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Biomedical subjects

David W Oslin

Publications and source records attributed to David W Oslin.

At least 19 recordsLinked to original sources
PubMed2006

Methodological challenges in constructing effective treatment sequences for chronic psychiatric disorders.

Psychiatric disorders are often chronic conditions that require sequential decision making to achieve the best clinical outcomes. Sequential decisions are necessary to accommodate treatment response heterogeneity, a variable course of illness, and the often heavy burden associated with intensive or longer-term treatment. Yet, only a few studies in this field have been designed to address sequential decisions. Most of the experimental designs and data analytic methods that are best suited for improving sequential clinical decision making are often found in nonmedical fields such as engineering, computer science, and statistics. Promising designs and methods are surveyed with a focus on those areas most immediately useful for informing clinical decision making.

Chronic Disease↗
PubMed2006

Family involvement in the care of healthy medical outpatients.

BACKGROUND: Although the involvement of patients' family members in office visits has been examined extensively, less is known about the involvement of family members in supporting patients' medical care outside of office visits. OBJECTIVE: This study examines two questions: What types of family involvement do family members have in the medical care of relatively healthy older outpatients, and does self-rated health moderate patients' reactions to this family involvement? METHODS: Patients from a large sample of medical practice outpatients (N = 1572) were assessed to determine perceived emotional support, involvement of family members in their medical care, as well as the presence of depressive symptoms. RESULTS: Approximately 50% of patients had some family involvement in their medical care (e.g. taking part in medical decisions, reminding the patient to take medication). Marital status was a stronger predictor of family involvement than self-ratings of poor physical health. Additionally, there was no evidence that older patients who report good health have less favourable reactions to family involvement in their medical care. CONCLUSION: Family involvement in medical care occurs routinely and is most likely to involve a spouse, and is consistent with family interaction patterns among older adults. These findings also suggest that when providers invite family members to support treatment outside the office visit, these invitations are appropriate for older adult patients across a continuum of good to poor health.

Aged↗
PubMed2006

The status of naltrexone in the treatment of alcohol dependence: specific effects on heavy drinking.

BACKGROUND: In almost 2 decades of naltrexone research for treating alcoholism, there have been 29 published randomized placebo-controlled trials of opioid antagonists, primarily naltrexone, for the treatment of alcohol dependence. The present review builds on prior systematic reviews while maximizing the number of included studies to date, for the purpose of resolving inconsistencies in naltrexone's reported efficacy across trials. Clinical trial results in this article are evaluated by the type of outcome measure used to determine naltrexone's treatment advantage, that is, measures related to reducing heavy drinking versus those related to increasing abstinence. METHODS: We conducted a Medline search to identify double-blind studies from 1990 to the present (2006) that evaluated the use of anopiate antagonist for the treatment of alcohol dependence. There were 29 studies identified, representing 5997 alcohol-dependent patients, which met our study inclusion criteria for this review. Studies were evaluated in this review on 4 prespecified drinking outcomes-2 related to "any drinking" and 2 related to "heavy or excessive drinking." RESULTS: In the treatment of alcohol dependence, we found that 19 (70%) of 27 clinical trials that measured reductions in "heavy or excessive drinking" demonstrated an advantage for prescribing naltrexone over placebo, whereas only 9 (36%) of 25 clinical trials that measured abstinence or "any drinking" found an advantage for medication over placebo. CONCLUSION: The majority of double-blind clinical trials in the literature favored prescribing naltrexone for alcohol dependence to reduce heavy drinking. This finding is consistent with our understanding of naltrexone's mechanism of action of decreasing excessive drinking by reducing the reward associated with drinking alcohol. Thus, we conclude that outcome measures related to heavy or excessive drinking are most relevant to defining naltrexone's therapeutic effects. Factors influencing naltrexone response (treatment adherence and distinct patient subgroups) are also discussed.

Adolescent↗
PubMed2006

No association between polymorphisms in the prostate apoptosis factor-4 gene and cocaine dependence.

