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Background: Severe and critical COVID-19 disease is characterized by hyperinflammation involving pro-inflammatory cytokines, particularly IL-6. Tocilizumab is a monoclonal antibody that blocks IL-6 receptors., Objectives: This study evaluated the efficacy of tocilizumab in Filipino patients with severe to critical COVID-19 disease., Methods: This phase 3 randomized double-blind trial, included patients hospitalized for severe or critical COVID-19 in a 1:1 ratio to receive either tocilizumab plus local standard of care or placebo plus standard of care. Patients were eligible for a repeat IV infusion within 24-48 hours if they deteriorated or did not improve. Treatment success or clinical improvement was defined as at least two categories of improvement from baseline in the WHO 7-point Ordinal Scale of patient status, in an intention-to-treat manner., Results: Forty-nine (49) patients were randomized in the tocilizumab arm and 49 in the placebo arm. There was no significant difference in age, comorbidities, COVID-19 severity, need for mechanical ventilation, presence of acute respiratory distress syndrome, or biomarker levels between groups. Use of adjunctive therapy was similar between groups, with corticosteroid used in 91.8% in tocilizumab group and 81.6% in the placebo group, while remdesivir was used in 98% of participants in both groups.There was no significant difference between groups in terms of treatment success in both the intention-to-treat analysis (relative risk=1.05, 95% CI: 0.85-1.30) and per-protocol analysis (relative risk=0.98, 95% CI: 0.80 to 1.21). There was no significant difference in time to improvement of at least two categories relative to baseline on the 7-point Ordinal Scale of clinical status., Conclusion: The use of tocilizumab on top of standard of care in the management of patients with severe to critical COVID-19 did not result in significant improvement as defined by the WHO 7-point Ordinal Scale of patient status, nor in significant improvement in incidence of mechanical ventilation, incidence of ICU admission, length of ICU stay, and mortality rate., Competing Interests: All authors declared no conflicts of interest., (© 2024 Acta Medica Philippina.)

Objectives: Community health workers (CHWs) fill in the insufficiency of health professionals in low-income countries. The CHWs' roles include health education of their constituents whose health they likewise take care. This study aimed to describe the concept and understanding of diabetes among CHWs in the Philippines., Methods: Fifty female CHWs currently working in rural and urban areas participated in six focus group discussions with guidance from Kleinman's eight questions. With the written informed consent of the participants, discussions were recorded and transcribed by the Research Assistant. A multi-disciplinary team manually analyzed the data. Disagreements were discussed among them and the physicians provided clinical analyses and explanations on the results. Quotations of an important point of view were also presented. Pseudonyms were utilized to uphold anonymity., Results: CHWs were aged 32 to 72 years; older participants reside in rural areas. Majority were married, housekeepers, and high school graduates. Some CHWs and their family were suffering from diabetes or dyabetis , the disease of the rich according to them. Its causes were food and lifestyle, and believed to be hereditary. Complications lead to death. Amputation was feared the most. Diabetes is incurable. Persons with diabetes should take maintenance medicines, and seek physicians' and family's help. Together with the patient, the family must decide on its management. Balanced diet, healthy lifestyle, maintenance medicines, food supplements, and herbal plants were perceived treatments. The internist should lower blood sugar level as well as prolong life span. Proper diet and regular check-up prevent diabetes., Conclusions: CHWs' concept and understanding of diabetes reflect some of the biomedical causes, effects, treatment, and prevention of diabetes as well as its social determinants. The efficacy and safety of herbal plants in the treatment of diabetes, however, should be further studied. Training on diabetes care should be provided to address their fears of amputation, insulin injection, and complications., Competing Interests: All authors declared no conflict of interest and no competing financial interest exists., (© 2024 Acta Medica Philippina.)

