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As clinical pharmacologists representing a truly generalist specialty, spanning all ages and organs, we welcome the call for rebalancing of specialist and generalist skills to improve care for patients with multimorbidity.1 Clinical pharmacology and therapeutics (CPT) arose in the last century in response to the explosive development of new drugs and parallel evolution of medicines regulation. In the 1970s, the …

How long someone has to live intuitively seems important in rationing decisions. Incorporating it into economic assessments, as described here, could make decisions fairer Explicit rationing—decisions not to fund certain treatments—has become a fact of life in many healthcare systems.1–4 Health economic assessments often underpin rationing decisions, although it remains unclear whether society's values are well reflected by the utilitarian approach of maximising the units of health attainable from available resources.5 6 Health economic assessments are used to determine the additional cost per unit of health gain for different treatment options. Cost effectiveness analysis is the most common method of assessment7 8 and, for life shortening conditions, primarily focuses on the additional cost per life year gained. We propose that prognosis without treatment is an important contextual modifier of life years gained in evaluating treatments for life shortening conditions. We present initial data supporting this hypothesis and describe resource allocation strategies that use this information. Life years gained represent the extra life expectancy resulting from a treatment. By definition, the comparison is with the life expectancy associated with an established standard of care for the condition. Depending on the condition, the established standard of care may be interventional or supportive. Using life years gained in health economic assessments has several problems. The first is that they are inapplicable to treatments that do not prolong life. Most of the other problems relate to the fact that a year of life in a particular clinical setting may not have the same value as a year of life in a different clinical setting. Initial attempts at improving the fairness of life years gained resulted in the development of quality adjusted life years (QALYs). In a QALY, each unit of time in a health state is weighted by both …

Objective: To investigate the time course of an epidemic of asthma after a thunderstorm, characteristics of patients affected, and the demand on emergency medical resources. Design: Study of registers and records in accident and emergency departments and questionnaire to staff. Setting: London area. Subjects: All patients presenting at 12 accident and emergency departments with asthma or other airways disease. Main outcome measures: Numbers of patients, clinical features, information on shortage of resources—equipment, drugs, and staff. Results: The epidemic had a sudden onset on 24 June 1994; 640 patients with asthma or other airways disease attended during 30 hours from 1800 on 24 June, nearly 10 times the expected number. Over half (365) the patients were aged 21 to 40 years. A history of hay fever was recorded in 403 patients; for 283 patients this was the first known attack of asthma; a history of chronic obstructive airways disease was recorded in 12 patients. In all, 104 patients were admitted (including five to an intensive care unit). Several departments ran out of equipment or drugs, called in additional doctors, or both. Conclusions: This study supports the view that this epidemic was larger than previously reported epidemics and the hypothesis that “thunderstorm associated asthma” is related to aeroallergens. Demands on resources were considerable; a larger proportion of patients needing intensive care would have caused greater problems. Key messages Key messages People affected by thunderstorm associated asthma are characteristically young atopic adults who either are not known to have previously had asthma or are asthmatic but probably do not have steroid inhaler prophylaxis Thunderstorm associated asthma seems to have had a benign course in most patients in this epidemic, but many patients presenting to accident and emergency departments should not induce complacency in the treatment of acute asthma This kind of “major incident” puts a strain on emergency medical services in a way not usually anticipated because all hospitals in an area may be affected

Henry Fok, David Webb, and Euan Sandilands explain the work of clinical toxicologists and how to get a foothold in this research oriented career

OBJECTIVE--To determine general practitioners' attitudes to medical audit and to establish what initiatives are already being undertaken; to define future ideas for audit and perceived difficulties in implementing audit in primary care. DESIGN--Analysis of responses to a self administered postal questionnaire. SETTING--Urban conurbation with a population of about 750,000. PARTICIPANTS--386 general practitioners on the general medical list of Leeds Family Practitioner Committee. MAIN OUTCOME MEASURES--Extent of recording of practice activity data and outcome measures and clinical data, use of data, and audit performed; ideas for audit and perceived difficulties. RESULTS--317 doctors responded to the questionnaire (individual response rate 82%) from 121 practices (practice response rate 88%). In all, 206 doctors thought that audit could improve the quality of care; 292 collected practice activity data, though 143 of them did not use it. A total of 111 doctors recorded some outcome measures, though half of them did not use them. Varying proportions of doctors had registers, for various diseases (136 had at least one register), disease management policies (60 doctors), and prescribing policies. In all, 184 doctors met monthly with other members of the primary health care team. CONCLUSIONS--Much poorly focused data collection is taking place. Some doctors have experience in setting up basic information systems and practice policies, and some audit is being performed. The family health services authorities need to take seriously the perceived difficulties of time, organisation, and resources concerned with audit.

