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Biomedical subjects

Richard Hubbard

Publications and source records attributed to Richard Hubbard.

At least 19 recordsLinked to original sources

Temporal association between the incidence of foot ulceration and the start of dialysis in diabetes mellitus.

BACKGROUND: The aim of this study was to seek a temporal association between the start of renal replacement therapy (RRT) and the first recorded foot ulcer in diabetes. METHODS: Details of all patients with diabetes who had received RRT were extracted from the renal database and were cross-checked with the database held in the specialist foot clinic. The date of onset of first registered foot ulcer was taken and compared with the date of onset of RRT. The self-controlled case-series method was used to establish any significant temporal association between the start of RRT and first recorded foot ulcer in diabetes. RESULTS: Of 466 patients with diabetes dialysed at our hospital since 1976, 94 (20.2%) were recorded as having at least one foot ulcer, with 15 of these undergoing major amputation. Incidence ratios (IRs) were calculated for 90 patients in whom complete data were available. A close temporal association was observed between the start of RRT and the first recorded foot ulceration: IR (95% CI) in the first and between the second and fifth years of dialysis were 3.35 (95% CI: 1.59-7.04), and 4.56 (2.19-9.50), respectively, relative to the time before dialysis. The IR for major amputation was 31.98 (2.09-490.3) in the first year and 34.01 (1.74-666.2) in the second to fifth years. CONCLUSION: These results reveal a close relationship between the onset of RRT in diabetes and the onset of foot ulceration, and confirm the high incidence of amputation in those on dialysis. Urgent steps should be taken to coordinate all aspects of diabetes foot care before and after the start of RRT.

Diabetic Foot↗

Risk of deep vein thrombosis and pulmonary embolism after acute infection in a community setting.

BACKGROUND: Acute infection increases the risk of arterial cardiovascular events, but effects on venous thromboembolic disease are less well established. Our aim was to investigate whether acute infections transiently increase the risk of venous thromboembolism. METHODS: We used the self-controlled case-series method to study the risk of first deep vein thrombosis (DVT) (n=7278) and first pulmonary embolism (PE) (n=3755) after acute respiratory and urinary tract infections. Data were obtained from records from general practices who had registered patients with the UK's Health Improvement Network database between 1987 and 2004. FINDINGS: The risks of DVT and PE were significantly raised, and were highest in the first two weeks, after urinary tract infection. The incidence ratio for DVT was 2.10 (95% CI 1.56-2.82), and that for PE 2.11 (1.38-3.23). The risk gradually fell over the subsequent months, returning to the baseline value after 1 year. The risk of DVT was also higher after respiratory tract infection, but possible diagnostic misclassification precluded a reliable estimate of the risk of PE after respiratory infection. INTERPRETATION: Acute infections are associated with a transient increased risk of venous thromboembolic events in a community setting. Our results confirm that infection should be added to the list of precipitants for venous thromboembolism, and suggest a causal relation.

Acute Disease↗

Use of inhaled corticosteroids and the risk of fracture.

BACKGROUND: Previous studies have found an association between the use of inhaled corticosteroids and fracture, but the extent to which this association is due to inhaled corticosteroids or to related factors, such as the severity of airflow obstruction, is disputed. We report a new approach in which we combine data on people with airflow obstruction from a large Medical Research Council study of the assessment and management of older people in the community with longitudinal data from their computerized general practice records. METHODS: Our cohort includes 1,671 study participants with a diagnosis of asthma or COPD (mean age, 80.6 years). We determined the dose-response relationship between inhaled corticosteroid exposure and time to first fracture using Cox regression, allowing for a wide range of potential confounding factors. RESULTS: During a mean follow-up period of 9.4 years, 982 patients (59%) received a prescription for an inhaled corticosteroid and 187 patients had a fracture. After adjusting for the effects of age and gender, we found a dose-related increase in fracture risk with exposure to inhaled corticosteroids (rate ratio for mean daily dose > 601 mug, 2.53; 95% confidence interval [CI], 1.65 to 3.89; overall trend p < 0.0001). The results were similar after adjusting for oral corticosteroid exposure, airflow obstruction diagnosis, historical fracture, and bronchodilator use (rate ratio, 4.21; 95% CI, 2.19 to 8.13), and also in the subset of people with no exposure to oral corticosteroids (rate ratio, 4.54; 95% CI, 1.23 to 16.74). CONCLUSIONS: Our findings provide further evidence that inhaled corticosteroid use is an independent risk factor for fracture.

Administration, Inhalation↗

Remote atmospheric breakdown for standoff detection by using an intense short laser pulse.

