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Biomedical subjects

Keith Humphreys

Publications and source records attributed to Keith Humphreys.

At least 19 recordsLinked to original sources
PubMed2007

Encouraging posttreatment self-help group involvement to reduce demand for continuing care services: two-year clinical and utilization outcomes.

BACKGROUND: Accumulating evidence indicates that addiction and psychiatric treatment programs that actively promote self-help group involvement can reduce their patients' health care costs in the first year after treatment, but such initially impressive effects may wane over time. This paper examines whether the positive clinical outcomes and reduced health care costs evident 1 year after treatment among substance-dependent patients who were strongly encouraged to attend 12-step self-help groups were sustained at 2-year follow-up. METHODS: A 2-year quasi-experimental analysis of matched samples of male substance-dependent patients who were treated in either 12-step-based (n=887 patients) or cognitive-behavioral (CB, n=887 patients) treatment programs. The 12-step-based programs placed substantially more emphasis on 12-step concepts, had more staff members "in recovery," had a more spiritually oriented treatment environment, and promoted self-help group involvement much more extensively than did the CB programs. The 2-year follow-up assessed patients' substance use, psychiatric functioning, self-help group affiliation, and mental health care utilization and costs. RESULTS: As had been the case in the 1-year follow-up of this sample, the only difference in clinical outcomes was a substantially higher abstinence rate among patients treated in 12-step (49.5%) versus CB (37.0%) programs. Twelve-step treatment patients had 50 to 100% higher scores on indices of 12-step self-help group involvement than did patients from CB programs. In contrast, patients from CB programs relied significantly more on outpatient and inpatient mental health services, leading to 30% lower costs in the 12-step treatment programs. This was smaller than the difference in cost identified at 1 year, but still significant ($2,440 per patient, p=0.01). CONCLUSIONS: Promoting self-help group involvement appears to improve posttreatment outcomes while reducing the costs of continuing care. Even cost offsets that somewhat diminish over the long term can yield substantial savings. Actively promoting self-help group involvement may therefore be a useful clinical practice for helping addicted patients recover in a time of constrained fiscal resources.

Adult↗
PubMed2006

Effect of ATM, CHEK2 and ERBB2 TAGSNPs and haplotypes on endometrial cancer risk.

Family history of endometrial cancer increases the risk of developing the disease, but it is still largely unknown which germ-line genetic factors are involved in the aetiology of endometrial cancer. In a Swedish population-based case-control study including 705 cases and 1565 controls, we examined common variation in the ATM, CHEK2 and ERBB2 genes in relation to endometrial cancer risk overall, restricted to tumours of certain characteristics or stratified by various endometrial cancer risk factors. We genotyped a large number of single-nucleotide polymorphisms (SNPs) in the genes and selected seven haplotype-tagging SNPs (tagSNPs) in ATM, six tagSNPs in CHEK2 and seven tagSNPs in ERBB2 that could predict common variants and haplotypes (frequency > or =0.03) in each gene with R(2) > or = 0.8. We included the tagSNPs or their haplotypes as explanatory variables in unconditional logistic regression models adjusted for age. Our results indicated an increased risk of developing endometroid endometrial cancer for homozygous carriers of the rare allele (AA) of a tagSNP (rs4987886) in CHEK2 (P = 0.005) when contrasted with GG carriers. We also found a decreased endometrial cancer risk among non-smoking carriers of a haplotype in ATM (P = 0.0007) and among carriers of a haplotype in CHEK2, who had experienced menopause below 49 years of age (P = 0.0009) compared with non-carriers of these haplotypes. We found no effect of genetic variation in ERBB2 on endometrial cancer risk. In conclusion, it is possible that common variants in the ATM and CHEK2 genes, in interaction with oestrogen-related exposures, are involved in endometrial cancer aetiology.

Age Factors↗
PubMed2006

Linkage disequilibrium mapping of CHEK2: common variation and breast cancer risk.

