Explore the vast range of titles available.

IntroductionThere has recently been increased interest in the assessment of body composition in patients with gastric cancer for the purpose of prognostication. This systematic review and meta-analysis aim to evaluate the current literature on body composition assessment in patients with gastric cancer and its impact on peri-operative outcomes.MethodsA systematic literature search was conducted for studies reporting assessment of body composition in patients with gastric cancers. Meta-analysis of postoperative outcomes (overall and major complications, anastomotic leaks, pulmonary complications) and survival was performed using random effects models.ResultsThirty-nine studies reported the assessment of body composition in 8402 patients. Methods used to assess body composition in patients with gastric cancers were computerized tomography (n = 26), bioelectrical impedance analysis (n = 9), and dual-energy-X-ray-absorptiometry (n = 3). Only 21 studies reported the impact of pre-operative sarcopenia on post-operative outcomes. Sarcopenic patients have significantly higher rates of postoperative major complications (n = 12, OR 1.67, CI95% 1.14–2.46, p = 0.009), and pulmonary (n = 8, OR 4.01, CI95% 2.23–7.21, p < 0.001) complications after gastrectomy. Meta-analysis of nine studies reporting overall survival after gastrectomy identified significantly worse survival in patients with pre-operative sarcopenia (HR 2.12, CI95% 1.89–2.38, p < 0.001).ConclusionsAssessment of body composition has the potential to become a clinically useful tool that could support decision-making in patients with gastric cancer. However, variation in methods of assessing and reporting body composition in this patient group limits assessment of current post-operative outcomes

ObjectivesTo identify the barriers and enablers to implementing clinical practice guidelines (CPGs) recommendations in primary care and to provide recommendations that could facilitate the uptake of CPGs recommendations.DesignAn overview of systematic reviews.Data sourcesNine electronic databases (PubMed, Cochrane Library, CINAHL, MEDLINE, PsycINFO, Web of Science, Journals @Ovid Full Text, EMBase, JBI) and three online data sources for guidelines (Turning Research Into Practice, the National Guideline Clearinghouse and the National Institute for Health and Care Excellence) were searched until May 2021.Eligibility criteriaSystematic reviews, meta-analyses or other types of systematic synthesis of quantitative, qualitative or mixed-methods studies on the topic of barriers and/or enablers for CPGs implementation in primary care were included.Data extraction and synthesisTwo authors independently screened the studies and extracted the data using a predesigned data extraction form. The methodological quality of the included studies was appraised by using the JBI Critical Appraisal Checklist for Systematic Reviews and Research Syntheses. Content analysis was used to synthesise the data.ResultsTwelve systematic reviews were included. The methodological quality of the included reviews was generally robust. Six categories of barriers and enablers were identified, which include (1) political, social and culture factors, (2) institutional environment and resources factors, (3) guideline itself related factors, (4) healthcare provider-related factors, (5) patient-related factors and (6) behavioural regulation-related factors. The most commonly reported barriers within the above-mentioned categories were suboptimal healthcare networks and interprofessional communication pathways, time constraints, poor applicability of CPGs in real-world practice, lack of knowledge and skills, poor motivations and adherence, and inadequate reinforcement (eg, remuneration). Presence of technical support (‘institutional environment and resources factors’), and timely education and training for both primary care providers (PCPs) (‘healthcare provider-related factors’) and patients (‘patient-related factors’) were the frequently reported enablers.ConclusionPolicy-driven strategies should be developed to motivate different levels of implementation activities, which include optimising resources allocations, promoting integrated care models, establishing well-coordinated multidisciplinary networks, increasing technical support, encouraging PCPs and patients’ engagement in guideline development, standardising the reporting of guidelines, increasing education and training, and stimulating PCPs and patients’ motivations. All the activities should be conducted by fully considering the social, cultural and community contexts to ensure the success and sustainability of CPGs implementation.

