Treatment pathway analysis of newly diagnosed dementia patients in four electronic health record databases in Europe.

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.

Comparison of long-term use of prolonged-release ropinirole and immediate-release dopamine agonists in an observational study in patients with Parkinson's disease.

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 < .0001) and had greater adherence to the medication. The median time to levodopa initiation was 417 days (IQR: 205-736) in R-PR vs 297 days (IQR: 111-552) in IR-DA cohort. CONCLUSIONS: The number of dyskinesia and ICD events was lower than expected, resulting in an underpowered study. A significantly longer persistence and greater adherence to medication was observed in patients receiving R-PR compared to IR-DA.

Dementia prevalence and incidence in a federation of European Electronic Health Record databases: The European Medical Informatics Framework resource.

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.

Pruritus in primary biliary cholangitis is under-recorded in patient medical records.

OBJECTIVE: Cholestatic pruritus in primary biliary cholangitis (PBC) reduces patients' health-related quality of life (HRQoL). Despite this, existing research suggests that pruritus is under-recorded in patients' health records. This study assessed the extent to which pruritus was recorded in medical records of patients with PBC as compared with patient-reported pruritus, and whether patients reporting mild itch were less likely to have pruritus recorded. We also evaluated clinico-demographic characteristics and HRQoL of patients with medical record-documented and patient-reported pruritus. DESIGN: This cross-sectional study used clinical information abstracted from medical records, together with patient-reported (PBC-40) data from patients with PBC in the USA enrolled in the PicnicHealth cohort. Medical record-documented pruritus was classified as 'recent' (at, or within 12 months prior to, enrolment) or 'ever' (at, or any point prior to, enrolment). Patient-reported pruritus (4-week recall) was assessed using the first PBC-40 questionnaire completed on/after enrolment; pruritus severity was classified by itch domain score (any severity: ≥1; clinically significant itch: ≥7). Patient clinico-demographic characteristics and PBC-40 domain scores were described in patients with medical record-documented and patient-reported pruritus; overlap between groups was evaluated. Descriptive statistics were reported. RESULTS: Pruritus of any severity was self-reported by 200/225 (88.9%) patients enrolled; however, only 88/225 (39.1%) had recent medical record-documented pruritus. Clinically significant pruritus was self-reported by 120/225 (53.3%) patients; of these, 64/120 (53.3%) had recent medical record-documented pruritus. Patients reporting clinically significant pruritus appeared to have higher mean scores across PBC-40 domains (indicating reduced HRQoL), versus patients with no/mild patient-reported pruritus or medical-record documented pruritus. CONCLUSION: Compared with patient-reported measures, pruritus in PBC is under-recorded in medical records and is associated with lower HRQoL. Research based only on medical records underestimates the true burden of pruritus, meaning physicians may be unaware of the extent and impact of pruritus, leading to potential undertreatment.

Potentially avoidable causes of hospitalisation in people with dementia: contemporaneous associations by stage of dementia in a South London clinical cohort.

OBJECTIVES: To estimate the frequency of all-cause and ambulatory care sensitive condition (ACSCs)-related hospitalisations among individuals with dementia. In addition, to investigate differences by stage of dementia based on recorded cognitive function. SETTING: Data from a large London dementia care clinical case register, linked to a national hospitalisation database. PARTICIPANTS: Individuals aged ≥65 years with a confirmed dementia diagnosis with recorded cognitive function. OUTCOME MEASURES: Acute general hospital admissions were evaluated within 6 months of a randomly selected cognitive function score in patients with a clinical diagnosis of dementia. To evaluate associations between ACSC-related hospital admissions (overall and individual ACSCs) and stage of dementia, an ordinal regression was performed, modelling stage of dementia as the dependant variable (to facilitate efficient model selection, with no implication concerning the direction of causality). RESULTS: Of the 5294 people with dementia, 2993 (56.5%) had at least one hospitalisation during a 12-month period of evaluation, and 1192 (22.5%) had an ACSC-related admission. Proportions with an all-cause or ACSC-related hospitalisation were greater in the groups with more advanced dementia (all-cause 53.9%, 57.1% and 60.9%, p 0.002; ACSC-related 19.5%, 24.0% and 25.3%, p<0.0001 in the mild, moderate and severe groups, respectively). An ACSC-related admission was associated with 1.3-fold (95% CI 1.1 to 1.5) increased odds of more severe dementia after adjusting for demographic factors. Concerning admissions for individual ACSCs, the most common ACSC was urinary tract infection /pyelonephritis (9.8% of hospitalised patients) followed by pneumonia (7.1%); in an adjusted model, these were each associated with 1.4-fold increased odds of more severe dementia (95% CI 1.2 to 1.7 and 1.1 to 1.7, respectively). CONCLUSIONS: Potentially avoidable hospitalisations were common in people with dementia, particularly in those with greater cognitive impairment. Our results call for greater attention to the extent of cognitive status impairment, and not just dementia diagnosis, when evaluating measures to reduce the risk of potentially avoidable hospitalisations.

The Impact of Dementia on Diabetes Control: An Evaluation of HbA1c Trajectories and Care Outcomes in Linked Primary and Specialist Care Data.

