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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.

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.

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.

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.

Background/Aims Telemedicine can be broadly defined as the use of telecommunication technologies to provide medical information and services. It can be audio, visual, or text. Its use has increased dramatically during the COVID-19 pandemic to ensure patient and healthcare worker safety. Any healthcare professional can engage with it. It carries benefits like reduced stress and expense of traveling, maintenance of social distancing, and reduced risk of infection. There are some potential drawbacks such as lack of physical examination, liability and technological issues. Methods A questionnaire was sent to 200 patients, selected from different virtual clinics (new and review, doctor and ANP led) run between March and May 2020 in the rheumatology department of University Hospital Waterford. We formulated 14 questions to cover the following aspects: demography, the purpose of the consult, punctuality, feedback, medico-legal concerns, and free text for comments. A self-addressed return envelope was included. Results 83 responses were received. 2 were excluded. The ratio of females to male respondents was 59: 41, with the majority over 60 years old. The main appointment type was review 67 (83%). 80% of patients were called either before or at the time of their scheduled appointment. The vast majority (98.8%) of our patients had confidence in our data protection and trusted our system to maintain their confidentiality. 95% stated that they felt comfortable, were given enough time to explain their health problem and felt free from stress. The respondents who preferred attending the clinic in person (17 in total) compared to the virtual were mostly follow up patients- 12 vs. 5 new. Conclusion Patient satisfaction among those surveyed was high, despite having to introduce the service abruptly during the COVID-19 pandemic. There are many improvements we can adopt to improve our service and even maintain after the pandemic as a way of communicating with our stable patients. As we are covering a large geographical catchment, we can continue to implement the virtual clinic for some appointments. We should prioritize our efforts on identifying the right patient and the type of service we can offer, further training of staff, and increasing awareness of the patients as to how to get the most out of a virtual appointment. Disclosure F.A. Altamimi: None. U. Martin: None. C. Sheehy: None.

Background Methotrexate (MTX) remains the standard treatment for inflammatory arthritis. For patients prescribed MTX they tell us that they find it difficult to source correct information. Patients require this at different time points in their disease and in different formats that encompass literacy and language challenges. Patients are usually given instruction about MTX at the time of their diagnosis when they are faced with absorbing a lot of information in a very short time frame, yet the majority of patients are required to take MTX for the duration of their disease. Methods Following on from the development of the MTX patient education guide in Ireland in 2017 we looked at developing the content into a different format. In partnership with a digital media company and the pharmaceutical industry the content was converted into a digital media card and website for use in the clinical setting. The content was designed as an additional support to patients prescribed MTX. The animation consists of both audio and images and provides the viewer with essential information and key messages required when taking MTX. The animation guides the patient through MTX, outlines how it works, how to take MTX, and highlights the important safety issues and monitoring required when taking MTX. Audio content was written by the author and designed in collaboration with a digital media company. The digital media card and website was launched nationally in September 2018 with the support of the Irish Rheumatology Nursing Forum and Arthritis Ireland. Rheumatology departments nationally were provided with copies of the digital media card and details of the website. Patients can use the digital media card and be signposted patients to www.methotrexate.ie. Results Since the launch of both the website and the digital media card there has been 1.5 K sessions, and 1.4K users on the website. The website has been accessed globally with over 781 users from Ireland, 220 from the United States and 144 from the United Kingdom. The website is accessed predominately by mobile device followed by tablet device. Conclusion To date the website continues to be accessed by patients and we have received very positive feedback. The digital media card has been adopted nationally and has become incorporated as part of the education of patients about MTX. Both the website and the digital media card are designed to support and enhance the education about MTX and not replace the formal education that nurses give to patients about MTX. The next step is to survey both the patients and healthcare professionals using the tools and identify what additions may enhance these tools. For further information go to www.methotrexate.ie to access the website and view the animation. Disclosures U.E.S. Martin Honoraria; U.M has received honoraria from Novartis, Abbvie Ireland. Grants/research support; U.M has received educational grants from Novartis, Janssen, Abbvie, Pfizer.

