Declination of Treatment, Racial and Ethnic Disparity, and Overall Survival in US Patients With Breast Cancer.

Importance: Declining treatment negatively affects health outcomes among patients with cancer. Limited research has investigated national trends of and factors associated with treatment declination or its association with overall survival (OS) among patients with breast cancer. Objectives: To examine trends and racial and ethnic disparities in treatment declination and racial and ethnic OS differences stratified by treatment decision in US patients with breast cancer. Design, Setting, and Participants: This retrospective cross-sectional study used data for patients with breast cancer from the 2004 to 2020 National Cancer Database. Four treatment modalities were assessed: chemotherapy, hormone therapy (HT), radiotherapy, and surgery. The chemotherapy cohort included patients with stage I to IV disease. The HT cohort included patients with stage I to IV hormone receptor-positive disease. The radiotherapy and surgery cohorts included patients with stage I to III disease. Data were analyzed from March to November 2023. Exposure: Race and ethnicity and other sociodemographic and clinicopathologic characteristics. Main Outcomes and Measures: Treatment decision, categorized as received or declined, was modeled using logistic regression. OS was modeled using Cox regression. Models were controlled for year of initial diagnosis, age, sex, health insurance, median household income, facility type, Charlson-Deyo comorbidity score, histology, American Joint Committee on Cancer stage, molecular subtype, and tumor grade. Results: The study included 2 837 446 patients (mean [SD] age, 61.6 [13.4] years; 99.1% female), with 1.7% American Indian, Alaska Native, or other patients; 3.5% Asian or Pacific Islander patients; 11.2% Black patients; 5.6% Hispanic patients; and 78.0% White patients. Of 1 296 488 patients who were offered chemotherapy, 124 721 (9.6%) declined; 99 276 of 1 635 916 patients (6.1%) declined radiotherapy; 94 363 of 1 893 339 patients (5.0%) declined HT; and 15 846 of 2 590 963 patients (0.6%) declined surgery. Compared with White patients, American Indian, Alaska Native, or other patients (adjusted odds ratio [AOR], 1.47; 95% CI, 1.26-1.72), Asian or Pacific Islander patients (AOR, 1.29; 95% CI, 1.15-1.44), and Black patients (AOR, 2.01; 95% CI, 1.89-2.14) were more likely to decline surgery; American Indian, Alaska Native, or other patients (AOR, 1.13; 95% CI, 1.05-1.21) and Asian or Pacific Islander patients (AOR, 1.21; 95% CI, 1.16-1.27) were more likely to decline chemotherapy; and Black patients were more likely to decline radiotherapy (AOR, 1.05; 95% CI, 1.02-1.08). Asian or Pacific Islander patients (AOR, 0.81; 95% CI, 0.77-0.85), Black patients (AOR, 0.86; 95% CI, 0.83-0.89), and Hispanic patients (AOR, 0.66; 95% CI, 0.63-0.69) were less likely to decline HT. Furthermore, Black patients who declined chemotherapy had a higher mortality risk than White patients (adjusted hazard ratio [AHR], 1.07; 95% CI, 1.02-1.13), while there were no OS differences between Black and White patients who declined HT (AHR, 1.05; 95% CI, 0.97-1.13) or radiotherapy (AHR, 0.98; 95% CI, 0.92-1.04). Conclusions and Relevance: This cross-sectional study highlights racial and ethnic disparities in treatment declination and OS, suggesting the need for equity-focused interventions, such as patient education on treatment benefits and improved patient-clinician communication and shared decision-making, to reduce disparities and improve patient survival.

Effect of neighborhood and individual-level socioeconomic factors on breast cancer screening adherence in a multi-ethnic study.

