Time to develop severe acute malnutrition and its predictors among children living with HIV in the era of test and treat strategies at South Gondar hospitals, northwest, Ethiopia, 2021: a multicentre retrospective cohort study

Background Although severe acute malnutrition is a major public issue among HIV infected children, there is no prior evidence in Ethiopia. Hence, this study aims to assess the time to develop severe acute malnutrition and its predictors among children living with human immunodeficiency virus in Ethiopia, 2012. Methods An institution based retrospective cohort study was conducted in South Gondar hospitals among 363 HIV infected children from February 10, 2014, to January 7, 2021. Epi-data version 3.1 was used to enter data, which was then exported to STATA version 14 for analysis. Besides, WHO (World Health Organization) Anthro Plus software was used to assess the nutritional status of the children. A standardized data extraction tool was used to collect the data. The Kaplan Meier survival curve was used to estimate the median survival time. The Cox-proportional hazard model assumption was checked via the Schoenfeld residual ph test and a stph plot. Bivariable and multivariable Cox proportional hazard models were employed at 95% confidence intervals (CI). A variable having a p-value < 0.05 was considered a statistically significant predictor of severe acute malnutrition. Results A total of 363 children living with HIV, 97 (26.72%) developed severe acute malnutrition during the follow-up period. The overall incidence rate was 5.4 (95% CI: 4.7–5.9) person per year with a total of 21, 492 months or 1791 years of observation. Moreover, the median survival time was 126 months. Treatment failure [AHR =3.4 (95% CI: 2.05–5.75)], CD4 count below threshold [AHR =2.5 (95% CI: 1.64–3.95)], and WHO stage III & IV [AHR =2.9 (95% CI: 1.74–4.73)] were all significant predictors of severe acute malnutrition. Conclusion The time to develop severe acute malnutrition was found to be very low. Treatment failure, CD4 count below threshold, and WHO stage III were all significant predictors of severe acute malnutrition. Hence, emphasizing those predictor variables is essential for preventing and controlling the occurrence of severe acute malnutrition among HIV infected children.

Improving Infant Hydrocephalus Outcomes in Uganda: A Longitudinal Prospective Study Protocol for Predicting Developmental Outcomes and Identifying Patients at Risk for Early Treatment Failure after ETV/CPC

Infant hydrocephalus poses a severe global health burden; 80% of cases occur in the developing world where patients have limited access to neurosurgical care. Surgical treatment combining endoscopic third ventriculostomy and choroid plexus cauterization (ETV/CPC), first practiced at CURE Children’s Hospital of Uganda (CCHU), is as effective as standard ventriculoperitoneal shunt (VPS) placement while requiring fewer resources and less post-operative care. Although treatment focuses on controlling ventricle size, this has little association with treatment failure or long-term outcome. This study aims to monitor the progression of hydrocephalus and treatment response, and investigate the association between cerebral physiology, brain growth, and neurodevelopmental outcomes following surgery. We will enroll 300 infants admitted to CCHU for treatment. All patients will receive pre/post-operative measurements of cerebral tissue oxygenation (SO2), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen consumption (CMRO2) using frequency-domain near-infrared combined with diffuse correlation spectroscopies (FDNIRS-DCS). Infants will also receive brain imaging, to monitor tissue/ventricle volume, and neurodevelopmental assessments until two years of age. This study will provide a foundation for implementing cerebral physiological monitoring to establish evidence-based guidelines for hydrocephalus treatment. This paper outlines the protocol, clinical workflow, data management, and analysis plan of this international, multi-center trial.

Greater Glycemic Burden Is Associated with Further Poorer Glycemic Control in Newly-Diagnosed Type 2 Diabetes Mellitus Patients

Aims: hyperglycemia impairs pancreatic β-cell function instantly, also known as glucotoxicity. It is unknown whether this insult is temporary or sustained, and little real-world evidence needs to reflect the relationship between hyperglycemic burden, per se, and glycemic durability. Materials and Methods: a retrospective observational cohort study was conducted to recruit newly-diagnosed type 2 diabetes mellitus (T2DM) patients. Durability was defined as the episode from first glycated hemoglobin A1c (HbA1c) below 7.0% to where it exceed 8.0% (with treatment failure) or where study ended (without treatment failure). Glycemic burden was defined with the area above a burden value line (HbA1c = 6.5%) but under the HbA1c curve (AUC), and it was then divided into two compartments with the demarcation timepoint once HbA1c was treated below or equal to 7.0%; the former AUC’ represented the initial insult; the latter AUC” represented the residual part. Multivariable regression models assessed factors associated with durability in whole participants and two distinct subgroups: patients with baseline HbA1c > 7.0% or ≤7.0%. Results: 1048 eligible participants were recruited and analyzed: 291 patients with treatment failure (durability 26.8 ± 21.1 months); 757 patients without treatment failure (durability 45.1 ± 31.8 months). Besides age, glycemic burden was the only constant determinant in the two subgroups. AUC’ or AUC” increased treatment failure, respectively, in baseline HbA1c > 7.0% or ≤7.0% subgroup [per 1%/90 days hazard ratio (95% confidence interval): 1.026 (1.018–1.034) and 1.128 (1.016–1.253)]. Other determinants include baseline HbA1c, initial OAD, and education level. Conclusions: in patients with newly-diagnosed T2DM, glycemic durability was negatively associated with greater glycemic burden.

