Policies for type 2 diabetes and non- communicable disease management during the COVID-19 pandemic in Kenya and Tanzania: A desk review and views of decision-makers

Background The COVID-19 pandemic caused disruptions in care that adversely affected the management of non-communicable diseases (NCDs) globally. Countries have responded in various ways to support people with NCDs during the pandemic. This study aimed to identify policy gaps, if any, in the management of NCDs, particularly diabetes, during COVID-19 in Kenya and Tanzania to inform recommendations for priority actions for NCD management during any future similar crises. Methods We undertook a desk review of pre-existing and newly developed national frameworks, policy models and guidelines for addressing NCDs including type 2 diabetes. This was followed by 13 key informant interviews with stakeholders involved in NCD decision-making: six in Kenya and seven in Tanzania. Thematic analysis was used to analyse the documents. Results Seventeen guidance documents were identified (Kenya=10; Tanzania=7). These included pre-existing and/or updated policies/strategic plans, guidelines, a letter, a policy brief and a report. Neither country had comprehensive policies/guidelines to ensure continuity of NCD care before the COVID-19 pandemic. However, efforts were made to update pre-existing documents and several more were developed during the pandemic to guide NCD care. Some measures were put in place during the COVID-19 period to ensure continuity of care for patients with NCDs such as longer supply of medicines. Inadequate attention was given to monitoring and evaluation and implementation issues. Conclusion Kenya and Tanzania developed and updated some policies/guidelines to include continuity of care in emergencies. However, there were gaps in the documents and between policy/guideline documents and practice. Health systems need to establish disaster preparedness plans that integrate attention to NCD care to enable them to better handle severe disruptions caused by emergencies such as pandemics. Such guidance needs to include contingency planning to enable adequate resources for NCD care and must also address evaluation of implementation effectiveness

Impact of the COVID-19 pandemic on type 2 diabetes care and factors associated with care disruption in Kenya and Tanzania

Background: The COVID-19 pandemic affected healthcare delivery globally, impacting care access and delivery of essential services. Objectives: We investigated the pandemic’s impact on care for patients with type 2 diabetes and factors associated with care disruption in Kenya and Tanzania. Methods: A cross-sectional study was conducted among adults diagnosed with diabetes pre-COVID-19. Data were collected in February–April 2022 reflecting experiences at two time-points, three months before and the three months most affected by the COVID-19 pandemic. A questionnaire captured data on blood glucose testing, changes in medication prescription and access, and healthcare provider access. Results: We recruited 1000 participants (500/country). Diabetes care was disrupted in both countries, with 34.8% and 32.8% of the participants reporting change in place and frequency of testing in Kenya, respectively. In Tanzania, 12.4% and 17.8% reported changes in location and frequency of glucose testing, respectively. The number of health facility visits declined, 14.4% (p < 0.001) in Kenya and 5.6% (p = 0.001) in Tanzania. In Kenya, there was a higher likelihood of severe care disruption among insured patients (adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI][1.05–2.34]; p = 0.029) and a lower likelihood among patients residing in rural areas (aOR, 0.35[95%CI, 0.22–0.58]; p < 0.001). Tanzania had a lower likelihood of severe disruption among insured patients (aOR, 0.51[95%CI, 0.33–0.79]; p = 0.003) but higher likelihood among patients with low economic status (aOR, 1.81[95%CI, 1.14–2.88]; p = 0.011). Conclusions: COVID-19 disrupted diabetes care more in Kenya than Tanzania. Health systems and emergency preparedness should be strengthened to ensure continuity of service provision for patients with diabetes

DAF-16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in Caenorhabditis elegans

The DAF-16/FoxO transcription factor controls growth, metabolism and aging in Caenorhabditis elegans. The large number of genes that it regulates has been an obstacle to understanding its function. However, recent analysis of transcript and chromatin profiling implies that DAF-16 regulates relatively few genes directly, and that many of these encode other regulatory proteins. We have investigated the regulation by DAF-16 of genes encoding the AMP-activated protein kinase (AMPK), which has ?, ? and ? subunits. C. elegans has 5 genes encoding putative AMP-binding regulatory ? subunits, aakg-1-5. aakg-4 and aakg-5 are closely related, atypical isoforms, with orthologs throughout the Chromadorea class of nematodes. We report that ?75% of total ? subunit mRNA encodes these 2 divergent isoforms, which lack consensus AMP-binding residues, suggesting AMP-independent kinase activity. DAF-16 directly activates expression of aakg-4, reduction of which suppresses longevity in daf-2 insulin/IGF-1 receptor mutants. This implies that an increase in the activity of AMPK containing the AAKG-4 ? subunit caused by direct activation by DAF-16 slows aging in daf-2 mutants. Knock down of aakg-4 expression caused a transient decrease in activation of expression in multiple DAF-16 target genes. This, taken together with previous evidence that AMPK promotes DAF-16 activity, implies the action of these two metabolic regulators in a positive feedback loop that accelerates the induction of DAF-16 target gene expression. The AMPK ? subunit, aakb-1, also proved to be up-regulated by DAF-16, but had no effect on lifespan. These findings reveal key features of the architecture of the gene-regulatory network centered on DAF-16, and raise the possibility that activation of AMP-independent AMPK in nutritionally replete daf-2 mutant adults slows aging in C. elegans. Evidence of activation of AMPK subunits in mammals suggests that such FoxO-AMPK interactions may be evolutionarily conserved

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

Modulation of the pH Stability of Influenza Virus Hemagglutinin: A Host Cell Adaptation Strategy

