How evidence based are therapeutic decisions taken on a medical admissions unit?

OBJECTIVES: To audit the proportion of drug treatments started on a medical admissions unit that is justified by published evidence, and the proportion for which no justification could be found. METHODS: Retrospective review of randomly selected case notes to identify drug treatments started and the problem(s) for which they were prescribed, followed by literature searches. RESULTS: A total of 132 treatment-problem pairs were found, comprising 85 unique treatment-problem pairs. An evidence base was found in support of 78 of the treatments started (59.1%). A further 41 treatment-problem pairs could be argued to be reasonable practice (sometimes included in guidelines), even though no published trial data support them. Ninety per cent of drug treatments started on the medical admissions unit have either an evidence base or are accepted practice. CONCLUSIONS: Regular audit of this nature could be carried out on units admitting acute medical patients. Similar audits in internal medicine have delivered consistent results (50%-60%); there is a baseline level against which units can compare themselves. Clinical audit is an integral feature of clinical governance; all wards admitting acute medial patients could conduct similar audits on a random sample of patients.

Determination of phenobarbitone population clearance values for physically and mentally handicapped Chinese children with epilepsy.

OBJECTIVE: To estimate population clearance values of phenobarbitone in epileptic children of Chinese origin in Hong Kong. METHOD: Steady-state concentration data were gathered during routine care at a special chronic centre for the physically and mentally handicapped. Age, gender, body weight and concurrent medication (taking additional carbamazepine (CBZ) or phenytoin (PTO)) were the four fixed effects tested simultaneously for their influence on the population mean of phenobarbitone clearance, using the nonlinear mixed-effects model. RESULTS: No age or gender-related effect was found. Both body weight and concurrent medication were the important determinants of phenobarbitone clearance. The population mean values of phenobarbitone clearance obtained were 0.250 litres/day/kg for children on phenobarbitone only and 0.208 litres/day/ kg for those on concomitant CBZ or PTO. Their corresponding interindividual and intraindividual variability values were 34.9% and 15.1% for mono-pharmacy and 29.3% and 7.84% for polypharmacy patient groups. CONCLUSION: The correlation between phenobarbitone clearance and body weight found may allow dosage adjustment to be made to achieve target steady-state plasma concentrations.

Isradipine treatment for hypertension in general practice in Hong Kong.

A 6-week open study of the introduction of isradipine treatment was conducted in general practice in Hong Kong. 303 Chinese patients with mild to moderate hypertension entered the study. Side effects were reported in 21% of patients and caused withdrawal from the study in 3 patients. The main side-effects were headache, dizziness, palpitation and flushing and these were not more frequent than reported in other studies with isradipine or with placebo. Supine blood pressure was reduced (P less than 0.01) from 170 +/- 20/102 +/- 6 mmHg to 153 +/- 19/92 +/- 8, 147 +/- 18/88 +/- 7 and 144 +/- 14/87 +/- 6 mmHg at 2, 4 and 6 weeks respectively in evaluable patients. Similar reductions occurred in standing blood pressure and there was no evidence of postural hypotension. Normalization and responder rates at 6 weeks were 86% and 69% respectively. Dosage was increased from 2.5 mg b.d. to 5 mg b.d. at 4 weeks in patients with diastolic blood pressure greater than 90 mmHg and their further response was greater than those remaining on 2.5 mg b.d.

Stroke subtypes among Chinese living in Hong Kong: the Shatin Stroke Registry.

The Shatin Stroke Registry is a prospective study of all patients admitted with acute stroke to a general hospital in Hong Kong where the population is predominantly Chinese. Each patient was examined by a neurologist and 95.5% of the patients had a brain CT. Of 777 patients included in the study, 44.0% had a cortical/subcortical infarct, 18.5% a supratentorial lacunar infarct, 24.2% a supratentorial intracerebral hemorrhage, 5.8% brainstem/cerebellar infarct, 2.9% a brainstem/cerebellar hemorrhage, and 4.5% an uncertain diagnosis. The overall 30-day case fatality rate was 25.4%. Comparison with five stroke registries from the West suggests that intracerebral hemorrhage occurs between two and three times more frequently in the Chinese than in Westerners. Whether there is any difference in the relative frequencies for lacunar infarction remains unclear.

Hypertension, lipoprotein(a), and apolipoprotein A-I as risk factors for stroke in the Chinese.

