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1.
Subst Abus ; : 1-12, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31638878

RESUMO

Background: The goal of this paper is to advance the understanding of mechanisms of action involved in behavioral-driven aftercare interventions for substance use disorders (SUDs) among youth populations. This paper reports data from a study that measured the impact of an aftercare intervention on primary substance use relapse among youth who completed treatment in Los Angeles County for SUDs. The aftercare intervention, Project ESQYIR-Educating and Supporting inQuisitive Youth In Recovery, utilized text messaging to monitor relapse and recovery processes, provide feedback, reminders, support, and education among youth from SUD specialty settings during the initial 3-month period following treatment completion. Method: Mediational modeling informed by Baron and Kenny was used to examine the extent to which select recovery processes including participation in extracurricular activities and self-help, were impacted by the texting intervention, and if such processes helped sustain recovery and prevent primary substance use relapse. The data come from a two-group randomized controlled pilot study testing the initial efficacy of a mobile health texting aftercare intervention among 80 youth (Mage= 20.7, SD = 3.5, range: 14-26 years) who volunteered to participate after completing SUD treatment between 2012 and 2013. Results: Among the two recovery processes examined in the mediational modeling, only involvement in extracurricular activities mediated the effects of the texting aftercare intervention on reductions in primary substance use relapse; not self-help participation. Conclusion: Findings from this pilot study offer greater understanding about potential recovery-related mechanisms of action of mobile aftercare interventions. Mobile texting was found to promote increased engagement in recovery-related behaviors such as participation in extracurricular activities, which mediated the effects of the mobile aftercare intervention on decreasing primary substance use relapse. Findings suggest mobile approaches may be effective for increasing adherence to a wide-array of recovery behavioral regiments among youth populations challenged by complex behavioral issues.

2.
EBioMedicine ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31648983

RESUMO

BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an aggressive disease related to asbestos exposure, with no effective therapeutic options. METHODS: We undertook unsupervised analyses of RNA-sequencing data of 284 MPMs, with no assumption of discreteness. Using immunohistochemistry, we performed an orthogonal validation on a subset of 103 samples and a biological replication in an independent series of 77 samples. FINDINGS: A continuum of molecular profiles explained the prognosis of the disease better than any discrete model. The immune and vascular pathways were the major sources of molecular variation, with strong differences in the expression of immune checkpoints and pro-angiogenic genes; the extrema of this continuum had specific molecular profiles: a "hot" bad-prognosis profile, with high lymphocyte infiltration and high expression of immune checkpoints and pro-angiogenic genes; a "cold" bad-prognosis profile, with low lymphocyte infiltration and high expression of pro-angiogenic genes; and a "VEGFR2+/VISTA+" better-prognosis profile, with high expression of immune checkpoint VISTA and pro-angiogenic gene VEGFR2. We validated the gene expression levels at the protein level for a subset of five selected genes belonging to the immune and vascular pathways (CD8A, PDL1, VEGFR3, VEGFR2, and VISTA), in the validation series, and replicated the molecular profiles as well as their prognostic value in the replication series. INTERPRETATION: The prognosis of MPM is best explained by a continuous model, which extremes show specific expression patterns of genes involved in angiogenesis and immune response.

3.
Stat Methods Med Res ; : 962280219877520, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31571526

RESUMO

Clinicians and researchers alike are increasingly interested in how best to personalize interventions. A dynamic treatment regimen is a sequence of prespecified decision rules which can be used to guide the delivery of a sequence of treatments or interventions that is tailored to the changing needs of the individual. The sequential multiple-assignment randomized trial is a research tool which allows for the construction of effective dynamic treatment regimens. We derive easy-to-use formulae for computing the total sample size for three common two-stage sequential multiple-assignment randomized trial designs in which the primary aim is to compare mean end-of-study outcomes for two embedded dynamic treatment regimens which recommend different first-stage treatments. The formulae are derived in the context of a regression model which leverages information from a longitudinal outcome collected over the entire study. We show that the sample size formula for a sequential multiple-assignment randomized trial can be written as the product of the sample size formula for a standard two-arm randomized trial, a deflation factor that accounts for the increased statistical efficiency resulting from a longitudinal analysis, and an inflation factor that accounts for the design of a sequential multiple-assignment randomized trial. The sequential multiple-assignment randomized trial design inflation factor is typically a function of the anticipated probability of response to first-stage treatment. We review modeling and estimation for dynamic treatment regimen effect analyses using a longitudinal outcome from a sequential multiple-assignment randomized trial, as well as the estimation of standard errors. We also present estimators for the covariance matrix for a variety of common working correlation structures. Methods are motivated using the ENGAGE study, a sequential multiple-assignment randomized trial aimed at developing a dynamic treatment regimen for increasing motivation to attend treatments among alcohol- and cocaine-dependent patients.

