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Objective: The goal of this study was to compare patient-reported efficacy of suburothelial versus intradetrusor onabotulinumtoxin A (BTX-A) in patients with refractory overactive bladder (OAB). Ma...

Neurosurgical patients with genetic syndromes often receive care from multidisciplinary teams. Successful models range from multiple providers in one clinic space seeing a patient together to specialists located at different institutions working together. Collaboration and bidirectional communication are key. Multidisciplinary care improves outcomes and patient satisfaction. Choosing the goal of the clinic, using ancillary staff, and obtaining institutional buy-in are important initial first steps to establishing a multidisciplinary team clinic. Multidisciplinary teams can leverage technology to expand care via telehealth in multidisciplinary clinics and more vitally communication between providers on the team.

Purpose Creating inclusive LGBTQ+ environments is important in the provision of inclusive care. This cross sectional study assessed whether patient intake forms in pediatric surgery departments were LGBTQ+ inclusive (L-I). Methods North American pediatric surgery departments affiliated with pediatric surgery fellowships or general surgery residencies were contacted to retrieve patient intake forms. Forms were assessed for LGBTQ+ inclusivity using a novel L -I scoring system consisting of 6 criteria: preferred name, pronouns, preferred language, gender identity, sex assigned at birth, and l -I guardianship. Institutions without intake forms were invited to comment on their use of l -I intake questions. Results 59/125 programs responded to our query, 10 of which provided intake forms. Median l -I score was 2/6 points (range 1–4). l -I guardianship was the most common question asked. No intake form asked for pronouns. Of the 49 institutions without forms, 30.5% reported asking l -I questions during initial visits. Narratives from these institutions varied widely. Some institutions supported routine l -I questions while others stated l -I questions were unnecessary, irrelevant, and/or offensive. Conclusions Few North American pediatric surgery departments consistently ask l -I questions during the intake process. Comments questioning the appropriateness and necessity of l -I questions highlight the need for LGBTQ+ education. Level of evidence Level III. Type of study Cross sectional study.

Batched network coding (BNC) is a low-complexity solution to network transmission in multi-hop packet networks with packet loss. BNC encodes the source data into batches of packets. As a network coding scheme, the intermediate nodes perform recoding on the received packets belonging to the same batch instead of just forwarding them. A recoding scheme that may generate more recoded packets for batches of a higher rank is also called adaptive recoding. Meanwhile, in order to combat burst packet loss, the transmission of a block of batches can be interleaved. Stream interleaving studied in literature achieves the maximum separation among any two consecutive packets of a batch, but permutes packets across blocks and hence cannot bound the buffer size and the latency. To resolve the issue of stream interleaver, we design an intrablock interleaver for adaptive recoding that can preserve the advantages of using a block interleaver when the number of recoded packets is the same for all batches. We use potential energy in classical mechanics to measure the performance of an interleaver, and propose an algorithm to optimize the interleaver with this performance measure. Our problem formulation and algorithm for intrablock interleaving are also of independent interest., This paper was presented in part at 2021 IEEE International Symposium on Information Theory

BACKGROUND: As treatments improve for colorectal cancer (CRC), interventions to improve quality of life and decrease long-term effects are needed. Physical activity (PA) is particularly important during cancer treatment because it may decrease treatment side effects, allow patients to more easily increase PA after treatment, and integrate with individuals’ motivation to make lifestyle changes after a cancer diagnosis. OBJECTIVES: This article aims to synthesize what is known about PA during CRC treatment. METHODS: A systematic literature search was conducted. Data were evaluated across 17 studies with a collective sample size of 1,184. Because of heterogeneity across studies, a narrative synthesis was conducted. FINDINGS: Studies included mostly college educated and married White men and women aged 50–60 years. Promising effects of PA were identified on several types of outcomes. The most common techniques to support PA included goal setting and providing instructions. The benefits of PA and how to best support PA during CRC treatment need to be better understood in future studies of racially and ethnically diverse patients with CRC.

