Efficacy of self-monitored blood pressure, with or without telemonitoring, for titration of antihypertensive medication (TASMINH4): an unmasked randomised controlled trial.

BACKGROUND: Studies evaluating titration of antihypertensive medication using self-monitoring give contradictory findings and the precise place of telemonitoring over self-monitoring alone is unclear. The TASMINH4 trial aimed to assess the efficacy of self-monitored blood pressure, with or without telemonitoring, for antihypertensive titration in primary care, compared with usual care. METHODS: This study was a parallel randomised controlled trial done in 142 general practices in the UK, and included hypertensive patients older than 35 years, with blood pressure higher than 140/90 mm Hg, who were willing to self-monitor their blood pressure. Patients were randomly assigned (1:1:1) to self-monitoring blood pressure (self-montoring group), to self-monitoring blood pressure with telemonitoring (telemonitoring group), or to usual care (clinic blood pressure; usual care group). Randomisation was by a secure web-based system. Neither participants nor investigators were masked to group assignment. The primary outcome was clinic measured systolic blood pressure at 12 months from randomisation. Primary analysis was of available cases. The trial is registered with ISRCTN, number ISRCTN 83571366. FINDINGS: 1182 participants were randomly assigned to the self-monitoring group (n=395), the telemonitoring group (n=393), or the usual care group (n=394), of whom 1003 (85%) were included in the primary analysis. After 12 months, systolic blood pressure was lower in both intervention groups compared with usual care (self-monitoring, 137·0 [SD 16·7] mm Hg and telemonitoring, 136·0 [16·1] mm Hg vs usual care, 140·4 [16·5]; adjusted mean differences vs usual care: self-monitoring alone, -3·5 mm Hg [95% CI -5·8 to -1·2]; telemonitoring, -4·7 mm Hg [-7·0 to -2·4]). No difference between the self-monitoring and telemonitoring groups was recorded (adjusted mean difference -1·2 mm Hg [95% CI -3·5 to 1·2]). Results were similar in sensitivity analyses including multiple imputation. Adverse events were similar between all three groups. INTERPRETATION: Self-monitoring, with or without telemonitoring, when used by general practitioners to titrate antihypertensive medication in individuals with poorly controlled blood pressure, leads to significantly lower blood pressure than titration guided by clinic readings. With most general practitioners and many patients using self-monitoring, it could become the cornerstone of hypertension management in primary care. FUNDING: National Institute for Health Research via Programme Grant for Applied Health Research (RP-PG-1209-10051), Professorship to RJM (NIHR-RP-R2-12-015), Oxford Collaboration for Leadership in Applied Health Research and Care, and Omron Healthcare UK.

A randomized controlled crossover trial evaluating differential responses to antihypertensive drugs (used as mono- or dual therapy) on the basis of ethnicity: The comparIsoN oF Optimal Hypertension RegiMens; part of the Ancestry Informative Markers in HYpertension program-AIM-HY INFORM trial.

BACKGROUND: Ethnicity, along with a variety of genetic and environmental factors, is thought to influence the efficacy of antihypertensive therapies. Current UK guidelines use a "black versus white" approach; in doing so, they ignore the United Kingdom's largest ethnic minority: Asians from South Asia. STUDY DESIGN: The primary purpose of the AIM-HY INFORM trial is to identify potential differences in response to antihypertensive drugs used as mono- or dual therapy on the basis of self-defined ethnicity. A multicenter, prospective, open-label, randomized study with 2 parallel, independent trial arms (mono- and dual therapy), AIM-HY INFORM plans to enroll a total of 1,320 patients from across the United Kingdom. Those receiving monotherapy (n = 660) will enter a 3-treatment (amlodipine 10 mg od; lisinopril 20 mg od; chlorthalidone 25 mg od), 3-period crossover, lasting 24 weeks, whereas those receiving dual therapy (n = 660) will enter a 4-treatment (amlodipine 5 mg od and lisinopril 20 mg od; amlodipine 5 mg od and chlorthalidone 25 mg od; lisinopril 20 mg od and chlorthalidone 25 mg od; amiloride 10 mg od and chlorthalidone 25 mg od), 4-period crossover, lasting 32 weeks. Equal numbers of 3 ethnic groups (white, black/black British, and Asian/Asian British) will ultimately be recruited to each of the trial arms (ie, 220 participants per ethnic group per arm). Seated, automated, unattended, office, systolic blood pressure measured 8 weeks after each treatment period begins will serve as the primary outcome measure. CONCLUSION: AIM-HY INFORM is a prospective, open-label, randomized trial which aims to evaluate first- and second-line antihypertensive therapies for multiethnic populations.

