Pre-treatment re-bleeding following aneurysmal subarachnoid hemorrhage: A systematic review of published prediction models with risk of bias and clinical applicability assessment.

BACKGROUND: Pre-treatment rebleeding following aneurysmal subarachnoid hemorrhage (aSAH) increases the risk of death and a poor neurological outcome. Current guidelines recommend aneurysm treatment "as early as feasible after presentation, preferably within 24 h of onset" to mitigate this risk, a practice termed ultra-early treatment. However, ongoing debate regarding whether ultra-early treatment is independently associated with reduced re-bleeding risk, together with the recognition that re-bleeding occurs even in centres practicing ultra-early treatment due to the presence of other risk-factors has resulted in a renewed need for patient-specific re-bleed risk prediction. Here, we systematically review models which seek to provide patient specific predictions of pre-treatment rebleeding risk. METHODS: Following registration on the International prospective register of systematic reviews (PROSPERO) CRD 42023421235; Ovid Medline (Pubmed), Embase and Googlescholar were searched for English language studies between 1st May 2002 and 1st June 2023 describing pre-treatment rebleed prediction models following aSAH in adults ≥18 years. Of 763 unique records, 17 full texts were scrutinised with 5 publications describing 4 models reviewed. We used the semi-automated template of Fernandez-Felix et al. incorporating the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist and the Prediction model Risk Of Bias ASsessment Tool (PROBAST) for data extraction, risk of bias and clinical applicability assessment. To further standardize risk of bias and clinical applicability assessment, we also used the published explanatory notes for the PROBAST tool and compared the aneurysm treatment practices each prediction model's formulation cohort experienced to a prespecified benchmark representative of contemporary aneurysm treatment practices as outlined in recent evidence-based guidelines and published practice pattern reports from four developed countries. RESULTS: Reported model discriminative performance varied between 0.77 and 0.939, however, no single model demonstrated a consistently low risk of bias and low concern for clinical applicability in all domains. Only the score of Darkwah Oppong et al. was formulated using a patient cohort in which the majority of patients were managed in accordance with contemporary, evidence-based aneurysm treatment practices defined by ultra-early and predominantly endovascular treatment. However, this model did not undergo calibration or clinical utility analysis and when applied to an external cohort, its discriminative performance was substantially lower that reported at formulation. CONCLUSIONS: No existing prediction model can be recommended for clinical use in centers practicing contemporary, evidence-based aneurysm treatment. There is a pressing need for improved prediction models to estimate and minimize pre-treatment re-bleeding risk.

Validity and reliability of the Sinhalese version of the perceived stress scale questionnaire among Sri Lankans.

Introduction: Despite the availability of validated psychometrics tools to assess depression, there has not been any validated and reliable tool established to test perceived stress among Sri Lankans. The objective of this study is to test the validity and reliability of the Sinhalese Version of the Sheldon Cohen Perceived Stress Scale. Materials and methods: Standard and systematic procedures were adopted to translate the original English version of the Perceived Stress Scale-10 questionnaire into Sinhalese. Consecutive sampling was employed to recruit the Type 2 Diabetes mellitus (T2DM) sample (n = 321), and a convenient sampling was used to recruit the Age and Sex matched Healthy Controls (ASMHC) (n = 101) and the Healthy Community Controls (HCC) groups (n = 75). Cronbach alpha was used to assess internal consistency and reliability was determined using test-retest method utilizing Spearman's correlation coefficient. Sensitivity was evaluated by comparing the mean scores of the Sinhalese Perceived Stress Scale (S-PSS-10) and Sinhalese Patient Health Questionnaire (S-PHQ-9) scores. Post-hoc comparisons were done using Bonferroni's method. Mean scores were compared between the T2DM, ASMHC, and HCC groups using the independent t-test. Explanatory Factor Analysis (EFA) was conducted using the principal component and Varimax rotation while the Confirmatory Factor Analysis (CFA) was performed to assess the goodness-of-fit of the factor structure extracted from the EFA. Concurrent validity was assessed using the Pearson correlation between the S-PSS-10 and Patient Health Questionnaire measured by S-PHQ-9 (p < 0.05). Results: Cronbach alpha values of the three groups T2DM, ASMHC and HCC were 0.85, 0.81, and 0.79, respectively. Results of the ANOVA test suggested that there was a significant difference in the mean scores between groups (p < 0.00). EFA analysis revealed the existence of two factors with eigenvalues greater than 1.0. The factor loadings for the items ranged from 0.71-0.83. The CFA analysis demonstrated a good model fit for the two-factor model S-PSS-10. The S-PSS-10 significantly correlated with S-PHQ-9, indicating an acceptable concurrent validity. Conclusion: Findings revealed that the S-PSS-10 questionnaire can be used to screen perceived stress among the majority of the Sri Lankan Sinhalese-speaking population specially with chronic illnesses. Further studies with higher sample sizes across different populations would enhance the validity and reliability of S-PSS-10.

