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Biomedical subjects

P L Padfield

Publications and source records attributed to P L Padfield.

At least 19 recordsLinked to original sources

Does a hospital formulary influence prescribing practice in an acute medical admissions unit?

AIM: To assess the extent to which prescribing of cardiovascular medications in a busy medical unit deviates from the local joint primary and secondary care drug formulary guidelines. METHOD: A retrospective audit of the case notes, prescription charts and discharge summaries of 150 randomly selected emergency medical admissions over a 4 month period. RESULTS: No patient receiving a non-formulary cardiovascular drug on admission had the choice reviewed in line with formulary recommendations. One third of new cardiovascular medications commenced in hospital were not compliant with formulary recommendations. Decisions about drug therapy were rarely justfied in the written hospital record. CONCLUSIONS: Our results demonstrate that in a busy acute medical admissions' unit there is a clear failure to amend or query non-formulary prescribing at the time of admission and a tendency to exacerbate it during the inpatient period. This potentially undermines the purpose of a joint drug formulary as a guideline for safe, evidence-based and cost-effective prescribing.

Acute Disease↗

Maximizing the benefit of treatment in mild hypertension:three simple steps to improve diagnostic accuracy.

BACKGROUND: Most patients only have three measurements of blood pressure before being labelled as hypertensive. This may lead to inaccurate classification, unnecessary treatment and dilution in treatment benefit for the population. AIM: To examine the accuracy of current methods of diagnosing mild hypertension, and to explore ways to improving targeting of antihypertensive treatment without entailing lengthy observation. DESIGN: Re-analysis of published data. METHODS: We tested current diagnostic methods using the data for 3965 individuals who were followed for a year in the placebo arm of the MRC Mild Hypertension Trial. We calculated the proportion selected for treatment by current methods and the diagnostic accuracy, using average blood pressure beyond 6 months as representing 'true' long-term blood pressure. We examined the benefit of averaging blood pressures, of prolonging observation modestly and of estimating within-person blood pressure variability. RESULTS: Prolonging observation to 3 months selects a smaller (by about 12%) proportion of the sample for treatment, a proportion similar to that defined as 'truly' hypertensive. The diagnostic accuracy of current methods is poor, with up to 69% discrepancy in classification. This discrepancy was improved by up to 18% in absolute terms by prolonging observation to 3 months and using average blood pressures. Identifying those individuals with low within-person variability allows marked improvement in the prediction of 'true' hypertension. DISCUSSION: Although some inaccuracy in the diagnosis of hypertension is inevitable, observation for 3 months, averaging blood pressures and estimating within-person blood pressure variability can markedly improve upon current practice.

Antihypertensive Agents↗

Direct access ambulatory BP monitoring--the Edinburgh experience.

The use of electronic measurement of blood pressure and, in particular, ambulatory blood pressure monitoring offers the opportunity to determine which patients with apparent hypertension have truly sustained elevation of their blood pressure levels. Given the high prevalence of hypertension and the even larger number of individuals who appear to be hypertensive but may not be so, it is difficult to deliver ambulatory blood pressure monitoring to all individuals who might benefit from it. In Edinburgh, Scotland, we have piloted a system of direct access ambulatory blood pressure monitoring whereby physicians in primary care can request of the hospital service, an ambulatory monitor on their patient without the patients attending a formal hospital clinic. In the 7 years since the service was first instituted, almost 6,000 monitors have been performed with referrals running at approximately 100 per month in recent times. The present study was set up to assess the impact of the ambulatory monitor result on clinical decision making in primary care. The referral form invited primary care physicians to indicate their planned management if an ambulatory monitor had not been available and we thereafter audited patient records to determine what ultimately happened following the advice given on the basis of the ambulatory monitoring record.A random sample of results was obtained on untreated patients and approximately 500 were analysed. It was clear that if the advice to the primary care physician based upon the ABPM was not to treat, that this was largely followed with some 94% of patients not receiving treatment within 3 months of the monitor. If, however, the advice given was to start treatment, this was less reliably followed and in only 76% of patients treatment was started within 3 months. At the time of the audit this figure had increased to 82%. Primary care physicians had indicated that they would have treated 60% of the individuals referred and in reality only treated 40%. The potential saving in drug costs from the reduction by 20% of those treated would have significant impact on health care budgets.

