Stereotactic radiosurgery versus whole-brain radiotherapy after resection of solitary brain metastasis: A systematic review and meta-analysis.

Objective: The standard of care in patients with solitary brain metastasis involves surgical resection and postoperative whole-brain radiotherapy (WBRT). However, WBRT is associated with adverse effects, mainly neurocognitive deterioration. Stereotactic radiosurgery (SRS) is a more targeted form of radiation therapy that could be as effective as WBRT without the detrimental neurocognitive decline. Methods: We performed the first systematic review and meta-analysis comparing postoperative SRS versus postoperative WBRT in patients with one resected brain metastasis. PubMed, Scopus, and Cochrane library were systematically searched for studies comparing the efficacy of the two radiation modalities in terms of local and distant brain control, leptomeningeal disease control, and overall survival. Additionally, we extracted patients' neurocognitive function and quality of life after each postoperative radiation form. Results: Four studies with 248 patients (128: WBRT, 120: SRS) were included in our analysis. There was no difference between SRS and WBRT in the risk of local recurrence (RR = 0.92, CI = 0.51-1.66, p = 0.78, I2 = 0%) and leptomeningeal disease (RR = 1.21, CI = 0.49-2.98, p = 0.67, I2 = 18%), neither in the patients' overall survival (HR = 1.06, CI = 0.61-1.85, p = 0.83, I2 = 63%). Nevertheless, SRS appeared to increase the risk of distant brain failure (RR = 2.03, CI = 0.94-4.40, p = 0.07, I2 = 61%). Neurocognitive function and quality of life in the SRS group were equal or superior to the WBRT group. Conclusions: Although SRS may increase the risk of distant brain failure, it appears to be as effective as WBRT in terms of local control, risk of leptomeningeal disease, and overall survival while sparing the patients of the detrimental, WBRT-associated cognitive deterioration.

Comparison of Transfemoral versus Transsubclavian/Transaxillary access for transcatheter aortic valve replacement: A systematic review and meta-analysis.

Femoral access is the gold standard for transcatheter aortic valve replacement (TAVR). Safe alternative access, that represents about 15 % of TAVR cases, remains important for patients without adequate transfemoral access. We aimed to perform a systematic review and meta-analysis of studies comparing transfemoral (TF) access versus transsubclavian or transaxillary (TSc/TAx) access in patients undergoing TAVR. We searched PubMed, Cochrane CENTRAL Register, EMBASE, Web of Science, Google Scholar and ClinicalTrials.gov (inception through May 24, 2022) for studies comparing (TF) to (TSc/TAx) access for TAVR. A total of 21 studies with 75,995 unique patients who underwent TAVR (73,203 transfemoral and 2,792 TSc/TAx) were included in the analysis. There was no difference in the risk of in-hospital and 30-day all-cause mortality between the two groups (RR 0.64, 95 % CI 0.36-1.13, P = 0.12) and (RR 0.95, 95 % CI 0.64-1.41, P = 0.81), while 1-year mortality was significantly lower in the TF TAVR group (RR 0.79, 95 % CI 0.67-0.93, P = 0.005). No significant differences in major bleeding (RR 0.82, 95 % CI 0.65-1.03, P = 0.09), major vascular complications (RR 1.14, 95 % CI 0.75-1.72, P = 0.53), and stroke (RR 0.66, 95 % CI 0.42-1.02, P = 0.06) were observed. In patients undergoing TAVR, TF access is associated with significantly lower 1-year mortality compared to TSc/TAx access without differences in major bleeding, major vascular complications and stroke. While TF is the preferred approach for TAVR, TSc/TAx is a safe alternative approach. Future studies should confirm these findings, preferably in a randomized setting.

Continuous positive airway pressure for term and ≥34+0 weeks' gestation newborns at birth: A systematic review.

