Causes, risks and care circumstances associated with death in older adults diagnosed with HIV in a tertiary centre in Malaysia.

BACKGROUND: A substantial number of older adults succumb soon after HIV diagnosis despite ART. We explored the causes, risk factors and circumstances before death among older adults acquring HIV. METHODS: We recruited individuals newly diagnosed at our centre from 2016-2020 and analysed data of those who died. Patients were stratified to older (≥50 years) or younger (<50 years) based on their age at diagnosis and attributes were compared. The Cox proportional multivariable model was used to identify factors associated with all-cause mortality. RESULTS: Among 75 deaths reported, the majority of deaths were AIDS-related and late presentation was common in both age groups. The majority of deaths occurred in the first 12 months after care presentation and over two-thirds in both groups disengaged from care prior to death. Older age remained an independent factor associated with death after adjusting for confounders including opportunistic infections, late presentation to care, ART initiation and chronic comorbidities at presentation. CONCLUSION: Most causes of death in our setting were AIDS-related and associated with late care presentation both in young and older individuals, although older age at diagnosis remained an independent risk factor. Our findings highlight the urgent need to encourage prompt ART initiation following diagnosis, especially in older adults.

Synergistic effects of miR-143 with miR-99a inhibited cell proliferation and induced apoptosis in breast cancer.

Breast cancer (BC) is the most common cancer type and the fifth leading cause of cancer-related deaths. The primary goals of BC treatment are to remove the tumor and prevent metastasis. Despite advances in BC treatment, more effective therapies are required. miRNAs can regulate many targets involved in biological processes and tumor progression; these molecules have emerged as a promising cancer treatment strategy. In the present study, we investigated the effects of miR-99a and miR-143 in single expression plasmids for BC inhibition. In this study, the precursor structure of miRNAs in the expression vector pEGFP-N1 entered single and double states, and MCF7 and T47D cells were transfected. The miRNAs expression level after transfection was then measured using qPCR. The MultiMiR package was used to obtain predicted and validated miRNA targets. MTT assay, qRT-PCR, migration test, and flow cytometry were used to assess the effect of miRNA and gene modulation. The qPCR results revealed that miRNA constructs were significantly expressed after the transfection of both cell lines. The biological function of miRNAs showed that upregulation of miR-99a and miR-143 in any of the two selected BC cells inhibited their proliferation and migration rate, significantly inducing apoptosis (p < 0.01). Also, miR-99a/miR-143 co-treatment has a synergistic anticancer effect in cancer cells via Akt1 and CDK6 targeting. These findings suggest that miR-99a/miR-143 plays synergistic regulatory roles in BC, possibly via a shared signaling pathway, providing a therapeutic strategy for BC treatment.

Treatment of Refractory Status Epilepticus With Continuous Intravenous Anesthetic Drugs: A Systematic Review.

Importance: Multiple continuous intravenous anesthetic drugs (CIVADs) are available for the treatment of refractory status epilepticus (RSE). There is a paucity of data comparing the different types of CIVADs used for RSE. Objective: To systematically review and compare outcome measures associated with the initial CIVAD choice in RSE in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Evidence Review: Data sources included English and non-English articles using Embase, MEDLINE, PubMed, and Web of Science (January 1994-June 2023) as well as manual search. Study selection included peer-reviewed studies of 5 or more patients and at least 1 patient older than 12 years with status epilepticus refractory to a benzodiazepine and at least 1 standard antiseizure medication, treated with continuously infused midazolam, ketamine, propofol, pentobarbital, or thiopental. Independent extraction of articles was performed using prespecified data items. The association between outcome variables and CIVAD was examined with an analysis of variance or χ2 test where appropriate. Binary logistic regressions were used to examine the association between outcome variables and CIVAD with etiology, change in mortality over time, electroencephalography (EEG) monitoring (continuous vs intermittent), and treatment goal (seizure vs burst suppression) included as covariates. Risk of bias was addressed by listing the population and type of each study. Findings: A total of 66 studies with 1637 patients were included. Significant differences among CIVAD groups in short-term failure, hypotension, and CIVAD substitution during treatment were observed. Non-epilepsy-related RSE (vs epilepsy-related RSE) was associated with a higher rate of CIVAD substitution (60 of 120 [50.0%] vs 11 of 43 [25.6%]; odds ratio [OR], 3.11; 95% CI, 1.44-7.11; P = .006) and mortality (98 of 227 [43.2%] vs 7 of 63 [11.1%]; OR, 17.0; 95% CI, 4.71-109.35; P < .001). Seizure suppression was associated with mortality (OR, 7.72; 95% CI, 1.77-39.23; P = .005), but only a small subgroup was available for analysis (seizure suppression: 17 of 22 [77.3%] from 3 publications vs burst suppression: 25 of 98 [25.5%] from 12 publications). CIVAD choice and EEG type were not predictors of mortality. Earlier publication year was associated with mortality, although the observation was no longer statistically significant after adjusting SEs for clustering. Conclusions and Relevance: Epilepsy-related RSE was associated with lower mortality compared with other RSE etiologies. A trend of decreasing mortality over time was observed, which may suggest an effect of advances in neurocritical care. The overall data are heterogeneous, which limits definitive conclusions on the choice of optimal initial CIVAD in RSE treatment.