4.
Hum Mol Genet ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31600786

RESUMO

We previously identified five SNPs at four susceptibility loci for diffuse large B-cell lymphoma (DLBCL) in individuals of European ancestry through a large genome-wide association study (GWAS). To further elucidate genetic susceptibility to DLBCL, we sought to validate 2 loci at 3q13.33 and 3p24.1 that were suggestive in the original GWAS with additional genotyping. In the meta-analysis (5,662 cases and 9,237 controls) of the four original GWAS discovery scans and three replication studies, the 3q13.33 locus (rs9831894; minor allele frequency [MAF]=0.40) was associated with DLBCL risk (OR=0.83, P=3.62x10-13). rs9831894 is in linkage disequilibrium (LD) with additional variants that are part of a super-enhancer that physically interacts with promoters of CD86 and ILDR1. In the meta-analysis (5,510 cases and 12,817 controls) of the four GWAS discovery scans and four replication studies, the 3p24.1 locus (rs6773363; MAF=0.45) was also associated with DLBCL risk (OR=1.20, P=2.31x10-12). This SNP is 29,426 bp upstream of the nearest gene EOMES and in LD with additional SNPs that are part of a highly lineage-specific and tumor-acquired super-enhancer that shows long-range interaction with AZI2 promoter. These loci provide additional evidence for the role of immune function in the etiology of DLBCL, the most common lymphoma subtype.

5.
Genet Epidemiol ; 43(7): 844-863, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31407831

RESUMO

Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.

6.
Subst Use Misuse ; 54(13): 2144-2155, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31322037

RESUMO

Background: Social networks that support recovery lead to enhanced treatment outcomes and sobriety regardless if this support stems from family, peer groups or 12-Step programs. Treatment process factors including readiness to change and commitment to abstinence also impact substance use. However, little is understood about the relationship between social support to treatment process factors during and after treatment for substance use disorders. Objectives: To identify the ways in which different social networks foster substance use change in a sample of individuals with cocaine dependence from intensive outpatient programs (IOPs). Methods: Data were drawn from two studies examining adults (N = 489) with cocaine dependence in IOPs for substance use disorders collected between 2004 and 2009. Assessment data were collected at 3- to 6-month intervals from baseline to 24-months and included the University of Rhode Island change assessment questionnaire, timeline followback, thoughts about abstinence, perceived social support - friend, and family versions and analyzed using GEE and mediational analyses. Results: Greater perceived friend social support was associated with greater readiness to change whereas greater perceived familial social support was associated with substance use goal; greater social support from both friends and family were associated with less substance use. Greater AA/NA participation was associated with substance use goal and readiness to change, and less substance use. Substance use goals partially mediated the impact of social support on later substance use. Conclusions/Importance: While peer and familial support are key to sustained recovery, their impact differentially affects treatment process variables. This information could be used to inform social support treatment interventions.