Background: Respiratory distress is common during transition after birth, but the effect of continuous positive airway pressure applied in the delivery room has not been systematically evaluated in spontaneously breathing term and ≥34+0 weeks' gestation infants.We aimed to compare delivery room continuous positive airway pressure with no delivery room continuous positive airway pressure for term and ≥34+0 weeks' gestation newborn infants at birth. Methods: Information sources: Medline, Embase, Cochrane Databases, Database of Abstracts of Reviews of Effects, and Cumulative Index to Nursing and Allied Health Literature. The Databases were last searched in October 2021.Eligibility criteria: Randomized, quasi-randomized, interrupted time series, controlled before-after, and cohort studies with English abstracts.Synthesis of results: Two authors independently extracted data, assessed risk of bias, and certainty of evidence. The main outcome was admission to the neonatal intensive care unit (NICU) or higher level of care receiving any positive pressure support. Data were pooled using fixed effects models.Risk of bias: Was assessed using the Cochrane Risk of Bias Tool for randomized trials and the Non-Randomized Studies of Interventions Tool (ROBINS-I) for observational studies. Results: In this meta-analysis, two randomized control trials (323 newborns delivered by cesarean section) showed that delivery room continuous positive airway pressure decreased the likelihood of NICU admission (risk ratio (RR) 95% confidence interval (CI) 0.27 (0.11-0.66), p < 0.005) and NICU respiratory support (RR (95% CI) 0.18 (0.05-0.60), p = 0.005) when compared with no delivery room continuous positive airway pressure. However, in two before-after studies (8,476 newborns), delivery room continuous positive airway pressure use was associated with an increased risk of air leak syndrome when compared with no delivery room continuous positive airway pressure. Discussion: Certainty of evidence was very low for all outcomes. Among term and ≥34+0 weeks' gestation infants having or at risk of having respiratory distress, there is insufficient evidence to suggest for or against routine use of continuous positive airway pressure in the delivery room.Funding: No Funding has been received to conduct this study.Clinical Trial Registration: This systematic review has been registered with the International Prospective Register of Systematic Reviews (http://www.crd.york.ac.uk/prospero/) [identifier: CRD42021225812].

Identification of predictive factors interacting with heart rate reduction for potential beneficial clinical outcomes in chronic heart failure: A systematic literature review and meta-analysis.

Background: There is an absence of clinical evidence on what factors modify the effect of heart rate (HR)-reducing treatment on mortality and morbidity in symptomatic heart failure patients with reduced ejection fraction (HFrEF). We performed a Bayesian meta-analysis and meta-regression to identify predictive factors that interact with HR-reducing therapy. Methods: A systematic review was performed to identify randomized placebo-controlled trials that enrolled symptomatic HFrEF patients. The primary objective was to evaluate how different predictive factors modify the efficacy of HR-reducing therapy on clinical outcomes. Secondary objectives included the evaluation of subgroups stratified by a HR reduction threshold of 10 bpm. Results: Data from 20 studies were synthesized and HR-reducing therapy was responsible for 16.7 %, 16.4 %, and 21.1 % risk reductions in all-cause mortality, cardiovascular (CV)-related mortality, and rehospitalization due to worsening HF (WHF), respectively. Empirical Bayes meta-regression showed that type 2 diabetes mellitus (T2DM) significantly modified the efficacy of HR-reducing therapy on all-cause mortality (slope = 0.012 in log risk ratio (RR) per 1 %-unit [95 % credible interval (CrI) 0.004, 0.021]) and CV-related mortality (0.01 in log RR per 1 %-unit [95 % CrI 0.0003, 0.0200]). There were insufficient studies to perform a meta-regression when stratifying by a HR reduction threshold of 10 bpm; however, when including all studies, we observed a significant effect modification for rehospitalization due to WHF (p = 0.004). Conclusions: This meta-analysis focused on the central tenet of HR-reducing therapy and revealed that T2DM is a predictor of HR-reducing treatment effect on all-cause mortality and CV-related mortality in HFrEF patients.

Effectiveness of screening for oral cancer and oral potentially malignant disorders (OPMD): A systematic review.

Oral cancer (OC) is a debilitating disease with a high mortality rate when diagnosed in advanced stage. Conversely, early-stage OC has a high survival rate, supporting a need for early detection programmes. A previous systematic review of clinical trials evaluating efficacy of screening for OC was inconclusive. This systematic review aimed to determine the impact of screening for oral lesions on reducing mortality and incidence of OC by looking at a broader spectrum of evidence. The search for randomized controlled trials and observational studies with a control group was conducted in PubMed, OVID, Cochrane, CINAHL and grey literature sources. Risk of bias for included studies was assessed with the tools developed by the Cochrane collaboration. Six out of two identified randomized trials and five observational studies had moderate to high risk of bias. Nevertheless, the predictions on impact of OC screening on incidence and mortality were similar across the majority of the studies. The meta-analysis concluded on a 26% decrease in OC mortality, and an 19% decrease in advanced OC cases as a result of OC screening in high-risk population. Three out of four studies did not identify an impact of screening on OC incidence. No positive impact of OC screening on incidence or mortality among general population was identified in the only available randomized trial. Consistency in the outcomes and the limitations of the few available studies suggest a need for real-life setting research to evaluate the overall effectiveness of screening for OC in high-risk population.