Rebleeding following aneurysmal subarachnoid hemorrhage before 'endovascular first' treatment: a retrospective case-control study of published scoring systems.

BACKGROUND: Pre-treatment re-bleeding following aneurysmal subarachnoid hemorrhage (aSAH) affects up to 7.2% of patients even with ultra-early treatment within 24 hours. We retrospectively compared the utility of three published re-bleed prediction models and individual predictors between cases who re-bled matched to controls using size and parent vessel location from a cohort of patients treated in an ultra-early, 'endovascular first' manner. METHODS: On retrospective analysis of our 9-year cohort of 707 patients suffering 710 episodes of aSAH, there were 53 episodes of pre-treatment re-bleeding (7.5%). Forty-seven cases who had a single culprit aneurysm were matched to 141 controls. Demographic, clinical and radiological data were extracted and predictive scores calculated. Univariate, multivariate, area under the receiver operator characteristic curve (AUROCC) and Kaplan-Meier (KM) survival curve analyses were performed. RESULTS: The majority of patients (84%) were treated using endovascular techniques at a median 14.5 hours post-diagnosis. On AUROCC analysis the score of Liu et al. had minimal utility (C-statistic 0.553, 95% confidence interval (CI) 0.463 to 0.643) while the risk score of Oppong et al. (C-statistic 0.645 95% CI 0.558 to 0.732) and the ARISE-extended score of van Lieshout et al. (C-statistic 0.53 95% CI 0.562 to 0.744) had moderate utility. On multivariate modeling, the World Federation of Neurosurgical Societies (WFNS) grade was the most parsimonious predictor of re-bleeding (C-statistic 0.740, 95% CI 0.664 to 0.816). CONCLUSIONS: For aSAH patients treated in an ultra-early timeframe matched on size and parent vessel location, WFNS grade was superior to three published models for re-bleed prediction. Future re-bleed prediction models should incorporate the WFNS grade.

Potential role of microRNAs in selective hepatic insulin resistance: From paradox to the paradigm.

The paradoxical action of insulin on hepatic glucose metabolism and lipid metabolism in the insulin-resistant state has been of much research interest in recent years. Generally, insulin resistance would promote hepatic gluconeogenesis and demote hepatic de novo lipogenesis. The underlying major drivers of these mechanisms were insulin-dependent, via FOXO-1-mediated gluconeogenesis and SREBP1c-mediated lipogenesis. However, insulin-resistant mouse models have shown high glucose levels as well as excess lipid accumulation. As suggested, the inert insulin resistance causes the activation of the FOXO-1 pathway promoting gluconeogenesis. However, it does not affect the SREBP1c pathway; therefore, cells continue de novo lipogenesis. Many hypotheses were suggested for this paradoxical action occurring in insulin-resistant rodent models. A "downstream branch point" in the insulin-mediated pathway was suggested to act differentially on the FOXO-1 and SREBP1c pathways. MicroRNAs have been widely studied for their action of pathway mediation via suppressing the intermediate protein expressions. Many in vitro studies have postulated the roles of hepato-specific expressions of miRNAs on insulin cascade. Thus, miRNA would play a pivotal role in selective hepatic insulin resistance. As observed, there were confirmations and contradictions between the outcomes of gene knockout studies conducted on selective hepatic insulin resistance and hepato-specific miRNA expression studies. Furthermore, these studies had evaluated only the effect of miRNAs on glucose metabolism and few on hepatic de novo lipogenesis, limiting the ability to conclude their role in selective hepatic insulin resistance. Future studies conducted on the role of miRNAs on selective hepatic insulin resistance warrant the understanding of this paradoxical action of insulin.

A Rare Case of Micro-Angiopathic Hemolytic Anemia Due to Envenoming by Giant Asian Honey Bee (Apis dorsata).

