Tocilizumab in the treatment of COVID-19-a meta-analysis.

BACKGROUND: Interleukin-6 inhibitors showed promising results in observational trials of patients with coronavirus disease 2019 (COVID-19). AIM: To evaluate whether interleukin-6 inhibitor tocilizumab (TCZ) reduces mortality among hospitalized COVID-19 patients. DESIGN: A systematic review and meta-analysis. METHODS: Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing TCZ vs. placebo/control, for treatment of adults with COVID-19. Primary outcome was 28-30 days all-cause mortality. Search was conducted up to 1 April 2021. Two independent reviewers screened citations, extracted data and assessed risk of bias. Relative risk (RR) with 95% confidence intervals (CI) were pooled. We performed subgroup analysis for patients with critical illness and sensitivity analyses. RESULTS: Eight RCTs were included, assessing 6481 patients with mostly severe non-critical COVID-19 infection. TCZ was associated with a reduction in all-cause 28-30-day mortality compared to placebo/control (RR = 0.89, 95% CI 0.82-0.96). Among the subgroup of critically ill patients no reduced mortality was demonstrated (RR = 0.94, 95% CI 0.74-1.19). No mortality benefit with TCZ was demonstrated in trials that used steroids for >80% of patients. TCZ was associated with significantly reduced risk for mechanical ventilation (MV); for combined endpoint of death or MV and for intensive care unit (ICU) admission. No significant difference in adverse events was demonstrated. Risk of serious superinfection was significantly lower with TCZ (RR = 0.57, 95% CI 0.35-0.93). CONCLUSION: The treatment with TCZ reduces 28-30 days all-cause mortality, ICU admission, superinfections, MV and the combined endpoint of death or MV. Among critically ill patients, and when steroids were used for most patients, no mortality benefit was demonstrated. Additional research should further define sub-groups that would benefit most and preferred timing of administration of TCZ in severe COVID-19.

Comparison of clinical outcomes of influenza A and B at the 2017-2018 influenza season: a cohort study.

Influenza has significant morbidity and mortality. Some experts consider infection with influenza B as milder than that with influenza A. The objective of this study is to evaluate the outcomes of hospitalized patients with laboratory-confirmed influenza A or B in 2017-2018 influenza season. All hospitalized patients between October 2017 and April 2018 with laboratory-confirmed influenza A and B were included. The primary composite outcomes were pneumonia/myocarditis/encephalitis, mechanical ventilation, ICU admission, and 30-day mortality. Secondary outcomes were 30-/90-day mortality, length of hospital stay, and readmission rates. The study included 201 influenza A and 325 influenza B. For the primary composite outcome, no significant difference was demonstrated between influenza A and B. Rates of mortality were similar at 30 and 90 days. Influenza A had higher pneumonia rates and mechanical ventilation. On multivariate analysis, higher Charlson's score, hypoalbuminemia, and vasopressor use were associated with 30-day mortality, while infection with either influenza A or B was not. Influenza A was associated with higher pneumonia and mechanical ventilation rates. However, influenza B resulted with similar 30-day mortality rate as influenza A.

High blood glucose variability is associated with bacteremia and mortality in patients hospitalized with acute infection.

BACKGROUND: Limited data are available regarding the association between glucose levels variability (GV) and outcomes of patients hospitalized with acute infectious diseases. AIM: To determine the association between GV and bacteremia, length of stay (LOS) and mortality. METHODS: A retrospective study of patients hospitalized in departments of medicine with respiratory tract, urinary tract and skin and soft tissue infections during 2011-17. GV was assessed by the coefficient of variation (CV) of glucose levels during hospitalization and was divided into tertiles (CV ≤ 16%, 17-29%, >29%). LOS, bacteremia rates and all-cause mortality (30 days, 90 days and after 5 years) were evaluated for the patients with and without DM according the three GV categories. RESULTS: The study consisted of 1485 patients, 838 (56%) were diabetic. There was no significant association between GV and LOS. Bacteremia rates were higher in the upper GV tertile compared with the lower one (6% vs. 2%, P = 0.007). Mid and upper tertiles compared with the lower one were significantly associated with increased 30-day mortality (13% vs. 5%, P = 0.005; and 40% vs. 5%, P = 0.002, respectively). A decreased 5 years survival was observed for both diabetic and non-diabetic patients in the mid and upper GV tertiles [adjusted HRs 0.8 (95% CI, 0.6-1.04) and 0.6 (95% CI, 0.5-0.9) in diabetic patients and 0.7 (95% CI, 0.5-0.9) and 0.5 (95% CI, 0.3-0.7) in the non-diabetic ones]. CONCLUSION: In diabetic and non-diabetic patients, hospitalized in non-ICU setting with acute infectious diseases, increased GV is associated with increased risk of bacteremia, short and long-term mortality.

