Iatrogenic botulism cases after gastric and axillary application of botulinum toxin and review of literature.

INTRODUCTION: Iatrogenic botulism is a rare, serious disease that progresses with descending paralysis and develops after cosmetic or therapeutic botulinum toxin-A (BoNT-A) application. CASE PRESENTATIONS: In this case series; six cases of iatrogenic botulism followed up in our center are presented. Four of these developed after gastric BoNT-A and two after axillary BoNT-A application. RESULTS: The most important cause for the disease was the use of unlicensed products and high-dose toxin applications. The first symptoms were blurred vision, double vision, difficulty in swallowing, and hoarseness. Symptoms appeared within 4-10 days after the application of BoNT-A. Symptoms progressed in the course of descending paralysis in the following days with fatigue, weakness in extremities and respiratory distress. Diagnosis was based on patient history and clinical findings. The main principles of foodborne botulism therapy were applied in the treatment of iatrogenic botulism. If clinical worsening continued, regardless of the time elapsed after BoNT-A application, the use of botulinum antitoxin made a significant contribution to clinical improvement and was recommended. CONCLUSIONS: Routine and new indications for BoNT-A usage are increasing and, as a result, cases of iatrogenic botulism will be encountered more frequently. Physicians should be alert for iatrogenic botulism in the follow-up after BoNT-A applications and in the differential diagnosis of neurological diseases that are presented with similar findings.

Multicentre, randomised, double-blind, placebo-controlled, proof of concept study of LSALT peptide as prevention of acute respiratory distress syndrome and acute kidney injury in patients infected with SARS-CoV-2 (COVID-19).

OBJECTIVE: Dipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed to evaluate the safety and efficacy of the DPEP-1 inhibitor, LSALT peptide, to prevent specific organ dysfunction in patients hospitalised with COVID-19. DESIGN: Phase 2a randomised, placebo-controlled, double-blinded, trial. SETTING: Hospitals in Canada, Turkey and the USA. PARTICIPANTS: A total of 61 subjects with moderate-to-severe COVID-19. INTERVENTIONS: Randomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was the proportion of subjects alive and free of respiratory failure and/or the need for renal replacement therapy (RRT). Numerous secondary and exploratory endpoints were assessed including ventilation-free days, and changes in kidney function or serum biomarkers. RESULTS: At 28 days, 27 (90.3%) and 28 (93.3%) of subjects in the placebo and LSALT groups were free of respiratory failure and the need for RRT (p=0.86). On days 14 and 28, the number of patients still requiring more intensive respiratory support (O2 ≥6 L/minute, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation) was 6 (19.4%) and 3 (9.7%) in the placebo group versus 2 (6.7%) and 2 (6.7%) in the LSALT group, respectively (p=0.14; p=0.67). Unadjusted analysis of ventilation-free days demonstrated 22.8 days for the LSALT group compared with 20.9 in the placebo group (p=0.4). LSALT-treated subjects had a significant reduction in the fold expression from baseline to end of treatment of serum CXCL10 compared with placebo (p=0.02). Treatment-emergent adverse events were similar between groups. CONCLUSION: In a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19. TRIAL REGISTRATION NUMBER: NCT04402957.

The clinical features, treatment and prognosis of neutropenic fever and Coronavirus disease 2019 results of the multicentre teos study.

