[Application and comparison of three occupational health risk assessment methods in an automobile manufacturing industry].

Objective: Three occupational health risk assessment methods were used to assess the occupational health risk of noise exposed posts in an automobile manufacturing enterprise. According to the results, the selection of risk assessment methods and risk management of such occupational noise enterprises were provided. Methods: Form April to November 2021, The occupational health field survey was carried out in an automobile manufacturing industry in Tianjin. The occupational health MES risk assessment method, occupational health risk index risk assessment method and Australian occupational hazard risk assessment method were used to evaluate the occupational health risk of noise-exposed posts in this enterprise, and the evaluation results of different methods were analyzed and compared. Results: The average value of L(Aeq, 8 h) in the four workshops of automobile manufacturing industry was 82.95 dB (A) , and the noise detection exceeding rate was 22.41% (26/116) . The LAeq, 8h and exceeding rate noise of welding workshop were higher than those of other workshops (χ(2)=23.56, 32.94, P<0.01) . The three occupational health risk assessment methods have the same risk assessment results for the four major workshops. The assembly and painting workshops are level 4 risk (possible risk) , and the stamping and welding workshops are level 3 risk (significant risk) . Conclusion: Occupational noise has certain potential hazards to workers in automobile manufacturing enterprises. Therefore, in the future work, corresponding organizational management measures should be taken to improve the working environment and reduce the actual exposure level of workers in order to protect the health of occupational workers.

[Effect of sedation on resting energy expenditure in patients with extremely severe burns and the choice of energy estimation formula].

Objective: To investigate the effect of sedation on resting energy expenditure (REE) in patients with extremely severe burns and the choice of REE estimation formula during the treatment. Methods: A retrospective non-randomized controlled clinical study was conducted. From April 2020 to April 2022, 21 patients with extremely severe burns who met the inclusion criteria and underwent mechanical ventilation treatment were admitted to the Department of Burn and Wound Repair of Second Affiliated Hospital of Zhejiang University School of Medicine, including 16 males and 5 females, aged 60 (50, 69) years. Early anti-shock therapy, debridement, skin transplantation, nutritional support, and other conventional treatments were applied to all patients. Patients were sedated when they had obvious agitation or a tendency to extubate, which might lead to aggravation of the disease. REE measurement was performed on patients using indirect calorimetry on post-injury day 3, 5, 7, 9, 11, 14 and every 7 days thereafter until the patient died or being successfully weaned from ventilator. Totally 99 times of measurements were carried out, of which 58 times were measured in the sedated state of patients, and 41 times were measured in the non-sedated state of patients. The age, weight, body surface area, residual wound area, post-injury days of patients were recorded on the day when REE was measured (hereinafter briefly referred to as the measurement day). The REE on the measurement day was calculated with intensive care unit conventional REE estimation formula Thumb formula and special REE estimation formulas for burns including the Third Military Medical University formula, the Peng Xi team's linear formula, Hangang formula. The differences between the sedated state and the non-sedated state in the clinical materials, measured and formula calculated values of REE of patients on the measurement day were compared by Mann-Whitney U test and independent sample t test. The differences between the REE formula calculated values and the REE measured value (reflecting the overall consistency) in the sedated state were compared by Wilcoxon signed rank-sum test. The Bland-Altman method was used to assess the individual consistency between the REE formula calculated value and the REE measured value in the sedated state, and to calculate the proportion of the REE formula calculated value within the range of ±10% of the REE measured value (hereinafter referred to as the accuracy rate). Root mean square error (RMSE) was used to evaluate the accuracy of the REE formula calculated value relative to the REE measured value. Results: Compared with those in the non-sedated state, there was no statistically significant change in patient's age or post-injury days on the measurement day in the sedated state (P>0.05), but the weight was heavier (Z=-3.58, P<0.01), and both the body surface area and the residual wound area were larger (with Z values of -2.99 and -4.52, respectively, P<0.01). Between the sedated state and the non-sedated state, the REE measured values of patients were similar (P>0.05). Compared with those in the non-sedated state, the REE values of patients calculated by Thumb formula, the Third Military Medical University formula, the Peng Xi team's linear formula, and Hangang formula on the measurement day in the sedated state were significantly increased (with Z values of -3.58 and -5.70, t values of -3.58 and -2.74, respectively, P<0.01). In the sedated state, compared with the REE measured value, there were statistically significant changes in REE values of patients calculated by Thumb formula, the Third Military Medical University formula, and Hangang formula on the measurement day (with Z values of -2.13, -5.67, and -3.09, respectively, P<0.05 or P<0.01), while the REE value of patients calculated by the Peng Xi team's linear formula on the measurement day did not change significantly(P>0.05). The analysis of the Bland-Altman method showed that in the sedated state, compared with the REE measured value, the individual consistency of the calculated value of each formula was good; Thumb formula and Hangang formula significantly underestimated the patients' REE value (with the average value of the difference between the formula calculated value and the measured value of -1 463 and -1 717 kJ/d, the 95% confidence interval of -2 491 to -434 and -2 744 to -687 kJ/d, respectively), but the individual differences were small; the Third Military Medical University formula significantly overestimated the patients' REE value (with the average value of the difference between the formula calculated value and the measured value of 3 530 kJ/d, the 95% confidence interval of 2 521 to 4 539 kJ/d), but the individual difference was small; the Peng Xi team's linear formula did not significantly overestimate the patients' REE value (with the average value of the difference between the formula calculated value and the measured value of 294 kJ/d, the 95% confidence interval of -907 to 1 496 kJ/d), while the difference standard deviation was 4 568 kJ/d, which showed a large individual difference. In the sedated state, relative to the REE measured value, the accuracy rates of REE values calculated by Thumb formula, the Third Military Medical University formula, the Peng Xi team's linear formula, and Hangang formula were 25.9% (15/58), 15.5% (9/58), 10.3% (6/58), and 15.5% (9/58), respectively, and RMSE values were 4 143.6, 5 189.1, 4 538.6, and 4 239.8 kJ/d, respectively. Conclusions: Sedative therapy leads to a significant decrease in REE in patients with extremely severe burns undergoing mechanical ventilation treatment. When REE cannot be regularly monitored by indirect calorimetry to determine nutritional support regimens, patients with extremely severe burns undergoing sedation may be prioritized to estimate REE using Thumb formula.

