Progression of HIV disease in a haemophilic cohort followed for 11 years and the effect of treatment.

OBJECTIVE--To describe the progression of HIV disease in a haemophilic cohort and to show the influence of treatment. DESIGN--11 year longitudinal clinical and laboratory study. SETTING--A haemophilia centre. PATIENTS--111 patients infected with HIV during October 1979 to July 1985. MAIN OUTCOME MEASURES--Symptoms of HIV infection, AIDs, and death. INTERVENTIONS--26 asymptomatic patients started taking zidovudine or placebo (1000 mg/day) during November 1988 to February 1990; 10 patients with CD4+ counts of 0.2 x 10(9)/l started zidovudine 500 mg/day during January to November 1990. 35 patients used pentamidine for primary or secondary prophylaxis. RESULTS--At 11 years from seroconversion the estimated rate of progression to AIDS was 42% (95% confidence interval 27% to 57%); to symptoms 85% (75% to 95%); and to death 41% (25% to 57%). Progression to AIDS was significantly faster in patients aged 25 and over than in those aged less than 25 (relative risk 5.0 (2.4 to 10.4); p less than 0.00001) and in those with previous cytomegalovirus infection than in those not infected (relative risk 3.0 (1.4 to 6.8); p = 0.006). 16 of 27 (59%) patients with p24 antigenaemia developed AIDS compared with 17 of 84 (20%) patients without p24 antigen (p less than 0.001). The risk of progression to AIDS before 30 November 1988 in patients with CD4+ counts less than or equal to 0.2 x 10(9)/l was higher than after November 1988 (relative risk 1.9 (0.85 to 4.43); p = 0.1). For 1989 and 1990 the observed cumulative numbers of AIDS cases (among 81 patients with sufficient CD4+ counts) were 22 and 25 compared with 29 and 37 predicted from the rate of fall of CD4+ counts up to the end of 1988 (p = 0.03). CONCLUSION--Treatment seems to be reducing the progression of HIV disease in this haemophilic cohort.     

Use of reminders to increase compliance with tetanus booster vaccination.

OBJECTIVE: To assess the effect of three computerized reminder systems on compliance with tetanus vaccination. DESIGN: Prospective randomized controlled trial. SETTING: Ottawa Civic Hospital Family Medicine Centre. PARTICIPANTS: Of 8069 patients 20 years of age or more who were not in a hospital or institution 5589 were randomly assigned, by family, to a control group, a physician reminder group, a telephone reminder group or a letter reminder group. The remaining 2480 patients were not included in the randomized portion of the study but were monitored. Results are presented for the 5242 randomized patients and the 2369 nonrandomized patients for whom there was no up-to-date record of tetanus vaccination at the start of the trial. INTERVENTIONS: For the patients in the physician reminder group the physician was reminded at an office visit to assess the patient''s tetanus vaccination status and to recommend vaccination; those in the other two reminder groups received a telephone call or letter enquiring about their tetanus vaccination status and recommending a booster dose. MAIN OUTCOME MEASURE: Proportion of patients who received tetanus toxoid during the study year or who had a claim of vaccination in the previous 10 years. MAIN RESULTS: The rate of recorded tetanus vaccination in the randomized control group was 3.2%. The difference between that rate and those for the three reminder groups was 19.6% in the physician reminder group (95% confidence interval [CI] 17.1% to 22.2%, p less than 0.00001), 20.8% in the telephone reminder group (95% CI 18.3% to 23.5%, p less than 0.00001) and 27.4% in the letter reminder group (95% CI 24.8% to 30.2%, p less than 0.00001)). The letter reminders were more effective than either the telephone reminders (p = 0.00013) or the physician reminders (p less than 0.00001) in improving compliance. The cost to the practice per additional vaccination recorded was 43 for the physician reminders, $5.43 for the telephone reminders and $6.05 for the letter reminders. CONCLUSIONS: Although all three reminder systems increased the rate of recorded tetanus vaccination they fell far short of achieving complete population coverage. More intensive interventions would be required to approach that goal. However, such interventions do not appear to be justified given the rarity of tetanus.     

Acute red ear in children: controlled trial of non-antibiotic treatment in general practice.

