The significance of haemochromatosis gene mutations in the general population: implications for screening

BACKGROUND: Haemochromatosis is associated with mutations in the HFE gene but the significance of these mutations in the general population is unknown. AIMS: To determine the frequency of HFE gene mutations in the general population, their effect on serum iron indexes, and their role in screening for haemochromatosis. METHODS: Deoxyribonucleic acid (DNA) from 1064 randomly selected subjects was analysed for the C282Y and H63D mutations in the HFE gene. Serum iron, transferrin saturation, and ferritin were measured and individuals with increased iron indexes were investigated to confirm or exclude a clinical diagnosis of haemochromatosis. RESULTS: Mutations were identified in 409 individuals (38.4%) with heterozygote (carrier) frequencies of 13.2% and 24.3% for the C282Y and H63D mutations respectively. Heterozygosity for either mutation significantly increased serum iron and transferrin saturation but despite a similar trend for ferritin, this was only significant for C282Y homozygotes. Five individuals (0.47%) were homozygous for the C282Y mutation, three of whom had haemochromatosis confirmed by liver biopsy (0.28%). The other two C282Y homozygotes would not have been detected by phenotypic screening alone. CONCLUSIONS: HFE mutations are present in 38.4% of the population, affect serum iron indexes, and are important determinants of iron status. The population frequency of genetically defined haemochromatosis (C282Y homozygosity) is approximately one in 200 and is higher than the prevalence of clinically apparent haemochromatosis.     

Prediction of the helix/strand content of globular proteins based on their primary sequences

Population screening for hemochromatosis done by using the transferrin saturation test has been advocated by experts to permit the initiation of therapeutic phlebotomy before the onset of clinical disease. The discovery of a gene associated with hemochromatosis has made DNA testing another option for screening and diagnosis. In this paper, U.S. Preventive Services Task Force criteria are used to evaluate the evidence for the usefulness of population screening done by using iron measures or genetic testing. Published clinical research offers little evidence to suggest that population screening for hemochromatosis done by using genetic testing improves clinical outcomes. Although one recently discovered mutation, C282Y, accounts for 60% to 92% of cases of the disease in series of patients with hemochromatosis, uncertainties remain about the clinical penetrance of various genotypes; the accuracy of genetic testing; and the ethical, legal, and social effects of genetic testing. Before population screening for hemochromatosis done by using transferrin saturation testing can be recommended, laboratory standardization needs to be addressed and questions about risk for clinical disease in asymptomatic persons with mutations or early biochemical expression of disease require resolution. Evidence from case series suggests that hemochromatosis may be associated with liver cancer, other liver disease, diabetes, bradyarrhythmias, and arthritis. In all studies but one, however, estimation of the magnitude and significance of this risk is limited by lack of adequate comparison groups. The need for population data to answer questions about penetrance among asymptomatic persons should not impede efforts to increase the detection and treatment of hemochromatosis in persons found to have elevated iron measures a family history of hemochromatosis, or consistent early signs and symptoms of the disease.     

Cost effectiveness of shortening screening interval or extending age range of NHS breast screening programme: computer simulation study

OBJECTIVE: To compare the cost effectiveness of two possible modifications to the current UK screening programme: shortening the screening interval from three to two years and extending the age of invitation to a final screen from 64 to 69. DESIGN: Computer simulation model which first simulates life histories for women in the absence of a screening programme for breast cancer and then assesses how these life histories would be changed by introducing different screening policies. The model was informed by screening and cost data from the NHS breast screening programme. SETTING: North West region of England. MAIN OUTCOME MEASURES: Numbers of deaths prevented, life years gained, and costs. RESULTS: Compared with the current breast screening programme both modifications would increase the number of deaths prevented and the number of life years saved. The current screening policy costs 2522 pounds per life year gained; extending the age range of the programme would cost 2612 pounds and shortening the interval 2709 pounds per life year gained. The marginal cost per life year gained of extending the age range of the screening programme is 2990 pounds and of shortening the screening interval is 3545 pounds. CONCLUSIONS: If the budget for the NHS breast screening programme were to allow for two more invitations per woman, substantial mortality reductions would follow from extending the age range screened or reducing the screening interval. The difference between the two policies is so small that either could be chosen.     

