Relationship of Cognitive and Social Engagement to Health and Psychological Outcomes in Community-Dwelling Older Adults.

BACKGROUND: Cognitive and social engagement is an important yet underdocumented aspect of older adult engagement and function. OBJECTIVE: The purpose of this study was to examine relationships between cognitive and social engagement and health and psychological outcomes in a cohort of community-dwelling older adults aged approximately 55-70 years. METHODS: Analysis of data from the Wisconsin Registry for Alzheimer's Prevention, a multiwave cohort study with 1,582 participants, using a 1:1 prospective case-control design to examine whether lower cognitive and social engagement at Visit 4 (baseline) is associated with worse health and psychological outcomes at Visit 5 (2 years after Visit 4). Wisconsin Registry for Alzheimer's Prevention participants were included in this study if they had complete data on cognitive and social engagement and self-rated health at both visits. RESULTS: After matching potential covariates using propensity scores, participants with low cognitive and social engagement (cases) at baseline continued to have significantly lower cognitive and social engagement than the controls (participants with high cognitive and social engagement at baseline) at Visit 5, and they had lower self-rated health and higher surgery rate. Depressive symptoms, cognitive status, and hospitalization at Visit 5 did not significantly differ between cases and controls. DISCUSSION: This study provides evidence supporting cognitive and social engagement as an important marker of early decline in activity engagement that may indicate a potential later decline in functional, psychological, and health outcomes.

Palbociclib and letrozole in hormone-receptor positive advanced breast cancer: Predictive response and prognostic factors.

CDK 4/6 inhibitors have been yielding propitious results when with hormone therapy in the management of Her2-negative and hormone-receptor (HR)-positive metastatic breast cancer, palbociclib being one of the first molecules investigated in this setting. However, the response to CDK4/6 inhibitors is variable. To identify predictive and prognostic factors of response to this therapeutic regimen. Eligible patients were females with HR+ and Her2- advanced breast cancer, receiving Palbociclib in combination with Letrozole. PFS was the primary endpoint in the evaluation of response to treatment. This survival was then further segregated according to various characteristics: histological (type, grade, hormone receptors), metastatic site, line of treatment, response type at initial assessment, and best response achieved. The data was then processed by two statistical analysis models: Kaplan-Meier and univariate preceding multivariate Cox proportional risks. Sixty patients were included and followed for a median follow-up duration of 15.98 months. PFS recorded a median of 19.07 months (95% CI=15.43-22.71). PFS had a median of 12.99 months in the absence of progesterone receptors (vs 20.05 months in the case of positive estrogen and progesterone receptors; P = 0.046), a median of 13.02 months in the presence of liver metastases (vs 22.98 months in the absence of liver metastases; P = 0.007), and 15.94 months in the case of second-line and beyond (vs 22.98 months in the case of first-line; P = 0.033). Regarding the Hazard Ratio of progression, we note age (HR 0.941; P = 0.019), liver metastases (HR 2.751; P = 0.051), response at initial evaluation (HR<1; P < 0.001) and best response (HR<1; P = 0.003). PFS reached similar figures to those of international studies. The absence of progesterone receptors, presence of liver metastases, and use as second-line or beyond are associated with a reduced median PFS. One year age increase (protective factor), liver metastases (risk factor), response at initial evaluation, and best response achieved are identified as the most predictive factors of the response to this treatment regimen and of the progression risk.

Risk stratifying gastric ulcers: development and validation of a scoring system.