Revolutionizing diabetes care: unveiling tirzepatide's potential in glycemic control and beyond.

INTRODUCTION: Diabetes is a global public health challenge with rising prevalence. This review explores current diabetes understanding, diagnostic and management guidelines, economic impact, and lifestyle modifications as the primary approach. AREAS COVERED: Focusing on pharmacological interventions, we discuss the roles of GLP-1 agonists and GLP/GIP agonists in diabetes management and cardiovascular risk reduction. Tirzepatide, a novel medication, is highlighted for its unique mechanism of action. Clinical trials demonstrate its effectiveness in glucose control, weight reduction, and its potential impact on diabetes, obesity, NASH, and cardiovascular risks. EXPERT OPINION: Tirzepatide shows promise in diabetes treatment, offering glucose control and weight loss. It also holds potential for addressing comorbidities. However, cautious use is vital due to potential adverse effects and contraindications, including hypersensitivity reactions, pregnancy, and breastfeeding precautions. This review underscores tirzepatide as a valuable addition to diabetes therapies, with evolving prospects for enhanced patient outcomes as research advances.

Sweet Syndrome With Vasculitis: Time To Adopt a New Criteria?

Sweet syndrome (SS) is an acute febrile neutrophilic dermatosis. Although perceived to be rare, the disease may well have been underreported due to lack of exposure in low-volume clinical settings and due to the use of rather strict clinical criteria for diagnosis. It presents as cutaneous papules, plaques, or nodules in an asymmetric distribution that follows fever and flu-like symptoms. Data on the disease is ever-expanding. Several associations have been identified, including drugs, infections, malignancies, and autoimmune diseases. Different disease patterns and histological variants have been identified. Pathophysiology is complex and multifactorial but appears to involve mechanisms that negatively influence neutrophil apoptosis and facilitate neutrophil recruitment. The existing diagnostic criteria exclude cases with vasculitis; over time, cases of neutrophilic dermatoses with vasculitis have been reported as SS as long as other criteria were met. Newer diagnostic models have been proposed, some arguing against the exclusion of vasculitis. Steroids continue to be the mainstay of treatment, and steroid responsiveness continues to be a part of the diagnostic criteria, although newer treatment modalities have been used and have shown promise. No established guidelines exist for management. We present a case of Idiopathic SS with vasculitis along with a brief review of the existing literature. We agree to the inclusion of vasculitis as proposed by the newer diagnostic criteria.

Digital Health for Patients Undergoing Cardiac Surgery: A Systematic Review.