[Health hazards and hearing loss risk assessment of workers exposed to noise in an automobile manufacturing enterprise].

Objective: To investigate the current situation of occupational exposure to noise among noise workers in an automobile manufacturing enterprise in Tianjin, understand the impact of noise on workers＇ nervous system and hearing, and assess the risk of hearing loss among noise workers. Methods: In May 2021, 3516 workers in an automobile manufacturing enterprise were investigated by using a self-made questionnaire＂Noise Workers Questionnaire＂ and cluster sampling method. The occupational noise hygiene survey and occupational hazards detection were carried out in their workplaces. They were divided into noise exposure group and non-noise exposure group according to whether they were exposed to noise or not. The general characteristics, hearing and nervous system symptoms of the two groups of workers were compared, and the risk of hearing loss was assessed. Results: There were 758 workers in the noise exposure group, aged (26±5) years old, with a working age of 3.0 (2.0, 6.0) years exposed to noise. 2758 workers in the non-noise exposure group, aged (25±6) years old, with a working age of 2.0 (1.0, 4.0) years. There were statistically significant differences in the distribution of workers＇education level, working age and memory loss between the two groups (χ(2)=37.98, 38.70, 5.20, P<0.05). The workers in the noise exposure group showed a decreasing trend of insomnia, dreaminess, sweating and fatigue with the increase of working age (χ(2trend)=6.16, 7.99, P<0.05). The risk classification of binaural high-frequency hearing loss for workers in all noise positions until the age of 50 and 60 was negligible, the risk of occupational noise deafness was low for workers in stamping and welding noise positions until the age of 60. Conclusion: The occupational noise exposed to automobile manufacturing workers may cause certain harm to their nervous and auditory systems. Noise protection measures should be taken to reduce the risk of hearing loss and occupational noise deafness.