Objective: Debate is ongoing regarding the need for universal endoscopic follow-up to ensure gastric ulcer healing. We aimed to assess the value of follow-up oesophago-gastro-duodenoscopies (OGDs) for gastric ulcer healing and stratify patients according to risk of malignancy by developing a risk score. Design/method: All patients in National Health Service (NHS) Lothian with an index OGD and a diagnosis of gastric ulcer between 1 January 2014 and 31 December 2018 were identified. Data were analysed with logistic regression to identify factors significantly associated with a diagnosis of cancer; a risk score was derived and externally validated. Results: 778 patients were identified and 60.3% (469/778) of patients had a follow-up OGD. 8.6% (66/778) of patients were diagnosed with cancer. No cases of cancer were found on follow-up OGD of a benign appearing ulcer with negative biopsies. Macroscopic suspicion of malignancy was present at index OGD in 100% (3/3) of those diagnosed with cancer on subsequent OGDs. Older age (p=0.014), increased ulcer size (p<0.001) and non-antral location (p=0.030) were significantly associated with malignancy. A risk score (area under the curve (AUC) 0.868, p<0.001, minimum score=0, maximum score=6) was derived from these variables. 78.0% of patients with malignant ulcers scored ≥3, only 15.8% with benign ulcers scored ≥3 (negative predictive value (NPV) 97.4%). External validation yielded an AUC of 0.862 (p<0.001) and NPV of 98.6%; 84.0% of those with malignant ulcers scored ≥3. Conclusion: Ulcers with a combination of macroscopically benign appearances, at least six negative biopsies and a low risk score do not necessarily need endoscopic follow-up.

Age-associated trends of vulvar cancer in the US.

OBJECTIVE: Medical societies have over the years moved away from recommending routine pelvic examinations in older, asymptomatic women above age 65. Consequently, vulvar examination is a largely neglected component of the physical examination, unless sent to a specialist for gynecological evaluation. In recognition of these recommendations, we analyzed US trends in vulvar cancer incidence, age, and stage at diagnosis, survival, and association with human papillomavirus (HPV). METHODS: Cases of vulvar and cervical cancer from 1992 to 2014 were extracted from the National Cancer Institute's Surveillance, Epidemiology, and End Results and Centers for Disease Control's data on age at diagnosis, stage of disease, and HPV-association were analyzed and compared. Incidence and mortality rates were extracted and calculated. RESULTS: From 1992-2014, there was a 14.3% increase in vulvar cancer rates. The absolute average incidence rate was 2.25, with HPV still being seen in vulvar carcinomas in women 65 years and above. Cervical cancer mortality rates declined by 34.2%, while vulvar cancer death rates were unchanged. We show increased intervals for cervical cancer screening is associated with later stage vulvar cancer detection. The proportion of vulvar cancer cases diagnosed in women age <50 steadily decreased, from 42.05% of cases in 1992-1996 to 19.75% of total cases in 2012-2015. Meanwhile, vulvar cancer cases diagnosed in women > 65 yo increased from 36.62% of cases in 1992-1996 to 49.82% of cases in 2012-2015. CONCLUSION: The incidence of vulvar cancer increases with age, with the median age of diagnosis 67 years, with HPV (+) tumors occurring into 70's and 80's. Though medical societies do not routinely recommend an external genital examination in women 65 years and above, we show this is a missed opportunity to improve cancer outcomes in some older females.

Video Summary:http://links.lww.com/MENO/A678.

Vocal pattern detection of depression among older adults.

Depression is a serious problem for many older adults but is too often undetected by the person, family or providers. Although vocal patterns have been successfully used to detect and predict depression in adults aged 18 to 65 years, no studies to date have included older adults. The study purpose was to determine whether vocal patterns associated with clinical depression in younger people also signify depression in older adults. An observational, repeated measures design was used to enroll 46 volunteer older adults who completed a semi-structured interview composed the 9-item Patient Health Questionnaire or PHQ-9 depression scale and selected speech measures. Recorded interviews were analysed by machine learning algorithms to evaluate whether vocal patterns may predict presence of depression in older adults. In this study, using the PHQ-9 and a supervised machine learning algorithm accurately predicted high and low depression scores between 86% and 92% of the time. Change in raw PHQ-9 scores between interview cycles was predicted within 1.17 points. These results provide strong and promising evidence that vocal patterns can be used effectively to detect clinical depression in adults who are 65 years and older.

Speed of processing training and depression in assisted and independent living: A randomized controlled trial.

