Diagnostic accuracy of physician review, expert algorithms and data-derived algorithms in adult verbal autopsies

BACKGROUND: The verbal autopsy (VA) is used to collect information on cause-specific mortality from bereaved relatives. A cause of death may be assigned by physician review of the questionnaires, or by an algorithm. We compared the diagnostic accuracy of physician review, an expert algorithm, and data-derived algorithms. METHODS: Data were drawn from a multicentre validation study of 796 adult deaths that occurred in hospitals in Tanzania, Ethiopia, and Ghana. A 'gold standard' cause of death was assigned using hospital records and death certificates. The VA interviews were carried out by trained fieldworkers 1-21 months after the subject's death. A cause of death was assigned by physician review and an expert algorithm. Data-derived algorithms that most accurately estimated the cause-specific mortality fraction (CSMF) for each cause of death were identified using logistic regression. RESULTS: The most common causes of death were tuberculosis/AIDS (CSMF = 18.6%), malaria (CSMF = 10.7%), meningitis (CSMF = 8.3%), and cardiovascular disorders (CSMF = 8.2%). The CSMF obtained using physician review was within +/-20% of the gold standard value for 12 causes of death including the four common causes. The CSMF obtained using the expert algorithm was within +/-20% of the gold standard for eight causes of death, including tuberculosis/AIDS, malaria, and meningitis. The CSMF obtained using the data-derived algorithms was within +/-20% of the gold standard for seven causes of death, including tuberculosis/ AIDS, meningitis, and cardiovascular disorders. All three methods yielded a specificity of at least 80% for all causes of death, and a sensitivity of at least 80% for deaths due to injuries and rabies. CONCLUSIONS: For those settings where physician review is not feasible, expert and data-derived algorithms provide an alternative approach for assigning many causes of death. We recommend that the algorithms proposed herein are validated further.     

Survey of smokeless tobacco use in basic trainees and armor basic course officers

In this study an all-male population of 256 U.S. Army basic trainees and 98 armor officer basic course students were surveyed concerning extent of use, knowledge of, and factors contributing to the use of smokeless tobacco (ST). The survey was administered at a dental clinic at Fort Knox, Kentucky. The data were analyzed using the SPSS computer software program. Results showed that more than 17% of this population were either occasional or regular users of ST. Nearly 24% had tried ST and more than 9% were former users. Exactly one-half had not tried ST. A typical user was white, had started ST use at age 14, had used it for 4 years, and was most likely to use snuff or dip. Higher educational level achieved was associated with increased likelihood of ST use. Nearly 22% of college graduates used ST, whereas only 15.3% of high school graduates or those with some college were users. Knowledge about the potential health effects of ST was generally high or moderately high, except for its ability to cause hypertension. This was true for both high school and college graduates, although college graduates were somewhat more informed. Few in this population had a personal attitude of approval toward ST use, and very few perceived that either their parents or their superiors in the military approved of ST use. Perceived attitude of approval was highest from friends and peers. The principle reasons for starting ST use were use by friends and curiosity about taste and effects. Influence from public figures, such as athletes, and from advertising was minimal. Enjoyment of flavor and taste was found to be the main reason for continued ST use. Health professionals were identified by the majority of respondents as the single most important information source on ST. Relatively few (27%), however, stated that their dentist or hygienist had ever discussed ST with them.     

Effect of paracentesis upon the blood-aqueous barrier of cynomolgus monkeys.

Anterior chamber paracentesis disrupts the blood aqueous barrier (BAB) of rabbits and nonhuman primates, but the magnitude and duration of breakdown in monkeys has not been clarified. We have studied anterior chamber paracentesis in cynomolgus monkeys as a potential model of postoperative BAB breakdown. The effect of a single paracentesis upon fluorescein sodium concentration in the anterior chamber after an intravenous injection was measured in 16 eyes of 8 animals. In an additional 10 eyes of 5 animals, aqueous humor was withdrawn for analysis 24 hours and one week following paracentesis. Anterior chamber fluorescein concentration was 57 +/- 22 ng/ml (mean +/- standard deviation) before paracentesis, rose to 81 +/- 47 ng/ml 24 hrs after paracentesis, and was 60 +/- 36 ng/ml at 72-96 hours. Twenty-four hours after paracentesis, total protein concentration was elevated, but ascorbic acid and transforming growth factor-beta levels were not. Paracentesis in monkeys has only a small and short lasting effect upon BAB integrity and is therefore unlikely to be a good model for assessing the effect of agents designed to stabilize the BAB. However, the short-lived effect of paracentesis may permit the repetitive collection of "primary aqueous" for physiologic and biochemical studies.     

Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy.

PURPOSE: To assess the efficacy of the marine-derived alkaloid ecteinascidin 743 (ET-743) in patients with soft tissue sarcomas that progressed despite prior conventional chemotherapy and to characterize the pharmacokinetic profiles of ET-743 in this patient population. PATIENTS AND METHODS: Thirty-six previously treated soft tissue sarcoma patients from three institutions received ET-743 as a 24-hour continuous intravenous (IV) infusion at a dose of 1,500 microg/m(2) every 3 weeks. Pharmacokinetic studies were also performed. Patients were restaged every two cycles for response by objective criteria. RESULTS: Objective responses were observed in three patients, with one complete response and two partial responses, for an overall response rate of 8% (95% CI, 2% to 23%). Responses were durable for up to 20 months. Two minor responses (43% and 47% tumor reduction) were observed, for an overall clinical benefit rate of 14%. The predominant toxicities were neutropenia and self-limited transaminitis of grade 3 to 4 severity in 34% and 26% of patients, respectively. The estimated 1-year time to progression and overall survival rates were 9% (95% CI, 3% to 27%) and 53% (95% CI, 39% to 73%), respectively. The maximum observed plasma concentration and total plasma clearance of ET-743 (mean +/- standard deviation), 1.04 +/- 0.48 ng/mL and 35.6 +/- 16.2 L/h/m(2), respectively, were consistent with previously reported values from phase I studies of the drug given as a 24-hour IV infusion. CONCLUSION: ET-743 is a promising new option for the management of several histologic subtypes of sarcoma. Durable objective responses were obtained in a subset of sarcoma patients with disease progression despite prior chemotherapy. Additionally, the relatively high survival rate noted in this series of previously treated patients further justifies development of this agent.     

阿片类药物在癌痛治疗中的作用

Columba Quigley是颐养关怀治疗领域中的一位专家，她为一个以医院为基础的支持团队（a hospital based support team）工作。同时她还服务于一所颐养关怀社团和一所临终关怀医院；在那里，患者得到临终护理，延续生命并控制症状。癌症患者特别是晚期癌症患者常常伴发疼痛。此外，疼痛还是癌症患者最令人恐惧的症状。适当应用镇痛药物（特别是阿片类药物）可以有效控制绝大多数患者的癌痛。     

Phase III randomized trial of doxorubicin and docetaxel versus doxorubicin and cyclophosphamide as primary medical therapy in women with breast cancer: an anglo-celtic cooperative oncology group study.

PURPOSE To compare the clinical and pathologic response rates of doxorubicin and cyclophosphamide (AC) with doxorubicin and docetaxel (AD) as primary chemotherapy in women with primary or locally advanced breast cancer. PATIENTS AND METHODS Eligible patients with histologically proven breast cancer with primary tumors >/= 3 cm, inflammatory or locally advanced disease, and no evidence of metastases were randomly assigned to receive a maximum of six cycles of either doxorubicin (60 mg/m(2)) plus cyclophosphamide (600 mg/m(2)) administered intravenously (IV) every 3 weeks or doxorubicin (60 mg/m(2)) plus docetaxel (75 mg/m(2)) IV every 3 weeks, followed by surgery on completion of chemotherapy. Results A total of 363 patients were randomly assigned to AC (n = 180) or AD (n = 183). A complete clinical response was observed in 17% and 20% of patients treated with AC and AD, respectively (P = .42). Overall (complete and partial) clinical response rates for AC and AD were 61% and 70%, respectively (P = .06). There was no significant difference in either the pathologic complete response rates in the breast with AC (24%) and AD (21%; P = .61) or in the number of patients with positive axillary nodes at surgery with AC (61%) and AD (66%; P = .28). At a median follow-up of 32 months, there is no significant difference between the two groups for the number of relapses. CONCLUSION In contrast to the positive results reported for sequential docetaxel after AC as primary chemotherapy of breast cancer, our data do not suggest a benefit for simultaneous AD over AC.