OBJECTIVE--To examine the efficacy and safety of conservative management of mild otitis media ("the acute red ear") in children. DESIGN--Double blind placebo controlled trial. SETTING--17 group general practices (48 general practitioners) in Southampton, Bristol, and Portsmouth. PATIENTS--232 children aged 3-10 years with acute earache and at least one abnormal eardrum (114 allocated to receive antibiotic, 118 placebo). INTERVENTIONS--Amoxycillin 125 mg three times a day for seven days or matching placebo; 100 ml paracetamol 120 mg/5 ml. MAIN OUTCOME MEASURES--Diary records of pain and crying, use of analgesic, eardrum signs, failure of treatment, tympanometry at one and three months, recurrence rate, and ear, nose, and throat referral rate over one year. RESULTS--Treatment failure was eight times more likely in the placebo than the antibiotic group (14.4% v 1.7%, odds ratio 8.21, 95% confidence interval 1.94 to 34.7). Children in the placebo group showed a significantly higher incidence of fever on the day after entry (20% v 8%, p less than 0.05), mean analgesic consumption (0.36 ml/h v 0.21 ml/h, difference 0.14, 95% confidence interval 0.07 to 0.23; p = 0.0022), mean duration of crying (1.44 days v 0.50 days, 0.94; 0.50 to 1.38; p less than 0.001), and mean absence from school (1.96 days v 0.52 days, 1.45; 0.46 to 2.42; p = 0.0132). Differences in recorded pain were not significant. The prevalence of middle ear effusion at one or three months, as defined by tympanometry, was not significantly different, nor was there any difference in recurrence rate or in ear, nose, and throat referral rate in the follow up year. No characteristics could be identified which predicted an adverse outcome. CONCLUSIONS--Use of antibiotic improves short term outcome substantially and therefore continues to be an appropriate management policy.     

Randomised controlled trial of lymphoblastoid interferon alfa in Europid men with chronic hepatitis B virus infection.

OBJECTIVE--To confirm the findings of pilot studies that interferon alfa is an effective treatment of Europid men with chronic hepatitis B virus infection. DESIGN--Randomised controlled trial of three months treatment with interferon alfa followed by 12 months of observation. SETTING--Outpatient clinic of a tertiary referral centre. PATIENTS--37 Treated men (six anti-HIV positive) and 34 untreated men (nine anti-HIV positive) who met the criteria for the trial. Four controls failed to complete follow up. INTERVENTIONS--The treated group received subcutaneous injections of 5-10 MU interferon alfa/m2 daily for five days, then 10 MU/m2 thrice weekly for 11 weeks. Follow up continued at monthly intervals for 12 months. Untreated controls were monitored over the same period. MAIN OUTCOME MEASURE--Hepatitis B e antigen and hepatitis B virus DNA state after 15 months of observation. RESULTS--12 Of the 37 treated patients cleared hepatitis B e antigen and hepatitis B virus DNA, whereas only one of 30 untreated controls seroconverted over the same period--an increased response rate of 29% (95% confidence interval 13% to 45%). The life table estimate of response at 15 months was 35% in treated patients, an increase of 32% above controls (95% confidence interval 16% to 48%). The response rates in groups by predictive pretreatment variables were 12 of 31 anti-HIV negative patients (excess response 34%; 95% confidence interval 14% to 54%), 12 of 26 with chronic active hepatitis before treatment (excess response 46%; 27% to 65%), and 12 of 21 with a pretreatment serum aspartate aminotransferase activity greater than 70 IU/l (excess response 46%; 16% to 76%). The combination of these factors predicted response with a sensitivity of 100% and a specificity of 80%. Four of the 12 responders, who had all been infected for less than two years, also lost hepatitis B surface antigen. Treatment was well tolerated. CONCLUSIONS--Interferon alfa is effective in the treatment of a proportion of Europid men with chronic hepatitis B virus infection, who might be identified before treatment. Additional strategies are required to improve the rate of response.     

Medical Research Council trial of treatment of hypertension in older adults: principal results. MRC Working Party.

