The Value of Warning Signs From the WHO 2009 Dengue Classification in Detecting Severe Dengue in Children.

BACKGROUND: World Health Organization proposed 7 warning signs to identify the risk of severe dengue in 2009. This study aimed to evaluate the value of these warning signs in detecting severe dengue in children. MATERIAL AND METHODS: A cross-sectional study was conducted utilizing data of children with clinical dengue infection obtained from medical records between January 2009 and December 2018 in Jakarta. Children with confirmed dengue were analyzed and stratified into 3 age groups: infants less than 1 year old, children 1-14 years and adolescents 15-18 years of age. Positive predictive value, negative predictive value (NPV), sensitivity and specificity of each warning sign present or absent on admission in detecting severe dengue were computed. RESULTS: Six hundred ninety-nine children with clinical dengue infection were enrolled, among whom 614 (87.8%) had confirmed dengue infection, either by antigen or antibody serological tests. Severe dengue occurred in 211/614 (34.4%) cases. In infants, important warning signs on admission to detect or exclude severe dengue were liver enlargement (NPV 80.8%) and clinical fluid accumulation (NPV 75%). In children and adolescents, warning sign with highest NPV (in children 76.6% and in adolescents 91.9%) was increase in hematocrit concurrent with a rapid decrease in platelet count. Other warning signs with high NPV values in children were abdominal pain (72%), vomiting (70%), clinical fluid accumulation (69.3%), and in adolescents' abdominal pain (80.7%), vomiting (75.7%), clinical fluid accumulation (82.7%). NPVs increase with more than 1 warning sign in all age groups. CONCLUSION: In infants, liver enlargement or clinical fluid accumulation are important warning signs for severe dengue, when both are absent, severe dengue is unlikely. In older children and adolescents, an increase in hematocrit with the concurrent rapid decrease in platelet count is most discriminative; followed by the absence of abdominal pain, vomiting or fluid accumulation are unlikely severe dengue.

Malnutrition Prevalence and Nutrient Intakes of Indonesian Older Adults in Institutionalized Care Setting: A Systematic Review of Observational Studies.

INTRODUCTION: Data on the prevalence of malnutrition and nutrient intakes among Indonesian older aduls in institutionalized care setting are scattered and scarce. Thus, we conducted a systematic review of published and grey literature to estimate (1) the prevalence of malnutrition, (2) the level and distribution of habitual energy and nutrient intakes, and (3) the prevalence of inadequacy of energy and nutrient intakes among hospitalized and institutionalized older adults in Indonesia. METHODS: This systematic review was written following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist. The population of this review was Indonesian older adults in institutionalized care settings, including hospital ward, orphanages, nursing homes, residential facilities, and rehabilitation centers . Malnutrition was assessed using body mass index, the mini nutritional assessment (MNA) score, or the subjective global assessment (SGA) score. The dietary intakes (from food recalls, food records, or food frequency questionnaire) were compared with the Indonesian recommended daily allowances (RDAs) for people aged 65 to 80. The prevalence of inadequacy was calculated using two-thirds of the RDA as a proxy for the estimated average requirement (EAR). RESULTS: The search yielded 330 studies from electronic databases, resulting in fifteen eligible studies. One report was obtained from an unpublished study. Based on the JBI criteria, most studies had low risk of bias and represented the target population. The prevalence of malnutrition in hospital, nursing home, and other institutionalized care ranged from 6.5%-48.3% in hospitals and 3.2%-61.0% in other institutionalized care units. In the hospital setting, there was a high prevalence of inadequacies for all nutrients, particularly protein (20%), calcium (more than 90%), and vitamin D intakes (more than 50%). In nursing homes, these proportions were exceptionally high for protein (66%) and calcium and vitamin D intakes (almost 100%). CONCLUSION: The high risk of malnutrition Indonesian older adults in institutionalized care setting is pronounced, along with poor intakes of macronutrients and micronutrients in both settings.

Cetuximab as first-line treatment for metastatic colorectal cancer (mCRC): a model-based economic evaluation in Indonesia setting.