Background While it is has been proven that tranexamic acid (TXA) reduces blood loss in primary total hip and knee arthroplasty (THA and TKA), there is little published evidence on the use of TXA beyond 3 h post-operatively. Most blood loss occurs after wound closure and the primary aim of this study is to determine if the use of oral TXA post-operatively for up to 24 h will reduce calculated blood loss at 48 h beyond an intra-operative intravenous bolus alone following primary THA and TKA. To date, most TXA studies have excluded patients with a history of thromboembolic disease. Methods/design This is a phase IV, single-centred, open-label, parallel-group, randomised controlled trial. Participants are randomised to one of three groups: group 1, an intravenous (IV) bolus of TXA peri-operatively plus oral TXA post-operatively for 24 h; group 2, an IV bolus of TXA peri-operatively or group 3, standard care (no TXA). Eligible participants, including those with a history of thromboembolic disease, are allocated to these groups with a 2:2:1 allocation ratio. The primary outcome is the indirectly calculated blood loss 48 h after surgery. Researchers and patients are not blinded to the treatment; however, staff processing blood samples are. Originally 1166 participants were required to complete this study, 583 THA and 583 TKA. However, following an interim analysis after 100 THA and 100 TKA participants had been recruited to the study, the data monitoring ethics committee recommended stopping group 3 (standard care). Discussion TRAC-24 will help to determine whether an extended TXA dosing regimen can further reduce blood loss following primary THA and TKA. By including patients with a history of thromboembolic disease, this study will add to our understanding of the safety profile of TXA in this clinical situation. Trial registration ISRCTN registry, ISRCTN58790500. Registered on 3 June 2016, EudraCT: 2015–002661-36. Electronic supplementary material The online version of this article (10.1186/s13063-018-2784-3) contains supplementary material, which is available to authorized users.

Aims The aim of this study was to determine whether the sequential application of povidone iodine-alcohol (PVI) followed by chlorhexidine gluconate-alcohol (CHG) would reduce surgical wound contamination to a greater extent than PVI applied twice in patients undergoing spinal surgery. Patients and Methods A single-centre, interventional, two arm, parallel group randomised controlled trial was undertaken, involving 407 patients who underwent elective spinal surgery. For 203 patients, the skin was disinfected before surgery using PVI (10% [w/w (1% w/w available iodine)] in 95% industrial denatured alcohol, povidone iodine; Videne Alcoholic Tincture) twice, and for 204 patients using PVI once followed by CHG (2% [w/v] chlorhexidine gluconate in 70% [v/v] isopropyl alcohol; Chloraprep with tint). The primary outcome measure was contamination of the wound determined by aerobic and anaerobic bacterial growth from samples taken after disinfection. Results The detection of viable bacteria in any one of the samples taken after disinfection (culture-positive) was significantly lower in the group treated with both PVI and CHG than in the group treated with PVI alone (59 (29.1%) versus 85 (41.7%), p = 0.009; odds ratio 0.574; 95% confidence interval, 0.380 to 0.866). Conclusions Antisepsis of the skin with the sequential application of PVI and CHG more effectively reduces the contamination of a surgical wound than PVI alone. Cite this article: Bone Joint J 2017;99-B:1354–65.

© The Author 2017. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. BACKGROUND: Interarm differences (IADs) ≥10 mm Hg in systolic blood pressure (BP) are associated with greater incidence of cardiovascular disease. The effect of ethnicity and the white coat effect (WCE) on significant systolic IADs (ssIADs) are not well understood.METHODS: Differences in BP by ethnicity for different methods of BP measurement were examined in 770 people (300 White British, 241 South Asian, 229 African-Caribbean). Repeated clinic measurements were obtained simultaneously in the right and left arm using 2 BPTru monitors and comparisons made between the first reading, mean of second and third and mean of second to sixth readings for patients with, and without known hypertension. All patients had ambulatory BP monitoring (ABPM). WCE was defined as systolic clinic BP ≥10 mm Hg higher than daytime ABPM.RESULTS: No significant differences were seen in the prevalence of ssIAD between ethnicities whichever combinations of BP measurement were used and regardless of hypertensive status. ssIADs fell between the 1st measurement (161, 22%), 2nd/3rd (113, 16%), and 2nd-6th (78, 11%) (1st vs. 2nd/3rd and 2nd-6th, P < 0.001). Hypertensives with a WCE were more likely to have ssIADs on 1st, (odds ratio [OR] 1.73 (95% confidence interval 1.04-2.86); 2nd/3rd, (OR 3.05 (1.68-5.53); and 2nd-6th measurements, (OR 2.58 (1.22-5.44). Nonhypertensive participants with a WCE were more likely to have a ssIAD on their first measurement (OR 3.82 (1.77 to -8.25) only.CONCLUSIONS: ssIAD prevalence does not vary with ethnicity regardless of hypertensive status but is affected by the number of readings, suggesting the influence of WCE. Multiple readings should be used to confirm ssIADs.

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.

Hypertension is one of the most important risk factors for cardiovascular disease, which is a significant cause of morbidity and mortality worldwide. Resistant (or difficult) hypertension is thought to affect 1 in 6 patients with treated hypertension and carries an increased risk of death and cardiovascular disease. It is generally defined as uncontrolled clinic blood pressure (>140/90 mmHg) after treatment with three or more antihypertensives to include optimal doses of an ACE inhibitor (or an angiotensin receptor blocker), a calcium channel blocker and a diuretic. There are some factors that must be taken into account before a diagnosis of resistant hypertension can be made. ‘Pseudo-resistant’ hypertension can be caused by poor clinic blood pressure measurement technique, patient non-adherence to prescribed medication, patient intolerance to certain anti-hypertensive medications and white coat hypertension (where blood pressure appears high in the clinic but is controlled out-of-the-office on home or ambulatory measurements). Pharmacological treatment of resistant hypertension is focused on the addition of fourth-line therapy and recent evidence supports the use of spironolactone. Lifestyle should be reviewed and patients encouraged to exercise regularly and lose weight, reduce their alcohol and sodium consumption and stop smoking. In patients who remain uncontrolled on optimal treatment, there are a number of alternative treatment options and surgical procedures which can be considered. However, the evidence supporting each of these is limited and in some cases, conflicting and therefore more prospective randomised controlled trials are required before any can be adopted into routine clinical practice.