BACKGROUND: Although mammography can significantly reduce breast cancer mortality, many women do not receive their annual breast cancer screening. Differences in screening adherence exist by race/ethnicity, socioeconomic status (SES), and insurance status. However, more detailed investigations into the impact of neighborhood disadvantage and access to resources on screening adherence are lacking. METHODS: We comprehensively examined the effect of individual social, economic, and demographic factors (n = 34 variables), as well as neighborhood level SES (nSES) indicators (n = 10 variables) on breast cancer screening adherence across a multi-ethnic population (n = 472). In this cross-sectional study, participants were surveyed from 2017 to 2018. The data was analyzed using univariate regression and LASSO for variable reduction. Significant predictors were carried forward into final multivariable mixed-effect logistic regression models where odds ratios (OR), 95% confidence intervals and p-values were reported. RESULTS: Nineteen percent of participants were non-adherent to breast screening guidelines. Race/ethnicity was not associated with adherence; however, increasing age (OR = 0.97, 95%CI = 0.95-0.99, p = 0.01), renting a home (OR = 0.53, 95%CI = 0.30-0.94, p = 0.04), food insecurity (OR 0.46, 95%CI = 0.22-0.94, p = 0.01), and overcrowding (OR = 0.58, 95% CI = 0.32-0.94, p = 0.01) were significantly associated with lower breast cancer screening adherence. CONCLUSION: Socioeconomic indicators at the individual and neighborhood levels impact low breast cancer screening adherence and may help to inform future screening interventions.

SARS-CoV-2 BNT162b2 vaccine-induced humoral response and reactogenicity in individuals with prior COVID-19 disease.

BACKGROUNDMost individuals with prior COVID-19 disease manifest long-term protective immune responses against reinfection. Accordingly, we tested the hypothesis that humoral immune and reactogenicity responses to a SARS-CoV-2 mRNA vaccine differ in individuals with and without prior COVID-19 disease.METHODSHealth care workers (n = 61) with (n = 30) and without (n = 31) prior COVID-19 disease received two 30 µg doses of Pfizer BNT162b2 vaccine 3 weeks apart. Serum IgG antibody against the spike receptor-binding domain; serum neutralizing activity; and vaccine reactogenicity were assessed longitudinally every 2 weeks for 56 days after the first injection.RESULTSThe COVID-19 group manifested more rapid increases in spike IgG antibody and serum neutralizing activity after the first vaccine dose but showed little or no increase after the second dose compared with the infection-naive group. In fact, spike IgG was at its maximum level after the first dose in 36% of the COVID-19 group versus 0% of the infection-naive group. Peak IgG antibody levels were lower but appeared to fall more slowly in the COVID-19 group versus the infection-naive group. Finally, adverse systemic reactions, e.g., fever, headache, and malaise, were more frequent and lasted longer after both the first and second injection in the COVID-19 group than in the infection-naive group.CONCLUSIONIndividuals with prior COVID-19 disease demonstrate a robust, accelerated humoral immune response to the first dose but an attenuated response to the second dose of BNT162b2 vaccine compared with controls. The COVID-19 group also experienced greater reactogenicity. Humoral responses and reactogenicity to BNT162b2 differ qualitatively and quantitatively in individuals with prior COVID-19 disease compared with infection-naive individuals.FUNDINGThis work was supported by Temple University institutional funds.

Outcomes of Premature Ventricular Contraction-Cardiomyopathy in the Veteran Population: A Secondary Analysis of the CHF-STAT Study.

