Prevalence of Cardiovascular Disease and Comparison of Risk Category Predictions of Systemic Coronary Risk Evaluation Score-2 and 4 Other Cardiovascular Disease Risk Assessment Tools Among People Living with Human Immunodefficiency Virus in Türkiye.

BACKGROUND: Cardiovascular disease (CVD) is a major cause of mortality among people living with HIV (PLWH). We aimed to assess the prevalence of diagnosed CVD and the risk of CVD among PLWH using 5 different tools. METHODS: This retrospective, cross-sectional study was conducted in 20 tertiary centers in Türkiye between October 2021 and March 2022, among 1425 PLWH aged 40-75 years. About 82.7% were male, with a median age of 51. Web-based tools for each score were used for CVD risk calculations. RESULTS: Of 1425 PLWH enrolled, 10.8% had confirmed CVD, and 1132 had their risk scores evaluated. Of those participants, 42.8% had a higher risk of CVD (10-year risk of atherosclerotic CVD risk score (ASCVD) above 7.5%), and according to the European Society of Cardiology systemic coronary risk evaluation 2 (SCORE2), 71.7% had a high- to very high-risk rate. The agreement between various CVD risk tools varied, with Framingham heart study risk score (FRS), modified FRS, data collection on adverse effects of anti-HIV drugs (DAD), and SCORE2 for high-risk countries showing overall agreement rates of 82%, 94%, 91%, and 36%, respectively, compared to ASCVD. According to the 2021 European and 2019 American Cardiology guidelines, 75.3% and 47.1% of PLWH would be eligible for lipid-lowering agents, respectively. CONCLUSION: The diagnosed CVD prevalence highlighted the importance of monitoring cardiovascular health and comorbidities in this population. SCORE2 identified a greater number of individuals at high/very high risk compared to other prediction tools. The implementation of CVD prevention through lipid-lowering therapy was far from desired levels in our cohort.

Efficacy of favipiravir in COVID-19: A retrospective two center comparative study.

INTRODUCTION: Favipiravir (FVP) is an antiviral, targeting RNA-dependent RNA polymerase. We aimed to evaluate the efficacy of FVP as a treatment for COVID-19. METHODS: We conducted a retrospective study in two centers (San Martino University Hospital in Genova, Italy, and Marmara University Pendik Training and Research Hospital, Turkey). Adult patients (inpatients) diagnosed with COVID-19 between March and June 2020 were included. All patients in the Italian center received the standard of care (SoC) treatment, while in the Turkish center patients received FVP in addition to SoC. RESULTS: Six hundred-nineteen patients were analyzed (225 from Turkey, all treated with FVP, and 394 from Italy, none treated with FVP). Propensity score-matching was done in 142 patients (71 from the SoC group vs. 71 from the SoC + FVP group). A Higher requirement of NIV/CPAP (n = 38; 53.5%) was registered in the SoC group compared to the SoC + FVP group (n = 9; 12.7%). A higher frequency of intubation was registered in the SoC + FVP group (n = 25; 35.2% vs n = 13, 18.3%). There was a trend towards better survival in SoC + FVP treated patients with HR = 0.64 (95% CI 0.30-1.34). At 28 days the OS was, respectively, 70.3% (95% CI: 53.2-82.1) vs 80.3% (95% CI: 69.0-87.8). CONCLUSIONS: The addition of FVP to SoC did not show a significant difference in survival and invasive and noninvasive (CPAP/NIMV) mechanical ventilation compared to standard of care in moderate and severe COVID-19-infected patients.

Clinical Pharmacist-Led Medication Review in Hospitalized Confirmed or Probable Patients with COVID-19 During the First Wave of COVID-19 Pandemic.