To establish whether treatment with diuretic or beta blocker in hypertensive older adults reduces risk of stroke, coronary heart disease, and death.Randomised, placebo controlled, single blind trial.226 general practices in the MRC general practice research framework.4396 patients aged 65-74 randomised to receive diuretic, beta blocker, or placebo. Patients had mean systolic pressures of 160-209 mm Hg and mean diastolic pressures less than 115 mm Hg during an eight week run in and were not taking antihypertensive treatment.Patients were randomised to atenolol 50 mg daily; hydrochlorothiazide 25 mg or 50 mg plus amiloride 2.5 mg or 5 mg daily; or placebo. The regimens were adjusted to achieve specified target pressures. Mean follow up was 5.8 years.Strokes, coronary events, and deaths from all causes.Both treatments reduced blood pressure below the level in the placebo group. Compared with the placebo group, actively treated subjects (diuretic and beta blocker groups combined) had a 25% (95% confidence interval 3% to 42%) reduction in stroke (p = 0.04), 19% (-2% to 36%) reduction in coronary events (p = 0.08), and 17% (2% to 29%) reduction in all cardiovascular events (p = 0.03). After adjusting for baseline characteristics the diuretic group had significantly reduced risks of stroke (31% (3% to 51%) p = 0.04), coronary events (44% (21% to 60%), p = 0.0009), and all cardiovascular events (35% (17% to 49%), p = 0.0005) compared with the placebo group. The beta blocker group showed no significant reductions in these end points. The reduction in strokes was mainly in non-smokers taking the diuretic.Hydrochlorothiazide and amiloride reduce the risk of stroke, coronary events, and all cardiovascular events in older hypertensive adults.     

Increased prevalence of mitral valve prolapse in patients with migraine.

Patients with classic migraine (69 women and 31 men) selected randomly from a practice list of over 1000 were matched for age, sex and neighbourhood with 100 people who did not have headache problems, and both groups underwent M-mode and two-dimensional echocardiography and clinical examination by cardiologists blinded to the subjects'' clinical status. The mean ages were 34.9 +/- 11.3 years for the migraine group and 33.1 +/- 9.9 years for the control group. Definite and possible mitral valve prolapse (MVP), diagnosed according to predefined echocardiographic criteria, were found about twice as often in the migraine group as in the control group (in 15 v. 7 and 16 v. 8 patients respectively); the echocardiograms were definitely normal in 69 migraine patients and 85 controls (chi 2 = 8.39, p less than 0.025). Altogether 25% of the migraine group and 11% of the control group had evidence of MVP from a combination of the echocardiographic and auscultatory findings (chi 2 = 5.72, p less than 0.025). The odds ratio was 2.7, with 95% confidence limits of 1.17 and 6.29. The association between migraine and MVP has implications for the understanding of platelet abnormalities and episodes of cerebral ischemia occurring in both these conditions.     

Antihypertensive effect of diet compared with drug treatment in obese men with mild hypertension.

OBJECTIVE--To determine whether dietary treatment has a similar antihypertensive effect to conventional drug treatment while being superior to drugs in improving serum lipid concentrations in obese men with mild hypertension. DESIGN--Six week run in period followed by randomisation to either diet or drug treatment groups for one year. SETTING--Outpatient clinic in city hospital. PATIENTS--61 Men aged 40-69 years, body mass index greater than or equal to 26, diastolic blood pressure 90-104 mm Hg when untreated. Exclusion criteria were signs of organ damage secondary to hypertension and diseases that might have interfered with compliance or with interpretation of results. INTERVENTIONS--Dietary treatment was based on weight reduction, restriction of sodium, and decrease of excess alcohol intake (defined as greater than or equal to 250 g alcohol per week). Drug treatment used a stepped care approach with atenolol as drug of first choice. MAIN OUTCOME MEASURES--Diastolic blood pressure less than 90 mm Hg; absolute reductions in blood pressure and serum lipid concentrations. RESULTS--Mean body weight decreased 7.6 kg in the diet group and increased 0.9 kg in the drug treatment group (p less than 0.0001), and mean sodium excretion decreased 42 and 10 mmol/24 h respectively (p = 0.019). There was no difference in reported alcohol intake. Mean systolic blood pressure decreased 4 mm Hg in the diet group and 16 mm Hg in the drug group (p = 0.003) and diastolic blood pressure 3 and 11 mm Hg respectively (p = 0.002). Diastolic blood pressure of 90 mm Hg was attained by 29% of the diet group (nine men) and 73% (22) of those receiving drug treatment (mean difference 44%, 95% confidence interval 21 to 67%, p = 0.001). Dietary treatment produced decreases in mean serum concentrations of total and low density lipoprotein cholesterol as well as triglycerides and an increase in high density lipoprotein cholesterol concentration. In the drug treatment group the changes were in the opposite direction, and the groups differed significantly in all but total cholesterol. CONCLUSIONS--Dietary treatment was inferior to conventional drug treatment in controlling mild hypertension but superior in lowering serum concentrations of lipids.     

