Stratum-specific health outcome estimation in Pakistan using double goal CART.

Post-stratification is applied when the subpopulation membership is observed only for sampled values and the goal is to estimate stratum-specific parameters which leads the survey statisticians towards primary goals i.e., classification of non-sampled units into different strata and prediction of the values of the study variables. Regression models, on one side, optimize the prediction of the study variable's non-sampled values while the classification algorithms, on the other side, look for the classification of non-sampled cases into different strata. Hence, it is crucial to deal with these two goals simultaneously for the estimation of stratum-specific parameters. This study introduces the idea of a double-objective classification and regression trees (CARTs) approach for estimating stratum-specific parameters. Theoretical properties of the total estimator are derived. An application on the estimation of health outcomes in different domains is given to delineate the practical significance as well as the efficiency of the proposed CART-based method. The proposed estimator of population total performs better than the existing stratum-specific estimator in terms of relative efficiency for all choices of parameters. As an ensemble model, the random forest CART outperforms the other competing tree-based models and homogenous population model without using any auxiliary variable.

Comment on "renal denervation for hypertension".

We have attentively reviewed the article "Renal Denervation for Hypertension" and commend the author's dedication to addressing this intricate subject. However, we wish to highlight a few points that, in our assessment, could enhance the overall quality of the article.

Mesoporous Cu-Doped Manganese Oxide Nano Straws for Photocatalytic Degradation of Hazardous Alizarin Red Dye.

The present work reports the photocatalytic degradation of alizarin red (AR) using Cu-doped manganese oxide (MH16-MH20) nanomaterials as catalysts under UV light irradiation. Cu-doped manganese oxides were synthesized by a very facile hydrothermal approach and characterized by energy dispersive X-ray spectroscopy, powder X-ray diffraction, scanning electron microscopy, Brunauer-Emmett-Teller analysis, UV-vis spectroscopy, and photoluminescence techniques. The structural, morphological, and optical characterization revealed that the synthesized compounds are nanoparticles (38.20-54.10 nm), grown in high mesoporous density (constant C > 100), possessing a tetragonal phase, and exhibiting 2.98-3.02 eV band gap energies. Synthesized materials were utilized for photocatalytic AR dye degradation under UV light which was monitored by UV-visible spectroscopy and % AR degradation was calculated at various time intervals from absorption spectra. More than 60% AR degradation at various time intervals was obtained for MH16-MH20 indicating their good catalytic efficiencies for AR removal. However, MH20 was found to be the most efficient catalyst showing more than 84% degradation, hence MH20 was used to investigate the effect of various catalytic doses, AR concentrations, and pH of the medium on degradation. More than 50% AR degradation was obtained for all studied parameters with MH20 whereas the pseudo-first-order kinetic model was found to be the best-fitted kinetic model for AR degradation with k = 0.0015 and R2 = 0.99 indicating a significant correlation between experimental data.

Case fatality rate and burden of snakebite envenoming in children - A systematic review and meta-analysis.

Snakebite is a major public health problem with an estimated global burden of 5 million people per annum. Data on snakebite envenoming in children are very limited and is unclear whether there is a significant difference in severity between adults and children. We therefore conducted a meta-analysis of observational studies on snakebite in children to obtain a more precise estimate of case fatality rate (CFR) as well as to explore the differences in outcome between children and adults. Studies from all over the world reported until the end of February 2023 were included. Analysis was conducted consistent with the Meta-analysis of Observational Studies in Epidemiology (MOOSE) criteria. Estimates were obtained from Random Effects Model (REM). Sub-analysis was conducted for studies from sub-Saharan Africa (SSA) to provide estimates for the continent. Adverse outcomes comprising composite endpoints (CE), defined as fatality and or complications, were compared between children and adults in sub-analysis of studies reporting on both groups. The annual burden and fatality of snakebite envenoming were derived based on lifetime prevalence of bite, meta-analysis estimates, and other data inputs. The pooled estimate of the CFR from 35 studies included worldwide was 1.98% [95%CI:1.38-2.58%] while the estimates from 6 studies within SSA was 2.43% (95%CI:0.67-4.20%). The odds of adverse outcomes were 2.52 times higher in children compared to adults. The estimated annual burden was 178,491 cases with 4346 deaths among children in SSA. These estimates compare favorably to those reported in the literature.

