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Biomedical subjects

William R Miller

Publications and source records attributed to William R Miller.

At least 19 recordsLinked to original sources
PubMed2007

Does subtle screening for substance abuse work? A review of the Substance Abuse Subtle Screening Inventory (SASSI).

AIM: Through a complex combination of direct (face-valid) and indirect (subtle) subscales, the Substance Abuse Subtle Screening Inventory (SASSI) is purported to detect substance use disorders with a high degree of validity regardless of respondent honesty or motivation. This review evaluates empirical evidence regarding the reliability and validity of this widely used screening instrument. METHODS: Source documents were 36 peer-reviewed reports yielding data regarding the SASSI's internal consistency, test-retest reliability, psychometric structure, convergent and divergent validity and criterion (predictive) validity. RESULTS: The total N of the studies reviewed equaled 22 110. Internal consistency is high for the overall SASSI and for its direct but not its indirect (subtle) subscales, suggesting that the instrument taps a single face-valid construct. SASSI classifications converged with those from other direct screening instruments, and were also correlated with ethnicity, general distress and social deviance. Studies found test-retest reliability lower than that reported in the test manuals. Sensitivity was found to be similar to that for public domain screening instruments, but on specificity the SASSI appears to yield a high rate of false positives. CONCLUSION: No empirical evidence was found for the SASSI's claimed unique advantage in detecting substance use disorders through its indirect (subtle) scales to circumvent respondent denial or dishonesty. Recommendations for screening and for future research with the SASSI are offered.

Adolescent↗
PubMed2006

Psychometrics of the Drinker Inventory of Consequences (DrInC).

The Drinker Inventory of Consequences (DrInC) was developed for Project MATCH to assess the consequences of drinking in five domains. The present study, using baseline data from the 1382 participants involved in the COMBINE Study, analyzed the psychometrics of the 50-item DrInC and its shorter form, the 15-item SIP. Findings indicate the DrInC is reliable, valid, and clinically useful and that DrInC subscales are internally consistent and non-redundant. In an examination of the shorter version of the DrInC, findings suggest that the SIP is suitable when assessing the overall level of drinking-related consequences.

Acamprosate↗
PubMed2006

Hormonal therapy for postmenopausal breast cancer: the science of sequencing.

Oestrogens play important roles in the natural history of breast cancer. Consequently, therapies have been developed to reduce oestrogen levels or to block signalling through oestrogen receptors (ER). These therapies include tamoxifen, selective oestrogen receptor modulators (SERMs), aromatase inhibitors (AIs) and selective oestrogen receptor downregulators (SERDs). All have proven clinical efficacy in postmenopausal women with ER-positive breast cancer and can be effective in the neoadjuvant and adjuvant settings, and in the management of advanced disease. This range of endocrine therapies offers the opportunity for prolonging benefit from treatment and delaying tumour recurrence/progression by combining the different classes of drugs or by using them sequentially. Evaluation of the potential clinical benefits of concomitant or sequential endocrine therapies should be based on considerations of efficacy and safety profiles, mechanisms of action/resistance and effects on tumour biology. Evidence from preclinical models and from randomized clinical trials in patients with postmenopausal breast cancer suggests that concomitant endocrine therapies are no more effective than AIs alone. However, using AIs either as initial therapy or sequentially after tamoxifen appears to produce more benefits beyond the use of tamoxifen alone.Currently, there are no proven algorithms for the planned, sequential use of the full range of endocrine therapies, particularly for the majority of patients who present with early breast cancer. Prospective, randomized clinical trials are needed to determine the best use of therapies in particular settings, taking into account the spectrum of molecular phenotypes in different tumours.

Aged↗
PubMed2006

Estrogen-independent proliferation is present in estrogen-receptor HER2-positive primary breast cancer after neoadjuvant letrozole.