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 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.

Patients often have lower (white coat effect) or higher (masked effect) ambulatory/home blood pressure readings compared with clinic measurements, resulting in misdiagnosis of hypertension. The present study assessed whether blood pressure and patient characteristics from a single clinic visit can accurately predict the difference between ambulatory/home and clinic blood pressure readings (the home–clinic difference). A linear regression model predicting the home–clinic blood pressure difference was derived in 2 data sets measuring automated clinic and ambulatory/home blood pressure (n=991) using candidate predictors identified from a literature review. The model was validated in 4 further data sets (n=1172) using area under the receiver operator characteristic curve analysis. A masked effect was associated with male sex, a positive clinic blood pressure change (difference between consecutive measurements during a single visit), and a diagnosis of hypertension. Increasing age, clinic blood pressure level, and pulse pressure were associated with a white coat effect. The model showed good calibration across data sets (Pearson correlation, 0.48–0.80) and performed well-predicting ambulatory hypertension (area under the receiver operator characteristic curve, 0.75; 95% confidence interval, 0.72–0.79 [systolic]; 0.87; 0.85–0.89 [diastolic]). Used as a triaging tool for ambulatory monitoring, the model improved classification of a patient’s blood pressure status compared with other guideline recommended approaches (93% [92% to 95%] classified correctly; United States, 73% [70% to 75%]; Canada, 74% [71% to 77%]; United Kingdom, 78% [76% to 81%]). This study demonstrates that patient characteristics from a single clinic visit can accurately predict a patient’s ambulatory blood pressure. Usage of this prediction tool for triaging of ambulatory monitoring could result in more accurate diagnosis of hypertension and hence more appropriate treatment.

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.

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. Conclusions: 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.

Background Ethnicity, along with a variety of genetic and environmental factors, is thought to influence the efficacy of anti-hypertensive therapies. Current UK guidelines employ a ‘black vs white’ approach; in doing so, they ignore the UK'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 multi-center, prospective, open-label, randomized study with two parallel, independent trial arms (mono- and dual-therapy), AIM-HY INFORM plans to enroll a total of 1320 patients from across the UK. Those receiving mono-therapy (n = 660) will enter a three-treatment (Amlodipine 10 mg od; Lisinopril 20 mg od; Chlorthalidone 25 mg od), three-period crossover, lasting 24 weeks, whilst those receiving dual-therapy (n = 660) will enter a four-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), four-period crossover, lasting 32 weeks. Equal numbers of three ethnic groups (White, Black/Black British, and Asian/Asian British) will ultimately be recruited to each of the trial arms (i.e., 220 participants per ethnic group per arm). Seated, automated, unattended, office, systolic blood pressure measured eight 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 anti-hypertensive therapies for multi-ethnic populations.

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.

Background Falls are common during hospital admissions and may occur more frequently in patients who are taking antihypertensive medications, particularly in the context of normal to low blood pressure. The review and adjustment of these medications is an essential aspect of the post-fall assessment and should take place as soon as possible after the fall. Our aim was to investigate whether appropriate post-fall adjustments of antihypertensive medications are routinely made in a large National Health Service (NHS) Trust. Methods Inpatient records over an eight-month period were captured from an electronic prescribing system to identify older adults (≥80 years old) with normal/low blood pressures (

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are effective and widely used antihypertensive drugs. Exposure to these agents is known to be harmful to the fetus in the second and third trimesters of pregnancy. Concerns have also been raised about the risk of congenital malformations if ACEIs or ARBs are taken during the first trimester of pregnancy. The evidence to date, however, is conflicting and observed malformations may be due to confounders such as undiagnosed diabetes or maternal obesity, other antihypertensive medications or the hypertension itself. Nonetheless, in women who become pregnant while taking an ACEI or ARB, the drug should be stopped as soon as possible. In women with chronic kidney disease and proteinuria, it may be appropriate to continue taking an ACEI or ARB until the pregnancy is confirmed because of the significant benefit to their kidney function and the lower fertility rate in these patients.

