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INTRODUCTION: Despite the widespread use of pre-exposure prophylaxis (PrEP) in preventing human immunodeficiency virus (HIV) transmission, scant information on HIV drug resistance mutations (DRMs) has been gathered over the past decade. This review aimed to estimate the pooled prevalence of pre-exposure prophylaxis and its two-way impact on DRM. METHODS: We systematically reviewed studies on DRM in pre-exposure prophylaxis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 guidelines. PubMed, Cochrane, and SAGE databases were searched for English-language primary studies published between January 2001 and December 2023. The initial search was conducted on 9 August 2021 and was updated through 31 December 2023 to ensure the inclusion of the most recent findings. The registration number for this protocol review was CRD42022356061. RESULTS: A total of 26,367 participants and 562 seroconversion cases across 12 studies were included in this review. The pooled prevalence estimate for all mutations was 6.47% (95% Confidence Interval-CI 3.65-9.93), while Tenofovir Disoproxil Fumarate/Emtricitabine-associated drug resistance mutation prevalence was 1.52% (95% CI 0.23-3.60) in the pre-exposure prophylaxis arm after enrolment. A subgroup analysis, based on the study population, showed the prevalence in the heterosexual and men who have sex with men (MSM) groups was 5.53% (95% CI 2.55-9.40) and 7.47% (95% CI 3.80-12.11), respectively. Notably, there was no significant difference in the incidence of DRM between the pre-exposure prophylaxis and placebo groups (log-OR = 0.99, 95% CI -0.20 to 2.18, I2 = 0%; p = 0.10). DISCUSSION: Given the constrained prevalence of DRM, the World Health Organization (WHO) advocates the extensive adoption of pre-exposure prophylaxis. Our study demonstrated no increased risk of DRM with pre-exposure prophylaxis (p > 0.05), which is consistent with these settings. These findings align with the previous meta-analysis, which reported a 3.14-fold higher risk in the pre-exposure prophylaxis group than the placebo group, although the observed difference did not reach statistical significance (p = 0.21). CONCLUSIONS: Despite the low prevalence of DRM, pre-exposure prophylaxis did not significantly increase the risk of DRM compared to placebo. However, long-term observation is required to determine further disadvantages of extensive pre-exposure prophylaxis use. PROSPERO Number: CRD42022356061.
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Anti-HIV Agents , Drug Resistance, Viral , HIV Infections , HIV-1 , Mutation , Pre-Exposure Prophylaxis , Humans , HIV Infections/prevention & control , HIV Infections/virology , HIV Infections/drug therapy , Drug Resistance, Viral/genetics , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/administration & dosage , HIV-1/drug effects , HIV-1/genetics , Male , Administration, Oral , Female , Tenofovir/therapeutic use , Tenofovir/administration & dosage , PrevalenceABSTRACT
INTRODUCTION: Bilateral secondary spontaneous pneumothorax due to tuberculosis and human immunodeficiency virus (TB-HIV) infection is a rare case which has a poor prognosis and high-risk mortality. CASE PRESENTATION: An Indonesian male, 31 years old, complained of shortness of breath, chest pain, and weight loss (15 kg for 2 months). He has a history of HIV and has been only on ARVs for 3 months since being diagnosed. He, his sister, and his mother had all experienced tuberculous lymphadenitis. The patient appears weak, dyspnea, visual analogue scale (VAS) of 5, blood pressure (BP) of 92/64 mmHg, heart rate (HR) of 112 ×/min, temperature of 37.7 °C, respiratory rate (RR) of 32 ×/min, oxygen saturation (SpO2) of 98 % (simple mask of 8 L/min). On inspection and fremitus, the development of left lung expansion was delayed. Percussion sound of left lung was hypersonor and decreased lung sounds on auscultation. A chest X-ray revealed pneumothorax sinistra. The patient underwent needle thoracocentesis with chest tube insertion and water seal drainage (WSD). During the continuation phase, the patient also took anti-retroviral (ARV) and anti-tuberculosis drug (ATD). The patient had improved but a few days later developed a pneumothorax dextra and received treatment. The patient only survived for 2 days afterwards and died caused by hypovolemic shock. DISCUSSION: Management of pneumothorax in TB-HIV patients shows only temporary improvement but poor prognosis. Adherence of HIV patients to ARVs minimizes the risk of infected with Mycobacterium tuberculosis in endemic areas. CONCLUSION: HIV patients are anticipated to remain committed to their treatment regimens in order to reduce the occurrence of pneumothorax induced by TB-HIV in endemic areas.
