National assessment of PID diagnosis, treatment and management in general practice: England and Wales.

A questionnaire based audit was used to evaluate the diagnosis and management of suspected pelvic inflammatory disease (PID) cases by general practitioners (GPs) in England and Wales. Responses were compared against a clinical management 'gold standard' devised by an independent group of GPs and specialists. Two hundred and ninety-seven (38%) of the 781 questionnaires were returned. Only 21 (7%) had all 'gold standard' sections correct. Diagnostic quality was significantly higher when the clinician was female compared with male (odds ratio [OR]=2.34; 95% confidence limits [CL]=1.19-4.63) and diagnostic quality increased with increasing socioeconomic deprivation. This is the first evaluation of the diagnosis and management of PID by GPs in England and Wales. The unusually poor response rate to a Medical Research Council General Practice Research Framework (MRC GPRF) study may reflect low disease awareness and sub-optimal management. This represents a fundamental obstacle to effective intervention and surveillance. Effective intervention will only be possible if diagnostic practice and management are improved substantially.

Regular inhaled salbutamol and asthma control: the TRUST randomised trial. Therapy Working Group of the National Asthma Task Force and the MRC General Practice Research Framework.

BACKGROUND: Previous work has suggested that the long-term regular use of inhaled beta2-agonist bronchodilators might lead to a deterioration in asthma control. The aim of TRUST (The Regular Use of Salbutamol Trial) was to study the effects of regular use of inhaled salbutamol, the most widely prescribed bronchodilator in the UK, on the control of asthma. METHODS: A randomised, double-blind, placebo-controlled trial was undertaken in 983 patients with asthma being treated at least twice a week with short-acting beta2-agonist, alone or in combination with inhaled steroids (2 mg or less) daily. Patients were aged 18 years and over and were recruited from 115 general practices in the UK. 90% (881) of the patients used inhaled corticosteroid therapy, and all patients continued to use their usual inhaled beta2-agonist for symptomatic relief. Patients were randomised to receive 400 microg salbutamol or matched placebo via a Diskhaler four times per day for 12 months. The primary outcome measure was rate of exacerbations of asthma, with criteria based on data from diary cards completed daily by each patient, treatment with additional corticosteroids, or both. FINDINGS: There were no differences in the annual rate, timing, or duration of exacerbations between the two groups. The mean morning peak expiratory flow was similar for the two groups. The mean evening peak expiratory flow (p<0.001) and the diurnal variation (p<0.001) were greater, and the use of rescue bronchodilator was less (p<0.001), in the group receiving regular salbutamol. INTERPRETATION: There was no evidence that regular use of inhaled salbutamol 400 microg four times daily for a year increased the exacerbation rate of asthma in the population studied.

Evaluation of two time-specific back pain outcome measures.

STUDY DESIGN: Postal questionnaire to individuals with back pain. OBJECTIVE: To assess the acceptability, validity, and reliability of two existing back pain outcome measures, the Roland-Morris Questionnaire and the Von Korff scales, modified to measure the preceding 4 weeks. SUMMARY OF BACKGROUND DATA: The ideal outcome measure for studies of low back pain and disability remains elusive. Most existing measures assess current pain and disability. Measuring these factors over a preceding 4-week period may be more appropriate. METHODS: Individuals with back pain identified in a community survey were asked to complete the modified questionnaires. Validity was assessed by comparison with the Medical Outcome Study Short Form 36 and two general comparator questions on self-reported pain and disability. Repeatability was assessed using retest questionnaires. RESULTS: Completed questionnaires were returned by 95 individuals with chronic back pain. The modified Roland-Morris Questionnaire and Von Korff pain and Von Korff disability scales were completed satisfactorily by 83 (87%), 89 (94%), and 87 (92%) participants, respectively. Mean scores of the modified measures changed significantly and in a predictable manner with increasing ratings of pain and disability. They also correlated with aspects of the Medical Outcome Study Short Form 36 questionnaire. Retest data suggest that these measures are repeatable. The modified Roland-Morris Questionnaire provided adequate analyzable data only if missing values were imputed, and it explained less of the variance in the comparator questions than the modified Von Korff scales. CONCLUSIONS: The modified Von Korff scales were completed easily and appear to be valid and repeatable in this format.

Is recruitment more difficult with a placebo arm in randomised controlled trials? A quasirandomised, interview based study.

