METHODS: The administered activity of 177 Lu-DOTATATE was 7.99 ± 0.36 GBq. SPECT/CT images were acquired 0.5, 4, 24, and 48 h after injection in Sunway Medical Centre. For the multiple VSV method, VSV kernels of 177 Lu in media with various densities were generated by Geant4 Application for Emission Tomography (GATE) simulation first. The second step involved the convolution of the time-integrated activity map with each kernel to produce medium-specific dose maps. Third, each medium-specific dose map was masked using binary medium masks, which were generated from CT-based density maps. Finally, all masked dose maps were summed to generate the final dose map. VSV methods with four different VSV sets (1, 4, 10, and 20 VSVs) were compared. Voxel-wise density correction for the single VSV method was also performed. The absorbed doses in the kidneys, bone marrow, and tumors were analyzed, and the relative errors between the VSV and Monte Carlo simulation approaches were estimated. Organ-based dosimetry using Organ Level INternal Dose Assessment/EXponential Modeling (OLINDA/EXM) was also compared.
RESULTS: The accuracy of the multiple VSV approach increased with the number of dose kernels. The average dose estimation errors of a single VSV with density correction and 20 VSVs were less than 6% in most cases, although organ-based dosimetry using OLINDA/EXM yielded an error of up to 123%. The advantages of the single VSV method with density correction and the 20 VSVs over organ-based dosimetry were most evident in bone marrow and bone-metastatic tumors with heterogeneous medium properties.
CONCLUSION: The single VSV method with density correction and multiple VSV method with 20 dose kernels enabled fast and accurate radiation dose estimation. Accordingly, voxel-based dosimetry methods can be useful for managing administration activity and for investigating tumor dose responses to further increase the therapeutic efficacy of 177 Lu-DOTATATE.
METHODS: Elderly outpatients aged at least 65 years with a primary diagnosis of moderate to severe episode of recurrent MDD were recruited by psychiatrists in 44 clinical centers in 10 countries from October 2013 to January 2016. Patients were randomly assigned to receive tianeptine (n = 105), placebo (n = 107), or escitalopram (n = 99) for 8 weeks. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS₁₇) total score.
RESULTS: Tianeptine improved depressive symptoms, as evaluated by the HDRS₁₇ total score in terms of absolute change from baseline (week 0) to week 8 (placebo-tianeptine difference [SE] of 3.84 [0.85] points, P < .001, using a last-observation-carried-forward approach) and response to treatment (tianeptine: 46.7%; placebo: 34.0%, estimate [SE] = 12.70% [6.70], P = .06). A sensitivity analysis using a mixed model for repeated measures confirmed the main results on HDRS total score. The placebo-tianeptine difference (SE) was 0.66 (0.15) for Clinical Global Impressions-Severity of Illness (95% CI, 0.37 to 0.96; P < .001) and 0.57 (0.14) for Clinical Global Impressions- Improvement (95% CI, 0.30 to 0.83; P < .001). Positive results were also obtained with the active control escitalopram (HDRS₁₇ total score placebo-escitalopram difference of 4.09 ± 0.86 points, P < .001), therefore validating the sensitivity of the studied population. Tianeptine was well tolerated, with only minimal differences in tolerability from placebo.
CONCLUSIONS: The present study provides robust evidence that an 8-week treatment period with tianeptine 25-50 mg is efficacious and well tolerated in depressed patients aged 65 years or older.
TRIAL REGISTRATION: EudraCT identifier: 2012-005612-26.
METHODS: This is a secondary analysis of the database of a multicentre study which recorded participants' basic demographical and clinical data in standardised format in 10 Asian countries and territories. The data were analysed using univariate and multivariate logistic regression analyses.
RESULTS: A total of 955 older adult psychiatric in- and outpatients were included in this study. The proportion of concurrent AP and AD use was 32.0%, ranging from 23.3% in Korea to 44.0% in Taiwan. Multivariate logistic regression analysis found that younger age, inpatient status and diagnosis of schizophrenia, anxiety and other mental disorders were significantly related to a higher proportion of concurrent use of APs and ADs.
CONCLUSION: Around a third of older adult psychiatric patients had concurrent AP and AD use in the Asian countries/regions surveyed. Considering the uncertain effectiveness and questionable safety of the AP and AD combination in this patient population, such should be cautiously used.