OBJECTIVES: This study sought to assess the rate and outcomes of premature ventricular contractions (PVC)-cardiomyopathy from the CHF-STAT (Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure) trial, a population with cardiomyopathy (left ventricular [LV] ejection fraction of <40%) and frequent PVCs (>10 PVCs per hour). BACKGROUND: PVCs are associated with heart failure and PVC-cardiomyopathy. The prevalence of PVC-cardiomyopathy and outcome benefits of PVC suppression are not clear. METHODS: A secondary analysis of the CHF-STAT study was performed to compare the rate of successful PVC suppression (≥80% PVC reduction), LV recovery (defined as improvement in LV ejection fraction of ≥10% points), and PVC-cardiomyopathy between amiodarone and placebo groups at 6 months. PVC-cardiomyopathy was defined if both PVC reduction of ≥80% and LV ejection fraction improvement of ≥10% were present at 6 months. Cardiac events (death or resuscitated cardiac arrest) were compared between PVC-cardiomyopathy versus non-PVC-cardiomyopathy during a 5-year follow-up. RESULTS: The rates of successful PVC suppression and LV recovery were significantly higher in the amiodarone (72% and 39%, respectively) when compared to the placebo group (12% and 16%, respectively; p < 0.001), regardless of cardiomyopathy etiology. PVC-cardiomyopathy was present in 29% and 1.8% of patients in the amiodarone and placebo groups, respectively (p < 0.001). Similar PVC-cardiomyopathy rates were found in ischemic (24% amiodarone vs. 2% placebo; p < 0.001) and nonischemic populations (41% amiodarone vs. 1.5% placebo; p < 0.001). Death and resuscitated cardiac arrest were significantly lower in patients with PVC-cardiomyopathy and those treated with amiodarone. CONCLUSIONS: The overall prevalence of PVC-cardiomyopathy in the CHF-STAT study was significant regardless of ischemic substrate (29%, overall population; 41%, nonischemic cardiomyopathy). Treatment of PVC-cardiomyopathy with amiodarone is likely to improve survival in this high-risk population.

Common sampling and modeling approaches to analyzing readmission risk that ignore clustering produce misleading results.

BACKGROUND: There is little consensus on how to sample hospitalizations and analyze multiple variables to model readmission risk. The purpose of this study was to compare readmission rates and the accuracy of predictive models based on different sampling and multivariable modeling approaches. METHODS: We conducted a retrospective cohort study of 17,284 adult diabetes patients with 44,203 discharges from an urban academic medical center between 1/1/2004 and 12/31/2012. Models for all-cause 30-day readmission were developed by four strategies: logistic regression using the first discharge per patient (LR-first), logistic regression using all discharges (LR-all), generalized estimating equations (GEE) using all discharges, and cluster-weighted (CWGEE) using all discharges. Multiple sets of models were developed and internally validated across a range of sample sizes. RESULTS: The readmission rate was 10.2% among first discharges and 20.3% among all discharges, revealing that sampling only first discharges underestimates a population's readmission rate. Number of discharges was highly correlated with number of readmissions (r = 0.87, P < 0.001). Accounting for clustering with GEE and CWGEE yielded more conservative estimates of model performance than LR-all. LR-first produced falsely optimistic Brier scores. Model performance was unstable below samples of 6000-8000 discharges and stable in larger samples. GEE and CWGEE performed better in larger samples than in smaller samples. CONCLUSIONS: Hospital readmission risk models should be based on all discharges as opposed to just the first discharge per patient and utilize methods that account for clustered data.

Development of an urban community-based cohort to promote health disparities research.

OBJECTIVES: Many academic medical centers are positioned amidst disadvantaged urban neighborhoods in which healthcare services are underutilized, participation in research studies is low, and need for health improvement is vast. The goal of Temple Health: Block-by-Block (THB3) is to establish a sustainable cohort of Philadelphia residents engaged in individual and community health improvement through health research. METHODS: Recruitment of a population-based sample from 11 Philadelphia zip codes began in August 2015. The cornerstone of the project is the in-home, biannual assessment of each subject. RESULTS: The first-year goal of 1000 enrolled subjects was met. Greater than 90% of subjects represent minority racial or ethnic groups; average age is 46 years; 65% of subjects have a high school education or less. A high burden of health conditions exists including obesity (54%), smoking (41%), hypertension (44%), and diabetes (17.8%). CONCLUSIONS: THB3 provides a research infrastructure to promote community participation in a health improvement initiative from which future translational research, health education and preventive services will emanate. The launch of this cohort study has provided extensive lessons regarding urban community-based research and health promotion initiatives.

Risk of Coronary Events 55 Years after Thymic Irradiation in the Hempelmann Cohort.

