A cross-sectional study on the prevalence and associated risk factors for intestinal parasitic infections among under-five aged children in Dabat primary hospital, north Gondar, Ethiopia.

Intestinal parasitic infections (IPIs) are the main public health problems in several developing countries, and under-five-aged children are the most vulnerable groups of the population. The current study aimed to determine the prevalence and associated risk factors of IPIs among under-five-aged children at Dabat primary hospital, northwest Ethiopia. A cross-sectional hospital-based study including 384 under-five-aged children was conducted from February to June 2022. A structured questionnaire was used to collect relevant information on risk factors, and stool samples were collected and examined using wet mount and sedimentation techniques to determine prevalence. Chi-square and logistic regression were used to evaluate the possible association and the strength of the association between dependent and independent variables. The overall prevalence of intestinal parasites was 32.81%. Ten species of intestinal parasites were identified. Entamoeba histolytica / dispar was the predominant intestinal parasite species, with a prevalence of 7.55%. Giardia lamblia and hookworm had prevalence of 6.77% and 5.47% respectively. Those children whose Mother/guardian do not wash their hand before feeding their child are more than five time infected than those who do wash (AOR = 5.26, CI = 2.28-12.2, p < 0.001). Children who do not wear shoe are more infected than who did (AOR = 14.5, CI = 5.77-36.5, p < 0.001). Several risk factors were identified in this study among these washing hands after toilet before touching child, washing hands before feeding their child, Child meal and habit of shoes wearing were the main predictors of IPI. Since the prevalence of IPI observed in this study is that of under-five-aged children; raising awareness of mothers/guardians about how to keep hygiene; transmission ways and health impacts of IPIs; and proper way of feeding their children to avoid risk is crucial.

Genetic associations of neuropathic pain and sensory profile in a deeply phenotyped neuropathy cohort.

ABSTRACT: We aimed to investigate the genetic associations of neuropathic pain in a deeply phenotyped cohort. Participants with neuropathic pain were cases and compared with those exposed to injury or disease but without neuropathic pain as control subjects. Diabetic polyneuropathy was the most common aetiology of neuropathic pain. A standardised quantitative sensory testing protocol was used to categorize participants based on sensory profile. We performed genome-wide association study, and in a subset of participants, we undertook whole-exome sequencing targeting analyses of 45 known pain-related genes. In the genome-wide association study of diabetic neuropathy (N = 1541), a top significant association was found at the KCNT2 locus linked with pain intensity (rs114159097, P = 3.55 × 10-8). Gene-based analysis revealed significant associations between LHX8 and TCF7L2 and neuropathic pain. Polygenic risk score for depression was associated with neuropathic pain in all participants. Polygenic risk score for C-reactive protein showed a positive association, while that for fasting insulin showed a negative association with neuropathic pain, in individuals with diabetic polyneuropathy. Gene burden analysis of candidate pain genes supported significant associations between rare variants in SCN9A and OPRM1 and neuropathic pain. Comparison of individuals with the "irritable" nociceptor profile to those with a "nonirritable" nociceptor profile identified a significantly associated variant (rs72669682, P = 4.39 × 10-8) within the ANK2 gene. Our study on a deeply phenotyped cohort with neuropathic pain has confirmed genetic associations with the known pain-related genes KCNT2, OPRM1, and SCN9A and identified novel associations with LHX8 and ANK2, genes not previously linked to pain and sensory profiles, respectively.

Healthcare-seeking behavior for diarrhea in under-five children and associated factors in sub-Saharan Africa: a multilevel robust Poisson regression model.

