Study of mid and long term outcome of hip fracture in elderly operated within 48 hours versus conservative management

Background: Hip fractures are commonly associated with high morbidities and mortalities. This study aimed to determine post-hip fracture outcomes and survival among patients who underwent operation within 48 hours of fracture diagnosis and among those being treated conservatively.Methods: This retrospective cohort study was conducted at the Hospital Seberang Jaya among patients diagnosed with hip fracture from January to December 2016; confirmed clinical and radiological method. Descriptive analysis was conducted using Statistical package for social sciences (SPSS) version 23.Results: The mean (SD) age of the 61 operated patients was 74 (7.7) years and for the 19 conservatively managed patients 79 (8.0) years. At 12 months, 30 (37.5%) of operated ones, required assisted mobility compared to 8 (10%) of conservatively managed patients. Other outcomes comparable between operated and conservative patients at 12 months post-intervention include: ability to feed on own 46 (57.5%) versus 7 (8.8%), able to dress on own, 45 (56.3%) versus 6 (7.5%); able to bathe on own; 43 (53.8%) versus 2 (2.5%), and independently attending to own toilet needs 44 (55.0%) versus 1 (1.3%). Our study revealed, overall survival were comparatively better among those operated to conservative at 12 months; 52 (85%) versus 9 (47.4%). The mortality at 12 months in the conservative group is much higher than operative group.Conclusions: Ambulatory mobility and survival are significantly better at 12 months post-fracture among the operated patients. Hip fracture must be treated as an emergency and its surgical management given priority.

The influence of OLR1 and PCSK9 gene polymorphisms on ischemic stroke: Evidence from a meta-analysis

It has been reported that both OLR1 and PCSK9 genes are related to various vascular diseases such as atherosclerosis, cardiovascular disease, peripheral artery disease and stroke, in particular ischemic stroke. The prevalence of PCSK9 rs505151 and OLR1 rs11053646 variants in ischemic stroke were 0.005 and 0.116, respectively. However, to date, association between OLR1 rs11053646 and PCSK9 rs505151 polymorphisms and the risk of ischemic stroke remains unclear and inconclusive. Therefore, this first meta-analysis was carried out to clarify the presumed influence of genetic polymorphisms on ischemic stroke, by analyzing the complete coverage of all relevant studies. All eligible case-control and cohort studies that met the search term were retrieved in multiple scientific databases. Data of interest such as demographic data and genotyping methods were extracted from each study, and the meta-analysis was performed using RevMan 5.3 and Metafor R 3.2.1. The pooled odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed- and random-effect models. A total of seven case-control studies encompassing 1897 ischemic stroke cases and 2119 healthy controls were critically evaluated. Pooled results from the genetic models indicated that OLR1 rs11053646 dominant (OR=1.33. 95%CI:1.11-1.58) and co-dominant models (OR=1.24, 95%CI:1.02-1.51) were significantly associated with ischemic stroke. For PCSK9 rs505151 polymorphism, the OR of co-dominant model (OR=1.36, 95%CI:1.01-1.58) was found to be higher among ischemic stroke patients. In conclusion, the current meta-analysis highlighted that variant allele of OLR1 rs11053646 G>C and PCSK9 rs505151 A>G may contribute to the susceptibility risk of ischemic stroke

What Is the Estimated COVID-19 Reproduction Number and the Proportion of the Population That Needs to Be Immunized to Achieve Herd Immunity in Malaysia? A Mathematical Epidemiology Synthesis

We aimed to determine Malaysia’s COVID-19 reproduction number and herd immunity threshold through a mathematical epidemiology synthesis. Using time-series incidence data, the time-dependent reproduction number (Rt) was yielded over time during the COVID-19 containment measures in Malaysia. The value of Rt at the beginning of the epidemic and prior to any interventions in place was used to determine the proportion of the population that needs to be immunized to achieve herd immunity. Rt was strongly influenced by interventions being put in place. We established that at least 74% of the Malaysian population needs to be vaccinated to achieve herd immunity against COVID-19. This threshold estimate is somewhat influenced by the availability of an efficacious vaccine. A vaccine with 95% efficacy would approximately synthesize a herd immunity threshold of 78%. We conclude that Rt is a valid estimator to determine the effectiveness of control measures and a parameter of use to synthesize herd immunity thresholds in the current COVID-19 pandemic

Gender disparities and thrombolysis use among patient with first-ever ischemic stroke in Malaysia

