Patient-Level Factors Associated with Oncology Provider-Delivered Brief Tobacco Treatment Among Recently Diagnosed Cancer Patients.

BACKGROUND: A cancer diagnosis is seen as a "teachable moment" for patients to consider changing their behavioral risk factors, such as smoking. It also offers an opportunity for oncology providers to engage in a dialogue about how they can support patients changing their smoking behaviors. Brief, evidence-based tobacco cessation treatment delivered by oncology providers through the 5As (Ask, Advise, Assess, Assist Arrange) model is recommended, but provision to cancer patients remains suboptimal. AIM: Explore patient-level factors associated with 5As receipt among current smokers with a newly diagnosed cancer. METHOD: A total of 303 patients self-reported whether they received each of the 5As during their most recent oncology care visit. Multivariable regression analyses were conducted to identify patient-level factors associated with 5As receipt. RESULTS: Oncology provider-delivered 5As rates ranged from 81.5% (Ask) to 30.7% (Arrange). 5As receipt was associated with: reporting lower illness-related stigma, diagnosis of a comorbid smoking-related disease, diagnosis of a smoking-related cancer, and diagnosis of a non-advanced cancer. CONCLUSION: Findings support previous literature in which smoking-related diagnoses were associated with greater receipt of 5As; however, disparities in the receipt of 5As existed for patients with more advanced cancer diagnoses and illness-related stigma. Inequities in the provision of quit assistance may further decrease treatment effectiveness and survival expectancy among certain patient populations. These findings are, therefore, important as they identify specific patient-level factors associated with lower 5As receipt among newly diagnosed cancer patients.

Lighten UP! A Community-Based Group Intervention to Promote Eudaimonic Well-Being in Older Adults: A Multi-Site Replication with 6 Month Follow-Up.

Objectives: Eudaimonic well-being (EWB), increasingly recognized as a critical component of health, typically declines in later life, and there are no existing programs to sustain or increase EWB in older adults. Lighten UP! is an 8-week program to promote EWB through facilitated group sessions in community settings and at-home practice. Building on earlier pilot research, the current study assessed the effect of the Lighten UP! Program using a longitudinal, multi-site design. Methods: Men and women (N = 169) aged 60 and over were recruited from three Wisconsin communities. EWB, life satisfaction, depression, and diverse aspects of health were assessed before and after the program and at 6-month follow up. Results: Participants reported significantly increased EWB; these changes were maintained 6 months later. The specific EWB domains of self-acceptance, positive relations, and personal growth showed the most robust gains. Participants also showed significant and sustained declines in depressive symptoms, anxiety, and hostility. Conclusions: Lighten UP! Program confirmed its positive effects for enhancing EWB in older adults living in multiple community settings. Clinical Implications: Programs that sustain or enhance EWB in older adults can be expected to yield improvements in diverse aspects of mental and physical health.

Companion animals and human health: benefits, challenges, and the road ahead for human-animal interaction.

There is ample evidence that human-animal interaction (HAI) is associated with health. Studies encompass three general categories: those that compare companion animal owners with individuals who do not own companion animals, those examining brief, 'one-off' contacts with animals, and those that review animal-assisted interventions. The health benefits demonstrated typically include reductions in depression and loneliness, while enhancing social interaction or social skills, and decreasing anxiety and arousal. Other health benefits associated with companion animals include the promotion of exercise or physical activity. The types of human-animal contact that have been evaluated include visual contact, physical contact, and looking at images of animals. The species used in interventions include dogs, cats, horses, rabbits, goats, hamsters and crickets. Despite these benefits, HAIs are also associated with problems, including allergies, asthma, zoonoses, animal bites and scratches, and human falls. Other problems include grief and negative emotions when a companion animal is injured or dies. Companion animal ownership is also expensive. Inconsistent policies concerning keeping animals in housing and enabling service animals to access public places make it difficult to live with companion animals or keep service animals in some circumstances. Additional research is needed to provide an evidence base to evaluate the efficacy of particular types of HAI using a given type of animal. This will document specific outcomes for an individual with certain characteristics and assist in promoting the future use of HAI to enhance human and animal health and well-being.