Context: A diminished muscle anabolic response to protein nutrition may underpin age-associated muscle loss. Objective: To determine how chronological and biological aging influence myofibrillar protein synthesis (MyoPS). Design: Cross-sectional comparison. Setting: Clinical research facility. Participants: Ten older lean [OL: 71.7 ± 6 years; body mass index (BMI) ≤25 kg ⋅ m−2], 7 older obese (OO: 69.1 ± 2 years; BMI ≥30 kg ⋅ m−2), and 18 young lean (YL) individuals (25.5 ± 4 years; BMI ≤25 kg ⋅ m−2). Intervention: Skeletal muscle biopsies obtained during a primed-continuous infusion of l-[ring-13C6]-phenylalanine. Main Outcome Measures: Anthropometrics, insulin resistance, inflammatory markers, habitual diet, physical activity, MyoPS rates, and fiber-type characteristics. Results: Fat mass, insulin resistance, inflammation, and type II fiber intramyocellular lipid were greater, and daily step count lower, in OO compared with YL and OL. Postprandial MyoPS rates rose above postabsorptive values by ∼81% in YL (P < 0.001), ∼38% in OL (P = 0.002, not different from YL), and ∼9% in OO (P = 0.11). Delta change in postprandial MyoPS from postabsorptive values was greater in YL compared with OL (P = 0.032) and OO (P < 0.001). Absolute postprandial MyoPS rates and delta postprandial MyoPS change were associated with step count (r2 = 0.33; P = 0.015) and leg fat mass (r2 = 0.4; P = 0.006), respectively, in older individuals. Paradoxically, lean mass was similar between groups, and muscle fiber area was greater in OO vs OL (P = 0.002). Conclusion: Age-related muscle anabolic resistance is exacerbated in obese inactive individuals, with no apparent detriment to muscle mass., We studied how chronological and biological aging influence muscle anabolism and found that nutrient-stimulated muscle protein synthesis rates are impaired in obese, inactive older individuals.

BACKGROUND: Self-monitoring of blood pressure is common but guidance on how it should be carried out varies and it is currently unclear how such guidance is viewed.AIM: To explore patients' and healthcare professionals' (HCPs) views and experiences of the use of different self-monitoring regimens to determine what is acceptable and feasible, and to inform future recommendations.DESIGN AND SETTING: Thirteen focus groups and four HCP interviews were held, with a total of 66 participants (41 patients and 25 HCPs) from primary and secondary care with and without experience of self-monitoring.METHOD: Standard and shortened self-monitoring protocols were both considered. Focus groups and interviews were recorded, transcribed verbatim, and analysed using the constant comparative method.RESULTS: Patients generally supported structured schedules but with sufficient flexibility to allow adaptation to individual routine. They preferred a shorter (3-day) schedule to longer (7-day) regimens. Although HCPs could describe benefits for patients of using a schedule, they were reluctant to recommend a specific schedule. Concerns surrounded the use of different schedules for diagnosis and subsequent monitoring. Appropriate education was seen as vital by all participants to enable a self-monitoring schedule to be followed at home.CONCLUSION: There is not a 'one size fits all approach' to developing the optimum protocol from the perspective of users and those implementing it. An approach whereby patients are asked to complete the minimum number of readings required for accurate blood pressure estimation in a flexible manner seems most likely to succeed. Informative advice and guidance should incorporate such flexibility for patients and professionals alike.

Learning objectives High blood pressure (hypertension) is one of the most important risk factors for cardiovascular disease,1 2 which is a significant cause of morbidity and mortality worldwide.3 Recent surveys from developed countries suggest that the prevalence of hypertension ranges from 20% to 30%, with 51%–80% receiving treatment but only 27%–66% with adequate blood pressure control.4 One subset of uncontrolled hypertensives who do not respond to treatment are known as resistant hypertensives. This article will describe how resistant hypertension is defined, its prevalence and prognosis, methods to diagnose it effectively in routine practice and strategies to effectively manage patients diagnosed with the condition. ### Definition of resistant hypertension Resistant hypertension is generally defined as uncontrolled clinic blood pressure (>140/90 mm Hg) after treatment with three or more antihypertensives.5 In the UK, National Institute for Health and Care Excellence (NICE) guidelines specify that these three should include optimal doses of an ACE inhibitor (or an angiotensin receptor blocker), a calcium channel blocker and a diuretic.6 However, there are some circumstances which preclude resistant hypertension, which must be ruled out before a formal diagnosis can be made. The so-called ‘pseudoresistant’ hypertension can be caused by poor clinic blood pressure measurement technique, patient non-adherence to prescribed medication, patient intolerance to certain antihypertensive medications and white coat hypertension (where blood pressure appears high in the clinic but is controlled out-of-the-office on home or ambulatory measurements).5 ### Prevalence and prognosis Most prevalence studies have been conducted in the USA using routine medical records and in that setting resistant hypertension is thought to be relatively common, affecting anywhere between 9% and 18% of patients with diagnosed hypertension (table 1 …