Factors associated with symptoms of poor mental health among women factory workers in China's supply chain.

OBJECTIVE: Foreign direct investment (FDI) to China has motivated increased labor migration to export processing zones (EPZs). Work environments with high occupational stress, such as production line jobs typical in EPZs, have been associated with adverse mental health symptoms. METHODS: A cross-sectional survey that examined occupational stress and symptoms of poor mental health was implemented among Chinese women factory workers in three electronic factories in the Tianjin Economic-Technological Development Area. Symptoms of mental health measured in the survey were hopelessness, depression, not feeling useful or needed, and trouble concentrating. Crude and adjusted prevalence odds ratios and their 95% confidence intervals were calculated with logistic regression. RESULTS: Responses were collected from 696 women factory workers. Participants were aged 18-56 years (mean 28 ± 5.8), 66% of whom were married and 25% of whom were migrants. Nearly 50% of participants reported at least one symptom of poor mental health. After adjusting for covariates associated with each outcome in the bivariate analysis, high job strain was associated with hopelessness (OR 2.68, 95% CI 1.58, 4.56), not feeling useful (OR 2.05, 95% CI 1.22, 3.43), and feeling depressed (OR 1.78, 95% CI 1.16, 2.72). CONCLUSION: This study expands on the international body of research on the well-being of women working in the global supply chain and provides evidence on the associations between occupational stressors, migration, and social support on symptoms of poor mental health among women workers. Future research to better understand and improve psychological health and to prevent suicide among workers in China's factories is critical to improve the health of China's labor force.

Use of the Patient-Generated Subjective Global Assessment to Identify Pre-Frailty and Frailty in Hospitalized Older Adults.

OBJECTIVES: The Scored Patient-Generated Subjective Global Assessment (PG-SGA) and Edmonton Frail Scale (EFS) are widely used in acute care settings to assess nutritional and frailty status, respectively. We aimed to determine whether the scored PG-SGA can identify pre-frailty and frailty status, to simultaneously evaluate malnutrition and frailty in clinical practice. DESIGN: Cross-sectional study. SETTINGS AND PARTICIPANTS: A convenience sample of 329 consecutive patients admitted to an acute medical unit in South Australia. MEASUREMENTS: Nutritional and frailty status were ascertained with scored PG-SGA and EFS, respectively. Optimal cut-off scores to identify pre-frailty and frailty were determined by calculating the Scored PG-SGA's sensitivity, specificity, positive and negative predictive values, Youden Index (YI), Liu index, Receiver Operator Curves (ROC) and Area Under Curve (AUC). Nutritional status and patient characteristics were analysed according to frailty categories. RESULTS: The optimal cut-off PG-SGA score as determined by the highest YI, to identify both pre-frailty and frailty was >3, with a sensitivity of 0.711 and specificity of 0.746. The AUC was 0.782 (95% CI 0.731-0.833). In this cohort, 64% of the patients were well-nourished, 26% were moderately malnourished and 10% were severely malnourished. Forty-three percent, 24% and 33% of the patients were classified as robust, pre-frail and frail, respectively. Bivariate analysis showed that those robust were significantly younger than those who were pre-frail (-2.8, 95% CI -5.5 to -0.1, p=0.036) or frail (-3.4, 95% CI -5.9 to -1.0, p=0.002). Robust patients had significantly lower Scored PG-SGA than those who were pre-frail (-2.5, 95%CI -3.8 to -1.1, p<0.001) or frail (-4.9, 95% CI -6.1 to -3.7, p<0.001). CONCLUSION: The Scored PG-SGA is moderately sensitive in identifying pre-frailty/frailty in older hospitalized adults and can be useful in identifying both conditions concurrently.

[Clinical effect and economic benefit evaluation of minimally invasive surgery for drivers with lumbar disc herniation].

