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Background: The sex- and gender-specific health (SGSH) multimedia case-based learning modules (MCBLMs) were developed to address the absence of validated or peer-reviewed material that incorporates topics of sex and gender differences into medical curricula. This article provides the methodology for development of the modules and reports the results of a field test of the modules in different medical educational settings. Methods: MCBLMs were created by a multidisciplinary committee of scientists, health profession educators, and students. Two modules, osteoporosis and diabetes, were tested in various settings based on the curricular needs at each of the five accredited institutions. Each module consisted of a pretest and three interactive, multimedia stand-alone sections with post-tests. Scores on the tests were compared using a paired-samples t -test. A postmodule survey was used to evaluate the format. Results: Four hundred eighteen students participated in the field testing. For the 194 who completed the osteoporosis module, the post-test scores (M = 13.71, standard deviation [SD] = 2.09) were significantly higher than the pretest scores (M = 10.54, SD = 2.41), p < 0.001. Post-test scores for the 285 who completed the diabetes module (M = 16.55, SD = 2.46) were also significantly higher than the pretest scores (M = 13.71, SD = 2.09), p < 0.001. The postmodule survey showed positive acceptance of the format with an average score of 3.54/4 for osteoporosis and 3.45/4 for diabetes. Conclusion: The SGSH MCBLM field testing results show that the modules have a positive effect on content knowledge in multiple settings and are well accepted by learners.

Aim Evaluation of cannabinoid receptor agonists in a preclinical model of medication overuse headache. Methods Female Sprague Dawley rats received graded intraperitoneal doses of WIN55,212-2 or Δ-9-tetrahydrocannabinol (Δ-9-THC). Antinociception (tail-flick test), catalepsy and hypomotility (open field test) and impairment of motor function (rotarod test) were assessed to establish effective dosing. Rats were then treated twice daily with equianalgesic doses of WIN55,212-2 or Δ-9-THC, or vehicle, for 7 days and cutaneous tactile sensory thresholds were evaluated during and three weeks following drug discontinuation. Rats then received a one-hour period of bright light stress (BLS) on two consecutive days and tactile sensory thresholds were re-assessed. Results WIN55,212-2 and Δ-9-THC produced antinociception as well as hypomotility, catalepsy and motor impairment. Repeated administration of WIN55,212-2 and Δ-9-THC induced generalized periorbital and hindpaw allodynia that resolved within 3 weeks after discontinuation of drug. Two episodes of BLS produced delayed and long-lasting periorbital and hindpaw allodynia selectively in rats previously treated with WIN55,212-2, and Δ-9-THC. Interpretation Cannabinoid receptor agonists including Δ-9-THC produce a state of latent sensitization characterized by increased sensitivity to stress, a presumed migraine trigger. Overuse of cannabinoids including cannabis may increase the risk of medication overuse headache in vulnerable individuals.

Summary Background Due to the paucity of targeted therapy for irritable bowel syndrome (IBS), many patients turn to dietary modifications for symptom management. The combination of five subgroups of poorly absorbed and rapidly fermented carbohydrates—fructans, galacto‐oligosaccharides, lactose, excess fructose and polyols—are thought to trigger gastrointestinal symptoms and are referred to collectively as “FODMAPs”. Aims To examine the biological plausibility and mechanisms by which foods high in specific FODMAP subgroups cause symptoms, and to use this information to explore the possibility of targeting select dietary components to allow for a more personalised approach to dietary adjustment Methods Recent literature was analysed via search databases including Medline, PubMed and Scopus. Results Lactose, fructans and galacto‐oligosaccharides have strong biologic plausibility for symptom generation due to lack of hydrolases resulting in distention from osmosis and rapid fermentation. However, excess fructose and polyols may only cause symptoms in specific individuals when consumed in high doses, but this remains to be established. There is evidence to suggest that certain patient characteristics such as ethnicity may predict response to lactose, but differentiation of other subgroups is difficult prior to dietary manipulation. Conclusions While some clear mechanisms of action for symptom generation have been established, further research is needed to understand which patients will respond to specific FODMAP subgroup restriction. We suggest that clinicians consider in some patients a tailored, personalised “bottom‐up” approach to the low‐FODMAP diet, such as dietary restriction relevant to the patients’ ethnicity, symptom profile and usual dietary intake.

Colorectal cancer (CRC) is the third most frequent neoplastic disorder and is a main cause of tumor-related mortality, as many patients progress to stage IV metastatic CRC. Standard care consists of combination chemotherapy (FOLFIRI or FOLFOX). Patients with WT KRAS typing are eligible to receive anti-EGFR therapy combined with chemotherapy. Unfortunately, predicting efficacy of CRC anti-EGFR therapy has remained challenging. Here we uncovered that the EGFR pathway component RasGRP1 acts as a CRC tumor suppressor in the context of aberrant Wnt signaling. We found that RasGRP1 suppresses EGF-driven proliferation of colonic epithelial organoids. Having established that RasGRP1 dosage levels impact biology, we next focused on CRC patients. Mining 5 different data platforms, we establish that RasGRP1 expression levels decrease with CRC progression and predict poor clinical outcome of patients. Last, deletion of 1 or 2 Rasgrp1 alleles made CRC spheroids more susceptible to EGFR inhibition. Retrospective analysis of the CALGB 80203 clinical trial showed that addition of anti-EGFR therapy to chemotherapy significantly improved outcome for CRC patients when tumors expressed low levels of RasGRP1 suppressor. In sum, our data support RasGRP1 as a biomarker in the EGFR pathway that has potential relevance to anti-EGFR therapy for CRC patients.