Vitamin D status can affect COVID-19 outcomes also in pediatric population.

Background: vitamin D influences the immune system and the inflammatory response. It is known that vitamin D supplementation reduces the risk of acute respiratory tract infection. In the last two years, many researchers have investigated vitamin D's role in the pathophysiology of COVID-19 disease. Results: the findings obtained from clinical trials and systematic reviews highlight that most patients with COVID-19 have decreased vitamin D levels and low levels of vitamin D increase the risk of severe disease. This evidence seems to be also confirmed in the pediatric population. Conclusions: further studies (systematic review and meta-analysis) conducted on children are needed to confirm that vitamin D affects COVID-19 outcomes and to determine the effectiveness of supplementation and the appropriate dose, duration and mode of administration.

Suctioning of clear amniotic fluid at birth: A systematic review.

Context: Upper airway suctioning at birth was considered standard procedure and is still commonly practiced. Negative effects could exceed benefits of suction. Question: In infants born through clear amniotic fluid (P) does suctioning of the mouth and nose (I) vs no suctioning (C) improve outcomes (O). Data sources: Information specialist conducted literature search (12th September 2021, re-run 17th June 2022) using Medline, Embase, Cochrane Databases, Database of Abstracts of Reviews of Effects, and CINAHL. RCTs, non-RCTs and observational studies with a defined selection strategy were included. Unpublished studies, reviews, editorials, animal and manikin studies were excluded. Data extraction: Two authors independently extracted data, risk of bias was assessed using the Cochrane ROB2 and ROBINS-I tools. Certainty of evidence was assed using the GRADE framework. Review Manager was used to analyse data and GRADEPro to develop summary of evidence tables. Meta-analyses were performed if ≥2 RCTs were available. Outcomes: Primary: assisted ventilation. Secondary: advanced resuscitation, oxygen supplementation, adverse effects of suctioning, unanticipated NICU admission. Results: Nine RCTs (n = 1096) and 2 observational studies (n = 418) were identified. Two RCTs (n = 280) with data concerns were excluded post-hoc. Meta-analysis of 3 RCTs, (n = 702) showed no difference in primary outcome. Two RCTs (n = 200) and 2 prospective observational studies (n = 418) found lower oxygen saturations in first 10 minutes of life with suctioning. Two RCTs (n = 200) showed suctioned newborns took longer to achieve target saturations. Limitations: Certainty of evidence was low or very low for all outcomes. Most studies selected healthy newborns limiting generalisability and insufficient data was available for planned subgroup analyses. Conclusions: Despite low certainty evidence, this review suggests no clinical benefit from suctioning clear amniotic fluid from infants following birth, with some evidence suggesting a resulting desaturation. These finding support current guideline recommendations that this practice is not used as a routine step in birth. Funding: The International Liaison Committee on Resuscitation provided access to software platforms, an information specialist and teleconferencing. Clinical Trial Registration: This systematic review was registered with the Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/prospero/) (identifier: CRD42021286258).

Phosphodiesterase inhibitor for heart failure with preserved ejection fraction: A systematic review and meta-analysis.

Background: Although heart failure with preserved ejection fraction (HFpEF) is a serious disease, only limited options are available for its treatment. Recent studies have analyzed the effects of phosphodiesterase (PDE) inhibitors, especially PDE5 and PDE3 inhibitors, in patients with HFpEF, with mixed outcomes. Methods: We searched PUBMED and EMBASE databases up to August 2021. Randomized controlled trials (RCTs) and clinical trials that tested the effects of PDE inhibitors on patients with HFpEF were included as eligible studies. Indicators of left ventricular (LV) function, pulmonary arterial pressure (PAP), right ventricular (RV) function, exercise capacity, and quality of life (QOL) were used to evaluate the efficacy of PDE inhibitors in HFpEF. Results: Six RCTs that reported in 7 studies were included to evaluate the efficiency of PDE inhibitors on HFpEF patients. In the pooled analysis, PDE inhibitors showed insignificant changes in the ratio of early diastolic mitral inflow to annular velocities, left atrial volume index, pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR), peak oxygen uptake, 6-minute walking test distance, as well as Kansas City Cardiomyopathy Questionnaire score. However, substantial improvement was observed in the tricuspid annular plane systolic excursion (TAPSE). Additionally, the regression analysis showed that PDE inhibitor administration time is a critical factor for the decrease in PASP. Conclusions: PDE inhibitors did not effectively improve LV function, PAP, exercise capacity, and QOL in patients with HFpEF. However, they improved RV function with significant difference, suggesting that PDE inhibitors might be a promising option for HFpEF patients with RV dysfunction.