PURPOSE: To investigate the impact of human epidermal growth factor receptor (HER) 1 and HER2 gene amplification on endocrine therapy responsiveness, a fluorescence in situ hybridization (FISH) study was conducted on tumor samples from 305 postmenopausal patients with stage II and III estrogen receptor (ER) -positive (ER > or = 10%) breast cancers treated on two independent neoadjuvant endocrine therapy trials. PATIENTS AND METHODS: FISH analysis focused on HER1 and/or HER2 immunohistochemistry (IHC) -positive patients and a random selection of HER1/2 IHC-negative patients. HER2 FISH status was correlated with response and changes in the proliferation marker Ki67. RESULTS: HER1 was rarely amplified (< 1%), and HER2 amplification was observed in 9.2% of patients. Letrozole response by clinical measurement (71% HER2 FISH positive v 71% HER2 FISH negative), mammogram (44% HER2 FISH positive v 47% HER2 FISH negative), or ultrasound (47% HER2 FISH positive v 54% HER2 FISH negative) was not impaired by HER2 FISH-positive status. In contrast, HER2 FISH-positive tumors showed higher histologic grade (P = .009), higher pretreatment Ki67 (P = .005), and less Ki67 suppression after letrozole when compared with HER2 FISH-negative tumors (P = .0001). Similar observations regarding Ki67 were made in a smaller cohort of tamoxifen-treated tumors. CONCLUSION: Neoadjuvant letrozole is clinically effective in ER-positive HER2 FISH-positive tumors, indicating sensitivity to short-term estrogen deprivation. However, continued proliferation despite ongoing letrozole or tamoxifen treatment in the majority of ER-positive HER2 FISH-positive samples (88%) could imply therapeutic resistance that may manifest later in the clinical course of the disease. Discordance between clinical and biomarker findings in this study serves to emphasize the need for surrogate end point validation in neoadjuvant endocrine trials through correlation with information on long-term outcomes.

Aged↗
PubMed2006

Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial.

CONTEXT: Alcohol dependence treatment may include medications, behavioral therapies, or both. It is unknown how combining these treatments may impact their effectiveness, especially in the context of primary care and other nonspecialty settings. OBJECTIVES: To evaluate the efficacy of medication, behavioral therapies, and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers (median age, 44 years) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnoses of primary alcohol dependence. INTERVENTIONS: Eight groups of patients received medical management with 16 weeks of naltrexone (100 mg/d) or acamprosate (3 g/d), both, and/or both placebos, with or without a combined behavioral intervention (CBI). A ninth group received CBI only (no pills). Patients were also evaluated for up to 1 year after treatment. MAIN OUTCOME MEASURES: Percent days abstinent from alcohol and time to first heavy drinking day. RESULTS: All groups showed substantial reduction in drinking. During treatment, patients receiving naltrexone plus medical management (n = 302), CBI plus medical management and placebos (n = 305), or both naltrexone and CBI plus medical management (n = 309) had higher percent days abstinent (80.6, 79.2, and 77.1, respectively) than the 75.1 in those receiving placebos and medical management only (n = 305), a significant naltrexone x behavioral intervention interaction (P = .009). Naltrexone also reduced risk of a heavy drinking day (hazard ratio, 0.72; 97.5% CI, 0.53-0.98; P = .02) over time, most evident in those receiving medical management but not CBI. Acamprosate showed no significant effect on drinking vs placebo, either by itself or with any combination of naltrexone, CBI, or both. During treatment, those receiving CBI without pills or medical management (n = 157) had lower percent days abstinent (66.6) than those receiving placebo plus medical management alone (n = 153) or placebo plus medical management and CBI (n = 156) (73.8 and 79.8, respectively; P<.001). One year after treatment, these between-group effects were similar but no longer significant. CONCLUSIONS: Patients receiving medical management with naltrexone, CBI, or both fared better on drinking outcomes, whereas acamprosate showed no evidence of efficacy, with or without CBI. No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management. Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment. Naltrexone with medical management could be delivered in health care settings, thus serving alcohol-dependent patients who might otherwise not receive treatment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00006206.

Acamprosate↗
PubMed2006

Is alcoholism typology a predictor of both Alcoholics Anonymous affiliation and disaffiliation after treatment?

Twelve Steps (TS) has demonstrated effectiveness; induction into Alcoholics Anonymous (AA) is a primary objective of TS and is a pivotal mechanism explaining its effectiveness. However, evidence suggests that, after treatment, dropout from AA is high. This study investigated whether alcohol problem severity predicted both AA affiliation and disaffiliation among clients receiving TS. This study of a Project MATCH sample included 453 alcohol-dependent clients randomly assigned to TS who reported AA attendance during treatment. Greater alcohol problem severity predicted AA attendance; opposite to prediction, less alcohol-impaired clients were more than twice as likely to discontinue AA attendance after treatment. When sustained AA attendance is desired, the evaluation of client pretreatment alcohol involvement may be useful for identifying potential AA dropout after TS treatment. Findings also indicate that, among treatment-seeking problem drinkers, AA dropout and disaffiliation are distinct, albeit correlated, constructs that require future investigation.

