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Purpose: Real-world studies to describe the use of first, second and third line therapies for the management and symptomatic treatment of dementia are lacking. This retrospective cohort study describes the first-, second- and third-line therapies used for the management and symptomatic treatment of dementia, and in particular Alzheimer’s Disease. Methods: Medical records of patients with newly diagnosed dementia between 1997 and 2017 were collected using four databases from the UK, Denmark, Italy and the Netherlands. Results: We identified 191,933 newly diagnosed dementia patients in the four databases between 1997 and 2017 with 39,836 (IPCI (NL): 3281, HSD (IT): 1601, AUH (DK): 4474, THIN (UK): 30,480) fulfilling the inclusion criteria, and of these, 21,131 had received a specific diagnosis of Alzheimer’s disease. The most common first line therapy initiated within a year (± 365 days) of diagnosis were Acetylcholinesterase inhibitors, namely rivastigmine in IPCI, donepezil in HSD and the THIN and the N-methyl-d-aspartate blocker memantine in AUH. Conclusion: We provide a real-world insight into the heterogeneous management and treatment pathways of newly diagnosed dementia patients and a subset of Alzheimer’s Disease patients from across Europe.

Purpose To estimate the risk of dyskinesia and impulse control disorders (ICDs) in patients with Parkinson's disease (PD) prescribed ropinirole prolonged‐release (R‐PR) compared to those prescribed immediate‐release dopamine agonists (IR‐DA) as monotherapy. Methods PD patients initiating R‐PR or IR‐DA as monotherapy between 2008 and 2013 were identified on the Clinical Practice Research Datalink. The cohorts were propensity score matched on a 1:1 basis. The incidence of dyskinesia and ICD in each treatment cohort and the incidence rate ratios were calculated. Adherence to medication and time to levodopa initiation were also evaluated. Results We identified 341 patients in each treatment cohort after propensity score matching. The baseline characteristics were generally comparable. Dyskinesia incidence in R‐PR and IR‐DA cohorts was 2.98 (95% CI: 0.74‐11.9) and 3.93 (95% CI: 0.98‐15.7) per 1000 person‐years, respectively (incidence rate ratio of R‐PR vs ID‐DA: 0.76, 95% CI: 0.11‐5.38). Less than five cases of ICD were identified and all occurred in the IR‐DA cohort. The patients in the R‐PR cohort remained on treatment for a significantly longer duration than those in the IR‐DA cohort (682 days vs 444 days; P

Diabetes self-care may become increasingly challenging as cognition declines. We sought to characterize glycated hemoglobin ARetrospective matched cohort study.Using a linkage between a primary care (Lambeth DataNet) and a secondary mental healthcare database, up to 5 individuals aged ≥65 y with preexisting T2D without dementia were matched to each individual with dementia based on age, sex, and general practice.Comparisons were made for HbAIn 725 incident dementia and 3154 matched comparators, HbAOur study has highlighted important differences in the monitoring, management, and control of diabetes in people with dementia. The effects of frailty and the extent of cognitive impairment on the ability to self-manage diabetes and on glycemic control may need to be considered in treatment guidelines and by primary care.