PurposeThe paper discusses the relationship between systemic inequity and wealth disparity and advocates for expanding employee share ownership as a strategy to address divides in income and wealth by race and gender. It targets diverse actors including policymakers, philanthropic leaders and social investors and presents a set of policy proposals and practice ideas that seek to advance a broader understanding of employee share ownership and build the capacity of key organizations to support employee-owned businesses.Design/methodology/approachThis paper draws on data indicating positive outcomes from employee share ownership programs (ESOPs) related to job quality, economic stability and wealth-building, as well as widespread political support for ESOPs.FindingsThis paper suggests that employee share ownership can help to strengthen job quality and address race and gender income and wealth gaps. It argues that there is both public support and a range of different strategies actors can implement to expand awareness and access to different forms of employee share ownership.Research limitations/implicationsAdditional research focused on other forms of employee share ownership (beyond ESOPs) is needed to deepen understanding of how each form can play a role in addressing racial and gender wealth inequities. The paper acknowledges that despite the potential of employee share ownership to mitigate racial and gender wealth gaps, additional simultaneous strategies are required to address the range of systemic barriers that have disproportionately limited women and people of color's participation in ESOPs.Practical implicationsPolicymakers are actively seeking new proposals, while philanthropic leaders, social investors and others are also eager to build awareness and understanding of employee ownership models and develop the institutional capacity necessary to support strong employee-owned businesses. This paper directly responds to these needs and contributes to a broader collaborative effort to spread employee share ownership policies and practices that support economic recovery and lay the foundation for a more equitable and resilient economy.Social implicationsEmployee share ownership is not yet a strategy that is well understood among policymakers and the public, but it connects to and supports outcomes that are top of mind for many, including increasing local ownership and bolstering local economies, helping small business owners retire in ways that preserve local jobs and businesses, strengthening job quality and workforce development, addressing racial inequity and economic inequality and providing workers greater voice and agency. This paper seeks to connect employee ownership to these high-priority issues and support efforts by a range of organizations to implement policy and practice solutions.Originality/valueThis paper fulfills an identified need to aggregate recent research on the relationship between employee share ownership and wealth inequities on the basis of race and gender. It also offers a timely argument that employee ownership strategies can play an important role in responding to the challenges facing communities and workers – particularly women workers and workers of color – as we rebuild from the COVID-19 pandemic.

PurposeAs a part of the authors’ continued efforts to understand the experience and trends related to small business cooperatives, the US Federation of Worker Cooperatives (USFWC) and the Democracy at Work Institute (DAWI) explored themes around the impact of the COVID-19 pandemic on worker cooperatives and democratic workplaces.Design/methodology/approachThe USFWC and DAWI conduct a biannual Economic Census of worker cooperatives and democratic workplaces. Survey themes this year included questions around the impact of the COVID-19 pandemic on individual firms.FindingsGeneral findings indicate that worker cooperatives experienced financial losses similar to conventional small businesses, but that this varied widely by industry. Although it has been found that BIPOC-owned conventional small businesses have been some of the hardest hit during the pandemic, the authors find that there may be some mitigating protective effects of the worker cooperative form when the authors explore the impacts on worker cooperatives with a majority BIPOC workforce. Additionally, the authors find that worker cooperatives and democratic workplaces strive to ensure the safety and wellbeing of their workers even when facing significant financial challenges throughout the pandemic.Research limitations/implicationsThis research utilizes non-random convenience sampling in data collection. The outreach for our biannual Economic Census is concentrated on a highly connected worker cooperative and democratic workplace network, the experiences of which may not generalize to the larger worker cooperative and democratic workplace landscape. Additionally, outreach efforts were hindered by challenges presented by the pandemic that were not present in prior census years, as was firm bandwidth to respond, which likely affected the sample composition in comparison to prior years.Originality/valueWorker cooperatives have been proven to be a resilient crisis response form of business, but little is known about how the worker cooperative ecosystem in the United States is faring in the face of the continuing COVID-19 crisis.

Certain foods are more vulnerable to foodborne pathogen growth and formation of toxins than others. Lack of time and temperature control for these foods can result in the growth of pathogens, such as Listeria monocytogenes, and lead to foodborne outbreaks. The Food and Drug Administration's (FDA) Food Code classifies these foods as time/temperature control for safety (TCS) foods and details safe cooking, holding, and storing temperatures for these foods. The FDA Food Code also includes a date-marking provision for ready-to-eat TCS foods that are held for >24 h. The provision states that these foods should not be held in refrigeration for >7 days and should be marked with the date or day by which the food should be “consumed on the premises, sold, or discarded.” To learn more about restaurants' date-marking practices, the Centers for Disease Control and Prevention's Environmental Health Specialists Network (EHS-Net) conducted observations and manager interviews in 359 restaurants in 8 EHS-Net jurisdictions. Managers reported that they date marked ready-to-eat TCS foods more often than data collectors observed this practice (91% vs. 77%). Observation data showed almost a quarter of study restaurants did not date-mark ready-to-eat TCS foods. In addition, restaurants with an internal date-marking policy date marked 5.04 times more often than restaurants without such a policy and chain restaurants date marked 1.24 times more often than independently owned restaurants. These findings suggest that regulators and the retail food industry may improve food safety and lower the burden of foodborne illness in the United States if they target interventions to independent restaurants and encourage strong date-marking policies.

