A potent therapy for the infectious coronavirus disease COVID-19 is urgently required with, at the time of writing, research in this area still ongoing. This study aims to evaluate the in vitro anti-viral activities of combinations of certain commercially available drugs that have recently formed part of COVID-19 therapy. Dual combinatory drugs, namely; Lopinavir-Ritonavir (LOPIRITO)-Clarithromycin (CLA), LOPIRITO-Azithromycin (AZI), LOPIRITO-Doxycycline (DOXY), Hydroxychloroquine (HCQ)-AZI, HCQ-DOXY, Favipiravir (FAVI)-AZI, HCQ-FAVI, and HCQ-LOPIRITO, were prepared. These drugs were mixed at specific ratios and evaluated for their safe use based on the cytotoxicity concentration (CC50) values of human umbilical cord mesenchymal stem cells. The anti-viral efficacy of these combinations in relation to Vero cells infected with SARS-CoV-2 virus isolated from a patient in Universitas Airlangga hospital, Surabaya, Indonesia and evaluated for IC50 24, 48, and 72 hours after viral inoculation was subsequently determined. Observation of the viral load in qRT-PCR was undertaken, the results of which indicated the absence of high levels of cytotoxicity in any samples and that dual combinatory drugs produced lower cytotoxicity than single drugs. In addition, these combinations demonstrated considerable effectiveness in reducing the copy number of the virus at 48 and 72 hours, while even at 24 hours, post-drug incubation resulted in low IC50 values. Most combination drugs reduced pro-inflammatory markers, i.e. IL-6 and TNF-α, while increasing the anti-inflammatory response of IL-10. According to these results, the descending order of effective dual combinatory drugs is one of LOPIRITO-AZI>LOPIRITO-DOXY>HCQ-AZI>HCQ-FAVI>LOPIRITO-CLA>HCQ-DOX. It can be suggested that dual combinatory drugs, e.g. LOPIRITO-AZI, can potentially be used in the treatment of COVID-19 infectious diseases.
Tools to accurately predict and detect adverse drug reactions (ADR) in elderly patients have not been developed. We aimed to identify and evaluate reports on tools that predict and detect ADR in elderly patients (≥ 60 years). In this review, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Databases were searched until January 2022 using key terms “elderly,” “adverse drug reaction,” and “detection instruments.” Eighteen studies met the inclusion criteria, and they examined assorted interventions: STOPP/START version 1/2 (n = 10), Beers Criteria 2012 or 2015 (n = 4), Systematic Tool to Reduce Inappropriate Prescribing (STRIP) (n = 2), Tool to Reduce Inappropriate Medications (TRIM) (n = 1), Medication Risk Score (MERIS) (n = 1), Computerized alert systems (n = 1), and Norwegian General Practice-Nursing Home criteria (n = 1). The interventions affected the number of potential prescription omissions (OR, 0.50 [0.37–0.69]; p < 0.0001; four studies). No apparent reduction in the number of drug interactions within 2 months (OR, 0.84 [0.70–1.02]; p = 0.08; two studies) and mortality (OR, 0.92 [0.76–1.12]; p = 0.41; three studies) was observed. In conclusion, there is no definitive and validated assessment tool for detecting and predicting ADR in elderly patients. Thus, more research on refining existing tools or developing new ones is warranted.
