Second Primary Malignancies After Commercial CAR T Cell Therapy: Analysis of FDA Adverse Events Reporting System (FAERS).

Second primary malignancies (SPMs) were reported in 536 out of 12,394 (4.3%) adverse event reports following CAR T cell therapies in the FDA Adverse Event Reporting System (FAERS). Myeloid and T-cell neoplasms were disproportionately more frequently reported, warranting further follow-up.

Cutaneous Angiosarcoma Subtypes: A Quantitative Systematic Review of Demographics, Treatments, and Outcomes Within Published Patient-Level Cases.

BACKGROUND: Cutaneous angiosarcoma (cAS) is a highly aggressive malignancy arising from the vascular endothelium. Given its rarity, there is insufficient data detailing patient demographics, management, and survival outcomes. OBJECTIVE: To systematically compile published patient-level cases of cAS and to quantify and analyze data on demographics, management, and outcomes while determining prognostic indicators. MATERIALS AND METHODS: Searches of EBSCOhost, MEDLINE, EMBASE, and the Cochrane Library generated 1,500 cases of cAS with individual level data available. PRISMA guidelines were followed. RESULTS: Cutaneous angiosarcoma presented most often on the scalp of elderly men. Metastasis occurred in 36.3% of cases. Aggregate 5-year survival was 31.6% with the median survival of 25 months. The best 5-year survival was in the radiation-associated subtype (48.8%), whereas the worst was in the Stewart-Treves subtype (21.6%). Using multivariate analysis, gender, age group, disease subtype, treatment modality, and metastasis at presentation had significant effects on survival outcomes (p < .05). CONCLUSION: The breadth of information obtained enables this study to serve as a resource that clinicians may reference when they encounter cAS.

Dietary Inflammatory Potential and Bone Outcomes in Midwestern Post-Menopausal Women.

Little is known about the inflammatory potential of diet and its relation to bone health. This cross-sectional study examined the association between the inflammatory potential of diet and bone-related outcomes in midwestern, post-menopausal women enrolled in the Heartland Osteoporosis Prevention Study (HOPS) randomized controlled trial. Dietary intake from the HOPS cohort was used to calculate Dietary Inflammatory Index (DII®) scores, which were energy-adjusted (E-DIITM) and analyzed by quartile. The association between E-DII and lumbar and hip bone mineral density (BMD) and lumbar trabecular bone scores (TBS; bone structure) was assessed using ANCOVA, with pairwise comparison to adjust for relevant confounders (age, education, race/ethnicity, smoking history, family history of osteoporosis/osteopenia, BMI, physical activity, and calcium intake). The cohort included 272 women, who were predominately white (89%), educated (78% with college degree or higher), with a mean BMI of 27 kg/m2, age of 55 years, and E-DII score of -2.0 ± 1.9 (more anti-inflammatory). After adjustment, E-DII score was not significantly associated with lumbar spine BMD (p = 0.53), hip BMD (p = 0.29), or TBS at any lumbar location (p > 0.05). Future studies should examine the longitudinal impact of E-DII scores and bone health in larger, more diverse cohorts.

Changes in Dietary Inflammatory Index Score over Time and Cancer Development in Rural Post-Menopausal Women.

Inflammation plays a key role in cancer development. As an important modulator of inflammation, the role of diet should be explored. The purpose of this study was to determine the association between diets with a higher inflammatory potential, as measured by the Dietary Inflammatory Index (DII®), and cancer development in a cohort of rural post-menopausal women. Dietary intake from a randomized controlled trial cohort of rural, post-menopausal women in Nebraska was used to compute energy-adjusted DII (E-DIITM) scores at baseline and four years later (visit 9). A linear mixed model analysis and multivariate logistic regression evaluated the association between E-DII scores (baseline, visit 9, change score) and cancer status. Of 1977 eligible participants, those who developed cancer (n = 91, 4.6%) had a significantly larger, pro-inflammatory change in E-DII scores (Non-cancer: Δ 0.19 ± 1.43 vs. Cancer: Δ 0.55 ± 1.43, p = 0.02). After adjustment, odds of cancer development were over 20% higher in those with a larger change (more pro-inflammatory) in E-DII scores than those with smaller E-DII changes (OR = 1.21, 95% CI [1.02, 1.42], p = 0.02). Shifting to a more pro-inflammatory diet pattern over four years was associated with increased odds of cancer development, but not with E-DII at baseline or visit 9 alone.

