per patient of the standardized strategy was 182.97 euros [CI 95% (173.14; 192.80)], and the mean cost per patient of the open strategy was 251.75 euros [CI 95% (229.24; 274.25)]. Therefore, the mean cost per patient of the standardized strategy was significantly lower than the mean cost per patient of the open strategy (p<0.001). There were significantly fewer visits (p<0.001), fewer radiological procedures (p<0.004) and fewer laboratory investigations (p<0.001) in the standardized group., Conclusion: A standardized strategy is a cost-saving approach for the etiological diagnosis of uveitis., Competing Interests: The authors have declared that no competing interests exist.

Introduction: For HIV-positive individuals on antiretroviral therapy (ART), the World Health Organization (WHO) recommends routine viral load (VL) monitoring. We report on the cascade of care in individuals with unsuppressed VL after introduction of routine VL monitoring in a district in Lesotho., Materials and Methods: In Butha-Buthe district 12 clinics (11 rural, 1 hospital) send samples for VL testing to the district laboratory. We included data from patients aged ≥15 years from Dec 1, 2015 to November 1, 2018. As per WHO guidelines VL <1000 copies/mL are considered suppressed, those ≥1000copies/mL unsuppressed. Patients with unsuppressed VL receive adherence counseling and follow-up VL within 8-12 weeks. Two consecutively unsuppressed VLs should trigger switch to second-line ART. For analysis of the VL monitoring cascade we defined care to be "according to guidelines" if patients with unsuppressed VL received a follow-up VL within <180 days and follow-up VL was either re-suppressed, or again unsuppressed and the individual was switched to second-line within 90 days., Results: For 9,949 individuals 24,948 VL tests were available. The majority were female (73%), median age 41 years (interquartile range 33-52), and 58% seen at rural clinics. Overall, 25% (260/1028) of individuals were managed according to guidelines: 40% (410/1028) had a follow-up VL within 180 days of their initial unsuppressed VL and 25% (260/1028) of those either re-suppressed or switched to second-line within 90 days. Female patients were more likely to have a follow-up VL done, (p = 0.015). In rural clinics rates of two consecutively unsuppressed VLs were higher than in the hospital (64% vs. 44%, p<0.001), and rural clinics were less likely to switch these patients to second-line (35% vs. 66%, p<0001)., Conclusions: Our data show that in a real-life setting availability of routine VL monitoring may not be exploited to its potential. A lack of timely follow-up after a first unsuppressed VL and reluctance to switch patients with confirmed virological failure, reduce the benefit of VL monitoring, i.e. in the rural clinics. Future studies will have to assess models of care which ensure that VL results are met with an action and make use of scalable innovative approaches., Competing Interests: The authors have declared that no competing interests exist.

Background: Hepatitis B virus (HBV) co-infection in HIV-infected individuals increases the risk of hepatic complications and mortality. Further, the risk of perinatal HBV transmission increases among HBV/HIV co-infected pregnant women. Although HBV is endemic in the Democratic Republic of Congo, there is little data on HBV/HIV co-infection. We aimed to assess the burden and risk factors of HBV surface antigen (HBsAg) positivity among HIV-infected pregnant and post-partum women., Methods: This cross-sectional study was conducted as part of an ongoing trial to assess the effect of data-driven continuous quality improvement interventions (CQI) for optimal prevention of mother-to-child transmission (PMTCT) of HIV (CQI-PMTCT study, NCT03048669). In each of the 35 health zones of Kinshasa province, all HIV-infected pregnant or breastfeeding women (≤1 year post-delivery) presenting for care in one of the three busiest maternal and child health clinics of the health zone were tested for HBsAg using Alere Determine, Japan. We used logistic regression with general estimating equation accounting for within-clinic clustering to assess risk factors of HBsAg positivity., Results: Between November 2016 and June 2018, a total of 1377 women, all on antiretroviral therapy, were tested for HBsAg. Overall, 4.7% [95% binomial confidence interval (CI): 3.7%-5.7%] tested positive for HBsAg. HBsAg prevalence was 3.3% (95% CI: 2.1%-4.8%) for women tested during pregnancy, 4.5% (2.5%-7.4%) for those tested at delivery, and 8.5% (5.6%-12.2%) for those tested post-partum (Ptrend = 0.001). In multivariate models including socio-economic status (SES), type of care facility, duration of antiretroviral therapy, HIV viral load, and self-reported intimate partner violence (IPV), lowest tertile of SES, ≤ 6 months of ART, and IPV were all consistently and positively associated with higher prevalence of HBsAg across pregnancy, delivery, and postpartum period while been tested in a health centre or having a viral load ≥ 1000 copies/mL were consistently associated with lower prevalence. However, only the association with IPV (OR = 2.74, 95% CI: 1.10-6.84) and viral load between 40-1000 copies/ml (OR = 4.28, 95% CI: 1.22-15.01) achieved statistical significance among pregnant women., Conclusion: This study revealed an overall high prevalence of HBsAg among HIV-infected pregnant and post-partum women in Kinshasa with the latter showing the highest HBsAg prevalence. Among pregnant women, intimate partner violence was independently and statistically associated with HBsAg positivity, requiring further investigation., Competing Interests: The authors have declared that no competing interests exist.