L'existence d'un lien entre la santé, d'une part, et l'interaction humains­animaux d'autre part, est amplement démontrée. Les études en la matière se répartissent en trois catégories principales : comparaisons entre la situation de propriétaires d'animaux de compagnie et celle d'individus ne possédant pas d'animal de compagnie ; études sur des contacts brefs et ponctuels avec des animaux ; études analysant les interventions thérapeutiques recourant à des animaux. Parmi les bénéfices pour la santé mis en évidence dans ces études figurent l'atténuation des états dépressifs et du sentiment de solitude, une meilleure interaction sociale, un renforcement des compétences sociales et une diminution des états d'anxiété et d'agitation. Les animaux de compagnie encouragent à avoir une activité physique, ce qui est un facteur bénéfique pour la santé. Les contacts humains­animaux étudiés sont le contact visuel, le contact physique et la contemplation d'images d'animaux. Les espèces suivantes sont utilisées à des fins thérapeutiques : chiens, chats, chevaux, lapins, chèvres, hamsters et grillons. En dépit de ces avantages, les interactions humains­animaux peuvent aussi provoquer certains problèmes tels qu'allergies, asthme, maladies zoonotiques, blessures dues à des morsures et griffures et chutes. Il y a aussi le chagrin et les émotions négatives qui peuvent s'emparer d'une personne en cas de blessures ou de mort de son animal de compagnie. La possession d'un animal de compagnie entraîne des coûts. L'incohérence des réglementations sur la présence d'animaux dans les logements et sur l'accès des animaux aidants dans les espaces publics rend parfois difficile la vie avec des animaux de compagnie ou le recours aux animaux aidants. Il convient de poursuivre les recherches afin de pouvoir évaluer l'efficacité de certaines catégories d'interactions humains­animaux suivant le type d'animal utilisé. Cela permettra de connaître les résultats spécifiques que l'on peut attendre chez un individu présentant des caractéristiques particulières et contribuera à promouvoir l'utilisation future d'interactions humains­animaux pour améliorer la santé et le bien-être humain et animal.

Existen abundantes pruebas de que la interacción de humanos y animales reporta salud. Los estudios realizados corresponden a tres grandes categorías: aquellos que comparan a las personas que tienen una mascota con las que no tienen; aquellos que estudian contactos breves y excepcionales con animales; y aquellos que se centran en las intervenciones auxiliadas por animales. Los beneficios para la salud más comúnmente observados y probados son un menor grado de depresión y sentimiento de soledad, acompañado de una mejora de las relaciones y aptitudes sociales, así como menores niveles de ansiedad y agitación. Entre otros beneficios para la salud asociados a la presencia de animales de compañía destaca el incremento del ejercicio físico. Los tipos de contacto entre humanos y animales que se han evaluado son el contacto visual, el contacto físico y la visión de imágenes de animales. Las especies utilizadas en las intervenciones son principalmente el perro, el gato, el caballo, el conejo, la cabra, el hámster y el grillo. Pese a todos los beneficios que deparan, las relaciones entre humanos y animales también pueden provocar problemas como alergias, asma, zoonosis, mordeduras y arañazos de animal o caídas de las personas. Asimismo, a veces surgen dificultades como el duelo o las emociones negativas que acompañan las lesiones o la muerte de una mascota. Además, la propiedad de un animal de compañía resulta cara. En algunas circunstancias, la aplicación de políticas incoherentes sobre el hecho de tener animales en las viviendas o de permitir el acceso de animales de servicio a lugares públicos dificulta la vida con mascotas o la posesión de animales de servicio. Para evaluar la eficacia de ciertas clases particulares de relación entre humanos y animales con el uso de un determinado tipo de animal se requieren más investigaciones que aporten una sólida base probatoria. Con ello será posible demostrar la obtención de resultados específicos con una persona de determinadas características y promover en el futuro la utilización de la relación entre humanos y animales para procurar a ambas partes mayores cotas de salud y bienestar.

CK2 regulates 5-HT4 receptor signaling and modulates depressive-like behavior.

