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Copyright of Contemporary Accounting Research is the property of Canadian Academic Accounting Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Real-world clinical experience of using anti-programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer (SCLC) patients has rarely been reported. In this study, we aimed to perform a retrospective multicenter clinical analysis of extensive-stage SCLC patients receiving first-line therapy with anti-PD-L1 ICIs combined with chemotherapy. Between November 2018 and March 2022, 72 extensive-stage SCLC patients receiving first-line atezolizumab or durvalumab in combination with chemotherapy, according to the cancer center databases of Linkou, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals, were retrospectively included in the analysis. Twenty-one patients (29.2%) received atezolizumab and fifty-one (70.8%) received durvalumab. Objective response (OR) and disease control (DC) rates of 59.7% and 73.6%, respectively, were observed with first-line ICI plus chemotherapy. The median progression-free survival (PFS) was 6.63 months (95% confidence interval (CI), 5.25–8.02), and the median overall survival (OS) was 16.07 months (95% CI, 15.12–17.0) in all study patients. A high neutrophil-to-lymphocyte ratio (NLR; >4) and a high serum lactate dehydrogenase (LDH) concentration (>260 UL) were identified as independent unfavorable factors associated with shorter OS in the multivariate analysis. Regarding safety, neutropenia was the most common grade 3 treatment-related adverse event (AE), but no treatment-related deaths occurred in the study patients. First-line anti-PD-L1 ICIs combined with chemotherapy are effective and safe for male extensive-stage SCLC patients. Further therapeutic strategies may need to be developed for patients with unfavorable outcomes (e.g., baseline high NLR and serum LDH level). [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the factors associated with prolonged progression‐free survival (PFS) (>36 months) of advanced non‐small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations treated with first‐line afatinib. Methods: We performed a retrospective analysis of data of patients with advanced EGFR‐mutated NSCLC receiving first‐line afatinib at two tertiary care referral centers, Linkou and Kaohsiung Chang Gung Memorial Hospital, in Taiwan between June 2014 and April 2022. Results: The data of 546 treatment‐naïve EGFR‐mutated advanced NSCLC patients were analyzed. Median PFS and overall survival were 14.5 months and 27.2 months, respectively. The PFS of 462 patients (84.6%) was less than 36 months and of 84 patients (15.4%) was more than 36 months. The PFS > 36 months group had a significantly higher percentage of patients with uncommon mutations (p = 0.002). The PFS ≤36 months group had significantly higher incidences of bone, liver, and adrenal metastases (all p < 0.05) and a higher rate of multiple distant metastases. Multivariate logistic regression analysis showed that liver metastasis was negatively and independently associated with prolonged PFS (adjusted odds ratio = 0.246 [95% CI: 0.067–0.908], p = 0.035). The median overall survival of the PFS >36 months group was 46.0 months and that of the PFS ≤36 months group was 22.9 months (log‐rank test, p < 0.001). Conclusions: We found that EGFR‐mutated NSCLC patients receiving first‐line afatinib were prone to shorter PFS if they had distant organ metastasis, especially liver metastasis. [ABSTRACT FROM AUTHOR]

In common-law systems, firms' litigation risk depends both on written laws and how courts interpret these laws. Using 321 US circuit court rulings, we introduce a novel measure capturing courts' attitudes toward defendants in securities lawsuits. Our results confirm that financial misreporting firms in more defendant-friendly circuits face fewer lawsuits. Consistent with lower expected litigation costs, firms in these circuits face less negative market reactions when misreporting is revealed, invest less in preventing misreporting, and are more likely to engage in aggressive misreporting. We conclude that defendant-friendly precedents reduce firms' legal liability and worsen their financial reporting quality. [ABSTRACT FROM AUTHOR]

Background: Substitution of methionine for threonine at codon 790 (T790M) of epidermal growth factor receptor (EGFR) represents the major mechanism of resistance to EGFR tyrosine kinase inhibitors (TKIs) in EGFR -mutant non-small-cell lung cancer. We determined the prognostic impact and association of secondary T790M mutations with the outcomes of osimertinib and chemotherapy. Methods: Patients (n = 460) progressing from first-line EGFR-TKI treatment were assessed. Tissue and/or liquid biopsies were used to determine T790M status; post-progression overall survival (OS) was analyzed. Results: Overall, 143 (31.1%) patients were T790M positive, 95 (20.7%) were T790M negative, and 222 (48.2%) had unknown T790M status. T790M status [T790M positive versus T790M negative: hazard ratio (HR) 0.48 (95% confidence interval (CI), 0.32–0.70); p < 0.001, T790M unknown versus T790M negative: HR 1.97 (95% CI, 1.47–2.64); p < 0.001] was significantly associated with post-progression OS. T790M positivity rates were similar for tissue (90/168, 53.6%) and liquid (53/90, 58.9%) biopsies (Fisher's exact test, p = 0.433). Tumor T790M-positive patients had significantly longer post-progression OS than tumor T790M-negative patients (34.1 versus 17.1 months; log-rank test, p = 8 × 10−5). Post-progression OS was similar between plasma T790M-positive and -negative patients (17.4 versus not reached; log-rank test, p = 0.600). In tumor T790M-positive patients, post-progression OS was similar after osimertinib and chemotherapy [34.1 versus 29.1 months; log-rank test, p = 0.900; HR 1.06 (95% CI, 0.44–2.57); p = 0.897]. Conclusion: T790M positivity predicts better post-progression OS than T790M negativity; tumor T790M positivity has a stronger prognostic impact than plasma T790M positivity. Osimertinib and chemotherapy provide similar OS benefits in patients with T790M-positive tumors. Plain language summary: Different prognostic meaning of tumor resistant gene detected from tumor or blood in patients with EGFR-mutant lung cancer The study demonstrates that patients with EGFR-mutant lung cancer who develop resistance due to a secondary T790M mutation, defined by tumor or blood T790M positivity, achieve better survival than patients without secondary T790M mutation; this association was mainly contributed by tumour T790M positivity. Oismertinib and chemotherapy led to similar survival in tumour T790M-positive patients. However, compared to osimertinib, chemotherapy was associated with longer survival in blood T790M-positive patients. [ABSTRACT FROM AUTHOR]

Background: Frailty is a complex condition that primary care providers (PCPs) are managing in increasing numbers, yet there is no clear guidance or training for frailty care. Objectives: The present study examined eConsult questions PCPs asked specialists about patients with frailty, the specialists' responses, and the impact of eConsult on the care of these patients. Design: Cross-sectional observational study. Setting: ChamplainBASE™ eConsult located in Eastern Ontario, Canada. Participants: Sixty one eConsult cases closed by PCPs in 2019 that use the terms "frail" or "frailty" to describe patients 65 years of age or older. Measurements: The Taxonomy of Generic Clinical Questions (TGCQ) was used to classify PCP questions and the International Classification for Primary Care 3 (ICPC-3) was used to classify the clinical content of each eConsult. The impact of eConsult on patient care was measured by PCP responses to a mandatory survey. Results: PCPs most frequently directed their questions to cardiology (n = 7; 11%), gastroenterology (n = 7; 11%), and endocrinology (n = 6; 10%). Specialist answers most often pertained to medications (n = 63, 46%), recommendations for clinical investigation (n = 24, 17%), and diagnoses (n = 22, 16%). Specialist responses resulted in PCPs avoiding referral in 57% (n = 35) of cases whereas referrals were still required in 15% (n = 9) of cases. Specialists responded to eConsults in a median 1.11 days (IQR = 0.3–4.7), and 95% (n = 58) of cases received a response within 7 days. Specialists recorded a median of 15 min to respond (IQR = 10–20), with a median cost of $50.00 CAD (IQR = 33.33 – 66.66) per eConsult. Conclusions: Through the analysis of questions and responses submitted to eConsult, this study provides novel information on PCP knowledge gaps and approaches to care for patients living with frailty. Furthermore, these analyses provide evidence that eConsult is a feasible and valuable tool for improving care for patients with frailty in primary care settings. [ABSTRACT FROM AUTHOR]

