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Fabry Registry data were analyzed among 83 agalsidase beta-treated patients with Fabry disease who switched to migalastat. Outcomes (estimated glomerular filtration rate [eGFR], urine protein-creatinine ratio [UPCR], plasma globotriaosylceramide [GL-3], plasma globotriaosylsphingosine [lyso-GL-3], interventricular septal wall thickness [IVST], left posterior wall thickness [LPWT], left ventricular mass index [LVMI]) were assessed using linear mixed models to estimate annual change over time in the pre- and postswitch periods. eGFR decreased throughout both periods (preswitch: -0.85 mL/min/1.73 m 2 /year; postswitch: -1.96 mL/min/1.73 m 2 /year; both p < 0.0001), with steeper decline postswitch (p pre/post  = 0.01) in both classic and late-onset patients. UPCR increased significantly postswitch (p pre/post  = 0.003) among classic patients and was stable in both periods among late-onset patients. GL-3 trajectories worsened postswitch across phenotypes (p pre/post  = 0.0005 classic, 0.02 late-onset). LPWT was stable preswitch (0.07 mm/year, p = 0.25) and decreased postswitch (-0.51 mm/year, p = 0.0005; p pre/post  = 0.0009), primarily among late-onset patients. IVST and LVMI slopes varied significantly by phenotype. Among classic patients, IVST and LVMI were stable and decreasing, respectively preswitch and increasing postswitch (p pre/post  = 0.02 IVST, 0.01 LVMI). Among late-onset patients, IVST significantly decreased postswitch (p pre/post  = 0.0003); LVMI was stable over time (p pre/post  = 0.89). Ultimately, eGFR and GL-3 trajectories worsened postswitch across phenotypes, while UPCR and cardiac measures worsened among classic and stabilized/improved among late-onset patients. These findings indicate variability in long-term outcomes after switching from ERT to migalastat, underscoring the importance of careful monitoring., (© 2024 The Author(s). Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Background: The World Cancer Research Fund classifies as "strong evidence" the link between obesity and the risk of advanced prostate cancer. In light of the different hormonal profiles associated with where adipose is stored, this study investigated the role of objectively measured body fat distribution and the risk of clinically relevant prostate cancer., Methods: This was a prospective study of 1832 men in the Age, Gene/Environment Susceptibility-Reykjavik study. From 2002 to 2006, participants underwent baseline computed tomography imaging of fat deposition, bioelectric impedance analysis, and measurement of body mass index (BMI) and waist circumference. Men were followed through linkage with nationwide cancer registries for the incidence of total (n = 172), high-grade (Gleason grade ≥8; n = 43), advanced (≥cT3b/N1/M1 at diagnosis or fatal prostate cancer over follow-up; n = 41), and fatal prostate cancer (n = 31) through 2015. Cox regression was used to evaluate the association between adiposity measures and prostate cancer outcomes., Results: Among all men, visceral fat (hazard ratio [HR], 1.31 per 1-standard deviation [SD] increase; 95% confidence interval [CI], 1.00-1.72) and thigh subcutaneous fat (HR, 1.37 per 1-SD increase; 95% CI, 1.00-1.88) were associated with risk of advanced and fatal disease, respectively. Among men who were leaner based on BMI, visceral fat was associated with both advanced and fatal disease. BMI and waist circumference were associated with a higher risk of advanced and fatal disease. No adiposity measures were associated with total or high-grade disease., Conclusions: Specific fat depots as well as BMI and waist circumference were associated with the risk of aggressive prostate cancer, which may help to elucidate underlying mechanisms and target intervention strategies., (© 2019 American Cancer Society.)

