Accuracy and validity of stereology as a quantitative method for assessment of human temporal lobe volumes acquired by magnetic resonance imaging.

The object of this study was to compare the accuracy and validity of stereology as a method for determining whole temporal lobe volume with the more established technique of semi-automated thresholding and tracing. Ten, fixed, post-mortem human brains, were imaged using a three dimensional (3D) acquisition protocol. The volume of the left temporal lobe, dissected from each brain, was determined by fluid displacement. Each volume was compared to measurements obtained from magnetic resonance images (MRI) of the post-mortem brain using each of the two segmentation methods. Post-acquisition processing was performed using MEASURE software. Three investigators performed each measurement three times using each method, yielding a total of 180 measurements. Stereology took, on average, half the time of thresholding/tracing. Using a clinically acceptable variation for 95% of repeat measures; both intra-observer and inter-observer variation were acceptable for each technique. However, validity, as demonstrated by graphs of agreement against water displacement showed that the "limits of agreement" using stereology were within the acceptable range, while those using the thresholding/tracing technique were not. Quantitative estimates of variation and a graphical representation of the limits of agreement show that stereology is at least as precise as the thresholding/tracing method but is superior in terms of speed and validity. This has broad implications for published estimates of brain region volumes in human diseases such as epilepsy, dementia and other neurodegenerative disorders.

Health and homelessness in Dublin.

This study examined health and related issues in the adult homeless population of Dublin. The data was collected over a five day period by trained interviewers using an anonymous questionnaire. The response rate was 64%. The population was made up of different demographic sub-groups. Almost 80% were smokers, 30% drank alcohol beyond recommended limits and 30% used illegal drugs. Almost half perceived their health as poor. Sixty six per cent of people had at least one physical or psychiatric problem. Chronic disease was reported by 41%. Health problems varied with demographic and behavioural factors. Utilisation of services varied with age, sex and other demographic factors. Many barriers to service utilisation were identified. Homeless people have increased risks for illness and suffer similar, but more prevalent, health problems to the general population for which they do not always receive adequate or appropriate care. Recommendations include further research and specific service developments.

Sources of information for acute poisoning in accident and emergency departments in Dublin, Ireland.

BACKGROUND: Access by accident and emergency staff to up-to-date information on poisoning is essential for optimal management of acute poisoning. Apart from the National Poisons Information Centre, other information sources can be used. The objectives of the study were to identify sources of information on acute poisoning in accidents and emergencies and satisfaction with their use. METHODS: In a cross-sectional survey of medical staff of accidents and emergencies in Dublin in 1997, data were collected by interviewer-administered questionnaire. RESULTS: All 11 accidents and emergencies participated, with a staff response rate of 95%. One hundred and twenty-eight respondents were included. Ninety-seven percent had managed cases of poisoning (median 3 per week). The National Poisons Information Centre had been used by 93% of respondents, textbooks by 80%, paper database by 63%, and disc database (CD-ROM) by 10%. Of those managing cases, the National Poisons Information Centre would always be contacted by 23% and by 53% in most cases. The National Poisons Information Centre and CD-ROMs were rated the most useful sources of information. Information provided by the National Poisons Information Centre was considered sufficient by 98% of respondents. Thirty-three percent considered that advice should always be confirmed by fax. Limitations with the National Poisons Information Centre were described by 55% (e.g., manual transcription), with textbooks (e.g., limited content) by 83%, with paper databases (e.g., incompleteness) by 85%, and with CD-ROMs (e.g., time-consuming) by 54%. CONCLUSION: For the optimal management of acute poisoning, direct access to computerized information databases in accidents and emergencies combined with telephone access to the National Poisons Information Centre is required, with information available in hard copy.

Surveillance of tuberculosis in Ireland.

The first disaggregate data on tuberculosis in Ireland were collected in 1998. A total of 424 cases were notified (rate 11.7/100 000 population), of which 241 cases were culture positive and 122 were smear positive pulmonary cases. Only 35 cases were fore

Lung-volume reduction surgery for end-stage chronic obstructive pulmonary disease.

