PubMed Health⌕ Search

Biomedical subjects

Timothy M E Davis

Publications and source records attributed to Timothy M E Davis.

At least 19 recordsLinked to original sources
PubMed2026

A narrative review of what cohorts have taught us and how they have laid the foundation for much of our understanding of type 2 diabetes.

This narrative review provides a historical perspective on how observational research on type 2 diabetes has been developed and consolidated over the last 50 years and how well-designed cohort studies will provide us with knowledge for research and practice in the future and aid guideline development. We have included data from a large number of cohorts from every continent that have been used to study the development and/or progression of type 2 diabetes, including cohorts that are general population-based, disease-based, intervention-based and registry-based. We have structured the results from the past 50 years based on the following themes: diagnosis and screening, complications, risk factors and pathophysiology. We also discuss the strengths and weaknesses of observational research when compared with other research designs. Finally, we discuss the emerging and future directions for type 2 diabetes research using cohorts, which include novel developments, such as artificial intelligence, precision health and the exposome. We conclude that cohort research has significantly advanced our understanding of type 2 diabetes and aided guideline development, and complements experimental work, such as human randomised controlled trials and animal studies. Both approaches are essential and complementary in our pursuit to provide a more comprehensive understanding of the development and progression of type 2 diabetes, and to change dogma, practice and policies for better outcomes.

Humans↗
PubMed2007

Common infections in diabetes: pathogenesis, management and relationship to glycaemic control.

Specific defects in innate and adaptive immune function have been identified in diabetic patients in a range of in vitro studies. However, the relevance of these findings to the integrated response to infection in vivo remains unclear, especially in patients with good glycaemic control. Vaccine efficacy seems adequate in most diabetic patients, but those with type 1 diabetes and high glycosylated haemoglobin levels are most likely to exhibit hypo-responsiveness. While particular infections are closely associated with diabetes, this is usually in the context of extreme metabolic disturbances such as ketoacidosis. The link between glycaemic control and the risk of common community-acquired infections is less well established but could be clarified if infection data from large community-based observational or intervention studies were available. The relationship between hospital-acquired infections and diabetes is well recognized, particularly among post-operative cardiac and critically ill surgical patients in whom intensive insulin therapy improves clinical outcome independent of glycaemia. Nevertheless, further research is needed to improve our understanding of the role of diabetes and glycaemic control in the pathogenesis and management of community- and hospital-acquired infections.

Blood Glucose↗
PubMed2006

Assessment of the effect of mefloquine on artesunate pharmacokinetics in healthy male volunteers.

The effect of mefloquine on artesunate pharmacokinetics was assessed in 20 volunteers given artesunate for 3 days, followed > or =21 days later by combination therapy for 3 days. The areas under the concentration-time curve from 0 h to infinity for dihydroartemisinin, the active metabolite of artesunate, were similar on day 3 of the two dosing periods (P = 0.12), implying no interaction.

Adult↗
PubMed2006

Cardiovascular risk factors in pre-pubertal Malays: effects of diabetic parentage.

Diabetes prevalence is increasing rapidly in Asian populations but the influence of a family history of diabetes on cardiovascular risk is unknown. To assess this relationship, 120 urban-dwelling Malays were recruited to a cross-sectional case-control study. Sixty were pre-pubertal children, 30 of diabetic parentage (Group 1) and 30 with no diabetes family history (Group 2). Group 1 and 2 subjects were the offspring of adults with (Group 3) or without (Group 4) type 2 diabetes. Subjects were assessed for clinical and biochemical variables defining cardiovascular risk. Principal component analysis assessed clustering of variables in the children. Group 1 subjects had a higher mean waist:hip ratio, diastolic blood pressure and HbA(1c) than those in Group 2, and a lower HDL:total cholesterol ratio (P<0.03). Although there were no correlations between Group 1 and 3 subjects for cardiovascular risk variables, significant associations were found in Groups 2 and 4, especially HbA(1c) and insulin sensitivity (P< or =0.004). Of five separate clusters of variables (factors) identified amongst the children, the strongest comprised diabetic parentage, HbA(1c), insulin sensitivity and blood pressure. Features of the metabolic syndrome are becoming evident in the young non-obese children of diabetic Malays, suggesting that lifestyle factors merit particular attention in this group.

Adult↗
PubMed2006

Evidence for undetected malaria infection in non-immune Australian travellers not taking chemoprophylaxis.

To determine whether travellers from malaria-free countries can develop unrecognised or asymptomatic malaria after visiting endemic areas, we analysed data from 751 prospective blood donors who had visited or resided in malaria-risk areas in the previous 3 years. Malarial antibodies were measured using an established commercial enzyme-linked immunoassay incorporating four recombinant blood-stage plasmodial antigens and with published sensitivity > or =83% and specificity 100%. Details of countries visited and antimalarial chemoprophylaxis used were obtained by questionnaire. Among the 606 subjects resident in malaria-free countries and with no past history of malaria, 176 had visited high-risk countries as categorised by the World Health Organisation (WHO). Of these, 89 took no chemoprophylaxis including 6 (6.7%) who were antibody-positive; there were no antibody-positive subjects in the 87 who took chemoprophylaxis (P=0.029), which was that recommended by WHO in 84% of cases. These data underscore the value of effective antimalarial prophylaxis in non-immune travellers visiting high malaria-risk areas but also suggest that unrecognised infections can occur in those unprotected by chemoprophylaxis.

Animals↗
PubMed2006

Role of P glycoprotein in absorption of novel antimalarial drugs.

Bidirectional transport of four novel antimalarial compounds was determined using Caco-2 cell monolayers. P glycoprotein-mediated efflux was greatest for pyronaridine (5 to 20 microM) and low for naphthoquine (5 microM). With 20 microM naphthoquine, net efflux was blocked, suggesting saturation of the transporter. Piperaquine and dihydroartemisinin were not transported by the system.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Glycaemic levels triggering intensification of therapy in type 2 diabetes in the community: the Fremantle Diabetes Study.

OBJECTIVE: To assess the effectiveness of the management of type 2 diabetes in an urban Australian setting. DESIGN AND SETTING: The Fremantle Diabetes Study (FDS), a community-based longitudinal observational study. PATIENTS: 531 FDS participants with type 2 diabetes, with mean age, 62.4 years (95% CI, 40.9-79.3 years), 54% male, median diabetes duration 3.0 years (interquartile range [IQR], 0.7-7.0 years), with valid data from the baseline FDS assessment and five subsequent annual reviews between 1993 and 2001. MAIN OUTCOME MEASURES: Glycated haemoglobin (HbA(1c)) levels at annual review visits before and after change in blood glucose-lowering therapy. RESULTS: Over 2893 patient-years of follow-up, 97 patients (18%) progressed from dietary management to therapy with oral hypoglycaemic agents (OHA), and 45 (9%) progressed from OHA to insulin therapy, after a median duration of diabetes of 4.0 years (IQR, 2.9-5.5 years) and 8.1 years (IQR, 5.5-13.0 years), respectively. Median HbA(1c) concentrations (IQR) at the review before OHA or insulin were started were 7.7% (6.9%-8.8%) and 9.4% (8.0%-10.7%), respectively. At the next annual review, HbA(1c) levels in the two groups had fallen to 7.4% (6.5%-8.1%) and 7.9% (7.2%-9.5%), respectively (P < or = 0.001). Intensification of therapy was associated with beneficial changes in serum lipid profiles, but not with an increase in frequency of hypoglycaemia. CONCLUSIONS: Most Australian patients with type 2 diabetes may be spending most of the duration of their disease with suboptimal glycaemic control (HbA(1c) > 7.0%), despite the availability of a range of effective therapies, including insulin.

Adult↗
PubMed2006

In vitro interactions between piperaquine, dihydroartemisinin, and other conventional and novel antimalarial drugs.

In an in vitro assessment of antimalarial combinations, dihydroartemisinin (DHA) showed no interaction or was mildly antagonistic when combined with piperaquine, pyronaridine, or naphthoquine. Interactions between 4-aminoquinolines and related drugs were also indifferent/antagonistic. The clinical significance of mildly antagonistic DHA combinations is uncertain but may become important if parasite drug sensitivity declines.

Animals↗
PubMed2006

Artesunate suppositories versus intramuscular artemether for treatment of severe malaria in children in Papua New Guinea.

Drug treatment of severe malaria must be rapidly effective. Suppositories may be valuable for childhood malaria when circumstances prevent oral or parenteral therapy. We compared artesunate suppositories (n = 41; 8 to 16 mg/kg of body weight at 0 and 12 h and then daily) with intramuscular (i.m.) artemether (n = 38; 3.2 mg/kg at 0 h and then 1.6 mg/kg daily) in an open-label, randomized trial with children with severe Plasmodium falciparum malaria in Papua New Guinea (PNG). Parasite density and temperature were measured every 6 h for > or = 72 h. Primary endpoints included times to 50% and 90% parasite clearance (PCT50 and PCT90) and the time to per os status. In a subset of 29 patients, plasma levels of artemether, artesunate, and their common active metabolite dihydroartemisinin were measured during the first 12 h. One suppository-treated patient with multiple complications died within 2 h of admission, but the remaining 78 recovered uneventfully. Compared to the artemether-treated children, those receiving artesunate suppositories had a significantly earlier mean PCT50 (9.1 versus 13.8 h; P = 0.008) and PCT90 (15.6 versus 20.4 h; P = 0.011). Mean time to per os status was similar for each group. Plasma concentrations of primary drug plus active metabolite were significantly higher in the artesunate suppository group at 2 h postdose. The earlier initial fall in parasitemia with artesunate is clinically advantageous and mirrors higher initial plasma concentrations of active drug/metabolite. In severely ill children with malaria in PNG, artesunate suppositories were at least as effective as i.m. artemether and may, therefore, be useful in settings where parenteral therapy cannot be given.

Antimalarials↗
PubMed2006

Is self-monitoring of blood glucose appropriate for all type 2 diabetic patients? The Fremantle Diabetes Study.

OBJECTIVE: We sought to determine whether self-monitoring of blood glucose (SMBG) is associated with better glycemic control in type 2 diabetes. RESEARCH DESIGN AND METHODS: We used cross-sectional and longitudinal data from type 2 diabetic participants in the observational, community-based Fremantle Diabetes Study (FDS) who reported SMBG status at study entry (n = 1,286) and annual reviews over 5 years (n = 531). RESULTS: At study entry, 70% of patients performed SMBG, with a median of four tests per week (interquartile range two to seven). Patients with shorter diabetes duration; who were attending diabetes education, diabetes-related clinics, or medical specialists; who were taking insulin with or without oral hypoglycemic agents (OHAs); and who were self-reporting hypoglycemic events were more likely to use SMBG. Both cross-sectional and longitudinal FDS data showed that HbA(1c) (A1C) was not significantly different between SMBG users and nonusers, either overall or within diabetes treatment groups (diet, OHAs, and insulin with or without OHAs). There was also no independent cross-sectional relationship between A1C and SMBG frequency. The average annual societal cost of using SMBG (in year 2000 Australian dollars [Adollars], excluding glucometers) was 162 Australian dollars per type 2 diabetic patient or 51 million Australian dollars when projected to the Australian diagnosed type 2 diabetic population. CONCLUSIONS: Neither SMBG testing nor its frequency was associated with glycemic benefit in type 2 diabetic patients regardless of treatment. Our data did not include methods of SMBG delivery and application, factors that require further assessment in the evaluation of SMBG utility in non-insulin-treated type 2 diabetes. SMBG may be still of value in the identification and prevention of hypoglycemia and in dose adjustment in insulin-treated patients.

Aged↗
PubMed2006

Peripheral arterial disease and risk of cardiac death in type 2 diabetes: the Fremantle Diabetes Study.

OBJECTIVE: The purpose of this study was to examine the natural history of peripheral arterial disease (PAD) complicating type 2 diabetes, in particular the influence of PAD on the risk of cardiac death and the adequacy of PAD risk factor management. RESEARCH DESIGN AND METHODS: The Fremantle Diabetes Study (FDS) was a prospective community-based observational study of diabetic patients recruited between 1993 and 1996. The present sample comprised the 1,294 FDS type 2 diabetic patients and a subgroup of 531 of these who had valid data at baseline and five or more subsequent consecutive annual reviews. Assessments consisted of a range of clinical and biochemical variables including the ankle/brachial index (ABI). PAD was defined as an ABI < or =0.90 at two consecutive reviews or any PAD-related lower-extremity amputation. RESULTS: The prevalence of PAD at study entry was 13.6% and the incidence of new PAD was 3.7 per 100 patient-years. Both prevalent and incident PAD was strongly and independently associated with increasing age, systolic blood pressure, total serum cholesterol, and especially smoking. Risk factor management improved but remained suboptimal during follow-up. An ABI of < or =0.90 was independently associated with an increased risk of cardiac death of 67%. CONCLUSIONS: Measurement of the ABI is a simple means of identifying PAD in diabetic patients. PAD is common in diabetic patients and predicts cardiac death. These data further support the role of regular screening for PAD in diabetes so that intensive management of vascular risk factors can be pursued.

Aged↗
PubMed2005

Nurse-based evaluation of point-of-care assays for glycated haemoglobin.

BACKGROUND: Various devices are now available to measure glycated haemoglobin (HbA1c) outside of the laboratory. The aim of this study was to assess the performance of these point-of-care instruments in the hands of non-laboratory trained personnel. METHODS: Two nursing staff tested samples from patients attending a diabetes research clinic using the following point-of-care devices for HbA1c-Metrica A1C Now, Bayer DCA 2000, Cholestech GDX and Axis-Shield Nycocard HbA1c. In addition they performed regular analysis of quality control samples. The effects on analytical performance of multiple operators as well as laboratory-trained staff, were also assessed. All measurements were compared to a boronate-affinity HPLC method in the central laboratory. RESULTS: The mean HbA1c difference of the point-of-care devices compared to the laboratory reference method ranged from -0.31% to +0.39%. Only the DCA device had a between batch imprecision of less than 5%. The analytical performance obtained by laboratory staff was similar to nursing staff for 3 devices and better for the Nycocard device. CONCLUSIONS: On the basis of the results obtained by nursing staff, only the DCA of the devices tested, can be recommended for measurement of HbA1c outside of the laboratory.

Chromatography, High Pressure Liquid↗
PubMed2005

Notifications of imported malaria in Western Australia, 1990-2001: incidence, associated factors and chemoprophylaxis.

OBJECTIVE: To assess changes in and factors associated with recent malaria notifications in Western Australia (WA). DESIGN: Retrospective analysis of the WA Notifiable Infectious Diseases Database and enhanced surveillance questionnaires completed by attending medical practitioners. PATIENTS: Cases of malaria notified between January 1990 and December 2001. MAIN OUTCOME MEASURES: Annual notifications by demographic variables (including age, sex, occupation and place of residence), region/country of acquisition, chemoprophylaxis used, Plasmodium species and outcome. RESULTS: 482 patients were notified (mean age, 31 years; 80% male); 57% lived in Perth, 31% in country areas and 12% in an immigration detention centre. Comparison between the 6-year periods 1990-1995 and 1996-2001 showed that Plasmodium falciparum cases increased from 29 (14%) to 108 (44%; P < 0.001), while Plasmodium vivax cases decreased from 157 (77%) to 122 (50%; P < 0.001); immigrants in detention, defence force personnel and cases from Africa were increasingly represented (P < 0.05 in each case). Only 31% of patients took regular chemoprophylaxis and, among these, the regimen was appropriate in only a quarter. There was a median period of 3 days between symptom onset and diagnosis. One patient died. CONCLUSIONS: There has been an increase in P. falciparum cases in WA since 1990. This reflects the influx of immigrants in detention, deployment of military personnel to East Timor and increasing numbers of cases from Africa. A significant number of Australian travellers who developed malaria had not taken chemoprophylaxis either regularly or at all, and, of those who had, the regimen was inadequate in most.

Adolescent↗
PubMed2005

Artemisinin-based combination therapies for uncomplicated malaria.

There has been a relentless increase in resistance of malaria parasites to conventional antimalarial drugs, including chloroquine, sulfadoxine-pyrimethamine and mefloquine. In response to this situation, short-course artemisinin-based combination therapies (ACTs) have been developed. The World Health Organization has endorsed ACT as first-line treatment where the potentially life-threatening parasite Plasmodium falciparum is the predominant infecting species. ACTs combine the rapid schizontocidal activity of an artemisinin derivative (artesunate, artemether or dihydroartemisinin) with a longer-half-life partner drug. Although the use of chloroquine and sulfadoxine-pyrimethamine as partners in ACT improves their efficacy, this may only have value as a short-term measure in patients with a degree of immunity to malaria. Alternative currently available partner drugs include mefloquine, lumefantrine and piperaquine. Artesunate-mefloquine is highly effective but is expensive and side effects (mainly neurotoxicity) can be problematic. Artemether-lumefantrine, the only ACT available in Australia, appears less effective than artesunate-mefloquine and needs to be administered with food to ensure adequate bioavailability. Dihydroartemisinin-piperaquine is highly effective, well tolerated and relatively inexpensive. The goal of potent, safe, easy-to-administer and inexpensive ACTs may see trioxolanes in place of artemisinin derivatives, as well as novel partner drugs such as pyronaridine or naphthoquine, in the future.

Antimalarials↗
PubMed2005

The current status and potential role of laboratory testing to prevent transfusion-transmitted malaria.

Malaria remains a rare but serious complication of transfusion because of the asymptomatic persistence of parasites in some donors. In nonendemic countries, the predominant strategy of deferral or cellular component discard from "risk" donors is effective in minimizing the incidence but is wasteful. In endemic countries where recipients are commonly immune, transfusion strategies focus on chemoprophylaxis for the donor and recipient or ensure that blood collected in highly endemic regions is not transfused to patients from areas of low endemicity. Donors implicated in transfusion-transmitted malaria are predominantly "semi-immune" with very low parasite loads. Their detection by even the most sensitive antigen or polymerase chain reaction (PCR) assays cannot be guaranteed and, in a number of cases, is unlikely because the infectious dose is estimated to be 1 to 10 parasites in a unit of blood. Retrospective analysis of implicated donors has confirmed the presence of high titer antibodies in such individuals. In regions of low immunity, serological assays offer an efficient method to identify such infectious donors. The recent development of enzyme immunoassays (EIAs) with improved sensitivity to Plasmodium falciparum and Plasmodium vivax , the predominant transfusion threats, has heightened the appeal of serological testing. Although universal serological screening in nonendemic regions is not cost-effective, targeted screening of donors identified at risk by travel-based questioning can significantly reduce wastage through reinstatement. Importantly, transfusion safety does not appear to be compromised by this approach as evidenced by the lack of a documented transmission in France between 1983 and September 2002, where such a strategy has been used since 1976. The development of automated protein microarray-based technology has the potential to further enhance antibody/antigen sensitivity; however, its application to donor screening is likely to be some years off. There is also the potential that pathogen inactivation techniques currently under development to address the bacterial contamination of blood components may also be effective against malaria parasites to make malarial testing redundant or at least reduce its cost/benefit ratio. Nonetheless, there are still significant problems to be solved in respect of validating and licensing these systems. Assuming that they are successfully marketed, their high cost may also impact their cost-effectiveness in comparison with targeted malaria testing strategies already in place in some jurisdictions.

Animals↗
PubMed2005

Effects of a high-fat meal on the relative oral bioavailability of piperaquine.

Piperaquine (PQ) is an antimalarial drug whose high lipid solubility suggests that its absorption can be increased by a high-fat meal. We examined the pharmacokinetics of PQ phosphate (500 mg given orally) in the fasting state and after a high-fat meal in eight healthy Caucasian volunteers (randomized crossover). Plasma PQ concentration-time profiles were analyzed by using noncompartmental pharmacokinetic analysis. In the fed state, the geometric mean Cmax increased by 213%, from 21.0 to 65.8 microg/liter (P<0.001). The time of Cmax was not significantly different between the fasting and fed states. The geometric mean area under the concentration-time curve from zero onward (AUC0-infinity) increased by 98%, from 3,724 to 7,362 microg h/liter (P=0.006). The oral bioavailability of PQ relative to the fasting state was 121% greater after the high-fat meal (95% confidence interval, 26 to 216% increase; P=0.020). The side effects, postural blood pressure changes, electrocardiographic corrected QT interval, serum glucose, and other biochemical and hematological indices were similar in the fasting and fed states over 28 days of follow-up.

Administration, Oral↗
PubMed2005

Piperaquine: a resurgent antimalarial drug.

Piperaquine is a bisquinoline antimalarial drug that was first synthesised in the 1960s, and used extensively in China and Indochina as prophylaxis and treatment during the next 20 years. A number of Chinese research groups documented that it was at least as effective as, and better tolerated than, chloroquine against falciparum and vivax malaria, but no pharmacokinetic characterisation was undertaken. With the development of piperaquine-resistant strains of Plasmodium falciparum and the emergence of the artemisinin derivatives, its use declined during the 1980s. However, during the next decade, piperaquine was rediscovered by Chinese scientists as one of a number of compounds suitable for combination with an artemisinin derivative. The rationale for such artemisinin combination therapies (ACTs) was to provide an inexpensive, short-course treatment regimen with a high cure rate and good tolerability that would reduce transmission and protect against the development of parasite resistance. This approach has now been endorsed by the WHO. Piperaquine-based ACT began as China-Vietnam 4 (CV4): dihydroartemisinin [DHA], trimethoprim, piperaquine phosphate and primaquine phosphate), which was followed by CV8 (the same components as CV4 but in increased quantities), Artecom (in which primaquine was omitted) and Artekin or Duo-Cotecxin (DHA and piperaquine phosphate only). Recent Indochinese studies have confirmed the excellent clinical efficacy of piperaquine-DHA combinations (28-day cure rates >95%), and have demonstrated that currently recommended regimens are not associated with significant cardiotoxicity or other adverse effects. The pharmacokinetic properties of piperaquine have also been characterised recently, revealing that it is a highly lipid-soluble drug with a large volume of distribution at steady state/bioavailability, long elimination half-life and a clearance that is markedly higher in children than in adults. The tolerability, efficacy, pharmacokinetic profile and low cost of piperaquine make it a promising partner drug for use as part of an ACT.

Animals↗