A prospective observational phase IV study on effectiveness of animal derived polyclonal antibody antivenoms against West African carpet viper (Echis romani) induced coagulopathy and mortality.

Conventional polyclonal antibody antivenoms are the mainstay of snakebite therapy. They have not been proven to be efficacious in randomized placebo controlled clinical trials among severely envenomed patients. There is also paucity of evidence on effectiveness especially in routine use. The current study evaluated their effectiveness in post marketing use among those managed with and without antivenom as regards to reversal of venom induced coagulopathy defined using the 20 min Whole Blood Clotting Test [20WBCT] and in averting death. The effectiveness of antivenom was evaluated among 5467 patients predominantly envenomed by the West African carpet viper (Echis romani) at 3 hospitals in Nigeria from 2021 to 2022. Two antivenoms Echitab G (EG) and Echitab ICP Plus (EP) were able to restore normal clotting within 6 h of administration in 58.0% [95% Confidence Interval (95%CI)] (51.2-64.5%) and 91.7% (90.4-93.0%) of patients respectively. They were able to restore normal clotting within 24 h of administration in 96.9% (94.0-98.7%) and 99.0% (98.4-99.4%) of patients respectively. The Odds Ratio [OR (95%CI)] of dying among patients with positive 20WBCT who were treated with ≥1 vial of either EG or EP compared to those not treated was 0.06 (0.02-0.23) and 0.07 (0.03-0.15) respectively. This equated to antivenom protection against in-hospital mortality of 93-94% among patients with confirmed coagulopathy though the benefit appeared abrogated among those without coagulopathy. The untreated natural mortality was 15.94% (95%CI:8.24-26.74%) without antivenom therapy while the overall mortality was 84/5105 (1.65%; 95%CI:1.32-2.03%. The Number Needed to Treat (NNT) to avert a death was 7 patients among those with coagulopathy. Antivenoms were safe with mild early adverse reactions observed among 2.6% (95%CI:2.13-3.08%) of antivenom recipients. Polyclonal antibody antivenoms are effective and safe for treating coagulopathic envenomed patients in Nigeria.

Curcumin nanoparticles: physicochemical fabrication, characterization, antioxidant, enzyme inhibition, molecular docking and simulation studies.

Curcumin is an extensively studied natural compound due to its extensive biological applications. However, there are some drawbacks linked to this compound such as poor absorption, low water-solubility, quick systemic elimination, fast metabolism, poor pharmacokinetics, low bioavailability, low penetration targeting efficacy and low stability. To overcome these drawbacks, curcumin is encapsulated in nano-carriers. In the current studies, we synthesized nanoparticles of curcumin without using nanocarriers by different methods such as nano-suspension (Cur-NSM), sonication (Cur-SM) and anti-solvent precipitation (Cur-ASP) to enhance the solubility of curcumin in water. The prepared nanoparticles were characterized by FTIR, SEM and XRD analysis. These curcumin nanoparticles were screened for their solubilities in water, DPPH scavenging, amylase, α-glucosidase and ß-glucosidase enzymatic activities. The particle size of nano-curcumin was found to be in the 47.4-98.7 nm range. The reduction in particle size of curcumin dramatically increases its solubility in water to 79.2 µg mL-1, whereas the solubility of curcumin is just 0.98 µg mL-1. Cur-ASP showed the highest free radical scavenging potential (48.84 ± 0.98%) which was comparable with standard BHT (50.48 ± 1.11%) at 75.0 µg mL-1. As well, Cur-ASP showed the highest inhibition of α-amylase (68.67 ± 1.02%), α-glucosidase (58.30 ± 0.52%), and ß-glucosidase (64.80 ± 0.43%) at 100 µg mL-1 which is comparable with standard drug acarbose. The greater surface area of nanoparticles exposes the various groups of curcumin for blocking the binding sites of enzymes. This strategy may be helpful in designing curcumin as a potent therapeutic agent against diabetes mellitus. Further, the molecular interactions of curcumin with α-amylase, α-glucosidase, ß-glucosidase, and polyphenol oxidase were assessed by analyzing the plausible binding modes of curcumin in the binding pocket of each receptor. The best binding mode of curcumin was used to make complexes with the target proteins and their stability was confirmed by 50 ns MD simulation.