Digital health interventions have shown promise in improving patient outcomes and experiences in various healthcare settings. However, their effectiveness in the context of cardiac surgery remains uncertain. This systematic review aims to evaluate the existing evidence on the use of digital health interventions for patients undergoing cardiac surgery. A comprehensive search of PubMed MEDLINE, Elsevier EMBASE, Elsevier Scopus databases, and ClinicalTrials.gov was conducted to identify relevant studies published up to the present. Studies that examined the effects of digital health interventions, including mobile applications and web-based interventions, on perioperative care and patient outcomes in cardiac surgery were included. The data were extracted and synthesized to provide a comprehensive overview of the findings. The search yielded 15 studies composed of 4041 patients, analyzing the feasibility and implementation of mobile or internet applications for patients undergoing cardiac surgery. The studies included the use of mobile applications (ManageMySurgery, SeamlessMD, mHeart, Telediaglog, ExSed, Soulage Tavie, Heart Health application, and Mayo Clinic Health Connection) and web-based interventions (Heartnet and Active Heart). The findings indicated that these digital health interventions were associated with improved patient engagement, satisfaction, and reduced healthcare utilization. Patients reported finding the interventions helpful in their recovery process, and there was evidence of enhanced symptom monitoring and timely intervention. The completion rates of modules varied depending on the phase of care, with higher engagement observed during the acute phase. Interest in using digital health applications was expressed by patients, regardless of age, gender, or complexity of the cardiac defect. The results demonstrated that web-based interventions resulted in improvements in mental health, quality of life, and eHealth literacy. This systematic review highlights the potential benefits of digital health interventions in the context of cardiac surgery. Further research, including randomized controlled trials, is needed to establish the effectiveness, feasibility, and generalizability of digital health interventions in cardiac surgery.

Ventriculostomy Associated with Reduced Mortality in Severe Traumatic Brain Injury Compared to Parenchymal ICP Monitoring: A Propensity Score-Adjusted Analysis.

BACKGROUND: There is a lack of data on whether intracranial pressure (ICP)-guided therapy with an intraparenchymal fiberoptic monitor (IPM) or an external ventricular drain (EVD) leads to superior outcomes. Our goal is to determine the relationship between ICP-guided therapy with an EVD or IPM and mortality. METHODS: Retrospective analysis of severe traumatic brain injury cases that required IPM or EVD placement for ICP-guided therapy from January 1, 2010 to December 31, 2020. The data were obtained from the Pennsylvania Trauma Systems Foundation registry. RESULTS: A total of 2305 patients met the inclusion criteria, with 1048 (45.5%) IPM and 1257 (54.5%) EVD placed. Inpatient mortality occurred in 337 (32.2%) and 334 (26.6%) patients in the IPM and EVD cohorts, respectively (P = 0.003). Even among those treated medically only, inpatient mortality occurred in 171 (30.8%) of those with an IPM and in 100 (23.4%) of those with an EVD (P = 0.010). Multivariable logistic regression analysis showed that older age (odds ratio [OR] 1.03, P < 0.001), lower Glasgow Coma Scale (GCS) score (OR 1.16, P < 0.001), requiring surgery (OR 1.22, P = 0.049), and an IPM (OR 1.40, P = 0.001) were significant predictors of mortality. Propensity score-adjusted analysis using inverse probability of treatment weighted method revealed a 28% decrease in mortality and a 14% decrease in length of hospital stay with EVD use when adjusting for age, sex, GCS, Injury Severity Score, surgery, and Hispanic ethnicity. CONCLUSIONS: A significant mortality benefit was associated with the use of EVD compared to IPM. This mortality benefit was observed regardless of whether patients required surgery or not.

A Rare Case of Hypothyroidism-Induced Rhabdomyolysis.

Rhabdomyolysis is a condition caused by muscle breakdown. It can be usually associated with pain, weakness, and elevated creatinine kinase levels on laboratory testing. There are various triggers, some of which can include trauma, dehydration, infections, and, as in this case, autoimmune disorders. Here, we present a case of a patient with worsening muscle pain who was found to have elevated creatinine kinase levels and undiagnosed hypothyroidism, with symptoms improving with intravenous hydration and thyroid supplementation.

Factors Associated With Nosocomial COVID-19 Infection Among Health Care Workers in an Urban-Setting Malaysia Hospital.

This single-center study aimed to explore the factors associated with coronavirus disease (COVID-19) transmission in a hospital. All laboratory-confirmed COVID-19 cases among health care workers (HCWs) in a tertiary hospital in Malaysia were analyzed cross-sectionally from January 25, 2020, to September 10, 2021. A total of 897 HCWs in the hospital had laboratory-confirmed COVID-19 infection during the study period. Around 37.4% of HCWs were suspected to acquire COVID-19 infection from the hospital workplace. Factors associated with lower odds of workplace COVID-19 transmission were being females, ≥30 years old, fully vaccinated, and working as clinical support staff. Involvement in COVID-19 patient care was significantly associated with higher odds (adjusted odds ratio = 3.53) of workplace COVID-19 transmission as compared with non-workplace transmission. Most HCWs in the tertiary hospital acquired COVID-19 infection from non-workplace settings. During a pandemic, it is important to communicate with HCWs about the risk of both workplace and non-workplace COVID-19 transmission and to implement measures to reduce both workplace and non-workplace COVID-19 transmission.

