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Biomedical subjects

L Carr

Publications and source records attributed to L Carr.

At least 19 recordsLinked to original sources

The cost-effectiveness of continuous subcutaneous insulin infusion compared with multiple daily injections for the management of diabetes.

AIMS: To estimate the cost effectiveness of continuous subcutaneous insulin infusion (CSII) compared with multiple daily injections (MDI) for patients using insulin pumps. METHODS: We constructed a Markov model to estimate the costs and outcomes for patients with insulin-dependent diabetes (IDDM) treated with CSII using an insulin pump compared with MDI. Key parameters were obtained from the published scientific literature. The primary outcome was quality-adjusted life years (QALYs). Monte Carlo simulations were undertaken for 10 000 hypothetical patients over 8 years of monthly cycles (the expected life of a pump). RESULTS: Over an 8-year period an average patient could expect to gain 0.48 [standard deviation (sd) 0.20] QALYs using CSII compared with MDI. The additional cost over 8 years for this gain was pounds 5462 (sd pounds 897). The incremental cost per QALY was pounds 11,461 (sd pounds 3656). CSII was most cost-effective in patients who had more than two severe hypoglycaemic events per year and who required admission to hospital at least once every year. Cases where CSII might be not economically viable are cases where diabetes is well controlled with few severe hypoglycaemic events. Results were most sensitive to the number of hypoglycaemic events per patient and the utility weights used to estimate QALYs. CONCLUSION: CSII is a worthwhile investment when targeted to those who might benefit most.

Cost-Benefit Analysis↗

Botulinum toxin treatment of spasticity in diplegic cerebral palsy: a randomized, double-blind, placebo-controlled, dose-ranging study.

This study evaluated the efficacy and safety of three doses of botulinum toxin A (BTX-A; Dysport) in 125 patients (mean age 5.2 years, SD 2; 54% male)with dynamic equinus spasticity during walking. Participants were randomized to receive Dysport (10, 20, or 30 units/kg) or placebo to the gastrocnemius muscle of both legs. Muscle length was calculated from electrogoniometric measurements and the change in the dynamic component of gastrocnemius shortening at four weeks was prospectively identified as the primary outcome measure. All treatment groups showed statistically significant decreases in dynamic component compared with placebo at 4 weeks. Mean improvement in dynamic component was most pronounced in the 20 units/kg group, being equivalent to an increase in dorsiflexion with the knee extended at 19 degrees, and was still present at 16 weeks. The safety profile of the toxin appears satisfactory.

Botulinum Toxins, Type A↗

Mapping of QTL influencing saccharin consumption in the selectively bred alcohol-preferring and -nonpreferring rat lines.

The inbred preferring (iP) and nonpreferring (iNP) rat strains were derived from the selectively bred alcohol-preferring (P) and alcohol-nonpreferring (NP) lines. Previously, 381 iP x iNP F2 progeny were generated to identify quantitative trait loci (QTLs) influencing alcohol consumption and preference. Saccharin consumption (ml/48 h) and saccharin intake (ml/kg/day) were also measured in the F2 sample and were significantly correlated with both alcohol consumption and preference (all r > or = .20, p < .0001), suggesting that there might be some QTLs influencing both saccharin and alcohol phenotypes. We have performed a genome screen using F2 animals with extreme saccharin or alcohol consumption to identify QTLs contributing to saccharin-related phenotypes. Lod scores greater than 2.0 were found on chromosomes 3, 16 and 18 in this sample. Additional genotyping was performed in these regions in the full sample of 381 F2 progeny to further characterize these putative QTLs. On chromosome 3, the maximum lod score in the full sample was 2.7 with saccharin consumption. This QTL appears to overlap with a QTL identified for alcohol consumption in the iP and iNP lines and has pleiotropic effects on both phenotypes. Interestingly, this region of rat chromosome 3 is syntenic with mouse chromosome 2, where a QTL influencing alcohol preference has been previously reported. The QTL on chromosome 16 has a maximum lod score of 4.0 with saccharin intake and 2.6 with saccharin consumption. The QTL on chromosome 18 has a maximum lod score of 2.7 with saccharin consumption. Taken together, these data provide the first results of a genome screen for QTLs contributing to saccharin phenotypes in the rat.

Alcohol Drinking↗

Use of cool perches by broiler chickens.