ObjectiveIn order to identify areas of unmet need in patients with primary biliary cholangitis (PBC), this study sought to use real-world observational healthcare data to characterise the burden in patients with PBC and in PBC patients with a recorded diagnosis of pruritus.DesignThis retrospective, cross-sectional database study compared prevalence of prespecified comorbidities and medications in the PBC population and PBC-pruritus subpopulation with non-cases using an indirect standardisation approach. The PBC population was identified from the US IBM MarketScan Commercial Claims and Medicare Supplemental Database during 2016 using International Classification of Diseases 10th Revision, Clinical Modification codes (≥2 claims for PBC); the PBC-pruritus subpopulation additionally had ≥1 claim for pruritus during this period. Non-cases had no claims for PBC. Indirect age-sex standardised prevalence ratios (iSPR) and 95% confidence intervals (CIs) were calculated for prespecified comorbidities and medications recorded during 2017.ResultsThe PBC population (N=1963) and PBC-pruritus subpopulation (N=139) had significantly higher prevalence of fatigue (19.9%, iSPR (95% CI): 1.51 (1.36 to 1.66); 26.6%, 2.10 (1.48 to 2.90)), depression/anxiety (21.3%, 1.09 (0.99 to 1.20); 28.1%, 1.46 (1.04 to 2.00)) and sleep-related issues (6.9%, 1.18 (0.99 to 1.40); 14.4%, 2.58 (1.58 to 3.99)) compared with non-cases. Bile acid sequestrants were prescribed in 5.8% and 18.0% of the PBC and PBC-pruritus populations, respectively. In general, a higher prevalence of comorbidities and medication use was observed in the PBC-pruritus subpopulation compared with the PBC population and non-cases.ConclusionDespite availability of treatments for PBC, the PBC population had a higher burden of comorbidities than non-cases. This burden was even greater among the PBC-pruritus subpopulation, with a particularly high prevalence of sleep disorders and depression/anxiety. Despite this, pruritus remains undertreated highlighting a need for treatments specifically indicated for cholestatic pruritus.

Summary Background Neurite outgrowth inhibitor A (Nogo-A) is thought to have a role in the pathophysiology of amyotrophic lateral sclerosis (ALS). A monoclonal antibody against Nogo-A showed a positive effect in the SOD1 G93A mouse model of ALS, and a humanised form of this antibody (ozanezumab) was well tolerated in a first-in-human trial. Therefore, we aimed to assess the safety and efficacy of ozanezumab in patients with ALS. Methods This randomised, double-blind, placebo-controlled, phase 2 trial was done in 34 centres in 11 countries. Patients aged 18–80 years with a diagnosis of familial or sporadic ALS were randomly assigned (1:1), centrally according to a computer-generated allocation schedule, to receive ozanezumab (15 mg/kg) or placebo as intravenous infusions over 1 h every 2 weeks for 46 weeks, followed by assessments at week 48 and week 60. Patients and study personnel were masked to treatment assignment. The primary outcome was a joint-rank analysis of function (ALS Functional Rating Scale-Revised) and overall survival, analysed at 48 weeks in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01753076, and with GSK-ClinicalStudyRegister.com, NOG112264, and is completed. Findings Between Dec 20, 2012, and Nov 1, 2013, we recruited 307 patients, of whom 303 were randomly assigned to receive placebo (n=151) or ozanezumab (n=152). The adjusted mean of the joint-rank score was −14·9 (SE 13·5) for the ozanezumab group and 15·0 (13·6) for the placebo group, with a least squares mean difference of −30·0 (95% CI −67·9 to 7·9; p=0·12). Overall, reported adverse events, serious adverse events, and adverse events leading to permanent discontinuation of study drug or withdrawal from study were similar between the treatment groups, except for dyspepsia (ten [7%] in the ozanezumab group vs four [3%] in the placebo group), depression (11 [7%] vs five [3%]), and diarrhoea (25 [16%] vs 12 [8%]). Respiratory failure was the most common serious adverse event (12 [8%] vs seven [5%]). At week 60, the number of deaths was higher in the ozanezumab group (20 [13%]) than in the placebo group (16 [11%]), mainly as a result of respiratory failure (ten [7%] vs five [3%]). Two deaths were considered related to the study drug (bladder transitional cell carcinoma in the ozanezumab group and cerebrovascular accident in the placebo group). Interpretation Ozanezumab did not show efficacy compared with placebo in patients with ALS. Therefore, Nogo-A does not seem to be an effective therapeutic target in ALS. Funding GlaxoSmithKline.

