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.

Aortic Valve Replacement with Single-Strip Autologous Pericardium.

BACKGROUND: Aortic valve replacement with mechanical valves is the standard treatment for aortic valve disease in Indonesia. Its usage is associated with high cost, risk of endocarditis and thromboembolic event, and lifetime consumption of anticoagulants. We performed a novel replacement technique of the aortic valve using an autologous pericardium and evaluated the short-term outcomes. METHODS: From April 2017 to April 2020, 16 patients underwent aortic valve replacement with a single-strip autologous pericardium. Outcomes of the left ventricular reverse remodeling (LVRR), 6-minute walk test (6MWT), and soluble suppression of tumorigenicity-2 (sST-2) were measured at 6 months postoperation. RESULTS: A total of 16 surgeries were performed using aortic valve replacement with single-strip pericardium without conversion to mechanical valve replacement. The patients included eight males and eight females, and the mean age was 49.63 ± 12.54 years. The most common diagnosis was mixed aortic valve stenosis and regurgitation (9 cases). Five patients underwent a concomitant coronary artery bypass graft (CABG) procedure and 12 patients underwent either mitral or tricuspid valve repair. The mean aortic cross-clamp time was 139.88 ± 23.21 minutes and cardiopulmonary bypass time was 174.37 ± 33.53 minutes. At 6 months postoperation, there was an increase in the distance walked at the 6MWT (p = 0.006) and a decrease of the sST-2 level (p = 0.098). Echocardiogram showed two patients had LVRR. Survival and freedom from reoperation are 100% at 1 year of follow-up. CONCLUSION: Aortic valve replacement with a single strip of pericardium is a good alternative to aortic valve replacement with a mechanical valve. Short-term evaluation at 6 months postoperation showed improvement in clinical status and echocardiographic parameters compared to baseline.

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.

Transcatheter Closure of Perimembranous Ventricular Septal Defect Using the Lifetech Konar-Multi Functional Occluder: Early to Midterm Results of the Indonesian Multicenter Study.

Background: The alternative device to close perimembranous ventricular septal defect (pmVSD) has been searched for better result, less complications and applicable for infants. However, the ideal device is still unavailable. We aimed to evaluate the effectiveness and outcome of transcatheter pmVSD closure using the KONAR-multi functional occluder (MFO). Methods: Clinical, procedural, follow-up data of pmVSD patients with symptom of heart failure or evidence of significant left to right shunt, growth failure, recurrent respiratory tract infection, and history of endocarditis who underwent transcatheter closure using the MFO were prospectively evaluated. Results: Between January 2016 and December 2017, there were complete records of 132 pmVSD children closed using MFO from eleven centers in Indonesia. The median of age was 4.5 (0.3-17.4) years; weight 14.8 (3.5-57) kg, defect size at the smallest part 3.4 (1.0-8.1) mm, flow ratio 1.6 (1.3-4.9), mean pulmonary artery pressure 18 (7-79) mmHg, fluoroscopy time 18 (3.8-91) and procedural time 75 (26-290) minutes. A retrograde approach was done in 41 (31%) patients. Procedures succeeded in first attempt in 126 (95.4%), failed in three and migration in three patients. Six of eight infants with congestive heart failure were closed successfully. Of 126 patients with successful VSD closure, 12 months follow-up were completed in all patients. The rate of complete occlusion at 1 month, 3 months, 6 months and 12 months after intervention were 95.2%, 97.6%, 99.2%, and 99.2%, respectively. New-onset aortic regurgitation and moderate tricuspid regurgitation developed only in five and three patients. Neither complete atrioventricular block, nor other complications occurred. Conclusion: Transcatheter closure of pmVSD using the MFO is safe, effective, and feasible in infants and children.

Risk factors predicting intractability in focal epilepsy in children under 3 years of age: A cohort study.

