Biomedical risk assessment as an aid for smoking cessation.

BACKGROUND: A possible strategy for increasing smoking cessation rates could be to provide smokers who have contact with healthcare systems with feedback on the biomedical or potential future effects of smoking, e.g. measurement of exhaled carbon monoxide (CO), lung function, or genetic susceptibility to lung cancer. OBJECTIVES: To determine the efficacy of biomedical risk assessment provided in addition to various levels of counselling, as a contributing aid to smoking cessation. SEARCH STRATEGY: We systematically searched the Cochrane Collaboration Tobacco Addiction Group Specialized Register, Cochrane Central Register of Controlled Trials 2008 Issue 4, MEDLINE (1966 to January 2009), and EMBASE (1980 to January 2009). We combined methodological terms with terms related to smoking cessation counselling and biomedical measurements. SELECTION CRITERIA: Inclusion criteria were: a randomized controlled trial design; subjects participating in smoking cessation interventions; interventions based on a biomedical test to increase motivation to quit; control groups receiving all other components of intervention; an outcome of smoking cessation rate at least six months after the start of the intervention. DATA COLLECTION AND ANALYSIS: Two assessors independently conducted data extraction on each paper, with disagreements resolved by consensus. Results were expressed as a relative risk (RR) for smoking cessation with 95% confidence intervals (CI). Where appropriate a pooled effect was estimated using a Mantel-Haenszel fixed effect method. MAIN RESULTS: We included eleven trials using a variety of biomedical tests. Two pairs of trials had sufficiently similar recruitment, setting and interventions to calculate a pooled effect; there was no evidence that CO measurement in primary care (RR 1.06, 95% CI 0.85 to 1.32) or spirometry in primary care (RR 1.18, 95% CI 0.77 to 1.81) increased cessation rates. We did not pool the other seven trials. One trial in primary care detected a significant benefit of lung age feedback after spirometry (RR 2.12; 95% CI 1.24 to 3.62). One trial that used ultrasonography of carotid and femoral arteries and photographs of plaques detected a benefit (RR 2.77; 95% CI 1.04 to 7.41) but enrolled a population of light smokers. Five trials failed to detect evidence of a significant effect. One of these tested CO feedback alone and CO + genetic susceptibility as two different intervention; none of the three possible comparisons detected significant effects. Three others used a combination of CO and spirometry feedback in different settings, and one tested for a genetic marker. AUTHORS' CONCLUSIONS: There is little evidence about the effects of most types of biomedical tests for risk assessment. Spirometry combined with an interpretation of the results in terms of 'lung age' had a significant effect in a single good quality trial. Mixed quality evidence does not support the hypothesis that other types of biomedical risk assessment increase smoking cessation in comparison to standard treatment. Only two pairs of studies were similar enough in term of recruitment, setting, and intervention to allow meta-analysis.

Superior outcome of women with stage I/II cutaneous melanoma: pooled analysis of four European Organisation for Research and Treatment of Cancer phase III trials.

PURPOSE: Several studies observed a female advantage in the prognosis of cutaneous melanoma, for which behavioral factors or an underlying biologic mechanism might be responsible. Using complete and reliable follow-up data from four phase III trials of the European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group, we explored the female advantage across multiple end points and in relation to other important prognostic indicators. PATIENTS AND METHODS: Patients diagnosed with localized melanoma were included in EORTC adjuvant treatment trials 18832, 18871, 18952, and 18961 and randomly assigned during the period of 1984 to 2005. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs for women compared with men, adjusted for age, Breslow thickness, body site, ulceration, performed lymph node dissection, and treatment. RESULTS: A total of 2,672 patients with stage I/II melanoma were included. Women had a highly consistent and independent advantage in overall survival (adjusted HR, 0.70; 95% CI, 0.59 to 0.83), disease-specific survival (adjusted HR, 0.74; 95% CI, 0.62 to 0.88), time to lymph node metastasis (adjusted HR, 0.70; 95% CI, 0.51 to 0.96), and time to distant metastasis (adjusted HR, 0.69; 95% CI, 0.59 to 0.81). Subgroup analysis showed that the female advantage was consistent across all prognostic subgroups (with the possible exception of head and neck melanomas) and in pre- and postmenopausal age groups. CONCLUSION: Women have a consistent and independent relative advantage in all aspects of the progression of localized melanoma of approximately 30%, most likely caused by an underlying biologic sex difference.