The serotonergic neurotransmitter system has been widely implicated in the pathophysiology of mood-related disorders such as anxiety and major depressive disorder (MDD). The onset of therapeutic efficacy of traditional antidepressants is delayed by several weeks. The 5-HT4 receptor has emerged as a new therapeutic target since agonists of this receptor induce rapid antidepressant-like responses in rodents. Here we show that the 5-HT4 receptor is regulated by CK2, at transcriptional and post-transcriptional levels. We present evidence, in two different CK2α knockout mouse lines, that this regulation is region-specific, with the 5-HT4 receptor upregulated in prefrontal cortex (PFC) but not striatum or hippocampus where CK2α is also ablated. 5-HT4 receptor signaling is enhanced in vitro, as evidenced by enhanced cAMP production or receptor plasma membrane localization in the presence of CK2 inhibitor or shRNA targeting CK2α. In vivo, 5-HT4 receptor signaling is also upregulated since ERK activation is elevated and sensitive to the inverse agonist, GR113808 in the PFC of CK2α KO mice. Behaviorally, KO mice as well as mice with AAV-mediated deletion of CK2α in the PFC show a robust 'anti-depressed-like' phenotype and display an enhanced response to antidepressant treatment when tested in paradigms for mood and anxiety. Importantly, it is sufficient to overexpress the 5-HT4 receptor in the mPFC to generate mice with a similar 'anti-depressed-like' phenotype. Our findings identify the mPFC as the region that mediates the effect of enhanced 5-HT4 receptor activity and CK2 as modulator of 5-HT4 receptor levels in this brain region that regulates mood-related phenotypes.

Oncotype-DX recurrence score distribution in breast cancer patients with BRCA1/2 mutations.

Oncotype-DX assay has never been validated for BRCA mutation carriers. This study compares the recurrence score (RS) distribution in BRCA-positive breast cancer patients with that of a general population (GP) of patients and reports their outcomes. Eligible patients were BRCA carriers who performed the Oncotype-DX assay. Two sets of databases were cross-linked: BRCA carriers at Rabin Medical Center and Sheba Medical Center with Oncotype-DX tests performed through Clalit Health Services HMO, from 2003 to 2015. Fifty-eight BRCA patients were included (20 BRCA1, 38 BRCA2). The GP included 1020 patients. Compared to the GP, BRCA1 patients were younger, had higher rate of grade three tumors, and higher Ki67. BRCA2 patients had lower PR index, higher rate of grade three tumors, and higher Ki67. Among the GP, 52.9, 37.9, and 9.1 % had low, intermediate, and high risk RS, respectively. Corresponding rates were 15, 35, and 50 % in BRCA1 patients, and 18.4, 52.6, and 29 % in BRCA2 patients. Subgroup analysis revealed a similar RS distribution pattern regardless of the nodal status. Median follow-up was 45 months. Four BRCA patients (7 %) developed disease recurrence. RS of these patients were in the intermediate and low range. All recurrences occurred in chemo-naïve patients who had not undergone bilateral oophorectomy. This study revealed significantly different RS distributions between BRCA patients and the GP. RS values shifted toward high and intermediate risk categories. This pattern held regardless of the nodal status and was more pronounced in the BRCA1 group.

Obesity, but not metabolic syndrome, negatively affects outcome in bipolar disorder.

OBJECTIVE: Examine the effects of obesity and metabolic syndrome on outcome in bipolar disorder. METHOD: The Comparative Effectiveness of a Second Generation Antipsychotic Mood Stabilizer and a Classic Mood Stabilizer for Bipolar Disorder (Bipolar CHOICE) study randomized 482 participants with bipolar disorder in a 6-month trial comparing lithium- and quetiapine-based treatment. Baseline variables were compared between groups with and without obesity, with and without abdominal obesity, and with and without metabolic syndrome respectively. The effects of baseline obesity, abdominal obesity, and metabolic syndrome on outcomes were examined using mixed effects linear regression models. RESULTS: At baseline, 44.4% of participants had obesity, 48.0% had abdominal obesity, and 27.3% had metabolic syndrome; neither obesity, nor abdominal obesity, nor metabolic syndrome were associated with increased global severity, mood symptoms, or suicidality, or with poorer functioning or life satisfaction. Treatment groups did not differ on prevalence of obesity, abdominal obesity, or metabolic syndrome. By contrast, among the entire cohort, obesity was associated with less global improvement and less improvement in total mood and depressive symptoms, suicidality, functioning, and life satisfaction after 6 months of treatment. Abdominal obesity was associated with similar findings. Metabolic syndrome had no effect on outcome. CONCLUSION: Obesity and abdominal obesity, but not metabolic syndrome, were associated with less improvement after 6 months of lithium- or quetiapine-based treatment.