BACKGROUND: Focal onset epilepsy carries a higher risk of intractability than generalized onset epilepsy. Knowledge of the risk factors of intractability will help guide the treatment of children with focal epilepsy. In addition to risk factors present at initial diagnosis, the evolution of clinical and electroencephalographic features may also play a role in predicting intractability. METHODS: A prospective cohort study was done on children aged one month to three years with newly diagnosed focal epilepsy. Initial treatment of carbamazepine was given according to a standard protocol after assessment of clinical manifestations, neurologic and developmental status, EEG, and brain MRI. Depending on response to therapy, subjects may also receive valproic acid or phenobarbitone following the protocol. Follow-up was done in the second week and every month thereafter. At the end of the study period, seizure type was re-assessed and a repeat neurological and developmental examination and EEG was obtained to evaluate the role of clinical and EEG evolution in predicting intractability. RESULTS: Out of 71 subjects, 21 (29.6%) had intractable epilepsy at the end of the study period. Age of onset (p = 0.216) and neurological status (p = 0.052) were not associated with intractable epilepsy. On logistic regression analysis, evolution of seizure type (p < 0.001; RR 56.45; 95%CI 6.56 to 485.85) and evolution of background EEG rhythm (p < 0.001; RR 56.51; 95%CI 2.77 to 1152.16) were significantly associated with intractable epilepsy. CONCLUSIONS: Changes in seizure type and baseline EEG rhythm may predict intractability in children one month to three years of age with focal epilepsy.

Economic Evaluation of Adding Bevacizumab to Chemotherapy for Metastatic Colorectal Cancer (mCRC) Patients in Indonesia.

OBJECTIVE: Since 2016, bevacizumab has been widely used to treat metastatic colorectal cancer (mCRC) in Indonesia. Nevertheless, the high cost of bevacizumab has raised the question of whether the therapy is considered cost-effective and should be included in the national health insurance system. This study aimed to assess the cost-effectiveness of bevacizumab plus chemotherapy versus chemotherapy alone for the treatment of mCRC patients. METHODS: A Markov model was applied using the perspective of the Indonesian healthcare system to assess cost-effectiveness. The health outcomes were expressed in terms of quality-adjusted life years (QALY) using the validated EuroQoL-5D-5L instrument. Data for medical costs were collected from hospital billings in four hospitals located in three different cities in Indonesia. Meanwhile, data for utility were obtained from interviewing 90 patients who came to the hospital. We compared those mCRC patients who received chemotherapy alone either with FOLFOX or FOLFIRI, versus patients who received the addition of bevacizumab. RESULTS: With the perspective of societal, the incremental cost-effectiveness ratio (ICER) of adding bevacizumab was USD 49,312 per QALY gained using secondary data and USD 28,446 per QALY using real world data. CONCLUSION: Using either a healthcare or societal perspective, the addition of bevacizumab for mCRC treatment was considered not cost-effective.

A landscape analysis of health technology assessment capacity in the Association of South-East Asian Nations region.

BACKGROUND: Progress towards achieving Universal Health Coverage and institutionalizing healthcare priority setting through health technology assessment (HTA) in the Association of South-East Asian Nations (ASEAN) region varies considerably across countries because of differences in healthcare expenditure, political support, access to health information and technology infrastructure. To explore the status and capacity of HTA in the region, the ASEAN Secretariat requested for member countries to be surveyed to identify existing gaps and to propose solutions to help countries develop and streamline their priority-setting processes for improved healthcare decision-making. METHODS: A mixed survey questionnaire with open- and closed-ended questions relating to HTA governance, HTA infrastructure, supply and demand of HTA and global HTA networking opportunities in each country was administered electronically to representatives of HTA nodal agencies of all ASEAN members. In-person meetings or email correspondence were used to clarify or validate any unclear responses. Results were collated and presented quantitatively. RESULTS: Responses from eight out of ten member countries were analysed. The results illustrate that countries in the ASEAN region are at different stages of HTA institutionalization. While Malaysia, Singapore and Thailand have well-established processes and methods for priority setting through HTA, other countries, such as Cambodia, Indonesia, Lao PDR, Myanmar, the Philippines and Vietnam, have begun to develop HTA systems in their countries by establishing nodal agencies or conducting ad-hoc activities. DISCUSSION AND CONCLUSION: The study provides a general overview of the HTA landscape in ASEAN countries. Systematic efforts to mitigate the gaps between the demand and supply of HTA in each country are required while ensuring adequate participation from stakeholders so that decisions for resource allocation are made in a fair, legitimate and transparent manner and are relevant to each local context.