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The mortality of COVID-19 patients has left the world devastated. Many scoring systems have been developed to predict the mortality of COVID-19 patients, but several scoring components cannot be carried out in limited health facilities. Herein, the authors attempted to create a new and easy scoring system involving mean arterial pressure (MAP), PF Ratio, or SF ratio-respiration rate (SF Ratio-R), and lymphocyte absolute, which were abbreviated as MPL or MSLR functioning, as a predictive scoring system for mortality within 30 days for COVID-19 patients. Of 132 patients with COVID-19 hospitalized between March and November 2021, we followed up on 96 patients. We present bivariate and multivariate analyses as well as the area under the curve (AUC) and Kaplan-Meier charts. From 96 patients, we obtained an MPL score of 3 points: MAP < 75 mmHg, PF Ratio < 200, and lymphocyte absolute < 1500/µL, whereas the MSLR score was 6 points: MAP < 75 mmHg, SF Ratio < 200, lymphocyte absolute < 1500/µL, and respiration rate 24/min. The MPL cut-off point is 2, while the MSLR is 4. MPL and MSLR have the same sensitivity (79.1%) and specificity (75.5%). The AUC value of MPL vs. MSLR was 0.802 vs. 0.807. The MPL ≥ 2 and MSLR ≥ 4 revealed similar predictions for survival within 30 days (p < 0.05). Conclusion: MPL and MSLR scores are potential predictors of mortality in COVID-19 patients within 30 days in a resource-limited country.
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INTRODUCTION: Prophylactic antibiotics in urological procedures are essential to prevent postoperative infections. A different approach in selecting antibiotic prophylaxis according to the type of procedure is needed. METHODOLOGY: A retrospective study was carried out at an academic hospital in Surabaya, Indonesia, by collecting medical records of patients who underwent urologic procedures within 2019- 2020, including microbiological data. RESULT: One hundred seventy-nine urological procedures were assessed. Antibiotic prophylaxis was administered in the clean-contaminated and clean procedures (93.2% and 6.8%, respectively). Ceftriaxone was commonly used (69.3%), single-dose, one day before the surgery. Gram-negative bacteria were widely found in the urinary culture of patients (75.2%). E. coli, K. pneumoniae, and P. aeruginosa were dominating with low susceptibility to cephalosporins. ESBL-producing bacteria were E. coli (64%) and K. pneumoniae (89%). CONCLUSIONS: The 3rd generation cephalosporins (ceftriaxone) are mostly used in urological procedures despite the low susceptibility against this antibiotic in cultured E coli, P. aeruginosa, and K. pneumonia. The aminoglycosides have relatively good activity and have been suggested in several guidelines for urologic procedures, such as prostate and urinary tract stone procedures. It is crucial to consider the incision site, type of procedure, and bacterial profile in the hospital to propose antibiotic prophylaxis guidelines.
Subject(s)
Anti-Bacterial Agents , Antibiotic Prophylaxis , Gram-Negative Bacterial Infections , Urologic Surgical Procedures , Antibiotic Prophylaxis/methods , Retrospective Studies , Humans , Male , Postoperative Complications/prevention & control , Anti-Bacterial Agents/therapeutic use , Gram-Negative Bacteria , Gram-Negative Bacterial Infections/drug therapy , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Aged , Urologic Surgical Procedures/adverse effectsABSTRACT
Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) ribonucleic acid (RNA) shedding is an important parameter for determining the optimal length of isolation period required for coronavirus disease 2019 (COVID-19) patients. However, the clinical (i.e., patient and disease) characteristics that could influence this parameter have yet to be determined. In this study, we aim to explore the potential associations between several clinical features and the duration of SARS-CoV-2 RNA shedding in patients hospitalized with COVID-19. A retrospective cohort study involving 162 patients hospitalized for COVID-19 in a tertiary referral teaching hospital in Indonesia was performed from June to December 2021. Patients were grouped based on the mean duration of viral shedding and were compared based on several clinical characteristics (e.g., age, sex, comorbidities, COVID-19 symptoms, severity, and therapies). Subsequently, clinical factors potentially associated with the duration of SARS-CoV-2 RNA shedding were further assessed using multivariate logistic regression analysis. As a result, the mean duration of SARS-CoV-2 RNA shedding was found to be 13 ± 8.44 days. In patients with diabetes mellitus (without chronic complications) or hypertension, the duration of viral shedding was significantly prolonged (≥13 days; p = 0.001 and p = 0.029, respectively). Furthermore, patients with dyspnea displayed viral shedding for longer durations (p = 0.011). The multivariate logistic regression analysis reveals that independent risk factors associated with the duration of SARS-CoV-2 RNA shedding include disease severity (adjusted odds ratio [aOR] = 2.94; 95% CI = 1.36-6.44), bilateral lung infiltrates (aOR = 2.79; 95% CI = 1.14-6.84), diabetes mellitus (aOR = 2.17; 95% CI = 1.02-4.63), and antibiotic treatment (aOR = 3.66; 95% CI = 1.74-7.71). In summary, several clinical factors are linked with the duration of SARS-CoV-2 RNA shedding. Disease severity is positively associated with the duration of viral shedding, while bilateral lung infiltrates, diabetes mellitus, and antibiotic treatment are negatively linked with the duration of viral shedding. Overall, our findings suggest the need to consider different isolation period estimations for specific clinical characteristics of patients with COVID-19 that affect the duration of SARS-CoV-2 RNA shedding.
