Estimate false-negative RT-PCR rates for SARS-CoV-2. A systematic review and meta-analysis.

BACKGROUND: Molecular-based tests used to identify symptomatic or asymptomatic patients infected by SARS-CoV-2 are characterized by high specificity but scarce sensitivity, generating false-negative results. We aimed to estimate, through a systematic review of the literature, the rate of RT-PCR false negatives at initial testing for COVID-19. METHODS: We systematically searched Pubmed, Embase and CENTRAL as well as a list of reference literature. We included observational studies that collected samples from respiratory tract to detect SARS-CoV-2 RNA using RT-PCR, reporting the number of false-negative subjects and the number of final patients with a COVID-19 diagnosis. Reported rates of false negatives were pooled in a meta-analysis as appropriate. We assessed the risk of bias of included studies and graded the quality of evidence according to the GRADE method. All information in this article is current up to February 2021. RESULTS: We included 32 studies, enrolling more than 18,000 patients infected by SARS-CoV-2. The overall false-negative rate was 0.12 (95%CI from 0.10 to 0.14) with very low certainty of evidence. The impact of misdiagnoses was estimated according to disease prevalence; a range between 2 and 58/1,000 subjects could be misdiagnosed with a disease prevalence of 10%, increasing to 290/1,000 misdiagnosed subjects with a disease prevalence of 50%. CONCLUSIONS: This systematic review showed that up to 58% of COVID-19 patients may have initial false-negative RT-PCR results, suggesting the need to implement a correct diagnostic strategy to correctly identify suspected cases, thereby reducing false-negative results and decreasing the disease burden among the population.

Accuracy of the serological detection of IgG and IgM to SARS-Cov-2: a prospective, cross-sectional study.

In response to the rapidly evolving of SARS-CoV-2 infection, numerous serological tests have been developed but their sensitivity and specificity are unclear. We collected serum samples of patients and health-care professionals to assess the accuracy of chemiluminescent (CLIA) and two lateral flow immunochromatographic assays (LFIA) to determine IgG and IgM antibodies to SARS-CoV-2 virus. We calculated the φ correlation for qualitative results and test accuracy, adopting the following case definition: either real-time-PCR positivity or serological positivity with at least two different tests. We analyzed 259 samples, obtaining strong correlation between CLIA and both LFIA for IgG (φ=0.9), and moderate correlation for IgM (φ=0.6). For patients, the sensitivity was suboptimal for all methods (CLIA 81%, LFIA A 85%, LFIA B 78%), while it was poor in asymptomatic health-care workers (CLIA 50%, LFIA A 50%, LFIA B 33%). Overall, CLIA is more sensitive and specific for the determination of both IgG and IgM, whilst both LFIA methods reported good sensitivity and specificity for IgG, but scarce sensitivity for the IgM determination. The determination of SARS-CoV-2-specific IgG is useful to detect infection 6 days from symptom onset.

Topical antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving mechanical ventilation.

