Computer-Assisted Cognitive-Behavior Therapy in Medical Care Settings.

PURPOSE OF REVIEW: We reviewed research on computer-assisted cognitive-behavior therapy (CCBT) performed in medical settings with the goals of assessing the effectiveness of this newer method of treatment delivery, evaluating the need for clinician support of therapeutic computer programs, and making suggestions for future research and clinical implementation. RECENT FINDINGS: The overall results of randomized, controlled trials suggest that CCBT can be an effective treatment for depression in primary care patients and health care anxiety. Also, it can be a useful component of treatment for somatic conditions including irritable bowel syndrome, diabetes, fibromyalgia, and chronic pain. The amount and type of clinician support needed for maximizing effectiveness remains unclear. CCBT offers promise for overcoming barriers to delivering effective psychotherapy in medical settings. We recommend that next steps for researchers include more definitive studies of the influence of clinician support, investigations focused on implementation in clinical practices, cost-benefit analyses, and use of technological advances.

Effect of Computer-Assisted Cognitive Behavior Therapy vs Usual Care on Depression Among Adults in Primary Care: A Randomized Clinical Trial.

Importance: Depression is a common disorder that may go untreated or receive suboptimal care in primary care settings. Computer-assisted cognitive behavior therapy (CCBT) has been proposed as a method for improving access to effective psychotherapy, reducing cost, and increasing the convenience and efficiency of treatment for depression. Objectives: To evaluate whether clinician-supported CCBT is more effective than treatment as usual (TAU) in primary care patients with depression and to examine the feasibility and implementation of CCBT in a primary care population with substantial numbers of patients with low income, limited internet access, and low levels of educational attainment. Design, Setting, and Participants: This randomized clinical trial included adult primary care patients from clinical practices at the University of Louisville who scored 10 or greater on the Patient Health Questionnaire-9 (PHQ-9) and were randomly assigned to CCBT or TAU for 12 weeks of active treatment. Follow-up assessments were conducted 3 and 6 months after treatment completion. Enrollment occurred from June 24, 2016, to May 13, 2019. The last follow-up assessment was conducted on January 30, 2020. Interventions: CCBT included use of the 9-lesson computer program Good Days Ahead, along with as many as 12 weekly telephonic support sessions of approximately 20 minutes with a master's level therapist, in addition to TAU, which consisted of the standard clinical management procedures at the primary care sites. TAU was uncontrolled, but use of antidepressants and psychotherapy other than CCBT was recorded. Main Outcomes and Measures: The primary outcome measure (PHQ-9) and secondary outcome measures (Automatic Thoughts Questionnaire for negative cognitions, Generalized Anxiety Disorder-7, and the Satisfaction with Life Scale for quality of life) were administered at baseline, 12 weeks, and 3 and 6 months after treatment completion. Satisfaction with treatment was assessed with the Client Satisfaction Questionnaire-8. Results: The sample of 175 patients was predominately female (147 of 174 [84.5%]) and had a high proportion of individuals who identified as racial and ethnic minority groups (African American, 44 of 162 patients who reported [27.2%]; American Indian or Alaska Native, 2 [1.2%]; Hispanic, 4 [2.5%]; multiracial, 14 [8.6%]). An annual income of less than $30 000 was reported by 88 of 143 patients (61.5%). Overall, 95 patients (54.3%) were randomly assigned to CCBT and 80 (45.7%) to TAU. Dropout rates were 22.1% for CCBT (21 patients) and 30.0% for TAU (24 patients). An intent-to-treat analysis found that CCBT led to significantly greater improvement in PHQ-9 scores than TAU at posttreatment (mean difference, -2.5; 95% CI, -4.5 to -0.8; P = .005) and 3 month (mean difference, -2.3; 95% CI, -4.5 to -0.8; P = .006) and 6 month (mean difference, -3.2; 95% CI, -4.5 to -0.8; P = .007) follow-up points. Posttreatment response and remission rates were also significantly higher for CCBT (response, 58.4% [95% CI, 46.4-70.4%]; remission, 27.3% [95% CI, 16.4%-38.2%]) than TAU (response, 33.1% [95% CI, 20.7%-45.5%]; remission, 12.0% [95% CI, 3.3%- 20.7%]). Conclusions and Relevance: In this randomized clinical trial, CCBT was found to have significantly greater effects on depressive symptoms than TAU in primary care patients with depression. Because the study population included people with lower income and lack of internet access who typically have been underrepresented or not included in earlier investigations of CCBT, results suggest that this form of treatment can be acceptable and useful in diverse primary care settings. Additional studies with larger samples are needed to address implementation procedures that could enhance the effectiveness of CCBT and to examine potential factors associated with treatment outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT02700009.