Determinants of Circulating Soluble Leptin Receptor and Free Leptin Index in Indonesian Pre-Pubertal Obese Male Children: A Preliminary Cross-Sectional Study.

PURPOSE: This study aimed to investigate the clinical and metabolic determinants of circulating soluble leptin receptor (CSLR) and free leptin index (FLI) in pre-pubertal obese male children. METHODS: We conducted a preliminary cross-sectional study at three tertiary hospitals and one public primary school. Eighty obese male children without growth and developmental abnormalities aged 5-9 years were recruited. In these children, obesity was solely caused by excessive food intake, and not by acute illness, medications, endocrine abnormalities, or any syndrome. Body mass index (BMI), body fat mass, carbohydrate intake, fat intake, high density lipoprotein cholesterol level, low density lipoprotein cholesterol level, triglyceride level, and Homeostatic Model Assessment for Insulin Resistance are the potential determinants for leptin regulation, which is represented by CSLR level and FLI. RESULTS: Carbohydrate was the main source of energy. BMI and body fat mass had negative weak correlation with CSLR and positive weak correlation with FLI. Furthermore, carbohydrate intake was found to be independently associated with CSLR based on the results of the multiple linear regression analysis. Following an increase in carbohydrate intake, CSLR level decreased progressively without any negative peak. CONCLUSION: Leptin regulation in prepubertal obese male children is associated with body composition and dietary intake. Carbohydrate intake is useful for predicting CSLR. Lipid profiles and insulin resistance are not related to both CSLR and FLI. Treatment and prevention of leptin resistance in obese children should focus on reducing BMI, fat mass, and carbohydrate intake.

Profile of Kawasaki Disease in Adolescents: Is It Different?

BACKGROUND: there is clearly growing population of young adults with potentially important coronary artery disease after Kawasaki disease (KD) during childhood, and cardiologist must be prepared to take care for them. As Kawasaki disease in adolescent and adult is rare and under-recognized, it is important to study data on patient presentations which may permit development of diagnostic criteria and treatment guidelines for this age group.This study aimed to compare the clinical profile of KD between adolescents (>10 years of age) and children ≤10 years. METHODS: This is a cross sectional study. A total of 1150 KD cases (age 1-192 months) during the period of January 2003-December 2016 were analyzed. The clinical profile of subjects aged >10 years (adolescents) and  ≤10 years (children) at acute phase of KD were compared. RESULTS: we found 17 cases of KD in adolescents among 1150 total cases (1.5%). Incomplete KD was more often seen in adolescents compared to children ≤ 10 years of age (59% vs. 29%). Some clinical features were more frequently seen in children than in adolescents, e.g. conjunctivitis (85% in ≤ 10 years of age vs. 65% in > 10 years), mucosal changes (94% vs. 77%), rash (86% vs. 59%), and hand/foot changes (68% vs. 41%). While other clinical features were more often seen in adolescents, e.g., cervical lymphadenopathy (82% vs. 39%) and coronary dilatation (47% vs. 29%). Laboratory results (hemoglobin, leukocytes, erythrocyte sedimentation rate and C-reactive protein) did not differ much between the two groups. CONCLUSION: Kawasaki disease in adolescents has some different clinical profile from that of younger age. Majority of adolescent patients have incomplete presentation. Some clinical features such as conjunctivitis, mucosal changes, rash, and hand/foot changes are more often seen in children ≤ 10 years compared to in adolescents, while cervical lymphadenopathy and coronary dilatation are more frequently seen in adolescents. The ratio of male to female is much higher in adolescents.

Quality analysis of randomized controlled trials reporting in the field of pediatrics by Indonesian researchers.