Purpose: This study was performed to determine the clinical biomarkers and cytokines that may be associated with disease progression and in-hospital mortality in a cohort of hospitalized patients with RT-PCR confirmed moderate to severe COVID-19 infection from October 2020 to September 2021, during the first wave of COVID-19 pandemic before the advent of vaccination., Patients and Methods: Clinical profile was obtained from the medical records. Laboratory parameters (complete blood count [CBC], albumin, LDH, CRP, ferritin, D-dimer, and procalcitonin) and serum concentrations of cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, IFN-γ, IP-10, TNF-α) were measured on Days 0-3, 4-10, 11-14 and beyond Day 14 from the onset of illness. Regression analysis was done to determine the association of the clinical laboratory biomarkers and cytokines with the primary outcomes of disease progression and mortality. ROC curves were generated to determine the predictive performance of the cytokines., Results: We included 400 hospitalized patients with COVID-19 infection, 69% had severe to critical COVID-19 on admission. Disease progression occurred in 139 (35%) patients, while 18% of the total cohort died (73 out of 400). High D-dimer >1 µg/mL (RR 3.5 95%CI 1.83-6.69), elevated LDH >359.5 U/L (RR 1.85 95%CI 1.05-3.25), lymphopenia (RR 1.91 95%CI 1.14-3.19), and hypoalbuminemia (RR 2.67, 95%CI 1.05-6.78) were significantly associated with disease progression. High D-dimer (RR 3.95, 95%CI 1.62-9.61) and high LDH (RR 5.43, 95%CI 2.39-12.37) were also significantly associated with increased risk of in-hospital mortality. Nonsurvivors had significantly higher IP-10 levels at 0 to 3, 4 to 10, and 11 to 14 days from illness onset ( p< 0.01), IL-6 levels at 0 to 3 days of illness ( p =0.03) and IL-18 levels at days 11-14 of illness ( p <0.001) compared to survivors. IP-10 had the best predictive performance for disease progression at days 0-3 (AUC 0.81, 95%CI: 0.68-0.95), followed by IL-6 at 11-14 days of illness (AUC 0.67, 95%CI: 0.61-0.73). IP-10 predicted mortality at 11-14 days of illness (AUC 0.77, 95%CI: 0.70-0.84), and IL-6 beyond 14 days of illness (AUC 0.75, 95%CI: 0.68-0.82)., Conclusion: Elevated D-dimer, elevated LDH, lymphopenia and hypoalbuminemia are prognostic markers of disease progression. High IP-10 and IL-6 within the 14 days of illness herald disease progression. Additionally, elevated D-dimer and LDH, high IP-10, IL-6 and IL-18 were also associated with mortality. Timely utilization of these biomarkers can guide clinical monitoring and management decisions for COVID-19 patients in the Philippines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Punzalan, Aherrera, de Paz-Silava, Mondragon, Malundo, Tan, Tantengco, Quebral, Uy, Lintao, Dela Rosa, Mercado, Avenilla, Poblete, Albay, David-Wang and Alejandria.)

Competing Interests: We declare no competing interests.

Competing Interests: We declare no competing interests.