Expression and regulation of a low-density lipoprotein receptor exon 12 splice variant.

As low-density lipoprotein receptor (LDLR) contributes to cholesterol and amyloid beta homeostasis, insights into LDLR regulation may facilitate our understanding of cardiovascular disease and Alzheimer's disease. Previously, we identified LDLR isoforms that lacked exon 12 or exons 11-12 and that are predicted to encode soluble, dominant negative, LDLR. Moreover, these isoforms were associated with rs688, an exon 12 polymorphism that was associated with LDL-cholesterol and Alzheimer's disease risk. In this study, we present evidence that although the truncated LDLR isoforms are translated in vitro, they represent < 0.1% of CSF proteins. As these LDLR isoforms likely represent a loss of mRNA-encoding functional LDLR, we then focused upon identifying intron-exon boundary and exonic splicing enhancer elements critical to splicing. Exon 12 inclusion is enhanced by altering the 5' splice site in intron 12 towards a consensus splice donor sequence, consistent with its being a weak 5' splice site. Additionally, of the nine evolutionarily conserved putative splicing enhancer regions within exon 12, two regions that flank rs688 were critical to exon 12 inclusion. Overall, these results suggest that LDLR splice variants represent a loss of mRNA encoding functional LDLR and provide insights into the regulatory elements critical for LDLR exon 12 splicing.

Sex-dependent association of a common low-density lipoprotein receptor polymorphism with RNA splicing efficiency in the brain and Alzheimer's disease.

Since apoE allele status is the predominant Alzheimer's disease (AD) genetic risk factor, functional single nucleotide polymorphisms (SNPs) in brain apoE receptors represent excellent candidates for association with AD. Recently, we identified a SNP, rs688, as modulating the splicing efficiency of low-density lipoprotein receptor (LDLR) exon 12 in female human liver and in minigene-transfected HepG2 cells. Moreover, the rs688T minor allele was associated with significantly higher LDL and total cholesterol in women within the Framingham Offspring Study cohort. Since LDLR is a major apoE receptor in the brain, we hypothesized that rs688 modulates LDLR splicing in neural tissues and associates with AD. To evaluate this hypothesis, we first transfected LDLR minigenes into SH-SY5Y neuroblastoma cells and found that the rs688T allele reduces exon 12 inclusion in this neural model. We then evaluated the association of rs688 allele with exon 12 splicing efficiency in vivo by quantifying LDLR splicing in human anterior cingulate tissue obtained at autopsy; the rs688T allele is associated with decreased LDLR exon 12 splicing efficiency in aged males, but not females. Lastly, we evaluated whether rs688 associates with AD by genotyping DNA from 1457 men and 2055 women drawn from three case-control series. The rs688T/T genotype was associated with increased AD odds in males [recessive model, odds ratio (OR) of 1.49, 95% confidence interval (CI) of 1.13-1.97, uncorrected P = 0.005], but not in females. In summary, these studies identify a functional apoE receptor SNP that is associated with AD in a sex-dependent fashion.

Current Bronchodilator Responsiveness Criteria Underestimate Asthma in Older Adults.