Broilers under commercial conditions might experience relatively high temperatures during summer and leg disorders year round that may be partially alleviated by providing them with access to cooled perches. It is unknown, however, how perch temperature and factors such as height and position of the perch affect perch use. Furthermore, little is known regarding gender effects. Eight thousand 1-d-old, mixed-sex broilers were exposed to three perch treatments to determine preferences for water-cooled perches over ambient temperature perches and preferences for height, location, and temperature section of the perch. The experimental treatments were as follows: 1) three cool perches 15 cm above the floor (Cool 15), 2) three ambient perches 7.5 cm off the floor (Ambient 7.5), 3) three ambient perches 15 cm high (Ambient 15), and 4) control chambers with no perches. Total number of birds perching, their positions, and temperature section within the perch were recorded. The results indicate a strong preference for high perches as birds grow (P < 0.0001). The cooler sections of the perch were utilized more than warmer sections within the cool treatments (P < 0.05). Females showed a stronger tendency to perch than males, particularly within the cool treatment (P < 0.0001). The higher perch use could be one of the reasons for the higher eviscerated body weight found in females with access to cool perches (P < 0.05). Differences in mean body weight were not significant (P = 0.07). Potential beneficial effects of perch access in final body weights needs to be further investigated.

Age Factors↗

Event-by-event fluctuations of the Kaon-to-Pion ratio in central Pb+Pb collisions at 158 GeV per nucleon.

We present the first measurement of fluctuations from event to event in the production of strange particles in collisions of heavy nuclei. The ratio of charged kaons to charged pions is determined for individual central Pb+Pb collisions. After accounting for the fluctuations due to detector resolution and finite number statistics we derive an upper limit on genuine nonstatistical fluctuations, which could be related to a first- or second-order QCD phase transition. Such fluctuations are shown to be very small.

Journal Article↗

Elliptic flow in Au+Au collisions at square root(S)NN = 130 GeV.

Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at square root(S)NN = 130 GeV using the STAR Time Projection Chamber at the Relativistic Heavy Ion Collider. The elliptic flow signal, v2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.

Journal Article↗

Foreign body ingestion in children with severe developmental disabilities: a case study.

Dysphagia is common in children with severe developmental disabilities. The nature of these difficulties can predispose them to foreign body ingestion. This article presents a case that highlights the need for vigilance in diagnosing dysphagia in children with multiple and complex developmental disabilities where severe cognitive impairment and an inability to communicate may mask the presence of underlying problems.

Barium Sulfate↗

Functional relevance of human adh polymorphism.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were C. J. Peter Eriksson and Tatsushige Fukunaga. The presentations were (1) 4-Methylpyrazole as a tool in the investigation of the role of ADH in the actions of alcohol in humans, by Taisto Sarkola and C. J. Peter Eriksson; (2) ADH2 polymorphism and flushing in Asian populations, by Wei J. Chen, C. C. Chen, J. M. Ju, and Andrew T. A. Cheng; (3) Role of ADH3 genotypes in the acute effects of alcohol in a Finnish population, by Hidetaka Yamamoto, Kathrin Kohlenberg-Müller, and C. J. Peter Eriksson; (4) Clinical characteristics and disease course of alcoholics with different ADH2 genotypes, by Mitsuru Kimura, Masanobu Murayama, Sachio Matsushita, Haruo Kashima, and Susumu Higuchi; (5) ADH2 polymorphism, alcohol drinking, and birth defects, by Lucinda Carr, D. Viljoen, L. Brooke, T. Stewart, T. Foroud, J. Su, and Ting-Kai Li; and (6) ADH genotypes and alcohol use in Europeans, by John B. Whitfield.

Adult↗

Association of the ADH2*3 allele with a negative family history of alcoholism in African American young adults.