We analyzed the serum concentrations of lipids and lipoproteins and the prevalence of other risk factors in a case-control study of 304 consecutive Chinese patients with acute stroke (classified as cerebral infarction, lacunar infarction, or intracerebral hemorrhage) and 304 age- and sex-matched controls. For all strokes we identified the following risk factors: a history of ischemic heart disease, diabetes mellitus, or hypertension; the presence of atrial fibrillation or left ventricular hypertrophy; a glycosylated hemoglobin A1 concentration of greater than 9.1%; a fasting plasma glucose concentration 3 months after stroke of greater than 6.0 mmol/l; a serum triglyceride concentration 3 months after stroke of greater than 2.1 mmol/l; and a serum lipoprotein(a) concentration of greater than 29.2 mg/dl. We found the following protective factors: a serum high density lipoprotein-cholesterol concentration of greater than 1.59 mmol/l and a serum apolipoprotein A-I concentration of greater than or equal to 106 mg/dl. The patterns of risk factors differed among the three stroke subtypes. When significant risk factors were entered into a multiple logistic regression model, we found a history of hypertension, a high serum lipoprotein(a) concentration, and a low apolipoprotein A-I concentration to be independent risk factors for all strokes. The attributable risk for hypertension was estimated to be 24% in patients aged greater than or equal to 60 years. In this population, in which cerebrovascular diseases are the third commonest cause of mortality, identification of risk factors will allow further studies in risk factor modification for the prevention of stroke.

Atrial natriuretic peptide in the central nervous system.

Atrial natriuretic peptide (ANP), first isolated from rat atrial cardiocytes, is a potent natriuretic, diuretic and vasorelaxant hormone when given intravenously. In keeping with increasing evidence that many bioactive peptides that were first discovered in peripheral organs, are often present in the central nervous system, ANP and its binding sites have been localized on neurons in different regions of the brain. Further, ANP binding sites have been found on primary astrocyte and glial cell lines and ligand binding results in cyclic GMP production. In this review, we shall discuss the possible role of ANP as a neuromodulator and its effects on astrocytes, the most numerous cell type in mammalian brain.

Response to control of hyperthyroidism in patients with myasthenia gravis and thyrotoxicosis.

Three patients presenting with both myasthenia gravis and thyrotoxicosis were treated initially with pyridostigmine and carbimazole respectively. Control of the hyperthyroidism was achieved in all cases but was accompanied by deterioration of the myasthenic symptoms in two and persistence in one. Thymectomy was performed with subsequent improvement in all three patients. Histology showed thymic hyperplasia in each case. The relationship of myasthenia gravis, thyrotoxicosis and the thymus is discussed.

Treatment of severe orthostatic hypotension with the somatostatin analogue octreotide.

The long-acting somatostatin analogue octreotide was used in a patient with severe orthostatic hypotension resistant to conventional treatment. 0.4 ug/kg octreotide given subcutaneously abolished the postural drop in systolic blood pressure for about four hours and was more effective than a combination of fludrocortisone and pindolol.

The influence of hyperglycemia and diabetes mellitus on immediate and 3-month morbidity and mortality after acute stroke.

Fasting serum glucose, glycosylated hemoglobin, and fructosamine concentrations were determined in 304 consecutive subjects admitted with acute stroke, within 48 hours of ictus. Based on the medical history and these results, subjects were divided into known diabetics, newly diagnosed diabetics, subjects with stress hyperglycemia, and nondiabetics. The type of stroke was classified as lacunar infarct, cerebral infarct, or intracerebral hemorrhage, based on clinical examination by a neurologist and computed tomographic brain scan and/or autopsy. Immediate and 3-month outcomes were examined in relation to (1) fasting glucose, glycosylated hemoglobin, and fructosamine levels by stroke subtypes, and (2) glucose tolerance categories by stroke subtypes. A high fasting glucose level was associated with an increased mortality, but this was observed only among patients with intracerebral hemorrhage. Patients with stress hyperglycemia, but not diabetics, had increased mortality. In spite of having similar glucose concentrations to those patients with stress hyperglycemia, diabetics did not have a worse outcome compared with nondiabetics. It is concluded that the association between glucose concentration and outcome is a reflection of stress relating to stroke severity, rather than a direct harmful effect of glucose on damaged neurons.

Acute and long-term changes in serum lipids after acute stroke.

We studied serum lipid profiles in 171 patients less than or equal to 48 hours after the onset of acute stroke and 3 months later. The 83 patients suffering cerebral infarction had significantly higher serum concentrations of total cholesterol, low density lipoprotein-cholesterol, and apolipoprotein B and significantly lower serum concentrations of triglycerides and lipoprotein (a) less than or equal to 48 hours after ictus than 3 months later. The lipid profiles of the 53 patients suffering lacunar infarction were similar on both occasions, the only significant differences being higher total cholesterol and low density lipoprotein-cholesterol concentrations less than or equal to 48 hours after ictus. No significant changes were observed among the 35 patients suffering cerebral hemorrhage apart from a significantly higher concentration of high density lipoprotein3-cholesterol less than or equal to 48 hours after ictus. Our study, with many patients classified according to stroke subtype, gives results different from those of previous studies with much fewer patients. We conclude that in studies of serum lipid and lipoprotein concentrations as risk factors for cerebral infarction, comparing values obtained less than or equal to 48 hours after admission with control values may incorrectly identify certain lipid fractions as risk factors.

Factors of prognostic significance in Chinese children with tuberculous meningitis.