First myocardial infarctions in Asian and white men.

OBJECTIVE--To compare the presentation and natural course of first myocardial infarctions in immigrant Asians and the indigenous white population in Britain and the subsequent risk states of the two groups. DESIGN--Prospective ethnic comparison of consecutive patients with first myocardial infarctions. SETTING--Secondary referrals to a coronary care unit of a district general hospital. PATIENTS--128 Men (77 white, 54 Asian) presenting consecutively with a first myocardial infarction diagnosed on the basis of clinical, biochemical, and electrocardiographic findings. END POINT--Identification of mechanisms accounting for the increased rate of ischaemic heart disease in Asians. MEASUREMENTS AND MAIN RESULTS--Infarct size was assessed by measuring the release of creatine phosphokinase (all patients), radionuclide ventriculography (50), and contrast ventriculography (103). Risk states after infarction were assessed from the degree of ventricular dysfunction as determined by exercise electrocardiography (82 patients) and from the extent of coronary atheroma as determined by coronary arteriography (103). Glucose state was measured in fasting venous blood samples. Overall the relative rate of infarction was 4.9 times higher in Asians (95% confidence interval 3.4 to 6.9) than in the white population. Moreover, the relative rate of infarction was higher in Asians in all 10 year age groups, the greatest difference being in 30-39 year olds. The mean age of the Asian denominator population was 47.1 years compared with 49.5 years in the white population. Age at infarction was less in Asians (50.2 years) than in white patients (55.5 years; mean difference 5.5 years (95% confidence interval 2.5 to 7.1]. In Asians the mean creatine phosphokinase activity was 777 (95% confidence interval 155 to 1399) U/1 higher, radionuclide ejection fraction 8.9% (1.0% to 16.9%) lower, and left ventricular fractional shortening 4.8% (1.4% to 8.2%) lower than in white patients. The extent of coronary atheroma was significantly greater in Asians. The mean numbers of plaques in vessels not associated with infarction were 3.66 (median 3.0, range 0-10) in Asians compared with 1.97 (median 2.0, range 0-6) in white patients (p less than 0.001), and a higher proportion of Asians had three vessel coronary artery disease (p less than 0.001). Asians with diabetes or impaired glucose tolerance did not differ from those with normal blood glucose values. CONCLUSIONS--Atherogenesis arises earlier in Asians, contributing to premature first myocardial infarctions. The increased incidence of diabetes in Asians may not in itself be relevant in the greater propensity to coronary atheroma in Asians.     

Comparison of high fibre diets,basal insulin supplements,and flexible insulin treatment for non-insulin dependent (type II) diabetics poorly controlled with sulphonylureas.

OBJECTIVE--To compare high fibre diet, basal insulin supplements and a regimen of insulin four times daily in non-insulin dependent (type II) diabetic patients who were poorly controlled with sulphonylureas. DESIGN--Run in period lasting 2-3 months during which self monitoring of glucose concentration was taught, followed by six months on a high fibre diet, followed by six months'' treatment with insulin in those patients who did not respond to the high fibre diet. SETTING--Teaching hospital diabetic clinics. PATIENTS--33 patients who had had diabetes for at least two years and had haemoglobin A1 concentrations over 10% despite receiving nearly maximum doses of oral hypoglycaemic agents. No absolute indications for treatment with insulin. INTERVENTIONS--During the high fibre diet daily fibre intake was increased by a mean of 16 g (95% confidence interval 12 to 20 g.) Twenty five patients were then started on once daily insulin. After three months 14 patients were started on four injections of insulin daily. ENDPOINT--Control of diabetes (haemoglobin A1 concentration less than or equal to 10% and fasting plasma glucose concentration less than or equal to 6 mmol/l) or completion of six months on insulin treatment. MEASUREMENTS AND MAIN RESULTS-- No change in weight, diet, or concentrations of fasting glucose or haemoglobin A1 occurred during run in period. During high fibre diet there were no changes in haemoglobin A1 concentrations, but mean fasting glucose concentrations rose by 1.7 mmol/l (95% confidence interval 0.9 to 2.5, p less than 0.01). With once daily insulin mean concentrations of fasting plasma glucose fell from 12.6 to 7.6 mmol/l (p less than 0.001) and haemoglobin A1 from 14.6% to 11.2% (p less than 0.001). With insulin four times daily concentrations of haemoglobin A1 fell from 11.5% to 9.6% (p less than 0.02). Lipid concentrations were unchanged by high fibre diet. In patients receiving insulin the mean cholesterol concentrations fell from 7.1 to 6.4 mmol/l (p less than 0.0001), high density lipoprotein concentrations rose from 1.1 to 1.29 mmol/l (p less than 0.01), and triglyceride concentrations fell from 2.67 to 1.86 mmol/l (p less than 0.05). Patients taking insulin gained weight and those taking it four times daily gained an average of 4.2 kg. CONCLUSIONS--High fibre diets worsen control of diabetes in patients who are poorly controlled with oral hypoglycaemic agents. Maximum improvements in control of diabetes were achieved by taking insulin four times daily.     