Subgroup analyses in randomised controlled trials: cohort study on trial protocols and journal publications

OBJECTIVE: To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications. DESIGN: Cohort of protocols of randomised controlled trial and subsequent full journal publications. SETTING: Six research ethics committees in Switzerland, Germany, and Canada. DATA SOURCES: 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications. RESULTS: Of 894 protocols of randomised controlled trials, 252 (28.2%) included one or more planned subgroup analyses. Of those, 17 (6.7%) provided a clear hypothesis for at least one subgroup analysis, 10 (4.0%) anticipated the direction of a subgroup effect, and 87 (34.5%) planned a statistical test for interaction. Industry sponsored trials more often planned subgroup analyses compared with investigator sponsored trials (195/551 (35.4%) v 57/343 (16.6%), P<0.001). Of 515 identified journal publications, 246 (47.8%) reported at least one subgroup analysis. In 81 (32.9%) of the 246 publications reporting subgroup analyses, authors stated that subgroup analyses were prespecified, but this was not supported by 28 (34.6%) corresponding protocols. In 86 publications, authors claimed a subgroup effect, but only 36 (41.9%) corresponding protocols reported a planned subgroup analysis. CONCLUSIONS: Subgroup analyses are insufficiently described in the protocols of randomised controlled trials submitted to research ethics committees, and investigators rarely specify the anticipated direction of subgroup effects. More than one third of statements in publications of randomised controlled trials about subgroup prespecification had no documentation in the corresponding protocols. Definitive judgments regarding credibility of claimed subgroup effects are not possible without access to protocols and analysis plans of randomised controlled trials.

Evaluation of a summary score of cognitive performance for use in trials in perioperative and critical care.

Background/Aims: Cognitive dysfunction after medical treatment is increasingly being recognized. Studies on this topic require repeated cognitive testing within a short time. However, with repeated testing, practice effects must be expected. We quantified practice effects in a demographically corrected summary score of a neuropsychological test battery repeatedly administered to healthy elderly volunteers. Methods: The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Neuropsychological Assessment Battery (for which a demographically corrected summary score was developed), phonemic fluency tests, and trail-making tests were administered in healthy volunteers aged 65 years or older on days 0, 7, and 90. This battery allows calculation of a demographically adjusted continuous summary score. Results: Significant practice effects were observed in the CERAD total score and in the word list (learning and recall) subtest. Based on these volunteer data, we developed a threshold for diagnosis of postoperative cognitive dysfunction (POCD) with the CERAD total score. Conclusion: Practice effects with repeated administration of neuropsychological tests must be accounted for in the interpretation of such tests. Ignoring practice effects may lead to an underestimation of POCD. The usefulness of the proposed demographically adjusted continuous score for cognitive function will have to be tested prospectively in patients.

Preliminary laboratory and field trials of a heated pheromone trap for the sandfly lutzomyia logipalpis (Diptera: Psychodidae)

A heated pheromone trap for the sandfly Lutzomyia longipalpis was tested in the laboratory using filter paper or plastic vial dispensers. Male pheromone extracted from 8 male tergal glands and absorbed on to filter paper dispensers attracted 82/120 (68.3%) of virgin females released in cages. Similarly plastic vial dispensers baited with the extract of 24 males caught 73/120 (61%). In field trials carried out near januária, Minas Gerais, Brazil using the plastic dispensers baited with extracts of 50 male tergal glands only 70 female L. longipalpis were captured. Over 1000 male flies were, however, caught during 6 nights, with greater numbers in the unbaited control traps than in the pheromone baited test traps. It is concluded that at excessive concentrations male L. longipalpis pheromone may act as a repellent to conspecific males.