Inclisiran adjuvant therapy to statins for the use of hypercholesterolemia: a commentary.

BACKGROUND: Hypercholesterolemia is a lipid disorder characterized by excessively high levels of low-density lipoproteins, which encourages fat accumulation in your arteries, hence escalating the chances of heart attack and stroke. Globally, 39% of individuals experience elevated total cholesterol levels with 98.6 million DALYs (disability-adjusted life years) caused by high non-HDL cholesterol in 2019, supposedly killing 4.4 million people. MAIN BODY: LDL cholesterol is the primary target of treatment for lowering the risk of cardiovascular events in both primary and secondary prevention. The usual drug to achieve this goal is HMG-CoA reductase inhibitors (statins), which constitute the most potent and effective class to reduce LDL cholesterol. The current treatment of choice for hypercholesterolemia is statin therapy; however, a considerable proportion of patients are unable to reach their desired low-density lipoproteins levels (LDL), while some cannot take statins at all. The regular use and possible non-adherence to long-term therapy of statins have prompted the development of novel PCSK9-targeting drugs such as inclisiran-a synthesized small interfering RNA. Inclisiran binds to the proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA causing its disintegration and hence preventing its formation. This results in reduced amounts of PCSK9 both within and outside the cells, which significantly lowers LDL levels. Multiple double-blind, placebo-controlled Osaka Emergency Information Research Intelligence Operation Network System (ORION) trials were conducted; ORION-9 was conducted on patients with familial hypercholesterolemia and LDL cholesterol levels higher than 100 mg/dl despite taking the maximum dose of statin therapy, whereas ORION-10 and ORION-11 were conducted on patients with cardiovascular disease or having its risk factors. These patients were administered Inclisiran injections on days 1, 90 (month 3), 270 (month 9), and 450 (month 15) and were followed for 540 days. The results showed decreased LDL levels by 51% compared to the placebo and further established a strong link with reduced major adverse cardiac events rates with no effect on creatinine kinase and liver function test levels. The drug's significant side effect was reported to be an injection site reaction. CONCLUSION: Inclisiran may be utilized alone or in conjunction with other lipid-lowering treatments in individuals who are unable to take statins or for whom they are contraindicated. Furthermore, its exceptional stability throughout a broad range of heat conditions makes its use well-suited for developing countries.

Diagnostic characteristics of the 20-minute whole blood clotting test in detecting venom-induced consumptive coagulopathy following carpet viper envenoming.