This study examines whether and when credit ratings are useful for accounting fraud prediction. We find that negative rating actions by Standard & Poor's (S&P), an issuer-paid credit rating agency (CRA), have predictive ability for fraud incremental to fraud prediction models (e.g., F-score) and other market participants. In contrast, rating actions by Egan-Jones Rating Company (EJR), an investor-paid CRA relying on public information, have less predictive ability, which is subsumed by S&P and other market participants. Our results are robust to including firms not covered by EJR, using only rating downgrades, controlling for firm characteristics, and using alternative benchmarks. We also find that the ability of negative S&P rating actions to predict fraud becomes stronger after the 2008–2009 financial crisis. Last, compared with EJR, S&P is quicker to take negative rating actions against fraud firms. In sum, our results suggest that issuer-paid CRAs' information advantage helps predict accounting fraud. Data Availability: Data are available from the public sources cited in the text. JEL classifications: G24; K22; M41. [ABSTRACT FROM AUTHOR]

Background: Frailty has emerged as an important prognostic marker of increased mortality after cardiac surgery, but its association with quality of life (QoL) and patient‐centered outcomes is not fully understood. We sought to evaluate the association between frailty and such outcomes in older patients undergoing cardiac surgery. Methods: This systematic review included studies evaluating the effect of preoperative frailty on QoL outcomes after cardiac surgery amongst patients 65 years and older. The primary outcome was patient's perceived change in QoL following cardiac surgery. Secondary outcomes included residing in a long‐term care facility for 1 year, readmission in the year following the intervention, and discharge destination. Screening, inclusion, data extraction, and quality assessment were performed independently by two reviewers. Meta‐analyses based on the random‐effects model were conducted. The evidential quality of findings was assessed with the GRADE profiler. Results: After the identification of 3105 studies, 10 observational studies were included (1580 patients) in the analysis. Two studies reported on the change in QoL following cardiac surgery, which was higher for patients with frailty than for patients without. Preoperative frailty was associated with both hospital readmission (pooled odds ratio [OR] 1.48 [0.80–2.74], low GRADE level) as well as non‐home discharge (pooled OR 3.02 [1.57–5.82], moderate GRADE level). Conclusion: While evidence in this field is limited by heterogeneity of frailty assessment and non‐randomized data, we demonstrated that baseline frailty may possibly be associated with improved QoL, but with increased readmission as well as discharge to a non‐home destination following cardiac surgery. These patient‐centered outcomes are important factors when considering interventional options for older patients. Study Registration: OSF registries (https://osf.io/vm2p8). [ABSTRACT FROM AUTHOR]

Background: Older adults with frailty are at an increased risk of adverse outcomes after surgery. Exercise before surgery (exercise prehabilitation) may reduce adverse events and improve recovery after surgery. However, adherence with exercise therapy is often low, especially in older populations. The purpose of this study was to qualitatively assess the barriers and facilitators to participating in exercise prehabilitation from the perspective of older people with frailty participating in the intervention arm of a randomized trial. Methods: This was a research ethics approved, nested descriptive qualitative study within a randomized controlled trial of home-based exercise prehabilitation vs. standard care with older patients (≥ 60 years) having elective cancer surgery, and who were living with frailty (Clinical Frailty Scale ≥ 4). The intervention was a home-based prehabilitation program for at least 3 weeks before surgery that involved aerobic activity, strength and stretching, and nutritional advice. After completing the prehabilitation program, participants were asked to partake in a semi-structured interview informed by the Theoretical Domains Framework (TDF). Qualitative analysis was guided by the TDF. Results: Fifteen qualitative interviews were completed. Facilitators included: 1) the program being manageable and suitable to older adults with frailty, 2) adequate resources to support engagement, 3) support from others, 4) a sense of control, intrinsic value, noticing progress and improving health outcomes and 5) the program was enjoyable and facilitated by previous experience. Barriers included: 1) pre-existing conditions, fatigue and baseline fitness, 2) weather, and 3) guilt and frustration when unable to exercise. A need for individualization and variety was offered as a suggestion by participants and was therefore described as both a barrier and facilitator. Conclusions: Home-based exercise prehabilitation is feasible and acceptable to older people with frailty preparing for cancer surgery. Participants identified that a home-based program was manageable, easy to follow with helpful resources, included valuable support from the research team, and they reported self-perceived health benefits and a sense of control over their health. Future studies and implementation should consider increased personalization based on health and fitness, psychosocial support and modifications to aerobic exercises in response to adverse weather conditions. [ABSTRACT FROM AUTHOR]

Objective: To determine how surgery, continuous positive airway pressure (CPAP), and no treatment impact health care utilization in patients who have obstructive sleep apnea (OSA). Study Design: This is a retrospective cohort study of patients between the ages of 18 and 65 that were diagnosed with OSA (9th International Classification of Diseases) from January 2007 to December 2015. Data were collected over 2 years, and prediction models were generated to evaluate trends over time. Setting: A population‐based study using real‐world data and insurance databases. Methods: A total of 4,978,649 participants were identified, all with at least 25 months of continuous enrollment. Patients with previous soft tissue procedures not approved for OSA (nasal surgery), or without continuous insurance coverage were excluded. A total of 18,050 patients underwent surgery, 1,054,578 were untreated, and 799,370 received CPAP. IBM Marketscan Research database was utilized to describe patient‐specific clinical utilization, and expenditures, across outpatient, and inpatient services, and medication prescriptions. Results: When the cost of the intervention was eliminated in the 2‐year follow‐up, the monthly payments of group 1 (surgery) were significantly less than group 3 (CPAP) in overall, inpatient, outpatient, and pharmaceutical payments (p <.001). The surgery group was associated with less cumulative payments compared to the other 2 groups when the cost of the intervention (CPAP or surgery) was eliminated in all comorbidities and age groups. Conclusion: Treating OSA with surgery can lessen overall health care utilization compared to no treatment and CPAP. [ABSTRACT FROM AUTHOR]

Background: Real-world clinical experience with afatinib as a treatment for advanced lung adenocarcinoma harboring uncommon epidermal growth factor receptor (EGFR) mutations (G719X, L861Q and S768I) has rarely been reported. Objective: We aimed to perform a retrospective multicenter study to analyze afatinib therapy in untreated advanced lung adenocarcinoma harboring uncommon EGFR mutations. Patients and Methods: Between May 2014 and June 2021, the data of 90 stage IIIB/IV lung adenocarcinoma patients with uncommon EGFR mutations (G719X/L861Q/S768I) treated with first-line afatinib from the cancer center database of Linkou, Tucheng, and Kaohsiung Chang Gung Memorial Hospitals were retrospectively retrieved and analyzed. Results: Afatinib had an objective response rate (ORR) of 63.3% and a disease control rate (DCR) of 86.7%. The median progression-free survival (PFS) with first-line afatinib therapy was 17.3 months (95% confidence interval (CI), 12.07–22.53), and the median overall survival (OS) was 28.5 months (95% CI, 20.22–36.77) in all study patients. In the multivariate analysis, poor performance (Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2) and brain and liver metastases were independent predictors of unfavorable PFS. The G719X mutation (alone+compound) was an independent predictor of favorable PFS (hazard ratio (HR) = 0.578; 95% CI, 0.355−0.941; P = 0.027). Most afatinib-related adverse events (AEs) were limited to grades 1 and 2 and were manageable. Conclusions: First-line afatinib therapy is effective and safe for advanced lung adenocarcinoma harboring uncommon EGFR mutations. The G719X mutation was an independent factor associated with a favorable outcome. Poor performance (ECOG PS ≥ 2), brain metastasis, and liver metastasis were predictive factors of shorter PFS with first-line afatinib therapy. [ABSTRACT FROM AUTHOR]