Background: Diarrhea is one of the leading causes of child death in sub-Saharan Africa (SSA). Children with diarrhea who do not receive medical advice or treatment are at high risk of poor health outcomes and increased mortality. Prompt and adequate treatment is essential to mitigate these risks. However, studies that have been conducted on the factors influencing healthcare-seeking behavior (HSB) for diarrhea in under-five children in SSA are scarce. Therefore, the purpose of this research was to determine the variables related to HSB for diarrhea in children under the age of five. Methods: A secondary data analysis was conducted on the most recent data from the Demographic and Health Surveys in 35 SSA countries. The study included a total weighted sample of 51,791 children under the age of five with diarrhea. We presented the adjusted prevalence ratio and the 95% confidence interval in the multivariable multilevel robust Poisson regression analysis to show the statistical significance and strength of the association between HSB and its determinants. Results: The pooled prevalence of HSB for diarrhea in under-five children was 58.71% (95%CI: 55.39 to 62.04). Factors found to be associated with HSB included maternal age, education and working status, antenatal care visits, postnatal checkups for the child, wasting, distance to a health facility, SSA region, and country income level. Conclusion: More than 40% of under-five children with diarrhea in SSA did not receive medical advice or treatment. To improve healthcare-seeking behavior, effective health policy interventions are necessary. These include enhancing the education and employment status of mothers, promoting regular antenatal and postnatal care visits, building health facilities in close proximity, and raising awareness in the community about the importance of seeking healthcare services for malnourished children.

Prevalence of Gastrointestinal Parasitic Infections and Associated Risk Factors Among Secondary School Students in Wonji Shoa, Adama District, East Shoa Zone, Oromia Region, Ethiopia.

Intestinal parasitic infections (IPIs) remain a significant contributor to morbidity and mortality globally, particularly in developing countries such as Ethiopia. Periodic assessments of IPI prevalence are essential prerequisite for effective control measures. Therefore, this cross-sectional study is aimed at determining the prevalence of gastrointestinal parasitic infections and associated risk factors among schoolchildren at Wonji Shoa Secondary School, East Shoa Zone, Adama district, Oromia region, Ethiopia, between January and June 2022. A simple random stratified sampling technique was employed to select participants. Sociodemographic and risk factor data were collected using a structured questionnaire. Stool samples were examined to identify parasites. Data were analyzed using SPSS version 20. Descriptive statistics, chi-square tests, and logistic regression were conducted to assess associations between variables and then the strength of the association. A p value < 0.05 was considered statistically significant. Of the 403 selected students, 330 completed the study that makes 81.89% response success. The overall IPI prevalence was 16.66% (55/330), with a higher prevalence among males (60%, 33/55) than females (40%, 22/55). Five parasite species were identified: two protozoa (Entamoeba histolytica and Giardia lamblia) with a combined prevalence of 9.70% (32/330) and three helminths (Ascaris lumbricoides, Hymenolepis nana, and Taenia spp.) with a combined prevalence of 6.97% (23/330). Cysts were detected in 62.5% of E. histolytica cases (15/24), and eggs were detected in 76.92% of A. lumbricoides cases (10/13). The study revealed a substantial IPI prevalence (16.66%) among the students. This finding underscores the need for effective prevention and control strategies. The predominance of parasitic infections among males is notable requiring further investigation of the factors. The identification of multiple parasite species indicates a complex epidemiological scenario. The presence of protozoan cysts and helminthic eggs highlights the potential for fecal-oral transmission and the importance of improved sanitation and hygiene practices.

Seroprevalence of hepatitis B, C, and its associated risk factors among clinically suspected patients attending poly and Maraki Health Centers, Gondar City, North West Ethiopia.

Background: Hepatitis B and C viruses are major global health problems with a high mortality rate, mostly due to serious liver diseases such as liver cirrhosis, liver failure, and hepatocellular carcinoma. The objective of this study was to determine the prevalence of the hepatitis B and C viruses and associated risk factors among clinically suspected patients attending Poly and Maraki Health Centers in Gondar City. Methods: An institution-based cross-sectional study was conducted to recruit 422 clinically suspected patients attending Poly and Maraki Health Centers between June and August 2020. The blood sample was tested for hepatitis B surface antigen and anti-Hepatitis C virus antibodies using commercially available rapid test kits. We used logistic regression and chi-square analysis to assess factors associated with Hepatitis B virus and Hepatitis C virus infections. Results: The overall prevalence of hepatitis B surface antigen and anti-Hepatitis C virus antibodies was 29 (6.9%) and 5 (1.2%), respectively. The prevalence of Hepatitis B virus and Hepatitis C virus was found to be significantly higher at Maraki Health Center. Multiple sexual partners (adjusted odd ratio (AOR = 12.299; 95% CI = 2.515-60.142), history of delivery by traditional birth attendants (AOR = 6.284; 95% CI = 2.373-16.637), surgical history (AOR = 3.679; 95% CI = 1.009-13.417), previous hepatitis infections (AOR = 10.374; 95% CI = 1.128-95.444), and upper abdominal pain (AOR = 3.382; 95% CI = 1.215-9.414) were significantly associated with an increased risk of Hepatitis B virus infections. On the other hand, a history of blood transfusion (AOR = 43.132; 95% CI = 1.385-1343.176) and a history of kidney dialysis (AOR = 71.199; 95% CI = 2.074-2444.646) were significantly associated with Hepatitis C virus infection. Conclusions: According to the WHO endemicity classification, the prevalence of the hepatitis B virus was intermediate, while that of the hepatitis C virus was low. Therefore, it is necessary to strengthen the efforts to control and prevent Hepatitis B virus and Hepatitis C virus infections.

