Significant association between vitamin D deficiency and sepsis: a systematic review and meta-analysis

Background: A number of observational studies have found an association between low vitamin D levels and risk of sepsis. We conducted a systematic review and meta-analysis to determine the overall estimate of risk. Methods: This was a systematic review and meta-analysis conducted by online searches (CENTRAL, PubMed/MEDLINE, and EMBASE) was registered in PROSPERO (CRD42014014767). Primary outcome was incidence, prevalence, relative risk or odds ratio of having sepsis or bloodstream infection between patients with vitamin D deficiency and controls. Results: The initial search yielded 647 articles. Twenty-one articles underwent full-length review and data were extracted from 10 observational studies. Pooled odds ratio of sepsis in participants with vitamin D deficiency was 1.78 (95 % confidence interval [CI] = 1.55 to 2.03, p < 0.01) compared with controls in studies that reported participant numbers and was 1.45 (95 % CI = 1.26 to 1.66, p < 0.01) in studies that reported an adjusted odds ratio of vitamin D deficiency for developing sepsis. Statistical between-study heterogeneity was low (I² = 0 % and 5 %, respectively). Standardized mean difference of 25-hydroxyvitamin D levels in patients with sepsis and controls was −0.24 (95 % CI = −0.49 to 0.00, p = 0.05) and lower in the sepsis group compared with non-sepsis or control participants. The statistical between-study heterogeneity (I²) was 0 %. Conclusion: Vitamin D deficiency were associated with an increased susceptibility of sepsis

Respiratory Syncytial Virus, Human Metapneumovirus, and Parainfluenza Virus Infections in Lung Transplant Recipients:A Systematic Review of Outcomes and Treatment Strategies

BACKGROUND: Respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV) are increasingly associated with chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTR). This systematic review primarily aimed to assess outcomes of RSV/PIV/hMPV infections in LTR and secondarily to assess evidence regarding the efficacy of ribavirin. METHODS: Relevant databases were queried and study outcomes extracted using a standardized method and summarized. RESULTS: Nineteen retrospective and 12 prospective studies were included (total 1060 cases). Pooled 30-day mortality was low (0-3%), but CLAD progression 180-360 days postinfection was substantial (pooled incidences 19-24%) and probably associated with severe infection. Ribavirin trended toward effectiveness for CLAD prevention in exploratory meta-analysis (odds ratio [OR] 0.61, [0.27-1.18]), although results were highly variable between studies. CONCLUSIONS: RSV/PIV/hMPV infection was followed by a high CLAD incidence. Treatment options, including ribavirin, are limited. There is an urgent need for high-quality studies to provide better treatment options for these infections

Diagnosis and Antifungal Prophylaxis for COVID-19 Associated Pulmonary Aspergillosis

The COVID-19 pandemic has redemonstrated the importance of the fungal-after-viral phenomenon, and the question of whether prophylaxis should be used to prevent COVID-19-associated pulmonary aspergillosis (CAPA). A distinct pathophysiology from invasive pulmonary aspergillosis (IPA), CAPA has an incidence that ranges from 5% to 30%, with significant mortality. The aim of this work was to describe the current diagnostic landscape of CAPA and review the existing literature on antifungal prophylaxis. A variety of definitions for CAPA have been described in the literature and the performance of the diagnostic tests for CAPA is limited, making diagnosis a challenge. There are only six studies that have investigated antifungal prophylaxis for CAPA. The two studied drugs have been posaconazole, either a liquid formulation via an oral gastric tube or an intravenous formulation, and inhaled amphotericin. While some studies have revealed promising results, they are limited by small sample sizes and bias inherent to retrospective studies. Additionally, as the COVID-19 pandemic changes and we see fewer intubated and critically ill patients, it will be more important to recognize these fungal-after-viral complications among non-critically ill, immunocompromised patients. Randomized controlled trials are needed to better understand the role of antifungal prophylaxis

Association between NSAIDs and Clostridium difficile-Associated Diarrhea: A Systematic Review and Meta-Analysis

Objective. Clostridium difficile infection is a leading cause of nosocomial diarrhea in developed countries. Studies evaluating the associations of increased risk of community-acquired CDAD and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) have yielded inconclusive results. We conducted a systematic review and meta-analysis to compare the odds of NSAID exposure in patients with CDAD versus patients without CDAD in both community-based and healthcare-associated settings. Methods. Relevant observational studies indexed in PubMed/MEDLINE and EMBASE up to February 2015 were analyzed and data were extracted from nine studies. Of these, eight studies were included in the meta-analysis. Results. A search of the databases resulted in 987 articles. The nine studies from which data were extracted involved over 39,000 subjects. The pooled odds ratio for history of NSAID use in participants with CDAD compared with controls was 1.41 (95% CI 1.06–1.87; p < 0.01), indicating a significant increased odds of CDAD among patients exposed to NSAIDs. Conclusions. To the best of our knowledge, this is the first study of its nature to demonstrate the association between the use of NSAIDs and increased risk of CDAD. Further studies to evaluate if any specific types of NSAIDs can increase the risk of CDAD are warranted

Does Post-Transplant Cytomegalovirus Increase the Risk of Invasive Aspergillosis in Solid Organ Transplant Recipients? A Systematic Review and Meta-Analysis

Background: Cytomegalovirus (CMV) and invasive aspergillosis (IA) cause high morbidity and mortality in solid organ transplant (SOT) recipients. There are conflicting data with respect to the impact of CMV on IA development in SOT recipients. Methods: A literature search was conducted from existence through to 2 April 2021 using MEDLINE, Embase, and ISI Web of Science databases. This review contained observational studies including cross-sectional, prospective cohort, retrospective cohort, and case-control studies that reported SOT recipients with post-transplant CMV (exposure) and without post-transplant CMV (non-exposure) who developed or did not develop subsequent IA. A random-effects model was used to calculate the pooled effect estimate. Results: A total of 16 studies were included for systematic review and meta-analysis. There were 5437 SOT patients included in the study, with 449 SOT recipients developing post-transplant IA. Post-transplant CMV significantly increased the risk of subsequent IA with pORs of 3.31 (2.34, 4.69), I2 = 30%. Subgroup analyses showed that CMV increased the risk of IA development regardless of the study period (before and after 2003), types of organ transplantation (intra-thoracic and intra-abdominal transplantation), and timing after transplant (early vs. late IA development). Further analyses by CMV definitions showed CMV disease/syndrome increased the risk of IA development, but asymptomatic CMV viremia/infection did not increase the risk of IA. Conclusions: Post-transplant CMV, particularly CMV disease/syndrome, significantly increased the risks of IA, which highlights the importance of CMV prevention strategies in SOT recipients. Further studies are needed to understand the impact of programmatic fungal surveillance or antifungal prophylaxis to prevent this fungal-after-viral phenomenon