OBJECTIVE: To determine the quality of reports of the randomized controlled trial (RCT) in the field of pediatrics conducted by Indonesian investigators. METHODS: All pediatric RCTs conducted by Indonesian researchers were sourced from international and national (local) publications. The assessment was done using both the Consolidated Standards of Reporting Trial (CONSORT) 2010 statement and Jadad Scale. Overall scores from each assessment are reported with a comparison of overall scores between studies in international and local publications. RESULTS: A total of 91 pediatric randomized control trials by Indonesian authors were gathered. National publications yielded a total of 44 studies (48.4%) whilst international publications yielded 47 studies (51.6%). Using the CONSORT statement the percentage of good reports was 38.3% in international journals and 33.3% in national journals. Using Jadad scale the percentage of good reports was 43.6% (international journals) and 37.0% (national journals). Both were not statistically significant. CONCLUSIONS: Even though Indonesian investigators still need to be familiarized with good RCT reporting, the overall quality of the reports is fairly satisfactory. There is no significant difference in quality between studies published in international or national journals.

Developing a workplace lactation promotion model in Indonesia using Delphi technique.

BACKGROUND: Working mothers have a higher risk to terminate breastfeeding earlier than stay-at-home mothers. Researchers reported that support from the workplace by creating lactation facilities and develop supportive programs are necessary to increase the success of exclusive breastfeeding. The aim was to achieve expert consensus on developing a workplace-based lactation promotion model. METHODS: A three-round online survey using Delphi approach was conducted to reach consensus on to the development of a lactation program at a workplace. RESULTS: Twenty-two experts from Indonesian health authority, community medicine, child health and obstetrics were invited to join the Delphi study; 15 (68.2%) enrolled in the first round. The response rate in the second and third round was 80.0% (12/15) and 86.7% (13/15), respectively. The first round categorized the workplace-based promotion model into seven dimensions, i.e. policy and regulation, facility, education material, target participants, promotion approach, human resources, and time. In the final round, "maternity leave of 3-6 months" (median (Q1;Q3):2 (1, 4)) and "employees have the right to breast-pumping every 3 hours" (median (Q1;Q3):3 (2, 4)) ranked as the two most important indicators regarding policy and regulation. A dedicated lactation room (median (Q1;Q3):1 (1)) is the highest ranked indicator regarding facility dimension. Regarding education materials, benefits of breast milk for babies ranked as the highest indicator while for the education and delivering methods dimensions, social media and interactive counseling were two highest ranked indicators. The top management in the company and lactation counselor are the two highest-ranked indicators in human resources dimension. CONCLUSION: In the view of experts, involvement of a dedicated policy maker in the company, a workplace-based lactation counselor, regular promotion with interactive education and dedicated facilities are necessary to develop an effective workplace-based lactation promotion model.

Challenges and Supports of Breastfeeding at Workplace in Indonesia.

Due to increased number of women workers in Indonesia in the last decade, numbers of women living as a worker and a housewife have increased. This also increases the potential risk of breastfeeding discontinuation. Three months of maternal leave policy and inadequate lactation promotion support in workplace have been identified as factors that hinder lactating practices. The World Health Organization recommendation of 6 months of exclusive breastfeeding and joined regulation of three Indonesia ministers (Ministry of Health, Ministry of Labour, and Ministry of Women Empower) have failed to improve the exclusive breastfeeding rate among female workers in Indonesia due to the lack of a standardized guideline on lactation promotion at workplace. In addition, very limited or no studies have been conducted to evaluate the impact of workplace-based lactation intervention programs on exclusive breastfeeding rate among female workers. This is because the relationship of lactation with working performance and productivity could not motivate employer to invest in workplace-based lactation promotion facility or program.

A Combined Dietary and Cognitive Intervention in 3⁻5-Year-Old Children in Indonesia: A Randomized Controlled Trial.