This multicentre (22 centres in Turkey) retrospective cohort study aimed to assess the clinical outcomes of patients with neutropenic fever and SARS-CoV-2 positivity. Study period was 15 March 2020-15 August 2021. A total of 170 cases (58 female, aged 59 ± 15.5 years) that fulfilled the inclusion criteria were included in the study. One-month mortality rate (OMM) was 44.8%. The logistic regression analysis showed the following significant variables for the mentioned dependent variables: (i) achieving PCR negativity: receiving a maximum of 5 days of favipiravir (p = 0.005, OR 5.166, 95% CI 1.639-16.280); (ii) need for ICU: receiving glycopeptide therapy at any time during the COVID-19/FEN episode (p = 0.001, OR 6.566, 95% CI 2.137-20.172), the need for mechanical ventilation (p < 0.001, OR 62.042, 95% CI 9.528-404.011); (iii) need for mechanical ventilation: failure to recover from neutropenia (p < 0.001, OR 17.869, 95% CI 3.592-88.907), receiving tocilizumab therapy (p = 0.028, OR 32.227, 95% CI 1.469-707.053), septic shock (p = 0.001, OR 15.4 96% CI 3.164-75.897), and the need for ICU (p < 0.001, OR 91.818, 95% CI 15.360-548.873), (iv) OMM: [mechanical ventilation (p = 0.001, OR 19.041, 95% CI 3.229-112.286) and septic shock (p = 0.010, OR 5.589,95% CI 1.509-20.700)]. Although it includes a relatively limited number of patients, our findings suggest that COVID-19 and FEN are associated with significant mortality and morbidity.

ANTIBIOTIC MANAGEMENT PROGRAM IN A TERTIARY INTENSIVE CARE UNIT: INVESTIGATION OF THE EFFECTS OF A CARBAPENEM-RESTRICTED PERIOD ON CLINICAL AND LABORATORY PARAMETERS AND COSTS OF INFECTIONS.

OBJECTIVES: The aim of this study was to investigate the effects of the carbapenem-restricted antimicrobial stewardship program (ASP) on changes in the resistance profiles of infectious agents, the amount of antibiotics used, length of stay in the intensive care unit (ICU), mortality and costs. MATERIALS AND METHODS: The patients hospitalized in ICU between July 1, 2020 - May 1, 2021 were included the study. The study was divided in to two different periods, carbapenem not-restricted period (CNRP) and carbapenem restricted period (CRP). During CNRP, carbapenem were used by any restriction, and in CRP, the alternative antibiotics to carbapenems were preferred during infection. The Defined Daily Dose (DDD)-100 Patient Day (PD) methodology was used to calculate the antibiotic consumption. RESULTS: Of the 572 patients included in the study, 62.2% of the patients were male, mean age was 70.5 years. In the blood culture the most frequently gram negative agent was A.baumannii (25%). A. baumannii bloodstream infections with MDR, XDR was significantly different between the two periods (CNRP: 95.6% (22), CRP: 66.6%(8) p=0.04). A gradual decrease in the incidence density and rate of nosocomial infection was noted (p=0.06). During the study, a significant decrease in meropenem consumption was detected between the two periods (CNRP-CRP: 21.19-6.37 DDD/100 PD p=0.007). ASP provided a 8600 USD of antibiotic cost savings and a total of 14% patient cost savings (p<0.05) per patient. CONCLUSION: We believe that combining an effective ASP with a comprehensive infection control program will mitigate the emergence of antimicrobial-resistant bacteria.

Point prevalence of antibiotic usage in major referral hospital in Turkey.

INTRODUCTION: The most important and undesirable consequence of inappropriate antibiotic use is the spread of antibiotic resistance, increased adverse effects, increased mortality and healthcare costs. We aimed to assess antibiotic usage characteristics in inpatient setting in our center. MATERIALS AND METHODS: A one-day, single center point-prevalence study was carried out on June 9th 2021, in Ankara City Hospital in Turkey. Data of antibiotic consumption, appropriateness of usage and predictors of inappropriate use in adult patients were evaluated. RESULTS: Out of 2640 adult patients, 893 (33.8%) were receiving at least one antibiotic. A total of 1212 antibiotic prescriptions with an average of 1.44±0.64 were found. Antibiotics were most commonly used for therapeutic purpose (84.7%), followed by surgical prophylaxis (11.6%). Majority of therapeutically used antibiotics were empirical (67.9%). Infectious diseases consultation was present in 68.3% with a compliance rate of 95.7%. Rate of inappropriate use was 20%. The most frequent cause of inappropriateness was unnecessary use (52.5%). Most commonly and most inappropriately used antibiotics were carbapenems (17.5%) and first generation cephalosporins (38.7%), respectively. Most of the inappropriateness observed in first-generation cephalosporins was due to inappropriate longer surgical prophylaxis. While age is an independent risk factor for inappropriate antibiotic use (p = 0.042), COVID-19 unit admission, use for therapeutic purpose and infectious diseases consultation were protective factors (p<0.001, p<0.001, p<0.001). CONCLUSION: Rate of inappropriate use was low, but inappropriate surgical prophylaxis remains an important problem in surgical units. There is a considerable need to implement an antimicrobial stewardship program that focuses on surgical prophylaxis practices.

