Learning the statistics of pronoun reference: By word or by category?

Evidence shows that readers tend to follow recently-encountered patterns for interpreting ambiguous pronouns. If recent exposure includes frequent pronouns with prepositional object antecedents (e.g., "Matt went to the library with Ana. She took out a book"), people adapt and are more likely to assign ambiguous pronouns to prepositional antecedents than if they were exposed to pronouns with subject antecedents (Johnson & Arnold, 2022). However, it is unclear how people categorize different referential structures and how broadly they make generalizations. Johnson and Arnold (2022) found that people can learn a referential relationship specific to third-person pronouns and an antecedent's syntactic or thematic properties. The current study uses this paradigm to test how broadly people generalize categories of different types of pronouns and antecedents. Do people adapt to the behavior of categorizing "he" and "she" as individual words, or as a general class? (Experiment 1). Do people learn about likely antecedents for pronouns separately for different verb constructions (transfer vs. joint-action) and thematic roles, or broadly by grammatical function? (Experiments 2 & 3). Participants were repeatedly exposed to a referential structure of a particular type of pronouns or antecedents, and then were tested on ambiguous pronouns. All experiments showed that pronoun adaptation generalizes to new instances from the broad categorization of pronouns and antecedents.

Country Image in COVID-19 Pandemic: A Case Study of China.

Country image has a profound influence on international relations and economic development. In the worldwide outbreak of COVID-19, countries and their people display different reactions, resulting in diverse perceived images among foreign public. Therefore, in this article, we take China as a specific and typical case and investigate its image with aspect-based sentiment analysis on a large-scale Twitter dataset. To our knowledge, this is the first study to explore country image in such a fine-grained way. To perform the analysis, we first build a manually-labeled Twitter dataset with aspect-level sentiment annotations. Afterward, we conduct the aspect-based sentiment analysis with BERT to explore the image of China. We discover an overall sentiment change from non-negative to negative in the general public, and explain it with the increasing mentions of negative ideology-related aspects and decreasing mentions of non-negative fact-based aspects. Further investigations into different groups of Twitter users, including U.S. Congress members, English media, and social bots, reveal different patterns in their attitudes toward China. This article provides a deeper understanding of the changing image of China in COVID-19 pandemic. Our research also demonstrates how aspect-based sentiment analysis can be applied in social science researches to deliver valuable insights.

PIK3CA alterations and benefit with neratinib: analysis from the randomized, double-blind, placebo-controlled, phase III ExteNET trial.

BACKGROUND: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor that inhibits PI3K/Akt and MAPK signaling pathways after HER2 receptor activation. The ExteNET study showed that neratinib significantly improved 5-year invasive disease-free survival (iDFS) in women who completed trastuzumab-based adjuvant therapy for early breast cancer (EBC). We assessed the prognostic and predictive significance of PIK3CA alterations in patients in ExteNET. METHODS: Participants were women aged ≥ 18 years (≥ 20 years in Japan) with stage 1-3c (modified to stage 2-3c in February 2010) operable breast cancer, who had completed (neo)adjuvant chemotherapy plus trastuzumab ≤ 2 years before randomization, with no evidence of disease recurrence or metastatic disease at study entry. Patients were randomized to oral neratinib 240 mg/day or placebo for 1 year. Formalin-fixed, paraffin-embedded primary tumor specimens underwent polymerase chain reaction (PCR) PIK3CA testing for two hotspot mutations in exon 9, one hot-spot mutation in exon 20, and fluorescence in situ hybridization (FISH) analysis for PIK3CA amplification. The primary endpoint (iDFS) was tested with log-rank test and hazard ratios (HRs) estimated using Cox proportional-hazards models. RESULTS: Among the intent-to-treat population (n = 2840), tumor specimens were available for PCR testing (991 patients) and PIK3CA FISH (702 patients). Overall, 262 samples were PIK3CA altered: 201 were mutated (77%), 52 (20%) were amplified, and 9 (3%) were mutated and amplified. iDFS was non-significantly worse in placebo-treated patients with altered vs wild-type PIK3CA (HR 1.34; 95% CI 0.72-2.50; P = 0.357). Neratinib's effect over placebo was significant in patients with PIK3CA-altered tumors (HR 0.41; 95% CI 0.17-0.90, P = 0.028) but not PIK3CA wild-type tumors (HR 0.72; 95% CI 0.36-1.41; P = 0.34). The interaction test was non-significant (P = 0.309). CONCLUSIONS: Although there was a greater absolute risk reduction associated with neratinib treatment of patients with PIK3CA-altered tumors in ExteNET, current data do not support PIK3CA alteration as a predictive biomarker of response to neratinib in HER2-positive EBC. TRIAL REGISTRATION: ClinicalTrials.gov , NCT00878709 . Trial registered April 9, 2009.

