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Advance Statements enable mental health patients to have their preferences considered in treatment decisions in the event of losing capacity, but their uptake is poor. This is for complex and often conflicting reasons and factors related to service user, clinician, and institutional priorities, which influence clinical practice. A Foucauldian discourse analysis approach was used to explore how 13 mental health clinicians positioned their role in relation to Advance Statements. Five positions emerged from the data: taking account of peoples’ wishes, enabling people to have their say (to a point), we know what’s best, firefighting with risk, and leverage and liability. Discursive practices demonstrated and reinforced power relations between patients, clinicians, and wider systems. These findings highlight the challenge of legitimizing the knowledge of patients and need for a cultural shift at a systems level, which recognizes the ways Advance Statements meet the needs of all stakeholders.

Our editorial consultants highlight the significant advances made in their therapeutic areas over the past 20 years. Here we look at developments in CVS and respiratory medicine and diabetes. Copyright © 2010 Wiley Interface Ltd

Our Drug review of hypertension discusses the properties of the wide range of antihypertensive agents available and their recommended use, both alone and in combination, followed by sources of further information in Resources. Copyright © 2009 Wiley Interface Ltd

Exforge is a combination of the ARB valsartan and the CCB amlodipine to treat patients whose blood pressure is not controlled with either component. In our review, Steve Chaplin presents the clinical data relating to its efficacy and adverse effects, and Professor McInnes comments on its role in hypertension. Copyright © 2007 Wiley Interface Ltd

Optimal drug treatment for patients with resistant hypertension is undefined. We aimed to test the hypotheses that resistant hypertension is most often caused by excessive sodium retention, and that spironolactone would therefore be superior to non-diuretic add-on drugs at lowering blood pressure.In this double-blind, placebo-controlled, crossover trial, we enrolled patients aged 18-79 years with seated clinic systolic blood pressure 140 mm Hg or greater (or ≥135 mm Hg for patients with diabetes) and home systolic blood pressure (18 readings over 4 days) 130 mm Hg or greater, despite treatment for at least 3 months with maximally tolerated doses of three drugs, from 12 secondary and two primary care sites in the UK. Patients rotated, in a preassigned, randomised order, through 12 weeks of once daily treatment with each of spironolactone (25-50 mg), bisoprolol (5-10 mg), doxazosin modified release (4-8 mg), and placebo, in addition to their baseline blood pressure drugs. Random assignment was done via a central computer system. Investigators and patients were masked to the identity of drugs, and to their sequence allocation. The dose was doubled after 6 weeks of each cycle. The hierarchical primary endpoints were the difference in averaged home systolic blood pressure between spironolactone and placebo, followed (if significant) by the difference in home systolic blood pressure between spironolactone and the average of the other two active drugs, followed by the difference in home systolic blood pressure between spironolactone and each of the other two drugs. Analysis was by intention to treat. The trial is registered with EudraCT number 2008-007149-30, and ClinicalTrials.gov number, NCT02369081.Between May 15, 2009, and July 8, 2014, we screened 436 patients, of whom 335 were randomly assigned. After 21 were excluded, 285 patients received spironolactone, 282 doxazosin, 285 bisoprolol, and 274 placebo; 230 patients completed all treatment cycles. The average reduction in home systolic blood pressure by spironolactone was superior to placebo (-8·70 mm Hg [95% CI -9·72 to -7·69]; p0·0001), superior to the mean of the other two active treatments (doxazosin and bisoprolol; -4·26 [-5·13 to -3·38]; p0·0001), and superior when compared with the individual treatments; versus doxazosin (-4·03 [-5·04 to -3·02]; p0·0001) and versus bisoprolol (-4·48 [-5·50 to -3·46]; p0·0001). Spironolactone was the most effective blood pressure-lowering treatment, throughout the distribution of baseline plasma renin; but its margin of superiority and likelihood of being the best drug for the individual patient were many-fold greater in the lower than higher ends of the distribution. All treatments were well tolerated. In six of the 285 patients who received spironolactone, serum potassium exceeded 6·0 mmol/L on one occasion.Spironolactone was the most effective add-on drug for the treatment of resistant hypertension. The superiority of spironolactone supports a primary role of sodium retention in this condition.The British Heart Foundation and National Institute for Health Research.

