Memantine and cholinesterase inhibitor combination therapy for Alzheimer's disease: a systematic review

BACKGROUND: Memantine is licensed for moderate-to-severe Alzheimer's disease (AD). National Institute for Clinical Excellence (NICE) guidance does not recommend the use of memantine in combination with cholinesterase inhibitors (acetylcholinesterase inhibitor (AChEI)). The underpinning meta-analysis was disputed by the manufacturer. OBJECTIVES: To compare the efficacy of AChEI monotherapy with combination memantine and AChEI therapy in patients with moderate-to-severe AD and to examine the impact of including unpublished data on the results. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: The Cochrane Dementia Group trial register, ALOIS, searched for the last time on 3 May 2011. DATA SYNTHESIS: Data from four domains (clinical global, cognition, function, behaviour and mood) were pooled. Sensitivity analyses examined the impact on the NICE-commissioned meta-analysis of restricting data to patients with moderate-to-severe AD and of including an unpublished trial of an extended release preparation of memantine. RESULTS: Pooled data from the trials, which were included in the NICE-commissioned meta-analysis but which were restricted to moderate-to-severe AD only, showed a small effect of combination therapy on cognition (standardised mean difference (SMD)=-0.29, 95% CI -0.45 to -0.14). Adding data from an unpublished trial of an extended release memantine (total three trials, 1317 participants) showed a small benefit of combination therapy on global scores (SMD=-0.20, 95% CI -0.31 to -0.09), cognition (SMD=-0.25, 95% CI -0.36 to -0.14) and behaviour and mood (SMD=-0.17, 95% CI -0.32 to -0.03) but not on function (SMD=-0.04, 95% CI -0.21 to 0.13) at 6 months. No clinical data have been reported from a 1-year trial, although this found 'no significant benefit' on any clinical measures at 1 year. CONCLUSIONS: These results suggest that there may be a small benefit at 6 months of adding memantine to AChEIs. However, the impact on clinical global impression depends on exactly which studies are included, and there is no benefit on function, so its clinical relevance is not robustly demonstrated. Currently available information from randomised controlled trails indicates no benefit of combination therapy over monotherapy at 1 year. Legislation on the form and content of registry posted results is needed in Europe

Specialist alcohol inpatient treatment admissions and non-specialist hospital admissions for alcohol withdrawal in England: an inverse relationship

© The Author(s) 2020. Medical Council on Alcohol and Oxford University Press. AIMS: We assessed the relationship between specialist and non-specialist admissions for alcohol withdrawal since the introduction of the UK government Health and Social Care Act in 2012. METHODS: Using publicly available national data sets from 2009 to 2019, we compared the number of alcohol withdrawal admissions and estimated costs in specialist and non-specialist treatment settings. RESULTS: A significant negative correlation providing strong evidence of an association was observed between the fall in specialist and rise in non-specialist admissions. Significant cost reductions within specialist services were displaced to non-specialist settings. CONCLUSIONS: The shift in demand from specialist to non-specialist alcohol admissions due to policy changes in England should be reversed by specialist workforce investment to improve outcomes. In the meantime, non-specialist services and staff must be resourced and equipped to meet the complex needs of these service users

The development and internal validation of a multivariable model predicting 6-month mortality for people with opioid use disorder presenting to community drug services in England: a protocol

BackgroundPeople with opioid use disorder have substantially higher standardised mortality rates compared to the general population; however, lack of clear individual prognostic information presents challenges to prioritise or target interventions within drug treatment services. Previous prognostic models have been developed to estimate the risk of developing opioid use disorder and opioid-related overdose in people routinely prescribed opioids but, to our knowledge, none have been developed to estimate mortality risk in people accessing drug services with opioid use disorder. Initial presentation to drug services is a pragmatic time to evaluate mortality risk given the contemporaneous routine collection of prognostic indicators and as a decision point for appropriate service prioritisation and targeted intervention delivery. This study aims to develop and internally validate a model to estimate 6-month mortality risk for people with opioid use disorder from prognostic indicators recorded at initial assessment in drug services in England.MethodsAn English national dataset containing records from individuals presenting to drug services between 1 April 2013 and 1 April 2023 (n > 800,000) (the National Drug Treatment Monitoring System (NDTMS)) linked to their lifetime hospitalisation and death records (Hospital Episode Statistics-Office of National Statistics (HES-ONS)). Twelve candidate prognostic indicator variables were identified based on literature review of demographic and clinical features associated with increased mortality for people in treatment for opioid use disorder. Variables will be extracted at initial presentation to drug services with mortality measured at 6 months. Two multivariable Cox regression models will be developed one for 6-month all-cause mortality and one for 6-month drug-related mortality using backward elimination with a fractional polynomial approach for continuous variables. Internal validation will be undertaken using bootstrapping methods. Discrimination of both models will be reported using Harrel’s c and d-statistics. Calibration curves and slopes will be presented comparing expected and observed event rates.DiscussionThe models developed and internally validated in this study aim to improve clinical assessment of mortality risk for people with opioid use disorder presenting to drug services in England. External validation in different populations will be required to develop the model into a tool to assist future clinical decision-making