Immune checkpoint inhibitors and potential risk of thromboembolic events: Analysis of the WHO global database of individual case safety reports.

Introduction: Thromboembolic events with the use of immune checkpoint inhibitors (ICIs) in patients with cancer have been reported in few studies. However, the detailed profile of these cases remains mostly uncertain. Method: A descriptive analysis of Thromboembolic events associated with ICIs retrieved from the VigiBase, between 1967 to November 2020. We extracted the data using the terms of 'pulmonary embolism' OR 'deep vein thrombosis' OR 'acute coronary syndrome' OR 'myocardial infarction' OR 'ischemic stroke' (preferred term (PT) (MedDRA). Results: We included 161 cases from 26 countries in our descriptive analysis. Patients' ages were reported in 141 (87.6%) cases, with a median of 68 years (interquartile range 61-74), and 63.4% of the patients were male. Indications for ICIs were reported in 151 (93.8%) cases, as follows: lung cancer (n = 85, 52.8%), renal cell carcinoma (n = 24, 14.9%), melanoma (n = 20, 12.4%), urethral carcinoma (n = 12, 7.45%), breast cancer (n = 4, 2.48%), adenocarcinoma of the gastroesophageal junction (n = 3, 1.9%), gastric cancer (n = 2, 1.24%), and skin cancer (n = 1, 0.62%). Nivolumab was reported as a suspected drug in 76 cases (47%), pembrolizumab in 46 cases (28.5%), atezolizumab in 21 cases (13%), durvalumab in 14 cases (8.6%), and avelumab in four cases (2.4%).The time to onset of thromboembolic events was reported in 127 (78.8%) cases. Most of these patients (n = 109, 85.8%) reported thromboembolic events within the first six months. The causality assessment of included cases showed that 50.3% of reported thromboembolic events were possibly related to the suspected reported medication, 13.7% were probably related, 13% were unlikely to be related, and 23% were not assessable due to insufficient information. Conclusion: This study demonstrates a possible association between the use of ICIs and thromboembolic events. Further epidemiological studies are needed to assess this association and to elucidate the underlying mechanism.

COVID information and masking behaviors in U.S. adolescents: Findings from the Adolescent Brain Cognitive Development (ABCD) Study.

Adolescents are particularly vulnerable to health misinformation and are at risk for suboptimal adherence to protective health behaviors in the COVID-19 pandemic. Guided by factors consistent with the theories of planned behavior and rumor transmission, this study sought to analyze the impact of multiple information sources, including social media, television media, internet and parental counseling, on masking behaviors in adolescents. Responses from the December 2020 COVID-19 survey, representing 4,106 U.S. adolescents ages 12-14 from the Adolescent Brain Cognitive Development Study (ABCD) were analyzed. The majority of parents (61.1%) reported counseling their children on the importance of wearing masks all the time in the past week. A minority of adolescents reported more than one hour of daily exposure to COVID-19 related information on social media (9.1%), the internet (4.3%) and television (10.2%). In unadjusted and adjusted models, greater frequency of parental counseling and exposure to COVID-19 television or social media were associated with 'always masking' behaviors. Our findings provide support for the importance of parent counseling and suggest that socialmedia and television may overall support rather than dissuade protective COVID-19 health behaviors in adolescents.

Associating factors of suicide and repetition following self-harm: A systematic review and meta-analysis of longitudinal studies.