Objective: This study aims to assess whether secondhand smoke (SHS) exposure has an impact on health-related quality of life (HRQOL) in children with acute respiratory illness (ARI)., Methods: This study was nested within a multicenter, prospective cohort study of children (two weeks to 16 years) with ARI (emergency department visits for croup and hospitalizations for croup, asthma, bronchiolitis, and pneumonia) between July 1, 2014 and June 30, 2016. Subjects were surveyed upon enrollment for sociodemographics, healthcare utilization, home SHS exposure (0 or ≥1 smoker in the home), and child HRQOL (Pediatric Quality of Life Physical Functioning Scale) for both baseline health (preceding illness) and acute illness (on admission). Data on insurance status and medical complexity were collected from the Pediatric Hospital Information System database. Multivariable linear mixed regression models examined associations between SHS exposure and HRQOL., Results: Home SHS exposure was reported in 728 (32%) of the 2,309 included children. Compared with nonexposed children, SHS-exposed children had significantly lower HRQOL scores for baseline health (mean difference -3.04 [95% CI -4.34, -1.74]) and acute illness (-2.16 [-4.22, -0.10]). Associations were strongest among children living with two or more smokers. HRQOL scores were lower among SHS-exposed children for all four conditions but only significant at baseline for bronchiolitis (-2.94 [-5.0, -0.89]) and pneumonia (-4.13 [-6.82, -1.44]) and on admission for croup (-5.71 [-10.67, -0.75])., Conclusions: Our study demonstrates an association between regular SHS exposure and decreased HRQOL with a dose-dependent response for children with ARI, providing further evidence of the negative impact of SHS.

Background: Worse outcomes among adults presenting for/receiving care on weekends (ie, "the weekend effect") have been observed for many diseases. However, little is known about the overall impact of the weekend effect in hospitalized children., Objective: o determine the association between weekend admission and length of stay (LOS) and between weekend discharge and 30-day all-cause readmission., Methods: We conducted a retrospective, cross-sectional study of children hospitalized between October 1, 2014 and September 30, 2015 using the Pediatric Health Information System. Birth hospitalizations and planned procedures were excluded. We used generalized linear mixed modeling to assess the independent association between weekend admission and LOS and weekend discharge and readmission risk., Results: Among 390,745 hospitalizations across 43 hospitals, the median LOS was 41 hours (interquartile range [IQR] 24-71) and the 30-day readmission rate was 8.2% (IQR 7.2-9.4). We observed no association between weekend admission and LOS (adjusted LOS [95% CI: weekend 63.70 [61.01-66.52] hours vs weekday 63.40 [60.73-66.19] hours, P = .112). Weekend discharge was associated with slightly increased odds of readmission compared with weekday discharge (adjusted probability of readmission [95% CI]: weekend 0.13 [0.12-0.13] versus weekday 0.11 [0.11-0.12], P < .001) but was variable among individual hospitals. Patient characteristics (ie, number of chronic conditions) were more strongly associated with LOS and readmission risk than weekend admission or discharge., Conclusions: Patient-level factors (ie, clinical and demographic characteristics) are more indicative of longer LOS and readmission risk than weekend admissions or discharges. The overall impact of the weekend effect across children's hospitals was minimal., (© 2018 Society of Hospital Medicine.)

Objective Unplanned readmission within 30 days is a contributor to health care costs in the United States. The use of predictive modeling during hospitalization to identify patients at risk for readmission offers a novel approach to quality improvement and cost reduction. Study Design Two-phase study including retrospective analysis of prospectively collected data followed by prospective longitudinal study. Setting Tertiary academic medical center. Subjects and Methods Prospectively collected data for patients undergoing surgical treatment for head and neck cancer from January 2013 to January 2015 were used to build predictive models for readmission within 30 days of discharge using logistic regression, classification and regression tree (CART) analysis, and random forests. One model (logistic regression) was then placed prospectively into the discharge workflow from March 2016 to May 2016 to determine the model's ability to predict which patients would be readmitted within 30 days. Results In total, 174 admissions had descriptive data. Thirty-two were excluded due to incomplete data. Logistic regression, CART, and random forest predictive models were constructed using the remaining 142 admissions. When applied to 106 consecutive prospective head and neck oncology patients at the time of discharge, the logistic regression model predicted readmissions with a specificity of 94%, a sensitivity of 47%, a negative predictive value of 90%, and a positive predictive value of 62% (odds ratio, 14.9; 95% confidence interval, 4.02-55.45). Conclusion Prospectively collected head and neck cancer databases can be used to develop predictive models that can accurately predict which patients will be readmitted. This offers valuable support for quality improvement initiatives and readmission-related cost reduction in head and neck cancer care.

