Breast cancer management and outcome according to surgeon's affiliation: a population-based comparison adjusted for patient's selection bias

Background Studies have reported that breast cancer (BC) units could increase the quality of care but none has evaluated the efficacy of alternative options such as private BC networks, which is our study objective. Patients and methods We included all 1404 BC patients operated in the public unit or the private network and recorded at the Geneva Cancer Registry between 2000 and 2005. We compared quality indicators of care between the public BC unit and the private BC network by logistic regression and evaluated the effect of surgeon's affiliation on BC-specific mortality by the Cox model adjusting for the propensity score. Results Both the groups had high care quality scores. For invasive cancer, histological assessment before surgery and axillary lymph node dissection when indicated were less frequent in the public sector (adjusted odds ratio (OR): 0.4, 95% confidence interval (CI) 0.3-0.7, and OR: 0.4, 95% CI 0.2-0.8, respectively), while radiation therapy after breast-conserving surgery was more frequent (OR: 2.5, 95% CI 1.4-4.8). Surgeon affiliation had no substantial effect on BC-specific mortality (adjusted hazard ratio (HR): 0.8, 95% CI 0.5-1.4). Conclusions This study suggests that private BC networks could be an alternative to public BC units with both structures presenting high quality indicators of BC care and similar BC-specific mortalit

Predictors and Implications of Early Clinical Stability in Patients Hospitalized for Moderately Severe Community-Acquired Pneumonia.

Assessment of early response to treatment is crucial for the management of community-acquired pneumonia (CAP). To describe the predictors and the outcomes of early clinical stability. We did a secondary analysis of a multicentre randomized controlled trial on CAP treatment in which 580 patients hospitalized for moderately severe CAP were included. The association between demographic, clinical and biological variables available at inclusion and early clinical stability (stabilization of vital signs within 72 hours with predetermined cut-offs) was assessed by multivariate logistic regression. The association between early clinical stability and mortality, severe adverse events, and length of stay was also tested. Younger age (OR 0.98, 95% CI 0.96-0.99), lower platelet count (OR per 10 G/L increment 0.96, 95% CI 0.94-0.98), lower respiratory rate (OR 0.94, 95% CI 0.90-0.97), absence of hypoxemia (OR 0.58, 95% CI 0.40-0.85), lower numbers of co-morbid conditions (OR 0.82, 95% CI 0.69-0.98) and signs or symptoms (OR 0.78, 95% CI 0.68-0.90) were significantly associated with early clinical stability. Patients with early clinical stability had lower 90-days mortality (3.4% vs. 11.9%, p<0.001), fewer admissions to the intensive care unit (2.7% vs. 8.0%, p = 0.005) and a shorter length of stay (6.0 days, IQR 4.0-10.0 vs. 10.0 days, IQR 7.0-15.0, p<0.001). Patients with younger age, less co-morbidity, fewer signs or symptoms, less respiratory compromise, and a lower platelet count are more likely to reach early clinical stability. Patients without early clinical stability have a worse prognosis and warrant close scrutiny

β-Lactam Monotherapy vs β-Lactam-Macrolide Combination Treatment in Moderately Severe Community-Acquired Pneumonia: A Randomized Noninferiority Trial.

IMPORTANCE: The clinical benefit of adding a macrolide to a β-lactam for empirical treatment of moderately severe community-acquired pneumonia remains controversial. OBJECTIVE: To test noninferiority of a β-lactam alone compared with a β-lactam and macrolide combination in moderately severe community-acquired pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Open-label, multicenter, noninferiority, randomized trial conducted from January 13, 2009, through January 31, 2013, in 580 immunocompetent adult patients hospitalized in 6 acute care hospitals in Switzerland for moderately severe community-acquired pneumonia. Follow-up extended to 90 days. Outcome assessors were masked to treatment allocation. INTERVENTIONS: Patients were treated with a β-lactam and a macrolide (combination arm) or with a β-lactam alone (monotherapy arm). Legionella pneumophila infection was systematically searched and treated by addition of a macrolide to the monotherapy arm. MAIN OUTCOMES AND MEASURES: Proportion of patients not reaching clinical stability (heart rate <100/min, systolic blood pressure >90 mm Hg, temperature <38.0°C, respiratory rate <24/min, and oxygen saturation >90% on room air) at day 7. RESULTS: After 7 days of treatment, 120 of 291 patients (41.2%) in the monotherapy arm vs 97 of 289 (33.6%) in the combination arm had not reached clinical stability (7.6% difference, P = .07). The upper limit of the 1-sided 90% CI was 13.0%, exceeding the predefined noninferiority boundary of 8%. Patients infected with atypical pathogens (hazard ratio [HR], 0.33; 95% CI, 0.13-0.85) or with Pneumonia Severity Index (PSI) category IV pneumonia (HR, 0.81; 95% CI, 0.59-1.10) were less likely to reach clinical stability with monotherapy, whereas patients not infected with atypical pathogens (HR, 0.99; 95% CI, 0.80-1.22) or with PSI category I to III pneumonia (HR, 1.06; 95% CI, 0.82-1.36) had equivalent outcomes in the 2 arms. There were more 30-day readmissions in the monotherapy arm (7.9% vs 3.1%, P = .01). Mortality, intensive care unit admission, complications, length of stay, and recurrence of pneumonia within 90 days did not differ between the 2 arms. CONCLUSIONS AND RELEVANCE: We did not find noninferiority of β-lactam monotherapy in patients hospitalized for moderately severe community-acquired pneumonia. Patients infected with atypical pathogens or with PSI category IV pneumonia had delayed clinical stability with monotherapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00818610

