Clinical outcomes of patients with seizure admitted for COVID-19: Findings from the Philippine CORONA study.

Objective: Seizure is one of the neurologic manifestations of coronavirus disease 2019 (COVID-19) infection. There are few studies focused on the outcome of hospitalized patients with COVID-19 and seizure. Methods: This was a subgroup analysis of patients with seizure based on a nationwide, multicenter, retrospective study of COVID-19 patients admitted in 37 hospitals in the Philippines. Results: A total of 10,881 patients with COVID-19 infection were included. Among these, 27 (0.2 %) patients had pre-existing seizure/epilepsy and 125 (1.1 %) had new-onset seizure. The patients with pre-existing seizure/epilepsy had a mean age of 49 years and majority were males (63.0 %). The patients with new-onset seizure had a mean age of 57 years and majority were males (60.5 %). Among patients with pre-existing seizure/epilepsy, there were no significant differences in the proportion of severe/critical COVID-19 (p = 0.131), all-cause mortality (p = 0.177), full/partial neurologic recovery (p = 0.190), ventilator use (p = 0.106), length of intensive care unit stay (p = 0.276), and length of hospitalization (p = 0.591). Patients with new-onset seizure were 2.65 times more likely to have severe/critical COVID-19 infection (p < 0.001), 3.12 times more likely to die (p < 0.001), and 3.51 times more likely to require a ventilator (p < 0.001) than those without new-onset seizure. New-onset seizure, however, was not significantly associated with full/partial neurologic recovery (p = 0.184) and prolonged length of hospitalization (p = 0.050). Conclusion: Severe/critical COVID-19 infection, higher mortality rate, and use of a ventilator were significantly higher among patients with new-onset seizure but not among patients with pre-existing seizure/epilepsy.

Outcomes of patients with COVID-19 and coronary artery disease and heart failure: findings from the Philippine CORONA study.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) and coronary artery disease (CAD) or heart failure (HF) are more likely to have poor outcomes. This study aimed to determine the characteristics and outcomes of COVID-19 patients with CAD/HF across various institutions in the Philippines. METHODS: We utilized the data from the Philippine CORONA Study and compared the outcomes of admitted COVID-19 patients with CAD/HF versus those without. The Student's t test, Mann-Whitney U test, binary logistic regression and multivariate regression analysis were utilized. Odds ratios (OR) and Kaplan-Meier curves were generated. RESULTS: We included a total of 512 patients with COVID-19 had CAD/HF and 10,369 were without. CAD/HF was significantly associated with COVID severity, all-cause mortality, death from cardiac causes, respiratory failure, and prolonged hospitalization. After adjusting for confounders, the presence of CAD/HF was still associated with death from a cardiac cause (OR 2.22, 95% CI 1.49-3.3, p < 0.01). CONCLUSIONS: The presence of CAD or HF was significantly associated with severity of COVID disease, all-cause mortality, death from cardiac causes, respiratory failure, and prolonged hospitalization.

Clinical Outcomes of COVID-19 Infection among Patients with Chronic Obstructive Pulmonary Disease: Findings from the Philippine CORONA Study.

BACKGROUND: The global pandemic caused by the coronavirus disease 2019 (COVID-19) resulted in many deaths from fulminant respiratory failure. Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality worldwide. There has been great concern regarding the impact of COPD on the COVID-19 illness. METHODS: Data from the Philippine CORONA study were analyzed to determine the association of COPD and COVID-19 in terms of mortality, disease severity, respiratory failure, mechanical ventilation, and lengths of stay in the intensive care unit (ICU) and hospital. RESULTS: A total of 10,881 patients were included in this study, and 156 (1.4%) patients had been diagnosed with COPD. A majority of COVID-19 patients with COPD had other existing comorbidities: hypertension, diabetes mellitus, chronic cardiac disease, and chronic kidney disease. COPD patients were 2.0× more likely to present with severe to critical COVID-19 disease. COVID-19 patients with COPD in our study have a 1.7× increased mortality, 1.6× increased respiratory failure, and 2.0× increased risk for ICU admission. Smokers with COVID-19 were 1.8× more likely to present with more severe disease and have a 1.9× increased mortality. CONCLUSION: Our study supports the growing evidence that COPD among COVID-19 patients is a risk factor for higher mortality, more severe form of COVID-19, higher ICU admission, and higher respiratory failure needing ventilatory support.

