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Biomedical subjects

Malcolm Law

Publications and source records attributed to Malcolm Law.

At least 19 recordsLinked to original sources
PubMed2006

Vitamin D supplementation and the prevention of fractures and falls: results of a randomised trial in elderly people in residential accommodation.

OBJECTIVES: To determine whether vitamin D supplementation reduces the risk of fracture or falls in elderly people in care home accommodation. DESIGN: A randomised controlled trial of cluster design. SETTING AND SUBJECTS: 223 Residential units (mainly identical 30-bedded units), within 118 homes for elderly people throughout Britain, with 3,717 participating residents (76% women, average age 85 years). The units provided mainly or entirely residential care (35% of residents), nursing care (42%) or care for elderly mentally infirm (EMI) residents (23%). METHODS: Participants were randomly allocated by residential unit (cluster design) to a treated group offered ergocalciferol 2.5 mg every 3 months (equivalent to a daily dose of 1,100 IU), or to a control group. Fractures were reported by staff and confirmed in hospital, and routinely collected data on reported falls were obtained. RESULTS: After median follow-up of 10 months (interquartile range 7-14 months), 64 (3.6%) of 1,762 vitamin D-treated residents and 51 (2.6%) of 1,955 controls had one or more non-vertebral fractures, and 24 (1.3%) and 20 (1.0%), respectively, had a hip fracture. The proportion reporting at least one fall was 44% in vitamin D-treated and 43% in control residents. The differences between the vitamin D and control groups were not statistically significant. The incidence of all non-vertebral fractures in the care homes (3.2% per year) and of hip fractures (1.1% per year) was low, similar to rates in elderly people in sheltered accommodation, and the pre-treatment serum 25-hydroxy vitamin D concentration was high [median 47 nmol/l, measured in a 1% (n = 18) sample]. CONCLUSIONS: We found no evidence that vitamin D prevents fractures or falls in elderly people in care home accommodation.

Accidental Falls↗
PubMed2006

Statin safety: a systematic review.

A systematic review of cohort studies, randomized trials, voluntary notifications to national regulatory authorities, and published case reports was undertaken to assess the incidence and characteristics of adverse effects in patients treated with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins. For statins other than cerivastatin, the incidence of rhabdomyolysis in 2 cohort studies was 3.4 (1.6 to 6.5) per 100,000 person-years, an estimate supported by data from 20 randomized controlled trials. Case fatality was 10%. Incidence was about 10 times greater when gemfibrozil was used in combination with statins. Incidence was higher (4.2 per 100,000 person-years) with lovastatin, simvastatin, or atorvastatin (which are oxidized by cytochrome P450 3A4 [CYP3A4], which is inhibited by many drugs) than pravastatin or fluvastatin (which are not oxidized by CYP3A4). In persons taking simvastatin, lovastatin, or atorvastatin, 60% of cases involved drugs known to inhibit CYP3A4 (especially erythromycin and azole antifungals), and 19% involved fibrates, principally gemfibrozil. The incidence of myopathy in patients treated with statins, estimated from cohort studies supported by randomized trials, was 11 per 100,000 person-years. For liver disease, randomized trials reported fewer hepatobiliary disorders in patients allocated statins than in those allocated placebo. The notification rate of liver failure to regulatory authorities was about 1 per million person-years of statin use. Randomized trials show no excess of renal disease or proteinuria in statin-allocated participants, and the decline in glomerular filtration rate was smaller with statins than with placebo. Evidence from 4 cohort studies and case reports suggests that statins cause peripheral neuropathy, but the attributable risk is small (12 per 100,000 person-years). No change in cognitive function was found in randomized trials of statins in elderly patients.

Adverse Drug Reaction Reporting Systems↗
PubMed2005

Headaches and the treatment of blood pressure: results from a meta-analysis of 94 randomized placebo-controlled trials with 24,000 participants.

BACKGROUND: Uncertainty exists over whether blood pressure-lowering drugs prevent headache. METHODS AND RESULTS: A meta-analysis was carried out of the 94 randomized placebo-controlled trials of 4 different classes of blood pressure-lowering drugs (thiazides, beta-blockers, ACE inhibitors, and angiotensin II receptor antagonists) in fixed doses in which data on headache were reported. There were 17,641 participants who were allocated blood pressure-lowering drugs and 6603 who were allocated placebo. Treatment lowered systolic and diastolic blood pressures by 9.4 and 5.5 mm Hg, respectively, on average. One third fewer people on average reported headache in the treated groups (8.0%) than the placebo groups (12.4%) (odds ratio, 0.67; 95% CI, 0.61 to 0.74; P<0.001). About 1 in 30 treated persons benefited by having headache prevented. The prevalence of headache was reduced (P<0.001) in trials of each of the 4 classes of drugs. CONCLUSIONS: Our results show that blood pressure-lowering drugs prevent a significant proportion of headaches. That this effect is seen with pharmacologically unrelated classes of drugs indicates that it is likely to be due to the reduction in blood pressure per se, the only recognized action that the drugs have in common. This in turn indicates that high blood pressure is a cause of headache, but this conclusion is not supported by observational studies of blood pressure and headache. The uncertainty over whether high blood pressure causes headache does not, however, detract from the practical benefits of the use of blood pressure-lowering drugs in preventing headaches and cardiovascular disease.