A remote atmospheric breakdown is a very rich source of UV and broadband visible light that could provide an early warning of the presence of chemical-biological warfare agents at extended standoff distances. A negatively chirped laser pulse propagating in air compresses in time and focuses transversely, which results in a rapid laser intensity increase and ionization near the focal region that can be located kilometers away from the laser system. Proof-of-principle laboratory experiments are performed on the generation of remote atmospheric breakdown and the spectroscopic detection of mock biological warfare agents. We have generated third harmonics at 267 nm and UV broadband radiation in air from the compression and focusing of femtosecond laser pulses. Fluorescence emission from albumin aerosols as they were illuminated by the femtosecond laser pulse has been observed.

Journal Article↗

Lung function and glucose metabolism: an analysis of data from the Third National Health and Nutrition Examination Survey.

Although people with diabetes have decreased lung function, the dose-response relation between measures of glucose control and lung function in nondiabetic people is not known. The authors used data from the Third National Health and Nutrition Examination Survey (1988-1994) to investigate the relation between glucose tolerance test response and other measures of glucose homeostasis and lung function in an adult population without a clinical diagnosis of diabetes. Plasma glucose level 2 hours after oral administration of 75 g of glucose was inversely related to forced expiratory volume in 1 second (FEV(1)), with a difference of -144.7 ml (95% confidence interval: -231.9, -57.4) for persons in the highest quintile of postchallenge glucose compared with the lowest. Similar inverse associations with FEV(1) were found for other measures of glucose autoregulation. Lung function did not appear to be related to fasting glucose level. Similar associations were seen for forced vital capacity (FVC) but not for the FEV(1):FVC ratio. In the total study population, persons with previously diagnosed diabetes had an FEV(1) 119.1 ml (95% confidence interval: -161.5, -76.6) lower than persons without diabetes. This effect was greater in those with poorly controlled diabetes. These findings suggest that impaired glucose autoregulation is associated with impaired lung function.

Adult↗

Early life risk factors for atopic dermatitis in Ethiopian children.

BACKGROUND: Atopic dermatitis (AD) has increased in prevalence in many countries in recent decades, but the risk factors for AD in developing countries are unknown. Helminthic parasites may play a role in protecting against allergic disease, but few studies have investigated the association of AD with parasitic infection. OBJECTIVE: To establish the independent effects of parasitic infection and other early life factors on the risk of AD in Ethiopia. METHODS: We conducted a cross-sectional survey and nested case-control study of children age 1 to 5 years in Jimma and surrounding rural areas in southwest Ethiopia. Cases were defined according to the International Study of Asthma and Allergies in Childhood criteria for AD and confirmed by clinical examination. Information on lifestyle and other potential risk factors was collected by parental questionnaire, and stool samples were analyzed for parasites. RESULTS: Complete data were obtained on 306 AD cases defined by International Study of Asthma and Allergies in Childhood criteria (prevalence, 4.4%) and 426 controls. There was no reduction in the risk of AD in relation to intestinal parasite infection; in fact, AD was increased in subjects with Trichuris (1.61; 95% CI, 1.14-2.26). The risk of AD was also unrelated to family size, crowding in the home, or breast-feeding, but was related to previously unrecognized factors including malaria and access to piped drinking water. Similar findings were apparent in cases and controls confirmed by clinical examination. CONCLUSION: Neither intestinal parasite infection nor other proposed risk factors for AD appear to be related to the presence of the condition in young children in Ethiopia, suggesting that other factors may be more important in this population.

Allergens↗

The cyclooxygenase-2-specific inhibitor parecoxib sodium is as effective as 12 mg of morphine administered intramuscularly for treating pain after gynecologic laparotomy surgery.

Parecoxib sodium, the injectable prodrug of valdecoxib, is a cyclooxygenase-2-specific inhibitor that is effective in the treatment of postoperative pain. In this randomized, double-blind, placebo-controlled study, we compared the efficacy of a single dose of parecoxib sodium 40 mg IM with single doses of morphine 6 and 12 mg IM in treating postoperative pain after gynecologic surgery requiring a laparotomy incision. By nearly all efficacy measures (including total pain relief and patient's global evaluation of study medication), parecoxib sodium 40 mg IM demonstrated pain relief and a decrease in pain intensity that was statistically similar to that with morphine 12 mg IM and superior to that with morphine 6 mg IM. Parecoxib sodium 40 mg IM-treated patients also demonstrated a longer time to use of rescue medication than patients treated with both morphine doses, and this dose provided sustained pain relief over the 12-h study period. The incidence of adverse events in the active treatment groups was similar to that observed with placebo. Parecoxib sodium, 40 mg IM, has been shown to be as effective as clinically relevant doses of morphine in patients after gynecologic laparotomy surgery.

Adult↗

Risk of myocardial infarction and stroke after acute infection or vaccination.