In low-resource settings, midwives are the first contact for women with preeclampsia and lead the coordination of care. Unfavourable preeclampsia outcomes create a burden for women, families, and the health system. It is therefore important to understand the unique context of midwives' practice and the complex factors that influence the delivery of maternal healthcare. This qualitative study explored the perspectives of key stakeholders in a tertiary hospital in Ghana regarding the facilitators and barriers influencing midwives' provision of preeclampsia care using a socioecological model. Semi-structured interviews were conducted with 42 participants comprising senior managers (n = 7) and hospital midwives (n = 35) in 2021. Thematic analysis used Braun and Clarke's six-step method, and the findings were organised within four levels of the socioecological model: individual, interpersonal, organisational, and public policy. Two main themes were identified: 1) Facilitators of preeclampsia management, and 2) Barriers to preeclampsia management. Facilitators were identified at three levels (individual, interpersonal, and organisational) and included midwives' knowledge of preeclampsia; midwives' self-efficacy; midwives' skillset to enhance preeclampsia care; collaborative practice; and strategies for preeclampsia care quality improvement. At the individual level, the barriers were inadequate pre-service preparation, lack of evidence-based midwifery care, and colleagues' work attitudes. Hierarchical decision-making and staff views of women's risk perceptions were identified as barriers at the interpersonal level. At the organisational level, the barriers were: scarce resources and staff shortages, and a lack of midwifery-specific guidelines. Two barriers were identified within the public policy level: the high cost of preeclampsia care and issues with the referral system. Multi-faceted factors play a significant role in midwives' management of preeclampsia. Hence context-specific multi-level interventions have the potential to improve the quality-of-care women in Ghana receive.

Intravenous tissue plasminogen activator (tPA) remains the cornerstone of recanalization therapy for acute ischemic stroke (AIS), albeit with varying degrees of response. The triglyceride-glucose (TyG) index is a novel marker of insulin resistance, but association with outcomes among AIS patients who have received tPA has not been well elucidated. We studied 698 patients with AIS who received tPA from 2006 to 2018 in a comprehensive stroke centre. TyG index was calculated using the formula: ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. TyG index was significantly lower in patients that survived at 90-days than those who died (8.61 [Interquartile Range: 8.27–8.99] vs 8.76 [interquartile range: 8.39–9.40], p = 0.007). In multivariate analysis, TyG index was significantly associated with 90-day mortality (OR: 2.12, 95% CI: 1.39–3.23, p = 0.001), poor functional outcome (OR: 1.41 95% CI: 1.05–1.90, p = 0.022), and negatively associated with early neurological improvement (ENI) (OR: 0.68, 95% CI: 0.52–0.89, p = 0.004). There was no association between TyG index and symptomatic intracranial hemorrhage. ‘High TyG’ (defined by TyG index ≥ 9.15) was associated with mortality, poor functional outcomes and no ENI. In conclusion, the TyG index, a measure of insulin resistance, was significantly associated with poorer clinical outcomes in AIS patients who received tPA.

The Covid-19 pandemic has placed unprecedented pressure on healthcare systems and workers around the world. Such pressures may impact on working conditions, psychological wellbeing and perception of safety. In spite of this, no study has assessed the relationship between safety attitudes and psychological outcomes. Moreover, only limited studies have examined the relationship between personal characteristics and psychological outcomes during Covid-19. From 22nd March 2020 to 18th June 2020, healthcare workers from the United Kingdom, Poland, and Singapore were invited to participate using a self-administered questionnaire comprising the Safety Attitudes Questionnaire (SAQ), Oldenburg Burnout Inventory (OLBI) and Hospital Anxiety and Depression Scale (HADS) to evaluate safety culture, burnout and anxiety/depression. Multivariate logistic regression was used to determine predictors of burnout, anxiety and depression. Of 3,537 healthcare workers who participated in the study, 2,364 (67%) screened positive for burnout, 701 (20%) for anxiety, and 389 (11%) for depression. Significant predictors of burnout included patient-facing roles: doctor (OR 2.10; 95% CI 1.49–2.95), nurse (OR 1.38; 95% CI 1.04–1.84), and ‘other clinical’ (OR 2.02; 95% CI 1.45–2.82); being redeployed (OR 1.27; 95% CI 1.02–1.58), bottom quartile SAQ score (OR 2.43; 95% CI 1.98–2.99), anxiety (OR 4.87; 95% CI 3.92–6.06) and depression (OR 4.06; 95% CI 3.04–5.42). Significant factors inversely correlated with burnout included being tested for SARS-CoV-2 (OR 0.64; 95% CI 0.51–0.82) and top quartile SAQ score (OR 0.30; 95% CI 0.22–0.40). Significant factors associated with anxiety and depression, included burnout, gender, safety attitudes and job role. Our findings demonstrate a significant burden of burnout, anxiety, and depression amongst healthcare workers. A strong association was seen between SARS-CoV-2 testing, safety attitudes, gender, job role, redeployment and psychological state. These findings highlight the importance of targeted support services for at risk groups and proactive SARS-CoV-2 testing of healthcare workers.