OBJECTIVES: Diabetes self-care may become increasingly challenging as cognition declines. We sought to characterize glycated hemoglobin A1c (HbA1c) trajectories, markers of diabetes-related management, health care utilization, and mortality in people with preexisting type 2 diabetes (T2D) with and without dementia and based on the extent of cognitive impairment at the time of dementia diagnosis. DESIGN: Retrospective matched cohort study. SETTING AND PARTICIPANTS: 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. METHODS: Comparisons were made for HbA1c trajectories (linear mixed effects models), markers of diabetes-related management and severity at dementia diagnosis (logistic regression), mortality (Cox regression), and health care utilization (multilevel mixed effects binomial regression). RESULTS: In 725 incident dementia and 3154 matched comparators, HbA1c trajectories differed by dementia status; HbA1c increased over time for mild dementia and non-dementia, but the increase was greater in the mild dementia group; for those with moderate-severe dementia, HbA1c decreased over time. Despite individuals with dementia having increased health care utilization around the time of dementia diagnosis, they were less likely to have had routine diabetes-related management. Patients with dementia had a higher prevalence of macrovascular complications and diabetes foot morbidity at dementia diagnosis and a higher mortality risk than those without dementia; these relationships were most marked in those with moderate-severe dementia. CONCLUSIONS AND IMPLICATIONS: Our 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.

Disease burden of primary biliary cholangitis and associated pruritus based on a cross-sectional US claims analysis.

OBJECTIVE: In 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. DESIGN: This 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. RESULTS: The 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. CONCLUSION: Despite 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.

Real-world effects of medications for stroke prevention in atrial fibrillation: protocol for a UK population-based non-interventional cohort study with validation against randomised trial results.

INTRODUCTION: Patients with atrial fibrillation experience an irregular heart rate and have an increased risk of stroke; prophylactic treatment with anticoagulation medication reduces this risk. Direct-acting oral anticoagulants (DOACs) have been approved providing an alternative to vitamin K antagonists such as warfarin. There is interest from regulatory bodies on the effectiveness of medications in routine clinical practice; however, uncertainty remains regarding the suitability of non-interventional data for answering questions on drug effectiveness and on the most suitable methods to be used. In this study, we will use data from Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE)-the pivotal trial for the DOAC apixaban-to validate non-interventional methods for assessing treatment effectiveness of anticoagulants. These methods could then be applied to analyse treatment effectiveness in people excluded from or under-represented in ARISTOTLE. METHODS AND ANALYSIS: Patient characteristics from ARISTOTLE will be used to select a cohort of patients with similar baseline characteristics from two UK electronic health record (EHR) databases, Clinical Practice Research Datalink Gold and Aurum (between 1 January 2013 and 31 July 2019). Methods such as propensity score matching and coarsened exact matching will be explored in matching between EHR treatment groups to determine the optimal method of obtaining a balanced cohort.Absolute and relative risk of outcomes in the EHR trial-analogous cohort will be calculated and compared with the ARISTOTLE results; if results are deemed compatible the methods used for matching EHR treatment groups can then be used to examine drug effectiveness over a longer duration of exposure and in special patient groups of interest not studied in the trial. ETHICS AND DISSEMINATION: The study has been approved by the Independent Scientific Advisory Committee of the UK Medicines and Healthcare Products Regulatory Agency. Results will be disseminated in scientific publications and at relevant conferences.

The association between dementia severity and hospitalisation profile in a newly assessed clinical cohort: the South London and Maudsley case register.

OBJECTIVES: To evaluate the risk and common causes of hospitalisation in patients with newly diagnosed dementia and variation by severity of cognitive impairment. SETTING: We used data from a large London mental healthcare case register linked to a national hospitalisation database. PARTICIPANTS: Individuals aged ≥65 years with newly diagnosed dementia with recorded cognitive function and the catchment population within the same geography. OUTCOME MEASURES: We evaluated the risk and duration of hospitalisation in the year following a dementia diagnosis. In addition we identified the most common causes of hospitalisation and calculated age-standardised and gender-standardised admission ratios by dementia severity (mild/moderate/severe) relative to the catchment population. RESULTS: Of the 5218 patients with dementia, 2596 (49.8%) were hospitalised in the year following diagnosis. The proportion of individuals with mild, moderate and severe dementia who had a hospital admission was 47.9%, 50.8% and 51.7%, respectively (p= 0.097). Duration of hospital stay increased with dementia severity (median 2 days in mild to 4 days in severe dementia, p 0.0001). After excluding readmissions for the same cause, the most common primary hospitalisation discharge diagnoses among patients with dementia were urinary system disorders, pneumonia and fracture of femur, accounting for 15%, 10% and 6% of admissions, respectively. Overall, patients with dementia were hospitalised 30% more than the catchment population, and this trend was observed for most of the discharge diagnoses evaluated. Standardised admission ratios for urinary and respiratory disorders were higher in those with more severe dementia at diagnosis. CONCLUSIONS: Individuals with a dementia diagnosis were more likely to be hospitalised than individuals in the catchment population. The length of hospital stay increased with dementia severity. Most of the common causes of hospitalisation were more common than expected relative to the catchment population, but standardised admission ratios only varied by dementia stage for certain groups of conditions.

Trends in penicillin and macrolide resistance among pneumococci in the UK and the Republic of Ireland in relation to antibiotic sales to pharmacies and dispensing doctors.

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.

Identifying risk factors for progression to critical care admission and death among individuals with acute pancreatitis: a record linkage analysis of Scottish healthcare databases.

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.

Prevalence, risk factors, clinical consequences, and treatment of enteral feed intolerance during critical illness.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Intolerance occurs frequently during EN in critically ill patients and is associated with poorer nutrition and clinical outcomes.

The epidemiology and control of hepatitis C infection.

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.

Pneumococcal polysaccharide vaccine uptake in England, 1989-2003, prior to the introduction of a vaccination programme for older adults.

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.