Intensified conventional insulin treatment and neuropsychological impairment.

OBJECTIVE--To assess whether intensified insulin treatment, with an increased frequency of hypoglycaemic episodes, leads to cognitive deterioration. DESIGN--Prospective randomised trial of intensified conventional treatment and standard treatment. SETTING--Outpatient clinic for patients with insulin dependent diabetes. SUBJECTS--96 patients with insulin dependent diabetes, high blood glucose concentrations, and non-proliferative retinopathy were randomised to intensified conventional treatment (n = 44) or standard treatment (n = 52). MAIN OUTCOME MEASURES--Glycated haemoglobin concentration (metabolic control); the number of hypoglycaemic episodes reported by patients at each visit; results of computerised neuropsychological tests performed at entry and after five years. RESULTS--Mean glycated haemoglobin concentration during the study was 7.2% (SE 0.1%) with intensified conventional treatment and 8.7 (0.1%) with standard treatment (p less than 0.001). During five years 34 (77%, 95% confidence interval 53% to 100%) of the patients given intensified treatment and 29 (56%, 36% to 75%) of the others had at least one episode of serious hypoglycaemia (p less than 0.05). The intensified conventional treatment group had a mean of 1.1 episodes of serious hypoglycaemia per patient per year compared with 0.4 episodes in the standard treatment group. Results of the neuropsychological tests were similar in the two groups after five years. CONCLUSIONS--Intensified conventional insulin treatment led to lower blood glucose concentrations and a higher frequency of hypoglycaemic episodes, but patients showed no signs of cognitive deterioration.     

A matched cohort comparison of the outcome of twin versus singleton pregnancies in Flanders, Belgium.

To compare perinatal outcome of singleton versus twin pregnancies a matched cohort study was performed in Flanders, Belgium. All twins delivered in the region of Flanders during 1998-1999 were compared to singletons, matched for gestational age, fetal sex and maternal parity, resulting in 4384 infants in each group. Above 32 weeks of gestation, birthweight was significantly lower in twins (2095 +/- 364 g versus 2315 +/- 523 g; p < 0.001, 95% confidence interval 193 to 246 g). Perinatal mortality was also significantly lower in twins (1.98% versus 1.26%; odds ratio for twins 0.63; 95% confidence interval 0.53-0.75; p < 0.001 ), this was mostly due to fetal and not to early neonatal mortality. Congenital malformations occurred less frequently in twins (2.5% versus 3.7%; odds ratio for twins 0.80, 95% confidence interval 0.69-0.92; p = 0.001). From gestational age of 32 weeks on, respiratory distress syndrome was less frequent in twins (6.7% versus 8.0%; odds ratio for twins 0.81; 95% confidence interval 0.68-0.97; p = 0.011 ). No significant differences were noted with regard to intraventricular haemorrhage, neonatal infections and retinopathy of prematurity. Although twins have a lower birthweight, their outcome is more favorable compared to singletons, when matched for gestational age.     

