We aimed to determine the burden of sepsis with focal infections in the resource-limited context of Indonesia and to propose national prices for sepsis reimbursement. We conducted a retrospective observational study on cost from 2013-2016 of surviving and non-surviving sepsis patients with payer perspective using inpatient billing records in 4 hospitals. We calculated the national burden of sepsis and developed proposed national prices for reimbursement. Of 14,076 sepsis patients in total, 5,876 (41.7%) survived and 8.200 (58.3%) deceased. The mean hospital costs incurred per surviving and deceased sepsis patient were US$1,011 (SE + 23.4) and US$1,406 (SE + 27.8), respectively. The national burden of sepsis in 100,000 patients was estimated to be US$130 million. Sepsis patients with multifocal infections and a single focal infection of lower-respiratory tract infections (LRTIs) were estimated as the two with the highest economic burden (US$48 million and US$33 million, respectively, within the 100,000 sepsis patients). Sepsis with cardiovascular infection was estimated to warrant the highest proposed national price for reimbursement (US$4,256). Multifocal infections and LRTIs are the major focal infections with the highest burden of sepsis. Our study shows varying cost estimates for sepsis, necessitating a new reimbursement system with adjustment of the national prices taking the particular foci into account.

The outbreak of coronavirus disease 2019 (COVID-19) in December 2019 in China, has become a pandemic in March 2020. Repurposing old and relatively safe drugs becomes an advantageous option to obtain the urgently needed effective treatment. Repurposing chloroquine, hydroxychloroquine, oseltamivir, lopinavir/ritonavir, and favipiravir, and the use of investigational drug remdesivir for treatment of COVID-19, are reviewed from the clinical pharmacology perspective, particularly its efficacy and safety. Limited clinical studies of chloroquine, hydroxychloroquine, favipiravir, and remdesivir showed some efficacy in COVID-19 treatment with tolerable adverse effects. Potential serious adverse effect of chloroquine and hydroxychloroquine is cardiac arrhythmia. Oseltamivir has no documented activity against SARS-CoV-2, while lopinavir/ritonavir showed limited efficacy in COVID-19. Currently, there is no sufficient evidence to recommend any specific anti-COVID-19 treatment. The decision to use these drugs during the COVID-19 pandemic must be based on careful consideration of the potential benefits and risks to the patient.

The effect of corticosteroid therapy in COVID-19 patients is mediated by its suppressive effect on the regulations of inflammatory response. However, its clinical outcome is often unpredictable. This study aimed to explore the role of glucocorticoid receptors in corticosteroid response in Moderate-Severe COVID-19 patients. In this cross-sectional study, we attempted to find the relationship between the expression of the glucocorticoid receptor (encoded by NR3C1), the variation of glucocorticoid receptors isoform, and the mutations of glucocorticoid receptors exon with clinical response to corticosteroids. In addition, the relationship between glucocorticoid receptors expression and the expression of IκBα (encoded by NFKBIA) and glucocorticoid-induced leucine zipper protein (GILZ; encoded by TSC22D3) as steroid pathways was also evaluated. Thirty-four COVID-19 patients were studied. Blood was drawn before and on day 5 of corticosteroid treatment. Glucocorticoid receptors expression, isoform, and mutation were determined by RNA sequencing from white blood cells. Based on the improvement of clinical and oxygen status, patients were classified into responder and non-responder groups. Of thirty-four patients, 23 (67.6%) showed excellent responses to corticosteroids, and 11 (32.4%) were non-responders. The NR3C1 gene expression was significantly higher in the responsive group at baseline and after five days of glucocorticoid treatment. Isoform variant and mutation of glucocorticoid receptors did not correlate with clinical response. The expression of IκBα and GILZ correlated positively with glucocorticoid receptors expression. This study elucidates the relationship between glucocorticoid receptor expression with therapeutic responses to corticosteroids in moderate-severe COVID-19.

