The rising tide of dementia deaths: triangulation of data from three routine data sources using the Clinical Practice Research Datalink.

BACKGROUND: Dementia is currently the leading certified underlying cause of death in England. We assess how dementia recording on Office for National Statistics death certificates (ONS) corresponded to recording in general practice records (GP) and Hospital Episode Statistics (HES). METHODS: Retrospective study of deaths (2001-15) in 153 English General Practices contributing to the Clinical Practice Research Datalink, with linked ONS and HES records. RESULTS: Of 207,068 total deaths from any cause, 19,627 mentioned dementia on the death certificate with 10,253 as underlying cause; steady increases occurred from 2001 to 2015 (any mention 5.3 to 15.4 %, underlying cause 2.7 to 10 %). Including all data sources, recording of any dementia increased from 13.2 to 28.6 %. In 2015, only 53.8 % of people dying with dementia had dementia recorded on their death certificates. Among deaths mentioning dementia on the death certificate, the recording of a prior diagnosis of dementia in GP and HES rose markedly over the same period. In 2001, only 76.3 % had a prior diagnosis in GP and/or HES records; by 2015 this had risen to 95.7 %. However, over the same period the percentage of all deaths with dementia recorded in GP or HES but not mentioned on the death certificate rose from 7.9 to 13.3 %. CONCLUSIONS: Dementia recording in all data sources increased between 2001 and 2015. By 2015 the vast majority of deaths mentioning dementia had supporting evidence in primary and/or secondary care. However, death certificates were still providing an inadequate picture of the number of people dying with dementia.

Effect of pedometer-based walking interventions on long-term health outcomes: Prospective 4-year follow-up of two randomised controlled trials using routine primary care data.

BACKGROUND: Data are lacking from physical activity (PA) trials with long-term follow-up of both objectively measured PA levels and robust health outcomes. Two primary care 12-week pedometer-based walking interventions in adults and older adults (PACE-UP and PACE-Lift) found sustained objectively measured PA increases at 3 and 4 years, respectively. We aimed to evaluate trial intervention effects on long-term health outcomes relevant to walking interventions, using routine primary care data. METHODS AND FINDINGS: Randomisation was from October 2012 to November 2013 for PACE-UP participants from seven general (family) practices and October 2011 to October 2012 for PACE-Lift participants from three practices. We downloaded primary care data, masked to intervention or control status, for 1,001 PACE-UP participants aged 45-75 years, 36% (361) male, and 296 PACE-Lift participants, aged 60-75 years, 46% (138) male, who gave written informed consent, for 4-year periods following randomisation. The following new events were counted for all participants, including those with preexisting diseases (apart from diabetes, for which existing cases were excluded): nonfatal cardiovascular, total cardiovascular (including fatal), incident diabetes, depression, fractures, and falls. Intervention effects on time to first event post-randomisation were modelled using Cox regression for all outcomes, except for falls, which used negative binomial regression to allow for multiple events, adjusting for age, sex, and study. Absolute risk reductions (ARRs) and numbers needed to treat (NNTs) were estimated. Data were downloaded for 1,297 (98%) of 1,321 trial participants. Event rates were low (<20 per group) for outcomes, apart from fractures and falls. Cox hazard ratios for time to first event post-randomisation for interventions versus controls were nonfatal cardiovascular 0.24 (95% confidence interval [CI] 0.07-0.77, p = 0.02), total cardiovascular 0.34 (95% CI 0.12-0.91, p = 0.03), diabetes 0.75 (95% CI 0.42-1.36, p = 0.34), depression 0.98 (95% CI 0.46-2.07, p = 0.96), and fractures 0.56 (95% CI 0.35-0.90, p = 0.02). Negative binomial incident rate ratio for falls was 1.07 (95% CI 0.78-1.46, p = 0.67). ARR and NNT for cardiovascular events were nonfatal 1.7% (95% CI 0.5%-2.1%), NNT = 59 (95% CI 48-194); total 1.6% (95% CI 0.2%-2.2%), NNT = 61 (95% CI 46-472); and for fractures 3.6% (95% CI 0.8%-5.4%), NNT = 28 (95% CI 19-125). Main limitations were that event rates were low and only events recorded in primary care records were counted; however, any underrecording would not have differed by intervention status and so should not have led to bias. CONCLUSIONS: Routine primary care data used to assess long-term trial outcomes demonstrated significantly fewer new cardiovascular events and fractures in intervention participants at 4 years. No statistically significant differences between intervention and control groups were demonstrated for other events. Short-term primary care pedometer-based walking interventions can produce long-term health benefits and should be more widely used to help address the public health inactivity challenge. TRIAL REGISTRATIONS: PACE-UP isrctn.com ISRCTN98538934; PACE-Lift isrctn.com ISRCTN42122561.

