Biomedical subjects

R Holman

Publications and source records attributed to R Holman.

At least 19 recordsLinked to original sources

PubMed2006

A Diabetes Outcome Progression Trial (ADOPT): baseline characteristics of Type 2 diabetic patients in North America and Europe.

AIMS: To examine baseline characteristics of patients recruited into ADOPT, a multinational trial comparing three oral glucose-lowering monotherapies. METHODS: Between April 2000 and June 2002, 4360 patients aged 30-75 years with Type 2 diabetes diagnosed for < 3 years and remaining on diet therapy alone with fasting plasma glucose levels (FPG) between 7.0 and 10.0 mmol/l were enrolled by 488 North American and European centres. Medical histories, anthropometric data and laboratory measurements were determined using common methodologies. RESULTS: The mean (SD) age of the patients was 57 (10) years, body mass index 32.2 (6.4) kg/m(2), HbA(1c) 7.4 (0.9)%; 58% were male, 88% Caucasian and 15% smoked. North American Caucasians (NAC) were younger, more obese, and more insulin resistant than European Caucasians (EUC), but had better pancreatic B-cell function. NAC had lower total, low-density lipoprotein- and high-density liporpotein-cholesterol concentrations with higher triglyceride concentrations and were more often on lipid-lowering treatment. They had lower blood pressure levels but were equally likely to be on antihypertensive treatment. Metabolic syndrome was more frequent and microalbuminuria less frequent in NAC. Within North America, NAC had lower HbA(1c) concentrations than Blacks, Hispanics and Asians despite similar or higher FPG and 30-min postchallenge glucose concentrations. CONCLUSIONS: Caucasian North American and European ADOPT patients differ with respect to adiposity, insulin resistance and metabolic syndrome prevalence. North American Blacks, Hispanics and Asians had lower HbA(1c) concentrations than NAC despite similar or higher glucose concentrations. These phenotypic differences may influence the progression of Type 2 diabetes and the response to initial oral glucose-lowering monotherapy.

Adult↗

PubMed2006

Comparison of the efficacies of disinfectants to control microbial contamination in dental unit water systems in general dental practices across the European Union.

Water delivered by dental unit water systems (DUWS) in general dental practices can harbor high numbers of bacteria, including opportunistic pathogens. Biofilms on tubing within DUWS provide a reservoir for microorganisms and should be controlled. This study compared disinfection products for their ability to meet the American Dental Association's guideline of <200 CFU x ml(-1) for DUWS water. Alpron, BioBlue, Dentosept, Oxygenal, Sanosil, Sterilex Ultra, and Ster4Spray were tested in DUWS (n = 134) in Denmark, Germany, Greece, Ireland, The Netherlands, Spain, and the United Kingdom. Weekly water samples were tested for total viable counts (TVCs) on yeast extract agar, and, where possible, the effects of products on established biofilm (TVCs) were measured. A 4- to 5-week baseline measurement period was followed by 6 to 8 weeks of disinfection (intermittent or continuous product application). DUWS water TVCs before disinfection ranged from 0 to 5.41 log CFU x ml(-1). Disinfectants achieved reductions in the median water TVC ranging from 0.69 (Ster4Spray) to 3.11 (Dentosept) log CFU x ml(-1), although occasional high values (up to 4.88 log CFU x ml(-1)) occurred with all products. Before treatment, 64% of all baseline samples exceeded American Dental Association guidelines, compared to only 17% following commencement of treatment; where tested, biofilm TVCs were reduced to below detectable levels. The antimicrobial efficacies of products varied (e.g., 91% of water samples from DUWS treated with Dentosept or Oxygenal met American Dental Association guidelines, compared to 60% of those treated with Ster4Spray). Overall, the continuously applied products performed better than those applied intermittently. The most effective products were Dentosept and Oxygenal, although Dentosept gave the most consistent and sustained antimicrobial effect over time.

Biofilms↗

PubMed2005

Reproducibility of meal-induced transient lower oesophageal sphincter relaxations in patients with gastro-oesophageal reflux disease.