Objectives: Drug-related problems (DRPs) result in serious problems among hospitalized patients, high rates of morbidity and mortality, and increased healthcare costs. This study aimed to identify DRPs by clinical pharmacist-led medication review in hospitalized probable patients with coronavirus disease-2019 (COVID-19) during the first wave of the COVID-19 pandemic. Materials and Methods: This retrospective cross-sectional study was conducted at the COVID-19 inpatient services of a tertiary university hospital in Türkiye for 3 months (between March 2020 and June 2020) and included hospitalized confirmed or probable COVID-19 patients. The World Health Organization and Turkish Ministry of Health Guidelines case definitions were used to define confirmed and probable COVID-19 patients. Six clinical pharmacy residents provided medication review services during their education and training. DRPs were classified based on the Pharmaceutical Care Network Europe V9.00. The physician's acceptance rate of clinical pharmacists' recommendations was assessed. Results: Among 202 hospitalized patients with probable or confirmed COVID-19, 132 (65.3%) had at least one drug-related problem. Two hundred and sixty-four DRPs were identified. Drug selection (85.6%) and dose selection (9.2%) were the most common causes of these problems. Among the 80 clinical pharmacist interventions, 48.8% were accepted by the physicians. Conclusion: Clinical pharmacists identified a significant number of DRPs during the COVID-19 pandemic, particularly those related to drug interactions and drug safety, such as adverse drug reactions. This study highlights the importance of detecting and responding to DRPs in the COVID-19 pandemic.

Attributable mortality of infections caused by carbapenem-resistant Enterobacterales: results from a prospective, multinational case-control-control matched cohorts study (EURECA).

OBJECTIVES: To assess the mortality attributable to infections caused by carbapenem-resistant Enterobacterales (CRE) and to investigate the effect of clinical management on differences in observed outcomes in a multinational matched cohort study. METHODS: A prospective matched-cohorts study (NCT02709408) was performed in 50 European hospitals from March 2016 to November 2018. The main outcome was 30-day mortality with an active post-discharge follow-up when applied. The CRE cohort included patients with complicated urinary tract infections, complicated intra-abdominal infections, pneumonia, or bacteraemia from other sources because of CRE. Two control cohorts were selected: patients with infection caused by carbapenem-susceptible Enterobacterales (CSE) and patients without infection. Matching criteria included type of infection for the CSE group, hospital ward of CRE detection, and duration of hospital admission up to CRE detection. Multivariable and stratified Cox regression was applied. RESULTS: The cohorts included 235 patients with CRE infection, 235 patients with CSE infection, and 705 non-infected patients. The 30-day mortality (95% CI) was 23.8% (18.8-29.6), 10.6% (7.2-15.2), and 8.4% (6.5-10.6), respectively. The difference in 30-day mortality rates between patients with CRE infection when compared with patients with CSE infection was 13.2% (95% CI, 6.3-20.0), (HR, 2.57; 95% CI, 1.55-4.26; p < 0.001), and 15.4% (95% CI, 10.5-20.2) when compared with non-infected patients (HR, 3.85; 95% CI, 2.57-5.77; p < 0.001). The population attributable fraction for 30-day mortality for CRE vs. CSE was 19.28%, and for CRE vs. non-infected patients was 9.61%. After adjustment for baseline variables, the HRs for mortality were 1.87 (95% CI, 0.99-3.50; p 0.06) and 3.65 (95% CI, 2.29-5.82; p < 0.001), respectively. However, when treatment-related time-dependent variables were added, the HR of CRE vs. CSE reduced to 1.44 (95% CI, 0.78-2.67; p 0.24). DISCUSSION: CRE infections are associated with significant attributable mortality and increased adjusted hazard of mortality when compared with CSE infections or patients without infection. Underlying patient characteristics and a delay in appropriate treatment play an important role in the CRE mortality.

The safety and adverse event profile of favipiravir in the treatment of COVID-19 patients, Turkey.

INTRODUCTION: Favipiravir (FVP) is an antiviral and used to treat COVID-19. We aimed to document the safety and adverse events associated with FVP on the outcome of COVID-19 treatment. METHODOLOGY: The study included 225 adult patients with moderate COVID-19 infection (World Health Organization scale-5). The adverse events (AEs) were evaluated using a grading scale supported by the Food and Drug Administration. Safety was assessed by the frequency of serious AEs. RESULTS: The AEs associated with FVP treatment were hepatotoxicity (87/225, 38.7%), weakness (32/225, 14.2%), nephrotoxicity (26/225, 11.6%), nausea (18/225, 8.0%), diarrhea (8/225, 3.6%), vomiting (5/225, 2.2%), and insomnia (4/225, 1.8%); rash was not detected. Hepatotoxicity was observed more frequently in patients who also developed nephrotoxicity (57.7% vs 36.2%, p = 0.03). The deceased patients were significantly older and had higher prevalence of hypertension, congestive heart failure (CHF), coronary artery disease, cancer, nephrotoxicity. and angiotensin- converting enzyme inhibitors/angiotensin receptor blocker use. While male gender (OR: 5.38 CI: 1.64-17.67) and CHF (OR: 6.8 CI: 1.92-24.74) were significantly associated with nephrotoxicity, age (OR: 1.06 CI: 1.02-1.10), cancer (OR: 3.9 CI: 1.10-14.22) and nephrotoxicity (OR: 5.5 CI: 1.74-17.74) were associated with mortality. CONCLUSIONS: Serious AEs were detected at very low levels that would not require discontinuation of treatment or any AE-related death. Since SARS-CoV-2 itself and drug interactions may differ, FVP-related AEs might vary in COVID-19 patients. Our study shows that FVP can be used safely with a low AE profile. More extensive evidence is required to evaluate the long-term AEs of FVP.