Objective: To investigate the clinical effect of minimally invasive surgery in the treatment of professional drivers with lumbar disc herniation. Methods: 126 patients with lumbar disc herniation admitted to hospital from June 1, 2015 to December 30, 2018 were selected and divided into observation group (59 cases treated by percutaneous transforaminal endoscopy) and control group (67 cases treated with conventional conservative treatment) according to the treatment methods. The Visual Analogue Scale (VAS) and Japanese Orthopaedic Association Scores (JOA) before and after treatment were analyzed retrospectively. Length of stay, time out of bed, hospitalization expenses and recurrence rate were evaluated. The measurement data was expressed by x±s, the comparison between groups was performed by t test, and the count data were analyzed by descriptive analysis. Results: Before treatment, there was no significant difference in gender, age, VAS score and JOA score between the two groups (P>0.05) . After treatment, compared with the control group, the VAS score of the observation group was lower, the JOA score was higher, the time out of bed was shorter, the average hospitalization time was reduced, the average hospitalization cost was higher, and the recurrence rates after Six months and one year were lower in the observation group, the differences were statistically significant (P<0.05) . Conclusion: The clinical effect of percutaneous transforaminal endoscopic treatment is better than that of conventional conservative treatment for driver＇s lumbar disc herniation.

MR Diffusional Kurtosis Imaging-Based Assessment of Brain Microstructural Changes in Patients with Moyamoya Disease before and after Revascularization.

BACKGROUND AND PURPOSE: Conventional imaging examinations are insufficient to accurately assess brain damage in patients with Moyamoya disease. Our aim was to observe brain microstructural changes in patients with Moyamoya disease by diffusional kurtosis imaging and provide support data for application of this technique in individualized assessment of disease severity and surgical outcome among patients with Moyamoya disease. MATERIALS AND METHODS: A total of 64 patients with Moyamoya disease and 15 healthy volunteers underwent diffusional kurtosis imaging, and a second scanning was offered to surgical patients 3-4 months after revascularization. The diffusional kurtosis imaging parameter maps were obtained for mean kurtosis, axial kurtosis, radial kurtosis, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. The parameter values were measured in sensory pathway-related regions for all subjects. Differences in diffusional kurtosis imaging parameters of these brain regions were examined for healthy volunteers, patients without acroparesthesia, and asymptomatic and symptomatic sides of patients with acroparesthesia. Changes in diffusional kurtosis imaging parameters of patients with Moyamoya disease before and after revascularization were compared. RESULTS: Compared with healthy volunteers, patients with Moyamoya disease showed decreased mean kurtosis, axial kurtosis, radial kurtosis, and fractional anisotropy in the corona radiata. Similarly, mean kurtosis, radial kurtosis, and fractional anisotropy decreased in the posterior limb of the internal capsule, whereas axial kurtosis decreased and radial kurtosis increased in the thalami of patients with Moyamoya disease compared with healthy volunteers. Compared with the asymptomatic contralateral hemisphere, the symptomatic group showed increased mean kurtosis in the contralateral primary somatosensory cortex, increased fractional anisotropy in the contralateral corona radiata and posterior limb of the internal capsule, and decreased axial kurtosis in the contralateral thalamus. Among patients with Moyamoya disease with acroparesthesia, mean kurtosis decreased in the primary somatosensory cortex on the operated side following revascularization. CONCLUSIONS: The diffusional kurtosis imaging technique is applicable to patients with Moyamoya disease for detecting brain microstructural changes in white and gray matter before and after revascularization; this feature is useful in the assessment of disease severity and surgical outcome.

The Canadian Assessment of Physical Literacy: Development of a Model of Children's Capacity for a Healthy, Active Lifestyle Through a Delphi Process.

BACKGROUND: The Canadian Assessment of Physical Literacy (CAPL) was conceptualized as a tool to monitor children's physical literacy. The original model (fitness, activity behavior, knowledge, motor skill) required revision and relative weights for calculating/interpreting scores were required. METHODS: Nineteen childhood physical activity/fitness experts completed a 3-round Delphi process. Round 1 was open-ended questions. Subsequent rounds rated statements using a 5-point Likert scale. Recommendations were sought regarding protocol inclusion, relative importance within composite scores and score interpretation. RESULTS: Delphi participant consensus was achieved for 64% (47/73) of statement topics, including a revised conceptual model, specific assessment protocols, the importance of longitudinal tracking, and the relative importance of individual protocols and composite scores. Divergent opinions remained regarding the inclusion of sleep time, assessment/ scoring of the obstacle course assessment of motor skill, and the need for an overall physical literacy classification. CONCLUSIONS: The revised CAPL model (overlapping domains of physical competence, motivation, and knowledge, encompassed by daily behavior) is appropriate for monitoring the physical literacy of children aged 8 to 12 years. Objectively measured domains (daily behavior, physical competence) have higher relative importance. The interpretation of CAPL results should be reevaluated as more data become available.