Transcranial magnetic resonance-guided focused ultrasound pallidothalamic tractotomy for patients with X-linked dystonia-parkinsonism: a study protocol.

Transcranial magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive method for controlling tremor and has recently been used in patients with X-linked dystonia-parkinsonism (XDP). This study aims to determine the improvement in dystonia and parkinsonism in patients with XDP after MRgFUS pallidothalamic tractotomy. This prospective study will be conducted at the Philippine General Hospital, University of the Philippines Manila. The primary outcome measure is the change in the pre- and post-treatment XDP-Movement Disorder Society of the Philippines Scale scores. In addition, demographic and clinical data will be collected, including the Burke-Fahn-Marsden Dystonia Rating Scale, Part III of the Movement Disorder Society-Unified Parkinson's disease Rating Scale score, XDP clinical and functional stage, the five-level EuroQol five-dimensional questionnaire, Montreal Cognitive Assessment scores, MRgFUS treatment parameters, and adverse events. Patients will be assessed within 24 hours of treatment, then at 2 weeks, 3 months, 6 months, 9 months, and 12 months post-treatment. This protocol was approved by the University of the Philippines Manila Research Ethics Board (UPMREB 2022-0271-01). Data collection began in January 2023. This protocol has been registered with ClinicalTrials.gov: Trial Registration number: NCT05592028.

Clinical Outcomes of COVID-19 Infection in Pregnant and Nonpregnant Women: Results from The Philippine CORONA Study.

OBJECTIVE: Our study determined the association of pregnancy with various clinical outcomes among women with COVID-19 infection. METHODS: We conducted a retrospective, cohort, subgroup analysis of the Philippine CORONA Study datasets comparing the clinical/neurological manifestations and outcomes of pregnant and nonpregnant women admitted in 37 Philippine hospitals for COVID-19 infection. RESULTS: We included 2448 women in the analyses (322 pregnant and 2.126 nonpregnant). Logistic regression models showed that crude odds ratio (OR) for mortality (OR 0.26 [95% CI 0.11, 0.66]), respiratory failure [OR 0.37 [95% CI 0.17, 0.80]), need for intensive care (OR 0.39 [95% CI 0.19, 0.80]), and prolonged length of hospital stay (OR 1.73 [95% CI 1.36, 2.19]) among pregnant women were significant. After adjusting for age, disease severity, and new-onset neurological symptoms, only the length of hospital stay remained significant (adjusted OR 1.99 [95% CI 1.56,2.54]). Cox regression models revealed that the unadjusted hazard ratio (HR) for mortality (HR 0.22 [95% CI 0.09, 0.55]) among pregnant women was statistically significant; however, after adjustment, the HR for mortality became nonsignificant. CONCLUSION: We did not find a significantly increased risk of mortality, respiratory failure, and need for ICU admission in pregnant women compared with nonpregnant women with COVID-19. However, the likelihood of hospital confinement beyond 14 days was twice more likely among pregnant women than nonpregnant women with COVID-19.

Clinical outcomes in COVID-19 among patients with hypertension in the Philippine CORONA Study.