Background AA living in rural areas of the southeastern U.S. experience a disproportionate burden of cardiovascular disease (CVD) morbidity and mortality. Neighborhood environmental factors contribute to this disparity and may decrease the effectiveness of lifestyle interventions aimed at preventing CVD. Furthermore, the influence of neighborhood factors on AA CVD risk behaviors (i.e. physical activity) may be obscured by the use of researcher-defined neighborhoods and researcher-defined healthy and unhealthy places. The objective of this study was to elucidate the effects of neighborhood environments on AA CVD risk behaviors among AA adults who recently completed a lifestyle intervention. We specifically sought to identify AA adults’ self-perceived places of significance and their perceptions of how these places impact CVD risk behaviors including diet, physical activity and smoking. Methods We conducted semi-structured interviews with AA adults (N = 26) living in two rural North Carolina counties (Edgecombe and Nash, North Carolina, USA). Participants were recruited from a community-based behavioral CVD risk reduction intervention. All had at least one risk factor for CVD. Participants identified significant places including where they spent the most time, meaningful places, and healthy and unhealthy places on local maps. Using these maps as a reference, participants described the impact of each location on their CVD risk behaviors. Data were transcribed verbatim and coded using NVivo 12. Results The average age of participants was 63 (SD = 10) and 92% were female. Places participants defined as meaningful and places where they spent the most time included churches and relatives’ homes. Healthy places included gyms and parks. Unhealthy places included fast food restaurants and relatives’ homes where unhealthy food was served. Place influenced CVD risk behaviors in multiple ways including through degree of perceived control over the environment, emotional attachment and loneliness, caretaking responsibilities, social pressures and social support. Conclusions As we seek to improve cardiovascular interventions for rural AA in the American South, it will be important to further assess the effect of significant places beyond place of residence. Strategies which leverage or modify behavioral influences within person-defined significant places may improve the reach and effectiveness of behavioral lifestyle interventions.

Cleaning chemistries are detergent-based formulations that are used during the processing of reusable medical devices. Manufacturers are responsible for demonstrating the safety of cleaning formulations when they are used during a device processing cycle, including the risk of device-associated cytotoxicity over the concentration ranges for recommended use and rinsing during cleaning. However, no regulation currently exists requiring manufacturers to demonstrate such safety. Although manufacturers' safety data sheets (SDSs) provide information on the safe use of chemicals for users, this information may not provide sufficient detail to determine the risks of residual chemicals on device surfaces. SDSs are not required to contain a comprehensive list of chemicals used, only those of risk to the user. They should be supplemented with information on the correct concentrations that should be used for cleaning, as well as instructions on the rinsing required to reduce the levels of chemicals to safe (nontoxic) levels prior to further processing. Supporting data, such as toxicity profiles or cytotoxicity data that support the instructions for use, would provide medical device manufacturers and healthcare personnel with the necessary information to make informed decisions about selection and correct use of detergents. In the current work, cytotoxicity profiles for eight commonly used cleaning formulations available internationally were studied. Although all of these products are indicated for use in the cleaning of reusable medical devices, results vary across the serial dilution curves and are not consistent among detergent types. The information presented here can be leveraged by both medical device manufacturers and processing department personnel to properly assess residual detergent risks during processing. This work also serves as a call to cleaning formulation manufacturers to provide this information for all chemistries.

Background The number and characteristics of pre-exposure prophylaxis (PrEP) health care providers in the United States have not been reported. Methods We analyzed a national pharmacy database that included >90% of all prescriptions dispensed by retail pharmacies and 60%-86% dispensed by mail-order outlets. We estimated the number of PrEP providers by year, provider type, physician specialty, and geographic location. We also measured the Gini coefficients for the distribution of PrEP patients among providers. Results The number of PrEP providers increased from 9621 in 2014 to 65,822 in 2019. In 2019, 68.1% of PrEP providers were physicians. The proportion of nurse practitioners or physician assistants increased from 18.0% in 2014 to 29.7% in 2019. Among all the US health care providers, those who prescribed PrEP increased from 0.7% in 2014 to 4.3% in 2019. Among all general practice/family medicine physicians, the percentage of who prescribed PrEP increased from 1.8% in 2014 to 13.6% in 2019 and from 14.2% to 34.2% among infectious disease physicians. The ratio of PrEP providers to 100 persons with PrEP indications was lowest in the South with 4.4. The Gini coefficient for the distribution of PrEP patients among providers was 0.75 in 2019, with 50% of the PrEP patients prescribed PrEP by 2.2% of PrEP providers. Conclusions An increasing number of providers prescribed PrEP during 2014-2019. The South had the largest number of new HIV diagnoses and greatest need for HIV prevention but had less PrEP service capacity compared with other regions. Expanded access to PrEP services is needed in the United States.