Giant Asian honey bee sting envenoming is a recognized cause of morbidity and mortality in rural Sri Lanka. Mass envenoming causes clinical effects, either as allergic and anaphylactic reactions or bee sting toxin-induced multiorgan damage. We report a patient who had mass envenoming from more than 1000 stingers who subsequently developed hematologic features suggestive of thrombotic microangiopathy-related hemolytic anemia. The transient acute kidney injury and acute hepatic failure seen in the patient were also considered to be secondary to thrombotic microangiopathy. A normal clotting profile and a high proportion of schistocytes in blood film ruled out disseminated intravascular coagulation as the underlying cause of the microangiopathic hemolytic anemia. The normal platelet count raised the possibility of a "partial" thrombotic microangiopathy, as has previously been reported in association with Shiga toxin-related hemolytic uremic syndrome and hump-nosed pit viper envenoming. Venom-induced direct toxicity on red cells was another possible explanation for the hemolysis, but the high proportion of schistocytes made it less likely. The place of therapeutic plasma exchange for venom-associated thrombotic microangiopathy is controversial. The patient recovered with symptomatic treatment and meticulous fluid management, without needing therapeutic plasma exchange as an adjunct treatment.

Preparedness of pre-intern medical graduates of three universities in Sri Lanka to diagnose and manage anaphylaxis.

BACKGROUND: Early recognition and the optimal management of anaphylaxis saves lives but studies from different countries have demonstrated gaps in knowledge and practices between healthcare workers. There is a paucity of such data from Sri Lanka. We assessed knowledge, perception and self-confidence in the diagnosis and management of anaphylaxis amongst pre-intern medical graduates who would soon become first-contact doctors attending emergencies. METHODS: This cross-sectional study included pre-interns who graduated with Bachelor of Medicine, Bachelor of Surgery (MBBS) degrees in 2019 from three Sri Lankan universities with differing undergraduate curricula. Using consecutive sampling data were collected within four months of the final-MBBS examinations with a self-administered questionnaire and the answers on case diagnosis and management were used as the basis of outcome scores. RESULTS: 385 participants responded (response rate: 91.5%). 16.4% correctly identified all anaphylaxis triggers. Only 7.3% correctly diagnosed all ten case scenarios and 34.5% all seven cases of anaphylaxis. 98.2 and 97.9% correctly identified 1:1000 adrenaline as the first-line treatment and the intramuscular route. 9.9% would preferentially but incorrectly use the intravenous route if access was available. Only 79.2 and 55.6% knew the correct adult and paediatric doses of adrenaline and 50% agreed that follow-up care was needed. The mean scores for case diagnosis and management of anaphylaxis were 7.7/10 ± 1.4 and 16.9/20 ± 1.9, respectively. Multiple linear regression indicated that the final MBBS results classification (class of degree or no class indicated) was a positive predictor of case diagnosis score [class vs no class: B = 0.662 (95% CI 0.347-0.978), p < 0.001] and being a graduate of University 2 [B = 1.568 (95% CI 1.182-1.953), p < 0.001] and passing with a class at final MBBS [B = 0.716 (95% CI 0.319-1.113), p < 0.001] were positive predictors of management score. Self confidence in diagnosing and managing anaphylaxis were rated as 79.7 and 62.1% and there was a positive correlation between knowledge and perception scores and self-confidence (case-diagnosis: rpb = 0.111, p = 0.03; management: rpb = 0.164, p = 0.001). CONCLUSIONS: Knowledge, perception and self confidence in the diagnosis and management of anaphylaxis was sub optimal amongst pre-interns and we identified areas that need improvement. A higher MBBS qualification classification was a predictor for correct diagnosis and management and confidence in diagnosis and management positively correlated with knowledge and perception scores. Further and enhanced educational and training strategies are needed for this life threatening emergency condition.

Modulation of saccades in humans by electrical stimulation of the posterior subthalamic area.