Lung-volume reduction surgery (LVRS) has been proposed as a palliative treatment for selected patients with diffuse emphysema and end-stage chronic obstructive pulmonary disease who have failed conventional therapy. A number of surgical techniques have been used that are designed to reduce lung volume by surgical resection or laser plication. These techniques are designed to restore previous compromised lung elastic recoil so that expiratory airflow obstruction is reduced, respiratory mechanics are improved, and disabling dyspnea is relieved. Preliminary data derived from both published and unpublished information indicate some favorable short-term benefits. However, objective postoperative data are available for only a small proportion of patients, and long-term followup data are not available. In addition, these surgeries are associated with significant morbidity (and a 6 percent [approximate] surgical mortality) and prolonged hospital stays in a substantial percentage of patients. Patient selection criteria are heterogeneous and in flux, and controversy continues concerning the most appropriate surgical techniques for various categories of patients. The current data do not permit a logical and scientifically defensible conclusion regarding the risks and benefits of LVRS.

Bone densitometry: patients receiving prolonged steroid therapy.

Bone mass loss and osteoporosis are associated with various conditions, such as asymptomatic primary hyperparathyroidism, and treatments, such as prolonged steroid therapy. Bone densitometry is used to measure bone mass density to determine the degree of osteoporosis and to estimate fracture risk. Bone densitometers measure the radiation absorption by the skeleton to determine bone mass of the peripheral, axial, and total skeleton. Common techniques include single-photon absorptiometry (SPA) of the forearm and heel, dual-photon (DPA) and dual-energy x-ray absorptiometry (DXA) of the spine and hip, quantitative computed tomography (QCT) of the spine or forearm, and radiographic absorptiometry (RA) of the hand. Part I of this report addresses important technical considerations of bone densitometers, including radiation dose, site selection, and accuracy and precision, as well as cost and charges. Part II evaluates the clinical utility of bone densitometry in the management of patients receiving prolonged steroid therapy. Steroids have broad effects on both immune and inflammatory processes and have been used to treat a wide variety of immunologically mediated diseases. Osteoporosis and vertebral compression fractures have been considered major complications of prolonged steroid therapy. Bone loss is also a direct result of many of the diseases treated with steroids. Issues addressed are the type and extent of bone loss associated with steroid therapy, risk for fracture, whether steroid dose reduction or alternative therapy is an option, and whether osteoporosis associated with prolonged steroid use can be prevented or treated. The other assessments in this series address the clinical utility of bone densitometry for patients with: asymptomatic primary hyperparathyroidism, end-stage renal disease, vertebral abnormalities, and estrogen-deficient women.

Bone densitometry: patients with end-stage renal disease.

Bone mass loss and osteoporosis are associated with various conditions, such as end-stage renal disease (ESRD), and treatments, such as prolonged steroid therapy. Bone densitometry is used to measure bone mass density to determine the degree of osteoporosis and to estimate fracture risk. Bone densitometers measure the radiation absorption by the skeleton to determine bone mass of the peripheral, axial, and total skeleton. Common techniques include single-photon absorptiometry (SPA) of the forearm and heel, dual-photon (DPA) and dual-energy x-ray absorptiometry (DXA) of the spine and hip, quantitative computed tomography (QCT) of the spine or forearm, and radiographic absorptiometry (RA) of the hand. Part I of this report addresses important technical considerations of bone densitometers, including radiation dose, site selection, and accuracy and precision, as well as cost and charges. Part II evaluates the clinical utility of bone densitometry in the management of patients with ESRD. End-stage renal disease affected more than 242,000 Americans in 1992, and each year 10,000 to 20,000 new cases are diagnosed. Although the survival rate of ESRD patients has improved, metabolic bone diseases that fall under the generic term "renal osteodystrophy" represent abnormal development of bone and major long-term complications. Issues addressed are the type and extent of bone loss associated with ESRD and whether these patients have an increased risk for fracture. The other assessments in this series address the clinical utility of bone densitometry for patients with asymptomatic primary hyperparathyroidism, steroid-dependent patients, estrogen-deficient women, and patients with vertebral abnormalities.

Cost-effectiveness modeling of simultaneous pancreas-kidney transplantation.

A cost-effectiveness model was developed to compare simultaneous pancreas-kidney transplantation (SPK) to kidney transplantation alone (KTA) with continued insulin therapy among type-1 diabetics with end-stage renal disease. It appeared that the two procedures were equally cost-effective only for diabetics whose annual costs for treatment of complications of hyper- and hypoglycemia were quite high.