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Vaccine effectiveness (VE) and the urgency of booster vaccination against SARS-CoV-2 Omicron variant need evaluation. A systematic search was conducted from 1−6 April, 2022. VE difference (VED) estimates were assessed using random-effects and meta-regression analyses were performed for evaluating VE over time. Compared to full dose, booster dose of overall vaccines provided better protection against any and severe Omicron infections within 3 months (p < 0.001), and within 3 months or more in any, severe, and symptomatic infections (p < 0.001). From meta-regression analysis of overall vaccines, the full-dose VE against any and symptomatic Omicron infections reduced per month by 2.45% and 5.5%, respectively; whereas booster dose effectiveness against any and symptomatic Omicron infections reduced per month by 1.79% and 1.14%, respectively. The VE estimates of booster dose provide excellent protection against symptomatic infection compared to full dose. The VE estimates of Ad26.COV2.S, BNT162b2, ChAdOx1 nCov-19, and mRNA-1273 against Omicron infection are generally moderate, despite the VE estimates declining over time.
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BACKGROUND: Coronavirus disease 2019 (COVID-19) often causes atypical clinical manifestations similar to other infectious diseases. In malaria-endemic areas, the pandemic situation will very likely result in co-infection of COVID-19 and malaria, although reports to date are still few. Meanwhile, this disease will be challenging to diagnose in areas with low malaria prevalence because the symptoms closely resemble COVID-19. CASE PRESENTATION: A 23-year-old male patient presented to the hospital with fever, anosmia, headache, and nausea 1 week before. He was diagnosed with COVID-19 and treated for approximately 10 days, then discharged to continue self-quarantine at home. 2 weeks later, he returned to the hospital with a fever raised intermittently every 2 days and marked by a chilling-fever-sweating cycle. A laboratory test for malaria and a nasopharyngeal swab for SARS CoV-2 PCR were conducted, confirming both diagnoses. The laboratory examination showed markedly elevated D-dimer. He was treated with dihydroartemisinin-piperaquine (DHP) 4 tablets per day for 3 days and primaquine 2 tablets per day for 14 days according to Indonesian National Anti-malarial Treatment Guidelines. After 6 days of treatment, the patient had no complaints, and the results of laboratory tests had improved. This report describes the key points in considering the differential diagnosis and prompt treatment of malaria infection during the pandemic of COVID-19 in an endemic country to prevent the worse clinical outcomes. COVID-19 and malaria may also cause a hypercoagulable state, so a co-infection of those diseases may impact the prognosis of the disease. CONCLUSION: This case report shows that considering the possibility of a co-infection in a COVID-19 patient who presents with fever can prevent delayed treatment that can worsen the disease outcome. Paying more attention to a history of travel to malaria-endemic areas, a history of previous malaria infection, and exploring anamnesis regarding the fever patterns in patients are important points in making a differential diagnosis of malaria infection during the COVID-19 pandemic.