Background: Hospitalization provides an ideal opportunity for immunization, but few studies have explored provider and parental attitudes toward pediatric inpatient vaccination against influenza., Objectives: The objectives were to determine provider and caregiver attitudes and explore potential barriers to inpatient influenza vaccination., Methods: We developed and distributed two surveys to parents/caregivers as well as providers of general pediatric inpatients at Children's Hospital Colorado between October 2014 and March 2015 assessing attitudes toward influenza and inpatient influenza vaccination. We analyzed the Likert scale responses using univariate analyses and multiple logistic regression to assess associations between responses and vaccination status., Results: The overall response rate was 95% and 58% for parents and providers, respectively. Parents of hospitalized children who agreed that flu vaccines are safe (adjusted OR 2.50 [95%CI 1.76-3.58]), and that the influenza vaccine is needed every year had higher odds of having a vaccinated child (adjusted OR 3.30 [95%CI 2.30-4.81]). Most providers (91%) agree that influenza vaccination is an important priority among inpatients, but believe that parental misconceptions and their reluctance for inpatient vaccination are the most important barriers to influenza vaccination. Providers forgetting to ask about vaccination status and order the vaccine are the next most commonly identified barriers. In contrast, most parents surveyed had favorable attitudes toward inpatient influenza vaccination and disagreed that their child was too sick to receive the vaccine during hospitalization., (© 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Background: The annual Pediatric Hospital Medicine (PHM) conference serves as a venue for the dissemination of research in this rapidly growing discipline. A measure of research validity is subsequent publication in peer-reviewed journals., Objective: To identify the publication rate of abstracts submitted to the 2014 PHM conference and determine whether presentation format was associated with subsequent journal publication or time to publication., Methods: We identified abstracts submitted to the 2014 PHM conference. Presentation formats included rejected abstracts and poster and oral presentations. Abstracts subsequently published in journals were identified by searching the author and abstract title in PubMed, MedEdPORTAL, and Google Scholar. We used logistic regression and Cox proportional hazards models to determine if presentation format was associated with publication, time to publication, and publishing journal impact factor., Results: Of 226 submitted abstracts, 19.0% were rejected, 68.0% were selected for posters, and 12.8% were selected for oral presentations; 36.3% were subsequently published within 30 months after the conference. Abstracts accepted for oral presentation had more than 7-fold greater odds of publication (adjusted odds ratio 7.8; 95% confidence interval [CI], 2.6-23.5) and a 4-fold greater likelihood of publication at each month (adjusted hazard ratio 4.5; 95% CI, 2.1-9.7) compared with rejected abstracts. Median journal impact factor was significantly higher for oral presentations than other presentation formats (P < 0.01)., Conclusions: Abstract reviewers may be able to identify methodologically sound studies for presentation; however, the low overall publication rate may indicate that presented results are preliminary or signify a need for increased mentorship and resources for research development in PHM.

