Viral cultures, cycle threshold values and viral load estimation for assessing SARS-CoV-2 infectiousness in haematopoietic stem cell and solid organ transplant patients: a systematic review.

BACKGROUND: Solid organ and haematopoietic stem cell transplant recipients are more vulnerable to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) than non-transplant recipients due to immunosuppression, and may pose a continued transmission risk, especially within hospital settings. Detailed case reports including symptoms, viral load and infectiousness, defined by the presence of replication-competent viruses in culture, provide an opportunity to examine the relationship between clinical course, burden and contagiousness, and provide guidance on release from isolation. OBJECTIVES: To investigate the relationship between serial SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) cycle threshold (Ct) value or cycle of quantification value, or other measures of viral burden and the likelihood and duration of the presence of infectious virus based on viral culture, including the influence of age, sex, underlying pathologies, degree of immunosuppression, and/or vaccination on this relationship, in transplant recipients. METHODS: LitCovid, medRxiv, Google Scholar and the World Health Organization COVID-19 database were searched from 1st November 2019 to 26th October 2022. Studies reporting relevant data (results from serial RT-PCR testing and viral culture data from the same respiratory samples) for transplant recipients with SARS-CoV-2 infection were included in this systematic review: Methodological quality was assessed using five criteria, and the data were synthesized narratively and graphically. RESULTS: Thirteen case reports and case series reporting on 41 transplant recipients (22 renal, five cardiac, one bone marrow, two liver, one bilateral lung and 10 blood stem cell) were included in this review. A relationship was observed between proxies of viral burden and likelihood of shedding replication-competent SARS-CoV-2. Three individuals shed replication-competent viruses for >100 days after symptom onset. Lack of standardization of testing and reporting platforms precludes establishing a definitive viral burden cut-off. However, the majority of transplant recipients stopped shedding replication-competent viruses when the Ct value was >30 despite differences across platforms. CONCLUSIONS: Viral burden is a reasonable proxy for infectivity when considered within the context of the clinical status of each patient. Standardized study design and reporting are essential to standardize guidance based on an increasing evidence base.

Utility of healthcare-worker-targeted antimicrobial stewardship interventions in hospitals of low- and lower-middle-income countries: a scoping review of systematic reviews.

BACKGROUND: Antimicrobial stewardship (AMS) initiatives in hospitals often include the implementation of clustered intervention components to improve the surveillance and targeting of antibiotics. However, impacts of the individual components of AMS interventions are not well known, especially in low- and lower-middle-income countries (LLMICs). OBJECTIVE: A scoping review was conducted to summarize evidence from systematic reviews (SRs) on the impact of common hospital-implemented healthcare-worker-targeted components of AMS interventions that may be appropriate for LLMICs. METHODS: Major databases were searched systematically for SRs of AMS interventions that were evaluated in hospitals. For SRs to be eligible, they had to report on at least one intervention that could be categorized according to the Effective Practice and Organisation of Care taxonomy. Clinical and process outcomes were considered. Primary studies from LLMICs were consulted for additional information. RESULTS: Eighteen SRs of the evaluation of intervention components met the inclusion criteria. The evidence shows that audit and feedback, and clinical practice guidelines improved several clinical and process outcomes in hospitals. An unintended consequence of interventions was an increase in the use of antibiotics. There was a cumulative total of 547 unique studies, but only 2% (N=12) were conducted in hospitals in LLMICs. Two studies in LLMICs reported that guidelines and educational meetings were effective in hospitals. CONCLUSION: Evidence from high- and upper-middle-income countries suggests that audit and feedback, and clinical practice guidelines have the potential to improve various clinical and process outcomes in hospitals. The lack of evidence in LLMIC settings prevents firm conclusions from being drawn, and highlights the need for further research.

Viral cultures for assessing fomite transmission of SARS-CoV-2: a systematic review and meta-analysis.

