Modeling in economic evaluation: an unavoidable fact of life.
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Clinical Trials as Topic↗
Biomedical subjects
M McKenna
Publications and source records attributed to M McKenna.
Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction.
DFNA9 is an autosomal dominant, nonsyndromic, progressive sensorineural hearing loss with vestibular pathology. Here we report three missense mutations in human COCH (previously described as Coch5b2), a novel cochlear gene, in three unrelated kindreds with DFNA9. All three residues mutated in DFNA9 are conserved in mouse and chicken Coch, and are found in a region containing four conserved cysteines with homology to a domain in factor C, a lipopolysaccharide-binding coagulation factor in Limulus polyphemus. COCH message, found at high levels in human cochlear and vestibular organs, occurs in the chicken inner ear in the regions of the auditory and vestibular nerve fibres, the neural and abneural limbs adjacent to the cochlear sensory epithelium and the stroma of the crista ampullaris of the vestibular labyrinth. These areas correspond to human inner ear structures which show histopathological findings of acidophilic ground substance in DFNA9 patients.
Amino Acid Sequence↗
Experience-dependent depression of vibrissae responses in adolescent rat barrel cortex.
A short period of vibrissae deprivation in an adolescent (approximately 1 month old) rat can lead to depression of the cortical response to stimulation of the regrown vibrissae. In a barrel column representing the deprived vibrissa, depression is greater for neurons located close to the barrel column representing the spared vibrissa. One possible explanation is that the spared vibrissa produces heterosynaptic depression of the principal vibrissa response (Glazewski & Fox, 1996). To test this idea further, we compared the effect of depriving all vibrissae (no heterosynaptic influence at all) with depriving a single vibrissa (maximal heterosynaptic influence expected). In addition we tested the origin of the depression by recording from subcortical structures. After 7 days' deprivation and 6-8 days' regrowth, we tested the responses of barrel cortex cells, thalamic VPm neurons and trigeminal ganglion cells to stimulation of the regrown vibrissae. We found that depression was greater in cortex if a single vibrissa had been deprived than if all vibrissae had been deprived. (Average principal vibrissae responses in single vibrissae deprived animals were 36% of those in all vibrissae deprived animals for layer II/III and 41% for layer IV.) This implicates the spared vibrissae in actively down-regulating responses to the deprived vibrissae. However, some depression could also be produced in animals deprived of all vibrissae (layers II/III were 39% and layer IV 74% of control levels). These results indicate that simple withdrawal of activation has a depressive effect on responses but that depression is far greater if some active inputs remain. Neither form of deprivation had an effect on responses to principal vibrissa stimulation in the thalamus or trigeminal ganglion however, suggesting that depression originates in the cortex. Within the cortex, intracortical connections seem most affected as the greatest depression was found in layers II/III and in layer IV among cells responding at intermediate latencies (9-14 ms).
Animals↗
Pseudoepitheliomatous hyperplasia versus squamous cell carcinoma of the external auditory canal.
Four case reports are presented to demonstrate the clinical and histopathologic similarity of pseudoepitheliomatous hyperplasia (PH) to squamous cell carcinoma (SCC) in the external auditory canal (EAC). In all four cases the original report of SCC on a biopsy specimen of an EAC lesion was corrected on review to PH. In one patient conservative management resulted in resolution of the EAC lesion. A second patient underwent radiation therapy and partial temporal bone resection with no SCC found in the surgical specimen. A third patient's ear canal had healed with conservative treatment and repeated biopsy revealed no malignancy. After a 6-year symptom-free interval, she developed invasive SCC with bone involvement that required surgery and radiation treatment. A fourth patient underwent a sleeve resection of the skin of the EAC that proved to be PH, and no evidence of SCC was found. A thoughtful clinical history, careful physical examination, response to conservative treatment, and close communication with the pathologist should be exercised in the evaluation of EAC lesions.
Adult↗
Dementia programme effectiveness in long-term care.