BACKGROUND: Checkpoint kinase 2 (CHEK2) averts cancer development by promoting cell cycle arrest and activating DNA repair in genetically damaged cells. Previous investigation has established a role for the CHEK2 gene in breast cancer aetiology, but studies have largely been limited to the rare 1100delC mutation. Whether common polymorphisms in this gene influence breast cancer risk remains unknown. In this study, we aimed to assess the importance of common CHEK2 variants on population risk for breast cancer by capturing the majority of diversity in the gene using haplotype tagging single nucleotide polymorphisms (tagSNPs). METHODS AND FINDINGS: We analyzed 14 common SNPs spanning 52 kilobases (kb) of the CHEK2 gene in 92 Swedish women. Coverage evaluation indicated that these typed SNPs would efficiently convey association signal also from untyped SNPs in the same region. Six of the 14 SNPs predicted well both the haplotypic and single SNP variations within CHEK2. We genotyped these six tagSNPs in 1,577 postmenopausal breast cancer cases and 1,513 population controls, but found no convincing association between any common CHEK2 haplotype and breast cancer risk. The 1100delC mutation was rare in our Swedish population--0.7% in cases and 0.4% in controls--with a corresponding odds ratio for carriers versus noncarriers of 2.26 (95% confidence interval, 0.99-5.15). Estimates of the population frequency and the odds ratio of 1100delC indicate that our sample is representative of a Northern European population. CONCLUSIONS: Notwithstanding the involvement of the CHEK2 gene in breast cancer aetiology, we show that common polymorphisms do not influence postmenopausal breast cancer risk.

Aged↗
PubMed2006

Formative evaluation and three-month follow-up of an online personalized assessment feedback intervention for problem drinkers.

BACKGROUND: In recent years, online services for problem drinkers have been developed. This paper describes ongoing efforts to improve one of these services, the Alcohol Help Center. OBJECTIVE: This report summarizes new modules added to the Check Your Drinking (CYD) screener, a component of the Alcohol Help Center, to make the CYD screener more useful to periodic heavy drinkers, as well as to regular alcohol consumers. Participants' initial reactions to the CYD screener and the changes in their drinking habits at a three-month follow-up are presented. METHODS: The CYD screener provides a free personalized Final Report that compares the user's drinking to that of others in the general population of the same age, gender, and country of origin. Current alcohol consumption and demographic characteristics are collected as part of the CYD screening process. After users were presented with a customized Final Report, they were hot-linked to a volunteer feedback survey. The voluntary feedback survey asked about impressions of the CYD Final Report. Respondents agreeing to participate were sent a follow-up survey after three months. RESULTS: We recruited 388 volunteers (69% female) who were registered users of another free-to-consumer online eHealth service. Of the 343 respondents agreeing to participate in the three-month follow-up, 138 accessed the survey, and 97 provided complete data (participation rate = 40%; completion rate = 70%). Compared to moderate drinkers, current problem drinkers judged the Final Report to be more useful (34% vs. 69%, chi2 (1) = 41.5, P < .001) and accurate (43% vs. 76%, chi2 (1) = 36.0, P < .001). Respondents who participated in the three-month follow-up displayed reductions in drinking compared to baseline (F(4,76) = 12.2, P = .001). CONCLUSIONS: Improvements can still be made to make the CYD screener more relevant to specific populations, particularly periodic heavy drinkers. There is a need to further tailor algorithms that can present questions only relevant to specific populations. There also appears to be a need to further customize the Final Report for respondents who identify themselves as infrequent heavy drinkers. These improvements will be made, and a randomized controlled trial is planned to conduct a rigorous evaluation of the CYD screener as an intervention to help problem drinkers.

Adult↗
PubMed2006

Liver X receptor gene polymorphisms and adipose tissue expression levels in obesity.