To date, nutritional epidemiology has relied heavily on relatively weak methods including simple observational designs and substandard measurements. Despite low internal validity and other sources of bias, claims of causality are made commonly in this literature. Nutritional epidemiology investigations can be improved through greater scientific rigor and adherence to scientific reporting commensurate with research methods used. Some commentators advocate jettisoning nutritional epidemiology entirely, perhaps believing improvements are impossible. Still others support only normative refinements. But neither abolition nor minor tweaks are appropriate. Nutritional epidemiology, in its present state, offers utility, yet also needs marked, reformational renovation. Changing the status quo will require ongoing, unflinching scrutiny of research questions, practices, and reporting—and a willingness to admit that “good enough” is no longer good enough. As such, a workshop entitled “Toward more rigorous and informative nutritional epidemiology: the rational space between dismissal and defense of the status quo” was held from July 15 to August 14, 2020. This virtual symposium focused on: (1) Stronger Designs, (2) Stronger Measurement, (3) Stronger Analyses, and (4) Stronger Execution and Reporting. Participants from several leading academic institutions explored existing, evolving, and new better practices, tools, and techniques to collaboratively advance specific recommendations for strengthening nutritional epidemiology.

INTRODUCTION A short floppy fundoplication has been the surgical dogma to prevent dysphagia and gas-bloat after laparoscopic fundoplication while adequately addressing gastroesophageal reflux disease. The literature on the ideal length of narrowing (LON) of the gastroesophageal junction after fundoplication is sparse. The functional luminal imaging probe (FLIP) can be used during anti-reflux surgery to produce a visual representation of the LON. We hypothesize that a longer LON provides relief of GERD symptoms, however worse dysphagia and gas-bloat. METHODS AND PROCEDURES Prospectively collected data was analyzed. Patients with FLIP measurements during laparoscopic fundoplication between August 2018 and December 2020 were included. FLIP measurements at the gastroesophageal junction were recorded without pneumoperitoneum at 40-mL balloon fill after fundoplication. Reflux Symptom Index (RSI), Gastroesophageal Reflux Disease-Health Related Quality of Life Questionnaire (GERD-HRQL), gas-bloat score, and Dysphagia Score were collected. Comparisons were made using Spearman correlation coefficients (r) and two-tailed Wilcoxon rank-sum tests, with statistical significance set at p

Coronavirus disease-19 (COVID-19) vaccine response data for patients with hematologic malignancy, who carry high risk for severe COVID-19 illness, are incomplete. In a study of 551 hematologic malignancy patients with leukemia, lymphoma, and multiple myeloma, anti–SARS-CoV-2 spike IgG titers and neutralizing activity were measured at 1 and 3 months from initial vaccination. Compared with healthy controls, patients with hematologic malignancy had attenuated antibody titers at 1 and 3 months. Furthermore, patients with hematologic malignancy had markedly diminished neutralizing capacity of 26.3% at 1 month and 43.6% at 3 months, despite positive seroconversion rates of 51.5% and 68.9% at the respective time points. Healthy controls had 93.2% and 100% neutralizing capacity at 1 and 3 months, respectively. Patients with leukemia, lymphoma, and multiple myeloma on observation had uniformly blunted responses. Treatment with Bruton tyrosine kinase inhibitors, venetoclax, phosphoinositide 3-kinase inhibitors, anti-CD19/CD20–directed therapies, and anti-CD38/B-cell maturation antigen–directed therapies substantially hindered responses, but single-agent immunomodulatory agents did not.Significance:Patients with hematologic malignancy have compromised COVID-19 vaccine responses at baseline that are further suppressed by active therapy, with many patients having insufficient neutralizing capacity despite positive antibody titers. Refining vaccine response parameters is critical to guiding clinical care, including the indication for booster vaccines, for this vulnerable population.See related article by Tamari et al., p. 577.This article is highlighted in the In This Issue feature, p. 549

PURPOSE In this study, we propose combining three-dimensional (3D) transrectal ultrasound (TRUS) and 3D transabdominal ultrasound (TAUS) images of gynecologic brachytherapy applicators to leverage the advantages of each imaging perspective, providing a broader field-of-view and allowing previously obscured features to be recovered. The aim of this study was to evaluate the feasibility of fusing these 3D ultrasound (US) perspectives based on the applicator geometry in a phantom prior to clinical implementation. METHODS In proof-of-concept experiments, 3D US images of application-specific multimodality pelvic phantoms were acquired with tandem-and-ring and tandem-and-ovoids applicators using previously validated imaging systems. Two TRUS images were acquired at different insertion depths and manually fused based on the position of the ring/ovoids to broaden the TRUS field-of-view. The phantom design allowed "abdominal thickness" to be modified to represent different body habitus and TAUS images were acquired at three thicknesses for each applicator. The merged TRUS images were then combined with TAUS images by rigidly aligning applicator components and manually refining the registration using the positions of source channels and known tandem length, as well as the ring diameter for the tandem-and-ring applicator. Combined 3D US images were manually, rigidly registered to images from a second modality (magnetic resonance (MR) imaging for the tandem-and-ring applicator and X-ray computed tomography (CT) for the tandem-and-ovoids applicator (based on applicator compatibility)) to assess alignment. Four spherical fiducials were used to calculate target registration errors (TREs), providing a metric for validating registrations, where TREs were computed using root-mean-square distances to describe the alignment of manually identified corresponding fiducials. An analysis of variance (ANOVA) was used to identify statistically significant differences (p