AIM: To calculate the number of subjects required in trials investigating drugs reducing the number of transient lower oesophageal sphincter relaxations (TLOSRs), the inter- and intra-individual variability of TLOSRs were determined, using meal ingestion as a trigger of TLOSRs and reflux. METHODS: A total of 23 gastro-oesophageal reflux disease (GORD) patients with no to grade B oesophagitis and a hiatal hernia < or =3 cm underwent oesophageal manometry and pHmetry 1 h before and 3 h after ingestion of a solid meal on two separate days approximately 4 weeks apart. Reflux episodes and the underlying mechanisms and the number of TLOSRs were evaluated. RESULTS: The number of TLOSRs, reflux episodes and % time with pH < 4 after meal ingestion did not differ significantly between the two sessions. The intra-individual variation of TLOSRs in the 3 h postprandial period (24.4) was smaller compared with the inter-individual variation (47.5). Transient lower oesophageal sphincter relaxations were the predominant cause of reflux accounting for 61 +/- 7 and 70 +/- 5% of the reflux episodes in visits 1 and 2, respectively. CONCLUSIONS: These data for the first time provide information on the variability of TLOSRs and reflux evoked by meal ingestion, which is of crucial importance for the design and power calculations of future clinical studies evaluating the efficacy of new drugs targeting TLOSRs.

Adolescent↗

PubMed2005

Assessment of visceral sensitivity using radio telemetry in a rat model of maternal separation.

Stress plays an important role in the development of visceral hypersensitivity, a key mechanism underlying the pathophysiology of the irritable bowel syndrome. Visceral sensitivity in rats is generally assessed under restrain conditions. To avoid this potential stress factor, we developed a model using implanted radio telemetry for remote measurement of the visceromotor response (VMR) to colorectal distention (CRD). Ten days after implantation of a radio telemetry transmitter and EMG electrodes, visceral sensitivity was evaluated by applying a standardized distension protocol (1, 1.5 and 2 mL) on three different days. In a second series, visceral sensitivity was assessed in maternally separated rats before, directly after and at 6 and 24 h after water avoidance (WA) stress. CRD resulted in a reproducible VMR response on the three different study days. In separated but not in non-handled rats, WA significantly increased visceral sensitivity at 6 h (P=0.006) and 24 h (P=0.004) after WA. Our results show that radio telemetry is a reliable and well tolerated new tool for evaluating visceral sensitivity in rats. These data further confirm that maternal separation is a good model for evaluating the mechanisms underlying visceral hypersensitivity.

Abdominal Muscles↗

PubMed2004

Rationale, design and recruitment characteristics of a large, simple international trial of diabetes prevention: the DREAM trial.

AIMS/HYPOTHESIS: Diabetes is a rapidly rising independent risk factor for atherosclerosis and serious illness. This risk can be reduced by lifestyle changes and/or various drugs. Novel therapies to prevent diabetes, as well as new risk factors for diabetes, atherosclerosis and obesity require testing and identification. METHODS: People with impaired fasting glucose or impaired glucose tolerance were randomised to ramipril (15 mg/day) or placebo and rosiglitazone (8 mg/day) or placebo with a 2x2 factorial design. They are assessed semi-annually for the primary outcome (diabetes or death). Diabetes is diagnosed if two consecutive plasma glucose levels exceed diagnostic thresholds (i.e. fasting >/=7.0 mmol/l or 2-h >/=11.1 mmol/l) within a 3-month period. Assuming an annual primary outcome incidence of 5%, there is more than 90% power to detect a 22% reduction. Approximately 20% of participants are having annual carotid ultrasounds to assess the effects on atherosclerosis. Patients screened but not randomised are being followed prospectively to identify determinants of obesity, diabetes and related disorders. RESULTS: A total of 24,872 individuals in 21 countries were screened over 2 years and are eligible for follow-up. Of these, 5269 were randomised: 1835 (35%) had isolated impaired glucose tolerance, 739 (14%) had isolated impaired fasting glucose, and 2692 (51%) had both disorders. Annual carotid ultrasounds are currently being performed in 1406 randomised individuals. CONCLUSIONS/INTERPRETATION: The DREAM trial and related studies will determine if ramipril or rosiglitazone reduces the number of cases of diabetes and atherosclerosis, and will identify novel risk factors for diabetes.

Adult↗

PubMed2004

Improved brief assessment of cognition in aging and dementia.

To enhance the score interpretation and practicality of the Cambridge Cognitive Examination (CAMCOG) neuropsychological test, the authors used item response theory (IRT) to calibrate the difficulty of the items using the scores of 797 subjects. Forty-seven items fitted the IRT model. Score agreement with equally difficult short forms was excellent. The practicality and interpretability of the CAMCOG was improved, while the diagnostic accuracy of the short forms was similar to that of the original 60-item instrument.

Aged↗

PubMed2004

[Qualitative malnutrition due to incorrect complementary feeding in Bush Negro children in Suriname].

