Cancer-related cognitive impairment and associated factors in a sample of older male oral-digestive cancer survivors.

OBJECTIVE: This study examines the demographic and clinical variables associated with cancer-related cognitive impairment (CRCI) in a sample of older, male, oral-digestive cancer survivors at VA Medical Centers in Boston and Houston. METHODS: A two-time point, longitudinal design was used, with cognitive assessment conducted at 6 and 18 months post-diagnosis. Using ANCOVA, the cognitive functioning of 88 older adults with head and neck, esophageal, gastric, or colorectal cancers was compared with that of 88 healthy controls. Paired t-tests examined cognitive change over time in the cancer group. Hierarchical linear regression examined variables potentially associated with cognitive impairment at 18 months. RESULTS: Forty-eight percent of cancer patients exhibited cognitive impairment 6 months post-cancer diagnosis, and 40% at 18 months. Cancer survivors were impaired relative to controls on measures of sustained attention, memory, and verbal fluency at 18 months, controlling for age. Older age, low hemoglobin, and cancer-related PTSD were associated with worse cognition at 18 months. CONCLUSIONS: CRCI is more frequent in older adults than reported in studies of younger adults and may be more frequent in men. Potential areas of intervention for CRCI include psychotherapy for cancer-related PTSD, treatment of anemia, and awareness of particularly vulnerable cognitive domains such as sustained attention, memory, and verbal fluency.

Development of a Bereavement Group in a Geriatric Mental Health Clinic for Veterans.

OBJECTIVES: This article describes the development and program evaluation of an 8-session outpatient geriatric mental health clinic bereavement group for United States military veterans who experienced the death of a loved one. METHODS: Group materials were developed based on a review of literature, with a focus on the dual process model of coping with bereavement and complicated grief treatment. Data are presented from 19 veterans who attended at least 4 of the 8 sessions across the five offerings of this group between 2013 and 2015. RESULTS: Self-report measures of complicated grief and depressive symptoms decreased significantly from the first to the final session. Veterans indicated that the group met their treatment goals and that they would recommend it to others. Adaptations made to the group over time based on feedback from members and facilitators are discussed. CONCLUSIONS: Preliminary evidence suggests that the group described in this manuscript is effective for bereaved older, male veterans. Future research would be helpful including larger samples and controlled studies. CLINICAL IMPLICATIONS: Most bereaved individuals do not require formal mental health treatment. However, for individuals with distressing symptoms, time-limited group therapy may be an effective treatment.

Program Evaluation of Group-based Cognitive Behavioral Therapy for Insomnia: a Focus on Treatment Adherence and Outcomes in Older Adults with Co-morbidities.

OBJECTIVE: To describe a program evaluation of the interrelationship of adherence and treatment outcomes in a sample of veteran older adults with co-morbidities who participated in group-based cognitive behavioral therapy for insomnia. METHODS: Retrospective data extraction was performed for 14 older adults. Adherence measures and sleep outcomes were measured with sleep diaries and Insomnia Severity Index. Demographic and clinical information was extracted through chart review. RESULTS: Adherence with prescribed time in bed, daily sleep diaries, and maintaining consistent time out of bed and time in bed was generally high. There were moderate, though not significant, improvements in consistency of time in bed and time out of bed over time. Adherence was not significantly associated with sleep outcomes despite improvements in most sleep outcomes. CONCLUSIONS: The non-significant relationship between sleep outcomes and adherence may reflect the moderating influence of co-morbidities or may suggest a threshold effect beyond which stricter adherence has a limited impact on outcomes. CLINICAL IMPLICATIONS: Development of multi-method adherence measures across all treatment components will be important to understand the influence of adherence on treatment outcomes as monitoring adherence to time in bed and time out of bed had limited utility for understanding treatment outcomes in our sample.

Valued life abilities among veteran cancer survivors.

BACKGROUND: When patients have multiple chronic illnesses, it is not feasible to provide disease-based care when treatments for one condition adversely affect another. Instead, health-care delivery requires a broader person-centred treatment plan based on collaborative, patient-oriented values and goals. OBJECTIVE: We examined the individual variability, thematic content, and sociodemographic correlates of valued life abilities and activities among multimorbid veterans diagnosed with life-altering cancer. SETTING AND PARTICIPANTS: Participants were 144 veterans in the 'Vet-Cares' study who completed a health-care values and goals scale 12 months after diagnosis of head and neck, gastro-oesophageal, or colorectal cancer. They had mean age of 65 years and one quarter identified as Hispanic and/or African American. DESIGN: At twelve months post-diagnosis, participants rated 16 life abilities/activities in their importance to quality of life on a 10-point Likert scale, during an in-person interview. Scale themes were validated via exploratory factor analysis and examining associations with sociodemographic variables. RESULTS: Participants rated most life abilities/activities as extremely important. Variability in responses was sufficient to identify three underlying values themes in exploratory factor analysis: self-sufficiency, enjoyment/comfort, and connection to family, friends and spirituality. Veterans with a spouse/partner rated self-sufficiency as less important. African American veterans rated connection as more important than did White veterans. CONCLUSIONS: It is feasible yet challenging to ask older, multimorbid patients to rate relative importance of values associated with life abilities/activities. Themes related to self-sufficiency, enjoyment/comfort in daily life and connection are salient and logically consistent with sociodemographic traits. Future studies should explore their role in goal-directed health care.

Positive Affect and Social Anxiety Across the Lifespan: An Investigation of Age as a Moderator.