A new p21waf1/cip1 isoform is an early event of cell response to oxidative stress

BACKGROUND: A population-based hemochromatosis screening program that uses serum transferrin saturation has been proposed, but few data exist on the number of U.S. adults that such a program would identify for further testing. OBJECTIVE: To determine the prevalence of an initially elevated serum transferrin saturation and the prevalence of concurrently elevated serum transferrin saturation and serum ferritin levels in the adult population of the United States. DESIGN: Nationally representative cross-sectional survey of the noninstitutionalized U.S. civilian population. PARTICIPANTS: 15 839 men and nonpregnant women 20 years of age and older who were examined in the third National Health and Nutrition Examination Survey (1988-1994). MEASUREMENTS: Single measurements of serum transferrin saturations and serum ferritin levels. Cut-off values used to define elevated serum transferrin saturation ranged from greater than 45% to greater than 62%. RESULTS: The prevalence of initially elevated serum transferrin saturation ranged from 1% to 6%. Approximately 11% to 22% of those with elevated serum transferrin saturation had concurrently elevated serum ferritin levels. The prevalence of elevated serum transferrin saturation was lower in women than in men when the same cut-off value was used to define elevated serum transferrin saturation. The prevalence of elevated serum transferrin saturation in non-Hispanic black persons and Mexican-Americans was similar to or slightly less than that in non-Hispanic white persons. The prevalence of elevated serum transferrin saturation in persons 20 to 49 years of age was as high as or higher than that in older adults. CONCLUSIONS: A hemochromatosis screening program that uses a cut-off value of greater than 60% to define elevated serum transferrin saturation would identify an estimated 1.4 to 2.5 million U.S. adults for further testing.     

Imaging-guided core biopsies in the breast

Screening mammography programs have contributed to an overall decline in breast cancer mortality. The screening process, however, also results in detection and biopsy of many nonpalpable lesions that eventually prove to be benign, contributing to the burden of costs to our health care system. Percutaneous imaging-guided core biopsy has proven to be a safe and accurate technique for obtaining a histologic diagnosis in most patients who have screening-detected lesions; it is done at lower cost with lower resultant morbidity to the patient compared with traditional surgical excisional biopsy. I review the indications, techniques, method of correlating the histology with mammographic findings, and accreditation requirements for imaging-guided core biopsies of the breast done under mammographic (ie, stereotactic) or sonographic guidance.     

Screening for renovascular hypertension in a population with relatively low prevalence

OBJECTIVE: To evaluate the accuracy and cost-efficacy of the diagnostic procedure and treatment for renovascular hypertension. SETTING AND PATIENTS: A total of 519 patients referred to the university clinic for hypertension were screened for renovascular hypertension with 405 captopril challenge tests (CCT) and 450 captopril renographies (CRG). INTERVENTIONS: Abdominal angiography was performed on 84 patients for positive screening. Fifteen patients underwent angiography for a sole suspicious clinical presentation. The angiography revealed 17 renal artery stenoses and five occlusions in 20 patients. Fifteen technically successful angioplasties and three nephrectomies were performed. RESULTS: In the patients who underwent angiography, CCT had a specificity of 39% and a sensitivity of 67% for renovascular hypertension. CRG had a sensitivity of 100% and a specificity of 68%. In the whole study population, the estimated specificity of CCT was 88% and that of CRG 95%. Invasive treatment reduced systolic/diastolic blood pressure from 157/99 to 140/87 mmHg and the number of antihypertensive drugs used from 2.6 to 1.4 in 16 patients (mean age 49 years). Angiotensin converting enzyme (ACE) inhibition was effective in four elderly patients. Cost-efficacy analysis Screening with CRG and invasive treatment cost US$15400 per successful invasive treatment Equally effective pharmacological treatment would have cost US$10400. Limiting the screening with CRG to the 173 patients with no obvious renal parenchymal disease and with hypertension at a younger age (< or =30 years) or unresponsive to two antihypertensive drugs (diastolic blood pressure > 90 mmHg) would have yielded a prevalence of 12% and missed only one elderly patient who responded to ACE inhibition. The limited screening, along with invasive treatment, would have cost US$7300 per patient CONCLUSIONS: CRG is superior to CCT for screening of renovascular hypertension. Screening with CRG is cost-effective when limited to patients with no obvious renal parenchymal disease and with hypertension that does not respond to two antihypertensive drugs or is detected in patients no older than 30 years.     

