Effectiveness of text message interventions with different behavior change techniques on alcohol consumption among young adults: a five-arm randomized controlled trial.

AIMS: This studys aim is to test the effectiveness of five interventions each utilizing a unique set of behavior change techniques on reducing alcohol consumption at 3 and 6 months among young adults with hazardous drinking. DESIGN, SETTING AND PARTICIPANTS: This study used a five-arm parallel randomized controlled trial with 3- and 6-month follow-ups. Recruitment occurred at four emergency departments in Pittsburgh, PA, USA. Participants were non-treatment-seeking young adults (mean age = 22.1 years; 68.5% female; 37.1% black) who reported hazardous drinking. INTERVENTIONS: Participants were randomized to one of five automated text message interventions for 12 weeks that interacted with participants on the 2 days per week that they typically drank: assisted self-monitoring (TRACK: control condition; n = 245), pre-drinking cognition feedback (PLAN; n = 226), alcohol consumption feedback (USE; n = 235), adaptive goal support (GOAL; n = 214) and a combination of interventions (COMBO; n = 221). MEASUREMENTS: Primary outcome was number of past month binge drinking days at 3-month post-randomization calculated from a 30-day time-line follow-back. Primary intention-to-treat analysis compared PLAN, USE, GOAL and COMBO against TRACK (control condition). The four active conditions were not compared against each other. A secondary outcome, durability of effects, was measured at 6 months. FINDINGS: From baseline to 3-month follow-up (retention = 81.1%), compared with TRACK, in which past-month mean binge drinking days increased from 2.7 to 3.4, mean binge drinking days decreased in COMBO from 3.0 to 2.3 [adjusted ß = -0.52; 95% confidence interval (CI) = -0.77, -0.26], GOAL from 3.0 to 2.6 (adjusted ß = -0.34; 95% CI = -0.59, -0.10) and USE from 3.3 to 2.9 (adjusted ß = -0.38; 95% CI = -0.62, -0.14). At 6 months (retention = 73.8%), COMBO, GOAL, USE and PLAN had significantly lower mean binge drinking days compared with TRACK. CONCLUSION: Text message interventions incorporating feedback on either drinking plans and/or alcohol consumption and/or drinking limit goal support produced small yet durable reductions in binge drinking days in non-treatment-seeking young adults with hazardous drinking.

Effectiveness of a Text Message Intervention Promoting Seat Belt Use Among Young Adults: A Randomized Clinical Trial.