Early childhood nutritional interventions typically combine nutritional and psychosocial stimulation. Such combined interventions result in long-lasting improvements of cognitive abilities in children who are malnourished. Here, we investigated potential cognitive abilities in normally developing children in Indonesia who were, however, at risk for suboptimal cognitive development due to little psychosocial stimulation in their home environment. In a randomized controlled intervention, children of the experimental group received nutritional supplementation combined with cognitive stimulation. Pre- and post-intervention measurements included cognitive development and functioning, behavior, and mother⁻child interaction. The experimental and control group received nutritional supplementation in the form of a fortified or unfortified milk powder, respectively. Additionally, the children and parents of the experimental group jointly engaged in daily learning activities at home and performed iPad-based tasks designed to foster cognitive abilities. The experimental group compared to the control group displayed a significantly higher increase in intelligence quotient as well as a significantly larger reduction in attentional problems after the intervention. These results indicate that low-level cognitive stimulation in combination with nutritional supplementation during early childhood can be an effective intervention that improves global cognitive functioning in healthy developing children. ClinicalTrials.gov Identifier: NCT02359669.

Long-term outcome of coronary artery dilatation in Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is an acute systemic vasculitis syndrome with a high incidence of coronary aneurysms in untreated children. The majority of aneurysms resulting from KD are known to regress with time. AIMS: This study aimed to determine the course and outcome of coronary artery dilatation in patients with KD and ascertain whether there are any differences in the outcomes in the different branches. SETTING AND DESIGN: This is a retrospective cohort study of patients diagnosed with KD with midterm follow-up data. METHODS: Serial echocardiography was performed in all KD patients with coronary dilatation for 1-10½ years. The Kaplan-Meier curve was used for statistical analysis. RESULTS: There were 154 patients with coronary dilatation studied. The frequency of coronary dilatation in acute phase was 33.3% and decreased to 7.9% 6-8 weeks later. Each patient could have dilatations at more than one branch, so the total number of dilatations was 245. The median time needed for regression was 2.6 months (mean: 10.5 months) while the median of follow-up duration was 41 months (mean: 23 months). Small- and medium-sized dilatations had more favorable outcomes compared to the giant ones. Location of dilatation did not influence the outcome. CONCLUSIONS: The majority (77.4%) of small- and medium-sized dilatations regress within 2 years, but giant aneurysms tend to persist. The outcome of coronary dilatation is determined by the diameter and not by the location. Regression rate is faster in smaller dilatations. Left main coronary artery is the most frequent location for dilatation.

Systemic corticosteroids for acute otitis media in children.

BACKGROUND: Acute otitis media (AOM) is a common acute infection in children. Pain is its most prominent and distressing symptom. Antibiotics are commonly prescribed for AOM, although they have only a modest effect in reducing pain at two to three days. There is insufficient evidence for benefits of other treatment options, including systemic corticosteroids. However, systemic corticosteroids are potent anti-inflammatory drugs, and so theoretically could be effective, either alone or as an addition to antibiotics. OBJECTIVES: To assess the effects of systemic corticosteroids (oral or parenteral), with or without antibiotics, for AOM in children. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) which contains the Cochrane ARI Group's Specialised Register, MEDLINE (Ovid), Embase (Elsevier), CINAHL (EBSCO), Web of Science (Thomson Reuters), and LILACS (BIREME) for published studies, and ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) for completed and ongoing studies, to 20 February 2018. We checked the reference lists of all primary studies and review articles for additional references and contacted experts in the field to identify additional unpublished materials. SELECTION CRITERIA: We included randomised controlled trials of children with AOM that compared any systemic corticosteroid (oral or parenteral) with placebo, either with antibiotics (corticosteroid plus antibiotic versus placebo plus antibiotic) or without antibiotics (corticosteroid versus placebo). DATA COLLECTION AND ANALYSIS: Three review authors (EDS, RR, YP) independently screened the titles and abstracts and retrieved the full texts of potentially relevant studies. We independently extracted study characteristics and outcome data from the included studies, and assessed the risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We assessed study quality using the GRADE method. MAIN RESULTS: We included two studies involving 252 children with AOM aged from three months to six years receiving hospital ambulatory care who were treated with intramuscular ceftriaxone, and who were then randomised to the corticosteroid group (corticosteroid and corticosteroid plus antihistamine) or the placebo group (antihistamine and double placebo). In one study, children also had a needle aspiration of middle ear fluid. Both studies were at unclear risk of bias for allocation concealment, and unclear to high risk of bias for selective reporting.One study (N = 179) included pain as an outcome, but we were unable to derive the proportion of children with persistent pain at Day 5 and Day 14. Reduction of overall or specific symptoms was presented as improvement in clinical symptoms and resolution of inflamed tympanic membranes without the need for additional antibiotic treatment: at Day 5 (94% of children in the treatment group (N = 89) versus 89% in the placebo group (N = 90); risk ratio (RR) 1.06, 95% confidence interval (CI) 0.97 to 1.16) and Day 14 (91% versus 87%; RR 1.05, 95% CI 0.95 to 1.17). Low-quality evidence meant that we are uncertain of the effectiveness of corticosteroids for this outcome.The second study (N = 73) reported a reduction of overall or specific symptoms without additional antibiotic treatment during the first two weeks as a favourable outcome. Children in the treatment group had more favourable outcomes (adjusted odds ratio 65.9, 95% CI 1.28 to 1000; P = 0.037), although the numbers were small. We were unable to pool the results with the other study because it did not report the proportion of children with this outcome by treatment group. Only one study reported adverse effects of corticosteroids (e.g. drowsiness, nappy rash), but did not quantify incidence, so we were unable to draw conclusions about adverse effects. Neither study reported a reduction in overall or specific symptom duration. AUTHORS' CONCLUSIONS: The evidence for the effect of systemic corticosteroids on AOM is of low to very low quality, meaning the effect of systemic corticosteroids on important clinical outcomes in AOM remains uncertain. Large, high-quality studies are required to resolve the question.