Prognostic values of baseline cortisol levels and neutrophil to lymphocyte ratio in COVID-19.

Background: The prediction of disease severity in COVID19 could be a valuable tool for providing early treatment and reducing mortality. We aimed to evaluate the predictor value of baseline cortisol values on disease severity and assess the correlation between the neutrophil to lymphocyte ratio (NLR) and cortisol levels. Methods: In this retrospective study, we compared the prognostic value of baseline NLR, morning cortisol, ferritin, and C-reactive protein (CRP) levels among patients with severe and non-severe COVID-19. The association was assessed with Spearman's correlation. Results: 37.7% of the patients (n=63) had severe disease, and their baseline cortisol levels were higher than those in the non-severe group (522 nmol/L vs 380.7 nmol/L, p=0.011). The baseline cortisol level and NLR had area under the curve (AUC) values of 0.62 (95% confidence interval CI 0.53-0.71) and 0.70 (CI 95% 0.62-0.78) for the prediction of severe COVID-19, respectively. Severe disease was predicted in patients with a baseline cortisol cutoff ≥ 522 nmol/L with a specificity of 75.0%, a sensitivity of 50.79%. The cutoff value for the NLR on day 1 was ≥ 6.2, with a specificity of 93.27% and a sensitivity of 32.79%. Baseline cortisol levels showed a significant weakmoderate positive correlation with the NLR and levels of CRP and ferritin on day 1 (r=0.33, r=0.29, r=0.28, respectively, p<0.001 for all). Conclusions: The baseline cortisol level in COVID-19 patients is a good predictive marker for disease severity and non-inferior to the NLR. However, it is inferior to CRP and ferritin.

Nosocomial infection of C. auris in COVID-19 Intensive Care Unit in Türkiye and Phylogenetic Analysis of Isolates.

BACKGROUND: The difficulties in the identification of C. auris and the delays in the implementation of infection control precautions contribute to outbreaks. This study analyzed 10 patients with COVID-19 and C. auris candidemia, their characteristic and clinical features and phylogenetic features, and the antifungal susceptibilities of the isolates. METHOD: C. auris were detected in the COVID-19 ICU of a university hospital between January and August 2021. Identification to species level was performed using MALDI-TOF MS. Antifungal susceptibilities were determined by the Sensititre YeastOne YO10 panel. The isolates were whole genome sequenced to assess genetic relatedness and a phylogenetic tree was drawn including various C. auris clades. RESULTS: The mean growth time in blood cultures was 38.8 h. C. auris candidemia developed on the average 27th day of ICU admission. All were susceptible to anidulafungin and micafungin, while they were resistant to fluconazole and amphotericin B. Only three isolates were found to be resistant to caspofungin. All patients died. With the WGS method, all isolates were found in a close resemblance to each other in terms of total nucleotide similarity (with a minimum of 96% pairwise alignment). Our isolates showed the closest similarity to South Asian clade (Clade I). CONCLUSIONS: This study is the first to evaluate the phylogenetic characteristics of C. auris using WGS and to determine antifungal susceptibilities in Türkiye on COVID-19 patients. The mortality rate was very high in patients who have both COVID-19 and C. auris candidemia.

Medication Reconciliation Service in Hospitalized Patients with Infectious Diseases During Coronavirus Disease-2019 Pandemic: An Observational Study.