OBJECTIVE: To determine whether the increase in the percentage of stunted growth in Bush Negro infants in the interior of Surinam is related to an absolute food (i.e. energy) shortage or to a shortage of protein. DESIGN: Descriptive. METHOD: In the villages of Dan and Botopasi, children aged 2-5 years from two schools and their mothers were examined. Growth during the first year of life, duration of breastfeeding, age of introduction of and composition of complementary feeding and current nutritional status of mother and child were determined. RESULTS: Sixteen children and their mothers were included. Compared to the Dutch growth charts, birth weight was significantly lower (p = 0.03). After the age of 6 months there was a significant dropping off in weight gain (p = 0.018). Five of the 16 children received protein-poor complementary feeding, which did not lead to catch-up growth. Between the ages of 2-5, 6 of the 16 children showed stunted growth but none of the children or their mothers was wasted. Five of the 16 mothers had a body mass index > 25. CONCLUSION: The nutritional status of the mothers showed that there was no absolute shortage of energy. The protein content coming from the complementary food for the Bush Negroes in our research group was below recommended levels. Stunted growth in these children is better explained by a shortage of well-balanced complementary feeding rather than by an absolute shortage of energy. Education about food recommendations for the young child is of great importance in the prevention of chronic malnutrition.

Body Height↗

PubMed2004

Scaling the sickness impact profile using item response theory: an exploration of linearity, adaptive use, and patient driven item weights.

BACKGROUND AND OBJECTIVE: The objective of the study was to enhance the clinical interpretation and practicality of the widely used comprehensive Sickness Impact Profile. METHOD: Item Response Theory (extension of the Rasch model) was used to calibrate the severity of the SIP items, to assess item bias and to construct equally severe short forms of the SIP that can be used interchangeably. The scores of 1507 subjects were analyzed. RESULTS: Of the 127 SIP items, 82 items fitted the extended Rasch model, i.e., the observed proportions of sickness level groups endorsing the items corresponded to the proportions expected by the model. The item severity hierarchy allowed a more straightforward interpretation of the calibrated SIP-82 scores. Some items showed bias in age, gender, or diagnosis groups. The equivalent short forms agreed sufficiently well with the calibrated SIP-82 item pool to be used interchangeably. We observed a moderate correlation between the original SIP item severity weights and the Rasch item severity calibrations (r=0.53). CONCLUSION: The interpretability and practicality of the SIP was enhanced by the IRT calibration. Using the item calibrations, short forms can be assembled that can be used interchangeably.

Calibration↗

PubMed2004

Artesunate with mefloquine at various intervals for non-severe Plasmodium falciparum malaria.

To study the efficacy, tolerance, population pharmacokinetics and pharmacodynamics of artesunate followed by mefloquine at various intervals, 360 patients with Plasmodium falciparum malaria received 4 mg/kg of artesunate and thereafter 15 mg/kg of mefloquine simultaneously (group A), after 8 hours (after group B), and after 24 hours (group C). Three dosages were completed with placebo. Follow-up was 28 days. All patients recovered rapidly except one case of failure within the first 24 hours. Mefloquine pharmacokinetics was similar in the three regimens. Parasites reappeared in 26%, 26%, and 33% of the patients in groups A, B, and C, respectively. Early recrudescence was associated with high initial parasite density, slow parasite clearance, and rapid mefloquine clearance and low plasma concentrations at day 28. Mefloquine plasma concentrations all reached therapeutic ranges, suggesting reduced parasite sensitivity. In conclusion, there is no interaction between artesunate and mefloquine with respect to tolerance, efficacy, and pharmacokinetics. Single-dose combination therapy with artemisinin drugs and 15 mg/kg of mefloquine does not completely prevent parasite recurrence and may not prevent mefloquine resistance.

Adolescent↗

PubMed2003

Radion-induced brane preheating.

When the interbrane separation in the compact Randall-Sundrum model is stabilized using the Goldberger-Wise mechanism, a potential is generated for the four-dimensional field, the radion, that encodes this separation. Coherent oscillations of the radion in the early universe will produce an exponential growth in the number of brane particles due to parametric amplification. We describe the conditions necessary for this process, which resembles the preheating phase in inflation, and show the exponential growth in the case of a scalar field confined to a brane.

Journal Article↗

PubMed2003

Activities of daily living instruments:optimizing scales for neurologic assessments.

