Evaluation of venous thromboembolism risk assessment models for hospital inpatients: the VTEAM evidence synthesis.

Background: Pharmacological prophylaxis during hospital admission can reduce the risk of acquired blood clots (venous thromboembolism) but may cause complications, such as bleeding. Using a risk assessment model to predict the risk of blood clots could facilitate selection of patients for prophylaxis and optimise the balance of benefits, risks and costs. Objectives: We aimed to identify validated risk assessment models and estimate their prognostic accuracy, evaluate the cost-effectiveness of different strategies for selecting hospitalised patients for prophylaxis, assess the feasibility of using efficient research methods and estimate key parameters for future research. Design: We undertook a systematic review, decision-analytic modelling and observational cohort study conducted in accordance with Enhancing the QUAlity and Transparency Of health Research (EQUATOR) guidelines. Setting: NHS hospitals, with primary data collection at four sites. Participants: Medical and surgical hospital inpatients, excluding paediatric, critical care and pregnancy-related admissions. Interventions: Prophylaxis for all patients, none and according to selected risk assessment models. Main outcome measures: Model accuracy for predicting blood clots, lifetime costs and quality-adjusted life-years associated with alternative strategies, accuracy of efficient methods for identifying key outcomes and proportion of inpatients recommended prophylaxis using different models. Results: We identified 24 validated risk assessment models, but low-quality heterogeneous data suggested weak accuracy for prediction of blood clots and generally high risk of bias in all studies. Decision-analytic modelling showed that pharmacological prophylaxis for all eligible is generally more cost-effective than model-based strategies for both medical and surgical inpatients, when valuing a quality-adjusted life-year at £20,000. The findings were more sensitive to uncertainties in the surgical population; strategies using risk assessment models were more cost-effective if the model was assumed to have a very high sensitivity, or the long-term risks of post-thrombotic complications were lower. Efficient methods using routine data did not accurately identify blood clots or bleeding events and several pre-specified feasibility criteria were not met. Theoretical prophylaxis rates across an inpatient cohort based on existing risk assessment models ranged from 13% to 91%. Limitations: Existing studies may underestimate the accuracy of risk assessment models, leading to underestimation of their cost-effectiveness. The cost-effectiveness findings do not apply to patients with an increased risk of bleeding. Mechanical thromboprophylaxis options were excluded from the modelling. Primary data collection was predominately retrospective, risking case ascertainment bias. Conclusions: Thromboprophylaxis for all patients appears to be generally more cost-effective than using a risk assessment model, in hospitalised patients at low risk of bleeding. To be cost-effective, any risk assessment model would need to be highly sensitive. Current evidence on risk assessment models is at high risk of bias and our findings should be interpreted in this context. We were unable to demonstrate the feasibility of using efficient methods to accurately detect relevant outcomes for future research. Future work: Further research should evaluate routine prophylaxis strategies for all eligible hospitalised patients. Models that could accurately identify individuals at very low risk of blood clots (who could discontinue prophylaxis) warrant further evaluation. Study registration: This study is registered as PROSPERO CRD42020165778 and Researchregistry5216. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR127454) and will be published in full in Health Technology Assessment; Vol. 28, No. 20. See the NIHR Funding and Awards website for further award information.

People who are admitted to hospital are at risk of blood clots that can cause serious illness or death. Patients are often given low doses of blood-thinning drugs to reduce this risk. However, these drugs can cause side effects, such as bleeding. Hospitals currently use complex risk assessment models (risk scores, which usually include patient, disease, mobility and intervention factors) to determine the individual risk of blood clots and identify people most likely to benefit from blood-thinning drugs. There are a lot of different risk scores and we do not know which one is best. We also do not know how these scores compare to each other or whether using scores to decide who should get blood-thinning drugs provides good value for money to the NHS. We reviewed all previous studies of risk scores. We found that they did not predict blood clots very well and we could not recommend one score over another. We then created a mathematical model to simulate the use of blood-thinning drugs in people admitted to hospital. The model suggested that giving blood-thinning drugs to everyone who could have them would probably provide the best value for money, in medical patients. Our findings were the same, but less certain, for surgical patients. We also collected information from four NHS hospitals to explore possibilities for future research. Our work showed that routinely collected electronic data on blood clots and bleeding events is not very accurate and that using different scores could result in variable use of blood-thinning medications. Our findings suggest that it may be better value to the NHS and better for patients if we were to offer blood-thinning medications to everyone on admission to hospital, without using any risk score. However, this approach needs further research to ensure it is safe and effective. Such research would not be able to rely on routine electronic data to identify blood clots or bleeding events, in isolation.

