Citations

Background: Patients hospitalized for first acute coronary syndrome (ACS) are frequently discharged on multiple new medications. The short-term tolerability of these medications is unknown. Methods: This single-center cohort study assessed 30-day health-care utilization and how it may be impacted by medication prescribing trends. We included Olmsted County patients presenting with ACS and previously undiagnosed coronary artery disease in 2008 to 2009. All health-care contacts were reviewed 30 days after index hospital discharge for potential adverse medication effects including documented hypotension or bradycardia, or symptoms likely attributed to the medications. Results: The study included 86 patients; their mean age was 63 (standard deviation: 15.5 years). Antianginal or antihypertensive cardiovascular (CV) medications were prescribed to 98% of patients at discharge; 76% were prescribed 2 or more. There were 233 health-care contacts in 30 days; 90 (39%) of these contacts were unscheduled. More CV medications tended to be prescribed to patients with unscheduled contacts, both pre-ACS ( P = .045) and upon hospital discharge ( P = .051). Hypotension and/or bradycardia at follow-up occurred in 52 patients (60%). Surprisingly, there was no association between hypotension and/or bradycardia at follow-up and increased health-care utilization ( P = .12). Potential adverse drug effects were reported in 34 (40%) patients. These patients had significantly more total health-care contacts ( P < .001) and unscheduled health-care contacts (median 0 vs 1.5; P < .001). Conclusions: Symptoms of adverse drug effects were associated with more frequent health-care utilization after ACS. Clinicians need to consider this while striving to increase patient compliance with post-ACS medications and optimize care transitions.

Cyclin A2 activates the cyclin-dependent kinases Cdk1 and Cdk2 and is expressed at elevated levels from S phase until early mitosis. We found that mutant mice that cannot elevate cyclin A2 are chromosomally unstable and tumor-prone. Underlying the chromosomal instability is a failure to up-regulate the meiotic recombination 11 (Mre11) nuclease in S phase, which leads to impaired resolution of stalled replication forks, insufficient repair of double-stranded DNA breaks, and improper segregation of sister chromosomes. Unexpectedly, cyclin A2 controlled Mre11 abundance through a C-terminal RNA binding domain that selectively and directly binds Mre11 transcripts to mediate polysome loading and translation. These data reveal cyclin A2 as a mechanistically diverse regulator of DNA replication combining multifaceted kinase-dependent functions with a kinase-independent, RNA binding–dependent role that ensures adequate repair of common replication errors.

Abstract Background: The precise mechanism by which the immune system is adversely affected in cancer patients remains poorly understood, but the accumulation of immunosuppressive/protumorigenic myeloid-derived suppressor cells (MDSCs) is thought to be a prominent mechanism contributing to immunologic tolerance of malignant cells in epithelial ovarian cancer (EOC). To this end, we hypothesized genetic variation in MDSC pathway genes would be associated with survival after EOC diagnoses. Methods: We measured the hazard of death due to EOC within 10 years of diagnosis, overall and by invasive subtype, attributable to SNPs in 24 genes relevant in the MDSC pathway in 10,751 women diagnosed with invasive EOC. Versatile Gene-based Association Study and the admixture likelihood method were used to test gene and pathway associations with survival. Results: We did not identify individual SNPs that were significantly associated with survival after correction for multiple testing (P &lt; 3.5 × 10−5), nor did we identify significant associations between the MDSC pathway overall, or the 24 individual genes and EOC survival. Conclusions: In this well-powered analysis, we observed no evidence that inherited variations in MDSC-associated SNPs, individual genes, or the collective genetic pathway contributed to EOC survival outcomes. Impact: Common inherited variation in genes relevant to MDSCs was not associated with survival in women diagnosed with invasive EOC. Cancer Epidemiol Biomarkers Prev; 26(3); 420–4. ©2016 AACR.

Purpose The purpose of this research note is to identify and prioritize diseases important for detection in adult hearing health care delivery systems. Method Through literature review and expert consultation, the authors identified 195 diseases likely to occur in adults complaining of hearing loss. Five neurotologists rated the importance of disease on 3 dimensions related to the necessity of detection prior to adult hearing aid fitting. Results Ratings of adverse health consequences, diagnostic difficulty, and presence of nonotologic symptoms associated with these diseases resulted in the identification of 104 diseases potentially important for detection prior to adult hearing aid fitting. Conclusions Current and evolving health care delivery systems, including direct-to-consumer sales, involve inconsistent means of disease detection vigilance prior to device fitting. The first steps in determining the safety of these different delivery methods are to identify and prioritize which diseases present the greatest risk for poor health outcomes and, thus, should be detected in hearing health care delivery systems. Here the authors have developed a novel multidimensional rating system to rank disease importance. The rankings can be used to evaluate the effectiveness of alternative detection methods and to inform public health policy. The authors are currently using this information to validate a consumer questionnaire designed to accurately identify when pre- fitting medical evaluations should be required for hearing aid patients.