Newborn screening for spinal muscular atrophy: Anticipating an imminent need.

Spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality. Children with type I SMA typically die by the age of 2 years. Recent progress in gene modification and other innovative therapies suggest that improved outcomes may soon be forthcoming. In animal models, therapeutic intervention initiated before the loss of motor neurons alters SMA phenotype and increases lifespan. Presently, supportive care including respiratory, nutritional, physiatry, and orthopedic management can ameliorate clinical symptoms and improve survival rates if SMA is diagnosed early in life. Newborn screening could help optimize these potential benefits. A recent report demonstrated that SMA detection can be multiplexed at minimal additional cost with the assay for severe combined immunodeficiency, already implemented by many newborn screening programs. The public health community should remain alert to the rapidly changing developments in early detection and treatment of SMA.

Physical inactivity of adults and 1-year health care expenditures in Brazil.

OBJECTIVES: To analyze the association between physical inactivity in different domains and direct public healthcare expenditures in adults and to identify whether the clustering of physical inactivity in different domains would contribute to increased public healthcare. METHODS: The sample composed of 963 adults randomly selected in a middle-size Brazilian city. Annual healthcare expenditure was estimated including all items registered in the medical records in the last 12 months prior to the interview. Habitual physical activity was estimated using Baecke questionnaire, which considers three components of physical activity (work, sports and leisure-time activities). RESULTS: Higher healthcare expenditures of medicines were associated with lower physical activity at work (OR 1.58 [1.06-2.35]), sport (OR 1.57 [1.12-2.18]) and physical inactivity in three domains (OR 2.12 [1.18-3.78]). Expenditures related to medicine (r = 0.109 [95 % CI 0.046-0.171]) and overall expenditures (r = 0.092 [95 % CI 0.029-0.155]) were related to physical inactivity, independently of age, sex, smoking, blood pressure and obesity. CONCLUSIONS: Physically inactive subjects in different domains of physical activity have increased likelihood to be inserted at groups of higher healthcare expenditure.

Assessment of the suitability of retroperitoneal laparoscopic ureterolithotomy as a treatment for complex proximal ureteral calculi.

AIM: This retrospective study aimed to evaluate the suitability of retroperitoneal laparoscopic ureterolithotomy (RPLU) in the treatment of complex proximal ureteral calculi. METHODS: Included were 24 patients who underwent RPLU for complex proximal ureteral stones from November 2008 to June 2010. RESULTS: A retroperitoneal approach was performed in 23 patients with a mean operative time of 79.6 min (range of 65-130 min) and mean intraoperative blood loss of 20.1 mL (10-50 mL). No postoperative complications were encountered within during the follow-up period of 9.1 months (3-22 months). Only one patient who underwent RPLU within one week of failed ESWL was converted to open surgery due to severe adhesions around ureter and the injury of aberrant renal artery at the lower pole of left kidney encountered during the RPLU. CONCLUSION: RPLU is safe and effective in the treatment of complex upper ureteral stones and can become a first-line surgical management of the disease.

Advertisement and knowledge of tobacco products among Ellisras rural children aged 11 to 18 years: Ellisras Longitudinal study.