Background: Obese men are at higher risk of advanced prostate cancer and cancer-specific mortality; however, the biology underlying this association remains unclear. This study examined gene expression profiles of prostate tissue to identify biological processes differentially expressed by obesity status and lethal prostate cancer., Methods: Gene expression profiling was performed on tumor (n = 402) and adjacent normal (n = 200) prostate tissue from participants in 2 prospective cohorts who had been diagnosed with prostate cancer from 1982 to 2005. Body mass index (BMI) was calculated from the questionnaire immediately preceding cancer diagnosis. Men were followed for metastases or prostate cancer-specific death (lethal disease) through 2011. Gene Ontology biological processes differentially expressed by BMI were identified using gene set enrichment analysis. Pathway scores were computed by averaging the signal intensities of member genes. Odds ratios (ORs) for lethal prostate cancer were estimated with logistic regression., Results: Among 402 men, 48% were healthy weight, 31% were overweight, and 21% were very overweight/obese. Fifteen gene sets were enriched in tumor tissue, but not normal tissue, of very overweight/obese men versus healthy-weight men; 5 of these were related to chromatin modification and remodeling (false-discovery rate < 0.25). Patients with high tumor expression of chromatin-related genes had worse clinical characteristics (Gleason grade > 7, 41% vs 17%; P = 2 × 10 -4 ) and an increased risk of lethal disease that was independent of grade and stage (OR, 5.26; 95% confidence interval, 2.37-12.25)., Conclusions: This study improves our understanding of the biology of aggressive prostate cancer and identifies a potential mechanistic link between obesity and prostate cancer death that warrants further study. Cancer 2017;123:4130-4138. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: Hospitalizations of children with medical complexity (CMC) account for one-half of hospital days in children, with lengths of stays (LOS) that are typically longer than those for children without medical complexity. The objective was to assess the impact of, risk factors for, and variation across children's hospitals regarding long LOS (≥10 days) hospitalizations in CMC., Methods: A retrospective study of 954,018 CMC hospitalizations, excluding admissions for neonatal and cancer care, during 2013 to 2014 in 44 children's hospitals. CMC were identified using 3M's Clinical Risk Group categories 6, 7, and 9, representing children with multiple and/or catastrophic chronic conditions. Multivariable regression was used to identify demographic and clinical characteristics associated with LOS ≥10 days. Hospital-level risk-adjusted rates of long LOS generated from these models were compared using a covariance test of the hospitals' random effect., Results: Among CMC, LOS ≥10 days accounted for 14.9% (n = 142,082) of all admissions and 61.8% ($13.7 billion) of hospital costs. The characteristics most strongly associated with LOS ≥10 days were use of intensive care unit (ICU) (odds ratio [OR]: 3.5, 95% confidence interval [CI]: 3.4-3.5), respiratory complex chronic condition (OR: 2.7, 95% CI: 2.6-2.7), and transfer from another medical facility (OR: 2.1, 95% CI: 2.0-2.1). After adjusting for severity, there was significant (P < 0.001) variation in the prevalence of LOS ≥10 days for CMC across children's hospitals (range, 10.3%-21.8%)., Conclusions: Long hospitalizations for CMC are costly. Their prevalence varies significantly by type of chronic condition and across children's hospitals. Efforts to reduce hospital costs in CMC might benefit from a focus on prolonged LOS. Journal of Hospital Medicine 2016;11:750-756. © 2016 Society of Hospital Medicine., (© 2016 Society of Hospital Medicine.)

Objective: To determine whether dexamethasone use in children undergoing tonsillectomy is associated with increased risk of postoperative bleeding., Study Design: Retrospective cohort study using a multihospital administrative database., Setting: Thirty-six US children's hospitals., Subjects: Children undergoing same-day tonsillectomy between the years 2004 and 2010., Methods: We used discrete time failure models to estimate the daily hazards of revisits for bleeding (emergency department or hospital admission) up to 30 days after surgery as a function of dexamethasone use. Revisits were standardized for patient characteristics, antibiotic use, year of surgery, and hospital., Results: Of 139,715 children who underwent same-day tonsillectomy, 97,242 (69.6%) received dexamethasone and 4182 (3.0%) had a 30-day revisit for bleeding. The 30-day cumulative standardized risk of revisits for bleeding was greater with dexamethasone use (3.11% vs 2.71%; standardized difference 0.40% [95% confidence interval, 0.13%-0.67%]; P = .003), and the increased risk was observed across all age strata. Dexamethasone use was associated with a higher standardized rate of revisits for bleeding in the postdischarge time periods of days 1 through 5 but not during the peak period for secondary bleeding, days 6 and 7., Conclusions: In a real-world practice setting, dexamethasone use was associated with a small absolute increased risk of revisits for bleeding. However, the upper bound of this risk increase does not cross published thresholds for a minimal clinically important difference. Given the benefits of dexamethasone in reducing postoperative nausea and vomiting and the larger body of evidence from trials, these results support guideline recommendations for the routine use of dexamethasone.