7.
Psychol Methods ; 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31318231

RESUMO

In recent years, there has been increased interest in the development of adaptive interventions across various domains of health and psychological research. An adaptive intervention is a protocolized sequence of individualized treatments that seeks to address the unique and changing needs of individuals as they progress through an intervention program. The sequential, multiple assignment, randomized trial (SMART) is an experimental study design that can be used to build the empirical basis for the construction of effective adaptive interventions. A SMART involves multiple stages of randomizations; each stage of randomization is designed to address scientific questions concerning the best intervention option to employ at that point in the intervention. Several adaptive interventions are embedded in a SMART by design; many SMARTs are motivated by scientific questions that concern the comparison of these embedded adaptive interventions. Until recently, analysis methods available for the comparison of adaptive interventions were limited to end-of-study outcomes. The current article provides an accessible and comprehensive tutorial to a new methodology for using repeated outcome data from SMART studies to compare adaptive interventions. We discuss how existing methods for comparing adaptive interventions in terms of end-of-study outcome data from a SMART can be extended for use with longitudinal outcome data. We also highlight the scientific utility of using longitudinal data from a SMART to compare adaptive interventions. A SMART study aiming to develop an adaptive intervention to engage alcohol- and cocaine-dependent individuals in treatment is used to demonstrate the application of this new methodology. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

8.
Psychol Addict Behav ; 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31246068

RESUMO

The purpose of this sequential multiple-assignment randomization treatment pilot study was to examine if (a) adding working memory training to contingency management (CM) for youth with cannabis use disorder (CUD) and (b) switching nonresponding youth to higher magnitude CM incentives boosts outcomes. In Phase 1, youth with CUD (n = 59, M age = 16, male = 71%) attending an intensive outpatient program were randomly assigned to 14 weeks of CM only or CM plus working memory training (WMT). In Week 4, a Phase 2 treatment was assigned. Those with negative urine drug tests (responders) continued in their Phase 1 treatment. Those who were drug positive (nonresponders) were randomly assigned to remain in their Phase 1 treatment or to higher magnitude CM. Zero-inflated negative binomial models comparing those assigned to CM versus CM + WMT indicated no differences in the likelihood of having ≥ 1 week of continuous abstinence or longer abstinence duration. Those assigned to WMT showed greater but nonsignificant improvements in working memory (n = 35; ß = .69, p = .06). Working memory improvements were associated with achieving any abstinence (odds ratio = 3.50, 95% CI [1.01, 12.10], p = .05). Phase 2 randomization to higher magnitude CM did not boost outcomes. Overall results suggest that WMT appears promising, but the sample size was small, attrition was high, and replication is important. Alternative strategies should continue to be explored to improve outcomes for adolescent substance use disorders, such as different approaches for nonresponders, tailoring to other baseline or response characteristics, or more robust first-line interventions. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

9.
N Z Med J ; 132(1494): 6-7, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31048819
10.
EBioMedicine ; 44: 431-438, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31122840

RESUMO

BACKGROUND: Recurrent mutations in the promoter of the telomerase reverse transcriptase (TERT) gene (C228T and C250T) detected in tumours and cells shed into urine of urothelial cancer (UC) patients are putative biomarkers for UC detection and monitoring. However, the possibility of detecting these mutations in cell-free circulating DNA (cfDNA) in blood and urine, or DNA from urinary exfoliated cells (cellDNA) with a single-gene sensitive assay has never been tested in a case-control setting. METHODS: We developed a single-plex assay (UroMuTERT) for the detection of low-abundance TERT promoter mutations. We tested 93 primary and recurrent UC cases and 94 controls recruited in France (blood, urine samples and tumours for the cases), and 50 primary UC cases and 50 controls recruited in Portugal (urinary exfoliated cell samples). We compared our assay with urine cytology. FINDINGS: In the French series, C228T or C250T were detected in urinary cfDNA or cellDNA in 81 cases (87·1%; 95% CI 78·6-93·2), and five controls (Specificity 94·7%; 95%CI 88·0-98·3), with 98·6% (95% CI 92·5-99·96) concordance in matched tumours. Detection rate in plasma cfDNA among cases was 7·1%. The UroMuTERT sensitivity was (i) highest for urinary cfDNA and cellDNA combined, (ii) consistent across primary and recurrent cases, tumour stages and grades, (iii) higher for low-risk non-muscle invasive UC (86·1%) than urine cytology (23·0%) (P < 0·0001) and (iv) 93·9% when combined with cytology. In the Portuguese series - the sensitivity and specificity for detection of UC with urinary cellDNA was 68·0% (95% CI 53·3-80·5) and 98·0% (95% CI 89·3-100·0). INTERPRETATION: TERT promoter mutations detected by the UroMuTERT assay in urinary DNA (cfDNA or cellDNA) show excellent sensitivity and specificity for the detection of UC, significantly outperforming that of urine cytology notably for detection of low-grade early stages UC. FUND: French Cancer League; French Foster Research in Molecular Biology and European Commission FP7 Marie Curie COFUND.