In 2005, the SEC mandated that firms disclose risk factors to provide useful information about firm risk. An unintended effect of the mandate is that mandatory risk factor (RF) disclosure may constitute "meaningful cautionary language" as defined in the Private Securities Litigation Reform Act, and may therefore provide legal protection for forward-looking statements (FLSs). Using both a difference-in-differences design and a two-stage least squares approach, we find that, following the mandate, firms that had not previously disclosed risk factors (late RF disclosers) became more willing to provide qualitative FLSs, particularly positive ones, than other firms. This finding is consistent with our prediction that, for late RF disclosers, the mandate reduces managers' perceived litigation risk. We also find that these firms experience improvement in their information environment. A path analysis reveals that the mandate improves firms' information environment not only directly but also indirectly by prompting more disclosure of positive FLSs, illustrating an unintended benefit of the 2005 RF mandate. Cross-sectional tests show that the RF mandate induces a larger increase in positive FLSs for firms whose managers perceive a higher level of benefit from safe harbor protection arising from meaningful cautionary statements. [ABSTRACT FROM AUTHOR]

Cardiorenal syndrome type I (CRS I) is defined as the development of acute kidney injury (AKI) following acute decompensated heart failure (ADHF). The clinical significance of endothelial markers in ADHF-associated AKI has yet to be clarified. This study therefore investigated the biological processes linking ADHF and AKI with the aim of determining whether the plasma markers of endothelial injury and activation are associated with AKI in patients with ADHF. The study prospectively recruited 125 consecutive patients admitted to a coronary critical unit due to ADHF. Patients with and without AKI were compared in terms of soluble thrombomodulin (sTM), angiopoietin (Ang)-1 and −2 plasma levels as well as baseline characteristics. Among the study population, 14 (11.2%) patients developed CRS within 7 days after admission. The hemoglobin levels (median [IQR]11.3[10.8–12.6] vs. 13.5 [12.2–15.0] g/dL, p = 0.003) and baseline eGFR (66.5[35.7–87.9] vs. 78.5 [64.9–107.5] mL/minute/1.73m2, p = 0.044) of patients with CRS were lower than those of patients without CRS. Patients with CRS also presented elevated plasma levels of BNP (1317.5 [222.6–3375.5] vs. 258.2 [63.2–925.8] pg/mL, p = 0.008), Ang-2 (3993.0 [1561.3–15722.7] vs. 1805.9 [1196.9–3302.3] pg/mL, p = 0.006), and sTM (6665.7 [4707.1–11947.3] vs. 4132.2 [3338.0–5531.8] ng/mL, p < 0.001), compared to patients without CRS. Multivariate logistic regression analysis based on forward stepwise method identified that log sTM was the only independent risk factor for AKI (OR, 13.83; 3.02–63.28, p = 0.001). Furthermore, higher sTM levels were associated with AKI in patients with ADHF. These findings suggest a novel approach to dealing with kidney injury in the context of ADHF, involving the use of baseline biomarker profiles to identify individuals at risk of developing AKI. The clinical significance of endothelial markers in acute decompensated heart failure (ADHF)-associated acute kidney injury (AKI) has not previously been clarified. This study revealed that markers of endothelial injury (i.e. plasma soluble thrombomodulin (sTM) levels) were higher in ADHF patients with AKI than in those without AKI. Multivariate analysis identified sTM level > cutoff value of 4,855.2 pg/mL as an independent factor associated with the development of AKI. sTM could potentially be used as a biomarker to predict the development of AKI in patients with heart failure. These findings suggest a novel approach to dealing with kidney injury in the context of ADHF, involving the use of baseline biomarker profiles to identify individuals at risk of developing AKI. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Anaesthesia / Journal Canadien d'Anesthésie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Although bevacizumab in combination with afatinib or erlotinib is an effective and safe first-line therapy for advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC), there are very few clinical data comparing afatinib and erlotinib combined with bevacizumab. We performed a retrospective multicenter analysis for the comparison of two combination therapies. Methods: Between May 2015 and October 2020, data of 135 stage IIIB/IV EGFR-mutated NSCLC patients receiving first-line afatinib or erlotinib combined with bevacizumab combination therapy in Linkou, Keelung, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals were retrieved and retrospectively analyzed. Results: In all, 67 patients received afatinib plus bevacizumab, and 68 patients received erlotinib plus bevacizumab. Afatinib combined with bevacizumab had an objective response rate (ORR) of 82.1% and a disease control rate (DCR) of 97.0%, and the ORR and DCR were 83.8 and 95.6%, respectively, in the erlotinib combined with bevacizumab group (p = 0.798 and p = 1.000). The median progression-free survival was 20.7 and 20.3 months for the afatinib plus bevacizumab group and the erlotinib plus bevacizumab group, respectively [hazard ratio (HR) = 1.02; 95% confidence interval (CI), 0.891–1.953; p = 0.167). The overall survival was 41.9 and 51.0 months for the afatinib plus bevacizumab group and erlotinib plus bevacizumab group, respectively (HR = 1.42; 95% CI, 0.829–2.436; p = 0.201). The secondary EGFR-T790M mutation rates after disease progression were 44% in the afatinib plus bevacizumab group and 58.8% in the erlotinib plus bevacizumab group (p = 0.165). Skin toxicity was the most frequent treatment-related adverse event (AE) in both treatment groups. Diarrhea, an AE, occurred significantly more frequently in the afatinib plus bevacizumab group than in the erlotinib plus bevacizumab group (p < 0.05). Conclusion: Afatinib combined with bevacizumab was equally as effective as erlotinib combined with bevacizumab for untreated advanced EGFR-mutated NSCLC. Prospective clinical studies that explore bevacizumab combined with afatinib or erlotinib for advanced EGFR-mutated NSCLC are warranted. Graphic abstract [ABSTRACT FROM AUTHOR]

This paper studies the long‐term consequences of actions induced by vesting equity, a measure of short‐term incentives. Vesting equity is positively associated with the probability of a firm repurchasing shares, the amount of shares repurchased, and the probability of the firm announcing a merger and acquisition (M&A). However, it is also associated with more negative long‐term returns over two to three years following repurchases and four years following M&A, as well as future M&A goodwill impairment. These results are inconsistent with CEOs buying underpriced stock or companies to maximize long‐run shareholder value, but consistent with these actions being used to boost the short‐term stock price and thus equity sale proceeds. CEOs sell their own stock shortly after using company money to buy the firm's stock, also inconsistent with repurchases being motivated by undervaluation. [ABSTRACT FROM AUTHOR]

The epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) afatinib improves survival in nonsmall cell lung cancer (NSCLC) patients with EGFR mutation. We analysed the outcome between EGFR mutation subtypes in a large afatinib‐treated cohort in which 516 EGFR‐mutated NSCLC patients receiving afatinib as front‐line treatment. EGFR uncommon mutations include exon 20 insertion, de novo T790M of high or low allele frequency (dT790MHAF/dT790MLAF), non‐T790M compound mutation and others, where EGFR exon 20 insertion and dT790MHAF were defined as type‐I and the rest as type‐II uncommon mutation. Four hundred and sixty‐one (89.3%) and 55 (10.7%) patients were common and uncommon mutation, respectively. Exon 20 insertion and dT790MHAF patients demonstrated a significantly shortened progression‐free survival (PFS) (2.6 and 4.1 months) compared to EGFR common mutation, dT790MLAF and other uncommon mutation patients (15.1, 27.0 and 18.4 months; P = 3 × 10−8). Type‐I uncommon mutation was an independent predictor of PFS (HR 4.46 [95% CI, 2.60‐7.64]; P <.001) and OS (HR 2.56 [95% CI, 1.37‐4.75]; P =.003). EGFR L858R patients demonstrated a significantly higher CNS progression (cause‐specific HR, 3.16; 95% CI 1.24‐8.08; P =.016), and type‐I uncommon mutation patients exhibited a significantly higher systemic progression (cause‐specific HR, 4.95; 95% CI 2.30‐10.60; P = 4.3 × 10−5). Tendencies of higher CNS and lower systemic progression were observed in type‐II uncommon mutation patients. A PFS ≥ 12 months (OR 2.38 [95% CI, 1.18‐4.89]; P =.016) and uncommon EGFR mutation (OR 0.08 [95% CI, 0.01‐0.48]; P =.021) were independent predictors of secondary T790M. Afatinib‐treated NSCLC patients presented an EGFR genotype‐specific pattern of disease progression and outcome. What's new? For patients with nonsmall cell lung cancer (NSCLC), epidermal growth factor tyrosine kinase inhibitors (EGFR‐TKIs) can significantly improve survival. EGFG‐TKI effectiveness, however, is compromised by acquired EGFR mutations, especially de novo T790M mutations. Here, the impact of EGFR genotypes on the efficacy of afatinib, a second‐generation EGFR‐TKI, was investigated in a cohort of EGFR‐mutated NSCLC patients. Afatinib efficacy was associated with T790M allele quantity in patients with de novo T790M mutation. In particular, front‐line afatinib therapy was associated with favourable survival in EGFR‐mutated patients, whereas resistance was marked by a genotype‐specific pattern of disease progression, with secondary T790M development. [ABSTRACT FROM AUTHOR]

Background: Frailty has emerged as an important prognostic marker of adverse outcomes after cardiac surgery, but evidence regarding its ability to predict quality of life after cardiac surgery is currently lacking. Whether frail patients derive the same quality of life benefit after cardiac surgery as patients without frailty remains unclear. Methods: This systematic review will include interventional studies (RCT and others) and observational studies evaluating the effect of preoperative frailty on quality-of-life outcomes after cardiac surgery amongst patients 65 years and older. Studies will be retrieved from major databases including the Cochrane Central Register of Controlled Trials, Embase, and Medline. The primary exposure will be frailty status, independent of the tool used. The primary outcome will be change in quality of life, independent of the tool used. Secondary outcomes will include readmission during the year following the index intervention, discharge to a long-term care facility and living in a long-term care facility at one year. Screening, inclusion, data extraction and quality assessment will be performed independently by two reviewers. Meta-analysis based on the random-effects model will be conducted to compare the outcomes between frail and non-frail patients. The evidential quality of the findings will be assessed with the GRADE profiler. Conclusion: The findings of this systematic review will be important to clinicians, patients and health policy-makers regarding the use of preoperative frailty as a screening and assessment tool before cardiac surgery. Study registration: OSF registries (https://osf.io/vm2p8). [ABSTRACT FROM AUTHOR]

Introduction Frailty is a robust predictor of adverse outcomes in older people. Practice guidelines recommend routine screening for frailty; however, this does not occur regularly. The Clinical Frailty Scale (CFS) is a validated, feasible instrument that can be used in a variety of clinical settings and is associated with many adverse outcomes. Our objective was to develop and evaluate an online training module to guide frailty assessment using the CFS. Methods A multidisciplinary team of clinical experts developed an evidence-based, theory-grounded online training module for users who wished to perform frailty assessment using the CFS. The module was prospectively evaluated for user satisfaction, effectiveness and feasibility using a standardised questionnaire. Qualitative feedback was analysed with thematic analysis. Results Version 1 of the CFS module was used 627 times from 21 October 2019 to 24 March 2020. Satisfaction, effectiveness and feasibility of the module were positively rated (≥4/5 on a 5-point Likert scale n  = 582 [93%], n  = 507, [81%], n  = 575, [91%], respectively). Qualitative feedback highlighted ease of use, likelihood of users to share the module with others and opportunities to increase multimedia content. Conclusion An online tutorial, designed using evidence and theory to guide frailty assessment using the CFS, was positively rated by users. The module's content and structure was rated effective and feasible, and users were satisfied with, and likely to share, the module. Research evaluating the module's impact on the accuracy of frailty assessment is required. [ABSTRACT FROM AUTHOR]

Introduction: The clinical features of patients with metastatic epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma receiving first-line therapy based on erlotinib combined with bevacizumab are unclear. Here, we sought to analyze the clinical features of this patient group. Methods: Data were analyzed for the period from January 2015 to August 2019 for 49 patients with metastatic EGFR-mutated lung adenocarcinoma receiving first-line erlotinib-and-bevacizumab combination therapy from the Linkou and Kaohsiung Chang Gung Memorial Hospitals. Results: The combination of erlotinib and bevacizumab showed an 83.7% objective response rate and a 97.9% disease control rate. The median progression-free survival (PFS) and overall survival (OS) were 22.0 [95% CI (19.7–22.33)] and 47.6 [95% CI (38.87–56.37)] months, respectively, for all patients. The secondary EGFR-T790M mutation rate in the patients with acquired resistance to the combination was 72.4%. No predictive factor associated with the appearance of secondary EGFR-T790M mutations was found. The most frequent adverse event (AE) caused by the combination therapy was dermatitis (100%), and most of the AEs were manageable and grades 1 and 2. Conclusion: Erlotinib combined with bevacizumab is an effective and safe therapy for untreated metastatic EGFR-mutated lung adenocarcinoma. The combination does not alter secondary EGFR-T790M mutations in patients with acquired resistance and is feasible in real-world clinical practice. [ABSTRACT FROM AUTHOR]

Background: There are limited comparisons of first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) in large, real-world cohorts of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. Methods: Patients with advanced NSCLC (N = 612) with common EGFR mutations receiving first-line gefitinib/erlotinib and afatinib were grouped and propensity-score matched. Progression-free survival (PFS), overall survival (OS) and secondary T790M mutations were analyzed. Results: The gefitinib/erlotinib and afatinib groups each contained 206 patients after matching. Compared with gefitinib/erlotinib, patients receiving afatinib achieved longer median PFS (16.3 versus 14.2 months; log-rank test p = 0.020) and had a lower risk of progression [hazard ratio (HR) 0.73 (95% confidence interval (CI), 0.57–0.94); p = 0.017]. Median OS (37.3 versus 34.2 months; log-rank test p = 0.500) and reduction in risk of death [HR 0.89 (95% CI, 0.65–1.23); p = 0.476] did not differ significantly between groups. T790M positivity was significantly higher in the gefitinib/erlotinib than afatinib group (70.9% versus 44.6%, p < 0.001). Multivariate analysis demonstrated that afatinib was independently associated with lower T790M positivity [odds ratio (OR) 0.27 (95% CI, 0.14–0.53); p < 0.001], whereas ⩾12 months PFS after EGFR-TKI treatment [OR 3.00 (95% CI, 1.56–5.98); p = 0.001] and brain metastasis [OR 2.12 (95% CI, 1.08–4.26); p = 0.030] were associated with higher T790M positivity. Sequential third-generation EGFR-TKI treatment was administered to 63 patients, in whom median OS after the second–third-generation and first–third-generation EGFR-TKI sequences were 38.8 and 29.1 months, respectively. Conclusion: Compared with gefitinib/erlotinib, afatinib had a higher treatment efficacy and a lower secondary T790M positivity in a large, real-world cohort of Asian patients with EGFR -mutated NSCLC. [ABSTRACT FROM AUTHOR]