Proteins undergo dynamic structural changes to function within the range of physical and chemical conditions of their microenvironments. Changes in these environments affect their activity unless the respective mutations preserve their proper function. Here, we examine the influenza A virus spike protein hemagglutinin (HA), which undergoes a dynamic conformational change that is essential to the viral life cycle and is dependent on endosomal pH. Since the cells of different potential hosts exhibit different levels of pH, the virus can only cross species barriers if HA undergoes mutations that still permit the structural change to occur. This key event occurs after influenza A enters the host cell via the endocytic route, during its intracellular transport inside endosomes. The acidic pH inside these vesicles triggers a major structural transition of HA that induces fusion of the viral envelope and the endosomal membrane, and permits the release of the viral genome. HA experiences specific mutations that alter its pH stability and allow the conformational changes required for fusion in different hosts, despite the differences in the degree of acidification of their endosomes. Experimental and theoretical studies over the past few years have provided detailed insights into the structural aspects of the mutational changes that alter its susceptibility to different pH thresholds. We will illustrate how such mutations modify the protein's structure and consequently its pH stability. These changes make HA an excellent model of the way subtle structural modifications affect a protein's stability and enable it to function in diverse environments.Fil: Di Lella, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universität zu Berlin; AlemaniaFil: Herrmann, Andreas. Universität zu Berlin; AlemaniaFil: Mair, Caroline M.. Universität zu Berlin; Alemani

Factors associated with COVID-19 vaccine uptake among people with type 2 diabetes in Kenya and Tanzania: a mixed-methods study

No abstract available

Transpulmonary thermodilution (TPTD) before, during and after Sustained Low Efficiency Dialysis (SLED). A Prospective Study on Feasibility of TPTD and Prediction of Successful Fluid Removal.

Acute kidney injury (AKI) is common in critically ill patients. AKI requires renal replacement therapy (RRT) in up to 10% of patients. Particularly during connection and fluid removal, RRT frequently impairs haemodyamics which impedes recovery from AKI. Therefore, "acute" connection with prefilled tubing and prolonged periods of RRT including sustained low efficiency dialysis (SLED) has been suggested. Furthermore, advanced haemodynamic monitoring using trans-pulmonary thermodilution (TPTD) and pulse contour analysis (PCA) might help to define appropriate fluid removal goals.Since data on TPTD to guide RRT are scarce, we investigated the capabilities of TPTD- and PCA-derived parameters to predict feasibility of fluid removal in 51 SLED-sessions (Genius; Fresenius, Germany; blood-flow 150 mL/min) in 32 patients with PiCCO-monitoring (Pulsion Medical Systems, Germany). Furthermore, we sought to validate the reliability of TPTD during RRT and investigated the impact of "acute" connection and of disconnection with re-transfusion on haemodynamics. TPTDs were performed immediately before and after connection as well as disconnection.Comparison of cardiac index derived from TPTD (CItd) and PCA (CIpc) before, during and after RRT did not give hints for confounding of TPTD by ongoing RRT. Connection to RRT did not result in relevant changes in haemodynamic parameters including CItd. However, disconnection with re-transfusion of the tubing volume resulted in significant increases in CItd, CIpc, CVP, global end-diastolic volume index GEDVI and cardiac power index CPI. Feasibility of the pre-defined ultrafiltration goal without increasing catecholamines by >10% (primary endpoint) was significantly predicted by baseline CPI (ROC-AUC 0.712; p = 0.010) and CItd (ROC-AUC 0.662; p = 0.049).TPTD is feasible during SLED. "Acute" connection does not substantially impair haemodynamics. Disconnection with re-transfusion increases preload, CI and CPI. The extent of these changes might be used as a "post-RRT volume change" to guide fluid removal during subsequent RRTs. CPI is the most useful marker to guide fluid removal by SLED

The Well London program--a cluster randomized trial of community engagement for improving health behaviors and mental wellbeing: baseline survey results.

BACKGROUND: The Well London program used community engagement, complemented by changes to the physical and social neighborhood environment, to improve physical activity levels, healthy eating, and mental wellbeing in the most deprived communities in London. The effectiveness of Well London is being evaluated in a pair-matched cluster randomized trial (CRT). The baseline survey data are reported here. METHODS: The CRT involved 20 matched pairs of intervention and control communities (defined as UK census lower super output areas (LSOAs); ranked in the 11% most deprived LSOAs in London by the English Indices of Multiple Deprivation) across 20 London boroughs. The primary trial outcomes, sociodemographic information, and environmental neighbourhood characteristics were assessed in three quantitative components within the Well London CRT at baseline: a cross-sectional, interviewer-administered adult household survey; a self-completed, school-based adolescent questionnaire; a fieldworker completed neighborhood environmental audit. Baseline data collection occurred in 2008. Physical activity, healthy eating, and mental wellbeing were assessed using standardized, validated questionnaire tools. Multiple imputation was used to account for missing data in the outcomes and other variables in the adult and adolescent surveys. RESULTS: There were 4,107 adults and 1,214 adolescent respondents in the baseline surveys. The intervention and control areas were broadly comparable with respect to the primary outcomes and key sociodemographic characteristics. The environmental characteristics of the intervention and control neighborhoods were broadly similar. There was greater between-cluster variation in the primary outcomes in the adult population compared to the adolescent population. Levels of healthy eating, smoking, and self-reported anxiety/depression were similar in the Well London adult population and the national Health Survey for England. Levels of physical activity were higher in the Well London adult population but this is likely to be due to the different measurement tools used in the two surveys. CONCLUSIONS: Randomization of social interventions such as Well London is acceptable and feasible and in this study the intervention and control arms are well-balanced with respect to the primary outcomes and key sociodemographic characteristics. The matched design has improved the statistical efficiency of the study amongst adults but less so amongst adolescents. Follow-up data collection will be completed 2012

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease