Self-monitoring of Blood Pressure in Patients With Hypertension-Related Multi-morbidity: Systematic Review and Individual Patient Data Meta-analysis.

BACKGROUND: Studies have shown that self-monitoring of blood pressure (BP) is effective when combined with co-interventions, but its efficacy varies in the presence of some co-morbidities. This study examined whether self-monitoring can reduce clinic BP in patients with hypertension-related co-morbidity. METHODS: A systematic review was conducted of articles published in Medline, Embase, and the Cochrane Library up to January 2018. Randomized controlled trials of self-monitoring of BP were selected and individual patient data (IPD) were requested. Contributing studies were prospectively categorized by whether they examined a low/high-intensity co-intervention. Change in BP and likelihood of uncontrolled BP at 12 months were examined according to number and type of hypertension-related co-morbidity in a one-stage IPD meta-analysis. RESULTS: A total of 22 trials were eligible, 16 of which were able to provide IPD for the primary outcome, including 6,522 (89%) participants with follow-up data. Self-monitoring was associated with reduced clinic systolic BP compared to usual care at 12-month follow-up, regardless of the number of hypertension-related co-morbidities (-3.12 mm Hg, [95% confidence intervals -4.78, -1.46 mm Hg]; P value for interaction with number of morbidities = 0.260). Intense interventions were more effective than low-intensity interventions in patients with obesity (P < 0.001 for all outcomes), and possibly stroke (P < 0.004 for BP control outcome only), but this effect was not observed in patients with coronary heart disease, diabetes, or chronic kidney disease. CONCLUSIONS: Self-monitoring lowers BP regardless of the number of hypertension-related co-morbidities, but may only be effective in conditions such obesity or stroke when combined with high-intensity co-interventions.

CYP3A5 as a candidate gene for hypertension: no support from an unselected indigenous West African population.

CYP3A5 (cytochrome P450, family 3, subfamily A, polypeptide 5) expression stimulates the sodium retentive actions of the mineralocorticoid receptor causative of hypertension, probably by means of its ability to substantially increase the level of 6ß-hydroxylase activity. Most Black individuals are functional CYP3A5 expressers, and this is a candidate gene for the high incidence of hypertension in Black populations. The study investigates whether CYP3A5 expression results in higher blood pressure in a Ghanaian population. Real-time PCR was used to genotype 898 DNA samples for the CYP3A5*3 and CYP3A5*6 single-nucleotide polymorphisms with technically adequate genotyping for 881 samples. Of these, 803 were genetic CYP3A5 expressers, 44 nonexpressers and 34 uncertain (CYP3A5*3/*6). Although there was a trend in the proportion of hypertensive individuals as CYP3A5 expression decreased, using a two-sided t-test, no statistically significant relationship was established between systolic or diastolic pressure and CYP3A5*3 or CYP3A5*6 genotypes, or their haplotypes (Systolic confidence interval: -8.44 to -7.70, P=0.93, Diastolic confidence interval: -4.89 to 4.85, P=0.99). We conclude, therefore, that there is either no association between CYP3A5 expression and blood pressure or, if there is a relationship, the strength of the association is very small.

Dichotomising continuous data while retaining statistical power using a distributional approach.

Dichotomisation of continuous data is known to be hugely problematic because information is lost, power is reduced and relationships may be obscured or changed. However, not only are differences in means difficult for clinicians to interpret, but thresholds also occur in many areas of medical practice and cannot be ignored. In recognition of both the problems of dichotomisation and the ways in which it may be useful clinically, we have used a distributional approach to derive a difference in proportions with a 95% CI that retains the precision and the power of the CI for the equivalent difference in means. In this way, we propose a dual approach that analyses continuous data using both means and proportions to replace dichotomisation alone and that may be useful in certain situations. We illustrate this work with examples and simulations that show good performance of the parametric approach under standard distributional assumptions from our own research and from the literature.

A community study of health promotion in rural West Africa: details of a household survey and population census.