Blood Pressure Monitoring, Ambulatory↗

Primary aldosteronism, a common entity? the myth persists.

Primary aldosterone excess or hyperaldosteronism is an important cause of hypertension which, when associated with an aldosterone secreting adenoma, is amenable to surgical cure. The biochemical hallmarks of the condition are a relative excess of aldosterone production with suppression of plasma levels of renin (a proxy for angiotensin II, the major trophic substance regulating aldosterone secretion). This combination of a high aldosterone and a low renin is however more commonly associated with 'nodular hyperplasia' of the adrenal glands, a condition not improved by surgery and variably responsive to the effects of the mineralocorticoid antagonist, spironolactone. Until recently the prevalence of either form of secondary hypertension has been thought to be low such that few clinicians 'hunted' for it in the absence of hypokalaemia (the traditional clue for the syndrome). This view has been challenged, firstly by the realisation that no more than 50% of such patients will have a low plasma potassium and secondly by the assumption that a 'normal' plasma aldosterone is in fact inappropriately elevated if the renin level is low. A single measurement of the ratio of aldosterone to renin levels is claimed to be highly predictive of patients who will have primary aldosterone excess. This paper examines the logic behind such claims and presents evidence from the literature that an abnormal ratio is simply a different description of the low renin state and that such patients do not necessarily have mineralocorticoid hypertension. Most patients 'discovered' by this test will have what many call low-renin hypertension, a condition not amenable to specific therapy. Claims that they are peculiarly sensitive to the hypotensive effects of spironolactone have not been tested in controlled trials. The test would however be expected to pick up those individuals with true Conn's syndrome but such patients remain too few in number to justify widespread use of an expensive screening test.

Aldosterone↗

Ambulatory blood pressure monitoring: is it necessary for the routine assessment of hypertension in people with diabetes?

AIMS: The British Hypertension Society (BHS) has recommended that, for people with diabetes, the target 'clinic' blood pressure should be < 140/80 mmHg. Ambulatory monitoring of blood pressure (ABPM) is used widely in the assessment of hypertension and the BHS has recommended that the target 'awake' ambulatory blood pressure for people with diabetes should be < 130/75 mmHg. The purpose of the present study was to determine the utility of ABPM in the assessment of hypertension in patients with diabetes, over and above a careful 'clinic' measurement of blood pressure. METHODS: The records of 540 patients with diabetes who underwent ABPM (using SpaceLabs monitors) were retrospectively analysed. With respect to current BHS recommendations, the positive and negative predictive values of 'clinic' blood pressure (measured by trained nurses using mercury sphygmomanometers) on 'awake' ambulatory blood pressure (ABP) were calculated. RESULTS: The positive predictive value of the 'clinic' BP, its ability to detect patients whose ABP was above BHS targets, was 99%. The negative predictive value of 'clinic' blood pressure was 27%. CONCLUSIONS: With regard to current BHS guidelines, ABPM is generally unnecessary in the assessment of hypertension in patients with diabetes, provided careful 'clinic' measurements of blood pressure are made.

Adult↗

Prognostic significance of self-measurements of blood pressure.