Spinal deformity surgery in patients for whom blood transfusion is not an option: a single-center experience.

OBJECTIVE: Spinal deformity surgery is associated with significant blood loss, often requiring the transfusion of blood and/or blood products. For patients declining blood or blood products, even in the face of life-threatening blood loss, spinal deformity surgery has been associated with high rates of morbidity and mortality. For these reasons, patients for whom blood transfusion is not an option have historically been denied spinal deformity surgery. METHODS: The authors retrospectively reviewed a prospectively collected data set. All patients declining blood transfusion who underwent spinal deformity surgery at a single institution between January 2002 and September 2021 were identified. Demographics collected included age, sex, diagnosis, details of any prior surgery, and medical comorbidities. Perioperative variables included levels decompressed and instrumented, estimated blood loss, blood conservation techniques used, length of surgery, length of hospital stay, and complications from surgery. Radiographic measurements included, where appropriate, sagittal vertical axis correction, Cobb angle correction, and regional angular correction. RESULTS: Spinal deformity surgery was performed in 31 patients (18 male, 13 female) over 37 admissions. The median age at surgery was 41.2 years (range 10.9-70.1 years), and 64.5% had significant medical comorbidities. A median of 9 levels (range 5-16 levels) were instrumented per surgery, and the median estimated blood loss was 800 mL (range 200-3000 mL). Posterior column osteotomies were performed in all surgeries, and pedicle subtraction osteotomies in 6 cases. Multiple blood conservation techniques were used in all patients. Preoperative erythropoietin was administered prior to 23 surgeries, intraoperative cell salvage was used in all, acute normovolemic hemodilution was performed in 20, and perioperative administration of antifibrinolytic agents was performed in 28 surgeries. No allogenic blood transfusions were administered. Surgery was staged intentionally in 5 cases, and there was 1 unintended staging due to intraoperative blood loss from a vascular injury. There was 1 readmission for a pulmonary embolus. There were 2 minor postoperative complications. The median length of stay was 6 days (range 3-28 days). Deformity correction and the goals of surgery were achieved in all patients. Two patients underwent revision surgery during the follow-up period: one for pseudarthrosis and the other for proximal junctional kyphosis. CONCLUSIONS: With proper preoperative planning and judicious use of blood conservation techniques, spinal deformity surgery may be performed safely in patients for whom blood transfusion is not an option. The same techniques can be applied widely to the general population in order to minimize blood loss and the need for allogeneic blood transfusion.

Poor HIV-Related Outcomes in Older Adults Newly Diagnosed With HIV: A 4-Year Retrospective Analysis From a Single Site in Asia.

BACKGROUND: In resource-limited settings, HIV-related services are often targeted to younger key populations, although increasing reports have found that adults ≥50 years now account for among the highest increase in new HIV diagnosis. We assessed the proportion of new HIV infections among older adults (≥50 years) and compared their sociodemographics, risk behaviors, and HIV-related outcomes to newly diagnosed younger adults (<50 years). METHODS: This retrospective analysis included all new HIV diagnosis from 2016 to 2019 at the University of Malaya Medical Centre, Malaysia. Trends of HIV diagnosis was assessed using join point regression analysis, and characteristics between the older and younger adults were compared using χ 2 test or Mann-Whitney U test. Kaplan-Meier analysis and log-rank test were used to compare the survival probability in both age groups. RESULTS: From a total of 594 new HIV diagnosis between 2016 and 2019, 11.5% (N = 68) were among older adults with an annual percent increase of 5.50%. Older adults were more likely ethnic Indians ( P < 0.001), acquired HIV through heterosexual contact ( P = 0.001), had late presentation to care ( P = 0.003), and multimorbidity ( P < 0.001). Immunological responses after 12 months on antiretroviral therapy were comparable in both the groups. Older adults had a higher probability of death compared with younger adults (adjusted hazard ratio 1.81, 95% confidence interval: 1.02 to 3.23, P = 0.043) after adjusting for sex, mode of HIV transmission, late presentation to care, antiretroviral therapy initiation, and multimorbidity. CONCLUSION: Older adults diagnosed with HIV were associated with late care presentation and increased mortality. There is an urgent need to enhance uptake of HIV testing and linkage to care among older individuals in our setting.