OBJECTIVE: To examine the effectiveness of dementia programmes and report factors related to programme outcomes. To describe the characteristics which placed hostel residents at risk for nursing home placement and to measure changes in dependencies and impairments over 2 years. DESIGN: Longitudinal, quasi-experimental using in situ resident groups matched on resident and facility characteristics. SETTING: Australian hostels for the elderly. SUBJECTS: 587 residents (programme group N = 184, comparison group N = 162, frail groups N = 241). MEASURES: Mini-Mental State Examination, Geriatric Depression Scale and staff-rated indices of functioning, including activities of daily living, problem behaviours, psychiatric symptomology and health status, were used to monitor changes in resident characteristics. Time to nursing home placement was another outcome measure. RESULTS: Residents in hostel dementia programmes remained significantly longer than those in the comparison group (2.5 months over 2 years) before exit to a nursing home. Quality of life for residents in dementia programmes was enhanced through higher levels of social contact with relatives and lower reported levels of depressive symptoms. CONCLUSIONS: Dementia programmes worked, but the reasons why were more difficult to establish. The programmes did not appear to modify the capacities of residents by slowing rates of decline. Dementia programmes provided specialist (non-personal care) staff focusing on the social and emotional needs of residents. These staff provided appropriate, targeted activities for residents with dementia, had a clearly defined role directed exclusively to these residents and felt directly responsible for them. Dementia programmes produced a system effect. They increased the capacity of hostels to care for residents with dementia for longer periods, before admission to a nursing home.
Activities of Daily Living↗
In vitro optimisation of a microdialysis system with potential for on-line monitoring of lactate and glucose in biological samples.
The optimisation and evaluation of the microdialysis component of a prototype miniaturised total analysis system for application in the continuous monitoring of lactate and glucose is reported. The complete unit comprises a high efficiency microdialysis sampling system, a miniaturised microflow manifold with an integrated biosensor array, together with the hardware and software necessary for controlling the flow parameters and monitoring the sensor signals. Sampling occurs via a microdialysis shunt probe which is perfused continuously with a physiological buffered saline solution. The continuous dialysate outflow is presented to the biosensor array, resulting in the appropriate amperometric signals. Aspects of technological significance addressed here include probe membrane size, perfusate flow rate, sample flow rate, temperature change, probe sterilisation procedures, and heparin content of the physiological saline solution employed.
Biosensing Techniques↗
Novel instrumentation for real-time monitoring using miniaturized flow systems with integrated biosensors.
A prototype miniaturized Total Chemical Analysis System (muTAS) has been developed and applied to on-line monitoring of glucose and lactate in the core blood of anaesthetized dogs. The system consists of a highly efficient microdialysis sampling interface sited in a small-scale extracorporeal shunt circuit ('MiniShunt'), a silicon machined microflow manifold and integrated biosensor array for glucose and lactate detection with associated computer software for analytical process control. During in-vivo testing the device allowed real-time on-screen monitoring of glucose and lactate with system response times of less than 5 min, made possible by the small dead volume of the microflow system. On-line glucose and lactate measurements were made in the basal state as well as during intravenous infusion of glucose or lactate. The prototype muTAS is currently suitable for trend monitoring but refinements are necessary before application of the system for determination of individual lactate values.
Animals↗
A model for analyzing the cost of main clinical events after cardiac transplantation.
Using information from the Papworth Hospital heart transplant service, a model was developed to link the main clinical events after cardiac transplantation to survival and costs. On the basis of the clinical and survival experience of 387 patients treated with triple-drug immunosuppression between 1986 and 1993, together with protocols for patient management, resource use, and costs, a 5-year Markov model with three time periods was used to simulate survival and estimate costs. The model accurately mirrors observed actuarial survival; 1- and 5-year survival rates were 81% and 65%, respectively. An average cost per patient of 26,000 pounds over 5 years (discounted at a rate of 6%) was estimated. The expense of routine care for patients accounts for the majority of the costs; a patient who remains well throughout the 5-year period would incur costs of 23,000 pounds. The sensitivity of the estimates to alternative assumptions is presented, and the way in which the model can be used to compare alternative future scenarios is explored.
Adolescent↗
A cost-utility analysis of laser-assisted angioplasty for peripheral arterial occlusions.