Role of terminal warm blood cardioplegia in complex congenital heart surgery.

Introduction Myocardial protection is vital to ensure successful open heart surgery. Cardioplegic solution is one method to achieve good myocardial protection. Inevitably, ischemia-reperfusion injury occurs with aortic crossclamping. Histidine-tryptophan-ketoglutarate solution is a frequently used cardioplegia for complex congenital heart surgery. We postulated that addition of terminal warm blood cardioplegia before removal of the aortic crossclamp might improve myocardial protection. Method A randomized controlled trial was conducted on 109 cyanotic patients aged, 1 to 5 years who underwent complex biventricular repair. They were divided into a control group of 55 patients who had histidine-tryptophan-ketoglutarate only and a treatment group of 54 who had histidine-tryptophan-ketoglutarate with terminal warm blood cardioplegia. Endpoints were clinical parameters, troponin I levels, and caspase-3 as an apoptosis marker. Results The incidence of low cardiac output syndrome was 34%, with no significant difference between groups (35.2% vs. 33.3%, p = 0.84). The incidence of arrhythmias in our treatment group was lower compared to the control group (36% vs. 12%, p = 0.005). Troponin I and caspase-3 results did not show any significant differences between groups. For cases with Aristotle score ≥ 10, weak expression of caspase-3 in the treatment group post-cardiopulmonary bypass was lower compared to the control group. Conclusion For complex congenital cardiac surgery, the addition of terminal warm blood cardioplegia does not significantly improve postoperative clinical or metabolic markers.

Economic evaluation of policy options for dialysis in end-stage renal disease patients under the universal health coverage in Indonesia.