BACKGROUND: Patients treated with mechanical ventilation in intensive care units (ICUs) have a high risk of developing respiratory tract infections (RTIs). Ventilator-associated pneumonia (VAP) has been estimated to affect 5% to 40% of patients treated with mechanical ventilation for at least 48 hours. The attributable mortality rate of VAP has been estimated at about 9%. Selective digestive decontamination (SDD), which consists of the topical application of non-absorbable antimicrobial agents to the oropharynx and gastroenteric tract during the whole period of mechanical ventilation, is often used to reduce the risk of VAP. A related treatment is selective oropharyngeal decontamination (SOD), in which topical antibiotics are applied to the oropharynx only. This is an update of a review first published in 1997 and updated in 2002, 2004, and 2009. OBJECTIVES: To assess the effect of topical antibiotic regimens (SDD and SOD), given alone or in combination with systemic antibiotics, to prevent mortality and respiratory infections in patients receiving mechanical ventilation for at least 48 hours in ICUs. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections (ARI) Group's Specialised Register, PubMed, and Embase on 5 February 2020. We also searched the WHO ICTRP and ClinicalTrials.gov for ongoing and unpublished studies on 5 February 2020. All searches included non-English language literature. We handsearched references of topic-related systematic reviews and the included studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and cluster-RCTs assessing the efficacy and safety of topical prophylactic antibiotic regimens in adults receiving intensive care and mechanical ventilation. The included studies compared topical plus systemic antibiotics versus placebo or no treatment; topical antibiotics versus no treatment; and topical plus systemic antibiotics versus systemic antibiotics. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included a total of 41 trials involving 11,004 participants (five new studies were added in this update). The minimum duration of mechanical ventilation ranged from 2 (19 studies) to 6 days (one study). Thirteen studies reported the mean length of ICU stay, ranging from 11 to 33 days. The percentage of immunocompromised patients ranged from 0% (10 studies) to 22% (1 study). The reporting quality of the majority of included studies was very poor, so we judged more than 40% of the studies as at unclear risk of selection bias. We judged all studies to be at low risk of performance bias, though 47.6% were open-label, because hospitals usually have standardised infection control programmes, and possible subjective decisions on who should be tested for the presence or absence of RTIs are unlikely in an ICU setting. Regarding detection bias, we judged all included studies as at low risk for the outcome mortality. For the outcome RTIs, we judged all double-blind studies as at low risk of detection bias. We judged five open-label studies as at high risk of detection bias, as the diagnosis of RTI was not based on microbiological exams; we judged the remaining open-label studies as at low risk of detection bias, as a standardised set of diagnostic criteria, including results of microbiological exams, were used. Topical plus systemic antibiotic prophylaxis reduces overall mortality compared with placebo or no treatment (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.73 to 0.96; 18 studies; 5290 participants; high-certainty evidence). Based on an illustrative risk of 303 deaths in 1000 people this equates to 48 (95% CI 15 to 79) fewer deaths with topical plus systemic antibiotic prophylaxis. Topical plus systemic antibiotic prophylaxis probably reduces RTIs (RR 0.43, 95% CI 0.35 to 0.53; 17 studies; 2951 participants; moderate-certainty evidence). Based on an illustrative risk of 417 RTIs in 1000 people this equates to 238 (95% CI 196 to 271) fewer RTIs with topical plus systemic antibiotic prophylaxis. Topical antibiotic prophylaxis probably reduces overall mortality compared with no topical antibiotic prophylaxis (RR 0.96, 95% CI 0.87 to 1.05; 22 studies, 4213 participants; moderate-certainty evidence). Based on an illustrative risk of 290 deaths in 1000 people this equates to 19 (95% CI 37 fewer to 15 more) fewer deaths with topical antibiotic prophylaxis. Topical antibiotic prophylaxis may reduce RTIs (RR 0.57, 95% CI 0.44 to 0.74; 19 studies, 2698 participants; low-certainty evidence). Based on an illustrative risk of 318 RTIs in 1000 people this equates to 137 (95% CI 83 to 178) fewer RTIs with topical antibiotic prophylaxis. Sixteen studies reported adverse events and dropouts due to adverse events, which were poorly reported with sparse data. The certainty of the evidence ranged from low to very low. AUTHORS' CONCLUSIONS: Treatments based on topical prophylaxis probably reduce respiratory infections, but not mortality, in adult patients receiving mechanical ventilation for at least 48 hours, whereas a combination of topical and systemic prophylactic antibiotics reduces both overall mortality and RTIs. However, we cannot rule out that the systemic component of the combined treatment provides a relevant contribution in the observed reduction of mortality. No conclusion can be drawn about adverse events as they were poorly reported with sparse data.

The NGS technology for the identification of genes associated with the ALS. A systematic review.

BACKGROUND: More than 30 causative genes have been identified in familial and sporadic amyotrophic lateral sclerosis (ALS). The next-generation sequencing (NGS) is a powerful and groundbreaking tool to identify disease-associated variants. Despite documented advantages of NGS, its diagnostic reliability needs to be addressed in order to use this technology for specific routine diagnosis. MATERIAL AND METHODS: Literature database was explored to identify studies comparing NGS and Sanger sequencing for the detection of variants causing ALS. We collected data about patients' characteristics, disease type and duration, NGS and Sanger properties. RESULTS: More than 200 bibliographic references were identified, of which only 14 studies matching our inclusion criteria. Only 2 out of 14 studies compared results of NGS analysis with the Sanger sequencing. Twelve studies screened causative genes associated to ALS using NGS technologies and confirmed the identified variants with Sanger sequencing. Overall, data about more 2,000 patients were analysed. The number of genes that were investigated in each study ranged from 1 to 32, the most frequent being FUS, OPTN, SETX and VCP. NGS identified already known mutations in 21 genes, and new or rare variants in 27 genes. CONCLUSIONS: NGS seems to be a promising tool for the diagnosis of ALS in routine clinical practice. Its advantages are represented by an increased speed and a lowest sequencing cost, but patients' counselling could be problematic due to the discovery of frequent variants of unknown significance.