Recent advances in pharmacologic study of natural anticancer agents in China

In this paper a number of anticancer agents of natural origin will be presented. Hydroxycamtothecin (HCPT) was found to produce a strong inhibitory action on a variety of animal tumors. It is also effective for treatment of patients with gastric carcinoma, liver carcinoma, tumor of head and neck or leukemia. Pharmacologic studies showed that it could depress S phase of tumor cells significantly and cause formation of cellular chromatid breaks. By means of alkaline elution and nick translation methods it has been proved that HCPT induced DNA singlo strand breaks remarkably. Homoharringyonine (hhrt) was shown to be effective against acute leukemia. Recent experiments in tumor-bearing mice inidcated that (HHRT) could diminish tumor metastasis. Using molecular hybridization technique it was demonstrated that (HHRT) decreased the content of c-myc RNA in the cytoplasm but not in the nuclei. Lycobetaine (LBT) poddrddrf dytnh inhibitory effects on a number of ascites tumors. In clinical trials it was against ovarian and gastric carcinomas. It is able to intercalate into DNA. Oxalysine (OXL) is a new antibiotic and shown to be effective against tumor metastatis. When used in combination with 5-FU, its anticancer action could be enhanced. Other natural compounds such as indirubin, ß-elemene, irisquinone, oridonine, norcantharidin and PSP have been also found to possess antitumor action.

Nonvitamin-k-antagonist oral anticoagulants in patients with atrial fibrillation and previous stroke or transient ischemic attack: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND PURPOSE: To assess whether the combined analysis of all phase III trials of nonvitamin-K-antagonist (non-VKA) oral anticoagulants in patients with atrial fibrillation and previous stroke or transient ischemic attack shows a significant difference in efficacy or safety compared with warfarin. METHODS: We searched PubMed until May 31, 2012, for randomized clinical trials using the following search items: atrial fibrillation, anticoagulation, warfarin, and previous stroke or transient ischemic attack. Studies had to be phase III trials in atrial fibrillation patients comparing warfarin with a non-VKA currently on the market or with the intention to be brought to the market in North America or Europe. Analysis was performed on intention-to-treat basis. A fixed-effects model was used as more appropriate than a random-effects model when combining a small number of studies. RESULTS: Among 47 potentially eligible articles, 3 were included in the meta-analysis. In 14 527 patients, non-VKAs were associated with a significant reduction of stroke/systemic embolism (odds ratios, 0.85 [95% CI, 074-0.99]; relative risk reduction, 14%; absolute risk reduction, 0.7%; number needed to treat, 134 over 1.8-2.0 years) compared with warfarin. Non-VKAs were also associated with a significant reduction of major bleeding compared with warfarin (odds ratios, 0.86 [95% CI, 075-0.99]; relative risk reduction, 13%; absolute risk reduction, 0.8%; number needed to treat, 125), mainly driven by the significant reduction of hemorrhagic stroke (odds ratios, 0.44 [95% CI, 032-0.62]; relative risk reduction, 57.9%; absolute risk reduction, 0.7%; number needed to treat, 139). CONCLUSIONS: In the context of the significant limitations of combining the results of disparate trials of different agents, non-VKAs seem to be associated with a significant reduction in rates of stroke or systemic embolism, hemorrhagic stroke, and major bleeding when compared with warfarin in patients with previous stroke or transient ischemic attack.