Low dose magnesium sulphate regimen and maternal outcome of patients with eclampsia

Background: Preeclampsia, a serious pregnancy complication which is commonly characterized by high blood pressure, presence of protein in the urine and sometimes swelling in women's feet, legs and hands. With this condition, patient’s high blood pressure often results in seizures. Generally, the outcome remains good, however, eclampsia can be life threatening and disastrous.Methods: This cross-sectional study considered 114 patients who meet inclusion criteria and agreed to will-fully participate in the study were evaluated for different parameters. Patients who developed eclampsia during intra-natal and postnatal period were included in the study. The aim of the study was to evaluate the maternal outcome among all patients of eclampsia treated with low magnesium sulphate dosage therapy. Results: The present study revealed, very low fit recurrence rate, low mortality rate, zero treatment failure rate, no toxicity and (99.12%) success rate.Conclusions: Apart from zero percent treatment failure rate, Low maternal mortality and fit recurrence rate encouraged us to continue the treatment with low dose MGSO4 regimen. Thus, low dose magnesium sulphate has been found very effective in treating the eclmpsia and at the same time maintains the high safety margin.

Predictors of cardio-kidney complications and treatment failure in patients with chronic kidney disease and type 2 diabetes treated with SGLT2 inhibitors

Background Clinical practice guidelines recommend sodium-glucose co-transporter 2 inhibitors (SGLT2is) to mitigate adverse kidney and cardiovascular outcomes in patients with type 2 diabetes (T2D), including patients with comorbid chronic kidney disease (CKD), also referred to as diabetic kidney disease (DKD), who are at even higher risk. In this study, we sought to identify predictors of cardio-kidney events, cardio-kidney complications, and treatment failure (i.e., addition/initiation of a new T2D class, insulin, or discontinuation of SGLT2is) after new initiation of SGLT2is in patients with CKD and T2D (DKD). Methods In this retrospective cohort study, we identified adult patients with DKD who initiated SGLT2is between April 1, 2012, and June 30, 2019, in Optum claims data. Outcome rates per 1000 person-years (PY) are reported with 95% confidence intervals (CIs). Cox proportional hazards regression identified patient characteristics associated with each outcome. Results The study population consisted of 6389 initiators of SGLT2is. The rate of CV hospitalization was 26.0 (95% CI 21.6, 30.4) per 1000 PY. Baseline characteristics associated with higher risk of CV hospitalization included age, atrial fibrillation, peripheral vascular disease (PVD), and cancer. The rate of kidney hospitalization was 12.0 (95% CI 9.0, 15.0) per 1000 PY. The risk increased significantly with baseline evidence of heart failure, hyperkalemia, respiratory failure, depression, and use of loop diuretics. In total, 55.0% of all SGLT2i initiators discontinued treatment during the follow-up period. The rate of treatment failure was 510.5 (95% CI 492.9, 528.1) per 1000 PY. Analysis of key time-dependent SGLT2i-associated adverse events showed that experiencing diabetic ketoacidosis and volume depletion were associated with risk of treatment failure. Conclusions Our study demonstrated high rates of residual cardio-kidney outcomes and treatment failure in patients with DKD treated with SGLT2is. Patients with high baseline CV risk and the presence of certain conditions, such as atrial fibrillation, PVD, and heart failure, were at higher risk for cardio-kidney events. Further research is needed to assess the potential relationship between adverse events and SGLT2i treatment failure.

The Use of High Initial Doses of Botulinum Toxin Therapy for Cervical Dystonia Is a Risk Factor for Neutralizing Antibody Formation—A Monocentric Cross-Sectional Pilot Study

Background and Objectives: The present study aims to analyze the complex patient/treating physician interaction at onset of botulinum toxin (BoNT) therapy in patients with idiopathic cervical dystonia (CD) and the influence of high initial doses on long-term outcomes. Materials and Methods: A total of 74 CD patients with well-documented courses of BoNT treatment were consecutively recruited after written informed consent. Patients had to rate the amount of improvement of CD in percent of severity of CD at onset of BoNT therapy. They had to draw the course of disease severity (CoD) of CD from the onset of symptoms until the onset of BoNT therapy and from the onset of BoNT therapy until recruitment. The remaining severity of CD was estimated by the treating physician using the TSUI score. Demographic- and treatment-related data were extracted from the charts of the patients. Seventeen patients with suspected secondary treatment failure (STF) were tested for the presence of antibodies. Results: Depending on the CoD before BoNT therapy, three patient subgroups could be distinguished: rapid onset, continuous onset and delayed onset groups. Time to BoNT therapy, increase in dose and improvement were significantly different between these three groups. In the rapid onset group, with the highest initial doses, the best improvement was reported, but the highest number of patients with an STF and with neutralizing antibodies was also observed. Conclusion: The use of high initial doses in the BoNT therapy of CD is associated with a rapid response and quick success; however, it leads to an elevated risk for the development of a secondary treatment failure and induction of neutralizing antibodies.