BACKGROUND: Hypertension is an important problem in sub-Saharan Africa. The low use of processed food in this area makes a population approach to reducing salt intake feasible. AIM: To create an age-sex register for 12 villages in Ghana as the first stage of a community study of the effect of dietary salt reduction on blood pressure and urinary sodium excretion in West African villagers. DESIGN: Household survey and population census. METHODS: Over three months, village maps were sketched and a complete list of total number of households, adults (with age and gender) and children in each village was obtained. RESULTS: The six semi-urban villages were larger than the six rural villages (10368 vs. 6597 inhabitants) and almost half the total population was under 16. CONCLUSIONS: Accurate census data are important in the design, implementation and interpretation of community studies and intervention trials. We outline the methods by which census data can be collected in rural and semi-urban sub-Saharan African villages, and emphasize the importance of painstaking, thorough work in the collection of such data.

Unequal cluster sizes for trials in English and Welsh general practice: implications for sample size calculations.

Cluster randomized trials are often used in primary care settings. In the U.K., general practices are usually the unit of allocation. The effect of variability in practice list size on sample size calculations is demonstrated using the General Medical Services Statistics for England and Wales, 1997. Summary statistics and tables are given to help design such trials assuming that a fixed proportion of patients are to be recruited from each cluster. Three different weightings of the cluster means are compared: uniform, cluster size and minimum variance weights. Minimum variance weights are shown to be superior to uniform, particularly when clusters are small, and to cluster size weights, particularly when clusters are large. Where there are large numbers of participants per cluster and cluster size weights are used, the power actually falls as more patients are recruited to large clusters. When minimum variance weights are used the increase in the design effect due to variation in list size is small, regardless of the size of intracluster correlation coefficient or the number of participants per cluster, provided there is no loss of randomized units. When the expected number of participants per practice is low a greater loss in power comes from practices which fail to recruit patients. A method to estimate the likely effect and allow for it is presented.

Trends in prescribing H2-receptor antagonists and proton pump inhibitors in primary care.

BACKGROUND: H2-receptor antagonists and proton pump inhibitors account for approximately 15% of primary care prescribing costs in the UK. AIM: To examine the use of antisecretory drugs in primary care between October 1991 and September 1996. METHOD: Analysis of prescribing data from an ongoing postal survey performed every 3 months on a rolling quota of 250 UK general practitioners (GPs), identified from a representative sampling frame of 1000 GPs. RESULTS: There were 8811 new courses of proton pump inhibitors and 11,948 new courses of H2-receptor antagonists during this study. The number of new prescriptions for proton pump inhibitors increased by 174.5%, but decreased for H2-receptor antagonists by 12.5%. Proton pump inhibitors were mostly prescribed for reflux disease (52.7%) and H2-receptor antagonists for non-specific dyspepsia (43.6%). Proton pump inhibitors (14.1%) were less likely to be stopped than H2-receptor antagonists (35.3%) overall, and they were less likely to be stopped because of perceived ineffectiveness (5.3%) than H2-receptor antagonists (23.8%). The rate of stopping treatment because of side-effects was about 3% for both classes of drug. CONCLUSIONS: Prescribing of proton pump inhibitors has increased sharply each year since 1991. One reason may be that GPs perceive proton pump inhibitors to be more effective than H2-receptor antagonists.

Trials which randomize practices I: how should they be analysed?

BACKGROUND: In some general practice intervention trials, patients must be randomized in practices rather than individually, and this must be taken into account in the analysis. OBJECTIVES: In this article we aim to show how failure to do this may lead to spurious statistical significance and CIs which are narrower than they should be, and to describe the use of summary measures for each practice as a simple method of analysis. METHOD: The statistical issues are demonstrated by an example of a trial in general practice. DISCUSSION: The choice of unit of analysis will be most important where there are large numbers of patients recruited from each practice or a high degree of variability between practices.

Trials which randomize practices II: sample size.

BACKGROUND: When practices are randomized in a trial and observations are made on the patients to assess the relative effectiveness of the different interventions, sample size calculations need to estimate the number of practices required, not just the total number of patients. OBJECTIVE: Our aims were to introduce the methodology for appropriate sample size calculation and discuss the implications for power. METHOD: A worked example from general practice is used. DISCUSSION: Designs which randomize practices are less powerful than designs which randomize patients to intervention groups, particularly where a large number of patients is recruited from each practice. Studies which randomize few practices should be avoided if possible, as the loss of power is considerable and simple randomization may not ensure comparability of intervention groups.