Cost-effectiveness analysis of two interventions to promote physical activity in a multiethnic population at high risk of diabetes: an economic evaluation of the 48-month PROPELS randomized controlled trial.

INTRODUCTION: Physical activity (PA) is protective against type 2 diabetes (T2D). However, data on pragmatic long-term interventions to reduce the risk of developing T2D via increased PA are lacking. This study investigated the cost-effectiveness of a pragmatic PA intervention in a multiethnic population at high risk of T2D. MATERIALS AND METHODS: We adapted the School for Public Health Research diabetes prevention model, using the PROPELS trial data and analyses of the NAVIGATOR trial. Lifetime costs, lifetime quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for each intervention (Walking Away (WA) and Walking Away Plus (WA+)) versus usual care and compared with National Institute for Health and Care Excellence's willingness-to-pay of £20 000-£30 000 per QALY gained. We conducted scenario analyses on the outcomes of the PROPELS trial data and a threshold analysis to determine the change in step count that would be needed for the interventions to be cost-effective. RESULTS: Estimated lifetime costs for usual care, WA, and WA+ were £22 598, £23 018, and £22 945, respectively. Estimated QALYs were 9.323, 9.312, and 9.330, respectively. WA+ was estimated to be more effective and cheaper than WA. WA+ had an ICER of £49 273 per QALY gained versus usual care. In none of our scenario analyses did either WA or WA+ have an ICER below £20 000 per QALY gained. Our threshold analysis suggested that a PA intervention costing the same as WA+ would have an ICER below £20 000/QALY if it were to achieve an increase in step count of 500 steps per day which was 100% maintained at 4 years. CONCLUSIONS: We found that neither WA nor WA+ was cost-effective at a limit of £20 000 per QALY gained. Our threshold analysis showed that interventions to increase step count can be cost-effective at this limit if they achieve greater long-term maintenance of effect. TRIAL REGISTRATION NUMBER: ISRCTN registration: ISRCTN83465245: The PRomotion Of Physical activity through structuredEducation with differing Levels of ongoing Support for those with pre-diabetes (PROPELS)https://doi.org/10.1186/ISRCTN83465245.

What are the cost-savings and health benefits of improving detection and management for six high cardiovascular risk conditions in England? An economic evaluation.

OBJECTIVES: To estimate the cost savings and health benefits of improving detection of individuals at high risk of cardiovascular disease (CVD) in England, to determine to which patient subgroups these benefits arise, and to compare different strategies for subsequent management. DESIGN: An economic analysis using the School for Public Health Research CVD Prevention Model. SETTING: England 2018. PARTICIPANTS: Adults aged 16 and older with one or more high cardiovascular risk conditions, including hypertension, diabetes, non-diabetic hyperglycaemia, atrial fibrillation, chronic kidney disease and high cholesterol. INTERVENTIONS: Detection of 100% of individuals with CVD high risk conditions compared with current levels of detection in England. Detected individuals are assumed to be managed either according to current levels of care or National Institute of Health and Care Excellence (NICE) guidelines. MAIN OUTCOME MEASURES: Incremental and cumulative costs, savings, quality adjusted life years (QALYs), CVD cases, and net monetary benefit, from a UK NHS and Personal Social Services perspective. RESULTS: £68 billion could be saved, 4.9 million QALYs gained and 3.4 million cases of CVD prevented over 25 years if all individuals in England with the six CVD high risk conditions were diagnosed and subsequently managed at current levels. Additionally, if all detected individuals were managed according to NICE guidelines, total savings would be £61 billion, 8.1 million QALYs would be gained and 5.2 million CVD cases prevented. Most benefits come from detection of high cholesterol in the short term and diabetes in the long term. CONCLUSIONS: Substantial cost savings and health benefits would accrue if all individuals with conditions that increase CVD risk could be diagnosed, with detection of undiagnosed diabetes producing greatest benefits. Ensuring all conditions are managed according to NICE guidelines would further increase health benefits. Projected cost-savings could be invested in developing acceptable and cost-effective solutions for improving detection and management.