Patterns of occurrence and implications of neratinib-associated diarrhea in patients with HER2-positive breast cancer: analyses from the randomized phase III ExteNET trial.

BACKGROUND: We characterized patterns of occurrence and the impact of neratinib-associated diarrhea in the absence of protocol-directed antidiarrheal prophylaxis or a formal diarrhea management plan using data from Extended Adjuvant Treatment of Breast Cancer with Neratinib (ExteNET). METHODS: ExteNET is a multicenter, double-blind, placebo-controlled, randomized phase III trial involving community-based and academic institutions in 40 countries. Women with HER2-positive early-stage breast cancer with prior standard primary therapy and trastuzumab-based (neo)adjuvant therapy were randomized to neratinib 240 mg/day or placebo for 12 months. Safety, a secondary outcome, was assessed using the National Cancer Institute Common Terminology Criteria version 3.0. Health-related quality of life by diarrhea grade was assessed using Functional Assessment of Cancer Therapy-Breast (FACT-B). RESULTS: Two thousand eight hundred sixteen women (1408 per group) were safety-evaluable. Grade 3 and 4 diarrhea occurred in 561 (39.8%) and 1 (0.1%) patients with neratinib versus 23 (1.6%) and 0 patients with placebo, respectively. In the neratinib group, 28.6% of patients had grade 3 events during month 1 decreasing to ≤ 6% after month 3. The median cumulative duration of grade 3/4 diarrhea with neratinib was 5 days (interquartile range, 2-9). Serious diarrheal events (n = 22, 1.6%) and diarrheal events requiring hospitalization (n = 20, 1.4%) were rare with neratinib. Changes in FACT-B total score by diarrhea grade in the neratinib group did not meet the threshold for clinically important differences. CONCLUSIONS: In the absence of antidiarrheal prophylaxis, neratinib-related diarrhea is short-lived and not associated with complications or long-term sequelae. This suggests that targeted preventive management with antidiarrheal prophylaxis early during neratinib treatment is appropriate. TRIAL REGISTRATION: ClinicalTrials.gov NCT00878709. Registered 9 April 2009.

Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Neratinib, an irreversible tyrosine-kinase inhibitor of HER1, HER2, and HER4, has clinical activity in patients with HER2-positive metastatic breast cancer. We aimed to investigate the efficacy and safety of 12 months of neratinib after trastuzumab-based adjuvant therapy in patients with early-stage HER2-positive breast cancer. METHODS: We did this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 495 centres in Europe, Asia, Australia, New Zealand, and North and South America. Eligible women (aged ≥18 years, or ≥20 years in Japan) had stage 1-3 HER2-positive breast cancer and had completed neoadjuvant and adjuvant trastuzumab therapy up to 2 years before randomisation. Inclusion criteria were amended on Feb 25, 2010, to include patients with stage 2-3 HER2-positive breast cancer who had completed trastuzumab therapy up to 1 year previously. Patients were randomly assigned (1:1) to receive oral neratinib 240 mg per day or matching placebo. The randomisation sequence was generated with permuted blocks stratified by hormone receptor status (hormone receptor-positive [oestrogen or progesterone receptor-positive or both] vs hormone receptor-negative [oestrogen and progesterone receptor-negative]), nodal status (0, 1-3, or ≥4), and trastuzumab adjuvant regimen (sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system. Patients, investigators, and trial sponsors were masked to treatment allocation. The primary outcome was invasive disease-free survival, as defined in the original protocol, at 2 years after randomisation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00878709. FINDINGS: Between July 9, 2009, and Oct 24, 2011, we randomly assigned 2840 women to receive neratinib (n=1420) or placebo (n=1420). Median follow-up time was 24 months (IQR 20-25) in the neratinib group and 24 months (22-25) in the placebo group. At 2 year follow-up, 70 invasive disease-free survival events had occurred in patients in the neratinib group versus 109 events in those in the placebo group (stratified hazard ratio 0·67, 95% CI 0·50-0·91; p=0·0091). The 2-year invasive disease-free survival rate was 93·9% (95% CI 92·4-95·2) in the neratinib group and 91·6% (90·0-93·0) in the placebo group. The most common grade 3-4 adverse events in patients in the neratinib group were diarrhoea (grade 3, n=561 [40%] and grade 4, n=1 [<1%] vs grade 3, n=23 [2%] in the placebo group), vomiting (grade 3, n=47 [3%] vs n=5 [<1%]), and nausea (grade 3, n=26 [2%] vs n=2 [<1%]). QT prolongation occurred in 49 (3%) patients given neratinib and 93 (7%) patients given placebo, and decreases in left ventricular ejection fraction (≥grade 2) in 19 (1%) and 15 (1%) patients, respectively. We recorded serious adverse events in 103 (7%) patients in the neratinib group and 85 (6%) patients in the placebo group. Seven (<1%) deaths (four patients in the neratinib group and three patients in the placebo group) unrelated to disease progression occurred after study drug discontinuation. The causes of death in the neratinib group were unknown (n=2), a second primary brain tumour (n=1), and acute myeloid leukaemia (n=1), and in the placebo group were a brain haemorrhage (n=1), myocardial infarction (n=1), and gastric cancer (n=1). None of the deaths were attributed to study treatment in either group. INTERPRETATION: Neratinib for 12 months significantly improved 2-year invasive disease-free survival when given after chemotherapy and trastuzumab-based adjuvant therapy to women with HER2-positive breast cancer. Longer follow-up is needed to ensure that the improvement in breast cancer outcome is maintained. FUNDING: Wyeth, Pfizer, Puma Biotechnology.

Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma.

PURPOSE: Talimogene laherparepvec (T-VEC) is a herpes simplex virus type 1-derived oncolytic immunotherapy designed to selectively replicate within tumors and produce granulocyte macrophage colony-stimulating factor (GM-CSF) to enhance systemic antitumor immune responses. T-VEC was compared with GM-CSF in patients with unresected stage IIIB to IV melanoma in a randomized open-label phase III trial. PATIENTS AND METHODS: Patients with injectable melanoma that was not surgically resectable were randomly assigned at a two-to-one ratio to intralesional T-VEC or subcutaneous GM-CSF. The primary end point was durable response rate (DRR; objective response lasting continuously ≥ 6 months) per independent assessment. Key secondary end points included overall survival (OS) and overall response rate. RESULTS: Among 436 patients randomly assigned, DRR was significantly higher with T-VEC (16.3%; 95% CI, 12.1% to 20.5%) than GM-CSF (2.1%; 95% CI, 0% to 4.5%]; odds ratio, 8.9; P < .001). Overall response rate was also higher in the T-VEC arm (26.4%; 95% CI, 21.4% to 31.5% v 5.7%; 95% CI, 1.9% to 9.5%). Median OS was 23.3 months (95% CI, 19.5 to 29.6 months) with T-VEC and 18.9 months (95% CI, 16.0 to 23.7 months) with GM-CSF (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P = .051). T-VEC efficacy was most pronounced in patients with stage IIIB, IIIC, or IVM1a disease and in patients with treatment-naive disease. The most common adverse events (AEs) with T-VEC were fatigue, chills, and pyrexia. The only grade 3 or 4 AE occurring in ≥ 2% of T-VEC-treated patients was cellulitis (2.1%). No fatal treatment-related AEs occurred. CONCLUSION: T-VEC is the first oncolytic immunotherapy to demonstrate therapeutic benefit against melanoma in a phase III clinical trial. T-VEC was well tolerated and resulted in a higher DRR (P < .001) and longer median OS (P = .051), particularly in untreated patients or those with stage IIIB, IIIC, or IVM1a disease. T-VEC represents a novel potential therapy for patients with metastatic melanoma.