BACKGROUND: The role of fomites in the transmission of SARS-CoV-2 is unclear. AIM: To assess whether SARS-CoV-2 can be transmitted through fomites, using evidence from viral culture studies. METHODS: Searches were conducted in the World Health Organization COVID-19 Database, PubMed, LitCovid, medRxiv, and Google Scholar to December 31st, 2021. Studies that investigated fomite transmission and performed viral culture to assess the cytopathic effect (CPE) of positive fomite samples and confirmation of SARS-CoV-2 as the cause of the CPE were included. The risk of bias using a checklist modified from the modified Quality Assessment of Diagnostic Accuracy Studies - 2 (QUADAS-2) criteria was assessed. FINDINGS: Twenty-three studies were included. The overall risk of bias was moderate. Five studies demonstrated replication-competent virus from fomite cultures and three used genome sequencing to match fomite samples with human clinical specimens. The mean cycle threshold (CT) of samples with positive viral culture was significantly lower compared with cultured samples that returned negative results (standardized mean difference: -1.45; 95% confidence interval (CI): -2.00 to -0.90; I2 = 0%; P < 0.00001). The likelihood of isolating replication-competent virus was significantly greater when CT was <30 (relative risk: 3.10; 95% CI: 1.32 to 7.31; I2 = 71%; P = 0.01). Infectious specimens were mostly detected within seven days of symptom onset. One study showed possible transmission of SARS-CoV-2 from fomites to humans. CONCLUSION: The evidence from published studies suggests that replication-competent SARS-CoV-2 is present on fomites. Replication-competent SARS-CoV-2 is significantly more likely when the PCR CT for clinical specimens and fomite samples is <30. Further studies should investigate the duration of infectiousness of SARS-CoV-2 and the frequency of transmission from fomites.

Healthcare-associated infections and the prescribing of antibiotics in hospitalized patients of the Caribbean Community (CARICOM) states: a mixed-methods systematic review.

BACKGROUND: Healthcare-associated infections (HCAIs) and variation in antibiotic prescribing pose a significant public health challenge in hospitals of low-resource countries. AIM: To critically appraise and synthesize the evidence on HCAI and the prescribing of antibiotics in Caribbean Community (CARICOM) states. METHODS: All primary qualitative and quantitative studies that addressed HCAI, and the prescribing of antibiotics in hospitalized patients of CARICOM states were included. Ovid Medline, Embase, Global Health, and regional databases were searched. Risk of bias was assessed using the Mixed Methods Appraisal Tool. Findings were presented in narrative and table formats. FINDINGS: Twenty-one studies met the inclusion criteria for this mixed-methods systematic review (MMSR). Studies were from four different CARICOM states: Trinidad and Tobago, Jamaica, Haiti, and Antigua and Barbuda. Intensive care units (ICUs) had the highest rate of infections (67% over four years). Surgical site infections were discussed by seven studies and ranged from 1.5% to 7.3%. For inpatients with contaminated or infected wounds, rates ranged from 29% to 83%. Empiric and prophylactic therapies were common and inappropriately prescribed. Resources and training for healthcare workers in infection control and antimicrobial stewardship were insufficient. Few qualitative studies existed, so it was not possible to integrate evidence from qualitative and quantitative paradigms. CONCLUSION: Evidence from CARICOM states shows high rates of HCAI and inappropriately prescribed antibiotics, primarily in ICUs. Disease surveillance, infection control, and antimicrobial stewardship programmes require urgent evidence-based improvements.

Commentary on Cochrane review of neuraminidase inhibitors for preventing and treating influenza in healthy adults and children.

In recent years there has been much debate and controversy surrounding the efficacy and safety of neuraminidase inhibitors for influenza, in part because the data underlying certain efficacy claims were not available for independent scrutiny. In 2014, a Cochrane review was published, based exclusively on an almost complete set of clinical study reports and other regulatory documents. Clinical study reports can run to thousands of pages, providing an extensive amount of information on the planning, conduct and results of each trial. After a protracted campaign to obtain the reports, the manufacturers of the medications provided them unconditionally. The review authors subsequently published the underlying documents simultaneously with the Cochrane review, endorsing the concept of open science. In the following commentary, the background to and results of this review are summarized and put into clinical context.

The effect of chlorogenic acid on blood pressure: a systematic review and meta-analysis of randomized clinical trials.