E-learning for health professionals.

BACKGROUND: The use of e-learning, defined as any educational intervention mediated electronically via the Internet, has steadily increased among health professionals worldwide. Several studies have attempted to measure the effects of e-learning in medical practice, which has often been associated with large positive effects when compared to no intervention and with small positive effects when compared with traditional learning (without access to e-learning). However, results are not conclusive. OBJECTIVES: To assess the effects of e-learning programmes versus traditional learning in licensed health professionals for improving patient outcomes or health professionals' behaviours, skills and knowledge. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, five other databases and three trial registers up to July 2016, without any restrictions based on language or status of publication. We examined the reference lists of the included studies and other relevant reviews. If necessary, we contacted the study authors to collect additional information on studies. SELECTION CRITERIA: Randomised trials assessing the effectiveness of e-learning versus traditional learning for health professionals. We excluded non-randomised trials and trials involving undergraduate health professionals. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, extracted data and assessed risk of bias. We graded the certainty of evidence for each outcome using the GRADE approach and standardised the outcome effects using relative risks (risk ratio (RR) or odds ratio (OR)) or standardised mean difference (SMD) when possible. MAIN RESULTS: We included 16 randomised trials involving 5679 licensed health professionals (4759 mixed health professionals, 587 nurses, 300 doctors and 33 childcare health consultants).When compared with traditional learning at 12-month follow-up, low-certainty evidence suggests that e-learning may make little or no difference for the following patient outcomes: the proportion of patients with low-density lipoprotein (LDL) cholesterol of less than 100 mg/dL (adjusted difference 4.0%, 95% confidence interval (CI) -0.3 to 7.9, N = 6399 patients, 1 study) and the proportion with glycated haemoglobin level of less than 8% (adjusted difference 4.6%, 95% CI -1.5 to 9.8, 3114 patients, 1 study). At 3- to 12-month follow-up, low-certainty evidence indicates that e-learning may make little or no difference on the following behaviours in health professionals: screening for dyslipidaemia (OR 0.90, 95% CI 0.77 to 1.06, 6027 patients, 2 studies) and treatment for dyslipidaemia (OR 1.15, 95% CI 0.89 to 1.48, 5491 patients, 2 studies). It is uncertain whether e-learning improves or reduces health professionals' skills (2912 health professionals; 6 studies; very low-certainty evidence), and it may make little or no difference in health professionals' knowledge (3236 participants; 11 studies; low-certainty evidence).Due to the paucity of studies and data, we were unable to explore differences in effects across different subgroups. Owing to poor reporting, we were unable to collect sufficient information to complete a meaningful 'Risk of bias' assessment for most of the quality criteria. We evaluated the risk of bias as unclear for most studies, but we classified the largest trial as being at low risk of bias. Missing data represented a potential source of bias in several studies. AUTHORS' CONCLUSIONS: When compared to traditional learning, e-learning may make little or no difference in patient outcomes or health professionals' behaviours, skills or knowledge. Even if e-learning could be more successful than traditional learning in particular medical education settings, general claims of it as inherently more effective than traditional learning may be misleading.

The New Test for Monitoring Infliximab Therapy: From Laboratory to Clinical Practice.

