Age- and sex-specific rates of gall bladder disease in children with sickle cell disease.

BACKGROUND: Children with sickle cell disease (SCD) have an increased risk for gallstones due to chronic hyperbilirubinemia from hemolysis. Although gallstones are a known complication, there is variability in estimates of disease burden and uncertainty in the association between sex and gall bladder disease (GBD). METHODS: This was a retrospective cohort study of children with SCD using administrative claims data (January 1, 2014-December 31, 2018). Population-averaged multivariable panel-data logistic regression models were used to evaluate the association between GBD clinical encounters (outcome) and two exposures (age and sex). Annual GBD risk was calculated using predictive margins, adjusting for disease severity, transfusion frequency, and hydroxyurea exposure. RESULTS: A total of 13,745 individuals (of 21,487 possible) met inclusion criteria. The population was evenly split across sex (49.5% female) with predominantly Medicaid insurance (69%). A total of 946 individuals (6.9%) had GBD, 432 (3.1%) had a gallstone complication, and 487 (3.5%) underwent cholecystectomy. The annual risk of GBD rose nonlinearly from 1 to 5% between ages 1 and 19 years with no difference between males and females. Cholecystectomy occurred primarily in individuals with GBD (87%), and neither age nor sex was associated with cholecystectomy in this population. High disease severity (compared with low) more than doubled the annual risk of GBD at all ages. CONCLUSIONS: GBD is associated with age but not sex in children with SCD. Neither age nor sex is associated with risk of cholecystectomy. High disease severity increases the rate of GBD at all ages.

Management of Magnet Ingestions at a Large Tertiary Care Children's Hospital.

OBJECTIVES: To review the clinical management and outcomes of magnet ingestions at a large tertiary children's hospital. To determine the association of frequency of high-powered magnet ingestion with the regulation of these magnets. METHODS: Children <18 years who presented to the emergency room and were admitted to the Children's Hospital of Philadelphia for ingestion of single or multiple magnets from January 2008 to December 2020 were included. Demographics, symptoms, management, and outcomes were analyzed. The frequency of magnet ingestion was compared over 3 eras: (1) pre-ban (2008-2012), (2) intra-ban (2013-2016), and (3) post-ban (2017-2020). RESULTS: There were 167 magnet ingestions, including 99 with multiple magnets. Most patients (59%) were male and median age was 6 (interquartile range, 3-9) years. Most single magnet ingestions (86%) were discharged with outpatient monitoring, and none experienced severe outcomes. Multiple magnet ingestions led to significant morbidity including hospitalizations (68%), endoscopic procedures (48%), surgical procedures (14%), and severe outcomes (12%). Most patients (75%) were asymptomatic, however, there was a higher risk of surgery and severe complications based on the presence of symptoms ( P = 0.003). The rate of surgical intervention was higher with ≥3 magnets (31.7%) compared to 2 magnets (2.4%) ( P < 0.003). Additionally, we found an 160% increase in children with magnet ingestions in the post-ban period ( P = 0.021). CONCLUSIONS: Multiple magnet ingestion is associated with high morbidity and rate of severe outcomes. There is a relationship between public policy of magnet sale and frequency of magnet ingestion.

Ascertainment Bias in a Historic Cohort Study of Residents in an Asbestos Manufacturing Community.

This paper describes follow-up for a cohort of 4530 residents living in the asbestos manufacturing community of Ambler, PA, U.S. in 1930. Using re-identified census data, cause and date of death data obtained from the genealogic website Ancestry.com, along with geospatial analysis, we explored relationships among demographic characteristics, occupational, paraoccupational and environmental asbestos exposures. We identified death data for 2430/4530 individuals. Exposure differed significantly according to race, gender, age, and recency of immigration to the U.S. Notably, there was a significant difference in the availability of year of death information for non-white vs. white individuals (odds ratio (OR) = 0.62 p-value < 0.001), females (OR = 0.53, p-value < 0.001), first-generation immigrants (OR = 0.67, p-value = 0.001), second-generation immigrants (OR = 0.31, p-value < 0.001) vs. non-immigrants, individuals aged less than 20 (OR = 0.31 p-value < 0.001) and individuals aged 20 to 59 (OR = 0.63, p-value < 0.001) vs. older individuals. Similarly, the cause of death was less often available for non-white individuals (OR = 0.42, p-value <0.001), first-generation immigrants and (OR = 0.71, p-value = 0.009), second-generation immigrants (OR = 0.49, p-value < 0.001), individuals aged less than 20 (OR = 0.028 p-value < 0.001), and individuals aged 20 to 59 (OR = 0.26, p-value < 0.001). These results identified ascertainment bias that is important to consider in analyses that investigate occupational, para-occupational and environmental asbestos exposure as risk factors for mortality in this historic cohort. While this study attempts to describe methods for assessing itemized asbestos exposure profiles for a community in 1930 using Ancestry.com and other publicly accessible databases, it also highlights how historic cohort studies likely underestimate the impact of asbestos exposure on vulnerable populations. Future work will aim to assess mortality patterns in this cohort.