Emergency nurse practitioner services in major accident and emergency departments: a United Kingdom postal survey.

OBJECTIVE: To establish the current and predicted distribution of formal emergency nurse practitioner services in major accident and emergency departments in the United Kingdom; to determine organisational variations in service provision, with specific reference to funding, role configuration, training, and scope of clinical activity. METHODS: Postal survey of senior nurses of all major accident and emergency departments in the United Kingdom (n = 293) in May/June 1996. RESULTS: There were 274 replies (94% response rate): 98 departments (36%) provided a formal service; a further 91 departments (33%) reported definite plans to introduce a service by the end of 1996; smaller departments, under 40000 new patient attendances annually, were less likely to provide a service than busier units (p < 0.001, chi2 for trend). Three different methods of making the role operational were identified: dedicated, integrated, and rotational. Only 16 (18%) were able to provide a 24 hour service; 91 departments (93%) employed emergency nurse practitioners who had received specific training, but wide variations in length, content, and academic level were noted; 82 departments (84%) authorised nurse practitioners to order x rays independently, but only 35 (36%) allowed them to interpret radiographs; 67 (68%) permitted "over the counter" drug supplying under local protocol, and 52 (54%), "prescription only" drug supplying from an agreed list. CONCLUSIONS: Formal emergency nurse practitioner services are provided in all parts of the United Kingdom, with predicted figures suggesting a rapidly accelerating upward trend. Wide variations in service organisation, training, and scope of activity are evident.

The impact of the October 1995 'pill scare' on oral contraceptive use in the United Kingdom: analysis of a general practice automated database.

OBJECTIVES: We aimed to measure the change in prescribing of oral contraceptives after the October 1995 UK 'pill-scare'. DESIGN: Analysis was undertaken of an automated database of 100 general practices (372 doctors) in England, Scotland and Wales which use the AAH Meditel computer system. Analysis involved two stages. First, we reviewed prescribing of oral contraceptives at three time periods: before the scare (18.10.95); the following three months (19.10.95-18.1.96); and 3-6 months post-scare (19.1.96-18.4.96). Second, we examined the cohort of women on the pill at the time of the scare to assess discontinuation rates and pill switches after 6 months. RESULTS: Six months after the scare the proportion of women between 16 and 50 years of age prescribed any contraceptive pill decreased by only 3.5% (95% confidence limits: 2.2%-4.8%). The proportion of pill-users prescribed third generation pills decreased from 53.4% to 18.1%, while prescribing of second generation pills increased from 20.1% to 48.4%. The proportion of women currently on third or second generation pills at the time of the scare, who were no longer prescribed any pill after 6 months, was the same as for the equivalent period in the previous year. CONCLUSIONS: The number of women prescribed the pill did not alter markedly after the pill-scare. The main change was a switch from third to second generation pill types. In any future pill-scare women should be warned about the risk of pill-failure if the correct procedure for switching pills is not followed.

Initial treatment choices, second-line therapy, and reasons for stopping medication in the treatment of hypertension by general practitioners in England, Scotland and Wales: 1990-1995.

Information on general practitioners' choices of initial and second-line antihypertensive treatment, and reasons for stopping therapy, are limited. We analysed data on the use of the four main classes of antihypertensive drugs (diuretics, beta-blockers, calcium antagonists and angiotensin-converting enzyme inhibitors) between 1990 and 1995 from an ongoing cross-sectional postal survey of general practitioners' prescribing activity (the New and Change Therapy Enquiry). There were 18,092 new courses and 9424 discontinuations between 1990 and 1995. Diuretics were the commonest first-line choice. Use of beta-blockers first-line decreased significantly in comparison with diuretics during the study period. Switches to calcium antagonists and angiotensin-converting enzyme inhibitors increased. The increased use of newer agents was not explained by increased use for concomitant conditions (diabetes or cardiovascular disease). Diuretics were most often discontinued because of poor efficacy (44% of diuretic stops). In contrast, most beta-blockers (55%), calcium antagonists (64%) and angiotensin-converting enzyme inhibitors (60%) were stopped because of side-effects. In conclusion, use of beta-blockers first-line decreased. Switches to calcium antagonists and angiotensin-converting enzyme inhibitors increased. The reasons may be due to greater perceived efficacy of newer agents rather than increased use for concomitant conditions.