Despite the perception of many people that lasers represent the cutting edge of high-technology medicine, this form of medical technology has been subject to relatively little rigorous evaluation. This dearth of research relates particularly to economic evaluation, where there have been few attempts to justify the high cost of laser equipment. This paper details an economic evaluation of the use of laser technology as a secondary adjunct to angioplasty to treat peripheral arterial occlusions. Using data from a range of sources, including a published randomized trial, a cost-utility model is developed to estimate the costs and benefits of the laser, relative to standard angioplasty. The best available data indicate a cost-effective role for the laser, but important areas of uncertainty exist, including the laser's secondary recanalization rate, which has been estimated on the basis of limited numbers of patients. This uncertainty suggests that further research is required before widespread diffusion of the laser for use in this clinical context.
Adult↗
A gene for non-syndromic autosomal dominant progressive postlingual sensorineural hearing loss maps to chromosome 14q12-13.
We report a novel locus responsible for postlingual progressive sensorineural hearing loss (designated DFNA9) that maps to chromosome 14q12-13. A large kindred with autosomal dominant transmission of non-syndromic hearing loss was clinically studied. Hearing in affected individuals deteriorated at approximately 20 years of age and progressed to anacusis in the fifth decade. A random genome-wide search using polymorphic short tandem repeats demonstrated linkage with D14S121 (maximum two point LOD score = 6.19, theta = 0). Haplotype analysis of recombination events defined a 9 cM disease interval, between D14S252 and D14S49.
Adult↗
The SECCAT survey: I. The costs and consequences of alcoholism.
The SECCAT survey assessed the Socio-Economic Costs and Consequences of Alcoholism Treatment. Basic demographic and health service resource use data (for a previous 6-month period) were obtained fro a cohort of 586 eligible patients who had had treatment at the Alcohol Problems Clinic (APC) in Edinburgh. The cohort was 75% male with a mean age of 46.0 years. Seventy-six per cent had an initial diagnosis of alcohol dependence and 21% alcohol abuse. Use of health services was highly variable. Thirty-six per cent agreed to be interviewed to provide data on their level of abstinence, on resource use, on quality of life (SF-36), on socio-economic characteristics and key adverse events. These 212 individuals had similar age and sex ratios to the full cohort, but alcohol abusers were under-represented. Nineteen patients reported no days of abstinence and 41 were abstinent over the whole 6-month period. Patients experienced a much poorer quality of life than a normal population in terms of all dimensions of the SF-36. The average total health care costs of the interviewed patients were 1134 pounds of which 38% were related to treatment at the APC. Analysis suggests that alcohol-dependent patients make substantially more costly use of resources than abusers and experience a much poorer quality of life. No clear relationship of cost to degree of abstinence has been found. There is a clear and consistent relationship of SF-36 scores and drinking behavior.
Adult↗
Epidemiology of tuberculosis among children in the United States: 1985 to 1994.
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Adolescent↗
What do rats find rewarding in play fighting?--an analysis using drug-induced non-playful partners.
Play fighting by juvenile rats involves playful attacks directed at the partner's nape, where successful contact leads to gentle rubbing of the snout into the nape area. In addition, the recipient of such contact may defend the nape by adopting tactics of playful defense. The two most common defensive tactics in the juvenile period are evasion, where the recipient swerves or leaps away and facing defense involving rotation to supine, where the attacker is faced and its further attempts to contact the nape are blocked. An unresolved issue is whether the nape contact itself or defense by the recipient alone or in combination with nape contact, are involved in rewarding play fighting. In this study, drug-induced non-playful partners were used to test the 'motivation' for play fighting when only playful nape contact was possible. In drug-trials compared to baseline and saline trials, both neonatally androgenized females (high players) and control, oil-treated, females (low players), decreased the frequency of launching nape attacks. These results suggest that nape contact alone, in the absence of defense by the recipient, is not sufficient reinforcement for such playful activity, irrespective of the initial playfulness of the subjects. However, while nape attacks decrease, other forms of social contact, such as anogenital investigation and climbing over the partner (i.e., crawl overs), increase in frequency. These results suggest that non-playful partners are not neutral targets for normal rats. Rather, the 'non-normal' behavior of the drugged target may affect the subjects' behavior in such a way as to reduce their playfulness for reasons other than reduced reinforcement for play.
