The objective was to determine whether a cannabis-based medicinal extract (CBME) benefits a range of symptoms due to multiple sclerosis (MS). A parallel group, double-blind, randomized, placebo-controlled study was undertaken in three centres, recruiting 160 outpatients with MS experiencing significant problems from at least one of the following: spasticity, spasms, bladder problems, tremor or pain. The interventions were oromucosal sprays of matched placebo, or whole plant CBME containing equal amounts of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) at a dose of 2.5-120 mg of each daily, in divided doses. The primary outcome measure was a Visual Analogue Scale (VAS) score for each patient's most troublesome symptom. Additional measures included VAS scores of other symptoms, and measures of disability, cognition, mood, sleep and fatigue. Following CBME the primary symptom score reduced from mean (SE) 74.36 (11.1) to 48.89 (22.0) following CBME and from 74.31 (12.5) to 54.79 (26.3) following placebo [ns]. Spasticity VAS scores were significantly reduced by CBME (Sativex) in comparison with placebo (P =0.001). There were no significant adverse effects on cognition or mood and intoxication was generally mild.

Cannabis medicinal extracts can improve neurogenic symptoms unresponsive to standard treatments. Unwanted effects are predictable and generally well tolerated. Larger scale studies are warranted to confirm these findings.

The object of this study was to monitor the safety and efficacy of long-term use of an oromucosal cannabis-based medicine (CBM) in patients with multiple sclerosis (MS). A total of 137 MS patients with symptoms not controlled satisfactorily using standard drugs entered this open-label trial following a 10-week, placebo-controlled study. Patients were assessed every eight weeks using visual analogue scales and diary scores of main symptoms, and were followed for an average of 434 days (range: 21 -814). A total of 58 patients (42.3%) withdrew due to lack of efficacy (24); adverse events (17); withdrew consent (6); lost to follow-up (3); and other (8). Patients reported 292 unwanted effects, of which 251 (86%) were mild to moderate, including oral pain (28), dizziness (20), diarrhoea (17), nausea (15) and oromucosal disorder (12). Three patients had five 'serious adverse events' between them--two seizures, one fall, one aspiration pneumonia, one gastroenteritis. Four patients had first-ever seizures. The improvements recorded and dosage taken in the acute study remained stable. Planned, sudden interruption of CBM for two weeks in 25 patients (of 62 approached) did not cause a consistent withdrawal syndrome, although 11 (46%) patients reported at least one of--tiredness, interrupted sleep, hot and cold flushes, mood alteration, reduced appetite, emotional lability, intoxication or vivid dreams. Twenty-two (88%) patients re-started CBM treatment. We conclude that long-term use of an oromucosal CBM (Sativex) maintains its effect in those patients who perceive initial benefit. The precise nature and rate of risks with long-term use, especially epilepsy, will require larger and longer-term studies.

Background There is limited understanding of the contribution made by older people and their caregivers to acute healthcare in the home and how this compares to hospital inpatient healthcare. Objectives To explore the work of older people and caregivers at the time of an acute health event, the interface with professionals in a hospital and hospital at home (HAH) and how their experiences relate to the principles underpinning comprehensive geriatric assessment (CGA). Design A qualitative interview study within a UK multi-site participant randomised trial of geriatrician-led admission avoidance HAH, compared with hospital inpatient care. Methods We conducted semi-structured interviews with 34 older people (15 had received HAH and 19 hospital care) alone or alongside caregivers (29 caregivers; 12 HAH, 17 hospital care), in three sites that recruited participants to a randomised trial, during 2017–2018. We used normalisation process theory to guide our analysis and interpretation of the data. Results Patients and caregivers described efforts to understand changes in health, interpret assessments and mitigate a lack of involvement in decisions. Practical work included managing risks, mobilising resources to meet health-related needs, and integrating the acute episode into longer-term strategies. Personal, relational and environmental factors facilitated or challenged adaptive capacity and ability to manage. Conclusions Patients and caregivers contributed to acute healthcare in both locations, often in parallel to healthcare providers. Our findings highlight an opportunity for CGA-guided services at the interface of acute and chronic condition management to facilitate personal, social and service strategies extending beyond an acute episode of healthcare.