Challenges in developing a validated biomarker for angiogenesis inhibitors: the motesanib experience.

PURPOSE: We sought to develop placental growth factor as a predictive pharmacodynamic biomarker for motesanib efficacy as first-line therapy in patients with advanced nonsquamous non-small-cell lung cancer. EXPERIMENTAL DESIGN: Placental growth factor was evaluated at baseline and study week 4 (after 3 weeks treatment) in an exploratory analysis of data from a randomized phase 2 study of motesanib 125 mg once daily plus carboplatin/paclitaxel and in a prespecified analysis of data from a randomized, double-blind phase 3 study of motesanib 125 mg once daily plus carboplatin/paclitaxel vs placebo plus carboplatin/paclitaxel (MONET1). Associations between fold-change from baseline in placental growth factor and overall survival were evaluated using Cox proportional hazards models. RESULTS: In the phase 2 study, serum placental growth factor increased from baseline a mean 2.8-fold at study week 4. Patients with ≥2.2-fold change from baseline in placental growth factor (n = 18) had significantly longer overall survival than those with <2.2-fold change (n = 19; 22.9 vs 7.9 months; hazard ratio, 0.30; 95% CI, 0.12-0.74; P = 0.009). Consequently, placental growth factor was investigated as a pharmacodynamic biomarker in the phase 3 MONET1 study. There was no association between log-transformed placental growth factor fold-change from baseline to week 4 (continuous variable) and overall survival (hazard ratio, 0.98; 95% CI, 0.79-1.22; P = 0.868). MONET1 did not meet its primary endpoint of overall survival. Likewise, median overall survival was similar among patients with ≥2.0-fold change in placental growth factor (n = 229) compared with <2.0-fold change (n = 127; 14.8 vs 13.8 months; hazard ratio, 0.88; 95% CI, 0.67-1.15, P = 0.340). CONCLUSIONS: Our results illustrate the challenges of successfully translating phase 2 biomarker results into phase 3 studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT00460317, NCT00369070.

An estimating function approach to the analysis of recurrent and terminal events.

In clinical and observational studies, the event of interest can often recur on the same subject. In a more complicated situation, there exists a terminal event (e.g., death) which stops the recurrent event process. In many such instances, the terminal event is strongly correlated with the recurrent event process. We consider the recurrent/terminal event setting and model the dependence through a shared gamma frailty that is included in both the recurrent event rate and terminal event hazard functions. Conditional on the frailty, a model is specified only for the marginal recurrent event process, hence avoiding the strong Poisson-type assumptions traditionally used. Analysis is based on estimating functions that allow for estimation of covariate effects on the recurrent event rate and terminal event hazard. The method also permits estimation of the degree of association between the two processes. Closed-form asymptotic variance estimators are proposed. The proposed method is evaluated through simulations to assess the applicability of the asymptotic results in finite samples and the sensitivity of the method to its underlying assumptions. The methods can be extended in straightforward ways to accommodate multiple types of recurrent and terminal events. Finally, the methods are illustrated in an analysis of hospitalization data for patients in an international multi-center study of outcomes among dialysis patients.