Background. At the present time, COVID-19 vaccines are at the testing stage, and an effective treatment for COVID-19 incorporating appropriate safety measures remains the most significant obstacle to be overcome. A strategic countermeasure is, therefore, urgently required. Aim. This study aims to evaluate the efficacy and safety of a combination of lopinavir/ritonavir-azithromycin, lopinavir/ritonavir-doxycycline, and azithromycin-hydroxychloroquine used to treat patients with mild to moderate COVID-19 infections. Setting and Design. This study was conducted at four different clinical study sites in Indonesia. The subjects gave informed consent for their participation and were confirmed as being COVID-19-positive by means of an RT-PCR test. The present study constituted a randomized, double-blind, and multicenter clinical study of patients diagnosed with mild to moderate COVID-19 infection. Materials and Methods. Six treatment groups participated in this study: a Control group administered with a 500 mg dose of azithromycin; Group A which received a 200/50 mg dose of lopinavir/ritonavir and 500 mg of azithromycin; Group B treated with a 200/50 mg dose of lopinavir/ritonavir and 200 mg of doxycycline; Group C administered with 200 mg of hydroxychloroquine and 500 mg of azithromycin; Group D which received a 400/100 mg dose of lopinavir/ritonavir and 500 mg of azithromycin; and Group E treated with a 400/100 mg dose of lopinavir/ritonavir and 200 mg of doxycycline. Results. 754 subjects participated in this study: 694 patients (92.4%) who presented mild symptoms and 57 patients (7.6%) classified as suffering from a moderate case of COVID-19. On the third day after treatment, 91.7%–99.2% of the subjects in Groups A–E were confirmed negative by a PCR swab test compared to 26.9% in the Control group. Observation of all groups which experienced a significant decrease in virus load between day 1 and day 7 was undertaken. Other markers, such as CRP and IL-6, were significantly lower in all treatment groups ( p < 0.05 and p < 0.0001 ) than in the Control group. Furthermore, IL-10 and TNF-α levels were significantly elevated in all treatment groups ( p < 0.0001 ). The administration of azithromycin to the Control group increased CRP and IL-6 levels, while reduced IL-10 and TNF-α on day 7 ( p < 0.0001 ) compared with day 1. Decreases in ALT and AST levels were observed in all groups ( p < 0.0001 ). There was an increase in creatinine in the serum level of the Control, C, D, and E groups ( p < 0.05 ), whereas the BUN level was elevated in all groups ( p < 0.0001 ). Conclusions. The study findings suggest that the administration of lopinavir/ritonavir-doxycycline, lopinavir/ritonavir-azithromycin, and azithromycin-hydroxychloroquine as a dual drug combination produced a significantly rapid PCR conversion rate to negative in three-day treatment of mild to moderate COVID-19 cases. Further studies should involve observation of older patients with severe clinical symptoms in order to collate significant amounts of demographic data.
Tujuan Penelitian untuk mengetahui Implementasi Kebijakan kampung KB DPPKB guna penanggulangan kemiskinan di Kecamatan Lemahwungkuk Kota Cirebon. Metode Penelitian menggunakan deskriptif dengan pendekatan kualitatif dengan tujuan untuk menganalisis secara komprehensif dan mendalam tentang kebijakan Kampung KB di Dinas Pengendalian Penduduk Keluarga Berencana Khususnya di Kecamatan Lemahwungkuk Kota Cirebon. Hasil dari Keberhasilan kebijakan program kampung KB diantaranya komitmen sumber daya manusia dan pendanaan yang komitmen pada tujuan tercapainya keberhasilan kebijakan untuk kesejahteraan masyarakat. Kelengkapan sarana prasarana pun menunjang keberhasilan program ini dan akan terus ditingkatkan oleh DPPKB dalam pencapaian sumber-sumber kebijakan, karakteristik, badan pelaksana dan kondisi ekonomi, sosial masyarakat serta kondisi politik yang ada. Tingkat social ekonomi pun mulai terlihat peningkatan dari jumlah konsumsi penduduk yang berkurang dan lebih dialokasikan kepada konsumsi yang lebih berkualitas seperti makan makanan yang bergizi tercukupi dikarenakan kebutuhan rumah tangga lebih ringan.
Purpose: This study aims to analyze the efficacy and safety of anticoagulants for COVID-19 patients in the intensive care unit. Methods: A comprehensive search was conducted using databases such as MEDLINE, PubMed, EuropePMC, Science Direct, Google Scholar, Clinicaltrial.gov, The Cochrane Central Register of Controlled Trial (CENTRAL, Cochrane Library) and several other published articles from the systematic review up to March 31, 2021. The Newcastle-Ottawa Scale (NOS) was used for the studies’ qualitative assessment. The primary outcome examined was mortality rate, while the secondary included the length of stay (LOS) in thei care unit; hospital length of stay (HOS), coagulation markers including D-dimer, Platelet count, aPTT, PT and fibrinogen; markers of inflammation specifically C-reactive protein; and other adverse events ranging from hemorrhage to thrombosis. Additionally, the quantitative synthesis was conducted using fixed and random effects model in “The Revman 5.4”, while heterogeneity was tested using the I-squared (I2) measure. Results: A total of 1,062 articles were found during the initial search step and eventually 12 were chosen to be analyzed quantitatively in a meta-analysis. Comparison of the results related to anticoagulant group with no anticoagulant or standard care treatment showed that anticoagulant group significantly reduced mortality rate with RR= 0.53; 95 % CI, 0.30-0.95; P= 0.03, with I2 = 88% and venous thromboembolism (VTE) RR = 0.53; 95% CI, 0.37-0.76; P = .0007 with I2 = 35%. Conclusions: Based on the results, anticoagulants can mitigate mortality rate and VTE in COVID-19 patients.
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