BACKGROUND: Two of the class I alcohol dehydrogenase (ADH) genes (ADH2 and ADH3) encode for multiple isozymes that differ in their kinetic properties. Polymorphisms at both of these gene loci have been linked to alcoholism and/or alcohol-induced disabilities in some populations. At the ADH2 locus, three polymorphisms are present (ADH2*1, ADH2*2, ADH2*3). ADH2*3 allele codes for a high Km and Vmax variant that has been reported to occur exclusively in African Americans and some tribes of Native Americans. In African Americans, the presence of the ADH2*3 allele is associated with protection from alcohol-related birth defects. However, its relationship to risk for alcoholism in African Americans remains relatively unexplored. METHODS: The participants were 97 African American young adults (18-25 years old). A structured interview was used to gather information on demographics, psychiatric diagnoses, personal drinking and drug use history, and familial history of alcohol use disorders. A blood sample was obtained from each participant and leukocyte DNA extracted and genotyped for the presence of ADH2*3 alleles. The specific aim of the study was to investigate the associations between the presence of the ADH2* 3 allele and personal and family history of alcohol use/abuse. RESULTS: Thirty participants (31%) had at least one ADH2*3 allele and two were homozygous for the allele. A significant association between the presence of an ADH2*3 allele and a negative family history of alcoholism was uncovered (p < 0.04). No significant associations of an ADH2*3 allele with personal history of alcohol use disorders or with current drinking were found; however, power to detect associations was limited in this population because half the population did not drink regularly. CONCLUSIONS: Because family history of alcoholism is one of the best predictors of the development of alcohol use disorders, this pilot study suggests that, in this sample of African American young adults, the ADH2*3 allele may be associated with a lowered risk for the development of alcoholism.

Adolescent↗

Evolution of mechanical heart valves.

The need for prosthetic heart valves was long recognized but seemed an impossible dream before 1952 when Dr Charles Hufnagel clinically introduced a ball valve that he placed into the descending thoracic aorta for treatment of aortic valvular insufficiency. Fulfillment of that dream became a reality with the advent of extracorporeal circulation in the early 1950s. Development of prosthetic heart valves involved the search for biologically compatible materials and hemologically tolerant designs. Success could not be achieved without the union of these two factors. As there was no satisfactory mechanism to scientifically achieve this goal, trial and error was the method of choice. The development of prosthetic heart valves became the purview of the cardiovascular surgeon who often collaborated with engineers. To distinguish one valve from another each prosthesis often became identified with the surgeon developer. The development of bioprostheses occurred later in the development of artificial heart valves and constitutes a separate subject not covered in this presentation.

Heart Valve Prosthesis↗

Worster-Drought syndrome, a mild tetraplegic perisylvian cerebral palsy. Review of 47 cases.

A retrospective case-note analysis was undertaken of 47 children with a congenital upper motor neurone bulbar palsy (excluding pure speech dyspraxia) to clarify the phenotype of Worster-Drought syndrome (WDS) and to record its associated features and complications. The results revealed that the study children had significant bulbar problems (with 80% still needing a modified diet and a similar number using augmentative communication methods at last review). There were also high rates of predictable bulbar complications (86% had dribbling, 60% had glue ear, gastro-oesophageal reflux in 40%, history of poor nutrition in 40% and aspiration in 40%). Most of the children had additional complex impairments (91% had mild pyramidal tetraplegia, 81% learning difficulties, 60% congenital defects, 41% neuropsychiatric problems and 28% epilepsy). Over half of the children had significant medical problems in the first year, but mean age at diagnosis was 6 years. There were no obvious causes in pregnancy or birth. Six children had a family history of WDS and 32% (12/37) had abnormal neuroimaging including five with bilateral perisylvian polymicrogyria. In our experience, WDS is not uncommon, is relatively easily diagnosed and is crucial not to miss as the management of these children's multiple impairments is complex and requires a careful team approach. WDS falls clearly within the cerebral palsies as a syndrome that includes motor impairment arising from static damage to the brain in early life. The common presence of cognitive, behavioural and seizure impairments strongly supports the cerebral cortical (presumably perisylvian) localization. Its core elements are a suprabulbar paresis, a mild spastic tetraplegia and a significant excess of cognitive and behavioural impairments and epilepsy. The complete overlap in phenotype between WDS and the bilateral perisylvian syndrome leads us to propose that they are the same condition. WDS is startlingly absent from epidemiological studies of the cerebral palsies and rarely diagnosed, presumably because of lack of clinical awareness of the condition and lack of major gross motor impairments.

Adolescent↗

Cost-effectiveness modeling of Dermagraft for the treatment of diabetic foot ulcers in the french context.

