Predicting dementia risk in primary care: development and validation of the Dementia Risk Score using routinely collected data.

BACKGROUND: Existing dementia risk scores require collection of additional data from patients, limiting their use in practice. Routinely collected healthcare data have the potential to assess dementia risk without the need to collect further information. Our objective was to develop and validate a 5-year dementia risk score derived from primary healthcare data. METHODS: We used data from general practices in The Health Improvement Network (THIN) database from across the UK, randomly selecting 377 practices for a development cohort and identifying 930,395 patients aged 60-95 years without a recording of dementia, cognitive impairment or memory symptoms at baseline. We developed risk algorithm models for two age groups (60-79 and 80-95 years). An external validation was conducted by validating the model on a separate cohort of 264,224 patients from 95 randomly chosen THIN practices that did not contribute to the development cohort. Our main outcome was 5-year risk of first recorded dementia diagnosis. Potential predictors included sociodemographic, cardiovascular, lifestyle and mental health variables. RESULTS: Dementia incidence was 1.88 (95% CI, 1.83-1.93) and 16.53 (95% CI, 16.15-16.92) per 1000 PYAR for those aged 60-79 (n = 6017) and 80-95 years (n = 7104), respectively. Predictors for those aged 60-79 included age, sex, social deprivation, smoking, BMI, heavy alcohol use, anti-hypertensive drugs, diabetes, stroke/TIA, atrial fibrillation, aspirin, depression. The discrimination and calibration of the risk algorithm were good for the 60-79 years model; D statistic 2.03 (95% CI, 1.95-2.11), C index 0.84 (95% CI, 0.81-0.87), and calibration slope 0.98 (95% CI, 0.93-1.02). The algorithm had a high negative predictive value, but lower positive predictive value at most risk thresholds. Discrimination and calibration were poor for the 80-95 years model. CONCLUSIONS: Routinely collected data predicts 5-year risk of recorded diagnosis of dementia for those aged 60-79, but not those aged 80+. This algorithm can identify higher risk populations for dementia in primary care. The risk score has a high negative predictive value and may be most helpful in 'ruling out' those at very low risk from further testing or intensive preventative activities.

Prescribing of neuraminidase inhibitors for influenza in UK primary care since the 2009 pandemic.

We determined prescribing rates of neuraminidase inhibitors (NIs) for influenza in UK primary care since 2009 in relation to national prescribing guidelines. All NI prescriptions issued during the influenza seasons between October 2010 and May 2013 were extracted from The Health Improvement Network (THIN), a large UK primary-care database. We calculated NI prescribing rates per 100,000 person-weeks (pw) by age group, sex, deprivation level, influenza season and presence of chronic conditions with 95% confidence intervals (CIs), and used negative binomial regression models to determine the independent association between these variables and NI prescribing. NI prescribing was rare. The prescribing rate was 1·7/100,000 pw (95% CI 1·7-1·8) during influenza-active periods, and 0·1/100,000 (95% CI 0·1-0·1) during non-active periods. Prescribing rates were highest in 25- to 44-year-olds in 2010/2011 and in persons aged ⩾85 years in 2011/2012 and 2012/2013. Individuals with chronic conditions had significantly higher prescribing rates than persons without (rate ratio 2·62, 95% CI 2·27-3·03). GPs are more likely to prescribe NIs to high-risk individuals and during influenza active periods, as per national guidelines. We could not assess the proportion of patients with influenza-like illness who were prescribed an NI.

Screening for dementia--is it a no brainer?

As people are living longer, dementia is becoming a significant issue for society. Dementia is now recognised as a major concern in society, and the numbers of people estimated to have dementia in the UK population appear to have stabilised at around 700,000 . Globally, 35.6 million people are estimated to meet criteria for dementia, a number predicted to double every 20 years . Given the absence of treatments that significantly alter the natural history of the clinical syndrome of dementia, there has been increased emphasis on early diagnosis, with research exploring assessment tools and biomarkers that might predict with certainty a particular clinical outcome. At the same time, there has been pressure to focus on biomedical profiles, which assume a very close link between the pathobiology and the manifest clinical syndrome.