BACKGROUND: Biological agents for anti-tumor necrosis factor-α therapy have revolutionized treatments for autoimmune diseases; however, approximately 20% of rheumatology and 40% of gastroenterology patients do not respond to the therapy, or they show reduced drug efficacy because of anti-drug antibody (ADA) formation. OBJECTIVES: To evaluate laboratory tools for individual monitoring of infliximab therapy and the relationship between ADA and infliximab serum levels, ADA and clinical response, and ADA and autoantibodies. METHODS: Our study comprised patients treated with infliximab and affected by selected rheumatology and gastroenterology diseases. Sera were analyzed for infliximab, total-anti-drug antibodies (Total-ADA), and free-anti-drug antibodies (Free-ADA) serum levels and for the detection of specific autoantibodies. RESULTS: We analyzed 73 patients. Total-ADA were detected in 26 rheumatology and 21 gastroenterology patients. Serum infliximab levels were significantly lower in Total-ADA positive patients (P = 0.01 for rheumatology group, P = 0.02 for gastroenterology group). A lack of response was observed in 7 rheumatology and 15 gastroenterology samples. Total-ADA serum levels were statistically significantly higher in patients with treatment failure in both groups (P = 0.01 and P = 0.001, respectively). There was no significant association between the presence of Total-ADA and other autoantibodies. Free-ADA were detected in only 27 rheumatology patients. Results showed a significant correlation with clinical outcome (P = 0.006). CONCLUSIONS: The correlation with clinical response suggests that the presence of ADA could interfere with efficacy of therapy. The tests for monitoring therapy may be an important tool to assist clinicians in early detection and prevention of therapy failure.

Neonatal inflammatory pain and systemic inflammatory responses as possible environmental factors in the development of autism spectrum disorder of juvenile rats.

BACKGROUND: Autism spectrum disorder (ASD) affects many children and juveniles. The pathogenesis of ASD is not well understood. Environmental factors may play important roles in the development of ASD. We examined a possible relationship of inflammatory pain in neonates and the development of ASD in juveniles. METHODS: Acute inflammation pain was induced by 5 % formalin (5 µl/day) subcutaneous injection into two hindpaws of postnatal day 3 to 5 (P3-P5) rat pups. Western blot, immunohistochemical, and behavioral examinations were performed at different time points after the insult. RESULTS: Formalin injection caused acute and chronic inflammatory responses including transient local edema, increased levels of inflammatory cytokines, TNF-α, and IL-1ß in the blood as well as in the brain, and increased microglia in the brain. One day after the pain insult, there was significant cell death in the cortex and hippocampus. Two weeks later, although the hindpaw local reaction subsided, impaired axonal growth and demyelization were seen in the brain of P21 juvenile rats. The number of bromodeoxyuridine (BrdU) and doublecortin (DCX) double-positive cells in the hippocampal dentate gyrus of P21 rats was significantly lower than that in controls, indicating reduced neurogenesis. In the P21 rat's brain of the formalin group, the expression of autism-related gene neurexin 1 (NRXN1), fragile X mental retardation 1 (FMR1), and oxytocin was significantly downregulated, consistent with the gene alteration in ASD. Juvenile rats in the formalin group showed hyperalgesia, repetitive behaviors, abnormal locomotion, sleep disorder, and distinct deficits in social memory and social activities. These alterations in neuroinflammatory reactions, gene expression, and behaviors were more evident in male than in female rats. Importantly, an anti-inflammation treatment using indomethacin (10 mg/kg, i.p.) at the time of formalin injections suppressed inflammatory responses and neuronal cell death and prevented alterations in ASD-related genes and the development of abnormal behaviors. CONCLUSIONS: These novel observations indicate that severe inflammatory pain in neonates and persistent inflammatory reactions may predispose premature infants to development delays and psychiatric disorders including ASD. The prevention of pain stimuli and prompt treatments of inflammation during development appear vitally important in disrupting possible evolution of ASD syndromes.

Optimisation of triple therapy for patients with chronic hepatitis C: a systematic review.

BACKGROUND: Triple therapy with Pegylated-Interferon α (PEG-IFNα)/Ribavirin (RBV) and Boceprevir (Boc) or Telaprevir (Tel) significantly improved sustained virological response (SVR) rates for patients with genotype 1 HCV infection compared to PEG-IFNα/RBV alone (dual therapy). However, less is known about factors associated with rates of SVR and of adverse events (AEs). MATERIAL AND METHODS: The aim of this systematic review was to evaluate the evidence regarding the factors affecting response and rate of AEs associated with triple therapy. We performed systematic electronic searches in Medline, Embase, Scopus and Central as well as a list of reference literature. We included randomised controlled trials examining triple therapy compared with dual therapy and reporting data according to patients features and about AEs. Odds ratios (OR) were pooled using either fixed or random effect model, as appropriate. RESULTS: We included data from 14 studies. Treatment with triple therapy increased SVR rate compared to dual therapy especially in patients previously treated with PEG-IFNα/RBV and with increased pretreatment alanine aminotransferase (ALT) levels. Higher rate of serious AEs and treatment discontinuation due to AEs was also observed particularly in treatment-experienced patients. CONCLUSIONS: The present study shows how improved results of triple therapy are mainly observed in some patients' subsets and are accompanied by increased risk of AEs compared to dual therapy. These results might be useful for optimising treatment of chronic hepatitis C when IFN-free regimens are unavailable.

