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? 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).

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.

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.

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.

COVID-19 Vaccination Intent and Perceptions Among Patients With Inflammatory Bowel Diseases.

Patients with inflammatory bowel disease (IBD) develop coronavirus disease 2019 (COVID-19) at similar rates as the general population, and there was initial concern regarding potential for severe illness.1-4 Vaccinations were authorized for emergency use in the United States in December 2020 and aim to halt the spread of COVID-19. However, there are concerns that people will be hesitant to receive the vaccine for a variety of reasons including insufficient data in certain populations including those with IBD. We surveyed patients with IBD to identify potential concerns regarding COVID-19 vaccination.

Creation of a Case-Finding Definition for Identifying Patients With Acute Pouchitis in Administrative Claims Data.

Acute pouchitis is the most common complication after a restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, affecting 40% of patients within the first year after surgery.1 Although up to 80% of patients can develop pouchitis symptoms,2,3 substantial gaps remain in our understanding of the epidemiology and burden of pouchitis. Administrative claims have been used to advance the knowledge of other areas of inflammatory bowel disease4-6; however, a prerequisite to conducting such studies in pouchitis is a valid, reliable case-finding algorithm. Given concerns that the International Classification of Diseases (ICD) code for pouchitis may not be reliably used by clinicians (resulting in a low sensitivity), the objectives of the study were to (1) develop a series of case-finding definitions for acute pouchitis and (2) compare the performance of these case-finding definitions to that of a single ICD code for pouchitis.

A qualitative exploration of the lived experience of GP trainees failing to progress in training.

Challenges facing general practice are multiple and extreme. Amongst them is the increasing difficulty of recruiting and retaining General Practitioners (GPs). GPs cite heavy workload, work-related stress, little family time and psychological ill-health as factors influencing their decisions to leave or reduce working hours. Analysis of the literature suggests that these factors, amongst others, are present in GP training and trainees have similar experiences. An in-depth understanding of the challenges trainees in difficulty face is lacking.Our research aim was to better understand the factors that trainees perceive contribute to their failure to progress in training. A qualitative approach was adopted using semi-structured interviews with GP trainees identified as failing to progress satisfactorily or failing the MRCGP examinations. Interviews were audio-recorded and transcribed. Thematic analysis was used to understand the unique experiences of GP trainees and find common themes.Twenty-three interview transcripts were analysed. Emergent themes were presented using a framework of three distinct categories to aid data organisation and allocating themes and sub-themes: professional factors, personal factors, and social factors. Difficulties with managing work-load, poor motivation, lack of family time and psychological ill-health were significant themes for many. This study supports the evidence that difficulties facing GPs take root in training. Failure to fully understand trainees' journeys and associated challenges reduces opportunities to provide bespoke packages of care and remediation that fully address their needs.

#Online harms or benefits? An ethnographic analysis of the positives and negatives of peer-support around self-harm on social media.

BACKGROUND: There is emerging evidence of the potentially detrimental impact of social media on young people's mental health. Against this background, online self-harm content has been a recent focus of concern across academia, policy and the media. It has been argued to encourage or even cause acts such as self-cutting through mechanisms of contagion. However, little is known about why a young person might engage with such content or about its impact on behaviour or well-being. METHODS: Online ethnographic observation of interactions around self-harm on Twitter, Reddit and Instagram: collection and analysis of 10,169 original posts and 36,934 comments, both written and pictorial, at two time-points in 2018 and 2019. Ten in-depth semi-structured interviews exploring engagements with self-harm content on social media. RESULTS: Our data show that peer support is the central component of online interactions around self-harm. Young people accessing such content are likely to already be self-harming; they may turn to social media to understand, and seek help for, their actions and feelings in a context of offline stigma and service support gaps. This paper engages with the mechanisms, complexities and impact of this peer-support, reflecting on the benefits and dangers to caring for oneself and others through social media. CONCLUSIONS: Self-harm content is a fraught issue at the centre of current debates around risks and opportunities for child and adolescent mental health in the digital age. Whilst the importance of supporting young people's online safety is clear, moves to eradicate self-harm content must be undertaken with caution so as not to cause unintentional harm. Our research highlights a need to think beyond a model of contagion, instead attending to other mechanisms of harm and benefit. In so doing, it challenges prevailing attitudes towards online communication about self-harm and accepted approaches to managing this.

Terlipressin versus other vasoactive drugs for hepatorenal syndrome.