Importance: Approximately 1 in 10 adults do not always wear a seat belt, with the lowest use rates reported among young adults. Objective: To determine the efficacy of a 6-week automated behavioral text message program promoting seat belt use compared with an attention control. Design, Setting, and Participants: This parallel, 2-group, single-blind, individually randomized clinical trial included a convenience sample of patients recruited from 4 emergency departments in 2 cities in Pennsylvania from December 2019 to September 2021, with follow-ups at 6 and 12 weeks after randomization. Patients in stable condition aged 18 to 25 years who, in standardized screening, reported driving or being a passenger in a car without always using a seat belt in the past 2 weeks were eligible for recruitment. Participants who completed a 2-week trial run-in phase were randomly assigned 1:1 to the intervention or the assessment control. Data were analyzed from October 2019 to January 2020. Interventions: The intervention group received Safe Vehicle Engagement (SAVE), a 6-week automated interactive text message program, including weekly seat belt use queries with feedback and goal support to promote consistent use of a seat belt. The control group received identical weekly seat belt use queries but no additional feedback. Main Outcomes and Measures: The primary outcome was the proportion of young adults reporting always wearing a seat belt over the past 2 weeks, collected at 6 weeks (after a 2-week run-in) via web-based self-assessments and analyzed under intent-to-treat models using multiple imputation procedures. Sensitivity analyses included complete-case analyses of ordered categorical outcomes by vehicle seat position. Secondary outcomes included seatbelt use at 12 weeks and select cognitive constructs related to seat belt use. Results: A total of 218 participants (mean [SD] age, 21.5 [2.1] years; 139 [63.8%] women) were randomized, with 110 randomized to SAVE and 108 randomized to the control group. A total of 158 individuals (72.4%) were included in the 6-week follow-up. The rate of always using a seat belt over the past 2 weeks at the 6-week follow-up was 41.3% (95% CI, 30.6%-52.0%) among SAVE participants and 20.0% (95% CI, 10.6%-29.3%) among control participants (odds ratio [OR], 2.8; 95% CI, 1.4-5.8; P = .005). A total of 140 individuals (64.2%) participated in the 12-week follow-up. At 12 weeks, the rate of always using a seat belt over the past 2-weeks was 42.8% (95% CI, 31.2%-54.2%) among SAVE participants and 30.7% (95% CI, 19.6%-41.6%) among control participants (OR, 1.7; 95% CI, 0.9-3.4; P = .13). When examining ordered categories of seat belt use by seat position, there were significantly greater odds of wearing a seat belt at 6 and 12 weeks among SAVE participants vs control participants (eg, 6 weeks for driver: OR, 5.2; 95% CI, 2.6-10.5; 6 weeks for front passenger: OR, 4.3; 95% CI, 2.2-8.2; 6 weeks for back passenger: OR, 4.3; 95% CI, 2.2-8.2). Conclusions and Relevance: In this randomized clinical trial, an interactive text message intervention was more effective at promoting seat belt use among targeted young adults than an attention control at 6 weeks. There was no significant difference between groups in always wearing a seat belt at 12 weeks. These findings, if replicated in a larger sample, suggest a scalable approach to improve seat belt use. Trial Registration: ClinicalTrials.gov Identifier: NCT03833713.

Effectiveness of a Text Message Intervention to Reduce Texting While Driving Among Targeted Young Adults: A Randomized Controlled Trial.

PURPOSE: This randomized clinical trial tested the efficacy of a 6-week text message program to reduce texting while driving (TWD) for young adults. METHODS: Eligible individuals recruited from four emergency departments from December 2019 to June 2021 were aged 18-25 years who reported TWD in the past 2 weeks. Participants were randomly assigned 1:1 to intervention:assessment control. The intervention arm (n = 57) received an automated interactive text message program, including weekly queries about TWD for 6 weeks with feedback and goal support to promote cessation of TWD. The assessment control arm (n = 55) received identical weekly TWD queries but no additional feedback. Outcomes were collected via web-based self-assessments at 6- and 12 weeks and analyzed under intent-to-treat models, presented as adjusted odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: The mean (SD) age was 21.7 (2.1) years, 73 (65%) were female, and 40 (36%) were White. The 6-week follow-up rate was 77.7% (n = 87) and 12-week follow-up rate was 64.3% (n = 72). At 6 weeks, 52.6% (95% CI, 39.0%-66.0%) of intervention participants reported TWD versus 63.6% (95% CI, 49.6%-76.2%) of control participants (adjusted OR, 0.71; 95% CI, 0.32-1.59). At 12 weeks, 38.2% (95% CI, 22.8%-53.5%) of intervention participants reported TWD versus 69.3% (95% CI, 53.8%-84.7%) of control participants (adjusted OR, 0.29; 95% CI, 0.11-0.80). DISCUSSION: An interactive text message intervention was more effective at reducing self-reported TWD among young adults than assessment control at 12 weeks.

Predicting falls within 3 months of emergency department discharge among community-dwelling older adults using self-report tools versus a brief functional assessment.