Anticoagulation therapy in patients with non-valvular atrial fibrillation hospitalized in the Department of Medicine in the NOACs era.

BACKGROUND: The treatment of atrial fibrillation (AF) includes anticoagulation (AC) therapy to prevent systemic emboli. Until recently, warfarin was the main AC agent, while in recent years, the new oral anticoagulants (NOACs) are increasingly being used. AIM: The aim of our study was to characterize the AC treatment policy of AF patients at the department of medicine in the NOACs era. METHODS AND DESIGN: An observational study of consecutive hospitalized patients with non-valvular AF for a period of 3 months in Beilinson hospital (January to March 2017). Demographic characteristics, clinical data and AC therapeutic approach were compared to those from the pre-NOACs era, based on a previous study. RESULTS: A total of 335 patients were hospitalized with either new (21%) or prior (79%) non-valvular AF. An increase in AC therapy among patients with prior and new AF was observed compared to the pre-NOACs era (76% vs. 59%; P < 0.001 and 68% vs. 49%; P < 0.001, respectively). Totally, 76% of all patients were discharged with AC therapy compared to 55% in the pre-NOACs era. As in the pre-NOACs era, prior AC therapy was the main predictor for the prescription of AC therapy during hospitalization and discharge (OR = 13, 95% CI; 7-25, P = 0.0001). CONCLUSION: There is a significant increase in the AC therapy prescription, mainly NOACs, in hospitalized non-valvular AF patients. This increase could be explained by the difficulties in warfarin treatment and the benefits of NOACs. Nevertheless, a large observational study is required to prove these findings.

How obesity impacts outcomes of infectious diseases.

Obesity is associated with co-morbidities and increased risk of acquiring infections with worse outcomes. Paradoxically, a few studies indicate that obesity may have a decreased mortality in hospitalized patients with pneumonia. The objective of this study was to determine the impact of body mass index (BMI) on short-term all-cause mortality and clinical outcomes among hospitalized adults with pneumonia, urinary tract infections, skin and soft tissue infections, and bacteremia. The study cohort included 1437 consecutive patients who were admitted with infectious disease including pneumonia (717), urinary tract infection (506), bacteremia (69), and skin and soft tissue infections (145), and hospitalized in internal medical departments, during 2013-2015. BMI was categorized as underweight (≤20 kg/m2), normal (20-25 kg/m2), overweight (25.1-29.9 kg/m2), and obese (≥30 kg/m2). Clinical outcomes of 30- and 90-day all-cause mortality rates, length of hospital stay, and transfer to the intensive care unit (ICU) were compared among groups, sorted according to BMI and different infectious diseases. Obesity was associated with decreased 30-day mortality in patients with pneumonia [odds ratio (OR) = 0.26, 95 % confidence interval (CI) 0.06-1.01; p = 0.052]. On the contrary, increased 30-day mortality was observed in the underweight patients (OR = 2.89, 95 % CI 1.1-7.6; p = 0.03). Similar impacts were not found for urinary tract infections, skin and soft tissue infections, or bloodstream infections. Furthermore, obesity had no effect on 90-day mortality, length of hospital stay, or transfer to the ICU in all kinds of infectious diseases. Obesity is associated with reduced short-term mortality among hospitalized patients with pneumonia. Whether gut microbiota in obese individuals plays a role in this protective effect remains to be investigated by further studies.

The effect of statins on the outcome of Clostridium difficile infection in hospitalized patients.