Tissue quantitative RT-PCR test for diagnostic significance of cytomegalovirus infection in patients with inflammatory bowel disease and treatment response: Cytomegalovirus infection in patients with inflammatory bowel disease.

Cytomegalovirus (CMV) is an opportunistic pathogen that exacerbates inflammatory bowel disease (IBD). There are no clear diagnostic criteria for CMV infection in IBD patients. The aim of this study was to evaluate the importance of the diagnosis of CMV infection with CMV-DNA polymerase chain reaction (PCR) in the colonic mucosa and the response to antiviral treatment. We retrospectively analyzed the clinical data of 30 patients with IBD (24 men, 6 women; median age: 42 years) who were hospitalized because of IBD exacerbation and whose samples were assessed by tissue CMV-DNA PCR positivity. Most of the IBD patients had ulcerative colitis (90%). The CMV-DNA PCR median value was 8848 copies/mL of tissue (range 90-242,936 copies/mL). Blood CMV-DNA PCR was found to be positive in a small group (33.3%, 10/30) of tissue CMV-DNA PCR-positive cases. immunohistochemistry tests were positive in only 5 of the 23 patients positive for CMV-DNA PCR in the colonic mucosa, and high remission (25/30, 83.3%) was detected with antiviral therapy. Recurrence of CMV colitis infection was observed in 9 of 25 patients who had remission with antiviral therapy. The tissue CMV-DNA PCR test was found to be more useful than blood CMV-DNA PCR and immunohistochemistry tests for diagnosing CMV colitis, and the tissue CMV-DNA PCR test enabled rapid and appropriate treatment.

Impact of Inflammation-Related Genes on COVID-19: Prospective Study at Turkish Cohort.

The pandemic coronavirus disease 2019 (COVID-19) has caused a high mortality rate and poses a significant threat to the population. The disease may progress with mild symptoms or may cause the need for intensive care, depending on many factors. In this study, it was aimed to determine if there is a tendency due to genetic factors in COVID-19 patients. Ninety-four of 188 patients with mild clinical and 94 with severe clinical symptoms were included in the study. The targeted panel including coagulopathy (F2, F5), viral invasion (ACE2), and inflammation (CXCL8, IFNAR2, IFNL4, IL10, IL2, IL6, IRF7, TLR3, TLR7, TNF) related genes was performed sequenced by the next generation sequencing (NGS). The variants found were classified and univariate analyses were performed to select candidate variables for logistic model. Risk factors and variants were compared. It was revealed that the presence of 2 or more risk factors caused the disease to progress severely (p < 0.001). Heterozygous IRF7:c.1357-23dup variant had a 2.5 times higher risk for mild disease compared to severe disease. Other variants were found to be more significant in mild disease. Since polymorphic variants were not evaluated in the literature, the findings of our study could not be compared with the literature. However, as variants that may be effective in the severity of infections may differ according to ethnicity. This study has the feature of being a guide for subsequent studies to be carried out especially in Turkish population. Clinical course of the COVID-19 is likely to depend on a variety of risk factors, including age, sex, clinical status, immunology and genetic factors.

Antimicrobial stewardship in the intensive care unit.