A group sequential Holm procedure with multiple primary endpoints.

We propose a group sequential Holm procedure when there are multiple primary endpoints. This method addresses multiplicities arising from multiple primary endpoints and from multiple analyses in a group sequential design. It has been shown to be a closed testing procedure and preserves the familywise error rate in the strong sense. When multiple endpoints are the only concern without an interim analysis, the method simplifies to the weighted Holm procedure. The proposed method is more powerful than the parallel group sequential method and avoids the need to anticipate the testing order as in the fixed sequence testing scheme.

Phase 1b dose-finding study of motesanib with docetaxel or paclitaxel in patients with metastatic breast cancer.

The purpose of this study was to investigate the safety, tolerability, and pharmacokinetics of motesanib when combined with docetaxel or paclitaxel in patients with metastatic breast cancer. In this open-label, dose-finding, phase 1b study, patients received motesanib 50 or 125-mg orally once daily (QD), beginning day 3 of cycle 1 of chemotherapy, continuously in combination with either paclitaxel 90 mg/m(2) on days 1, 8, and 15 every 28-day cycle (Arm A) or docetaxel 100 mg/m(2) on day 1 every 21-day cycle (Arm B). Dose escalation to motesanib 125 mg QD occurred if the incidence of dose-limiting toxicities (DLTs, primary endpoint) was ≤ 33 %. If the maximum tolerated dose (MTD) of motesanib was established in Arm B, additional patients could receive motesanib at the MTD plus docetaxel 75 mg/m(2). Forty-six patients were enrolled and 45 received ≥ 1 dose of motesanib. The incidence of DLTs was <33 % in all cohorts; thus, motesanib 125 mg QD was established as the MTD. Seven patients (16 %) had grade 3 motesanib-related adverse events including cholecystitis (2 patients) and hypertension (2 patients). Pharmacokinetic parameters of motesanib were similar to those reported in previous studies. The objective response rate was 56 % among patients with measurable disease at baseline who received motesanib in combination with taxane-based chemotherapy. The addition of motesanib to either paclitaxel or docetaxel was generally tolerable up to the 125-mg QD dose of motesanib. The objective response rate of 56 % suggests a potential benefit of motesanib in combination with taxane-based chemotherapy.

Safety and pharmacokinetics of motesanib in combination with panitumumab and gemcitabine-Cisplatin in patients with advanced cancer.

Purpose. The aim of this study was to assess the safety and tolerability of motesanib (an orally administered small-molecule antagonist of vascular endothelial growth factor receptors 1, 2, and 3, platelet-derived growth factor receptor, and Kit) when administered in combination with panitumumab, gemcitabine, and cisplatin. Methods. This was an open-label, multicenter phase 1b study in patients with advanced solid tumors with an ECOG performance status ≤1 and for whom a gemcitabine/cisplatin regimen was indicated. Patients received motesanib (0 mg [control], 50 mg once daily [QD], 75 mg QD, 100 mg QD, 125 mg QD, or 75 mg twice daily [BID]) with panitumumab (9 mg/kg), gemcitabine (1250 mg/m(2)) and cisplatin (75 mg/m(2)) in 21-day cycles. The primary endpoint was the incidence of dose-limiting toxicities (DLTs). Results. Forty-one patients were enrolled and received treatment (including 8 control patients). One of eight patients in the 50 mg QD cohort and 5/11 patients in the 125 mg QD cohort experienced DLTs. The maximum tolerated dose was established as 100 mg QD. Among patients who received motesanib (n = 33), 29 had motesanib-related adverse events. Fourteen patients had serious motesanib-related events. Ten patients had motesanib-related venous thromboembolic events and three had motesanib-related arterial thromboembolic events, two of which were considered serious. One patient had a complete response and nine had partial responses as their best objective response. Conclusions. The combination of motesanib, panitumumab, and gemcitabine/cisplatin could not be administered consistently and, at the described doses and schedule, may be intolerable. However, encouraging antitumor activity was noted in some cases.