Recent literature has supported a moderate, inverse relationship between social anxiety and positive affect. It has been proposed, but not clearly established, that the inverse relationship between the constructs may be stronger in younger adults than in adults who are older. We tested this hypothesis in two archival data sets of community participants. The expected age-related interaction was not found in Study 1, which used a measure capturing a conflation of valence and arousal known as activated positive affect. Conversely, the interaction was present in Study 2, in which the positive affect measure was primarily based on valence. We found only partial support for the hypothesis, and results highlight the need for a more comprehensive measure of positive affect.

Cancer-related PTSD symptoms in a veteran sample: association with age, combat PTSD, and quality of life.

OBJECTIVE: The diagnosis and treatment of cancer is a potentially traumatic experience that may evoke posttraumatic stress symptoms (PTSS) among survivors. This paper describes the rates of endorsement of cancer-related PTSS along with the relationship of demographic, cancer, and combat variables on PTSS and quality of life. METHODS: Veterans (N = 166) with head and neck, esophageal, gastric, or colorectal cancers were recruited through tumor registries at two regional Veterans Administration Medical Centers. Standardized scales were used to assess self-report of PTSS, combat, and quality of life. RESULTS: Most participants (86%) reported experiencing at least some cancer-related PTSS; 10% scored above a clinical cutoff for probable PTSD. In linear regressions, younger age and current combat PTSS were associated with cancer-related PTSS, whereas disease and treatment characteristics were not; in turn, cancer-related PTSS were negatively associated with physical and social quality of life. CONCLUSIONS: Individual characteristics and psychosocial factors may play a larger role than disease-related variables in determining how an individual responds to the stress of cancer diagnosis and treatment. Given the rates of reported cancer-related PTSS in this sample, and other non-veteran samples, clinicians should consider screening these following diagnosis and treatment, particularly in younger adults and those with previous trauma histories.

Cancer as a Criterion A Traumatic Stressor for Veterans: Prevalence and Correlates.

The diagnosis of cancer is an uncontrollable stressor posing the threat of death and disfigurement, often followed by repeated exposure to aversive reminders in the form of noxious treatments, persisting side effects, reengagement at times of surveillance, and the threat of recurrence. The phenomenon of cancer as a traumatic stressor is explored in this study, with a focus on the prevalence and correlates of posttraumatic stress disorder (PTSD) Criterion A in a sample of 170 mostly male adults who received health care at VA Medical Centers in Boston or Houston. Participants were interviewed 6 months after diagnosis with head and neck, gastro-esophageal, or colorectal cancers. Approximately half-42.9% to 65.9% depending on cut-score used-perceived cancer to be a traumatic stressor involving actual/threatened death or injury or threat to physical integrity as well as fear, helplessness, or horror. Younger veterans and those with current combat PTSD symptoms were more likely to perceive cancer as a traumatic stressor, as were those who perceived their prognosis as uncertain; 12% had PTSD symptoms above a PCLC cut score of 50, which is similar to incidence rates of PTSD associated with other traumatic stressors. Cancer, therefore, appears to be a serious and for some, traumatic stressor, suggesting the importance of screening for cancer related PTSD in cancer survivors, particularly those most at risk.

Differential binding of Escherichia coli McrA protein to DNA sequences that contain the dinucleotide m5CpG.

The Escherichia coli McrA protein, a putative C(5)-methylcytosine/C(5)-hydroxyl methylcytosine-specific nuclease, binds DNA with symmetrically methylated HpaII sequences (Cm5CGG), but its precise recognition sequence remains undefined. To determine McrA's binding specificity, we cloned and expressed recombinant McrA with a C-terminal StrepII tag (rMcrA-S) to facilitate protein purification and affinity capture of human DNA fragments with m5C residues. Sequence analysis of a subset of these fragments and electrophoretic mobility shift assays with model methylated and unmethylated oligonucleotides suggest that N(Y > R) m5CGR is the canonical binding site for rMcrA-S. In addition to binding HpaII-methylated double-stranded DNA, rMcrA-S binds DNA containing a single, hemimethylated HpaII site; however, it does not bind if A, C, T or U is placed across from the m5C residue, but does if I is opposite the m5C. These results provide the first systematic analysis of McrA's in vitro binding specificity.

Cloning, purification and initial characterization of E. coli McrA, a putative 5-methylcytosine-specific nuclease.

Expression strains of Escherichia coli BL21(DE3) overproducing the E. coli m(5)C McrA restriction protein were produced by cloning the mcrA coding sequence behind a T7 promoter. The recombinant mcrA minus BL21(DE3) host produces active McrA as evidenced by its acquired ability to selectively restrict the growth of T7 phage containing DNA methylated in vitro by HpaII methylase. The mcrA coding region contains several non-optimal E. coli triplets. Addition of the pACYC-RIL tRNA encoding plasmid to the BL21(DE3) host increased the yield of recombinant McrA (rMcrA) upon induction about 5- to 10-fold. McrA protein expressed at 37 degrees C is insoluble but a significant fraction is recovered as soluble protein after autoinduction at 20 degrees C. rMcrA protein, which is predicted to contain a Cys(4)-Zn(2+) finger and a catalytically important histidine triad in its putative nuclease domain, binds to several metal chelate resins without addition of a poly-histidine affinity tag. This feature was used to develop an efficient protocol for the rapid purification of nearly homogeneous rMcrA. The native protein is a dimer with a high alpha-helical content as measured by circular dichroism analysis. Under all conditions tested purified rMcrA does not have measurable nuclease activity on HpaII methylated (Cm(5)CGG) DNA, although the purified protein does specifically bind HpaII methylated DNA. These results have implications for understanding the in vivo activity of McrA in "restricting" m(5)C-containing DNA and suggest that rMcrA may have utility as a reagent for affinity purification of DNA fragments containing m(5)C residues.