11.
Genome Res ; 29(4): 521-531, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30846532

RESUMO

Humans are frequently exposed to acrylamide, a probable human carcinogen found in commonplace sources such as most heated starchy foods or tobacco smoke. Prior evidence has shown that acrylamide causes cancer in rodents, yet epidemiological studies conducted to date are limited and, thus far, have yielded inconclusive data on association of human cancers with acrylamide exposure. In this study, we experimentally identify a novel and unique mutational signature imprinted by acrylamide through the effects of its reactive metabolite glycidamide. We next show that the glycidamide mutational signature is found in a full one-third of approximately 1600 tumor genomes corresponding to 19 human tumor types from 14 organs. The highest enrichment of the glycidamide signature was observed in the cancers of the lung (88% of the interrogated tumors), liver (73%), kidney (>70%), bile duct (57%), cervix (50%), and, to a lesser extent, additional cancer types. Overall, our study reveals an unexpectedly extensive contribution of acrylamide-associated mutagenesis to human cancers.


Assuntos
Acrilamidas/toxicidade , Carcinogênese/genética , Exposição Ambiental , Mutagênicos/toxicidade , Mutação , Neoplasias/genética , Animais , Carcinogênese/induzido quimicamente , Células Cultivadas , Compostos de Epóxi/toxicidade , Genoma Humano , Humanos , Camundongos , Neoplasias/induzido quimicamente , Proteína Supressora de Tumor p53/genética
12.
Arthritis Rheumatol ; 71(7): 1125-1134, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30771238

RESUMO

OBJECTIVE: To investigate the long-term safety and efficacy of intravenous (IV) belimumab plus standard of care (SOC) therapy for systemic lupus erythematosus (SLE) in patients with active, autoantibody-positive SLE. METHODS: The study was designed as a multicenter, open-label, continuation study of IV belimumab given every 4 weeks in conjunction with SOC therapy in patients with SLE who completed a phase II, double-blind study. Adverse events (AEs) and laboratory data were monitored from the first belimumab dose (in either study) until 24 weeks after the final dose. Efficacy assessments included SLE Responder Index (SRI) and flare index scores (each assessed at 16-week intervals) and glucocorticoid use (assessed at 4-week intervals). RESULTS: Of the 476 patients in the parent study, 298 (62.6%) entered the continuation study, of whom 96 (32.2%) remained in the study. Patients received belimumab for up to 13 years (median duration of exposure 3,334.0 days [range 260-4,332 days], total belimumab exposure 2,294 patient-years, median number of infusions 115.5 [range 7-155]). The percentage of patients with AEs each year remained stable or decreased. Normal serum IgG levels were maintained in the majority of patients over the study, and the rate of infections remained stable. The percentage of patients who achieved an SRI response increased from 32.8% (year 1) to 75.6% of those remaining on treatment at year 12. The glucocorticoid dose was decreased in patients who had been receiving >7.5 mg/day at baseline. CONCLUSION: This study is the longest to date to assess belimumab treatment in patients with SLE in clinical trials. Belimumab was well tolerated with no new safety concerns, and efficacy was maintained in patients who continued the study. For patients who initially exhibited a satisfactory response to belimumab, the treatment continues to be well tolerated and provides long-term disease control.

