The dilemma of monotherapy or combination therapy in community-acquired pneumonia.

SCOPE: To study the factors associated with mortality in hospitalized patients with community-acquired pneumonia treated with monotherapy or combination therapy. METHODS: PubMed and Scopus were searched. Patients receiving macrolides, ß-lactams and fluoroquinolones, as monotherapy or in combination, were included. Meta-analyses and meta-regressions were performed. RESULTS: Fifty studies were included. Overall, monotherapy was not associated with higher mortality than combination (RR 1.14, 95% CI 0.99-1.32, I2 84%). Monotherapy was associated with higher mortality than combination in North American and retrospective studies. ß-lactam monotherapy was associated with higher mortality than ß-lactam/macrolide combination in the primary (1.32, 1.12-1.56, I2 85%) and most sensitivity analyses. There was no difference in mortality between fluoroquinolone monotherapy and ß-lactam/macrolide combination (0.98, 0.78-1.23, I2 73%). In meta-regressions, the moderators that could partially explain the observed statistical heterogeneity were the frequency of cancer patients (P = .03) and Pneumonia Severity Index score IV (P = .008). CONCLUSION: Due to the considerable heterogeneity and inclusion of unadjusted data, it is difficult to recommend a specific antibiotic regimen over another. Specific antibiotic regimens, study design and the characteristics of the population under study seem to influence the reported outcomes.

Sodium glucose co-transporter 2 inhibitors and their nephroprotective potential
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Chronic kidney disease among patients with diabetes is on the rise. The sodium glucose co-transporters 2 inhibitors are a new class of glucose-lowering agents, which act through a novel mechanism by producing a decline in glucose reabsorption in the kidney, thereby increasing glucosuria and decreasing serum glucose levels. Data suggest that they possess nephroprotective properties. It is noteworthy that the efferent glomerular arteriole is 10 - 100 times more sensitive to the vasoconstrictive properties of angiotensin II than the afferent one and this might account for the consequently higher intra-glomerular capillary pressure, which is believed to be the cornerstone of diabetic nephropathy. These drugs are demonstrated to restore intra-glomerular pressure by increasing angiotensin (1 - 7), which exerts vasodilatory and anti-inflammatory effects. In this review, the nephroprotective potential of this novel class of glucose-lowering drugs will be further discussed.
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EARLY TRAJECTORY OF VENOUS EXCESS ULTRASOUND SCORE IS ASSOCIATED WITH CLINICAL OUTCOMES OF GENERAL ICU PATIENTS.

ABSTRACT: Background: Systemic venous congestion, assessed by the venous excess ultrasound (VExUS) score, has been associated with adverse effects, including acute kidney injury (AKI), in patients with cardiac disease. In general intensive care unit (ICU) patients, the association between VExUS score and outcomes is understudied. We aimed to investigate the association between the trajectory of VExUS score within the first 3 days of ICU admission and the composite clinical outcome of major adverse kidney events within 30 days (MAKE30). Methods: In this prospective observational study, including patients consecutively admitted to the ICU, VExUS score was calculated within 24 h after ICU admission (day 1) and at 48 to 72 h (day 3). D-VExUS was calculated as the difference between the VExUS score on day 3 minus that on day 1. Development of AKI within 7 days and all-cause mortality within 30 days were recorded. Results: A total of 89 patients (62% men; median age, 62 years; median Acute Physiology and Chronic Health Evaluation II score, 24) were included. Sixty (67%) patients developed AKI within 7 days, and 17 (19%) patients died within 30 days after ICU admission. D-VExUS was associated with MAKE30, even after adjustment for confounders (hazard ratio, 2.07; 95% confidence interval, 1.17-3.66; P = 0.01). VExUS scores on days 1 or 3 were not associated with MAKE30. Also, VExUS scores on day 1 or on day 3 and D-VExUS were not associated with development of AKI or mortality. Conclusions: In a general ICU cohort, early trajectory of VExUS score, but not individual VExUS scores at different time points, was associated with the patient-centered MAKE30 outcome. Dynamic changes rather than snapshot measurements may unmask the adverse effects of systemic venous congestion on important clinical outcomes.

Visceral Leishmaniasis in a patient with rheumatoid arthritis undergoing treatment with methotrexate: Case report and review of the literature.

There is growing concern regarding the emergence of visceral leishmaniasis (VL), a disseminated parasitic disease caused by protozoa of the genus Leishmania, as an opportunistic infection in immunocompromised patients. This association has been principally studied in the context of human immunodeficiency virus infection, but VL has also been reported in patients undergoing treatment with immunosuppressive medication for various indications. Here a case of VL in a patient with rheumatoid arthritis undergoing treatment with methotrexate and corticosteroid is presented. Despite the rarity of such incidents, physicians should include VL in the differential diagnosis because this infection, if left untreated, is characterized by significant mortality.

