Toward reducing racialized pain care disparities: Approaching cannabis research and access through the lens of equity and inclusion.

There is growing interest in cannabis use for cancer pain. This commentary aims to discuss the evidence surrounding cannabis use for cancer pain in the context of the long-racialized landscape of cannabis policies and the disparity in pain control among cancer patients holding minoritized racial identities. Much evidence surrounding both the benefits and harms of cannabis use in cancer patients, and all patients in general, is lacking. Although drawing on the research in cancer that is available, it is also important to illustrate the broader context about how cannabis' deep roots in medical, political, and social history impact patient use and health care policies. There are lessons we can learn from the racialized disparities in opioid risk mitigation strategies, so they are not replicated in the settings of cannabis for cancer symptom management. Additionally, the authors intentionally use the term "cannabis" here rather than "marijuana.: In the early 1900s, the lay press and government popularized the use of the word "marijuana" instead of the more common "cannabis" to tie the drug to anti-Mexican prejudice.

Experiences of Aging with Opioid Use Disorder and Comorbidity in Opioid Treatment Programs: A Qualitative Analysis.

BACKGROUND: The number of older adults entering opioid treatment programs (OTPs) to treat opioid use disorder (OUD) is increasing. However, the lived experiences of aging in OTPs have not been examined. OBJECTIVE: To explore the aging experience with OUD and barriers to medical care for older adults who receive care in OTPs. DESIGN: From November 2021 to July 2022, we conducted 1-to-1, semi-structured qualitative interviews in English and Spanish, audio-recorded, transcribed, systematically coded, and analyzed to identify key themes regarding the challenges of aging with OUD and managing chronic diseases. PARTICIPANTS: Thirty-six adults aged ≥ 55 enrolled in OTPs in San Diego, California. APPROACH: A descriptive qualitative approach was used. Major themes and subthemes were identified through thematic analysis until thematic saturation was reached. KEY RESULTS: All participants were on methadone and had a mean age of 63.4 (SD 5.1) years; 11 (30.6%) identified as female, 14 (39%) as Hispanic/Latino, and 11 (36%) as Black, with a mean duration of methadone treatment of 5.6 years. Chronic diseases were common, with 21 (58.3%) reporting hypertension, 9 (25%) reporting untreated hepatitis C, and 32 (88.9%) having ≥ 2 chronic diseases. Three major themes emerged: (1) avoidance of medical care due to multiple intersectional stigmas, including those related to drug use, substance use disorder (SUD) treatment, ageism, and housing insecurity; (2) increasing isolation with aging and loss of family and peer groups; (3) the urgent need for integrating medical and aging-focused care with OUD treatment in the setting of increasing health and functional challenges. CONCLUSIONS: Older adults with OUD reported increasing social isolation and declining health while experiencing multilevel stigma and discrimination. The US healthcare system must transform to deliver age-friendly care that integrates evidence-based geriatric models of care incorporated with substance use disorder treatment and addresses the intersectional stigma this population has experienced in healthcare settings.

Developing a Tanshinone IIA Memetic by Targeting MIOS to Regulate mTORC1 and Autophagy in Glioblastoma.

Tanshinone IIA (T2A) is a bioactive compound that provides promise in the treatment of glioblastoma multiforme (GBM), with a range of molecular mechanisms including the inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) and the induction of autophagy. Recently, T2A has been demonstrated to function through sestrin 2 (SESN) to inhibit mTORC1 activity, but its possible impact on autophagy through this pathway has not been investigated. Here, the model system Dictyostelium discoideum and GBM cell lines were employed to investigate the cellular role of T2A in regulating SESN to inhibit mTORC1 and activate autophagy through a GATOR2 component MIOS. In D. discoideum, T2A treatment induced autophagy and inhibited mTORC1 activity, with both effects lost upon the ablation of SESN (sesn-) or MIOS (mios-). We further investigated the targeting of MIOS to reproduce this effect of T2A, where computational analysis identified 25 novel compounds predicted to strongly bind the human MIOS protein, with one compound (MIOS inhibitor 3; Mi3) reducing cell proliferation in two GBM cells. Furthermore, Mi3 specificity was demonstrated through the loss of potency in the D. discoideum mios- cells regarding cell proliferation and the induction of autophagy. In GBM cells, Mi3 treatment also reduced mTORC1 activity and induced autophagy. Thus, a potential T2A mimetic showing the inhibition of mTORC1 and induction of autophagy in GBM cells was identified.