Several dietary supplements are currently marketed for management of hypertension, but the evidence for effectiveness is conflicting. Our objective was to critically appraise and evaluate the evidence for the effectiveness of chlorogenic acids (CGAs) on blood pressure, using data from published randomized clinical trials (RCTs). Electronic searches were conducted in Medline, Embase, Amed, Cinahl and The Cochrane Library. We also hand-searched the bibliographies of all retrieved articles. Two reviewers independently determined the eligibility of studies and extracted the data. The reporting quality of all included studies was assessed by the use of a quality assessment checklist adapted from the Consolidated Standard of Reporting Trials Statement. Disagreements were resolved through discussion. Seven eligible studies were identified, and five including 364 participants were included. There were variations in the reporting quality of the included RCTs. Meta-analysis revealed a statistically significant reduction in systolic blood pressure in favour of CGA (mean difference (MD): -4.31 mm Hg; 95% confidence interval (CI): -5.60 to -3.01; I(2)=65%; P<0.00001). Meta-analysis also showed a significant reduction in diastolic blood pressure favouring CGA (MD: -3.68 mm Hg; 95% CI: -3.91 to -3.45; I(2)=97%; P<0.00001). All studies reported no adverse events. In conclusion, the evidence from published RCTs suggests that CGA intake causes statistically significant reductions in systolic and diastolic blood pressures. The size of the effect is moderate. Few clinical trials have been conducted; they vary in design and methodology and are confined to Asian populations and funded by CGA manufacturers. Large independent trials evaluating the effects of CGA on blood pressure are warranted.

The effect of green tea on blood pressure and lipid profile: a systematic review and meta-analysis of randomized clinical trials.

INTRODUCTION: Many different dietary supplements are currently marketed for the management of hypertension, but the evidence for effectiveness is mixed. The aim of this systematic review was to evaluate the evidence for or against the effectiveness of green tea (Camellia sinensis) on blood pressure and lipid parameters. METHODS AND RESULTS: Electronic searches were conducted in Medline, Embase, Amed, Cinahl and the Cochrane Library to identify relevant human randomized clinical trials (RCTs). Hand searches of bibliographies were also conducted. The reporting quality of included studies was assessed using a checklist adapted from the CONSORT Statement. Two reviewers independently determined eligibility, assessed the reporting quality of the included studies, and extracted the data. As many as 474 citations were identified and 20 RCTs comprising 1536 participants were included. There were variations in the designs of the RCTs. A meta-analysis revealed a significant reduction in systolic blood pressure favouring green tea (MD: -1.94 mmHg; 95% CI: -2.95 to -0.93; I(2) = 8%; p = 0.0002). Similar results were also observed for total cholesterol (MD: -0.13 mmol/l; 95% CI: -0.2 to -0.07; I(2) = 8%; p < 0.0001) and LDL cholesterol (MD: -0.19 mmol/l; 95% CI: -0.3 to -0.09; I(2) = 70%; p = 0.0004). Adverse events included rash, elevated blood pressure, and abdominal discomfort. CONCLUSION: Green tea intake results in significant reductions in systolic blood pressure, total cholesterol, and LDL cholesterol. The effect size on systolic blood pressure is small, but the effects on total and LDL cholesterol appear moderate. Longer-term independent clinical trials evaluating the effects of green tea are warranted.

Chromium supplementation in overweight and obesity: a systematic review and meta-analysis of randomized clinical trials.

The increased prevalence of obesity has made the use of dietary supplements as weight reducing agents highly popular, but their efficacy has not been proven. One such supplement is chromium. The purpose of this review was to evaluate the evidence for or against the efficacy of chromium supplementation in overweight and obese individuals. Electronic searches were conducted in Medline, Embase, Amed and The Cochrane Library. The bibliographies of located articles were also searched. No age, gender or language restrictions were imposed. The reporting quality of identified randomized clinical trials (RCTs) was assessed using a methodological checklist adapted from the Consolidated Standard of Reporting Trials Statement and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Thirty-nine trials were identified and 20 were included. There were variations in reporting quality of included studies. A meta-analysis of 11 studies showed a statistically significant difference in weight loss favouring chromium over placebo (mean difference (MD): -0.50 kg; 95% confidence interval (CI): -0.97, -0.03). There was a high statistical heterogeneity. Adverse events included watery stools, vertigo, headaches and urticaria. The evidence from available RCTs shows that chromium supplementation generates statistically significant reductions in body weight. The magnitude of the effect is small, and the clinical relevance is uncertain. Future trials should last at least 16 weeks and greater uniformity in the measuring and assessment tools for body composition is recommended.