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Biomedical subjects

Timothy M E Davis

Publications and source records attributed to Timothy M E Davis.

At least 37 records · Page 2Linked to original sources
PubMed2005

Longitudinal predictors of reduced mobility and physical disability in patients with type 2 diabetes: the Fremantle Diabetes Study.

OBJECTIVE: The purpose of this study was to determine longitudinal predictors of impaired mobility and physical disability in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied patients with type 2 diabetes who participated in a prospective, community-based study. A wide range of baseline variables were examined to determine whether they predicted future difficulties with 1) mobility and 2) basic activities of daily living (ADLs) in patients free of ADLs difficulty at baseline. To study mobility impairment, subjects with baseline mobility problems were also excluded. RESULTS: After an average 4.6 +/- 2.3 and 4.8 +/- 2.3 years of follow-up in 818 and 934 patients, respectively, 28.5% of subjects had developed new mobility impairment and 18.1% had developed new ADL disability. In Cox proportional hazards models, the risk of mobility impairment was significantly increased by older age (6%/year), peripheral neuropathy (40% increase), stroke history (123%), insulin treatment (117%), albuminuria, and arthritis (82%); taking exercise and being married lowered the risk (by 39 and 32%, respectively). The risk of new ADL disability was increased by baseline mobility problems (222% increase), stroke (92%), claudication (67%), and depression (41%) and was also influenced by age, smoking, lack of exercise, non-fluency in English, and indigenous Australian ethnicity. CONCLUSIONS: Both mobility impairment and ADL disability in type 2 diabetes have multiple causes that are due to diabetes complications and common comorbidities. The specific causes of each functional problem are largely distinct, and different approaches may be required to prevent their onset or progression.

Activities of Daily Living↗
PubMed2005

Determinants of diabetes-attributable non-blood glucose-lowering medication costs in type 2 diabetes: the Fremantle Diabetes Study.

OBJECTIVE: To prospectively examine the magnitude and predictors of diabetes-attributable non-blood glucose-lowering (non-BGL) medication costs in type 2 diabetes. RESEARCH DESIGN AND METHODS: Detailed data from 593 community-dwelling patients were available over 4.3 +/- 0.4 years. Diabetes-attributable costs (in year 2000 Australian dollars [A$]) were calculated by applying a range of attributable proportions for each complication for which medication was prescribed. RESULTS: Non-BGL medications accounted for 75% of all prescription medication costs over the study period, and one-third were attributable to diabetes. The median annual cost (in A$) of non-BGL medications per patient increased from A$220 to A$429 over 4 years (P < 0.001), whereas the diabetes-attributable contribution increased from A$31 (range 15-40) to A$159 (range 95-219) per patient (P < 0.001). Diabetes-attributable hospital costs remained stable during the study. Diabetes-attributable non-BGL costs were skewed and, therefore, square root transformed before regression analysis. Independent baseline determinants of square root cost/year were coronary heart disease, systolic blood pressure, total serum cholesterol, ln(serum triglycerides), ln(albumin-to-creatinine ratio), serum creatinine, education, and, negatively, male sex and fasting plasma glucose (P </= 0.043; R(2) = 29%). Projected to the Australian population, diabetes-attributable non-BGL medication costs for patients with type 2 diabetes totaled A$79 million/year. CONCLUSIONS: The median annual cost of diabetes-attributable non-BGL medications increased fivefold over 4 years. This increase was predicted by vascular risk factors and complications at baseline. Better-educated patients had higher costs, probably reflecting improved health care access. Men and patients with higher fasting plasma glucose levels had lower costs, suggesting barriers to health care and/or poor self-care. The contemporaneous containment of hospital costs may be due to the beneficial effect of increased medication use.

Aged↗
PubMed2005

Effect of a pharmaceutical care program on vascular risk factors in type 2 diabetes: the Fremantle Diabetes Study.