Background: Longitudinal evidence for sociodemographic and clinic factors deviating risk for suicide and repetition following SH (self-harm) varied greatly. Methods: A comprehensive search of PubMed, Web of Science, EMBASE, and PsycINFO was conducted from January 1st, 2010 to April 5th, 2022. Longitudinal studies focusing on examining associating factors for suicide and repetition following SH were included. PROSPERO registration CRD42021248695. Findings: The present meta-analysis synthesized data from 62 studies published from Jan. 1st, 2010. The associating factors of SH repetition included female gender (RR, 95%CI: 1.11, 1.04-1.18, I2=82.8%), the elderly (compared with adolescents and young adults, RR, 95%CI: 0.67, 0.52-0.87, I2=86.3%), multiple episodes of SH (RR, 95%CI: 1.97, 1.51-2.57, I2=94.3%), diagnosis (RR, 95%CI: 1.60, 1.27-2.02, I2=92.7%) and treatment (RR, 95%CI: 1.59, 1.40-1.80, I2=93.3%) of psychiatric disorder. Male gender (RR, 95%CI: 2.03, 1.80-2.28, I2=83.8%), middle-aged adults (compared with adolescents and young adults, RR, 95%CI: 2.40, 1.87-3.08, I2=74.4%), the elderly (compared with adolescents and young adults, RR, 95%CI: 4.38, 2.98-6.44, I2=76.8%), physical illness (RR, 95%CI: 1.95, 1.56-2.43, I2=0), multiple episodes of SH (RR, 95%CI: 2.02, 1.58-2.58, I2=87.4%), diagnosis (RR, 95%CI: 2.13, 1.67-2.71, I2=90.9%) and treatment (RR, 95%CI: 1.36, 1.16-1.58, I2=58.6%) of psychiatric disorder were associated with increased risk of suicide following SH. Interpretation: Due to the substantial heterogeneity for clinic factors of suicide and repetition following SH, these results need to be interpreted with caution. Clinics should pay more attention to the cases with SH repetition, especially with poor physical and psychiatric conditions. Funding: This work was supported by National Natural Science Foundation of China (NSFC) [No: 82103954; 30972527; 81573233].

Urban density differences in colorectal cancer screening participation and screening yield in The Netherlands.

Lower socioeconomic status has been associated with higher colorectal cancer incidence and lower participation in population-based screening with faecal immunochemical testing (FIT) but regional variations in participation may also exist. We analysed differences in participation and yield in colorectal cancer screening by urban density level. Data of all invitees to the Dutch colorectal cancer screening programme in 2014-2015 were included. Primary outcomes were participation (returning FIT), FIT positive predictive value, and screening yield (advanced neoplasia detected in invitees). Differences were explored across five levels of urban density. In total 1,873,639 screening invitees were included. FIT participation was 77.3% in the lowest versus 62.8% in the highest urban areas (RR 1.23; 95%CI 1.23-1.24). FIT positive predictive value was 58.6% in the lowest versus 55.2% in the highest urban areas (RR 1.06; 95% CI 1.04-1.09). Screening yield was also higher in the lowest (2.1%-2.3%) compared to the highest urban areas (1.8%). Compared to socioeconomic status, differences in urban density were associated with larger differences in screening participation. In conclusion, participation is lower and fewer cases of advanced neoplasia are detected in areas with a high urban density in the Dutch colorectal cancer screening programme. Differences in urban density could be used in tailoring regional strategies to target barriers in colorectal cancer screening.

Minimally invasive surgery or stenting for left anterior descending artery disease - meta-analysis.

Minimally invasive direct coronary artery bypass (MIDCAB) surgery and percutaneous coronary intervention (PCI) are both well-established minimally invasive revascularization strategies in patients with proximal left anterior descending (LAD) lesions. We aimed to evaluate the 20-years' experience by performing a systematic review and meta-analysis comparing MIDCAB versus PCI in adults with proximal LAD disease. We searched MEDLINE, EMBASE and Cochrane on October 1st, 2021 for articles published in the year 2000 or later. The primary outcome was all-cause mortality. Secondary outcomes included cardiac mortality, repeat target vessel revascularization (rTVR), myocardial infarction (MI), and cerebrovascular accident (CVA). Outcomes were analysed at short-term, mid-term, and long-term follow-up. Random effects meta-analyses were performed. Events were compared using risk ratios (RR) with 95% confidence intervals (CI). Our search yielded 17 studies pooling 3847 patients. At short-term follow-up, cardiac mortality was higher with MIDCAB than with PCI (RR 7.30, 95% CI: 1.38 to 38.61). At long-term follow-up, MIDCAB showed a decrease in all-cause mortality (RR 0.66, 95% CI: 0.46 to 0.93). MIDCAB showed a decrease in rTVR at mid-term follow-up (RR 0.16, 95% CI: 0.11 to 0.23) and at long-term follow-up (RR 0.25, 95% CI: 0.17 to 0.38). MI and CVA comparisons were not significant. In conclusion, in patients with proximal LAD lesions, MIDCAB showed a higher short-term mortality in the RCTs, but the cohort studies suggested a lower all-cause mortality at long-term follow-up. We confirm a decreased rTVR at mid-term follow-up in the RCTs and long-term follow-up in the cohort studies.