Assessing the potential return on investment of the proposed UK NHS diabetes prevention programme in different population subgroups: an economic evaluation.

OBJECTIVES: To evaluate potential return on investment of the National Health Service Diabetes Prevention Programme (NHS DPP) in England and estimate which population subgroups are likely to benefit most in terms of cost-effectiveness, cost-savings and health benefits. DESIGN: Economic analysis using the School for Public Health Research Diabetes Prevention Model. SETTING: England 2015-2016. POPULATION: Adults aged ≥16 with high risk of type 2 diabetes (HbA1c 6%-6.4%). Population subgroups defined by age, sex, ethnicity, socioeconomic deprivation, baseline body mass index, baseline HbA1c and working status. INTERVENTIONS: The proposed NHS DPP: an intensive lifestyle intervention focusing on dietary advice, physical activity and weight loss. Comparator: no diabetes prevention intervention. MAIN OUTCOME MEASURES: Incremental costs, savings and return on investment, quality-adjusted life-years (QALYs), diabetes cases, cardiovascular cases and net monetary benefit from an NHS perspective. RESULTS: Intervention costs will be recouped through NHS savings within 12 years, with net NHS saving of £1.28 over 20 years for each £1 invested. Per 100 000 DPP interventions given, 3552 QALYs are gained. The DPP is most cost-effective and cost-saving in obese individuals, those with baseline HbA1c 6.2%-6.4% and those aged 40-74. QALY gains are lower in minority ethnic and low socioeconomic status subgroups. Probabilistic sensitivity analysis suggests that there is 97% probability that the DPP will be cost-effective within 20 years. NHS savings are highly sensitive to intervention cost, effectiveness and duration of effect. CONCLUSIONS: The DPP is likely to be cost-effective and cost-saving under current assumptions. Prioritising obese individuals could create the most value for money and obtain the greatest health benefits per individual targeted. Low socioeconomic status or ethnic minority groups may gain fewer QALYs per intervention, so targeting strategies should ensure the DPP does not contribute to widening health inequalities. Further evidence is needed around the differential responsiveness of population subgroups to the DPP.

Differences in organ system of distant metastasis by renal cell carcinoma subtype.

PURPOSE: The majority of the published data regarding the rates of renal cell carcinoma metastasis to specific locations has examined renal cell carcinoma as a whole. We evaluated site of distant metastasis by renal cell carcinoma histological subtype. MATERIALS AND METHODS: We studied 910 patients treated with radical nephrectomy for clear cell, papillary or chromophobe renal cell carcinoma at the Mayo Clinic between 1970 and 2000 who had distant metastasis at nephrectomy or who had metastasis during followup. The sites of metastases were compared by histological subtype using the chi-square and Fisher exact tests. RESULTS: There were 853 (94%) patients with clear cell, 39 (4%) with papillary and 18 (2%) with chromophobe renal cell carcinoma. Median followup for the 65 patients who were still alive at last followup was 11.6 years. Patients with clear cell renal cell carcinoma were more likely to have metastasis to the lungs (53.6%) compared to those with papillary (33.3%) and chromophobe (33.3%) renal cell carcinoma (p = 0.012). Patients with chromophobe renal cell carcinoma were more likely to have metastasis to the liver compared to those with clear cell renal cell carcinoma (33.3% vs 9.7%, p = 0.007), but there was not a statistically significantly difference in the incidence of liver metastases between patients with chromophobe and papillary renal cell carcinoma (33.3% vs 18.0%, p = 0.308). CONCLUSIONS: Site of distant metastasis varies significantly by renal cell carcinoma histological subtype. Patients with clear cell renal cell carcinoma are more likely to have metastasis to the lungs while patients with chromophobe renal cell carcinoma are more likely to experience liver metastasis.

Low IGF-1 levels are associated with cardiovascular risk factors in haemodialysis patients.

Cardiovascular diseases (CVD) constitute a significant risk and may, in part, explain the high morbidity and mortality rates among haemodialysis (HD) patients. Several studies have implicated reduced insulin like growth factor (IGF-1) levels in the development of CVD. However, it is not clear whether IGF-1, and its relationship with other hormones such as leptin, insulin, and growth hormone (GH), as well as anthropometric variables may explain the high incidence of vascular complications in chronic kidney disease (CKD) patients. This study was designed to measure total serum IGF-1, leptin, insulin and GH levels in CKD patients and in age-matched control subjects and to elucidate the relationship between IGF-1 and GH, leptin, and insulin as well as other known aetiological risk factors for CVD including blood pressure, body mass index (BMI), and age. The study consisted of 50 CKD patients [36 M and 14 F; mean age; 41.8 +/- 10.3 years) on maintenance haemodialysis and 50 healthy control subjects (36 M and 14 F; mean age 41.6 +/- 10.2 years) matched for age and sex. None of the subject among patients and controls reported either smoking or history of diabetes mellitus. The circulating levels of IGF-1 were significantly lower (P < 0.001) in both male and female patients compared to the control subjects. Moreover, IGF-1 was strongly and inversely correlated with both systolic blood pressure (SBP) (r = -0.360; P < 0.01) and diastolic blood pressure (DBP) (r = -0.512; P < 0.001) in the CKD group, and when the two groups were combined SBP (r = -0.396; P < 0.001) and DBP (r = -0.296; P < 0.01). When adjusted for age, the correlation was more significant, however, when adjusted for BMI no significant correlation was observed between IGF-1 and blood pressure. IGF-1 was inversely correlated with age (r = -0.367; P < 0.01) and BMI (r = -0.310; P < 0.05) in the control group, but not the patient group. In controls and patients, respectively, a positive correlation between leptin and BMI (r = 0.358; P < 0.01; r = 0.640, P < 0.001) was observed. The results show that circulating levels of IGF-1 were significantly lower in CKD patients as compared to healthy normal subjects and were inversely correlated with SBP and DBP independent of age, but not BMI indicative of a strong relationship between cardiovascular risk factors and low IGF-1 levels. Although, the data do not clearly indicate low IGF-1 levels as a cause or an effect of these cardiovascular risk factors, they do point to an interesting relationship between low IGF-1 levels and increased cardiovascular risk factors among CKD patients as compared to age-matched healthy control subjects.

Predicting the impact of population level risk reduction in cardio-vascular disease and stroke on acute hospital admission rates over a 5 year period--a pilot study.