High resistance rates to antimicrobials continue to be a global health threat. The incidence of multidrug-resistant (MDR) microorganisms in intensive care units (ICUs) is quite high compared to in the community and other units in the hospital because ICU patients are generally older, have higher numbers of co-morbidities and immune-suppressed; moreover, the typically high rates of invasive procedures performed in the ICU increase the risk of infection by MDR microorganisms. Antimicrobial stewardship (AMS) refers to the implementation of coordinated interventions to improve and track the appropriate use of antibiotics while offering the best possible antibiotic prescription (according to dose, duration, and route of administration). Broad-spectrum antibiotics are frequently preferred in ICUs because of greater infection severity and colonization and infection by MDR microorganisms. For this reason, a number of studies on AMS in ICUs have increased in recent years. Reducing the use of broad-spectrum antibiotics forms the basis of AMS. For this purpose, parameters such as establishing an AMS team, limiting the use of broad-spectrum antimicrobials, terminating treatments early, using early warning systems, pursuing infection control, and providing education and feedback are used. In this review, current AMS practices in ICUs are discussed.

Modeling the Health Economic Burden of Hepatitis C Virus Infection in Turkey: Cost-Effectiveness of Targeted Screening.

BACKGROUND/AIMS: In 2016, World Health Organization introduced global goals to eliminate hepatitis C virus by 2030. The aim of this study is to analyze the epidemiologic and economic burden of hepatitis C virus in Turkey and compare current practice (regular care) with a hypothetical active screening and treatment approach (active scenario). MATERIALS AND METHODS: A Markov model was used to analyze and compare regular care with a scenario developed by experts including the screening and treatment of all acute and chronic hepatitis C virus infections between 2020 and 2050. General and targeted populations were focused. The model reflected the natural history of the disease, and the inputs were based on a literature review and expert opinions. Costs were provided by previous studies and national regulations. RESULTS: The active scenario resulted in higher spending for all groups compared with regular care in the first year. Cumulative costs were equalized in the 8th, 12th, 13th, and 16th year and followed by cost-savings of 49.7 million, 1.1 billion, 288.6 million, and 883.4 million Turkish liras in 20 years for prisoners, refugees, people who inject drugs (PWID), and all population, respectively. In all groups, the mortality was found to be lower with the active scenario. In total, 62.8% and 50.6% of expected deaths with regular care in 5 and 20 years, respectively, were prevented with the active scenario. CONCLUSIONS: An active screening and treatment approach for hepatitis C virus infection could be cost-effective for PWID, prisoners, and refugees. Almost two-thirds of deaths in regular care could be prevented in 5 years' time with this approach.

Prospective analysis of febrile neutropenia patients with bacteraemia: the results of an international ID-IRI study.

OBJECTIVES: Bacteraemia during the course of neutropenia is often fatal. We aimed to identify factors predicting mortality to have an insight into better clinical management. METHODS: The study has a prospective, observational design using pooled data from febrile neutropenia patients with bacteraemia in 41 centres in 16 countries. Polymicrobial bacteraemias were excluded. It was performed through the Infectious Diseases-International Research Initiative platform between 17 March 2021 and June 2021. Univariate analysis followed by a multivariate binary logistic regression model was used to determine independent predictors of 30-d in-hospital mortality (sensitivity, 81.2%; specificity, 65%). RESULTS: A total of 431 patients were enrolled, and 85 (19.7%) died. Haematological malignancies were detected in 361 (83.7%) patients. Escherichia coli (n = 117, 27.1%), Klebsiellae (n = 95, 22% %), Pseudomonadaceae (n = 63, 14.6%), Coagulase-negative Staphylococci (n = 57, 13.2%), Staphylococcus aureus (n = 30, 7%), and Enterococci (n = 21, 4.9%) were the common pathogens. Meropenem and piperacillin-tazobactam susceptibility, among the isolated pathogens, were only 66.1% and 53.6%, respectively. Pulse rate (odds ratio [OR], 1.018; 95% confidence interval [CI], 1.002-1.034), quick SOFA score (OR, 2.857; 95% CI, 2.120-3.851), inappropriate antimicrobial treatment (OR, 1.774; 95% CI, 1.011-3.851), Gram-negative bacteraemia (OR, 2.894; 95% CI, 1.437-5.825), bacteraemia of non-urinary origin (OR, 11.262; 95% CI, 1.368-92.720), and advancing age (OR, 1.017; 95% CI, 1.001-1.034) were independent predictors of mortality. Bacteraemia in our neutropenic patient population had distinctive characteristics. The severity of infection and the way to control it with appropriate antimicrobials, and local epidemiological data, came forward. CONCLUSIONS: Local antibiotic susceptibility profiles should be integrated into therapeutic recommendations, and infection control and prevention measures should be prioritised in this era of rapidly increasing antibiotic resistance.