To assess the cost-effectiveness of Dermagraft(R) (human dermal replacement) in the treatment of the diabetic foot ulcer, compared to standard treatment. A Markov model was developed, to simulate, over a 52-week period, the health status of a cohort of 100 patients with a diabetic foot ulcer treated either with conventional therapy or with Dermagraft(R). The considered health states were: healed, same site recurrence, unhealed not infected, cellulitis, osteomyelitis, amputation and death. Each week, the patient may progress among states according to a set of transition probabilities directly derived from the original clinical trial conducted in the USA. The cost of each health state was estimated by a Delphi panel of French diabetologists (direct costs only, valuated from a societal perspective). A sensitivity analysis was performed. The total number of healed ulcers included first ulcers healed (76.38% for Dermagraft(R) vs. 69.35% for standard treatment; median time to heal is 14-15 weeks for Dermagraft(R) compared with 28-29 weeks for standard treatment) plus recurrences which are subsequently healed within the 52-week period (14.29 for Dermagraft(R) vs. 25.09 for standard treatment; median time to heal is 3-4 weeks for Dermagraft(R) compared with 5-6 weeks for standard treatment). The average expected cost per treated patient (C/E) using standard treatment for the considered 52-week period is 47,418 FF vs. 54,384 FF for Dermagraft(R) (including 18,200 FF for Dermagraft(R) acquisition and 36,184 FF for standard treatment). Because Dermagraft(R) heals more ulcers within 52 weeks, the average cost per healed ulcer is lower (53,522 FF vs. 56,687 FF for standard treatment). The incremental cost-effectiveness ratio of Dermagraft(R) (DeltaC/DeltaE) equals 38,784 FF, indicating the extra investment that the decision-maker has to accept for an additional ulcer healed with Dermagraft(R) compared with conventional treatment.

Cost-Benefit Analysis↗

Comparative cost-effectiveness of four-layer bandaging in the treatment of venous leg ulceration.

This paper reports the results of an analysis designed to estimate the expected annual cost per patient of treating venous leg ulcers, and to evaluate the relative cost-effectiveness of a systematic treatment regimen using a four-layer compression bandaging system (Profore) compared with usual care. A Markov model has been developed which simulates the transition of patients between health states (healed and unhealed) over a 52-week period. Healing rates used in the model are derived from those reported in the literature. By running the model for a cohort of 100 patients over 52 weeks it is possible to estimate expected outcomes and annual budgetary costs for alternative treatment regimens. Results suggest that, when compared with usual care, a systematic treatment regimen using Profore is unambiguously more cost-effective. Patient outcomes are improved and annual treatment costs reduced. An important implication is that failure to co-ordinate treatment policies and to use the most cost-effective treatments may result in substantial inefficiency in the use of NHS resources. This inefficiency could represent the equivalent of between 350,000 Pounds and 1.08 million Pounds annually for a typical health authority.

Bandages↗

The development and evaluation of a probe hybridization method for subtyping HIV type 1 infection in Uganda.

We developed a method for large-scale screening of HIV-1 genotypic variation based on DNA probe hybridization. Nested PCR amplifications were performed to generate fragments in the env C2-V3 region and also in the gp41 region, which encompasses the immunodominant domain. The proviral DNA sequences were derived from 68 samples and phylogenetically analyzed. For comparison, the C2-V3 fragment was used in DNA probe hybridization to rapidly determine the infecting HIV subtype. The hybridizing probes were designed on the basis of the two most prevalent subtypes in Uganda, A and D. The results were compared to evaluate the feasibility of using this hybridization method for large-scale genotypic screening. Sequence analysis of the 68 amplified PCR fragments showed that 39 were subtype A and 29 were subtype D. The results of DNA hybridization to the amplified products with A and D subtype-specific probes were more than 90% concordant with the subtypes determined by sequence analysis. Our findings suggest that probe hybridization with subtype-specific probes is effective for large-scale screening of HIV-infected populations. Application of this method will significantly reduce the time needed for large, population-based investigations.

DNA Probes↗

Dejerine-Sottas neuropathy and PMP22 point mutations: a new base pair substitution and a possible "hot spot" on Ser72.

The occurrence of mutations in peripheral myelin protein 22 is one of the genetic mechanisms associated with Dejerine-Sottas neuropathy (DSN). On direct sequencing 2 of such patients we have found the first mutation in the third transmembrane domain associated with this neuropathy and the fourth Ser72Leu. We propose that the Ser72 may be a "hot spot" for DSN and that this should be considered for molecular analysis.

Adult↗