13.
Cancer Epidemiol Biomarkers Prev ; 28(5): 935-942, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30700444

RESUMO

BACKGROUND: Platelets are a critical element in coagulation and inflammation, and activated platelets are linked to cancer risk through diverse mechanisms. However, a causal relationship between platelets and risk of lung cancer remains unclear. METHODS: We performed single and combined multiple instrumental variable Mendelian randomization analysis by an inverse-weighted method, in addition to a series of sensitivity analyses. Summary data for associations between SNPs and platelet count are from a recent publication that included 48,666 Caucasian Europeans, and the International Lung Cancer Consortium and Transdisciplinary Research in Cancer of the Lung data consisting of 29,266 cases and 56,450 controls to analyze associations between candidate SNPs and lung cancer risk. RESULTS: Multiple instrumental variable analysis incorporating six SNPs showed a 62% increased risk of overall non-small cell lung cancer [NSCLC; OR, 1.62; 95% confidence interval (CI), 1.15-2.27; P = 0.005] and a 200% increased risk for small-cell lung cancer (OR, 3.00; 95% CI, 1.27-7.06; P = 0.01). Results showed only a trending association with NSCLC histologic subtypes, which may be due to insufficient sample size and/or weak effect size. A series of sensitivity analysis retained these findings. CONCLUSIONS: Our findings suggest a causal relationship between elevated platelet count and increased risk of lung cancer and provide evidence of possible antiplatelet interventions for lung cancer prevention. IMPACT: These findings provide a better understanding of lung cancer etiology and potential evidence for antiplatelet interventions for lung cancer prevention.

14.
Multivariate Behav Res ; 54(5): 613-636, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30663401

RESUMO

Sequential multiple assignment randomized trials (SMARTs) are a useful and increasingly popular approach for gathering information to inform the construction of adaptive interventions to treat psychological and behavioral health conditions. Until recently, analysis methods for data from SMART designs considered only a single measurement of the outcome of interest when comparing the efficacy of adaptive interventions. Lu et al. proposed a method for considering repeated outcome measurements to incorporate information about the longitudinal trajectory of change. While their proposed method can be applied to many kinds of outcome variables, they focused mainly on linear models for normally distributed outcomes. Practical guidelines and extensions are required to implement this methodology with other types of repeated outcome measures common in behavioral research. In this article, we discuss implementation of this method with repeated binary outcomes. We explain how to compare adaptive interventions in terms of various summaries of repeated binary outcome measures, including average outcome (area under the curve) and delayed effects. The method is illustrated using an empirical example from a SMART study to develop an adaptive intervention for engaging alcohol- and cocaine-dependent patients in treatment. Monte Carlo simulations are provided to demonstrate the good performance of the proposed technique.

15.
Nat Commun ; 9(1): 4182, 2018 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-30305637

RESUMO

Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40-31.03, P = 1.36 × 10-54) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45-6.96, P = 8.75 × 10-19). Both risk alleles are observed at a low frequency among controls (~2-3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy.

16.
Nat Commun ; 9(1): 3927, 2018 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-30254314

RESUMO

Lung cancer has several genetic associations identified within the major histocompatibility complex (MHC); although the basis for these associations remains elusive. Here, we analyze MHC genetic variation among 26,044 lung cancer patients and 20,836 controls densely genotyped across the MHC, using the Illumina Illumina OncoArray or Illumina 660W SNP microarray. We impute sequence variation in classical HLA genes, fine-map MHC associations for lung cancer risk with major histologies and compare results between ethnicities. Independent and novel associations within HLA genes are identified in Europeans including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In Asians, associations are driven by two independent HLA allele sets that both increase risk in HLA-DQB1*0401 and HLA-DRB1*0701; the latter better represented by the amino acid Ala-104. These results implicate several HLA-tumor peptide interactions as the major MHC factor modulating lung cancer susceptibility.