Clinical utility of the (-2)proPSA and evaluation of the evidence: a systematic review.

BACKGROUND: Diagnostic studies usually provide important information about the analytical and diagnostic performances. We investigated the clinical utility of (-2)proPSA in identifying patients with prostate cancer (PCa). METHODS: We performed electronic searches in five databases as well as a list of reference literature. Studies were included if they evaluated the diagnostic accuracy of (-2)proPSA in men with PSA value ranged from 2.0 to 10 µg/L. We also analyzed data about total PSA (tPSA), %(-2)proPSa, freePSA (fPSA), its percentage (%fPSA) and the prostate health index (phi). The selection of the studies, the screening of the full texts and the data extraction, as well as the assessment of risk of bias using the QUADAS-2 tool were conducted independently by two authors. Grading the quality of the evidence was carried out according to the GRADE method. The random effects model was used for the meta-analyses. RESULTS: We included 17 studies, including 6912 patients. The pooled sensitivity of (-2)proPSA was 90% and the summary specificity was 13%. The tPSA sensitivity and specificity were 89% and 25%, respectively. Considering (-2)proPSA, 225 men out of 1000 have been identified having PCa true positives (TP). However, 652 persons have been incorrectly identified and undergo biopsy. The majority of studies were judged to carry a moderate risk of bias. Therefore, the overall quality of evidences was deemed to be low. CONCLUSIONS: The (-2)proPSA could be useful to identify men at risk of PCa, but its accuracy still remains uncertain and the level of evidence does not support an improved clinical utility.

Most appropriate animal models to study the efficacy of statins: a systematic review.

BACKGROUND: In animal models and clinical trials, statins are reported as effective in reducing cholesterol levels and lowering the risk of cardiovascular diseases. We have aggregated the findings in animal models - mice, rats and rabbits - using the technique of systematic review and meta-analysis to highlight differences in the efficacy of statins. MATERIALS AND METHODS: We searched Medline and Embase. After examining all eligible articles, we extracted results about total cholesterol and other blood parameters, blood pressure, myocardial infarction and survival. Weighted and standard mean difference random effects meta-analysis was used to measure overall efficacy in prespecified species, strains and subgroups. RESULTS: We included in systematic review 161 animal studies and we analysed 120 studies, accounting for 2432 animals. Statins lowered the total cholesterol across all species, although with large differences in the effect size: -30% in rabbits, -20% in mice and -10% in rats. The reduction was larger in animals fed on a high-cholesterol diet. Statins reduced infarct volume but did not consistently reduce the blood pressure or effect the overall survival. Few studies considered strains at high risk of cardiovascular diseases or hard outcomes. CONCLUSIONS: Although statins showed substantial efficacy in animal models, few preclinical data considered conditions mimicking human pathologies for which the drugs are clinically indicated and utilized. The empirical finding that statins are more effective in lowering cholesterol derived from an external source (i.e. diet) conflicts with statin's supposed primary mechanism of action.

Flaws in animal studies exploring statins and impact on meta-analysis.

BACKGROUND: Animal experiments should be appropriately designed, correctly analysed and transparently reported to increase their scientific validity and maximise the knowledge gained from each experiment. This systematic review of animal experiments investigating statins evaluates their quality of reporting and methodological aspects as well as their implications for the conduction of meta-analyses. METHODS: We searched medline and embase for studies reporting research on statins in mice, rats and rabbits. We collected detailed information about the characteristics of studies, animals and experimental methods. RESULTS: We retrieved 161 studies. A little over half did not report randomisation (55%) and most did not describe blinding (88%). All studies reported details on the experimental procedure, although many omitted information about animal gender, age or weight. Four percent did not report the number of animals used. None reported the sample size. Fixed- and random-effects models gave different results (ratio of effect size increased by five folds). Heterogeneity was consistently substantial within animal models, for which accounting for covariates had minimal impact. Publication bias is highly suspected across studies. CONCLUSIONS: Although statins showed efficacy in animal models, preclinical studies highlighted fundamental problems in the way in which such research is conducted and reported. Results were often difficult to interpret and reproduce. Different meta-analytic approaches were highly inconsistent: a reliable approach to estimate the true parameter was imperceptible. Policies that address these issues are required from investigators, editors and institutions that care about the quality standards and ethics of animal research.