Measuring change in trials of physical activity interventions: a comparison of self-report questionnaire and accelerometry within the PACE-UP trial.

BACKGROUND: Few trials have compared estimates of change in physical activity (PA) levels using self-reported and objective PA measures when evaluating trial outcomes. The PACE-UP trial offered the opportunity to assess this, using the self-administered International Physical Activity Questionnaire (IPAQ) and waist-worn accelerometry. METHODS: The PACE-UP trial (N = 1023) compared usual care (n = 338) with two pedometer-based walking interventions, by post (n = 339) or with nurse support (n = 346). Participants wore an accelerometer at baseline and 12 months and completed IPAQ for the same 7-day periods. Main outcomes were weekly minutes, all in ≥10 min bouts as per UK PA guidelines of: i) accelerometer moderate-to-vigorous PA (Acc-MVPA) ii) IPAQ moderate+vigorous PA (IPAQ-MVPA) and iii) IPAQ walking (IPAQ-Walk). For each outcome, 12 month values were regressed on baseline to estimate change. RESULTS: Analyses were restricted to 655 (64%) participants who provided data on all outcomes at baseline and 12 months. Both intervention groups significantly increased their accelerometry MVPA minutes/week compared with control: postal group 42 (95% CI 22, 61), nurse group 43 (95% CI 24, 63). IPAQ-Walk minutes/week also increased: postal 57 (95% CI 2, 112), nurse 43 (95% CI -11, 97) but IPAQ-MVPA minutes/week showed non-significant decreases: postal -11 (95% CI -65, 42), nurse -34 (95% CI -87, 19). CONCLUSIONS: Our results demonstrate the necessity of using a questionnaire focussing on the activities being altered, as with IPAQ-Walk questions. Even then, the change in PA was estimated with far less precision than with accelerometry. Accelerometry is preferred to self-report measurement, minimising bias and improving precision when assessing effects of a walking intervention. TRIAL REGISTRATION: ISRCTN, ISRCTN98538934 . Registered 2 March 2012.

Evaluation of reliability and validity of the General Practice Physical Activity Questionnaire (GPPAQ) in 60-74 year old primary care patients.

BACKGROUND: GPPAQ (General Practice Physical Activity Questionnaire) is a self-assessment physical activity questionnaire widely used in primary care. Reliability and validity data in older people are lacking. The study aims were: to assess GPPAQ's reliability and validity in 60-74 year olds from the PACE-Lift (Pedometer Accelerometer Consultation Evaluation-Lift) physical activity trial; and to assess whether adding brisk walking to the GPPAQ score improves its validity when assessing if physical activity guidelines are being met. METHOD: Physical activity was assessed objectively by accelerometry and by self-report GPPAQ over one week periods at baseline, and three and twelve months later, in 60-74 year old participants from three United Kingdom general practices enrolled in PACE-Lift. Reliability: GPPAQ scores in controls (n = 148) were compared for repeatability at baseline, 3 and 12 months. VALIDITY: we compared the GPPAQ "active" rating (those not requiring physical activity advice) with those achieving physical activity guidelines using accelerometry, in all baseline subjects (n = 298). Using accelerometry as an objective comparator, GPPAQ sensitivity and specificity were calculated and repeated after adding brisk walking into the GPPAQ score (GPPAQ-WALK). RESULTS: For reliability, GPPAQ showed 56 % (70/126) and 67 % (87/129) of controls scored the same at 3 and 12 months respectively, as they scored at baseline. At baseline 24 % (69/289) achieved physical activity guidelines according to accelerometry, whilst 16 % (47/289) were classified as GPPAQ "active". GPPAQ had 19 % (13/69) sensitivity and 85 % (186/220) specificity. GPPAQ-WALK had 39 % (27/69) sensitivity and 70 % (155/220) specificity. CONCLUSIONS: GPPAQ has reasonable reliability but results from this study measuring validity in older adults indicates poor agreement with objective accelerometry for accurately identifying physical activity levels. Including brisk walking in GPPAQ increased sensitivity, but reduced specificity and did not improve overall screening performance. GPPAQ's use in National Health Service health checks in primary care in this age group cannot therefore be supported by this validity study comparing to accelerometry.