OBJECTIVE: To describe the association between hypertension and clinical outcomes in a cohort of patients with coronavirus disease 2019 (COVID-19). DESIGN: Retrospective cohort study. SETTING: Thirty-seven (37) hospitals in the Philippines. PATIENTS: 10,881 patients admitted for COVID-19 from February to December 2020. MEASUREMENTS AND MAIN RESULTS: Among the 10,881 patients included in the Philippine CORONA Study, 3647 (33.5%) had hypertension. On regression analysis adjusted for confounders (age group, sex, smoking history, diabetes, chronic cardiac disease, chronic kidney disease, chronic respiratory disease, chronic neurologic disease, chronic liver disease, HIV/AIDS, and malignancy), patients with hypertension had significantly greater odds of in-hospital mortality (OR 1.33, 95% CI 1.17-1.52), respiratory failure (OR 1.99, 95% CI 1.75-2.28), ICU admission (OR 2.16, 95% CI 1.90-2.45) and severe/critical disease (OR 1.57, 95% CI 1.41-1.75), compared to patients without hypertension. The time-to-event analysis with confounder adjustment also showed that hypertension was significantly associated with shorter time-to-event outcomes of in-hospital mortality (HR 1.13, 95% CI 1.01-1.26), respiratory failure (HR 1.86, 95% CI 1.65-2.10), and ICU admission (HR 1.99, 95% CI 1.76-2.23). CONCLUSIONS: Our analysis of nationwide data confirmed previous findings that hypertension is an independent risk factor for worse clinical outcomes among patients hospitalized for COVID-19, with increased odds of in-hospital mortality, respiratory failure, ICU admission, and severe/critical COVID-19. More specific studies should be done to elucidate the impact of hypertension characteristics, such as chronicity, severity, drug therapy, and level of control on these clinical outcomes.

Incidence and risk factors for stroke in patients with COVID-19 in the Philippines: An analysis of 10,881 cases.

BACKGROUND: While most large studies on the possible association of COVID-19 and stroke were done in high-income countries, only a few studies consisting of small sample populations have been done in low- to middle-income countries like the Philippines. OBJECTIVES: To determine the risk factors of stroke among hospitalized COVID19 patients in the Philippines; to determine the possible association between these risk factors and stroke among the same cohort; and to determine if there is an association between mortality and stroke in this same group. METHODOLOGY: We obtained relevant clinical and neurological, including stroke data from the Philippine CORONA study, an observational study involving 10,881 patients with COVID-19 admitted in 37 referral hospitals from all over the Philippines. RESULTS: The incidence of stroke among patients with COVID-19 was 3.4% (n = 367). There were more deaths among patients with stroke and COVID-19 than those without stroke and COVID-19 (42.2% vs 14.7%, p < 0.01). In addition, more patients with stroke were admitted in the ICU (43.3% vs 15.0%, p < 0.01) regardless of cause. Smoking (OR: 1.5, 95% CI: 1.3 to 1.7, p < 0.0001), hypertension (OR:1.75, 95% CI:1.53 to 1.97, p < 0.0001), presence of heart failure (OR: 1.4, 95% CI: 1.07 to 1.86, p = 0.01), presence of any neurologic co-morbidities (OR: 1.4, 95% CI:1.11 to 1.46, p = 0.004), and history of stroke (OR:2.3, 95% CI:1.82 to 2.97, p < 0.0001) had direct significant correlation with stroke; while being a health care worker (OR: 0.5, 95% CI: 0.33 to 0.70, p < 0.0004) had an inverse significant association with stroke. CONCLUSION: COVID-19 stroke patients in the Philippines have a higher mortality and ICU admission rates than patients with COVID-19 alone or COVID-19 stroke patients from developed countries. Our cohort has similar cardiovascular and metabolic risk factors to western patients with stroke, highlighting that COVID-19 may only have a small contribution to stroke incidence.

Global Frequency and Clinical Features of Stroke in Patients With Tuberculous Meningitis: A Systematic Review.