Trends in HIV testing and recording of HIV status in the UK primary care setting: a retrospective cohort study 1995-2005.

OBJECTIVES: To provide nationally representative data on trends in HIV testing in primary care and to estimate the proportion of diagnosed HIV positive individuals known to general practitioners (GPs). METHODS: We undertook a retrospective cohort study between 1995 and 2005 of all general practices contributing data to the UK General Practice Research Database (GPRD), and data on persons accessing HIV care (Survey of Prevalent HIV Infections Diagnosed). We identified all practice-registered patients where an HIV test or HIV positive status is recorded in their general practice records. HIV testing in primary care and prevalence of recorded HIV positive status in primary care were estimated. RESULTS: Despite 11-fold increases in male testing and 19-fold increases in non-pregnant female testing between 1995 and 2005, HIV testing rates remained low in 2005 at 71.3 and 61.2 tests per 100,000 person years for males and females, respectively, peaking at 162.5 and 173.8 per 100,000 person years at 25-34 years of age. Inclusion of antenatal tests yielded a 129-fold increase in women over the 10-year period. In 2005, 50.7% of HIV positive individuals had their diagnosis recorded with a lower proportion in London (41.8%) than outside the capital (60.1%). CONCLUSION: HIV testing rates in primary care remain low. Normalisation of HIV testing and recording in primary care in antenatal testing has not been accompanied by a step change in wider HIV testing practice. Recording of HIV positive status by GPs remains low and GPs may be unaware of HIV-related morbidity or potential drug interactions.

Primary care consultations and costs among HIV-positive individuals in UK primary care 1995-2005: a cohort study.

OBJECTIVES: To investigate the role of primary care in the management of HIV and estimate primary care-associated costs at a time of rising prevalence. METHODS: Retrospective cohort study between 1995 and 2005, using data from general practices contributing data to the UK General Practice Research Database. Patterns of consultation and morbidity and associated consultation costs were analysed among all practice-registered patients for whom HIV-positive status was recorded in the general practice record. RESULTS: 348 practices yielded 5504 person-years (py) of follow-up for known HIV-positive patients, who consult in general practice frequently (4.2 consultations/py by men, 5.2 consultations/py by women, in 2005) for a range of conditions. Consultation rates declined in the late 1990s from 5.0 and 7.3 consultations/py in 1995 in men and women, respectively, converging to rates similar to the wider population. Costs of consultation (general practitioner and nurse, combined) reflect these changes, at pound100.27 for male patients and pound117.08 for female patients in 2005. Approximately one in six medications prescribed in primary care for HIV-positive individuals has the potential for major interaction with antiretroviral medications. CONCLUSION: HIV-positive individuals known in general practice now consult on a similar scale to the wider population. Further research should be undertaken to explore how primary care can best contribute to improving the health outcomes of this group with chronic illness. Their substantial use of primary care suggests there may be potential to develop effective integrated care pathways.

Biliary tract infection and bacteraemia: presentation, structural abnormalities, causative organisms and clinical outcomes.

BACKGROUND: Biliary tract infection is a common cause of bacteraemia and is associated with high morbidity and mortality. Few papers describe blood culture isolates, underlying structural abnormalities and clinical outcomes in patients with bacteraemia. AIMS: To determine the proportion of bacteraemias caused by biliary tract infection and to describe patient demographics, underlying structural abnormalities and clinical outcomes in patients with bacteraemia. DESIGN: Prospective cohort study. METHODS: Biliary tract infection that caused bacteraemia was defined as a compatible clinical syndrome and a blood culture isolate consistent with ascending cholangitis. Patients aged 16 years and over were included in the study. From June 2003 to May 2005, demographic and clinical data were collected prospectively on all adult patients with bacteraemia. Radiological and endoscopic retrograde cholangiopancreatography findings were collected retrospectively. RESULTS: In 49 patients, the biliary tract was the site of infection for 39/592 (6.6%) community-acquired and 19/466 (4.1%) hospital-acquired episodes of bacteraemia. Three patients had mixed bacteraemias, and four had recurrent bacteraemia. The proportion of patients presenting with a structural abnormality was 34/49 (69%), and, of these structural abnormalities, 18/34 (53%) were pre-existing or newly diagnosed malignancies. Gram-negative organisms caused 55/58 (95%) episodes of bacteraemia. The most common Gram-negative organisms were Escherichia coli (34/55; 62%) and Klebsiella pneumoniae (14/55; 26%). Of the E coli isolates, 6/34 (18%) were extended spectrum beta-lactamase producers or multiply drug resistant. Thirty-day mortality was 7/49 (14%). There was no difference in time taken to administer an effective antibiotic to survivors and non-survivors (0.86 vs 1.05 days, respectively, p = 0.92). Of the seven who died, four died from septic shock within 48 h of admission caused by "susceptible" Gram-negative organisms. Two others died from disseminated malignancy. CONCLUSIONS: The proportion of bacteraemias caused by biliary tract infection was 5.5%. The most common infecting organisms were E coli and K pneumoniae. There was a strong association with choledocholithiasis and malignancies, both pre-existing and newly diagnosed. Death was uncommon but when it occurred was often caused by septic shock within 48 h of presentation.