Measurement of blood pressure for the diagnosis and management of hypertension in different ethnic groups: one size fits all.

BACKGROUND: Hypertension is a major risk factor for cardiovascular disease and prevalence varies by ethnic group. The diagnosis and management of blood pressure are informed by guidelines largely based on data from white populations. This study addressed whether accuracy of blood pressure measurement in terms of diagnosis of hypertension varies by ethnicity by comparing two measurement modalities (clinic blood pressure and home monitoring) with a reference standard of ambulatory BP monitoring in three ethnic groups. METHODS: Cross-sectional population study (June 2010 - December 2012) with patients (40-75 years) of white British, South Asian and African Caribbean background with and without a previous diagnosis of hypertension recruited from 28 primary care practices. The study compared the test performance of clinic BP (using various protocols) and home-monitoring (1 week) with a reference standard of mean daytime ambulatory measurements using a threshold of 140/90 mmHg for clinic and 135/85 mmHg for out of office measurement. RESULTS: A total of 551 participants had complete data of whom 246 were white British, 147 South Asian and 158 African Caribbean. No consistent difference in accuracy of methods of blood pressure measurement was observed between ethnic groups with or without a prior diagnosis of hypertension: for people without hypertension, clinic measurement using three different methodologies had high specificity (75-97%) but variable sensitivity (33-65%) whereas home monitoring had sensitivity of 68-88% and specificity of 64-80%. For people with hypertension, detection of a raised blood pressure using clinic measurements had sensitivities of 34-69% with specificity of 73-92% and home monitoring had sensitivity (81-88%) and specificity (55-65%). CONCLUSIONS: For people without hypertension, ABPM remains the choice for diagnosing hypertension compared to the other modes of BP measurement regardless of ethnicity. Differences in accuracy of home monitoring and clinic monitoring (higher sensitivity of the former; higher specificity of the latter) were also not affected by ethnicity.

Telemonitoring and/or self-monitoring of blood pressure in hypertension (TASMINH4): protocol for a randomised controlled trial.

BACKGROUND: Self-monitoring of hypertension is associated with lower systolic blood pressure (SBP). However, evidence for the use of self-monitoring to titrate antihypertensive medication by physicians is equivocal. Furthermore, there is some evidence for the efficacy of telemonitoring in the management of hypertension but it is not clear what this adds over and above self-monitoring. This trial aims to evaluate whether GP led antihypertensive titration using self-monitoring results in lower SBP compared to usual care and whether telemonitoring adds anything to self-monitoring alone. METHODS/DESIGN: This will be a pragmatic primary care based, unblinded, randomised controlled trial of self-monitoring of BP with or without telemonitoring compared to usual care. Eligible patients will have poorly controlled hypertension (>140/90 mmHg) and will be recruited from primary care. Participants will be individually randomised to either usual care, self-monitoring alone, or self-monitoring with telemonitoring. The primary outcome of the trial will be difference in clinic SBP between intervention and control groups at 12 months adjusted for baseline SBP, gender, BP target and practice. At least 1110 patients will be sufficient to detect a difference in SBP between self-monitoring with or without telemonitoring and usual care of 5 mmHg with 90% power with an adjusted alpha of 0.017 (2-sided) to adjust for all three pairwise comparisons. Other outcomes will include adherence of anti-hypertensive medication, 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 sub study will gain insights into the views, experiences and decision making processes of patients and health care professionals focusing on the acceptability of self-monitoring and telemonitoring in the routine management of hypertension. DISCUSSION: The results of the trial will be directly applicable to primary care in the UK. If successful, self-monitoring of BP in people with hypertension would be applicable to hundreds of thousands of individuals in the UK. TRIAL REGISTRATION: ISRCTN 83571366 . Registered 17 July 2014.

Cost-effectiveness of options for the diagnosis of high blood pressure in primary care: a modelling study.

