Opioid antagonist detoxification under anaesthesia versus traditional clonidine detoxification combined with an additional week of psychosocial support: a randomised clinical trial.

BACKGROUND: While detoxification under anaesthesia accelerates the detoxification procedure, there is a lack of randomised clinical trials evaluating its effectiveness compared to traditional detoxification procedures, and a lack of data on long-term abstinence. METHODS: Prospective randomised clinical trial. Analysis by intention to treat and per protocol. Setting: Specialised substance abuse unit in a psychiatric teaching hospital and an intensive care unit of a general hospital. Participants: Seventy patients with opiate mono-dependence requesting detoxification: 36 randomised to RODA (treatment as allocated received by 26) and 34 randomised to classical clonidine detoxification (treatment as allocated received by 21). Main outcome measures: Successful detoxification, safety and self-reported abstinence at 3, 6 and 12 months after detoxification. RESULTS: Socio-demographics were similar in both groups at baseline. No complications were reported during or after anaesthesia. According to the intention to treat analysis, 28/36 (78%) RODA patients and 21/34 (62%) of the clonidine group successfully completed the detoxification process (p=0.14). In the intention to treat analysis, 30% of RODA patients were abstinent after 3 months compared to 14% in the clonidine group (p=0.11). No difference was found at 6 and 12 months (both groups showed less than 5% abstinence after 12 months). The per-protocol analysis showed similar results with no statistical differences either for ASI mean scores or for the SF36 questionnaire. CONCLUSION: Although the detoxification success rate and abstinence after 3 months were slightly better for the RODA procedure compared to clonidine treatment, these differences were not statistically significant and disappeared completely after 6 and 12 months.

Blood pressure and low-density lipoprotein-cholesterol lowering for prevention of strokes and cognitive decline: a review of available trial evidence.

BACKGROUND AND OBJECTIVES: It is well established by a large number of randomized controlled trials that lowering blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) by drugs are powerful means to reduce stroke incidence, but the optimal BP and LDL-C levels to be achieved are largely uncertain. Concerning BP targets, two hypotheses are being confronted: first, the lower the BP, the better the treatment outcome, and second, the hypothesis that too low BP values are accompanied by a lower benefit and even higher risk. It is also unknown whether BP lowering and LDL-C lowering have additive beneficial effects for the primary and secondary prevention of stroke, and whether these treatments can prevent cognitive decline after stroke. RESULTS: A review of existing data from randomized controlled trials confirms that solid evidence on optimal BP and LDL-C targets is missing, possible interactions between BP and LDL-C lowering treatments have never been directly investigated, and evidence in favour of a beneficial effect of BP or LDL-C lowering on cognitive decline is, at best, very weak. CONCLUSION: A new, large randomized controlled trial is needed to determine the optimal level of BP and LDL-C for the prevention of recurrent stroke and cognitive decline.

Mediastinal lymph node clearance after docetaxel-cisplatin neoadjuvant chemotherapy is prognostic of survival in patients with stage IIIA pN2 non-small-cell lung cancer: a multicenter phase II trial.

PURPOSE: A multicenter, phase II trial investigated the efficacy and toxicity of neoadjuvant docetaxel-cisplatin in locally advanced non-small-cell lung cancer (NSCLC) and examined prognostic factors for patients not benefiting from surgery. PATIENTS AND METHODS: Ninety patients with previously untreated, potentially operable stage IIIA (mediastinoscopically pN2) NSCLC received three cycles of docetaxel 85 mg/m2 day 1 plus cisplatin 40 mg/m2 days 1 and 2, with subsequent surgical resection. RESULTS: Administered dose-intensities were docetaxel 85 mg/m2/3 weeks (range, 53 to 96) and cisplatin 95 mg/m2/3 weeks (range, 0 to 104). The 265 cycles were well tolerated, and the overall response rate was 66% (95% confidence interval [CI], 55% to 75%). Seventy-five patients underwent tumor resection with positive resection margin and involvement of the uppermost mediastinal lymph node in 16% and 35% of patients, respectively (perioperative mortality, 3%; morbidity, 17%). Pathologic complete response occurred in 19% of patients with tumor resection. In patients with tumor resection, downstaging to N0-1 at surgery was prognostic and significantly prolonged event-free survival (EFS) and overall survival (OS; P =.0001). At median follow-up of 32 months, the median EFS and OS were 14.8 months (range, 2.4 to 53.4) and 33 months (range, 2.4 to 53.4), respectively. Local relapse occurred in 27% of patients with tumor resection, with distant metastases in 37%. Multivariate analyses identified mediastinal clearance (hazard ratio, 0.22; P =.0003) and complete resection (hazard ratio, 0.26; P =.0006) as strongly prognostic for increased survival. CONCLUSION: Neoadjuvant docetaxel-cisplatin is effective and tolerable in stage IIIA pN2 NSCLC. Resection is recommended only for patients with mediastinal downstaging after chemotherapy.

