Safety and efficacy of a digital therapeutic for substance use disorder: Secondary analysis of data from a NIDA clinical trials network study.

Background: Traditional treatments for substance use disorders (SUDs) rely heavily on face-to-face interactions, which pose substantial limitations for patients. A clinical trial of a digital therapeutic (DT), delivering behavioral therapy demonstrated safety and efficacy in a population including patients with opioid use disorder (OUD) not treated with buprenorphine, which is not a guideline-recommended approach. This study re-analyzed the data excluding patients with OUD to more closely approximate real-world patient populations. Methods: Secondary analysis of patients with substance use disorders related to alcohol, cannabis, cocaine, or other stimulants (n = 399, patients with OUD excluded) from a previously-published randomized controlled trial. Patients received 12-weeks of outpatient treatment-as-usual (TAU; n = 193) or TAU with reduced counseling plus a DT (n = 206) providing computerized cognitive behavioral therapy and contingency management. Primary outcomes were abstinence in weeks 9-12 and retention in treatment. Results: The 399 patients in this analysis (206 in the DT group and 193 in the TAU group) reported substance use disorders related to alcohol, cannabis, cocaine, or other stimulants (e.g., methamphetamines). Demographic and baseline characteristics including age, sex, race, education, and reported primary substance use disorder were balanced between treatment groups. Abstinence was significantly higher in the DT group compared to TAU (40.3 vs. 17.6%; p < 0.001) as was retention in therapy (76.2 vs. 63.2%, p = 0.004). Intergroup adverse event rates were not significantly different (p = 0.68). Conclusions: The results demonstrate that use of a DT safely increased abstinence (reduced substance use) and retention in treatment among patients with substance use disorders related to alcohol, cannabis, cocaine, or other stimulants (including methamphetamines).

First-time-in-human study of GSK923295, a novel antimitotic inhibitor of centromere-associated protein E (CENP-E), in patients with refractory cancer.

PURPOSE: GSK923295 is an inhibitor of CENP-E, a key cellular protein important in the alignment of chromosomes during mitosis. This was a Phase I, open-label, first-time-in-human, dose-escalation study, to determine the maximum-tolerated dose (MTD), safety, and pharmacokinetics of GSK923295. PATIENTS AND METHODS: Adult patients with previously treated solid tumors were enrolled in successive cohorts at GSK923295 doses ranging from 10 to 250 mg/m(2). GSK923295 was administered by a 1-h intravenous infusion, once weekly for three consecutive weeks, with treatment cycles repeated every 4 weeks. RESULTS: A total of 39 patients were enrolled. The MTD for GSK923295 was determined to be 190 mg/m(2). Observed dose-limiting toxicities (all grade 3) were as follows: fatigue (n = 2, 5%), increased AST (n = 1, 2.5%), hypokalemia (n = 1, 2.5%), and hypoxia (n = 1, 2.5%). Across all doses, fatigue was the most commonly reported drug-related adverse event (n = 13; 33%). Gastrointestinal toxicities of diarrhea (n = 12, 31%), nausea (n = 8, 21%), and vomiting (n = 7, 18%) were generally mild. Frequency of neutropenia was low (13%). There were two reports of neuropathy and no reports of mucositis or alopecia. GSK923295 exhibited dose-proportional pharmacokinetics from 10 to 250 mg/m(2) and did not accumulate upon weekly administration. The mean terminal elimination half-life of GSK923295 was 9-11 h. One patient with urothelial carcinoma experienced a durable partial response at the 250 mg/m(2) dose level. CONCLUSIONS: The novel CENP-E inhibitor, GSK923295, had dose-proportional pharmacokinetics and a low number of grade 3 or 4 adverse events. The observed incidence of myelosuppression and neuropathy was low. Further investigations may provide a more complete understanding of the potential for GSK923295 as an antiproliferative agent.

Technetium Tc 99m sestamibi sensitivity in oxyphil cell-dominant parathyroid adenomas.