Sero-Prevalence of Visceral Leishmaniasis and Associated Risk Factors among Febrile Patients Attending Metema Hospital, West Gondar Zone, North West Ethiopia.

INTRODUCTION: In Ethiopia, visceral leishmaniasis (VL) is a public health concern that has been spreading to new endemic foci in recent years. An estimated 3.2 million people are at risk of infection, with 3700-7400 new cases yearly. Thus, the study aimed to determine the prevalence of VL and associated risk factors among febrile patients attending Metema Hospital, North West Ethiopia. METHODS: A hospital-based cross-sectional study was conducted on 404 febrile patients attending Metema Hospital from February 2021 to June 2021. The test for VL was done using an immune-chromatographic test (RK39) according to the manufacturer's instructions (InBios International Inc., USA). An interviewer-administered, pretested questionnaire was used to collect data on risk factors associated with VL. Logistic regression and Chi-square assessed the association between VL and the associated risk factors. REULTS: The overall prevalence of visceral leishmaniasis was 18.8% (76/404), with a higher prevalence of VL in males, in the age category between 21 and 30, in study participants who completed elementary school, and in those who earned less than 500 birr monthly compared to their counterparts. Houses with thatched roofs (adjusted odd ratio (AOR) = 17.648, 95CI = 6.549,47.563), houses with mud walls (AOR = 2.538, 95% CI = 1.187-5.411), cattle ownership (AOR = 3.173, 95% CI = 1.286-7.826), dog ownership (AOR = 2,533, 95% CI = 1.256-5.111), presence of Acacia trees near houses (AOR = 1.975, 95% CI:1.004-3.886), presence of Balanites tree (AOR = 3.015, 95% CI = 1.610-5.992), and outdoor sleeping (AOR = 2.259, 95% CI: 1.107-14.607) were the predictors of VL in the present study. CONCLUSIONS: In the study area, VL is still very common. Thus, preventing and controlling infection in the area is largely dependent on raising community awareness of VL prevention and control measures and implementing the necessary interventions on the determinants that have been identified.

Eleven neurology-related proteins measured in serum are positively correlated to the severity of diabetic neuropathy.

About 20% of patients with diabetes suffer from chronic pain with neuropathic characteristics. We investigated the multivariate associations between 92 neurology-related proteins measured in serum from 190 patients with painful and painless diabetic neuropathy. Participants were recruited from the Pain in Neuropathy Study, an observational cross-sectional multicentre study in which participants underwent deep phenotyping. In the exploration cohort, two groups were defined by hierarchical cluster analyses of protein data. The proportion of painless vs painful neuropathy did not differ between the two groups, but one group had a significantly higher grade of neuropathy as measured by the Toronto Clinical Scoring System (TCSS). This finding was replicated in the replication cohort. Analyzing both groups together, we found that a group of 11 inter-correlated proteins (TNFRSF12A, SCARB2, N2DL-2, SKR3, EFNA4, LAYN, CLM-1, CD38, UNC5C, GFR-alpha-1, and JAM-B) were positively associated with TCSS values. Notably, EFNA4 and UNC5C are known to be part of axon guidance pathways. To conclude, although cluster analysis of 92 neurology-related proteins did not distinguish painful from painless diabetic neuropathy, we identified 11 proteins which positively correlated to neuropathy severity and warrant further investigation as potential biomarkers.

Sheffield One-Stop Service: A potential model to improve the screening uptake of diabetic peripheral neuropathy and other microvascular complications of diabetes.