INTRODUCTION: Envenoming by Echis spp. (carpet or saw-scaled vipers) causes haemorrhage and coagulopathy and represents a significant proportion of snakebites in the savannah regions of West Africa. Early diagnosis of envenoming is crucial in the management of these patients and there is limited evidence on the utility of the 20-minute whole blood clotting test (20WBCT) in diagnosing venom-induced consumptive coagulopathy (VICC) following envenoming by Echis ocellatus. METHODS: A prospective observational cohort study was conducted at the Kaltungo General Hospital in North-eastern Nigeria from September 2019 to September 2021. Standardised 20WBCTs were conducted by trained hospital staff and citrated plasma samples were collected at numerous timepoints. Prothrombin time (PT) and international normalised ratio (INR) were determined using a semi-automated analyser and INR values were calculated using international sensitivity indices (ISI). The sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and likelihood ratios of the 20WBCT compared to an INR ≥ 1.4 were calculated, alongside 95% confidence intervals. RESULTS: We enrolled 121 patients into our study, with a median age of 26 (18.0-35.0) years and a male predominance (75.2%). The 20WBCT was positive (abnormal) in 101 out of 121 patients at timepoint 0h, of which 95 had an INR ≥ 1.4, giving a sensitivity of 87.2% (95%CI 79.4-92.8). Among patients with a negative 20WBCT (normal), six had an INR < 1.4 giving a specificity of 50% (95%CI 21.1-78.9). The positive and negative likelihood ratios were 1.7 (95%CI 1.6-1.9) and 0.3 (95%CI 0.1-0.4) respectively. CONCLUSION: The 20WBCT is a simple, cheap, and easily accessible bedside test with a high sensitivity for the detection of patients with venom induced consumptive coagulopathy (VICC) following envenoming by E. ocellatus, although false positives do occur. Repeated 20WBCTs can identify patients with new, persistent, and rebound coagulopathy.

Comparison of snakebite in children and adults in Nigeria.

Snakebite envenoming is a major global public health problem and disproportionately affects children. To study the differences in clinical presentation and outcomes between children and adults, 2922 snakebite patients of whom 30.3% were children were analysed. Most bites (>75%) were in the lower. Features of local envenoming were commoner among children compared to adults (p < 0.05), while systemic envenoming features, mortality and complications were similar, p = 0.356, p = 0.12, and p = 0.16 respectively.

Determinants of mortality among hospitalized patients with COVID-19 during first and second waves of the pandemic: A retrospective cohort study from an isolation center in Kano, Nigeria.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has emerged as an important cause of morbidity and mortality worldwide. The aim of this study is to identify the clinical predictors of mortality among patients with COVID-19 pneumonia during first and second waves in a treatment center in northwestern Nigeria. METHODS: This was a retrospective cohort study of 195 patients hospitalized with COVID-19 between April 2020 to March 2021 at a designated COVID-19 isolation center in Kano State, Northwest Nigeria. Data were summarized using frequencies and percentages. Unadjusted odds ratios and 95% confidence intervals and p-values were obtained. To determine independent determinants of mortality, we performed a stepwise multivariate logistic regression model. RESULTS: Of 195 patients studied, 21(10.77%) patients died. Males comprised 158 (81.03%) of the study population. In the adjusted stepwise logistic regression analysis, age>64 years (OR = 9.476, 95% CI: 2.181-41.165), second wave of the pandemic (OR = 49.340, 95% CI:6.222-391.247), cardiac complications (OR = 24.984, 95% CI: 3.618-172.508), hypertension (OR = 5.831, 95% CI:1.413-24.065) and lowest systolic blood pressure while on admission greater than or equal to 90mmHg were independent predictors of mortality (OR = 0.111, 95%CI: 0.021-0.581). CONCLUSION: Strategies targeted to prioritize needed care to patients with identified factors that predict mortality might improve patient outcome.

Performance of the 20 minutes Whole Blood Clotting Test in detection, monitoring and antivenom therapy of West African Carpet viper (Echis romani) envenoming in resource constrained settings in Nigeria.

The 20 minutes Whole Blood Clotting Test (20WBCT) was evaluated in 1541 snakebite patients at 3 hospitals in Nigeria. It was useful in detection, monitoring, guiding antivenom therapy and prognostication of coagulopathy, with initial sensitivity of 84.7% (95%CI:82.7-86.5%) and specificity of 64.3% (95%CI:50.4-76.7%) compared to clinical envenoming. It led to correct decisions regarding administration or withholding antivenom in 97.93% of patients. The proportion of carpet viper (Echis romani) envenomed patients who restored clotting rose steadily following effective antivenom therapy. Patients with positive 20WBCT had severer envenoming, required more blood transfusion, had longer hospital stay and derived higher antivenom protection against death from carpet viper. However, there was no association between positive 20WBCT and fatality or complications.

