M Sayeed Haque

Effect of Self-monitoring and Medication Self-titration on Systolic Blood Pressure in Hypertensive Patients at High Risk of Cardiovascular Disease The TASMIN-SR Randomized Clinical Trial

IMPORTANCE Self-monitoring of blood pressure with self-titration of antihypertensives (self-management) results in lower blood pressure in patients with hypertension, but there are no data about patients in high-risk groups. OBJECTIVE To determine the effect of self-monitoring with self-titration of antihypertensive medication compared with usual care on systolic blood pressure among patients with cardiovascular disease, diabetes, or chronic kidney disease. DESIGN, SETTING, AND PATIENTS A primary care, unblinded, randomized clinical trial involving 552 patients who were aged at least 35 years with a history of stroke, coronary heart disease, diabetes, or chronic kidney disease and with baseline blood pressure of at least 130/80 mm Hg being treated at 59 UK primary care practices was conducted between March 2011 and January 2013. INTERVENTIONS Self-monitoring of blood pressure combined with an individualized self-titration algorithm. During the study period, the office visit blood pressure measurement target was 130/80 mm Hg and the home measurement target was 120/75 mm Hg. Control patients received usual care consisting of seeing their health care clinician for routine blood pressure measurement and adjustment of medication if necessary. MAIN OUTCOMES AND MEASURES The primary outcome was the difference in systolic blood pressure between intervention and control groups at the 12-month office visit. RESULTS Primary outcome data were available from 450 patients (81%). The mean baseline blood pressure was 143.1/80.5 mm Hg in the intervention group and 143.6/79.5 mm Hg in the control group. After 12 months, the mean blood pressure had decreased to 128.2/73.8 mm Hg in the intervention group and to 137.8/76.3 mm Hg in the control group, a difference of 9.2 mm Hg (95% CI, 5.7-12.7) in systolic and 3.4 mm Hg (95% CI, 1.8-5.0) in diastolic blood pressure following correction for baseline blood pressure. Multiple imputation for missing values gave similar results: the mean baseline was 143.5/80.2 mm Hg in the intervention group vs 144.2/79.9 mm Hg in the control group, and at 12 months, the mean was 128.6/73.6 mm Hg in the intervention group vs 138.2/76.4 mm Hg in the control group, with a difference of 8.8 mm Hg (95% CI, 4.9-12.7) for systolic and 3.1 mm Hg (95% CI, 0.7-5.5) for diastolic blood pressure between groups. These results were comparable in all subgroups, without excessive adverse events. CONCLUSIONS AND RELEVANCE Among patients with hypertension at high risk of cardiovascular disease, self-monitoring with self-titration of antihypertensive medication compared with usual care resulted in lower systolic blood pressure at 12 months. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN87171227.

Interleukin-6 promoter polymorphism: risk and pathology of Alzheimer's disease

Inflammatory and immune responses are involved in the pathogenesis of Alzheimers disease (AD). Interleukin-6 (IL-6), an inflammatory cytokine, is thought to play a role in neurodegeneration of the central nervous system and has been associated with increased amyloid precursor protein expression in vitro and greater cognitive decline. Previously a C-174G polymorphism in the promoter of IL-6, which influences expression in vitro, has been found associated in some studies but not all. We investigated this polymorphism in a large independent UK sample of AD cases (n = 356) and controls (n 434) but found no association. We extended the study to genotype/phenotype correlations but found no correlation with age of onset (n = 338), brain amyloid load (n = 126) or Tau load (n = 101), brain microglial cell load (n = 65) or brain reactive astrocytes (n = 127). Our data do not support a pathogenic role in AD for the C-174G polymorphism in isolation.

Insight, Social Knowledge and Working Memory in Schizophrenia

Background: There is evidence that insight and social judgements are impaired in schizophrenia. The influence of these factors on the decision to treat compulsorily in schizophrenia is poorly understood. Aims: To investigate the contribution of insight, social knowledge, and working memory to the determination to treat coercively in schizophrenia. Method: Insight rating scale, social knowledge questionnaire and working memory tests were administered to detained patients with schizophrenia. Results were compared with those of a control group of voluntary in-patients with schizophrenia. Results: Detained patients scored worse on insight and social knowledge, yet there was no significant correlation between these scores. There was no significant difference in severity of psychopathology between the experimental and control groups. Results for working memory were inconclusive. Conclusion: Insight and social knowledge are significantly, but independently, associated with the determination to treat coercively in schizophrenia. This suggests that insight and social knowledge are distinct skills. The contribution of working memory remains unclear.