Objectives: To determine the prevalence and type of medication discrepancies and factors associated with unintentional discrepancies and identify the rate of hospital readmission and emergency service visit within 30 days after discharge among hospitalized patients with infectious diseases and receiving clinical pharmacist-led medication reconciliation during the coronavirus disease-2019 (COVID-19) pandemic. Materials and Methods: This observational study was conducted in the internal medicine and infectious diseases wards of a tertiary university hospital between July 2020 and February 2021 among hospitalized adult patients with infectious diseases. Medication reconciliation service (including patient counseling) was provided in person or by telephone. The number and type of medication discrepancies detected during the medication reconciliation services, the acceptance rate of pharmacists' recommendation, and factors associated with having at least one unintentional medication discrepancy at admission were evaluated. At follow-up, hospital readmission and emergency service visit within 30 days after discharge were assessed by telephone. Results: Among 146 patients, 84 (57.5%) had at least one unintentional discrepancy at admission. Only three unintentional discrepancies were determined in three patients at hospital discharge. All the pharmacists' recommendations for medication discrepancies were accepted by the physicians. Having COVID-19 [odds ratio (OR): 2.25, 95% confidence interval (CI): 1.15-4.40; p<0.05], being at a high risk for medication error (OR: 2.01, 95% CI: 1.03-3.92; p<0.05), and higher number of medications used at home (OR: 1.41, 95% CI: 1.23-1.61; p<0.001) were associated with having at least one unintentional discrepancy at admission. The rates of 30 day hospital readmission and admission to the emergency medical service were 12.3% and 15.8%, respectively. Conclusion: Medication reconciliation service provided by in-person or by telephone was useful for detecting and solving unintentional medication discrepancies during the COVID-19 pandemic.

Modeling the future of HIV in Turkey: Cost-effectiveness analysis of improving testing and diagnosis.

AIMS: This study aimed to determine HIV incidence and prevalence in Turkey and to estimate the cost-effectiveness of improving testing and diagnosis in the next 20 years. BACKGROUND: HIV incidence in Turkey has been rapidly increasing in the last decade with a particularly high rate of infection for younger populations, which underscores the urgent need for a robust prevention program and improved testing capacity for HIV. METHODS: We developed a dynamic compartmental model of HIV transmission and progression among the Turkish population aged 15-64 and assessed the effect of improving testing and diagnosis. The model generated the number of new HIV cases by transmission risk and CD4 level, HIV diagnoses, HIV prevalence, continuum of care, the number of HIV-related deaths, and the expected number of infections prevented from 2020 to 2040. We also explored the cost impact of HIV and the cost-effectiveness of improving testing and diagnosis. RESULTS: Under the base case scenario, the model estimated an HIV incidence of 13,462 cases in 2020, with 63% undiagnosed. The number of infections was estimated to increase by 27% by 2040, with HIV incidence in 2040 reaching 376,889 and HIV prevalence 2,414,965 cases. Improving testing and diagnosis to 50%, 70%, and 90%, would prevent 782,789, 2,059,399, and 2,336,564 infections-32%, 85%, and 97% reduction in 20 years, respectively. Improved testing and diagnosis would reduce spending between $1.8 and $8.8 billion. CONCLUSIONS: In the case of no improvement in the current continuum of care, HIV incidence and prevalence will significantly increase over the next 20 years, placing a significant burden on the Turkish healthcare system. However, improving testing and diagnosis could substantially reduce the number of infections, ameliorating the public health and disease burden aspects.

Prevalence of Polypharmacy and Potential Drug-Drug Interactions Associated with Risk Factors in the Era of HIV Integrase Inhibitors: A Prospective Clinical Study.

People living with human immunodeficiency virus (PLWH), with the availability of modern antiretroviral drugs, have multiple comorbidities, which increase the risk of polypharmacy and potential drug-drug interactions (PDDIs). This is a particularly important issue for the aging population of PLWH. This study aims to review the prevalence and risk factors for PDDIs and polypharmacy in the era of HIV integrase inhibitors. A cross-sectional, two-center, prospective observational study was conducted on Turkish outpatients between October 2021 and April 2022. Polypharmacy was defined as the use of ≥5 non-HIV medications, excluding over-the-counter (OTC) drugs, and PDDIs were classified using the University of Liverpool HIV Drug Interaction Database (harmful/red flagged and potentially clinically relevant/amber flagged). The median age of the 502 PLWH included in the study was 42 ± 12.4 years and 86.1% were males. Most individuals (96.4%) were given integrase-based regimens (unboosted 68.7% and boosted 27.7%). In total, 30.7% of individuals were taking at least one OTC drug. The prevalence of polypharmacy was 6.8% (9.2% when OTC drugs were included). During the study period, the prevalence of PDDIs was 1.2% for red flag PDDIs and 16% for amber flag PDDIs. CD4+ T cell count >500 cells/mm3, number of comorbidities ≥3, comedication with drugs affecting blood and blood-forming organs, cardiovascular drugs, and vitamin/mineral supplements were associated with red flag or amber flag PDDIs. Drug interaction prevention is still important in HIV care. Individuals with multiple comorbidities should be closely monitored for non-HIV medications to prevent PDDIs.