The relationship between nutrition, gut dysbiosis, and pediatric sickle cell pain outcomes: A pilot study.

BACKGROUND: Nutritional deficiencies are prevalent in sickle cell disease (SCD) and may be associated with worse pain outcomes. Gut dysbiosis has been reported in patients with SCD and may contribute to both nutritional deficiencies and pain. OBJECTIVES: We tested the association of nutrition, fat-soluble vitamin (FSV) deficiency, and gut microbiome composition on clinical outcomes in SCD. Second, we measured the association between diet and exocrine pancreatic function on FSV levels. METHODS: Using case control design, we enrolled children with SCD (n = 24) and matched healthy controls (HC; n = 17, age, sex, race/ethnicity). Descriptive statistics summarized demographic and clinical data. Wilcoxson-rank tests compared FSV levels between cohorts. Regression modeling tested the association between FSV levels and SCD status. Welch's t-test with Satterthwaite adjustment evaluated associations between microbiota profiles, SCD status, and pain outcomes. RESULTS: Vitamin A and D levels were significantly decreased in participants with HbSS as compared to HC (vitamin A, p = < .0001, vitamin D, p = .014) independent of nutritional status. FSV correlated with dietary intake in SCD and HC cohorts. Gut microbial diversity was reduced in hemoglobin SS (HbSS) compared to hemoglobin SC (HbSC) and HC, p = .037 and .059, respectively. The phyla Erysipelotrichaceae and Betaproteobacteria were higher in SCD children reporting the highest quality-of-life (QoL) scores (p = .008 and .049, respectively), while Clostridia were higher in those with lower QoL scores (p = .03). CONCLUSION: FSV deficiencies and gut dysbiosis are prevalent in children with SCA. Gut microbial composition is significantly different in children with SCD with low QoL scores.

Impact of specialty on the self-reported practice of using oral antibiotic therapy for definitive treatment of bloodstream infections.

Background: No established guidelines exist regarding the role of oral antibiotic therapy (OAT) to treat bloodstream infections (BSIs), and practices may vary depending on clinician specialty and experience. Objective: To assess practice patterns regarding oral antibiotic use for treatment of bacteremia in infectious diseases clinicians (IDCs, including physicians and pharmacists and trainees in these groups) and non-infectious diseases clinicians (NIDCs). Design: Open-access survey. Participants: Clinicians caring for hospitalized patients receiving antibiotics. Methods: An open-access, web-based survey was distributed to clinicians at a Midwestern academic medical center using e-mail and to clinicians outside the medical center using social media. Respondents answered questions regarding confidence prescribing OAT for BSI in different scenarios. We used χ2 analysis for categorical data evaluated association between responses and demographic groups. Results: Of 282 survey responses, 82.6% of respondents were physicians, 17.4% pharmacists, and IDCs represented 69.2% of all respondents. IDCs were more likely to select routine use of OAT for BSI due to gram-negative anaerobes (84.6% vs 59.8%; P < .0001), Klebsiella spp (84.5% vs 69.0%; P < .009), Proteus spp (83.6% vs 71.3%; P < .027), and other Enterobacterales (79.5% vs 60.9%; P < .004). Our survey results revealed significant differences in selected treatment of Staphylococcus aureus syndromes. Fewer IDCs than NIDCs selected OAT to complete treatment for methicillin-resistant S. aureus (MRSA) BSI due to gluteal abscess (11.9% vs 25.6%; P = .012) and methicillin-susceptible S. aureus (MSSA) BSI due to septic arthritis (13.9% vs 20.9%; P = .219). Conclusions: Practice variation and discordance with evidence for the use of OAT for BSIs exists among IDCs versus NIDCs, highlighting opportunities for education in both clinician groups.