Background: Administrative health data are increasingly used to detect adverse drug events (ADEs). However, the few studies evaluating diagnostic codes for ADE detection demonstrated low sensitivity, likely due to narrow code sets, physician under-recognition of ADEs, and underreporting in administrative data. The objective of this study was to determine if combining an expanded ICD code set in administrative data with e-prescribing data improves ADE detection.Methods: We conducted a prospective cohort study among patients newly prescribed antidepressant or antihypertensive medication in primary care and followed for 2 months. Gold standard ADEs were defined as patient-reported symptoms adjudicated as medication-related by a clinical expert. Potential ADEs in administrative data were defined as physician, ED, or hospital visits during follow-up for known adverse effects of the study medication, as identified by ICD codes. Potential ADEs in e-prescribing data were defined as study drug discontinuations or dose changes made during follow-up for safety or effectiveness reasons.Results: Of 688 study participants, 445 (64.7%) were female and mean age was 64.2 (SD 13.9). The study drug for 386 (56.1%) patients was an antihypertensive, and for 302 (43.9%) an antidepressant. Using the gold standard definition, 114 (16.6%) patients experienced an ADE, with 40 (10.4%) among antihypertensive users and 74 (24.5%) among antidepressant users. The sensitivity of the expanded ICD code set was 7.0%, of e-prescribing data 9.7%, and of the two combined 14.0%. Specificities were high (86.0-95.0%). The sensitivity of the combined approach increased to 25.8% when analysis was restricted to the 27% of patients who indicated having reported symptoms to a physician.Conclusion: Combining an expanded diagnostic code set with e-prescribing data improves ADE detection. As few patients report symptoms to their physician, higher detection rates may be achieved by collecting patient-reported outcomes via emerging digital technologies such as patient portals and mHealth applications. [ABSTRACT FROM AUTHOR]

Background: Crizotinib is the approved treatment for advanced non-small cell lung cancers (NSCLCs) of anaplastic lymphoma kinase (ALK) fusion. Failure of crizotinib treatment frequently involves drug intolerance or resistance. Comparison of using second-generation ALK inhibitors in this setting remains lacking.Methods: Sixty-five ALK-positive advanced NSCLC patients receiving second-generation ALK inhibitors following treatment failure of crizotinib were retrospectively analyzed for the therapeutic efficacy.Results: Forty-three (66.2%) and 22 (33.8%) patients received alectinib and ceritinib, respectively. Comparing alectinib to ceritinib treatment: the 12-month progression-free survival (PFS) rate (61.0% [95% confidence interval, 47.1 to 78.9%] vs. 54.5% [95% CI, 37.3 to 79.9%]); the hazard ratio (HR) for disease progression or death, 0.61 (95% CI, 0.31-1.17; p = 0.135). Multivariate Cox regression showed ECOG PS (0-1 vs. 2-3 HR 0.09 [95% CI, 0.02-0.33]; p < 0.001) and cause of crizotinib treatment failure (resistance vs. intolerance HR 2.75 [95% CI, 1.26-5.99]; p = 0.011) were the independent predictors for the PFS of second-generation ALK inhibitors. Treatment of alectinib, compared to ceritinib, was associated with a lower incidence of CNS progression (cause-specific HR, 0.10; 95% CI 0.01-0.78; p = 0.029) and a higher efficacy in patients whose cause of crizotinib treatment failure was intolerance (HR 0.29 [95% CI, 0.08-1.06]; p = 0.050). The most commonly noted adverse events were elevated AST/ALT in 10 (23.3%) patients treated with alectinib and diarrhea in 8 (36.4%) patients treated with ceritinib.Conclusion: Second-generation ALK inhibitors in crizotinib-treated patients showed a satifactory efficacy. Alectinib treatment demonstrated a CNS protection activity and a higher PFS in selected patients failing crizotinib treatment. [ABSTRACT FROM AUTHOR]

Background: There are limited comparisons of first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) in large, real-world cohorts of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. Methods: Patients with advanced NSCLC (N = 612) with common EGFR mutations receiving first-line gefitinib/erlotinib and afatinib were grouped and propensity-score matched. Progression-free survival (PFS), overall survival (OS) and secondary T790M mutations were analyzed. Results: The gefitinib/erlotinib and afatinib groups each contained 206 patients after matching. Compared with gefitinib/erlotinib, patients receiving afatinib achieved longer median PFS (16.3 versus 14.2 months; log-rank test p = 0.020) and had a lower risk of progression [hazard ratio (HR) 0.73 (95% confidence interval (CI), 0.57–0.94); p = 0.017]. Median OS (37.3 versus 34.2 months; log-rank test p = 0.500) and reduction in risk of death [HR 0.89 (95% CI, 0.65–1.23); p = 0.476] did not differ significantly between groups. T790M positivity was significantly higher in the gefitinib/erlotinib than afatinib group (70.9% versus 44.6%, p < 0.001). Multivariate analysis demonstrated that afatinib was independently associated with lower T790M positivity [odds ratio (OR) 0.27 (95% CI, 0.14–0.53); p < 0.001], whereas ⩾12 months PFS after EGFR-TKI treatment [OR 3.00 (95% CI, 1.56–5.98); p = 0.001] and brain metastasis [OR 2.12 (95% CI, 1.08–4.26); p = 0.030] were associated with higher T790M positivity. Sequential third-generation EGFR-TKI treatment was administered to 63 patients, in whom median OS after the second–third-generation and first–third-generation EGFR-TKI sequences were 38.8 and 29.1 months, respectively. Conclusion: Compared with gefitinib/erlotinib, afatinib had a higher treatment efficacy and a lower secondary T790M positivity in a large, real-world cohort of Asian patients with EGFR -mutated NSCLC. [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVES Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection causes high morbidity and mortality in older adults with chronic illnesses. Several trials are currently underway evaluating the antimalarial drug hydroxychloroquine as a potential treatment for acute infection. However, polypharmacy predisposes patients to increased risk of drug‐drug interactions with hydroxychloroquine and may render many in this population ineligible to participate in trials. We aimed to quantify the degree of polypharmacy and burden of potentially inappropriate medications (PIMs) that older hospitalized adults are taking that would interact with hydroxychloroquine. METHODS: We reanalyzed data from the cohort of patients 65 years and older enrolled in the MedSafer pilot study. We first identified patients taking medications with potentially harmful drug‐drug interactions with hydroxychloroquine that might exclude them from participation in a typical 2019 coronavirus disease (COVID‐19) therapeutic trial. Next, we identified medications that were flagged by MedSafer as potentially inappropriate and crafted guidance around medication management if contemplating the use of hydroxychloroquine. RESULTS: The cohort contained a total of 1,001 unique patients with complete data on their home medications at admission. Of these 1,001 patients, 590 (58.9%) were receiving one or more home medications that could potentially interact with hydroxychloroquine, and of these, 255 (43.2%) were flagged as potentially inappropriate by the MedSafer tool. Common classes of PIMs observed were antipsychotics, cardiac medications, and antidiabetic agents. CONCLUSION: The COVID‐19 pandemic highlights the importance of medication optimization and deprescribing PIMs in older adults. By acting now to reduce polypharmacy and use of PIMs, we can better prepare this vulnerable population for inclusion in trials and, if substantiated, pharmacologic treatment or prevention of COVID‐19. J Am Geriatr Soc 68:1636‐1646, 2020. [ABSTRACT FROM AUTHOR]

