A three-arm phase III randomised trial comparing combinations of platinum derivatives, ifosfamide and/or gemcitabine in stage IV non-small-cell lung cancer.

OBJECTIVE: To determine, in stage IV non-small-cell lung cancer (NSCLC), if the combination of gemcitabine-a new active drug-with ifosfamide (IG) or with the cisplatin-carboplatin association (CCG) will improve survival (primary end point) in comparison with a first-generation regimen, cisplatin-carboplatin-ifosfamide (CCI). PATIENTS AND METHODS: A total of 284 chemotherapy-na?ve patients with metastatic NSCLC were randomised. Four were ineligible and 16 were not assessable for responses. Cisplatin was given at 60 mg/m2 on day 1, carboplatin AUC 3 mg.min/ml on day 1, ifosfamide 4.5 g/m2 on day 1 and gemcitabine 1 g/m2 on days 1, 8 and 15. Courses were repeated every 4 weeks. Response was assessed after three courses and chemotherapy was continued in responding patients until best response. There were 94 eligible patients in the CCI arm, 92 in CCG and 94 in the IG arm. RESULTS: The objective response rates for CCI, CCG and IG were 23% [95% confidence interval (CI) 15% to 32%], 29% (95% CI 20% to 39%) and 25% (95% CI 16% to 33%), respectively ( P = 0.61). Median survival time was 24, 34 and 30 weeks, respectively (P = 0.20). One-year survival was 23, 33 and 35%, and 2-year survival was 11, 14 and 17%, respectively. In some subgroups (older patients, women), there was a significant survival advantage for CCG and IG compared with CCI. Toxicity was tolerable: severe alopecia was less frequent in the CCG arm, and IG was associated with significantly more thrombopenia while CCG was associated with more leucopenia. CONCLUSION: In stage IV NSCLC, treatment with regimens including the new drug gemcitabine were associated with a better but not statistically significant observed survival compared with a classical first-generation cisplatin-containing regimen. The non-platinum combination of gemcitabine was as effective as its combination with platinum.     

Remembering one year later: role of the amygdala and the medial temporal lobe memory system in retrieving emotional memories

The memory-enhancing effect of emotion can be powerful and long-lasting. Most studies investigating the neural bases of this phenomenon have focused on encoding and early consolidation processes, and hence little is known regarding the contribution of retrieval processes, particularly after lengthy retention intervals. To address this issue, we used event-related functional MRI to measure neural activity during the retrieval of emotional and neutral pictures after a retention interval of 1 yr. Retrieval activity for emotional and neutral pictures was separately analyzed for successfully (hits) vs. unsuccessfully (misses) retrieved items and for responses based on recollection vs. familiarity. Recognition performance was better for emotional than for neutral pictures, and this effect was found only for recollection-based responses. Successful retrieval of emotional pictures elicited greater activity than successful retrieval of neutral pictures in the amygdala, entorhinal cortex, and hippocampus. Moreover, in the amygdala and hippocampus, the emotion effect was greater for recollection than for familiarity, whereas in the entorhinal cortex, it was similar for both forms of retrieval. These findings clarify the role of the amygdala and the medial temporal lobe memory regions in recollection and familiarity of emotional memory after lengthy retention intervals.     

Toxicity from the use of niacin to beat urine drug screening

Niacin (vitamin B3) is promoted for rapidly clearing the body of drugs of abuse, such as cocaine and cannabis, and is alleged to interfere with urine drug screening. We present 4 cases of such novel use associated with significant adverse effects. Two cases had isolated skin manifestations, whereas the other 2 presented with life-threatening manifestations, including nausea, vomiting, dizziness, hepatotoxicity, metabolic acidosis, and hypoglycemia evolving into hyperglycemia. One patient also had profound neutrophilia and QT(C)-interval prolongation. All patients improved after cessation of the drug use and supportive treatment. Health care providers should be aware of these potential adverse effects of niacin and of the misguided use of this vitamin by patients seeking to interfere with urine drug screening.     

Cross-sectional study to evaluate factors associated with adherence to antiretroviral therapy by Brazilian HIV-infected patients

Antiretroviral therapy success is highly dependent on the ability of the patient to fully adhere to the prescribed treatment regimen. We present the results of a cross-sectional study that evaluates the predictive value of a self-administered questionnaire of adherence to antiretroviral (ARV) therapy. Study participants were interviewed using a 36-item Patient Medication Adherence Questionnaire (PMAQ) designed to assess knowledge about ARV therapy, motivation to adhere to treatment, and behavioral skills. Plasma HIV-1 RNA levels were correlated with the results obtained from the PMAQ. Of the 182 study participants, 82 (45%) were receiving their initial ARV regimen. Of the remaining patients, 39 (21%) and 61 (34%) were on a second or additional ARV regimen, respectively. An undetectable viral load was documented in 47/62 (76%) patients on their first regimen who reported missing medication on less than 4 days in the last 3 months. The PMAQ had a higher predictive value of plasma viral suppression for patients in the initial regimen than for patients in salvage therapy. The overall predictive value of the PMAQ to identify adherence was 74%, and 59% for nonadherence, with an overall efficacy of 64%. Of the 74 patients (45%) who did not understand the concept of antiretroviral therapy, 80% were failing or had previously failed the ARV treatment. Of 35 patients with doubts about their HIV status or skeptical of the benefits of ARV therapy, 29 (84%) were nonadherent. Despite the positive predictive value of PMAQ in identifying adherence, self-reported adherence is not a sufficiently precise predictor of treatment success to substitute for viral load monitoring. On the other hand, the use of such an instrument to identify factors associated with nonadherence provides an excellent opportunity to apply early intervention designed to specifically address factors that might be contributing to the lack of adherence prior to regimen failure.     

Scientific uncertainty and the role of expert advice: the case of health checks for coronary heart disease prevention by general practitioners in the UK.

This paper examines some of the ways in which scientific evidence influenced the development of the policy for the payment of general practitioners for coronary heart disease (CHD) prevention in the UK, in particular the introduction of 'health checks'. The specific policy events which are examined are the 1990 and 1993 contracts for health promotion by general practitioners. Data for this paper were provided by oral history interviews with key informants including general practitioners, public health doctors, civil servants and academics. The study shows the way in which complex scientific evidence interacted with other, professional and political, factors to produce a policy for which there was variable scientific evidence. The relationship between science and policy was complicated and tortuous but two aspects were particularly salient, the way in which scientific uncertainty influenced the content of the policy and the contribution of expert advice to policy making. The existence of social and technical uncertainty about the effectiveness of health checks allowed different players to hold different views depending on their professional affiliation or other agendas. The mechanisms by which scientific advice was given to policy makers were primarily by medical civil servants and through informal contacts and networks. There was no independent systematic formal system to assess and disseminate scientific advice to policy makers, for instance by an expert committee. These factors in turn allowed policy makers to ignore or misinterpret scientific evidence according to other policy imperatives.