© The Author 2015. Published by Oxford University Press on behalf of the American Journal of Hypertension. BACKGROUND: Patients may have lower (white coat hypertension) or higher (masked hypertension) blood pressure (BP) at home compared to the clinic, resulting in misdiagnosis and suboptimal management of hypertension. This study aimed to systematically review the literature and establish the most important predictors of the home-clinic BP difference. METHODS: A systematic review was conducted using a MEDLINE search strategy, adapted for use in 6 literature databases. Studies examining factors that predict the home-clinic BP difference were included in the review. Odds ratios (ORs) describing the association between patient characteristics and white coat or masked hypertension were extracted and entered into a random-effects meta-analysis. RESULTS: The search strategy identified 3,743 articles of which 70 were eligible for this review. Studies examined a total of 86,167 patients (47% female) and reported a total of 60 significant predictors of the home-clinic BP difference. Masked hypertension was associated with male sex (OR 1.47, 95% confidence interval (CI) 1.18-1.75), body mass index (BMI, per kg/m2increase, OR 1.07, 95% CI 1.01-1.14), current smoking status (OR 1.32, 95% CI 1.13-1.50), and systolic clinic BP (per mm Hg increase, OR 1.10, 95% CI 1.01-1.19). Female sex was the only significant predictor of white coat hypertension (OR 3.38, 95% CI 1.64-6.96). CONCLUSIONS: There are a number of common patient characteristics that predict the home-clinic BP difference, in particular for people with masked hypertension. There is scope to incorporate such predictors into a clinical prediction tool which could be used to identify those patients displaying a significant masked or white coat effect in routine clinical practice.

Medical students need to have a sound theoretical knowledge of pharmacology and a training in the practical aspects of therapeutics in order to prescribe effectively, safely and rationally when they qualify. Students have traditionally sat written exams and the practical aspects have been largely ignored. At the University of Birmingham we set up an objective structured clinical examination (OSCE) style examination to test the practical aspects of therapeutics. Over the last 2 years, 434 students have been examined in this way to determine competency in various clinical skills including, for example prescription writing, the drawing up and giving of injections, setting up nebulizers, and patient counselling about drug effects. Over that time we found the therapeutics OSCE to be feasible and useful. It has demonstrated serious practical deficiencies that were not apparent from written examinations in some students' ability to prescribe and administer drugs. Since its introduction, performance in the OSCE has improved. Whether this will result in safer and more effective prescribing in the preregistration house officer year has not been formally evaluated but it appears that they approach this aspect of patient care with greater confidence than graduates from other schools.

Objective: To assess whether using intensive blood pressure targets leads to lower blood pressure in a community population of people with prevalent cerebrovascular disease. Design: Open label randomised controlled trial. Setting: 99 general practices in England, with participants recruited in 2009-11. Participants: People with a history of stroke or transient ischaemic attack whose systolic blood pressure was 125 mm Hg or above. Interventions: Intensive systolic blood pressure target (Main outcome measure: Change in systolic blood pressure between baseline and 12 months. Results: 529 patients (mean age 72) were enrolled, 266 to the intensive target arm and 263 to the standard target arm, of whom 379 were included in the primary analysis (182 (68%) intensive arm; 197 (75%) standard arm). 84 patients withdrew from the study during the follow-up period (52 intensive arm; 32 standard arm). Mean systolic blood pressure dropped by 16.1 mm Hg to 127.4 mm Hg in the intensive target arm and by 12.8 mm Hg to 129.4 mm Hg in the standard arm (difference between groups 2.9 (95% confidence interval 0.2 to 5.7) mm Hg; P=0.03). Conclusions: Aiming for target below 130 mm Hg rather than 140 mm Hg for systolic blood pressure in people with cerebrovascular disease in primary care led to a small additional reduction in blood pressure. Active management of systolic blood pressure in this population using a

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 to usual care.

Reduced perception of somatosensory stimulation in patients with essential hypertension may be due to deficits in the ascending somatosensory pathway. Function in the ascending somatosensory pathway was assessed by measuring N9, N13, and N20 somatosensory-evoked potentials in 14 unmedicated essential hypertensives and 22 normotensives. N9 amplitudes were smaller and N13 amplitudes marginally smaller in hypertensives than normotensives. N9 amplitudes were inversely associated with blood pressure. N20 amplitudes and N9, N13, and N20 latencies did not differ between groups. In addition, plexus-to-cord, cord-to-cortex, and plexus-to-cortex conduction times were not different between groups. These data suggest that hypertension affects the peripheral nervous system by reducing the number of active sensory nerve fibers without affecting myelination. However, hypertension does not seem to affect the afferent somatosensory pathway within the brain.