Adaptation, Psychological↗
PubMed2006

Disseminating evidence-based practices in substance abuse treatment: a review with suggestions.

Although substance abuse professionals are generally open to new and better therapeutic methods, most evidence-based treatments do not easily find their way into practice. Natural diffusion processes for innovations in substance abuse treatments are relatively informal and have yielded a widely acknowledged gap between science and community practice. This review focuses on methods for effectively disseminating new treatment methods into practice. Therapist manuals and one-time workshops are in themselves relatively ineffective in helping practitioners gain proficiency in new clinical approaches. Individual performance feedback and coaching improve the acquisition of clinical skills. Specific incentives for implementation may also be needed to encourage treatment providers, programs, and systems to adopt new approaches.

Behavior Therapy↗
PubMed2006

Trauma center brief interventions for alcohol disorders decrease subsequent driving under the influence arrests.

BACKGROUND: A substantial number of trauma center admissions are related to driving under the influence (DUI); however, there has been no prior report of brief intervention (BI) after injury reducing subsequent DUI arrests. The hypothesis of this study was that injured patients receiving BI would have a lower risk of DUI arrest within 3 years of discharge than those receiving standard care (SC). METHODS: This prospective, randomized clinical trial randomly allocated patients involved in motor vehicle collisions to receive SC or a BI regarding alcohol use. The primary outcome measure was DUI arrest within 3 years of hospital discharge. DUI arrests were documented by matching demographic information to state traffic safety data. RESULTS: After randomization (N = 126), BI and SC groups were similar in age, prior DUI arrests, and alcohol screening score. BI sessions lasted an average of 30 minutes and were performed by either a social worker or a trauma surgeon. Approximately one in six participants (n = 21, 16.7%) had a DUI arrest within 3 years of hospital discharge. Within 3 years of hospital discharge, 14 of 64 patients (21.9%) in the SC group had an arrest for DUI compared with only 7 of 62 patients (11.3%) who received the BI. Multivariate analysis demonstrated that BI was the strongest protective factor against DUI arrest (odds ratio [OR], 0.32; 95% confidence interval < or =CI], 0.11-0.96). Prior number of DUIs (OR, 1.43; 95% CI, 1.03-2.01) and age (OR, 0.94; 95% CI, 0.88-0.99) were also associated with DUI arrest post-hospitalization, but alcohol screening score (OR, 1.06; 95% CI, 0.99-1.13) was not. The absolute risk reduction implies that only nine patients would need to receive a BI to prevent one DUI arrest. CONCLUSION: Patients who receive BI during a trauma center admission are less likely to be arrested for DUI within 3 years of discharge. BI represents a viable intervention to reduce DUI after trauma center admission.

Accidents, Traffic↗
PubMed2006

Addressing substance abuse in health care settings.

This article summarizes the proceedings of a roundtable discussion at the 2005 annual meeting of the Research Society on Alcoholism in Santa Barbara, California. The chair was William R. Miller. The presentations were as follows: (1) Screening and Brief Intervention for Alcohol Problems, by Allen Zweben; (2) Three Intervention Models and Their Impact on Medical Records, by Denise Ernst; (3) Pharmacotherapies for Managing Alcohol Dependence in Health Care Settings, by Roger D. Weiss; (4) The Trauma Center as an Opportunity, by Carol R. Schermer; (5) Motivational Interviewing by Telephone and Telemedicine, by Catherine Baca; (6) Health Care as a Context for Treating Drug Abuse and Dependence, by Wilson M. Compton; and (7) Interventions for Heavy Drinking in Health Care settings: Barriers and Strategies, by Mark L. Willenbring.

Alcohol Deterrents↗
PubMed2006

Neoadjuvant endocrine therapy models.