Potassium depletion by thiazide diuretics is associated with a rise in blood glucose. We assessed whether addition or substitution of a potassium-sparing diuretic, amiloride, to treatment with a thiazide can prevent glucose intolerance and improve blood pressure control.We did a parallel-group, randomised, double-blind trial in 11 secondary and two primary care sites in the UK. Eligible patients were aged 18-80 years; had clinic systolic blood pressure of 140 mm Hg or higher and home systolic blood pressure of 130 mmHg or higher on permitted background drugs of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β blockers, calcium-channel blockers, or direct renin inhibitors (previously untreated patients were also eligible in specific circumstances); and had at least one component of the metabolic syndrome in addition to hypertension. Patients with known diabetes were excluded. Patients were randomly assigned (1:1:1) to 24 weeks of daily oral treatment with starting doses of 10 mg amiloride, 25 mg hydrochlorothiazide, or 5 mg amiloride plus 12·5 mg hydrochlorothiazide; all doses were doubled after 12 weeks. Random assignment was done via a central computer system. Both participants and investigators were masked to assignment. Our hierarchical primary endpoints, assessed on a modified intention-to-treat basis at 12 and 24 weeks, were the differences from baseline in blood glucose measured 2 h after a 75 g oral glucose tolerance test (OGTT), compared first between the hydrochlorothiazide and amiloride groups, and then between the hydrochlorothiazide and combination groups. A key secondary endpoint was change in home systolic blood pressure at 12 and 24 weeks. This trial is registered with ClinicalTrials.gov, number NCT00797862, and the MHRA, Eudract number 2009-010068-41, and is now complete.Between Nov 18, 2009, and Dec 15, 2014, 145 patients were randomly assigned to amiloride, 146 to hydrochlorothiazide, and 150 to the combination group. 132 participants in the amiloride group, 134 in the hydrochlorothiazide group, and 133 in the combination group were included in the modified intention-to-treat analysis. 2 h glucose concentrations after OGTT, averaged at 12 and 24 weeks, were significantly lower in the amiloride group than in the hydrochlorothiazide group (mean difference -0·55 mmol/L [95% CI -0·96 to -0·14]; p=0·0093) and in the combination group than in the hydrochlorothiazide group (-0·42 mmol/L [-0·84 to -0·004]; p=0·048). The mean reduction in home systolic blood pressure during 24 weeks did not differ significantly between the amiloride and hydrochlorothiazide groups, but the fall in blood pressure in the combination group was significantly greater than that in the hydrochlorothiazide group (p=0·0068). Hyperkalaemia was reported in seven (4·8%) patients in the amiloride group and three (2·3%) patients in the combination group; the highest recorded potassium concentration was 5·8 mmol/L in a patient in the amiloride group. 13 serious adverse events occurred but the frequency did not differ significantly between groups.The combination of amiloride with hydrochlorothiazide, at doses equipotent on blood pressure, prevents glucose intolerance and improves control of blood pressure compared with montherapy with either drug. These findings, together with previous data about morbidity and mortality for the combination, support first-line use of amiloride plus hydrochlorothiazide in hypertensive patients who need treatment with a diuretic.British Heart Foundation and National Institute for Health Research.

Introduction Resistant hypertension is inadequately controlled blood pressure (BP) despite treatment with at least three BP-lowering drugs. A popular hypothesis is that resistant hypertension is due to excessive Na+-retention, and that ‘further diuretic therapy’ will be superior to alternative add-on drugs. Methods and analysis Placebo-controlled, random crossover study of fourth-line treatment when added to standard (A+C+D) triple drug therapy: ACE inhibitor or Angiotensin receptor blocker (A) +Calcium channel blocker (C)+Diuretic (D). Patients (aged 18–79 years) with clinical systolic BP≥140 mm Hg (135 mm Hg in diabetics) and Home BP Monitoring (HBPM) systolic BP average ≥130 mm Hg on treatment for at least 3 months with maximum tolerated doses of A+C+D are randomised to four consecutive randomly allocated 12-week treatment cycles with an α-blocker, β-blocker, spironolactone and placebo. The hierarchical coprimary end point is the difference in HBPM average systolic BP between (in order) spironolactone and placebo, spironolactone and the average of the other two active drugs, spironolactone and each of the other two drugs. A key secondary outcome is to determine whether plasma renin predicts the BP response to the different drugs. A sample size of 346 (allowing 15% dropouts) will confer 90% power to detect a 3 mm Hg HBPM average systolic BP difference between any two drugs. The study can also detect a 6 mm Hg difference in HBPM average systolic BP between each patient's best and second-best drug predicted by tertile of plasma renin. Ethics and dissemination The study was initiated in May 2009 and results are expected in 2015. These will provide RCT evidence to support future guideline recommendations for optimal drug treatment of resistant hypertension. Trial registration number Clinicaltrials.gov NCT02369081, EUDract number: 2008-007149-30.