A Flexible Ensemble Learning Method for Survival Extrapolation.

OBJECTIVES: Survival extrapolation is an important statistical concept for estimating long-term survival from short-term clinical trial data. It is widely used in health technology assessment (HTA). Survival extrapolation is often performed by fitting one or two parametric models selected based on experience or selecting a model based on some goodness of fit statistics from a predefined collection of models. The main challenge in survival extrapolation is that the result is sensitive to model misspecification. In this study, we aim to propose a new approach that has a robust performance for survival extrapolation. METHODS: We propose a new method called Ensemble Learning for Survival Extrapolation (ELSE). Instead of selecting one best model from a predefined collection, ELSE builds an ensemble model based on a collection of models from the model library. Under this framework, we construct a point estimate of the long-term survival with a weighted average of the estimates of all candidate models and derive confidence intervals using nonparametric bootstrap. RESULTS: With our extensive numerical simulation studies, the proposed ELSE method shows better performance than the traditionally used model selection procedure based on Akaike Information Criterion (AIC). With a real data application to the Therapeutically Applicable Research to Generate Effective Treatment Wilms Tumor project (TARGET-WT) data, the ELSE method produces better survival extrapolation results in point estimate accuracy and confidence interval coverage. CONCLUSIONS: We developed an ensemble learning method for survival extrapolation (ELSE) which is robust for the underline data model and has good real data performance.

Racial/Ethnic Disparities in the Management of Pediatric Acute Pancreatitis Across Children's Hospitals.

OBJECTIVES: Racial or ethnic disparities in health care delivery and resource utilization have been reported in a variety of pediatric diseases. In acute pancreatitis (AP), there is an association between Black race and increased inpatient mortality. Data on the association of race and ethnicity and resource use for managing pediatric AP are lacking. The aim of this study is to investigate this potential association in pediatric AP. METHODS: Retrospective study of children 0-18 years diagnosed with AP in the Pediatric Health Information System (PHIS) database from 2012 to 2018. Descriptive statistics were used to summarize cohort characteristics. Race/ethnicity classifications included non-Hispanic Black (NHB), non-Hispanic White (NHW, used as reference), Hispanic, and "Other." Associations between patient characteristics and race/ethnicity were determined using χ2 tests. Generalized linear mixed regression model was used to determine the association of race/ethnicity with odds of resource utilization, costs, and length of hospital stay after adjusting for covariates with a random intercept for site. RESULTS: Five thousand nine hundred sixty-three patients from 50 hospitals were included. Adjusted analysis showed that NHB children hospitalized with AP were at lower odds of receiving opioids in the first 24 hours [adjusted odds ratio (aOR) = 0.82, 95% confidence interval (CI) = 0.70-0.98] and receiving intravenous fluids during the hospitalization (aOR = 0.64, 95% CI = 0.43-0.96) when compared with NHW children. Additionally, NHB and Hispanic children had a prolonged adjusted mean length of hospital stay and higher hospital costs when compared with NHW children. Although there was no significant association between race/ethnicity and diagnosis of pancreatic necrosis or sepsis, Hispanic and "Other" children were at higher odds of receiving antibiotics during hospitalization for AP (aOR = 1.33, 95% CI = 1.13-1.57 and aOR = 1.37, 95% CI = 1.09-1.73, respectively) than NHW children. CONCLUSIONS: Disparities exist in utilization of health care interventions for pediatric AP patients by race/ethnicity. Future studies should investigate why these disparities exist and if these disparities affect outcomes.

Antibiotic Prescribing for Acute Respiratory Illnesses in Persons With HIV Compared With Persons Without HIV.