Late life depression is widely associated with lower quality of life and greater disability, making it an important target for prevention. Earlier randomized controlled trials [RCTs] demonstrated that speed of processing training [SOPT] led to reductions in depressive symptoms and clinical depression in community-dwelling adults. Our purpose was to evaluate depression outcomes related to SOPT among older adults who live in supported senior living settings. This two-arm, parallel RCT included 351 participants aged 55-102 years who resided in assisted and independent settings in 31 senior living communities. Participants were randomized within sites to computerized SOPT vs. computerized crossword puzzles with a targeted dose of 10 hours of playtime at baseline plus 4 hours of booster training at five and eleven months. Depression outcomes included the 9-item Patient Health Questionnaire [PHQ-9] scores, categorical levels, and dichotomous indicators. Random effects linear mixed effect models estimated SOPT effects in intention-to-treat complete case and multiple imputation analyses. Mean age of the sample was 81.0 years, 72.2% were women, and 41.0% resided in assisted living. At baseline 65.7% had no depression [PHQ-9 scores < 5] and 6.6% had clinically meaningful depression [PHQ-9 scores ≥ 10]. At 12 months we found significantly increased PHQ-9 scores [p = 0.006] and categorical levels [p = 0.003], and higher percentages of PHQ-2 scores > 3 [p = 0.016] and major depressive syndrome [p = 0.045] among the assisted living SOPT group. No significant change in depression was observed in the independent living SOPT or attention control groups. In summary, the SOPT known as Road Tour/Double Decision significantly increased, rather than decreased, the burden of depressive symptoms among participants residing in assisted living. Given these risks, this SOPT program should be avoided among older people in assisted living settings, and other SOPT interventions should be combined with systematic depression monitoring.

Speed-of-Processing Training in Assisted and Independent Living: A Randomized Controlled Trial.

OBJECTIVES: To examine speed-of-processing training (SOPT) in older adults in senior living communities, especially those in assisted living. DESIGN: Two-arm, parallel, randomized controlled trial. SETTING: Assisted and independent residence settings in 31 senior living communities. PARTICIPANTS: Individuals aged 55 to 102 (mean 81.0, 73.8% female, 76.4% living alone, 47.0% residing in assisted living; N=351). INTERVENTION: The intervention was 10 hours of computerized SOPT at baseline with 4-hour boosters at 5 and 11 months; the attention control was 10 hours of solving computerized crossword puzzles at baseline with 4-hour boosters at 5 and 11 months. MEASURES: Outcomes were useful field of view (UFOV) scores and improvements of 0.5 standard deviations (SDs) or more (> 158.4 ms). Data collection occurred at baseline, after training, and 6 and 12 months. Random-effects linear mixed-effect models were used to estimate SOPT effects in intention-to-treat complete-case and multiple imputation analyses. RESULTS: We found statistically significantly small standardized effect sizes (Cohen's ds 0.25-0.40) for SOPT, reflecting processing speed improvements on UFOV scores (of 39-63 ms) and greater percentages (9.8 to 14.9 percentage point advantages) for achieving more than 0.5 SD improvements (> 158.4 ms) over the 3 time periods. CONCLUSION: These findings support public health messaging about the potential benefits of SOPT for older adults in senior living communities and support the feasibility and acceptability of SOPT in assisted and independent living for older adults.

Nonmammalian Models of Huntington's Disease.

Flies, worms, yeast and more recently zebra fish have all been engineered to express expanded polyglutamine repeat versions of Huntingtin with various resulting pathologies including early death, neurodegeneration, and loss of motor function. Each of these models present particular features that make it useful in studying the mechanisms of polyglutamine pathology. However, one particular unbiased readout of mHTT pathology is functional loss of motor control. Loss of motor control is prominent in patients, but it remains unresolved whether pathogenic symptoms in patients result from overt degeneration and loss of neurons or from malfunctioning of surviving neurons as the pathogenic insult builds up. This is why a functional assay such as motor control can be uniquely powerful in revealing early as well as late neurological deficits and does not rely on assumptions such as that the level of inclusions or the degree of neuronal loss can be equated with the level of pathology. Drosophila is well suited for such assays because it contains a functioning nervous system with many parallels to the human condition. In addition, the ability to readily express mHTT transgenes in different tissues and subsets of neurons allows one the possibility of isolating a particular effect to a subset of neurons where one can correlate subcellular events in response to mHTT challenge with pathology at both the cellular and organismal levels. Here we describe methods to monitor the degree of motor function disruption in Drosophila models of HD and we include a brief summary of other nonmammalian models of HD and discussion of their unique strengths.