Disparities in Human Papillomavirus Vaccine Series Completion by Adolescent Males: A Retrospective Cohort Study.

OBJECTIVE: Human papillomavirus (HPV) vaccine has been recommended for male patients for the prevention of genital warts and precancerous anal lesions since 2009. Our objective was to characterize race and insurance-based disparities in HPV vaccine completion among male patients who initiated the HPV vaccine series. METHODS: This was a retrospective cohort study of adolescent male patients in a primary care network who initiated the HPV vaccine series from October 2009 to December 2013. We measured vaccine series completion as the primary outcome. We evaluated associations between outcomes and race and insurance status, controlling for potential confounders and effect modification with multivariable logistic regression. Analyses were stratified by vaccine recommendation era (permissive vs routine). RESULTS: In total, 42% of males in the cohort (16,691) completed the vaccine series. In the permissive vaccine era (2009-2011), non-black patients (53%) were more likely to complete than black patients (32%) and non-Medicaid patients (49%) were more likely to complete than Medicaid patients (33%). These differences persisted in the routine recommendation era (2012-2013). In both the permissive and routine eras, Medicaid insurance was associated with a larger reduction in the predicted probability of vaccine series completion for non-black patients. Adherence to the recommended vaccination schedule was low, with a median time to completion of 8.9 months. Using the updated completion schedule (2016), we found that completion rates were greater (54.1%) with continued differences based on race (60% vs 45.7% for non-black vs black patients) and insurance (57.4% vs 46.4% completion for non-Medicaid vs Medicaid patients). CONCLUSIONS: We found significant disparities in HPV vaccine series completion rates among male patients based on race and insurance, unchanged based on era of initiation or visit frequency.

A case report of a challenging diagnosis of biliary atresia in a patient receiving total parenteral nutrition.

BACKGROUND: Total parenteral nutrition (TPN) and biliary atresia (BA) are common causes of cholestasis in infancy. The diagnosis of BA is time sensitive due to an inverse correlation between age at intervention (hepatic portoenterostomy - HPE) and survival without liver transplantation. Clinical, laboratory, and histologic features of BA and parenteral nutrition associated cholestasis (PNAC) are similar, creating a diagnostic dilemma for cholestatic infants on parenteral nutrition. There is limited published information about the natural history of PNAC including time to resolution, or diagnostic tests that distinguish BA from other etiologies of cholestasis. CASE PRESENTATION: We present a case of a child diagnosed with BA whose cholestasis began while receiving TPN. His clinical course was notable for transient resolution of his cholestasis after stopping parenteral nutrition and ultimate intraoperative diagnosis. CONCLUSIONS: Clinicians who care for patients who frequently receive TPN should be aware that clinical, laboratory, imaging, and biopsy findings can be similar between BA and PNAC.

Disparities in staging prostate magnetic resonance imaging utilization for nonmetastatic prostate cancer patients undergoing definitive radiation therapy.