BACKGROUND: Studies of cancer survivors treated with older radiotherapy (RT) techniques (pre-1990s) strongly suggest that ionizing radiation to the chest increases the risk of coronary heart disease (CHD). Our goal was to evaluate the impact of more modern cardiac shielding techniques of RT on the magnitude and timing of CHD risk by studying a cohort exposed to similar levels of cardiac irradiation years ago. METHODS: Between 2004 and 2008, we re-established a population-based, longitudinal cohort of 2,657 subjects exposed to irradiation for an enlarged thymus during infancy between 1926 and 1957 and 4,388 of their non-irradiated siblings. CHD events were assessed using a mailed survey and from causes of death listed in the National Death Index. We used Poisson regression methods to compare incidence rates by irradiation status and cardiac radiation dose. Results were adjusted for the CHD risk factors of attained-age, sex, diabetes, dyslipidemia hypertension and smoking. RESULTS: Median age at time of follow-up was 57.5 years (range 41.2 - 88.8 yrs) for irradiated and non-irradiated siblings. The mean estimated cardiac dose amongst the irradiated was 1.45 Gray (range 0.17 - 20.20 Gy), with 91% receiving <3.00 Gy. During a combined 339,924 person-years of follow-up, 213 myocardial infarctions (MI) and 350 CHD events (MI, bypass surgery and angioplasty) occurred. After adjustment for attained age, gender, and other CHD risk factors, the rate ratio for MI incidence in the irradiated group was 0.98 (95%CI, 0.74 - 1.30), and for any CHD event was 1.07 (95%CI, 0.86 - 1.32). Higher radiation doses were not associated with more MIs or CHD events in this dose range, in either the crude or the adjusted analyses. CONCLUSIONS: Radiation to the heart during childhood of <3 Gy, the exposure in most of our cohort, does not increase the lifelong risk of CHD. Reducing cardiac radiation to this amount without increasing other cardiotoxic therapies may eliminate the increased CHD risk associated with radiotherapy for childhood cancer. By extension there is unlikely to be increased CHD risk from relatively higher dose imaging techniques, such as CT, because such techniques use much smaller radiation doses than received by our cohort.

Association of Variants in BAG3 With Cardiomyopathy Outcomes in African American Individuals.

Importance: The prevalence of nonischemic dilated cardiomyopathy (DCM) is greater in individuals of African ancestry than in individuals of European ancestry. However, little is known about whether the difference in prevalence or outcomes is associated with functional genetic variants. Objective: We hypothesized that Bcl2-associated anthanogene 3 (BAG3) genetic variants were associated with outcomes in individuals of African ancestry with DCM. Design: This multicohort study of the BAG3 genotype in patients of African ancestry with dilated cardiomyopathy uses DNA obtained from African American individuals enrolled in 3 clinical studies: the Genetic Risk Assessment of African Americans With Heart Failure (GRAHF) study; the Intervention in Myocarditis and Acute Cardiomyopathy Trial-2 (IMAC-2) study; and the Genetic Risk Assessment of Cardiac Events (GRACE) study. Samples of DNA were also acquired from the left ventricular myocardium of patients of African ancestry who underwent heart transplant at the University of Colorado and University of Pittsburgh. Main Outcomes and Measures: The primary end points were the prevalence of BAG3 mutations in African American individuals and event-free survival in participants harboring functional BAG3 mutations. Results: Four BAG3 genetic variants were identified; these were expressed in 42 of 402 African American individuals (10.4%) with nonischemic heart failure and 9 of 107 African American individuals (8.4%) with ischemic heart failure but were not present in a reference population of European ancestry (P < .001). The variants included 2 nonsynonymous single-nucleotide variants; 1 three-nucleotide in-frame insertion; and 2 single-nucleotide variants that were linked in cis. The presence of BAG3 variants was associated with a nearly 2-fold (hazard ratio, 1.97 [95% CI, 1.19-3.24]; P = .01) increase in cardiac events in carriers compared with noncarriers. Transfection of transformed adult human ventricular myocytes with plasmids expressing the 4 variants demonstrated that each variant caused an increase in apoptosis and a decrease in autophagy when samples were subjected to the stress of hypoxia-reoxygenation. Conclusions and Relevance: This study demonstrates that genetic variants in BAG3 found almost exclusively in individuals of African ancestry were not causative of disease but were associated with a negative outcome in patients with a dilated cardiomyopathy through modulation of the function of BAG3. The results emphasize the importance of biological differences in causing phenotypic variance across diverse patient populations, the need to include diverse populations in genetic cohorts, and the importance of determining the pathogenicity of genetic variants.