Bone densitometry: patients with asymptomatic primary hyperparathyroidism part I. Technical report.

Many studies document bone loss at diagnosis in patients with PHPT (including mild PHPT) that is greater than would be expected in comparable persons without this condition. However, there is no general agreement regarding the severity of bone mass loss in these patients and the rate at which it progresses. A few studies suggest that such accelerated osteoporosis may be self-limited, with patients showing no further decline in BMD after diagnosis. There is insufficient evidence to conclude that PTH-related bone loss is associated with an increased risk of fracture. The few studies that have evaluated the risk of fracture in these patients are conflicting. Some evidence also suggest that, like bone loss in these patients, fracture risk may change during the course of the disease. One study found that patients with PHPT (including those with mild hypercalcemia) were more likely than matched controls to have a history of fractures prior to diagnosis, but that both groups had similar rates of fractures during followup. Moreover, the studies of fractures suffer from several limitations, such as nonrandomization of patients, different definitions of vertebral fractures, small study populations, and short followup times. There is also insufficient evidence to determine the effect of parathyroidectomy on the incidence of fractures in patients with mild PHPT, partly because the natural history of this condition is incompletely understood. Although studies demonstrate that patients with PHPT gain bone mass following parathyroidectomy, the bone reparation is incomplete and bone mass density remains below normal, even though the hyperparathyroidism is cured. Currently, decisions to perform parathyroidectomy are based on signs and symptoms of bone disease, metabolically active renal stones, decreased renal function, fatigue and/or depression, and high levels of serum calcium. Although the use of bone mass measurements has been advocated to aid clinical decisions regarding the risks and benefits of surgery, specific bone changes that indicate the need for parathyroidectomy have not been clearly established. There are virtually no prospective data that evaluate decisions to operate based upon bone mass measurements nor randomized clinical trials comparing the outcome of surgically treated patients with those who have not had surgery. Based on the literature, bone mass measurements cannot predict who among asymptomatic patients will require parathyroidectomy. There is some evidence that nonsurgically treated patients and those who remained hypercalcemic after unsuccessful surgery lost bone at the same percentage rate as normal control subjects.

Simultaneous pancreas-kidney and sequential pancreas-after-kidney transplantation.

Simultaneous pancreas-kidney (SPK) or pancreas-after-kidney (PAK) transplantation has been advocated as an alternative to kidney transplant alone (KTA) for type 1 diabetics with end-stage renal disease. Advocates of combined transplant assert that the procedure reduces, prevents, or mitigates secondary complications of diabetes and improves the quality of life (QOL) of recipients. The combined procedures may be accomplished with a relatively low mortality, but the morbidity significantly exceeds that of KTA. The published data did not provide unambiguous support for the contention that SPK or PAK improved or ameliorated the secondary diabetic complications of retinopathy, neuropathy, and nephropathy, and it cannot be reasonably concluded that such benefit is likely to result. The majority of studies of QOL subsequent to combined transplant had significant methodologic deficiencies which made generalizations problematic. Notwithstanding, improvements in objective measures, such as return to employment or school, reduction in medical care requirements, days spent in hospital, social or physical activity, etc, have not been demonstrated for combined transplant; improvements in subjective measures were inconsistently reported. The United Network for Organ Sharing (UNOS) registry indicated that SPK represents 83 percent, and PAK about 8 percent of all pancreas transplants in the United States. Pancreas graft survival data are limited; UNOS reported 3-year survival rates of approximately 65 percent following SPK, and 35 percent after PAK. Renal graft survival following SPK appears comparable to that reported for most cadaver KTA. However, selection of SPK in lieu of KTA with a living-related donor or HLA-matched cadaver kidney may result in significant reduction in expected renal graft survival, in the range of 40-70 percent to as much as 350 percent. A cost-effectiveness analysis (CEA) model compared SPK with KTA and continued insulin therapy. The model employed a wide range of reported charges/payments, and postulated that SPK would provide significant improvements in quality of life. Sensitivity analyses indicated that SPK was equal in cost effectiveness to KTA only in patients who incurred very high annual costs for the treatment of hyper- or hypoglycemia. The literature does not indicate that such patients comprise the majority of SPK recipients. Additional evidence is necessary to unequivocally demonstrate the risks, costs, and ultimate benefits of combined transplant. Such information should include detailed and unambiguous patient selection criteria, prospective comparative studies of the effects of SPK/PAK upon secondary complications and quality of life, and accurate cost data for the transplant procedures and required followup care.