BackgroundAn increasing number of studies have shown an association between migraine and cardiovascular disease, in particular cardio- and cerebro-vascular events.MethodsThree electronic databases (PubMed, Embase and Scopus) were searched from inception to May 22, 2021 for prospective cohort studies evaluating the risk of myocardial infarction, stroke and cardiovascular mortality in migraine patients. A random effects meta-analysis model was used to summarize the included studies.ResultsA total of 18 prospective cohort studies were included consisting of 370,050 migraine patients and 1,387,539 controls. Migraine was associated with myocardial infarction (hazard ratio, 1.36; 95% CI, 1.23–1.51; p =  < 0.001), unspecified stroke (hazard ratio, 1.30; 95% CI, 1.07–1.60; p = 0.01), ischemic stroke (hazard ratio, 1.35; 95% CI, 1.03–1.78; p = 0.03) and hemorrhagic stroke (hazard ratio, 1.43; 95% CI, 1.07–1.92; p = 0.02). Subgroup analysis of migraine with aura found a further increase in risk of myocardial infarction and both ischemic and hemorrhagic stroke, as well as improved substantial statistical heterogeneity. Migraine with aura was also associated with an increased risk of cardiovascular mortality (hazard ratio, 1.27; 95% CI, 1.14–1.42; p =  < 0.001).ConclusionMigraine, especially migraine with aura, is associated with myocardial infarction and stroke. Migraine with aura increases the risk of overall cardiovascular mortality.

In pancreatic ductal adenocarcinoma, the CCL2–CCR2 chemokine axis is used to recruit tumour-associated macrophages for construction of an immunosuppressive tumour microenvironment. This pathway has prognostic implications in pancreatic cancer, and blockade of CCR2 restores anti-tumour immunity in preclinical models. We aimed to establish the safety, tolerability, and recommended phase 2 oral dose of the CCR2 inhibitor PF-04136309 in combination with FOLFIRINOX chemotherapy (oxaliplatin and irinotecan plus leucovorin and fluorouracil). We did this open-label, dose-finding, non-randomised, phase 1b study at one centre in the USA. We enrolled treatment-naive patients aged 18 years or older with borderline resectable or locally advanced biopsy-proven pancreatic ductal adenocarcinoma, an Eastern Cooperative Oncology Group performance status of 1 or less, measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1, and normal end-organ function. Patients were allocated to receive either FOLFIRINOX alone (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and bolus fluorouracil 400 mg/m2, followed by 2400 mg/m2 46-h continuous infusion), administered every 2 weeks for a total of six treatment cycles, or in combination with oral PF-04136309, administered at a starting dose of 500 mg twice daily in a standard 3 + 3 dose de-escalation design. Both FOLFIRINOX and PF-04136309 were simultaneously initiated with a total treatment duration of 12 weeks. The primary endpoints were the safety, tolerability, and recommended phase 2 dose of PF-04136309 plus FOLFIRINOX, with an expansion phase planned at the recommended dose. We analysed the primary outcome by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01413022. Between April 19, 2012, and Nov 12, 2014, we treated 47 patients with FOLFIRINOX alone (n=8) or with FOLFIRINOX plus PF-04136309 (n=39). One patient had a dose-limiting toxic effect in the dose de-escalation group receiving FOLFIRINOX plus PF-04136309 at 500 mg twice daily (n=6); this dose was established as the recommended phase 2 dose. We pooled patients in the expansion-phase group (n=33) with those in the dose de-escalation group that received PF-04136309 at the recommended phase 2 dose for assessment of treatment-related toxicity. Six (75%) of the eight patients receiving FOLFIRINOX alone were assessed for treatment toxicity, after exclusion of two (25%) patients due to insurance coverage issues. The median duration of follow-up for treatment toxicity was 72·0 days (IQR 49·5–89·0) in the FOLFIRINOX alone group and 77·0 days (70·0–90·5) in the FOLFIRINOX plus PF-04136309 group. No treatment-related deaths occurred. Two (5%) patients in the FOLFIRINOX plus PF-04136309 group stopped treatment earlier than planned due to treatment-related toxic effects. Grade 3 or higher adverse events reported in at least 10% of the patients receiving PF-04136309 included neutropenia (n=27), febrile neutropenia (n=7), lymphopenia (n=4), diarrhoea (n=6), and hypokalaemia (n=7). Grade 3 or higher adverse events reported in at least 10% of patients receiving FOLFIRINOX alone were neutropenia (n=6), febrile neutropenia (n=1), anaemia (n=2), lymphopenia (n=1), diarrhoea (n=2), hypoalbuminaemia (n=1), and hypokalaemia (n=3). Therapy was terminated because of treatment-related toxicity in one (17%) of the six patients receiving FOLFIRINOX alone. 16 (49%) of 33 patients receiving FOLFIRINOX plus PF-04136309 who had undergone repeat imaging achieved an objective tumour response, with local tumour control achieved in 32 (97%) patients. In the FOLFIRINOX alone group, none of the five patients with repeat imaging achieved an objective response, although four (80%) of those patients achieved stable disease. CCR2-targeted therapy with PF-04136309 in combination with FOLFIRINOX is safe and tolerable. Washington University–Pfizer Biomedical Collaborative.

