Citations

Dysphagia is associated with aspiration, pneumonia, and malnutrition, but remains challenging to identify at the bedside. A variety of exam protocols and maneuvers are commonly used, but the efficacy of these maneuvers is highly variable. We conducted a comprehensive search of 7 databases, including MEDLINE, Embase, and Scopus, from each database's earliest inception through June 9, 2014. Studies reporting diagnostic performance of a bedside examination maneuver compared to a reference gold standard (videofluoroscopic swallow study or flexible endoscopic evaluation of swallowing with sensory testing) were included for analysis. From each study, data were abstracted based on the type of diagnostic method and reference standard study population and inclusion/exclusion characteristics, design, and prediction of aspiration. The search strategy identified 38 articles meeting inclusion criteria. Overall, most bedside examinations lacked sufficient sensitivity to be used for screening purposes across all patient populations examined. Individual studies found dysphonia assessments, abnormal pharyngeal sensation assessments, dual axis accelerometry, and 1 description of water swallow testing to be sensitive tools, but none were reported as consistently sensitive. A preponderance of identified studies was in poststroke adults, limiting the generalizability of results. No bedside screening protocol has been shown to provide adequate predictive value for presence of aspiration. Several individual exam maneuvers demonstrated reasonable sensitivity, but reproducibility and consistency of these protocols was not established. More research is needed to design an optimal protocol for dysphagia detection. Journal of Hospital Medicine 2015;10:256–265. © 2015 Society of Hospital Medicine

Abstract Background: The potential for exploiting BRCA deficiencies with DNA repair inhibitors has both pre-clinical and clinical support. ABT-888 (veliparib), a DNA repair inhibitor initially thought to target Poly(ADP-Ribose) Polymerases (PARP), has demonstrated in vitro inhibition of BRCA1 and BRCA2 deficient mouse embryonic stell cells, with a larger effect on BRCA1 cells. We report on the pre-planned interim analysis of the efficacy of single agent veliparib in patients with either BRCA1 or BRCA2-associated stage IV breast cancer. Methods: BRCA 1 or 2 carrier patients with stage IV breast cancer, with measurable disease, without prior exposure to a PARP inhibitor or a platinum compound in the metastatic setting, were eligible. Velapirib was administered orally, at doses of 400 mg twice daily. Dose adjustments based on toxicity were permitted. Patients progressing on velapirib alone received carboplatin at an AUC of 5, IV, given Q 21 days, and velapirib 150 mg twice daily (the maximum tolerated dose [MTD] of the combination from our completed Phase I study: J Clin Oncol 30, 2012 [suppl; abstr 1024]). Patients were to be accrued from 7 NCI NO1- supported consortia. Initially 10 patients were to be accrued to each stratum (BRCA1 and BRCA2) to provide evidence of single agent activity. If there was sufficient activity to warrant consideration of velapirib as single agent therapy (defined as 2 or more confirmed partial [PR] or better responses out of 10 per stratum), an additional 12 patients would be accrued per stratum. Results: 20 evaluable patients (11 BRCA1 and 9 BRCA2 [1 in screening]) have been accrued, the majority with lung or liver as visceral metastatic sites of disease. Median age (range) is 46 (29-68) years. Tumors from 9 patients were hormone receptor positive. BRCA1 cohort: 4 of 11 patients are off treatment at a median of 2 months (1-4); 1 patient stopped velapirib due to toxicity (grade 2 rash/pruritus, grade 2 vomiting), 3 stopped for progressive disease (one with an unconfirmed PR). Seven patients are still on single agent veliparib with 1 unconfirmed PR, and 1 patient with two evaluations showing stable disease. BRCA2 cohort: 2 patients are off treatment at 2 months for progressive disease, 7 are still on treatment with 1 confirmed PR, and 3 unconfirmed PRs. Data on patients receiving combination of velapirib and carboplatin after progression is too early. Treatment-related toxicity is being updated and has so far been reported from 14 patients: 1 patient had grade 3 fatigue, 1 patient with liver metastasis had both grade 3 alanine aminotransferase elevation and grade 3 abdominal pain. Grade 2 toxicities occurring in more than 1 patient included nausea/vomiting (6 patients), chills (2 patients), and fatigue (2 patients). Conclusion: Velapirib has single agent activity in both BRCA1 and BRCA2-associated stage IV breast cancer patients, and is well-tolerated. Mature response, treatment, and toxicity data will be presented. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-16-05.