Nurses in health policy: Lessons learned from one cohort of the American Academy of Nursing Jonas Policy Scholars Program.

Nurses are underrepresented in health policy. The Jonas Policy Scholars Program is a vital and effective program that promotes mentoring, health policy, and engagement among early nurse researchers. The Jonas Policy Scholars Program should continue and be replicated by other organizations. Nurses must serve as health policy leaders within and beyond the field of nursing. Health policy content and immersion should be integrated throughout nursing education.

Expert consensus-based guidance on approaches to opioid management in individuals with advanced cancer-related pain and nonmedical stimulant use.

BACKGROUND: Clinicians treating cancer-related pain with opioids regularly encounter nonmedical stimulant use (i.e., methamphetamine, cocaine), yet there is little evidence-based management guidance. The aim of the study is to identify expert consensus on opioid management strategies for an individual with advanced cancer and cancer-related pain with nonmedical stimulant use according to prognosis. METHODS: The authors conducted two modified Delphi panels with palliative care and addiction experts. In Panel A, the patient's prognosis was weeks to months and in Panel B the prognosis was months to years. Experts reviewed, rated, and commented on the case using a 9-point Likert scale from 1 (very inappropriate) to 9 (very appropriate) and explained their responses. The authors applied the three-step analytical approach outlined in the RAND/UCLA to determine consensus and level of clinical appropriateness of management strategies. To better conceptualize the quantitative results, they thematically analyzed and coded participant comments. RESULTS: Consensus was achieved for all management strategies. The 120 Experts were mostly women (47 [62%]), White (94 [78%]), and physicians (115 [96%]). For a patient with cancer-related and nonmedical stimulant use, regardless of prognosis, it was deemed appropriate to continue opioids, increase monitoring, and avoid opioid tapering. Buprenorphine/naloxone transition was inappropriate for a patient with a short prognosis and of uncertain appropriateness for a patient with a longer prognosis. CONCLUSION: Study findings provide urgently needed consensus-based guidance for clinicians managing cancer-related pain in the context of stimulant use and highlight a critical need to develop management strategies to address stimulant use disorder in people with cancer. PLAIN LANGUAGE SUMMARY: Among palliative care and addiction experts, regardless of prognosis, it was deemed appropriate to continue opioids, increase monitoring, and avoid opioid tapering in the context of cancer-related pain and nonmedical stimulant use. Buprenorphine/naloxone transition as a harm reduction measure was inappropriate for a patient with a short prognosis and of uncertain appropriateness for a patient with a longer prognosis.

Eliminate the buprenorphine DEA X waiver: Justification using a policy analysis approach.