BACKGROUND: Tobacco products use is the leading cause of chronic diseases morbidity and mortality. This study explores an exposure to tobacco advertisements factors and knowledge, an association with snuff/pipe usage and cigarette smoking among Ellisras rural children aged between 11 to 18 years. METHODS: A total of 1654 subjects (854 boys and 800 girls) who were part of the Ellisras Longitudinal Study completed the questionnaire. RESULTS: A significant (p < 0.05) number of boys (11.7%) compared to girls (8.8%) received free cigarettes from the members of the community. Bill boards were successful in advertising tobacco products among the Ellisras rural boys (17% boys and 12.8% for girls, p < 0.022). Multivariate analyses found significant association between cigarette smoking (OR = 1.7 95%CI 1.1-2.7 and Model 2 OR 1.6 95%CI 1.0-2.6 adjusted for age and gender) and advertisements of tobacco products on the TV screens, videos or movies. CONCLUSIONS: Exposure to tobacco products advertisements was high among Ellisras rural children. Though tobacco products legislation exists in South Africa, efforts should be taken by the health professionals to emphasize the danger of using tobacco products even among the illiterate. Teachers and parents should refrain from advertising tobacco products at schools and at homes.

Evaluating the cost-effectiveness of prenatal surgery for myelomeningocele: a decision analysis.

OBJECTIVE: To determine whether prenatal myelomeningocele repair is a cost-effective strategy compared to postnatal repair. METHODS: Decision-analysis modeling was used to calculate the cumulative costs, effects and incremental cost-effectiveness ratio of prenatal myelomeningocele repair compared with postnatal repair in singleton gestations with a normal karyotype that were identified with myelomeningocele between T1 and S1. The model accounted for costs and quality-adjusted life years (QALYs) in three populations: (1) myelomeningocele patients; (2) mothers carrying myelomeningocele patients; and (3) possible future siblings of these patients. Sensitivity analysis was performed using one-way, two-way and Monte Carlo simulations. RESULTS: Prenatal myelomeningocele repair saves $ 2 066 778 per 100 cases repaired. Additionally, prenatal surgery results in 98 QALYs gained per 100 repairs with 42 fewer neonates requiring shunts and 21 fewer neonates requiring long-term medical care per 100 repairs. However, these benefits are coupled to 26 additional cases of uterine rupture or dehiscence and one additional case of neurologic deficits in future offspring per 100 repairs. Results were robust in sensitivity analysis. CONCLUSION: Prenatal myelomeningocele repair is cost effective and frequently cost saving compared with postnatal myelomeningocele repair despite the increased likelihood of maternal and future pregnancy complications associated with prenatal surgery.

Method transfer for ligand-binding assays: recommendations for best practice.

To support clinical trials, bioanalytical methods are often transferred from one laboratory to another. With the rising number of large-molecule therapeutic proteins submitted for US FDA approval, the demand for large-molecule bioanalytical support and, subsequently, method transfer increases. Ligand-binding assays are the methods most commonly used to quantify endogenous and therapeutic proteins for the assessment of biomarkers and pharmacokinetic parameters. The goal of this review is to provide an overview of ligand-binding assay method transfer, essential parameters for partial method validation and to lay out a strategy to increase the chance of success. The recommendations herein are based on a summary of current publications and the authors' specific experiences, to help increase workload efficiency, maintain positive collaborations with partners and meet program timelines.

Universal cervical-length screening to prevent preterm birth: a cost-effectiveness analysis.

OBJECTIVE: To determine whether routine measurement of second-trimester transvaginal cervical length by ultrasound in low-risk singleton pregnancies is a cost-effective strategy. METHODS: We developed a decision analysis model to compare the cost-effectiveness of two strategies for identifying pregnancies at risk for preterm birth: (1) no routine cervical length screening and (2) a single routine transvaginal cervical length measurement at 18-24 weeks' gestation. In our model, women identified as being at increased risk (cervical length < 1.5 cm) for preterm birth would be offered daily vaginal progesterone supplementation. We assumed that vaginal progesterone reduces preterm birth at < 34 weeks' gestation by 45%. We also assumed that a decreased cervical length could result in additional costs (ultrasound scans, inpatient admission) without significantly improved neonatal outcomes. The main outcome measure was incremental cost-effectiveness ratio. RESULTS: Our model predicts that routine cervical-length screening is a dominant strategy when compared to routine care. For every 100,000 women screened, $12,119,947 can be potentially saved (in 2010 US dollars) and 423.9 quality-adjusted life-years could be gained. Additionally, we estimate that 22 cases of neonatal death or long-term neurologic deficits could be prevented per 100,000 women screened. Screening remained cost-effective but was no longer the dominant strategy when cervical-length ultrasound measurement costs exceeded $187 or when vaginal progesterone reduced delivery risk at < 34 weeks by less than 20%. CONCLUSION: In low-risk pregnancies, universal transvaginal cervical length ultrasound screening appears to be a cost-effective strategy under a wide range of clinical circumstances (varied preterm birth rates, predictive values of a shortened cervix and costs).