A case-control study comparing the incidence of early symptoms in pancreatic and biliary tract cancer.

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancers (BTC) are often diagnosed late and at an advanced stage. Population-based screening programmes do not exist and diagnosis is primarily dependent on symptom recognition. Recently symptom-based cancer decision support tools (CDSTs) have been introduced into primary care practices throughout the UK to support general practitioners (GPs) in identifying patients with suspected PDAC. However, future refinement of these tools to improve their diagnostic accuracy is likely to be necessary. SETTING: The Health Improvement Network (THIN) is a primary care database, which includes more than 11 million electronic patient records, from 562 GP practices in the UK. PARTICIPANTS: All patients with a diagnosis of PDAC or BTC between 2000 and 2010 were included in the study along with six matched controls; 2773 patients with PDAC, 848 patients with BTC and 15,395 controls. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary aim of this study was to determine the early symptom profiles of PDAC and BTC. Secondary aims included comparing early symptom trends between BTC and PDAC, defining symptom onset in PDAC and evaluating trends in routine blood tests nearest to the time of diagnosis. RESULTS: In the year prior to diagnosis, patients with PDAC visited their GP on a median of 18 (IQR 11-27) occasions. PDAC was associated with 11 alarm symptoms and BTC with 8. Back pain (OR 1.33 (95% CI 1.18 to 1.49) p<0.001), lethargy (1.42 (95% CI 1.25 to 1.62) p<0.001) and new onset diabetes (OR 2.46 (95% CI 2.16 to 2.80)) were identified as unique features of PDAC. CONCLUSIONS: PDAC and BTC are associated with numerous early alarm symptoms. CDSTs are therefore likely to be useful in identifying these tumours at an early stage. Inclusion of unique symptoms, symptoms with an early onset and routinely performed blood tests is likely to further improve the sensitivity of these tools.

Strategies to improve retention in randomised trials: a Cochrane systematic review and meta-analysis.