A case of severe carbamazepine overdose treated successfully with combined hemoperfusion and hemodialysis technique.

Carbamazepine intoxication manifests as altered mental status ranging from drowsiness to a coma and/or cardiac abnormalities such as sinus tachycardia, prolongation of the QRS interval, ventricular tachycardia, and hypotension. The patient may be agitated, but central nervous system (CNS) depression and presentation with coma is more common and could be lethal. Serious CNS toxicity often requires hemoperfusion and/or hemodialysis (HD). Herein, we present a case of a comatose patient, who was treated with a combination of hemoperfusion and HD in series. Our approach to treat the patient with a combination of hemoperfusion and HD was based on evidence from the literature supporting that the hemoperfusion and HD in series might provide the best clearance of carbamazepine.

Clostridium difficile infection following systemic antibiotic administration in randomised controlled trials: a systematic review and meta-analysis.

Antibiotics have been the most important risk factor for Clostridium difficile infection (CDI). However, only data from non-randomised studies have been reviewed. We sought to evaluate the risk for development of CDI associated with the major antibiotic classes by analysing data from randomised controlled trials (RCTs). The PubMed, Cochrane and Scopus databases were searched and the references of selected RCTs were also hand-searched. Eligible studies should have compared only one antibiotic versus another administered systemically. Inclusion of studies comparing combinations of antibiotics was allowed only if the second antibiotic was the same or from the same class or if it was administered in a subset of the enrolled patients who were equally distributed in the two arms. Only a minority of the selected RCTs (79/1332; 5.9%) reported CDI episodes. Carbapenems were associated with more CDI episodes than fluoroquinolones [risk ratio (RR) = 2.44, 95% confidence interval (CI) 1.32-4.49] and cephalosporins (RR = 2.24, 95% CI 1.46-3.42), but not penicillins (RR = 2.53, 95% CI 0.87-7.41). Cephalosporins were associated with more CDIs than penicillins (RR = 2.36, 95% CI 1.32-4.23) and fluoroquinolones (RR = 2.84, 95% CI 1.60-5.06). There was no difference in CDI frequency between fluoroquinolones and penicillins (RR = 1.34, 95% CI 0.55-3.25). Finally, clindamycin was associated with more CDI episodes than cephalosporins and penicillins (RR = 3.92, 95% CI 1.15-13.43). In conclusion, data from RCTs showed that clindamycin and carbapenems were associated with more CDIs than other antibiotics.

Inhaled antibiotics beyond aminoglycosides, polymyxins and aztreonam: A systematic review.

We sought to evaluate published evidence regarding clinical or microbiological outcomes related to the use of inhaled antibiotics other than aminoglycosides, polymyxins and aztreonam. A systematic search of PubMed and Scopus databases as well as bibliographies of eligible articles was performed. In total, 34 eligible studies were identified. Among several inhaled ß-lactams, ceftazidime was used with varying success in the prevention and treatment of ventilator-associated pneumonia (VAP) and improved clinical outcomes in chronic Pseudomonas aeruginosa lower respiratory tract infections (LRTIs) in patients with cystic fibrosis (CF) or bronchiectasis. Inhaled vancomycin, as an adjunctive therapy, was effective in treating Gram-positive VAP, whilst inhaled levofloxacin, ciprofloxacin and an inhaled combination of fosfomycin and tobramycin were associated with improved microbiological or clinical outcomes in chronic LRTI in patients with CF or bronchiectasis. In conclusion, published evidence is heterogeneous with regard to antibiotics used, studied indications, patient populations and study designs. Therefore, although the currently available data are encouraging, no safe conclusion regarding the effectiveness and safety of the drugs in question can be reached.

Medical training in Greece: A crisis in progress.

OBJECTIVES: We sought to evaluate the opinions of medical students and graduates regarding the quality of medical education in Greece. METHODS: Two online questionnaires concerning the undergraduate medical education and specialty training respectively were distributed. RESULTS: Regarding the quality of undergraduate medical education, 52.1% of participants replied favorably while clinical training was found satisfactory by 45.1. Dissatisfaction rates with research opportunities and support from tutors reached 88.4 and 83.3%, respectively. The majority (75.3%) supported the introduction of examinations for commencing specialty training. 52.3% of physicians were satisfied with the quality of specialty training. The most common complaint was the absence of a formal educational program. 67.2% of participants were dissatisfied with working conditions during their specialty training, with 70.1% working >60 h per week. Physicians practicing medical specialties were more satisfied with the quality of specialty training than those practicing surgical specialties (odds ratio: 1.43; 95% confidence limits: 1.09-1.87) and were less likely to work for >60 h per week (odds ratio: 0.66; 95% confidence limits: 0.48-0.9). CONCLUSION: Opinions expressed in this survey highlight the need for reforming medical education in Greece.