Abstract: Genetic variation is known to affect response to calcium channel blockers (CCBs) among different populations. This study aimed to determine the genetic variations associated with poor response to this class of antihypertensive drugs among Filipinos.One hundred eighty one hypertensive participants on CCBs therapy were included in an unmatched case-control study. Genomic deoxyribonucleic acid were extracted and genotyped for selected genetic variants. Regression analysis was used to determine the association of genetic and clinical variables with poor response to medication.The variant rs1458038 near fibroblast growth factor 5 gene showed significant association with poor blood pressure-lowering response based on additive effect (CT genotype: adjusted OR 3.41, P = .001; TT genotype: adjusted OR 6.72, P < .001).These findings suggest that blood pressure response to calcium channels blockers among Filipinos with hypertension is associated with gene variant rs1458038 near fibroblast growth factor 5 gene. Further studies are recommended to validate such relationship of the variant to the CCB response., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: We aim to determine the cost-effectiveness of dapagliflozin in addition to standard therapy versus standard therapy alone among patients with heart failure with reduced ejection fraction (HFrEF) using the public healthcare provider's perspective in the Philippines., Methods and Results: A thousand Filipino patients with HFrEF (with or without type 2 diabetes mellitus) were included in a simulation cohort using a lifetime Markov model. The model, which was developed based on the results of the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial, was composed of three health states. These were 'alive without an event' (chronic heart failure state), 'alive but was hospitalized for heart failure' (worsening heart failure), and 'dead' (death from any cause). Data regarding costs and utilities were obtained from previous studies and local data. These were used to estimate the incremental cost per quality-adjusted life-year (ICER). A 3% annual discount rate was used for both costs and effects. One-way (deterministic) and probabilistic sensitivity analyses as well as scenario analyses were performed. The ICER for the addition of dapagliflozin to standard therapy among HFrEF patients was PHP177 868 (US$3434) and PHP160 983 (US$3108), respectively, if the present price (PHP44.00) and possible negotiated unit cost of dapagliflozin 10 mg tablet (PHP40.00) were used. These were deemed cost-effective because they were both below the threshold ICER which was equivalent to the gross domestic product per capita of the Philippines in 2019, PHP180 500 (US$3485). Using the unit costs of dapagliflozin previously mentioned, the ICERs among HFrEF patients with diabetes were PHP132 582 (US$2560) and PHP120 249 (US$2321), respectively. Doing PSA involving Monte Carlo simulation of 10 000 iterations and plotting the resulting ICERs against the threshold ICER in the cost-effectiveness acceptability curves, these ICERs for HFrEF among diabetics were determined to be 72% and 76% cost-effective., Conclusion: Dapagliflozin added to standard therapy for HFrEF patients is likely to be cost-effective using the perspective of the Philippine public healthcare provider., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Increased uric acid levels have been known to be associated with different cardiovascular and renal diseases. Over the past few years, several studies have examined the role of urate-lowering therapy (ULT) in hypertension and major adverse cardiac events (MACE) and suggest a potential role of elevated serum uric acid as an independent cardiovascular risk factor. This meta-analysis was done to determine the association of 2 ULTs commonly used in clinical practice (febuxostat vs. allopurinol) on hypertension and MACE and resolve the conflicting results of the outcomes of earlier studies. Randomized controlled trials comparing febuxostat versus allopurinol published with outcomes on blood pressure, all-cause mortality, myocardial infarction (MI), and stroke were searched through PubMed, Google Scholar, and Cochrane database. A total of 10 studies were subsequently included in the meta-analysis. Pooled analysis of the mean differences (MD) were done for the outcomes on blood pressure (systolic and diastolic) and risk ratios (RRs) for the outcomes on MACE with corresponding 95% confidence intervals (CIs). Pooled analysis of studies on hyperuricemic patients showed that febuxostat 40 mg has no significant difference compared with allopurinol 100/300 mg with respect to diastolic (MD, -0.56 with 95% CI of -4.28 to 3.15) and systolic blood pressure (MD, 0.30 with 95% CI of -3.33 to 3.93). No significant differences were also noted on all-cause mortality (RR, 1.18 with 95% CI of 0.99-1.41), MI (RR, 0.92 with 95% CI of 0.72-1.18), and stroke (RR, 1.05 with 95% CI of 0.77-1.43). The results of this meta-analysis showed that the 2 ULTs (febuxostat vs. allopurinol) have no significant association with respect to blood pressure among adult patients with hyperuricemia. No significant association was also noted of either ULT with all-cause mortality, MI, and stroke.

Background: Patients 65 years old and older largely represent (>50%) hospital-admitted patients with acute coronary syndrome (ACS). Data are conflicting comparing efficacy of early routine invasive (within 48-72 hours of initial evaluation) versus conservative management of ACS in this population., Objective: We aimed to determine the effectiveness of routine early invasive strategy compared to conservative treatment in reducing major adverse cardiovascular events in patients 65 years old and older with non-ST elevation (NSTE) ACS., Data Sources: We conducted a systematic review of randomized controlled trials (RCTs) through PubMed, Cochrane, and Google Scholar database., Study Selection: The studies included were RCTs that evaluated the effectiveness of invasive strategy compared to conservative treatment among patients ≥ 65 years old diagnosed with NSTEACS. Studies were included if they assessed any of the following outcomes of death, cardiovascular mortality, myocardial infarction (MI), stroke, recurrent angina, and need for revascularization. Six articles were subsequently included in the meta-analysis., Data Extraction: Three independent reviewers extracted the data of interest from the articles using a standardized data collection form that included study quality indicators. Disparity in assessment was adjudicated by another reviewer., Data Synthesis: All pooled analyses were initially done using Fixed Effects model. For pooled analyses with significant heterogeneity (I2≥ 50%), the Random Effects model was used. A total of 3,768 patients were included, 1,986 in the invasive strategy group, and 1,782 in the conservative treatment group., Results: Meta-analysis showed less incidence of revascularization in the invasive (2%) over conservative treatment groups (8%), with overall risk ratio of 0.29 (95% CI 0.14 to 0.59). Across all pooled studies, no significant effect of invasive strategy on all-cause mortality, cardiovascular mortality, stroke, and MI was observed. Only one study assessed the outcome of recurrent angina., Conclusion: There was a significantly lower rate of revascularization in the invasive strategy group compared to the conservative treatment group. In the reduction of all-cause mortality, cardiovascular mortality, MI, and stroke there was no significant effect of invasive strategy versus conservative treatment. This finding does not support the bias against early routine invasive intervention in patients ≥ 65 years old with NSTEACS. Further studies focusing on these patients with larger population sizes are still needed., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: RRC is a member of advisory board or speakers’ pool of Servier, Boehringer Ingelheim, Menarini, LRI-Therapharma, Sanofi, UAP Pharma, Unilab; MTR is a member of speakers’ pool of Novartis, Servier, Astra Zeneca; the rest declare no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