The world is experiencing an enormous rise in the prevalence of diabetes, which is associated with massive healthcare costs that threaten to overwhelm many healthcare systems. Most of the diabetes expenditure is attributed to the management of chronic diabetes complications, including diabetic peripheral neuropathy (DPN)/diabetic foot complications, chronic kidney disease, sight-threatening retinopathy and cardiovascular diseases. Of these complications, the most overlooked is DPN. Most consultations around the world do not even involve taking off shoes and socks to carry out a foot examination, and even when carried out, the peripheral neurological examination using the 10-g monofilament diagnoses DPN when it is already at an advanced stage. Thus, all too often diabetes complications are diagnosed late, resulting in devastating outcomes, particularly in low- to middle-income countries. There is, therefore, an urgent need to instigate new strategies to improve microvascular screening uptake using a holistic protocol for annual diabetes health checks outside the busy diabetes clinic. One such approach, the Sheffield One-Stop Microvascular Screening Service, which involves modern point of care devices to diagnose DPN, has been shown to be feasible and effective, resulting in high uptake and early management of diabetes complications. This article outlines the advantages of this One-Stop Microvascular Screening Service and a plan to trial an adapted version of this service to a resource-limited country, the Philippines. If successful, this model has the potential for implementation in other countries around the world.

Efficacy and Safety of Trazodone and Gabapentin Fixed-Dose Combination in Patients Affected by Painful Diabetic Neuropathy: Randomized, Controlled, Dose-Finding Study.

INTRODUCTION: Up to 50% of diabetic patients with neuropathy suffer from chronic pain, namely painful diabetic neuropathy (PDN), an unmet medical need with significant impact on quality of life. Gabapentin is widely used for PDN, albeit with frequent dose-limiting effects. Trazodone, an antidepressant with multi-modal action, has shown promising results when given at low doses as an add-on to gabapentin. Upon previous clinical trials and experimental evidence, a fixed-dose combination (FDC) of both compounds, at low doses, was developed for neuropathic pain. METHODS: This was a phase II, randomized, double-blind, placebo and reference controlled, dose-finding, multicenter, international, prospective study. Male and female diabetic patients aged 18-75 years and affected by PDN were eligible for enrolment. Patients were randomized (1:1:1:1:2 ratio) to trazodone and gabapentin (Trazo/Gaba) 2.5/25 mg t.i.d. for 8 weeks, Trazo/Gaba 5/50 mg t.i.d. for 8 weeks, Trazo/Gaba 10/100 mg t.i.d. for 8 weeks, gabapentin (Gaba), or placebo (PLB). The aim of the study was to collect preliminary information on the effect of the 3 different FDCs of Trazo/Gaba on pain intensity based on the 11-point numeric rating score (NRS) after 8 weeks of treatment. The secondary objectives were the evaluation of the percentage of responders, neuropathic pain symptoms, anxiety, sleep, quality of life, safety, and tolerability. The primary efficacy endpoint was evaluated with last observation carried out forward (LOCF), using an analysis of covariance (ANCOVA), including treatment and centers as factors and baseline as covariate and applying linear contrast test, excluding the active treatment. Only if the linear contrast test was significant (p < 0.05), the step-down Dunnett test would be used to determine the minimum effective dose significantly different from PLB. If linearity was not verified, an adjusted ANCOVA model and comparisons with Dunnett test were performed. Before the application of the ANCOVA model, the non-significance of interaction treatment per baseline was verified. RESULTS: A total of 240 patients were included in the modified intention-to-treat (m-ITT) population: 39 in Trazo/Gaba 2.5/25 mg, 38 in Trazo/Gaba 5/50 mg, 37 in Trazo/Gaba 10/100 mg, 83 in PLB, and 43 in Gaba. After 8 weeks of treatment, changes of the average daily pain score based on the 11-point NRS from baseline were - 2.52 ± 2.31 in Trazo/Gaba 2.5/25 mg group, - 2.24 ± 1.96 in Trazo/Gaba 5/50 mg group, - 2.46 ± 2.12 in Trazo/Gaba 10/100 mg group, - 1.92 ± 2.21 in Gaba group, and - 2.02 ± 1.95 in the PLB group. The linear contrast test did not result in significant differences (p > 0.05) among treatment groups. Consequently, the minimum effective dose against PLB was not determined. The multiple comparison with Dunnett adjustment did not show any statistically significant differences vs. PLB after 8 weeks of treatment: Trazo/Gaba 2.5/25 mg (95% confidence interval (CI) - 1.2739, 0.2026; p = 0.1539); Trazo/Gaba 5/50 mg (95% CI - 0.9401, 0.5390; p = 0.5931); Trazo/Gaba 10/100 mg (95% CI - 1.0342, 0.4582; p = 0.4471). However, patients receiving the lowest dose of Trazo/Gaba 2.5/25 mg showed a statistically significant difference to PLB after 6 weeks of treatment (95% CI - 1.6648, - 0.2126; p = 0.0116). Positive results were also found for responder patients, other items related to the pain, anxiety, depression, sleep, and quality of life, consistently in favor to the lowest Trazo/Gaba FDC. Two serious adverse events (SAEs) occurred but were judged unrelated to the study treatment. Treatment-emergent adverse events (TEAEs) were mainly mild-to-moderate in intensity and involved primarily nervous system, gastrointestinal disorders, and investigations. CONCLUSIONS: The primary end point of the study was the change from baseline of the average daily pain score based on the 11-point NRS after 8 weeks of treatment. While the primary endpoint was not reached, patients treated with Trazo/Gaba 2.5/25 mg t.i.d. showed statistically significant improvement of pain and other scores after 6 weeks and reported consistent better results in comparison to PLB on primary and secondary endpoints for the overall study duration. According to these results, the lowest dose of Trazo/Gaba FDC may be the best candidate for further clinical development to confirm the potential benefits of the FDC drug for this condition. CLINICAL TRIAL REGISTRATION: NCT03749642.