The Role of Cardioprotection in Cancer Therapy Cardiotoxicity: JACC: CardioOncology State-of-the-Art Review.

Cardiotoxicity is a relatively frequent and potentially serious side effect of traditional and targeted cancer therapies. Both general measures and specific pharmacologic cardioprotective interventions as well as imaging- and biomarker-based surveillance strategies to identify patients at high risk have been tested in randomized controlled trials to prevent or attenuate cancer therapy-related cardiotoxic effects. Although meta-analyses including early trials suggest an overall beneficial effect, there is substantial heterogeneity in results. Recent randomized controlled trials of neurohormonal inhibitors in patients receiving anthracyclines and/or human epidermal growth factor receptor 2-targeted therapies have shown a lower rate of cancer therapy-related cardiac dysfunction than previously reported and a modest or no sustained effect of the interventions. Data on preventive cardioprotective strategies for novel cancer drugs are lacking. Larger, prospective multicenter randomized clinical trials testing traditional and novel interventions are required to more accurately define the benefit of different cardioprotective strategies and to refine risk prediction and identify patients who are likely to benefit.

Comparative efficacy and safety of vaccines to prevent seasonal influenza: A systematic review and network meta-analysis.

Background: Influenza is one of the most common respiratory viral infections worldwide. Numerous vaccines are used to prevent influenza. Their selection should be informed by the best available evidence. We aimed to estimate the comparative efficacy and safety of seasonal influenza vaccines in children, adults and the elderly. Methods: We conducted a systematic review and network meta-analysis (NMA). We searched the Cochrane Library Central Register of Controlled Trials, MEDLINE and EMBASE databases, and websites of regulatory agencies, through December 15th, 2020. We included placebo- or no vaccination-controlled, and head-to-head randomized clinical trials (RCTs). Pairs of reviewers independently screened the studies, abstracted the data, and appraised the risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was laboratory-confirmed influenza. We also synthesized data for hospitalization, mortality, influenza-like illness (ILI), pneumonia or lower respiratory-tract disease, systemic and local adverse events (AEs). We estimated summary risk ratios (RR) using pairwise and NMA with random effects. This study is registered with PROSPERO, number CRD42018091895. Findings: We identified 13,439 citations. A total of 231 RCTs were included after screening: 11 studies did not provide useful data for the analysis; 220 RCTs [100,677 children (< 18 years) and 329,127 adults (18-60 years) and elderly (≥ 61 years)] were included in the NMA. In adults and the elderly, all vaccines, except the trivalent inactivated intradermal vaccine (3-IIV ID), were more effective than placebo in reducing the risk of laboratory-confirmed influenza, with a RR between 0.33 (95% credible interval [CrI] 0.21-0.55) for trivalent inactivated high-dose (3-IIV HD) and 0.56 (95% CrI 0.41-0.74) for trivalent live-attenuated vaccine (3-LAIV). In adults and the elderly, compared with trivalent inactivated vaccine (3-IIV), no significant differences were found for any, except 3-LAIV, which was less efficacious [RR 1.41 (95% CrI 1.04-1.88)]. In children, compared with placebo, RR ranged between 0.13 (95% CrI 0.03-0.51) for trivalent inactivated vaccine adjuvanted with MF59/AS03 and 0.55 (95% CrI 0.36-0.83) for trivalent inactivated vaccine. Compared with 3-IIV, 3-LAIV and trivalent inactivated adjuvanted with MF59/AS03 were more efficacious [RR 0.52 (95% CrI 0.32-0.82) and RR 0.23 (95% CrI 0.06-0.87)] in reducing laboratory-confirmed influenza. With regard to safety, higher systemic AEs rates after vaccination with 3-IIV, 3-IIV HD, 3-IIV ID, 3-IIV MF59/AS03-adj, quadrivalent inactivated (4-IIV), quadrivalent adjuvanted (4-IIV MF59/AS03-adj), quadrivalent recombinant (4-RIV), 3-LAIV or quadrivalent live attenuated (4-LAIV) vaccines were noted in adults and the elderly [RR 1.5 (95% CrI 1.18-1.89) to 1.15 (95% CrI 1.06-1.23)] compared with placebo. In children, the systemic AEs rate after vaccination was not significantly higher than placebo. Interpretation: All vaccines cumulatively achieved major reductions in the incidence of laboratory-confirmed influenza in children, adults, and the elderly. While the live-attenuated was more efficacious than the inactivated vaccine in children, many vaccine types can be used in adults and the elderly. Funding: The directorate general of welfare, Lombardy region.