Use of Larynx-Preservation Strategies in the Treatment of Laryngeal Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update.

Purpose To update the guideline recommendations on the use of larynx-preservation strategies in the treatment of laryngeal cancer. Methods An Expert Panel updated the systematic review of the literature for the period from January 2005 to May 2017. Results The panel confirmed that the use of a larynx-preservation approach for appropriately selected patients does not compromise survival. No larynx-preservation approach offered a survival advantage compared with total laryngectomy and adjuvant therapy as indicated. Changes were supported for the use of endoscopic surgical resection in patients with limited disease (T1, T2) and for initial total laryngectomy in patients with T4a disease or with severe pretreatment laryngeal dysfunction. New recommendations for positron emission tomography imaging for the evaluation of regional nodes after treatment and best measures for evaluating voice and swallowing function were added. Recommendations Patients with T1, T2 laryngeal cancer should be treated initially with intent to preserve the larynx by using endoscopic resection or radiation therapy, with either leading to similar outcomes. For patients with locally advanced (T3, T4) disease, organ-preservation surgery, combined chemotherapy and radiation, or radiation alone offer the potential for larynx preservation without compromising overall survival. For selected patients with extensive T3 or large T4a lesions and/or poor pretreatment laryngeal function, better survival rates and quality of life may be achieved with total laryngectomy. Patients with clinically involved regional cervical nodes (N+) who have a complete clinical and radiologic imaging response after chemoradiation do not require elective neck dissection. All patients should undergo a pretreatment baseline assessment of voice and swallowing function and receive counseling with regard to the potential impact of treatment options on voice, swallowing, and quality of life. Additional information is available at www.asco.org/head-neck-cancer-guidelines and www.asco.org/guidelineswiki .

SLC44A2 single nucleotide polymorphisms, isoforms, and expression: Association with severity of Meniere's disease?

SLC44A2 was discovered as the target of an antibody that causes hearing loss. Knockout mice develop age related hearing loss, loss of sensory cells and spiral ganglion neurons. SLC44A2 has polymorphic sites implicated in human disease. Transfusion related acute lung injury (TRALI) is linked to rs2288904 and genome wide association studies link rs2288904 and rs9797861 to venous thromboembolism (VTE), coronary artery disease and stroke. Here we report linkage disequilibrium of rs2288904 with rs3087969 and the association of these SLC44A2 SNPs with Meniere's disease severity. Tissue-specific isoform expression differences suggest that the N-terminal domain is linked to different functions in different cell types. Heterozygosity at rs2288904 CGA/CAA and rs3087969 GAT/GAC showed a trend for association with intractable Meniere's disease compared to less severe disease and to controls. The association of SLC44A2 SNPs with VTE suggests that thrombi affecting cochlear vessels could be a factor in Meniere's disease.

Evidence of prostate cancer "reverse stage migration" toward more advanced disease at diagnosis: Data from the Pennsylvania Cancer Registry.

PURPOSE: The widespread adoption of prostate-specific antigen-based prostate cancer screening caused a stage migration toward earlier stage disease at diagnosis. We investigated whether this stage migration has persisted in a contemporary analysis of a population-based statewide cancer registry. MATERIALS AND METHODS: We analyzed the Pennsylvania Cancer Registry, a statewide registry of all newly diagnosed cancers. Data were collected on prostate cancers diagnosed between 1992 and 2012. We determined age-adjusted prostate cancer incidence and mortality rates, as well as the distribution of tumor stage (localized, regional, or metastatic) at diagnosis, and assessed for changes in these variables over time using joinpoint analysis. RESULTS: Between 1992 and 2012, 210,831 new cases of prostate cancer were diagnosed in Pennsylvania, and 33,948 men died of disease. Age-adjusted prostate cancer incidence rates, and specifically the incidence of localized disease, have decreased dramatically since 2007 to 2008. Due to the decreased diagnosis of localized disease, regional and metastatic tumors have made up a greater percentage of all prostate cancer diagnoses in recent years, despite a relatively stable incidence of these advanced stage tumors. CONCLUSIONS: Over the past 2 decades, age-adjusted prostate cancer incidence rates in Pennsylvania have decreased, primarily because of the decreased detection of early-stage disease. There has been a corresponding shift toward more advanced disease at diagnosis. These findings may be explained by the decreased use of prostate-specific antigen-based screening, among other factors. The 2012 United States Preventative Services Task Force recommendations against prostate cancer screening may exacerbate this concerning trend, potentially resulting in an increase in prostate cancer-specific mortality.