Importance: Stroke in tuberculous meningitis (TBM) is associated with significant morbidity and mortality. Objective: To determine the country-specific, regional, and overall prevalence of stroke among patients with TBM, including their clinical manifestations, stroke locations, and outcomes. Evidence Review: This systematic review searched records in MEDLINE by PubMed, Scopus, and EMBASE until July 2020 for relevant articles on the occurrence and characteristics of stroke in TBM. Randomized clinical trials and cohort studies that included a population of patients with TBM were analyzed for clinical manifestations, type of stroke, area of stroke, vascular territory, and outcomes. Studies that did not report the occurrence of stroke, reported as abstract only with no full-texts available, and articles not in English were excluded. The country-specific, regional, and overall frequencies of stroke among patients with TBM were determined; secondary analysis enumerated the summary estimates of the clinical presentations, common locations of stroke, and outcomes. The Murad tool was used to assess methodological quality. Findings: From 852 articles identified, 71 studies involving 2194 patients with stroke in TBM were included. The sample size for each study ranged from 17 to 806 patients. The frequency of stroke in TBM showed an estimate of 0.30 (95% CI, 0.26-0.33). The most common clinical manifestations were fever and headache. The lateral striate, middle cerebral, and medial striate arteries were typically affected. The basal ganglia, cortex and lobar, and internal capsule were the frequently involved areas of the brain. The pooled proportions of mortality and poor outcomes were 0.22 (95% CI, 0.16-0.29) and 0.51 (95% CI, 0.37-0.66), respectively. Conclusions and Relevance: The results of this systematic review suggest that stroke is considerably frequent among patients with TBM. The reported frequencies of stroke in TBM and its clinical features vary across the studies and populations.

Body mass index and its association with COVID-19 clinical outcomes: Findings from the Philippine CORONA study.

BACKGROUND AND AIMS: To explore the association between body mass index (BMI) and adverse outcomes in a large cohort of patients with coronavirus disease 2019 (COVID-19). METHODS: This is a secondary analysis of a 37-site, nationwide, multicenter, retrospective cohort study that investigated the clinical and neurological outcomes of adult patients with confirmed COVID-19 admitted from February to December 15, 2020. RESULTS: We analyzed 4,463 patients with BMI and outcome data. A total of 790 (17.7%) and 710 (15.9%) had the primary outcome of in-hospital mortality and need for invasive mechanical ventilation (IMV), respectively. There was no significant association between WHO BMI groups and these outcomes. Using Asia-Pacific cutoffs showed a significant association between obesity and in-hospital mortality risk (P = 0.012). Being underweight was an independent predictor of prolonged IMV requirement regardless of BMI criteria used (P < 0.01). Obesity correlated with the need for intensive care unit admission using Asia-Pacific cutoffs (P = 0.029). There was a significant association between any BMI abnormality and odds of severe/critical COVID-19 (P < 0.05). Obese patients with concomitant acute neurological presentation/diagnosis during their COVID-19 admission were shown to have lower odds of neurologic recovery (P < 0.05). CONCLUSIONS: We found BMI abnormalities to be associated with several adverse clinical and neurologic outcomes, although such associations may be more evident with the use of race-specific BMI criteria.

Outcomes and Risk Factors of Patients With COVID-19 and Cancer (ONCORONA): Findings from The Philippine CORONA Study.

Background: A study conducted in China on patients with coronavirus disease 2019 (COVID-19) showed that cancer conferred a five times increased risk for needing intensive care admission and mortality; No data has yet been collected and published from the Philippines. Thus, the investigators conducted this substudy to determine the association of having a history of cancer with clinical outcomes among patients included in the Philippine CORONA Study. Methodology: Multi-center, retrospective cohort design. Results: A total of 244 patients had a history of cancer, out of 10,881 COVID-19 hospital admissions. After adjusting for different confounding variables of interest, having cancer was significantly associated with a 75% increased odds of having severe/critical COVID-19 at nadir (CI 95% 1.32, 2.33; p < 0.001). After adjusting for different confounding variables of interest, having cancer was significantly associated with the following time-to-event outcomes: 72% increase in hazard of in-hospital mortality (CI 95% 1.37, 2.16; p < 0.001), 65% increase in hazard of respiratory failure (CI 95% 1.31, 2.08; p < 0.001), and 57% increase in hazard of being admitted to ICU (CI 95% 1.24, 1.97; p < 0.001). Conclusion: A history of cancer conferred poorer clinical outcomes on adult, hospitalized COVID-19 patients.