OBJECTIVE: A number of studies have investigated the genes underlying dopamine, serotonin, and glutamine neurotransmitter systems in order to find a genetic basis for the pathology of cocaine dependence. The gene that encodes the prostate apoptosis factor-4 (Par-4) protein is located in the 12q21 region and has been shown to directly interact with the D2 dopamine receptor and through such interaction is thought to directly affect the activity of D2 receptors. The aim of this study is to investigate whether polymorphisms in the human Par-4 gene contribute to the etiology of cocaine dependence. METHODS: To test this hypothesis, we used a case-control design in which the genotype and allele frequencies for five single nucleotide polymorphisms in the human Par-4 gene were compared between cocaine-dependent individuals (n=172) and controls (n=92) of African descent. RESULTS: The genotype results failed to detect any associations between polymorphisms in the Par-4 gene and the cocaine-dependent phenotype. CONCLUSIONS: The results of this study suggest that variations in the human Par-4 gene are unlikely to play a major role in the pathophysiology of cocaine dependence. This study, however, should be repeated in larger cocaine-dependent and control populations to determine that this is indeed the case.

Adult↗
PubMed2006

Analysis of variations in the tryptophan hydroxylase-2 (TPH2) gene in cocaine dependence.

While the exact physiological mechanisms underlying cocaine dependence remain unclear, a growing body of evidence indicates a role for the serotonergic neurotransmitter system in the pathology of this substance use disorder. The focus of the present study is to determine whether genetic variation in the tryptophan hydroxylase-2 (TPH2) gene, which encodes the enzyme responsible for synthesis of the majority of the serotonin contained in neurons of the central nervous system, contributes to the pathophysiology of cocaine dependence. To examine this hypothesis, we used a case-control study design in which the genotype and allele distributions for six single nucleotide polymorphisms (SNPs) in the TPH2 gene were compared between cocaine-dependent (n = 299) and control individuals (n = 208) of African descent. The results indicate that none of the SNPs in the TPH2 gene examined in this study associate with the cocaine-dependent phenotype. This work suggests that variations in the TPH2 gene are not a risk factor for the development of cocaine dependence, but these findings require confirmation in larger, independent samples of cocaine-dependent and control subjects.

Adult↗
PubMed2006

Targeting treatments for alcohol dependence: the pharmacogenetics of naltrexone.

Alcohol dependence is one of the leading causes of morbidity worldwide, yet only a minority of those afflicted engages in treatment. While increasing access to treatment is an important public health approach, increasing the success of treatment is also likely to lead to greater engagement. However, alcohol dependence is a complex disorder likely to consist of several biological subtypes. Recent evidence from a number of different studies has suggested that genetic variation in the mu-opioid receptor has a significant influence on clinical presentation of alcohol problems and response to treatment with an opioid antagonist. Most notably, the A118G polymorphism of the mu-receptor gene has been demonstrated to predict clinical response to naltrexone in alcohol-dependent individuals. This article reviews the biological correlates and outlines a scientific agenda for better understanding the role of opioid neurotransmission in the etiology, maintenance and treatment of alcohol dependence.

Alcoholism↗
PubMed2006

Screening, assessment, and management of depression in VA primary care clinics. The Behavioral Health Laboratory.

OBJECTIVES: The purpose of this project was to assess the utility and feasibility of a telephone-based systematic clinical assessment service, the Behavioral Health Laboratory (BHL), in the context of primary care. The BHL is a clinical service that provides primary care providers with an assessment and a summary of mental health and substance abuse (MH/SA) symptoms and provides treatment decision support, including triage to specialty MH/SA services. The BHL was implemented to assist in the evaluation of patients who screened positively for depression at an annual clinical appointment or who were identified through routine care. METHODS: Results from systematic screening of primary care patients were extracted during a period of 6 months prior to implementation of the BHL and after implementation of the BHL. Descriptive results of the 580 evaluations conducted during this time were available. RESULTS: Results suggest an association between the implementation of the BHL and an increase in the proportion of patients screened for depression in primary care. In addition, there was an increase in the proportion of patients who screened positively (2.8% vs 7.0%). The BHL was successful in providing a comprehensive assessment for 78% of those referred. Significant co-occurring mental illness and substance misuse were found among those assessed. CONCLUSIONS: Introducing the BHL into primary care was associated with an apparent change in clinical practice in primary care at the Philadelphia VA Medical Center. Not only were more patients identified, the broad-based approach of the BHL identified significant comorbidity with alcohol misuse, illicit drugs, and suicidal ideation, symptoms likely to have been missed in routine clinical practice. The BHL offers a practical, low-cost method of assessment, monitoring, and treatment planning for patients identified in primary care with MH/SA needs.