Electrical neuroimaging of memory discrimination based on single-trial multisensory learning.

Multisensory experiences influence subsequent memory performance and brain responses. Studies have thus far concentrated on semantically congruent pairings, leaving unresolved the influence of stimulus pairing and memory sub-types. Here, we paired images with unique, meaningless sounds during a continuous recognition task to determine if purely episodic, single-trial multisensory experiences can incidentally impact subsequent visual object discrimination. Psychophysics and electrical neuroimaging analyses of visual evoked potentials (VEPs) compared responses to repeated images either paired or not with a meaningless sound during initial encounters. Recognition accuracy was significantly impaired for images initially presented as multisensory pairs and could not be explained in terms of differential attention or transfer of effects from encoding to retrieval. VEP modulations occurred at 100-130ms and 270-310ms and stemmed from topographic differences indicative of network configuration changes within the brain. Distributed source estimations localized the earlier effect to regions of the right posterior temporal gyrus (STG) and the later effect to regions of the middle temporal gyrus (MTG). Responses in these regions were stronger for images previously encountered as multisensory pairs. Only the later effect correlated with performance such that greater MTG activity in response to repeated visual stimuli was linked with greater performance decrements. The present findings suggest that brain networks involved in this discrimination may critically depend on whether multisensory events facilitate or impair later visual memory performance. More generally, the data support models whereby effects of multisensory interactions persist to incidentally affect subsequent behavior as well as visual processing during its initial stages.

Long-term follow-up of European APL 2000 trial, evaluating the role of cytarabine combined with ATRA and Daunorubicin in the treatment of nonelderly APL patients.

All-trans retinoic acid (ATRA) combined to anthracycline-based chemotherapy is the reference treatment of acute promyelocytic leukemia (APL). Whereas, in high-risk patients, cytarabine (AraC) is often considered useful in combination with anthracycline to prevent relapse, its usefulness in standard-risk APL is uncertain. In APL 2000 trial, patients with standard-risk APL [i.e., with baseline white blood cell (WBC) count <10,000/mm(3) ] were randomized between treatment with ATRA with Daunorubicin (DNR) and AraC (AraC group) and ATRA with DNR but without AraC (no AraC group). All patients subsequently received combined maintenance treatment. The trial had been prematurely terminated due to significantly more relapses in the no AraC group (J Clin Oncol, (24) 2006, 5703-10), but follow-up was still relatively short. With long-term follow-up (median 103 months), the 7-year cumulative incidence of relapses was 28.6% in the no AraC group, compared to 12.9% in the AraC group (P = 0.0065). In standard-risk APL, at least when the anthracycline used is DNR, avoiding AraC may lead to an increased risk of relapse suggesting that the need for AraC is regimen-dependent.

Quality assurance of the EORTC 22043-30041 trial in post-operative radiotherapy in prostate cancer: Results of the Dummy Run procedure.

BACKGROUND AND PURPOSE: The EORTC 22043-30041 trial investigates the role of the addition of androgen suppression to post-operative radiotherapy in patients who have undergone radical prostatectomy. As part of the quality assurance of radiotherapy (QART) a Dummy Run (DR) procedure was performed. MATERIALS AND METHOD: The protocol included detailed and published delineation guidelines. Participating institutions digitally submitted radiotherapy treatment volumes and a treatment plan for a standard clinical case. Submissions were centrally reviewed using the VODCA software platform. RESULTS: Thirty-eight submissions from thirty-one institutions were reviewed. Six were accepted without comments. Twenty-three were accepted with comments on one or more items: target volume delineation (22), OAR delineation (23), planning and dosimetry (3) or treatment verification (1). Nine submissions were rejected requiring resubmission, seven for target volume delineation reasons alone. Intervention to highlight the importance of delineation guidelines was made prior to the entry of the first patient in the trial. After this, a lower percentage of resubmissions was required. CONCLUSIONS: The EORTC 22043-30041 Dummy Run highlights the need for timely and effective QART in clinical trials. The variation in target volume and OAR definition demonstrates that clinical guidelines and radiotherapy protocols are not a substitute for QART procedures. Early intervention in response to the Dummy Run improved protocol understanding.