Background: Treatment for stage III non‐small cell lung cancer (NSCLC) of unresectable disease mainly involves concurrent chemoradiation (CRT). Post‐CRT consolidation treatment with durvalumab is a major therapeutic advance that provides survival benefit in this group of patients. However, the performance of this treatment strategy remains to be studied in a real‐world setting. Methods: A total of 31 patients who had disease control post‐CRT were included in the durvalumab early access program (EAP) as an intent‐to‐treat cohort and retrospectively reviewed for post‐CRT progression‐free survival (PFS) and time to metastatic disease or death (TMDD). The neutrophil‐to‐lymphocyte ratio (NLR) at the initiation of durvalumab was analyzed in 29 patients. Results: The median time from the completion of concurrent CRT to the initiation of durvalumb was 2.8 months. The objective response was 25.8% and the 12 month PFS and TMDD‐free rate were 56.4% and 66.9%, respectively. The low NLR patients showed a significantly longer post‐CRT PFS (not reach vs. 12.0 months [95% CI: 5.5–not estimable]; P = 0.040; the hazard ratio for disease progression or death, 0.23 [95% CI: 0.05–1.00]; P = 0.048) and the 12 month post‐CRT PFS rate (82.5 vs. 42.6%). The post‐CRT TMDD (not reach vs. 12.6 months, [95% CI: 10.8–not estimable]; P = 0.010; the hazard ratio for distant metastasis or death, 0.11 [95% CI: 0.01–0.88]; P = 0.037) and 12 month post‐CRT TMDD‐free rate (90.9 vs. 57.1%) were also significantly higher in the low NLR patients. Conclusions: Durvalumab consolidation treatment in real‐world patients showed substantial efficacy and the correlation with the NLR level warrants further investigation. [ABSTRACT FROM AUTHOR]

Background We have designed a prospective adverse event (AE) surveillance method. We performed this study to evaluate this method's performance in several hospitals simultaneously. Objectives To compare AE rates obtained by prospective AE surveillance in different hospitals and to evaluate measurement factors explaining observed variation. Methods We conducted a multicentre prospective observational study. Prospective AE surveillance was implemented for 8 weeks on the general medicine wards of five hospitals. To determine if population factors may have influenced results, we performed mixed-effects logistic regression. To determine if surveillance factors may have influenced results, we reassigned observers to different hospitals midway through surveillance period and reallocated a random sample of events to different expert review teams. Results During 3560 patient days of observation of 1159 patient encounters, we identified 356 AEs (AE risk per encounter=22%). AE risk varied between hospitals ranging from 9.9% of encounters in Hospital D to 35.8% of encounters in Hospital A. AE types and severity were similar between hospitals--the most common types were related to clinical procedures (45%), hospital-acquired infections (21%) and medications (19%). Adjusting for age and comorbid status, we observed an association between hospital and AE risk. We observed variation in observer behaviour and moderate agreement between clinical reviewers, which could have influenced the observed rate difference. Conclusion This study demonstrated that it is possible to implement prospective surveillance in different settings. Such surveillance appears to be better suited to evaluating hospital safety concerns within rather than between hospitals as we could not definitively rule out whether the observed variation in AE risk was due to population or surveillance factors. [ABSTRACT FROM AUTHOR]

Background: Approximately 3%–5% of lung adenocarcinoma is driven by anaplastic lymphoma kinase (ALK) fusion oncogene, whose activity can be suppressed by multiple ALK inhibitors. Crizotinib and ceritinib have demonstrated superior efficacy to platinum‐based chemotherapy as front‐line treatment for patients with ALK‐positive advanced non‐small cell lung cancer (NSCLC). However, the direct comparison between them in the front‐line setting remains lacking. Methods: A total of 48 patients with ALK‐positive, previously untreated advanced NSCLC, who received crizotinib and ceritinib as front‐line treatment were retrospectively investigated. The efficacy and pattern of disease progression were analyzed. Results: Patients receiving ceritinib treatment were significantly younger than those receiving crizotinib treatment (52.0 vs. 63.0, P = 0.016). The median progression‐free survival (PFS) was significantly longer with ceritinib than with crizotinib treatment (32.3 vs. 12.9 months; log‐rank P = 0.020); the hazard ratio for disease progression or death, 0.27 (95% CI, 0.08–0.90; P = 0.033). An objective response was noted in all patients in the ceritinib group and in 23 patients in the crizotinib group (74.2%; 95% CI, 59.0 to 88.5). The rate of systemic progression was significantly lower over time with ceritinib treatment compared to crizotinib treatment (cause‐specific hazard ratio, 0.21; 95% CI 0.06–0.73; P = 0.014). Serious adverse events were noted in one (2.9%) patient showing elevated liver function in the crizotinib group and three (23.1%) patients showing diarrhea in the ceritinib group. Dose reduction was needed in five out of 13 (38.5%) patients receiving ceritinib treatment. Conclusion: Ceritinib showed higher efficacy associated with a better control of systemic progression compared to crizotinib for the front‐line treatment of ALK‐positive advanced NSCLCs. [ABSTRACT FROM AUTHOR]

Introduction: Positive fluid balance is a prognostic factor for mortality in patients with sepsis; however, the association between cumulated fluid balance (CFB) and sepsis-induced multi-organ dysfunction syndrome (MODS) has yet to be elucidated. In this study, we sought to determine whether CFB is correlated with MODS and mortality in cases of septic shock. Methods: The study retrospectively recruited patients with septic shock from the intensive care unit of a tertiary care hospital. Multiple organ dysfunction syndrome (MODS) was identified as sequential organ failure assessment (SOFA) score ≥ 2 in more than one organ system. The CFB is the sum of all daily intake and output. An independent t-test, single and multivariate logistic regression, the receiver operating characteristic (ROC) curves, and the Pearson correlation coefficient were used to determine whether a relationship exists between CFB and the development of MODS and mortality. Results: Among the 104 patients enrolled in the study, 58 (55.8%) survived more than 28 days, and 73 (70.2%) developed MODS on day 3. The values of CFB in the first 24 hours and 72 hours after diagnosis of septic shock in patients with MODS were higher than these in patients without MODS (1086.6 ± 176.3 vs. 325.5 ± 205.7 ml, p = 0.013 and 2408 ± 361 vs. 873.1 ± 489 ml, p < 0.0001). In a multivariate logistic regression, the independent factors associated with the development of MODS on day 3 were APACHE II score at ICU admission (27.6 ± 7.6 in patients with MODS vs. 20.5 ± 6.4 in those without; O.R. 1.18; 95% C.1 I. 1.08–1.30; p < 0.001), disseminated intravascular coagulopathy (DIC) (n = 28; 38.4% vs. n = 2; 6.5%; O.R. 23.67; 95% C.I. 3.58–156.5; p = 0.001), and CFB in the first 72 hours (72-hr CFB) > median (1767.50ml) (n = 41; 56.2% vs. n = 11; 35.5%; O.R. 3.67; 95% C.I., 1.18–11.40; p = 0.024). Moreover, a multivariate logistic regression also identified neoplasm (n = 25; 54.3% vs. n = 17; 29.3%; O.R. 3.45; 95% C.I. 1.23–10.0; p = 0.019) and 72-hr CFB > median (n = 30; 65.2% vs. n = 21; 36.2%; O.R. 4.13; 95% C.I. 1.34–12.66; p = 0.013) as independent factors associated with 28-day mortality. 72-hr CFB values were strongly correlated with the SOFA score (r = 0.445, p < 0.0001). The area under the ROC curve revealed that 72-hr CFB has good discriminative power in associating the development of MODS (0.644, p = 0.002) and predicting subsequent 28-day mortality (0.704, p < 0.0001). Conclusions: 72-hr CFB appears to be correlated with the likelihood of developing MODS and mortality in patients with septic shock. Thus, it appears that 72-hr CFB could perhaps be used as an indicator for MODS and a predictor for mortality in those patients. [ABSTRACT FROM AUTHOR]