Effect of video camera monitoring feedback on hand hygiene compliance in neonatal intensive care unit, an interventional study.

BACKGROUND: The purpose of this study was to determine whether use of a video camera surveillance system for hand hygiene (HH) monitoring, video-based education, and feedback could improve the HH compliance in a neonatal intensive care unit (NICU). METHODS AND MATERIALS: This was an interventional before-after trial conducted in a level-III NICU between July 2019 and June 2020. HH compliance was measured using randomly selected video-camera footage in the baseline, intervention, and maintenance periods. After the baseline, an intervention consisting of feedback and education with video scenarios was implemented. The primary outcome was change in HH compliance. The compliance rates were analyzed as an interrupted time series (ITS) with a segmented regression model adjusted for autocorrelation for each study period. RESULTS: We identified a total of 8335 HH indications. There were non significant increases in the total compliance rate (9.0%, 95% CI -2% to 20%) at the time of intervention and in the compliance rate after intervention (0.26%, 95% CI -0.31% to 0.84%) per day. The hand hygiene compliance before patient contact significantly increased (19.8%, 95% CI, 4.8%-34.8%). Incorrect glove use improved non-significantly with the intervention (-3.4%, 95% CI -13.4% to 6.7%). CONCLUSION: In this study of HH monitoring using video-camera footage combined with an intervention including feedback and education, there were inconsistent improvements in HH compliance. However, these improvements were not sustained in the long term. Frequent feedback and education may be required to sustain high compliance.

Factors Associated with 28-day Critical Illness Development During the First Wave of COVID-19.

Objective: This study aimed to define the predictors of critical illness development within 28 days postadmission during the first wave of the COVID-19 pandemic. Materials and Methods: We conducted a prospective cohort study including 477 PCR-positive COVID-19 patients admitted to a tertiary care hospital in Istanbul from March 12 to May 12, 2020. Results: The most common presenting symptoms were cough, dyspnea, and fatigue. Critical illness developed in 45 (9.4%; 95% CI=7.0%-12.4%) patients. In the multivariable analysis, age (hazard ratio (HR)=1.05, p<0.001), number of comorbidities (HR=1.33, p=0.02), procalcitonin ≥0.25 µg/L (HR=2.12, p=0.03) and lactate dehydrogenase (LDH) ≥350 U/L (HR=2.04, p=0.03) were independently associated with critical illness development. The World Health Organization (WHO) ordinal scale for clinical improvement on admission was the strongest predictor of critical illness (HR=4.15, p<0.001). The patients hospitalized at the end of the study period had a much better prognosis compared to the patients hospitalized at the beginning (HR=0.14; p=0.02). The C-index of the model was 0.92. Conclusion: Age, comorbidity number, the WHO scale, LDH, and procalcitonin were independently associated with critical illness development. Mortality from COVID-19 seemed to be decreasing as the first wave of the pandemic advanced. Graphic Abstract: Graphic Abstract.

Clinical characteristics and risk factors associated with severe disease and outcome of patients with COVID-19.