17.
J Subst Abuse Treat ; 94: 97-104, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30243425

RESUMO

BACKGROUND: People in reentry from prison or jail (returning citizens) living with HIV and substance use problems often experience numerous stressors and are at high risk for resumed substance use. Interventions are needed to manage stress as a pathway to reduced substance use. OBJECTIVE: This study explored the effect of a hatha yoga intervention as compared to treatment as usual on stress and substance use among returning citizens living with HIV and substance use problems. METHODS: Participants were randomized to either a 12-session, 90-minute weekly yoga intervention or treatment as usual. All participants were clients of a service provider for returning citizens that offered case management, health care, and educational classes. Outcomes included stress as measured by the Perceived Stress Scale at the completion of the yoga intervention (three-months) and substance use as measured by the Timeline Followback at one-month, two-months, and three-months. RESULTS: Seventy-five people were enrolled, two of whom were withdrawn from the study because they did not have HIV. Of the 73 remaining participants, 85% participated in the three-month assessment. At three-months, yoga participants reported less stress than participants in treatment as usual [F (1,59) = 9.24, p < .05]. Yoga participants reported less substance use than participants in treatment as usual at one-month, two-months, and three-months [X2 (1) = 11.13, p < .001]. CONCLUSION: Yoga interventions for returning citizens living with HIV and substance use problems may reduce stress and substance use. This finding is tentative because the control group did not receive an intervention of equal time and intensity.

18.
J Med Internet Res ; 20(8): e255, 2018 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-30139724

RESUMO

BACKGROUND: The development and evaluation of digital interventions aimed at preventing or treating substance use-related problems and disorders is a rapidly growing field. Previous reviews of such interventions reveal a large and complex picture with regard to targeted users, use, and efficacy. OBJECTIVE: The objective of this review was to investigate the feasibility and effects of interventions developed specifically for digital platforms. These interventions are focused on supporting people in recovery from substance use disorders by helping them achieve their substance use goals and develop a more satisfying life situation. METHODS: The review is based on a systematic search in MEDLINE, Embase, PsycInfo, and Cochrane Library databases. Of the 1149 identified articles, 722 were excluded as obviously not relevant. Of the remaining articles, 21 were found to be previous reviews, 269 were on interventions aimed at reducing hazardous alcohol or cannabis use, and 94 were on digitized versions of standard treatment methods. The remaining 43 articles were all read in full and systematically scored by both authors. RESULTS: The 43 articles cover 28 unique interventions, of which 33 have been published after 2013. The interventions are aimed at different target groups (defined by age, substance, or comorbidity). Based on the number of features or modules, the interventions can be categorized as simple or complex. Fourteen of the 18 simple interventions and 9 of the 10 complex interventions have been studied with quantitative controlled methodologies. Thirteen of the 18 simple interventions are integrated in other treatment or support systems, mainly delivered as mobile phone apps, while 6 of the 10 complex interventions are designed as stand-alone interventions, most often delivered on a platform combining desktop/Web and mobile phone technologies. The interventions were generally easy to implement, but in most cases the implementation of the complex interventions was found to be dependent on sustained organizational support. Between 70% and 90% of the participants found the interventions to be useful and easy to use. The rates of sustained use were also generally high, except for simple interventions with an open internet-based recruitment and some information and education modules of the complex interventions. Across all interventions, slightly more than half (55%) of the studies with control groups generated positive findings on 1 or more substance use outcomes, with 57% of the interventions also found to be efficacious in 1 or more studies. In the positive studies, effects were typically in the small to moderate range, with a few studies yielding larger effects. Largely due to the inclusion of stronger control conditions, studies of simple interventions were less likely to produce positive effects. CONCLUSIONS: The digital interventions included in this review are in general feasible but are not consistently effective in helping people in recovery from substance use disorder reduce their substance use or achieving other recovery goals.

19.
Nat Commun ; 9(1): 3221, 2018 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-30104567

RESUMO

Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.

20.
J Subst Abuse Treat ; 92: 46-50, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30032944

RESUMO

The purpose of this paper is to reanalyze data from two studies to determine if anhedonia specifically, rather than depression overall, predicts treatment outcome for patients with cocaine use disorders. Measures of baseline anhedonia symptoms were created using anhedonia items from the Beck Depression Inventory (BDI) to re-examine National Institute on Drug Abuse Cocaine Collaborative Treatment study data (Crits-Christoph et al., 1999) and the contingency management group from the McKay et al. (2010) trial. Baseline anhedonia was used to predict cocaine abstinence rates across the treatment period in both studies. Anhedonia was a significant predictor of cocaine abstinence, even when overall depression scores excluding anhedonia were included in the models. The development of treatments to target individuals with cocaine use disorder who have symptoms of anhedonia has the potential to improve overall outcomes for those with this disorder.

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