Association between Early Antibiotic Administration and In-Hospital Mortality in Moderate and Severe COVID-19 Patients

Introduction. Patients with moderate and severe COVID-19 generally receive antibiotic therapy with consideration of the possibility of co-infection or secondary bacterial infection which clinically is difficult to distinguish from COVID-19 symptoms. Overuse of antibiotics can lead to an increased risk of bacterial resistance to antibiotics which is associated with poor outcomes in COVID-19 patients. This study aimed to assess the effect of early antibiotic administration on mortality in moderate and severe COVID-19 patients. Methods. An observational study with a retrospective cohort design was conducted at Dr. Cipto Mangunkusumo Hospital. Data were obtained from medical records of patients admitted from March to September 2020. Patients who received early antibiotics were defined as patients who received antibiotics hospital, 108 subjects were included in this study, 74 (68.5%) with moderate degrees and 34 (31.5%) with severe degrees. Early antibiotics were administered to 79 (73.1%) subjects with a median start time of one day. The results of the bivariate analysis did not find a significant effect of early antibiotic administration on mortality in moderate or severe COVID-19 patients (p=0.42). Subgroup analysis based on the degree of disease also found no significant results. Conclusion. There is no relationship between early antibiotic administration and mortality of moderate and severe COVID-19 patients

Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial

BACKGROUND: Passive immunotherapy using hyperimmune intravenous immunoglobulin (hIVIG) to SARS-CoV-2, derived from recovered donors, is a potential rapidly available, specific therapy for an outbreak infection such as SARS-CoV-2. Findings from randomised clinical trials of hIVIG for the treatment of COVID-19 are limited. METHODS: In this international randomised, double-blind, placebo-controlled trial, hospitalised patients with COVID-19 who had been symptomatic for up to 12 days and did not have acute end-organ failure were randomly assigned (1:1) to receive either hIVIG or an equivalent volume of saline as placebo, in addition to remdesivir, when not contraindicated, and other standard clinical care. Randomisation was stratified by site pharmacy; schedules were prepared using a mass-weighted urn design. Infusions were prepared and masked by trial pharmacists; all other investigators, research staff, and trial participants were masked to group allocation. Follow-up was for 28 days. The primary outcome was measured at day 7 by a seven-category ordinal endpoint that considered pulmonary status and extrapulmonary complications and ranged from no limiting symptoms to death. Deaths and adverse events, including organ failure and serious infections, were used to define composite safety outcomes at days 7 and 28. Prespecified subgroup analyses were carried out for efficacy and safety outcomes by duration of symptoms, the presence of anti-spike neutralising antibodies, and other baseline factors. Analyses were done on a modified intention-to-treat (mITT) population, which included all randomly assigned participants who met eligibility criteria and received all or part of the assigned study product infusion. This study is registered with ClinicalTrials.gov, NCT04546581. FINDINGS: From Oct 8, 2020, to Feb 10, 2021, 593 participants (n=301 hIVIG, n=292 placebo) were enrolled at 63 sites in 11 countries; 579 patients were included in the mITT analysis. Compared with placebo, the hIVIG group did not have significantly greater odds of a more favourable outcome at day 7; the adjusted OR was 1·06 (95% CI 0·77–1·45; p=0·72). Infusions were well tolerated, although infusion reactions were more common in the hIVIG group (18·6% vs 9·5% for placebo; p=0·002). The percentage with the composite safety outcome at day 7 was similar for the hIVIG (24%) and placebo groups (25%; OR 0·98, 95% CI 0·66–1·46; p=0·91). The ORs for the day 7 ordinal outcome did not vary for subgroups considered, but there was evidence of heterogeneity of the treatment effect for the day 7 composite safety outcome: risk was greater for hIVIG compared with placebo for patients who were antibody positive (OR 2·21, 95% CI 1·14–4·29); for patients who were antibody negative, the OR was 0·51 (0·29–0·90; pinteraction=0·001). INTERPRETATION: When administered with standard of care including remdesivir, SARS-CoV-2 hIVIG did not demonstrate efficacy among patients hospitalised with COVID-19 without end-organ failure. The safety of hIVIG might vary by the presence of endogenous neutralising antibodies at entry. FUNDING: US National Institutes of Health