OBJECTIVE: To examine the effect of a 12-month pharmaceutical care (PC) program on vascular risk in type 2 diabetes. RESEARCH DESIGN AND METHODS: We recruited 198 community-based patients randomized to PC or usual care. PC patients had face-to-face goal-directed medication and lifestyle counseling at baseline and at 6 and 12 months plus 6-weekly telephone assessments and provision of other educational material. Clinical, biochemical, and medication-related data were sent regularly to each patient's physician(s). The main outcome measure was change in HbA(1c). A diabetes-specific risk engine was used to estimate changes in 10-year coronary heart disease (CHD) and stroke risk in patients without a history of cardiovascular disease. RESULTS: At total of 180 patients (91%) completed the study. Mean (95% CI) reductions were greater in PC case subjects (n = 92) than control subjects (n = 88) for HbA(1c) (-0.5% [95% CI -0.7 to -0.3] vs. 0 [-0.2 to 0.2]) and systolic (-14 mmHg [-19 to -9] vs. -7 [-11 to -2]) and diastolic (-5 mmHg [-8 to -3] vs. -2 [-4 to 1]) blood pressure (P < or = 0.043). The improvement in HbA(1c) persisted after adjustment for baseline value and demographic and treatment-specific variables. The median (interquartile range) 10-year estimated risk of a first CHD event decreased in the PC case subjects (25.1% [15.6-36.2] to 20.3 [14.6-30.2]; n = 42, P = 0.002) but not in the control subjects (26.1% [17.2-39.4] vs. 26.4 [16.7-38.0]; n = 52, P = 0.17). CONCLUSIONS: A 12-month PC program in type 2 diabetes reduced glycemia and blood pressure. Pharmacist involvement contributed to improvement in HbA(1c) independently of pharmacotherapeutic changes. PC could prove a valuable component of community-based multidisciplinary diabetes care.

Administration, Oral↗
PubMed2005

Tesaglitazar.

AstraZeneca plc is developing tesaglitazar, an oral dual peroxisome proliferator-activated receptor alpha/gamma agonist, for the potential improvement of dyslipidemia and glycemic control in type 2 diabetic patients.

Alkanesulfonates↗
PubMed2004

Safety evaluation of fixed combination piperaquine plus dihydroartemisinin (Artekin) in Cambodian children and adults with malaria.

AIMS: To assess the haemodynamic, electrocardiographic and glycaemic effects of piperaquine-dihydroartemisinin (Artekin) fixed combination therapy in uncomplicated malaria. METHODS: Sixty-two Cambodians (32 children and 30 adults) with falciparum or vivax malaria were given Artekin given as four age-based oral doses over 32 h. Supine and erect blood pressure, the electrocardiographic QT interval and plasma glucose were measured before treatment and then at regular intervals during a 4-day admission period as part of efficacy and safety monitoring. QT intervals were rate-corrected (QTc) using Bazett's formula. RESULTS: Artekin therapy was well tolerated and all patients responded to treatment. Average parasite and fever clearance times were 19 and 12 h, respectively. The pretreatment mean fall in systolic blood pressure on standing was 8 +/- 6 mmHg and 6-hourly measurements over 72 h showed no significant change (P = 0.48). There was a significant lengthening of the mean QTc to a maximum of 11 ms(0.5) (95% confidence interval 4-18 ms(0.5)) relative to baseline at 24 h (P = 0.003). The maximal QTc prolongation observed in any patient was 53 ms(0.5). There was a mean 0.4 mmol l(-1) reduction in the post-absorptive plasma glucose during the first 48 h but no episodes of hypoglycaemia (plasma glucose < 3.0 mmol l(-1)) were observed at any time. CONCLUSIONS: Artekin is safe and effective combination therapy for uncomplicated malaria in children and adults. Although piperaquine is a long half-life drug related to other quinoline compounds including chloroquine and quinine, no clinically significant cardiovascular or metabolic effects were observed.

Adolescent↗
PubMed2004

Population pharmacokinetics of piperaquine in adults and children with uncomplicated falciparum or vivax malaria.