Ambulatory Care Facilities↗
PubMed2006

PRISM-E: comparison of integrated care and enhanced specialty referral models in depression outcomes.

OBJECTIVE: This study, entitled Primary Care Research in Substance Abuse and Mental Health for the Elderly, examined six-month outcomes for older primary care patients with depression who received different models of treatment. METHODS: Clinical outcomes were compared for patients who were randomly assigned to integrated care or enhanced specialty referral. Integrated care consisted of mental health services co-located in primary care in collaboration with primary care physicians. Enhanced specialty referral consisted of referral to physically separate, clearly identified mental health or substance abuse clinics. RESULTS: A total of 1,531 patients were included; their mean age was 73.9 years. Remission rates and symptom reduction for all depressive disorders were similar for the two models at the three- and six-month follow-ups. For the subgroup with major depression, the enhanced specialty referral model was associated with a greater reduction in depression severity than integrated care, but rates of remission and change in function did not differ across models of care for major depression. CONCLUSIONS: Six-month outcomes were comparable for the two models. For the subgroup with major depression, reduction in symptom severity was superior for those randomly assigned to the enhanced specialty referral group.

Aged↗
PubMed2006

PRISM-E: comparison of integrated care and enhanced specialty referral in managing at-risk alcohol use.

OBJECTIVE: This study was part of the Primary Care Research in Substance Abuse and Mental Health for the Elderly study (PRISM-E) and determined the relative effectiveness of two different models of care for reducing at-risk alcohol use among primary care patients aged 65 and older. METHODS: This multisite study was a randomized clinical trial comparing integrated care with enhanced specialty referral for older primary care patients screened and identified to have at-risk drinking. RESULTS: Before the study, the 560 participants consumed a mean of 17.9 drinks per week and had a mean of 21.1 binge episodes in the prior three months. At six months, both treatment groups reported lower levels of average weekly drinking (p<.001) and binge drinking (p<.001), despite low levels of treatment engagement. However, the declines did not differ significantly between treatment groups. CONCLUSIONS: These results suggest that older persons with at-risk drinking can substantially modify their drinking over time. Although no evidence suggested that the model of care was important in achieving this result, the magnitude of reduction in alcohol use was comparable with other intervention studies.

Aged↗
PubMed2005

Older patients' aversion to antidepressants. A qualitative study.

BACKGROUND: Depression is common among older patients yet is often inadequately treated. Patient beliefs about antidepressants are known to affect treatment initiation and adherence, but are often not expressed in clinical settings. OBJECTIVE: To explore attitudes toward antidepressants in a sample of depressed, community-dwelling elders who were offered treatment. DESIGN. Cross-sectional, qualitative study utilizing semi-structured interviews. PARTICIPANTS: Primary care patients age 60 years and over with depression, from academic and community primary care practices of the University of Pennsylvania Health System and the Philadelphia Department of Veterans Affairs. Patients participated in either the Prevention of Suicide in Primary Care Elderly: Collaborative Trial or the Primary Care Research in Substance Abuse and Mental Health for the Elderly Trial. Sixty-eight patients were interviewed and responses from 42 participants with negative attitudes toward medication for depression were analyzed. MEASUREMENTS: Interviews were audiotaped, transcribed, and entered into a qualitative software program for coding and analysis. A multidisciplinary team of investigators coded the transcripts and identified key features of narratives expressing aversion to antidepressants. RESULTS: Four themes characterized resistance to antidepressants: (1) fear of dependence; (2) resistance to viewing depressive symptoms as a medical illness; (3) concern that antidepressants will prevent natural sadness; (4) prior negative experiences with medications for depression. CONCLUSIONS: Many elders resisted the use of antidepressants. Patients expressed concerns that seem to reflect their concept of depression as well as their specific concerns regarding antidepressants. These findings may enhance patient-provider communication about depression treatment in elders.

Aged↗
PubMed2005

Confirmation of the association between a polymorphism in the promoter region of the prodynorphin gene and cocaine dependence.