Kidney fibrosis constitutes the shared final pathway of nearly all chronic nephropathies, but biomarkers for the non-invasive assessment of kidney fibrosis are currently not available. To address this, we characterize five candidate biomarkers of kidney fibrosis: Cadherin-11 (CDH11), Sparc-related modular calcium binding protein-2 (SMOC2), Pigment epithelium-derived factor (PEDF), Matrix-Gla protein, and Thrombospondin-2. Gene expression profiles in single-cell and single-nucleus RNA-sequencing (sc/snRNA-seq) datasets from rodent models of fibrosis and human chronic kidney disease (CKD) were explored, and Luminex-based assays for each biomarker were developed. Plasma and urine biomarker levels were measured using independent prospective cohorts of CKD: the Boston Kidney Biopsy Cohort, a cohort of individuals with biopsy-confirmed semiquantitative assessment of kidney fibrosis, and the Seattle Kidney Study, a cohort of patients with common forms of CKD. Ordinal logistic regression and Cox proportional hazards regression models were used to test associations of biomarkers with interstitial fibrosis and tubular atrophy and progression to end-stage kidney disease and death, respectively. Sc/snRNA-seq data confirmed cell-specific expression of biomarker genes in fibroblasts. After multivariable adjustment, higher levels of plasma CDH11, SMOC2, and PEDF and urinary CDH11 and PEDF were significantly associated with increasing severity of interstitial fibrosis and tubular atrophy in the Boston Kidney Biopsy Cohort. In both cohorts, higher levels of plasma and urinary SMOC2 and urinary CDH11 were independently associated with progression to end-stage kidney disease. Higher levels of urinary PEDF associated with end-stage kidney disease in the Seattle Kidney Study, with a similar signal in the Boston Kidney Biopsy Cohort, although the latter narrowly missed statistical significance. Thus, we identified CDH11, SMOC2, and PEDF as promising non-invasive biomarkers of kidney fibrosis.

Background Combination CDK4/6 inhibitor and endocrine therapy has been shown to significantly improve progression‐free survival (PFS) in patients with hormone receptor (HR)‐positive, HER2‐negative metastatic breast cancer (mBC). The aim of this retrospective study was to evaluate the real‐world benefit of first‐line combination therapy in this cohort and to correlate treatment efficacy with neutropenia, a common toxicity of CDK4/6 inhibitors. Methods This study included HR‐positive, HER2‐negative advanced or mBC patients who were treated with palbociclib plus endocrine therapy, mainly letrozole, between 1 January 2015 and 1 March 2018. Progression‐free survival (PFS) was determined using Kaplan–Meier analysis. The predictive value of absolute neutrophil count (ANC) and neutrophil‐to‐lymphocyte ratio (NLR) for PFS were explored using Cox regression models. Both ANC and NLR were used as a time‐dependent variable. Results In total, 165 patients were included with median PFS of 24.19 months (95% CI 18.93–NR). Median PFS for patients with bone‐only metastases (n = 54) was not reached (95% CI 18.21–NR). Among patients with all other metastases (n = 111), median PFS was 24.19 months (95% CI 16.33–33.82). Lower ANC was correlated with decreased risk of progression (HR 0.84, 95% CI 0.71–0.97, p = 0.008). There was no significant association between NLR and the risk of disease progression (HR 1.07, 95% CI 0.97–1.18, p = 0.203). Conclusion The effectiveness of palbociclib and endocrine therapy in the treatment of HR‐positive, HER2‐negative mBC in the real‐world setting is similar to the efficacy reported in the PALOMA‐2 trial. Patients with lower neutrophil count may have a lower risk of early disease progression., The real‐world benefit of combination CDK4/6 inhibitor and endocrine therapy is similar to that reported in clinical trials. Treatment‐related neutropenia, assessed by absolute neutrophil count (ANC), may be correlated with lower risk of disease progression and a lower ANC threshold for dose reduction may be warranted.