Clinical Outcomes of Older Persons and Persons with Dementia Admitted for Coronavirus Disease 2019: Findings from the Philippine CORONA Study.

INTRODUCTION: The Philippine CORONA Study was a multicenter, retrospective, cohort study of 10,881 coronavirus disease 2019 (COVID-19) admissions between February and December 2020. METHODS: Subgroup analysis was done on clinical outcomes of mortality, respiratory failure, duration of ventilator dependence, intensive care unit (ICU) admission, length of ICU stay, and length of hospital stay among older persons and persons with dementia. RESULTS: The adjusted hazard ratios for mortality among the mild and severe cases were significantly higher by 3.93, 95% CI [2.81, 5.50] and by 1.81, 95% CI [1.43, 2.93], respectively, in older persons compared to younger adults. The adjusted hazard ratios for respiratory failure in older persons were increased by 2.65, 95% CI [1.92, 3.68] and by 1.27, 95% CI [1.01, 1.59] among the mild and severe cases, respectively. The adjusted hazard ratio for ICU admission in older persons was higher by 1.95, 95% CI [1.47, 2.59] among the mild cases. The adjusted hazard ratios for mortality and ICU admission in persons with dementia were higher by 7.25, 95% CI [2.67, 19.68] and by 4.37, 95% CI [1.08, 17.63], respectively, compared to those without dementia. CONCLUSION: Older age and dementia significantly increased the risk of mortality, respiratory failure, and ICU admission among COVID-19 patients.

The outcomes of patients with diabetes mellitus in The Philippine CORONA Study.

Patients diagnosed with diabetes mellitus (DM) who are infected with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) belong to the most vulnerable patient subgroups. Emerging data has shown increased risks of severe infections, increased in ICU admissions, longer durations of admission, and increased mortality among coronavirus disease 2019 (COVID-19) patients with diabetes. We performed a subgroup analysis comparing the outcomes of patients diagnosed with DM (n = 2191) versus patients without DM (n = 8690) on our data from our study based on a nationwide, comparative, retrospective, cohort study among adult, hospitalized COVID-19 patients involving 37 hospital sites from around the Philippines. We determined distribution differences between two independent samples using Mann-Whitney U and t tests. Data on the time to onset of mortality, respiratory failure, intensive care unit (ICU) admission were used to build Kaplan-Meier curves and to compute for hazard ratios (HR). The odds ratios (OR) for longer ventilator dependence, longer ICU stay, and longer hospital stays were computed via multivariate logistic regression. Adjusted hazard ratios (aHR) and ORs (aOR) with 95% CI were calculated. We included a total of 10,881 patients with confirmed COVID-19 infection (2191 have DM while 8690 did not have DM). The median age of the DM cohort was 61, with a female to male ratio of 1:1.25 and more than 50% of the DM population were above 60 years old. The aOR for mortality was significantly higher among those in the DM group by 1.46 (95% CI 1.28-1.68; p < 0.001) as compared to the non-DM group. Similarly, the aOR for respiratory failure was also significantly higher among those in the DM group by 1.67 (95% CI 1.46-1.90). The aOR for developing severe COVID-19 at nadir was significantly higher among those in the DM group by 1.85 (95% CI 1.65-2.07; p < 0.001). The aOR for ICU admission was significantly higher among those in the DM group by 1.80 (95% CI 1.59-2.05) than those in the non-DM group. DM patients had significantly longer duration of ventilator dependence (aOR 1.33, 95% CI 1.08-1.64; p = 0.008) and longer hospital admission (aOR 1.13, 95% CI 1.01-1.26; p = 0.027). The presence of DM among COVID-19 patients significantly increased the risk of mortality, respiratory failure, duration of ventilator dependence, severe/critical COVID-19, ICU admission, and length of hospital stay.