Field trials of an improved cost-effective device for detecting peridomestic populations of Triatoma infestans (Hemiptera: Reduviidae) in rural Argentina

An improved device for detecting peridomestic Triatoma infestans consisting of one-liter recycled Tetra Brik milk boxes with a central structure was tested using a matched-pair study design in two rural areas in Argentina. In Olta (La Rioja), the boxes were installed beneath the thatched roofs and on the vertical wooden posts of each peridomestic structure. After a 5-month exposure, at least one of the recovered boxes detected 88% of the 24 T. infestans-positive sites, and 86% of the 7 negative sites by timed manual collections at baseline. In Amamá (Santiago del Estero), the boxes were paired with the best performing prototype tested before (shelter unit). After 3 months, some evidence of infestation was detected in 89% (boxes) and 79% (shelters) of 18-19 sites positive by timed collections, whereas 19% and 16% of 32 negative sites were positive, respectively. Neither device differed significantly in the qualitative or quantitative collection of every sign of infestation. The installation site did not modify significantly the boxes' sampling efficiency in both study areas. As the total cost of each box was half as expensive as each shelter unit, the boxes are thus the most cost-effective and easy-to-use tool for detecting peridomestic T. infestans currently available.

Recent clinical trials with omapatrilat: new developments.

Omapatrilat belongs to the vasopeptidase inhibitors, ie, drugs that possess the ability to inhibit simultaneously the membrane-bound zinc metalloproteases, angiotensin-converting enzyme (ACE), and the neutral endopeptidase EC 3.4.24.11 (NEP). Omapatrilat was targeted to treat patients with hypertension and congestive heart failure. The preclinical and early clinical studies conducted with omapatrilat were very promising. Indeed, omapatrilat appeared to be a very potent antihypertensive agent with very favorable effects on cardiac function in heart failure patients. In contrast to these early studies, the large clinical trials were more disappointing. The results of the OCTAVE trial confirmed the antihypertensive efficacy of omapatrilat, but at the price of an angioedema rate more than threefold higher than that of an ACE inhibitor in the overall population (2.17% vs 0.68%), and close to fourfold higher in the black population. In OVERTURE, a large randomized control trial in heart failure, angioedema was also more common with omapatrilat, but the incidence was much lower (0.8% with omapatrilat vs 0.5% with enalapril). However, omapatrilat was not convincingly superior to the ACE inhibitor. Because angioedema is probably a class side effect of vasopeptidase inhibitors, the higher incidence of this potentially life-threatening complication with omapatrilat has likely stopped the development of this new class of agents. The future of vasopeptidase inhibitors will depend on the ability to improve the risk/benefit ratio either by developing agents that produce less angioedema, or by defining more precisely a high-risk population that could take advantage of dual ACE/NEP inhibition.

Gemcitabine, oxaliplatin and 5-FU in advanced bile duct and gallbladder carcinoma: two parallel, multicentre phase-II trials.

BACKGROUND: Gemcitabine, oxaliplatin and 5-fluorouracil (5-FU) are active in biliary tract cancer and have a potentially synergistic mode of action and non-overlapping toxicity. The objective of these trials was to determine response, survival and toxicity separately in patients with bile duct cancer (BDC) and gallbladder cancer (GBC) treated with gemcitabine/oxaliplatin/5-FU chemotherapy. METHODS: Eligible patients with histologically proven, advanced or metastatic BDC (n=37) or GBC (n=35) were treated with gemcitabine (900 mg m(-2) over 30 min), oxaliplatin (65 mg m(-2)) and 5-FU (1500 mg m(-2) over 24 h) on days 1 and 8 of a 21-day cycle. Tumour response was the primary outcome measure. RESULTS: Response rates were 19% (95% CI: 6-32%) and 23% (95% CI: 9-37%) for BDC and GBC, respectively. Median survivals were 10.0 months (95% CI: 8.6-12.4) and 9.9 months (95% CI: 7.5-12.2) for BDC and GBC, respectively, and 1- and 2-year survival rates were 40 and 23% in BDC and 34 and 6% in GBC (intention-to-treat analysis). Major grade III and IV adverse events were neutropenia, thrombocytopenia, elevated bilirubin and anorexia. CONCLUSION: Triple-drug chemotherapy achieves comparable results for response and survival to previously reported regimens, but with more toxicity.