Stopping long-acting beta2-agonists (LABA) for adults with asthma well controlled by LABA and inhaled corticosteroids.

BACKGROUND: Poorly controlled asthma often leads to preventable exacerbations that require additional medications, as well as unscheduled hospital and clinic visits.Long-acting beta2-agonists (LABA) are commonly given to adults with asthma whose symptoms are not well controlled by inhaled corticosteroids (ICS). US and UK regulators have issued warnings for LABA in asthma, and now recommend they be used "for the shortest duration of time required to achieve control of asthma symptoms and discontinued, if possible, once asthma control is achieved". OBJECTIVES: To compare cessation of long-acting beta2-agonists (LABA) versus continued use of LABA/inhaled corticosteroids (LABA/ICS) for adults whose asthma is well controlled, and to determine whether stopping LABA:1. results in loss of asthma control or deterioration in quality of life;2. increases the likelihood of asthma attacks or 'exacerbations'; or3. increases or decreases the likelihood of serious adverse events of any cause. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register (CAGR), www.ClinicalTrials.gov, www.who.int/ictrp/en/, reference lists of primary studies and existing reviews and manufacturers' trial registries (GlaxoSmithKline (GSK) and AstraZeneca). We searched all databases from their inception to April 2015, and we imposed no restriction on language of publication. SELECTION CRITERIA: We looked for parallel randomised controlled trials (RCTs) of at least eight weeks' duration, in which adults whose asthma was well controlled by any dose of ICS+LABA combination therapy were randomly assigned to (1) step-down therapy to ICS alone versus (2) continuation of ICS and LABA. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all records identified by the search strategy. We used an Excel extraction tool to manage searches, document reasons for inclusion and exclusion and extract descriptive and numerical data from trials meeting inclusion criteria.Prespecified primary outcomes were (1) exacerbations requiring oral steroids, (2) asthma control and (3) all-cause serious adverse events. MAIN RESULTS: Six randomised, double-blind studies between 12 and 24 weeks' long met the inclusion criteria. Five studies contributed data to the meta-analysis, assigning 2781 people with stable asthma to the comparison of interest. The definition of stable asthma and inclusion criteria varied across studies, and Global Initiative for Asthma (GINA) criteria were not used. Risk of bias across studies was generally low, and most evidence was rated as moderate quality.Stopping LABA might increase the number of people having exacerbations and requiring oral corticosteroids (odds ratio (OR) 1.74, 95% confidence interval (CI) 0.83 to 3.65; participants = 1257; studies = 4), although the confidence intervals did not exclude the possibility that stopping LABA was beneficial; over 17 weeks, 19 people per 1000 who continued their LABA had an exacerbation, compared with 32 per 1000 when LABA were stopped (13 more per 1000, 95% CI 3 fewer to 46 more).People who stopped LABA had worse scores on the Asthma Control Questionnaire (mean difference (MD) 0.24, 95% CI 0.13 to 0.35; participants = 645; studies = 3) and on measures of asthma-related quality of life (standardised mean difference (SMD) 0.36, 95% CI 0.15 to 0.57; participants = 359; studies = 2) than those who continued LABA, but the effects were not clinically relevant.Too few events occurred for investigators to tell whether stopping LABA has a greater effect on serious adverse events compared with continuing LABA+ICS (OR 0.82, 95% CI 0.28 to 2.42; participants = 1342; studies = 5), and no study reported exacerbations requiring an emergency department visit or hospitalisation as a separate outcome. Stopping LABA may result in fewer adverse events of any kind compared with continuing, although the effect was not statistically significant (OR 0.83, 95% CI 0.66 to 1.05; participants = 1339; studies = 5), and stopping LABA made people more likely to withdraw from participation in research studies (OR 1.95, 95% CI 1.47 to 2.58; participants = 1352; studies = 5). AUTHORS' CONCLUSIONS: This review suggests that stopping LABA in adults who have stable asthma while they are taking a combination of LABA and ICS inhalers may increase the likelihood of asthma exacerbations that require treatment with oral corticosteroids, but this is not certain. Stopping LABA may slightly reduce asthma control and quality of life, but evidence was insufficient to show whether this had an effect on important outcomes such as serious adverse events and exacerbations requiring hospital admission, and longer trials are warranted. Trialists should include patient-important outcomes such as asthma control and quality of life and should use validated measurement tools. Definitions of exacerbations should be provided.