UNLABELLED: The brief for this study was to produce a practical, evidence based, financial planning tool, which could be used to present an economic argument for funding a public health-based prevention programme in coronary heart disease (CHD) related illness on the same basis as treatment interventions. OBJECTIVES: To explore the possibility of using multivariate risk prediction equations, derived from the Framingham and other studies, to estimate how many people in a population are likely to be admitted to hospital in the next 5-10 years with cardio vascular disease (CVD) related events such as heart attacks, strokes, heart failure and kidney disease. To estimate the potential financial impact of reductions in hospital admissions, on an 'invest to save' basis, if primary care trusts (PCTs) were to invest in public health based interventions to reduce cardiovascular risk at a population level. STUDY DESIGN: The populations of five UK PCTs were entered into a spreadsheet based decision tree model, in terms of age and sex (this equated to around 620,000 adults). An estimation was made to determine how many people, in each age group, were likely to be diabetic. Population risk factors such as smoking rates, mean body mass index (BMI), mean total cholesterol and mean systolic blood pressure were entered by age group. The spreadsheet then used a variant of the Framingham equation to calculate how many non-diabetic people in each age group were likely to have a heart attack or stroke in the next 5 years. In addition heart failure and dialysis admission rates were estimated based upon risk factors for incidence. The United Kingdom Prospective Diabetes Study (UKPDS) risk engines 56 and 60 were used to calculate the risk of CHD and stroke, respectively, in people with type 2 diabetes. The spreadsheet deducted the number of people likely to die before reaching hospital and produced a predicted number of hospital admissions for each category over a 5-year period. The final part of the calculation attached a cost to the hospital activity using the UK Health Resource Grouping (HRG) tariffs. The predicted number of events in each of the primary care trusts was then compared with the actual number of events the previous year (2004/2005). METHODOLOGY: The study used a decision tree type model, which was populated with data from the research literature. The model applied the risk equations to population data from five primary care trusts to estimate how many people would suffer from an acute CVD related event over the next 5 years. The predicted number of events was then compared with the actual number of acute admissions for heart attacks, strokes, heart failure, acute hypoglycaemic attacks, renal failure and coronary bypass surgery the previous year. RESULTS: The first outcome of the model was to compare the estimated number of people in each PCT likely to suffer from a heart attack, a stroke, heart failure or chronic kidney failure with the actual number the previous year 2004/2005. The predicted number was remarkably accurate in the case of heart attack and stroke. There was some over-prediction of chronic kidney disease (CKD) which could be accounted for by known under-diagnosis in this illness group and the inability of the model to pick up, at this stage, the fact that many CKD patients die of a CHD related event before they reach the stage of requiring renal replacement. The second outcome of the model was to estimate the financial consequence of risk reduction. Moderate reductions in risk in the order of around 2-4% were estimated to lead to saving in acute admission costs or around pounds sterling 5.4 million over 5 years. More ambitious targets of risk reduction in the order of 5-6% led to estimated savings of around pounds sterling 8.7 million. CONCLUSIONS: This study is not presented as the definitive approach to predicting the economic consequences of investment in public health on the cost of secondary care. It is simply a logical, systematic approach to quantifying these issues in order to present a business case for such investment. The research team do not know if the predicted savings would accrue from such investments; it is theoretical at this stage. The point is, however, that if the predictions are correct then the savings will accrue from over 4000 people, from an adult population of around 185,000 not having a heart attack or a stroke or an acute exacerbation of heart failure.

Circulating levels of endothelin-1 in a homogenous Gulf Arab population with untreated essential hypertension.

BACKGROUND: Racial variations are reported in the natural history of hypertension. For example, hypertension is significantly more prevalent in blacks than whites. Endothelial cells are important regulators of vascular tone and homeostasis, in part through secretions of vasoactive substances including endothelin-1 (ET-1), a small peptide with potent vasopressor actions. In black hypertensives, ET-1 levels are higher than in normotensive blacks and in both hypertensive and normotensive whites. Since ET-1 might play a significant role in the development and severity of hypertension in the indigenous Arab population of the United Arab Emirates, we investigated the circulating levels of ET-1 in this homogenous population. PATIENTS AND METHODS: ET-1 levels were measured in plasma samples from 60 untreated hypertensive Arabs and compared with 60 age- and sex-matched normotensive controls. RESULTS: ET-1 levels were significantly higher in hypertensives (mean 10.1 +/- 1 pmol/L) than normotensives (mean 2.2 +/- 0.5 pmol/L). Body mass index (BMI) was slightly higher among the hypertensives. For all subjects these levels significantly (P < 0.001) correlated with systolic blood pressure and less significantly (P < 0.05) with diastolic blood pressure and body weight. The correlation between ET-1 and both systolic and diastolic blood pressure was persistently significant after adjusting for BMI. CONCLUSION: Plasma concentrations of ET-1 are significantly higher in hypertensive Gulf Arabs as compared with reported levels in white hypertensives and ET-1 could be a risk factor for cardiovascular diseases in this population. The endothelial system might be particularly important with respect to hypertension in this racial group and merits further study.

Case report: intraoperative anaphylactoid reaction and hydroxyethyl starch in balanced electrolyte solution (Hextend).