Increased Thalamocortical Functional Connectivity on Discontinuation of Treatment in Painful Diabetic Peripheral Neuropathy.

Altered functional connectivity has been demonstrated in key brain regions involved in pain processing in painful diabetic peripheral neuropathy. However, the impact of neuropathic pain treatment on functional connectivity does not appear to have been investigated. Sixteen participants underwent resting state functional MRI when optimally treated for neuropathic pain during their involvement in the Optimal Pathway for Treating Neuropathic Pain in Diabetes Mellitus trial and 1 week following withdrawal of treatment. On discontinuation of pain treatment, there was an increase in functional connectivity between the left thalamus and primary somatosensory cortex (S1) and the left thalamus and insular cortex, key brain regions that are involved in cerebral processing of pain. The changes in functional connectivity between scans also correlated with measures of pain (baseline pain severity and Neuropathic Pain Symptom Inventory). Moreover, when participants were stratified into higher- and lower-than-average baseline pain subgroups, the change in thalamic-S1 cortical functional connectivity between scans was significantly greater in those with high baseline pain compared with the lower-baseline-pain group. This study shows that thalamo-cortical functional connectivity has the potential to act as an objective biomarker for neuropathic pain in diabetes for use in clinical pain trials.

Reduced Thalamic γ-Aminobutyric Acid (GABA) in Painless but Not Painful Diabetic Peripheral Neuropathy.

Alterations in the structure, function, and microcirculation of the thalamus, a key brain region involved in pain pathways, have previously been demonstrated in patients with painless and painful diabetic peripheral neuropathy (DPN). However, thalamic neurotransmitter levels including γ-aminobutyric acid (GABA) (inhibitory neurotransmitter) and glutamate (excitatory neurotransmitter) in different DPN phenotypes are not known. We performed a magnetic resonance spectroscopy study and quantified GABA and glutamate levels within the thalamus, in a carefully characterized cohort of participants with painless and painful DPN. Participants with DPN (painful and painless combined) had a significantly lower GABA:H2O ratio compared with those without DPN (healthy volunteers [HV] and participants with diabetes without DPN [no DPN]). Participants with painless DPN had the lowest GABA:H2O ratio, which reached significance compared with HV and no DPN, but not painful DPN. There was no difference in GABA:H2O in painful DPN compared with all other groups. A significant correlation with GABA:H2O and neuropathy severity was also seen. This study demonstrates that lower levels of thalamic GABA in participants with painless DPN may reflect neuroplasticity due to reduced afferent pain impulses, whereas partially preserved levels of GABA in painful DPN may indicate that central GABAergic pathways are involved in the mechanisms of neuropathic pain in diabetes.