OBJECTIVE: LXRA and LXRB genes regulate adiposity, energy dissipation, as well as glucose and lipid homeostasis in mice. We investigated the LXR genes in human obesity. METHODS: LXRA and LXRB mRNAs were quantified in abdominal subcutaneous adipose tissue of obese and nonobese women. The LXRA and LXRB genes were screened for polymorphisms and common single nucleotide polymorphisms genotyped in obese and nonobese women. RESULTS: Relative LXRA mRNA expression levels were higher in obese women (P=0.03). One LXRA single nucleotide polymorphism, rs2279238, and one common haplotype, CAAGCC, as well as two LXRB single nucleotide polymorphisms, LB44732G>A and rs2695121, were associated with obesity phenotypes (nominal P values of 0.0075, 0.0014, 0.008 and 0.02, respectively). Furthermore, there was evidence of interaction between LXRA and LXRB alleles in determining body mass index. CONCLUSION: Our results support a role for LXRA in human adipose tissue. The nominal associations of LXRA and LXRB alleles with obesity are interesting and should be further investigated in independent data sets.

Adipose Tissue↗
PubMed2006

Variation in DNA repair genes ERCC2, XRCC1, and XRCC3 and risk of follicular lymphoma.

The reasons for the positive association between skin cancer and non-Hodgkin's lymphoma are not known but may be due to common susceptibility involving suboptimal DNA repair. Therefore, we investigated selected polymorphisms and haplotypes in three DNA repair genes, previously associated with skin cancer and DNA repair capacity, in risk of follicular lymphoma, including possible gene interaction with cigarette smoking and sun exposure. We genotyped 19 single nucleotide polymorphisms (SNP) in the ERCC2, XRCC1, and XRCC3 genes in 430 follicular lymphoma patients and 605 controls within a population-based case-control study in Denmark and Sweden. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression and haplotype associations were assessed with a global score test. We observed no associations between variation in the ERCC2 and XRCC1 genes and follicular lymphoma risk. In XRCC3, increased risk of follicular lymphoma was suggested for rare homozygotes of three SNPs [Rs3212024: OR, 1.8 (95% CI, 1.1-2.8); Rs3212038: OR, 1.5 (95% CI, 1.0-2.4); Rs3212090: OR, 1.5 (95% CI, 1.0-2.5)]. These results were strengthened in current cigarette smokers. However, evidence of differences in XRCC3 haplotype distributions between follicular lymphoma cases and controls was weak, both overall and in current smokers. We conclude that polymorphic variation in the XRCC3 gene, but not in ERCC2 or XRCC1, may be of importance for susceptibility to follicular lymphoma, perhaps primarily in current smokers. The link between skin cancer and follicular lymphoma is unlikely to be mediated through common variation in the studied DNA repair gene polymorphisms.

Adolescent↗
PubMed2006

Comprehensive analysis of the ATM, CHEK2 and ERBB2 genes in relation to breast tumour characteristics and survival: a population-based case-control and follow-up study.

BACKGROUND: Mutations in the ataxia-telangiectasia mutated (ATM) and checkpoint kinase 2 (CHEK2) genes and amplification of the v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ERBB2) gene have been suggested to have an important role in breast cancer aetiology. However, whether common variation in these genes has a role in the development of breast cancer or breast cancer survival in humans is still not clear. METHODS: We performed a comprehensive haplotype analysis of the ATM, CHEK2 and ERBB2 genes in a Swedish population-based study, which included 1,579 breast cancer cases and 1,516 controls. We followed the cases for 8.5 years, on average, and retrieved information on the date and cause of death during that period from the nationwide Swedish causes of death registry. We selected seven haplotype-tagging SNPs (tagSNPs) in the ATM gene, six tagSNPs in the CHEK2 gene and seven tagSNPs in the ERBB2 gene that predicted both haplotypic and single locus variations in the respective genes with R2 values > or = 0.8. These tagSNPs were genotyped in the complete set of cases and controls. We computed expected haplotype dosages of the tagSNP haplotypes and included the dosages as explanatory variables in Cox proportional hazards or logistic regression models. RESULTS: We found no association between any genetic variation in the ATM, CHEK2 or ERBB2 genes and breast cancer survival or the risk of developing tumours with certain characteristics. CONCLUSION: Our results indicate that common variants in the ATM, CHEK2 or ERBB2 genes are not involved in modifying breast cancer survival or the risk of tumour-characteristic-defined breast cancer.