The ability to perform activities of daily living (ADL) is an important part of assessment in neurologic patients. A literature search was carried out to identify multi-item ADL scales developed for the assessment of neurologic patients, comparing item content, range, and detail of ADL scales. Of the 113 ADL scales identified, 27 (24%) were designed for use in neurology. In the basic ADL (BADL) domains (basic mobility and self-care), individual items were present in 44% to 81% of instruments. In the extended ADL (EADL) domains (e.g., outdoor mobility, housekeeping), items were present in up to 67% of the instruments identified. A typical trade-off was observed between the range, the detail (number of items), and hence the practicality of a scale. In general, scales focus on either BADL or EADL domains or, on occasion, some of both, rather than measuring the full range of functioning. There are many ADL scales in neurology, with much overlap in item content, leading to redundancy. New scales developed with the traditional methods will not solve the existing difficulties associated with range and detail, ordinal scale scores, and cross-instrument comparability. The possibilities of a modern psychometric method known as item response theory that was designed to solve these problems are discussed.

Activities of Daily Living↗

PubMed2003

The impact of diabetes-related complications on healthcare costs: results from the United Kingdom Prospective Diabetes Study (UKPDS Study No. 65).

AIMS: To develop a model for estimating the immediate and long-term healthcare costs associated with seven diabetes-related complications in patients with Type 2 diabetes participating in the UK Prospective Diabetes Study (UKPDS). METHODS: The costs associated with some major complications were estimated using data on 5102 UKPDS patients (mean age 52.4 years at diagnosis). In-patient and out-patient costs were estimated using multiple regression analysis based on costs calculated from the length of admission multiplied by the average specialty cost and a survey of 3488 UKPDS patients' healthcare usage conducted in 1996-1997. RESULTS: Using the model, the estimate of the cost of first complications were as follows: amputation pound 8459 (95% confidence interval pound 5295, pound 13 200); non-fatal myocardial infarction pound 4070 ( pound 3580, pound 4722); fatal myocardial infarction pound 1152 ( pound 941, pound 1396); fatal stroke pound 3383 ( pound 1935, pound 5431); non-fatal stroke pound 2367 ( pound 1599, pound 3274); ischaemic heart disease pound 1959 ( pound 1467, pound 2541); heart failure pound 2221 ( pound 1690, pound 2896); cataract extraction pound 1553 ( pound 1320, pound 1855); and blindness in one eye pound 872 ( pound 526, pound 1299). The annual average in-patient cost of events in subsequent years ranged from pound 631 ( pound 403, pound 896) for heart failure to pound 105 ( pound 80, pound 142) for cataract extraction. Non-in-patient costs for macrovascular complications were pound 315 ( pound 247, pound 394) and for microvascular complications were pound 273 ( pound 215, pound 343) in the year of the event. In each subsequent year the costs were, respectively, pound 258 ( pound 228, pound 297) and pound 204 ( pound 181, pound 255). CONCLUSIONS: These results provide estimates of the immediate and long-term healthcare costs associated with seven diabetes-related complications.

Ambulatory Care↗

PubMed2002

[Measuring the functional status of patients in clinical trials using modern clinimetric methods].

In clinical medicine numerous measurement instruments have been developed to assess the functional outcome of patients in clinical trials. The majority are questionnaires with multiple-choice items. The responses of the patients are used to calculate a sum score. However, there are some disadvantages associated with the use of sum scores. Modern clinimetric methods, based on item response theory (IRT) in combination with a calibrated item bank, can overcome these problems. When using this measurement technique, it is possible to arrange both the item difficulty and the patient's ability on a single, hierarchical linear scale. This allows the user to obtain a sufficiently detailed clinical picture using a small number of items. In addition to being efficient, this method makes it possible to present different sets of items to different groups of patients. Since all of the items are calibrated, the measurements remain comparable. The application of this innovative method of measuring is being studied in the ongoing 'Amsterdam linear disability score' (ALDS) project.

Clinical Trials as Topic↗

PubMed2002

Sequence of two new HLA-Cw alleles: HLA-Cw0313 and HLA-Cw1208.

Two new HLA-C alleles have been identified by reverse line blot assay and direct sequencing of polymerase chain reaction (PCR) products. The first polymorphism encodes an amino acid change from lysine in Cw*12022 to asparagine in Cw*1208 at residue 66. The second polymorphism encodes two amino acid changes from isoleucine in Cw*03031 to threonine in Cw*0313 at residue 93 and isoleucine to leucine at residue 94. The functional significance of these polymorphisms on peptide-binding and/or T-cell recognition is unknown.

Alleles↗

PubMed2002

Identification of HLA-B*1566.

A novel polymorphism was identified in a B*15 allele. B*1566 possesses a nucleotide substitution of C to G at nucleotide 272. This polymorphism encodes an amino acid difference from serine in B*1501101 to cysteine in B*1566 at residue 67. Residue 67 is a constituent of the B pocket and is situated on the alpha1 helix facing into the groove. This mutation may have arisen through interallelic recombination as it has been seen in other B*15 alleles and is also present in most B*14, B*27, B*38, B*39 alleles and in B*7301.