PURPOSE: There is growing evidence supporting incorporating multiparametric (mp) magnetic resonance imaging (MRI) scans into risk stratification, active surveillance, and treatment paradigms for prostate cancer. The purpose of our study was to determine whether demographic disparities exist in staging MRI utilization for prostate cancer patients. METHODS AND MATERIALS: An institutional database of 705 nonmetastatic prostate cancer patients treated with radiation therapy from 2005 through 2013 was used to identify patients undergoing versus not undergoing pretreatment diagnostic prostate mpMRI. Uni- and multivariable logistic regression evaluated the relationship of clinical and demographic characteristics with MRI utilization. RESULTS: All demographic variables assessed, except the other race category, were significantly associated with MRI utilization (all P < .05), including age (odds ratio [OR], 0.92), black race (OR, 0.51), poverty (OR, 0.53), closer distance to radiation facility (OR, 1.79), and nonprivate primary insurance (OR, 0.57) on univariable analysis, while clinical stage T3 (OR, 3.37) was the only clinical characteristic. On multivariable analysis stratified by D'Amico risk group, age remained significant across all risk groups, whereas the black versus white racial (OR, 0.21; 95% confidence interval, 0.08-0.55) and nonprivate versus private insurance type (OR, 0.37; 95% confidence interval, 0.16-0.86) disparities persisted in the low-risk group. Clinical stage T3 remained associated in the high-risk group. For race specifically, the percentages of whites, blacks, and others undergoing MRI in the overall cohort and by risk group were, respectively: overall, 80% (343/427), 68% (156/231), and 85% (40/47); low risk, 86%, 56%, and 63%; intermediate risk, 79%, 72%, and 95%; and high risk, 72%, 72%, and 100%. CONCLUSIONS: In this urban, academic center cohort, older patients across all risk groups and black or nonprivate insurance patients in the low risk group were less likely to undergo staging prostate MRI scans. Further research should investigate these differences to ensure equitable utilization across all demographic groups considering the burden of prostate cancer disparities.

Sociodemographic Differences in Human Papillomavirus Vaccine Initiation by Adolescent Males.

PURPOSE: The purpose of this study was to describe patterns of human papillomavirus (HPV) vaccine initiation by males and characterize sociodemographic differences. METHODS: We conducted a retrospective cohort study of 11- to 18-year-old males in a large primary care network who had a preventive or acute visit between October 2009 and December 2013. Outcomes measured were HPV vaccine series initiation and initiation at the first eligible visit. Logistic regression measured independent associations between outcomes and sociodemographic characteristics, adjusting for potential confounders including visit frequency, insurance changes, and the presence of complex medical conditions. RESULTS: Of 58,757 eligible patients, most were white (57%) with private insurance (77%). During the study period, 39% of the cohort initiated the vaccine series, and 7% initiated at their first eligible visit. Black patients with private (adjusted odds ratio [aOR], 1.99; 95% confidence interval [CI], 1.73-2.30) and Medicaid insurance (aOR, 2.90; 95% CI, 2.56-3.30) had significantly higher odds of HPV vaccine initiation compared with white patients with private insurance. A similar trend was found for Hispanic patients with private (aOR, 1.45; 95% CI, 1.26-1.67) and Medicaid insurance (aOR, 2.15; 95% CI, 1.78-2.60). These differences were present both in the preroutine recommendation period (2009-2011) and the postroutine recommendation period (2012-2013). CONCLUSIONS: Traditionally marginalized populations have higher odds of HPV vaccine initiation, both at the first eligible visit and overall. Although the true mechanism underlying these differences remains unknown, potential candidates include provider recommendation patterns and differential vaccine acceptance within these groups.

Combination delivery of TGF-ß inhibitor and IL-2 by nanoscale liposomal polymeric gels enhances tumour immunotherapy.

The tumour microenvironment thwarts conventional immunotherapy through multiple immunologic mechanisms, such as the secretion of the transforming growth factor-ß (TGF-ß), which stunts local tumour immune responses. Therefore, high doses of interleukin-2 (IL-2), a conventional cytokine for metastatic melanoma, induces only limited responses. To overcome the immunoinhibitory nature of the tumour microenvironment, we developed nanoscale liposomal polymeric gels (nanolipogels; nLGs) of drug-complexed cyclodextrins and cytokine-encapsulating biodegradable polymers that can deliver small hydrophobic molecular inhibitors and water-soluble protein cytokines in a sustained fashion to the tumour microenvironment. nLGs releasing TGF-ß inhibitor and IL-2 significantly delayed tumour growth, increased survival of tumour-bearing mice, and increased the activity of natural killer cells and of intratumoral-activated CD8(+) T-cell infiltration. We demonstrate that the efficacy of nLGs in tumour immunotherapy results from a crucial mechanism involving activation of both innate and adaptive immune responses.