Trends in Firearm Injury Prevention Research Funding, Clinical Trials, and Publications in the US, 1985-2022.

This cross-sectional study examines federal funding, registered clinical trials, and publications to quantify trends in firearm injury prevention research in the US from 1985 to 2022.

Core Descriptor Sets for Rectal Prolapse Outcomes Research Using a Modified Delphi Consensus.

BACKGROUND: There is wide variation in prolapse care. OBJECTIVE: To determine core descriptor sets for rectal prolapse to enhance outcomes research. DESIGN: Descriptors for patients undergoing rectal prolapse surgery were generated through a systematic review and expert opinion. Stakeholders were recruited internationally via listserv and social media. Experts were encouraged to consider the minimum descriptors that could be considered during clinical care, and descriptors were grouped into core descriptor sets. Consensus was defined as greater than 70% agreement. SETTING: A 3-round Delphi process using a 9-point Likert scale based on expert results was distributed via survey. The final interactive meeting used a polling platform. PARTICIPANTS: The Pelvic Floor Disorders Consortium interdisciplinary group convened to advance the clinical care of pelvic floor disorders. MAIN OUTCOME MEASURES: To achieve expert consensus for core descriptor sets for rectal prolapse using a modified Delphi method. RESULTS: A total of 206 providers participated, with survey response rates of 82% and 88%, respectively. Responders were from North America (56%), Europe (29%), and Latin America, Asia, Australia, New Zealand, and Africa (15%). Ninety-one percent of participants identified as colorectal surgeons and 80% reported >5 years of experience (35% reported >15 years). Fifty-seven attendees participated in the final meeting and voted on core descriptor sets. Ninety-three percent of participants agreed that descriptors such as age, BMI, frailty, nutrition, and the American Society of Anesthesiology score correlated to physiologic status. One hundred percent of participants agreed to include baseline bowel function. One hundred percent of participants reported willingness to complete a synoptic operative report. Follow-up intervals 1, 3, and 5 years after surgery (76%) with a collection of recurrence and functional outcomes at those time periods reached an agreement. LIMITATIONS: Individual bias, self-identification of experts, and paucity of knowledge related to rectal prolapse. CONCLUSIONS: This represents the first steps toward international consensus to unify language and data collection processes for rectal prolapse. See Video Abstract . CONJUNTOS DE DESCRIPTORES BSICOS PARA LA INVESTIGACIN DE RESULTADOS DE PROLAPSO RECTAL MEDIANTE UN CONSENSO DELPHI MODIFICADO: ANTECEDENTES:Existe una amplia variación en la atención del prolapso.OBJETIVO:Determinar conjuntos de descriptores básicos para el prolapso rectal para mejorar los resultados de la investigación.DISEÑO:Los descriptores para pacientes sometidos a cirugía de prolapso rectal se generaron a través de una revisión sistemática y la opinión de expertos. Las partes interesadas fueron reclutadas internacionalmente a través de listas de servicio y redes sociales. Se animó a los expertos a considerar los descriptores mínimos que podrían considerarse durante la atención clínica, y los descriptores se agruparon en conjuntos de descriptores básicos. El consenso se definió como > 70% de acuerdo.AJUSTE:Se distribuyó mediante encuesta un proceso Delphi de tres rondas que utiliza una escala Likert de 9 puntos basada en resultados de expertos. La reunión interactiva final utilizó una plataforma de votación.PARTICIPANTES:El grupo interdisciplinario del Consorcio de Trastornos del Suelo Pélvico se reunió para avanzar en la atención clínica de los trastornos del suelo pélvico.MEDIDAS PRINCIPALES DE RESULTADOS:Lograr el consenso de expertos para los conjuntos de descriptores básicos para el prolapso rectal utilizando un método Delphi modificado.RESULTADOS:Participaron 206 proveedores con tasas de respuesta a la encuesta del 82% y 88% respectivamente. Los encuestados procedían de América del Norte (56%), Europa (29%) y América Latina, Asia, Australia, Nueva Zelanda y África (15%). El noventa y uno por ciento se identificó como cirujanos colorrectales y el 80% reportó más de 5 años de experiencia (35% > 15 años). Cincuenta y siete asistentes participaron en la reunión final y votaron sobre conjuntos de descriptores básicos. El noventa y tres por ciento estuvo de acuerdo en que descriptores como edad, índice de masa corporal, fragilidad, nutrición y puntuación de la Sociedad Estadounidense de Anestesiología se correlacionaban con el estado fisiológico. El cien por ciento estuvo de acuerdo en incluir la función intestinal inicial. El 100% refirió disposición para realizar un informe operativo sinóptico. Los intervalos de seguimiento 1,3,5 años después de la cirugía (76%) con un conjunto de recurrencias y los resultados funcionales en esos períodos de tiempo coincidieron.LIMITACIONES:Sesgo individual, autoidentificación de los expertos y escasez de conocimientos relacionados con el prolapso rectal.CONCLUSIONES:Esto representa los primeros pasos hacia un consenso internacional para unificar el lenguaje y los procesos de recolección de datos para el prolapso rectal. (Traducción-Yesenia Rojas-Khalil ).