The article presents an examination of the association between chief executive officer (CEO) reputation and the quality of the firm's earnings. It tested three explanations for an association between these constructs: the efficient contracting hypothesis suggests that reputed CEOs are associated with good earnings quality, while the rent extraction and matching explanations argue that reputed CEOs are associated with poor earnings quality. It is concluded that the reason for more reputed CEOs are associated with poor earnings quality firms is that such firms require more talented managers and, therefore, employ more reputed CEOs.

OBJECTIVES: Polypharmacy is common, costly, and harmful for hospitalized older adults. Scalable strategies to reduce the burden of potentially inappropriate medications (PIMs) are needed. We sought to leverage medication reconciliation in hospitalized older adults by pairing with MedSafer, an electronic decision support tool for deprescribing. DESIGN: This was a nonrandomized controlled before‐and‐after study. SETTING: The study took place on four internal medicine clinical teaching units. PARTICIPANTS: Subjects were aged 65 years and older, had an expected prognosis of 3 or more months, and were taking five or more usual home medications. INTERVENTION: In the baseline phase, patients received usual care that was medication reconciliation. Patients in the intervention arm also had a "deprescribing opportunity report" generated by MedSafer and provided to their in‐hospital treating team. MEASUREMENTS: The primary outcome was ascertained at the time of hospital discharge and was the proportion of patients who had one or more PIMs deprescribed. RESULTS: A total of 1066 patients were enrolled, and deprescribing opportunities were present for 873 (82%; 418 during the control and 455 during the intervention phases, respectively). The proportion of patients with one or more PIMs deprescribed at discharge increased from 46.9% in the control period to 54.7% in the intervention period with an adjusted absolute risk difference of 8.3% (2.9%‐13.9%). Not all classes of drugs in the intervention arm were associated with an increase in deprescribing, and new PIM starts were equally common in both arms of the study. CONCLUSION: Using an electronic decision support tool for deprescribing, we increased the proportion of patients with one or more PIMs deprescribed at hospital discharge as compared with usual care. Although this type of intervention may help address medication overload in hospitalized patients, it also underscores the importance of powering future trials for a reduction in adverse drug events. Trial registration: NCT02918058. J Am Geriatr Soc 67:1843–1850, 2019 [ABSTRACT FROM AUTHOR]

This paper examines whether board gender diversity affects corporate cash holdings using S&P 1500 index firms in the US for the period 2006–2015. We document a significantly negative relationship between board gender diversity and cash holdings. We also find a strong negative effect of female independent directors consistent with monitoring function. Moreover, in accordance with the critical mass theory, we find a negative effect of female directors' presence and voice on cash holdings. Our findings are robust to alternative econometric specifications, alternative measures of cash holdings and corporate governance, difference‐in‐differences, propensity score matching, and two‐stage least squares. This study offers useful insights into the current global debate on gender diversity and its implications for firms. [ABSTRACT FROM AUTHOR]

Drawing on the political theory of judicial decision making, our paper proposes a new and parsimonious ex ante litigation risk measure: federal judge ideology. We find that judge ideology complements existing measures of litigation risk based on industry membership and firm characteristics. Firms in liberal circuits (the third quartile in ideology) are 33.5% more likely to be sued in securities class action lawsuits than those in conservative circuits (the first quartile in ideology). This result is stronger after the U.S. Supreme Court's ruling in the Tellabs case. We next show that the effect of judge ideology on litigation risk is greater for firms with more sophisticated shareholders and with higher expected litigation costs. Furthermore, judicial appointments affect litigation risk and the value of firms in the circuit, highlighting the economic consequences of political appointments of judges. Finally, using our new measure, we document that litigation risk deters managers from providing long‐term earnings guidance, a result that existing measures of litigation risk cannot show. [ABSTRACT FROM AUTHOR]

Rechargeable lithium‐ion, lithium‐sulfur, zinc‐air, and redox‐flow batteries are the most anticipated multipurpose platforms for future generations of electric vehicles, consumer devices, and portable electronics because of their high‐energy density and cost‐effective electrochemical energy storage. Over the past decades, a variety of novel separator membranes and electrolytes have been developed to improve rechargeable battery performance while not thoroughly addressing the issue of flammability, safety, and low cycling stability of high‐energy‐density batteries. This comprehensive review mainly underlines the optimization and modification of porous membranes for battery separator applications, covering four significant types: microporous separators, nonwoven mat separators, polymer electrolyte membranes, and composite membrane separators. Furthermore, the present trends in material selection for batteries are reviewed, and different choices of cathode, anode, separator, and electrolyte materials are discussed, which will also serve as key components to boost the development of next‐generation rechargeable batteries. The development of different separator membranes for battery applications has opened the door for better physiochemical and electrochemical properties using different types of separator membranes in simple and environmentally friendly ways. Since higher porosity and ionic conductivity influence the cycling performance, energy density, power density, and safety of the batteries, different membranes were tested to show their influence on the current batteries as well as property development. [ABSTRACT FROM AUTHOR]

This study examines analyst information intermediary roles using a textual analysis of analyst reports and corporate disclosures. We employ a topic modeling methodology from computational linguistic research to compare the thematic content of a large sample of analyst reports issued promptly after earnings conference calls with the content of the calls themselves. We show that analysts discuss exclusive topics beyond those from conference calls and interpret topics from conference calls. In addition, we find that investors place a greater value on new information in analyst reports when managers face greater incentives to withhold value-relevant information. Analyst interpretation is particularly valuable when the processing costs of conference call information increase. Finally, we document that investors react to analyst report content that simply confirms managers' conference call discussions. Overall, our study shows that analysts play the information intermediary roles by discovering information beyond corporate disclosures and by clarifying and confirming corporate disclosures. [ABSTRACT FROM AUTHOR]

Introduction Exercise prehabilitation may improve outcomes after surgery. Frailty is a key predictor of adverse postoperative outcomes in older people; the multidimensional nature of frailty makes this a population who may derive substantial benefit from exercise prehabilitation. The objective of this trial is to test the efficacy of exercise prehabilitation to improve postoperative functional outcomes for people living with frailty having cancer surgery with curative intent. Methods and analysis We will conduct a single-centre, parallel-arm randomised controlled trial of home-based exercise prehabilitation versus standard care among consenting patients >60 years having elective cancer surgery (intra-abdominal and intrathoracic) and who are frail (Clinical Frailty Scale >4). The intervention consists of > 3 weeks of exercise prehabilitation (strength, aerobic and stretching). The primary outcome is the 6 min walk test at the first postoperative clinic visit. Secondary outcomes include the short physical performance battery, health-related quality of life, disability-free survival, complications and health resource utilisation. The primary outcome will be analysed by intention to treat using analysis of covariance. Outcomes up to 1 year after surgery will be ascertained through linkage to administrative data. Ethics and dissemination Ethical approval has been granted by our ethics review board (Protocol Approval #2016009-01H). Results will be disseminated through presentation at scientific conferences, through peer-reviewed publication, stakeholder organisations and engagement of social and traditional media. Trial registration number NCT02934230; Pre-results. [ABSTRACT FROM AUTHOR]