OBJECTIVES: To assess the cost-effectiveness of cetuximab in combination with chemotherapy fluorouracil, oxaliplatin, and leucovorin (FOLFOX) or fluorouracil, irinotecan and leucovorin (FOLFIRI) compared to standard chemotherapy alone as a first-line treatment for metastatic colorectal cancer (mCRC) with positive KRAS wild type patients in Indonesia. METHODS: A cost-utility analysis applying Markov model was constructed, with a societal perspective. Clinical evidence was derived from published clinical trials. Direct medical costs were gathered from hospital billings. Meanwhile, direct non-medical costs, indirect costs, and utility data were collected by directly interviewing patients. We applied 3% discount rate for both costs and outcomes. Probabilistic sensitivity analysis was performed to explore the model's uncertainty. Additionally, using payer perspective, budget impact analysis was estimated to project the financial impact of treatment coverage. RESULTS: There was no significant difference in life years gained (LYG) between cetuximab plus FOLFOX/FOLFIRI and chemotherapy alone. The incremental QALY was only one month, and the incremental cost-effectiveness ratio (ICER) was approximately IDR 3 billion/QALY for cetuximab plus chemotherapy. Using 1-3 GDP per capita (IDR 215 million or USD 14,350) as the current threshold, the cetuximab plus chemotherapy was not cost-effective. The budget impact analysis resulted that if cetuximab plus chemotherapy remain included in the benefits package under the Indonesian national health insurance (NHI) system, the payer would need more than IDR 1 trillion for five years. CONCLUSIONS: The combination of cetuximab and chemotherapy for mCRC is unlikely cost-effective and has a substantial financial impact on the system.

Comparison of vitamin D levels in diabetes mellitus patients with and without diabetic foot ulcers: An analytical observational study in Jakarta, Indonesia.

Diabetic foot ulcer (DFU) is a form of chronic wound which becomes a serious complication in diabetes mellitus (DM). Recently, the role of vitamin D on T cell-mediated immunity, pancreatic insulin secretion, and its mechanism on cell growth and healing processes have been reported. This study aims to compare the vitamin D level of DM patients with DFU and without DFU to assess the duration and severity of DFU and its correlation with vitamin D levels. The sociodemographic characteristics and DFU duration were documented. The severity was examined in accordance with PEDIS classification. 25-hydroxyvitamin D (25[OH]D) was analysed using in-vitro chemiluminescent immunoassay (CLIA). Statistical analysis was performed and the P-value <.05 was considered as statistically significant. The vitamin D levels in DM patients with and without DFU were 8.90 ng/mL (6.52-10.90) and 16.25 ng/mL (13-19.59), respectively, with P < .001. There was no correlation between the duration of DFU and DFU severity by PEDIS score with vitamin D levels. Vitamin D levels in DM patients with DFU are lower than those in patients without DFU. However, there was insufficient evidence to conclude that there is no correlation between the DFU duration and DFU severity by PEDIS score with vitamin D levels.

Adding rituximab to chemotherapy for diffuse large B-cell lymphoma patients in Indonesia: a cost utility and budget impact analysis.

BACKGROUND: Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has been used to treat patients with diffuse large B-cell lymphoma (DLBCL) under National Health Insurance (NHI) scheme in Indonesia. This study aims to estimate its cost-effectiveness and budget impact. METHODS: We conducted a cost utility analysis using Markov model over a lifetime horizon, from a societal perspective. Clinical evidence was derived from published clinical trials. Direct medical costs were gathered from hospital data. Direct non-medical costs, indirect costs, and utility data were primarily gathered by interviewing the patients. We applied 3% discount rate for both costs and effect. All monetary data are converted into USD (1 USD = IDR 14,000, 2019). Probabilistic sensitivity analysis was performed. In addition, from a payer perspective, budget impact analysis was estimated using price reduction scenarios. RESULTS: The incremental cost-effectiveness ratio (ICER) of R-CHOP was USD 4674/LYG and 9280/QALY. If we refer to the threshold three times the GDP per capita (USD 11,538), R-CHOP could thus be determined as a cost-effective therapy. Its significant health benefit has contributed to the considerable ICER result. Although the R-CHOP has been considered a cost-effective intervention, the financial consequence of R-CHOP if remain in benefit package under National Health Insurance (NHI) system in Indonesia is considerably substantial, approximately USD 35.00 million with 75% price reduction scenario. CONCLUSIONS: As a favorable treatment for DLBCL, R-CHOP ensures value for money in Indonesia. Budget impact analysis provides results which can be used as further consideration for decision-makers in matters related to benefit packages.

Malnutrition Prevalence and Nutrient Intakes of Indonesian Community-Dwelling Older Adults: A Systematic Review of Observational Studies.