Usage of Calendula officinalis in the prevention and treatment of radiodermatitis: a randomized double-blind controlled clinical trial

OBJECTIVE To evaluate the efficacy of Calendula officinalis in relation to Essential Fatty Acids for the prevention and treatment of radiodermatitis. METHOD This is a randomized double-blind controlled clinical trial with 51 patients with head and neck cancer in radiotherapy treatment divided into two groups: control (27) and experimental (24). RESULTS There is statistically significant evidence (p-value = 0.0120) that the proportion of radiodermatitis grade 2 in Essential Fatty Acids group is higher than Calendula group. Through the Kaplan-Meier survival curve we observed that Essential Fatty Acids group has always remained below the Calendula group survival curve, due to the lower risk of developing radiodermatitis grade 1, which makes the usage of Calendula more effective, with statistical significance (p-value = 0.00402). CONCLUSION Calendula showed better therapeutic response than the Essential Fatty Acids in the prevention and treatment of radiodermatitis. Brazilian Registry of Clinical Trials: RBR-237v4b.

Immunization with H1, HASPB1 and MML Leishmania proteins in a vaccine trial against experimental canine leishmaniasis.

The protective capabilities of three Leishmania recombinant proteins - histone 1 (H1) and hydrophilic acylated surface protein B1 (HASPB1) immunized singly, or together as a protein cocktail vaccine with Montanide, and the polyprotein MML immunized with MPL-SE adjuvant - were assessed in beagle dogs. Clinical examination of the dogs was carried out periodically under blinded conditions and the condition of the dogs defined as asymptomatic or symptomatic. At the end of the trial, we were able to confirm that following infection with L. infantum promastigotes, five out of eight dogs immunized with H1 Montanide, and four out of eight dogs immunized with either the combination of HASPB1 with Montanide or the combination of H1+HASPB1 with Montanidetrade mark, remained free of clinical signs, compared with two out of seven dogs immunized with the polyprotein MML and adjuvant MPL-SE, and two out of eight dogs in the control group. The results demonstrate that HASPB1 and H1 antigens in combination with Montanide were able to induce partial protection against canine leishmaniasis, even under extreme experimental challenge conditions.

Preoperative immunonutrition in patients at nutritional risk: results of a double-blinded randomized clinical trial.

Background/Objectives:To evaluate the impact of preoperative immunonutrition (IN) on postoperative morbidity in patients at risk of malnutrition undergoing major gastrointestinal (GI) surgery.Subjects/Methods:The combination of malnutrition and major GI surgery entails high morbidity. The Nutritional Risk Score (NRS) reliably identifies patients who need preoperative nutrition; the optimal nutritional formula for these patients still needs to be defined. In all, 152 patients with a NRS3 and undergoing elective major GI surgery were randomized between IN or isocaloric-isonitrogenous nutrition (ICN) given for 5 days preoperatively. Patients and caregivers were blinded for the allocated intervention. Thirty days complication rate was the primary endpoint. Infections, length of hospital stay and compliance were considered as secondary outcomes.Results:Overall, 145 patients were available for analysis; the 73 patients in the IN group matched well with the 72 ICN patients with regards to patient's and surgical characteristics. In all, 39 IN and 33 ICN patients experienced a total of 48 and 50 postoperative complications, respectively (P=0.723). Both groups did not differ significantly concerning infectious (13 vs 9) complications. Independent risk factors for overall complications were malignant disease (odds ratio (OR)=4.304; confidence interval (CI) 1.317-14.002) and operative time (OR=1.004; CI 1.000-1.008).Conclusion:In patients at nutritional risk, complications, infections and hospital stay after major GI surgery were comparable regardless of preoperative supplementation with IN or ICN.

Need of reduced and harmonized bureaucracy in multi-centre clinical research - a case-report from a Swiss trial

Introduction: We launched an investigator-initiated study (ISRCTN31181395) to evaluate the potential benefit of pharmacokinetic-guided dosage individualization of imatinib for leukaemiapatients followed in public and private sectors. Following approval by the research ethics committee (REC) of the coordinating centre, recruitment throughout Switzerland necessitatedto submit the protocol to 11 cantonal RECs.Materials and Methods: We analysed requirements and evaluation procedures of the 12 RECs with associated costs.Results: 1-18 copies of the dossier, in total 4300 printed pages, were required (printing/posting costs: ~300 CHF) to meet initial requirements. Meeting frequencies of RECs ranged between 2 weeks and 2 months, time from submission to fi rst feedback took 2-75 days. Study approval was obtained from a chairman, a subor the full committee, the evaluation work being invoiced by0-1000 CHF (median: 750 CHF, total: 9200 CHF). While 5 RECs gave immediate approval, the other 6 rose in total 38 queries before study release, mainly related to wording in the patient information, leading to 7 different fi nal versions approved. Submission tasks employed an investigator half-time over about 6 months.Conclusion: While the necessity of clinical research evaluation by independent RECs is undisputed, there is a need of further harmonization and cooperation in evaluation procedures. Current administrative burden is indeed complex, time-consuming and costly. A harmonized electronic application form, preferably compatible with other regulatory bodies and European countries, could increase transparency, improve communication, and encourage academic multi-centre clinical research in Switzerland.