Introduction Previous studies have suggested that more intensive initial therapy for hypertension results in better long-term blood pressure (BP) control. We test this hypothesis comparing initial monotherapy with dual therapy in the management of essential hypertension. Methods and analysis The study is a prospective, multicentre, double-blind, active-controlled trial in patients with essential hypertension. Around 50% of patients studied will be newly diagnosed and the others will be known hypertensives who previously received only monotherapy. The trial is divided into three phases as follows: Phase 1 (Week 0–Week 16): Randomised, parallel-group, masked assignation to either combination or monotherapy. Phase 2 (Week 17–Week 32): Open-label combination therapy. Phase 3 (Week 33–Week 52): Open-label combination therapy plus open-label add-on (if BP is above 140/90 mm Hg). Hierarchical primary end points are: a comparison of home BP (home systolic blood pressure (HSBP)) averaged over the duration of phase 1 and 2 in the combination versus monotherapy arms. If combination is superior in this analysis, then the averaged mean HSBP between initial monotherapy and initial combination therapy at the end of phase 2 will be compared. Secondary end points include: BP control at 1 year; the role of age, baseline renin, sodium status, plasma volume, haemodynamic compensation and peripheral resistance on BP control; validation of the National Institute for Clinical Excellence/British Hypertension Society joint guideline algorithm; safety and tolerability of combination therapy; and the impact of combination versus monotherapy on left ventricular mass and aortic pulse wave velocity. A sample size of 536 (268 in each group) will have 90% power to detect a difference in means of 4 mm Hg. Ethics and dissemination PATHWAY 1 was approved by UK ethics (REC Reference 09/H0308/132). Trial results will be published and all participating subjects will be informed of the results. Trial registration number UKCRN 4499 and EudraCT number 2008-007749-29 registered 27/08/2009.

Introduction: Recent data suggest self-reported acetaminophen use is associated with increased risk of cardiovascular events and that acetaminophen causes a modest rise in arterial blood pressure. There are no randomized studies, studies using verified prescription data or studies in high risk patients that investigate this relationship. Hypothesis: We aimed to assess the relationship between acetaminophen prescription data and risk of stroke and myocardial infarction in patients with hypertension. Methods: We performed a retrospective data analysis using data contained within the UK Clinical Research Practice Datalink. This includes verified prescription data. Multivariable Cox proportional hazard models were used to estimate hazard ratios for stroke or MI associated with acetaminophen use over a 10-year period. Acetaminophen exposure was a time dependent variable. A propensity matched design was also used to reduce potential for confounding. Results: We included 24496 hypertensive individuals aged 65-years or older. Of these, 10878 were acetaminophen exposed and 13618 were not. There was no relationship between risk of stroke, MI or any vascular event and acetaminophen exposure on adjusted analysis (OR 1.09, 95% CI 0.86 to 1.38; OR 0.98, 95% CI 0.76 to 1.27; OR 1.17, 95% CI 0.99 to 1.37 respectively). Results in the propensity matched sample (n=4000 per group) were similar and high frequency users (defined as receiving a prescription for >75% of months) were also not at increased risk. Conclusions: In summary, use of acetaminophen was not associated with an increased risk of stroke or myocardial infarction in a large cohort of hypertensive patients.

Introduction How practice nurses can tackle the hyertension epidemic Salt: old or new villain? Ethnic differences in cardiovascular disease: focus on Afro-Caribbeans Ethnic: differences in cardiovascular disease: focus on Asians Cardiovascular disease and cholesterol guidlines: can the UK aford them? A revolution in diabetic care? AT1 receptor blockers: an overview Experience with valsartan Health Survey for England: the state of hypertension managment

People with pre-hypertension (high blood pressure but below the conventional threshold for intervention with antihypertensive drugs) undoubtedly have increased risk of cardiovascular and other complications. However, the vast majority has low absolute risk and whether treatment would be beneficial is uncertain. While pharmacotherapy has attractions from a public health perspective, clinicians and crucially those with pre-hypertension require robust evidence that drug treatment will lead to short term as well as long term gains. Any changes in recommendations should await adequately powered outcome studies which provide solid evidence of the magnitude of absolute risk reduction in treating pre-hypertension and assessment of the cost-effectiveness.

Steve Chaplin and Professor Gordon McInnes provide an overview of the indications, properties and current recommended place in therapy of the angiotensin-II receptor antagonists. Copyright © 2009 Wiley Interface Ltd

This paper will present an overview of the role of the European Environment Agency (EEA) in environmental information at the European level for policy making and assessment as well as present and analyse some of the latest information on national, EU 15 and European emission estimates, projections and reduction goals for the main greenhouse gases (GHGs).

We report a case of severe mesenteric ischemia in a patient with essential thrombocythemia. The standard treatment of mesenteric ischemia is surgical, but in view of the presence of a combined clotting and bleeding tendency, this patient was treated nonsurgically with iv prostacyclin

The Weekly Returns System of the Royal College of General Practitioners was used to assess the effect on respiratory illness of the acid transport event that occurred during January 1985. The pollution event, as assessed by SO2 and smoke levels measured at pollution monitoring stations within and without the affected area showed only modest rises in SO2 levels, which were less than levels that occurred 4 years earlier. January is the peak time of year for reporting of acute respiratory episodes, and the minor increase in pollution was not reflected in any rise in respiratory morbidity, both for all ages and for different age bands. There was a rise in rates for children up to the age of 14, but this was seen each year and in both polluted and nonpolluted areas. This was probably due to children returning to school after the winter vacation and the subsequent spread of viral infections. The limitations of the two data sets in this analysis are discussed, including the relative insensitivity of weekly data in picking out a short-lived event, the distribution of the practices and pollution monitoring stations, and the effect of the extreme cold weather and the coal miners' strike on domestic coal burning during this event.