Pendekatan holistik penyakit kardiovaskular X

x, 209 hl

Peranan Gejala Klinis dan Pemeriksaan Darah Tepi dalam Diagnosis Dini Influenza pada Pasien dengan Gejala Influenza Like Illness

Pendahuluan. Influenza merupakan penyakit infeksi yang disebabkan oleh virus influenza. Pada manusia, influenza sering menimbulkan penyakit pernapasan akut dengan manifestasi klinis berupa influenza like illness. Penegakkan diagnosis influenza seringkali sulit oleh karena manifestasi klinis yang tidak khas. Demam disebut sebagai gejala klinis terpenting dan limfopenia didapatkan sebagai suatu temuan laboratoris yang konsisten. Usaha untuk mengetahui proporsi dan mengelaborasi gejala klinis dan pemeriksaan darah tepi sederhana diperkirakan dapat meningkatkan probabilitas diagnosis influenza. Tujuan. Mengetahui proporsi influenza serta mengevaluasi peranan gejala klinis dan pemeriksaan laboratorium sederhana pada pasien penyakit pernapasan akut dengan influenza like illness sehingga dapat digunakan sebagai faktor prediktif terhadap diagnosis influenza. Metode. Studi potong lintang berbasis diagnostic research pada pasien penyakit pernapasan akut dewasa dengan gejala influenza like illness di Puskesmas Kecamatan Pulo Gadung dan Puskesmas Kelurahan Rawamangun antara Maret hingga Juni 2011. Spesimen analisis virus menggunakan bahan apus nasofaringeal, dengan teknik analisis PCR kualitatif dan imunokromatografi antigen. Hasil. Dari 90 orang subyek penelitian didapatkan 13 orang (14,4%) terbukti terinfeksi virus influenza A melalui teknik PCR. Variabel demam menunjukkan hasil uji kemaknaan yang signifikan terhadap influenza (p 0,003) dengan prevalence ratio 6,28 (95% CI 1,476-26,759). Sensitifitas demam, batuk dan pilek terhadap influenza masing-masing adalah 85% dan negative predictive value demam sebesar 98%. Variabel determinan lainnya tidak menunjukkan hasil yang bermakna terhadap influenza pada uji kemaknaan statistik. Simpulan. Proporsi influenza pada pasien dengan gejala ILI diperoleh cukup tinggi dengan proporsi demam yang terbukti lebih tinggi pada pasien influenza. Sensitivitas demam, batuk dan pilek terhadap influenza tinggi dengan negative predictive value yang memuaskan untuk seluruh variabel determinan

Risk Factors for Temporary Vascular Access Infection in Patients with End-Stage Renal Disease Undergoing Hemodialysis in Cipto Mangunkusumo Hospital

Background: Temporary vascular access is used to provide adequate hemodialysis for patients who are initiating dialysis or are awaiting maturation of a more permanent vascular access. However, infection is one of the most frequent complications of using temporary vascular access and is the second leading cause of death in patients undergoing hemodialysis after cardiovascular events. There has been no research on the risk factors for the incidence of infection in patients using temporary vascular access in Indonesia. Methods: This is a retrospective cohort study utilizing secondary data from medical records of 318 subjects aged 18 years and older with end-stage renal disease and undergoing hemodialysis using temporary vascular access at Cipto Mangunkusumo Hospital. Results: Temporary vascular access infection was found in 125 of 318 subjects (39.3%). The risk factors of temporary vascular catheter infection in the multivariate analysis were females (OR 1.731; 95% CI 1.050-2.854; p=0.032), low hemoglobin levels (OR 2.293; 95% CI 1.353-3.885; p=0.002), presence of diabetes mellitus (OR 2.962; 95% CI 1.704-5.149; p<0.001) and duration of catheter insertion (OR 5.322; 95% CI 1.871-15-135; p=0.002). The association between ferritin and catheter insertion site was not analyzed as a risk factor because it was not performed in all subjects. Conclusion: The incidence of infection in patients with end -stage renal disease undergoing hemodialysis using temporary vascular access at Cipto Mangunkusumo Hospital was 39.3%. Female gender, low hemoglobin level, diabetes mellitus, and duration of catheter insertion were risk factors for temporary vascular access infection