Aggression↗
Private costs associated with abdominal aortic aneurysm screening: the importance of private travel and time costs.
OBJECTIVES: To assess the importance of the private costs incurred by patients when making a judgment on the economics of screening for abdominal aortic aneurysm (AAA), and to explore the variation in such costs depending on screening location. SETTING: A district general hospital and general practitioner surgeries. METHODS: Four hundred and ninety nine consecutive subjects attending for AAA screening completed a questionnaire asking about travel arrangements for the journey to and from the clinic, the distance travelled, the time taken, the mode of transport, and any out-of-pocket expenses incurred. In addition, at the clinic each subject was asked what activities they had forgone in attending the clinic. Time was valued differently depending on whether work or leisure activities were forgone. The total private cost for each attender was calculated and comparison was made between attenders at hospital and at general practice. RESULTS: A significantly greater proportion of subjects were accompanied when attending hospital than when attending general practitioner (GP) surgeries. Most attenders travelled by car, but the journey time was significantly longer for those visiting hospital. The expected total private cost associated with attendance for AAA screening was 5.47 pounds. Attendance at GP surgeries had a lower private cost (4.21 pounds) than attendance at hospital (6.87 pounds). Only 7.3% of all men surveyed, and 6.5% of all companions, would have been taking part in some form of paid occupation if they had not attended for screening. CONCLUSION: Despite the fact that most attenders for AAA screening will be retired, the associated private costs are appreciable and should be considered in assessing the economics of such screening programmes. The level of private costs varied depending on the location of screening; clinics held at GP practices had lower private costs than those held at hospital.
Aged↗
Transmission of tuberculosis.
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Cluster Analysis↗
Effects of gamma-irradiation on the M-CSF-promoter linked to a chloramphenicol aminoacyl transferase reporter gene expressed in a clonal murine bone marrow stromal cell line.
The effects of cytokines produced by bone marrow stromal cells on closely associated hematopoietic cells constitute a major component of the physiology of the hematopoietic microenvironment. A major cytokine produced by marrow stromal cells is macrophage colony-stimulating factor (M-CSF). To determine the effect of gamma-irradiation on the M-CSF promoter in bone marrow stromal cells, we selected a clonal cell line from the C3H/HeJ mouse marrow stromal cell line D2XRII and stably transfected a reporter construct containing the murine M-CSF-promoter linked to a chloramphenicol aminoacyl transferase (CAT) gene. CAT activity was measured at serial time points after gamma-irradiation in vitro to doses between 500 and 10,000 cGy at a dose rate of 116 cGy/min. D2XRII marrow stromal cells treated with phorbol myristate acetate (40 micrograms/ml, four h), demonstrated a significant two-fold increase in CAT activity. In contrast, CAT activity measured immediately, 24 h, 72 h or 1 week after gamma-irradiation, showed no significant increase or decrease in CAT activity. An increase in CAT activity was detected 48 h after irradiation with cells that received 5,000 cGy. Thus, single fraction gamma-irradiation of plateau phase bone marrow stromal cells did not decrease M-CSF-promoter activity. These results are consistent with prior experimental data demonstrating stable levels of release of M-CSF protein following gamma-irradiation of bone marrow stromal cells and imply that the stability of transcription of the gene for this important cytokine is protected from irradiation.
Animals↗
Patient-controlled analgesia: a comparison with nurse-controlled intravenous opioid infusions.
Patient-controlled analgesia (PCA) with intravenous pethidine was compared with nurse-controlled pethidine infusions for pain relief in 200 patients after major abdominal or thoracic surgery. Pain, level of sedation, nausea and presence of other adverse effects, in addition to cumulative pethidine requirement, were measured for the first 24 hours after surgery. Both groups were similar for age, weight and type of surgery. There was no significant difference between the quality of analgesia achieved in both groups. The frequency and severity of adverse effects was also similar. The cumulative pethidine dose administered to both groups was identical. It is concluded that nurse-controlled opioid infusions are as effective as PCA and may be used as an alternative to PCA where this is either unavailable or unsuitable.
Analgesia↗