Previous research has demonstrated that the nociceptive flexion reflex (NFR) and pain-related evoked potentials are reduced in amplitude when elicited during the middle of the cardiac cycle. Despite these findings, suggesting a baroreceptor mechanism of antinociception during systole, pain intensity ratings reported in these studies were not modulated across the cardiac cycle. This discrepancy between the neurophysiological correlates of pain and its subjective experience was the focus of the current study that used a mixed block design to assess the effects of natural arterial baroreceptor activity on both the NFR and pain intensity and unpleasantness reports. Specifically, electrocutaneous stimuli were randomly delivered to the sural nerve at one of five intensities (50% pain threshold, 75% pain threshold, pain threshold, midway between pain threshold and pain tolerance, pain tolerance) at five intervals (0, 150, 300, 450, and 600 ms) after the R-wave of the electrocardiogram. Under painful stimulation, intensity and unpleasantness varied in a quadratic manner across the cardiac cycle; pain was highest at R + 300 ms and lowest at R + 0 and R + 600 ms. Under non-painful stimulation, ratings declined linearly as the cycle progressed. Finally, nociceptive responses did not differ among the R-wave to stimulation intervals for both painful and non-painful intensities. The observed phasic modulation of pain may be explained by a central nervous system alarm/defence reaction triggered by the unpredictability of the potentially damaging stimulation. The absence of systolic attenuation of nociceptive responding is compatible with previous evidence that baroreceptor modulation of the NFR is abolished under conditions of heightened arousal.

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.

Systemic lupus erythematosus (SLE) patients suffer from excess cardiac deaths due to accelerated atherosclerosis. Endothelial dysfunction is a marker of early atherosclerosis. We tested the hypothesis that SLE patients have impaired endothelial function and assessed the relationship between endothelial function and clinical outcome over the subsequent five years. Thirty-six female SLE patients were compared with 22 healthy age and sex matched controls. Endothelial dependent vasodilatation (EDD) was assessed at the brachial artery in response to shear stress. Endotheliumindependent dilatation induced by glyceryl trinitrate was also measured. Patients were followed for up to five years and the development of damage in the cardiovascular and other systems recorded. SLE patients showed significantly impaired endothelial function (median EDD 5.6%, IQR 3.1–7.2%) compared with healthy controls (median EDD 8.0%, IQR 6.3–9.3%; P = 0.001). Endothelium independent dilatation did not differ between the two groups. Endothelial function was significantly worse in postmenopausal compared with premenopausal women (median EDD 6.6%, IQR 3.9–7.8% versus 3.1%, IQR 2.6–5.1%; P = 0.016). Total cholesterol was inversely correlated with endothelial function in SLE patients (Spearman correlation r = -0.422, P = 0.025). There was no relationship between endothelial function and the development of damage in any organ system, including the cardiovascular system during patient follow-up. Patients with SLE have impaired endothelial function. In the small number of patients studied impaired endothelial function was not associated with a worse cardiovascular outcome over five years.

Measurement of ambulatory blood pressure is recommended by the National Institute for Health and Care Excellence guidelines to confirm the diagnosis of hypertension in the UK. This article describes the use of ambulatory devices, and discusses the benefits and disadvantages of their use in clinical practice.

Background Renal denervation (RDN) may lower blood pressure (BP); however, it is unclear whether medication changes may be confounding results. Furthermore, limited data exist on pattern of ambulatory blood pressure (ABP) response—particularly in those prescribed aldosterone antagonists at the time of RDN. Methods We examined all patients treated with RDN for treatment-resistant hypertension in 18 UK centres. Results Results from 253 patients treated with five technologies are shown. Pre-procedural mean office BP (OBP) was 185/102 mmHg (SD 26/19; n = 253) and mean daytime ABP was 170/98 mmHg (SD 22/16; n = 186). Median number of antihypertensive drugs was 5.0: 96 % ACEi/ARB; 86 % thiazide/loop diuretic and 55 % aldosterone antagonist. OBP, available in 90 % at 11 months follow-up, was 163/93 mmHg (reduction of 22/9 mmHg). ABP, available in 70 % at 8.5 months follow-up, was 158/91 mmHg (fall of 12/7 mmHg). Mean drug changes post RDN were: 0.36 drugs added, 0.91 withdrawn. Dose changes appeared neutral. Quartile analysis by starting ABP showed mean reductions in systolic ABP after RDN of: 0.4; 6.5; 14.5 and 22.1 mmHg, respectively (p 0.2). Conclusion In 253 patients treated with RDN, office BP fell by 22/9 mmHg. Ambulatory BP fell by 12/7 mmHg, though little response was seen in the lowermost quartile of starting blood pressure. Fall in BP was not explained by medication changes and aldosterone antagonist use did not affect response. Electronic supplementary material The online version of this article (doi:10.1007/s00392-015-0959-4) contains supplementary material, which is available to authorized users.