Application of machine learning methods for predicting childhood anaemia: Analysis of Ethiopian Demographic Health Survey of 2016.

Childhood anaemia is a public health problem in Ethiopia. Machine learning (ML) is a growing in medicine field to predict diseases. Diagnosis of childhood anaemia is resource intensive. The aim of this study is to apply machine learning (ML) algorithm to predict childhood anaemia using socio-demographic, economic, and maternal and child related variables. The study used data from 2016 Ethiopian demographic health survey (EDHS). We used Python software version 3.11 to apply and test ML algorithms through logistic regression, Random Forest (RF), Decision Tree, and K-Nearest Neighbours (KNN). We evaluated the performance of each of the ML algorithms using discrimination and calibration parameters. The predictive performance of the algorithms was between 60% and 66%. The logistic regression model was the best predictive model of ML with accuracy (66%), sensitivity (82%), specificity (42%), and AUC (69%), followed by RF with accuracy (64%), sensitivity (79%), specificity (42%), and AUC (63%). The logistic regression and the RF models of ML showed poorest family, child age category between 6 and 23 months, uneducated mother, unemployed mother, and stunting as high importance predictors of childhood anaemia. Applying logistic regression and RF models of ML can detect combinations of predictors of childhood anaemia that can be used in primary health care professionals.

CVOT Summit Report 2023: new cardiovascular, kidney, and metabolic outcomes.

The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD); advances in the management of type 1 diabetes (T1D) and its comorbidities; advances in the management of CKD with SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists (nsMRAs); and advances in the treatment of obesity with GLP-1 and dual GIP/GLP-1 receptor agonists. The association of diabetes and obesity with nonalcoholic steatohepatitis (NASH; metabolic dysfunction-associated steatohepatitis, MASH) and cancer and possible treatments for these complications were also explored. It is generally assumed that treatment of chronic diseases is equally effective for all patients. However, as discussed at the Summit, this assumption may not be true. Therefore, it is important to enroll patients from diverse racial and ethnic groups in clinical trials and to analyze patient-reported outcomes to assess treatment efficacy, and to develop innovative approaches to tailor medications to those who benefit most with minimal side effects. Other keys to a successful management of diabetes and comorbidities, including dementia, entail the use of continuous glucose monitoring (CGM) technology and the implementation of appropriate patient-physician communication strategies. The 10th Cardiovascular Outcome Trial Summit will be held virtually on December 5-6, 2024 ( http://www.cvot.org ).

Non-pharmacological interventions to improve cardiovascular risk factors in people with diabetic foot disease: A systematic review and meta-analysis.

Cardiovascular disease (CVD) risk in those with diabetic foot disease is very high. Non-pharmacological interventions may improve this risk, though no previous evidence synthesis has been completed. This systematic review aimed to investigate the impact of non-pharmacological interventions on CVD risk factors in diabetic ulcer disease. Multiple databases and trials registers were searched from inception to December 6th 2023. We included reports of randomised controlled trials investigating the impact of non-pharmacological interventions on cardiovascular risk in those with type 1 or type 2 diabetes and current or previous diabetic foot disease. Twenty studies were included. Extracted data included: study design and setting; participant sociodemographic factors; and change in cardiovascular risk factors. Data were synthesised using random effects meta-analyses and narrative syntheses. Interventions included nutritional supplementation, collaborative care, hyperbaric oxygen therapy, patient education, nurse-led intervention, self-management, family support, relaxation and exercise, over a median duration of 12 weeks. Significant post-intervention changes were observed in fasting plasma glucose, serum insulin levels, insulin sensitivity and resistance, glycated haemoglobin, triglycerides, total cholesterol, low-density lipoprotein-cholesterol and C-reactive protein. No effects were detected in very low- or high-density lipoprotein-cholesterol or body mass index. Non-pharmacological interventions show promise in improving CVD risk in diabetic foot disease.

Brain alterations in regions associated with end-organ diabetic microvascular disease in diabetes mellitus: A UK Biobank study.