Effectiveness of computerized decision support systems linked to electronic health records: a systematic review and meta-analysis.

We systematically reviewed randomized controlled trials (RCTs) assessing the effectiveness of computerized decision support systems (CDSSs) featuring rule- or algorithm-based software integrated with electronic health records (EHRs) and evidence-based knowledge. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Abstracts of Reviews of Effects. Information on system design, capabilities, acquisition, implementation context, and effects on mortality, morbidity, and economic outcomes were extracted. Twenty-eight RCTs were included. CDSS use did not affect mortality (16 trials, 37395 patients; 2282 deaths; risk ratio [RR] = 0.96; 95% confidence interval [CI] = 0.85, 1.08; I(2) = 41%). A statistically significant effect was evident in the prevention of morbidity, any disease (9 RCTs; 13868 patients; RR = 0.82; 95% CI = 0.68, 0.99; I(2) = 64%), but selective outcome reporting or publication bias cannot be excluded. We observed differences for costs and health service utilization, although these were often small in magnitude. Across clinical settings, new generation CDSSs integrated with EHRs do not affect mortality and might moderately improve morbidity outcomes.

Point-of-care testing: where is the evidence? A systematic survey.

Point-of-care testing (POCT) has had rapid technological development and their use is widespread in clinical laboratories to assure reduction of turn-around-time and rapid patient management in some clinical settings where it is important to make quick decisions. Until now the papers published about the POCT have focused on the reliability of the technology used and their analytical accuracy. We aim to perform a systematic survey of the evidence of POCT efficacy focused on clinical outcomes, selecting POCT denoted special analytes characterized by possible high clinical impact. We searched in Medline and Embase. Two independent reviewers assessed the eligibility, extracted study details and assessed the methodological quality of studies. We analyzed 84 studies for five POCT instruments: neonatal bilirubin, procalcitonin, intra-operative parathyroid hormone, troponin and blood gas analysis. Studies were at high risk of bias. Most of the papers (50%) were studies of correlation between the results obtained by using POCT instruments and those obtained by using laboratory instruments. These data showed a satisfactory correlation between methods when similar analytical reactions were used. Only 13% of the studies evaluated the impact of POCT on clinical practice. POCT decreases the time elapsed for making decisions on patient management but the clinical outcomes have never been adequately evaluated. Our work shows that, although POCT has the potential to provide beneficial patient outcome, further studies may be required, especially for defining its real utility on clinical decision making.

A novel multistep approach to standardize the reported risk factors for in-hospital falls: a proof-of-concept study.

Background: Uncertainty and inconsistency in terminology regarding the risk factors (RFs) for in-hospital falls are present in the literature. Objective: (1) To perform a literature review to identify the fall RFs among hospitalized adults; (2) to link the found RFs to the corresponding categories of international health classifications to reduce the heterogeneity of their definitions; (3) to perform a meta-analysis on the risk categories to identify the significant RFs; (4) to refine the final list of significant categories to avoid redundancies. Methods: Four databases were investigated. We included observational studies assessing patients who had experienced in-hospital falls. Two independent reviewers performed the inclusion and extrapolation process and evaluated the methodological quality of the included studies. RFs were grouped into categories according to three health classifications (ICF, ICD-10, and ATC). Meta-analyses were performed to obtain an overall pooled odds ratio for each RF. Finally, protective RFs or redundant RFs across different classifications were excluded. Results: Thirty-six articles were included in the meta-analysis. One thousand one hundred and eleven RFs were identified; 616 were linked to ICF classification, 450 to ICD-10, and 260 to ATC. The meta-analyses and subsequent refinement of the categories yielded 53 significant RFs. Overall, the initial number of RFs was reduced by about 21 times. Conclusion: We identified 53 significant RF categories for in-hospital falls. These results provide proof of concept of the feasibility and validity of the proposed methodology. The list of significant RFs can be used as a template to build more accurate measurement instruments to predict in-hospital falls.