Computerized Cognitive Training to Improve Mood in Senior Living Settings: Design of a Randomized Controlled Trial.

PURPOSE: This two-arm, randomized controlled trial was designed to evaluate a computerized cognitive speed of processing (SOP) training known as Road Tour in the generally older group of adults residing in assisted living (AL) and related senior housing. Study aims focused on depression-related outcomes that were observed in earlier SOP studies using Road Tour with younger, home-dwelling seniors. Study design and baseline outcomes are discussed. PARTICIPANTS AND METHODS: A community-based design engaged AL and related senior living settings as partners in research. Selected staff served as on-site research assistants who were trained to recruit, consent, and train a target of 300 participants from AL and independent living (IL) programs to use the intervention and attention-control computerized training. Ten hours of initial computerized training was followed by two booster sessions at 5 and 11 months. Outcome measures included Useful Field of View (UFOV), 9-item Patient Health Questionnaire (PHQ-9), 12-item Centers for Epidemiological Studies Depression scale (CESD-12), 7-item Generalized Anxiety Disorders GAD-7), Brief Pain Inventory (BPI) and SF-36 Health Survey. Assessments occurred before randomization (pre-training), post-training, 26 and 52 weeks. RESULTS: A total of 351 participants were randomized to the intervention (n=173) and attention-control (n=178) groups. There were no significant differences between groups in demographic characteristics with the exception of education and reported osteoporosis. There were no significant differences in study outcomes between groups at baseline. Participants in AL had significantly lower SOP and self-rated health, and significantly higher depression, anxiety and pain when compared to those in IL programs on the same campus. CONCLUSIONS: Compared to earlier SOP training studies using Road Tour, this sample of senior living participants were older, reported more health conditions and poorer overall health, had lower UFOV scores and greater depressive symptoms at baseline. Moreover, participants in AL had greater health challenges than those in IL.

Impact of programs to reduce antipsychotic and anticholinergic use in nursing homes.

INTRODUCTION: Antipsychotics are used for managing behavioral and psychological symptoms of dementia (BPSD) but have risks. Anticholinergics can worsen outcomes in dementia. The Improving Antipsychotic Appropriateness in Dementia Patients educational program (IA-ADAPT) and Centers for Medicare and Medicaid Services Partnership to Improve Dementia Care (CMS Partnership) promote improved care for BPSD. The purpose of this study was to evaluate the impact of these programs on medication use and BPSD among nursing home residents. METHODS: This quasi-experimental longitudinal study used Medicare and assessment data for Iowa nursing home residents from April 2011 to December 2012. Residents were required to be eligible for six continuous months for inclusion. Antipsychotic use and anticholinergic use were evaluated on a monthly basis, and changes in BPSD were tracked using assessment data. Results are presented as odds ratios (ORs) per month after exposure to the IA-ADAPT or the start of the CMS Partnership. RESULTS: Of 426 eligible Iowa nursing homes, 114 were exposed to the IA-ADAPT in 2012. Nursing home exposure to the IA-ADAPT was associated with reduced antipsychotic use (OR [95% CI] = 0.92 [0.89-0.95]) and anticholinergic use (OR [95% CI] = 0.95 [0.92-0.98]), reduced use of excessive antipsychotic doses per CMS guidance (OR [95% CI] = 0.80 [0.75-0.86]), increased odds of a potentially appropriate indication among antipsychotic users (OR [95% CI] = 1.04 [1.00-1.09]), and decreased documentation of verbal aggression (OR [95% CI] = 0.96 [0.94-0.99]). Facilities with two or more IA-ADAPT exposures had greater reductions in antipsychotic and anticholinergic use than those with only one. The CMS Partnership was associated with reduced antipsychotic use (OR [95% CI] = 0.96 [0.94-0.98]) and decreased documentation of any measured BPSD (OR [95% CI] = 0.98 [0.97-0.99]) as well as delirium specifically (OR [95% CI] = 0.98 [0.96-0.99]). DISCUSSION: This study suggests that the IA-ADAPT and the CMS Partnership improved medication use with no adverse impact on BPSD.