General practitioners' perceptions of the tolerability of antidepressant drugs: a comparison of selective serotonin reuptake inhibitors and tricyclic antidepressants.

OBJECTIVE: To examine inceptions and discontinuations of antidepressants in general practice. DESIGN: An observational study analysing data from an ongoing cross sectional postal survey. Every three months a representative sample of 250 doctors recorded prescribing activity for four weeks. This provided 4000 general practitioner weeks of recording per year. SETTING: A representative panel of general practitioners in England, Wales, and Scotland. SUBJECTS: Patients who began a new course of an antidepressant or had their treatment stopped or changed by the general practitioner between 1 July 1990 and 30 June 1995. MAIN OUTCOME MEASURES: Numbers of patients prescribed a new course of antidepressant; numbers discontinuing treatment; the ratio of antidepressant discontinuations to antidepressant inceptions; reasons for discontinuation; proportion of switches to another antidepressant. RESULTS: There were 13,619 inceptions and 3934 discontinuations of selective serotonin reuptake inhibitors and tricyclic antidepressants during the study. The number of newly prescribed courses of antidepressants increased by 116%, mostly due to an increase in prescribing of serotonin reuptake inhibitors. The ratio of total discontinuations to inceptions was significantly lower for serotonin reuptake inhibitors (22%) than for tricyclic antidepressants (33%). Differences persisted when controlled for age and sex of patients and severity of depression. However, there was more switching away from selective serotonin reuptake inhibitors when they failed (72%) than from tricyclic antidepressants (58%). CONCLUSIONS: Selective serotonin reuptake inhibitors are less likely than tricyclic antidepressants to be discontinued. A prospective study is needed in general practice to assess the implications of differences in discontinuation rates and switches on clinical and economic outcomes.

Randomized controlled trial of the effect of the Royal College of Radiologists' guidelines on general practitioners' referrals for radiographic examination.

BACKGROUND: The Royal College of Radiologists' guidelines aim to encourage more appropriate use of diagnostic radiology and so reduce the use of clinically unhelpful x-ray examinations. AIM: The object of this study was to conduct a randomized controlled trial of the introduction of the guidelines into general practice. METHOD: A total of 62 practices (170 general practitioners) referring patients to St George's Hospital, London for diagnostic radiology were randomly allocated into two groups. Guidelines were sent to the 30 practices in the intervention group. Radiological referral patterns were compared in both groups before and after the introduction of guidelines. RESULTS: Practices which had received guidelines requested significantly fewer examinations of the spine, and made a significantly higher proportion of requests which conformed to the guidelines compared with practices which had not received the guidelines. There were no significant differences in the proportion of forms giving physical findings or in the proportion of positive findings at radiology. CONCLUSION: Introduction of guidelines can influence general practitioners' radiological referrals in the short term. Wider use of guidelines might help to reduce unnecessary irradiation of patients.

Platelet alpha 2-adrenoceptors, defined with agonist and antagonist ligands, in depressed patients, prior to and following treatment.

Saturation binding of the alpha 2-adrenoceptor antagonist, 3H-yohimbine, and displacement of 3H-yohimbine with the alpha 2-adrenoceptor agonist, UK-14,304, were performed concurrently in platelet membranes obtained from drug-free depressed patients and healthy volunteers. Where possible platelet binding was repeated in depressed patients following treatment. The number and affinity of 3H-yohimbine binding sites did not differ between controls and depressed patients, or when depressed patients were divided on the basis of endogenicity (Newcastle or RDC criteria) or dexamethasone test result. The proportion of alpha 2-adrenoceptor binding sites with high affinity for UK-14,304 and KD values for the two states of the receptor did not differ in the total sample of depressed patients compared to controls. The KD for both states of the receptor and the proportion of sites with high affinity for UK-14,304 was lower in RDC non-endogenous patients than RDC endogenous patients. Treatment did not alter the total number of alpha 2-adrenoceptors or the proportion of sites with high affinity for UK-14,304, but reduced the KD for 3H-yohimbine and the KD of UK-14,304 for the low affinity state of the alpha 2-adrenoceptor.