Effect of 2 Different High-Dose Methylprednisolone Treatments on Clinical Outcomes in Severe COVID-19 Patients.

OBJECTIVE: The present study aimed to evaluate and compare the use of 2 different high-dose methylprednisolone posology in treating severe coronavirus disease 2019 pneumonia regarding mortality and recovery time between themselves and against steroidal/ non-steroidal treatment. MATERIAL AND METHODS: Severe coronavirus disease 2019 patients followed up between March 2020 and January 2021 were included. The steroid-free treatment protocol was applied before August 2020 (non-pulse group) and a treatment algorithm containing normal and high doses of methylprednisolone was applied after August 2020 (pulse group). Patients with clinical deterioration under the normal dose of methylprednisolone were administered 250 mg or 1000 mg of methylprednisolone for 3 days. We compared the pulse and non-pulse groups, in addition to pulse subgroups with each other, for clinical outcomes. RESULTS: A total of 138 patients were included, including 36 patients in the non-pulse group and 102 in the pulse group. In the pulse group, 70 patients received 1000 mg/day and 32 received 250 mg/day of high-dose methylprednisolone therapy. In the comparison of pulse and non-pulse patient groups, mortality rate was lower in the pulse group (P < .001), and the time to discharge without oxygen support was shorter. Although the patients in the 250 mg subgroup were older, there was no difference between the 250 mg and 1000 mg subgroups in terms of end of oxygen requirement, discharge with oxygen support, and mortality. In addition, the required time to reach the oxygen-free period in patients discharged without oxygen support was similar in the 2 subgroups, and the majority of patients in both subgroups reached the oxygen-free period on the 20th day after initiating methylprednisolone. CONCLUSION: Since there was no difference in clinical improvement between the use of 250 mg or 1000 mg methylprednisolone in patients with severe coronavirus disease 2019 infection, 1000 mg methylprednisolone was not required.

Impact of COVID-19 pandemic on diagnosis and treatment access of patients with viral hepatitis in Turkey.

INTRODUCTION: We aimed to evaluate access to diagnosis, treatment and follow-up in patients with viral hepatitis during the COVID-19 pandemic. METHODOLOGY: Patients who started treatment for hepatitis B and hepatitis C were included in the study and analyzed in two periods: before-pandemic and during-pandemic. Indication for treatment and frequency of laboratory follow-up was obtained from hospital records. A telephone survey was administered to evaluate treatment access and compliance. RESULTS: Four centers with 258 patients were included in the study. Of these 161 (62.4%) were male, median age was 50 years. The number of patients, admitted to outpatient clinics was 134647 in the before-pandemic period and 106548 in the during-pandemic period. Number of patients who started treatment for hepatitis B were significantly high during-pandemic period compared with before-pandemic (78 (0.07%); 73 (0.05%) respectively; p = 0.04). The number who received treatment for hepatitis C was similar in both periods: 43 (0.04%); 64 (0.05%), respectively (p = 0.25). Prophylactic treatment for hepatitis B, due to immunosuppressive agents was significantly higher in during-pandemic period (p = 0.001). In the laboratory follow-ups at 4th, 12th and 24th weeks of treatment, worse adherence was detected in during-pandemic (for all p < 0.05). Access to treatment and compliance of all patients was over 90% and did not differ in the two periods. CONCLUSIONS: During-pandemic, hepatitis patients' access to diagnosis, treatment initiation and follow-up had worsened in Turkey. The health policy implemented during the pandemic had a positive impact on patients' access to and compliance to treatment.

