Single and Combined Effects of Cannabigerol (CBG) and Cannabidiol (CBD) in Mouse Models of Oxaliplatin-Associated Mechanical Sensitivity, Opioid Antinociception, and Naloxone-Precipitated Opioid Withdrawal.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most prevalent and dose-limiting complications in chemotherapy patients, with estimates of at least 30% of patients experiencing persistent neuropathy for months or years after treatment cessation. An emerging potential intervention for the treatment of CIPN is cannabinoid-based pharmacotherapies. We have previously demonstrated that treatment with the psychoactive CB1/CB2 cannabinoid receptor agonist Δ9-tetrahydrocannabinol (Δ9-THC) or the non-psychoactive, minor phytocannabinoid cannabidiol (CBD) can attenuate paclitaxel-induced mechanical sensitivity in a mouse model of CIPN. We then showed that the two compounds acted synergically when co-administered in the model, giving credence to the so-called entourage effect. We and others have also demonstrated that CBD can attenuate several opioid-associated behaviors. Most recently, it was reported that another minor cannabinoid, cannabigerol (CBG), attenuated cisplatin-associated mechanical sensitivity in mice. Therefore, the goals of the present set of experiments were to determine the single and combined effects of cannabigerol (CBG) and cannabidiol (CBD) in oxaliplatin-associated mechanical sensitivity, naloxone-precipitated morphine withdrawal, and acute morphine antinociception in male C57BL/6 mice. Results demonstrated that CBG reversed oxaliplatin-associated mechanical sensitivity only under select dosing conditions, and interactive effects with CBD were sub-additive or synergistic depending upon dosing conditions too. Pretreatment with a selective α2-adrenergic, CB1, or CB2 receptor selective antagonist significantly attenuated the effect of CBG. CBG and CBD decreased naloxone-precipitated jumping behavior alone and acted synergistically in combination, while CBG attenuated the acute antinociceptive effects of morphine and CBD. Taken together, CBG may have therapeutic effects like CBD as demonstrated in rodent models, and its interactive effects with opioids or other phytocannabinoids should continue to be characterized.

Clinical Outcomes at 8-16 Weeks After Upadacitinib Initiation for Acute Severe Ulcerative Colitis: A Case Series in the United States.

In 9 patients hospitalized for acute severe ulcerative colitis, 8 were successfully discharged without the need for colectomy. Six of 7 patients with sufficient follow-up achieved steroid-free clinical remission at 8 to 16 weeks, and 1 of 2 patients achieved endoscopic response.

On the need for empathy in the acute hospital setting.

This article reviews the need for empathy, and what happens in its absence in an acute hospital setting, using the example of a homeless man in an emergency department. Three simple but meaningful changes that all healthcare practitioners can make are recommended to promote empathy.

Grouping groupers in the Mediterranean: Ecological baselines revealed by ancient proteins.

Marine historical ecology provides a means to establish baselines to inform current fisheries management. Groupers (Epinephelidae) are key species for fisheries in the Mediterranean, which have been heavily overfished. Species abundance and distribution prior to the 20th century in the Mediterranean remains poorly known. To reconstruct the past biogeography of Mediterranean groupers, we investigated whether Zooarchaeology by Mass Spectrometry (ZooMS) can be used for identifying intra-genus grouper bones to species level. We discovered 22 novel, species-specific ZooMS biomarkers for groupers. Applying these biomarkers to Kinet Höyük, a Mediterranean archaeological site, demonstrated 4000 years of regional Epinephelus aeneus dominance and resiliency through millennia of fishing pressures, habitat degradation and climatic changes. Combining ZooMS identifications with catch size reconstructions revealed the Epinephelus aeneus capacity for growing 30 cm larger than hitherto documented, revising the maximum Total Length from 120 to 150 cm. Our results provide ecological baselines for a key Mediterranean fishery which could be leveraged to define and assess conservation targets.

Factors prompting and deterring suicides on the roads.

BACKGROUND: In addition to the devastating impact on the individual and their families, suicides on the roads can cause distress and harm to other people who might be involved in a collision or witness an attempt. Despite an increased focus on the characteristics and circumstances of road-related suicides, little is known about why people choose to end their lives in this way. AIMS: The aim of the current study was to investigate the factors prompting and deterring the decision to attempt suicide on the roads. METHOD: We conducted a secondary analysis of survey data, as well as seven in-depth qualitative interviews. Participants had lived experience of suicidal ideation or behaviour at a bridge or road location. We also carried out an online ethnography to explore interactions in different online communities relating to this method of suicide. RESULTS: Participants perceived a road-related suicide to be quick, lethal, easy and accessible and to have the potential to appear accidental. The proportion of participants who described their thoughts and attempts as impulsive appeared to be higher than had been observed with other method choices. The potential impact on other people was a strongly dissuasive factor. CONCLUSIONS: Measures designed to prevent access to potentially lethal sites may be particularly important, given that many participants described their thoughts and behaviour as impulsive. In addition, fostering a culture of care and consideration for other road users may help to dissuade people from taking action on the roads.