AIMS: To study the population pharmacokinetics of piperaquine after co-administration with dihydroartemisinin in uncomplicated malaria. METHODS: The disposition of piperaquine was studied in 85 Cambodian patients with uncomplicated falciparum or vivax malaria treated with the piperaquine-dihydroartemisinin coformulation Artekin. All patients were given Artekin orally at 0, 6, 24 and 32 h with a total piperaquine dose of 32-35 mg base kg-1. Adults were given tablets while children received either tablets or a dispersible granule formulation. Patients underwent either intensive (17-19 samples) or sparse (2-5 samples) blood sampling schedules over 35 days and clinical/parasitological follow-up over > 28 days. Piperaquine in plasma was quantified by high performance liquid chromatography. RESULTS: All patients achieved fever clearance within 24 h and parasite clearance within 72 h. The 28-day cure rate was 97% in adults and 98% in children. A covariate-free two-compartment population model with first-order absorption and elimination gave the most robust representation of the plasma concentration-time data in both adults and children. In adults (n = 38), the median (interquartile range) derived pharmacokinetic descriptors CL/F, Vss/F and t1/2,z were 0.9 l h-1 kg-1 (0.79-1.02 l h-1 kg-1), 574 l kg-1(371-711 l kg-1) and 23 days (19-28 days), respectively. In children (n = 47), corresponding values were 1.8 l h-1 kg-1 (1.29-2.3 l h-1 kg-1), 614 l kg-1 (332-1205 l kg-1) and 14 days (10-18 days), respectively. CONCLUSIONS: Piperaquine is a highly lipid-soluble drug with a large Vss/F, long t1/2,z and a clearance that is markedly higher in children than in adults.

Adult↗
PubMed2004

Protein binding and alpha : beta anomer ratio of dihydroartemisinin in vivo.

AIMS: To determine the ratio of alpha : beta anomers and the protein binding of dihydroartemisinin (DHA) in vivo. METHODS: 10-[(3)H]-DHA was synthesized by reduction of artemisinin with sodium boro-[(3)H]-hydride and purified with preparative thin layer chromatography. A solution of (3)H-DHA (2000 ng in 20 micro l) was added to 2 ml whole blood from 15 healthy volunteers and 22 Vietnamese patients with falciparum or vivax malaria. The blood was centrifuged and the plasma stored at -25 degrees C until analysed by HPLC with radiochromatographic detection. Protein-free ultrafiltrate of the plasma was assayed to determine the free fraction of DHA and the in vivo ratio of alpha-DHA : beta-DHA. RESULTS: The DHA fraction unbound (mean +/- SD) was 0.068 +/- 0.032 in Vietnamese patients with falciparum malaria (n = 17), 0.065 +/- 0.009 in Vietnamese patients with vivax malaria (n = 5), 0.117 +/- 0.015 in Vietnamese volunteers (n = 7) and 0.092 +/- 0.020 in Caucasian volunteers (n = 8). The ratios of alpha-DHA : beta-DHA for the four groups were 6.3 +/- 0.9, 6.9 +/- 0.8, 6.9 +/- 0.6 and 5.4 +/- 0.8, respectively. CONCLUSIONS: DHA is approximately 93% protein-bound in patients with malaria infection and there is a preferential existence in vivo of the alpha-DHA anomer. Knowledge of this stereochemistry may be valuable in elucidation of the mechanisms of DHA action and/or toxicity, and in the synthesis of new trioxane antimalarials.

Adult↗
PubMed2004

Disposition of artesunate and dihydroartemisinin after administration of artesunate suppositories in children from Papua New Guinea with uncomplicated malaria.

A detailed pharmacokinetic analysis was performed with 47 children from Papua New Guinea with uncomplicated falciparum or vivax malaria treated with artesunate (ARTS) suppositories (Rectocaps) given in two doses of approximately 13 mg/kg of body weight 12 h apart. Following an intensive sampling protocol, samples were assayed for ARTS and its primary active metabolite, dihydroartemisinin (DHA), by liquid chromatography-mass spectrometry. A population pharmacokinetic model was developed to describe the data. Following administration of the first dose, the mean maximal concentrations of ARTS and DHA were 1,085 nmol/liter at 0.9 h and 2,525 nmol/liter at 2.3 h, respectively. The absorption half-life for ARTS was 2.3 h, and the conversion half-life (ARTS to DHA) was 0.27 h, while the elimination half-life of DHA was 0.71 h. The mean common volumes of distribution for ARTS and DHA relative to bioavailability were 42.8 and 2.04 liters/kg, respectively, and the mean clearance values relative to bioavailability were 6 and 2.2 liters/h/kg for ARTS and DHA, respectively. Substantial interpatient variability was observed, and the bioavailability of the second dose relative to that of the first was estimated to be 0.72. The covariates age, sex, and alpha-thalassemia genotype were not influential in the pharmacokinetic model development; but the inclusion of weight as a covariate significantly improved the performance of the model. An ARTS suppositories dose of 10 of 20 mg/kg is appropriate for use in children with uncomplicated malaria.

Aging↗
PubMed2004

Greater use of insulin by southern European compared with Anglo-Celt patients with type 2 diabetes: the Fremantle Diabetes Study.

OBJECTIVE: To investigate the relationship between blood glucose-lowering therapy, glycaemia and ethnicity in urban Australians with type 2 diabetes. DESIGN: Prospective observational community-based study of diabetes care, control and complications. METHODS: We analysed cross-sectional data from 1057 patients, 238 from a southern European (SE) migrant background and 819 Anglo-Celts (AC). Follow-up data were available for 539 patients (113 SE, 426 AC) who had annual reviews over 4 years. RESULTS: The SE patients were of similar age to the AC patients but had longer diabetes duration, were less fluent in English and had less formal education. After adjustment for diabetes duration, glycosylated haemoglobin and glutamic acid decarboxylase antibody positivity in a logistic regression model, insulin use at study entry was approximately twice as frequent amongst SE as AC patients (odds ratio (95% confidence interval); 1.90 (1.20-3.02)). In the prospective arm, progression to insulin increased in both groups, from 18.0% at baseline to 22.1% at 4 years in SE and from 7.1% to 14.4% in AC patients. beta-cell function (%B) and insulin sensitivity (%S) using the homoeostasis model assessment in a subset of diet-treated patients at baseline showed that SE ethnicity was associated with lower %B and greater %S than in the AC group. CONCLUSIONS: SE patients with early non-antibody-mediated beta-cell failure progress to insulin requirement within the first 4-5 years of type 2 diabetes. This could reflect either a longer period of undiagnosed diabetes or a more rapid loss of beta-cell function after diagnosis.

Aged↗
PubMed2004

Glycemic exposure is associated with reduced pulmonary function in type 2 diabetes: the Fremantle Diabetes Study.

OBJECTIVE: To examine prospectively the relationship between diabetes, glycemic control, and spirometric measures. RESEARCH DESIGN AND METHODS: From a community-based cohort, 495 Europid (i.e., of European descent) patients with type 2 diabetes who had no history of pulmonary disease underwent baseline spirometry between 1993 and 1994. A subset of 125 patients was restudied a mean of 7.0 years later. The main outcome measures included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), vital capacity (VC), and peak expiratory flow (PEF) corrected for body temperature, air pressure, and water saturation and were expressed either in absolute terms or as percentage-predicted value for age, sex, and height. RESULTS: Mean percentage-predicted values of each spirometric measure were decreased >10% in the whole cohort at baseline and absolute measures continued to decline at an annual rate of 68, 71, and 84 ml/year and 17 l/min for FVC, FEV1, VC, and PEF, respectively, in the 125 prospectively studied patients. Declining lung function measures were consistently predicted by poor glycemic control in the form of a higher updated mean HbA1c, follow-up HbA1c, or follow-up fasting plasma glucose. In a Cox proportional hazards model, decreased FEV1 percentage-predicted value was an independent predictor of all-cause mortality. CONCLUSIONS: Reduced lung volumes and airflow limitation are likely to be chronic complications of type 2 diabetes, the severity of which relates to glycemic exposure. Airflow limitation is a predictor of death in type 2 diabetes after adjusting for other recognized risk factors.

