Evaluating real-time internet therapy and online self-help for problematic alcohol consumers: a three-arm RCT protocol

<p>Abstract</p> <p>Background</p> <p>Only a minority of all alcohol- and drug abusers is receiving professional care. In an attempt to narrow this treatment gap, treatment facilities experiment with online healthcare. Therefore, it is important to test the (cost-)effectiveness of online health interventions in a randomized clinical trial.</p> <p>Methods</p> <p>This paper presents the protocol of a three-arm randomized clinical trial to test the (cost-) effectiveness of online treatment for problem drinkers. Self-help online, therapy online and a waiting list are tested against each other. Primary outcome is change in alcohol consumption. Secondary outcome measures include quality of life and working ability. Incremental cost-effectiveness ratios for self-help online alcohol and therapy online alcohol will be calculated. The predictive validity of participant characteristics on treatment adherence and outcome will be explored.</p> <p>Discussion</p> <p>To our best knowledge, this randomized clinical trial will be the first to test the effectiveness of therapy online against both self-help online and a waiting-list. It will provide evidence on (cost-) effectiveness of online treatment for problem drinkers and investigate outcome predictors.</p> <p>Trial registration</p> <p>This trial is registered in the Dutch Trialregister (Cochrane Collaboration) and traceable as NTR-TC1155.</p

Evaluation of a weighting approach for performing sensitivity analysis after multiple imputation

Abstract Background Multiple imputation (MI) is a well-recognised statistical technique for handling missing data. As usually implemented in standard statistical software, MI assumes that data are ‘Missing at random’ (MAR); an assumption that in many settings is implausible. It is not possible to distinguish whether data are MAR or ‘Missing not at random’ (MNAR) using the observed data, so it is desirable to discover the impact of departures from the MAR assumption on the MI results by conducting sensitivity analyses. A weighting approach based on a selection model has been proposed for performing MNAR analyses to assess the robustness of results obtained under standard MI to departures from MAR. Methods In this article, we use simulation to evaluate the weighting approach as a method for exploring possible departures from MAR, with missingness in a single variable, where the parameters of interest are the marginal mean (and probability) of a partially observed outcome variable and a measure of association between the outcome and a fully observed exposure. The simulation studies compare the weighting-based MNAR estimates for various numbers of imputations in small and large samples, for moderate to large magnitudes of departure from MAR, where the degree of departure from MAR was assumed known. Further, we evaluated a proposed graphical method, which uses the dataset with missing data, for obtaining a plausible range of values for the parameter that quantifies the magnitude of departure from MAR. Results Our simulation studies confirm that the weighting approach outperformed the MAR approach, but it still suffered from bias. In particular, our findings demonstrate that the weighting approach provides biased parameter estimates, even when a large number of imputations is performed. In the examples presented, the graphical approach for selecting a range of values for the possible departures from MAR did not capture the true parameter value of departure used in generating the data. Conclusions Overall, the weighting approach is not recommended for sensitivity analyses following MI, and further research is required to develop more appropriate methods to perform such sensitivity analyses

Rotterdam Criteria for Sentinel Node (SN) Tumor Burden and the Accuracy of Ultrasound (US) -Guided Fine-Needle Aspiration Cytology (FNAC): Can US-Guided FNAC Replace SN Staging in Patients With Melanoma?