BACKGROUND: The diagnosis of hypertension has traditionally been based on blood-pressure measurements in the clinic, but home and ambulatory measurements better correlate with cardiovascular outcome, and ambulatory monitoring is more accurate than both clinic and home monitoring in diagnosing hypertension. We aimed to compare the cost-effectiveness of different diagnostic strategies for hypertension. METHODS: We did a Markov model-based probabilistic cost-effectiveness analysis. We used a hypothetical primary-care population aged 40 years or older with a screening blood-pressure measurement greater than 140/90 mm Hg and risk-factor prevalence equivalent to the general population. We compared three diagnostic strategies-further blood pressure measurement in the clinic, at home, and with an ambulatory monitor-in terms of lifetime costs, quality-adjusted life years, and cost-effectiveness. FINDINGS: Ambulatory monitoring was the most cost-effective strategy for the diagnosis of hypertension for men and women of all ages. It was cost-saving for all groups (from -£56 [95% CI -105 to -10] in men aged 75 years to -£323 [-389 to -222] in women aged 40 years) and resulted in more quality-adjusted life years for men and women older than 50 years (from 0·006 [0·000 to 0·015] for women aged 60 years to 0·022 [0·012 to 0·035] for men aged 70 years). This finding was robust when assessed with a wide range of deterministic sensitivity analyses around the base case, but was sensitive if home monitoring was judged to have equal test performance to ambulatory monitoring or if treatment was judged effective irrespective of whether an individual was hypertensive. INTERPRETATION: Ambulatory monitoring as a diagnostic strategy for hypertension after an initial raised reading in the clinic would reduce misdiagnosis and save costs. Additional costs from ambulatory monitoring are counterbalanced by cost savings from better targeted treatment. Ambulatory monitoring is recommended for most patients before the start of antihypertensive drugs. FUNDING: National Institute for Health Research and the National Institute for Health and Clinical Excellence.

High incidence of intolerance to tuberculosis chemoprophylaxis.

The outlook of inflammatory joint diseases has changed significantly with the advent of TNF blockers. However, these advances come with a trade off-risk of infections, especially tuberculosis. The Irish society of rheumatology has proposed guidelines to investigate and treat latent TB infection (LTBI), which is in accordance with majority of international recommendations. This protocol requires that every patient with LTBI should have chemoprophylaxis. INH and different anti-rheumatic drugs are known to cause hepatic and gastrointestinal complications. We sought to investigate the toxicity of adding prophylactic anti-TB medications to different DMARDs and anti-TNF agents. We prospectively documented the course of all patients who were prescribed chemoprophylaxis for LTBI, from August 2007 to August 2008. Arrangements were made for central re-issuing of prescription of INH or rifampicin, after reviewing monthly liver function tests and following telephone interview seeking presence of adverse events. Out of 132 patients who were commenced on different TNF blockers, only 23 patients (17%) were diagnosed with LTBI and were given prophylaxis as per recommended guidelines. Thirty-nine percent (9 out of 23) of patients discontinued INH because of adverse events. Primary reason for discontinuation in these 9 patients was as follows: 3 patients got marked transaminitis (transaminases >5 times the normal limit), 5 patients had non-resolving gastrointestinal intolerance (mainly nausea), and one patient developed non-resolving rash. We have found a significant number of our patients (39%) who could not continue anti-TB prophylaxis due to either gastrointestinal intolerance or hypertransaminesemia.

Measuring adherence to antihypertensive medication using an objective test in older adults attending primary care: cross-sectional study.

Analysis of urine samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS) has previously revealed high rates of non-adherence to antihypertensive medication. It is unclear whether these rates represent those in the general population. This study aimed to investigate whether it is feasible to collect urine samples in a primary care setting and analyse them using LC-MS/MS to detect non-adherence to antihypertensive medication. This study used a prospective, observational cohort design. Consecutive patients were recruited opportunistically from five general practices in UK primary care. They were aged ≥65 years with hypertension and had at least one antihypertensive prescription. Participants were asked to provide a urine sample for analysis of medication adherence. Samples were sent to a laboratory via post and analysed using LC-MS/MS. Predictors of adherence to medication were explored with multivariable logistic regression. Of 349 consecutive patients approached for the study, 214 (61.3%) gave informed consent and 191 (54.7%) provided a valid urine sample for analysis. Participants were aged 76.2 ± 6.6 years and taking a median of 2 antihypertensive medications (IQR 1-3). A total of 27/191 participants (14.2%) reported not taking all of their medications on the day of urine sample collection. However, LC-MS/MS analysis of samples revealed only 4/27 (9/191 in total; 4.7%) were non-adherent to some of their medications. Patients prescribed more antihypertensive medications were less likely to be adherent (OR 0.24, 95%CI 0.09-0.65). Biochemical testing for antihypertensive medication adherence is feasible in routine primary care, although non-adherence to medication is generally low, and therefore widespread testing is not indicated.