BACKGROUND: Diabetes mellitus (DM) is associated with structural grey matter alterations in the brain, including changes in the somatosensory and pain processing regions seen in association with diabetic peripheral neuropathy. In this case-controlled biobank study, we aimed to ascertain differences in grey and white matter anatomy in people with DM compared with non-diabetic controls (NDC). METHODS: This study utilises the UK Biobank prospective, population-based, multicentre study of UK residents. Participants with diabetes and age/gender-matched controls without diabetes were selected in a three-to-one ratio. We excluded people with underlying neurological/neurodegenerative disease. Whole brain, cortical, and subcortical volumes (188 regions) were compared between participants with diabetes against NDC corrected for age, sex, and intracranial volume using univariate regression models, with adjustment for multiple comparisons. Diffusion tensor imaging analysis of fractional anisotropy (FA) was performed along the length of 50 white matter tracts. RESULTS: We included 2404 eligible participants who underwent brain magnetic resonance imaging (NDC, n = 1803 and DM, n = 601). Participants with DM had a mean (±standard deviation) diagnostic duration of 18 ± 11 years, with adequate glycaemic control (HbA1C 52 ± 13 mmol/mol), low prevalence of microvascular complications (diabetic retinopathy prevalence, 5.8%), comparable cognitive function to controls but greater self-reported pain. Univariate volumetric analyses revealed significant reductions in grey matter volume (whole brain, total, and subcortical grey matter), with mean percentage differences ranging from 2.2% to 7% in people with DM relative to NDC (all p < 0.0002). The subcortical (bilateral cerebellar cortex, brainstem, thalamus, central corpus callosum, putamen, and pallidum) and cortical regions linked to sensorimotor (bilateral superior frontal, middle frontal, precentral, and postcentral gyri) and visual functions (bilateral middle and superior occipital gyri), all had lower grey matter volumes in people with DM relative to NDC. People with DM had significantly reduced FA along the length of the thalamocortical radiations, thalamostriatal projections, and commissural fibres of the corpus callosum (all; p < 0·001). INTERPRETATION: This analysis suggests that anatomic differences in brain regions are present in a cohort with adequately controlled glycaemia without prevalent microvascular disease when compared with volunteers without diabetes. We hypothesise that these differences may predate overt end-organ damage and complications such as diabetic neuropathy and retinopathy. Central nervous system alterations/neuroplasticity may occur early in the natural history of microvascular complications; therefore, brain imaging should be considered in future mechanistic and interventional studies of DM.

Serum levels of endocannabinoids and related lipids in painful vs painless diabetic neuropathy: results from the Pain in Neuropathy Study.

ABSTRACT: N-arachidonoylethanolamine (also known as anandamide) and 2-arachidonoylglycerol are activators of the cannabinoid receptors. The endocannabinoid system also includes structurally and functionally related lipid mediators that do not target cannabinoid receptors, such as oleoylethanolamide, palmitoylethanolamide, and stearoylethanolamide. These bioactive lipids are involved in various physiological processes, including regulation of pain. The primary aim of the study was to analyze associations between serum levels of these lipids and pain in participants in the Pain in Neuropathy Study, an observational, cross-sectional, multicentre, research project in which diabetic patients with painless or painful neuropathy underwent deep phenotyping. Our hypothesis was that painful neuropathy would be associated with higher levels of the 5 lipids compared with painless neuropathy. Secondary aims were to analyze other patient-reported outcome measures and clinical data in relationship to lipid levels. The lipid mediators were analyzed in serum samples using liquid chromatography tandem mass spectrometry (LC-MS/MS). Serum levels of anandamide were significantly higher in the painful group, but the effect size was small (Cohen d = 0.31). Using cluster analysis of lipid data, patients were dichotomized into a "high-level" endocannabinoid group and a "low-level" group. In the high-level group, 61% of patients had painful neuropathy, compared with 45% in the low-level group ( P = 0.039). This work is of a correlative nature only, and the relevance of these findings to the search for analgesics targeting the endocannabinoid system needs to be determined in future studies.

Efficacy and safety of eliapixant in diabetic neuropathic pain and prediction of placebo responders with an exploratory novel algorithm: results from the randomized controlled phase 2a PUCCINI study.