One world, one hope: the cost of providing antiretroviral therapy to all nations

OBJECTIVE: To estimate the potential direct cost of making triple combination antiretroviral therapy widely available to HIV-positive adults and children living in countries throughout the world. METHODS: For each country, antiretroviral costs were obtained by multiplying the annual cost of triple antiretroviral therapy by the estimated number of HIV-positive persons accessing therapy. Per capita antiretroviral costs were computed by dividing the antiretroviral costs by the country's total population. The potential economic burden was calculated by dividing per capita antiretroviral costs by the gross national product (GNP) per capita. All values are expressed in 1997 US dollars. RESULTS: The potential cost of making triple combination antiretroviral therapy available to HIV-positive individuals throughout the world was estimated to be over US$ 65.8 billion. By far the greatest financial burden was on sub-Saharan Africa. The highest per capita drug cost in this region would be incurred in the subregions of Southern Africa (US$ 149) followed by East Africa (US$ 116), Middle Africa (US$ 44), and West Africa (US$ 42). In the Americas, subregional data indicated the highest per capita drug cost would be in the Latin Caribbean (US$ 22), followed by the Caribbean (US$ 17), Andean Area (US$ 7), the Southern Cone (US$ 6), North America (US$ 6), and Central American Isthmus (US$ 5). In Asia and Europe the percentage of the GNP necessary to finance drug therapy was less than 1% in most countries examined. CONCLUSION: Our results demonstrate that the cost of making combination antiretroviral therapy available worldwide would be exceedingly high, especially in countries with limited financial resources.     

Current diagnosis: hereditary metabolic diseases of the liver (primary hemochromatosis, Wilson disease)

Primary hemochromatosis is characterized by a specific pattern of clinical manifestations. It includes liver disease with hepatomegaly, glucose intolerance, e.g. diabetes, hyperpigmentation oft the skin, impotence/ amenorrhea, arthropathy, cardiomyopathy and fatigue. Laboratory investigation reveals significantly elevated serum ferritin and transferrin saturation with iron. The diagnosis is confirmed by liver biopsy and quantitative determination of elevated liver iron content. Wilson's disease represents a copper storage disease. Prominent clinical features are hepatomegaly and splenomegaly. Neurological alterations and detection of Kayser-Fleischer corneal rings are typical. In the acute initial phase the often young patients present with Coombs-negative hemolysis. Psychiatric alterations, cardiomyopathy, arthropathy, nephropathy, as well as thrombocytopenia and leucopenia are other clinical features. Laboratory parameters of Wilson's disease include low serum ceruloplasmin and serum copper. There is an elevated urinary copper excretion and elevated serum free copper concentration. The diagnosis is confirmed by liver biopsy with quantitative determination of an elevated liver copper content.     

Comparison of key informant and survey methods for ascertainment of childhood epilepsy in West Bengal, India

BACKGROUND: This study aimed to compare efficacy and cost of key informants and survey for ascertainment of childhood epilepsy within a treatment context in rural India. METHODS: The study was set in a non-governmental, community programme for the functional and socioeconomic rehabilitation of children with disabilities in rural West Bengal, India. Ascertainment was by two methods: house-to-house survey of 15000 households and also by 430 key informants including village leaders, health workers and 670 schoolchildren. Methods were compared for positive predictive value, and sensitivity by capture-recapture technique. Ninety four children were enrolled into treatment. Predictors of treatment success were determined by multiple logistic regression analysis, giving adjusted odds ratios for remission. The costs of identifying one case and one treatment success were measured by costing personnel, materials and overheads. RESULTS: The survey was four times as sensitive as key informants although the positive predictive values were similar (36%, 40%). The survey had an absolute sensitivity of only 59%. Identification by key informants strongly predicted successful treatment outcome (odds ratio [OR] = 4.74, 95% confidence interval [CI] : 1.19-18.85). The cost of finding one case was US$11 and US$14, and of finding one successful treatment outcome US$35 and US$67 for informants and survey respectively. Key informants were essential in attaining longer term programme objectives. CONCLUSIONS: In the context of a treatment programme, key informants were the more cost-effective method, but community involvement was traded against low sensitivity in the short term. Overall ascertainment costs were significant in the context of primary health care in India.     