Molecular Characterization of Bacterial Isolates from Soil Samples and Evaluation of their Antibacterial Potential against MDRS.

Some soil microbes, with their diverse inhabitance, biologically active metabolites, and endospore formation, gave them characteristic predominance and recognition among other microbial communities. The present study collected ten soil samples from green land, agricultural and marshy soil sites of Khyber Pakhtunkhwa, Pakistan. After culturing on described media, the bacterial isolates were identified through phenotypic, biochemical and phylogenetic analysis. Our phylogenetic analysis revealed three bacterial isolates, A6S7, A1S6, and A1S10, showing 99% nucleotides sequence similarity with Brevibacillus formosus, Bacillus Subtilis and Paenibacillus dendritiformis. The crude extract was prepared from bacterial isolates to assess the anti-bacterial potential against various targeted multidrug-resistant strains (MDRS), including Acinetobacter baumannii (ATCC 19606), Methicillin-resistant Staphylococcus aureus (MRSA) (BAA-1683), Klebsiella pneumoniae (ATCC 13883), Pseudomonas aeruginosa (BAA-2108), Staphylococcus aureus (ATCC 292013), Escherichia coli (ATCC25922) and Salmonella typhi (ATCC 14028). Our analysis revealed that all bacterial extracts possess activity against Gram-negative and Gram-positive bacteria at a concentration of 5 mg/mL, efficiently restricting the growth of E. coli compared with positive control ciprofloxacin. The study concluded that the identified species have the potential to produce antimicrobial compounds which can be used to control different microbial infections, especially MDRS. Moreover, the analysis of the bacterial extracts through GC-MS indicated the presence of different antimicrobial compounds such as propanoic acid, oxalic acid, phenol and hexadecanoic acid.

A Case of Pulmonary Tumor Thrombotic Microangiopathy: A Rare and Fatal Phenomenon.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a pulmonary hypertensive arteriopathy thought to be caused by activation of the coagulation cascade at the surface of circulating tumor microemboli along with intimal proliferation in small pulmonary arteries in patients with metastatic carcinomas. The subsequent stenosis of the pulmonary vasculature leads to pulmonary hypertension (PH) and, cor pulmonale with eventual respiratory compromise leading to respiratory failure. PTTM is always a nearly fatal disease with most cases diagnosed postmortem. Most cases reported on this condition are from Japan where the incidence of gastric malignancy is relatively higher than other parts of the world. We report a case of a Caucasian man with a classic presentation of PTTM to help make physicians aware of this rare, rapidly progressive and usually fatal phenomenon.

Stress-level glucocorticoids increase fasting hunger and decrease cerebral blood flow in regions regulating eating.

CONTEXT: The neural regulation of appetite and energy homeostasis significantly overlaps with the neurobiology of stress. Frequent exposure to repeated acute stressors may cause increased allostatic load and subsequent dysregulation of the cortico-limbic striatal system leading to inefficient integration of postprandial homeostatic and hedonic signals. It is therefore important to understand the neural mechanisms by which stress generates alterations in appetite that may drive weight gain. OBJECTIVE: To determine glucocorticoid effects on metabolic, neural and behavioral factors that may underlie the association between glucocorticoids, appetite and obesity risk. METHODS: A randomized double-blind cross-over design of overnight infusion of hydrocortisone or saline followed by a fasting morning perfusion magnetic resonance imaging to assess regional cerebral blood flow (CBF) was completed. Visual Analog Scale (VAS) hunger, cortisol and metabolic hormones were also measured. RESULTS: Hydrocortisone relative to saline significantly decreased whole brain voxel based CBF responses in the hypothalamus and related cortico-striatal-limbic regions. Hydrocortisone significantly increased hunger VAS pre-scan, insulin, glucose and leptin, but not other metabolic hormones versus saline CBF groups. Hydrocortisone related increases in hunger were predicted by less reduction of CBF (hydrocortisone minus saline) in the medial OFC, medial brainstem and thalamus, left primary sensory cortex and right superior and medial temporal gyrus. Hunger ratings were also positively associated with plasma insulin on hydrocortisone but not saline day. CONCLUSIONS: Increased glucocorticoids at levels akin to those experienced during psychological stress, result in increased fasting hunger and decreased regional cerebral blood flow in a distinct brain network of prefrontal, emotional, reward, motivation, sensory and homeostatic regions that underlie control of food intake.