Abstract Background: With over 13 million cancer survivors in the United States today, second cancers are of rapidly growing importance. However, data on nontreatment risk factors for second cancers are sparse. We explored the feasibility of pooling data from cohort studies of cancer incidence to investigate second cancer etiology. Methods: We combined data from five prospective studies including more than 800,000 individuals. We compared study designs and populations; evaluated availability of and ability to harmonize risk factor data; compared incidence and survival for common first primary malignancies and incidence of second primary malignancies; and estimated sample size requirements. Results: Overall, 96,513 incident, first primary malignancies were diagnosed during 1985 to 2009. Incidence rates and survival following the first primary varied among the cohorts, but most of the heterogeneity could be explained by characteristics of the study populations (age, sex, smoking, and screening rates). A total of 7,890 second primary cancers (excluding original primary site) were identified, yielding sufficient statistical power (≥80%) for detecting modest associations with risk of all second cancers among survivors of common first primary malignancies (e.g., colorectal cancer); however, there were insufficient events for studying survivors of rarer cancers or identifying risk factors for specific second cancers. Conclusions: Pooling data from cohort studies to investigate nontreatment risk factors for second primary cancers seems feasible but there are important methodologic issues—some of which are barriers to specific research questions—that require special attention. Impact: Increased understanding of nontreatment risk factors for second cancers will provide valuable prevention and surveillance information. Cancer Epidemiol Biomarkers Prev; 23(8); 1598–608. ©2014 AACR.

Objectives Growing evidence suggests that gender-blind assessment of exposure may introduce exposure misclassification, but few studies have characterised gender differences across occupations and industries. We pooled control responses to job-specific, industry-specific and exposure-specific questionnaires (modules) that asked detailed questions about work activities from three US population-based case–control studies to examine gender differences in work tasks and their frequencies. Methods We calculated the ratio of female-to-male controls that completed each module. For four job modules (assembly worker, machinist, health professional, janitor/cleaner) and for subgroups of jobs that completed those modules, we evaluated gender differences in task prevalence and frequency using χ2 and Mann–Whitney U tests, respectively. Results The 1360 female and 2245 male controls reported 6033 and 12 083 jobs, respectively. Gender differences in female:male module completion ratios were observed for 39 of 45 modules completed by ≥20 controls. Gender differences in task prevalence varied in direction and magnitude. For example, female janitors were significantly more likely to polish furniture (79% vs 44%), while male janitors were more likely to strip floors (73% vs 50%). Women usually reported more time spent on tasks than men. For example, the median hours per week spent degreasing for production workers in product manufacturing industries was 6.3 for women and 3.0 for men. Conclusions Observed gender differences may reflect actual differences in tasks performed or differences in recall, reporting or perception, all of which contribute to exposure misclassification and impact relative risk estimates. Our findings reinforce the need to capture subject-specific information on work tasks.