OBJECTIVE: To investigate whether including a placebo arm in a clinical trial of hormone replacement therapy influenced women's stated willingness to participate. DESIGN: Quasirandomised, interview based study. SETTING: 10 group practices in the Medical Research Council's General Practice Research Framework. PARTICIPANTS: 436 postmenopausal women aged 45-64 who had not had a hysterectomy. MAIN OUTCOME MEASURES: Stated willingness to enter a trial and reasons for the decisions made. RESULTS: Of 218 women told about the trial without a placebo arm, 85 (39%) indicated their willingness to enter compared with 65 (30%) of the 218 women told about the trial with the placebo arm (P=0.06). Part of this difference was due to explicit reluctance to take a placebo. Altruism and personal benefit were the reasons most frequently given for wanting to take part in a trial. The reasons most frequently cited for not wanting to take part were reluctance to restart periods, not wanting to take unknown or unnecessary tablets, or not wanting to interfere with present good health. CONCLUSION: For preventive trials the inclusion of a placebo arm may reduce patients' willingness to participate.

HRT and cardiovascular disease.

Conclusions influencing clinical decisions about the effects of hormone replacement therapy (HRT) on cardiovascular disease have undergone major revisions over the last 30 years. Assumptions in the early 1970s that HRT would increase thromboembolic conditions were reversed in the 1980s, when the first formal studies seemed to indicate a cardioprotective effect. The Heart and Estrogen/progestin Replacement Study (HERS) has, however, very recently suggested that HRT does not affect the incidence of coronary heart disease (CHD) one way or the other. These roller-coaster changes of direction have made decisions by doctors and their patients about the long-term use of HRT extremely difficult and need to be replaced by the stability that only further randomised controlled trials (RCTs) can now provide.

Community studies of the health service implications of low back pain.

STUDY DESIGN: Retrospective study using primary care physician case notes and a self-report questionnaire on the same randomly selected population sample. OBJECTIVES: To assess the prevalence, management, and outcomes of low back pain in the community, comparing, in the same random sample of registered patients, self-report questionnaire data and primary care physicians' records. SUMMARY OF BACKGROUND DATA: The financial and resource implications of low back pain are extensive. Data on consultations, investigations, and the management of low back pain are fragmentary and there are no comparisons estimating prevalence from case notes and self-report. METHODS: A retrospective study of prevalence, management, referral, and outcome covering the previous 12 months was carried out in three general practices using case notes and a self-report postal questionnaire on a sample of 900 patients over 18 years. RESULTS: Lifetime prevalence of low back pain was 62%. Annual prevalence was 48%, with 16% reporting low back pain at the time of report. Twenty-four percent consulted their primary care physician for low back pain, of whom 17% were referred to a hospital specialist. The annual consultation rate of patients with low back pain was similar to the rate for patients with chronic conditions. The activities of daily living were restricted in less than half, with few taking sick leave. The general health status of those reporting recent low back pain was significantly lower than those not reporting low back pain. Most felt that low back pain was self-limiting and would not consult health professionals for future episodes. There were substantial discrepancies between case notes recorded at consultation with the primary care physician and self-report regarding consultation and investigations. CONCLUSIONS: Prevalence rates were comparable with those reported in other studies. The significant discrepancies between data sources suggest patient recall bias or underrecording in case notes. The low consultation rate, time off, and day-to-day disability indicate that most episodes are self-limiting.

Availability of services to treat patients with acute low back pain.

Guidelines for the management of acute low back pain were published in 1994. This national survey, conducted soon after, showed that the availability of services for general practitioners (GPs) to treat acute back pain fell short of the guideline recommendations. A repeat survey will be performed to measure the impact of guideline publication and dissemination.

Hormone replacement therapy and cardiovascular disease: the case for a randomized controlled trial.

The menopause is associated with an increased risk of developing cardiovascular disease. Oestrogen may influence various metabolic pathways which contribute to the pathogenesis of cardiovascular disease, and observational studies suggest that in postmenopausal women oral oestrogen replacement therapy confers some protection against coronary heart disease and to a lesser extent against stroke. What is not clear is the magnitude of the cardioprotective effect and the overall balance of long-term benefits and hazards. Research is also required to establish the relative effects of oestrogen replacement therapy and combined or opposed hormone replacement therapy (HRT) where progestogen is added to counter the proliferative action of oestrogen on the endometrium. A large randomized controlled trial is the only way to provide accurate estimates of the cardioprotective effect of HRT and of other long-term benefits and hazards. Feasibility studies undertaken through the UK Medical Research Council (MRC) General Practice Research Framework show that such a trial is acceptable to patients and their doctors. Recruitment and withdrawal rates indicate that a trial of sufficient size to show a 25% reduction in cardiovascular disease with 90% power at the 1% level would be feasible. The full trial is costly and it is proposed that the UK collaborates with other countries in a major international trial to complement the Women's Health Initiative trial in the USA. Feasibility studies in Europe are underway, the design and scientific rationale for the trial have been approved by the UK MRC and it is hoped that recruitment to the full-scale trial can begin soon.