Targets and self-management for the control of blood pressure in stroke and at risk groups (TASMIN-SR): protocol for a randomised controlled trial

BackgroundSelf-monitoring of hypertension with self-titration of antihypertensives (self-management) results in lower systolic blood pressure for at least one year. However, few people in high risk groups have been evaluated to date and previous work suggests a smaller effect size in these groups. This trial therefore aims to assess the added value of self-management in high risk groups over and above usual care.Methods/DesignThe targets and self-management for the control of blood pressure in stroke and at risk groups (TASMIN-SR) trial will be a pragmatic primary care based, unblinded, randomised controlled trial of self-management of blood pressure (BP) compared to usual care. Eligible patients will have a history of stroke, coronary heart disease, diabetes or chronic kidney disease and will be recruited from primary care. Participants will be individually randomised to either usual care or self-management. The primary outcome of the trial will be difference in office SBP between intervention and control groups at 12 months adjusted for baseline SBP and covariates. 540 patients will be sufficient to detect a difference in SBP between self-management and usual care of 5 mmHg with 90% power. Secondary outcomes will include self-efficacy, lifestyle behaviours, health-related quality of life and adverse events. An economic analysis will consider both within trial costs and a model extrapolating the results thereafter. A qualitative analysis will gain insights into patients’ views, experiences and decision making processes.DiscussionThe results of the trial will be directly applicable to primary care in the UK. If successful, self-management of blood pressure in people with stroke and other high risk conditions would be applicable to many hundreds of thousands of individuals in the UK and beyond.Trial RegistrationISRCTN87171227

Cost-effectiveness of self-management of blood pressure in hypertensive patients over 70 years with suboptimal control and established cardiovascular disease or additional cardiovascular risk diseases (TASMIN-SR)

Background A previous economic analysis of self-management, that is, self-monitoring with self-titration of antihypertensive medication evaluated cost-effectiveness among patients with uncomplicated hypertension. This study considered cost-effectiveness of self-management in those with raised blood pressure plus diabetes, chronic kidney disease and/or previous cardiovascular disease. Design and methods A Markov model-based economic evaluation was undertaken to estimate the long-term cost-effectiveness of self-management of blood pressure in a cohort of 70-year-old ‘high risk’ patients, compared with usual care. The model used the results of the TASMIN-SR trial. A cost–utility analysis was undertaken from a UK health and social care perspective, taking into account lifetime costs of treatment, cardiovascular events and quality adjusted life years. A subgroup analysis ran the model separately for men and women. Deterministic sensitivity analyses examined the effect of different time horizons and reduced effectiveness of self-management. Results Base-case results indicated that self-management was cost-effective compared with usual care, resulting in more quality adjusted life years (0.21) and cost savings (–£830) per patient. There was a 99% chance of the intervention being cost-effective at a willingness to pay threshold of £20,000 per quality adjusted life year gained. Similar results were found for separate cohorts of men and women. The results were robust to sensitivity analyses, provided that the blood pressure lowering effect of self-management was maintained for more than a year. Conclusion Self-management of blood pressure in high-risk people with poorly controlled hypertension not only reduces blood pressure, compared with usual care, but also represents a cost-effective use of healthcare resources.

The role of social deprivation in severe neovascular age-related macular degeneration

Background/aims Advances in therapy have improved outcomes for patients with neovascular age-related macular degeneration (nAMD). Prompt access to treatment is a priority and may be used as a key performance indicator. In this study, we investigate how social deprivation may impact on access to services, treatment and visual impairment registration. Methods Patients were identified retrospectively through the Certificate of Visual Impairment system for the University Hospitals Birmingham Medical Retina service. The Index of Multiple Deprivation (IMD) 2007 score was calculated for each patient. The impact of deprivation, age, gender and ethnicity on key stages in the care pathway was assessed. Results 120 patients were identified. Patients with greater social deprivation were under-represented, had worse visual acuity at first presentation (correlation of the better-seeing eye with IMD 0.225 (p=0.013)) and had sight-impairment registration earlier (correlation −0.246; p=0.007). Deprivation did not affect time to first appointment, and was not associated with a higher rate of non-attendance. Conclusions The late presentation and under-representation of patients with greater social deprivation is a serious concern. Our study strongly suggests that this vulnerable group is encountering barriers in accessing treatment in nAMD, and that these occur prior to entry into the Hospital Eye Service.

Influence of ethnicity on acceptability of method of blood pressure monitoring: a cross-sectional study in primary care