Amino Acid Substitution↗

PubMed2002

Effect of the low-affinity, noncompetitive N-methyl-d-aspartate receptor antagonist dextromethorphan on visceral perception in healthy volunteers.

BACKGROUND: The use of N-methyl-d-aspartate (NMDA) receptor antagonists may hold promise for the treatment of pain of visceral origin, in particular in conditions characterized by visceral hypersensitivity. AIM: To study the effect of dextromethorphan, a low affinity, non-competitive NMDA receptor antagonist, on visceral perception in healthy volunteers. METHODS: Nine healthy volunteers (5 female, median age 22 years) underwent a gastric barostat study after oral administration of placebo, dextromethorphan 10 mg or dextromethorphan 30 mg, on three separate days in a double-blind, randomised order. Sensations induced by step-wise isobaric gastric distension (2 mmHg/2 min) were studied during fasting and 30 min after a meal. In addition, proximal gastric tone was measured during fasting and postprandially. RESULTS: Compared to placebo, dextromethorphan 30 mg significantly increased the distension-evoked sensation scores for nausea (P=0.004) and satiation (P=0.004) during fasting; and for bloating (P= 0.001), nausea (P=0.000) and satiation (P=0.01) 30 min postprandially. Dextromethorphan did not alter pain scores, proximal gastric tone or gastric compliance. CONCLUSIONS: Dextromethorphan increases the perception of non-painful sensations during gastric distension, without altering the perception of pain. Therefore, application of dextromethorphan as a visceral analgesic is questionable. Future studies with more specific NMDA receptor antagonist are warranted.

Adult↗

PubMed2001

Cost-effectiveness analysis of intensive blood-glucose control with metformin in overweight patients with type II diabetes (UKPDS No. 51).

AIMS/HYPOTHESIS: To estimate the economic efficiency of intensive blood-glucose control with metformin compared with conventional therapy primarily with diet in overweight patients with Type II (non-insulin-dependent) diabetes mellitus. METHODS: Cost-effectiveness analysis based on patient level data from a randomised clinical controlled trial involving 753 overweight (> 120% ideal body weight) patients with newly diagnosed Type II diabetes conducted in 15 hospital-based clinics in England, Scotland and Northern Ireland as part of the UK Prospective Diabetes Study. Subjects were allocated at random to an intensive blood-glucose control policy with metformin (n = 342) or a conventional policy primarily with diet (n = 411). The analysis was based on the cost of health care resources associated with metformin and conventional therapy and the estimated effectiveness in terms of life expectancy gained from within-trial effects. RESULTS: Intensive blood-glucose control with metformin produced a net saving of 258 Pounds per patient (1997 United Kingdom prices) over the trial period (median duration of 10.7 years) due to lower complication costs, and increased life expectancy by 0.4 years (costs and benefits discounted at 6%). CONCLUSIONS/INTERPRETATION: As metformin is both cost-saving in the United Kingdom and extends life expectancy when used as first line pharmacological therapy in overweight Type II diabetic patients, its use should be attractive to clinicians and health care managers alike.

Adult↗

PubMed2001

The UKPDS: implications for the dyslipidaemic patient.

The UK Prospective Diabetes Study (UKPDS) is the largest intervention trial to date of patients with type 2 diabetes, involving 5102 newly diagnosed diabetic patients. Results showed that 59% of patient deaths were from cardiovascular disease. While intensive treatment of glucose produced a significant 25% reduction in microvascular endpoints compared with diet only (p=0.0099), patients with type 2 diabetes usually have a lipid profile that is highly atherogenic. In the UKPDS, intensive treatment of hyperglycaemia and hypertension did not improve lipid levels. In patients without diabetes, lipid-lowering therapy has been shown to reduce the risk of cardiovascular events in both primary and secondary prevention trials. Currently, a number of large-scale trials of lipid-lowering therapy in patients with diabetes are ongoing. For example, the Lipids in Diabetes Study will determine whether lipid lowering with a statin or fibrate can substantially reduce cardiovascular morbidity and mortality in 5000 patients with type 2 diabetes. The Atorvastatin Study for the Prevention of coronary heart disease ENdpoints (ASPEN) is comparing double-blind treatment with atorvastatin and placebo in 2250 US diabetic patients without coronary heart disease, while a sister trial in the UK, the Collaborative AtoRvastatin Diabetes Study (CARDS), is enrolling 1820 diabetic patients. The results from these trials may provide information that which will help determine the future management of diabetic dyslipidaemia.

Clinical Trials as Topic↗