BACKGROUND: There is evidence that chronic inflammation may promote atherosclerotic disease. We tested the hypothesis that acute infection and vaccination increase the short-term risk of vascular events. METHODS: We undertook within-person comparisons, using the case-series method, to study the risks of myocardial infarction and stroke after common vaccinations and naturally occurring infections. The study was based on the United Kingdom General Practice Research Database, which contains computerized medical records of more than 5 million patients. RESULTS: A total of 20,486 persons with a first myocardial infarction and 19,063 persons with a first stroke who received influenza vaccine were included in the analysis. There was no increase in the risk of myocardial infarction or stroke in the period after influenza, tetanus, or pneumococcal vaccination. However, the risks of both events were substantially higher after a diagnosis of systemic respiratory tract infection and were highest during the first three days (incidence ratio for myocardial infarction, 4.95; 95 percent confidence interval, 4.43 to 5.53; incidence ratio for stroke, 3.19; 95 percent confidence interval, 2.81 to 3.62). The risks then gradually fell during the following weeks. The risks were raised significantly but to a lesser degree after a diagnosis of urinary tract infection. The findings for recurrent myocardial infarctions and stroke were similar to those for first events. CONCLUSIONS: Our findings provide support for the concept that acute infections are associated with a transient increase in the risk of vascular events. By contrast, influenza, tetanus, and pneumococcal vaccinations do not produce a detectable increase in the risk of vascular events.

Acute Disease↗

Lessons learned from a multiple-dose post-operative analgesic trial.

Patients undergoing major surgery often require several days of post-operative analgesic management. However, little data are available on the course of post-operative pain during this period. Such data would be extremely helpful in planning treatment, formulating pain management guidelines, and determining how to construct multiple-dose post-operative analgesic clinical trials. The objectives of this study were to determine (1) if post-operative pain severity, as measured by a modified version of the Brief Pain Inventory (BPI), can be categorized as mild, moderate, or severe in terms of modified BPI pain interference scores, (2) the relationship between modified BPI pain ratings and responses to a categorical item that specifically measures post-sternotomy pain, and (3) the relationship between global ratings of study medication effectiveness and other pain measures. This study is a reanalysis of data from patients who underwent coronary artery bypass graft procedures. We found that the pain severity level cut points developed for chronic pain apply equally well to post-operative pain. Based on this classification scheme, 18% of patients reported moderate pain after day 3, while 14% reported severe pain. Only 9% of patients reported experiencing moderate-to-severe pain approximately 2 weeks later, at the end of the study. Describing pain as mild, moderate, or severe could be a simple, meaningful clinical trial outcome measure. Because most patients experience only mild pain 6 days after surgery, long-term clinical trials of post-operative pain control may be more efficient and cost-effective if they focus on the subset of patients with persistent moderate or severe pain.

Aged↗

Vaccination and allergic disease: a birth cohort study.

OBJECTIVES: We examined the effect of vaccination for diphtheria; polio; pertussis and tetanus; or measles, mumps, and rubella on the incidence of physician-diagnosed asthma and eczema. METHODS: We used a previously established birth cohort in the West Midlands General Practice research database. RESULTS: We found an association between vaccination and the development of allergic disease; however, this association was present only among children with the fewest physician visits and can be explained by this factor. CONCLUSIONS: Our data suggest that currently recommended routine vaccinations are not a risk factor for asthma or eczema.

Asthma↗

Inhaled corticosteroids, bone mineral density and fracture in older people.

The efficacy of inhaled corticosteroids in the treatment of asthma has been firmly established in a variety of settings. The majority of asthma management plans now recommend the use of inhaled corticosteroids at an early stage. This means that most patients with asthma will be prescribed an inhaled corticosteroid at some point in time and many patients with asthma will use these drugs for several years. Inhaled corticosteroids are also used in the treatment of other conditions, particularly chronic obstructive pulmonary disease (COPD). Since inhaled corticosteroids are absorbed into the systemic circulation, they can have systemic adverse effects, such as suppression of the hypothalamic-pituitary-adrenal axis and increasing the risk of bruising. However, perhaps the greatest concern for patients is whether the regular use of inhaled corticosteroids has an adverse impact on the bone mineral density and increases the risk of fracture. There is now accumulating evidence from epidemiological studies that the use of inhaled corticosteroids is inversely related to bone mineral density in a dose-dependent fashion. However, data from two clinical trials of moderately high doses of inhaled corticosteroids in patients with COPD have produced conflicting results and while the larger study of triamcinolone found a significant impact of this drug on bone mineral density, a smaller study of budesonide found no effect. Epidemiological research into the relationship between inhaled corticosteroids and fracture is at an early stage. To date, only three studies in this area have been reported, all of which have used different approaches to try to minimise the impact of bias and confounding. There is a lack of consistency between the final estimates of the impact of inhaled corticosteroids on fracture risk. However, taken together these data suggest that the short to medium term use of inhaled corticosteroids is associated with a small adverse effect on bone. Doctors and patients need to be aware of this risk and balance it against the known beneficial effects of inhaled corticosteroids.