Antihypertensive Agents↗
PubMed2004

Mortality from hypertrophic cardiomyopathy in England and Wales: clinical and screening implications.

OBJECTIVES: Hypertrophic cardiomyopathy is considered a relatively common cause of death in the young. Screening for the disorder has been advocated, but its potential value cannot be assessed because the number of deaths in asymptomatic cases in the general population has not been investigated. We determined the annual number of deaths (and death rates) from hypertrophic cardiomyopathy in England and Wales according to age, sex and the presence or absence of symptoms so that an affected individual's risk of dying from the disorder and the implications of screening could be assessed. METHODS: Ascertainment of all deaths from hypertrophic cardiomyopathy over a 3-year period (1996-1998), using death certification data from the Office of National Statistics. Deaths in people without symptoms were identified from coroner's reports and correspondence with pathologists who conducted the necropsies. RESULTS: There were 184 deaths per year from hypertrophic cardiomyopathy in England and Wales (about 15% of all deaths from cardiomyopathy) of which one third (65) were in people without symptoms. Most (110) of the 184 deaths each year were in people over age 55. Under age 55 there were only 37 deaths each year in asymptomatic people, out of an estimated 60,000 people with the disorder in the population. Of the 37 deaths, 14 (20%) occurred in relation to physical activity and 2 after competitive sport. CONCLUSIONS: In young people without symptoms hypertrophic cardiomyopathy is fairly common (1 in 500) but it rarely causes death; the case-fatality rate is about 6 per 10,000 per year. Current risk estimates from the study of patients in tertiary referral centers or general hospital clinics (420 and 110 deaths per 10,000 per year, respectively) are not applicable to asymptomatic people in the general population; such people, if incidentally identified can be reassured of their low risk of death. Screening would not be worthwhile unless a satisfactory test becomes available that can detect those few cases likely to die.

Autopsy↗
PubMed2004

The dose-response relation between serum homocysteine and cardiovascular disease: implications for treatment and screening.

BACKGROUND: With the recognition that serum homocysteine may cause cardiovascular disease there is clinical interest in homocysteine measurement to guide treatment with folic acid. It is uncertain whether treatment is best directed at those with high homocysteine or those at high risk irrespective of initial homocysteine. DESIGN AND METHODS: Dose-response plots of the associations between serum homocysteine and ischaemic heart disease and deep vein thrombosis were determined from retrospective (case-control) studies (a meta-analysis of 12 age-matched studies) prospective studies and studies of the C677T MTHFR polymorphism (a comparison of risk in three genotypes in a meta-analysis of 72 studies). The value of serum homocysteine as a screening test was assessed from distributions of serum homocysteine in men who did and did not die from ischaemic heart disease in a large prospective study. RESULTS: There were straight-line relationships between serum homocysteine and disease events in the three types of study; a given decrease in homocysteine would produce a similar proportional risk reduction from any pre-treatment level. There was substantial overlap between the distributions of serum homocysteine in men who did and did not die of ischaemic heart disease, indicating poor screening performance; there was no serum homocysteine cut-off that concentrated the majority of disease events into a small minority of the population. CONCLUSION: Interventions to lower serum homocysteine, if judged to be worthwhile, should not be limited to people with a high homocysteine but should be offered to everyone at high risk, regardless of pre-treatment homocysteine.

Adult↗
PubMed2003

Contact tracing and population screening for tuberculosis--who should be assessed?

BACKGROUND: The aim of the study was to investigate the relative effectiveness of four strategies in detecting and preventing tuberculosis: contact tracing of smear-positive pulmonary disease, of smear-negative pulmonary disease and of non-pulmonary disease, and screening new entrants. METHODS: An analysis of patient records and a TB database was carried out for an NHS Trust-based tuberculosis service in a socio-economically deprived area. Subjects were contacts of all patients treated for TB between 1997 and 1999. New entrants were screened in 1999. Outcomes measured were numbers of cases of active tuberculosis detected and numbers of those screened given chemoprophylaxis. RESULTS: A total of 643 contacts of 227 cases of active TB were seen, and 322 new entrants to the United Kingdom. The highest proportion of contacts requiring full treatment or chemoprophylaxis were contacts of smear-positive index cases (33 out of 263 contacts; 12.5 per cent). Tracing contacts of those with smear-negative pulmonary tuberculosis (12 out of 156; 7.7 per cent) and non-pulmonary disease (14 out of 277; 6.2 per cent) was significantly more effective in identifying individuals requiring intervention (full treatment or chemoprophylaxis) than routine screening of new entrants (10 out of 322; 3.1 per cent). CONCLUSIONS: Screening for TB of new entrants to the United Kingdom is part of the national programme for control and prevention of TB, whereas tracing contacts of those with smear-negative and non-pulmonary disease is not. This study demonstrates that, in our population, the contact-tracing strategy is more effective than new entrant screening. It is not likely that the contacts have caught their disease from the index case, but rather that in high-incidence areas such as ours such tracing selects extended families or communities at particularly high risk.

Antitubercular Agents↗