UNLABELLED: Several studies have shown an association between exposure to statins and favorable clinical outcomes for various types of infections. We aimed to assess the impact of statin use on mortality, disease severity and complications among hospitalized patients with Clostridium difficile infection (CDI). Data were analyzed from a retrospectively collected database of 499 patients diagnosed with CDI during 2009-2014. We compared infection outcomes between 178 statin (36 %) users and 321 (64 %) non-users. On multivariate analysis, we found that statin use did not have a significant impact on 30-day mortality (OR = 1.54; 95 % CI, 0.85-2.79; p = 0.15) or any significant effect on CDI severity and complication. Concomitant statin use has no significant impact on short-term mortality or effect on CDI severity and complications among hospitalized patients with CDI. However, patients in the statin group were older and had higher Charlson score compared with the non-statin group. Whether these factors affected a possible impact of statins on the disease course remains to be investigated. KEY MESSAGES: • Clostridium difficile is the most common cause of infectious nosocomial diarrhea among hospitalized adult patients in the developed countries. • There is an increasing morbidity and mortality of CDI patients due to the emergence of new strains of high virulence. • Recent studies demonstrated that prior statin use has protective and ameliorating effects on morbidity and mortality among CDI patients. • Our study showed that concomitant statin use has no significant impact on short-term mortality, CDI severity and its complications.

Adult-onset diabetes among Arabs and Jews in Israel: a population-based study.

AIMS: To study the age at presentation and factors associated with adult-onset diabetes (≥ 20 years) among Arabs and Jews in Israel. METHODS: Participants (n = 1100) were randomly selected from the urban population of the Hadera District in Israel. The study sample was stratified into equal groups according to sex, ethnicity (Arabs and Jews) and age. Information on age at diabetes presentation, family history of diabetes, history of gestational diabetes, socio-demographic and lifestyle characteristics was obtained through personal interviews. Self reports of diabetes were compared with medical records and were found reliable (κ = 0.87). The risk for diabetes was calculated using Kaplan-Meier survival analysis. Factors associated with diabetes in both ethnic groups were studied using Cox proportional hazard model. RESULTS: The prevalence of adult-onset diabetes was 21% among Arabs and 12% among Jews. Arab participants were younger than Jews at diabetes presentation. By the age of 57 years, 25% of Arabs had diagnosed diabetes; the corresponding age among Jews was 68 years, a difference of 11 years (P < 0.001). The greater risk for diabetes among Arabs was independent of lifestyle factors, family history of diabetes and, among women, history of gestational diabetes; adjusted hazard ratio 1.70; 95% confidence interval 1.19-2.43. CONCLUSIONS: Arabs in Israel are at greater risk for adult-onset diabetes than Jews and are younger at diabetes presentation. Culturally sensitive interventions aimed at maintaining normal body weight and active lifestyle should be targeted at this population. Possible genetic factors and gene-environmental interactions underlying the high risk for diabetes among Arabs should be investigated.

Tuberculosis outbreak among students in a boarding school.

Tuberculosis (TB) outbreaks present a public health challenge. Six cases of active TB emerged in a boarding school in Israel during 1 yr. An epidemiological outbreak investigation was performed, followed by implementation of control measures. The investigation included interviews, tuberculin skin test (TST) and chest radiographs of the students. Close contact (n = 155) was defined as being in the same class or dormitory with a patient. Remote contact (n = 246) was defined as being in the school. An epidemiological association was detected among five of the cases and a distinct pattern was found in molecular analysis. TST was performed in 398 (99.2%) students. Repeated (two-step) TST was applied to the close contacts. The degree of contact, country of origin and previous bacille Calmette-Guérin vaccination were significantly associated with TST reactions. Preventive directly observed therapy was completed by 157 (91.3%) students. During 5 yrs follow-up, no additional cases emerged. While investigating a tuberculosis outbreak, the definition of degree of contact is a significant predictor for detecting positive tuberculin test. Immigration from an endemic country, as well as previous bacille Calmette-Guérin vaccination have a major effect on tuberculin skin-test results. The directly observed therapy approach was found to be successful in preventing further morbidity.