Bullous pemphigoid and pemphigus vulgaris—incidence and mortality in the UK: population based cohort study

Objective To determine the incidence of and mortality from bullous pemphigoid and pemphigus vulgaris in the United Kingdom.Design Retrospective historical cohort study.Setting Computerised medical records from the health improvement network, a large population based UK general practice database.Participants Patients with pemphigus vulgaris and bullous pemphigoid diagnostic codes and age, sex, and practice matched controls.Main outcome measures Incidence and mortality compared with the control population by calendar period, age group, sex, geographical region, and degree of social deprivation.Results 869 people with bullous pemphigoid and 138 people with pemphigus vulgaris were identified. The median age at presentation for bullous pemphigoid was 80 (range 23-102) years, and 534 (61%) patients were female. The median age at presentation for pemphigus vulgaris was 71 (21-102) years, and 91 (66%) patients were female. Incidences of bullous pemphigoid and pemphigus vulgaris were 4.3 (95% confidence interval 4.0 to 4.6) and 0.7 (0.6 to 0.8) per 100 000 person years. The incidence of bullous pemphigoid increased over time; the average yearly increase was 17% (incidence rate ratio=1.2, 95% confidence interval 1.1 to 1.2). An average yearly increase in incidence of pemphigus vulgaris of 11% (incidence rate ratio=1.1, 1.0 to 1.2) occurred. The risk of death for patients with bullous pemphigoid was twice as great as for controls (adjusted hazard ratio=2.3, 95% confidence interval 2.0 to 2.7). For pemphigus vulgaris, the risk of death was three times greater than for controls (adjusted hazard ratio=3.3, 2.2 to 5.2).Conclusions Incidences of bullous pemphigoid and pemphigus vulgaris are increasing. The reasons for the changes in incidence are not clearly understood but have implications for identifying causative factors. Both disorders are associated with a high risk of death. Previous estimates may have underestimated the risk of death associated with these diseases.     

Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus,Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group.

OBJECTIVES: To test the hypothesis that intensive metabolic treatment with insulin-glucose infusion followed by multidose insulin treatment in patients with diabetes mellitus and acute myocardial infarction improves the prognosis. DESIGN: Patients with diabetes mellitus and acute myocardial infarction were randomly allocated standard treatment plus insulin-glucose infusion for at least 24 hours followed by multidose insulin treatment or standard treatment (controls). SUBJECTS: 620 patients were recruited, of whom 306 received intensive insulin treatment and 314 served as controls. MAIN OUTCOME MEASURE: Long term all cause mortality. RESULTS: The mean (range) follow up was 3.4 (1.6-5.6) years. There were 102 (33%) deaths in the treatment group compared with 138 (44%) deaths in the control group (relative risk (95% confidence interval) 0.72 (0.55 to 0.92); P = 0.011). The effect was most pronounced among the predefined group that included 272 patients without previous insulin treatment and at a low cardiovascular risk (0.49 (0.30 to 0.80); P = 0.004). CONCLUSION: Insulin-glucose infusion followed by intensive subcutaneous insulin in diabetic patients with acute myocardial infarction improves long term survival, and the effect seen at one year continues for at least 3.5 years, with an absolute reduction in mortality of 11%. This means that one life was saved for nine treated patients. The effect was most apparent in patients who had not previously received insulin treatment and who were at a low cardiovascular risk.     

Effectiveness of geriatric rehabilitative care after fractures of the proximal femur in elderly women: a randomised clinical trial.

OBJECTIVE--To compare postoperative collaborative care between orthopaedic surgeons and physicians in geriatric medicine with routine orthopaedic care in elderly women with proximal femoral fracture. DESIGN--Exclusion of patients dying before fit enough to enter trial, those with pathological fractures, those likely to be discharged within seven days of entering the trial, and those remaining unfit for transfer to a peripheral hospital. Remainder allocated to two groups: treatment group and control group. SETTING--District hospital acute admission ward and rehabilitation ward. PATIENTS--144 sequentially admitted elderly women with proximal fracture of the femur; 36 excluded on above criteria and remainder entered into trial. INTERVENTION--Both treatment and control groups (n = 54 in each) received physiotherapy and other services. The treatment group also received thrice weekly supervision by a geriatrician. END POINTS--Physical independence, residence after discharge, and length of hospital stay. MEASUREMENTS AND MAIN RESULTS--At discharge significantly more patients in treatment group were independent in terms of activities of daily living than controls (41 v 25) and their median stay was 24 days (range 8-197) compared with 41 (9-365) (95% confidence intervals for difference 2 to 25). Significantly fewer treatment patients were discharged to institutional care (10% v 32%; 95% confidence interval for difference 6% to 37%) and more to their own homes (63% v 38%; 95% confidence interval for difference 6% to 44%). These beneficial effects were consistent across a range of ages and mental state. CONCLUSIONS--Both hospital and patient benefited when postoperative rehabilitation was provided in a setting specialising in such care for elderly patients with trauma.     