BACKGROUND: Self-measurements of blood pressure may offer some advantage in diagnostic and therapeutic evaluation and in management of patients. However, the most important limitation of self-measurement is that there are limited data available about the prognostic value of this information. RESULTS: Authors of several previous reports demonstrated that self-measurement reflects target-organ damage better than does casual measurement of blood pressure. So far, investigators in Tecumseh and Ohasama studies have provided pilot data on prognostic value of self-measurements. Investigators in Ohasama study demonstrated that self-measurements predict cardiovascular morbidity and mortality and all-cause mortality better than do casual measurements of blood pressure. Investigators in Tecumseh study demonstrated that self-measurement can predict future development of sustained hypertension and of diastolic dysfunction. These preliminary results suggest that self-measurements have strong predictive power for endpoints and surrogate measures of cardiovascular target-organ damage. CONCLUSION: The final answer on the prognostic significance of self-measurement has not been given. Prognostic studies designed to compare casual measurement of blood pressure, self-measurement, and ambulatory blood pressure monitoring are needed.

Blood Pressure Determination↗

Diabetic nephropathy is associated with an increased familial risk of stroke.

OBJECTIVE: To test the hypothesis that genetic susceptibility to diabetic nephropathy is associated with an increased familial risk of vascular disease, we have examined the causes and rates of death of parents of individuals with type 1 diabetes complicated by diabetic nephropathy compared with the causes and rates of death of parents of control subjects with diabetes uncomplicated by nephropathy. RESEARCH DESIGN AND METHODS: Individuals with at least a 14-year duration of type 1 diabetes complicated by diabetic nephropathy were identified and matched for age, sex, and duration of diabetes to control subjects. A total of 118 patients and 118 matched control subjects were identified and approached to obtain information on parental age and cause of death. For parents who had died, the cause of death was ascertained from the death certificate. RESULTS: Kaplan-Meier curves showed that parents of subjects with nephropathy (PN) had reduced survival compared with parents of diabetic subjects without nephropathy (PC) (log rank test P < 0.05). There was an excess of all vascular deaths and, in particular, strokes in the parents of subjects with nephropathy (PN: 20 of 103 deaths, 19% vs. PC: 3 of 66 deaths, 4%; Fisher's exact test P < 0.01). CONCLUSIONS: Parents of diabetic patients with nephropathy have reduced survival. This seems to be largely explained by an increase in vascular deaths and, in particular, a four-fold increase in the number of strokes. This supports the hypothesis that a common hereditary risk factor predisposes to both vascular death and diabetic renal disease.

Adult↗

Growth hormone replacement inhibits renal and hepatic 11 beta-hydroxysteroid dehydrogenases in ACTH-deficient patients.

OBJECTIVES: The commonest side-effects of GH replacement therapy relate to sodium retention but its mechanism is unclear. In rats, GH inhibits renal and hepatic 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) activities. In man, this action might impair inactivation of cortisol to cortisone in the distal nephron thereby allowing cortisol to activate mineralocorticoid receptors. In this study, we examined the effects of GH replacement on cortisol metabolism. DESIGN: A randomized double-blind study comparing 6 months GH replacement with placebo in adults with GH deficiency due to pituitary or hypothalamic disease. PATIENTS: 6 men and 8 women received placebo and 8 men and 9 women received GH. MEASUREMENTS: Cortisol and its metabolites were measured in overnight urine samples and in a fasting morning plasma sample at baseline and at 6 months. RESULTS: Five patients withdrew from the study, 4 because of adverse effects of GH. Amongst those who completed the study, the effects of GH on cortisol metabolism differed between patients with and without ACTH deficiency. Amongst those receiving hydrocortisone replacement (n = 18), GH had no effect on plasma cortisol/cortisone ratio, or urine tetrahydrocortisols/tetrahydrocortisone ratio, but produced a substantial reduction in total urinary cortisol metabolites (from 1326 +/- 191 to 777 +/- 229 micrograms/mmol creatinine; P < 0.01) and an increase in urinary free cortisol/cortisone ratio (from 0.88 +/- 0.10 to 2.57 +/- 0.74; P < 0.02). By contrast, GH had none of these effects in patients with normal ACTH secretion. There were no changes in blood pressure or plasma electrolytes, aldosterone, or renin activity with GH, and no changes in any variables with placebo. CONCLUSIONS: The increase in cortisol/cortisone ratio in urine but not in plasma, and the lack of effect on hepatic cortisol metabolites, suggests that GH inhibits both the conversion of cortisol to cortisone by renal 11 beta-HSD2 and the conversion of cortisone to cortisol by hepatic 11 beta-HSD1. It is unclear why this action of GH only affects patients with ACTH deficiency. The reduction in total cortisol metabolite excretion suggests that GH also affects bioavailability of hydrocortisone tablets. These observations suggest that glucocorticoid replacement therapy may need to be adjusted in hypopituitary patients who are commenced on GH replacement.