INTRODUCTION: Drug overdoses have reached a historic milestone of over 100,000 deaths in a single year, 75,673 related to opioids. The acceleration in opioid-related deaths coupled with stark health inequities demands a close examination of opioid use disorder (OUD) treatment barriers and swift consideration of policy changes. DESIGN: The aim of this buprenorphine policy analysis is to summarize existing buprenorphine barriers and present policy solutions to improve access and actualize the contributions of Advanced Practice Registered Nurses (APRNs). METHODS: The policy analysis follows five sequential steps: (1) defining the problem, (2) identifying key stakeholders, (3) assessing the landscape of relevant policies, (4) describing viable policy options, and (5) making final recommendations. RESULTS: Although there are laudable efforts to improve buprenorphine access, such as the new buprenorphine guidelines issued in April 2021, without larger-scale changes to federal, state, and scope of practice laws, overdose rates will continue to rise. We recommend a multipronged policy approach to improve buprenorphine treatment access, including eliminating the DEA X waiver, improving OUD education, and adopting full practice authority for APRNs in all states. CONCLUSION: Incremental change is no longer sufficient to address opioid overdose deaths. Bolder and coordinated policy action is possible and necessary to empower the full clinical workforce to apply evidence-based life-saving treatments for OUD. The critical contributions of nurses in advancing equitable access to OUD care are emphasized in the National Academy of Medicine's Report, Future of Nursing: Charting a Path to Achieve Health Equity. Nurses are named as instrumental in improving buprenorphine access. Policy changes that acknowledge and build on evidence-based treatment expansion strategies are sorely needed. CLINICAL RELEVANCE: One of the most robust tools to combat opioid overdose deaths is buprenorphine, a partial opioid agonist, and gold standard medication treatment for OUD, but only 5% of the prescribing workforce possess the required Drug Enforcement Agency (DEA) X waiver. A growing body of evidence demonstrates that Advanced Practice Registered Nurses are accelerating the growth in waiver update and buprenorphine use, despite the considerable barriers and limitations described in this policy analysis.

Approaches to opioid prescribing in cancer survivors: Lessons learned from the general literature.

LAY SUMMARY: Guidance on how to approach opioid decisions for people beyond active cancer treatment is lacking. This editorial discusses strategies from the general literature that can be thoughtfully tailored to cancer survivors to provide patient-centered pain and opioid care.

A qualitative analysis of feelings and experiences associated with perinatal distress during the COVID-19 pandemic.

BACKGROUND: Rates of perinatal mental health difficulties (experienced during pregnancy and the 12-months postpartum) increased worldwide during the COVID-19 pandemic. In the UK, anxiety and depression were estimated to affect more than half of perinatal women during the first national lockdown. However, little is known about women's qualitative experiences of distress. This study aimed to extend published quantitative findings resulting from the same data set (Harrison et al., Women Birth xxxx, 2021;  Harrison et al., J Reprod Infant Psychol 1-16, 2021) to qualitatively explore: 1) the feelings and symptoms associated with maternal perinatal distress during the COVID-19 pandemic; and 2) the associated sources of distress. METHODS: As part of an online survey during May 2020, 424 perinatal women responded to an open-ended question regarding a recent experience of distress. Qualitative data were analysed using an initial content analysis, followed by an inductive thematic analysis adopting a realist approach. Data were explored in the context of self-reported perinatal anxiety and depression symptoms. RESULTS: Initial content analysis of the data identified twelve distinct categories depicting participants' feelings and symptoms associated with psychological distress. Despite the high rates of probable depression in the sample, women's descriptions were more indicative of anxiety and general distress, than of symptoms traditionally related to depression. In terms of the associated psychosocial stressors, a thematic analysis identified five themes: Family wellbeing; Lack of support; Mothering challenges; Loss of control due to COVID-19; and Work and finances. Unsurprisingly given the context, isolation was a common challenge. Additionally, psychological conflict between maternal expectations and the reality of pregnancy and motherhood, loss of autonomy and control, and fears surrounding family health, safety, and wellbeing underlay many of the themes. CONCLUSIONS: This study presents an array of feelings and symptoms expressed by perinatal mothers which may be useful to consider in relation to perinatal wellbeing. Furthermore, our data highlights several common sources of distress, including multiple COVID-19 specific factors. However, many were related to more general perinatal/maternal experiences. Our findings also point to considerations that may be useful in alleviating distress in pregnancy and early motherhood, including social support, realistic perinatal/maternal expectations, and support for those with perceived perinatal trauma.

Support from friends moderates the relationship between repetitive negative thinking and postnatal wellbeing during COVID-19.