The endogenous opioid system has been shown to have a role in the biological processes involved in addiction to numerous drugs of abuse including cocaine. It has recently been reported that the variable nucleotide tandem repeat (VNTR) polymorphism in the 5' promoter region of the prodynorphin gene, which encodes the precursor for three endogenous opioid peptides, is associated with the cocaine dependent phenotype. In order to confirm this finding, we genotyped the prodynorphin promoter polymorphism in cocaine dependent (n = 167) and control (n = 88) individuals of African descent. The results from this experiment indicate a statistically significant (chi2 = 5.64, OR = 1.59, P = 0.018) association between the prodynorphin promoter VNTR polymorphism and the cocaine dependent phenotype. In contrast to previous work showing increased risk conferred by one or two copies of the prodynorphin VNTR, the genotyping results from this study indicate that persons with three or four copies of this polymorphism are more likely to become cocaine dependent. This disparity suggests that the prodynorphin promoter VNTR may not be the functional polymorphism associating with the cocaine dependent phenotype. It is possible that different alleles of the prodynorphin promoter VNTR in the independent populations used for this and the previous study may be in linkage disequilibrium with a yet to be identified functional polymorphism in this gene.

Adult↗
PubMed2005

Novel exonic mu-opioid receptor gene (OPRM1) polymorphisms not associated with opioid dependence.

The mu-opioid receptor (MOR) mediates reward and dependence associated with opioids and other commonly abused substances. Variability in the MOR gene, OPRM1, may influence risk for opioid dependence. In this study, associations between two single nucleotide polymorphisms (SNPs), dbSNP rs540825 and dbSNP rs562859, and opioid dependence were investigated. The two SNPs are located in the protein coding region of the novel exon X of an alternative splice variant of OPRM1, and can be detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Genotyping at the two SNPs was performed for 170 severe opioid dependent individuals and 128 carefully screened controls. Although no differences were found between cases and controls, there were significant prevalence differences between African-American (AA) subjects and European-American (EA) subjects for SNP 540825 allele and genotype frequencies. The 540825 and 562859 polymorphisms were found to be in complete linkage disequilibrium (LD) for both ethnic groups, and LD existed between the 562859 SNP and the A(-1320)G SNP in the promoter region of OPRM1 in AAs, based on genotyping data previously carried out on the same subjects. LD between these two markers, separated by 55 kb, links the entire distance studied in this project. The results indicate that polymorphisms in the novel splice variant are not associated with opioid dependence, but are in LD with other polymorphisms in OPRM1.

Alleles↗
PubMed2005

Lack of association between single nucleotide polymorphisms in the corticotropin releasing hormone receptor 1 (CRHR1) gene and alcohol dependence.

While the physiological mechanisms that contribute to the development of alcohol dependence remain unclear, a number of recent studies have indicated a role for the corticotropin releasing hormone receptor 1 (CRHR 1) in modulating the response of the central nervous system to ethanol. Based on these data, the present study aims to identify associations between variations in the CRHR 1 gene and alcohol dependence in a population of individuals of European ancestry. In order to identify such putative associations, five single nucleotide polymorphisms (SNPs) in the CRHR 1 gene were analyzed in 120 alcohol dependent and 180 control subjects. In comparing both allele and genotype frequencies at these five loci between alcohol dependent and control populations, no significant associations between variations in the CRHR 1 gene and alcohol dependence were detected. The results of this study suggest that polymorphisms in the CRHR 1 gene are not major risk factors for the development of alcohol dependence in persons of European ancestry.

Alcoholism↗
PubMed2005

Treatment outcomes for alcohol dependence among middle-aged and older adults.

AIMS: The purpose of this study was to examine differences in the clinical presentation and treatment outcomes of older adults with a diagnosis of alcohol dependence compared to middle-aged adults. DESIGN: The study is a prospective naturalistic study. Participants included 1358 patients admitted to a residential rehabilitation program for alcohol dependence. RESULTS: Older adults entering an alcohol rehabilitation program are less impaired on a number measures of psychiatric distress and addiction severity but more impaired in somatic health. While there were no significantly different outcomes in abstinence rates at 1 month, older adults engaged in formal post-discharge aftercare less than middle-aged adults. CONCLUSIONS: These results confirm impressions that older adults seeking alcohol treatment may have a lower severity of alcohol dependence compared to those at younger ages. However, results suggest that traditional outpatient substance abuse care is not accepted at the same rates as middle-aged adults. The low rates of engagement suggest the need for age appropriate treatment options and are potentially of concern if treatment is necessary to maintain short-term success.