Investigating the debate of home birth safety: A critical review of cohort studies focusing on selected infant outcomes.

AIM: There is a debate within the medical community regarding the safety of planned home births. The presumption of increased risk of maternal and infant morbidity and mortality at home due to limited access to life-saving interventions is not clearly supported by research. The aim of the present study was to assess strengths and limitations of the methodological approaches of cohort studies that compare home births with hospital births by focusing on selected infant outcomes. METHODS: Studies were identified that assess the risk for at least one of three infant outcomes (mortality, Apgar score, and admission to the neonatal intensive care unit [NICU]) of home births compared with hospital births. RESULTS: Fifteen cohort studies were included. Two studies of low-risk births and two including higher risk births found home births to be at an increased risk of neonatal mortality. However, mortality is rare in developed nations and may not be the best measure of safety. When studies focused on low-risk pregnancies, planned birth location, and well-trained birth attendants, there was no difference in neonatal morbidity (Apgar score and NICU admission). CONCLUSION: Many methodological challenges were identified among these studies. This review contributes to the home birth published work by identifying key strengths and limitations that need to be accounted for in the interpretation of study findings and the development of future studies. Based on this review, the key variables that would strengthen future studies are birth attendant identification, documented planned birth location, and specification of the birth risk level. Uniformity of data collection and minimizing missing data are also critical.

Parent and Child Independent Report of Emotional Responses to Asthma-Specific Vignettes: The Relationship Between Emotional States, Self-Management Behaviors, and Symptoms.

UNLABELLED: Little is known about the emotional intelligence (EI) of parents and their children with asthma. Objectives of this study were to assess: 1) parent's and children's report of emotions in response to an asthma vignette (proxy for EI) and 2) the relationship between emotions, self-management behaviors, and symptoms. DESIGN AND METHODS: We conducted a descriptive, mixed methods study of children 7-12 years old with asthma. Parent-Child dyads (n=104) responded to an asthma vignette to gain insight into emotions, symptoms, and self-management behaviors. Additional questions assessed confidence and worry using a 5-point Likert scale. Thematic analyses and descriptive statistics were used to assess qualitative and quantitative outcomes. RESULTS: Children were predominantly male (58%), 7-9 (58%), and White (46%). The most common negative emotions reported by children were scared and sad. Children who sought help from an adult were less likely to report using medications compared to children who did not seek help (39.5% vs. 62.3%, p=.029). Children with low worry and high confidence had fewer symptoms compared to children reporting high worry and low confidence (symptoms: days 3.24 vs. 6.77, p=.012, nights 2.71 vs. 5.36, p=.004). CONCLUSIONS: Children provided appropriate emotional responses to the asthma vignette; emotions were related to self-management behaviors and symptoms. More studies are needed to specifically assess EI in this population. PRACTICE IMPLICATIONS: Parents and children with greater EI may be better able to understand their needs, engage in self-management behaviors, and communicate with their nurses, to improve their support network and ability to access services.

Prehospital Trauma Triage Decision-making: A Model of What Happens between the 9-1-1 Call and the Hospital.