Background: Antibiotic overuse increases health care cost and promotes antimicrobial resistance. People with HIV (PWH) who develop acute respiratory infections (ARIs) may be assumed to be "higher risk," compared with non-PWH, but comparative antibiotic use evaluations have not been performed. Methods: This observational, single-center study compared antibiotic prescribing in independent clinical encounters for PWH and non-PWH diagnosed with ARI in outpatient clinical practices using International Classification of Diseases, 10th Revision, codes between January 1, 2014, and April 30, 2018. The Fisher exact test compared categorical variables with antibiotic prescribing patterns. Results: There were 209 patients in the PWH cohort vs 398 patients in the non-PWH cohort. PWH had a median CD4+ count of 610 cells/mm3, with 91% on antiretroviral therapy and 78% virally suppressed. Thirty-seven percent of all visits resulted in an antibiotic prescription, and 89% were inappropriate. Antibiotics were prescribed more frequently in non-PWH (35% PWH vs 40% non-PWH; P = .172) and managed according to guidelines more often in PWH (37% PWH vs 30% non-PWH; P = .039). Antibiotics were prescribed appropriately most frequently in PWH managed by HIV clinicians (29% PWH managed by HIV clinician vs 12% PWH managed by non-HIV clinician vs 8% non-PWH; P = .010). HIV clinicians prescribed antibiotics for a mean duration of 5.9 days vs PWH managed by a non-HIV clinician for 9.1 days vs non-PWH for 7.6 days (P < .0001). Conclusions: Outpatient antibiotic overuse remains prevalent among patients evaluated for ARI. We found less frequent inappropriate antibiotic use in PWH. Prescriber specialty, rather than HIV diagnosis, was related to appropriateness of antimicrobial prescribing.

Therapeutic effect of NLRP3 inhibition on hearing loss induced by systemic inflammation in a CAPS-associated mouse model.

BACKGROUND: Cryopyrin-associated periodic syndrome (CAPS) is an inherited autoinflammatory disease caused by a gain-of-function mutation in NLRP3. Although CAPS patients frequently suffer from sensorineural hearing loss, it remains unclear whether CAPS-associated mutation in NLRP3 is associated with the progression of hearing loss. METHODS: We generated a mice with conditional expression of CAPS-associated NLRP3 mutant (D301N) in cochlea-resident CX3CR1 macrophages and examined the susceptibility of CAPS mice to inflammation-mediated hearing loss in a local and systemic inflammation context. FINDINGS: Upon lipopolysaccharide (LPS) injection into middle ear cavity, NLRP3 mutant mice exhibited severe cochlear inflammation, inflammasome activation and hearing loss. However, this middle ear injection model induced a considerable hearing loss in control mice and inevitably caused an inflammation-independent hearing loss possibly due to ear tissue damages by injection procedure. Subsequently, we optimized a systemic LPS injection model, which induced a significant hearing loss in NLRP3 mutant mice but not in control mice. Peripheral inflammation induced by a repetitive low dose of LPS injection caused a blood-labyrinth barrier disruption, macrophage infiltration into cochlea and cochlear inflammasome activation in an NLRP3-dependent manner. Interestingly, both cochlea-infiltrating and -resident macrophages contribute to peripheral inflammation-mediated hearing loss of CAPS mice. Furthermore, NLRP3-specific inhibitor, MCC950, as well as an interleukin-1 receptor antagonist significantly alleviated systemic LPS-induced hearing loss and inflammatory phenotypes in NLRP3 mutant mice. INTERPRETATION: Our findings reveal that CAPS-associated NLRP3 mutation is critical for peripheral inflammation-induced hearing loss in our CAPS mice model, and an NLRP3-specific inhibitor can be used to treat inflammation-mediated sensorineural hearing loss. FUNDING: National Research Foundation of Korea Grant funded by the Korean Government and the Team Science Award of Yonsei University College of Medicine.

Survival characteristics of fibrolamellar hepatocellular carcinoma: A Surveillance, Epidemiology, and End Results database study.