OBJECTIVE: To quantify the effect of strategies to improve retention in randomised trials. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Sources searched: MEDLINE, EMBASE, PsycINFO, DARE, CENTRAL, CINAHL, C2-SPECTR, ERIC, PreMEDLINE, Cochrane Methodology Register, Current Controlled Trials metaRegister, WHO trials platform, Society for Clinical Trials (SCT) conference proceedings and a survey of all UK clinical trial research units. REVIEW METHODS: Included trials were randomised evaluations of strategies to improve retention embedded within host randomised trials. The primary outcome was retention of trial participants. Data from trials were pooled using the fixed-effect model. Subgroup analyses were used to explore the heterogeneity and to determine whether there were any differences in effect by the type of strategy. RESULTS: 38 retention trials were identified. Six broad types of strategies were evaluated. Strategies that increased postal questionnaire responses were: adding, that is, giving a monetary incentive (RR 1.18; 95% CI 1.09 to 1.28) and higher valued incentives (RR 1.12; 95% CI 1.04 to 1.22). Offering a monetary incentive, that is, an incentive given on receipt of a completed questionnaire, also increased electronic questionnaire response (RR 1.25; 95% CI 1.14 to 1.38). The evidence for shorter questionnaires (RR 1.04; 95% CI 1.00 to 1.08) and questionnaires relevant to the disease/condition (RR 1.07; 95% CI 1.01 to 1.14) is less clear. On the basis of the results of single trials, the following strategies appeared effective at increasing questionnaire response: recorded delivery of questionnaires (RR 2.08; 95% CI 1.11 to 3.87); a 'package' of postal communication strategies (RR 1.43; 95% CI 1.22 to 1.67) and an open trial design (RR 1.37; 95% CI 1.16 to 1.63). There is no good evidence that the following strategies impact on trial response/retention: adding a non-monetary incentive (RR=1.00; 95% CI 0.98 to 1.02); offering a non-monetary incentive (RR=0.99; 95% CI 0.95 to 1.03); 'enhanced' letters (RR=1.01; 95% CI 0.97 to 1.05); monetary incentives compared with offering prize draw entry (RR=1.04; 95% CI 0.91 to 1.19); priority postal delivery (RR=1.02; 95% CI 0.95 to 1.09); behavioural motivational strategies (RR=1.08; 95% CI 0.93 to 1.24); additional reminders to participants (RR=1.03; 95% CI 0.99 to 1.06) and questionnaire question order (RR=1.00, 0.97 to 1.02). Also based on single trials, these strategies do not appear effective: a telephone survey compared with a monetary incentive plus questionnaire (RR=1.08; 95% CI 0.94 to 1.24); offering a charity donation (RR=1.02, 95% CI 0.78 to 1.32); sending sites reminders (RR=0.96; 95% CI 0.83 to 1.11); sending questionnaires early (RR=1.10; 95% CI 0.96 to 1.26); longer and clearer questionnaires (RR=1.01, 0.95 to 1.07) and participant case management by trial assistants (RR=1.00; 95% CI 0.97 to 1.04). CONCLUSIONS: Most of the trials evaluated questionnaire response rather than ways to improve participants return to site for follow-up. Monetary incentives and offers of monetary incentives increase postal and electronic questionnaire response. Some strategies need further evaluation. Application of these results would depend on trial context and follow-up procedures.

Use of strategies to improve retention in primary care randomised trials: a qualitative study with in-depth interviews.

OBJECTIVE: To explore the strategies used to improve retention in primary care randomised trials. DESIGN: Qualitative in-depth interviews and thematic analysis. PARTICIPANTS: 29 UK primary care chief and principal investigators, trial managers and research nurses. METHODS: In-depth face-to-face interviews. RESULTS: Primary care researchers use incentive and communication strategies to improve retention in trials, but were unsure of their effect. Small monetary incentives were used to increase response to postal questionnaires. Non-monetary incentives were used although there was scepticism about the impact of these on retention. Nurses routinely used telephone communication to encourage participants to return for trial follow-up. Trial managers used first class post, shorter questionnaires and improved questionnaire designs with the aim of improving questionnaire response. Interviewees thought an open trial design could lead to biased results and were negative about using behavioural strategies to improve retention. There was consensus among the interviewees that effective communication and rapport with participants, participant altruism, respect for participant's time, flexibility of trial personnel and appointment schedules and trial information improve retention. Interviewees noted particular challenges with retention in mental health trials and those involving teenagers. CONCLUSIONS: The findings of this qualitative study have allowed us to reflect on research practice around retention and highlight a gap between such practice and current evidence. Interviewees describe acting from experience without evidence from the literature, which supports the use of small monetary incentives to improve the questionnaire response. No such evidence exists for non-monetary incentives or first class post, use of which may need reconsideration. An exploration of barriers and facilitators to retention in other research contexts may be justified.

Computer-based interventions for sexual health promotion: systematic review and meta-analyses.