BACKGROUND: Identifying older adults with risk for falls prior to discharge home from the Emergency Department (ED) could help direct fall prevention interventions, yet ED-based tools to assist risk stratification are under-developed. The aim of this study was to assess the performance of self-report and functional assessments to predict falls in the 3 months post-ED discharge for older adults. METHODS: A prospective cohort of community-dwelling adults age 60 years and older were recruited from one urban ED (N = 134). Participants completed: a single item screen for mobility (SIS-M), the 12-item Stay Independent Questionnaire (SIQ-12), and the Timed Up and Go test (TUG). Falls were defined through self-report of any fall at 1- and 3-months and medical record review for fall-related injury 3-months post-discharge. We developed a hybrid-convolutional recurrent neural network (HCRNN) model of gait and balance characteristics using truncal 3-axis accelerometry collected during the TUG. Internal validation was conducted using bootstrap resampling with 1000 iterations for SIS-M, FRQ, and GUG and leave-one-out for the HCRNN. We compared performance of M-SIS, FRQ, TUG time, and HCRNN by calculating the area under the receiver operating characteristic area under the curves (AUCs). RESULTS: 14 (10.4%) of participants met our primary outcome of a fall or fall-related injury within 3-months. The SIS-M had an AUC of 0.42 [95% confidence interval (CI) 0.19-0.65]. The SIQ-12 score had an AUC of 0.64 [95% confidence interval (CI) 0.49-0.80]. The TUG had an AUC of 0.48 (95% CI 0.29-0.68). The HCRNN model using generated accelerometer features collected during the TUG had an AUC of 0.99 (95% CI 0.98-1.00). CONCLUSION: We found that self-report and functional assessments lack sufficient accuracy to be used in isolation in the ED. A neural network model using accelerometer features could be a promising modality but research is needed to externally validate these findings.

A Preliminary Study Using Smartphone Accelerometers to Sense Gait Impairments Due to Alcohol Intoxication.

OBJECTIVE: Sensing the effects of alcohol consumption in real time could offer numerous opportunities to reduce related harms. This study sought to explore accuracy of gait-related features measured by smartphone accelerometer sensors on detecting alcohol intoxication (breath alcohol concentration [BrAC] > .08%). METHOD: In a controlled laboratory study, participants (N = 17; 12 male) were asked to walk 10 steps in a straight line, turn, and walk 10 steps back before drinking and each hour, for up to 7 hours after drinking a weight-based dose of alcohol to reach a BrAC of .20%. Smartphones were placed on the lumbar region and 3-axis accelerometer data was recorded at a rate of 100 Hz. Accelerometer data were segmented into task segments (i.e., walk forward, walk backward). Features were generated for each overlapping 1-second windows, and the data set was split into training and testing data sets. Logistic regression models were used to estimate accuracy for classifying BrAC ≤ .08% from BrAC > .08% for each subject. RESULTS: Across participants, BrAC > .08% was predicted with a mean accuracy of 92.5% using logistic regression, an improvement from a naive model accuracy of 88.2% (mean sensitivity = .89; specificity = .92; positive predictive value = .77; and negative predictive value = .97). The two most informative accelerometer features were mean signal amplitude and variance of the signal in the x-axis (i.e., gait sway). CONCLUSIONS: We found preliminary evidence supporting use of gait-related features measured by smartphone accelerometer sensors to detect alcohol intoxication. Future research should determine whether these findings replicate in situ.

The effect of SMS behavior change techniques on event-level desire to get drunk in young adults.

Text messaging (SMS) interventions incorporating a combination of behavior change techniques can assist reductions in alcohol consumption among young adult hazardous drinkers, but mechanisms of action remain unknown. In this secondary analysis, we test the hypothesis that desire to get drunk (DD) recorded prior to drinking episodes would mediate SMS intervention effects on the likelihood of event-level heavy drinking (4 +/5 + drinks for women/men). We recruited young adult hazardous drinkers to a trial where they were randomized to 1 of 5 SMS interventions: TRACK (self-monitoring of alcohol use), PLAN (feedback on drinking plans and DD), USE (postdrinking feedback on alcohol consumed), GOAL (goal prompts/support), and COMBO (i.e., 4 interventions combined). Up to 3 days per week for 14 weeks, when participants reported a plan to drink, they were asked to report DD on a scale from 0 (none) to 8 (completely) and next day asked to recall drink quantity. Multilevel structural equation models showed that DD mediated the treatment effect of GOAL on heavy drinking. This work illustrates the importance of goal support features in digital alcohol interventions and the utility of measuring desire to get drunk as a key mediator in alcohol studies. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Enhanced suppression of melanoma tumor growth and metastasis by combined therapy with anti-VEGF receptor and anti-TYRP-1/gp75 monoclonal antibodies.