A Pilot Study Examining the Association of Parental Stress and Household Food Insecurity with Dietary Quality in Pre-School-Aged Children.

Adequate dietary quality is necessary for children's appropriate development and may be influenced by family factors. This study with 24 healthy 3-5-year-old children assessed the associations of parental stress and household food insecurity (HFI) with a child's dietary quality. Parents completed three 24 h dietary recalls, and the Healthy Eating Index was calculated to assess dietary quality. Parents also completed a questionnaire, including The Perceived Stress Scale (assessing overall parental stress) and the Hunger Vital Sign screen (assessing HFI). Children's height/weight were measured, and BMIz was calculated. Separate multivariable linear regression models assessed the association of dietary quality components with HFI and parental stress, adjusting for household income, child sex, and child BMI z-score. In bivariate analyses, children with HFI consumed more added sugars, and parental stress was associated with the child's greens/beans intake. In multivariable analysis, HFI was associated with lower total protein scores and higher added sugar intake, while parental stress was associated with lower greens/beans intake. Higher household income was associated with higher total vegetable and sodium intake, and children with a higher BMIz had a lower total protein intake. Parental stress and HFI can impact a child's dietary quality; providers should counsel families on strategies to improve diet quality.

Age-dependent Microglial Disease Phenotype Results in Functional Decline in Gut Macrophages.

BACKGROUND AND AIMS: Muscularis macrophages (MMs) are tissue-resident macrophages in the gut muscularis externa which play a supportive role to the enteric nervous system. We have previously shown that age-dependent MM alterations drive low-grade enteric nervous system inflammation, resulting in neuronal loss and disruption of gut motility. The current studies were designed to identify the MM genetic signature involved in these changes, with particular emphasis on comparison to genes in microglia, the central nervous system macrophage population involved in age-dependent cognitive decline. METHODS: Young (3 months) and old (16-24 months) C57BL/6 mice and human tissue were studied. Immune cells from mouse small intestine, colon, and spinal cord and human colon were dissociated, immunophenotyped by flow cytometry, and examined for gene expression by single-cell RNA sequencing and quantitative real-time PCR. Phagocytosis was assessed by in vivo injections of pHrodo beads (Invitrogen). Macrophage counts were performed by immunostaining of muscularis whole mounts. RESULTS: MMs from young and old mice express homeostatic microglial genes, including Gpr34, C1qc, Trem2, and P2ry12. An MM subpopulation that becomes more abundant with age assumes a geriatric state (GS) phenotype characterized by increased expression of disease-associated microglia genes including Cd9, Clec7a, Itgax (CD11c), Bhlhe40, Lgals3, IL-1ß, and Trem2 and diminished phagocytic activity. Acquisition of the GS phenotype is associated with clearance of α-synuclein aggregates. Human MMs demonstrate a similar age-dependent acquisition of the GS phenotype associated with intracellular α-synuclein accumulation. CONCLUSION: MMs demonstrate age-dependent genetic changes that mirror the microglial disease-associated microglia phenotype and result in functional decline.

The Robert Wood Johnson Foundation Future of Nursing Scholars program: The scholar experience.