PURPOSE: To report a first case of probable anaphylactoid reaction to 6% hydroxyethyl starch reconstituted in balanced electrolyte and glucose solution (Hextend). CLINICAL FEATURES: A 22-yr-old man was admitted for a partial nephrectomy. Near the end of the four-hour operation, an infusion of Hextend was initiated. Shortly thereafter, mechanical ventilation became difficult, peak inspiratory pressure increased to 55 cm H2O with audible wheezing over the patient's lungs. Blood pressure suddenly decreased to 68/46 mmHg. Multiple doses of phenylephrine, ephedrine and epinephrine were required to restore the patient's blood pressure. Postoperatively, a diffuse urticarial rash was apparent on his upper torso. The patient recovered uneventfully. His postoperative serum tryptase was 26.3 ng x mL(-1) (reference range, < 11.5 ng x mL(-1)) and the urine N-methyl-histamine was 2448 microg x g(-1) creatinine (reference range, 30-200 microg x g(-1) creatinine). Two months after the event, skin testing was conducted to test for possible allergy to latex, lidocaine, propofol, cisatracurium, succinylcholine, vecuronium, midazolam, fentanyl, ondansetron, neostigmine, and cephazolin, and all were negative. Hextend was also tested, starting with a 1:100,000 dilution and the results were negative. CONCLUSIONS: The temporal relationship of severe hypotension, bronchospasm and skin rash within ten minutes from administration of Hextend in this patient suggests an immediate hypersensitivity reaction to hetastarch. The elevated levels of serum tryptase and urinary N-methyl-histamine suggest that this hypersensitivity was mediated from mast cell degranulation. Negative skin testing suggests that the reaction was anaphylactoid.

Costimulatory molecule B7-H1 in primary and metastatic clear cell renal cell carcinoma.

BACKGROUND: Cancer cell expression of costimulatory molecule B7-H1 has been implicated as a potent inhibitor of T-cell-mediated antitumoral immunity. The authors recently reported that B7-H1 is aberrantly expressed in primary renal cell carcinoma (RCC). Blockade of B7-H1, as demonstrated in several murine cancer models, now represents a promising therapeutic target in RCC. However, the potential expression of B7-H1 in metastatic RCC has not been investigated. In the current study, the authors updated their primary RCC results with additional follow-up and investigated the potential role of B7-H1 in metastatic RCC. METHODS: Between 2000 and 2004, 196 patients underwent nephrectomy and 26 patients had resection of RCC metastases for clear cell RCC. Immunohistochemical analysis was performed on tumor cryosections using a B7-H1 monoclonal antibody (clone 5H1). A urologic pathologist quantified the percentage of B7-H1-positive tumor cells and lymphocytes. RESULTS: Variable levels of B7-H1 were expressed on primary RCC tumor cells (n = 130 [66.3%]) and primary tumor-infiltrating lymphocytes (n = 115 [58.7%]). Patients with high expression of B7-H1 on primary tumor cells and/or lymphocytes were significantly more likely to die of RCC compared with patients with low B7-H1 expression (risk ratio [RR] = 4.17; 95% confidence interval [95% CI], 1.97-8.84; P < 0.001) and this risk persisted in multivariate analysis after adjusting for the Mayo Clinic stage, size, grade, and necrosis score (RR = 2.63; 96% CI, 1.23-5.64; P = 0.013). Of the 26 metastatic specimens, cancer cell and lymphocyte B7-H1 expression were demonstrated in 17 (65.4%) and 18 (69.2%) specimens, respectively. In total, 14 (54.3%) metastatic specimens had high aggregate B7-H1 levels compared with 44.4% in primary RCC specimens. CONCLUSIONS: Patients with RCC with high B7-H1 expression were significantly more likely to die even after multivariate analysis. The authors also demonstrated that a high percentage of RCC metastases similarly harbored B7-H1. The authors surmised that B7-H1 blockade may augment current immunotherapy, including patients treated for metastases after cytoreductive nephrectomy.

Should the upper tracts be imaged for microscopic haematuria?