The notion of somatization: an artefact of the conceptualization of body and mind

In this review published data are used to determine the benefits and costs of antenatal screening for hepatitis B carriers to prevent the later occurrence of hepatoma and chronic liver disease in their offspring. In Britain, babies born to carrier mothers have a 25% risk of perinatal infection and of becoming carriers themselves (the risk is 82% if their mothers are positive for the e antigen and 10% if negative). The carrier state increases the risk of hepatoma an estimated 86 times and the risk of chronic liver disease 20 times. Life table analysis showed that there is an 11% lifetime risk in carriers in Britain of dying from hepatoma (which results in seven years of life lost on average) and a 7% risk of chronic liver disease (14 years of life lost). Neonatal vaccination reduces the risk of the infant becoming a carrier by about 90%. Perinatal transmission occurs in 38 of every 100,000 neonates in Britain. Antenatal screening of all women and vaccinating babies of carrier mothers would prevent perinatal transmission in 34 of the 38 children (90%), or 255 per year in Britain. Of these 34, 8.4 children would be Chinese in ethnic origin, 4.2 African, 11.5 South Asian (from the Indian subcontinent), 2.0 Caribbean, and 7.3 would be white. Six deaths in the 34 from hepatoma or chronic liver disease caused by hepatitis B would then be prevented. The direct cost in Britain of screening all women, irrespective of ethnicity, at their first pregnancy only, would be 1300 pounds for each year of life saved (undiscounted) or 2500 pounds if screening at every pregnancy. Screening just Chinese, Africans, and South Asians, at first pregnancy only, would cost 330 pounds for each year of life saved but would prevent only 64% of these deaths. Vaccinating the infants of carrier mothers is likely also to prevent horizontal transmission of hepatitis B in early childhood and prevent the carrier state developing in an estimated three extra children for each child protected from vertical transmission. When this is taken into account the number of deaths prevented increases fourfold, reducing the cost for each year of life saved by 75%. Screening all women at first pregnancy only is an acceptably cost effective policy in Britain (1300 pounds for each year of life saved), actually preventing 45 deaths a year from hepatoma and chronic liver disease (or about 180 deaths if those horizontally infected are included), at a total cost of 540,000 pounds a year. It has the advantage of being comprehensive, equitable, and easier to implement than a policy based on screening of high risk ethnic groups.     

Pretreatment evaluation of chronic hepatitis C: risks, benefits, and costs

CONTEXT: Chronic hepatitis C (CHC) infection affects nearly 4 million people in the United States. Treatment with interferon alfa-2b has been limited by its cost and low likelihood of long-term response. OBJECTIVE: To examine the cost-effectiveness of alternative pretreatment management strategies for patients with CHC. DESIGN: Decision and cost-effectiveness analysis using a Markov model to examine prevalence of genotypes, viral load, and histological characteristics in relation to the sustained response rate with treatment. Data were based on a previously published decision model and a MEDLINE literature search for hepatitis C, biopsy, and liver from 1966 to 1996. PATIENTS: A hypothetical population of patients with CHC infection and elevated serum alanine aminotransferase level. INTERVENTIONS: Combinations of liver biopsy, genotyping, and quantitative viral load determination prior to a single 6-month course of interferon alfa-2b; empirical interferon treatment; and conservative management. MAIN OUTCOME MEASURES: Proportion of sustained responders, lifetime costs, life expectancy, and quality-adjusted life expectancy. RESULTS: Strategies involving hepatitis C virus (HCV) RNA testing had marginal cost-effectiveness ratios up to $4400 per discounted quality-adjusted life-year gained but would miss up to 36% of sustained responders. Empirical interferon treatment had a marginal cost-effectiveness ratio of $12400 per discounted quality-adjusted life-year gained and reached all potential sustained responders. Strategies involving liver biopsy were more expensive and would miss 6% of sustained responders and yield slightly lower life expectancies. CONCLUSIONS: Routine liver biopsy before treatment with interferon increases the cost of managing patients with CHC without improving health outcomes. Using quantitative HCV RNA testing to guide therapy misses some potential sustained responders. Empirical interferon treatment has a marginal cost-effectiveness ratio within the bounds of other commonly accepted therapies and misses none of the sustained responders.     