Administration, Inhalation↗

Exposure to tricyclic and selective serotonin reuptake inhibitor antidepressants and the risk of hip fracture.

The use of tricyclic antidepressants is associated with an increased risk of hip fracture. Despite a better side effect profile, this adverse effect has also been reported for selective serotonin reuptake inhibitors. To determine whether these findings result from bias arising from the case-control method, the authors have performed a case-control analysis and a self-controlled case-series analysis using 1987-1999 diagnosis data for 16,341 cases of hip fracture and 29,889 controls drawn from the United Kingdom General Practice Research Database. Both analyses showed an association between hip fracture and antidepressant treatment, and this was most marked during the first 15 days of treatment. The estimates from the case-control study were larger than those from the case-series analysis: The odds ratios for fracture within the first 15 days of a prescription for tricyclic antidepressants and serotonin reuptake inhibitors were 4.76 (95% confidence interval (CI): 3.06, 7.41) and 6.30 (95% CI: 2.65, 14.97), whereas the equivalent incidence ratios were 2.30 (95% CI: 1.82, 2.90) and 1.96 (95% CI: 1.35, 2.83). Tricyclic antidepressants and serotonin reuptake inhibitors are both associated with an independent increase in hip fracture incidence during the first weeks of treatment. The estimates from the case-series analyses were smaller than those from the case-control analyses, suggesting that the case-control method is subject to bias.

Aged↗

Wheezing, allergy, and parasite infection in children in urban and rural Ethiopia.

Epidemiological studies in developing countries suggest that intestinal parasite infection may reduce the risk of asthma. Because this evidence is all derived from adults and older children, we have investigated the relation between parasite infection, wheezing, and allergen skin sensitization in nested case-control studies drawn from a survey of 7,155 children aged 1 to 4 years living in urban and rural areas of Jimma, Ethiopia. Infection with parasites was common, predominantly with Trichuris (54%), Ascaris (38%), and hookworm (10%). Wheezing in the past year was significantly more prevalent in urban (4.4%) than rural children (2.0%), and was less prevalent in those infected with Ascaris (age, sex, and urban/rural adjusted odds ratio, 0.5; 95% confidence interval, 0.3 to 0.9), particularly in relation to high-intensity infection. Similar, although nonsignificant, associations were found for hookworm (adjusted odds ratio, 0.6; 95% confidence interval, 0.2 to 1.8), but there was no suggestion of any relation to Trichuris infection. Dermatophagoides pteronyssinus and cockroach (Blattella germanica) skin sensitization was more prevalent in rural than urban children, and was unrelated to wheeze. We conclude that Ascaris and possibly hookworm infection protects against wheeze in young Ethiopian children, and that this effect is not mediated by inhibition of allergen sensitization.

Age Distribution↗

Fracture risk in people with celiac disease: a population-based cohort study.

BACKGROUND & AIMS: People with celiac disease are at risk of developing osteoporosis, but the extent of any increased fracture risk is unclear. We performed a population-based cohort study by using the General Practice Research Database to quantify the fracture risk in people with celiac disease compared with the general population. METHODS: We identified 4732 people with celiac disease, of whom 1589 were "incident" cases, and 23,620 age- and sex-matched control subjects. We used Cox regression to estimate the hazard ratios for any fracture, hip fracture, and ulna or radius fracture in the celiac disease cohort compared with the general population. RESULTS: In the incident subjects with celiac disease, the mean age at diagnosis was 44 years, and 67% were women. The overall hazard ratio for any fracture was 1.30 (95% confidence interval, 1.16-1.46), for hip fracture was 1.90 (95% confidence interval, 1.20-3.02), and for ulna or radius fracture was 1.77 (95% confidence interval, 1.35-2.34). The absolute difference in the overall fracture rate was 3.20 per 1000 person-years and for hip fracture it was 0.97 per 1000 person-years in those older than 45 years. In 1589 incident subjects, the excess fracture risk was slightly lower compared with the "prevalent" subjects (hazard ratio for any fracture, 1.19 vs. 1.40, respectively). CONCLUSIONS: There were small increases in both the absolute and relative fracture risks in people with celiac disease; the excess risks were slightly lower in those with a more recent diagnosis. Our data indicate that concerns regarding a markedly increased fracture risk in celiac disease are unwarranted.

Adolescent↗