Background:MAIA, an ongoing phase 3 trial of transplant‐ineligible patients with NDMM, demonstrated significant improvement in progression‐free survival with D‐Rd vs Rd alone. Assessment of patient‐reported outcomes (PRO) alongside efficacy endpoints provides patient perspective on their quality of survival and overall value of health‐related quality of life (HRQoL) while on treatments.Aims:To utilize PRO assessments as a tool in capturing the patient perspective on quality of survival and HRQoL changes in MAIA.Methods:The EORTC QLQ‐C30 and EQ‐5D‐5L questionnaires were completed by patients using an electronic device at baseline and every 3 months during treatment; interim results are presented for first 12 months. Treatment effects were assessed using repeated measures, mixed effects models and thresholds for clinically meaningful benefit were based on established criterion from the literature.Results:Compliance rates in completing the assessment tools were high and comparable at baseline (>90%) and through month 12 (>80%) for both groups (D‐Rd [n = 368]; Rd [n = 369]). Improvement in Global Health Status (GHS) occurred in both groups; however, for D‐Rd, significantly greater improvement was observed at cycle 3 (LS mean change; D‐Rd: 4.5 [95% CI: 2.4, 6.6], Rd: 1.5 [95% CI: −0.7, 3.7]; [p = 0.0454]) and increasing improvement occurred across all time points. Significant improvement and clinically meaningful benefit in HRQoL for D‐Rd was also observed in EQ‐5D‐5L Visual Analog Scale (VAS) scores (LS mean change; D‐Rd: 10.1 [95% CI: 8.1, 12.1], Rd: 4.9 [95% CI: 2.8, 7.0]; [p = 0.0002]). The VAS median time to worsening was 10 mo longer for D‐Rd. Of note, meaningful differences were observed between the treatment groups in two subscale scores, pain symptoms and cognitive functioning. Statistically significant less pain was reported early with D‐Rd (LS mean change at cycle 3; D‐Rd: −17.9 [95% CI: −20.7, −15.0], Rd: −11.0 [95% CI: −14.0, −8.1]; [p = 0.0007]); clinically meaningful reduction in pain symptoms was sustained with D‐Rd. There was a decline in cognitive functioning through Cycle 12 in both treatment arms with the peak difference occurring at Cycle 9, but mean differences between groups were not statistically significant.Summary/Conclusion:Faster and sustained improvement in patients treated with D‐Rd was observed using HRQoL assessments compared with Rd, with similar findings reflected across the pain subscale.

Background. Kidneys from deceased donors with acute kidney injury (AKI) are more likely to be discarded because of concerns for poor outcomes after transplantation. The aim of this study was to determine the long-term outcomes of a large cohort of patients transplanted utilizing kidneys from deceased donors with AKI. Methods. All patients receiving a deceased donor kidney transplant during a recent 10-year period were included. Acute Kidney Injury Network (AKIN) criteria were used to classify the donors. Donor kidneys with >10% cortical necrosis or more than mild chronic changes were discarded. The primary outcome is the combined endpoint of death or graft loss. Results. The cohort included 1313 kidneys from 974 donors, AKIN stage 0 (no AKI) in 319 (24.3%), stage 1 in 370 (28.2%), stage 2 in 177 (13.5), and stage 3 in 447 (34.0%). Estimated 5-year graft survival (95% confidence interval) was 78.5% (72.5-84.5), 77.8% (72.8-82.1), 83.8% (76.8-88.9), and 84.6% (79.5-88.7) for AKIN donor stage 0 to 3, respectively (log-rank P = 0.10). After adjusting for baseline differences, the hazard ratio (95% confidence interval) for the combined endpoint for the AKIN stage 3 group (relative to AKIN 0 group) was 0.70 (0.45-1.10). Delayed graft function occurred in 44.6% and 75.4% of AKIN 2 and 3 groups, as compared to 33.9% and 33.5% in AKIN 0 and 1 ( P < 0.001). Conclusion. We conclude that transplanting selected kidneys from deceased donors with AKI with preimplantation biopsy showing <10% cortical necrosis and no more than mild chronic changes have excellent long-term graft survival.

Abstract Knowledge of individuals’ everyday preferences is a cornerstone of person-centered care (PCC). Initial evidence demonstrates the positive impact of honoring preferences in care for older adults receiving long-term services and supports (LTSS). Yet, the mechanisms through which preference-based care affects individual well-being remain poorly understood. This article proposes a theoretical model of PCC entitled the Preference-Based Model of Care that integrates the Theory of Human Motivation, Self-determination Theory, the Competence-Press Model of person and environment fit, the Living Systems Framework, and the Broaden-and-Build theory of positive emotions to deepen our understanding of the processes through which preference-based care affects well-being among older adults receiving LTSS. The Preference-Based Model of Care illustrates how goal-directed behaviors facilitate need fulfillment through the expression of individual preferences and how these behaviors mediate the relationship between person–environment fit and affect balance within a particular social, cultural, and political context. The Preference-Based Model of Care can advance research on PCC in LTSS and can inform LTSS clinical practice guidelines for older adults, regardless of functional or cognitive capacity.