Aged↗
PubMed2006

Determining effective methadone doses for individual opioid-dependent patients.

BACKGROUND: Randomized clinical trials of methadone maintenance have found that on average high daily doses are more effective for reducing heroin use, and clinical practice guidelines recommend 60 mg/d as a minimum dosage. Nevertheless, many clinicians report that some patients can be stably maintained on lower methadone dosages to optimal effect, and clinic dosing practices vary substantially. Studies of individual responses to methadone treatment may be more easily translated into clinical practice. METHODS AND FINDINGS: A volunteer sample of 222 opioid-dependent US veterans initiating methadone treatment was prospectively observed over the year after treatment entry. In the 168 who achieved at least 1 mo of heroin abstinence, methadone dosages on which patients maintained heroin-free urine samples ranged from 1.5 mg to 191.2 mg (median = 69 mg). Among patients who achieved heroin abstinence, higher methadone dosages were predicted by having a diagnosis of posttraumatic stress disorder or depression, having a greater number of previous opioid detoxifications, living in a region with lower average heroin purity, attending a clinic where counselors discourage dosage reductions, and staying in treatment longer. These factors predicted 42% of the variance in dosage associated with heroin abstinence. CONCLUSIONS: Effective and ineffective methadone dosages overlap substantially. Dosing guidelines should focus more heavily on appropriate processes of dosage determination rather than solely specifying recommended dosages. To optimize therapy, methadone dosages must be titrated until heroin abstinence is achieved.

Adult↗
PubMed2006

Opioid substitution treatment reduces substance use equivalently in patients with and without posttraumatic stress disorder.

OBJECTIVE: The purpose of this study was to determine whether opioid-dependent patients with diagnosed posttraumatic stress disorder (PTSD) have poorer long-term outcomes in opioid substitution treatment than do patients without PTSD. METHOD: This prospective observational study examined outcomes of 255 opioid-dependent patients (men = 248) entering opioid substitution treatment at eight clinics in the Veterans Health Administration (VHA). Subjects were interviewed at treatment entry, 6 months, and 1 year about substance use and related problems, health status, treatment satisfaction, and non-VHA health care utilization. Medical records were reviewed to obtain toxicology results, health care utilization data, and diagnoses. Medical record review identified a diagnosis of PTSD in 71 (28%) patients. Substance-use and mental-health outcomes and health care utilization in the first year following treatment entry were compared between patients with and without a diagnosis of PTSD. RESULTS: Patients with and without PTSD had similar treatment responses. Although patients with PTSD had longer histories of drug use at intake, at 1-year follow-up they showed reductions in heroin, cocaine, and alcohol use, comparable to patients without the disorder. PTSD patients received higher doses of opiate medication, attended more psychosocial treatment sessions for substance-use disorder, and had better treatment retention. Psychiatric symptoms for patients with PTSD were more severe at intake and showed little improvement throughout treatment. CONCLUSIONS: Opioid substitution therapy is as effective at reducing substance use in PTSD patients as it is in patients without the disorder, but additional services are needed for treatment of psychological problems that are largely unchanged by treatment for addiction.

Adult↗
PubMed2005

Fine-scale mapping in case-control samples using locus scoring and haplotype-sharing methods.

Both haplotype-based and locus-based methods have been proposed as the most powerful methods to employ when fine mapping by association. Although haplotype-based methods utilize more information, they may lose power as a result of overparameterization, given the large number of haplotypes possible over even a few loci. Recently methods have been developed that cluster haplotypes with similar structure in the hope that this reflects shared genealogical ancestry. The aim is to reduce the number of parameters while retaining the genotype information relating to disease susceptibility. We have compared several haplotype-based methods with locus-based methods. We utilized 2 regions (D2 and D4) simulated to be in linkage disequilibrium and to be associated with disease susceptibility, combining 5 replicates at a time to produce 4 datasets that were analyzed. We found little difference in the performance of the haplotype-based methods and the locus-based methods in this dataset.