Tocilizumab as a Treatment for ‘Cytokine Storm Syndrome’ in COVID-19: A Case Report

Coronavirus disease 19 (COVID-19) which is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has been a problem worldwide, particularly due to the high rate of transmission and wide range of clinical manifestations. Acute respiratory distress syndrome (ARDS) and multiorgan failure are the most common events observed in severe cases and can be fatal. Cytokine storm syndrome emerges as one of the possibilities for the development of ARDS and multiorgan failure in severe cases of COVID-19. This case report describes a case of a 53-year-old male patient who has been diagnosed with COVID-19. Further evaluation in this patient showed that there was a marked increase in IL-6 level in blood accompanied with hyperferritinemia, which was in accordance with the characteristic of cytokine storm syndrome. Patient was treated with tocilizumab, a monoclonal antibody and is an antagonist to IL-6 receptor. The binding between tocilizumab and IL-6 receptors effectively inhibit and manage cytokine storm syndrome. Although this case report reported the efficacy of tocilizumab in managing cytokine storm syndrome, tocilizumab has several adverse effects requiring close monitoring. Further clinical randomized control trial is required to evaluate the efficacy and safety of tocilizumab administration in participants with various clinical characteristics and greater number of subjects.

Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial.

BACKGROUND: Passive immunotherapy using hyperimmune intravenous immunoglobulin (hIVIG) to SARS-CoV-2, derived from recovered donors, is a potential rapidly available, specific therapy for an outbreak infection such as SARS-CoV-2. Findings from randomised clinical trials of hIVIG for the treatment of COVID-19 are limited. METHODS: In this international randomised, double-blind, placebo-controlled trial, hospitalised patients with COVID-19 who had been symptomatic for up to 12 days and did not have acute end-organ failure were randomly assigned (1:1) to receive either hIVIG or an equivalent volume of saline as placebo, in addition to remdesivir, when not contraindicated, and other standard clinical care. Randomisation was stratified by site pharmacy; schedules were prepared using a mass-weighted urn design. Infusions were prepared and masked by trial pharmacists; all other investigators, research staff, and trial participants were masked to group allocation. Follow-up was for 28 days. The primary outcome was measured at day 7 by a seven-category ordinal endpoint that considered pulmonary status and extrapulmonary complications and ranged from no limiting symptoms to death. Deaths and adverse events, including organ failure and serious infections, were used to define composite safety outcomes at days 7 and 28. Prespecified subgroup analyses were carried out for efficacy and safety outcomes by duration of symptoms, the presence of anti-spike neutralising antibodies, and other baseline factors. Analyses were done on a modified intention-to-treat (mITT) population, which included all randomly assigned participants who met eligibility criteria and received all or part of the assigned study product infusion. This study is registered with ClinicalTrials.gov, NCT04546581. FINDINGS: From Oct 8, 2020, to Feb 10, 2021, 593 participants (n=301 hIVIG, n=292 placebo) were enrolled at 63 sites in 11 countries; 579 patients were included in the mITT analysis. Compared with placebo, the hIVIG group did not have significantly greater odds of a more favourable outcome at day 7; the adjusted OR was 1·06 (95% CI 0·77-1·45; p=0·72). Infusions were well tolerated, although infusion reactions were more common in the hIVIG group (18·6% vs 9·5% for placebo; p=0·002). The percentage with the composite safety outcome at day 7 was similar for the hIVIG (24%) and placebo groups (25%; OR 0·98, 95% CI 0·66-1·46; p=0·91). The ORs for the day 7 ordinal outcome did not vary for subgroups considered, but there was evidence of heterogeneity of the treatment effect for the day 7 composite safety outcome: risk was greater for hIVIG compared with placebo for patients who were antibody positive (OR 2·21, 95% CI 1·14-4·29); for patients who were antibody negative, the OR was 0·51 (0·29-0·90; pinteraction=0·001). INTERPRETATION: When administered with standard of care including remdesivir, SARS-CoV-2 hIVIG did not demonstrate efficacy among patients hospitalised with COVID-19 without end-organ failure. The safety of hIVIG might vary by the presence of endogenous neutralising antibodies at entry. FUNDING: US National Institutes of Health