Age Factors↗
PubMed2005

Association of a polymorphism in the Homer1 gene with cocaine dependence in an African American population.

OBJECTIVE: While twin and adoption studies have demonstrated that up to 70% of the risk for becoming addicted to cocaine is due to genetic factors, identifying specific genes involved in the development or progression of cocaine dependence has been difficult. The purpose of this study is to determine whether single-nucleotide polymorphisms in the Homer1 and Homer2 genes associate with the cocaine-dependent phenotype in an African American population. METHODS: This study utilized a case-control design in which the genotype and allele frequencies for four single-nucleotide polymorphisms in the Homer1 gene and three single-nucleotide polymorphisms in the Homer2 gene were compared between African American individuals with a diagnosis of cocaine dependence (n=170) and African American individuals with no history of substance abuse (n=90). RESULTS: The data indicate that one single-nucleotide polymorphism, rs6871510, located in intron 1 of the Homer1 gene significantly (P=0.029) associates with cocaine dependence at the genotype level, and trends toward a significant association at the allele frequency level (chi=2.62, df=1, P=0.106, OR=1.71). None of the single-nucleotide polymorphisms analyzed in the Homer2 gene associates with cocaine dependence. CONCLUSIONS: The results of this study suggest that a polymorphism in the Homer1 gene, rs6871510, is a potential risk factor for the development of cocaine dependence in an African American population, whereas polymorphisms in the Homer2 gene are not.

Black People↗
PubMed2005

A functional prodynorphin promoter polymorphism and opioid dependence.

OBJECTIVES: The prodynorphin gene (PDYN) promoter has a repeat polymorphism that is functionally important in association with substance abuse. We examined this polymorphism for association in our sample of 168 opioid-dependent patients and 122 ethnically and geographically matched controls. METHODS: Patients were selected from university-affiliated residential and non-residential addiction treatment programs in the Philadelphia area. A sample of blood was drawn from consenting individuals and genomic DNA was isolated. Polymerase chain reaction amplification of the PDYN promoter was performed and various genotypes were determined on the basis of differing sizes of the polymerase chain reaction products. The genotype and allele data were analyzed by Fisher's exact test. RESULT: A significant difference in genotype (P<0.0006) and allele (P<10) frequencies was found between the African American and European American populations. We did not detect any significant difference in genotype or allele frequencies between the patients and controls within the European American ethnic group. However, we detected a weak association (P=0.013) when we compared allele frequencies of patients and controls in the African American population. CONCLUSIONS: These data suggest that the PDYN repeat polymorphism should be studied in additional opioid-dependent populations.

Enkephalins↗
PubMed2005

Gambling among older, primary-care patients: an important public health concern.

OBJECTIVES: Authors assessed the prevalence rate of gambling in a sample of elderly patients (over age 65) and evaluated the sociodemographic characteristics, health, cognitive status, and psychiatric comorbidities of elderly gamblers. METHODS: This study is a cross-sectional survey of gambling habits. A random sample of older adults with a scheduled primary-care clinic appointment was selected and screened with the General Health Questionnaire and questions about suicidality and alcohol use. Also, participants were asked about their gambling habits. RESULTS: Of 843 screened patients completing the gambling questionnaire, 69.6% reported that they had participated in at least one gambling activity in the last year. At-risk gamblers were defined as those who reported having bet more than $100 on a single bet and/or having bet more than they could afford to lose in the last year. Of those responding, 10.9% were identified as at-risk gamblers. The strongest predictors of at-risk gambling behavior were being a binge drinker, presence of current posttraumatic stress disorder symptoms, minority race/ethnicity, and being a VA clinic patient. Subjects with mild-to-moderate cognitive impairment were just as likely as those without impairment to gamble and to report at-risk gambling behavior. At-risk gambling behavior was not significantly associated with gender, current or past depressive symptoms, or cigarette smoking. CONCLUSIONS: These data raise a significant public health concern that gambling behaviors are prevalent in older adults. Additional research is needed to further define the determinants of gambling behavior in older adults and evaluate the social, health, and economic costs and benefits of gambling by older adults, especially among those groups determined to be at risk.

Aged↗