Objective: To investigate association between genetic polymorphisms of GST, CYP and renal outcome or occurrence of adverse drug reactions (ADRs) in lupus nephritis (LN) treated with cyclophosphamide (CYC). CYC, as a pro-drug, requires bioactivation through multiple hepatic cytochrome P450s and glutathione S transferases (GST)., Methods: We carried out a multicentric retrospective study including 70 patients with proliferative LN treated with CYC. Patients were genotyped for polymorphisms of the CYP2B6, CYP2C19, GSTP1, GSTM1 and GSTT1 genes. Complete remission (CR) was defined as proteinuria ≤0.33g/day and serum creatinine ≤124 µmol/l. Partial remission (PR) was defined as proteinuria ≤1.5g/day with a 50% decrease of the baseline proteinuria value and serum creatinine no greater than 25% above baseline., Results: Most patients were women (84%) and 77% were Caucasian. The mean age at LN diagnosis was 41 ± 10 years. The frequency of patients carrying the GST null genotype GSTT1-, GSTM1-, and the Ile→105Val GSTP1 genotype were respectively 38%, 60% and 44%. In multivariate analysis, the Ile→105Val GSTP1 genotype was an independent factor of poor renal outcome (achievement of CR or PR) (OR = 5.01 95% CI [1.02-24.51]) and the sole factor that influenced occurrence of ADRs was the GSTM1 null genotype (OR = 3.34 95% CI [1.064-10.58]). No association between polymorphisms of cytochrome P450s gene and efficacy or ADRs was observed., Conclusion: This study suggests that GST polymorphisms highly impact renal outcome and occurrence of ADRs related to CYC in LN patients.

Background: In sub-Saharan Africa there is an increasing need to leverage available health care workers to provide care for non-communicable diseases (NCDs). This study was conducted to evaluate adherence to Médecins Sans Frontières clinical protocols when the care of five stable NCDs (hypertension, diabetes mellitus type 2, epilepsy, asthma, and sickle cell) was shifted from clinical officers to nurses., Methods: Descriptive, retrospective review of routinely collected clinic data from two integrated primary health care facilities within an urban informal settlement, Kibera, Nairobi, Kenya (May to August 2014)., Results: There were 3,554 consultations (2025 patients); 733 (21%) were by nurses out of which 725 met the inclusion criteria among 616 patients. Hypertension (64%, 397/616) was the most frequent NCD followed by asthma (17%, 106/616) and diabetes mellitus (15%, 95/616). Adherence to screening questions ranged from 65% to 86%, with an average of 69%. Weight and blood pressure measurements were completed in 89% and 96% of those required. Laboratory results were reviewed in 91% of indicated visits. Laboratory testing per NCD protocols was higher in those with hypertension (88%) than diabetes mellitus (67%) upon review. Only 17 (2%) consultations were referred back to clinical officers., Conclusion: Nurses are able to adhere to protocols for managing stable NCD patients based on clear and standardized protocols and guidelines, thus paving the way towards task shifting of NCD care to nurses to help relieve the significant healthcare gap in developing countries.