Investigation of SARS-CoV-2 using RT-PCR in vaginal swab samples of female patients with a diagnosis of severe COVID-19.

OBJECTIVE: It is important to determine the presence of SARS-CoV-2 in the vaginal fluid samples of reproductive-aged women with severe disease during the acute stage of the disease and to determine the risks of transmission by sexual or vertical transmission. MATERIAL AND METHODS: Adult women with confirmed severe COVID-19 who were admitted to Ankara City Hospital intensive care unit (ICU) between December 1st, 2020, and January 1st, 2021, were enrolled in the study. Vaginal swab samples were collected within 48 h in the ICU using Dacron or rayon swabs and tested for SARS-CoV-2 using reverse transcription real-time polymerase chain reaction (RT PCR). RESULTS: Thirty women of reproductive age were included in the study, five (16.7%) of whom were pregnant. The mean age was 44.9 (±10.5) years. The most common symptoms were headache (100%), muscle soreness (86.7%), cough (76.7%), fever (60%), and nausea and vomiting (20%). Nineteen (63.3%) patients had underlying medical conditions. The time interval from obtaining vaginal swab samples to admission to the ICU was 48 h. The time between vaginal sampling and PCR positivity ranged from 2 to 18 days. SARS-CoV-2 was not detected in any vaginal samples. CONCLUSION: Our study showed that women with severe COVID-19 did not have SARS-CoV-2 in their vaginal fluids. Investigation of the presence of SARS-CoV-2 in vaginal secretions may help in determining the risks of sexual transmission and vertical transmission from mother to baby. Information on this subject is still limited. Larger studies on comprehensive biological samples are needed.

Development and validation of COVID-19 associated candidemia score (CAC-Score) in ICU patients.

BACKGROUND: The development of candidemia is a highly fatal condition in severe COVID-19 infection. OBJECTIVES: This study aimed to develop a candidemia prediction score in COVID-19 patient based on the patient's clinical characteristics, and healthcare-related factors during intensive care units (ICU) follow-up. PATIENTS/METHODS: Severe COVID-19 patients hospitalised in ICU in Ankara City Hospital during the one-year period (August 15, 2020, and August 15, 2021) were included. After univariate analysis, multivariate analysis was applied using variable selection approach to investigate the effects of variables together and to create a score model for candidemia. Statistically significant factors were included in the development process of candida prediction score. RESULTS: Of 1305 COVID-19 ICU patients, 139 had a candidemia episode. According to the final model, four variables, presence of central venous catheter (CVC) (OR 19.07, CI 8.12-44.8, p < .0001), multifocal colonisation (OR 2.28, CI 1.39-3.72, p 0.001), length of ICU stays ≥14 days (OR 3.62, CI 2.42-5.44, p < .0001) and corticosteroids (OR 0.51, CI 0.34-0.76, p 0.0011) were the only statistically significant independent risk factors for candidemia. Score model was demonstrated by a nomogram, and the risk for candidemia was calculated to be high in patients who scored ≥56 points by using the criteria [CVC = 51, multifocal colonisation = 14, prolonged hospitalisation = 23, no steroid use = 12 points]. The AUC of the score is 0.84 (CI 0.81-0.87). CONCLUSION: We developed and validated an easy-to-use clinical prediction score for candidemia in severe COVID-19 infection. In COVID-19 ICU patients, the risk of candidemia is high if one of the other risk factors is present together with CVC.

Surveillance of hemodialysis related infections: a prospective multicenter study.