ABPM is best for diagnosing hypertension in primary care.

Ambulatory blood pressure monitoring (ABPM) is more accurate than clinic and home monitoring in diagnosing hypertension. A diagnostic strategy for hypertension using ABPM following an initial raised clinic reading would reduce misdiagnosis and NHS costs. If the first and second measurements taken during a consultation are both > or = 140/90 mmHg, 24-hour ABPM should be used to confirm the diagnosis of hypertension. Home monitoring can be used to confirm the diagnosis if the patient cannot tolerate ABPM. In cases of severe hypertension (clinic BP > or = 180/110 mmHg) and evidence of target organ damage, antihypertensive drug treatment should be started immediately without waiting for the results of ABPM or home monitoring. ABPM estimates true mean BP more accurately than clinic measurement because multiple readings are taken. It has been shown to have better correlation with a range of cardiovascular outcomes and end organ damage, Out-of-office methods can enable a diagnosis to be made more quickly. The benefits of these techniques, in particular ABPM, include the correct diagnosis of white coat hypertension and improved diagnostic accuracy. The weight of evidence suggests ABPM is the best prognostic indicator, followed by home then clinic monitoring. Stage 1 patients should only be offered antihypertensives if they have increased cardiovascular risk due to concurrent diabetes, chronic kidney disease, established CVD, target organ damage or a 10-year CVD risk >20%. Stage 2 patients should all be offered antihypertensives following ABPM or home monitoring, irrespective of their background cardiovascular risk.

Oral tranexamic acid for an additional 24 hours postoperatively versus a single preoperative intravenous dose for reducing blood loss in total knee arthroplasty: results of a randomized controlled trial (TRAC-24).

AIMS: In total knee arthroplasty (TKA), blood loss continues internally after surgery is complete. Typically, the total loss over 48 postoperative hours can be around 1,300 ml, with most occurring within the first 24 hours. We hypothesize that the full potential of tranexamic acid (TXA) to decrease TKA blood loss has not yet been harnessed because it is rarely used beyond the intraoperative period, and is usually withheld from 'high-risk' patients with a history of thromboembolic, cardiovascular, or cerebrovascular disease, a patient group who would benefit greatly from a reduced blood loss. METHODS: TRAC-24 was a prospective, phase IV, single-centre, open label, parallel group, randomized controlled trial on patients undergoing TKA, including those labelled as high-risk. The primary outcome was indirect calculated blood loss (IBL) at 48 hours. Group 1 received 1 g intravenous (IV) TXA at the time of surgery and an additional 24-hour postoperative oral regime of four 1 g doses, while Group 2 only received the intraoperative dose and Group 3 did not receive any TXA. RESULTS: Between July 2016 and July 2018, 552 patients were randomized to either Group 1 (n = 241), Group 2 (n = 243), or Group 3 (n = 68), and 551 were included in the final analysis. The blood loss did differ significantly between the two intervention groups (733.5 ml (SD 384.0) for Group 1 and 859.2 ml (SD 363.6 ml) for Group 2; mean difference -125.8 ml (95% confidence interval -194.0 to -57.5; p < 0.001). No differences in mortality or thromboembolic events were observed in any group. CONCLUSION: These data support the hypothesis that in TKA, a TXA regime consisting of IV 1 g perioperatively and four oral 1 g doses over 24 hours postoperatively significantly reduces blood loss beyond that achieved with a single IV 1 g perioperative dose alone. TXA appears safe in patients with history of thromboembolic, cardiovascular, and cerebrovascular disease. Cite this article: Bone Joint J 2021;103-B(10):1595-1603.

Oral tranexamic acid for an additional 24 hours postoperatively versus a single preoperative intravenous dose for reducing blood loss in total hip arthroplasty: results of a randomized controlled trial (TRAC-24).