We describe the decision-making process used by emergency medical services (EMS) providers in order to understand how 1) injured patients are evaluated in the prehospital setting; 2) field triage criteria are applied in-practice; and 3) selection of a destination hospital is determined. We conducted separate focus groups with advanced and basic life support providers from rural and urban/suburban regions. Four exploratory focus groups were conducted to identify overarching themes and five additional confirmatory focus groups were conducted to verify initial focus group findings and provide additional detail regarding trauma triage decision-making and application of field triage criteria. All focus groups were conducted by a public health researcher with formal training in qualitative research. A standardized question guide was used to facilitate discussion at all focus groups. All focus groups were audio-recorded and transcribed. Responses were coded and categorized into larger domains to describe how EMS providers approach trauma triage and apply the Field Triage Decision Scheme. We conducted 9 focus groups with 50 EMS providers. Participants highlighted that trauma triage is complex and there is often limited time to make destination decisions. Four overarching domains were identified within the context of trauma triage decision-making: 1) initial assessment; 2) importance of speed versus accuracy; 3) usability of current field triage criteria; and 4) consideration of patient and emergency care system-level factors. Field triage is a complex decision-making process which involves consideration of many patient and system-level factors. The decision model presented in this study suggests that EMS providers place significant emphasis on speed of decisions, relying on initial impressions and immediately observable information, rather than precise measurement of vital signs or systematic application of field triage criteria.

Hair Cell Loss, Spiral Ganglion Degeneration, and Progressive Sensorineural Hearing Loss in Mice with Targeted Deletion of Slc44a2/Ctl2.

SLC44A2 (solute carrier 44a2), also known as CTL2 (choline transporter-like protein 2), is expressed in many supporting cell types in the cochlea and is implicated in hair cell survival and antibody-induced hearing loss. In mice with the mixed C57BL/6-129 background, homozygous deletion of Slc44a2 exons 3­10 (Slc44a2(Δ/Δ)resulted in high-frequency hearing loss and hair cell death. To reduce effects associated with age-related hearing loss (ARHL) in these strains, mice carrying the Slc44a2Δ allele were backcrossed to the ARHL-resistant FVB/NJ strain and evaluated after backcross seven(N7) (99 % FVB). Slc44a2(Δ/Δ) mice produced abnormally spliced Slc44a2 transcripts that contain a frame shift and premature stop codons. Neither full-length SLC44A2 nor a putative truncated protein could be detected in Slc44a2(Δ/Δ) mice, suggesting a likely null allele. Auditory brain stem responses (ABRs) of mice carrying the Slc44a2Δ allele on an FVB/NJ genetic background were tested longitudinally between the ages of 2 and 10 months. By 6 months of age,Slc44a2(Δ/Δ) mice exhibited hearing loss at 32 kHz,but at 12 and 24 kHz had sound thresholds similar to those of wild-type Slc44a2(+/+) and heterozygous +/Slc44a2Δ mice. After 6 months of age, Slc44a2(Δ/Δ) mutants exhibited progressive hearing loss at all frequencies and +/Slc44a2(Δ) mice exhibited moderate threshold elevations at high frequency. Histologic evaluation of Slc44a2(Δ/Δ) mice revealed extensive hair cell and spiral ganglion cell loss, especially in the basal turn of the cochlea. We conclude that Slc44a2 function is required for long-term hair cell survival and maintenance of hearing.

An observational pre-post study of re-structuring Medicine inpatient teaching service: Improved continuity of care within constraint of 2011 duty hours.

BACKGROUND: Implementation of more stringent regulations on duty hours and supervision by the Accreditation Council for Graduate Medical Education in July 2011 makes it challenging to design inpatient Medicine teaching service that complies with the duty hour restrictions while optimizing continuity of patient care. OBJECTIVE: To prospectively compare two inpatient Medicine teaching service structures with respect to residents' impression of continuity of patient care (primary outcome), time available for teaching, resident satisfaction and length-of-stay (secondary endpoints). DESIGN: Observational pre-post study. METHODS: Surveys were conducted both before and after Conventional Medicine teaching service was changed to a novel model (MegaTeam). SETTINGS: Academic General Medicine inpatient teaching service. RESULTS: Surveys before and after MegaTeam implementation were completed by 68.5% and 72.2% of internal medicine residents, respectively. Comparing conventional with MegaTeam, the % of residents who agreed or strongly agreed that the (i) ability to care for majority of patients from admission to discharge increased from 29.7% to 86.6% (p<0.01); (ii) the concern that number of handoffs was too many decreased from 91.9% to 18.2% (p<0.01); (iii) ability to provide appropriate supervision to interns increased from 38.1% to 70.7% (p<0.01); (iv) overall resident satisfaction with inpatient Medicine teaching service increased from 24.7% to 56.4% (p<0.01); and (v) length-of-stay on inpatient Medicine service decreased from 5.3±6.2 to 4.9±6.8 days (p<0.03). CONCLUSIONS: According to our residents, the MegaTeam structure promotes continuity of patient care, decreases number of handoffs, provides adequate supervision and teaching of interns and medical students, increases resident overall satisfaction and decreases length-of-stay.