This systematic review was conducted to determine the effects of self-help interactive computer-based interventions (ICBIs) for sexual health promotion. We searched 40 databases for randomized controlled trials (RCTs) of computer-based interventions, defining 'interactive' as programmes that require contributions from users to produce personally relevant material. We conducted searches and analysed data using Cochrane Collaboration methods. Results of RCTs were pooled using a random-effects model with standardized mean differences for continuous outcomes and odds ratios (ORs) for binary outcomes, with heterogeneity assessed using the I(2) statistic. We identified 15 RCTs of ICBIs (3917 participants). Comparing ICBIs to minimal interventions, there were significant effects on sexual health knowledge (standardized mean difference [SMD] 0.72, 95% confidence interval [CI] 0.27-1.18); safer sex self-efficacy (SMD 0.17, 95% CI 0.05-0.29); safer-sex intentions (SMD 0.16, 95% CI 0.02-0.30); and sexual behaviour (OR 1.75, 95% CI 1.18-2.59). ICBIs had a greater impact on sexual health knowledge than face-to-face interventions did (SMD 0.36, 95% CI 0.13-0.58). ICBIs are effective tools for learning about sexual health, and show promising effects on self-efficacy, intention and sexual behaviour. More data are needed to analyse biological outcomes and cost-effectiveness.

Trials in primary care: statistical issues in the design, conduct and evaluation of complex interventions.

Trials carried out in primary care typically involve complex interventions that require considerable planning if they are to be implemented successfully. The role of the statistician in promoting both robust study design and appropriate statistical analysis is an important contribution to a multi-disciplinary primary care research group. Issues in the design of complex interventions have been addressed in the Medical Research Council's new guidance document and over the past 7 years by the Royal Statistical Society's Primary Health Care Study Group. With the aim of raising the profile of statistics and building research capability in this area, particularly with respect to methodological issues, the study group meetings have covered a wide range of topics that have been of interest to statisticians and non-statisticians alike. The aim of this article is to provide an overview of the statistical issues that have arisen over the years related to the design and evaluation of trials in primary care, to provide useful examples and references for further study and ultimately to promote good practice in the conduct of complex interventions carried out in primary care and other health care settings. Throughout we have given particular emphasis to statistical issues related to the design of cluster randomised trials.

Beliefs about the causes of osteoarthritis among primary care patients.

OBJECTIVE: Beliefs about the causes of osteoarthritis (OA) have been examined infrequently. The purpose of this study was to provide insight into patients' beliefs about the causes of OA in a primary care population. METHODS: This study involved 31 individuals with OA who were purposively sampled to reflect age, sex, and self-efficacy scores from the intervention arm of a randomized controlled trial examining the effectiveness of an arthritis self-management program in primary care. Participants took part in face-to-face interviews. Data were analyzed using interpretative phenomenologic analysis. RESULTS: A total of 31 patients with OA (17 [55%] men) with a median age of 68 years (range 56-84 years) were recruited. OA and painful joints were considered to be an inevitable aspect of aging rather than an indication of disease. Participants attributed the cause of OA to multiple factors, the most commonly reported being wear and tear. CONCLUSION: Insight into beliefs about the causes of OA among older people may help explain attitudes towards the uptake of health care among this group of patients.

Appreciating background and culture: the South Asian elderly and mental health.

In the next decade there will be an increase in the number of elderly people from a South Asian background. All too often minority groups are treated as homogeneous, leading to inappropriate generalisations, unmet need, and unsuitable treatment and management. In order to understand and manage a person's illness it is necessary to appreciate the effects of their culture, experiences and environment. The South Asian community is well established in the UK and the attitudes of the growing elderly population towards mental illness, their expressions of distress, and views on management and treatment are only now being canvassed. Awareness of these issues is essential before epidemiological studies of depression and dementia and use of health services by this group will provide beneficial results.

Validating screening instruments for cognitive impairment in older South Asians in the United Kingdom.