BACKGROUND: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare and distinct type of hepatocellular carcinoma that frequently presents in an advanced stage in younger patients with no underlying liver disease. Currently, there is a limited understanding of factors that impact outcomes in FL-HCC. AIM: To characterize the survival of FL-HCC by age, race, and surgical intervention. METHODS: This is a retrospective study of The Surveillance, Epidemiology, and End Results database. We identified patients with FL-HCC between 2000-2018 by using an ICD-O-3 site code C22.0 and a histology code 8171/3: Hepatocellular carcinoma, fibrolamellar. In addition, demographics, tumor characteristics, types of surgical procedure, stages, and survival data were obtained. We conducted three separate survival analyses by age groups; ≤ 19, 20-59, and ≥ 60-year-old, and race; White, Black, Hispanic, Asian and Pacific islanders (API), and surgical types; Wedge resection or segmental resection, lobectomy, extended lobectomy (lobectomy + locoregional therapy or resection of the other lobe), and transplant. The Chi-Square test analyzed categorical variables, and continuous variables were examined using the Mann-Whitney U test. The Kaplan-Meier survival curve was used to compare survival. Multivariate analysis was done with Cox regression analysis. RESULTS: We identified 225 FL-HCC patients with a mean age of 36.9. Overall median survival was 34 (95%CI: 27-41) mo. Patients ≤ 19-years-old had more advanced disease with positive lymph nodes status. However, they received more surgical interventions such as a wedge, segmental resection, lobectomy, extended lobectomy, and transplant. Survival for ≤ 19 was 85 (95%CI: 37-137) mo, age 20-59 was 29 (95%CI: 18-41) mo, and age ≥ 60 years was 12 (95%CI: 7-31) mo (P < 0.001). There were no differences in stage, lymph node status, metastasis status, and surgical treatment among races. The median survival were; Whites had 39 (95%CI: 29-63), Blacks 26 (95%CI: 5-92), Hispanics 31 (95%CI: 11-54), and APIs 28 (95%CI: 5-39) mo (P = 0.28). Of 225 patients, 111 FL-HCC patients had surgical procedures. Median survivals for a wedge or segmental resection was 112 (95%CI: 78-NA), lobectomy was 92 (95%CI: 57-NA), extended lobectomy was 54 (95%CI: 23-NA), and a transplant was 63 (95%CI: 20-NA) mo (P < 0.001). The median survival was better in patients who had surgical treatments regardless of lymph nodes or metastasis status (P < 0.001). CONCLUSION: FL-HCC occurs in a primarily younger population, but survival can be prolonged despite the aggressive disease. There were no racial differences in the survival of FL-HCC; however, Asians with FL-HCC tended to be older than in other races. Surgical treatment provided better survival even in those patients with nodal disease or metastases. Although future studies are needed to explore other therapies for FL-HCC, surgical options should be considered in all cases of FL-HCC unless contraindicated.

Abusive Head Trauma and a Delay in Presentation for Care.

OBJECTIVES: Abusive head trauma (AHT) is the leading cause of death from trauma in children less than 2 years of age. A delay in presentation for care has been reported as a risk factor for abuse; however, there has been limited research on this topic. We compare children diagnosed with AHT to children diagnosed with accidental head trauma to determine if there is a delay in presentation. METHODS: We retrospectively studied children less than 6 years old who had acute head injury and were admitted to the pediatric intensive care unit at a pediatric hospital from 2013 to 2017. Cases were reviewed to determine the duration from symptom onset to presentation to care and the nature of the head injury (abusive vs accidental). RESULTS: A total of 59 children met inclusion criteria. Patients who had AHT were significantly more likely to present to care more than 30 minutes after symptom onset (P = 0.0015). Children who had AHT were more likely to be younger (median, 4 vs 31 months; P < 0.0001) and receive Medicaid (P < 0.0001) than those who had accidental head trauma. Patients who had AHT were more likely to have a longer length of stay (median, 11 vs 3 days; P < 0.0001) and were less likely to be discharged home than patients who had accidental head trauma (38% vs 84%; P = 0.0005). CONCLUSIONS: Children who had AHT were more likely to have a delayed presentation for care as compared with children whose head trauma was accidental. A delay in care should prompt clinicians to strongly consider a workup for abusive injury.

System Redesign: The Value of a Primary Care Liaison Model to Address Unmet Social Needs among Older Primary Care Patients.