A randomized study of two doses of abdominopelvic radiation therapy for patients with optimally debulked Stage I, II, and III ovarian cancer

BACKGROUND & AIMS: An elevated transferrin saturation is the earliest phenotypic abnormality in hereditary hemochromatosis. Determination of transferrin saturation remains the most useful noninvasive screening test for affected individuals, but there is debate as to the appropriate screening level. The aims of this study were to estimate the mean transferrin saturation in hemochromatosis heterozygotes and normal individuals and to evaluate potential transferrin saturation screening levels. METHODS: Statistical mixture modeling was applied to data from a survey of asymptomatic Australians to estimate the mean transferrin saturation in hemochromatosis heterozygotes and normal individuals. To evaluate potential transferrin saturation screening levels, modeling results were compared with data from identified hemochromatosis heterozygotes and homozygotes. RESULTS: After removal of hemochromatosis homozygotes, two populations of transferrin saturation were identified in asymptomatic Australians (P < 0.01). In men, 88.2% of the truncated sample had a lower mean transferrin saturation of 24.1%, whereas 11.8% had an increased mean transferrin saturation of 37.3%. Similar results were found in women. A transferrin saturation threshold of 45% identified 98% of homozygotes without misidentifying any normal individuals. CONCLUSIONS: The results confirm that hemochromatosis heterozygotes form a distinct transferrin saturation subpopulation and support the use of transferrin saturation as an inexpensive screening test for hemochromatosis. In practice, a fasting transferrin saturation of > or = 45% identifies virtually all affected homozygous subjects without necessitating further investigation of unaffected normal individuals.     

Choosing options for ultrasound screening in pregnancy and comparing cost effectiveness: a decision analysis approach

OBJECTIVE: To compare the cost effectiveness of different programmes of routine antenatal ultrasound screening to detect four key fetal anomalies: serious cardiac anomalies, spina bifida, Down's syndrome and lethal anomalies, using existing evidence. DESIGN: Decision analysis was used based on the best data currently available, including expert opinion from the Royal College of Obstetricians and Gynaecologists, Working Party and secondary data from the literature, to predict the likely outcomes in terms of malformations detected by each screening programme. SETTING: Results applicable in clinics, hospitals or GP practices delivering antenatal screening. MAIN OUTCOME MEASURE: The number of cases with a 'target' malformation correctly detected antenatally. RESULTS: There was substantial overlap between the cost ranges of each screening programme demonstrating considerable uncertainty about the relative economic efficiency of alternative programmes for ultrasound screening. The cheapest, but not the most effective, screening programme consisted of one second trimester ultrasound scan. The cost per target anomaly detected (cost effectiveness) for this programme was in the range 5,000 pound silver-109,000, pound silver but in any 1000 women it will also fail to detect between 3.6 and 4.7 target anomalies. CONCLUSIONS: The range of uncertainty in the costs did not allow selection of any one programme as a clear choice for NHS purchasers. The results suggested that the overall allocation of resources for routine ultrasound screening in the UK is not currently economically efficient, but that certain scenarios for ultrasound screening are potentially within the range of cost effectiveness reached by other, possibly competing, screening programmes. The model highlighted the weakness of available evidence and demonstrated the need for more information both about current practice and costs.     

A workplace breast cancer screening program. Costs and components

Screening for breast cancer can result in early detection of malignancies and lives saved. Many employers now offer periodic screening as an employee health benefit, and some have established screening programs in the workplace. This study was performed to identify the employer costs of breast cancer screening in the workplace, referrals for suspicious findings, and initial treatment of malignant disease. Additionally, the costs for these same services, had they been obtained outside of a workplace screening program, were estimated. Data on program components and associated costs for an established employer based breast cancer screening program were obtained. These costs were compared to those among a hypothetical cohort of women not enrolled in the workplace screening program. From 1989 through 1995, 1,416 women participated in the program. Nearly 2,500 screening mammograms and approximately 2,773 clinical breast examinations were performed, resulting in 292 referrals to physicians outside of the program for additional diagnostic procedures and treatment as needed. These referrals resulted in the detection of 12 malignancies: 8 Stage I; 3 Stage II; and 1 Stage III. Mammographic and clinical breast examination screening cost $249,041; referrals resulting in benign disease or no detectable disease cost $185,002; and referrals resulting in malignant disease, followed by initial treatment, cost $148,530. Therefore, the total cost was $582,573. Approximately 47% of the cost of referrals and initial treatment were due to employee lost productivity. Total cost in the hypothetical cohort was $1,067,948 under the assumptions that all women received screening outside of the workplace, and that the same number of malignancies were detected at the same stage as in the workplace program. These findings indicate referrals resulting in detection of benign disease or no disease accounted for a substantial proportion of the total cost of the program. In addition, employee lost productivity accounted for almost 50% of the cost of all referrals and initial treatment. Workplace screening is a relatively efficient approach for early detection of breast cancer when compared to off site screening or no screening. The efficiency could be improved with a reduction in the number and cost of unnecessary referrals.     