AIMS: A typical pattern of blood loss associated with total hip arthroplasty (THA) is 200 ml intraoperatively and 1.3 l in the first 48 postoperative hours. Tranexamic acid (TXA) is most commonly given as a single preoperative dose only and is often withheld from patients with a history of thromboembolic disease as they are perceived to be "high-risk" with respect to postoperative venous thromboembolism (VTE). The TRanexamic ACid for 24 hours trial (TRAC-24) aimed to identify if an additional 24-hour postoperative TXA regime could further reduce blood loss beyond a once-only dose at the time of surgery, without excluding these high-risk patients. METHODS: TRAC-24 was a prospective, phase IV, single centre, open label, parallel group, randomized controlled trial (RCT) involving patients undergoing primary unilateral elective THA. The primary outcome measure was the indirect calculated blood loss (IBL) at 48 hours. The patients were randomized into three groups. Group 1 received 1 g intravenous (IV) TXA at the time of surgery and an additional oral regime for 24 hours postoperatively, group 2 only received the intraoperative dose, and group 3 did not receive any TXA. RESULTS: A total of 534 patients were randomized, with 233 in group 1, 235 in group 2, and 66 in group 3; 92 patients (17.2%) were considered high-risk. The mean IBL did not differ significantly between the two intervention groups (848.4 ml (SD 463.8) for group 1, and 843.7 ml (SD 478.7) for group 2; mean difference -4.7 ml (95% confidence interval -82.9 to 92.3); p = 0.916). No differences in mortality or incidence of VTE were observed between any group. CONCLUSION: The addition of oral TXA for 24 hours postoperatively does not reduce blood loss beyond that achieved with a single 1 g IV perioperative dose alone. There may be a clinically relevant difference in patients with a normal BMI, which warrants further investigation. Critically, there were no safety issues in patients with a history of thromboembolic, cardiovascular, or cerebrovascular disease. Cite this article: Bone Joint J 2021;103-B(7):1197-1205.

Arm Based on LEg blood pressures (ABLE-BP): can systolic leg blood pressure measurements predict systolic brachial blood pressure? Protocol for an individual participant data meta-analysis from the INTERPRESS-IPD Collaboration.

INTRODUCTION: Blood pressure (BP) is normally measured on the upper arm, and guidelines for the diagnosis and treatment of high BP are based on such measurements. Leg BP measurement can be an alternative when brachial BP measurement is impractical, due to injury or disability. Limited data exist to guide interpretation of leg BP values for hypertension management; study-level systematic review findings suggest that systolic BP (SBP) is 17 mm Hg higher in the leg than the arm. However, uncertainty remains about the applicability of this figure in clinical practice due to substantial heterogeneity. AIMS: To examine the relationship between arm and leg SBP, develop and validate a multivariable model predicting arm SBP from leg SBP and investigate the prognostic association between leg SBP and cardiovascular disease and mortality. METHODS AND ANALYSIS: Individual participant data (IPD) meta-analyses using arm and leg SBP measurements for 33 710 individuals from 14 studies within the Inter-arm blood pressure difference IPD (INTERPRESS-IPD) Collaboration. We will explore cross-sectional relationships between arm and leg SBP using hierarchical linear regression with participants nested by study, in multivariable models. Prognostic models will be derived for all-cause and cardiovascular mortality and cardiovascular events. ETHICS AND DISSEMINATION: Data originate from studies with prior ethical approval and consent, and data sharing agreements are in place-no further approvals are required to undertake the secondary analyses proposed in this protocol. Findings will be published in peer-reviewed journal articles and presented at conferences. A comprehensive dissemination strategy is in place, integrated with patient and public involvement. PROSPERO REGISTRATION NUMBER: CRD42015031227.

Protocol for Past BP: a randomised controlled trial of different blood pressure targets for people with a history of stroke of transient ischaemic attack (TIA) in primary care.

BACKGROUND: Blood pressure (BP) lowering in people who have had a stroke or transient ischaemic attack (TIA) leads to reduced risk of further stroke. However, it is not clear what the target BP should be, since intensification of therapy may lead to additional adverse effects. PAST BP will determine whether more intensive BP targets can be achieved in a primary care setting, and whether more intensive therapy is associated with adverse effects on quality of life. METHODS/DESIGN: This is a randomised controlled trial (RCT) in patients with a past history of stroke or TIA. Patients will be randomised to two groups and will either have their blood pressure (BP) lowered intensively to a target of 130 mmHg systolic, (or by 10 mmHg if the baseline systolic pressure is between 125 and 140 mmHg) compared to a standard group where the BP will be reduced to a target of 140 mmHg systolic. Patients will be managed by their practice at 1-3 month intervals depending on level of BP and followed-up by the research team at six monthly intervals for 12 months.610 patients will be recruited from approximately 50 general practices. The following exclusion criteria will be applied: systolic BP <125 mmHg at baseline, 3 or more anti-hypertensive agents, orthostatic hypotension, diabetes mellitus with microalbuminuria or other condition requiring a lower treatment target or terminal illness.The primary outcome will be change in systolic BP over twelve months. Secondary outcomes include quality of life, adverse events and cardiovascular events.In-depth interviews with 30 patients and 20 health care practitioners will be undertaken to investigate patient and healthcare professionals understanding and views of BP management. DISCUSSION: The results of this trial will inform whether intensive blood pressure targets can be achieved in people who have had a stroke or TIA in primary care, and help determine whether or not further research is required before recommending such targets for this population. TRIAL REGISTRATION: ISRCTN29062286.