BACKGROUND: Hepatorenal syndrome is defined as severe renal failure occurring in people with cirrhosis and ascites. Systematic reviews of randomised clinical trials found that, compared with placebo, terlipressin may reduce mortality and improve renal function in people with hepatorenal syndrome, but we need current evidence from systematic reviews on the benefits and harms of terlipressin versus other vasoactive drugs. OBJECTIVES: To evaluate the beneficial and harmful effects of terlipressin versus other vasoactive drugs for people with hepatorenal syndrome. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, and Science Citation Index Expanded; conducted manual searches of references in relevant literature; and wrote to experts and pharmaceutical companies (date of last search November 2016). SELECTION CRITERIA: Randomised clinical trials comparing terlipressin versus any other type of vasoactive drugs for hepatorenal syndrome. We allowed albumin and other cointerventions if provided equally in the comparison groups. DATA COLLECTION AND ANALYSIS: Three authors independently extracted data. The primary outcomes were mortality, hepatorenal syndrome (persistent hepatorenal syndrome despite treatment), and serious adverse events. We conducted meta-analyses and present the results as risk ratios (RR) with 95% confidence intervals (CI). We performed sensitivity, subgroup, and Trial Sequential Analyses and evaluated bias control based on the Cochrane Hepato-Biliary Group domains. MAIN RESULTS: We included 10 randomised clinical trials with 474 participants. The trials compared terlipressin versus noradrenaline (seven trials), octreotide (one trial), midodrine and octreotide (one trial), or dopamine (one trial). All participants in both groups received albumin as cointervention. We classified two trials at low risk of bias and eight trials at high risk of bias in the assessment of mortality and all trials at high risk of bias for remaining outcomes. In five trials, investigators specifically stated that they did not receive funding from for-profit organisations. We had no information about the funding source from the remaining five trials.Terlipressin was not superior or inferior compared with other vasoactive drugs in regard to mortality when including the two trials with a low risk of bias (RR 0.92, 95% CI 0.63 to 1.36; 94 participants, very low quality evidence) or when including all 10 trials (RR 0.96, 95% CI 0.88 to 1.06; 474 participants; I² = 0%; very low quality evidence). One meta-analysis including nine trials suggested a beneficial effect of terlipressin on hepatorenal syndrome (RR 0.79, 95% CI 0.63 to 0.99; 394 participants; I² = 26%; very low quality evidence). Due to the high mortality of hepatorenal syndrome, the registration of other serious adverse events is uncertain, but comparing terlipressin and other vasoactive drugs we found no significant difference (RR 0.96, 95% CI 0.88 to 1.06; 474 participants; I² = 0%; very low quality evidence). Several trials did not report systematically of adverse events, but terlipressin seemed to increase the risks of diarrhoea or abdominal pain, or both (RR 3.50, 95% CI 1.19 to 10.27; 221 participants; 5 trials, I² = 0%). However, Trial Sequential Analyses found insufficient evidence to support or refute any differences between interventions for all outcomes. Considering reversal of hepatorenal syndrome, subgroup analyses on the type of other vasoactive drugs found that terlipressin was superior compared with midodrine and octreotide (RR 0.47, 95% CI 0.30 to 0.72) or octreotide alone (RR 0.56, 95% CI 0.33 to 0.96), but each subgroup only included one small trial. None of the remaining subgroup or sensitivity analyses found differences between terlipressin and other vasoactive drugs. We downgraded the evidence to very low quality because of the high risk of bias, imprecision, and the results of the Trial Sequential Analyses. AUTHORS' CONCLUSIONS: This review found insufficient evidence to support or refute beneficial or harmful effects of terlipressin and albumin versus other vasoactive drugs and albumin. Additional research is needed to evaluate if clinically meaningful differences exist between interventions.

Terlipressin versus placebo or no intervention for people with cirrhosis and hepatorenal syndrome.