BACKGROUND: Increasing evidence has linked repetitive negative thinking (RNT) to postnatal depression and anxiety, yet the factors moderating this relationship have been minimally investigated. During the COVID-19 pandemic of 2020, social restrictions imposed to reduce viral transmission limited access to social support, which is critical to postnatal psychological wellbeing - potentially intensifying RNT. OBJECTIVE: We examined whether perceived social support (from friends, family, and a significant other) played a moderating role in the relationship between RNT and maternal postnatal anxiety and depressive symptoms. METHODS: A sample of women (N = 251) who had given birth in the preceding 12 months completed an online battery of standardised measures during the COVID-19 'lockdown' of May 2020. RESULTS: As predicted, social support moderated the relationship between RNT and depression such that the association between RNT and depression was stronger for women who reported lower levels of social support. Interestingly, this finding emerged for social support from friends only; for support from family and significant other, social support did not play a moderating role. Further, and unexpectedly, overall social support did not moderate the relationship between RNT and postnatal anxiety, however, social support from friends was a significant moderator. CONCLUSIONS: High levels of perceived social support from friends (but not family or significant others) buffered the effects of RNT on depression and anxiety during the postpartum period. Strategies to bolster peer social support may be a valuable inclusion in interventions to prevent and treat postnatal depression and anxiety.

Representing young men's experience of anorexia nervosa: a French-language case study.

This article analyses two young adult (YA) novels about young men's experience of anorexia nervosa (AN), within the dual contexts of medical humanities research into literary depictions of illness, and the broader field of YA literature about AN. While emphasising the importance of diverse literary narratives in order to raise awareness of the prevalence of AN in men and boys, and to contribute to the reduction of stigma, it also considers current research into the potentially harmful triggering effects of AN literature on vulnerable readers. It identifies Anne Percin's Point de côté (Side Stitch) (2006) and Simon Boulerice's Jeanne Moreau a le sourire à l'envers (Jeanne Moreau Has An Upside-Down Smile) (2013) as examples of good practice in AN literature, due to their thematic focus on male experience, and because they employ narrative strategies that disrupt reader identification with the anorexic character, and avoid focusing directly on potentially triggering descriptions of anorexic ideas and behaviour. They also contribute to diversifying the portrayal of AN via non-judgmental portrayal of lesbian, gay, bisexual, and transgender (LGBT) themes, a topic absent from equivalent YA novels currently available in English. The article further argues that literature-including fiction-contributes to the overall social and cultural discourse surrounding specific illnesses and is likely to affect patients' real-world experiences, but that it is a specific kind of discourse in its own right, which demands to be read with the appropriate tools. Its detailed analysis of narrative voice alongside thematic content demonstrates how specific approaches from the field of literary studies may complement empirical research into literature and its place within mental health discourse.

CD154-expressing CMV-specific T cells associate with freedom from DNAemia and may be protective in seronegative recipients after liver or intestine transplantation.

Cell-mediated immunity to CMV, if known, could improve antiviral drug therapy in at-risk children and young adults with LT and IT. Host immunity has been measured with CMV-specific T cells, which express IFNγ, but not those which express CD154, a possible substitute for IFNγ. CMV-specific CD154+ T cells and their subsets were measured with flow cytometry after stimulating PBL from recipient blood samples with an overlapping peptide mix of CMV-pp65 antigen for up to 6 hours. CMV-specific CD154+ T cells co-expressed IFNγ in PBL from three healthy adults and averaged 3.8% (95% CI 3.2%-4.4%) in 40 healthy adults. CMV-specific T cells were significantly lower in 19 CMV DNAemic LT or IT recipients, compared with 126 non-DNAemic recipients, 1.3% (95% CI 0.8-1.7) vs 4.1 (95% CI 3.6-4.6, P < .001). All T-cell subsets demonstrated similar between-group differences. In logistic regression analysis of 46 training set samples, 12 with DNAemia, all obtained between days 0 and 60 from transplant, CMV-specific T-cell frequencies ≥1.7% predicted freedom from DNAemia with NPV of 93%. Sensitivity, specificity, and PPV were 83%, 74%, and 53%, respectively. Test performance was replicated in 99 validation samples. In 32 of 46 training set samples, all from seronegative recipients, one of 19 recipients with CMV-specific T-cell frequencies ≥1.7% experienced DNAemia, compared with 8 of 13 recipients with frequencies <1.7% (P = .001). CMV-specific CD154+ T cells are associated with freedom from DNAemia after LT and IT. Among seronegative recipients, CMV-specific T cells may protect against the development of CMV DNAemia.