Subacute thyroiditis in the SARS-CoV-2 era: a multicentre prospective study.

Objective: Many cases of subacute thyroiditis (SAT) have been described related to SARS-CoV-2 infection, but no prospective data about follow-up are known. This prospective, longitudinal, 3-year, multicentre study aims to explore the clinical peculiarities and outcome of SAT in relation to SARS-CoV-2 infection, ascertained with antibody dosage. Methods: All patients receiving SAT diagnosis from November 2020 to May 2022 were enrolled. Data on anamnesis, physical examination, blood tests (TSH, freeT4, freeT3, thyroglobulin, anti-thyroid antibodies, C-reactive protein, erythrocyte sedimentation rate, complete blood count), and thyroid ultrasound were collected. At baseline, the presence of IgG against the SARS-CoV-2 spike protein or nucleocapsid was investigated. Patients were evaluated after 1, 3, 6, and 12 months. Results: Sixty-six subjects were enrolled. At baseline, 54 presented with pain, 36 (67%) for at least 15 days. Serum SARS-CoV-2 IgG measurements documented that 7 out of 52 subjects (13.5%) had infection before SAT diagnosis (COVID+). No significant differences between the COVID+ and COVID- groups were found at baseline, except for respiratory symptoms and fever, which were more common in COVID+ (P = 0.039 and P = 0.021, respectively). Among the 41 subjects who completed follow-up, COVID+ and COVID- did not differ for therapeutic approach to SAT or outcome, all having an improvement in neck pain, inflammation parameters, and ultrasound features. Conclusion: This is the first prospective study investigating any difference both at diagnosis and at follow-up between SAT presentation in patients with previous SARS-CoV-2 infection and those without. Our data demonstrate that SARS-CoV-2 does not impact on SAT onset, evolution, and outcome.

Remote magnetic with open-irrigated catheter vs. manual navigation for ablation of atrial fibrillation: a systematic review and meta-analysis.

The aim of this study was to determine the efficacy and safety of remote magnetic navigation (RMN) with open-irrigated catheter vs. manual catheter navigation (MCN) in performing atrial fibrillation (AF) ablation. We searched in PubMed (1948-2013) and EMBASE (1974-2013) studies comparing RMN with MCN. Outcomes considered were AF recurrence (primary outcome), pulmonary vein isolation (PVI), procedural complications, and data on procedure's performance. Odds ratios (OR) and mean difference (MD) were extracted and pooled using a random-effect model. Confidence in the estimates of the obtained effects (quality of evidence) was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. We identified seven controlled trials, six non-randomized and one randomized, including a total of 941 patients. Studies were at high risk of bias. No difference was observed between RMN and MCN on AF recurrence [OR 1.18, 95% confidence interval (CI) 0.85 to 1.65, P = 0.32] or PVI (OR 0.41, 95% CI 0.11-1.47, P = 0.17). Remote magnetic navigation was associated with less peri-procedural complications (Peto OR 0.41, 95% CI 0.19-0.88, P = 0.02). Mean fluoroscopy time was reduced in RMN group (-22.22 min; 95% CI -42.48 to -1.96, P = 0.03), although the overall duration of the procedure was longer (60.91 min; 95% CI 31.17 to 90.65, P < 0.0001). In conclusion, RMN is not superior to MCN in achieving freedom from recurrent AF at mid-term follow-up or PVI. The procedure implies less peri-procedural complications, requires a shorter fluoroscopy time but a longer total procedural time. For the low quality of the available evidence, a proper designed randomized controlled trial could turn the direction and the effect of the dimensions explored.

Evidence of SARS-CoV-2 reinfection: analysis of 35,000 subjects and overview of systematic reviews.