This study sought to investigate the impact of pre-existing cognitive impairment on outcomes after transcatheter aortic valve implantation (TAVI). TAVI has been increasingly used in seniors, and evidence suggests better outcomes than surgical aortic valve replacement. Although frailty has been shown to be associated with poorer outcomes after TAVI, the effect of pre-existing cognitive impairment on patient outcomes after TAVI remains unclear. We searched the Medline, Embase, Scopus and Cochrane databases until May 14, 2022. The risk of bias was assessed using the Newcastle-Ottawa scale. The primary outcome was short-term (6 months to 1 year) mortality, and secondary outcomes included long-term (1 year to 3 years) mortality, in-hospital mortality, and postoperative delirium. A total of 14 studies with 32,746 patients (5,098 patients with cognitive impairment at baseline, 27,648 without) were included in our meta-analysis. Among studies that reported the raw proportion of patients with mortality of postoperative delirium, cognitive impairment significantly increased mortality (risk ratio 2.10, 95% confidence intervals [CIs] 1.43 to 3.08, p = 0.0002) and postoperative delirium (risk ratio 2.27, 95% CI 1.76 to 2.93, p <0.0001). Studies which reported the hazards for mortality (pooled hazards ratio 1.97, 95% CI 1.50 to 2.60, p <0.0001) and odds of postoperative delirium (pooled odds ratio 2.40, 95% CI: 1.51 to 3.80, p = 0.0002) yielded results consistent with the primary meta-analysis. In conclusion, pre-existing cognitive impairment is a significant risk factor for poorer outcomes after TAVI and should be carefully considered in this group of patients. Guidelines and future studies should take cognitive impairment into consideration for preoperative risk stratification.

BackgroundProgrammed death-ligand 1 (PD-L1) monoclonal antibody therapy has recently gained approval for treating metastatic triple-negative breast cancer (TNBC) -, in particular in the PD-L1+ patient subgroup of the recent IMpassion130 trial. The SP142 PD-L1 antibody clone was used as a predictive assay in this trial, but this clone was found to be an outlier in previous harmonisation studies in lung cancer.AimsTo address the comparability of PD-L1 clones in TNBC, we evaluated the concordance between conventional immunohistochemistry (IHC) and multiplex immunohistochemistry/immunofluorescence (mIHC/IF) that allowed simultaneous quantification of three different PD-L1 antibodies (22C3, SP142 and SP263).MethodsOur cohort comprised 25 TNBC cases, 12 non-small-cell lung carcinomas and 8 other cancers. EpCAM labelling was used to distinguish tumour cells from immune cells.ResultsModerate-to-strong correlations in PD-L1 positivity were found between results obtained through mIHC/IF and IHC. Individual concordance rates in the study ranged from 67% to 100%, with Spearman’s rank correlation coefficient values up to 0.88.ConclusionsmIHC/IF represents a promising tool in the era of cancer immunotherapy, as it can simultaneously detect and quantify PD-L1 labelling with multiple antibody clones, and allow accurate evaluation of tumour and immune cells. Clinicians and pathologists require this information to predict patient response to anti-PD-1/PD-L1 therapy. The adoption of this assay may represent a significant advance in the management of therapeutically challenging cancers. Further analysis and assay harmonisation are essential for translation to a routine diagnostic setting.