Is this what a lesbian looks like? Lesbian fashion and the fashionable lesbian in the United States press, 1960s to 2010s.

We explored articulations of lesbian styles, fashions, and ways of dressing in mainstream fashion and media outlets within the United States during the twentieth and twenty-first centuries. Based upon our findings, we propose that there was trending ambivalence and multiple assemblages across space and time where the mainstream media did not necessarily perpetuate a single stereotypical or essentialist way of conceptualizing fashionable lesbians or lesbian fashions. However, we also noted across time a divide between representations of celebrity lesbians and the contemporary lived experience of ordinary lesbians. Though the press acknowledged this divide on occasion, they also established, circulated, and reinforced this difference. According to the press, while lesbians have been 'chic' since the 1990s-whether they embraced a butch or femme esthetic-the best way to be lesbian was to be rich, white, and fashionably dressed.

Donor mucosal immunocytes perpetuate refractory GVHD after intestinal transplantation without engrafting in recipient bone marrow: Case report and review of the literature.

GVHD as a complication of SOT presents both a diagnostic and therapeutic challenge. Typically affecting the skin, gastrointestinal tract, and liver, GVHD occurs when donor lymphocytes engrafted in recipient tissues are activated by host antigen-presenting cells resulting in cytokine release and donor cell-mediated cytotoxicity to host tissue. Here, we describe a 5-year-old girl who developed fatal, refractory GVHD after isolated intestinal transplantation when recipient immune cells failed to repopulate the allograft in the setting of CMV viremia. Persistence of the donor immune cells in the allograft mucosa, rather than engraftment in the recipient bone marrow, likely perpetuated this refractory GVHD. Early diagnosis and intervention are critical to reduce morbidity and mortality. Thus, periodic monitoring of peripheral blood and allograft mucosal chimerism with sensitive detection methods may allow early detection and potentially curative enterectomy in similar cases of refractory GVHD.

Evolution of comprehensive cancer control plans and partnerships.

This article explores how comprehensive cancer control plans and partnerships have evolved, over the past 20 years, to meet the ever-changing environment of cancer prevention and control. This evolution has resulted in plans that take a more focused approach in identifying cancer-related priorities and coalitions with structures that have been redesigned to better engage a more wide-ranging group of partners to help address the priorities. Presented in this paper are examples from three states that describe how recognizing the need for change has led to improved processes in updating a cancer plan; strengthened and more diverse partnerships; and coalition sustainment by leveraging and maximizing resources.

Prevalence of Active Long-term Problems in Patients With Anorectal Malformations: A Systematic Review.

BACKGROUND: Anorectal malformations are a spectrum of congenital anomalies of the rectum with high infantile survival rates and variable outcomes. Long-term (>10 years old) active problems associated with this condition have been poorly investigated. OBJECTIVE: The purpose of this review was to systematically define the prevalence of the most common active long-term problems in patients with a history of anorectal malformation repair. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Library were searched electronically using the OVID search platform. STUDY SELECTION: Original articles from August 1, 1994, to October 20, 2015, that included outcome data for patients aged ≥10 years with anorectal malformation. Cloaca was excluded from the study. INTERVENTIONS: Prevalence estimates of anorectal malformations were obtained from published articles. CIs were ascertained in the logit scale after transforming prevalence into log odds and were then transformed into the original scale. The same method was used for subgroup analysis investigating high and low anorectal malformations. MAIN OUTCOME MEASURES: The overall prevalences of fecal, urinary, and sexual dysfunction were analyzed. RESULTS: Twelve studies including 455 patients with a history of anorectal malformation repair were included for analysis. The range of reported prevalence of long-term active problems was as follows: fecal incontinence, 16.7% to 76.7%; chronic constipation, 22.2% to 86.7%; urinary incontinence, 1.7% to 30.5%; ejaculatory dysfunction, 15.6% to 41.2%; and erectile dysfunction, 5.6% to 11.8%. LIMITATIONS: The study was limited by its retrospective, small size; multiple complex associated anomalies often not reported; and heterogeneous composition of patients with limited stratification analysis. CONCLUSIONS: There is an overall high prevalence of active long-term issues in adolescents and young adults with anorectal malformations. Additional multicenter research is needed to define characteristics and predictors of long-term outcome, to implement effective follow-up, and to transition to adult health care.