Author(s): Savarirayan, Ravi; Tofts, Louise; Irving, Melita; Wilcox, William R; Bacino, Carlos A; Hoover-Fong, Julie; Font, Rosendo Ullot; Harmatz, Paul; Rutsch, Frank; Bober, Michael B; Polgreen, Lynda E; Ginebreda, Ignacio; Mohnike, Klaus; Charrow, Joel; Hoernschemeyer, Daniel; Ozono, Keiichi; Alanay, Yasemin; Arundel, Paul; Kotani, Yumiko; Yasui, Natsuo; White, Klane K; Saal, Howard M; Leiva-Gea, Antonio; Luna-Gonzalez, Felipe; Mochizuki, Hiroshi; Basel, Donald; Porco, Dania M; Jayaram, Kala; Fisheleva, Elena; Huntsman-Labed, Alice; Day, Jonathan RS | Abstract: PurposeAchondroplasia is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene that lead to impaired endochondral ossification. Vosoritide, an analog of C-type natriuretic peptide, stimulates endochondral bone growth and is in development for the treatment of achondroplasia. This phase 3 extension study was conducted to document the efficacy and safety of continuous, daily vosoritide treatment in children with achondroplasia, and the two-year results are reported.MethodsAfter completing at least six months of a baseline observational growth study, and 52 weeks in a double-blind, placebo-controlled study, participants were eligible to continue treatment in an open-label extension study, where all participants received vosoritide at a dose of 15.0 μg/kg/day.ResultsIn children randomized to vosoritide, annualized growth velocity increased from 4.26 cm/year at baseline to 5.39 cm/year at 52 weeks and 5.52 cm/year at week 104. In children who crossed over from placebo to vosoritide in the extension study, annualized growth velocity increased from 3.81 cm/year at week 52 to 5.43 cm/year at week 104. No new adverse effects of vosoritide were detected.ConclusionVosoritide treatment has safe and persistent growth-promoting effects in children with achondroplasia treated daily for two years.

Vosoritide, an analog of C-type natriuretic peptide, has been developed for the treatment of children with achondroplasia. The pharmacokinetics of vosoritide and relationships between plasma exposure and efficacy, biomarkers, and safety endpoints were evaluated in a phase II, open-label, dose-escalation study (N = 35 patients aged 5–14 years who received daily subcutaneous injections for 24 months) and a phase III, double-blind, placebo-controlled study (N = 60 patients aged 5–18 years randomized to receive daily subcutaneous injections for 52 weeks). Pharmacokinetic parameters for both studies were obtained from non-compartmental analysis. Potential correlations between vosoritide exposure and changes in annualized growth velocity, collagen type X marker (CXM; a biomarker of endochondral ossification), cyclic guanosine monophosphate (cGMP; a biomarker of pharmacological activity), heart rate, and systolic and diastolic blood pressures were then evaluated. The exposure–response relationships for changes in both annualized growth velocity and the CXM biomarker saturated at 15 μg/kg, while systemic pharmacological activity, as measured by urinary cGMP, was near maximal or saturated at exposures obtained at the highest dose studied (i.e. 30 μg/kg). This suggested that the additional bioactivity was likely in tissues not related to endochondral bone formation. In the phase III study, following subcutaneous administration at the recommended dose of 15 μg/kg to patients with achondroplasia aged 5–18 years, vosoritide was rapidly absorbed with a median time to maximal plasma concentration (Cmax) of 15 minutes, and cleared with a mean half-life of 27.9 minutes after 52 weeks of treatment. Vosoritide exposure (Cmax and area under the concentration-time curve [AUC]) was consistent across visits. No evidence of accumulation with once-daily dosing was observed. Total anti-vosoritide antibody (TAb) responses were detected in the serum of 25 of 60 (42%) treated patients in the phase III study, with no apparent impact of TAb development noted on annualized growth velocity or vosoritide exposure. Across the exposure range obtained with 15 µg/kg in the phase III study, no meaningful correlations between vosoritide plasma exposure and changes in annualized growth velocity or CXM, or changes from predose heart rate, and systolic or diastolic blood pressures were observed. The results support the recommended dose of vosoritide 15 µg/kg for once-daily subcutaneous administration in patients with achondroplasia aged ≥ 5 years whose epiphyses are not closed. NCT02055157, NCT03197766, and NCT01603095.

Pediatrician Screening, Brief Intervention, and Referral to Treatment (SBIRT) practices vary widely, though little is known about the correlates of SBIRT implementation. Using data from a national sample of US pediatricians who treat adolescents (n = 250), we characterized self-reported utilization rates of SBIRT among US pediatricians and identified provider- and practice-level characteristics and barriers associated with SBIRT utilization. All participants completed an electronic survey querying the demographics, practice patterns, and perceived barriers related to SBIRT practices. Our results showed that 88% of respondents reported screening for substance use annually, but only 26% used structured/validated screening instruments. Furthermore, 40% of respondents provided evidence-based brief interventions, and only 11% implemented all core SBIRT practices. Common barriers (eg, confidentiality and insufficient time) and unique provider- and setting-specific barriers to implementation were identified. These findings indicate that although most pediatricians deliver some SBIRT components in their practice, few implement the full SBIRT model, and barriers persist.