INTRODUCTION: The European Medical Information Framework consortium has assembled electronic health record (EHR) databases for dementia research. We calculated dementia prevalence and incidence in 25 million persons from 2004 to 2012. METHODS: Six EHR databases (three primary care and three secondary care) from five countries were interrogated. Dementia was ascertained by consensus harmonization of clinical/diagnostic codes. Annual period prevalences and incidences by age and gender were calculated and meta-analyzed. RESULTS: The six databases contained 138,625 dementia cases. Age-specific prevalences were around 30% of published estimates from community samples and incidences were around 50%. Pooled prevalences had increased from 2004 to 2012 in all age groups but pooled incidences only after age 75 years. Associations with age and gender were stable over time. DISCUSSION: The European Medical Information Framework initiative supports EHR data on unprecedented number of people with dementia. Age-specific prevalences and incidences mirror estimates from community samples in pattern at levels that are lower but increasing over time. The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under European Medical Informatics Framework (EMIF) grant agreement no. 115372, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies’ in kind contribution. R.S. and G.P. are partly funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London.

It is widely believed that reducing antimicrobial usage should reduce resistance, although observational evidence is mixed. Pneumococci make ideal subjects to test this belief as they are widely surveyed and lack an animal reservoir. Accordingly, susceptibility data for pneumococci in the UK and Ireland were retrieved from the Health Protection Agency's LabBase/CoSurv system and from the European Antimicrobial Resistance Surveillance System (EARSS) and British Society for Antimicrobial Chemotherapy (BSAC) databases. The BSAC surveillance examines respiratory pneumococci; the other systems focus upon invasive organisms only, with the LabBase/CoSurv system being the most comprehensive, capturing data on most bacteraemias in England and Wales. National pharmacy sales data were obtained from the IMS Health MIDAS database and were modelled to the resistance data by logistic and linear regression analysis. All systems except for the BSAC respiratory surveillance data indicated that penicillin resistance has fallen significantly since 1999 in the UK, whereas macrolide resistance has been essentially stable, or has risen slightly. The data for Ireland were based on smaller sample sizes but suggested a fall in penicillin non-susceptibility from 1999 to 2004, with conflicting evidence for macrolide resistance. The recent decreasing trend in penicillin resistance is in contrast to a rising trend in England and Wales until (at least) 1997 and strongly rising macrolide resistance from 1989 to 1993. UK pharmacy sales of macrolides and oral beta-lactams fell by ca. 30% in the late 1990s following increased concern about resistance, before stabilising or rising weakly; sales in Ireland were stable or rose slightly in the study period. We conclude that falling penicillin resistance in pneumococci followed reduced sales of oral beta-lactams to pharmacies in the UK, but a similar fall in macrolide sales was not associated with any fall in resistance. Stabilisation or decline in penicillin resistance has occurred in Ireland despite stable or increasing oral beta-lactam sales.

We aimed to determine the incidence of enteral feed intolerance and factors associated with intolerance and to assess the influence of intolerance on nutrition and clinical outcomes.We conducted a retrospective analysis of data from an international observational cohort study of nutrition practices among 167 intensive care units (ICUs). Data were collected on nutrition adequacy, ventilator-free days (VFDs), ICU stay, and 60-day mortality. Intolerance was defined as interruption of enteral nutrition (EN) due to gastrointestinal (GI) reasons (large gastric residuals, abdominal distension, emesis, diarrhea, or subjective discomfort). Logistic regression was used to determine risk factors for intolerance and their clinical significance. A sensitivity analysis restricted to sites specifying a gastric residual volume ≥200 mL to identify intolerance was also conducted.Data from 1,888 ICU patients were included. The incidence of intolerance was 30.5% and occurred after a median 3 days from EN initiation. Patients remained intolerant for a mean (±SD) duration of 1.9 ± 1.3 days . Intolerance was associated with worse nutrition adequacy vs the tolerant (56% vs 64%, P.0001), fewer VFDs (2.5 vs 11.2, P.0001), increased ICU stay (14.4 vs 11.3 days, P.0001), and increased mortality (30.8% vs 26.2, P = .04). The sensitivity analysis demonstrated that intolerance remained associated with negative outcomes. Although mortality was greater among the intolerant patients, this was not statistically significant.Intolerance occurs frequently during EN in critically ill patients and is associated with poorer nutrition and clinical outcomes.