11-beta-Hydroxysteroid Dehydrogenases↗

Ambulatory blood pressure on and off continuous positive airway pressure therapy for the sleep apnea/hypopnea syndrome: effects in "non-dippers".

Ambulatory blood pressure (BP) monitoring was performed in 13 patients with the sleep apnea/ hypopnea syndrome (SAHS) during a randomized, placebo controlled crossover trial of the effects of continuous positive airway pressure (CPAP) therapy. BP was monitored at half-hourly intervals for a 24-hour period both on CPAP and on an oral placebo, each given for a minimum of 3 weeks. Objective effective CPAP use averaged 4.3 hours per night. Weight and anti-hypertensive medications remained stable over the study period. Systolic, diastolic and mean arterial BP for 24-hour, daytime and nighttime periods were not significantly different on placebo compared to CPAP. Those patients with no significant overnight fall in BP on placebo ("non-dippers") showed a significant improvement in daytime mean arterial BP on CPAP (98 +/- 4 mm Hg) compared to placebo (102 +/- 4 mm Hg; p = 0.01). These findings, in a well-controlled trial, suggest that BP is not reduced by CPAP in a heterogeneous group of SAHS patients, but it may be selectively improved in those patients most at risk for cardiovascular morbidity and mortality.

Adult↗

Increased vasoconstrictor sensitivity to glucocorticoids in essential hypertension.

Glucocorticoids raise blood pressure but were thought not to play a pathophysiological role in essential hypertension when it was demonstrated that cortisol secretion rates and circulating concentrations are normal in this disease. However, recent observations suggest that increased tissue sensitivity to cortisol, mediated by either abnormal glucocorticoid receptors or impaired inactivation of cortisol by 11 beta-dehydrogenase, may allow cortisol to raise blood pressure despite normal circulating concentrations. We studied 11 patients with essential hypertension and 11 matched normotensive control subjects. Dermal vasoconstriction after topical application of both cortisol (16 +/- 4 versus 32 +/- 5 U, control subjects versus hypertensive patients; P < .02) and beclomethasone dipropionate (75 +/- 10 versus 100 +/- 7 U; P < .05) was increased in the hypertensive patients. Hypothalamic-pituitary glucocorticoid receptor sensitivity was normal, as judged by basal cortisol secretion rates and suppression of plasma cortisol during sequential overnight dexamethasone suppression tests. 11 beta-Dehydrogenase activity was impaired in essential hypertension, as judged by prolonged half-lives of [11 alpha-3H]cortisol (44 +/- 4 versus 58 +/- 4 minutes, control subjects versus hypertensive patients; P < .02). However, this did not correlate with the dermal vasoconstrictor response. We conclude that vasoconstrictor sensitivity to glucocorticoids is increased in essential hypertension and that this may initiate and/or sustain the increased peripheral vascular resistance that characterizes this disease. The mechanism of increased sensitivity remains uncertain, but it will be important to establish whether it relates to genetic abnormalities of the glucocorticoid receptor that have been observed in animal models and young individuals who are predisposed to essential hypertension.

Administration, Oral↗

Thyroid cancer management.