The Characteristics of Pain in Patients Diagnosed with Depression and Heart Failure.

Heart failure (HF) is a costly and growing health problem that is routinely complicated by chronic pain and depression. The purpose of this paper is to describe the characteristics of pain and pain management in depressed HF patients. In this descriptive cross-sectional study, we analyzed data from 62 participants with depression and class II-IV HF. Study variables of interest were collected from the Brief Pain Inventory, Beck Depression Inventory, and Rand-36. Almost all participants (98%) had some pain in the past month and most had pain in the last 24 hours (66%). The median pain score was 4 (0-10 scale) with the majority reporting moderate to severe pain. The median pain interference score was 4.42 (0-10 scale) with the majority reporting moderate to extreme interference. Medication to treat pain was used by all participants who reported pain, with only 5% also using nonpharmacologic treatment. The majority of participants reported moderate or severe pain while also having moderate to extreme pain interference. Nonpharmacologic pain treatments were severely underused. Women were more likely to have higher levels of pain intensity and more pain interference than men, suggesting that additional screening for the impact of pain is especially important in women. The wide variety of body areas affected, along with moderate to high intensity pain and considerable interference scores reported, indicate that pain was ineffectively treated. Nonpharmacologic treatments should be considered to decrease the impact of pain.

The Relationships Among Pain, Depression, and Physical Activity in Patients With Heart Failure.

INTRODUCTION: Increasing patients' physical activity levels holds many opportunities to facilitate health and well-being among those with heart failure (HF) by improving HF symptoms and decreasing depression and pain. Given low exercise participation rates, an essential first step to increase exercise rates is to evaluate how pain and depression may further influence engagement in exercise programs. AIMS: The aims of this study were to describe the level of physical activity and exercise that patients with HF with depression achieve and to investigate the relationships among pain, depression, total activity time, and sitting time. METHODS: In this correlational cross-sectional study, we analyzed data from 61 participants with depression and New York Heart Association class II to IV HF. RESULTS AND CONCLUSIONS: The total time spent being active was less than 1 hour per day. Depressed patients with HF have much lower physical activity levels than the general public. Decreasing sitting time and increasing light activity levels hold promise to improve pain and depression symptoms.

Cardiorespiratory Fitness in Internal Medicine Residents: Are Future Physicians Becoming Deconditioned?

BACKGROUND: Previous studies have shown a falloff in physicians' physical activity from medical school to residency. Poor fitness may result in stress, increase resident burnout, and contribute to mortality from cardiovascular disease and other causes. Physicians with poor exercise habits are also less likely to counsel patients about exercise. Prior studies have reported resident physical activity but not cardiorespiratory fitness age. OBJECTIVE: The study was conducted in 2 residency programs (3 hospitals) to assess internal medicine residents' exercise habits as well as their cardiorespiratory fitness age. METHODS: Data regarding physical fitness levels and exercise habits were collected in an anonymous cross-sectional survey. Cardiopulmonary fitness age was determined using fitness calculator based on the Nord-Trøndelag Health Study (HUNT). RESULTS: Of 199 eligible physicians, 125 (63%) responded to the survey. Of respondents, 11 (9%) reported never having exercised prior to residency and 45 (36%) reported not exercising during residency (P < .001). In addition, 42 (34%) reported exercising every day prior to residency, while only 5 (4%) reported exercising daily during residency (P < .001), with 99 (79%) participants indicating residency obligations as their main barrier to exercise. We found residents' calculated mean fitness age to be 5.6 years higher than their mean chronological age (P < .001). CONCLUSIONS: Internal medicine residents reported significant decreases in physical activity and fitness. Residents attributed time constraints due to training as a key barrier to physical activity.

Evaluation of an innovative late-life depression training program.

PURPOSE: This paper describes evaluation findings associated with an innovative, CD-based, self-directed training program that was designed to improve general practice nurses' abilities to identify and care for older adults with depression. DESIGN AND METHODS: A voluntary sample of nurses completed an evaluation that focused on participants' perceptions of changes in their knowledge and skills and usefulness of the program. FINDINGS: Quantitative items received high ratings, and narrative responses to open-ended questions were largely positive. PRACTICE IMPLICATIONS: Many opportunities exist for psychiatric nurses to facilitate, support, and extend training principles to promote late-life depression recognition and treatment.