INTRODUCTION: Since the beginning of the pandemic, factors associated with mortality in patients with corona virus infection disease 2019 (COVID-19) have been investigated. Comorbidities and increased age have been frequently reported to be associated with mortality. We aimed to evaluate the factors associated with unfavorable outcome of patients with COVID-19 at an early period of the pandemic. METHODOLOGY: This single center, retrospective, observational study was conducted among laboratory confirmed COVID-19 patients hospitalized between March 11 and May 5, 2020, at Umraniye Training and Research Hospital, Istanbul, Turkey. The effects of the severity of illness, comorbidities, symptoms, and laboratory findings on the clinical outcome were evaluated. Factors associated with unfavorable outcome (necessity of mechanical ventilation or death) were examined using Cox proportional hazards models. RESULTS: Out of a total of 728 patients, 53.8% were men and median age 54 years. The 30-day mortality rate was 4.9% among all hospitalized patients. A logistic regression model identified six predictors of unfavorable clinical outcome: age, severity of illness, the numbers of comorbidities, lymphopenia, high levels of C-reactive protein, and procalcitonin. CONCLUSIONS: The mortality rate was lower among the patients with COVID-19, hospitalized during the early period of the pandemic. Older age, higher severity score on admission, the numbers of comorbidities, higher levels of C-reactive protein, procalcitonin, and lymphopenia were identified to be associated with unfavorable outcome of the hospitalized patients with COVID-19.

Comparison of Turkish version of the medical outcomes study-HIV health survey with short form health survey-36 in people living with human immunodeficiency virus.

BACKGROUND/AIM: Several questionnaires have been developed to evaluate the quality of life (QoL) for people living with human immunodeficiency virus (HIV). The aim of this study was to compare Turkish version of the Medical Outcomes Study-HIV Health Survey (MOS-HIV) with Short Form Health Survey (SF-36) in people with HIV. PATIENTS AND METHODS: A hundred and 14 patients with HIV were consecutively included. The MOS-HIV and SF-36 questionnaires were applied to all patients at the same day. MOS HIV included 35 items and assessed general health perceptions (GH), physical functioning (PF), social functioning (SF), mental health (MH), bodily pain (P), cognitive functioning, health distress, overall QoL, health transition, role functioning (RF), energy/vitality (EV), physical (Physical health summary score) and mental (MHSS) health summary scores. SF-36 included 36 items and measured eight domains of health concepts including SF, PF, P, RF, GH, role emotional, vitality (V) and MH. Correlation analysis and Bland- Altman plots were used to compare the MOS-HIV and SF-36 questionnaires. RESULTS: GH, PF, P, RF, EV, SF, and MH domains of the MOS-HIV were significantly correlated with those of SF 36. The agreement between the tests were 91.2% for PF, 92.1% for RF and pain, 94.7% for GH, 95.6% for EV, 92.1% for SF and 93.9% for MH. CONCLUSION: Turkish version of the MOS HIV showed moderate correlations and agreement with SF 36 suggesting its use as an alternative to SF 36 in assessing QoL in these patients.

Pharmacokinetic characterization of favipiravir in patients with COVID-19.

This prospective observational study describes the pharmacokinetic characteristics of favipiravir in adult patients hospitalized for mild to moderate COVID-19 with a positive RT-PCR test. Favipiravir was administered for 5 days, with a loading dose of 3200 mg and a maintenance dose of 1200 mg/day. Serial blood samples were collected on Day 2 and Day 4 of the therapy. Laboratory findings of the patients (n = 21) and in-hospital mortality were recorded. Favipiravir concentrations exhibited substantial variability and a significant decrease during the treatment of COVID-19. The median favipiravir trough concentration (C0-trough ) on Day 2 was 21.26 (interquartile range [IQR], 8.37-30.78) µg/mL, whereas it decreased significantly to 1.61 (IQR, 0.00-6.41) µg/mL on Day 4, the area under the concentration-time curve decreased by 68.5%. Day 2 C0-trough of female patients was higher than male patients. Our findings indicate that favipiravir concentrations show significant variability during the treatment of COVID-19 and therapeutic drug monitoring may be necessary to maintain targeted concentrations.

Diversity of HIV-1 Subtypes and Transmitted Drug-resistance Mutations Among Minority HIV-1 Variants in a Turkish Cohort.