Iron-related indexes in chronic alcoholics. Effect of alcohol withdrawal

BACKGROUND: Increased serum transferrin saturation and ferritin levels have been reported in chronic alcoholics. AIM: To evaluate modifications in serum iron-related indexes in chronic alcohol abusers with and without cirrhosis, at enrolment and after complete alcohol withdrawal. PATIENTS: Fifty-one consecutive chronic alcohol abusers, 33 without and 18 with cirrhosis. METHODS: Liver function tests were performed and transferrin saturation percent and serum ferritin levels measured at time 0 and after 7 and 14 days of complete alcohol withdrawal. RESULTS: Duration of alcohol abuse was significantly longer in patients with cirrhosis than in those without (24 +/- 13 SD vs 18 +/- 13 SD years, p < 0.01). A concomitant increase in transferrin saturation percent and serum ferritin was found in 60% of the cirrhotics and 45% of the non cirrhotic group. During the observation period, transferrin saturation percent and serum ferritin fell significantly in both groups (from 59 +/- 33 SD to 36 +/- 22% SD, p < 0.05, and from 900 +/- 933 SD to 469 +/- 457 SD ng/ml, p < 0.01, in cirrhotics, and from 46 +/- 30 SD to 27 +/- 12% SD, p < 0.01, and from 702 +/- 602 SD to 340 +/- 29 SD ng/ml, p < 0.01, in non cirrhotics). CONCLUSIONS: Iron-related indexes increase with chronic alcohol abuse and return to normal rapidly after complete alcohol withdrawal. In chronic alcoholics the timing of determinations of iron-related indexes is crucial, and screening for possible concomitant genetic haemochromatosis must be postponed.     

A tale of Danbury hatters, detectives and Dartmouth chemists

Using case note review, a retrospective analysis was carried out of all patients referred with haemochromatosis and suspected hepatocellular carcinoma between 1988 and 1997 to define the mode of presentation, management and outcome of such patients. All 12 patients were male with a mean age of 67 years. Four patients presented whilst asymptomatic by alpha-fetoprotein screening. Mean time interval between diagnosis of haemochromatosis and hepatocellular carcinoma was 6.7 years. One patient underwent right hepatectomy, seven patients were treated by chemoembolisation and the remaining four patients were treated symptomatically. The median survival of the chemoembolised patients was 13 months. Of those patients treated symptomatically, the median survival was four months. Screening for hepatocellular carcinoma is often not undertaken in patients with haemochromatosis. Survival prospects are poor in patients whose tumour presents symptomatically.     

Costs of intensive treatment and follow-up of patients with multiple myeloma

In a retrospective study, we calculated the treatment and follow-up costs of patients with newly diagnosed multiple myeloma. The total treatment programme consisted of eight phases: VAD or VAMP chemotherapy, follow-up I, high-dose melphalan followed by transplantation of whole blood, follow-up II, collection of peripheral blood progenitor cells by leukapheresis, follow-up III, high-dose chemotherapy (busulfan/cyclophosphamide) followed by reinfusion of peripheral stem cells and follow-up IV (until 3 months from hospital discharge after peripheral stem cell transplantation). For each phase the average costs were calculated for all patients who were on treatment/follow-up in each particular phase. The total average cumulative costs of treatment and follow-up of all patients amounted to US$49850. Considering only the patients who completed the total treatment programme as it was scheduled, the average total treatment and follow-up costs were US$44800. The average costs of treatment and follow-up of patients who did not complete the programme as it was scheduled (patients who died, patients who were withdrawn from treatment and patients who received additional treatment) were US$57025.     