Evaluation of a novel continuous glucose monitoring guided system for adjustment of insulin dosing - PumpTune: a randomized controlled trial.

OBJECTIVE: Retrospective continuous glucose monitoring (CGM) can guide insulin pump adjustments, however, interpretation of data and recommending new pump settings is complex and subjective. We aimed to compare the safety and glycaemic profiles of children after their diabetologist or a novel algorithm (PumpTune) adjusted their insulin pump settings. RESEARCH DESIGN AND METHODS: In a randomized cross-over trial of 22 patients aged 6-14 yr with type 1 diabetes with mean Hba1c 7.4% (57 mmol/mol) using CSII, CGM was used over two periods each of 6.5 d to assess percentage time glucose remained within, above and below 3.9-10.0 mmol/L. Before the start of one period pump settings were adjusted by the patient's diabetologist, and before the other insulin pump settings were adjusted by PumpTune. RESULTS: A total of 63.4% of the sensor glucose levels were within target range with PumpTune settings and 57.4% were within range with the clinician settings (p = 0.016). The time spent above target range with PumpTune was 26.9% and with clinician settings was 33.5% (p = 0.021). The time spent below target range with PumpTune was 9.7% and with clinician settings was 9.2% (p = 0.77). The mean number of times when a sensor glucose level <2.75 mmol/L was recorded with PumpTune settings was 2.9 compared with 3.7 with clinician settings (p = 0.39). There were no serious adverse outcomes and no difference in parent-assessed satisfaction. CONCLUSIONS: Automated insulin pump adjustment with PumpTune is feasible and warrants testing in a larger more varied population over a longer time. In this well-controlled group of children, PumpTune achieved a more favorable glucose profile.

Exome sequencing reveals frequent deleterious germline variants in cancer susceptibility genes in women with invasive breast cancer undergoing neoadjuvant chemotherapy.

When sequencing blood and tumor samples to identify targetable somatic variants for cancer therapy, clinically relevant germline variants may be uncovered. We evaluated the prevalence of deleterious germline variants in cancer susceptibility genes in women with breast cancer referred for neoadjuvant chemotherapy and returned clinically actionable results to patients. Exome sequencing was performed on blood samples from women with invasive breast cancer referred for neoadjuvant chemotherapy. Germline variants within 142 hereditary cancer susceptibility genes were filtered and reviewed for pathogenicity. Return of results was offered to patients with deleterious variants in actionable genes if they were not aware of their result through clinical testing. 124 patients were enrolled (median age 51) with the following subtypes: triple negative (n = 43, 34.7%), HER2+ (n = 37, 29.8%), luminal B (n = 31, 25%), and luminal A (n = 13, 10.5%). Twenty-eight deleterious variants were identified in 26/124 (21.0%) patients in the following genes: ATM (n = 3), BLM (n = 1), BRCA1 (n = 4), BRCA2 (n = 8), CHEK2 (n = 2), FANCA (n = 1), FANCI (n = 1), FANCL (n = 1), FANCM (n = 1), FH (n = 1), MLH3 (n = 1), MUTYH (n = 2), PALB2 (n = 1), and WRN (n = 1). 121/124 (97.6%) patients consented to return of research results. Thirteen (10.5%) had actionable variants, including four that were returned to patients and led to changes in medical management. Deleterious variants in cancer susceptibility genes are highly prevalent in patients with invasive breast cancer referred for neoadjuvant chemotherapy undergoing exome sequencing. Detection of these variants impacts medical management.