OBJECTIVE: Thyroid cancer is the commonest endocrine malignancy, yet management remains controversial. Many endocrinologists advocate diagnosis by fine needle aspiration (FNA), treatment by thyroidectomy, ablative radioiodine (131I) and TSH suppression, together with follow-up with 131I scans or thyroglobulin (Tg) measurements. 131I (therapy or diagnosis) is given only when TSH is > 30 mIU/I. With this strategy in mind, the aim of the present study was to audit existing clinical practice in a large Edinburgh teaching hospital to establish whether a need existed for local guidelines for the management of thyroid cancer. DESIGN AND PATIENTS: Retrospective case-note audit of 46 patients, aged 55 (range 26-86) years, admitted between 1988 and 1993 with a diagnosis of thyroid cancer. RESULTS DIAGNOSIS: Our FNA false negative rate was high (13%), aspiration technique varied considerably, and cytological reporting was not standardized. TREATMENT: Three (11%) patients received 131I despite suboptimal TSH levels because of poorly developed mechanisms to prevent this, and 7 (25%) patients had inadequate suppression of TSH as a result of poor interspecialty communication. FOLLOW-UP: Three (11%) patients were scanned despite TSH levels < 30 mIU/I, and in 5 (18%) Tg checks were incomplete. CONCLUSIONS: This audit identifies several shortcomings from what might be considered optimum management of thyroid cancer; practice was far from uniform even among the endocrinologists within a single hospital and interdisciplinary communication was poor. A locally agreed and implemented protocol should address most of these problems and improve the care of thyroid cancer patients.

Adult↗

The triple-phase response--problems of water balance after pituitary surgery.

A 29-year-old woman presenting with persistent headache and oligomenorrhoea was found to have a pituitary adenoma which was treated surgically. Postoperatively she developed diabetes insipidus which resolved on treatment with desmopressin acetate. She represented 11 days post surgery with nausea and vomiting and inappropriate antidiuresis was diagnosed in an infectious diseases unit. On re-admission to our unit cranial diabetes insipidus was confirmed by water deprivation. This case demonstrates the need for careful monitoring of patients after pituitary and suprasellar surgery or head injury.

Adult↗

Endogenous inhibitors of 11 beta-hydroxysteroid dehydrogenase in hypertension.

Exogenous inhibitors of 11 beta-hydroxysteroid dehydrogenase (e.g. glycyrrhetinic acid, a constituent of licorice) raise blood pressure by allowing cortisol to activate mineralocorticoid receptors. Endogenous 11 beta-dehydrogenase inhibitors called glycyrrhetinic acid-like factors (GALFs), have been extracted from urine. Increased GALFs could explain the impairment of 11 beta-dehydrogenase in essential hypertension and ectopic ACTH syndrome. We extracted urine on Sep-Paks and quantified GALFs by their inhibition of 11 beta-dehydrogenase bioactivity in microsomes from rat liver. GALFs have no diurnal rhythm and were no different after dexamethasone treatment, in patients with low ACTH, on in 4 patients with ectopic ACTH secretion. In 79 subjects, GALF excretion did not correlate with blood pressure. In 17 subjects, GALF excretion did not correlate with indices of mineralocorticoid receptor activation on 11 beta-dehydrogenase activity. We conclude that GALFs are not ACTH dependent and have no measurable effect on 11 beta-dehydrogenase in vivo. In hypertension associated with impaired 11 beta-dehydrogenase activity GALFs are unlikely to play a pathophysiological role.

11-beta-Hydroxysteroid Dehydrogenases↗

Ambulatory blood pressure monitoring: from research to clinical practice.

Evidence from the medical literature is reviewed to indicate that ambulatory monitoring of blood pressure (ABPM) is a better predictor of target organ damage and clinical outcome in the hypertensive patient than clinic measurements of blood pressure (BP). A re-analysis of the documented BPs from the placebo limb of the Medical Research Council's treatment trial of mild hypertension is presented to indicate the difficulties inherent in the advice given by the various published guidelines on the diagnosis and management of hypertension. Finally, it is argued that because ABPM identifies a similar proportion of patients for treatment as a more prolonged follow-up, its use should be considered in the evaluation of all patients with mild hypertension as they can be categorised rapidly with less risk of being 'lost to follow-up'.

Blood Pressure↗