Aged↗
PubMed2004

Prevalence and predictors of Helicobacter pylori infection in children and adults from the Penan ethnic minority of Malaysian Borneo.

To determine the prevalence of Helicobacter pylori antigen carriage in stool in the Penan ethnic minority in Malaysian Borneo, we studied 295 Penans 0.6-89.0 years of age from 1) the remote Limbang Division, 2) Mulu regional center, and 3) Belaga village. Overall, 37.7% of the subjects tested positive. Peak prevalence was reached by 10 years of age. There were no differences in age, sex, body mass index, and socioeconomic/domestic variables between antigen-positive and antigen-negative subjects. In a logistic regression analysis, subjects from Limbang were least likely to be antigen-positive (odds ratio [OR] = 0.23, 95% confidence interval [CI] = 0.12-0.44 versus other sites, P < 0.001). Availability of a flushing toilet was protective against H. pylori carriage (OR = 0.51, 95% CI = 0.27-0.95, P = 0.031). Infection with H. pylori among the Penan was less than reported in other low socioeconomic groups. The lowest prevalence in the most remote setting suggests that the infection has been a recent arrival in previously isolated communities.

Adolescent↗
PubMed2003

Treatment of uncomplicated falciparum malaria in southern Vietnam: can chloroquine or sulfadoxine-pyrimethamine be reintroduced in combination with artesunate?

The effectiveness of chloroquine or sulfadoxine-pyrimethamine administered with artesunate for treating uncomplicated falciparum malaria was assessed in 2 Vietnamese provinces where the sensitivity of parasites in vitro to conventional therapies had increased with the removal of drug pressure. In the province of Dac Lac, where potential malaria exposure begins at birth, 57 subjects (mean age, 9.6 years) were randomized to receive artesunate-chloroquine (group 1) or artesunate-sulfadoxine-pyrimethamine (group 2). In the province of Binh Phuoc, 66 nonimmune workers and their relatives (mean age, 24.2 years) were similarly randomized. By day 28 of follow-up, >96% of Dac Lac patients and <52% of Binh Phuoc patients in group 1 and group 2 had an in vivo response that demonstrated sensitivity to therapy. PCR-confirmed cure rates paralleled in vivo results among patients in Binh Phuoc, but PCR results identified 9 (15.7%) of the Dac Lac patients as having experienced asymptomatic, submicroscopic recrudescences. In Dac Lac, pfcrt K76T was near fixation, but infection with parasites with this mutation predicted recrudescence among group 1 patients in Binh Phuoc. Common pfdhfr mutations did not predict outcome in group 2. The successful reintroduction of conventional therapies in combination with artesunate depends on epidemiological and/or parasitological factors.

Adolescent↗
PubMed2003

Prospective evaluation of carotid bruit as a predictor of first stroke in type 2 diabetes: the Fremantle Diabetes Study.