Neoadjuvant therapy is therapy administered before surgical intervention and while the tumor remains in the breast. It may be given to treat large, locally advanced tumors, with the aim of shrinking them and thus making their surgical excision either simply possible or less radical. Most neoadjuvant therapy is chemotherapy, but adjuvant endocrine therapy is increasingly used in hormone-sensitive tumors; for example, those responsive to tamoxifen. Repeat biopsies aimed at assessing response to treatment--for example, by examining estrogen receptor status or markers of proliferation in tumor tissue--may be taken during the course of adjuvant therapy. In this chapter, the essential protocols associated with designing neoadjuvant trials are described, methods of assessing response to neoadjuvant therapy are detailed, and various approaches to collecting appropriate clinical samples and their assessment are presented.

Biopsy↗
PubMed2006

Examining the effects of alcoholism typology and AA attendance on self-efficacy as a mechanism of change.

OBJECTIVE: Existing research indicates that increased self-efficacy to sustain abstinence is a strong causal mechanism explaining later reduction of drinking. Little is known about how mechanisms of change may differ among distinct subgroups of alcoholics. The purpose of this study was to evaluate the mediational role of self-efficacy on changes in drinking associated with Alcoholics Anonymous (AA) attendance in Type-A and Type-B alcoholics. METHOD: Analysis of covariance and structural equation modeling were used to model 6-, 9-, 12-, and 15-month data from Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity) participants who were classified as Type-A or Type-B alcoholics (N=1,284; 72% male). Measures of AA attendance and percent days abstinent were taken from the Form 90. Self- efficacy was assessed with the Alcohol Abstinence Self-Efficacy Scale. RESULTS: Alcoholism typology and AA attendance were independent predictors of later self-efficacy, but there was no interaction between typology and AA attendance. Abstinence self-efficacy mediated a modest proportion of the effect of posttreatment AA attendance on later abstinence in both Type-A and Type-B alcoholics. The strength of this mediation did not differ by typology. CONCLUSIONS: Self-efficacy for abstinence has a strong direct relationship to abstinence across treatment conditions and typologies. Increases in self-efficacy mediate some of the beneficial effects of AA for Type-A and Type-B alcoholics. Further work is necessary to determine whether self-efficacy plays a different role in the recovery of Type-A versus Type-B alcoholics.

Adult↗
PubMed2006

Endocrine therapy resistance can be associated with high estrogen receptor alpha (ERalpha) expression and reduced ERalpha phosphorylation in breast cancer models.

Hormone-dependent estrogen receptor (ER)-positive breast cancer cells may adapt to low estrogen environments such as produced by aromatase inhibitors. In many instances, cells become insensitive to the effects of estrogen but may still retain dependence on ER. We have investigated the expression, function, and activation of ERalpha in two endocrine-resistant MCF-7 models to identify mechanisms that could contribute to resistance. While MCF-7/LCC1 cells are partially estrogen dependent, MCF-7/LCC9 cells are fully estrogen insensitive and fulvestrant and tamoxifen resistant. In both MCF-7/LCC1 and MCF-7/LCC9 cell lines, high expression of ERalpha was associated with enhanced binding to the trefoil factor 1 (TFF1) promoter in the absence of estrogen and increased transcription of TFF1 and progesterone receptor. In contrast to the observations derived from hypersensitive and supersensitive models, these cells were truly estrogen independent; nevertheless, removal of ERalpha by siRNA, or fulvestrant, a specific ER downregulator, inhibited growth indicating dependence on ERalpha. In the absence of estrogen, neither ERalpha Ser118 nor Ser167 were phosphorylated as frequently found in other ligand-independent cell line models. Addition of estrogen activated ERalpha Ser118 in MCF-7 and LCC1 cells but not in LCC9 cells. We suggest that the estrogen-independent growth within these cell lines is accounted for by high levels of ERalpha expression driving transcription and full estrogen independence explained by lack of ERalpha activation through Ser118.

Antineoplastic Agents, Hormonal↗
PubMed2006

Estrogen receptor alpha positive breast tumors and breast cancer cell lines share similarities in their transcriptome data structures.