BACKGROUND: Neuregulins (NRGs) are one of the epidermal growth factors (EGF) superfamily, which released in cellular injuries, such as neurons and myocardial cells. Neuregulin-1β (NRG-1β) could be activated when stress happens to myocardial cells, acting as a survival factor to repair the injury. Malondialdehyde (MDA) is also produced during oxidative stress in cardiac injury. In vivo study of myocardial cells in rats and dogs that got ischemic, dilated, and viral cardiomyopathy showed that NRG-1 could improve the injured cardiac performance, attenuated pathological changes, and prolonged survival of the cells. AIM: We aimed to observe NRG-1 levels in CAD patients in Indonesia, mainly focused in Minang ethnicity. This study also analyzes the relationship between NRG-1 and MDA with CAD’s severity. METHODS: We measured plasma NRG-1 in 61 nondiabetic patients within 38–82 years old range with STEMI, NSTEMI, and UAP. RESULTS: We found their plasma NRG1, respectively, was 10.3 (1.9–38.2) ng/ml, 14.3 ± 7.2 ng/ml, and 7.05 (4.5–0.4) ng/mL. Plasma NRG 1 increased in AMI patients. CONCLUSION: This study concludes that NRG1’s activated during cardiac cells injury, in any AMI.

Sepsis has become the most common condition in critical care, the leading cause of morbidity and mortality, and one of ten common causes of death. Its treatment is consistently costly. However, the studies revealing the actual costs are not available widely because of the controversy regarding the typical comorbidity that accompanies sepsis itself. Universal health coverage is achieved by implementing national health insurance in Indonesia. It provides sepsis cost coverage for all populations with all various economic levels. However, in some cases, the funds estimated for sepsis by the insurance are not suitable for the amount that health services expect. We did implementation research on the national health insurance in Indonesia by observing how much the health services expend cost for sepsis patients. Knowing the charge generated by sepsis can assess the insurance and make the appropriate cost estimation for that case. We compare the sepsis cost expenditure with the insurance cost estimation for sepsis. A retrospective cohort study was performed in the Internal Medicine Department of Dr. M. Djamil Hospital in West Sumatera, Indonesia, from January through December 2017. All needed data were collected from the sepsis patients’ medical records and analyzed statistically using SPSS 16. Among all sepsis patients, men are dominant. Most patients were under 60 years, with the youngest patients aged 17 years. These sepsis patients have four kinds of sites of infection. The number of comorbid most had by these patients is 2 to 4 comorbid. They were hospitalized for 5-24 days. The most commonly used antibiotic combination for patients with sepsis is Ceftriaxone-Ciprofloxacin. The cost difference in CBG estimation with a hospital bill for each patient varies from -35,894,613.00 IDR to 19,662,093.00 IDR. Each sepsis case causes different hospital bills, but the estimated cost of the CBG is considered sufficient to cover the losses that several cases can cause for the hospital. Several factors affect the hospital bill, including length of stay, comorbidity, the severity of sepsis, choice of medicines, and survival of the patients.

In experimental animals, the induction of isoproterenol which is a synthetic of catecholamine, can cause acute myocardial infarction where the pathophysiology and morphology are the same as myocardial infarction in humans. Isoproterenol induction will increase oxidative stress, which will damage the enzyme dimethylarginine dimethylaminohydrolase (DDAH), thus causing asymmetric dimethylarginine (ADMA) levels to increase in circulation. Increased levels of ADMA will inhibit the activity of the enzyme nitric oxide synthase, which results in decreased nitric oxide resulting in endothelial damage. This study aims to determine the effect of Ramipril on asymmetric dimethylarginine (ADMA) levels in rats (Rattus norvegicus) Wistar strain with acute myocardial infarction. Eighteen male Wistar rats (150-250 g) were randomly allocated into three groups: negative control group, positive control, and treatment group. The treatment group was pretreated with Ramipril at dose 3 mg/kg BW orally for seven days. Acute myocardial infarction was induced in positive control groups and treatment groups by subcutaneous injection of isoproterenol (85 mg/kg BW) for two consecutive days. Twenty-four hours after the last administration, rats from all groups were anesthetized and sacrificed for blood sample collection to evaluate the level of Asymmetric Dimethylarginine with Enzym-linked Immunosorbent Assay (ELISA) method. The result showed that ADMA levels were increased in the treatment group after pretreated with Ramipril. This study concluded that pretreatment with Ramipril increased ADMA concentration in acute myocardial infarction rats induced by isoproterenol.