The SLANT Score Predicts Poor Neurologic Outcome in Comatose Survivors of Cardiac Arrest: An External Validation Using a Retrospective Cohort.

BACKGROUND: Hypoxic brain injury is the leading cause of death in comatose patients following resuscitation from cardiac arrest. Neurological outcome can be difficult to prognosticate following resuscitation, and goals of care discussions are often informed by multiple prognostic tools. One tool that has shown promise is the SLANT score, which encompasses five metrics including initial nonshockable rhythm, leukocyte count after targeted temperature management, total adrenaline dose during resuscitation, lack of bystander cardiopulmonary resuscitation, and time to return of spontaneous circulation. This cohort study aimed to provide an external validation of this score by using a database of comatose cardiac arrest survivors from our institution. METHODS: We retrospectively queried our database of cardiac arrest survivors, selecting for patients with coma, sustained return of spontaneous circulation, and use of targeted temperature management to have a comparable sample to the index study. We calculated SLANT scores for each patient and separated them into risk levels, both according to the original study and according to a Youden index analysis. The primary outcome was poor neurologic outcome (defined by a cerebral performance category score of 3 or greater at discharge), and the secondary outcome was in-hospital mortality. Univariable and multivariable analyses, as well as a receiver operator characteristic curve, were used to assess the SLANT score for independent predictability and diagnostic accuracy for poor outcomes. RESULTS: We demonstrate significant association between a SLANT group with increased risk and poor neurologic outcome on univariable (p = 0.005) and multivariable analysis (odds ratio 1.162, 95% confidence interval 1.003-1.346, p = 0.046). A receiver operating characteristic analysis indicates that SLANT scoring is a fair prognostic test for poor neurologic outcome (area under the curve 0.708, 95% confidence interval 0.536-0.879, p = 0.024). Among this cohort, the most frequent SLANT elements were initial nonshockable rhythm (84.5%) and total adrenaline dose ≥ 5 mg (63.9%). There was no significant association between SLANT score and in-hospital mortality (p = 0.064). CONCLUSIONS: The SLANT score may independently predict poor neurologic outcome but not in-hospital mortality. Including the SLANT score as part of a multimodal approach may improve our ability to accurately prognosticate comatose survivors of cardiac arrest.

Rhinovirus/enterovirus was the most common respiratory virus detected in adults with severe acute respiratory infections pre-COVID-19 in Kuala Lumpur, Malaysia.

BACKGROUND: Severe acute respiratory infections (SARI) pose a great global burden. The contribution of respiratory viruses to adult SARI is relatively understudied in Asia. We aimed to determine viral aetiology of adult SARI patients in Kuala Lumpur, Malaysia. METHODS: The prevalence of 20 common (mainly viral) respiratory pathogens, and MERS-CoV, SARS-CoV and 5 bacterial select agents was investigated from May 2017 to October 2019 in 489 SARI adult patients in Kuala Lumpur, Malaysia, using molecular assays (Luminex NxTAG-RPP kit and qPCR assays). Viral metagenomics analysis was performed on 105 negative samples. RESULTS: Viral respiratory pathogens were detected by PCR in 279 cases (57.1%), including 10 (2.0%) additional detections by metagenomics analysis. The most detected viruses were rhinovirus/enterovirus (RV/EV) (49.1%) and influenza virus (7.4%). Three melioidosis cases were detected but no SARS-CoV, MERS-CoV or other bacterial select agents. Bacterial/viral co-detections and viral co-detections were found in 44 (9.0%) and 27 (5.5%) cases respectively, mostly involving RV/EV. Independent predictors of critical disease were male gender, chronic lung disease, lack of runny nose and positive blood culture with a significant bacterial pathogen. Asthma and sore throat were associated with increased risk of RV/EV detection, while among RV/EV cases, males and those with neurological disease were at increased risk of critical disease. CONCLUSIONS: Prior to the COVID-19 pandemic, the high prevalence of respiratory viruses in adults with SARI was mainly attributed to RV/EV. Continued surveillance of respiratory virus trends contributes to effective diagnostic, prevention, and treatment strategies.