As in many countries, there is neither a surveillance system nor a study to reveal the hemodialysis (HD) related infection rates in Turkey. We aimed to investigate the infection rate among HD outpatients and implement CDC's surveillance system. A multicenter prospective surveillance study is performed to investigate the infection rate among HD patients. CDC National Healthcare Safety Network (NHSN) dialysis event (DE) protocol is adopted for definitions and reporting. During April 2016-April 2018, 9 centers reported data. A total of 199 DEs reported in 10,035 patient-months, and the overall DE rate was 1.98 per 100 patient-months. Risk of blood culture positivity is found to be 17.6 times higher when hemodialysis was through a tunneled catheter than through an arteriovenous fistula. DE rate was significantly lower in patients educated about the care of their vascular access site. Staphylococcus aureus was the most causative microorganism among mortal patients. Outcomes of DEs were hospitalization (73%), loss of vascular access (18.2%), and death (7.7%). This first surveillance study revealed the baseline status of HD related infections in Turkey and showed that CDC National Healthcare Safety Network (NHSN) DE surveillance system can be easily implemented even in a high workload dialysis unit and be adopted as a nationwide DE surveillance program.

Comparison of anakinra and tocilizumab in management of severe COVID-19: a retrospective cohort study.

BACKGROUND: Studies regarding effectiveness of anakinra and tocilizumab treatments in coronavirus disease 2019 (COVID-19) have contradictory results. Furthermore, there is scarce comparative data regarding superiority of any agent. To further elucidate any superiority between these two agents, we retrospectively investigated and compared outcomes in hospitalized COVID-19 patients of our inpatient cohort who received anakinra or tocilizumab. METHODS: This study was designed as a single-center, retrospective, cross-sectional cohort study. Hospitalized patients with confirmed diagnosis of COVID-19 who had Brescia-COVID respiratory severity scale score ≥3 and hyperinflammation (defined as elevation of C reactive protein ≥50 g/L or ferritin ≥700 ng/mL) and received anakinra or tocilizumab in addition to standard care were enrolled in the study. Length of hospital stay after initiation of antiinflammatory treatment, need for mechanical ventilation, need for intensive care unit admission, mortality were set as primary outcomes and compared between tocilizumab and anakinra recipients after propensity score matching. RESULTS: One hundred and six patients were placed in each group after propensity score matching. In the anakinra group, relative risk reduction for intensive care unit admission was 50% when compared to the tocilizumab group and the number needed to treat to avert an intensive care unit admission was 3 (95% CI, 2-5). In terms of mortality, a 52% relative risk reduction was observed with anakinra treatment and the number needed to treat to avert an intensive care unit admission was 8 (95% CI, 4-50). Significantly more patients were observed to receive glucocorticoids in the anakinra group. DISCUSSION: Anakinra administration in severe COVID-19 patients was significantly associated with better survival and greater clinical improvement compared to the tocilizumab administration in our study. Increased rate of glucocorticoid use in the anakinra group might have contributed to better outcomes.

In a Real-Life Setting, Direct-Acting Antivirals to People Who Inject Drugs with Chronic Hepatitis C in Turkey.

BACKGROUND: People who inject drugs (PWID) should be treated in order to eliminate hepatitis C virus in the world. The aim of this study was to compare direct-acting antivirals treatment of hepatitis C virus for PWID and non-PWID in a real-life setting. METHODS: We performed a prospective, non-randomized, observational multicenter cohort study in 37 centers. All patients treated with direct-acting antivirals between April 1, 2017, and February 28, 2019, were included. In total, 2713 patients were included in the study among which 250 were PWID and 2463 were non-PWID. Besides patient characteristics, treatment response, follow-up, and side effects of treatment were also analyzed. RESULTS: Genotype 1a and 3 were more prevalent in PWID-infected patients (20.4% vs 9.9% and 46.8% vs 5.3%). The number of naïve patients was higher in PWID (90.7% vs 60.0%), while the number of patients with cirrhosis was higher in non-PWID (14.1% vs 3.7%). The loss of follow-up was higher in PWID (29.6% vs 13.6%). There was no difference in the sustained virologic response at 12 weeks after treatment (98.3% vs 98.4%), but the end of treatment response was lower in PWID (96.2% vs 99.0%). In addition, the rate of treatment completion was lower in PWID (74% vs 94.4%). CONCLUSION: Direct-acting antivirals were safe and effective in PWID. Primary measures should be taken to prevent the loss of follow-up and poor adherence in PWID patients in order to achieve World Health Organization's objective of eliminating viral hepatitis.