A study was undertaken to identify factors of prognostic importance for 199 Chinese children with tuberculous meningitis treated in Hong Kong between 1961 and 1984 inclusive. During the period under study rifampicin and then pyrazinamide were introduced into treatment regimens and intrathecal therapy was abandoned. An analysis of pretreatment characteristics and details of chemotherapy by multivariate logistic regression identified two independent variables that predicted prognosis, namely clinical stage at the time of diagnosis, and age. Changes in treatment policies and the introduction of new anti-tuberculosis drugs did not appear to influence prognosis.

Sympathetic nervous system during converting enzyme inhibition.

Angiotensin II can stimulate the sympathetic system and inhibit vagal (parasympathetic) outflow under experimental circumstances in animals. Blockade of angiotensin II formation by angiotensin-converting enzyme (ACE) inhibitors might therefore be expected to result in a reduction of sympathetic activity and enhanced parasympathetic activity. Whether this is so in normotensive or hypertensive humans and in human cardiac failure is unclear, since available techniques for recording activity of the sympathetic and parasympathetic systems are imperfect. Nevertheless, most evidence that comes from measurements of venous norepinephrine suggests that the ACE inhibitors have little or no effect on sympathetic activity in normotension and hypertension, although the activated sympathetic system in severe cardiac failure is probably suppressed. It appears that the ACE inhibitors have a parasympathomimetic action that may contribute to the hemodynamic effects of these drugs. Additional information using direct recordings of sympathetic traffic or measurements of norepinephrine "spillover" is needed to clarify the effects of ACE inhibitors on the sympathetic system.

Increased incidence of thymoma in Chinese myasthenia gravis: possible relationship with Epstein-Barr virus.

Thymectomy was carried out for treatment of myasthenia gravis in 27 unselected Chinese patients and thymoma was found in 13 of them. This 48% incidence of thymomas is two to three times greater than in Japanese and European patients, respectively. The reason for the higher incidence of thymomas observed in Chinese patients may be related to the presence of the Epstein-Barr virus genome in thymoma. Furthermore, all of the thymomas in our patients were lymphoepithelial and histologically resemble nasopharyngeal carcinoma and undifferentiated carcinoma of the salivary gland. Both these tumours are closely linked to the Epstein-Barr virus and in Hong Kong, nasopharyngeal carcinoma is the third commonest cause of death from malignancy. We recommend early thymectomy for patients with myasthenia gravis particularly in geographical areas where there is a high incidence of nasopharyngeal carcinoma and undifferentiated carcinoma of the salivary gland.

Functional substance P receptors on a human astrocytoma cell line (U-373 MG).

[125I]Bolton Hunter conjugate of substance P ([125I]BHSP) can bind to human astrocytoma membranes in a monophasic and saturable manner with a Kd of 0.57 +/- 0.17 nM and a Bmax of 67.8 +/- 5.5 fmol/mg protein. The rank order of potency of tachykinins and related analogues as inhibitors of [125I]BHSP binding to astrocytoma membranes and intact cells correlated with their relative abilities to stimulate uridine incorporation into nucleic acid. The observed specificity pattern conformed to that reported for the NK1 tachykinin receptor with SP much greater than eledoisin greater than neurokinin A greater than neurokinin B and [Glp6, L-Pro9]SP(6-11) much greater than [Glp6, D-Pro9]SP(6-11).

Mouse astrocytes possess specific ANP receptors which are linked to cGMP production.

1. Receptors for atrial natriuretic peptide (ANP) have been identified on mouse astrocytes in primary culture, and have similar characteristics to those found on previously recognized ANP-target tissues. 2. Scatchard analysis revealed one class of high affinity receptors with a Kd of 0.32 nmol/L. The IC50 for specific binding was 0.5 nmol/L. 3. Ligand binding resulted in stimulation of guanylate cyclase. 4. Under reducing conditions, the covalently cross-linked receptor-ANP complex migrated on SDS-polyacrylamide gels as a single band with an apparent molecular weight of 66 kDa. 5. Although the physiological relevance of our observations remains to be determined, these data document that cultured mouse astrocytes contain specific high-affinity ANP receptors which are linked to the production of cGMP.

Internuclear ophthalmoplegia in tuberculous meningitis.

Two patients with tuberculous meningitis and internuclear ophthalmoplegia are described. Despite treatment with anti-tuberculosis chemotherapy and corticosteroids, both patients died. In one case autopsy showed severe basal meningitis with diffuse brain stem infarction secondary to widespread vasculitis.

Clinical correlation of CT changes in 64 Chinese patients with tuberculous meningitis.

CT changes in 64 Chinese patients with proven tuberculous meningitis were compared with the clinical features at diagnosis. In patients presenting with advanced disease, hydrocephalus and cerebral infarction were common, and the hydrocephalus in these patients was more likely to require surgery at a later date for control of raised intracranial pressure. New infarctions were only seen in follow-up scans of patients who had presented with disturbed consciousness. Meningeal enhancement, the commonest finding, and intracranial tuberculomata were not related to the severity of disease at presentation. A normal scan in a drowsy patient virtually excludes the diagnosis of tuberculous meningitis.