Barriers and Facilitators to Implementing Project ECHO in Malaysia During the COVID-19 Pandemic.

Objective: In Malaysia, HIV is concentrated among key populations who experience barriers to care due to stigma and healthcare discrimination. The COVID-19 pandemic has increased barriers to healthcare. Project ECHO (Extension for Community Healthcare Outcomes) is a transformative tele-education strategy that could improve HIV prevention and treatment. Methods: Practicing physicians who were aged 18 years or older and had internet access participated in asynchronous online focus groups. Results: Barriers to Project ECHO were conflicting priorities, time constraints, and technology. Facilitators included content and format, dedicated time, asynchronized flexible programming, incentives, and ensuring technology was available. Conclusion: Project ECHO is a promising intervention that can increase physicians' knowledge and skill set in specialty medicine during the COVID-19 pandemic. Interventionists in Malaysia in particular, but also in general, should consider these barriers and facilitators when developing Project ECHO as they may aid in developing a more robust program and increase participation.

Adverse events following immunization and psychological distress among cancer patients/survivors following vaccination against SARS-CoV-2 infection.

Purpose: This study aims to describe the adverse events following immunization (AEFIs) of SARS-CoV-2 vaccination in cancer patients/survivors associated with their psychological distress. Methods: A cross-sectional study was conducted to assess AEFIs after the receipt of SARS-CoV-2 vaccines in cancer patients/survivors attending a university hospital in Malaysia. Psychological distress was measured using the Hospital Anxiety and Depression Scale (HADS) before and after the first and second doses of COVID-19 vaccine. Results: A total of 217 complete responses were received. Compared with before vaccination, both HADS Anxiety (HADS-A) and HADS Depression (HADS-D) scores were significantly reduced after the first and second dose of the SARS-CoV-2 vaccine. Most of the participants had mild-or-moderate systemic and local AEFIs, with the most common being pain at the injection site, tiredness, and headache for both the first and second doses of the vaccine. Positive correlations between the total AEFI score and HADS-A (r = 0.309, p < 0.001) and HADS-D (r = 0.214, p = 0.001) scores were observed after the first dose of the SARS-CoV-2 vaccine. Similarly, positive associations were observed between the total AEFI score and HADS-A (r = 0.305, p < 0.001) and HADS-D (r = 0.235, p < 0.001) scores after the second dose of the SARS-CoV-2 vaccine. Conclusion: Mild-to-moderate AEFIs found in this study help address vaccine hesitancy in cancer patients/survivors. Receiving the SARS-CoV-2 vaccine had a positive effect on decreasing psychological distress in cancer patients/survivors. High severity of an AEFI was associated with higher anxiety and depressive symptoms.

Regional Variability in the Care and Outcomes of Subarachnoid Hemorrhage Patients in the United States.

Background and Objectives: Regional variability in subarachnoid hemorrhage (SAH) care is reported in physician surveys. We aimed to describe variability in SAH care using patient-level data and identify factors impacting hospital outcomes and regional variability in outcomes. Methods: A retrospective multi-center cross-sectional cohort study of consecutive non-traumatic SAH patients in the Vizient Clinical Data Base, between January 1st, 2009 and December 30th, 2018 was performed. Participating hospitals were divided into US regions: Northeast, Midwest, South, West. Regional demographics, co-morbidities, severity-of-illness, complications, interventions and discharge outcomes were compared. Multivariable logistic regression was performed to identify factors independently associated with primary outcomes: hospital mortality and poor discharge outcome. Poor discharge outcome was defined by the Nationwide Inpatient Sample-SAH Outcome Measure, an externally-validated outcome measure combining death, discharge disposition, tracheostomy and/or gastrostomy. Regional variability in the associations between care and outcomes were assessed by introducing an interaction term for US region into the models. Results: Of 109,034 patients included, 24.3% were from Northeast, 24.9% Midwest, 34.9% South, 15.9% West. Mean (SD) age was 58.6 (15.6) years and 64,245 (58.9%) were female. In-hospital mortality occurred in 21,991 (20.2%) and 44,159 (40.5%) had poor discharge outcome. There was significant variability in severity-of-illness, co-morbidities, complications and interventions across US regions. Notable findings were higher prevalence of surgical clipping (18.8 vs. 11.6%), delayed cerebral ischemia (4.3 vs. 3.1%), seizures (16.5 vs. 14.8%), infections (18 vs. 14.7%), length of stay (mean [SD] days; 15.7 [19.2] vs. 14.1 [16.7]) and health-care direct costs (mean [SD] USD; 80,379 [98,999]. vs. 58,264 [74,430]) in the West when compared to other regions (all p < 0.0001). Variability in care was also associated with modest variability in hospital mortality and discharge outcome. Aneurysm repair, nimodipine use, later admission-year, endovascular rescue therapies reduced the odds for poor outcome. Age, severity-of-illness, co-morbidities, hospital complications, and vasopressor use increased those odds (c-statistic; mortality: 0.77; discharge outcome: 0.81). Regional interaction effect was significant for admission severity-of-illness, aneurysm-repair and nimodipine-use. Discussion: Multiple hospital-care factors impact SAH outcomes and significant variability in hospital-care and modest variability in discharge-outcomes exists across the US. Variability in SAH-severity, nimodipine-use and aneurysm-repair may drive variability in outcomes.