COVID-19 outcomes of 10,881 patients: retrospective study of neurological symptoms and associated manifestations (Philippine CORONA Study).

Our study aimed to determine the effects of new-onset neurological symptoms (NNS) on clinically relevant outcomes in hospitalized patients with COVID-19 infection. We conducted a nationwide, comparative, retrospective, cohort study among adult, hospitalized COVID-19 patients involving 37 hospital sites from various regions in the Philippines. We included a total of 10,881 patients with confirmed COVID-19 infection (2008 had NNS while 8873 did not have NNS). The adjusted hazard ratios (aHRs) for mortality among the mild and severe cases were significantly higher by 1.660 (95% CI 1.132-2.435) and by 1.352 (95% CI 1.042-1.752), respectively, in the NNS group compared to those in the non-NNS group. The aHRs for respiratory failure in the NNS group were significantly increased by 1.914 (95% CI 1.346-2.722), by 1.614 (95% CI 1.260-2.068), and by 1.234 (95% CI 1.089-1.398) among the mild, severe, and critical cases, respectively. The aHRs for ICU admission in the NNS group were still significantly higher by 1.973 (95% CI 1.457-2.673) and by 1.831 (95% CI 1.506-2.226) among the mild and severe cases, respectively. Patients who had NNS were not significantly associated with a longer duration of ventilator dependence (adjusted odds ratio (aOR) 0.954, 95% CI 0.772-1.179), longer ICU stay (aOR 0.983, 95% CI 0.772-1.252) and longer hospital admission (aOR 1.045, 95% CI 0.947-1.153). The presence of NNS significantly increases the risk of mortality, respiratory failure and ICU admission among COVID-19 patients. Registration and associated protocol publication: ClinicalTrials.gov website (NCT04386083); Espiritu AI, Sy MCC, Anlacan VMM, Jamora RDG. The Philippine COVID-19 Outcomes: a Retrospective study Of Neurological manifestations and Associated symptoms (The Philippine CORONA study): a protocol study. BMJ Open. 2020;10:e040944.

Cardiocerebral Infarction: A Single Institutional Series.

OBJECTIVES: Cardiocerebral infarction (CCI) is the rare occurrence of acute ischemic stroke (AIS) and acute myocardial infarction (AMI), either at the same time (simultaneous or synchronous) or one after the other (metachronous). The aim of this study is to describe the clinical profile, management and treatment outcomes of patients with CCI. MATERIALS AND METHODS: This is a 3-year cross-sectional study of patients with CCI describing their clinical presentation, management, and outcomes. The primary outcome measures were all-cause mortality and functional outcome measured with the modified Rankin Scale score (mRS) at discharge and at 30 days post-CCI. We also described the frequency of major and minor hemorrhagic events. RESULTS: Out of 1683 AIS patients and 1983 AMI patients admitted during our time period, 29 patients fulfilled the inclusion criteria (mean age 60 ±12, 79% males, median admission NIHSS 16 [range 1-26]). Of these, 20 (69%) had metachronous CCI while 9 (31%) had synchronous CCI. Most of the patients were given antithrombotics and only 14% were given reperfusion therapies. The all-cause mortality is 45% and 69% of which were cardiovascular deaths. Seventeen and 21% of CCI patients had a good functional outcome on discharge and at 30 days from CCI onset respectively. A total of 8 (28%) patients had hemorrhagic events. CONCLUSIONS: We present the largest single institutional series showing the prevalence rate of cardiocerebral infarction to be 0.79% (0.55% for metachronous, 0.25% for synchronous), with patients presenting as moderate-severe acute ischemic strokes and high-risk acute myocardial infarction. These patients have a high mortality rate with a significant proportion having cardiovascular deaths.