A common drug used for hypertension among Filipinos is beta-blockers. Variable responses to beta-blockers are observed, and genetic predisposition is suggested. This study investigated the association of genetic variants with poor response to beta-blockers among Filipinos. A total of 76 Filipino adult hypertensive participants on beta-blockers were enrolled in an unmatched case-control study. Genotyping was done using DNA from blood samples. Candidate variants were correlated with clinical data using χ 2 and logistic regression analysis. The deletion of at least one copy of allele A of rs36217263 near Klotho showed statistically significant association with poor response to beta-blockers (dominant; odds ratio (OR) = 3.89; P = 0.017), adjusted for diabetes and dyslipidemia. This association is observed among participants using cardioselective beta-blockers (crude OR = 5.60; P = 0.008) but not carvedilol (crude OR = 2.56; P = 0.67). The genetic variant rs36217263 is associated with poor response to cardioselective beta-blockers, which may become a potential marker to aid in the management of hypertension., (© 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics.)

Objectives: Hospitalisation for congestive heart failure (CHF) was reported to be 1648 cases for every 100 000 patient claims in 2014 in the Philippines; however, there are no data regarding its economic impact. This study determined CHF hospitalisation cost and its total economic burden. It compared the healthcare-related hospitalisation cost from the societal perspective with the payer's perspective, the Philippine Health Insurance Corporation (PhilHealth)., Methods: This is a cost analysis study. Data were obtained from representative government/private hospitals and a drugstore in all regions of the country. Healthcare costs included cost of diagnostics/treatment, professional fees and other CHF-related hospital charges, while non-healthcare costs included production losses, transportation and food expenses., Results: The overall mean healthcare-related cost for CHF hospitalisation (class III) in government hospitals in the Philippines in 2014 was PHP19 340-PHP28 220 (US$436-US$636). In private hospitals, it was PHP28 370-PHP41 800 (US$639-US$941). In comparison, PhilHealth's coverage/CHF case rate payment is PHP15 700 (US$354). The mean non-healthcare cost was PHP10 700-PHP14 600 (US$241-US$329). Using PhilHealth's case rate payment and the prevalence of CHF hospitalisation in 2014, the total economic burden was PHP691 522 200 (US$15 574 824). Using the study results on healthcare-related cost meant that the total economic burden for CHF hospitalisation would instead be PHP851 850 000-PHP1 841 563 000 (US$19 185 811-US$41 476 644)., Conclusions: The calculated healthcare-related hospitalisation cost for CHF in the Philippines in 2014 demonstrates the disparity between the actual cost and PhilHealth's coverage. This implies a need for policymakers to review its coverage to make healthcare delivery affordable., Competing Interests: Competing interests: None declared.

Background: Symptoms of mitral stenosis (MS) are worsened during tachycardia and exercise. Beta-blockers are used in controlling heart rate (HR) in MS, resulting in symptom improvement, but coming with significant side effects. Ivabradine has a selective action on the sinus node devoid of the usual side effects of beta-blockers. Small studies have recently investigated the role of ivabradine in MS in sinus rhythm. Our aim was to determine the efficacy of ivabradine, compared to beta-blockers, in terms of exercise duration, maximum HR achieved, resting HR, mean gradient, and working capacity among patients with MS in sinus rhythm., Methods: We conducted a systematic search of studies using MEDLINE, Google Scholar, ScienceDirect, Scopus, Clinical Key, Cochrane, and clinicaltrials.gov databases in all languages and examined reference lists of studies. We included studies if they are: 1) randomized controlled trials comparing ivabradine and beta-blockers; 2) of adults ≥ 19 years old with MS in sinus rhythm; and 3) reported data on exercise duration, maximum HR achieved, resting HR, mean gradient, and working capacity. Studies identified were assessed for risk of bias using the Cochrane Collaboration Tool for Assessing Risk of Bias. We used inverse variance analysis of fixed effects to compute for mean difference, carried out using Review Manager (RevMan) 5.3., Results: Pooled analysis from five identified trials showed that among patients with MS in sinus rhythm, ivabradine was better compared to beta-blockers in total exercise duration (mean difference: 32.73 s (95% CI: 12.19, 53.27; P = 0.002; I 2 = 0%)), maximum HR achieved after exercise (mean difference: -3.87 beats per minute (95% CI: -5.88, -1.860; P = 0.0002; I 2 = 23%)), and work capacity (mean difference: 0.56 METS (95% CI: 0.33, 0.80; P < 0.00001; I 2 = 0%)); inferior to beta-blockers in resting HR achieved (mean difference: 1.83 s (95% CI: 0.39, 3.28; P = 0.01; I 2 = 91%)); and comparable to beta-blockers in terms of mean gradient (mean difference: -0.52 mm Hg (95% CI: -1.20, 0.16; P = 0.13; I 2 = 6%))., Conclusions: Ivabradine is better or comparable to beta-blockers in terms of the outcomes measured, and may be considered as an alternative for patients with MS in sinus rhythm who are intolerant to beta-blockers.