Screening to prevent renal failure in insulin dependent diabetic patients: an economic evaluation

OBJECTIVE: To examine the conditions necessary to make screening for microalbuminuria in patients with insulin dependent diabetes mellitus cost effective. DESIGN: This economic evaluation compared two strategies designed to prevent the development of end stage renal disease in patients with insulin dependent diabetes with disease for five years. Strategy A, screening for microalbuminuria as currently recommended, was compared with strategy B, a protocol in which patients were screened for hypertension and macroproteinuria. INTERVENTION: Patients identified in both strategies were treated with an angiotensin converting enzyme inhibitor. SETTING: Computer simulation. MAIN OUTCOME MEASURES: Strategy costs and quality adjusted life years (QALYs). RESULTS: The model predicted that strategy A would produce an additional 0.00967 QALYs at a present value cost of $261.53 (1990 US$) per patient (or an incremental cost/QALY of $27,041.69) over strategy B. The incremental cost/QALY for strategy A over B was sensitive to several variables. If the positive predictive value of screening for microalbuminuria (impact of false label and unnecessary treatment) is < 0.72, the effect of treatment to delay progression from microalbuminuria to macroproteinuria is < 1.6 years, the cumulative incidence of diabetic nephropathy falls to < 20%, or > 64% of patients demonstrate hypertension at the onset of microalbuminuria, then the incremental costs/QALY will exceed $75,000. CONCLUSION: Whether microalbuminuria surveillance in this population is cost effective requires more information. Being aware of the costs, recommendation pitfalls, and gaps in our knowledge should help focus our efforts to provide cost effective care to this population.     

Hereditary hemochromatosis

Genetic (hereditary) hemochromatosis is probably the most common autosomal recessive disorder found in white Americans, of whom about 5/1,000 (0.5 percent) are homozygous for the associated gene. The hemochromatosis gene is probably located close to the HLA-A locus on the short arm of chromosome 6. Homozygous individuals may develop severe and potentially lethal hemochromatosis, especially after age 39. Hereditary hemochromatosis involves an increased rate of iron absorption from the gut with subsequent progressive storage of iron in soft organs of the body. Excess iron storage eventually produces pituitary, pancreatic, cardiac, and liver dysfunction and death may result from cardiac arrhythmias, congestive heart failure, and/or hepatic failure or cancer. Early diagnosis can prevent these excess iron-induced problems. Iron overload owing to HLA-linked hereditary hemochromatosis can be distinguished from other causes of hemochromatosis by liver biopsies and interpretations. Patients at risk for genetic hemochromatosis should be screened, identified, and treated as early as age 20 to prevent or minimize the deadly complications of hemochromatosis. Population screening should include measurements of serum iron concentration, total iron binding capacity (TIBC), percent saturation of transferrin, and serum ferritin concentrations. Family members of hereditary hemochromatosis patients are at increased risk and should be tested. Screening, identification and early treatment (phlebotomies, sometimes in combination with the use of Desferal or other iron-chelating agents) may help prevent or reduce iron-related organ damage and premature deaths. Early diagnosis and treatment will reduce the population of aging individuals with severe, complicated hemochromatosis and dramatically reduce medical costs (billions of U.S. dollars per annum) associated with the management of this disease.     

Cost effectiveness of screening for primary open angle glaucoma

OBJECTIVES AND SETTING: To determine the cost effectiveness of screening for glaucoma. METHODS: Information on treatment efficacy, diagnostic methods, epidemiological characteristics of glaucoma, and costs were determined from the literature, from administrative databases, and from experts. Scenarios with different screening frequency, age, participation in screening, compliance with treatment, treatment efficacy, and diagnostic tests were examined. RESULTS: The initial scenario comprised three-yearly screening of subjects aged 40-79 by funduscopy and tonometry, followed by perimetry when abnormalities were discovered. The assumption of levels of participation in screening and of compliance with treatment of 75%, and treatment efficacy of 50% resulted in a cost of $C100,000 per year of blindness prevented. A scenario in which screening was restricted to subjects aged 65-79, with the same input variables, would prevent 81% of the cases of blindness prevented with scenario 1, at a cost of $C42,000 per year of blindness prevented. Screening with tonometry only as the initial diagnostic test in subjects aged 65-79 would result in a cost of $C36,000 per year of blindness prevented, but would only prevent 59% of the cases prevented with scenario 1. CONCLUSIONS: There is as yet no proof that treatment of glaucoma or of high intraocular pressure will arrest the progression of glaucoma to blindness. Even when treatment efficacy is assumed to be as high as 50%, however, the cost effectiveness of most glaucoma screening programmes considered would not be competitive.