Remdesivir treatment for patients with moderate to severe COVID-19.

BACKGROUND: Remdesivir, which was first developed for the treatment of Ebola disease but failed to meet expectations, has become hope in the fight against the COVID-19 pandemic. This study aimed to evaluate risk factors for mortality and prognosis of adult moderate/severe COVID-19 patients treated with remdesivir, and safety and tolerability of 5 days of remdesivir treatment. METHODS: This multicenter prospective observational study was conducted in 14 centers in Turkey. Pregnancy or breastfeeding, multiorgan failure, or usage of vasopressors for septic shock, ALT > 5 × the upper limit of the normal range, or eGRF <30 mL/min or dialysis and receiving favipiravir were the exclusion criteria of the study. RESULTS: Among 500 patients, 494 patients were included in the study. On admission, 392 (79.3%) patients had moderate and 102 (20.6%) patients had severe COVID-19. The 28-day mortality was 10.1%. The median of the scores of the seven-category ordinal scale assessed on days 0, 3, 5, 7 were 4 and 3 on day 14. When the survival status of the patients was evaluated according to the time between the remdesivir start date and the end date of the symptoms, no statistically significant difference was found between the medians of the groups (p = 0.404). In multivariable analysis, age (OR, 1.05; 95%CI, 1.02-1.08; p = 0.003), SpO2 level on admission (OR, 3.03; 95%CI, 1.35-6.81; p = 0.007), heart rate (OR, 2.48; 95%CI, 1.01-6.07; p = 0.047), follow-up site at the hospital (clinic/ICU) (OR, 26.4; 95%CI, 11.6-60.17; p < 0.001) were independently associated with increased mortality. Grade 3 adverse event (AE) was observed in 4 (0.8%) patients. None of the patients experienced grade 4 or 5 AEs. DISCUSSION: Remdesivir is a safe and well-tolerated drug and older age, low SpO2 level on admission, tachycardia, and ICU admission are independently associated with increased mortality among patients with moderate/severe COVID-19 receiving remdesivir treatment.

Efficacy, Immunogenicity, and Safety of the Two-Dose Schedules of TURKOVAC versus CoronaVac in Healthy Subjects: A Randomized, Observer-Blinded, Non-Inferiority Phase III Trial.

We present the interim results of the efficacy, immunogenicity, and safety of the two-dose schedules of TURKOVAC versus CoronaVac. This was a randomized, observer-blinded, non-inferiority trial (NCT04942405). Volunteers were 18-55 years old and randomized at a 1:1 ratio to receive either TURKOVAC or CoronaVac at Day 0 and Day 28, both of which are 3 µg/0.5 mL of inactivated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) adsorbed to aluminum hydroxide. The primary efficacy outcome was the prevention of polymerase chain reaction (PCR)-confirmed symptomatic coronavirus disease 2019 (COVID-19) at least 14 days after the second dose in the modified per-protocol (mPP) group. Safety analyses were performed in the modified intention-to-treat (mITT) group. Between 22 June 2021 and 7 January 2022, 1290 participants were randomized. The mITT group consisted of 915 participants, and the mPP group consisted of 732 participants. During a median follow-up of 90 (IQR 86-90) days, the relative risk reduction with TURKOVAC compared to CoronaVac was 41.03% (95% CI 12.95-60.06) for preventing PCR-confirmed symptomatic COVID-19. The incidences of adverse events (AEs) overall were 58.8% in TURKOVAC and 49.7% in CoronaVac arms (p = 0.006), with no fatalities or grade four AEs. TURKOVAC was non-inferior to CoronaVac in terms of efficacy and demonstrated a good safety and tolerability profile.