Background: Malnutrition and inadequate nutrient intake are associated with functional decline, frailty, and bad clinical outcomes among community-dwelling older adults. Despite the growing proportion of the elderly population in Indonesia, data on the prevalence of malnutrition and adequacy of macronutrient and micronutrient intakes among Indonesian older adults are scattered and vary between studies. Therefore, our study aims to obtain data on malnutrition prevalence, level and distribution of nutrient intakes, and prevalence of macronutrient and micronutrient inadequacies in Indonesian community-dwelling older adults. Methods: We carried out a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and registered in PROSPERO. A systematic electronic database search of MEDLINE, CENTRAL, EMBASE, ProQuest, HINARI, IMSEAR, GARUDA, and Indonesian Publication Index was undertaken. Additional searches were conducted in gray literature sources, hand-searching, retrospective searching, and personal communication with authors of the relevant publication. Observational studies presenting the malnutrition prevalence of habitual dietary intakes of older adults (60 years or older) were included. The risk of bias of studies was assessed using the Joanna Briggs Institute critical appraisal form. Sex-specific mean (and standard deviation) habitual macronutrient and a selection of micronutrients (calcium, vitamin D, and vitamin B12) intakes were extracted from each article to calculate the percentage of older people who were at risk for inadequate micronutrient intakes using a proxy of estimated average requirement (EAR) cut-point method, which is calculated from the national guideline of recommended dietary allowance (RDA). Prevalence of malnutrition, based on body mass index (BMI) categories and mini-nutritional assessment (MNA) criteria. and the population at risk of malnutrition were presented descriptively. Results: Nine studies retrieved from electronic databases and gray literature were included in the pooled systematic analysis. According to BMI criteria, the underweight prevalence ranged from 8.0 to 26.6%. According to the MNA, the prevalence of malnutrition ranged from 2.1 to 14.6%, whereby the prevalence of at risk of malnutrition amounted to 18-78%. Our systematic review identified a high prevalence of nutrient inadequacies, most markedly for protein, calcium, vitamin D, and vitamin B12. Conclusion: We signal a high risk of malnutrition along with poor macronutrients and micronutrients intakes among Indonesian community-dwelling older adults. These findings provide important and robust evidence on the magnitude of malnutrition and nutrient inadequacy concerns that call for appropriate nutrition, as well as public health policies and prompt intervention. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42018102268.

The Effect of Vitamin D Supplementation on Symptoms of Depression in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The effect of vitamin D supplementation on depressive  symptoms in people with type 2 diabetes is still up for debate. The aim of this paper was to investigate the effect of vitamin D supplementation on symptoms of depression in type 2 diabetic patients. METHODS: The protocol for this review has been registered in PROSPERO:CRD42021231713. Searching for literature was conducted using Pubmed, EBSCOhost, and EMBASE. Randomised controlled trials (RCTs) regarding vitamin D supplementation in type 2 diabetic patients with depression were retrieved through a systematic search. The outcome measured was a change in depressive symptoms evaluated with any validated rating scale. Independent data extraction was conducted, and the study quality was assessed. A meta-analysis was carried out to calculate the improvement in depressive symptoms in the group receiving vitamin D and the control group. The available evidence in RCTs was analysed using the PRISMA approach, and clinical significance was determined using the GRADE system. Risk of bias was assessed using the Cochrane Risk of Bias Tool. RESULTS: Four RCTs were reviewed and three RCTs were meta-analysed. In two studies, vitamin D was statistically effective in improving depressive symptoms in type 2 diabetic patients. Three randomised controlled trials  were included in the meta-analysis with 161 subjects using depression score as an outcome assessment. Vitamin D is significantly more effective than placebo (95% CI: -0.70 to - 0.08, p = 0.01). CONCLUSION: Vitamin D supplementation is effective in improving depressive symptoms in type 2 diabetic patients. Future research with different geographical areas and larger samples should be done to further assess the benefits.

Prognostic Scoring System for Mortality of Hospitalized COVID-19 Patients in Resource-Limited Settings: A Multicenter Study from COVID-19 Referral Hospitals.

BACKGROUND: Many studies identified the risk factors and prognostic factors related to in-hospital COVID-19 mortality using sophisticated laboratory tests. Cost and the availability of supporting blood tests may be problematic in resource-limited settings. This multicenter cohort study was conducted to assess the factors associated with mortality of COVID-19 patients aged 18 years and older, based on history taking, physical examination, and simple blood tests to be used in resource-limited settings. METHODS: The study was conducted between July 2020 and January 2021 in five COVID-19 referral hospitals in Indonesia. Among 1048 confirmed cases of COVID-19, 160 (15%) died during hospitalization. RESULTS: Multivariate analysis showed eight predictors of in-hospital mortality, namely increased age, chronic kidney disease, chronic obstructive pulmonary disease, fatigue, dyspnea, altered mental status, neutrophil-lymphocyte ratio (NLR) ≥ 5.8, and severe-critical condition. This scoring system had an Area-under-the-curve (AUC) of 84.7%. With cut-off score of 6, the sensitivity was 76.3% and the specificity was 78.2%. CONCLUSION: The result of this practical prognostic scoring system may be a guide to decision making of physicians and help in the education of family members related to the possible outcome.