BACKGROUND: Hepatorenal syndrome is a potentially reversible renal failure associated with severe liver disease. The disease is relatively common among people with decompensated cirrhosis. Terlipressin is a drug that increases the blood flow to the kidneys by constricting blood vessels. The previous version of this systematic review found a potential beneficial effect of terlipressin on mortality and renal function in people with cirrhosis and hepatorenal syndrome. OBJECTIVES: To assess the beneficial and harmful effects of terlipressin versus placebo/no intervention for people with cirrhosis and hepatorenal syndrome. SEARCH METHODS: We identified eligible trials through searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, and Science Citation Index Expanded, and manual searches until 21 November 2016. SELECTION CRITERIA: Randomised clinical trials (RCTs) involving participants with cirrhosis and type 1 or type 2 hepatorenal syndrome allocated to terlipressin versus placebo or no intervention. We allowed co-administration with albumin administered to both comparison groups. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from trial reports and undertook correspondence with the authors. Primary outcomes were mortality, hepatorenal syndrome, and serious adverse events. We conducted sensitivity analyses of RCTs in which participants received albumin, subgroup analyses of participants with type 1 or type 2 hepatorenal syndrome, and Trial Sequential Analyses to control random errors. We reported random-effects meta-analyses with risk ratios (RR) and 95% confidence intervals (CI). We assessed the risk of bias based on the Cochrane Hepato-Biliary Group domains. We graded the quality of the evidence using GRADE. MAIN RESULTS: We included nine RCTs with a total of 534 participants with cirrhosis and ascites. One RCT had a low risk of bias for mortality and a high risk of bias for the remaining outcomes. All included trials had a high risk of bias for non-mortality outcomes. In total, 473 participants had type 1 hepatorenal syndrome. Seven RCTs specifically evaluated terlipressin and albumin. Terlipressin was associated with a beneficial effect on mortality when including all RCTs (RR 0.85, 95% CI 0.73 to 0.98; 534 participants; number needed to treat for an additional beneficial outcome (NNTB) 10.3 people; low-quality evidence). Trial Sequential Analysis including all RCTs also found a beneficial effect of terlipressin. Additional analyses showed a beneficial effect of terlipressin and albumin on reversal of hepatorenal syndrome (RR 0.63, 95% CI 0.48 to 0.82; 510 participants; 8 RCTs; NNTB 4 people; low-quality evidence). Terlipressin increased the risk of serious cardiovascular adverse events (RR 7.26, 95% CI 1.70 to 31.05; 234 participants; 4 RCTs), but it had no effect on the risk of serious adverse events when analysed as a composite outcome (RR 0.91, 95% CI 0.68 to 1.21; 534 participants; 9 RCTs; number needed to treat for an additional harmful outcome 24.5 people; low-quality evidence). Non-serious adverse events were mainly gastrointestinal, including diarrhoea (RR 5.76, 95% CI 2.19 to 15.15; 240 participants; low-quality evidence) and abdominal pain (RR 1.54, 95% CI 0.97 to 2.43; 294 participants; low-quality evidence).We identified one ongoing trial on terlipressin versus placebo in participants with cirrhosis, ascites, and hepatorenal syndrome type 1.Three RCTs reported funding from a pharmaceutical company. The remaining trials did not report funding or did not receive funding from pharmaceutical companies. AUTHORS' CONCLUSIONS: This review suggests that terlipressin may be associated with beneficial effects on mortality and renal function in people with cirrhosis and type 1 hepatorenal syndrome, but it is also associated with serious adverse effects. We downgraded the strength of the evidence due to methodological issues including bias control, clinical heterogeneity, and imprecision. Consequently, additional evidence is needed.

A Qualitative Exploration of the Help-Seeking Behaviors of Students Who Experience Psychological Distress Around Assessment at Medical School.

OBJECTIVE: Medical students are at high risk of experiencing psychological distress at medical school and developing mental ill-health during professional practice. Despite efforts by faculty to raise awareness about this risk, many students choose to suffer in silence in the face of psychological distress. The aim of this study was to explore drivers that prompted help-seeking behavior and barriers that prevented individuals prioritizing their well-being around the time of high-stakes assessment at medical school. METHODS: Semi-structured interviews were conducted with fifty-seven students who failed high-stakes assessment at two UK medical schools, exploring their experience of academic difficulty and perceptions about causes. A thematic analysis of twenty transcripts that met inclusion criteria was completed to identify key factors that influenced participants' decisions around seeking help for their psychological distress, and in some cases, mental health problems. Twenty participants who specifically described a deterioration in their mental health around the time of assessment were included in this study. RESULTS: Barriers to seeking help in these instances included: normalization of symptoms or situation; failure to recognize a problem existed; fear of stigmatisation; overt symptoms of mental distress; and misconceptions about the true nature of the medical school, for example beliefs about a punitive response from the school if they failed. Drivers for seeking help appropriately included: building trust with someone in order to confide in them later on, and self-awareness about the need to maintain good mental health. CONCLUSION: There are various drivers and barriers for students' help seeking behaviors when experiencing psychological distress around the time of assessment, particularly self-awareness about the problem and prioritisation of well-being. Students who fail to recognize their own deteriorating mental health are at risk of academic failure and medical schools need to develop strategies to tackle this problem in order to protect these students from harm.