Vesicle transport sorts proteins between compartments and is thereby responsible for generating the non-uniform protein distribution along the eukaryotic secretory and endocytic pathways. The mechanistic details of specific vesicle targeting are not yet well characterized at the molecular level. We have developed a cell-free assay that reconstitutes vesicle targeting utilizing the recycling of resident enzymes within the Golgi apparatus. The assay has physiological properties, and could be used to show that the two lobes of the conserved oligomeric Golgi tethering complex play antagonistic roles in trans-Golgi vesicle targeting. Moreover, we can show that the assay is sensitive to several different congenital defects that disrupt Golgi function and therefore cause glycosylation disorders. Consequently, this assay will allow mechanistic insight into the targeting step of vesicle transport at the Golgi, and could also be useful for characterizing some novel cases of congenital glycosylation disorders., (©2013 The Authors. Traffic published by John Wiley & Sons Ltd.)

Background: Considerable efforts have been undertaken in the United States to reduce cervical cancer incidence and mortality by increasing screening; however, disparities in screening rates continue to exist among certain racial and ethnic minority groups. The objective of the current study was to determine the effectiveness of a lay health worker-delivered intervention-AMIGAS (Ayudando a las Mujeres con Informacion, Guia, y Amor para su Salud [helping women with information, guidance, and love for their health])-to increase Papanicolaou (Pap) test screening among 3 populations of women of Mexican origin., Methods: Six hundred thirteen women of Mexican origin in 3 treatment sites were randomized among 4 study arms: the full AMIGAS program with a video and a flip chart (n = 151), the AMIGAS program without the video (n = 154), the AMIGAS program without the flip chart (n = 155), and a usual care control group (n = 153). Six months after enrollment, women were surveyed and reported whether or not they had been screened., Results: Women in any of the intervention arms were statistically significantly more likely to report being screened than those in the usual care group in both an intent-to-treat analysis and a per-protocol analysis. In the intent-to-treat analysis, 25% of women in the control group and 52% in the full AMIGAS program group reported having had Pap tests (P < .001); in the per-protocol analysis, the percentages were 29% and 62%, respectively (P < .001)., Conclusions: AMIGAS was effective in increasing Pap test screening among women of Mexican descent when used in a 1-to-1 setting. Future research should compare the 1-on-1 intervention with the group-based intervention., (Copyright © 2012 American Cancer Society.)

Public health is currently faced with an array of critical challenges and disconnects. Research and evaluation have identified a number of evidence-based strategies for effecting behavior change at individual, group, organizational, and environmental levels, all of which hold promise for leading to substantial reductions in morbidity and mortality, and increased quality of life. Unfortunately, there is huge variability across the public health system in awareness of the value of using evidence to inform decision making, let alone in capacity to locate, assess, compare, select, justify, adapt, implement, and evaluate evidence-based strategies, or to participate in building the evidence base for practice-based innovations. As a result, many communities may not be benefitting from research-tested and practice-based strategies that could help them to meet their public health goals more efficiently and effectively. CDC's Interactive Systems Framework for Dissemination and Implementation (ISF), released in 2008, was designed to help close this gap between research and practice. This commentary identifies the ways in which the ISF framework is useful in addressing the research practice gap; revisits the elements of the framework that have continued to guide research and practice in fruitful ways; and highlights areas that need further development to meet current public health challenges.