Phase 1b study of motesanib, an oral angiogenesis inhibitor, in combination with carboplatin/paclitaxel and/or panitumumab for the treatment of advanced non-small cell lung cancer.

PURPOSE: Motesanib is a small-molecule antagonist of vascular endothelial growth factor receptor 1, 2, and 3, platelet-derived growth factor receptor, and Kit. This phase 1b study assessed the safety, maximum tolerated dose (MTD), and pharmacokinetics, and explored the objective response of motesanib plus carboplatin/paclitaxel and/or the fully human anti-epidermal growth factor receptor monoclonal antibody panitumumab in advanced non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Patients with unresectable NSCLC received sequentially escalating doses of motesanib [50, 125 mg once daily; 75 mg twice daily] orally continuously plus carboplatin/paclitaxel (arm A; first line) or panitumumab (arm B; first and second line) once every 21-day cycle or 125 mg once daily plus carboplatin/paclitaxel and panitumumab (arm C; first line). RESULTS: Forty-five patients received motesanib. Three dose-limiting toxicities occurred: grade 4 pulmonary embolism (n = 1; arm A, 50 mg once daily) and grade 3 deep vein thrombosis (n = 2; arm A, 125 mg once daily; arm C). The MTD was 125 mg once daily. Common motesanib-related adverse events were fatigue (60% of patients), diarrhea (53%), hypertension, (38%), anorexia (27%), and nausea (22%). Three cases of cholecystitis occurred but only in the 75-mg twice-daily schedule, which was subsequently discontinued. At 125 mg once daily, motesanib pharmacokinetics were not markedly changed with carboplatin/paclitaxel coadministration; however, exposure to paclitaxel was moderately increased. The objective response rates were 17%, 0%, and 17% in arms A, B, and C, respectively. CONCLUSIONS: Treatment with motesanib was tolerable when combined with carboplatin/paclitaxel and/or panitumumab, with little effect on motesanib pharmacokinetics at the 125-mg once daily dose level. This dose is being investigated in an ongoing phase 3 study in NSCLC.

Predictors of habitual snoring and obstructive sleep apnea risk in patients with asthma.

BACKGROUND: A high prevalence of obstructive sleep apnea (OSA) symptoms was reported in patients with asthma. Our goal was to evaluate factors associated with habitual snoring and OSA risk in these patients. METHODS: Patients with asthma were surveyed at specialty clinics with the Sleep Apnea scale of the Sleep Disorders Questionnaire (SA-SDQ) and questions about the frequency of asthma symptoms (National Asthma Education and Prevention Program guidelines), followed by medical record review. SA-SDQ scores >or= 36 for men and >or= 32 for women defined high OSA risk. Logistic regression was used to model associations with habitual snoring and high OSA risk. RESULTS: Among 244 patients, 37% snored habitually and 40% demonstrated high OSA risk. Independent predictors of habitual snoring included gastroesophageal reflux disease (GERD) [odds ratio (OR), 2.19; 95% confidence interval (CI), 1.19 to 4.02] and use of an inhaled corticosteroid (ICS) [OR, 2.66; 95% CI, 1.05 to 6.72]. High OSA risk was predicted by asthma severity step (OR, 1.59; 95% CI, 1.23 to 2.06), GERD (OR, 2.70; 95% CI, 1.51 to 4.83), and ICS use (OR, 4.05; 95% CI, 1.56 to 10.53). Linear, dose-dependent relationships of ICS with habitual snoring and high OSA risk were seen (p = 0.004 and p = 0.0006, respectively). Women demonstrated a 2.11 times greater odds for high OSA risk (95% CI, 1.10 to 4.09) when controlling for the above covariates. CONCLUSIONS: Symptoms of OSA in patients with asthma are predicted by asthma severity, coexistent GERD, and use of an ICS in a dose-dependent fashion. The well-recognized male gender predominance for OSA symptoms is not apparent in these patients. Further exploration of these relationships may help to explain the increased prevalence of OSA in asthma and provide new insights into the reported female predominance of asthma morbidity.