Targeted immunotherapy against tumors or angiogenesis has shown promise as an alternative approach for the treatment of malignant disease. Whether or not combining these two treatment modalities would enhance the antitumor effect was tested in mouse models of malignant melanoma. C57BL/6 mice bearing established subcutaneous B16 tumors were treated with anti-vascular endothelial growth factor receptor (anti-VEGFR) fetal liver kinase-1 (Flk-1) monoclonal antibody (mAb) DC101 and/or anti-TYRP-1/gp75 (tyrosinase-related protein-1) mAb TA99. The growth of subcutaneous B16 tumors was significantly suppressed by the mAb DC101 (63%, p<0.001) and by mAb TA99 (75%, p<0.001) treatment alone. The combined antibody (TA99+DC101) treatment resulted in a significant enhancement (93%, p<0.001) of tumor growth suppression. In a B16 pulmonary metastasis model, combined therapy with mAb DC101 and mAb TA99 resulted in a significant reduction of lung metastases compared to the control (p<0.001) and the single agent treatment groups (p<0.05). A combined modality approach that provides passive immunity to melanoma differentiation antigens as well as inhibiting tumor neovascularization may be valuable for the treatment of malignant melanoma.

Anti-vascular endothelial growth factor receptor-1 antagonist antibody as a therapeutic agent for cancer.

PURPOSE: Vascular endothelial growth factor receptor-1 (VEGFR-1) plays important roles in promotion of tumor growth by mediating cellular functions in tumor vascular endothelium and cancer cells. Blockade of VEGFR-1 activation has been shown to inhibit pathologic angiogenesis and tumor growth, implicating VEGFR-1 as a potential therapeutic target for the treatment of cancer. We have thus developed a VEGFR-1 antagonist human monoclonal antibody designated as IMC-18F1 and evaluated its antitumor activity in preclinical experimental models to show the therapeutic potential of the antibody for cancer treatment in clinic. EXPERIMENTAL DESIGN: Human IgG transgenic mice were used for generation of anti-VEGFR-1 antibodies. Anti-VEGFR-1-specific blocking antibodies were identified using solid-phase binding and blocking assays. Inhibitory antitumor cell activity of IMC-18F1 was assessed in cell-based kinase and growth assays. Pharmacokinetic/pharmacodynamic studies were done to determine the association of antibody blood level with antitumor efficacy of the antibody in vivo. Antitumor efficacy of the anti-VEGFR-1 antibodies as monotherapy and in combination with cytotoxic agents was evaluated in human breast cancer xenograft models. RESULTS: A fully human neutralizing antibody, IMC-18F1, was shown to be a high-affinity (KD=54 pmol) inhibitor of VEGFR-1 ligand binding (VEGF-A, VEGF-B, and placental growth factor). IMC-18F1 inhibited ligand-induced intracellular activation of VEGFR-1 and mitogen-activated protein kinase signaling and prevented ligand-stimulated in vitro growth of breast cancer cells. In vivo, IMC-18F1 suppressed the growth of human breast tumor xenografts in association with reduced mitogen-activated protein kinase and Akt activation, reduced tumor cell proliferation, and increased tumor cell apoptosis. Pharmacokinetic/pharmacodynamic studies established a plasma elimination half-life of 5 days for IMC-18F1 and a steady-state trough plasma therapeutic threshold of 88 microg/mL. Importantly, inhibition of mouse and human VEGFR-1 with MF1 and IMC-18F1, respectively, enhanced the antitumor efficacy of cytotoxic agents commonly used to treat breast cancer. CONCLUSIONS: Based on preclinical validation studies, IMC-18F1 anti-VEGFR-1 has potential to provide clinical benefit to cancer patients.

Increased plasma vascular endothelial growth factor (VEGF) as a surrogate marker for optimal therapeutic dosing of VEGF receptor-2 monoclonal antibodies.