Mortality of people with chronic fatigue syndrome: a retrospective cohort study in England and Wales from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Clinical Record Interactive Search (CRIS) Register

SummaryBackgroundMortality associated with chronic fatigue syndrome is uncertain. We investigated mortality in individuals diagnosed with chronic fatigue syndrome in secondary and tertiary care using data from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Clinical Record Interactive Search (CRIS) register.MethodsWe calculated standardised mortality ratios (SMRs) for all-cause, suicide-specific, and cancer-specific mortality for a 7-year observation period using the number of deaths observed in SLaM records compared with age-specific and sex-specific mortality statistics for England and Wales. Study participants were included if they had had contact with the chronic fatigue service (referral, discharge, or case note entry) and received a diagnosis of chronic fatigue syndrome.FindingsWe identified 2147 cases of chronic fatigue syndrome from CRIS and 17 deaths from Jan 1, 2007, to Dec 31, 2013. 1533 patients were women of whom 11 died, and 614 were men of whom six died. There was no significant difference in age-standardised and sex-standardised mortality ratios (SMRs) for all-cause mortality (SMR 1·14, 95% CI 0·65–1·85; p=0·67) or cancer-specific mortality (1·39, 0·60–2·73; p=0·45) in patients with chronic fatigue syndrome when compared with the general population in England and Wales. This remained the case when deaths from suicide were removed from the analysis. There was a significant increase in suicide-specific mortality (SMR 6·85, 95% CI 2·22–15·98; p=0·002).InterpretationWe did not note increased all-cause mortality in people with chronic fatigue syndrome, but our findings show a substantial increase in mortality from suicide. This highlights the need for clinicians to be aware of the increased risk of completed suicide and to assess suicidality adequately in patients with chronic fatigue syndrome.FundingNational Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London

Pattern and prevalence of vaping nicotine and non-nicotine drugs in the United Kingdom: a cross-sectional study

Objectives: Electronic vaping devices are being used to consume nicotine and non-nicotine psychoactive drugs. We aimed to determine the pattern and prevalence of using vaping devices for nicotine and/or non-nicotine drug administration in the United Kingdom and how these differ by drug type and individual sociodemographic characteristics. We explored reasons for vaping onset and continuation. Design: An online cross-sectional survey Participants: A convenience sample of adults (aged ≥18 years) in the UK. Primary and secondary outcome measures: The primary outcome was prevalence of current use (within the last 30 days) of a vaping device to administer either nicotine or 18 types of non-nicotine drugs. We additionally evaluated reasons for onset and continuation of vaping. Sociodemographic characteristics were compared between the UK general population using census data and those vaping non-nicotine drugs. Results: We recruited 4027 participants of whom 1637 (40.7%) had ever used an electronic vaping device; 1495 (37.1%) had ever vaped nicotine and 593 (14.7%) had ever vaped a non-nicotine drug. Overall, 574 (14.3%) currently vaped nicotine and 74 (1.8%) currently vaped a non-nicotine drug. The most common currently vaped non-nicotine drug was cannabis (n=58, 1.4%). For nicotine, people’s modal reasons to start and continue vaping was to quit smoking tobacco. For almost all other drugs, people’s modal reason to start vaping was curiosity and to continue was enjoyment. Compared with the general population, the population who had ever vaped a non-nicotine drug were significantly younger, had more disabilities and fewer identified as white, female, heterosexual or religious. Conclusions: A non-trivial number of people report current use and ever use of an electronic vaping device for non-nicotine drug administration. As vaping technology advances and drug consumption changes, understanding patterns of use and associated behaviours are likely to be increasingly important to both users and healthcare professionals

Systematic review of fit note use for workers in the UK

ObjectivesThe fit note, introduced in England, Wales and Scotland in 2010, was designed to change radically the sickness certification process from advising individuals on their inability to work to advising them on what they could do if work could be adapted. Our review aimed to evaluate the following: (1) Is the ‘maybe fit’ for work option being selected for patients? (2) Are work solutions being recommended? (3) Has the fit note increased return to work? (4) Has the fit note reduced the length of sickness absence? We considered the way in which outcomes vary according to patient demographics including type of health problem.MethodsStudies were identified by a systematic search. We included all studies of any design conducted in the UK with working age adults, aged 16 or over, from 1 April 2010 to 1 Nov 2017. Risk of bias was assessed using a modified Newcastle-Ottawa Scale.ResultsThirteen papers representing seven studies met inclusion criteria. In the largest study, ‘maybe fit’ for work was recommended in 6.5% of fit notes delivered by general practitioners (GP; n=361 801) between April 2016 and March 2017. ‘Maybe fit’ recommendations were made in 8.5%–10% of fit notes received by primary care patients in employment, and in 10%–32% of patients seen by GPs trained in the Diploma in Occupational Medicine. ‘Maybe fit’ was recommended more for women, those with higher socioeconomic status, and for physical, as opposed to psychiatric disorders. The majority of fit notes with the ‘maybe fit’ option selected included work solutions. There was inconclusive evidence to suggest that the introduction of the fit note has reduced sickness absence among patients in employment.ConclusionsFit notes represent a major shift in public policy. Our review suggests that they have been incompletely researched and not implemented as intended.</jats:sec