Clinical Profile of Elderly Patients with COVID-19 hospitalised in Indonesia's National General Hospital.

Latar BelakangSebanyak 38.6% kasus kematian pasien COVID-19 di Indonesia terjadi di populasi lansia. Data mengenai profil klinis pasien rawat inap lansia dengan COVID-19 masih tidak ada. Padahal kelompok pasien ini adalah pasien risiko tinggi selama pandemi ini yang memerlukan perhatian lebih.MetodeStudi deskriptif ini menggunakan data lengkap pasien lansia dengan COVID-19 yang dirawat inap di Rumah Sakit Umum Pusat Nasional Cipto Mangunkusumo (RSUPN Cipto Mangunkusumo) dari April hingga akhir Agustus 2020. Data termasuk karakteristik klinis, gejala, komorbiditas, multimorbiditas dan luaran mortalitas pasien.HasilDi populasi pasien lansia (n=44), mayoritas berusia di antara 60-69 tahun (68%), berjenis kelamin laki-laki (66%), dan tidak memiliki riwayat kontak erat dengan pasien COVID-19 sebelumnya (86%). Gejala tersering ialah demam, batuk, dan sesak yang merupakan gejala khas COVID-19, sedangkan penyakit kronis tersering adalah diabetes melitus, hipertensi, dan keganasan. Multimorbiditas ditemukan hanya di 14% pasien lansia, dan para pasien tersebut bertahan hidup pasca infeksi virus SARS-CoV-2. Angka kematian pasien lansia rawat inap dengan COVID-19 di studi ini adalah 23%, dan 90% dari kasus kematian berjenis kelamin laki-laki.KesimpulanPasien laki-laki mendominasi kasus terkonfirmasi dan kasus kematian lansia dengan COVID-19. Gejala khas COVID-19 hanya ditemukan di sekitar setengah pasien penelitian. Pasien yang meninggal dunia memiliki persentase gejala khas lebih tinggi. Gejala tidak khas pun mungkin ditemukan di pasien lansia. Immunosenescence dan fungsi imunoregulasi jenis kelamin tertentu dihipotesiskan memiliki peran penting dalam menyebabkan kematian lansia di studi ini.Kata Kunci: Profil Klinis, Lansia, Pasien Geriatri, COVID-19, Indonesia  ABSTRACTBackgroundOlder people contributed to 38.6% of death cases related to COVID-19 in Indonesia. Data regarding clinical profile of hospitalised elderly with COVID-19 in Indonesia were still lacking. Older people are at-risk population in the pandemic, whom we should pay attention to.MethodsThis single centre descriptive study utilised complete data of elderly inpatients with COVID-19 in Indonesia's national general hospital from April to late August 2020. The data consisted of clinical characteristics, symptoms, comorbidities, multimorbidity, and mortality outcome.ResultsAmong elderly patients (n=44), a majority of patients were aged 60-69 years (68%), were male (66%), and had no history of close contact with COVID-19 patient (86%). The most common symptoms were fever, cough and shortness of breath (classic symptoms of COVID-19), whereas the most common chronic diseases were diabetes mellitus, hypertension, and malignancy. Multimorbidity was only found in 14% of patients, all of whom remained alive following SARS-CoV-2 infection. The death rate among elderly inpatients with COVID-19 in this study was 23%, and male older adults contributed to 90% of death cases.ConclusionMale patients dominated both confirmed cases and death cases among elderly with COVID-19. Classic symptoms of COVID-19 were only found in about half of the study patients. Non-survivors had higher percentage of the classic symptoms of COVID-19 than survivors. Atypical COVID-19 presentations are possible in older adults. We postulated that immunosenescence and sex-specific immunoregulatory function play an important role in causing death in this study cohort. Keywords: Clinical Profile, Elderly, Geriatric Patient, COVID-19, Indonesia.

Risk factors and laboratory test results associated with severe illness and mortality in COVID-19 patients: A systematic review.