Objective: To determine the efficacy of proton-pump inhibitor (PPI) therapy for chronic laryngo-pharyngitis treated with lifestyle modification., Study Design and Methods: Double-blind, randomized trial comparing two-month Rabeprazole (20 mg b.i.d.) to placebo control., Results: Compared to baseline, both PPI and control patients had significant improvement in total reflux symptoms (P = 0.002 and P = 0.03 respectively), with significant improvement in "laryngo-pharyngeal" but not "typical" reflux symptoms. No significant difference was noted for change in reflux symptoms between PPI-treated and control patients (P = 0.44). Significant global improvement was noted by 50% of control and 53% of PPI-treated patients (P = 1.0). No significant differences were noted within or between treatment groups for change in health status or videostrobolaryngoscopy grade. Lifestyle modification compliance correlated significantly with global improvement., Conclusion: Compared to baseline, lifestyle modification for 2 months significantly improved chronic laryngo-pharyngitis symptoms. When compared to control, treatment with a PPI failed to demonstrate significantly greater improvement in reflux symptoms, health status, or laryngeal appearance.

The authors draw on the lessons highlighted in preceding articles in the current supplement to provide recommendations for cancer screening intervention research and to highlight some of the many questions that will require further investigation.

A large gap exists between the results of research concerning efficacious cancer screening programs and the programs delivered in practice. In this article, the authors discuss issues in, barriers to, and lessons learned regarding the dissemination of interventions. They summarize previous reviews, exemplary studies, and theories regarding the diffusion and dissemination of cancer screening interventions. Six lessons learned address the involvement of key stakeholders, factors influencing diffusion, the need for different types of efficacy and effectiveness studies with greater attention to external validity, replication, the use of theoretical and evaluation models, and the importance of policy infrastructure. In this article, the authors make recommendations for future research and practice, including improving the understanding of the intervention process and changing the types of grants funded and review criteria used. Also needed are an enhanced infrastructure, including policies to support dissemination, and the involvement of researchers, health care administrators, clinicians, and funding organizations in dissemination if the gap between research and practice in cancer screening is to be reduced.

This article provides an overview of behavioral and social science cancer screening intervention research and introduces the scope of topics addressed in this supplement to Cancer. The authors identify and address issues to consider before conducting interventions to promote the uptake of screening tests, such as the benefits and harms associated with screening. Trends in the use of cancer screening tests are discussed in the context of their efficacy and adoption over time. Both the development and breadth of social and behavioral intervention research intended to increase the use of effective tests are reviewed as background for the articles that follow. The application of the lessons from this extensive knowledge base not only should accelerate the uptake of the effective cancer screening tests currently available, but also can guide future directions for research.

Objective: The goal was to identify factors associated with the outcome of salvage therapy for patients with isolated cervical recurrences of squamous cell carcinoma in the previously treated neck (ICR-PTN)., Study Design and Settings: A tumor registry search for ICR-PTN patients was performed at 7 participating institutions, and the charts were reviewed. Kaplan-Meier plots for survival and time until re-recurrence were used to evaluate the significance of associated variables., Results: Median survival and time until re-recurrence were both 11 months. Survival was better in patients with the following characteristics: nonsurgical initial neck treatment, negative initial disease resection margins, no history of prior recurrence, ipsilateral location of the ICR-PTN relative to the primary, and use of surgical salvage., Conclusions: By pooling the experience of 7 US tertiary care medical centers, we have identified 5 factors that are associated with outcome of salvage therapy for ICR-PTN., Significance: Consideration of these factors, as well as the reviewed literature, should facilitate patient selection for salvage protocols.

Nicotine was given intravenously to subjects during acid and alkaline urine conditions in doses and a dosing schedule to simulate cigarette smoking. Total clearances were greater, terminal half-lifes shorter, but volumes of distribution much the same in acid (pH < 5) and alkaline (pH > 7) urine conditions. The effect of urinary pH on total clearance was due entirely to changes in renal clearance, which accounted for 23% and 2% of total clearance in acid and alkaline urine conditions. Nicotine injections induced a sensation of arousal and increased heart rate and blood pressure over the short term, but with repeated injections tolerance to these effects developed rapidly. No differences in subjective or physiologic responses to intravenous nicotine were observed and we consider it unlikely that the effects of smoking a cigarette differ as a function of urinary pH.