Established human breast cancer cell lines are widely used as experimental models in breast cancer research. While these cell lines and their variants share many phenotypic characteristics with human breast tumors, the extent to which they reflect the underlying molecular biology of breast cancer remains controversial. We explored this issue using a probabilistic rather than heuristic approach. Data from gene expression microarrays were used to compare the global structures of the transcriptomes of three estrogen receptor alpha positive (ER+) human breast cancer cell lines (MCF-7, T47D, ZR-75-1) and 13 human breast tumors (11 ER+; 2 ER-). Linear representations of the respective data structures were obtained by deriving those top principal components (PCs) required to capture > or =80% of the cumulative variance for each data set (M PCs). We then identified those genes most highly correlated with the M PCs (Pearson's correlation coefficient r > or =0.800) and identified a group of 36 genes commonly correlated with both the cell line (M = 5 PCs) and tumor (M = 6 PCs) data structures. All 36 common genes were correlated with PC1 from the breast tumor data: 21/36 genes were correlated with PC1, 14/36 genes correlated with PC2, and 1/36 genes correlated with PC3 from the cell line data. Genes important in defining the data structures include NFkappaB p65, IGFBP-6, ornithine decarboxylase-1, and paxillin. When data from MDA-MB-435 xenografts (ER-) were included in the analysis, we were unable to find any common genes between these xenografts and the breast tumors. These data clearly imply that MCF-7, T47D, and ZR-75-1 cells and ER+ breast tumors share substantial global similarities in the structures of their respective transcriptomes, and that these cell lines are good models in which to identify molecular events that are likely to be important in some ER+ human breast cancers.

Animals↗
PubMed2005

Translation elongation factor eEF1A2 is a potential oncoprotein that is overexpressed in two-thirds of breast tumours.

BACKGROUND: The tissue-specific translation elongation factor eEF1A2 was recently shown to be a potential oncogene that is overexpressed in ovarian cancer. Although there is no direct evidence for an involvement of eEF1A2 in breast cancer, the genomic region to which EEF1A2 maps, 20q13, is frequently amplified in breast tumours. We therefore sought to establish whether eEF1A2 expression might be upregulated in breast cancer. METHODS: eEF1A2 is highly similar (98%) to the near-ubiquitously expressed eEF1A1 (formerly known as EF1-alpha) making analysis with commercial antibodies difficult. We have developed specific anti-eEF1A2 antibodies and used them in immunohistochemical analyses of tumour samples. We report the novel finding that although eEF1A2 is barely detectable in normal breast it is moderately to strongly expressed in two-thirds of breast tumours. This overexpression is strongly associated with estrogen receptor positivity. CONCLUSION: eEF1A2 should be considered as a putative oncogene in breast cancer that may be a useful diagnostic marker and therapeutic target for a high proportion of breast tumours. The oncogenicity of eEF1A2 may be related to its role in protein synthesis or to its potential non-canonical functions in cytoskeletal remodelling or apoptosis.

Apoptosis↗
PubMed2005

Assessing competence in the use of motivational interviewing.

This report presents reliability, validity and sensitivity indices for the Motivational Interviewing Treatment Integrity (MITI) scale. Factor analysis of MI treatment sessions coded with the Motivational Interviewing Skills Code (MISC) was used to derive 10 elements of MI practice, forming the MITI. Canonical correlation revealed that the MITI captured 59% of the variability in the MISC. Reliability estimates for the MITI were derived using three masked, independent coders. Intra-class coefficients ranged from .5 to .9 and were generally in the good to excellent range. Comparison of MITI scores before and after MI workshops indicate good sensitivity for detecting improvement in clinical practice as result of training. Implications for the use of this instrument in research and supervision are discussed.

Clinical Competence↗
PubMed2005

Evidence-based treatment: why, what, where, when, and how?

Research and clinical perspectives are blended in this commentary on the rapidly emerging requirement for evidence-based treatment (EBT) in substance abuse programs. Although, historically, it has not been a standard of care in behavioral health, there are sound scientific, ethical, and compassionate reasons to learn and deliver an EBT as it becomes available. This article explores a series of issues, including the following: (1) Why should EBTs be used in substance abuse treatment? (2) What kinds of treatment are EBTs, and how are they determined? (3) Where can EBTs be implemented--at what levels of service delivery? (4) When should EBTs be used? and (5) How do clinicians learn EBTs? Potential pitfalls in implementing EBTs are also considered.

Evidence-Based Medicine↗