A comparison between cryosurgery and conventional stripping in varicose vein surgery: perioperative features and complications.

Cryosurgery is a relatively new treatment option for vein stripping in case of insufficiency of the great saphenous vein (GSV). A prospective randomized trial was performed to compare operation time, extracted vein length, and postoperative outcomes of cryosurgery with conventional short stripping. Forty patients with one-sided, duplex-proven insufficiency of the GSV were included. Operation time was shorter with cryosurgery, 17.6 +/- 1.11 vs. 20 +/- 0.80 min. Extracted vein length was significantly longer with conventional stripping, 40 +/- 1.45 vs. 28 +/- 1.46 cm. After the operation, all symptoms of venous insufficiency decreased significantly in both groups. In the first 2 weeks after operation, pain scores were higher in the cryosurgery group, but the difference was only significant on the fifth postoperative day. Postoperative mobility, hematoma formation, and complications were not significantly different. Cryosurgery has comparable postoperative results with conventional short stripping. Operation time is reduced with cryosurgery, but postoperative pain scores are higher. Patients favor cryosurgery because of better cosmetic results.

In vivo drug target discovery: identifying the best targets from the genome.

A vast number of genes of unknown function threaten to clog drug discovery pipelines. To develop therapeutic products from novel genomic targets, it will be necessary to correlate biology with gene sequence information. Industrialized mouse reverse genetics is being used to determine gene function in the context of mammalian physiology and to identify the best targets for drug development.

A phase II study of razoxane, an antiangiogenic topoisomerase II inhibitor, in renal cell cancer with assessment of potential surrogate markers of angiogenesis.

Renal cell carcinoma (RCC) is an angiogenic tumor resistant to standard cytotoxic chemotherapeutic agents. Although often responsive to immunomodulatory agents including interleukin 2 and IFN-alpha, the overall results in randomized Phase III studies are disappointing with only modest improvements in overall survival. This Phase II study evaluated the efficacy and tolerability of razoxane, an antiangiogenic topoisomerase II inhibitor, in 40 patients (32 men, 8 women; age: range, 31-76 years; median, 58 years) with inoperable RCC. Twenty patients received razoxane 125 mg p.o., twice a day for 5 days each week for 8 weeks (one cycle). This was repeated in patients with stable disease (StD), but was discontinued after 16 weeks if there was no evidence of an objective response. Because minimal toxicity was seen, subsequent patients (n = 20) were treated until progressive disease (PD) was documented. Of 38 evaluable patients, 11 (29%) had StD for a minimum of 4 months, and the remainder had PD. Median overall survival was 7.3 months. Duration of survival was significantly better in patients with StD compared with those with PD (P = 0.003). The effect of treatment on six potential surrogate serum/plasma (vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), urokinase plasminogen activator soluble receptor (uPAsr), E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and von Willebrand's factor (vWF) and two urinary (VEGF and bFGF) markers of angiogenesis was evaluated before and after 1 cycle of treatment. Pretreatment serum VEGF and E-selectin levels above the median value were associated with a poor prognosis. Serum VCAM-1 levels and urinary VEGF levels rose significantly after one cycle in patients with PD but not in those with StD. Serum VEGF, bFGF, VCAM-1 and vWF, plasma uPAsr and urinary bFGF levels were significantly higher in PD patients compared with StD patients before and/or after 1 cycle of treatment. In conclusion, razoxane is an antiangiogenic agent that has minimal toxicity and that requires further evaluation in combination with other active agents in the treatment of RCC. Surrogate serum and urinary markers of angiogenesis may have a role to play in predicting disease response and overall survival in RCC.