Objective To estimate risk of colorectal cancer (CRC) for first-degree relatives of CRC cases based on CRC molecular subtypes and tumour pathology features. Design We studied a cohort of 33 496 first-degree relatives of 4853 incident invasive CRC cases (probands) who were recruited to the Colon Cancer Family Registry through population cancer registries in the USA, Canada and Australia. We categorised the first-degree relatives into four groups: 28 156 of 4095 mismatch repair (MMR)-proficient probands, 2302 of 301 MMR-deficient non-Lynch syndrome probands, 1799 of 271 suspected Lynch syndrome probands and 1239 of 186 Lynch syndrome probands. We compared CRC risk for first-degree relatives stratified by the absence or presence of specific tumour molecular pathology features in probands across each of these four groups and for all groups combined. Results Compared with first-degree relatives of MMR-proficient CRC cases, a higher risk of CRC was estimated for first-degree relatives of CRC cases with suspected Lynch syndrome (HR 2.06, 95% CI 1.59 to 2.67) and with Lynch syndrome (HR 5.37, 95% CI 4.16 to 6.94), but not with MMR-deficient non-Lynch syndrome (HR 1.04, 95% CI 0.82 to 1.31). A greater risk of CRC was estimated for first-degree relatives if CRC cases were diagnosed before age 50 years, had proximal colon cancer or if their tumours had any of the following: expanding tumour margin, peritumoral lymphocytes, tumour-infiltrating lymphocytes or synchronous CRC. Conclusions Molecular pathology features are potentially useful to refine screening recommendations for first-degree relatives of CRC cases and to identify which cases are more likely to be caused by genetic or other familial factors.

Abstract Objective Risk scores and accelerated diagnostic protocols can identify chest pain patients with low risk of major adverse cardiac event who could be discharged early from the ED , saving time and costs. We aimed to derive and validate a chest pain score and accelerated diagnostic protocol ( ADP ) that could safely increase the proportion of patients suitable for early discharge. Methods Logistic regression identified statistical predictors for major adverse cardiac events in a derivation cohort. Statistical coefficients were converted to whole numbers to create a score. Clinician feedback was used to improve the clinical plausibility and the usability of the final score (Emergency Department Assessment of Chest pain Score [ EDACS ]). EDACS was combined with electrocardiogram results and troponin results at 0 and 2 h to develop an ADP ( EDACS‐ADP ). The score and EDACS‐ADP were validated and tested for reproducibility in separate cohorts of patients. Results In the derivation ( n = 1974) and validation ( n = 608) cohorts, the EDACS‐ADP classified 42.2% (sensitivity 99.0%, specificity 49.9%) and 51.3% (sensitivity 100.0%, specificity 59.0%) as low risk of major adverse cardiac events, respectively. The intra‐class correlation coefficient for categorisation of patients as low risk was 0.87. Conclusion The EDACS‐ADP identified approximately half of the patients presenting to the ED with possible cardiac chest pain as having low risk of short‐term major adverse cardiac events, with high sensitivity. This is a significant improvement on similar, previously reported protocols. The EDACS‐ADP is reproducible and has the potential to make considerable cost reductions to health systems.

Background: Hypoglycemia is often cited as a barrier to achieving inpatient glycemic targets. We sought to characterize hypoglycemic events in our institution by work-shift cycle and by specific treatment area. Methods: Capillary (bedside) and blood (laboratory) glucose values of <70 mg/dl for patients with either a known diagnosis of diabetes or with evidence of hyperglycemia were abstracted from our laboratory database for hospitalizations between October 1, 2007, and February 3, 2008. Hypoglycemic events were analyzed by 12 h nursing work-shift cycles (day shift, 07:00 to 18:59; night shift, 19:00 to 06:59) and by the six medical, surgical, and intensive care areas in the hospital (designated areas 1 to 6). Results: We identified 206 individual patients with either diabetes or hyperglycemia (mean age, 67 years; 56% men; 83% white) who had 423 hypoglycemic events. There were 78% more hypoglycemic events during the night shift ( n = 271 events in 128 individual patients) than during the day shift ( n = 152 events in 96 individual patients). Most of the night-shift hypoglycemic measurements were detected between 04:00 and 04:59 or 06:00 and 06:59. The mean hypoglycemic level was comparable between shifts ( p = .79) and across the six inpatient areas. The number of hypoglycemic events per person increased with lengths of hospital stay >5 days. The prevalence of hypoglycemia varied across patient care areas within the hospital, with most (28%) detected in one area of the hospital. Conclusion: There are temporal and geographic patterns in the occurrence of hypoglycemia among patients with diabetes or hyperglycemia in our hospital. Further study should focus on the reasons underlying these variations so that specific interventions can address the risk of hypoglycemia during peak times and places.