A major obstacle compromising the successful application of many of the new targeted anticancer drugs, including angiogenesis inhibitors, is the empiricism associated with determining an effective biological/therapeutic dose because many of these drugs express optimum therapeutic activity below the maximum tolerated dose, if such a dose can be defined. Hence, surrogate markers are needed to help determine optimal dosing. Here we describe such a molecular marker, increased plasma levels of vascular endothelial growth factor (VEGF), in normal or tumor-bearing mice that received injections of an anti-VEGF receptor (VEGFR)-2 monoclonal antibody, such as DC101. Rapid increases of mouse VEGF (e.g., within 24 hours) up to 1 order of magnitude were observed after single injections of DC101 in non-tumor-bearing severe combined immunodeficient or nude mice; similar increases in human plasma VEGF were detected in human tumor-bearing mice. RAFL-1, another anti-VEGFR-2 antibody, also caused a significant increase in plasma VEGF. In contrast, increases in mouse VEGF levels were not seen when small molecule VEGFR-2 inhibitors were tested in normal mice. Most importantly, the increases in plasma VEGF were induced in a dose-dependent manner, with the maximum values peaking when doses previously determined to be optimally therapeutic were used. Plasma VEGF should be considered as a possible surrogate pharmacodynamic marker for determining the optimal biological dose of antibody drugs that block VEGFR-2 (KDR) activity in a clinical setting.

Responses to antiangiogenesis treatment of spontaneous autochthonous tumors and their isografts.

Preclinical studies typically use human tumor xenografts or murine tumor isografts. Tumor growth may be accelerated by in vivo passage, thus making these tumors more sensitive to some therapies than the original tumors. In the present study, by comparing the effects of DC101, an antimurine vascular endothelial growth factor receptor 2 (VEGFR2) monoclonal antibody, on spontaneous autochthonous tumors and their early generation transplants, we show that this growth acceleration is diminished by DC101 treatment. Spontaneous autochthonous tumors in aged C3H mice consisted of s.c. sarcomas and adenocarcinomas, and their growth rate was accelerated by in vivo passages. Anti-VEGFR2 treatment decreased vessel density, increased apoptosis, and reduced tumor growth in large (500 mm(3)) spontaneous autochthonous tumors. Anti-VEGFR2 treatment significantly delayed tumor growth and extended animal survival. Tumor growth acceleration by in vivo passage was diminished by DC101 treatment. To our knowledge, this is the first evaluation of antiangiogenic therapy in a spontaneous autochthonous tumor model, which may more closely resemble human tumors. Additionally, this is the first study to compare treatment response between the parental tumor and its isografts. Although passaged tumors behave differently, it is encouraging that the tumor growth rates under DC101 treatment are comparable among different passage generations.

Synergistic effect of basic fibroblast growth factor and vascular endothelial growth factor in murine hepatocellular carcinoma.

The growth of any solid tumor depends on angiogenesis. Among the known angiogenic factors, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), are potent and representative factors involved in tumor development. It has been reported that bFGF and VEGF showed a synergistic effect in both in vitro and in vivo angiogenesis. However, the interaction of these factors on tumor development and angiogenesis, including hepatocellular carcinoma (HCC), has not yet been elucidated. In this study, we examined the combined effect of bFGF and VEGF overexpression by means of a combination of a retroviral tetracycline (tet)-regulated (Retro-Tet) gene expression system, which can manipulate the gene expression in vivo by providing tet in the drinking water, and a conventional plasmid gene expression system. In an allograft study, bFGF and VEGF overexpression synergistically increased tumor growth and angiogenesis in the murine HCC cells. This synergistic effect also was found in established tumors. VEGF messenger RNA (mRNA) expression in the tumor was increased 3.1-fold by bFGF-overexpression, and the bFGF-induced tumor development was significantly attenuated by treatment with KDR/Flk-1 neutralizing monoclonal antibody. In conclusion, these results suggest that bFGF synergistically augments VEGF-mediated HCC development and angiogenesis at least partly by induction of VEGF through KDR/Flk-1.