Early oral stepdown antibiotic therapy versus continuing intravenous therapy for uncomplicated Gram-negative bacteraemia (the INVEST trial): study protocol for a multicentre, randomised controlled, open-label, phase III, non-inferiority trial.

BACKGROUND: The incidence of Gram-negative bacteraemia is rising globally and remains a major cause of morbidity and mortality. The majority of patients with Gram-negative bacteraemia initially receive intravenous (IV) antibiotic therapy. However, it remains unclear whether patients can step down to oral antibiotics after appropriate clinical response has been observed without compromising outcomes. Compared with IV therapy, oral therapy eliminates the risk of catheter-associated adverse events, enhances patient quality of life and reduces healthcare costs. As current management of Gram-negative bacteraemia entails a duration of IV therapy with limited evidence to guide oral conversion, we aim to evaluate the clinical efficacy and economic impact of early stepdown to oral antibiotics. METHODS: This is an international, multicentre, randomised controlled, open-label, phase III, non-inferiority trial. To be eligible, adult participants must be clinically stable / non-critically ill inpatients with uncomplicated Gram-negative bacteraemia. Randomisation to the intervention or standard arms will be performed with 1:1 allocation ratio. Participants randomised to the intervention arm (within 72 h from index blood culture collection) will be immediately switched to an oral fluoroquinolone or trimethoprim-sulfamethoxazole. Participants randomised to the standard arm will continue to receive IV therapy for at least 24 h post-randomisation before clinical re-assessment and decision-making by the treating doctor. The recommended treatment duration is 7 days of active antibiotics (including empiric therapy), although treatment regimen may be longer than 7 days if clinically indicated. Primary outcome is 30-day all-cause mortality, and the key secondary outcome is health economic evaluation, including estimation of total healthcare cost as well as assessment of patient quality of life and number of quality-adjusted life years saved. Assuming a 30-day mortality of 8% in the standard and intervention arms, with 6% non-inferiority margin, the target sample size is 720 participants which provides 80% power with a one-sided 0.025 α-level after adjustment for 5% drop-out. DISCUSSION: A finding of non-inferiority in efficacy of oral fluoroquinolones or trimethoprim-sulfamethoxazole versus IV standard of care antibiotics may hypothetically translate to wider adoption of a more cost-effective treatment strategy with better quality of life outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05199324 . Registered 20 January 2022.

Changing predominant SARS-CoV-2 lineages drives successive COVID-19 waves in Malaysia, February 2020 to March 2021.

Malaysia has experienced three waves of coronavirus disease 2019 (COVID-19) as of March 31, 2021. We studied the associated molecular epidemiology and SARS-CoV-2 seroprevalence during the third wave. We obtained 60 whole-genome SARS-CoV-2 sequences between October 2020 and January 2021 in Kuala Lumpur/Selangor and analyzed 989 available Malaysian sequences. We tested 653 residual serum samples collected between December 2020 to April 2021 for anti-SARS-CoV-2 total antibodies, as a proxy for population immunity. The first wave (January 2020) comprised sporadic imported cases from China of early Pango lineages A and B. The second wave (March-June 2020) was associated with lineage B.6. The ongoing third wave (from September 2020) was propagated by a state election in Sabah. It is due to lineage B.1.524 viruses containing spike mutations D614G and A701V. Lineages B.1.459, B.1.470, and B.1.466.2 were likely imported from the region and confined to Sarawak state. Direct age-standardized seroprevalence in Kuala Lumpur/Selangor was 3.0%. The second and third waves were driven by super-spreading events and different circulating lineages. Malaysia is highly susceptible to further waves, especially as alpha (B.1.1.7) and beta (B.1.351) variants of concern were first detected in December 2020/January 2021. Increased genomic surveillance is critical.