Text-message reminders increase uptake of routine breast screening appointments: a randomised controlled trial in a hard-to-reach population.

BACKGROUND: There is a need for interventions to promote uptake of breast screening throughout Europe. METHODS: We performed a single-blind randomised controlled trial to test whether text-message reminders were effective. Two thousand two hundred and forty women receiving their first breast screening invitation were included in the study and randomly assigned in a 1 : 1 ratio to receive either a normal invitation only (n=1118) or a normal invitation plus a text-message reminder 48 h before their appointment (n=1122). FINDINGS: In the intention-to-treat analysis, uptake of breast screening was 59.1% among women in the normal invitation group and 64.4% in the text-message reminder group (χ(2)=6.47, odds ratio (OR): 1.26, 95% confidence intervals (CI): 1.05-1.48, P=0.01). Of the 1122 women assigned to the text-message reminder group, only 456 (41%) had a mobile number recorded by their GP and were thereby sent a text. In the per-protocol analysis, uptake by those in the control group who had a mobile number recorded on the GP system was 59.77% and by those in the intervention group who were sent a reminder 71.7% (χ(2)=14.12, OR=1.71, 95% CI=1.29-2.26, P<0.01). INTERPRETATION: Sending women a text-message reminder before their first routine breast screening appointment significantly increased attendance. This information can be used to allocate resources efficiently to improve uptake without exacerbating social inequalities.

Low-level constitutional mosaicism of a de novoBRCA1 gene mutation.

BACKGROUND: Pathogenic BRCA1 mutations are usually inherited. Constitutional low-level BRCA1 mosaicism has never been reported. METHODS: Next-generation sequencing (NGS) of cancer gene panel of germline and tumour DNA in a patient with early onset, triple-negative breast cancer. RESULTS: Constitutional de novo mosaicism (5%) for a pathogenic (c.1953dupG; p.Lys652Glufs*21) BRCA1mutation was detected in leukocytes, buccal tissue and normal breast tissue DNA, with ∼50% mutation in tumorous breast tissue. CONCLUSION: This is the first reported case of low-level, multiple tissue, constitutional mosaicism in BRCA1, and highlights the need to consider deep sequencing in affected individuals clinically suspected of having cancer predisposition whose tumours display a BRCA mutation.

Hormonal treatment before and after artificial insemination differentially improves fertility in subpopulations of dairy cows during the summer and autumn.

Reduced conception rate (CR) during the hot summer and subsequent autumn is a well-documented phenomenon. Intensive use of cooling systems can improve summer and autumn reproductive performance, but is unable to increase CR to winter and spring levels. We examined whether combined hormonal treatments--to increase follicular turnover before artificial insemination (AI) and progesterone supplementation post-AI--might improve fertility of cooled cows during the summer and autumn. The experiment was conducted from July to November in 3 commercial herds in Israel and included 707 Holstein cows at 50 to 60 d in milk (DIM). Cows were hormonally treated to induce 2 consecutive 9-d cycles, with GnRH administration followed by PGF2α injection 7 d later, followed by an intravaginal insert containing progesterone on d 5 ± 1 post-AI for 14 d. Both untreated controls (n=376) and treated cows (n=331) were inseminated following estrus, and pregnancy was determined by palpation 42 to 50 d post-AI. First-AI CR data revealed a positive interaction between treatment and cows previously diagnosed with postpartum uterine disease [odds ratio (OR) 2.24]. Interaction between treatment and low body condition score tended to increase the probability of first-AI CR (OR 1.95) and increased pregnancy rate at 90 DIM (OR 2.50) and at 120 DIM (OR 1.77). Low milk production increased the probability of being detected in estrus at the end of synchronization within treated cows (OR 1.67), and interacted with treatment to increase probability of pregnancy at 90 DIM (OR 2.39) relative to control counterparts. It is suggested that when administered with efficient cooling, combined hormonal treatment in specific subgroups of cows, that is, those previously diagnosed with postpartum uterine disease or those with low body condition score or low milk yield might improve fertility during the summer and autumn. Integration of such an approach into reproductive management during the hot seasons might improve treatment efficiency and reduce expenses.

Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers.

BACKGROUND: The BRCA1/2 proteins are involved in regulation of cellular proliferation by DNA damage repair via homologous recombination. Therefore, BRCA1/2 mutation carriers with pancreatic cancer may have distinct biologic outcomes. METHODS: Patients with BRCA1/2-associated pancreatic ductal adenocarcinoma (PDAC) diagnosed between January 1994 and December 2012 were identified from databases at three participating institutions. Clinical data were collected. Disease-free survival and overall survival (OS) were analysed. RESULTS: Overall, 71 patients with PDAC and BRCA1 (n=21), BRCA2 (n=49) or both (n=1) mutations were identified. Mean age at diagnosis was 60.3 years (range 33-83), 81.7% (n=58) had any family history of malignancy; 30% (n=21) underwent primary resection. Out of 71 participants, 12 received experimental therapy; one patient had missing data, these 13 cases were excluded from OS analysis. Median OS for 58 patients was 14 months (95% CI 10-23 months). Median OS for patients with stage 1/2 disease has not been reached with 52% still alive at 60 months. Median OS for stage 3/4 was 12 months (95% CI 6-15). Superior OS was observed for patients with stage 3/4 treated with platinum vs those treated with non-platinum chemotherapies (22 vs 9 months; P=0.039). CONCLUSION: Superior OS was observed for advanced-disease BRCA-associated PDAC with platinum exposure.

Great expectations for the World Health Organization: a Framework Convention on Global Health to achieve universal health coverage.

Establishing a reform agenda for the World Health Organization (WHO) requires understanding its role within the wider global health system and the purposes of that wider global health system. In this paper, the focus is on one particular purpose: achieving universal health coverage (UHC). The intention is to describe why achieving UHC requires something like a Framework Convention on Global Health (FCGH) that have been proposed elsewhere,(1) why WHO is in a unique position to usher in an FCGH, and what specific reforms would help enable WHO to assume this role.

Medication adherence in a comparative effectiveness trial for bipolar disorder.

OBJECTIVE: Psychopharmacology remains the foundation of treatment for bipolar disorder, but medication adherence in this population is low (range 20-64%). We examined medication adherence in a multisite, comparative effectiveness study of lithium. METHOD: The Lithium Moderate Dose Use Study (LiTMUS) was a 6-month, six-site, randomized effectiveness trial of adjunctive moderate dose lithium therapy compared with optimized treatment in adult out-patients with bipolar I or II disorder (N=283). Medication adherence was measured at each study visit with the Tablet Routine Questionnaire. RESULTS: We found that 4.50% of participants reported missing at least 30% of their medications in the past week at baseline and non-adherence remained low throughout the trial (<7%). Poor medication adherence was associated with more manic symptoms and side-effects as well as lower lithium serum levels at mid- and post-treatment, but not with poor quality of life, overall severity of illness, or depressive symptoms. CONCLUSION: Participants in LiTMUS were highly adherent with taking their medications. The lack of association with possible predictors of adherence, such as depression and quality of life, could be explained by the limited variance or other factors as well as by not using an objective measure of adherence.

Using comparative effectiveness design to improve the generalizability of bipolar treatment trials data: contrasting LiTMUS baseline data with pre-existing placebo controlled trials.