Why might medical student empathy change throughout medical school? a systematic review and thematic synthesis of qualitative studies.

BACKGROUND: Several studies suggest that medical student empathy declines throughout medical school. However, no studies have synthesised the evidence regarding why empathy declines. OBJECTIVE: To conduct a systematic review and thematic synthesis of qualitative studies investigating why student empathy may change throughout medical school. METHODS: We included any qualitative study that investigated why empathy might change during medical school. We searched the Medline, Scopus, CINAHL, ERIC, and APA PsycInfo databases for relevant studies. All databases were searched from their inception to 18 July 2022. We also searched the reference lists of the included studies and contacted experts to identify additional studies. We used the Joanna Briggs Institute tool to evaluate the risk of bias in the included studies. Overall confidence in our results was assessed using the Confidence in the Evidence from Reviews of Qualitative research (CERQual) approach. We used thematic methods to synthesise our findings. RESULTS: Our searches yielded 2523 records, and 16 studies involving a total of 771 students were eligible for analysis. Most studies (n = 11) were from Europe or North America. The descriptive themes and sub-themes were identified for each study. Increased complexity in patients and their diseases, together with the 'hidden curriculum' (including a stressful workload, prioritisation of biomedical knowledge, and (sometimes) poor role models), led to student adaptations, such as cynicism and desensitisation. Students' prior lives and professional experiences appeared to exacerbate the decline in empathy. However, there were bias concerns for most of the included studies. DISCUSSION: Many of the included studies included were small, and some did not include demographic participant data. Given the likely benefits of providing empathic care for patients and practitioners, medical education interventions should focus on developing an 'empathic hidden curriculum' that mitigates the decline in medical student empathy. TRIAL REGISTRATION: A protocol for this systematic review was submitted for registration with the International Prospective Register of Systematic Reviews (PROSPERO) on 28 July 2022 (registration number CRD42022347856).

A survey of clinical empathy training at UK medical schools.

BACKGROUND: The benefits of enhancing practitioner empathy include better patient outcomes and improved job satisfaction for practitioners. Evidence suggests empathy can be taught and empathy is listed as an outcome for graduates in the General Medical Council requirements. Despite this, empathy training is not mandatory on medical school curricula and the extent to which medical students are given empathy-specific training is unknown. AIM: To conduct a survey of empathy training currently offered to medical students in UK medical schools. METHODS: An invitation to participate in an online survey was sent to all UK medical schools (n = 40). The survey was developed through a consultancy and pilot process to ensure validity and reliability. Questions explored what empathy-focused training is offered, and asked educators whether or not they believed that current provision of empathy training is sufficient. In parallel, medical school websites were searched to identify what information regarding empathy-focused training is described as being part of the degree course. Descriptive statistics were used to describe empathy training delivery from the results of the online materials survey and closed survey questions. Thematic analysis was used to explore free text comments. RESULTS: Response rate was 70% (28/40), with 28 medical schools included in the analysis. Twenty-six schools reported that their undergraduate curriculum included some form of empathy-focused training with variation in what, when and how this is delivered. Thematic analysis revealed two overarching themes with associated sub-themes: (i) empathy-focused training and development (considering where, when and how empathy training should be integrated); (ii) challenges presented by including empathy on the curriculum (considering the system, students and faculty). All schools agreed empathy training should be on the undergraduate curriculum. CONCLUSION: This is the first nationwide survey of empathy-focused training at UK medical schools. While some form of empathy-focused training appears to be provided on the undergraduate curriculum at most UK medical schools, empathy is rarely specifically assessed. Most medical educators do not feel their school does enough to promote empathy and the majority would like to offer more.

Why might medical student empathy change throughout medical school? Protocol for a systematic review and thematic synthesis of qualitative studies.