Assessing and addressing social determinants of health can improve health outcomes of older adults. The Nebraska Geriatrics Workforce Enhancement Program implemented a primary care liaison (PCL) model of care, including training primary care staff to assess and address unmet social needs, patient counseling to identify unmet needs, and mapping referral services through cross-sectoral partnerships. A PCL worked with three patient-centered medical homes (PCMHs) that are part of a large integrative health system. A mixed-methods approach using a post-training survey and a patient tracking tool, was used to understand the reach, adoption, and implementation of the PCL model. From June 2020 to May 2021, the PCL trained 61 primary care staff to assess and address unmet social needs of older patients. A total of 327 patients, aged 65 years and older and within 3-5 days of acute-care hospital discharges, were counseled by the PCL. For patients with unmet needs, support services were arranged through community agencies: transportation (37%), in-home care (33%), food (16%), caregiver support (2%), legal (16%), and other (16%). Our preliminary results suggest that the PCL model is feasible and implementable within PCMH settings to address unmet social needs of older patients to improve their health outcomes.

Increased morbidity and mortality of hepatocellular carcinoma patients in lower cost of living areas.

BACKGROUND: The incidence and mortality rates of hepatocellular carcinoma (HCC) are increasing in the United States. However, the increases in different racial and socioeconomic groups have not been homogeneous. Access to healthcare based on socioeconomic status and cost of living index (COLI), especially in HCC management, is under characterized. AIM: The aim was to investigate the relationship between the COLI and tumor characteristics, treatment modalities, and survival of HCC patients in the United States. METHODS: A retrospective study of the Surveillance, Epidemiology, and End Results (SEER) database was conducted to identify patients with HCC between 2007 and 2015 using site code C22.0 and the International Classification of Disease for Oncology, 3rd edition (ICD-O-3) codes 8170-8173, and 8175. Cases of fibrolamellar HCC were excluded. Variables collected included demographics, COLI, insurance status, marital status, stage, treatment, tumor size, and survival data. Interquartile ranges for COLI were obtained. Based on the COLI, the study population was separated into four groups: COLI ≤ 901, 902-1044, 1045-1169, ≥ 1070. The χ 2 test was used to compare categorical variables, and the Kruskal-Wallis test was used to compare continuous variables without normal distributions. Survival was estimated by the Kaplan-Meier method. We defined P < 0.05 as statistically significant. RESULTS: We identified 47,894 patients with HCC. Patients from the highest COLI areas were older (63 vs 61 years of age), more likely to be married (52.8% vs 48.0%), female (23.7% vs 21.1%), and of Asian and Pacific Islander descent (32.7% vs 4.8%). The patients were more likely to have stage I disease (34.2% vs 32.6%), tumor size ≤ 30 mm (27.1% vs 23.1%), received locoregional therapy (11.5% vs 6.1%), and undergone surgical resection (10.7% vs 7.0%) when compared with the lowest quartile. The majority of patients with higher COLIs resided in California, Connecticut, Hawaii, and New Jersey. Patients with lower COLIs were more likely to be uninsured (5.7% vs 3.4%), have stage IV disease (15.2% vs 13%), and have received a liver transplant (6.6% vs 4.4%) compared with patients from with the highest COLI. Median survival increased with COLI from 8 (95%CI: 7-8), to 10 (10-11), 11 (11-12), and 14 (14-15) mo (P < 0.001) among patients with COLIs of ≤ 901, 902-1044, 1045-1169, ≥ 1070, respectively. After stratifying by year, a survival trend was present: 2007-2009, 2010-2012, and 2013-2015. CONCLUSION: Our study suggested that there were racial and socioeconomic disparities in HCC. Patients from lower COLI groups presented with more advanced disease, and increasing COLI was associated with improved median survival. Future studies should examine this further and explore ways to mitigate the differences.

Milk Consumption and Respiratory Function in Asthma Patients: NHANES Analysis 2007-2012.