Nonadherence to antihypertensive medications is related to pill burden in apparent treatment-resistant hypertensive individuals.

OBJECTIVE: Nonadherence to medication is present in at least 50% of patients with apparent treatment-resistant hypertension. We examined the factors associated with nonadherence as detected by a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based urine antihypertensive drug assay. METHODS: All urine antihypertensive test results, carried out for uncontrolled hypertension (BP persistently >140/90 mmHg) between January 2015 and December 2016 at a single toxicology laboratory were analysed. Drugs detected were compared with the antihypertensive drugs prescribed. Patients were classified as adherent (all drugs detected), partially nonadherent (at least one prescribed drug detected) or completely nonadherent (no drugs detected). Demographic and clinical parameters were compared between the adherent and nonadherent groups. Binary logistic regression analysis was performed to determine association between nonadherence and demographic and clinical factors. RESULTS: Data on 300 patients from nine hypertension centres across the United Kingdom were analysed. The median age was 59 years, 47% women, 71% Caucasian, median clinic BP was 176/95 mmHg and the median number of antihypertensive drugs prescribed was four. One hundred and sixty-six (55%) were nonadherent to prescribed medication with 20% of these being completely nonadherent. Nonadherence to antihypertensive medication was independently associated with younger age, female sex, number of antihypertensive drugs prescribed, total number of all medications prescribed (total pill burden) and prescription of a calcium channel blocker. CONCLUSION: This LC-MS/MS urine analysis-based study suggests the majority of patients with apparent treatment-resistant hypertension are nonadherent to prescribed treatment. Factors that are associated with nonadherence, particularly pill burden, should be taken into account while treating these patients.

Development of a methotrexate educational guide/information/monitoring booklet for inflammatory arthritis.

INTRODUCTION: There are over 40,000 people living in Ireland with inflammatory arthritis (IA), a condition that is potentially destructive in nature and can have personal, social and economic consequences. Although we have witnessed dramatic changes in the treatment of IA in the last two decades, methotrexate (MTX) remains the first-line treatment for patients with a diagnosis of IA. Despite the fact that MTX is so commonly prescribed, there is a lack of educational materials both for healthcare professionals (HCPs) and patients. The aim of the present study was to develop a suite of MTX material for patients. METHODS: A comprehensive literature review of MTX (evidence, educational materials and practice guidelines) in the treatment of IA was undertaken. The content of the documents was developed, and the format and structure of the documents were agreed. A tailored patient educational guide, information/monitoring booklet and alert card were designed to address the lack of educational materials for this condition. A national pilot study of the documents was conducted (a postal questionnaire for patients and electronic survey for clinical nurse specialists). Results and recommendations were incorporated into the final documents. These documents were also incorporated into the National Clinical Care Programme-rheumatology-methotrexate pathway. RESULTS: A 26-page evidence-based educational guide was produced to support the HCP in educating patients taking MTX, in conjunction with a patient information/monitoring booklet and alert card to support the patient. CONCLUSIONS: These documents are now widely available and used in clinical practice in Ireland, providing patients with standardized, evidence-based information about MTX.

Defining the relationship between arm and leg blood pressure readings: a systematic review and meta-analysis.