Objective: Gender as an independent predictor in stroke has been well documented. However, data on gender differences among first-ever ischemic stroke in developing country are limited. We aim to describe gender effects on clinical characteristics, thrombolysis treatment received, and outcomes of patients with first-ever ischemic stroke. Methods: Data were extracted from the prospective multiethnic stroke registry, National Neurology Registry (NNEUR). Descriptive analysis and logistic regression were performed. Results: A total of 4762 first-ever ischemic stroke patients admitted to 13 government hospitals from July 2009 to June 2015 were available for this study. Slightly over half were male (55.1%), and they were 1.7 years younger than female (mean age, 63.6 versus 61.9 years, p < 0.001). Gender–age-adjusted incidence was observed to be higher in females (66.7 per 100,000) compared to males (57.4 per 100,000). First-ever ischemic stroke incidence increased by 24.3 and 11.2% among female and male annually. Female experienced significantly poorer functional outcome and greater 30-day in-hospital mortality compared to male. In subgroup analysis, only 31 (0.65%) patients were treated with thrombolysis. Discussion: First-ever ischemic stroke incidence increased by 24.3 and 11.2% among female and male annually. There were distinct symptoms at hospital presentation between genders. All our patients discharged home regardless of genders. In summary, Malaysian female first-ever ischemic stroke was older, present with severe stroke, greater number of risk factors and poorer functional outcome and 30-day in-hospital mortality compared to male

Phenytoin toxicity presenting with acute visual loss and acute delirium, a case report

Phenytoin is a widely prescribed antiepileptic agent for both focal and generalized seizure. We report a case of a 20-year-old man with focal epilepsy presented with acute bilateral visual loss, and delirium. His random phenytoin serum concentration on admission was 43.6 mg/L, well above the recommended therapeutic range of 10-20 mg/L. Extensive investigations have ruled out other vascular or demyelinating causes. His visual symptoms completely resolved after discontinuing phenytoin for 84 hours. This case shows that acute phenytoin toxicity can result in reversible visual failure

Association of NOTCH3 gene polymorphisms with ischemic stroke and its subtypes: A meta-analysis

Background and objectives: NOTCH3 gene variations play a significant role in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, the role of NOTCH3 gene polymorphisms in the risk of ischemic stroke, and its subtypes such as atherothrombotic or lacunar strokes, remains unclear. Aims: Hence, we carried out a meta-analysis to examine whether the NOTCH3 rs1043994, rs1044009 and rs3815188 polymorphisms are associated with ischemic stroke and its major subtypes. Materials and Methods: All relevant studies were systematically screened and meta-analyzed using Review Manager (Revman) version 5.3. The strength of the association between NOTCH3 polymorphisms and ischemic stroke risk and its subtypes were measured as odds ratios and 95% confidence intervals, under different genetic models. Results: A total of ten studies were identified, five of which considered NOTCH3 rs1043994 (2077 cases/2147 controls), five of which considered NOTCH3 rs1044009 (2315 cases/3053 controls), and nine of which considered NOTCH3 rs3815188 (2819 cases/2769 controls). These studies were meta-analyzed for their association with ischemic stroke risk. Four studies (874 cases/2002 controls) of the NOTCH3 rs3815188 polymorphism and three studies of the NOTCH3 rs1043994 (643 cases/1552 controls) polymorphism were meta-analyzed for lacunar stroke risk. Three studies (1013 cases/1972 controls) of the NOTCH3 rs3815188 polymorphism were meta-analyzed for atherothrombotic stroke risk. The meta-analysis results showed a lack of association between all of the studied polymorphisms and the risk of ischemic stroke and its major subtypes (i.e., atherothrombotic and lacunar). Conclusions: NOTCH3 polymorphisms are not significantly associated with the risk of ischemic stroke and its subtypes (p < 0.05).</p

Clinicians’ Perceived Understanding of Biostatistical Results in the Medical Literature: A Cross-Sectional Study

Background and objectives: The continuum of evidence-based medicine (EBM) depends solely on clinicians&#8217; commitment to keep current with the latest clinical information. Exploration on clinicians&#8217; understanding of biostatistical results in the medical literature is sparse to date. This study aimed to evaluate clinicians&#8217; perceived understanding of biostatistical results in the medical literature and the factors influencing them. Materials and Methods: A cross-sectional study was conducted among 201 clinicians at the Seberang Jaya Hospital, a cluster-lead research hospital in Northern Malaysia. A self-administered questionnaire that consisted of items on sociodemographics, validated items on clinicians&#8217; confidence level in interpreting statistical concepts, perceived understanding of biostatistics, and familiarity with different statistical methods were used. Descriptive, univariate, and multivariate analyses were conducted. Results: Perceived understanding of biostatistical results among clinicians in our sample was nearly 75%. In the final regression model, perceived understanding was significantly higher among clinicians who were able to interpret p-values with complete confidence (AOR = 3.0, 95% CI 1.1&#8722;8.1), clinicians who regularly encounter measures of central tendencies (AOR = 2.3, 95% CI 1.1&#8722;5.2), and clinicians who regularly encounter inferential statistics (AOR = 2.2, 95% CI 1.1&#8722;4.5) while appraising the medical literature. Conclusions: High perceived understanding was significantly associated with clinicians&#8217; confidence in interpreting statistical concepts and familiarity with different statistical methods. Our findings form a platform to understand clinicians&#8217; ability to appraise rigorous biostatistical results in the medical literature for the retrieval of evidence-based data to be used in routine clinical practice

The impact of APOA5 , APOB , APOC3 and ABCA1 gene polymorphisms on ischemic stroke: Evidence from a meta-analysis