Breast feeding and vitamin A deficiency among children attending a diarrhoea treatment centre in Bangladesh: a case-control study.

OBJECTIVE--To determine the effect of breast feeding on the risk of xerophthalmia in children aged 6 months to 3 years attending a diarrhoea treatment centre in Bangladesh. DESIGN--Case-control study based on stratified analysis (Mantel-Haenszel) and multivariate analysis (logistic regression) of data from a treatment centre based surveillance system. SETTING--A large diarrhoea treatment centre in Dhaka, Bangladesh. PATIENTS--2687 children aged 6 months to 3 years representing a 4% systematic sample of all children in this age group treated yearly at the centre over three consecutive years. 66 of the children were cases of xerophthalmia (that is, they had Bitot''s spots or corneal lesions or night blindness or night blindness plus conjunctival xerosis or any combination of these) and the remaining 2621 did not have signs or symptoms of vitamin A deficiency. This second group served as controls. MAIN OUTCOME MEASURE--Xerophthalmia and breast fed at onset of diarrhoea or presentation. RESULTS--The odds ratio relating breast feeding to vitamin A deficiency after adjustment for a large number of confounding variables (0.26 (95% confidence interval 0.14 to 0.49); p less than 0.001) reflected a 74% reduction in the risk of vitamin A deficiency among breast fed children. The estimated reduction of risk did not decline with age, and some 49% of children aged 24-35 months were still being breast fed. The odds ratio relating breast feeding to xerophthalmia in the third year of life (0.35 (95% confidence interval 0.35 to 0.86) reflected a 65% reduced risk of vitamin A deficiency. Other important risk factors or prognostic indicators for xerophthalmia as identified by multivariate analysis were recent measles, prolonged diarrhoea, severe protein energy malnutrition, and poor socioeconomic state. CONCLUSIONS--These results indicate that breast feeding was associated with a substantial reduction of the risk of vitamin A deficiency extending to the third year of life and support the recommendation that mothers in developing countries should be advised to breast feed for as long as possible.     

Late recurrence of localized cutaneous melanoma: its influence on follow-up policy

This paper reports 11 cases of recurrence 10 years or more after primary treatment of clinically local cutaneous melanoma at the Peter MacCallum Cancer Institute. Using the product-limit method for estimating recurrence-free survival, two late recurrence rates have been calculated. The estimated late recurrence rate among all treated patients is 5 percent (95 percent confidence interval: 2 to 8 percent), and the estimated late recurrence rate for the group who survived the first 10 years without recurrence is 7 percent (95 confidence interval: 3 to 11 percent). No prognostic factors were found that could identify a patient subgroup significantly at risk of late recurrence. Recurrence-free survival curves show that most recurrences have presented by the end of 6 years, but later recurrences are seen, the latest in this series being 18.2 years following treatment. While patients probably do not require long-term follow-up in specialist clinics provided they are adequately educated in the nature of their disease, this paper shows the value of long-term statistical surveillance.     

Efficacy of captopril in postponing nephropathy in normotensive insulin dependent diabetic patients with microalbuminuria.

OBJECTIVE--To assess the effectiveness of angiotensin converting enzyme inhibition in preventing the development of diabetic nephropathy (albuminuria greater than 300 mg/24h). DESIGN--Open randomised controlled study of four years'' duration. SETTING--Outpatient diabetic clinic in tertiary referral centre. PATIENTS--44 normotensive (mean blood pressure 127/78 (SD 12/10) mm Hg) insulin dependent diabetic patients with persistent microalbuminuria (30-300 mg/24h). INTERVENTIONS--The treatment group (n = 21) was initially given captopril (25 mg/24 h). The dose was increased to 100 mg/24 h during the first 16 months and thiazide was added after 30 months. The remaining 23 patients were left untreated. MAIN OUTCOME MEASURES--Albuminuria, kidney function, development of diabetic nephropathy (albuminuria greater than 300 mg/24 h), and arterial blood pressure. RESULTS--Clinical and laboratory variables were comparable at baseline. Urinary excretion of albumin was gradually reduced from 82 (66-106) to 57 (39-85) mg/24 h (geometric mean (95% confidence interval)) in the captopril treated group, whereas an increase from 105(77-153) to 166 (83-323) mg/24 h occurred in the control group (p less than 0.05). Seven of the untreated patients progressed to diabetic nephropathy, whereas none of the captopril treated patients developed clinical overt diabetic nephropathy (p less than 0.05). Systemic blood pressure, glomerular filtration rate, haemoglobin A1c concentration, and urinary excretion of sodium and urea remained practically unchanged in the two groups. CONCLUSIONS--The findings suggest that angiotensin converting enzyme inhibition postpones the development of clinical overt diabetic nephropathy in normotensive insulin dependent diabetic patients with persistent microalbuminuria.     