Background and Objective: Many countries require hospitals to implement medication reconciliation for accreditation, but the process is resource-intensive, thus adherence is poor. We report on the impact of prepopulating and aligning community and hospital drug lists with data from population-based and hospital-based drug information systems to reduce workload and enhance adoption and use of an e-medication reconciliation application, RightRx.Methods: The prototype e-medical reconciliation web-based software was developed for a cluster-randomized trial at the McGill University Health Centre. User-centered design and agile development processes were used to develop features intended to enhance adoption, safety, and efficiency. RightRx was implemented in medical and surgical wards, with support and training provided by unit champions and field staff. The time spent per professional using RightRx was measured, as well as the medication reconciliation completion rates in the intervention and control units during the first 20 months of the trial.Results: Users identified required modifications to the application, including the need for dose-based prescribing, the role of the discharge physician in prescribing community-based medication, and access to the rationale for medication decisions made during hospitalization. In the intervention units, both physicians and pharmacists were involved in discharge reconciliation, for 96.1% and 71.9% of patients, respectively. Medication reconciliation was completed for 80.7% (surgery) to 96.0% (medicine) of patients in the intervention units, and 0.7% (surgery) to 82.7% of patients in the control units. The odds of completing medication reconciliation were 9 times greater in the intervention compared to control units (odds ratio: 9.0, 95% confidence interval, 7.4-10.9, P < .0001) after adjusting for differences in patient characteristics.Conclusion: High rates of medication reconciliation completion were achieved with automated prepopulation and alignment of community and hospital medication lists. [ABSTRACT FROM AUTHOR]

Background: Giant cell arteritis (GCA) is an immune mediated inflammatory disease of medium and large arteries which afflicts older people. The classical presentation features include: headache, visual disturbances, and jaw claudication. Patients diagnosed with GCA have also been observed to be at higher risk for the subsequent development of strokes.Case Presentation: We describe a case of an 84-year old right-handed man who presented to hospital with dysarthria, dysphagia, right-sided facial drop, a history of generalized weakness and multiple falls. He was admitted to geriatric medicine with the working diagnosis of a posterior circulation stroke syndrome. He was also started on antibiotic treatment for a possible community-acquired pneumonia because of the presence of a low-grade fever and a chest radiograph showing ill-defined left lower lobe airspace disease. Initial lab results were remarkable for an erythrocyte sedimentation rate (ESR) of 112 mm/h and a C-reactive protein (CRP) level of 110 mg/L consistent with an active inflammatory state. Neurovascular imaging showed mild atherosclerotic changes of the aortic arch and proximal great vessels without significant stenosis. The patient was started on daily high-dose prednisone because of the possibility of a cerebral vasculitis. Bilateral biopsy of temporal arteries showed giant cell arteritis. The patient's neurologic status and inflammatory markers significantly improved (ESR 52 mm/h, CRP 7.0 mg/L) and he was eventually discharged to a seniors home with services.Conclusion: The initial presentation of giant cell arteritis as a stroke syndrome, especially in the posterior circulation territory, is exceedingly rare. Other atypical presenting symptoms may include chronic cough and fever of unknown origin. The elevated ESR and CRP levels were clues to the diagnosis and clinical decision-making should be driven by a high index of suspicion since no single test (ESR, CRP, temporal artery biopsy) has perfect sensitivity. Elevated CRP may have a role in increasing stroke risk. This case report illustrates that in older people clinicians must consider atypical presentations of disease more often since timely diagnosis and initiation of treatment can result in optimal outcomes. [ABSTRACT FROM AUTHOR]

Background: Drug expenditures are responsible for an increasing proportion of health costs, accounting for $1.1 trillion in annual expenditure worldwide. As hundreds of billions of dollars are being spent each year on overtreatment with prescribed medications that are either unnecessary or are in excess of lowest cost-effective therapy, programs are needed that optimize fiscally appropriate use. We evaluated whether providing physicians with information on the patient out-of-pocket payment consequences of prescribing decisions that were in excess of lowest cost-effective therapy would alter prescribing decisions using the treatment of uncomplicated hypertension as an exemplar.Methods: A single-blind cluster randomized trial was conducted over a 60-month follow-up period in 76 primary care physicians in Quebec, Canada, and their patients with uncomplicated hypertension who were using the MOXXI integrated electronic health record for drug and health problem management. Physicians were randomized to an out-of-pocket expenditure module that provided alerts for comparative out-of-payment costs, thiazide diuretics as recommended first-line therapy, and tools to monitor blood pressure targets and medication compliance, or alternatively the basic MOXXI system. System software and prescription claims were used to analyze the impact of the intervention on treatment choice, adherence, and overall and out-of-pocket payment costs using generalized estimating equations.Results: Three thousand five-hundred ninety-two eligible patients with uncomplicated hypertension were enrolled, of whom 1261 (35.1%) were newly started (incident patient) on treatment during follow-up. There was a statistically significant increase in the prescription of diuretics in the newly treated intervention (26.6%) compared to control patients (19.8%) (RR 1.65, 95% CI 1.17 to 2.33). For patients already treated (prevalent patient), there was a statistically significant interaction between the intervention and patient age, with older patients being less likely to be switched to a diuretic. Among the incident patients, physicians with less than 15 years of experience were much more likely to prescribe a diuretic (OR 10.69; 95% CI 1.49 to 76.64) than physicians with 15 to 25 years (OR 0.67; 95%CI 0.25 to 1.78), or more than 25 years of experience (OR 1.80; 95% CI 1.23 to 2.65). There was no statistically significant effect of the intervention on adherence or out-of-pocket payment cost.Conclusions: The provision of comparative information on patient out-of-pocket payments for treatment of uncomplicated hypertension had a statistically significant impact on increasing the initiation of diuretics in incident patients and switching to diuretics in younger prevalent patients. The impact of interventions to improve the cost-effectiveness of prescribing may be enhanced by also targeting patients with tools to participate in treatment decision-making and by providing physicians with comparative out-of-pocket information on all evidence-based alternatives that would enhance clinical decision-making.Trial Registration: ISRCTN96253624. [ABSTRACT FROM AUTHOR]

Purpose of Review Non-adherence to medications for the secondary prevention of myocardial infarction (MI) is a major contributor to morbidity and mortality in these patients. This review describes recent advances in promoting adherence to therapies for coronary artery disease (CAD). Recent Findings Two large randomized controlled trials to “incentivize” adherence were somewhat disappointing; neither financial incentives nor “peer pressure” successfully increased rates of adherence in the post-MI population. Patient education and provider engagement appear to be critical aspects of improving adherence to CAD therapies, where the provider is a physician, pharmacist, or nurse and follow-up is performed in person or by telephone. Fixed-dose combinations of CAD medications, formulated as a so-called “polypill,” have shown some early efficacy in increasing adherence. Technological advances that automate monitoring and/or encouragement of adherence are promising but seem universally dependent on patient engagement. For example, medication reminders via text message perform better if patients are required to respond. Multifaceted interventions, in which these and other interventions are combined together, appear to be most effective. Summary There are several available types of proven interventions through which providers, and the health system at large, can advance patient adherence to CAD therapies. No single intervention to promote adherence will be successful in all patients. Further study of multifaceted interventions and the interactions between different interventions will be important to advancing the field. The goal is a learning healthcare system in which a network of interventions responds and adapts to patients’ needs over time. [ABSTRACT FROM AUTHOR]