Subject(s)
COVID-19 , Coinfection , Malaria, Vivax , Malaria , Adult , COVID-19/diagnosis , Coinfection/diagnosis , Coinfection/epidemiology , Fever/epidemiology , Humans , Malaria/complications , Malaria/diagnosis , Malaria/drug therapy , Malaria, Vivax/epidemiology , Male , Pandemics , Recurrence , Young AdultABSTRACT
Introduction: Various mortality predictive score models for coronavirus disease-2019 (COVID-19) have been deliberated. We studied how sequential organ failure assessment (SOFA), quick sequential organ failure assessment (qSOFA), acute physiology and chronic health evaluation II (APACHE II), and new early warning signs (NEWS-2) scores estimate mortality in COVID-19 patients. Materials and methods: We conducted a prospective cohort study of 53 patients with moderate-to-severe COVID-19. We calculated qSOFA, SOFA, APACHE II, and NEWS-2 on initial admission and re-evaluated on day 5. We performed logistic regression analysis to differentiate the predictors of qSOFA, SOFA, APACHE II, and NEWS-2 scores on mortality. Result: qSOFA, SOFA, APACHE II, and NEWS-2 scores on day 5 exhibited a difference between survivors and nonsurvivors (p <0.05), also between ICU and non-ICU admission (p <0.05). The initial NEWS-2 revealed a higher AUC value than the qSOFA, APACHE II, and SOFA score in estimating mortality (0.867; 0.83; 0.822; 0.794). In ICU, APACHE II score revealed a higher AUC value than the SOFA, NEWS-2, and qSOFA score (0.853; 0.832; 0.813; 0.809). Concurrently, evaluation on day 5 showed that qSOFA AUC had higher scores than the NEWS-2, APACHE II, and SOFA (0.979; 0.965; 0.939; 0.933) in predicting mortality, while SOFA and APACHE II AUC were higher in ICU admission than NEWS-2 and qSOFA (0.968; 0.964; 0.939; 0.934). According to the cutoff score, APACHE II on day 5 revealed the highest sensitivity and specificity in predicting the mortality (sensitivity 95.7%, specificity 86.7%). Conclusion: All scores signify good predictive values on COVID-19 patients mortality following the evaluation on the day 5. Nonetheless, APACHE-II appears to be the best at predicting mortality and ICU admission rate. How to cite this article: Asmarawati TP, Suryantoro SD, Rosyid AN, Marfiani E, Windradi C, Mahdi BA, et al. Predictive Value of Sequential Organ Failure Assessment, Quick Sequential Organ Failure Assessment, Acute Physiology and Chronic Health Evaluation II, and New Early Warning Signs Scores Estimate Mortality of COVID-19 Patients Requiring Intensive Care Unit. Indian J Crit Care Med 2022;26(4):464-471.
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Background: COVID-19 has a high risk of mortality, especially in patients with comorbid diseases such as cardiac disease, type 2 diabetes mellitus, chronic kidney disease, and hypertension. The National Early Warning Score (NEWS) is a tool that helps in identifying changes in patient conditions that require intensive treatment. Objective: Analyzing NEWS-2 to identify the risk of death in COVID-19 patients. Methods: This research was conducted from June to July 2020 by using quota sampling. The number of participants in this study was 112 participants (case group = 56 participants and control group = 56 participants). Participants were assessed for NEWS-2 and evaluated for their treatment outcomes. The analysis used in this study was the Chi-squared test and logistic regression with p < 0.05. Results: 45 participants died of having NEWS-2 score >5, and as many as 50 participants showed an improvement in their condition by having NEWS-2 score 5 (OR = 34.091; p < 0.001). The accuracy of NEWS-2's assessment of mortality of COVID-19 patients had a sensitivity of 80.4% and a specificity of 89.3%. There were several comorbid diseases that had a significant relationship on mortality of COVID-19 patients such as cardiac disease (ß = 5.907; 1.107-31.527 95% CI; p = 0.038), T2DM (ß = 3.143; 1.269-7.783 95% CI; p = 0.013), CKD (ß = 3.851; 1.195-12.416 95% CI; p = 0.024), and hypertension (ß = 2.820; 1.075-7.399 95% CI; p = 0.035). Conclusion: The NEWS-2 can be used to identify the risk of death of COVID-19 patients.