ABSTRACT: Phase 2a of the PUCCINI study was a placebo-controlled, double-blind, parallel-group, multicenter, proof-of-concept study evaluating the efficacy and safety of the selective P2X3 antagonist eliapixant in patients with diabetic neuropathic pain (DNP) ( ClinicalTrials.gov NCT04641273). Adults with type 1 or type 2 diabetes mellitus with painful distal symmetric sensorimotor neuropathy of >6 months' duration and neuropathic pain were enrolled and randomized 1:1 to 150 mg oral eliapixant twice daily or placebo for 8 weeks. The primary endpoint was change from baseline in weekly mean 24-hour average pain intensity score at week 8. In total, 135 participants completed treatment, 67 in the eliapixant group and 68 in the placebo group. At week 8, the change from baseline in posterior mean 24-hour average pain intensity score (90% credible interval) in the eliapixant group was -1.56 (-1.95, -1.18) compared with -2.17 (-2.54, -1.80) for the placebo group. The mean treatment difference was 0.60 (0.06, 1.14) in favor of placebo. The use of a model-based framework suggests that various factors may contribute to the placebo-responder profile. Adverse events were mostly mild or moderate in severity and occurred in 51% of the eliapixant group and 48% of the placebo group. As the primary endpoint was not met, the PUCCINI study was terminated after completion of phase 2a and did not proceed to phase 2b. In conclusion, selective P2X3 antagonism in patients with DNP did not translate to any relevant improvement in different pain intensity outcomes compared with placebo. Funding: Bayer AG.

The potential of Ethiopian medicinal plants to treat emergent viral diseases.

Ethiopians have deep-rooted traditions of using plants to treat ailments affecting humans and domesticated animals. Approximately 80% of the population continues to rely on traditional medicine, including for the prevention and treatment of viral diseases. Many antiviral plants are available to and widely used by communities in areas where access to conventional healthcare systems is limited. In some cases, pharmacological studies also confirm the potent antiviral properties of Ethiopian plants. Building on traditional knowledge of medicinal plants and testing their antiviral properties may help to expand options to address the global pandemic of COVID-19 including its recently isolated virulent variants and prepare for similar outbreaks in the future. Here, we provide an ethnobotanical and pharmacological inventory of Ethiopian medicinal plants that might contribute to the prevention and treatment of viral diseases. We identified 387 species, about 6% of Ethiopia's known flora, for which records of use by local communities and traditional herbalists have been documented for the treatment of viral diseases. We provide a framework for further investigation and development of this vital resource much anticipated to help combat emergent viral diseases along with existing ones in Ethiopia and elsewhere.

Female sex is a risk factor for painful diabetic peripheral neuropathy: the EURODIAB prospective diabetes complications study.

AIMS/HYPOTHESIS: While the risk factors for diabetic peripheral neuropathy (DPN) are now well recognised, the risk factors for painful DPN remain unknown. We performed analysis of the EURODIAB Prospective Complications Study data to elucidate the incidence and risk factors of painful DPN. METHODS: The EURODIAB Prospective Complications Study recruited 3250 participants with type 1 diabetes who were followed up for 7.3±0.6 (mean ± SD) years. To evaluate DPN, a standardised protocol was used, including clinical assessment, quantitative sensory testing and autonomic function tests. Painful DPN (defined as painful neuropathic symptoms in the legs in participants with confirmed DPN) was assessed at baseline and follow-up. RESULTS: At baseline, 234 (25.2%) out of 927 participants with DPN had painful DPN. At follow-up, incident DPN developed in 276 (23.5%) of 1172 participants. Of these, 41 (14.9%) had incident painful DPN. Most of the participants who developed incident painful DPN were female (73% vs 48% painless DPN p=0.003) and this remained significant after adjustment for duration of diabetes and HbA1c (OR 2.69 [95% CI 1.41, 6.23], p=0.004). The proportion of participants with macro- or microalbuminuria was lower in those with painful DPN compared with painless DPN (15% vs 34%, p=0.02), and this association remained after adjusting for HbA1c, diabetes duration and sex (p=0.03). CONCLUSIONS/INTERPRETATION: In this first prospective study to investigate the risk factors for painful DPN, we definitively demonstrate that female sex is a risk factor for painful DPN. Additionally, there is less evidence of diabetic nephropathy in incident painful, compared with painless, DPN. Thus, painful DPN is not driven by cardiometabolic factors traditionally associated with microvascular disease. Sex differences may therefore play an important role in the pathophysiology of neuropathic pain in diabetes. Future studies need to look at psychosocial, genetic and other factors in the development of painful DPN.