BACKGROUND: The numbers of older South Asians in the United Kingdom are rising. Investigation of their mental health has been neglected compared to their physical health. OBJECTIVES: This study aimed to determine the sensitivity and specificity of modified versions of two screening instruments for cognitive impairment (Mini-Mental State Examination and Abbreviated Mental Test) in a community-based population. DESIGN: Two-stage study comparing screening instruments against diagnostic interview. SETTING: South, central and north Manchester. SUBJECTS: Community-resident South Asians aged 60 years and over. METHODS: Subjects were approached via their general practitioners and interviewed at home. Sensitivity and specificity for the screening instruments were calculated using receiver operating characteristic (ROC) curve analysis. RESULTS: For the Gujarati population, the MMSE cutoff was >/=24 (sensitivity 100%, specificity 95%) and AMT>/=6 (sensitivity 100%, specificity 95%). For the Pakistani population, the MMSE cutoff was >/=27 (sensitivity 100%, specificity 77%) and AMT>/=7 (sensitivity 100%, specificity 87%). CONCLUSIONS: Culturally modified versions of the Mini-Mental State Examination and Abbreviated Mental Test are acceptable and may have a high degree of sensitivity. They may assist with the recognition of cognitive impairment, if an appropriate cutoff is used.

Screening for cognitive impairment in older African-Caribbeans.

BACKGROUND: There are increasing numbers of older African-Caribbeans in the United Kingdom. Screening instruments are commonly used in the detection of cognitive impairment, but have not been assessed within this population. This study aimed to develop culturally modified versions of screening instruments for cognitive impairment (Mini-Mental State Examination (MMSE) and Abbreviated Mental Test (AMT)) and to determine their sensitivity and specificity in the diagnosis of dementia. METHODS: The instruments were modified using a process involving a community group of African-Caribbeans and an academic group of health professionals. They were used in a two-stage study involving community resident African-Caribbeans aged 60 years or over in inner-city Manchester, comparing the screening instruments against a computerized diagnostic interview. RESULTS: One hundred and thirty people completed the study. The results for the largest subgroup, the Jamaicans (N = 96) were analysed. Effects of gender, age and education on the MMSE and AMT scores were evaluated. The correlations between the screening instruments and diagnostic interview were highly significant (P < 0.001). At appropriate cut-offs both screening instruments demonstrated high sensitivity and acceptable specificity levels. CONCLUSIONS: A defined process with lay input has assisted in producing culturally modified versions of the MMSE and AMT that perform well compared with a diagnostic interview, if an appropriate cut-off is used. They are easy to administer and acceptable to older African-Caribbean people. The results need to be viewed within the limitations of the current study.

Screening for depression in African-Caribbean elders.

BACKGROUND: There are increasing numbers of older African-Caribbeans in the UK. Primary care staff often feel less confident about diagnosing depression in this group. Screening instruments may assist in making diagnoses in cross-cultural consultations. OBJECTIVE: We aimed to determine the sensitivity and specificity of screening instruments for depression in older African-Caribbean people in Manchester, UK. METHODS: We carried out a two-stage study to compare three screening instruments for depression (Geriatric Depression Scale, Brief Assessment Schedule Depression Cards, Caribbean Culture Specific Screen), with a computerized diagnostic interview for mental health disorders in older adults (Geriatric Mental State). The study was set in inner-city Manchester. The subjects were community-resident African-Caribbeans aged 60 years and over; 227 subjects were approached. Of the 160 people screened, 130 agreed to diagnostic interview. The main outcome measures were Spearman correlation coefficients; these were calculated between each screening instrument and the diagnostic interview. Receiver-operating characteristic (ROC) curve analysis was used to determine appropriate sensitivity and specificity for each instrument. RESULTS: The results for the largest subgroup, the Jamaicans (n = 96/130), demonstrated highly significant correlations between screening instruments and diagnostic interview (P < 0.001). Each instrument had a high sensitivity: Brief Assessment Schedule depression cards (cut-off > or =6; sensitivity 90.9% (95% CI 58.8-99.8), specificity 82.1% (95% CI 74.0-90.3)), Caribbean Culture Specific Screen (cut-off > or =6; sensitivity 90.9% (95% CI 58.8-99.8), specificity 74.1% (95% CI 64.8-83.4)), and Geriatric Depression Scale (cut-off > or =4; sensitivity 100% (95% CI 97.1-100), specificity 69.1% (95% CI 59.6-79.2)). CONCLUSIONS: These screening instruments demonstrate high sensitivity levels, if an appropriate cut-off point is used. The culture-specific instrument did not perform better than the traditional instruments. Health professionals should approach the consultation in a culturally sensitive manner and use the validated instrument they are most familiar with.