<b>BACKGROUND AND AIMS</b>\ud \ud Genetic studies have been reported on the association between APOA5, APOB, APOC3 and ABCA1 gene polymorphisms and ischemic stroke, but results remain controversial. Hence, this meta-analysis aimed to infer the causal relationships of APOA5 (rs662799, rs3135506), APOB (rs693, rs1042031, rs1801701), APOC3 (rs4520, rs5128, rs2854116, rs2854117) and ABCA1 rs2230806 with ischemic stroke risk.\ud \ud <b>METHODS</b>\ud \ud A systematic review was performed for all the articles retrieved from multiple databases, up until March 2017. Data were extracted from all eligible studies, and meta-analysis was carried out using RevMan 5.3 and R package 3.2.1. The strength of association between each studied polymorphism and ischemic stroke risk was measured as odds ratios (ORs) and 95% confidence intervals (CIs), under fixed- and random-effect models.\ud \ud <b>RESULTS</b>\ud \ud A total of 79 studies reporting on the association between the studied polymorphisms and ischemic stroke risk were identified. The pooled data indicated that all genetic models of APOA5 rs662799 (ORs = 1.23-1.43), allelic and over-dominant models of APOA5 rs3135506 (ORs = 1.77-1.97), APOB rs1801701 (ORs = 1.72-2.13) and APOB rs1042031 (ORs = 1.66-1.88) as well as dominant model of ABCA1 rs2230806 (OR = 1.31) were significantly associated with higher risk of ischemic stroke. However, no significant associations were observed between ischemic stroke and the other five polymorphisms, namely ApoB (rs693) and APOC3 (rs4520, rs5128, rs2854116 and rs2854117), under any genetic model.\ud \ud <b>CONCLUSIONS:</b>\ud \ud The present meta-analysis confirmed a significant association of APOA5 rs662799 CC, APOA5 rs3135506 CG, APOB rs1801701 GA, APOB rs1042031 GA and ABCA1 rs2230806 GG with increased risk of ischemic stroke

Influence of Population Density for COVID-19 Spread in Malaysia: An Ecological Study

The rapid transmission of highly contagious infectious diseases within communities can yield potential hotspots or clusters across geographies. For COVID-19, the impact of population density on transmission models demonstrates mixed findings. This study aims to determine the correlations between population density, clusters, and COVID-19 incidence across districts and regions in Malaysia. This countrywide ecological study was conducted between 22 January 2021 and 4 February 2021 involving 51,476 active COVID-19 cases during Malaysia’s third wave of the pandemic, prior to the reimplementation of lockdowns. Population data from multiple sources was aggregated and spatial analytics were performed to visualize distributional choropleths of COVID-19 cases in relation to population density. Hierarchical cluster analysis was used to synthesize dendrograms to demarcate potential clusters against population density. Region-wise correlations and simple linear regression models were deduced to observe the strength of the correlations and the propagation effects of COVID-19 infections relative to population density. Distributional heats in choropleths and cluster analysis showed that districts with a high number of inhabitants and a high population density had a greater number of cases in proportion to the population in that area. The Central region had the strongest correlation between COVID-19 cases and population density (r = 0.912; 95% CI 0.911, 0.913; p &lt; 0.001). The propagation effect and the spread of disease was greater in urbanized districts or cities. Population density is an important factor for the spread of COVID-19 in Malaysia

Assessment of the nlmixr R package for population pharmacokinetic modeling: A metformin case study

AIM: nlmixr offers first-order conditional estimation with or without interaction (FOCE or FOCEi) and stochastic approximation estimation-maximisation (SAEM) to fit nonlinear mixed-effect models (NLMEM). We modelled metformin's pharmacokinetic data using nlmixr and investigated SAEM and FOCEi's performance with respect to bias and precision of parameter estimates, and robustness to initial estimates. METHOD: Compartmental models were fitted. The final model was determined based on the objective function value and inspection of goodness-of-fit plots. The bias and precision of parameter estimates were compared between SAEM and FOCEi using stochastic simulations and estimations. For robustness, parameters were re-estimated as the initial estimates were perturbed 100-times and resultant changes evaluated. RESULTS: Absorption kinetics of metformin depends significantly on food status. Under the fasted state, the first-order absorption into the central compartment was preceded by zero-order infusion into the depot compartment, whereas for the fed state, the absorption into the depot was instantaneous followed by first-order absorption from depot into the central compartment. The mean of relative mean estimation error (rMEE) ( ME E SAEM ME E FOCEi ) and rRMSE ( RMS E SAEM RMS E FOCEi ) was 0.48 and 0.35 respectively. All parameter estimates given by SAEM appeared to be narrowly distributed and were close to the true value used for simulation. In contrast, the distribution of estimates from FOCEi were skewed and more biased . When initial estimates were perturbed, FOCEi estimates were more biased and imprecise. DISCUSSION: nlmixr is reliable for NLMEM. SAEM was superior to FOCEi in terms of bias and precision, and more robust against initial estimate perturbations