A potent and selective Sirtuin 1 inhibitor alleviates pathology in multiple animal and cell models of Huntington's disease.

Protein acetylation, which is central to transcriptional control as well as other cellular processes, is disrupted in Huntington's disease (HD). Treatments that restore global acetylation levels, such as inhibiting histone deacetylases (HDACs), are effective in suppressing HD pathology in model organisms. However, agents that selectively target the disease-relevant HDACs have not been available. SirT1 (Sir2 in Drosophila melanogaster) deacetylates histones and other proteins including transcription factors. Genetically reducing, but not eliminating, Sir2 has been shown to suppress HD pathology in model organisms. To date, small molecule inhibitors of sirtuins have exhibited low potency and unattractive pharmacological and biopharmaceutical properties. Here, we show that highly selective pharmacological inhibition of Drosophila Sir2 and mammalian SirT1 using the novel inhibitor selisistat (selisistat; 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide) can suppress HD pathology caused by mutant huntingtin exon 1 fragments in Drosophila, mammalian cells and mice. We have validated Sir2 as the in vivo target of selisistat by showing that genetic elimination of Sir2 eradicates the effect of this inhibitor in Drosophila. The specificity of selisistat is shown by its effect on recombinant sirtuins in mammalian cells. Reduction of HD pathology by selisistat in Drosophila, mammalian cells and mouse models of HD suggests that this inhibitor has potential as an effective therapeutic treatment for human disease and may also serve as a tool to better understand the downstream pathways of SirT1/Sir2 that may be critical for HD.

Morphometric analysis of Huntington's disease neurodegeneration in Drosophila.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. The HD gene encodes the huntingtin protein (HTT) that contains polyglutamine tracts of variable length. Expansions of the CAG repeat near the amino terminus to encode 40 or more glutamines (polyQ) lead to disease. At least eight other expanded polyQ diseases have been described. HD can be faithfully modeled in Drosophila with the key features of the disease such as late onset, slowly progressing degeneration, formation of abnormal protein aggregates and the dependence on polyQ length being evident. Such invertebrate model organisms provide powerful platforms to explore neurodegenerative mechanisms and to productively speed the identification of targets and agents that are likely to be effective at treating diseases in humans. Here we describe an optical pseudopupil method that can be readily quantified to provide a fast and sensitive assay for assessing the degree of HD neurodegeneration in vivo. We discuss detailed crossing schemes as well as factors including different drivers, various constructs, the number of UAS sites, genetic background, and temperature that can influence the result of pseudopupil measurements.

Improving antipsychotic agent use in nursing homes: development of an algorithm for treating problem behaviors in dementia.

Many issues related to safety and quality care emerge from reports that nearly one in three nursing home residents is treated with antipsychotic medication, a rate that exceeds levels that led to nursing home reform more than 2 decades ago. Atypical antipsychotic medications have become the mainstay of treatment for behavioral problems among residents with dementia, despite federal "black box" warnings about health risks and research demonstrating their limited effectiveness. The purpose of this article is to briefly describe a dissemination research project designed to increase appropriate antipsychotic prescribing for older adults with dementia. A step-wise problem-solving algorithm designed to reduce unnecessary psychotropic medication use is described. Formative evaluation results provided by nursing home personnel are reviewed. Discussion focuses on nursing home culture as an important influence on the adoption of evidence-based practices and changes needed to promote use of behavioral interventions in dementia care and reduction of reliance on antipsychotic medications.

Depression training in nursing homes: lessons learned from a pilot study.

Late-life depression is common among nursing home residents, but often is not addressed by nurses. Using a self-directed CD-based depression training program, this pilot study used mixed methods to assess feasibility issues, determine nurse perceptions of training, and evaluate depression-related outcomes among residents in usual care and training conditions. Of 58 nurses enrolled, 24 completed the training and gave it high ratings. Outcomes for 50 residents include statistically significant reductions in depression severity over time (p < 0.001) among all groups. Depression training is an important vehicle to improve depression recognition and daily nursing care, but diverse factors must be addressed to assure optimal outcomes.