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1.

Objective

Comparative survival between neoadjuvant chemotherapy and adjuvant chemotherapy for patients with cT2-4N0-1M0 non–small cell lung cancer has not been extensively studied.

Methods

Patients with cT2-4N0-1M0 non–small cell lung cancer who received platinum-based chemotherapy were retrospectively identified. Exclusion criteria included stage IV disease, induction radiotherapy, and targeted therapy. The primary end point was disease-free survival. Secondary end points were overall survival, chemotherapy tolerance, and ability of Response Evaluation Criteria In Solid Tumors response to predict survival. Survival was estimated using the Kaplan–Meier method, compared using the log-rank test and Cox proportional hazards models, and stratified using matched pairs after propensity score matching.

Results

In total, 330 patients met the inclusion criteria (n = 92/group after propensity-score matching; median follow-up, 42 months). Five-year disease-free survival was 49% (95% confidence interval, 39-61) for neoadjuvant chemotherapy versus 48% (95% confidence interval, 38-61) for adjuvant chemotherapy (P = .70). On multivariable analysis, disease-free survival was not associated with neoadjuvant chemotherapy or adjuvant chemotherapy (hazard ratio, 1.1; 95% confidence interval, 0.64-1.90; P = .737), nor was overall survival (hazard ratio, 1.21; 95% confidence interval, 0.63-2.30; P = .572). The neoadjuvant chemotherapy group was more likely to receive full doses and cycles of chemotherapy (P = .014/0.005) and had fewer grade 3 or greater toxicities (P = .001). Response Evaluation Criteria In Solid Tumors response to neoadjuvant chemotherapy was associated with disease-free survival (P = .035); 15% of patients receiving neoadjuvant chemotherapy (14/92) had a major pathologic response.