Case-Control Studies↗
PubMed2005

Analysis of binary traits: testing association in the presence of linkage.

Most methods for testing association in the presence of linkage, using family-based studies, have been developed for continuous traits. FBAT (family-based association tests) is one of few methods appropriate for discrete outcomes. In this article we describe a new test of association in the presence of linkage for binary traits. We use a gamma random effects model in which association and linkage are modelled as fixed effects and random effects, respectively. We have compared the gamma random effects model to an FBAT and a generalized estimating equation-based alternative, using two regions in the Genetic Analysis Workshop 14 simulated data. One of these regions contained haplotypes associated with disease, and the other did not.

Genetic Linkage↗
PubMed2005

Predictors of retention in methadone programs: a signal detection analysis.

Retention in Opioid Agonist Therapy (OAT) is associated with reductions in substance use, HIV risk behavior, and criminal activities in opioid dependent patients. To improve the effectiveness of treatment for opioid dependence, it is important to identify predisposing characteristics and provider-related variables that predict retention in OAT. Participants include 258 veterans enrolled in 8 outpatient methadone/l-alpha-acetylmethadol (LAAM) treatment programs. Signal detection analysis was utilized to identify variables predictive of 1-year retention and to identify the optimal cut-offs for significant predictors. Provider-related variables play a vital role in predicting retention in OAT programs, as higher methadone dose (> or =59 mg/day) and greater treatment satisfaction were among the strongest predictors of retention at 1-year follow-up.

Adult↗
PubMed2005

Response to methadone maintenance treatment of opiate dependent patients with and without significant pain.

BACKGROUND: Both clinicians and researchers have expressed doubt that opiate dependent patients with significant pain can be effectively treated in methadone maintenance treatment (MMT) programs; however, little research exists on this topic. Patients who report significant pain in the month preceding entry to MMT present with a distinct and more severe pattern of polysubstance use, medical and psychosocial problems than do those without pain. The present study investigated the 1-year treatment outcomes of MMT patients with opiate dependence and pain. METHODS: Analyses were based on a national sample of 200 patients presenting in MMT programs for treatment of opiate dependence. Substance use and related problems were measured at treatment entry and 12 months later. Patients reported pain severity over the month preceding treatment entry. RESULTS: Compared to patients without significant pain, patients who reported significant pain at baseline (n = 103) showed similar substance-related functioning, but poorer psychosocial functioning at 1 year. CONCLUSIONS: Patients with and without significant pain experience comparable reductions in substance use when provided with standard care in MMT programs. However, additional medical and/or mental health treatment is needed for their pain and other problems.

Adult↗
PubMed2005

CYP17 gene polymorphism in relation to breast cancer risk: a case-control study.

INTRODUCTION: The c.1-34T>C 5' promoter region polymorphism in cytochrome P450c17 (CYP17), a key enzyme in the biosynthesis of estrogen, has been associated with breast cancer risk, but most previous studies have been relatively small. METHODS: We genotyped 1,544 incident cases of primary breast cancer and 1,502 population controls, all postmenopausal Swedish women, for the CYP17 c.1-34T>C polymorphism and calculated odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression models. RESULTS: No overall association was found between CYP17 c.1-34T>C and breast cancer risk, OR 1.0 (95% CI 0.8-1.3) for the A2/A2 (CC) carriers compared to the A1/A1 (TT) carriers, regardless of histopathology. We detected an interaction between CYP17 c.1-34T>C and age at menarche (P = 0.026) but regarded that as a chance finding as no dose-response pattern was evident. Other breast cancer risk factors, including menopausal hormone use and diabetes mellitus, did not modify the overall results. CONCLUSION: It is unlikely that CYP17 c.1-34T>C has a role in breast cancer etiology, overall or in combination with established non-genetic breast cancer risk factors.

Aged↗