Formation and activity of NLRP3 inflammasome and histopathological changes in the lung of corpses with COVID-19.

COVID-19 is a contagious disease that attacks many organs but the lungs are the main organs affected. The inflammasome activation results in the exacerbation of inflammatory response in infectious disease. The aim of this study is to investigate the formation and activity of the NLRP3 inflammasome complex and the histopathological changes caused by the coronavirus in the lung of deceased persons with COVID-19. In total, 10 corpses; 5 corpses with no history of any infectious diseases and COVID-19 and 5 corpses with the cause of death of COVID-19 were included in this study. Lung tissue samples were harvested during autopsy under safe conditions. Fresh tissues in each group were used to measure the genes expression and proteins level of NLRP3, ASC, Caspase-1, IL-1ß, IL-6 and TNF-α and a routine hematoxylin and eosin staining was performed for histological assessment. Data are represented as the means ± SD. Statistical significance difference was accepted at a p-value less than 5%. The NLRP3, ASC, Caspase-1, IL-1ß, IL-6 and TNF-α genes expression and proteins level were elevated in the lung of the COVID-19 group in comparison with the control group. Histological findings presented the increasing number of polymorphonuclear leukocytes, macrophages and also pulmonary fibrosis in the lungs of corpses with the cause of death of COVID-19. High expression of NLRP3 inflammasome components and its relation with the pathophysiology of the coronavirus-infected lung suggested that targeting the NLRP3 inflammasome could be helpful in achieving a more effective treatment in patients with COVID-19.

Safety of glucose-6 phosphate dehydrogenase deficient donors in living right lobe liver donation.

BACKGROUND: The literature lacks data on World Health Organization (WHO) class II and III deficient liver donors who underwent right hepatectomy during living donor liver transplantation (LDLT). METHODS: In this prospective cohort study, we compared the perioperative outcomes of 15 glucose-6 phosphate dehydrogenase (G6PD) deficient living liver donors with a matched cohort of 39 nondeficient living liver donors undergoing right lobe donation. RESULTS: Out of 15 G6PD deficient donors, four (26.67%) donors had class II, and 11 (73.34%) had class III G6PD deficiency. The mean postoperative trough hemoglobin level was significantly lower in the deficient group than the nondeficient group (9.38 ± 1.59 g/dL vs. 10.27 ± .91 g/dL, p = .046). The mean peak indirect bilirubin level was significantly higher in the deficient group than the nondeficient group (2.22 ± 1.38 mg/dL vs. 1.40 ± .89 mg/dL, p = .047), and a similar trend was observed in total serum bilirubin (3.99 ± 2.57 mg/dL vs. 2.99 ± 1.46 mg/dL, p = .038). Biochemical evidence of hemolysis was found only in three (20%) deficient donors, but none of them needed a blood transfusion. No mortality was observed in either group. All other parameters, including demographics, operative parameters, graft characteristics, and hospital stay were comparable between both groups (p > .05). CONCLUSION: G6PD deficiency with WHO class II and above should not be considered a contraindication for right lobe donation.