Background Ambulatory and/or home monitoring are recommended in the UK and the US for the diagnosis of hypertension but little is known about their acceptability. Aim To determine the acceptability of different methods of measuring blood pressure to people from different minority ethnic groups. Design and setting Cross-sectional study with focus groups in primary care in the West Midlands. Method People of different ethnicities with and without hypertension were assessed for acceptability of clinic, home, and ambulatory blood pressure measurement using completion rate, questionnaire, and focus groups. Results A total of 770 participants were included, who were white British (n = 300), South Asian (n = 241), and African Caribbean (n = 229). White British participants had significantly higher successful completion rates across all monitoring modalities compared with the other ethnic groups, especially for ambulatory monitoring: white British (n = 277, 92% [95% confidence interval [CI] = 89% to 95%]) versus South Asian (n = 171, 71% [95% CI = 65% to 76%], P<0.001) and African Caribbean (n = 188, 82% [95% CI = 77% to 87%], P<0.001), respectively. There were significantly lower acceptability scores for minority ethnic participants across all monitoring methods compared with white British participants. Focus group results highlighted self-monitoring as most acceptable and ambulatory monitoring least acceptable without consistent differences by ethnicity. Clinic monitoring was seen as inconvenient and anxiety provoking but with the advantage of immediate professional input. Conclusion Reduced acceptability and completion rates among minority ethnic groups raise important questions for the implementation and interpretation of blood pressure monitoring. Selection of method of blood pressure monitoring should take into account clinical need, patient preference, and potential cultural barriers to monitoring.

A Simple Method to Ensure Plausible Multiple Imputation for Continuous Multivariate Data

Multiple Imputation (MI) is an established approach for handling missing values. We show that MI for continuous data under the multivariate normal assumption is susceptible to generating implausible values. Our proposed remedy, is to: (1) transform the observed data into quantiles of the standard normal distribution; (2) obtain a functional relationship between the observed data and its corresponding standard normal quantiles; (3) undertake MI using the quantiles produced in step 1; and finally, (4) use the functional relationship to transform the imputations into their original domain. In conclusion, our approach safeguards MI from imputing implausible values.

Depression during first episode psychosis and subsequent suicide risk: A systematic review and meta-analysis of longitudinal studies

BACKGROUND Evidence suggests first episode psychosis (FEP) is associated with suicide, and the influence of depression on suicidal behaviour in cross sectional studies is clear. However the influence of depression during FEP on longer-term mortality is not certain. Existing evidence was synthesised to understand the influence of depressive symptoms during FEP on subsequent suicidal behaviour. METHODS Medline, Embase, PsycINFO, Cochrane Library, Web of Science, OpenGrey, and NICE Evidence were searched from inception to Jan 25, 2017. Longitudinal observational studies assessing the relationship between depressive symptoms during FEP with a measure of s at a specified follow-up time were included. Summary estimates were extracted. The Downs and Black Instrument was used to appraise study quality. Odds ratio (OR) of suicidal behaviour were calculated using random effects meta-analyses. The study protocol was registered with PROSPERO (CRD42017055881). RESULTS Of 4210 articles found, 23 fulfilled eligibility criteria. 13 were included in meta-analysis (n=3002). 428 participants demonstrated suicidal behaviour in the study periods. Odds of suicidal behaviour during follow-up were significantly higher among patients with depressive symptoms during FEP compared to those without (OR=1.59, 95% CI 1.14-2.21; I2=50.0%, p=0.02). Meta-regression demonstrated no evidence of influence of length of follow-up on results. CONCLUSIONS Depressive symptoms during FEP are associated with increased longer-term risk of suicidal behaviour. This association should be acknowledged during early management planning. Large-scale clinical trials are needed to identify efficacious management of depression during FEP.

Acute Whiplash Injury Study (AWIS): a protocol for a cluster randomised pilot and feasibility trial of an Active Behavioural Physiotherapy Intervention in an insurance private setting

Introduction Whiplash-associated disorder (WAD) causes substantial social and economic burden internationally. Up to 60% of patients with WAD progress to chronicity. Research therefore needs to focus on effective management in the acute stage to prevent the development of chronicity. Approximately 93% of patients are classified as WADII (neck complaint and musculoskeletal sign(s)), and in the UK, most are managed in the private sector. In our recent systematic review, a combination of active and behavioural physiotherapy was identified as potentially effective in the acute stage. An Active Behavioural Physiotherapy Intervention (ABPI) was developed through combining empirical (modified Delphi study) and theoretical (social cognitive theory focusing on self-efficacy) evidence. This pilot and feasibility trial has been designed to inform the design of an adequately powered definitive randomised controlled trial. Methods and analysis Two parallel phases. (1) An external pilot and feasibility cluster randomised double-blind (assessor and participants), parallel two-arm (ABPI vs standard physiotherapy) clinical trial to evaluate procedures and feasibility. Six UK private physiotherapy clinics will be recruited and cluster randomised by a computer-generated randomisation sequence. Sixty participants (30 each arm) will be assessed at recruitment (baseline) and at 3 months postbaseline. The planned primary outcome measure is the neck disability index. (2) An embedded exploratory qualitative study using semistructured indepth interviews (n=3–4 physiotherapists) and a focus group (n=6–8 patients) and entailing the recruitment of purposive samples will explore perceptions of the ABPI. Quantitative data will be analysed descriptively. Qualitative data will be coded and analysed deductively (identify themes) and inductively (identify additional themes). Ethics and dissemination This trial is approved by the University of Birmingham Ethics Committee (ERN_15-0542). Trial registration number ISRCTN84528320.