Outcome of renal replacement treatment in patients with diabetes mellitus.

OBJECTIVE--To compare the outcome of renal replacement treatment in patients with diabetes mellitus and in non-diabetic patients with end stage renal failure. DESIGN--Retrospective comparison of cases and matched controls. SETTING--Renal unit, Western Infirmary, Glasgow, providing both dialysis and renal transplantation. PATIENTS--82 Diabetic patients starting renal replacement treatment between 1979 and 1988, compared with 82 matched non-diabetic controls with renal failure and 39 different matched controls undergoing renal transplantation. MAIN OUTCOME MEASURES--Patient characteristics, history of smoking, prevalence of left ventricular hypertrophy and myocardial ischaemia at start of renal replacement treatment; survival of patients with renal replacement treatment and of patients and allografts with renal transplantation. RESULTS--The overall survival of the diabetic patients during the treatment was 83%, 59%, and 50% at one, three, and five years. Survival was significantly poorer in the diabetic patients than the controls (p less than 0.001). Particularly adverse features for outcome at the start of treatment were increasing age (p less than 0.01) and current cigarette smoking (relative risk (95% confidence interval) 2.28 (0.93 to 4.84), p less than 0.05). Deaths were mainly from cardiac and vascular causes. The incidence of peritonitis in patients on continuous ambulatory peritoneal dialysis was the same in diabetic patients and controls (49% in each group remained free of peritonitis after one year), and the survival of renal allografts was not significantly worse in diabetic patients (p less than 0.5). CONCLUSIONS--Renal replacement treatment may give good results in diabetic patients, although the outlook remains less favourable than for non-diabetic patients because of coexistent, progressive vascular disease, which is more severe in older patients.     

Risk of cancer in relation to serum concentrations of selenium and vitamins A and E: matched case-control analysis of prospective data.

The independent and joint associations of serum selenium and vitamin A (retinol) and E (alpha tocopherol) concentrations with the risk of death from cancer were studied in 51 case-control pairs--that is, 51 patients with cancer, each paired with a control matched for age, sex, and smoking. Case-control pairs came from a random sample of some 12000 people aged 30-64 years resident in two provinces of eastern Finland who were followed up for four years. Patients who died of cancer during the follow up period had a 12% lower mean serum selenium concentration (p = 0.015) than the controls. The difference persisted when deaths from cancer in the first follow up year were excluded. The adjusted risk of fatal cancer was 5.8-fold (95% confidence interval 1.2-29.0) among subjects in the lowest tertile of selenium concentrations compared with those with higher values. Subjects with both low selenium and low alpha tocopherol concentrations in serum had an 11.4-fold adjusted risk. Among smoking men with cancer serum retinol concentrations were 26% lower than in smoking controls (p = 0.002). These data suggest that dietary selenium deficiency is associated with an increased risk of fatal cancer, that low vitamin E intake may enhance this effect, and that decreased vitamin or provitamin A intake contributes to the risk of lung cancer among smoking men with a low selenium intake.     

Acute and chronic arterial and venous effects of captopril in congestive cardiac failure.

OBJECTIVE--To determine whether captopril alters peripheral venous tone in patients with congestive cardiac failure. DESIGN--Open study of patients at start of captopril treatment and three months later. SETTING--A hospital gamma camera laboratory. PATIENTS--16 Men with congestive cardiac failure in New York Heart Association class II or III, aged 57-73. INTERVENTIONS--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. MAIN OUTCOME MEASURES--Previously validated non-invasive radionuclide techniques were used to measure changes in central haemodynamic variables and peripheral venous volumes in the calf. RESULTS--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). CONCLUSIONS--Captopril is an important venodilator. Venous and arterial dilatation are produced short term and during long term treatment.