OBJECTIVES: This study aims to assess the value for money and budget impact of offering hemodialysis (HD) as a first-line treatment, or the HD-first policy, and the peritoneal dialysis (PD) first policy compared to a supportive care option in patients with end-stage renal disease (ESRD) in Indonesia. METHODS: A Markov model-based economic evaluation was performed using local and international data to quantify the potential costs and health-related outcomes in terms of life years (LYs) and quality-adjusted life years (QALYs). Three policy options were compared, i.e., the PD-first policy, HD-first policy, and supportive care. RESULTS: The PD-first policy for ESRD patients resulted in 5.93 life years, equal to the HD-first policy, with a slightly higher QALY gained (4.40 vs 4.34). The total lifetime cost for a patient under the PD-first policy is around 700 million IDR, which is lower than the cost under the HD-first policy, i.e. 735 million IDR per patient. Compared to supportive care, the incremental cost-effectiveness ratio of the PD-first policy is 193 million IDR per QALY, while the HD-first policy resulted in 207 million IDR per QALY. Budget impact analysis indicated that the required budget for the PD-first policy is 43 trillion IDR for 53% coverage and 75 trillion IDR for 100% coverage in five years, which is less than the HD-first policy, i.e. 88 trillion IDR and 166 trillion IDR. CONCLUSIONS: The PD-first policy was found to be more cost-effective compared to the HD-first policy. Budget impact analysis provided evidence on the enormous financial burden for the country if the current practice, where HD dominates PD, continues for the next five years.

Oral Triiodothyronine for Infants and Children Undergoing Cardiopulmonary Bypass.

BACKGROUND: This study evaluated the efficacy and safety of oral triiodothyronine (T3; Tetronine, Dalim BioTech, Korea) for infants and children undergoing cardiopulmonary bypass in an Indonesian population. METHODS: We performed a single-center, randomized, double-blind, and placebo-controlled trial in children aged 3 years and younger undergoing congenital heart disease operations with cardiopulmonary bypass. We administered oral T3 (1 µg/kg per body weight/dose) or placebo (saccharum lactis) by nasogastric tube every 6 hours for 60 hours after induction of anesthesia. The primary end point, time to extubation, was compared with Cox regression. RESULTS: The modified intention-to-treat group included 101 placebo and 104 treated patients. The stratified log-rank test did not show a significant treatment difference (p = 0.061) for time to extubation, but after adjustment for age, the nutritional Z score, and Aristotle surgical complexity, the hazard ratio was 1.33 (95% confidence interval, 1.00 to 1.76; p = 0.049). The effect of T3 was stronger in the strata aged 5 months and younger (hazard ratio, 1.86; 95% confidence interval 1.02 to 3.39; p = 0.043). Median intubation time was 47.3 hours for the placebo and 32.1 hours for the T3 group in aged 5 months and younger. Adverse events rates, including arrhythmia, were similar between groups, although sepsis was more frequent with placebo. CONCLUSIONS: Oral T3 supplementation may shorten time to extubation in children undergoing congenital heart disease operations, particularly infants aged 5 months or younger. Administration is relatively safe, simple and inexpensive.

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.

Transcatheter Closure of Patent Ductus Arteriosus in Adolescents and Adults: A Case Series.

During 11 years period from January 2005 to December 2015 there were 18 adolescent and adult patients  who underwent transcatheter closure of PDA using PDA Amplatzer Duct Occluder (ADO). There were 9 cases with age of 14 to 18 years and 9 cases with age of more than 18 years where the oldest case was 46 years old. Two cases were male and 16 cases were female. Prior to procedures, clinical assessment, ECG, chest x-ray and transthoracic echocardiography (TTE) were performed to confirm the diagnosis of PDA. The procedures of device implantation was performed under conscious sedation in adults and using general anesthesia in adolescents.The size of PDA ranged from 1.6 mm to 11.1 mm. Based on Kritchenko classification, the type of PDA were 15 type A1 and 3type A2. Flow ratio between pulmonary to systemic circulation was between 1.1 and 5.9. The procedure time ranged from 60-189 minutes and the fluoroscopic time 7.1-77.3 minutes. The PA pressure ranged from 22 to 63 mmHg. Immediate results after procedures as seen in angiography showed complete closure in 14 cases and smoky residual shunt or minimal residual shunts in 4 cases, which probably due to the temporary leaking through the devices. In 24 hours, complete closure was achieved in all cases (100%) and continued until 1months. At 6 month follow up, there was no residual shunts detected and also there was no significant complications, such as device embolization or recanalization. This case series suggest that transcatheter closure of PDA in adolescents and adults using Amplatzer duct occluder (ADO) is effective and has excellent resultswithout significant complication. However, long-term follow up is required to assess long term efficacy and safety.