Utilization of healthcare and prescription medicines after non-pharmacological interventions for depression - A 3-year register follow-up of an RCT in primary care.

Depression is a common, recurrent disorder. There is a need for readily available treatments with few negative side effects, that demands little resources and that are effective both in the short- and long term. Our aim was to investigate the long-term effectiveness of two different interventions; physical exercise and internet-based cognitive behavioural therapy (internet-CBT), compared to usual care in patients with mild to moderate depression in a Swedish primary care setting. We performed a register-based 3-year follow-up study of participants in the randomized controlled trial REGASSA (n = 940) using healthcare utilization and dispensed medicines as outcomes. We found no difference between the three groups regarding proportion of participants consulting healthcare due to mental illness or pain during follow-up. Regarding number of consultations, there was no difference between the groups, except for consultations related to pain. For this outcome both treatment arms had significantly fewer consultations compared to usual care, during year 2-3, the risk ratio (RR) for physical exercise and internet-CBT was 0.64 (95% CI = 0.43-0.95) and 0.61 (95% CI = 0.41-0.90), respectively. A significantly lower proportion of patients in both treatment arms were dispensed hypnotics and sedatives year 2-3 compared to the usual care arm, RR for both physical exercise and internet-CBT was 0.72 (95% CI = 0.53-0.98). No other differences between the groups were found. In conclusion, considering long-term effects, both physical exercise and internet-CBT, being resource-efficient treatments, could be considered as appropriate additions for patients with mild to moderate depression in primary care settings. Trial registration: The original RCT was registered with the German Clinical Trial Register (DRKS study ID: DRKS00008745).

Metabolic syndrome; associations with adverse outcome after colorectal surgery. A systematic review and meta-analysis.

BACKGROUND: Increasing evidence shows that patients with Metabolic Syndrome (MetS) are at risk for adverse outcome after abdominal surgery. The aim of this study was to investigate the impact of MetS and preoperative hyperglycemia, as an individual component of MetS, on adverse outcome after colorectal surgery. METHODS: A literature review was systematically performed according to the PRISMA guidelines. Inclusion criteria were observational studies that evaluated the relationship between MetS or preoperative hyperglycemia and outcomes after colorectal surgery (i.e. any complication, severe complication defined as Clavien-Dindo grade ≥ III, anastomotic leakage, surgical site infection, mortality and length of stay). RESULTS: Six studies (246.383 patients) evaluated MetS and eight studies (9.534 patients) reported on hyperglycemia. Incidence rates of MetS varied widely from 7% to 68% across studies. Meta-analysis showed that patients with MetS are more likely to develop severe complications than those without MetS (RR 1.62, 95% CI 1.01-2.59). Moreover, a non-significant trend toward increased risks for any complication (RR 1.35, 95% CI 0.91-2.00), anastomotic leakage (RR 1.67, 95% CI 0.47-5.93) and mortality (RR 1.19, 95% CI 1.00-1.43) was found. Furthermore, preoperative hyperglycemia was associated with an increased risk of surgical site infection (RR 1.35, 95% CI 1.01-1.81). CONCLUSION: MetS seem to have a negative impact on adverse outcome after colorectal surgery. As a result of few studies meeting inclusion criteria and substantial heterogeneity, evidence is not conclusive. Future prospective observational studies should improve the amount and quality in order to verify current results.

Impact of early kangaroo mother care versus standard care on survival of mild-moderately unstable neonates <2000 grams: A randomised controlled trial.