OBJECTIVE: Posterior subthalamic area (PSA) deep brain stimulation (DBS) targeting the zona incerta (ZI) is an emerging treatment for tremor syndromes, including Parkinson's disease (PD) and essential tremor (ET). Evidence from animal studies has indicated that the ZI may play a role in saccadic eye movements via pathways between the ZI and superior colliculus (incerto-collicular pathways). PSA DBS permitted testing this hypothesis in humans. METHODS: Sixteen patients (12 with PD and 4 with ET) underwent DBS using the MRI-directed implantable guide tube technique. Active electrode positions were confirmed at the caudal ZI. Eye movements were tested using direct current electrooculography (EOG) in the medicated state pre- and postoperatively on a horizontal predictive task subtending 30°. Postoperative assessments consisted of stimulation-off, constituting a microlesion (ML) condition, and high-frequency stimulation (HFS; frequency = 130 Hz) up to 3 V. RESULTS: With PSA HFS, the first saccade amplitude was significantly reduced by 10.4% (95% CI 8.68%-12.2%) and 12.6% (95% CI 10.0%-15.9%) in the PD and ET groups, respectively. With HFS, peak velocity was reduced by 14.7% (95% CI 11.7%-17.6%) in the PD group and 27.7% (95% CI 23.7%-31.7%) in the ET group. HFS led to PD patients performing 21% (95% CI 16%-26%) and ET patients 31% (95% CI 19%-38%) more saccadic steps to reach the target. CONCLUSIONS: PSA DBS in patients with PD and ET leads to hypometric, slowed saccades with an increase in the number of steps taken to reach the target. These effects contrast with the saccadometric findings observed with subthalamic nucleus DBS. Given the location of the active contacts, incerto-collicular pathways are likely responsible. Whether the acute finding of saccadic impairment persists with chronic PSA stimulation is unknown.

Health promotion in workplaces as a strategy for modification of risk factors for Non Communicable Diseases (NCDs): A practical example from Sri Lanka.

BACKGROUND: Non communicable diseases (NCDs) are emerging as a major public health concern worldwide and became a leading cause of mortality in Sri Lanka accounting for 65% of deaths. Health promotion strategies aimed at lifestyle modification are helpful in modifying risk factors for NCDs. OBJECTIVES: To transform a workplace to a health promotion setting where lifestyle changes in workers lead to a modification of risk factors for NCDs. METHODS: A health promotion program was conducted in a divisional administrative office, in Sri Lanka. An office health promotion committee was established and an action plan was prepared with participation of the workers. An interviewer administrated questionnaire was used to assess risk factors for NCDs. Workers were then screened for NCDs. Behavioral change and communication (BCC) programs were conducted to improve physical activity and dietary modifications. RESULTS: Workers actively participated realizing the ownership of their health. 32 males and 49 females (mean age of 40.8 years) were assessed. Among them, 23.4% were overweight and obese while 26% reported physical inactivity. Among males, 12.5% were smokers. Hypertension and dyslipidaemia were present among 9.9% and 12.3%, respectively. 6.2% had high fasting blood glucose values. The program resulted in identifying 12 new patients with NCDs. After initiating health promotion activities, smoking rate dropped by 75%. Physical inactivity was reduced by 14% and consumption of fresh fruits and vegetables increased by 19%. CONCLUSIONS: Programs targeting office settings are a new strategy for reduction of NCDs in Sri Lanka. True benefit of risk factor modification through BCC programs will become apparent in longitudinal assessments.

What cardioversion protocol for ventricular fibrillation should be followed for patients who arrest shortly post-cardiac surgery?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was how many cardioversion attempts should be performed for patients who have gone into ventricular fibrillation post-cardiac surgery prior to performing chest reopening. Using the reported search, 1183 papers were identified. Fifteen papers represented the best evidence on the subject. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study comments and weaknesses were tabulated. The quality and level of evidence was assessed using the International Liaison Committee of Resuscitation guideline recommendations. The most recent European Resuscitation Council guidelines suggest single attempts at cardioversion, spaced at 2-min intervals, for all patients going into ventricular fibrillation or pulseless ventricular tachycardia. Cardiac surgery presents a unique challenge for these guidelines in that emergency re-sternotomy may provide additional lifesaving interventions once it is deemed that external cardioversion is unlikely to succeed. The 15 papers identified demonstrated that the success of the first attempt at cardioversion for VF/VT was around 78%. The chance of the second shock succeeding was around 35%. The chance of a third shock succeeding was 14%. Very little data were found on the chance of further shocks succeeding. Of note none of these papers were in patients on the intensive care after cardiac surgery. We conclude that, due to the importance of minimising the delay to chest reopening, three shocks should be quickly delivered. If these do not succeed the chance of a 4th shock succeeding is likely to be <10% and, thus, immediate chest reopening should be performed. (This is a Class-IIa recommendation using ILCOR guideline recommendations.).