Downsizing a human inflammatory protein to a small molecule with equal potency and functionality

A significant challenge in chemistry is to rationally reproduce the functional potency of a protein in a small molecule, which is cheaper to manufacture, non-immunogenic, and also both stable and bioavailable. Synthetic peptides corresponding to small bioactive protein surfaces do not form stable structures in water and do not exhibit the functional potencies of proteins. Here we describe a novel approach to growing small molecules with protein-like potencies from a functionally important amino acid of a protein. A 77-residue human inflammatory protein (complement C3a) important in innate immunity is rationally transformed to equipotent small molecules, using peptide surrogates that incorporate a turn-inducing heterocycle with correctly positioned hydrogen-bond-accepting atoms. Small molecule agonists (molecular weigh

Is positive communication sufficient to modulate procedural pain and anxiety in the emergency room? A randomized controlled trial.

Research suggests that therapeutic communication could enhance patient comfort during medical procedures. Few studies have been conducted in clinical settings, with adequate blinding. Our hypothesis was that a positive message could lead to analgesia and anxiolysis, and that this effect would be enhanced by an empathetic interaction with the nurse performing the procedure, compared to an audio-taped message. This study aimed to modulate the contents and delivery vector of a message regarding peripheral intravenous catheter (PIC) placement in the emergency room (ER). This study was a 2 + 2 randomized controlled trial registered on clinicaltrials.gov (NCT03502655). A positive versus standard message was delivered through audio tape (double blind) in the first phase (N = 131) and through the nurse placing the catheter (single blind) in the second phase (N = 120). By design, low practitioner empathic behavior was observed in the first phase (median 1 out of 5 points). In the second phase, higher empathic behavior was observed in the positive than in the standard message (median 2 vs. 3, p < 0.001). Contrary to our hypothesis, the intervention did not affect pain nor anxiety reports due to PIC placement in either phase (all p values>0.2). The positive communication intervention did not impact pain nor anxiety reports following PIC. There might have been a floor effect, with low PIC pain ratings in a context of moderate pain due to the presenting condition. Hence, such a therapeutic communication intervention might not be sufficient to modulate a mild procedural pain in the ER

Perceived Hospital Preparedness Is Negatively Associated With Pandemic-Induced Psychological Vulnerability in Primary Care Employees: A Multicentre Cross-Sectional Observational Study.

The COVID-19 pandemic had a profound negative impact on the psychological wellbeing of healthcare providers (HPs), but little is known about the factors that positively predict mental health of primary care staff during these dire situations. We conducted an online questionnaire survey among 702 emergency department workers across 10 hospitals in Switzerland and Belgium following the first COVID-19 wave in 2020, to explore their psychological vulnerability, perceived concerns, self-reported impact and level of pandemic workplace preparedness. Participants included physicians, nurses, psychologists and nondirect care employees (administrative staff). We tested for predictors of psychological vulnerability through both an exploratory cross-correlation with rigorous correction for multiple comparisons and model-based path modelling. Findings showed that the self-reported impact of COVID-19 at work, concerns about contracting COVID-19 at work, and a lack of personal protective equipment were strong positive predictors of Depression, Anxiety, and Stress, and low Resilience. Instead, knowledge of the degree of preparedness of the hospital/department, especially in the presence of a predetermined contingency plan for an epidemic and training sessions about protective measures, showed the opposite effect, and were associated with lower psychological vulnerability. All effects were confirmed after accounting for confounding factors related to gender, age, geographical location and the role played by HPs in the hospital/department. Difficult working conditions during the pandemic had a major impact on the psychological wellbeing of emergency department HPs, but this effect might have been lessened if they had been informed about adequate measures for minimizing the risk of exposure

Safety of the pulmonary embolism rule-out criteria rule: Findings from the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) registry.