OBJECTIVES: To define the relationship between arm and leg blood pressure (BP) to inform the interpretation of leg BP readings in routine clinical practice where arm readings are not available. METHODS: Systematic review of all existing studies comparing arm and leg BP measurements. A search strategy was designed in MEDLINE and adapted to be run across six further databases. Articles were deemed eligible for inclusion if they measured and reported arm and leg BP taken in the supine position and/or the difference between the two. Mean values for arm-leg BP difference and measures of precision [95% confidence intervals (CIs) or SD] were extracted and entered into a random-effects meta-analysis. RESULTS: A total of 887 articles were screened and 44 were included in the descriptive analyses, including 9771 patients. In the general population, ankle SBP was 17.0 mmHg (95% CI 15.4-21.3 mmHg) higher than arm BP in the supine position. For DBP, there was no difference between arm and ankle BP (-0.3 mmHg, 95% CI -1.5-1.0 mmHg). In patients with vascular disease, SBP was -33.3 mmHg (95% CI -59.1 to -7.6 mmHg) lower in the ankle compared with the arm. CONCLUSION: This is the first review to provide empirical data defining the difference between BP in the arm and leg in the general population. Findings suggest a diagnostic threshold of 155/90 mmHg could be used for diagnosing hypertension when only ankle measurements are available in routine practice.

Schedules for Self-monitoring Blood Pressure: A Systematic Review.

BACKGROUND: Self-monitoring of blood pressure better predicts prognosis than clinic measurement, is popular with patients, and endorsed in hypertension guidelines. However, there is uncertainty over the optimal self-monitoring schedule. We therefore aimed to determine the optimum schedule to predict future cardiovascular events and determine "true" underlying blood pressure. METHODS: Six electronic databases were searched from November 2009 (updating a National Institute for Health and Care Excellence [NICE] systematic review) to April 2017. Studies that compared aspects of self-monitoring schedules to either prognosis or reliability/reproducibility in hypertensive adults were included. Data on study and population characteristics, self-monitoring regime, and outcomes were extracted by 2 reviewers independently. RESULTS: From 5,164 unique articles identified, 25 met the inclusion criteria. Twelve studies were included from the original NICE review, making a total of 37 studies. Increasing the number of days of measurement improved prognostic power: 72%-91% of the theoretical maximum predictive value (asymptotic maximum hazard ratio) was reached by 3 days and 86%-96% by 7 days. Increasing beyond 3 days of measurement did not result in better correlation with ambulatory monitoring. There was no convincing evidence that the timing or number of readings per day had an effect, or that ignoring the first day's measurement was necessary. CONCLUSIONS: Home blood pressure should be measured for 3 days, increased to 7 only when mean blood pressure is close to a diagnostic or treatment threshold. Other aspects of a monitoring schedule can be flexible to facilitate patient uptake of and adherence with self-monitoring.

Effects of naltrexone on electrocutaneous pain in patients with hypertension compared to normotensive individuals.

An opioid mechanism may help explain hypertensive hypoalgesia. A double-blind placebo-controlled design compared the effects of opioid blockade (naltrexone) and placebo on electrocutaneous pain threshold, pain tolerance, and retrospective McGill Pain Questionnaire ratings in 35 unmedicated patients with essential hypertension and 28 normotensive individuals. The hypertensives experienced less pain than normotensives during the assessment of their pain tolerance; however, this manifestation of hypertensive hypoalgesia was not moderated by naltrexone. These findings fail to support the hypothesis that essential hypertension is characterised by relative opioid insensitivity.

Effects of opioid blockade on nociceptive flexion reflex thresholds and nociceptive responding in hypertensive and normotensive individuals.

Hypertension and risk for hypertension have been associated with reduced pain sensitivity. It has been hypothesised that endogenous opioids contribute to this hypertensive hypoalgesia. The nociceptive flexion reflex can be used as a tool to investigate modulation of nociceptive transmission at spinal level. The current study employed a double-blind placebo-controlled design to compare the effects of naltrexone, an opioid antagonist, and placebo on nociceptive flexion reflex thresholds and nociceptive responding in unmedicated patients with essential hypertension and normotensive individuals. Neither nociceptive flexion reflex thresholds nor nociceptive responding differed between hypertensives and normotensives during placebo or naltrexone. These data provide no support for the hypothesis that essential hypertension is characterised by higher levels of endogenous opioids in the central nervous system and reveal no association between blood pressure status and nociceptive flexion reflex responses.

Association of guideline and policy changes with incidence of lifestyle advice and treatment for uncomplicated mild hypertension in primary care: a longitudinal cohort study in the Clinical Practice Research Datalink.