BACKGROUND: Asthma is common in older adults and is confirmed by demonstration of variable expiratory air-flow limitations, typically evaluated by spirometric assessment of bronchodilator responsiveness. However, many patients with clinically suspected asthma and documented air-flow obstruction do not exhibit a post-bronchodilator response that meets or exceeds current established guidelines. We investigated if extending the time from bronchodilator administration to assessment of bronchodilator response increases the yield of spirometry for the diagnosis of asthma in older adults. METHODS: This was a cross-sectional study. The subjects were non-smokers, ≥ 60 y old, and with suspected asthma. Subjects were characterized as (1) those with a positive bronchodilator response on the 30-min post-bronchodilator spirometry, (2) those with a positive bronchodilator response on the 60-min post-bronchodilator spirometry, and (3) those without a positive bronchodilator response but with a positive methacholine challenge test. Factors associated with a late response to bronchodilator were evaluated by using bivariate analysis and by multivariate analysis by using a logistic regression model. RESULTS: This study enrolled 165 subjects. Of these, 81 (49.1%) had a positive bronchodilator response on 30-min post-bronchodilator spirometry; 25 (15.2%) had a positive bronchodilator response on the 1-h post-bronchodilator spirometry; and 59 (35.8%) had no positive bronchodilator response but had a positive methacholine challenge test. On multivariable regression analysis, those with a higher baseline percentage of predicted FEV1, higher scores on a standard asthma control test, and wheezing and/or cough after exercise were more likely to either have a late bronchodilator response or no bronchodilator response. CONCLUSIONS: Our study showed that a late positive response to bronchodilator use was more common than previously presumed in older subjects with suspected asthma. Pulmonary function testing laboratories should consider routinely reassessing spirometry at 1 h after bronchodilator use if the earlier assessment did not reveal a significant response.

Predicting asthma in older adults on the basis of clinical history.

BACKGROUND: The diagnosis of asthma is not always straightforward and can be even more challenging in older adults. Asthma is ideally confirmed by demonstration of variable expiratory airflow limitation. However, many patients with asthma do not demonstrate airflow obstruction nor show bronchodilator reversibility. We aimed to investigate predictors for a positive bronchial challenge test with methacholine in older adults being evaluated for asthma. METHODS: This is a diagnostic accuracy study with a cross-sectional design. Participants ≥60 years with suspected asthma and a negative postbronchodilator response on spirometry were included. All participants underwent a methacholine challenge test (MCT). We assessed the value of standard asthma screening questions and additional clinical questions to predict the MCT results. A multivariable logistic regression model was developed to assess the variables independently impacting the odds of a positive MCT result. RESULTS: Our study included 71 participants. The majority were female (n = 52, 73.2%) and the average age was 67.0 years. Those with a positive MCT (n = 55, 77.5%) were more likely to have wheezing or coughing due to allergens (n = 51, 92.7% vs. n = 12, 75.0%; P = 0.004) and difficulty walking several blocks (n = 14, 25.5% vs. n = 1, 6.3%, P = 0.009). After adjustment, having wheezing or coughing due to allergens (OR = 4.2, 95% CI 1.7-7.8, P = 0.012) remained the only significant independent predictor of a positive MCT. CONCLUSIONS: In older adults with suspected asthma, questioning about wheezing or coughing due to allergens provides a modest independent value to predict a MCT result in those who previously had a negative postbronchodilator response on spirometry.

Implementing Chief Resident Immersion Training (CRIT) in the Care of Older Adults: Overcoming Barriers and Promoting Facilitators.

The Chief Resident Immersion Training (CRIT) in the Care of Older Adults curriculum was developed at Boston University School of Medicine to improve the care of older adults through an educational intervention. The curriculum targeted chief residents (CRs) because their role as mediators between learners and faculty provides the greatest potential impact for transmitting knowledge. The goals of CRIT are to: (1) provide education on geriatric principles and on teaching/leadership skills, (2) foster interdisciplinary collaboration, and (3) complete an action project. This study demonstrates successful implementation of CRIT at a different academic institution in a rural state. The CRs indicated that their confidence in their ability to apply and teach geriatrics improved after CRIT. In addition, the CRs indicated that CRIT improved their confidence in their overall skills as CRs. The barriers and facilitators to implementation are addressed in order to promote successful adoption of CRIT at other institutions, including those in rural states.

Overcoming barriers to interprofessional education in gerontology: the Interprofessional Curriculum for the Care of Older Adults.