BACKGROUND: Robert Wood Johnson Foundation Future of Nursing Scholars program used multi-pronged approach to support nurses completing accelerated PhD programs. PURPOSE: The purpose of this manuscript was to describe scholars' experiences completing PhDs, their dissertation characteristics, program leadership development sessions, scholar perceptions of program components. METHODS: Of 201 scholars, 157 (78%) completed quantitative exit surveys, providing: satisfaction with doctoral programs and FNS curricula, types of dissertation data used, dissertation formats. Interviews held with five scholars to capture representative themes. FINDINGS: Scholars utilized primary and secondary data for dissertations; 53% primarily used secondary data. The majority (68%) used manuscript dissertation formats. Approximately 64% completely agreed program curricula helped prepare them for professional transitions, to work collaboratively, lead confidently. Proportion of FNS graduates (42%) pursuing postdoctoral positions exceeded national trends. DISCUSSION: Despite stresses posed by accelerated PhD programs, scholars are well-situated to advance nursing science. Findings suggest secondary data analyses work well for accelerated programs. Scholar program experiences were positive.

Combined Chronic Oral Methylphenidate and Fluoxetine Treatment During Adolescence: Effects on Behavior.

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) can be comorbid with depression, often leading to the prescription of both methylphenidate (MP) and selective serotonin reuptake inhibitor (SSRI) antidepressants, such as fluoxetine (FLX). Moreover, these drugs are often misused as cognitive enhancers. This study examined the effects of chronic oral co-administration of MP and FLX on depressive- and anxiety-like behaviors. METHODS: Adolescent rats received daily either water (control), MP, FLX, or the combination of MP plus FLX in their drinking water over the course of 4 weeks. RESULTS: Data analysis shows a decrease in food consumption and body weight for rats exposed to FLX or the combination of MP and FLX. Sucrose consumption was significantly greater in FLX or MP+FLX groups compared to controls. FLX-treated rats showed no effect in the elevated plus maze (EPM; open arm time) and forced swim test (FST; latency to immobility). However, rats treated with the combination (MP+FLX) showed significant anxiolytic-like and anti-depressive-like behaviors (as measured by EPM and FST), as well as significant increases in overall activity (distance traveled in open field test). Finally, the combined MP+FLX treatment induced a decrease in anxiety and depressive- like behaviors significantly greater than the response from either of these drugs alone. CONCLUSION: These behavioral results characterize the long-term effects of these drugs (orally administered) that are widely co-administered and co-misused and provide important insight into the potential neurobiological and neurochemical effects. Future research will determine the potential risks of the long-term use of MP and FLX together.

Chronic oral methylphenidate plus fluoxetine treatment in adolescent rats increases cocaine self-administration.

Background: Depression and attention deficit hyperactivity disorder are known to be comorbid. Treatment of these commonly coexisting diseases typically involves the combined prescription of methylphenidate (MP), a psychostimulant, and fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI). MP and cocaine have similar mechanisms of action and this study examined the effects of chronic treatment of MP combined with FLX on cocaine consumption in rats. Methods: Four groups of rats received access to drinking solutions of water (control), MP (30/60 mg/kg/day), FLX (20 mg/kg/day), or the combination of MP (30/60 mg/kg/day) plus FLX (20 mg/kg/day), during 8 h per day for one month. Following these drug treatments, rats were allowed to self-administer cocaine for 14 days. Results: Our results showed that, during the first week of cocaine self-administration, the MP-treated rats had significantly greater numbers of active lever presses (plus 127%) and increased consumption of cocaine compared to the control rats. In contrast, during week two of cocaine self-administration, the rats treated with the MP + FLX combination showed significantly more lever presses (plus 198%) and significantly greater cocaine consumption (plus 84%) compared to the water controls. Conclusion: Chronic oral treatment during adolescence with the combination of MP plus FLX resulted in increased cocaine use after 2 weeks of cocaine self-administration in rats. These novel findings suggest that the combined exposure to these two drugs chronically, during adolescence, may produce increased vulnerability towards cocaine abuse during young adulthood.

College Undergraduates in the Operating Room: an Educational Model for Early Surgical Education.

Undergraduate pre-medical education in the USA has not traditionally offered opportunities for hands-on surgical education to college-level students. The absence of exposure has been studied, but an educational model to remedy this has not been shared. This course was designed to share a replicable model for college surgical education. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01577-y.

Non-ablative Er:YAG laser is an effective tool in the treatment arsenal of androgenetic alopecia.