Per the Centers for Disease Control and Prevention, asthma prevalence has steadily risen since the 1980s. Using data from the National Health and Nutrition Examination Survey (NHANES), we investigated associations between milk consumption and pulmonary function (PF). Multivariable analyses were performed, adjusted for a priori potential confounders for lung function, within the eligible total adult population (n = 11,131) and those self-reporting asthma (n = 1,542), included the following variables: milk-consumption, asthma diagnosis, forced vital capacity (FVC), FVC%-predicted (%), forced expiratory volume in one-second (FEV1), FEV1% and FEV1/FVC. Within the total population, FEV1% and FVC% were significantly associated with regular (5+ days weekly) consumption of exclusively 1% milk in the prior 30-days (ß:1.81; 95% CI: [0.297, 3.325]; p = 0.020 and ß:1.27; [0.16, 3.22]; p = 0.046). Among participants with asthma, varied-regular milk consumption in a lifetime was significantly associated with FVC (ß:127.3; 95% CI: [13.1, 241.4]; p = 0.002) and FVC% (ß:2.62; 95% CI: [0.44, 4.80]; p = 0.006). No association between milk consumption and FEV1/FVC was found, while milk-type had variable influence and significance. Taken together, we found certain milk consumption tendencies were associated with pulmonary function values among normal and asthmatic populations. These findings propound future investigations into the potential role of dairy consumption in altering lung function and asthma outcomes, with potential impact on the protection and maintenance of pulmonary health.

Sociodemographic Differences and Factors Affecting Patient Portal Utilization.

BACKGROUND: The primary function of the patient portal is to give patients greater access to their personal health information. Granting patients electronic access allows them to make well-informed health care decisions. OBJECTIVE: This study aimed to identify sociodemographic differences in patient portal use and examine factors affecting patient portal utilization following the final stage of the Meaningful Use program which aimed to promote the use of certified electronic health record (EHR) technology. RESEARCH DESIGN: Survey data from Health Information National Trends Survey (HINTS) 5, cycles 1, 2, and 3 were analyzed. The sample included 8291 completed surveys. Multivariable logistic regression on a selected response for each surveyed question was used to assess the racial and ethnic difference after controlling for age, sex, income, and education. SUBJECTS: Subjects included English and Spanish speaking adults in the USA. MEASURES: Measures included assessment of patient portal use, patient portal access, understanding health information, usefulness of health records, and privacy and security. RESULTS: After adjusting for age, sex, income, and education, there was a significant association between race/ethnicity and patient portal non-users responding, "no need to use online medical record" as the reason for not using the patient portal (P = 0.005). Among the portal users, there were significant associations between race/ethnicity and health care provider maintaining an EHR (P = 0.006), being offered access to their portal (P < 0.001), understanding health information in the portal (P = 0.004), finding the portal useful for health monitoring (P < 0.001), reporting concern about unauthorized access (P = 0.017), and keeping information from health care providers (P = 0.012). CONCLUSIONS: Race/ethnicity affects perceptions on the need for the patient portal, being offered access to a portal, and the reasons to access information online. Understanding the factors affecting patient portal use can inform future strategies aimed at increasing adoption.

Dysregulation of sonic hedgehog signaling causes hearing loss in ciliopathy mouse models.

Defective primary cilia cause a range of diseases known as ciliopathies, including hearing loss. The etiology of hearing loss in ciliopathies, however, remains unclear. We analyzed cochleae from three ciliopathy mouse models exhibiting different ciliogenesis defects: Intraflagellar transport 88 (Ift88), Tbc1d32 (a.k.a. bromi), and Cilk1 (a.k.a. Ick) mutants. These mutants showed multiple developmental defects including shortened cochlear duct and abnormal apical patterning of the organ of Corti. Although ciliogenic defects in cochlear hair cells such as misalignment of the kinocilium are often associated with the planar cell polarity pathway, our results showed that inner ear defects in these mutants are primarily due to loss of sonic hedgehog signaling. Furthermore, an inner ear-specific deletion of Cilk1 elicits low-frequency hearing loss attributable to cellular changes in apical cochlear identity that is dedicated to low-frequency sound detection. This type of hearing loss may account for hearing deficits in some patients with ciliopathies.

Factors associated with 5-year survival of combined hepatocellular and cholangiocarcinoma.