© 2016 British Journal of General Practice. Background Free blood pressure (BP) checks offered by community pharmacies provide a potentially useful opportunity to diagnose and/or manage hypertension, but the accuracy of the sphygmomanometers in use is currently unknown. Aim To assess the accuracy of validated automatic BP monitors used for BP checks in a UK retail pharmacy chain. Design and setting Cross-sectional, observational study in 52 pharmacies from one chain in a range of locations (inner city, suburban, and rural) in central England. Method Monitor accuracy was compared with a calibrated reference device (Omron PA-350), at 50 mmHg intervals across the range 0-300 mmHg (static pressure test), with a difference from the reference monitor of +/-3 mmHg at any interval considered a failure. The results were analysed by usage rates and length of time in service. Results Of 61 BP monitors tested, eight (13%) monitors failed (that is, were >3 mmHg from reference), all of which underestimated BP. Monitor failure rate from the reference monitor of +/-3 mmHg at any testing interval varied by length of time in use (2/38, 5% 18 months, P = 0.038) and to some extent, but non-significantly, by usage rates (4/22, 18% in monitors used more than once daily; 2/33, 6% in those used less frequently, P = 0.204). Conclusion BP monitors within a pharmacy setting fail at similar rates to those in general practice. Annual calibration checks for blood pressure monitors are needed, even for new monitors, as these data indicate declining performance from 18 months onwards.

BACKGROUND: This study investigated the relationship of ethnicity to the differences between blood pressure (BP) measured in a clinic setting and by ambulatory blood pressure monitoring (ABPM) in individuals with a previous diagnosis of hypertension (HT) and without a previous diagnosis of hypertension (NHT). METHODS: A cross-sectional comparison of BP measurement was performed in 770 participants (white British (WB, 39%), South Asian (SA, 31%), and African Caribbean (AC, 30%)) in 28 primary care clinics in West Midlands, United Kingdom. Mean differences between daytime ABPM, standardized clinic (mean of 3 occasions), casual clinic (first reading on first occasion), and last routine BP taken at the general practitioner practice were compared in HT and NHT individuals. RESULTS: Daytime systolic and diastolic ABPM readings were similar to standardized clinic BP (systolic: 128 (SE 0.9) vs. 125 (SE 0.9) mm Hg (NHT) and 132 (SE 0.7) vs. 131 (SE 0.7) mm Hg (HT)) and were not associated with ethnicity to a clinically important extent. When BP was taken less carefully, differences emerged: casual clinic readings were higher than ABPM, particularly in the HT group where the systolic differences approached clinical relevance (131 (SE 1.2) vs. 129 (SE 1.0) mm Hg (NHT) and 139 (SE 0.9) vs. 133 (SE 0.7) mm Hg (HT)) and were larger in SA and AC hypertensive individuals (136 (SE 1.5) vs. 133 (SE 1.2) mm Hg (WB), 141 (SE 1.7) vs. 133 (SE 1.4) mm Hg (SA), and 142 (SE 1.6) vs. 134 (SE 1.3) mm Hg (AC); mean differences: 3 (0-7), P = 0.03 and 4 (1-7), P = 0.01, respectively). Differences were also observed for the last practice reading in SA and ACs. CONCLUSIONS: BP differences between ethnic groups where BP is carefully measured on multiple occasions are small and unlikely to alter clinical management. When BP is measured casually on a single occasion or in routine care, differences appear that could approach clinical relevance.

© 2014 © The Author 2014. Published by Oxford University Press on behalf of the American Journal of Hypertension. BACKGROUND An exaggerated morning blood pressure surge (MBPS) may be associated with stroke and other cardiovascular events, but the threshold at which an MBPS becomes pathological is unclear. This study aimed to systematically review the existing literature and establish the most appropriate definition of pathological MBPS. METHODS A MEDLINE search strategy was adapted for a range of literature databases to identify all prospective studies relating an exaggerated MBPS to cardiovascular endpoints. Hazard ratios (HRs) were extracted and synthesized using random-effects meta-analysis. RESULTS The search strategy identified 2,964 unique articles, of which 17 were eligible for the study. Seven different definitions of MBPS were identified; the most common was a prewaking surge (mean blood pressure for 2 hours after wake-up minus mean blood pressure for 2 hours before wake-up; n = 6 studies). Summary meta-analysis gave no clear evidence that prewaking MBPS (defined by a predetermined threshold: >25-55mm Hg) was associated with all cardiovascular events (n = 2 studies; HR = 0.94, 95% confidence interval (CI) = 0.39-2.28) or stroke (n = 2 studies; HR = 1.26, 95% CI = 0.92-1.71). However, using a continuous scale, which has more power to detect an association, there was evidence that a 10 mm Hg increase in MBPS was related to an increased risk of stroke (n = 3 studies; HR = 1.11, 95% CI = 1.03-1.20). CONCLUSIONS These findings suggest that when measured and analyzed as a continuous variable, increasing levels of MBPS may be associated with increased risk of stroke. Large, protocol-driven individual patient data analyses are needed to accurately define this relationship further.