BACKGROUND: Reinfection by SARS-CoV-2 is a rare but possible event. We evaluated the prevalence of reinfections in the Province of Modena and performed an overview of systematic reviews to summarize the current knowledge. METHODS: We applied big data analysis and retrospectively analysed the results of oro- or naso-pharyngeal swab results tested for molecular research of viral RNA of SARS-CoV-2 between 1 January 2021 and 30 June 2021 at a single center. We selected individuals with samples sequence of positive, negative and then positive results. Between first and second positive result we considered a time interval of 90 days to be sure of a reinfection. We also performed a search for and evaluation of systematic reviews reporting SARS-CoV-2 reinfection rates. Main information was collected and the methodological quality of each review was assessed, according to A Measurement Tool to Assess systematic Reviews (AMSTAR). RESULTS: Initial positive results were revealed in more than 35,000 (20%) subjects; most (28%) were aged 30-49 years old. Reinfection was reported in 1,258 (3.5%); most (33%) were aged 30-49 years old. Reinfection rates according to vaccinated or non-vaccinated subjects were 0.6% vs 1.1% (p < 0.0001). Nine systematic reviews were identified and confirmed that SARS-CoV-2 reinfection rate is a rare event. AMSTAR revealed very low-moderate levels of quality among selected systematic reviews. CONCLUSIONS: There is a real, albeit rare risk of SARS-CoV-2 reinfection. Big data analysis enabled accurate estimates of the reinfection rates. Nevertheless, a standardized approach to identify and report reinfection cases should be developed.

Genetic polymorphisms of ACE1, ACE2, IFTM3, TMPRSS2 and TNFα genes associated with susceptibility and severity of SARS-CoV-2 infection: a systematic review and meta-analysis.

BACKGROUND: Some human polymorphisms of ACE1, ACE2, IFITM3, TMPRSS2 and TNFα genes may have an effect on the susceptibility to SARS-CoV-2 infection and increase the risk to develop severe COVID-19. We conducted a systematic review of current evidence to investigate the association of genetic variants of these genes with the susceptibility to virus infection and patient prognosis. METHODS: We systematically searched Medline, Embase and The Cochrane Library for articles published until May 2022, and included observational studies covering genetic association of ACE1, ACE2, IFITM3, TMPRSS2 and TNFα genes with COVID-19 susceptibility or prognosis. We evaluated the methodological quality of included studies, and pooled data as convenient in meta-analysis (MA). Odds ratio (OR) values and 95% confidence intervals were calculated. RESULTS: We included 35 studies (20 on ACE, 5 each on IFITM3, TMPRSS2, TNFα), enrolling 21,452 participants, of them 9401 were COVID-19 confirmed cases. ACE1 rs4646994 and rs1799752, ACE2 rs2285666, TMPRSS2 rs12329760, IFITM3 rs12252 and TNFα rs1800629 were identifies as common polymorphisms. Our MA showed an association between genetic polymorphisms and susceptibility to SARS-CoV-2 infection for IFITM3 rs12252 CC (OR 5.67) and CT (OR 1.64) genotypes. Furthermore, MA uncovered that both ACE DD (OR 1.27) and IFITM3 CC (OR 2.26) genotypes carriers had a significantly increased risk of developing severe COVID-19. DISCUSSION: These results provide a critical evaluation of genetic polymorphisms as predictors in SARS-CoV-2 infection. ACE1 DD and IFITM3 CC polymorphisms would lead to a genetic predisposition for severe lung injury in patients with COVID-19.

Mammalian In Vitro Translation Systems.

Under cellular stress, tight and coordinated regulation of the gene expression allows to minimize cellular damage, maintains cellular homeostasis, and ensures cell survival. Among stress-induced cellular responses, alteration of translation rates represents one of the most effective and rapid regulatory mechanisms available for cells. Here we report on detailed protocols of mammalian in vitro translation systems. While most of the available in vitro translation methods are based on bacterial or yeast components, tailor-made and robust mammalian systems are sparse. Our protocols allow measuring global translation of the total mRNA pool as well as translation of one specific reporter mRNA. Furthermore, it provides access to measuring translational activity of isolated ribosomes combined with non-ribosomal cytosolic fractions using reduced amounts of biological starting material. The herein described method can be applied to (1) investigate the effects of stress-dependent soluble factors regulating translation (such as tRNA fragments or ribosome-associated ncRNAs), (2) compare translational activity and translational fidelity of different ribosomes supplemented with the same non-ribosomal fractions, and (3) to investigate protein biosynthesis in various mammalian cell lines as well as tissue samples.