This study was commissioned by GSK through the Farr Institute/SHIP/eDRIS single portal. DJM is a Clinician Scientist Fellow funded by the Health Foundation/Academy of Medical Sciences. Objectives: Acute pancreatitis (AP) can initiate systemic complications that require support in critical care (CC). Our objective was to use the unified national health record to define the epidemiology of AP in Scotland, with a specific focus on deterministic and prognostic factors for CC admission in AP. Setting: Health boards in Scotland (n=4). Participants: We included all individuals in a retrospective observational cohort with at least one episode of AP (ICD10 code K85) occurring in Scotland from 1 April 2009 to 31 March 2012. 3340 individuals were coded as AP. Methods: Data from 16 sources, spanning general practice, community prescribing, Accident and Emergency attendances, hospital in-patient, CC and mortality registries, were linked by a unique patient identifier in a national safe haven. Logistic regression and gamma models were used to define independent predictive factors for severe AP (sAP) requiring CC admission or leading to death. Results: 2053 individuals (61.5% (95% CI 59.8% to 63.2%)) met the definition for true AP (tAP). 368 patients (17.9% of tAP (95% CI 16.2% to 19.6%)) were admitted to CC. Predictors of sAP were pre-existing angina or hypertension, hypocalcaemia and age 30-39 years, if type 2 diabetes mellitus was present. The risk of sAP was lower in patients with multiple previous episodes of AP. In-hospital mortality in tAP was 5.0% (95% CI 4.1% to 5.9%) overall and 21.7% (95% CI 19.9% to 23.5%) in those with tAP necessitating CC admission. Conclusions: National record-linkage analysis of routinely collected data constitutes a powerful resource to model CC admission and prognosticate death during AP. Mortality in patients with AP who require CC admission remains high. Publisher PDF

Objective Following the licensure of 23-valent pneumococcal polysaccharide vaccine (23vPPV) in 1989, a risk-group–only immunization policy was implemented in 1992 in England. The PPV programme was extended in 2003 to include all individuals 65 years and over. In England, this was phased in over 3 years. To ascertain the performance of the risk group policy in those 65 years of age and over and provide a baseline to estimate the impact of the universal elderly programme. Methods Information was gathered on vaccine uptake for the period 1989–2003 in England from a national survey of general practitioners (GPs) through NHS primary care trusts (PCTs), the prescription cost analysis (PCA) system and the General Practice Research Database (GPRD). Results Between 1991 and 2003, 4.5 million doses of PPV were prescribed. The GP survey found that by 2003, 29% of those 65 years and over of age and 36% of those 80 years of age over had received PPV. Sixty-two per cent of general practices had implemented a risk-group–only policy, 14.4% had targeted all those 65 years of age over and 14.2% had targeted all those 75 years of age over. The GPRD study found that 38% of those 65 years over and 41% of those 80 years over fell into one or more high-risk groups. By 2003, 36.6% of the high-risk group and 30.2% of all those 65 years over had ever been vaccinated. Vaccine uptake increased with age, with 52.3% of the high-risk group and 37% of all those 80 years over having ever been vaccinated. Conclusions A large proportion of those in risk groups remained unvaccinated with PPV in 2003. Formal evaluation of the impact and effectiveness of the universal elderly immunization programme will be required.

Hepatitis C is a global public health problem, and a major cause of chronic hepatitis. The virus can cause cirrhosis, liver failure and primary liver cancer. Combination therapy is effective in 50-60 per cent of patients with chronic infection. Prevention initiatives should target high-risk groups, such as injecting drug users.

Provision of early and adequate enteral nutrition (EN) to critically ill patients is associated with improved clinical outcomes; however, 50 to 60% of prescribed EN is received. We aimed to characterise the incidence and determinants of intolerance and assess its influence on nutritional and clinical outcomes using the 2009 Critical Care Nutrition Survey (CCNS).