BACKGROUND: Combined hepatocellular and cholangiocarcinoma (HCC/CC) is a rare primary hepatic malignancy which carries a poor prognosis due to its aggressive nature. Few centers have enough cases to draw definitive conclusions and there is limited understanding of prognosis. Given the rarity of HCC/CC, an analysis of large national cancer database was needed to obtain larger number of HCC/CC cases. AIM: To identify associated factors for 5-year survival of HCC/CC. METHODS: We conducted a retrospective study of The Surveillance, Epidemiology, and End Results (SEER) database obtained from SEER*Stat 8.3.6 software. Previously defined histology code 8180 for the International Classification of Disease for Oncology, 3rd edition was used to identify HCC/CC cases from 2004 to 2015. We collected demographics, American Joint Committee on Cancer (AJCC) stage, treatment, tumor size, and survival data. These data were converted to categorical variables. The Shapiro-Wilk normality test was used to assess normal distribution. Mann-Whitney U test was used to compare continuous variables without normal distribution, and t-test was used to compare continuous variables with a normal distribution. The Kaplan-Meier survival curve analyzed 5-year survival. Univariate and multivariate logistic regression model was used to analyze factors associated with 5-year survival. Multivariate Cox proportional hazard regression was done on 5-year survival. We defined P < 0.05 was statistically significant. RESULTS: We identified 497 patients with the following characteristics: Mean age 62.4 years (SD: 11.3), 149 (30.0%) were female, racial distribution was: 276 (55.5%) white, 53 (10.7%) black, 84 (16.9%) Asian and Pacific Islander (API), 77 (15.5%) Hispanic, and 7 (1.4%) others or unknown. Stage I/II disease occurred in 41.5% and tumor size < 50 mm was seen in 35.6% of patients. Twenty-four (4.8%) received locoregional therapy (LRT), 119 (23.9%) underwent resection, and 50 (10.1%) underwent liver transplantation. The overall median survival was 6 mo [Interquartile range (IQR): 1-22]. After multivariate logistic regression, tumor size < 50 mm [Odds ratios (OR): 2.415, P = 0.05], resection (OR: 12.849, P < 0.01), and transplant (OR: 27.129, P < 0.01) showed significance for 5-year survival. Age > 60, sex, race, AJCC stages, metastasis, and LRT were not significant. However, API vs white showed significant OR of 2.793 (CI: 1.120-6.967). Cox proportional hazard regression showed AJCC stages, tumor size < 50 mm, LRT, resection, and transplant showed significant hazard ratio. CONCLUSION: HCC/CC patients with tumor size < 50 mm, resection, and transplant were associated with an increase in 5-year survival. API showed advantageous OR and hazard ratios over white, black.

Distinct roles of stereociliary links in the nonlinear sound processing and noise resistance of cochlear outer hair cells.

Outer hair cells (OHCs) play an essential role in hearing by acting as a nonlinear amplifier which helps the cochlea detect sounds with high sensitivity and accuracy. This nonlinear sound processing generates distortion products, which can be measured as distortion-product otoacoustic emissions (DPOAEs). The OHC stereocilia that respond to sound vibrations are connected by three kinds of extracellular links: tip links that connect the taller stereocilia to shorter ones and convey force to the mechanoelectrical transduction channels, tectorial membrane-attachment crowns (TM-ACs) that connect the tallest stereocilia to one another and to the overlying TM, and horizontal top connectors (HTCs) that link adjacent stereocilia. While the tip links have been extensively studied, the roles that the other two types of links play in hearing are much less clear, largely because of a lack of suitable animal models. Here, while analyzing genetic combinations of tubby mice, we encountered models missing both HTCs and TM-ACs or HTCs alone. We found that the tubby mutation causes loss of both HTCs and TM-ACs due to a mislocalization of stereocilin, which results in OHC dysfunction leading to severe hearing loss. Intriguingly, the addition of the modifier allele modifier of tubby hearing 1 in tubby mice selectively rescues the TM-ACs but not the HTCs. Hearing is significantly rescued in these mice with robust DPOAE production, indicating an essential role of the TM-ACs but not the HTCs in normal OHC function. In contrast, the HTCs are required for the resistance of hearing to damage caused by noise stress.