OBJECTIVE: To determine the relative prevalence of various definitions of microscopic haematuria (MH) in patients with renal neoplasms and controls, and to predict the likely outcome of renal imaging for those definitions. PATIENTS AND METHODS: In a retrospective case-control study 278 adult men and woman seen between 1998 and 2003 with untreated renal neoplasms were compared to controls matched for age and sex. All cases and controls had renal imaging within 6 months of a urine analysis. Patients were excluded for gross haematuria or other conditions associated with MH but not relevant to upper tract imaging. Adjusted odds ratios (OR) computed for 13 definitions of MH by conditional logistic regression were the primary outcome measures. Additional outcome measures were ORs in selected subsets. Hypothetical performance characteristics of a positive urine analysis were then derived to predict the likely results of detecting renal neoplasms for each definition of MH. RESULTS: The OR (95% confidence interval) for the entire series of cases and controls, both symptomatic and asymptomatic, was 2.0 (1.02-3.92, P = 0.04) for MH defined as > or = 4 red blood cells per high-power field (RBC/HPF) and 2.2 (1.09-4.52, P = 0.03) for > or = 5 RBC/HPF. No significant OR was calculated for < or = 3 RBC/HPF, nor for a subgroup of patients with MH in a routine urine analysis obtained during a periodic health examination. Symptomatic patients had an OR of 13.68 (1.6-117.1, P = 0.02) for MH defined as > or = 5 RBC/HPF. The sensitivity of a positive test decreased from 24.8% to 5.04% as the definition for MH became more stringent. The theoretical positive predictive value (assuming a prevalence of renal cell neoplasms of 0.25%) of the most stringent definition of MH was 0.58%. CONCLUSIONS: Patients with renal neoplasms have about twice the prevalence of MH with > or = 4 or 5 RBC/HPF in a single urine sample compared with matched controls, but this difference has little impact on the hypothetical detection rate of renal cancer. Imaging the kidney for low-grade MH in a routine urine analysis discovered at a periodic health examination in an otherwise asymptomatic patient is tantamount to screening without cause, and can be deferred for selected patients. The clinical context is as important as the degree of MH when deciding to image the kidneys.

Comparison of presentation and outcome for patients 18 to 40 and 60 to 70 years old with solid renal masses.

PURPOSE: We compared histological subtype, pathological features and outcome of patients with solid renal masses who were 18 to 40 years old vs patients who were 60 to 70 years old. MATERIALS AND METHODS: We conducted a retrospective review of the Mayo Clinic Nephrectomy Registry from 1970 to 2000, and identified 124 patients 18 to 40 years old and 1,067 patients 60 to 70 years old available for analysis. RESULTS: There was no significant difference in the incidence of benign solid renal masses between patients 18 to 40 years old and those 60 to 70 years old (13.7% vs 10.2%). Among patients with renal cell carcinoma (RCC), younger patients were more likely to have chromophobe RCC (13.1% vs 3.6%) and less likely to have clear cell RCC (70.1% vs 81.5%) than older patients. Among patients with clear cell RCC, younger patients were more likely to have stage pT2b or lower tumors (82.7% vs 69.9%) and a higher incidence of cystic clear cell RCC (10.7% vs 2.2%) than older patients. Younger patients had an improved cancer specific survival compared with older patients but this difference was not statistically significant (risk ratio 0.71, p =0.127). CONCLUSIONS: We found that patients 18 to 40 years old were more likely to have chromophobe and less likely to have clear cell RCC compared with patients 60 to 70 years old. We did not identify a higher incidence of papillary RCC in younger patients. Patients with clear cell RCC 18 to 40 years old had a higher incidence of low stage and cystic tumors compared with patients 60 to 70 years old, features which have been shown to have a favorable prognosis. These factors likely contributed to improved cancer specific survival for younger patients.

Split-thickness skin graft for the management of concealed penis.

PURPOSE: We review the use of split-thickness skin grafting in children with concealed penis. MATERIALS AND METHODS: Medical records were retrospectively reviewed for all patients younger than 20 years seen at our institution from 1995 to 2003 with a diagnosis of concealed penis. Patients were separated into "primary" and "secondary" groups based on the cause of concealment. Primary factors were prominent prepubic fat pad, dysgenetic dartos fascia or both. Secondary factors were post-circumcision phimosis and overzealous circumcision. RESULTS: A total of 26 patients 1 month to 19 years old were treated. In the primary group of 23 patients 11 underwent lysis of dartos fascia. Four of these 11 patients had insufficient skin, and split-thickness skin grafting was necessary to resurface the penile shaft. Five of the patients underwent excision of the fat pad only, and 2 underwent excision of the fat pad and lysis of fascia. Five patients are being observed. Of the 3 patients in the secondary group 1 underwent manual reduction of post-circumcision phimosis, 1 underwent scrotal flaps and 1 is being observed. Followup ranged from 2 weeks to 46 months (mean 13 months). Of 20 surgically repaired patients 19 (95%) had an excellent cosmetic result, were satisfied with penile length and reported no voiding complaints. CONCLUSIONS: The surgical approach for correcting concealed penis varies, depending on the cause. Of our 26 patients 4 (15%) had insufficient penile skin to resurface the penile shaft. In these select children split-thickness skin grafting provided a good cosmetic appearance and functional result.