Extracranial-intracranial bypass to reduce the risk of ischemic stroke.

Extracranial-intracranial (EC-IC) bypass surgery is an operative procedure in which the superficial temporal artery is anastomosed to the middle cerebral artery. The operation, first described in 1969, was employed to circumvent otherwise surgically inaccessible atherosclerotic lesions high in the internal carotid system or in the middle cerebral artery. This assessment compares the findings from 13 surgical series of EC-IC bypass (1464 patients) with those reported in the only prospective, randomized, cooperative trial of this procedure (1377 patients). Analysis of the outcomes in the 1464 patients included in the surgical series produced insufficient evidence to support a conclusion that post-EC-IC bypass stroke rates were lower than the rates of either the medically or surgically treated groups in the controlled clinical trial. In the absence of reliable, objective evidence of the existence of a group of patients in whom surgical intervention is superior to medical treatment in reducing the frequency of stroke, the results of the single controlled clinical trial, which demonstrated no benefit of bypass, must be accepted as the best evidence currently available.

Extracranial-intracranial bypass to reduce the risk of ischemic stroke.

Extracranial-intracranial bypass surgery is an operative procedure in which the superficial temporal artery is anastomosed to the middle cerebral artery. The operation, first described in 1969, was employed to circumvent otherwise surgically inaccessible atherosclerotic lesions high in the internal carotid system or in the middle cerebral artery. This assessment compares the findings from 13 surgical series of EC-IC (1,464 patients) with those reported in the only prospective, randomized, cooperative trial of this procedure (1,377 patients). Analysis of the outcomes in the 1,464 patients included in the surgical series produced insufficient evidence to support a conclusion that post-EC-IC bypass stroke rates were lower than the rates of either the medically or surgically treated groups in the controlled clinical trial. In the absence of reliable, objective evidence of the existence of a group of patients in whom surgical intervention is superior to medical treatment in reducing the frequency of stroke, the results of the single controlled clinical trial, which demonstrated no benefit of bypass, must be accepted as the best evidence currently available.

A prospective randomized trial of HLA-matched versus mismatched single-donor platelet transfusions in cancer patients.

The use of histocompatability antigen (HLA)-matched platelets has been advocated for the support of thrombocytopenic cancer patients. We randomized 78 newly diagnosed cancer patients prospectively (before thrombocytopenia) to receive either HLA-matched or mismatched single-donor platelet transfusions. Three hundred forty-one platelet transfusions were given for 80 separate episodes of therapy-induced thrombocytopenia in 33 patients. Forty-five patients receiving intensive chemotherapy did not develop significant (less than 20,000 platelets/mm3) thrombocytopenia and did not receive a platelet transfusion. No marked difference was observed between the matched and mismatched groups in regard to number of total platelet transfusions per patient (median, 3 vs. 5, respectively; P = 0.076), number of platelet transfusions per episode (median, 3.0 vs. 3.5, respectively; P = 0.28), or days between transfusions (median, 2 vs. 2, respectively, P greater than 0.4). Bleeding episodes, although rare, tended to be of increased severity in the mismatched group. Febrile patients receiving mismatched platelets tended to have a lower posttransfusion increment increase than their nonfebrile counterparts (P = 0.068), although a similar trend could not be demonstrated between febrile and nonfebrile patients who received matched platelets (P = 0.22). Patients treated as outpatients had significantly higher posttransfusion increments than when transfused as inpatients when they were given mismatched platelets (P less than 0.0005). Development of antiplatelet antibody did not appear to affect response to platelet transfusions. Only one patient developed sustained high-level antibody titers. In patients where thrombocytopenia was significant, the transfusion of HLA-matched platelets did not appear to offer a significant advantage. However, HLA-matched platelet transfusions tended to be associated with higher posttransfusion increments in febrile patients and a trend toward fewer severe bleeding episodes. A multi-institution trial containing a large number of patients is needed to evaluate trends observed in this study.