BACKGROUND: Efficacy-based double-blind placebo controlled trials were conducted to establish efficacy and safety for FDA approval. Such designs allowed and encouraged the use of exclusion criteria to improve assay sensitivity and internal validity. The LiTMUS trial increased the representation of real-world individuals with bipolar disorder despite the acknowledgment that this compromises assay sensitivity. METHOD: To maximize generalizability, LiTMUS used broad inclusion and narrow exclusion criteria: participants experiencing mood symptoms of sufficient intensity (at least with a CGI-BP ≥ 3) that would warrant a change in treatment, and that lithium treatment would be a reasonable therapeutic option if they were randomized to it. At baseline demographic, illness, clinical, and treatment characteristics were collected. The LiTMUS study design and baseline sociodemographic data were compared to previous efficacy studies. RESULTS: As compared to the previous bipolar disorder efficacy studies, LiTMUS participants were of similar age, gender, weight and illness severity; however LiTMUS participants were more racially and ethnically representative of the general population, had a greater number of mood episodes in the past 12 months, more Axis I/II comorbidity, a greater number of prior suicide attempts, and higher functional capacity. CONCLUSIONS: LiTMUS was a comparative effectiveness trial that had broad inclusion and minimal exclusion criteria that produced a more representative sample comprised of real-world participants. This design enables the results of the LiTMUS study to be a more representative of real world pharmacotherapuetic outcomes. LIMITATIONS: Limitations include possible selection bias, paucity of sociodemographic data in efficacy trials, and lack of a placebo.

Rates of risk-reducing surgery in Israeli BRCA1 and BRCA2 mutation carriers.

The frequency of BRCA1 and BRCA2 mutations is higher in Israel than in almost all other countries. One strategy to reduce the burden of hereditary breast and ovarian cancers is to offer genetic testing followed by risk-reducing surgery (mastectomy and salpingo-oophorectomy) for mutation carriers. The extent to which Israeli women who carry mutations undergo these surgeries is not well characterized. Israeli women who are BRCA1 or BRCA2 mutation carriers and followed at a single high-risk clinic were asked to complete a questionnaire detailing their clinical histories at the time of genetic results disclosure and a follow-up questionnaire was completed 18 or more months thereafter. A total of 205 mutation carriers completed the questionnaires. Of 170 women with no cancer history, 84 (49%) had a risk-reducing bilateral salpingo-oophorectomy and 22 (13%) had a risk-reducing mastectomy. Five of 35 (14.3%) women with breast cancer opted for contralateral mastectomy. Approximately one half of Israeli women with a BRCA1 or BRCA2 mutation opt for risk-reducing oophorectomy, but the rate of risk-reducing mastectomy is only 13%.

General medical burden in bipolar disorder: findings from the LiTMUS comparative effectiveness trial.

OBJECTIVE: This study examined general medical illnesses and their association with clinical features of bipolar disorder. METHOD: Data were cross-sectional and derived from the Lithium Treatment - Moderate Dose Use Study (LiTMUS), which randomized symptomatic adults (n = 264 with available medical comorbidity scores) with bipolar disorder to moderate doses of lithium plus optimized treatment (OPT) or to OPT alone. Clinically significant high and low medical comorbidity burden were defined as a Cumulative Illness Rating Scale (CIRS) score ≥4 and <4 respectively. RESULTS: The baseline prevalence of significant medical comorbidity was 53% (n = 139). Patients with high medical burden were more likely to present in a major depressive episode (P = .04), meet criteria for obsessive-compulsive disorder (P = .02), and experience a greater number of lifetime mood episodes (P = 0.02). They were also more likely to be prescribed a greater number of psychotropic medications (P = .002). Sixty-nine per cent of the sample was overweight or obese as defined by body mass index (BMI), with African Americans representing the racial group with the highest proportion of stage II obesity (BMI ≥35; 31%, n = 14). CONCLUSION: The burden of comorbid medical illnesses was high in this generalizable sample of treatment-seeking patients and appears associated with worsened course of illness and psychotropic medication patterns.

Gene-expression differences in peripheral blood between lithium responders and non-responders in the Lithium Treatment-Moderate dose Use Study (LiTMUS).

This study was designed to identify genes whose expression in peripheral blood may serve as early markers for treatment response to lithium (Li) in patients with bipolar disorder. Although changes in peripheral blood gene-expression may not relate directly to mood symptoms, differences in treatment response at the biochemical level may underlie some of the heterogeneity in clinical response to Li. Subjects were randomized to treatment with (n=28) or without (n=32) Li. Peripheral blood gene-expression was measured before and 1 month after treatment initiation, and treatment response was assessed after 6 months. In subjects treated with Li, 62 genes were differentially regulated in treatment responders and non-responders. Of these, BCL2L1 showed the greatest difference between Li responders and non-responders. These changes were specific to Li responders (n=9), and were not seen in Li non-responders or patients treated without Li, suggesting that they may have specific roles in treatment response to Li.