A fragmented workforce consisting of multiple disciplines with varying levels of training and limited ability to work as a team often provides care to older adults. Interprofessional education (IPE) is essential for preparing practitioners for the effective teamwork required for community-based, holistic, person-centered care of the older adults. Despite numerous programs and offerings to advance education and interdisciplinary patient care, there is an unmet need for geriatric IPE, especially as it relates to community-dwelling older adults and caregivers in medically underserved areas. A core group of university faculty from multiple disciplines received funding from the Health Resources and Services Administration Geriatric Workforce Enhancement Program to collaborate with community-based providers from several Area Agencies on Aging in the creation and implementation of the Interprofessional Curriculum for the Care of Older Adults (iCCOA). This geriatric curriculum is interprofessional, comprehensive, and community-based. Learners include third-year nursing students, nurse practitioner students, third-year medical students, internal medicine and family medicine residents, master's level social work students, third-year pharmacy students, pharmacy residents, third-year dental students, dental hygiene students, community-based organization professionals, practicing community organizers, and community health navigators. This article describes the efforts, successes, and challenges experienced with this endeavor, including securing funding, ensuring equal representation of the disciplines, adding new components to already crowded curricula, building curriculum on best practices, improving faculty expertise in IPE, managing logistics, and ensuring comprehensive evaluation. The results summarize the iCCOA components, as well as the interprofessional domains, knowledge, and competencies.

The Older Adult with Diabetes and The Busy Clinicians.

Busy primary care providers are in the frontline and see the bulk of older adults with diabetes. This vulnerable population is more prone to diabetic complications and hypoglycemia. In contrast to the younger patients with diabetes, lifestyle interventions are even more effective in older adults while the target A1c levels may need to be more relaxed for frail individuals. Geriatric syndromes can adversely affect diabetes care. A team with experts in different fields who understand the needs of older adults is essential for the adequate quality care of the whole individual with diabetes.

Genetic association of low density lipoprotein receptor and Alzheimer's disease.

The low density lipoprotein receptor (LDLR) is an attractive candidate gene for genetic association with Alzheimer's disease (AD) because: (i) the LDLR is an apolipoprotein E (apoE) receptor, alleles of which have been associated with AD, (ii) LDLR resides at chromosome 19p13.3 within a region linked to AD, and (iii) LDLR modulates the homeostasis of cholesterol, which itself appears associated with AD. Therefore, we evaluated whether LDLR haplotypes alter the odds of AD by performing an association study examining three LDLR single nucleotide polymorphisms (SNPs) in 118 AD patients and 133 non-AD subjects. LDLR genotypes were obtained by TaqMan allelic discrimination assays. Although individual LDLR SNPs were not associated with AD, analyses of unambiguous haplotypes suggested the hypothesis that the 211 LDLR haplotype was associated with reduced odds of AD. We then evaluated this hypothesis in a second study cohort, i.e., the Religious Orders Study. These results supported the hypothesis that the 211 LDLR haplotype is associated with reduced odds of AD. Moreover, these data suggested further associations between LDLR variants and AD. Thus, LDLR variants appear significantly associated with AD and merit additional study.

Lack of genetic association of cholesteryl ester transfer protein polymorphisms with late onset Alzheimers disease.

Dysregulation of cholesterol homeostasis may be associated with the pathogenesis of coronary artery disease (CAD) and Alzheimers disease (AD). Recently, several single nucleotide polymorphisms (SNPs) in cholesteryl ester transfer protein (CETP) were associated with altered plasma CETP concentrations, cholesterol concentrations and CAD. Hence, these CETP SNPs represent excellent candidates for evaluating association with AD. To date, one study has evaluated the association between a single CETP SNP and AD. In this study, we examined three CETP SNPs to evaluate the genetic association of CETP with late onset AD on two study cohorts: the Religious Orders Study (ROS) series, including 85 AD and 70 non-AD individuals, and the University of Kentucky (UKY) series, including 78 AD and 84 non-AD individuals. Significant association between CETP genotypes or haplotypes and late onset AD was not detected in these two study cohorts. Moreover, the CETP genotypes and haplotypes were not significantly associated with AD when the populations were stratified for the presence or absence of apolipoprotein E4 (apoE4). In summary, CETP genetic variants were not associated with AD in two series.