BACKGROUND AND PURPOSE: We sought to examine prospectively the relationship between asymptomatic carotid bruit and stroke in type 2 diabetes. METHODS: We studied 1181 (91.3%) of a community-based sample of 1294 patients with type 2 diabetes. These patients had no history of cerebrovascular disease at recruitment during 1993-1996 and were followed until the end of January 2002. Hospital morbidity and death register data relating to cerebrovascular events were also available. Cox proportional hazards models were used to determine whether carotid bruit status was an independent predictor of stroke and to identify other significant cerebrovascular risk factors. RESULTS: One hundred thirty-four patients (11.3%) suffered a first stroke during 6.5+/-2.2 (mean+/-SD) years of follow-up. In the first 2 years after study entry, first stroke (n=45/1181; 3.8%) was strongly predicted by the presence of carotid bruit(s) after adjustment for known cardiovascular risk factors and other potentially confounding variables (hazard ratio, 6.7; 95% CI, 3.0 to 14.9; P<0.001). Between 2 years and census, first stroke (n=89/1083; 8.2%) was not associated with carotid bruit(s) (P=0.97). Age and diastolic blood pressure were other determinants of stroke in the first 2 years, while age, atrial fibrillation/flutter, and microalbuminuria were independent predictors of subsequent stroke. CONCLUSIONS: Type 2 diabetic patients found to have incidental carotid bruits have >6 times the risk of first stroke in the first 2 years than patients without a bruit and should receive intensified management of vascular risk factors. Carotid imaging with a view to surgical intervention in these patients remains controversial.

Aged↗
PubMed2003

Measurement of piperaquine in plasma by liquid chromatography with ultraviolet absorbance detection.

Piperaquine (PQ) is an antimalarial drug enjoying a resurgence of use in combination with an artemisinin derivative because of parasite resistance to standard treatments. Its pharmacokinetic properties have not been characterised. An assay for PQ in plasma was developed using solvent extraction and liquid chromatographic separation on a Waters XTerra RP(18) column, with a mobile phase of 7% acetonitrile in water (containing 0.025% trifluoroacetic acid, 0.1% NaCl and 0.008% triethylamine) and UV detection at 340 nm. The assay was linear up to 1000 microg/l. Intra- and inter-day relative standard deviations were <10% (5-500 microg/l) and <21% (5-500 microg/l), respectively. Inter-day limits of quantitation and detection were 5 microg/l and 3 microg/l, respectively. A preliminary pharmacokinetic study in a patient who received 2.56 g of PQ phosphate orally with dihydroartemisinin as four doses over 32 h found an apparent steady-state volume of distribution of 447 l/kg, an apparent oral clearance 0.93 l/h/kg and a terminal half-life of 17.3 days.

Antimalarials↗
PubMed2003

Cognitive impairment, physical disability and depressive symptoms in older diabetic patients: the Fremantle Cognition in Diabetes Study.

OBJECTIVE: To determine whether the prevalence of dementia, depression and/or disability in older diabetic subjects warrants an active screening approach by diabetes health care workers. PATIENTS AND METHODS: The initial 223 members of a cohort of 529 eligible diabetic subjects, aged 70 years or over, were screened for cognitive impairment (using the Mini-Mental State Examination (MMSE) and Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE)), physical impairments and depressive symptoms. RESULTS: Virtually all subjects were community-dwelling (99%) and mobile (86%) and relatively few had moderate or severe deficits in activities of daily living (ADL) (17.5%). The prevalences of cognitive impairment and probable dementia estimated from the screening tests were high (range 10.8-17.5%) compared with population studies. Any deficit with ADL was reported by 53% of the subjects and common problems included urinary and faecal incontinence. Scores consistent with clinical depression were reported by 14.2% of the sample but 50.2% of the remainder reported one or more depressive symptoms below the cut-off point for clinical depression. Only 36% of the study subjects were free of deficits in any domain. CONCLUSIONS: Community-living older diabetic subjects have high rates of cognitive impairment, deficits in physical function and depressive symptomatology suggesting that screening programs for functional impairments and depression may be beneficial in health care systems that manage older diabetic patients.

Activities of Daily Living↗
PubMed2003

Parasites and biosecurity--the example of Australia.

Biosecurity issues as they impact on agriculture, health and the environment are becoming increasingly important. Surveillance is crucial in maintaining a country's biosecurity and this article looks at some of the issues in the context of Australia and its neighbors in the Asia-Pacific region, and emerging threats from parasitic diseases. The important threats to agriculture, public health and wildlife are highlighted, and attention is given to how future surveillance activities must be undertaken on a regional basis and involve neighboring countries if they are to be effective and lead to the protection of both the trade and health of the population.

Animals↗