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BACKGROUND: Most COVID-19 patients have mild or moderate illnesses that can progress to severe illness, leading to hospitalization and/or mortality. The use of antivirals to prevent the progression of COVID-19 in non-hospitalized patients shows conflicting result and efficacy remain unclear. This study evaluates the efficacy and safety of antivirals therapy in COVID-19 outpatients. METHODS: Search were conducted in Pubmed, ScienceDirect, Cochrane Library, Springer, medRxiv, Journal Storage [JSTOR], and Directory of Open Access Journals [DOAJ] for articles investigating antivirals in COVID-19 outpatients. In addition, clinical and virological outcomes, COVID-19 hospitalization, all caused mortality, and adverse events were assessed. RESULTS: Thirteen studies were included in this review. The consecutive data from these studies suggested that favipiravir is more optimally used in early disease, but improvement in symptoms shows inconsistent results. Meanwhile, molnupiravir shows consistent results, which can reduce hospitalization and mortality risk. In addition, remdesivir and nirmatrelvir-ritonavir have the potential to prevent the progression of COVID-19 in outpatients, but the data provided in this study are very limited. Finally, there is no significant difference in serious and non-serious adverse events, highlighting that antivirals have a good safety profile. CONCLUSION: This study provides an overview of the role of various antivirals therapy in COVID-19 outpatients. Molnupiravir, remdesivir, and nirmatrelvir-ritonavir have shown potential to prevent the progression of COVID-19 in early disease. However, this review was based on very limited data. Therefore, further clinical trials are needed to confirm this finding.
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COVID-19 , Humans , Antiviral Agents/therapeutic use , Ritonavir , SARS-CoV-2 , Outpatients , Randomized Controlled Trials as TopicABSTRACT
Background : This research aimed to examine and analyze risk factors for death, hematologic parameters and coagulation in COVID-19 patients at RSUD Dr. Soetomo Surabaya, one of the referral centers for probable COVID-19 patient cases in East Java. Method : This was a retrospective analytical study by taking secondary data on patients with probable COVID-19 cases who were treated in hospital isolation rooms from May to September, 2020. Result : Of 538 probable COVID-19 patients, 217 tested positive, with an average age of 52.11±13.12 years, and there were 38 death cases. Hematologic parameters, such as white blood cell, neutrophil and lymphocyte counts, were significantly different in the deceased group. On the other hand, coagulation parameters, consisting of D-dimer, CRP, PT, and aPTT showed significantly similar value in the deceased group. Univatiate analysis concluded that chronic kidney disease, diabetes mellitus, coronary heart disease, WBC, NLR, and PPT counts could predict the mortality, while multivariate analysis revealed that coronary heart disease was the only significant independent predictor of mortality. Conclusion : This research shows that hematologic and coagulation parameters were increased in the majority of COVID-19 patients and the deceased group. While the number of neutrophils and WBC increases, the number of lymphocytes decreases significantly with increasing disease severity. Coronary heart disease is an independent predictor of mortality.
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COVID-19 , Adult , Aged , Hospitals , Humans , Indonesia/epidemiology , Intensive Care Units , Middle Aged , Referral and Consultation , Retrospective Studies , SARS-CoV-2ABSTRACT
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.
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Anti-Bacterial Agents/pharmacology , Antiviral Agents/pharmacology , COVID-19 Drug Treatment , Hydroxychloroquine/pharmacology , SARS-CoV-2/drug effects , Animals , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/virology , Cell Survival/drug effects , Cells, Cultured , Chlorocebus aethiops , Drug Combinations , Hospitalization , Host-Pathogen Interactions/drug effects , Humans , Hydroxychloroquine/therapeutic use , Indonesia , Inhibitory Concentration 50 , Inpatients , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Time Factors , Vero Cells , Viral Load/drug effectsABSTRACT
Background: Data on the prevalence of bacterial co-infections among COVID-19 patients are limited, especially in our country, Indonesia. We aimed to assess the rate of bacterial co-infections in hospitalized COVID-19 patients and report the most common microorganisms involved and the antibiotic use in these patients. Methods: This study is a retrospective cohort study, among COVID-19 adult patients admitted to Universitas Airlangga Hospital Surabaya from 14 March-30 September 2020. The bacterial infection is defined based on clinical assessment, laboratory parameters, and microbiology results. Results: A total of 218 patients with moderate to critical illness and confirmed COVID-19 were included in this study. Bacterial infection was confirmed in 43 patients (19.7%). COVID-19 patients with bacterial infections had longer hospital length of stay (17.6 ± 6.62 vs 13.31±7.12), a higher proportion of respiratory failure, intensive care treatment, and ventilator use. COVID-19 patients with bacterial infection had a worse prognosis than those without bacterial infection (p<0.04). The empirical antibiotic was given to 75.2% of the patients. Gram-negative bacteria were commonly found as causative agents in this study (n = 39; 70.37%). Conclusion: COVID-19 patients with bacterial infection have a longer length of stay and worse outcomes. Healthcare-associated infections during intensive care treatment for COVID-19 patients must be carefully prevented.