BackgroundWe aimed to systematically review all relevant studies related to the risk factors and laboratory test results associated with severe illness and mortality in COVID-19 patients.MethodsWe utilised PubMed, Scopus, ProQuest, Wiley Online Library, ScienceDirect and MedRxiv to search for studies, with additional hand-searched journals. We included systematic reviews/meta-analyses, cohort and case control studies of suspected and/or confirmed COVID-19 cases with severe illness and/or mortality as outcomes. We included laboratory test results and risk factors. We assessed risk of bias using ROBIS-I and Newcastle-Ottawa Scale assessment tool. Type of study, risk of bias, and precision of results determined evidence sufficiency.ResultsOf 26 records included, sufficient evidence suggested the association between age >60 years, hypertension, coronary heart disease, DM, serum LDH 250-500 U/L, LDH >500 U/L, and lymphopenia (lymphocyte count ≤1.0 x 109 /L) and severe illness of COVID-19. CD3+CD8+ cell count ≤ 75 cell/µl, D-dimer > 1 mg/L, AKI stage 2 and 3, proteinuria ≥1+, hematuria ≥1+, and peak serum creatinine > 13.26 µmol/L are associated with mortality.ConclusionAge >60 years, hypertension, DM, and coronary heart disease are the risk factors for severe illness of COVID-19. Laboratory test results associated with severe illness are serum LDH 250-500 U/L, LDH >500 U/L, and lymphopenia, whereas test results associated with mortality are CD3+CD8+ cell count ≤ 75 cell/µl, AKI stage 2 and 3, proteinuria ≥1+, hematuria ≥1+, D-dimer > 1 mg/L, peak serum creatinine > 13.26 µmol/L.

Factors Affecting Virological Outcome When First-Line Antiretroviral Therapy Is Reintroduced After Unplanned Interruption.

There is no guideline concerning choice of antiretroviral therapy (ART) for HIV-infected patients after unplanned interruption. We conducted a retrospective cohort study of HIV-infected patients reintroduced to first-line ART after having unplanned interruption for at least 1 month. Viral load was evaluated at 6 to 18 months after the reintroduction. There were 100 patients included in our study, and 55 of them achieved virological success. History of single interruption (adjusted odds ratio [aOR] 5.51%, 95% confidence interval [CI] 1.82-16.68, P = .003) and CD4 count ≥200 cell/mm3 at the time of reintroduction (aOR 4.33, 95% CI 1.14-16.39, P = .031) increased likelihood to achieve virological success.

BReastfeeding Attitude and Volume Optimization (BRAVO) trial: study protocol for a randomized controlled trial.

BACKGROUND: A growing body of evidence shows the short-term benefits of breastfeeding, which include protection against infections, allergies, and lung diseases. However, evidence on the long-term benefits of breastfeeding is scarce and often conflicting. The BReastfeeding Attitude and Volume Optimization (BRAVO) trial is designed to study the effect of breastfeeding on early signs of later chronic diseases, particularly cardiovascular, respiratory, and metabolic risks later in life. In addition, the effectiveness of breastfeeding empowerment in promoting breastfeeding will also be evaluated. METHODS/DESIGN: This study is an ongoing randomized trial in Jakarta, Indonesia, that began in July 2012. Pregnant women are being screened for their breastfeeding plan in the third trimester, and those with low intention to breastfeed are randomly allocated to either receiving an add-on breastfeeding-optimization program or usual care. Primary outcomes include breastfeeding rate, lung function, and blood pressure during the first year of life and vascular/cardiac characteristics, which will be measured at the age of 4 to 5 years. Child growth and infection/illness episodes are measured, whereas cognitive testing is planned for the children at 5 years of age. DISCUSSION: To date, 784 women (80 %) have been randomized of the 1,000 planned, with satisfactory completeness of the 1-year follow up (90.1 %). Included mothers are of lower socioeconomic status and more often have blue-collar jobs, similar to what was observed in the pilot study. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01566812 . Registered on 27 March 2012.

Quality and reporting of publications by Indonesian researchers: a literature survey.

OBJECTIVES: To evaluate the quality of reporting of the risk of bias of the Indonesian medical research. METHODS: Publications from PubMed and non-PubMed indexed Indonesian medical journals between January 2008 to December 2010 were assessed for risk of bias based on criterion combination from Hedges-criteria and the Oxford Center for Evidence-Based Medicine. We assessed whether the publications addressed the risk of bias adequately (quality of reporting) and whether the risk of bias criterion was fulfilled (quality of methods). The quality (both of reporting and of methods) of a study was classified as "high" if, for at least two-thirds of the criteria were adequately reported and fulfilled. It was classified as "low" when only one-third of the criteria were reported and or fulfilled. RESULTS: Of the 1753 publications, 29% (n = 507) were original medical research. For 21% (109/507) the quality of reporting was high; for 15% (77/507) the quality of methods was high. The proportion of high quality was significantly higher among PubMed than non-PubMed, with difference between proportions: (95%CI of difference: 3 to 23). CONCLUSION: A small proportion of Indonesian studies have high quality of reporting or methods. When international reporting guidelines are endorsed and followed, the quality of future studies may improve.