Background: Red cell distribution width (RDW), a routine component of the complete blood count (CBC), measures variation in the size of circulating erythrocytes. It has been associated with several clinical outcomes in cardiovascular disease. We sought to strengthen the association between RDW and mortality in patients admitted for acute coronary syndrome (ACS) by pooling together data from available studies., Methods: Studies that fulfilled the following were identified for analysis: 1) observational; 2) included patients admitted for ACS; 3) reported data on all-cause or cardiovascular (CV) mortality in association with a low or high RDW; and 4) used logistic regression analysis to control for confounders. Using MEDLINE, Clinical Key, ScienceDirect, Scopus, and Cochrane Central Register of Controlled Trials databases, a search for eligible studies was conducted until January 9, 2017. The quality of each study was evaluated using the Newcastle-Ottawa Quality Assessment Scale. Our primary outcome of interest was all-cause or CV mortality. We also investigated the impact of RDW on major adverse cardiovascular events (MACEs) for the studies that reported these outcomes. Review Manager (RevMan) 5.3 was utilized to perform Mantel-Haenzel analysis of random effects and compute for relative risk., Results: We identified 13 trials involving 10,410 patients, showing that in ACS, a low RDW is associated with a statistically significant lower all-cause or CV mortality (RR 0.35, (95% CI 0.30 to 0.40), P < 0.00001, I 2 = 53%), a finding that was consistent both in the short- and long-term., Conclusions: A low RDW is also associated with lower risk for MACEs after an ACS (RR 0.56, (95% CI 0.51 to 0.61), P < 0.00001, I 2 = 91%). A low RDW during an ACS is associated with lower all-cause or CV mortality and lower risk of subsequent MACEs, providing us with a convenient and inexpensive risk stratification tool in ACS patients.

Objectives: To determine 1) the cost of hospitalization, the 1-week postdischarge cost, the total cost, and the economic burden of community-acquired pneumonia among patients aged 19 years or older in the Philippines and 2) the difference between the estimated costs and the Philippine Health Insurance Corporation (PhilHealth) pneumonia case rate payments., Methods: The study involved two tertiary private hospitals in the Philippines. Using the societal perspective, both health care and non-health care costs were determined. A base-case analysis and sensitivity analyses were performed, and the economic burden of pneumonia was determined using PhilHealth claims., Results: The estimated cost of hospitalization for community-acquired pneumonia-moderate risk (CAP-MR) ranged from Philippine peso (PHP) 36,153 to 113,633 (US $852-2678) and its 1-week postdischarge cost ranged from PHP1450 to 8800 (US $34-207). The cost of hospitalization for community-acquired pneumonia-high risk (CAP-HR) ranged from PHP104,544 to 249,695 (US $2464-5885) and PHP101,248 to 243, 495 (US $2386-5739) using invasive and noninvasive ventilation, respectively. The postdischarge cost for CAP-HR ranged from PHP1716 to 10,529 (US $40-248). If only health care cost was considered, the cost ranged from PHP24,403 to 89,433 for CAP-MR and PHP92,848 to 213,395 for CAP-HR. The present PhilHealth case rate payments are PHP15,000 (US $354) and PHP32,000 (US $754) for CAP-MR and CAP-HR, respectively. Based on the number of PhilHealth claims for 2012 and the estimated health care cost, the economic burden of pneumonia in 2012 was PHP8.48 billion for CAP-MR and PHP643.76 million for CAP-HR., Conclusions: The estimated health care cost of hospitalization is markedly higher than the PhilHealth case rate payments. As per the study results, the economic burden of pneumonia is, thus, significantly higher than PhilHealth estimates., (Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)