In 2011 the National Institute for Health and Care Excellence (NICE) updated UK hypertension guidance.1 Bendroflumethiazide 2.5 mg, still the most commonly prescribed UK antihypertensive,2 was replaced by chlortalidone (12.5-50 mg) as the recommended thiazide-like diuretic, because of its much stronger evidence …

The potential dangers of hyperoxia need to be recognised Oxygen is cheap, widely available, and used in a range of settings and conditions to relieve or prevent tissue hypoxia. Since its discovery by Scheele and Priestley in the 1770s, it has remained one of the most effective therapeutic agents available. However, as a result of poor prescribing and monitoring, inappropriate doses are often given.1 Oxygen is most commonly delivered by devices with variable performance such as face masks and nasal cannulae. These can produce unexpectedly high concentrations of inspired oxygen, particularly when ventilation is depressed.2 In addition, masks that incorporate a reservoir bag are often used in emergencies, following the widespread adoption of advanced trauma life support style (or ATLS) guidelines. These appliances can produce systemic hyperoxia that is generally assumed to be harmless. However, emerging evidence suggests that for some patients with acute medical conditions, hyperoxia may be harmful. Oxygen therapy is often …

The Joint British Societies’ (JBS) charts use a “traffic lights” system to emphasise different categories of cardiovascular risk.1 They were published in 2005 in conjunction with the societies’ guidelines2 and are reproduced biannually in the BNF . We recently observed that the green (

EDITOR—An editorial should bring an important topic to readers' attention and engage their interest, provoke a reaction, and trigger debate. We are delighted that the recent editorial on poor prescribing in the United Kingdom seems to have done all of these things.1 We did not give a thorough account of all the evidence, but we are surprised that Rubin thinks that we provided no evidence at all.2 We cited …

EDITOR, — Because of their proved benefit in reducing cardiovascular morbidity and mortality and their low cost compared with the costs of other antihypertensive agents, thiazide diuretics have been widely recommended for the initial treatment of essential hypertension.¢RF 1-3¢ Indeed, the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure in the United States recently returned to recommending these agents, or s blockers, as first line treatment in preference to newer drugs.2 Roy Harper and colleagues highlight the benefits of low doses of thiazide diuretic in essential hypertension.4 They show that, compared with 5 mg bendrofluazide, a dose of 1.25 mg has substantially less effect on serum potassium concentration and no effect on hepatic insulin action. This complements an earlier paper showing that low doses of bendrofluazide (1.25 mg and 2.5 mg) are effective in lowering blood pressure in patients with mild to moderate hypertension but are substantially less likely than higher doses to cause hypokalaemia, hyperglycaemia, or hyperuricaemia.5 Given this information, it might be expected that bendrofluazide 1.25 mg was …

Editor—We were disappointed to hear that a doctor in India has been criticised for treating pulmonary hypertension in three neonates (so called blue babies) with the phosphodiesterase type 5 inhibitor sildenafil (Viagra), a drug not licensed for this purpose.1 Many drugs are widely and appropriately used outside their product licence.2 Such prescribing practice is common in adult medicine, but is particularly prevalent in paediatrics because companies rarely undertake the work necessary to gain a licence for children. The decision to prescribe outwith a drug's licence should be supported by evidence of safety and potential benefit and, when possible, by a reasonable body of supporting professional opinion. Of course, controlled clinical trials should be performed when possible to evaluate new treatments for specific indications. But these data are not always available, and then clinicians must make difficult decisions as to whether other information, such as efficacy and safety in other groups of patients, justifies unlicensed drug use. Subsequently, case reports should be published, facilitating scientific debate and informing the design of clinical trials. Evidence is growing that sildenafil acts as a vasodilator in the pulmonary circulation and is effective in lowering pulmonary artery pressure in pulmonary arterial hypertension. This effect has been shown in adults with pulmonary hypertension and healthy volunteers with pulmonary hypertension induced by hypoxia.3,4 Intravenous sildenafil also normalised pulmonary artery pressure in an animal model of neonatal pulmonary hypertension.5 The evidence currently available is not sufficient generally to recommend the use of sildenafil in neonates with pulmonary hypertension. Assuming, however, that sildenafil was used as a last resort, after standard treatment, we believe that there are sufficient data to support the actions of this doctor. Perhaps the publicity that has arisen about this action will encourage further clinical research into the potential of inhibiting phosphodiesterase type 5 as a treatment for neonatal pulmonary hypertension, which may ultimately result in wider benefit to patients.