BACKGROUND: Understanding the effect of early kangaroo mother care on survival of mild-moderately unstable neonates <2000 g is a high-priority evidence gap for small and sick newborn care. METHODS: This non-blinded pragmatic randomised clinical trial was conducted at the only teaching hospital in The Gambia. Eligibility criteria included weight <2000g and age 1-24 h with exclusion if stable or severely unstable. Neonates were randomly assigned to receive either standard care, including KMC once stable at >24 h after admission (control) versus KMC initiated <24 h after admission (intervention). Randomisation was stratified by weight with twins in the same arm. The primary outcome was all-cause mortality at 28 postnatal days, assessed by intention to treat analysis. Secondary outcomes included: time to death; hypothermia and stability at 24 h; breastfeeding at discharge; infections; weight gain at 28d and admission duration. The trial was prospectively registered at www.clinicaltrials.gov (NCT03555981). FINDINGS: Recruitment occurred from 23rd May 2018 to 19th March 2020. Among 1,107 neonates screened for participation 279 were randomly assigned, 139 (42% male [n = 59]) to standard care and 138 (43% male [n = 59]) to the intervention with two participants lost to follow up and no withdrawals. The proportion dying within 28d was 24% (34/139, control) vs. 21% (29/138, intervention) (risk ratio 0·84, 95% CI 0·55 - 1·29, p = 0·423). There were no between-arm differences for secondary outcomes or serious adverse events (28/139 (20%) for control and 30/139 (22%) for intervention, none related). One-third of intervention neonates reverted to standard care for clinical reasons. INTERPRETATION: The trial had low power due to halving of baseline neonatal mortality, highlighting the importance of implementing existing small and sick newborn care interventions. Further mortality effect and safety data are needed from varying low and middle-income neonatal unit contexts before changing global guidelines.

Effect of real-time and post-event feedback in out-of-hospital cardiac arrest attended by EMS - A systematic review and meta-analysis.

OBJECTIVES: A systematic review to determine if cardiopulmonary resuscitation (CPR) guided by either real-time or post-event feedback could improve CPR quality or patient outcome compared to unguided CPR in out-of-hospital cardiac arrest (OHCA). METHODS: Four databases were searched; PubMed, Embase, CINAHL, and Cochrane Library in August 2020 for post 2010 literature on OHCA in adults. Critical outcomes were chest compression depth, rate and fraction. Important outcomes were any return of spontaneous circulation, survival to hospital and survival to discharge. RESULTS: A total of 9464 studies were identified with 61 eligibility for full text screening. A total of eight studies was included in the meta-analysis. Five studies investigated real-time feedback and three investigated post-event feedback. Meta-analysis revealed that real-time feedback statistically improves compression depth and rate while post-event feedback improved depth and fraction. Feedback did not statistically improve patient outcome but an improvement in absolute numbers revealed a clinical effect of feedback. Heterogenity varied from "might not be important" to "considerable". CONCLUSION: To significantly improve CPR quality real-time and post-event feedback should be combined. Neither real-time nor post event feedback could statistically be associated with patient outcome however, a clinical effect was detected. The conclusions reached were based on few studies of low to very low quality. PROSPERO REGISTRATION: CRD42019133881.

Real-world experience with obeticholic acid in patients with primary biliary cholangitis.

BACKGROUND & AIMS: Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions. METHODS: Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to Poise criteria; the secondary endpoint was the biochemical response according to normal range criteria, defined as normal levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) at 12 months. Safety and tolerability were also assessed. RESULTS: We analysed 191 patients until at least 12 months of follow-up. Median age was 57 years, 94% female, 61 (32%) had cirrhosis, 28 (15%) had histologically proven overlap with autoimmune hepatitis (PBC-AIH). At 12 months, significant median reductions of ALP (-32.3%), ALT (-31.4%), and bilirubin (-11.2%) were observed. Response rates were 42.9% according to Poise criteria, and 11% by normal range criteria. Patients with cirrhosis had lower response than patients without cirrhosis (29.5% vs. 49.2%, p = 0.01), owing to a higher rate of OCA discontinuation (30% vs. 12%, p = 0.004), although with similar ALP reduction (29.4% vs. 34%, p = 0.53). Overlap PBC-AIH had a similar response to pure PBC (46.4% vs. 42.3%, p = 0.68), with higher ALT reduction at 6 months (-38% vs. -29%, p = 0.04). Thirty-three patients (17%) prematurely discontinued OCA because of adverse events, of whom 11 experienced serious adverse events. Treatment-induced pruritus was the leading cause of OCA discontinuation (67%). CONCLUSIONS: Effectiveness and safety of OCA under real-world conditions mirror those in the Poise trial. Patients with cirrhosis had lower tolerability. Overlap PBC-AIH showed higher ALT reduction at 6 months compared with patients with pure PBC. LAY SUMMARY: Obeticholic acid (OCA) was shown to be effective in more than one-third of patients not responding to ursodeoxycholic acid in a real-world context in Italy. Patients with cirrhosis had more side effects with OCA, and this led to suspension of the drug in one-third of patients. OCA was also effective in patients who had overlap between autoimmune hepatitis and primary biliary cholangitis.