Conclusions

Timing of chemotherapy, before or after surgery, is not associated with an improvement in overall or disease-free survival among patients with cT2-4N0-1M0 non–small cell lung cancer who undergo complete surgical resection.  相似文献   
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BACKGROUND: The validity of parent reports regarding children's attention-deficit/hyperactivity disorder (ADHD) symptoms has been questioned. This study assessed whether parent reports were as sensitive as teacher reports to document change in ADHD symptoms during clinical trials with atomoxetine. METHODS: Data were compared from two randomized, double-blind, placebo-controlled clinical trials of atomoxetine using different versions (parent or teacher) of the same rating scale (Attention-Deficit/Hyperactivity Disorder Rating Scale-IV [parent or teacher] Version: Investigator Administered and Scored - ADHD RS). Exclusion criteria included history of bipolar disorder, psychosis, seizures, alcohol abuse, or positive drug screen. Patients (6-16 years old) were treated with atomoxetine (titrated to a maximum dose of 1.8 mg/kg/day) administered once daily for up to 7 weeks. Parent and teacher ratings were compared using an analysis of covariance (ANCOVA) model. RESULTS: The analysis (n = 318) showed that treatment effects (mean change, baseline to endpoint) were similar between parent and teacher ratings (total, p = .762; inattention, p = .519; hyperactive/impulsive, p = .955). Effect sizes also were similar based on total scores (parent ratings = .69; teacher ratings = .63). CONCLUSIONS: Parent reports are as sensitive as teacher reports in assessing the efficacy of long-acting pharmacologic treatment for ADHD in children during clinical trials using the nonstimulant atomoxetine.  相似文献   
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Implantation of left ventricular assist devices (LVAD) is associated with HLA antibody sensitization. The objective of this study was to determine the specificity of antibodies produced by LVAD recipients using a combination of ELISA, Luminex and microcytotoxicity assays. Fifty-one LVAD patients were studied, from 44 to 838 days post-implantation. No patient developed HLA antibodies, although 24 produced IgG antibodies detectable in both ELISA and Luminex assays. These antibodies manifest as positive reactions with class I and class II wells of the ELISA and also blank wells. In Luminex assays, they produce high MFI readings with the negative control beads. Antibodies were detected 18 to 228 days after implantation. This reactivity was found to be directed against bovine serum albumin (BSA), commonly used to block non-specific binding in ELISA and Luminex assays; absorption of sera with BSA-coated beads completely abrogated reactivity in all solid phase assays, but did not eliminate anti-HLA antibodies in control sera. Ten of the 24 patients have proceeded to transplantation, with a 1-year graft survival of 69%. In conclusion, it appears that implantation of LVADS disrupts immunoregulatory pathways leading to production of anti-albumin antibodies. These can be misinterpreted as anti-HLA antibodies in solid phase assays.  相似文献   
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Background.Computers that collect data from patients and provide both patients and practitioners with printed feedback on a range of health risks are a tool for assisting general practitioners with preventive care. This study assessed the impact of computer-generated printed feedback on cervical screening among women who were underscreened for cervical cancer.Method.Female attenders at two Australian general practices were randomly allocated to Experimental or Control groups. Women in both groups completed a health risk survey on a touch screen computer prior to their consultation. Those in the Experimental group received printed pages summarizing their results, including their eligibility for cervical screening and last Pap test, for themselves and their doctor. The number and proportion of underscreened women who had a Pap test in the 6 months after completing the computer survey, as determined by pathology records, were examined.Results.Of the 679 participants, 139 were classified as underscreened on the basis of self-report (74 Experimental, 65 Control) and 272 on the basis of their pathology records (148 Experimental, 124 Control). Overall about one-third of women had a test in the 6-month period, and the differences between the groups were not significant for women overall (18–70 years) or for women 18–49 years. Among women 50–70 who were underscreened based on self-report, those receiving the printout were more likely to have a Pap test in the next 6 months (P< 0.05). This pattern was also evident, but did not reach statistical significance, for older women who were underscreened based on pathology records.Conclusions.We are unable to draw conclusions regarding the effectiveness of the computer system due to the modest proportions of women screened, the small numbers, and the fact that the computer survey may have created an intervention effect in the Control group. As the study suggests the computer system is acceptable to women and may be effective for encouraging screening among older women, further exploration of the system is desirable.  相似文献   
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The adult mammalian central nervous system (CNS) lacks the capacity to support axonal regeneration. There is increasing evidence to suggest that astrocytes, the major glial population in the CNS, may possess both axon-growth promoting and axon-growth inhibitory properties and the latter may contribute to the poor regenerative capacity of the CNS. In order to examine the molecular differences between axon-growth permissive and axon-growth inhibitory astrocytes, a panel of astrocyte cell lines exhibiting a range of axon-growth promoting properties was generated and analysed. No clear correlation was found between the axon-growth promoting properties of these astrocyte cell lines with: (i) the expression of known neurite-outgrowth promoting molecules such as laminin, fibronectin andN-cadherin; (ii) the expression of known inhibitory molecules such tenascin and chondroitin sulphate proteoglycan; (iii) plasminogen activator and plasminogen activator inhibitor activity; and (iv) growth cone collapsing activity. EM studies on aggregates formed from astrocyte cell lines, however, revealed the presence of an abundance of extracellular matrix material associated with the more inhibitory astrocyte cell lines. When matrix deposited by astrocyte cell lines was assessed for axon-growth promoting activity, matrix from permissive lines was found to be a good substrate, whereas matrix from the inhibitory astrocyte lines was a poor substrate for neuritic growth. Our findings, taken together, suggest that the functional differences between the permissive and the inhibitory astrocyte cell lines reside largely with the ECM.  相似文献   
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The potential role of adrenaline, both circulating and in the central nervous system, in the maintenance of high blood pressure was examined in stroke-prone spontaneously hypertensive rats (SHRSP). alpha-Monofluoromethyldopa, a long-lasting inhibitor of dopa decarboxylase, was used to induce rapid depletion of central and peripheral catecholamine stores. Subsequent inhibition of phenylethanolamine-N-methyltransferase (PNMT) allowed the gradual restoration of dopamine and noradrenaline but not adrenaline, resulting in a greater relative depletion of adrenaline. Adrenaline was almost totally depleted in the circulation and peripheral tissues. The resting level of blood pressure, however, was unaffected, excepting after administration of a vasopressin (AVP) antagonist. Moreover, there was no reduction in the magnitude of acute pressor responses to electrical stimulation of the rostral ventrolateral medulla oblongata (C1 area), despite extensive loss of adrenaline from the brainstem and spinal cord. The results suggest that adrenaline contributes to the resting level of blood pressure but that its loss can be offset by the pressor activity of AVP. Thus neither central nor peripheral adrenaline stores appear to be essential for the maintenance of hypertension or for centrally-evoked vasoconstriction in adult SHRSP.  相似文献   
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