Do licensing and accreditation matter in outpatient substance abuse treatment programs?

Licensing and accreditation are widely used to improve and convey organizational quality. The objective of this study was to provide substance abuse treatment stakeholders with better evidence about how well licensing and accreditation actually correlate with staffing and treatment practices. Regressions using data from national surveys of outpatient substance abuse treatment facilities indicated that no form of licensing or accreditation was associated with better staff-to-client ratios or with one important aspect of comprehensive treatment -- the percentage of clients receiving routine medical care. There were several positive associations between licensing/accreditation and other aspects of treatment comprehensiveness. Three categories of licensure/accreditation were also positively associated with use of after-treatment plans. Post hoc analyses revealed that accreditation was associated with units' organizational contexts and referral sources as well as the nature of the competitive environment. Licensing/accreditation may reveal as much about units' institutional environments as about the quality of treatment provided.

Semiparametric analysis of correlated recurrent and terminal events.

In clinical and observational studies, recurrent event data (e.g., hospitalization) with a terminal event (e.g., death) are often encountered. In many instances, the terminal event is strongly correlated with the recurrent event process. In this article, we propose a semiparametric method to jointly model the recurrent and terminal event processes. The dependence is modeled by a shared gamma frailty that is included in both the recurrent event rate and terminal event hazard function. Marginal models are used to estimate the regression effects on the terminal and recurrent event processes, and a Poisson model is used to estimate the dispersion of the frailty variable. A sandwich estimator is used to achieve additional robustness. An analysis of hospitalization data for patients in the peritoneal dialysis study is presented to illustrate the proposed method.

The effects of governing board configuration on profound organizational change in hospitals.

This study extends the literature on governing boards and organizational change by examining how governing board configurations have influenced profound organizational change in U.S. hospitals, and the conditions under which such change occurs. Hospitals governed by boards that more closely resembled a corporate governance model were more likely to experience positive changes such as diversification and merger and less likely to undergo negative changes such as closure. Organizational performance influenced change, but largely independent of governance configurations. Only in the case of closure did we find that governance configuration operated jointly with organizational performance.

Recurrent stroke risk is higher than cardiac event risk after initial stroke/transient ischemic attack.

BACKGROUND AND PURPOSE: Patients with ischemic stroke and transient ischemic attack (TIA) are at risk for recurrent cerebrovascular and cardiac events. Understanding which of these adverse events is more likely to occur next is instructive for preventive therapy planning. METHODS: Subjects (n=1923) were identified from a sample of hospital discharges from administrative claims for the Michigan Medicare population from January 2001 to June 2001 using International Classification of Diseases, 9th Revision codes for ischemic stroke/TIA. Outcomes (cardiac events, myocardial infarction [MI], percutaneous transluminal coronary angioplasty [PTCA], coronary artery bypass grafting [CABG] and ischemic strokes) were identified for 2001 to 2003. Comparison between cardiac and stroke as secondary events were made using cumulative incidence estimates. RESULTS: Over the follow-up period, 172 patients had a cardiac event (62.8% MI, 7.6% CABG, 14.5% PTCA, 9.3% MI and PTCA, and 5.8% MI and CABG) and 239 had a stroke as their first event. Cardiac event at 2 years had occurred in 7.7%, and stroke occurred in 11.8%. CONCLUSIONS: The risk of stroke after initial stroke/TIA is higher than the risk of cardiac events. The propensity after stroke/TIA to have the first recurrent ischemic event in the brain, rather than in the heart, has implications for prophylactic therapy selection.