OBJECTIVE: A subset of parathyroid adenomas contains a relative overabundance of oxyphil cells that are capable of greater technetium Tc 99m sestamibi tracer uptake and retention than other cell types. We examined whether the presence of oxyphil cells augments the sensitivity of technetium Tc 99m sestamibi preoperative localization and whether the histologic findings of a lesion could be predicted based on the adenoma mass and serum calcium and parathyroid hormone levels. DESIGN: Retrospective, single-blinded comparison of technetium Tc 99m sensitivity rates, lesion mass, and preoperative serum calcium and parathyroid hormone values of patients with chief and mixed cell-dominant adenomas and those with oxyphil-dominant parathyroid adenomas. SETTING: Tertiary care university hospital. PATIENTS: Sixty-three patients diagnosed as having a parathyroid adenoma. INTERVENTION: All patients underwent resection of a parathyroid adenoma following a preoperative technetium Tc 99m sestamibi localization study and serum calcium and parathyroid hormone level analysis. MAIN OUTCOME MEASURE: Technetium Tc 99m sensitivity rate. RESULTS: The overall technetium Tc 99m sestamibi sensitivity rate was 76.2%. The sensitivity within the chief and mixed cell-dominant (n = 52) and oxyphil cell-dominant groups (n = 11) were 71.2% and 100%, respectively (P = .04). There was no correlation between histologic findings of the lesion and its size or serum calcium and parathyroid hormone levels. CONCLUSIONS: Oxyphil cell predominance within an adenoma augments technetium Tc 99m sestamibi scan sensitivity in a statistically significant manner. The use of technetium Tc 99m sestamibi preoperative localization may therefore be differentially greater in patients with these types of lesions.

Predictors of regional nodal disease in patients with thin melanomas.

BACKGROUND: Most melanoma patients present with thin (0, vertical growth phase (VGP), male sex, and ulceration were statistically significant predictors of RND. Patients at the highest risk according to a classification tree analysis (VGP and MR>0) had an RND rate of 11.9%. The regression model developed predicted well the SLN status in the validation sample. CONCLUSIONS: Investigation of a large pre-SLN population identified MR>0, ulceration, VGP, and male sex as independently predictive of RND in patients with thin melanomas. These factors may help to identify subgroups of these patients that have clinically significant risks of SLN positivity.

Mitotic rate as a predictor of sentinel lymph node positivity in patients with thin melanomas.

BACKGROUND: Lymphatic mapping and sentinel lymphadenectomy (LM/SL) provide important prognostic information for patients with early-stage melanoma. Although the use of this technique in patients with thin melanomas (< or =1.00 mm) is not routine, risk factors that may predict sentinel lymph node (SLN) positivity in this patient population are under investigation. We sought to determine whether mitotic rate (MR) is associated with SLN positivity in thin-melanoma patients and, therefore, whether it may be used to risk-stratify and select patients for LM/SL. METHODS: Clinical and histopathologic variables were reviewed for 181 patients with thin melanomas who underwent LM/SL from January 1996 through January 2004. Univariate and multivariate logistic regression analyses were performed to identify factors associated with SLN positivity. Risk groups were defined on the basis of the development of a classification tree. RESULTS: The overall SLN positivity rate was 5%. All patients with positive SLNs had an MR of >0. By univariate analysis, MR and thickness were significant predictors of SLN positivity. The association between MR and SLN positivity remained significant controlling for each of the other variables evaluated. On the basis of a classification tree, patients with an MR >0 and tumor thickness > or =.76 mm were identified as a higher-risk group, with an SLN positivity rate of 12.3%. CONCLUSIONS: In patients with thin melanomas, MR >0 seems to be a significant predictor of SLN positivity that may be used to risk-stratify and select patients for LM/SL. To confirm these results, the predictive value of MR for SLN positivity needs to be validated in other populations of thin-melanoma patients.