Nanotechnology, photonics, and immunotherapy are far-reaching technologies with the potential to revolutionize the field of cancer diagnostics and therapeutics. While each technology has limitations in cancer treatment, they can be synergized to exert profound impact on the balance and modulation of immunoediting in tumor microenvironment (TME) and in the entire host immune system. We provide our perspectives on how nano-photo-immuno interactions can be used as an effective therapy, particularly when combined with other treatment modalities, such as checkpoint immune therapy, chemotherapy, and TME modulation, to provide a long-term, tumor-specific immunity against tumor metastasis and tumor recurrence.

Immunotherapy has provided a new avenue to treat metastatic cancers, which result in ∼90% of cancer related deaths. However, current immunotherapies, such as immune checkpoint therapy (ICT), have met with limited success, primarily due to tumor intrinsic and extrinsic factors that inhibit antitumor immune responses. To overcome the immune suppression of the tumor microenvironment (TME) and enhance the tumoricidal activity of ICT, phototherapy, particularly photothermal therapy (PTT), combined with nanomedicine has become a viable option. PTT disrupts target tumor homeostasis, releasing tumor associated antigens (TAAs), tumor specific antigens (TSAs), danger associated molecular patterns (DAMPs), and scarce nutrients required to “feed” activated antitumor immune cells. While nanoparticles localize and specify the phototherapeutic effect, they can also be loaded with immune stimulants, TME modulators, and/or chemotherapeutic agents to greatly enhance immune stimulation and tumor killing. Combining these three technologies, which we term nano-ablative immunotherapy (NAIT), with ICT can greatly enhance their therapeutic effects. In this review, we will discuss the successes and limitations of NAIT + ICT. Specifically, we will discuss how the TME limits tumoricidal activity and what should be considered to overcome these limitations.

As radiation detector arrays in nuclear physics applications become larger and physically more separated, the time synchronization and trigger distribution between many channels of detector readout electronics become more challenging. Clocks and triggers are traditionally distributed through dedicated cabling, but newer methods such as the IEEE 1588 Precision Time Protocol and White Rabbit allow clock synchronization through the exchange of timing messages over Ethernet. Consequently, we report here the use of White Rabbit in a new detector readout module, the Pixie-Net XL. The White Rabbit core, data capture from multiple digitizing channels, and subsequent pulse processing for pulse height and constant fraction timing are implemented in a Kintex 7 field programmable gate array (FPGA). The detector data records include White Rabbit timestamps and are transmitted to storage through the White Rabbit core’s gigabit Ethernet data path or a slower diagnostic/control link using an embedded Zynq processor. The performance is characterized by time-of-flight style measurements and by time correlation of high energy background events from cosmic showers in detectors separated by longer distances. Software for the Zynq processor can implement “software triggering,” for example to limit recording of data to events where a minimum number of channels from multiple modules detect radiation at the same time.

Introduction: Thyroglossal duct cysts (TGDCs) are the most common form of congenital neck cysts. They may become infected causing dysphagia or respiratory distress. Accordingly, the treatment is always surgical removal. Objectives: The objectives of this article were to examine complications following TGDC excision by surgical specialty, demographics, and comorbid conditions. Methods: A retrospective review of the National Surgical Quality Improvement Program database was performed. Pediatric cases from January 1, 2014 to November 1, 2015 with a current procedure terminology code of 60,280 (excision of TGDC or sinus) were included. Statistical analysis was performed to assess associations between complications and surgical specialty, demographics, and comorbidities. Results: Of the 867 cases that met inclusion criteria, the median age was 4 years. There were 448 males (52.3%) and 408 females (47.7%). Thirty-six patients (4.2%) experienced at least one 30-day complication. The most predominant complications were reoperation (19 patients, 2.2%), readmission (18 patients, 2.1%), and surgical site infection (16 patients, 1.9%). There was no statistically significant difference between complications and surgical specialty. In those experiencing a complication, there was a statistically significant difference between males (86.1%) and females (13.9%). Of patients with at least one comorbidity, 36.67% had a complication, while 17.22% did not have a complication. There was also a statistically significant difference in the percentage of patients with a past medical history of asthma between those with at least one complication (16.67%) compared to those without any complications (4.76%). Conclusions: excision is a generally safe procedure across surgical specialties. There is a higher complication rate in males compared to females as well as those with a history of at least one medical comorbidity and those with asthma. The most common 30-day complications are reoperation, readmission, and surgical site infection.