Propagation of a hospital-associated cluster of COVID-19 in Malaysia.

BACKGROUND: Hospitals are vulnerable to COVID-19 outbreaks. Intrahospital transmission of the disease is a threat to the healthcare systems as it increases morbidity and mortality among patients. It is imperative to deepen our understanding of transmission events in hospital-associated cases of COVID-19 for timely implementation of infection prevention and control measures in the hospital in avoiding future outbreaks. We examined the use of epidemiological case investigation combined with whole genome sequencing of cases to investigate and manage a hospital-associated cluster of COVID-19 cases. METHODS: An epidemiological investigation was conducted in a University Hospital in Malaysia from 23 March to 22 April 2020. Contact tracing, risk assessment, testing, symptom surveillance, and outbreak management were conducted following the diagnosis of a healthcare worker with SARS-CoV-2 by real-time PCR. These findings were complemented by whole genome sequencing analysis of a subset of positive cases. RESULTS: The index case was symptomatic but did not fulfill the initial epidemiological criteria for routine screening. Contact tracing suggested epidemiological linkages of 38 cases with COVID-19. Phylogenetic analysis excluded four of these cases. This cluster included 34 cases comprising ten healthcare worker-cases, nine patient-cases, and 15 community-cases. The epidemic curve demonstrated initial intrahospital transmission that propagated into the community. The estimated median incubation period was 4.7 days (95% CI: 3.5-6.4), and the serial interval was 5.3 days (95% CI: 4.3-6.5). CONCLUSION: The study demonstrated the contribution of integrating epidemiological investigation and whole genome sequencing in understanding disease transmission in the hospital setting. Contact tracing, risk assessment, testing, and symptom surveillance remain imperative in resource-limited settings to identify and isolate cases, thereby controlling COVID-19 outbreaks. The use of whole genome sequencing complements field investigation findings in clarifying transmission networks. The safety of a hospital population during this COVID-19 pandemic may be secured with a multidisciplinary approach, good infection control measures, effective preparedness and response plan, and individual-level compliance among the hospital population.

Detection of respiratory viruses in adults with suspected COVID-19 in Kuala Lumpur, Malaysia.

BACKGROUND: Reports of co-circulation of respiratory viruses during the COVID-19 pandemic and co-infections with SARS-CoV-2 vary. However, limited information is available from developing countries. OBJECTIVES: We aimed to investigate the incidence of respiratory viruses in adult patients with suspected COVID-19 in Kuala Lumpur, Malaysia. STUDY DESIGN: We collected 198 respiratory samples from adult patients hospitalized with suspected COVID-19 in a single teaching hospital in Kuala Lumpur in February-May 2020 and tested combined oro-nasopharyngeal swabs with the NxTAG Respiratory Pathogen Panel (Luminex) and Allplex RV Essential (Seegene) assays. Forty-five negative samples further underwent viral metagenomics analysis. RESULTS: Of the 198 samples, 74 (37.4%) had respiratory pathogens, including 56 (28.3%) with SARS-CoV-2 and 18 (9.1%) positive for other respiratory pathogens. There were five (2.5%) SARS-CoV-2 co-infections, all with rhinovirus/enterovirus. Three samples (6.7%; 3/45) had viruses identified by metagenomics, including one case of enterovirus D68 and one of Saffold virus genotype 6 in a patient requiring ICU care. Most of the COVID-19 patients (91.1%; 51/56) had mild symptoms but 5.4% (3/56) died. CONCLUSION: During the early COVID-19 period, common respiratory viruses other than SARS-CoV-2 only accounted for 9.1% of hospitalization cases with ARI and co-infections with SARS-CoV-2 were rare. Continued surveillance is important to understand the impact of COVID-19 and its associated public health control measures on circulation of other respiratory viruses. Metagenomics can identify unexpected or rare pathogens, such as Saffold virus, which is rarely described in adults.