BackgroundThe Comprehensive Geriatric Assessment (CGA) is a multidisciplinary process that determines a frail older person’s medical, functional, psychological and social capability to ensure that they have a co-ordinated plan for treatment and follow-up.ObjectivesTo improve our understanding of the effectiveness, cost-effectiveness and implementation of the CGA across hospital and hospital-at-home settings.MethodsWe used a variety of methods. We updated a Cochrane review of randomised trials of the CGA in hospital for older people aged ≥ 65 years, conducted a national survey of community CGA, analysed data from three health boards using propensity score matching (PSM) and regression analysis, conducted a qualitative study and used a modified Delphi method.ResultsWe included 29 trials recruiting 13,766 participants in the Cochrane review of the CGA. Older people admitted to hospital who receive the CGA are more likely to be living at home at 3–12 months’ follow-up [relative risk (RR) 1.06, 95% confidence interval (CI) 1.01 to 1.10] (high certainty). The probability that the CGA would be cost-effective at a £20,000 ceiling ratio for quality-adjusted life-years (QALYs), life-years (LYs) and LYs living at home was 0.50, 0.89, and 0.47, respectively (low-certainty evidence). After PSM and regression analysis comparing CGA hospital with CGA hospital at home, we found that the health-care cost (from admission to 6 months after discharge) in site 1 was lower in hospital at home (ratio of means 0.82, 95% CI 0.76 to 0.89), in site 2 there was little difference (ratio of means 1.00, 95% CI 0.92 to 1.09) and in site 3 it was higher (ratio of means 1.15, 95% CI 0.99 to 1.33). Six months after discharge (excluding the index admission), the ratio of means cost in site 1 was 1.27 (95% CI 1.14 to 1.41), in site 2 was 1.09 (95% CI 0.95 to 1.24) and in site 3 was 1.70 (95% CI 1.40 to 2.07). At 6 months’ follow-up (excluding the index admission), there may be an increased risk of mortality (adjusted) in the three hospital-at-home cohorts (site 1: RR 1.09, 95% CI 1.00 to 1.19; site 2: RR 1.29, 95% CI 1.15 to 1.44; site 3: RR 1.27, 95% CI 1.06 to 1.54). The qualitative research indicates the importance of relational aspects of health care, incorporating caregivers’ knowledge in care planning, and a lack of clarity about the end of an episode of health care. Core components that should be included in CGA focus on functional, physical and mental well-being, medication review and a caregiver’s ability to care.LimitationsThe risk of residual confounding limits the certainty of the findings from the PSM analysis; a second major limitation is that the research plan did not include an investigation of social care or primary care.ConclusionsThe CGA is an effective way to organise health care for older people in hospital and may lead to a small increase in costs. There may be an increase in cost and the risk of mortality in the population who received the CGA hospital at home compared with those who received the CGA in hospital; randomised evidence is required to confirm or refute this. Caregiver involvement in the CGA process could be strengthened.FundingThe National Institute for Health Research Health Services and Delivery Research programme.

Evidence suggests that manipulating spatial information within working memory depends upon a circuitry organized around the prefrontal cortex (PFC) and the activity of the catecholamine systems. Other evidence attests to the effects of D-9 tetrahydrocannabinol (THC) on short-term spatial memory function, most probably involving CB 1 receptor activity within hippocampal circuitries. At the current time, there have been no systematic studies of the effects of THC on spatial working memory in human subjects using tasks known to depend upon frontotemporal neural circuitries. We examined the effects of a single sublingual 5 mg dose of THC on a test of spatial working memory (requiring active manipulation of remembered spatial information for the management of future behavior) and a test of spatial span (requiring only the reproduction of sequences of previously presented spatial cues). In all, 19 healthy adults were administered 5 mg THC and placebo in a double-blind, placebo-controlled, within-subject, crossover design. Male participants performed more accurately than female participants. THC significantly enhanced spatial working memory performance of female participants. By contrast, male and female participants produced more intrusion errors during performance of the Spatial Span task. These results suggest that THC has relatively complex effects on spatial memory in human subjects, perhaps reflecting altered CB 1 receptor activity within frontotemporal circuits or altered activity of mesocortical dopaminergic pathways in PFC areas associated with spatial memory.

Background Supported self‐management (SSM) is a recognized approach for people with long‐term conditions but, despite the prevalence of unmet needs, little is known about its role for people with traumatic brain injury (TBI). Objectives To codesign an SSM intervention with people with TBI and evaluate feasibility of implementation through multidisciplinary staff across a trauma pathway. Setting and participants People who had previously been admitted to a Major Trauma Centre following TBI and family members participated in a series of codesign activities. Staff attended SSM workshops and used the intervention with patients in acute and rehabilitation settings. Methods We used Normalization Process Theory constructs to guide and interpret implementation. Knowledge, beliefs and confidence of staff in SSM were assessed through pre‐ and post‐training questionnaires, and staff, patients' and families' experiences were explored through semi‐structured interviews. Qualitative data were analysed thematically, and clinical measures were mapped against a matched sample. Results Codesigned resources were created and used within an SSM approach for which 110 staff participated in training. Evaluation demonstrated significant differences in staff SSM confidence and skills, following training. Qualitative evaluation revealed adoption by staff, and patients' and families' experiences of using the resources. Challenges included reaching staff across complex pathways to achieve collective implementation. Conclusion This is the first project to demonstrate feasibility of SSM for people after TBI starting in an acute trauma setting. Through an open approach to codesign with a marginalized group, the SSM resources were valued by them and held meaning and relevance for staff.

Older people who live with a combination of conditions experience fluctuations over time, which others may interpret as a need for medical attention. For some nursing home residents, this results in transitions in and out of hospital. Such transfers may be arranged without expectation of improved quality of life, can be associated with significant morbidity and mortality, and may preclude end-of-life preferences. Factors affecting avoidable hospitalization for nursing home residents are not well understood. I aim to explore potential drivers, moving beyond deficit explanations relating to funding, training, and resources. I use a framework of analysis that firstly considers medicalization of frailty, as a state of vulnerability that provides focus for others' action. I then draw on Judith Butler's theory of performativity, to explore nursing homes as sites of identity work for staff, residents and families. I consider ways subjectivities can be effected through reiterative practice that is compelled by normative conventions. Trouble may arise when citational practice of health care staff, and performative acquiescence of residents and families, culminates in an inevitability of hospitalization when navigating grey areas of assumed clinical risk. Principles of coproduction could present a disruptive opening, to rework power asymmetries, and move toward aspirations for residents and their relatives to be at the centre of decisions about care.