Purpose Sentinel node (SN) status is the most important prognostic factor for overall survival (OS) for patients with stage I/II melanoma, and the role of the SN procedure as a staging procedure has long been established. However, a less invasive procedure, such as ultrasound (US) -guided fine-needle aspiration cytology (FNAC), would be preferred. The aim of this study was to evaluate the accuracy of US-guided FNAC and compare the results with histology after SN surgery was performed in all patients. Patients and Methods Four hundred consecutive patients who underwent lymphoscintigraphy subsequently underwent a US examination before the SN procedure. When the US examination showed a suspicious or malignant pattern, patients underwent an FNAC. Median Breslow thickness was 1.8 mm; mean follow-up was 42 months (range, 4 to 82 months). We considered the US-guided FNAC positive if either US and/or FNAC were positive. If US was suggestive of abnormality, but FNAC was negative, the US-guided FNAC was considered negative. Results US-guided FNAC identified 51 (65%) of 79 SN metastases. Specificity was 99% (317 of 321), with a positive predictive value of 93% and negative predictive value of 92%. SN-positive identification rate by US-guided FNAC increased from 40% in stage pT1a/b disease to 79% in stage pT4a/b disease. US-guided FNAC detected SN tumors more than 1.0 mm in 86% of cases, SN tumors of 0.1 to 1.0 mm in 46% of cases, and SN tumors less than 0.1 mm in 23% of cases. Estimated 5-year OS rates were 92% for patients with negative US-guided FNAC results and 51% for patients with positive results. Conclusion US-guided FNAC of SNs is highly accurate. Up to 65% of the patients with SN-positive results in our institution could have been spared an SN procedure

Ultrasound Morphology Criteria Predict Metastatic Disease of the Sentinel Nodes in Patients With Melanoma

Purpose We have shown that ultrasound (US) -guided fine needle aspiration cytology (FNAC) can accurately identify the sentinel node (SN). Moreover, US-guided FNAC before the surgical SN procedure could identify up to 65% of all SN metastases. Herein we analyzed in detail the different US morphologic patterns of SN metastases. Patients and Methods From July 2001 to December 2007, a total of 650 patients with melanoma scheduled for sentinel lymph node dissection were examined. We present the first 400 with sufficient follow-up (mean 40, median 39 months). Several morphologic characteristics were scored. In case of suspicious/clearly malignant US patterns a FNAC was performed. The final histology was considered the gold standard. Results Median Breslow was 1.8 mm. The sensitivity and positive predictive value of the most important factors were: peripheral perfusion (PP) present (77% and 52%, respectively), loss of central echoes (LCE; 60% and 65% respectively), and balloon shape (BS; 30% and 96% respectively). Together these factors have a sensitivity of 82% and PPV of 52% (P < .001). PP identified more patients with lower volume disease. PP and combined BS and LCE were independent prognostic factors for survival (hazard ratio, 2.19; P < .015; and hazard ratio, 5.50; P < .001, respectively). Conclusion Preoperative US and FNAC can identify 65% of SN metastases and thus reduce the need for surgical SN procedures. Peripheral perfusion is an early sign of involvement and of crucial importance to achieve a high identification rate. Balloon shape and loss of central echoes are late signs of metastases. We recommend US evaluation to identify those patients, who can directly proceed to a complete lymph node dissection after a positive US-guided FNAC of the SN

Sentinel Node Tumor Burden According to the Rotterdam Criteria Is the Most Important Prognostic Factor for Survival in Melanoma Patients A Multicenter Study in 388 Patients With Positive Sentinel Nodes

Background Data: The more intensive sentinel node (SN) pathologic workup, the higher the SN-positivity rate. This is characterized by an increased detection of cases with minimal tumor burden (SUB-micrometastasis 1 mm) maximum diameter of the largest metastasis. The predictive value for additional nodal metastases in the completion lymph node dissection (CLND) and disease. outcome as disease-free survival (DFS) and overall Survival (OS) was calculated. Results: In 388 SN positive patients, with primary melanoma, median Breslow thickness was 4.00 mm; ulceration was present in 56%. Forty patients (10%) had metastases 1.0 mm (P < 0.001). SN tumor burden increased significantly with tumor thickness. When the cut-off value for SUB-micrometastases was taken at <0.2 mm (such as in breast cancer), the survival was 89%, and 10% had additional non-SN nodal positivity. Conclusion: This large multicenter dataset establishes that patients with SUB-micrometastases <0.1 mm have the same prognosis as SN negative patients and can be spared a CLND. A <0.2 mm cut-off for SLTB-micrometastases does not seem correct for melanoma, as 10% additional nodal positivity is found