BACKGROUND: The World Health Organization (WHO) recommends the surveillance of transmitted drug resistance mutations (TDRMs) to ensure the effectiveness and sustainability of HIV treatment programs. OBJECTIVE: Our aim was to determine the TDRMs and evaluate the distribution of HIV-1 subtypes using and compared next-generation sequencing (NGS) and Sanger-based sequencing (SBS) in a cohort of 44 antiretroviral treatment-naïve patients. METHODS: All samples that were referred to the microbiology laboratory for HIV drug resistance analysis between December 2016 and February 2018 were included in the study. After exclusions, 44 treatment-naive adult patients with a viral load of >1000 copies/mL were analyzed. DNA sequencing for reverse transcriptase and protease regions was performed using both DeepChek ABL single round kit and Sanger-based ViroSeq HIV-1 Genotyping System. The mutations and HIV-1 subtypes were analyzed using the Stanford HIVdb version 8.6.1 Genotypic Resistance software, and TDRMs were assessed using the WHO surveillance drug-resistance mutation database. HIV-1 subtypes were confirmed by constructing a maximum-likelihood phylogenetic tree using Los Alamos IQ-Tree software. RESULTS: NGS identified nucleos(t)ide reverse transcriptase inhibitor (NRTI)-TDRMs in 9.1 % of the patients, non-nucleos(t)ide reverse transcriptase inhibitor (NNRTI)-TDRMs in 6.8 % of the patients, and protease inhibitor (PI)-TDRMs in 18.2 % of the patients at a detection threshold of ≥ 1 %. Using SBS, 2.3 % and 6.8 % of the patients were found to have NRTI- and NNRTI-TDRMs, respectively, but no major PI mutations were detected. M41L, L74I, K65R, M184V, and M184I related to NRTI, K103N to NNRTI, and N83D, M46I, I84V, V82A, L24I, L90M, I54V to the PI sites were identified using NGS. Most mutations were found in low-abundance (frequency range: 1.0 % - 4.7 %) HIV-1 variants, except M41L and K103N. The subtypes of the isolates were found as follows; 61.4 % subtype B, 18.2 % subtype B/CRF02_AG recombinant, 13.6 % subtype A, 4.5 % CRF43_ 02G, and 2.3 % CRF02_AG. All TDRMs, except K65R, were detected in HIV-1 subtype B isolates. CONCLUSION: The high diversity of protease site TDRMs in the minority HIV-1 variants and prevalence of CRFs were remarkable in this study. All minority HIV-1 variants were missed by conventional sequencing. TDRM prevalence among minority variants appears to be decreasing over time at our center.

Tocilizumab treatment in severe COVID-19: a multicenter retrospective study with matched controls.

Coronavirus disease-2019 (COVID-19) associated pneumonia may progress into acute respiratory distress syndrome (ARDS). Some patients develop features of macrophage activation syndrome (MAS). Elevated levels of IL-6 were reported to be associated with severe disease, and anti-IL-6R tocilizumab has been shown to be effective in some patients. This retrospective multicenter case-control study aimed to evaluate the efficacy of tocilizumab in hospitalized COVID-19 patients, who received standard of care with or without tocilizumab. Primary outcome was the progression to intubation or death. PSMATCH (SAS) procedure was used to achieve exact propensity score (PS) matching. Data from 1289 patients were collected, and study population was reduced to 1073 based on inclusion-exclusion criteria. The composite outcome was observed more frequently in tocilizumab-users, but there was a significant imbalance between arms in all critical parameters. Primary analyses were carried out in 348 patients (174 in each arm) after exact PS matching according to gender, ferritin, and procalcitonin. Logistic regression models revealed that tocilizumab significantly reduced the intubation or death (OR 0.40, p = 0.0017). When intubation is considered alone, tocilizumab-users had > 60% reduction in odds of intubation. Multiple imputation approach, which increased the size of the matched patients up to 506, provided no significant difference between arms despite a similar trend for intubation alone group. Analysis of this retrospective cohort showed more frequent intubation or death in tocilizumab-users, but PS-matched analyses revealed significant results for supporting tocilizumab use overall in a subset of patients matched according to gender, ferritin and procalcitonin levels.

An outbreak investigation of Burkholderia cepacia infections related with contaminated chlorhexidine mouthwash solution in a tertiary care center in Turkey.