Evaluation of Cataract Surgery Outcomes at the Ban Phaeo Mobile Eye Clinic, Thailand.

PURPOSE: To evaluate the quality and efficacy of the Ban Phaeo Mobile Eye Clinic (BPMEC) model in providing cataract surgery to rural Thailand. METHODS: Retrospective review of 4-week postoperative visual acuity (VA) of 7040 patients receiving unilateral cataract surgery at 75 sites from October 2008 to March 2011. BPMEC conducted screening, surgery, and follow-up at partnering local hospitals that otherwise do not offer eye care. The primary outcome was achievement of VA ≥20/70, which was secondarily analyzed by cataract extraction method (phacoemulsification, phaco, or extracapsular cataract extraction, ECCE) and intraocular lens (IOL) type (foldable acrylic or rigid polymethylmethacrylate). RESULTS: Preoperatively, 249 eyes (4%) had uncorrected VA ≥20/70. Four weeks postoperatively, 5957 (85%) had VA ≥20/70, 3288 (47%) had VA ≥20/40, and 69 (1%) were lost to follow-up. Phaco was performed in 6324 eyes (90%), 1581 (25%) receiving foldable IOLs. A total of 1403 eyes (89%) undergoing phaco with a foldable IOL had postoperative VA ≥20/70, compared to 4058 (85%) and 496 (69%) of those undergoing phaco with a rigid IOL (p < 0.05) and ECCE with a rigid IOL (p < 0.001), respectively. Overall, 37 eyes were left aphakic. Reported intraocular complications included zonular dehiscence (37 eyes), retained lens fragment (2 eyes), wound leakage (1 eye), and posterior capsule tear (1 eye). CONCLUSIONS: The 4-week uncorrected postoperative VAs met the World Health Organization's quality target of VA ≥20/70 for eyes undergoing phaco and were comparable to those published by an urban hospital in Bangkok.

Health care workers' knowledge, attitudes and practices on tobacco use in economically disadvantaged dominican republic communities.

Tobacco use is increasing globally, particularly in low and middle-income countries like the Dominican Republic (DR) where data have been lacking. Health care worker (HCW) interventions improve quit rates; asking patients about tobacco use at each visit is an evidence-based first step. This study provides the first quantitative examination of knowledge, attitudes and practices of DR HCWs regarding tobacco use. All HCWs (N = 153) in 7 economically disadvantaged DR communities were targeted with anonymous surveys. Approximately 70% (N = 107) completed the primary outcome item, asking about tobacco use at each encounter. Despite >85% strongly agreeing that they should ask about tobacco use at each encounter, only 48.6% reported doing so. While most (94.39%) strongly agreed that smoking is harmful, knowledge of specific health consequences varied from 98.13% for lung cancer to 41.12% for otitis media. Few received training in tobacco intervention (38.32%). Exploratory analyses revealed that always asking even if patients are healthy, strongly agreeing that tobacco causes cardiac disease, and always advising smoke-free homes were associated with always asking. Overall, results demonstrate a disconnect between HCW belief and practice. Though most agreed that always asking about tobacco was important, fewer than half did so. Gaps in HCW knowledge and practices suggest a need for education and policy/infrastructure support. To our knowledge, this is the first reported survey of DR HCWs regarding tobacco, and provides a foundation for future tobacco control in the DR.