Histamine receptors on leukocytes: the binding of histamine serum albumin conjugates is non-specific.

It is commonly held that certain leukocyte sub-populations adhere selectively to histamine-serum albumin conjugates. A large number of soluble histamine, ethylamine and dimethylaminopropylamine conjugates were synthesised and labelled with fluorescein isothiocyanate (FITC). Although a number of conjugates bound to mononuclear cells and granulocytes our data showed this binding to be non-specific. The binding of histamine conjugates to leukocytes was not inhibited by preincubation of cells with free histamine at concentrations of up to 10(-1) M nor was it pH sensitive. In addition, conjugates of ethylamine and dimethylaminopropylamine showed a similar binding pattern to that of histamine conjugates. We suggest that the observed binding may be due to modifications to the net charge of the carrier protein molecule.

The effects of histamine H2-receptor antagonists on PHA induced lymphocyte proliferation.

Histamine H2-receptor antagonists must be used with caution to define the pharmacology of histamine effects on lymphocyte mitogenesis induced by PHA, because they can enhance and/or suppress in their own right, because these effects are similar to those of histamine itself, because mitogenic doses of PHA can release significant amounts of histamine from supposedly pure mononuclear cell preparations.

Histamine-induced inhibition of lymphocyte proliferation and lysosomal enzyme release from polymorphs may not be mediated via H1- or H2-receptors.

Histamine, selective histamine H1- and H2-receptor agonists, and chemical analogues of these compounds lacking activity at histamine receptors, were tested as inhibitors of phytohaemagglutinin-induced human lymphocyte proliferation and zymosan-induced release of lysosomal enzymes from human polymorphs. No correlation was found between their inhibitory potency in these systems and their relative activity at histamine H1- or H2-receptors.

The effect of histamine on the development of adjuvant arthritis in the rat.

Histamine, injected subcutaneously (0.3-10 mg/kg), produced a dose-related inhibition of the primary and secondary inflammation, and the development of the secondary lesions of rat adjuvant arthritis. Histamine was effective when given for short periods around the time of adjuvant administration and could also delay and possibly reverse an established arthritic response. The histamine H1-agonist, 2-(2-pyridyl)-ethylamine, inhibited rat adjuvant arthritis, whereas the histamine H2-agonists, impromidine and dimaprit, failed to affect the response. Metiamide, a histamine H2-antagonist (5 mg/kg), reduced the inflammation in the uninjected hind-paw and the development of secondary lesions. Histamine may have two effects on rat adjuvant arthritis, inhibiting the response via stimulation of H1-receptors and augmenting the response via stimulation of H2-receptors. Since histamine is known to bind to and to alter the reactivity of cells which are involved in the regulation of immune responsiveness, it is suggested that interactions with these cells are responsible for the observed effects of histamine.

The effects of H2-receptor antagonists on anaphylaxis in the guinea-pig.

Histamine has been shown to inhibit a variety of immune responses including the antigen-induced, IgE mediated, release of histamine from sensitized human leucocytes and from sensitized monkey and dog mast cells. The inhibitory action of histamine appears to be mediated by action at a histamine H2-receptor. In in vitro experiments the H2-receptor antagonist metiamide has been shown to block this histamine effect and it has been suggested that H2-receptor antagonists could intensify immediate hypersensitivity reactions in vivo. The effects of the H2-receptor antagonist metiamide and cimetidine have been studied in in vitro and in vivo models of anaphylaxis in the guinea-pig. The amount of extracellular histamine found after antigen challenge is greater when an H2-receptor antagonist is present during the incubation of mast cells with antigen. Bronchoconstriction induced by antigen in sensitized guinea-pig is exacerbated only by high doses of cimetidine. Possible explanations for the mechanism of action involved are discussed.

Investigation of the response to some haptenic determinants in penicillin allergy by skin and in vitro allergy tests.

The role of three penicillin metabolites in human allergic reaction to penicillin has been assessed using sensitive in vitro tests in addition to skin testing. Conjugates of the benzylpenicilloyl (BPO), benzylpenicillenate (BPE) and penicillamine (PA) groups with human serum albumin (HSA) and bovine gamma globulin (BGG) have been made. In the passive haemagglutination test antibodies specific for all three determinants were found but there was no difference between allergic and non-allergic groups. However, the ratio IgG/IgM, specific for each determinant, was higher in normals than in allergics. In skin tests, histamine release from leucocytes and the lymphocyte transformation test, the BPO group was confirmed as the major determinant, but in some individuals the BPE or PA groups are more important.