BACKGROUND: Up to 70% of the adult population worldwide is affected by androgenetic alopecia (AGA) hair loss. Laser therapy offers an addition or alternative to pharmaceutical and surgical treatment of hair regrowth, with non-ablative lasers being preferred over ablative lasers in terms of safety and downtime. Combining laser therapy with different topical agents may result in better hair regrowth. OBJECTIVE: The aim was to evaluate the effectiveness and safety of non-ablative Er:YAG laser used in clinical practice, alone or in combination with other treatment modalities, in patients with both early and advanced stages of AGA. METHODS AND PATIENTS: Sixteen patients (7 male and 9 female) with active AGA in different stages were treated with the non-ablative Er:YAG laser (SMOOTHTM mode, 7 mm spot size, 7.00 J/cm2 pulse fluence, 3.3 Hz frequency) as a monotherapy or in combination with injections of platelet-rich plasma (PRP) to the scalp, topical minoxidil, and oral supplements for the promotion and support of hair growth. Efficacy was assessed with clinical assessment of AGA grade (Ludwig scale for female / Norwood-Hamilton scale for male) and with blind evaluation of hair quality in global photographs before and after treatment. Patients subjectively rated their satisfaction with the laser treatment on a scale from 0-3 and pain on a VAS scale from 0-10. RESULTS: AGA grade after treatment was lower compared to baseline (p = 0.015 and p = 0.125 in female and male patients, respectively). Blind evaluation indicated an improvement in hair quality in 93% of patients, either being described as much better (14%) or as better (79%), which was not correlated with age or AGA grade. The median satisfaction score was 3, and the median VAS score for pain was 2. The positive effect of the treatment on the hair quality is ongoing. No adverse reactions were reported. CONCLUSIONS: The treatment was effective in treating AGA, confirmed by a decrease in AGA grade and by blinded evaluation of global photographs. Although the possible additive or complementary effect of topical minoxidil or nutraceuticals cannot be excluded, our results suggest that the non-ablative Er:YAG laser SMOOTH™ mode as a monotherapy, or in combination with PRP, is an efficient and safe treatment for AGA-with a high satisfaction rate among patients regardless of patient age, AGA duration, or AGA stage.

Ethical challenges of prospective clinical trials during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has created an unprecedented opportunity to reimagine clinical research. While much has been written about the challenges associated with generating real-world evidence during the COVID-19 pandemic, comparatively little attention has been paid to the ethical challenges facing patients, clinicians, researchers, and regulatory bodies. AREAS COVERED: In this manuscript, we examine these challenges through the lens of informed consent and explore how the consenting process changes as our understanding of the disease is altered. EXPERT OPINION: We also suggest ways to limit these ethical hurdles through the use of embedded pragmatic clinical trials, which generate real-world data without the limitations associated with observational trials or the resources and lack of generalizability that are obstacles to conducting conventional randomized clinical trials. We argue that clinical research must become more nimble, and must include embedded researchers to ensure that relevant questions and ethical issues are properly addressed.

Hair regrowth and maintenance in alopecia universalis patient treated with nonablative Er:YAG laser.

Hair regrowth with no adverse effects following nonablative 2940-nm Er:YAG laser treatment in alopecia universalis patient resulted in high patient satisfaction and compliance. As the main challenge in alopecia universalis is maintenance of regrown hair, patient compliance associated with this treatment might represent an advantage over traditional treatment modalities.

Treatments Administered to the First 9152 Reported Cases of COVID-19: A Systematic Review.

The emergence of SARS-CoV-2/2019 novel coronavirus (COVID-19) has created a global pandemic with no approved treatments or vaccines. Many treatments have already been administered to COVID-19 patients but have not been systematically evaluated. We performed a systematic literature review to identify all treatments reported to be administered to COVID-19 patients and to assess time to clinically meaningful response for treatments with sufficient data. We searched PubMed, BioRxiv, MedRxiv, and ChinaXiv for articles reporting treatments for COVID-19 patients published between 1 December 2019 and 27 March 2020. Data were analyzed descriptively. Of the 2706 articles identified, 155 studies met the inclusion criteria, comprising 9152 patients. The cohort was 45.4% female and 98.3% hospitalized, and mean (SD) age was 44.4 years (SD 21.0). The most frequently administered drug classes were antivirals, antibiotics, and corticosteroids, and of the 115 reported drugs, the most frequently administered was combination lopinavir/ritonavir, which was associated with a time to clinically meaningful response (complete symptom resolution or hospital discharge) of 11.7 (1.09) days. There were insufficient data to compare across treatments. Many treatments have been administered to the first 9152 reported cases of COVID-19. These data serve as the basis for an open-source registry of all reported treatments given to COVID-19 patients at www.CDCN.org/CORONA . Further work is needed to prioritize drugs for investigation in well-controlled clinical trials and treatment protocols.