Cerebellar ataxia as a primary manifestation of neuropsychiatric systemic lupus erythematosus.

Acute cerebellar ataxia is a rare primary manifestation of neuropsychiatric systemic lupus erythematosus (NPSLE). We report a case of a 22-year-old woman who presented with gait instability, behavioural changes and new-onset seizures. The tempo of disease progression was explained by an autoimmune cause, eventually fulfilling the criteria for systemic lupus erythematosus. The patient's neurological symptoms improved markedly following administration of steroids and immunomodulators. A review of literature on cerebellar ataxia in NPSLE and a summary of all reported cases to date are also presented.

Bibliometric analysis of bacterial central nervous system infection research in Southeast Asia.

BACKGROUND: The status of research and scientific outputs with regards to bacterial central nervous system (CNS) infection in southeast Asia (SEA) is unknown. This study aimed to analyze and compare bacterial CNS infection research output of SEA countries in terms of bibliometric indices. METHODS: The major electronic databases (MEDLINE, Scopus, Embase, CENTRAL, Clinicaltrials.gov and WPRIM) were searched for studies on bacterial CNS infection in SEA until August 31, 2020. Frequencies, percentages and Spearman's rho correlations were used. RESULTS: There was a total of 648 unique studies on bacterial CNS infection in SEA and it was 657 when double-counted (collaborative studies between SEA countries). Thailand (n=148, 22.5%) and Vietnam (n=142, 21.6%) had the highest number of publications. The most common type of research publication was the case report / case series (n=160, 24.7%). Tuberculous meningitis/tuberculoma (n=176, 26.7%) was the most common topic. This study showed that the %GDP for research and development (R&D) was associated with a higher number of research output. However, the GDP per capita was not associated with any of the bibliometric indices. The total number of neurologists was associated with all of the bibliometric analysis. CONCLUSION: Bacterial CNS infection research output in SEA countries was low in terms of quantity. The %GDP for R&D was associated with the number of research publications. The total number of neurologists was associated with all of the bibliometric indices.

Neurological Manifestations in COVID-19 Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Growing evidence showed that coronavirus disease 2019 (COVID-19) infection may present with neurological manifestations. This review aimed to determine the neurological manifestations and complications in COVID-19. METHODS: We conducted a systematic review and meta-analysis that included cohort and case series/reports involving a population of patients confirmed with COVID-19 infection and their neurologic manifestations. We searched the following electronic databases until April 18, 2020: PubMed, Embase, Scopus, and World Health Organization database (PROSPERO registration number: CRD42020180658). RESULTS: From 403 articles identified, 49 studies involving a total of 6,335 confirmed COVID-19 cases were included. The random-effects modeling analysis for each neurological symptom showed the following proportional point estimates with 95% confidence intervals: "headache" (0.12; 0.10-0.14; I2 = 77%), "dizziness" (0.08; 0.05-0.12; I2 = 82%), "headache and dizziness" (0.09; 0.06-0.13; I2 = 0%), "nausea" (0.07; 0.04-0.11; I2 = 79%), "vomiting" (0.05; 0.03-0.08; I2 = 74%), "nausea and vomiting" (0.06; 0.03-0.11; I2 = 83%), "confusion" (0.05; 0.02-0.14; I2 = 86%), and "myalgia" (0.21; 0.18-0.25; I2 = 85%). The most common neurological complication associated with COVID-19 infection was vascular disorders (n = 23); other associated conditions were encephalopathy (n = 3), encephalitis (n = 1), oculomotor nerve palsy (n = 1), isolated sudden-onset anosmia (n = 1), Guillain-Barré syndrome (n = 1), and Miller-Fisher syndrome (n = 2). Most patients with neurological complications survived (n = 14); a considerable number of patients died (n = 7); and the rest had unclear outcomes (n = 12). CONCLUSION: This review revealed that neurologic involvement may manifest in COVID-19 infection. What has initially been thought of as a primarily respiratory illness has evolved into a wide-ranging multi-organ disease.