BACKGROUND: We report a nosocomial outbreak caused by Burkholderia cepacia that occurred among six patients admitted in the medical and surgical intensive care unit between 04 March 2019 and 02 April 2019 in Istanbul, Turkey. METHODS: The outbreak investigation was launched on 11 March 2019 five days after the detection of B. cepacia in four different patients. We defined potential reservoirs and started environmental screening. We sampled the liquid solutions used in patient care activities. Pulse-field gel electrophoresis (PFGE) was performed to determine the genetic relatedness of environmental and patient samples. RESULTS: Burkholderia cepacia was isolated in tracheal aspiration cultures of six patients. Three out of six patients developed healthcare-associated pneumoniae due to B. cepacia. Environmental cultures in the ICUs revealed B. cepacia growth in 2% chlorhexidine-gluconate mouthwash solution that been used in the colonized patients as well as in samples obtained from the unused products. PFGE revealed the patient and a specific batch of chlorhexidine mouthwash solution samples had a 96% similarity. CONCLUSION: Contamination of medical solutions used in critical patient care could cause outbreaks and should be detected early by infection control teams.

Comparison of SARS-COV-2 antibody assays in PCR negative and PCR positive Turkish patients.

BACKGROUND: To the Editor, Serology may offer valuable information during COVID-19 pandemic; however, published papers mainly reported the results of symptomatic patients having positive RT-PCR on upper respiratory tract specimens [1]. More studies are needed to address whether asymptomatic patients, or patients with chest imaging compatible with COVID-19 but negative RT-PCR, have different antibody response that could influence assays performances. We wanted to share our data from Turkey where 4,323,596 COVID-19 cases were detected out of 44,087,628 PCR tests by April 20, 2021 but there are only a couple of published studies about serodiagnosis of the infection. DISCUSSION: The authors have no funding source for the study. The authors have no conflicts of interest to declare.

Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey.

BACKGROUND: CoronaVac, an inactivated whole-virion SARS-CoV-2 vaccine, has been shown to be well tolerated with a good safety profile in individuals aged 18 years and older in phase 1/2 trials, and provided a good humoral response against SARS-CoV-2. We present the interim efficacy and safety results of a phase 3 clinical trial of CoronaVac in Turkey. METHODS: This was a double-blind, randomised, placebo-controlled phase 3 trial. Volunteers aged 18-59 years with no history of COVID-19 and with negative PCR and antibody test results for SARS-CoV-2 were enrolled at 24 centres in Turkey. Exclusion criteria included (but were not limited to) immunosuppressive therapy (including steroids) within the past 6 months, bleeding disorders, asplenia, and receipt of any blood products or immunoglobulins within the past 3 months. The K1 cohort consisted of health-care workers (randomised in a 1:1 ratio), and individuals other than health-care workers were also recruited into the K2 cohort (randomised in a 2:1 ratio) using an interactive web response system. The study vaccine was 3 µg inactivated SARS-CoV-2 virion adsorbed to aluminium hydroxide in a 0·5 mL aqueous suspension. Participants received either vaccine or placebo (consisting of all vaccine components except inactivated virus) intramuscularly on days 0 and 14. The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 at least 14 days after the second dose in the per protocol population. Safety analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT04582344) and is active but no longer recruiting. FINDINGS: Among 11 303 volunteers screened between Sept 14, 2020, and Jan 5, 2021, 10 218 were randomly allocated. After exclusion of four participants from the vaccine group because of protocol deviations, the intention-to-treat group consisted of 10 214 participants (6646 [65·1%] in the vaccine group and 3568 [34·9%] in the placebo group) and the per protocol group consisted of 10 029 participants (6559 [65·4%] and 3470 [34·6%]) who received two doses of vaccine or placebo. During a median follow-up period of 43 days (IQR 36-48), nine cases of PCR-confirmed symptomatic COVID-19 were reported in the vaccine group (31·7 cases [14·6-59·3] per 1000 person-years) and 32 cases were reported in the placebo group (192·3 cases [135·7-261·1] per 1000 person-years) 14 days or more after the second dose, yielding a vaccine efficacy of 83·5% (95% CI 65·4-92·1; p<0·0001). The frequencies of any adverse events were 1259 (18·9%) in the vaccine group and 603 (16·9%) in the placebo group (p=0·0108) with no fatalities or grade 4 adverse events. The most common systemic adverse event was fatigue (546 [8·2%] participants in the vaccine group and 248 [7·0%] the placebo group, p=0·0228). Injection-site pain was the most frequent local adverse event (157 [2·4%] in the vaccine group and 40 [1·1%] in the placebo group, p<0·0001). INTERPRETATION: CoronaVac has high efficacy against PCR-confirmed symptomatic COVID-19 with a good safety and tolerability profile. FUNDING: Turkish Health Institutes Association.