INTRODUCTION: Several studies suggest that medical student empathy declines throughout medical school. However, no studies have systematically investigated why. The objective of our proposed review is to conduct a systematic review and thematic synthesis of qualitative studies investigating the reasons empathy may change throughout medical school. METHODS AND ANALYSIS: This systematic review protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We have searched MEDLINE, Scopus, CINAHL, ERIC and APA PsycINFO for relevant studies. We will also search reference lists of included studies and contact experts to identify additional studies. We will include any qualitative study investigating the reasons why empathy changes throughout medical school. We will use the Joanna Briggs Institute tool to evaluate the risk of bias in the included studies. We will use thematic analysis to synthesise our results. For all included studies, we will summarise the main characteristics including the number of participants, medical school year, country and gender. In our discussion, we will summarise the limitations of the evidence (including the risk of bias and inconsistency), and provide a general interpretation of the results and important implications. ETHICS AND DISSEMINATION: This study will not require ethical approval since no original data will be collected. The results of this review will be published through peer-reviewed publications and conference presentations. Additionally, this review will inform changes to the enhanced empathy curriculum at the Leicester Medical School.

Experiences of empathy training in healthcare: A systematic review of qualitative studies.

OBJECTIVE: To synthesise qualitative studies reporting student, practitioner, or patient experiences of empathy-training in healthcare. METHODS: We included qualitative studies exploring (i) student or practitioner experiences of empathy training, or (ii) patient experiences of being treated by someone who has undergone empathy training. We used the Critical Appraisal Skills Programme (CASP) tool to assess study quality. Thematic synthesis was used to integrate findings from studies and to generate new insights. RESULTS: Our search yielded 2768 citations, of which 23 (1487 participants) met inclusion criteria. Two clusters of themes were identified from included studies. Firstly, themes related to practitioner/trainee professionalism and wellbeing, where the main finding was that participants experienced benefit from therapeutic empathy training. Secondly, themes related to the understanding and treatment of patients, where the main finding was practitioners' deeper recognition of the positive impact of empathic care. CONCLUSIONS: This review found that taking part in empathy-focused training can benefit practitioner/student personal growth and professional development, and benefits patient care. This review is limited by the difficulty in defining empathy and heterogeneity amongst included studies. PRACTICE IMPLICATIONS: These results support a rationale for empathy training and the development of a framework to ensure training is having the desired effect.

Recruiting and retaining participants in three randomised controlled trials of psychological interventions conducted on acute psychiatric wards: top ten tips for success.

BACKGROUND: It is essential to conduct randomised controlled trials of psychological interventions on acute psychiatric wards to build a robust evidence base for clinical practice. AIMS: This paper aims to share strategies from three different in-patient trials that successfully recruited and retained participants, to disseminate good practice for the conduct of future trials in this challenging and complex clinical setting. METHOD: We present strategies from three in-patient trials of psychological interventions: TULIPS (Talk, Understand, Listen for Inpatient Settings), amBITION (Brief Talking Therapies on Wards) and INSITE (Inpatient Suicide Intervention and Therapy Evaluation). All studies recruited participants from acute in-patient wards, initiated therapy within the in-patient setting and followed up on participants post-discharge. RESULTS: We summarise our recommendations for good practice in the form of ten top tips for success, based on our collective experience of conducting trials on psychiatric wards. Key themes relate to the importance of relationships between the research team and clinical staff; good stakeholder involvement and getting early buy-in from the team; and adapting to the particular demands of the clinical setting. CONCLUSIONS: Sharing good practice recommendations can help reduce research waste arising from poor recruitment and/or retention in future in-patient clinical trials.

Infliximab Is Not Associated With a General Long-Term Weight Gain in Patients With Inflammatory Bowel Disease: A Nationwide Study.

INTRODUCTION: Patients with Crohn's disease (CD) and ulcerative colitis (UC) may lose weight during periods of active disease and may gain weight when inflammation heals. Studies have hypothesized an association between antitumor necrosis factor-alpha (anti-TNF-α) and unintended weight gain during maintenance therapy, and this association has not been previously clarified. METHODS: In a nationwide observational study based on Danish national health registries, we included patients who initiated therapy with infliximab and followed changes in weight during induction therapy (0-90 days) and maintenance therapy (91-270 days). The association between the use of infliximab and weight gain was analyzed by a multilevel mixed-effects linear regression model. RESULTS: Among 851 patients with CD and UC who initiated infliximab therapy, long-term weight gain was not observed during maintenance therapy in most of the patients. Women with CD who were underweight at the initiation of therapy had an average weight gain of 7.5 kg. Men and women with CD and UC with normal or increased body mass index had an average weight gain of <2 kg during maintenance therapy. Underweight men with CD and UC gained 2.9 kg (95% confidence interval 2.1-3.6) and 2.9 kg (95% confidence interval 1.9-3.9), respectively, in the first 90 days, although neither group had statistically significant weight gain in the maintenance period. Less than 3% of the patients had weight gain greater than 10% of their baseline body weight during the study period. DISCUSSION: Weight gain among patients treated with anti-TNF-α therapies is unlikely to be due to an effect from anti-TNF-α therapy.