Plasma concentrations of non-esterified fatty acids in chronic renal failure in the United Arab Emirates.

OBJECTIVE: In end-stage renal failure, dyslipoproteinemia is linked to risk of cardiovascular disease. Increased concentrations of triacylglycerol-rich, very low density lipoproteins (VLDL) and decreased concentrations of high density lipoproteins (HDL) are usual, whilst total cholesterol and low density lipoprotein (LDL) concentrations are not increased. Non-esterified fatty acids (NEFA) are not transported by lipoproteins, but increased concentrations may also be associated with cardiovascular disease risk. In this study, plasma concentrations of NEFA and other lipids were compared in healthy subjects and patients with end-stage chronic renal failure who were either undialyzed or undergoing peritoneal dialysis or hemodialysis. METHODS: Fasted blood samples for measurement of albumin, total, free and HDL-cholesterol, triacylglycerols and NEFA were taken from 56 apparently healthy subjects and from 48, 28 and 46 patients from the United Arab Emirates during 2002 who were either untreated or on peritoneal or hemodialysis. Hemodialysis subjects were studied immediately before and after a single treatment session. RESULTS: For all groups of patients, total, and LDL-cholesterol were unchanged, triacylglycerols and free cholesterol were raised and HDL-cholesterol concentrations and the percentage of esterified cholesterol were significantly decreased compared to controls. Plasma NEFA concentrations for untreated patients were similar to controls, but were decreased in peritoneal dialysis patients and markedly increased both before and, even more so, after dialysis in hemodialysis patients. CONCLUSION: Patients with end-stage renal failure share common features of dyslipoproteinemia irrespective of whether they are untreated or on peritoneal dialysis or hemodialysis. However, only hemodialysis patients show significantly increased concentrations of NEFA.

Tissue ablation technologies for localized prostate cancer.

Traditional treatments for men with localized prostate cancer have included both surgical removal and radiation therapy, with their potential adverse effects on patient quality of life. Thus, there has been increasing interest in the development of minimally invasive procedures that use various technologies to deliver lethal doses of heat or cold to the prostate in an attempt to kill cancer cells. At the same time, it is vital that these newer techniques ablate prostate tissue and spare vital periprostatic organs essential for maintaining function and quality of life. In this article, we evaluate the current status of tissue ablation modalities in the treatment of clinically localized prostate cancer, focusing on the different methods, early results, and possible future directions. Although still in the beginning stages, these newer forms of treatment offer exciting potential for first-line and second-line treatment of this common urologic malignancy.

Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target.

Expression of B7-H1, a costimulating glycoprotein in the B7 family, is normally restricted to macrophage-lineage cells, providing a potential costimulatory signal source for regulation of T cell activation. In contrast, aberrant expression of B7-H1 by tumor cells has been implicated in impairment of T cell function and survival, resulting in defective host antitumoral immunity. The relationship between tumor-associated B7-H1 and clinical cancer progression is unknown. Herein, we report B7-H1 expression by both renal cell carcinoma (RCC) tumors of the kidney and RCC tumor-infiltrating lymphocytes. In addition, our analysis of 196 clinical specimens reveals that patients harboring high intratumoral expression levels of B7-H1, contributed by tumor cells alone, lymphocytes alone, or tumor and/or lymphocytes combined, exhibit aggressive tumors and are at markedly increased risk of death from RCC. In fact, patients with high tumor and/or lymphocyte B7-H1 levels are 4.5 times more likely to die from their cancer than patients exhibiting low levels of B7-H1 expression (risk ratio 4.53; 95% confidence interval 1.94-10.56; P < 0.001.) Thus, our study suggests a previously undescribed mechanism whereby RCC may impair host immunity to foster tumor progression. B7-H1 may prove useful as a prognostic variable for RCC patients both pre- and posttreatment. In addition, B7-H1 may represent a promising target to facilitate more favorable responses in patients who require immunotherapy for treatment of advanced RCC.