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Bacterial Infections , COVID-19 , Coinfection , Adult , Bacterial Infections/complications , Bacterial Infections/epidemiology , Coinfection/epidemiology , Critical Illness , Hospitals , Humans , Indonesia/epidemiology , Referral and Consultation , Retrospective Studies , SARS-CoV-2ABSTRACT
Background: Several studies have revealed the potential use of tocilizumab in treating COVID-19 since no therapy has yet been approved for COVID-19 pneumonia. Tocilizumab may provide clinical benefits for cytokine release syndrome in COVID-19 patients. Methods: We searched for relevant studies in PubMed, Embase, Medline, and Cochrane published from March to October 2020 to evaluate optimal use and baseline criteria for administration of tocilizumab in severe and critically ill COVID-19 patients. Research involving patients with confirmed SARS-CoV-2 infection, treated with tocilizumab and compared with the standard of care (SOC) was included in this study. We conducted a systematic review to find data about the risks and benefits of tocilizumab and outcomes from different baseline criteria for administration of tocilizumab as a treatment for severe and critically ill COVID-19 patients. Results: A total of 26 studies, consisting of 23 retrospective studies, one prospective study, and two randomised controlled trials with 2112 patients enrolled in the tocilizumab group and 6160 patients in the SOC group, were included in this meta-analysis. Compared to the SOC, tocilizumab showed benefits for all-cause mortality events and a shorter time until death after first intervention but showed no difference in hospital length of stay. Upon subgroup analysis, tocilizumab showed fewer all-cause mortality events when CRP level ≥100 mg/L, P/F ratio 200-300 mmHg, and P/F ratio <200 mmHg. However, tocilizumab showed a longer length of stay when CRP <100 mg/L than the SOC. Conclusion: This meta-analysis demonstrated that tocilizumab has a positive effect on all-cause mortality. It should be cautiously administrated for optimal results and tailored to the patient's eligibility criteria.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19 Drug Treatment , Humans , Multicenter Studies as Topic , Observational Studies as Topic , Randomized Controlled Trials as TopicABSTRACT
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.
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BACKGROUND: Dengue virus (DENV) causes the hospitalisation of an estimated 500,000 people every year. Outbreaks can severely stress healthcare systems, especially in rural settings. It is difficult to discriminate patients who need to be hospitalized from those that do not. Earlier work identified thrombocyte count and subsequent function as a promising prognostic marker of DENV severity. Herein, we investigated the potential of quantitative thrombocyte function tests in those admitted in the very early phase of acute DENV infections, using Multiplate™ multiple-electrode aggregometry to explore its potential in triage. METHODS: In this prospective cohort study all patients aged ≥13 admitted to Universitas Airlangga Hospital in Surabaya, Indonesia with a fever (≥38 °C) between 25 January and 1 August 2018 and with a clinical suspicion of DENV, were eligible for inclusion. Exclusion criteria were a thrombocyte count below 100 × 109/L and the use of any medication with a known anticoagulant effect, nonsteroidal anti-inflammatory drugs and acetyl salicylic acid. Clinical data was collected and blood was taken on admission, day 1 and day 7. Samples were tested for acute DENV, using Panbio NS1 ELISA. Platelet aggregation using ADP-, TRAP- and COL-test were presented as Area Under the aggregation Curve (AUC). Significance was tested between DENV+, probably DENV, fever of another origin, and healthy controls (HC). RESULTS: A total of 59 patients (DENV+ n = 10, DENV probable n = 25, fever other origin n = 24) and 20 HC were included. We found a significantly lower thrombocyte aggregation in the DENV+ group, compared with both HCs and the fever of another origin group (p < .001). Low ADP AUC values on baseline correlated to a longer hospital stay in DENV+ and probable DENV cases. CONCLUSION: Thrombocyte aggregation induced by Adenosine diphosphate, Collagen and Thrombin receptor activating peptide-6 is impaired in human DENV cases, compared with healthy controls and other causes of fever. This explorative study provides insights to thrombocyte function in DENV patients and could potentially serve as a future marker in DENV disease.