Lansoprazole orally disintegrating tablets (ODTs) can be administered orally or through a nasogastric (NG) tube for patients who are unable to swallow. In addition, off-label administration through...

Background: The influence of prenatal diethylstilbestrol (DES) exposure on cancer incidence among middle-aged men has not been well-characterized. We investigated whether exposure to DES before birth impacts overall cancer risk, and risk of site-specific cancers. Methods: Men (mean age in 2016 = 62.0 years) who were or were not prenatally DES exposed were identified between 1953 and 1994 and followed for cancer primarily via questionnaire approximately every 5 years between 1994 and 2016. The overall and site-specific cancer rates of the two groups were compared using Poisson regression and proportional hazards modeling with adjustment for age. Results: DES exposure was not associated with either overall cancer [hazard ratio (HR), 0.94; 95% confidence interval (CI), 0.77–1.15] or total prostate cancer rates (HR, 0.95; 95% CI, 0.68–1.33), but was inversely associated with urinary tract cancer incidence (HR, 0.48; 95% CI, 0.23–1.00). Conclusions: There was no increase in either overall or prostate cancer rates among men prenatally DES exposed relative to those unexposed. An unexpected risk reduction was observed for urinary system cancers among the exposed relative to those unexposed. These findings suggest that prenatal DES exposure is unlikely to be an important contributor to cancer development in middle-aged men. Impact: The results of this study could lend reassurance to middle-aged men who were prenatally DES exposed that their exposure does not adversely influence their overall cancer risk.

We aim to analyze survival outcomes for sentinel lymph node biopsy (SLNB) versus axillary lymph node dissection (ALND) in human epidermal growth factor receptor (HER2)+ infiltrative ductal carcinoma (IDC) that demonstrate complete clinical response (cCR) to neoadjuvant systemic therapy (NAST) after initial presentation with clinical N1 (cN1) disease. NCDB 2004–2017 was utilized for the analysis. Female patients with unilateral HER2+ IDC, stage cT1–T4 cN1, who demonstrated cCR to NAST with reported definitive axillary surgical management were included. Patients were propensity score matched, and overall survival (OS) was compared. Cox regression analysis was used to identify survival predictors. 6453 patients were selected, of whom 2461 (38.1%) had SLNB and 3992 (69.1%) had ALND as definitive axillary surgical management. The trend of SLNB utilization increased from 20% in 2012 to 50% in 2017. A total of 2454 patients were matched from each group with adequate adjustment for all variables. There was no difference in OS between SLNB versus ALND (84.03 ± 0.36 versus 84.62 ± 0.42 months; p = 0.522). Cox regression identified age, cT stage, primary tumor response to NAST, ypN+, and endocrine therapy as significant OS predictors. In subgroup analysis of patients with ypN+ who had SLNB as a definitive procedure, primary tumor response to NAST and continuation of adjuvant chemotherapy were associated with improved OS. In cN1 HER2+ IDC patients who demonstrate cCR to NAST, SLNB is a reasonable definitive procedure for axillary management with comparable OS outcomes to ALND. However, higher-level data are required to determine the appropriate management in the case of ypN+.

BACKGROUND: Children of parents with substance use disorders are at greater risk for mental and physical health co-morbidities. Despite guidelines, pediatricians rarely screen for substance use in the family/household, citing fear of offending parents. The objectives of this study were to examine 1) caregiver acceptance of pediatricians screening for family/household substance use during well-child visits, 2) prevalence of family/household substance use, and 3) the association between family/household substance use and trust in their child’s pediatrician. METHODS: This cross-sectional study surveyed adult caregivers presenting a child for medical care at two urban pediatric outpatient clinics using a brief anonymous computer-based survey. The primary outcome measured acceptability of pediatrician screening for family/household substance use. Substance use and concerns about use in the family/household were also assessed. RESULTS: Adult caregivers (N=271) surveyed were mean age 35 years, 73% mothers, 90% African American, and 85% on Medicaid. Over half (51%) of caregivers reported substance use by someone in the family/household, most commonly cigarettes (38%), followed by alcohol (19%) and marijuana (10%). Sixty-one percent of caregivers who reported family substance use, expressed concern about use of this substance. The majority (87%) agreed it is appropriate for pediatricians to ask caregivers about family/household substance use. No differences were found between caregivers who did and did not report substance use in their family/household. Caregivers with concerning substance use in their family/household were less likely to trust their pediatrician [OR=0.21, 95%CI:0.05, 0.85] CONCLUSIONS: Caregivers endorsed acceptance of universal screening for substance use, including illicit substances, and substance use disorders in the family/household during well-child visits. Pediatricians are trusted professionals with expertise in communicating with parents to maximize the health of their patients; assessing family history of substance use and substance use disorders is a natural extension of their role.