Summary Aim: The aim of this study was to examine the effect of the cadioselective B1-adrenoceptor blocker nebivolol on glycaemic control, lipid profile and markers of oxidative stress in patients with type 2 diabetes over a 6-month period. Methods: Twenty-six patients with mild to moderate hypertension (140–160 mmHg systolic, 90–105 mmHg diastolic) confirmed on 24-h blood pressure monitoring, were treated with nebivolol 5 mg daily for 6 months. Total serum cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) subfractions, lipid hydroperoxides (LHPs) and total antioxidant capacity (TAC) were measured before and after 6 months of treatment. Results: Nebivolol, as expected, reduced mean daytime systolic and diastolic pressures on ambulatory monitoring (149 ± 9 to 140 ± 13 mmHg, P = 0·02 and 84 ± 7 to 77 ± 9 mmHg, P

The nociceptive flexion reflex has been regarded as an objective correlate of pain perception. This study examined whether the nociceptive flexion reflex is modulated by physiological arousal in the same manner as pain. Cardiovascular activity, nociceptive flexion reflex thresholds, and pain ratings were measured in 40 healthy adults under three conditions that demanded varying degrees of physiological arousal: Rest, number repetition, and mental arithmetic. Heart rates were faster and R-wave to pulse intervals shorter during mental arithmetic than number repetition, whereas heart rates were slower and R-wave to pulse intervals longer during rest compared to number repetition. Both mental arithmetic and number repetition were associated with reduced nociceptive flexion reflex thresholds compared to rest. Although the nociceptive flexion reflex thresholds were the same during mental arithmetic and number repetition, pain ratings were lower during mental arithmetic than number repetition and rest. The results indicate that nociception was facilitated but pain was inhibited by increased physiological arousal. This dissociation suggests that the nociceptive flexion reflex threshold is not a suitable correlate of pain during states of increased arousal.

Summary Background: Treatment of hypertension in the elderly people reduces the risk of cardiovascular and cerebrovascular events. Effective treatment often will require the use of two or more antihypertensive agents. Elderly people are at increased risk of adverse events from medication because of physiological changes in pharmacokinetics and pharmacodynamics, polypharmacy and drug interactions. They might not tolerate conventional add-on regimens of antihypertensives as a result. Objective: To investigate the use of the I1-imidazoline receptor agonist moxonidine as an ‘add-on’ agent in elderly patients with resistant hypertension. Methods: We investigated the safety and efficacy of moxonidine (200–400 μg) in a group of elderly patients whose blood pressure (BP) control remained poor despite treatment with two or more antihypertensives. BP was assessed by ambulatory BP monitoring with Spacelabs oscillometric equipment (Model 90207) before and after 6 weeks of treatment with moxonidine used as an ‘add-on’ agent with the patients normal medication. Results: Following treatment with moxonidine, the mean daytime systolic BP fell from 169·2 to 153·8 mmHg, a significant reduction of 15·4 ± 8·9 mmHg (P = 0·003). The mean daytime diastolic BP fell from 91·6 to 84·2 mmHg, a reduction of 7·4 ± 5·8 mmHg (P = 0·017). For the night-time readings, the systolic BP fell from 151·1 to 141·2 mmHg, a reduction of 9·3 ± 9·3 mmHg (P = 0·05). The corresponding diastolic fall in BP was not significant (77·9–74·7 mmHg). The 24 h-readings showed a significant reduction in the mean systolic BP from 163·0 to 148·6 mmHg (P = 0·004). The mean diastolic BP also fell significantly from 87·2 to 80·2 mmHg (P = 0·013). Clinical BP readings also showed a significant reduction from 195·9 ± 19·6 to 174 ± 17·8 mmHg (P = 0·002) and 103·6 ± 9·5 to 99·0 ± 12·4 mmHg (P = 0·013) for systolic and diastolic readings respectively. Moxonidine was well tolerated in 11 of the14 patients. Conclusion: These results suggest that moxonidine might have a place as an ‘add-on’ treatment in elderly patients whose hypertension is poorly controlled despite treatment with two or more antihypertensive agents.

The arterial baroreflex may mediate hypertensive hypoalgesia. Carotid baroreceptors can be artificially stimulated by neck suction and inhibited by compression. Effects of brief neck suction and compression on nociceptive responding and pain were studied in 25 normotensive adults. The sural nerve was electrocutaneously stimulated at threshold intensity during systole or diastole combined with neck suction, neck compression, or no pressure. Nociceptive responding was indexed by electromyographic activity elicited in the biceps femoris. Participants rated the intensity of sural stimulation. Although artificial baroreceptor stimulation (suction) did not affect nociceptive responding, baroreceptor inhibition (compression) reduced pain ratings. In contrast, natural baroreceptor stimulation during systole reduced nociceptive responding compared to diastole, but did not affect pain ratings. The data provide partial support for baroreflex modulation of pain.