The Philippine COVID-19 Outcomes: a Retrospective study Of Neurological manifestations and Associated symptoms (The Philippine CORONA study): a protocol study.

INTRODUCTION: The SARS-CoV-2, virus that caused the COVID-19 global pandemic, possesses a neuroinvasive potential. Patients with COVID-19 infection present with neurological signs and symptoms aside from the usual respiratory affectation. Moreover, COVID-19 is associated with several neurological diseases and complications, which may eventually affect clinical outcomes. OBJECTIVES: The Philippine COVID-19 Outcomes: a Retrospective study Of Neurological manifestations and Associated symptoms (The Philippine CORONA) study investigators will conduct a nationwide, multicentre study involving 37 institutions that aims to determine the neurological manifestations and factors associated with clinical outcomes in COVID-19 infection. METHODOLOGY AND ANALYSIS: This is a retrospective cohort study (comparative between patients with and without neurological manifestations) via medical chart review involving adult patients with COVID-19 infection. Sample size was determined at 1342 patients. Demographic, clinical and neurological profiles will be obtained and summarised using descriptive statistics. Student's t-test for two independent samples and χ2 test will be used to determine differences between distributions. HRs and 95% CI will be used as an outcome measure. Kaplan-Meier curves will be constructed to plot the time to onset of mortality (survival), respiratory failure, intensive care unit (ICU) admission, duration of ventilator dependence, length of ICU stay and length of hospital stay. The log-rank test will be employed to compare the Kaplan-Meier curves. Stratified analysis will be performed to identify confounders and effects modifiers. To compute for adjusted HR with 95% CI, crude HR of outcomes will be adjusted according to the prespecified possible confounders. Cox proportional regression models will be used to determine significant factors of outcomes. Testing for goodness of fit will also be done using Hosmer-Lemeshow test. Subgroup analysis will be performed for proven prespecified effect modifiers. The effects of missing data and outliers will also be evaluated in this study. ETHICS AND DISSEMINATION: This protocol was approved by the Single Joint Research Ethics Board of the Philippine Department of Health (SJREB-2020-24) and the institutional review board of the different study sites. The dissemination of results will be conducted through scientific/medical conferences and through journal publication. The lay versions of the results may be provided on request. TRIAL REGISTRATION NUMBER: NCT04386083.

Dementia Research Productivity and Associations with Socioeconomic Factors and Burden of Disease in Southeast Asia.

BACKGROUND: Scientific output in Southeast Asia (SEA) on the topic of dementia is postulated to be low in quality and quantity. It is also speculated that certain socioeconomic variables and measures of disease burden for dementia may play a significant role in driving the research output of a particular country. OBJECTIVE: This study aimed to determine the research impact of published journal articles on dementia in SEA and its association with country-level socioeconomic factors and measures of disease burden for dementia. METHODS: A systematic search was conducted using electronic healthcare databases. We included articles published on dementia until August 2019 with at least 1 author affiliated with any SEA institution. We obtained bibliometric indices, relevant socioeconomic factors, and measures of disease burden for dementia from published sources. RESULTS: One thousand six articles fulfilled the inclusion criteria. The majority of publications were related to Alzheimer's disease (n = 775, 77.0%). Singapore contributed the highest number of publications (n = 457, 45.4%). Gross domestic product (GDP) per capita, % GDP for research and development, and total neurologists significantly correlated with several bibliometric indices. On the other hand, the measures of disease burden for dementia in SEA countries were not significantly associated with research productivity. CONCLUSION: Research productivity in SEA on dementia has substantially increased in recent years. Augmenting GDP per capita and expanding the apportionment of resources to research and development (R&D) may have a significant role in the advancement of dementia research in SEA.