Objective/HypothesisEosinophilic otitis media (EOM) is a variant of chronic otitis media that is characterized by the development of thick mucoid middle ear effusion, adult onset bronchial asthma, sinonasal polyposis, and aspirin sensitivity. EOM is typically refractory to corticosteroid therapy and surgical intervention. Pegylated interferon (PEG‐IFN) has effectively treated hypereosinophilic syndrome in clinical trials; however, the efficacy of this medication for EOM treatment remains undefined.Study DesignRetrospective, case series, tertiary academic center.MethodsA retrospective chart review was performed on EOM patients from 2008–2014. A total of 32 patients met the clinical criteria for EOM according to established diagnostic guidelines. Outcomes of all patients with severe, refractory EOM who initiated PEG‐IFN therapy are reported.ResultsEight patients were treated with pegylated interferon‐α 2a or 2b for refractory EOM. Half of the patients had significant side effects with interferon treatment. Three of these were able to continue at a reduced dosage without side effect reoccurrence, and one patient stopped the medication permanently. Four of eight (50%) patients had a complete clinical response with total resolution of otorrhea and normalization of middle ear mucosa, and were able to discontinue corticosteroid treatment. Two patients attempted to stop PEG‐IFN therapy after prolonged symptom remission and had recurrent otorrhea. Both patients had symptom resolution after PEG‐IFN reinitiation.ConclusionsThese data demonstrate that pegylated interferon‐α 2a and 2b therapy may benefit patients with severe, refractory EOM. Further larger studies with long‐term follow‐up are required to validate these early but promising results.Level of Evidence4. Laryngoscope, 127:1208–1216, 2017

OBJECTIVE Recently, 2 surgeon rating websites (Consumers' Checkbook and ProPublica) were published to allow the public to compare surgeons through identifying surgeon volume and complication rates. Among neurosurgeons and orthopedic surgeons, only cervical and lumbar spine, hip, and knee procedures were included in this assessment. METHODS The authors examined the methodology of each website to assess potential sources of inaccuracy. Each online tool was queried for reports on neurosurgeons specializing in spine surgery and orthopedic surgeons specializing in spine, hip, or knee surgery. Surgeons were chosen from top-ranked hospitals in the US, as recorded by a national consumer publication ranking system, within the fields of neurosurgery and orthopedic surgery. The results were compared for accuracy and surgeon representation, and the results of the 2 websites were also compared. RESULTS The methodology of each site was found to have opportunities for bias and limited risk adjustment. The end points assessed by each site were actually not complications, but proxies of complication occurrence. A search of 510 surgeons (401 orthopedic surgeons [79%] and 109 neurosurgeons [21%]) showed that only 28% and 56% of surgeons had data represented on Consumers' Checkbook and ProPublica, respectively. There was a significantly higher chance of finding surgeon data on ProPublica (p < 0.001). Of the surgeons from top-ranked programs with data available, 17% were quoted to have high complication rates, 13% with lower volume than other surgeons, and 79% had a 3-star out of 5-star rating. There was no significant correlation found between the number of stars a surgeon received on Consumers' Checkbook and his or her adjusted complication rate on ProPublica. CONCLUSIONS Both the Consumers' Checkbook and ProPublica websites have significant methodological issues. Neither site assessed complication occurrence, but rather readmissions or prolonged length of stay. Risk adjustment was limited or nonexistent. A substantial number of neurosurgeons and orthopedic surgeons from top-ranked hospitals have no ratings on either site, or have data that suggests they are low-volume surgeons or have higher complication rates. Consumers' Checkbook and ProPublica produced different results with little correlation between the 2 websites in how surgeons were graded. Given the significant methodological issues, incomplete data, and lack of appropriate risk stratification of patients, the featured websites may provide erroneous information to the public.

Hematopoietic cell transplantation (HCT) is an important and complex treatment modality for a variety of hematologic malignancies and some solid tumors. Although outcomes of patients who have undergone HCT and require care in intensive care units (ICUs) have improved over time, mortality rates remain high and there are significant associated costs. Lack of a team-based approach to care, especially during critical illness, is detrimental to patient autonomy and satisfaction, and to team morale, ultimately leading to poor quality of care. In this manuscript, we describe the case of a patient who had undergone HCT and was in the ICU setting, where inconsistent team interaction among the various stakeholders delivering care resulted in a lack of shared goals and poor outcomes. Team cognition is cognitive processing at the team level through interactions among team members and is reflected in dynamic communication and coordination behaviors. Although the patient received multidisciplinary care as needed in a medically complicated case, a lack of team cognition and, particularly, inconsistent communication among the dynamic teams caring for the patient, led to mixed messages being delivered with high-cost implications for the health-care system and the family. This article highlights concepts and recommendations that begin a necessary in-depth assessment of implications for clinical care and initiate a research agenda that examines the effects of team cognition on HCT teams, and, more generally, critical care of the patient with cancer.