OBJECTIVES: Evidence to support initiation of pharmacological treatment in patients with uncomplicated (low risk) mild hypertension is inconclusive. As such, clinical guidelines are contradictory and healthcare policy has changed regularly. The aim of this study was to determine the incidence of lifestyle advice and drug therapy in this population and whether secular trends were associated with policy changes. DESIGN: Longitudinal cohort study. SETTING: Primary care practices contributing to the Clinical Practice Research Datalink in England. PARTICIPANTS: Data were extracted from the linked electronic health records of patients aged 18-74 years, with stage 1 hypertension (blood pressure between 140/90 and 159/99 mm Hg), no cardiovascular disease (CVD) risk factors and no treatment, from 1998 to 2015. Patients exited if follow-up records became unavailable, they progressed to stage 2 hypertension, developed a CVD risk factor or received lifestyle advice/treatment. PRIMARY OUTCOME MEASURES: The association between policy changes and incidence of lifestyle advice or treatment, examined using an interrupted time-series analysis. RESULTS: A total of 108 843 patients were defined as having uncomplicated mild hypertension (mean age 51.9±12.9 years, 60.0% female). Patientsspent a median 2.6 years (IQR 0.9-5.5) in the study, after which 12.2% (95% CI 12.0% to 12.4%) were given lifestyle advice, 29.9% (95% CI 29.7% to 30.2%) were prescribed medication and 19.4% (95% CI 19.2% to 19.6%) were given both. The introduction of the quality outcomes framework (QOF) and subsequent changes to QOF indicators were followed by significant increases in the incidence of lifestyle advice. Treatment prescriptions decreased slightly over time, but were not associated with policy changes. CONCLUSIONS: Despite secular trends that accord with UK guidance, many patients are still prescribed treatment for mild hypertension. Adequately powered studies are needed to determine if this is appropriate.

Benefits and Harms of Antihypertensive Treatment in Low-Risk Patients With Mild Hypertension.

Importance: Evidence to support initiation of pharmacologic treatment in low-risk patients with mild hypertension is inconclusive, with previous trials underpowered to demonstrate benefit. Clinical guidelines across the world are contradictory. Objective: To examine whether antihypertensive treatment is associated with a low risk of mortality and cardiovascular disease (CVD) in low-risk patients with mild hypertension. Design, Setting, and Participants: In this longitudinal cohort study, data were extracted from the Clinical Practice Research Datalink, from January 1, 1998, through September 30, 2015, for patients aged 18 to 74 years who had mild hypertension (untreated blood pressure of 140/90-159/99 mm Hg) and no previous treatment. Anyone with a history of CVD or CVD risk factors was excluded. Patients exited the cohort if follow-up records became unavailable or they experienced an outcome of interest. Exposures: Prescription of antihypertensive medication. Propensity scores for likelihood of treatment were constructed using a logistic regression model. Individuals treated within 12 months of diagnosis were matched to untreated patients by propensity score using the nearest-neighbor method. Main Outcomes and Measures: The rates of mortality, CVD, and adverse events among patients prescribed antihypertensive treatment at baseline, compared with those who were not prescribed such treatment, using Cox proportional hazards regression. Results: A total of 19 143 treated patients (mean [SD] age, 54.7 [11.8] years; 10 705 [55.9%] women; 10 629 [55.5%] white) were matched to 19 143 similar untreated patients (mean [SD] age, 54.9 [12.2] years; 10 631 [55.5%] female; 10 654 [55.7%] white). During a median follow-up period of 5.8 years (interquartile range, 2.6-9.0 years), no evidence of an association was found between antihypertensive treatment and mortality (hazard ratio [HR], 1.02; 95% CI, 0.88-1.17) or between antihypertensive treatment and CVD (HR, 1.09; 95% CI, 0.95-1.25). Treatment was associated with an increased risk of adverse events, including hypotension (HR, 1.69; 95% CI, 1.30-2.20; number needed to harm at 10 years [NNH10], 41), syncope (HR, 1.28; 95% CI, 1.10-1.50; NNH10, 35), electrolyte abnormalities (HR, 1.72; 95% CI, 1.12-2.65; NNH10, 111), and acute kidney injury (HR, 1.37; 95% CI, 1.00-1.88; NNH10, 91). Conclusions and Relevance: This prespecified analysis found no evidence to support guideline recommendations that encourage initiation of treatment in patients with low-risk mild hypertension. There was evidence of an increased risk of adverse events, which suggests that physicians should exercise caution when following guidelines that generalize findings from trials conducted in high-risk individuals to those at lower risk.