Stopping long-acting beta2-agonists (LABA) for children with asthma well controlled on LABA and inhaled corticosteroids.

BACKGROUND: Asthma is the most common chronic medical condition among children and is one of the most common causes of hospitalisation and medical visits. Poorly controlled asthma often leads to preventable exacerbations that require additional medications, hospital stays, or treatment in the emergency department.Long-acting beta2-agonists (LABA) are the preferred add-on treatment for children with asthma whose symptoms are not well controlled on inhaled corticosteroids (ICS). The US Food and Drug Administration has issued a 'black box' warning for LABA in asthma, and now recommends that they be used "for the shortest duration of time required to achieve control of asthma symptoms and discontinued, if possible, once asthma control is achieved". OBJECTIVES: To compare the effect on asthma control and adverse effects of stepping down to inhaled corticosteroids (ICS)-only therapy versus continuing ICS plus LABA in children whose asthma is well controlled on combined ICS and LABA therapy. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register, and also searched www.ClinicalTrials.gov, www.who.int/ictrp/en/, reference lists of primary studies and existing reviews, and manufacturers' trial registries (GlaxoSmithKline and AstraZeneca). We searched all databases from their inception to the present, and imposed no restriction on language of publication. The most recent search was done in April 2015. SELECTION CRITERIA: We looked for parallel randomised controlled trials of at least eight weeks' duration, available as published full text, abstract only, or unpublished data. We excluded studies including participants with other chronic respiratory comorbidities (for example bronchiectasis).We looked for studies in which children (18 years or younger) whose asthma was well controlled on any dose of ICS and LABA combination therapy were randomised to: a) step-down therapy to ICS alone or b) continued use of ICS and LABA.We included any dose of LABA (formoterol, salmeterol, vilanterol) and any dose of ICS (beclomethasone, budesonide, ciclesonide, mometasone, flunisolide, fluticasone propionate, fluticasone furoate, triamcinolone) delivered in a combination inhaler or in separate inhalers. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all records identified in the searches. We used a data extraction tool in Microsoft Excel to manage searches and document reasons for inclusion and exclusion, and to extract descriptive and numerical data from trials meeting the inclusion criteria.The prespecified primary outcomes were exacerbations requiring oral steroids, asthma control, and all-cause serious adverse events. MAIN RESULTS: Despite conducting extensive searches of electronic databases, trial registries and manufacturers' websites we identified no trials matching the inclusion criteria.After removing duplicates, we screened 1031 abstracts, and assessed 43 full-text articles for inclusion. We identified several adult studies, which will be summarised in a separate review (Ahmad 2014). The most common reasons for exclusion after viewing full texts were 'wrong comparison' (n = 22) and 'adult population' (n = 18).Some adult studies recruited adolescents from age 15, but none reported data separately for those under 18. AUTHORS' CONCLUSIONS: There is currently no evidence from randomised trials to inform the discontinuation of LABAs in children once asthma control is achieved with ICS plus LABA. It is disappointing that such an important issue has not been studied, and a randomised double-blind trial recruiting children who are controlled on ICS plus LABA is warranted. The study should be large enough to assess children of different ages, and to measure the important safety and efficacy outcomes suggested in this review over at least six months.The only randomised evidence for stopping LABA has been conducted in adults; it will be summarised in a separate review.