The diagnostic strategy for pulmonary embolism (PE) includes a D-dimer test when PE probability is low or intermediate, but false-positive D-dimer results are frequent and can result in an unnecessary computed tomography pulmonary angiogram. The PE rule-out criteria (PERC) rule excludes PE without D-dimer testing when pretest probability is <15%. The aim of this study was to assess the safety of the PERC rule strategy in patients included in the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) registry. This retrospective cohort study used data from the RIETE registry, an ongoing, international prospective registry of patients with objectively confirmed venous thromboembolism. The primary outcome was the failure rate of the PERC strategy, represented by the proportion of PERC-negative (PERC-N) patients with a PE included in the registry. Secondary outcomes were a comparison of the clinical characteristics, treatment strategy, and outcome of PERC-N versus PERC-positive (PERC-P) patients at 3 months. From 2001 to 2021, a total of 49,793 patients with acute PE were enrolled in the RIETE registry. We included 48,903 in the final analysis after exclusion of 890 patients with an undetermined PERC status. Only 346 patients were PERC-N with a failure rate of 0.7% (95% confidence interval 0.6%-0.8%). PERC-N patients presented more frequently with chest pain but less often with dyspnea, syncope, or hypotension. They also had subsegmental or segmental PE more frequently, were more often treated with direct oral anticoagulants, and received mechanical or pharmacological thrombolysis less often. In addition, PERC-N patients had a lower incidence of recurrent deep vein thrombosis, major bleeding, and death attributed to PE during the 3-month follow-up. A low failure rate of the PERC rule was observed in the RIETE registry, thus supporting its use to safely identify patients with an unlikely probability of PE

Reliability of the revised Swiss Emergency Triage Scale: a computer simulation study.

The Swiss Emergency Triage Scale (SETS) is a four-level emergency scale that previously showed moderate reliability and high rates of undertriage due to a lack of standardization. It was revised to better standardize the measurement and interpretation of vital signs during the triage process. The aim of this study was to explore the inter-rater and test-retest reliability, and the rate of correct triage of the revised SETS. Thirty clinical scenarios were evaluated twice at a 3-month interval using an interactive computerized triage simulator by 58 triage nurses at an urban teaching emergency department admitting 60 000 patients a year. Inter-rater and test-retest reliabilities were determined using κ statistics. Triage decisions were compared with a gold standard attributed by an expert panel. Rates of correct triage, undertriage, and overtriage were computed. A logistic regression model was used to identify the predictors of correct triage. A total of 3387 triage situations were analyzed. Inter-rater reliability showed substantial agreement [mean κ: 0.68; 95% confidence interval (CI): 0.60-0.78] and test-retest almost perfect agreement (mean κ: 0.86; 95% CI: 0.84-0.88). The rate of correct triage was 84.1%, and rates of undertriage and overtriage were 7.2 and 8.7%, respectively. Vital sign measurement was an independent predictor of correct triage (odds ratios for correct triage: 1.29 for each additional vital sign measured, 95% CI: 1.20-1.39). The revised SETS incorporating standardized vital sign measurement and interpretation during the triage process resulted in high reliability and low rates of mistriage

The role of resection in hepatocellular carcinoma BCLC stage B: A multi-institutional patient-level meta-analysis and systematic review

Purpose: The Barcelona Clinic Liver Cancer (BCLC) staging schema is widely used for hepatocellular carcinoma (HCC) treatment. In the updated recommendations, HCC BCLC stage B can become candidates for transplantation. In contrast, hepatectomy is currently not recommended. Methods: This systematic review includes a multi-institutional meta-analysis of patient-level data. Survival, postoperative mortality, morbidity and patient selection criteria for liver resection and transplantation in BCLC stage B are explored. All clinical studies reporting HCC patients with BCLC stage B undergoing liver resection or transplantation were included. Results: A total of 31 studies with 3163 patients were included. Patient level data was available for 580 patients from 9 studies (423 after resection and 157 after transplantation). The overall survival following resection was 50 months and recurrence-free survival was 15 months. Overall survival after transplantation was not reached and recurrence-free survival was 45 months. The major complication rate after resection was 0.11 (95%-CI, 0.0-0.17) with the 90-day mortality rate of 0.03 (95%-CI, 0.03–0.08). Child-Pugh A (93%), minor resection (60%), alpha protein level less than 400 (64%) were common in resected patients. Resected patients were mostly outside the Milan criteria (99%) with mean tumour number of 2.9. Studies reporting liver transplantation in BCLC stage B were scarce. Conclusion: Liver resection can be performed safely in selected patients with HCC BCLC stage B, particularly if patients present with preserved liver function. No conclusion can done on liver transplantation due to scarcity of reported studies

Determination of the Relative Sign of the Higgs Boson Couplings to W and Z Bosons Using WH Production via Vector-Boson Fusion with the ATLAS Detector

The associated production of Higgs and W bosons via vector-boson fusion is highly sensitive to the relative sign of the Higgs boson couplings to W and Z bosons. In this Letter, two searches for this process are presented, using 140 fb^{-1} of proton-proton collision data at sqrt[s]=13 TeV recorded by the ATLAS detector at the LHC. The first search targets scenarios with opposite-sign couplings of the W and Z bosons to the Higgs boson, while the second targets standard model-like scenarios with same-sign couplings. Both analyses consider Higgs boson decays into a pair of b quarks and W boson decays with an electron or muon. The data exclude the opposite-sign coupling hypothesis with a significance beyond 5σ, and the observed (expected) upper limit set on the cross section for vector-boson fusion WH production is 9.0 (8.7) times the standard model value at 95% confidence level