EDITOR—Academic clinical research, including the evaluation of new treatments, is central to providing high quality, cost effective care to patients, and it requires the cooperation and goodwill of the patients who volunteer to participate. The research process is externally regulated and monitored by ethics committees to ensure that patients are protected. We welcome the debate on the Data Protection Act and access to patients' records,1–3 and wish to raise a related concern about the General Medical Council's recent guidelines on …

The association between hypertension and a “hardening” of the pulse and apoplexy has been recognised for hundreds of years. The major problem in elderly people is isolated systolic hypertension, defined as a raised systolic pressure but normal diastolic pressure. It affects around half of people aged over 60 years.1 Originally, because isolated systolic hypertension was so common it was considered part of ageing and, like essential hypertension, benign. However, there is now compelling evidence from cross sectional, longitudinal, and randomised controlled trials that show that isolated systolic hypertension confers a substantial cardiovascularrisk.2 3 Despite this, it remains underdiagnosed and largely untreated.4 The roots of this lie in a century of overreliance on the importance of diastolic pressure and largely unjustified concerns about the potential adverse consequences of treating systolic pressure. After the mercury sphygmomanometer …

The four blood glucose monitors available in the United Kingdom were compared by asking the opinions of 24 patients who used each monitor for two weeks, by correlating their blood glucose results with those obtained in the laboratory, and by having the monitors examined by an electronics engineer. Of the battery-operated monitors, patients preferred the Hypocount (15) to the Glucochek (9). The mains-operated units were less popular, with little to choose between Eyetone and Reflomat. Under field conditions the blood glucose results obtained with the Glucochek correlated poorly with the standard reference method. In contrast the Hypocount, Eyetone, and Reflomat machines produced good correlations. Poor results with the Glucochek were mainly due to faulty timing systems. The patients' preference for the Hypocount was supported by tests of performance under laboratory conditions and by the electronics engineer's report.

A recognised problem with the cervical screening programme in the United Kingdom is the failure to include women who have never had a cervical smear test, who are a high risk group. The implementation of a district based call scheme in East Berkshire in 1986 is described whereby women aged 20-64 with no record of a cervical smear test who were judged to be eligible for testing by their general practitioner were sent a personal invitation from their general practitioner to attend for a test. A list of high risk unscreened women was kept by each practice, and a duplicate sent to the cytology laboratory to update the central records. Six months after each batch of invitations had been sent the resulting number of women having a smear test was assessed. Forty three of 51 practices approached agreed to participate in the five year scheme. During the first year lists were sent to the 43 participating practices. The first list was returned to the cytology laboratory by 37 practices and the second by 33; practices varied in their responses, however, some needing considerable persuasion to return the lists. Of 972 identified unscreened women from the total 3757 women listed in the lists of the family practitioner committee, 247 (25%) had a cervical smear test in response to the invitation, representing an overall increase of 7% in the screened population. The preliminary findings of the five year study have shown that screening can be improved by a systematic call scheme. Coordinated support from the area health authority in health education, monitoring of screening, and feedback of data from the scheme to practices is required to reduce the proportion of unscreened women.

To determine whether captopril alters peripheral venous tone in patients with congestive cardiac failure.Open study of patients at start of captopril treatment and three months later.A hospital gamma camera laboratory.16 Men with congestive cardiac failure in New York Heart Association class II or III, aged 57-73.Patients were initially given 500 micrograms sublingual glyceryl trinitrate followed by 25 mg oral captopril. The study was then repeated after three months' captopril treatment.Previously validated non-invasive radionuclide techniques were used to measure changes in central haemodynamic variables and peripheral venous volumes in the calf.After 25 mg captopril there were falls in blood pressure and relative systemic vascular resistance and increases in cardiac index and left ventricular ejection fraction. This was accompanied by a 16% increase in peripheral venous volume (95% confidence interval 13.4% to 18.4%, p less than 0.01), which compared with an 11% increase after 500 micrograms glyceryl trinitrate (10% to 12%, p less than 0.01). Eleven patients were restudied after three months' continuous treatment with captopril. The resting venous volume was higher than it had been initially, by about 10%, and increased by a further 8.4% after 25 mg captopril (5.4% to 11.4%, p less than 0.05).Captopril is an important venodilator. Venous and arterial dilatation are produced short term and during long term treatment.