A cluster randomised controlled trial of a ward-based intervention to improve access to psychologically-informed care and psychological therapy for mental health in-patients.

BACKGROUND: There is good evidence that psychological interventions improve patient well-being and independent living, but patients on acute mental health wards often do not have access to evidence-based psychological therapies which are strongly advised by NICE guidance for severe mental health problems. The overall aim of this programme of work is to increase patient access to psychological therapies on acute mental health inpatient wards. Stage one of the programme (which is complete) aimed to identify barriers and facilitators to delivering therapy in these settings through a large qualitative study. The key output of stage one was an intervention protocol that is designed to be delivered on acute wards to increase patient access to psychologically-informed care and therapy. Stage two of the programme aims to test the effects of the intervention on patient wellbeing and serious incidents on the ward (primary outcomes), patient social functioning and symptoms, staff burnout, ward atmosphere from staff and patient perspectives and cost effectiveness of the intervention (secondary outcomes). METHODS: The study is a single blind, pragmatic, cluster randomised controlled trial and will recruit thirty-four wards across England that will be randomised to receive the new intervention plus treatment as usual, or treatment as usual only. Primary and secondary outcomes will be assessed at baseline and 6-month and 9-month follow-ups, with serious incidents on the ward collected at an additional 3-month follow-up. DISCUSSION: The key output will be a potentially effective and cost-effective ward-based psychological intervention that increases patient access to psychological therapy in inpatient settings, is feasible to deliver in inpatient settings and is acceptable to patients. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03950388. Registered 15th May 2019. https://clinicaltrials.gov/ct2/show/NCT03950388.

Representing suicide: Giving voice to a desire to die?

Drawing on interview and online ethnographic data from a study of suicide on the railways, this paper describes the ways in which many of the concepts, assumptions and practices of mainstream suicide prevention are challenged in the accounts of those who are planning, or have enacted, a suicide attempt. We reflect on the ethical dilemmas which can arise for researchers (and practitioners) when lived experience accounts diverge - theoretically, morally and in terms of practical implications - from present-day expert ones. In online, 'pro-choice' suicide discussions, people describe beliefs, attitudes, ways of thinking and acting which stand in contrast to existing professional and clinical descriptions of suicide and suicidal behaviour. Most obviously, there is often a rejection of 'pro-life' positions, which are framed as ideological, oppressive and naïve. For researchers engaging in online ethnography of 'pro-choice' spaces, dilemmas can arise in relation to the representation of perspectives which fundamentally challenge not only prevailing norms within suicide research and prevention practice but socio-cultural norms more widely. Similar issues can arise when considering how best to represent research participants when their accounts diverge from accepted 'expert' knowledge and beliefs. In-depth qualitative interviews with those who have thought about or attempted to take their own life indicate that existing theories and models of suicide which start from assumptions of deficit and pathology underestimate the extent to which suicide, as the end result of an often-complex series of actions, requires a person to engage in logistical processes of planning, decision-making, imagination and adaptation. The accounts described here, gathered using two different methodological approaches, highlight the ethical issues which can surface when there are competing claims to (expert) knowledge, as well as differences in beliefs, attitudes and moral stance towards life and death. We argue that researchers need to reflect on their own ethical-moral position in relation to suicide, and on the practical consequences of their privileging of some voices at the expense of other, less well represented, ones.

Lymphoma in Pediatric-Onset Inflammatory Bowel Disease Treated with Infliximab Monotherapy: A Case Series.

BACKGROUND: Inflammatory bowel diseases (IBD) are often treated with anti-tumor necrosis factor alpha (anti-TNFα) medications. Concomitant treatment of IBD with anti-TNFα agents and immunomodulators appears to be associated with an increased risk for lymphoma. METHODS: Patients who developed lymphoma while on monotherapy with an anti-TNFα agent were identified at three centers. Institutional Review Board approval was obtained. RESULTS: Five adolescents and young adult patients with pediatric-onset IBD who were treated with infliximab (IFX) without exposure to thiopurines were subsequently diagnosed with lymphoma. Three of the five patients had bone involvement at presentation. Epstein-Barr virus was positive in 2 cases. Median time from diagnosis of IBD and exposure to IFX prior to diagnosis of lymphoma was 5 and 4.3 years, respectively. CONCLUSIONS: This case series reports long-term follow-up for young patients with IBD who were treated with IFX monotherapy and developed lymphoma. Three of the five patients had bone involvement. In general, the risk of lymphoma following exposure to anti-TNFα medications alone remains low, but the incidence of primary bone lymphomas in IBD has not been reported. Studies examining longer exposure times may be needed to determine the true lymphoma risk in patients treated with IFX monotherapy.