Sequential Combination Therapy Versus Monotherapy: A Lack of Benefit in Time to Inflammatory Bowel Disease-Related Surgery.

BACKGROUND: The benefits of combination therapy with infliximab and azathioprine have been demonstrated in clinical trials of patients with ulcerative colitis (UC) and Crohn's disease (CD). Concerns remain regarding the ideal duration and benefits of adding therapies in a sequential manner. AIMS: We aim to compare long-term outcomes among patients with inflammatory bowel disease (IBD) treated with sequentially added combination therapy or monotherapy strategies . METHODS: We performed a retrospective cohort study involving adult patients with UC and CD. One cohort included patients treated with infliximab, adalimumab, or a thiopurine as monotherapy. A second cohort included patients treated with sequentially added combination therapy including infliximab or adalimumab and a thiopurine. The primary outcome was the rate of IBD-related surgery. RESULTS: Among 462 patients, 181 (39 %) were treated with combination therapy. 12 % of patients treated with combination therapy underwent an IBD-related surgery compared to 18 % of patients treated with monotherapy (p = 0.091), with no overall difference in time to IBD-related surgery demonstrated (log-rank test, p = 0.063). When evaluating the subtypes of IBD, there was a significant benefit in time to IBD-related surgery among patients with CD treated with sequentially added combination therapy (HR 0.46, 95 % CI 0.25-0.85) but not UC (HR 0.82, 95 % CI 0.30-2.22). CONCLUSIONS: The benefits of sequentially added combination therapy seem blunted when evaluating long-term clinical outcomes. This may be due to a decreased effectiveness of sequential combination therapy, a loss of benefit over time, or a differential effect between subtypes of IBD.

Genetic variants synthesize to produce paneth cell phenotypes that define subtypes of Crohn's disease.

BACKGROUND & AIMS: Genetic susceptibility loci for Crohn's disease (CD) are numerous, complex, and likely interact with undefined components of the environment. It has been a challenge to link the effects of particular loci to phenotypes of cells associated with pathogenesis of CD, such as Paneth cells. We investigated whether specific phenotypes of Paneth cells associated with particular genetic susceptibility loci can be used to define specific subtypes of CD. METHODS: We performed a retrospective analysis of 119 resection specimens collected from patients with CD at 2 separate medical centers. Paneth cell phenotypes were classified as normal or abnormal (with disordered, diminished, diffuse, or excluded granule phenotypes) based on lysozyme-positive secretory granule morphology. To uncover the molecular basis of the Paneth cell phenotypes, we developed methods to determine transcriptional profiles from whole-thickness and laser-capture microdissected, formalin-fixed, paraffin-embedded tissue sections. RESULTS: The proportion of abnormal Paneth cells was associated with the number of CD-associated NOD2 risk alleles. The cumulative number of NOD2 and ATG16L1 risk alleles had an additive effect on the proportion of abnormal Paneth cells. Unsupervised clustering analysis of demographic and Paneth cell data divided patients into 2 principal subgroups, defined by high and low proportions of abnormal Paneth cells. The disordered and diffuse abnormal Paneth cell phenotypes were associated with an altered transcriptional signature of immune system activation. We observed an inverse correlation between abnormal Paneth cells and presence of granuloma. In addition, high proportions of abnormal Paneth cells were associated with shorter time to disease recurrence after surgery. CONCLUSIONS: Histologic analysis of Paneth cell phenotypes can be used to divide patients with CD into subgroups with distinct pathognomonic and clinical features.

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.

Evaluation of organisational culture and nurse burnout.

A survey of nurses working with older adults across three NHS trusts was conducted to explore how perceptions of the workplace affect nurse wellbeing. Standardised validated measures were used to assess burnout, perceived organisational support and organisational culture. Significant associations were found between innovative organisational culture and nurses' sense of personal accomplishment, which reduce the likelihood of burnout. Multiple regression showed experience of burnout to be predicted by the nature of organisational culture. It seems therefore that nurses' wellbeing may be affected by their perceptions of the working environment. Applications of this knowledge and suggestions for future research are discussed.