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Zaira Khalid,1 Hasina Momotaz,2 Farren Briggs,3 Kristin A Cassidy,1,2 Naomi S Chaytor,4 Robert T Fraser,5 Mary R Janevic,6 Barbara Jobst,7 Erica K Johnson,8 Peter Scal,9 Tanya M Spruill,10 Betsy K Wilson,2 Martha Sajatovic1,2 1Department of Psychiatry, Case Western Reserve University School of Medicine, University Hospitals Cleveland Medical Center , Cleveland, OH, USA; 2Department of Neurology, Case Western Reserve University School of Medicine, Neurological and Behavioral Outcomes Center, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; 3Department of Population Health and Quantitative Science, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; 4Department of Medical Education and Clinical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, USA; 5Department of Rehabilitation Medicine, University of Washington, Seattle, WA, USA; 6Center for Managing Chronic Disease, University of Michigan School of Public Health, Ann Arbor, MI, USA; 7Department of Neurology, Geisel School of Medicine at Dartmouth, Dartmouth College, Lebanon, NH, USA; 8Health Promotion Research Center, University of Washington, Seattle, WA, USA; 9Department of Pediatrics and Adolescent Health, University of Minnesota, Minneapolis, MN, USA; 10Department of Population Health, NYU School of Medicine, New York, NY, USACorrespondence: Martha SajatovicPrevention Research Center, Case Western Reserve University School of Medicine, University Hospitals Cleveland Medical Center, 10524 Euclid Avenue, Cleveland, OH 44106, USATel +1 216 844-2808Fax +1 216 844-2742Email Martha.sajatovic@uhhospitals.orgAim: There are limited data on psychological outcomes in older people with epilepsy (PWE). This analysis, from a large pooled dataset of clinical studies from the Managing Epilepsy Well (MEW) Network, examined clinical variables including depressive symptom severity, quality of life and epilepsy self-management competency among older (age 55+) vs younger (

Carol Blixen,1,2 Jennifer B Levin,2 Kristin A Cassidy,2 Adam T Perzynski,1 Martha Sajatovic2–4 1Center for Health Care Research and Policy, MetroHealth Medical Center, 2Department of Psychiatry, 3Department of Neurology, Neurological Institute, 4Department of Biostatistics & Epidemiology, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA Background: Bipolar disorder (BD) is a chronic mental illness associated with reduced quality of life, high rates of suicide, and high financial costs. Evidence indicates that psychosocial stress might play an important role in the onset and course of BD. Objective: The objective of this study was to address the gap between coping theory and the clinical use of coping strategies used to self-manage BD.Methods: In-depth interviews were conducted with a sample of 21 poorly adherent patients with BD. All interviews were audiotaped, transcribed verbatim, and analyzed using content analysis with an emphasis on dominant themes.Results: Transcript-based analysis generated two major domains of coping strategies used to self-manage BD: 1) problem focused (altering eating habits, managing mood-stabilizing medications, keeping psychiatric appointments, seeking knowledge, self-monitoring, and socializing) and 2) emotion focused (distracting activities, denial, isolation, modifying/avoiding, helping others, and seeking social support). Participants used both types of coping strategies to deal with stressful situations brought about by the internal and external demands associated with self-management of BD.Conclusion: This qualitative study provided a first step in evaluating coping strategies as a possible mediator in the self-management of BD and has implications for health care providers. Being able to characterize an individual’s coping behaviors can help patients modify or replace more maladaptive coping with better coping strategies in the self-management of this chronic mental illness. Keywords: bipolar disorder, coping strategies, self-management

Martha Sajatovic,1 Michael S Davis,2 Kristin A Cassidy,3 Joseph Nestor,2 Johnny Sams,3 Edna Fuentes-Casiano3 1Department of Psychiatry and Neurological and Behavioral Outcomes Center, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, USA; 2MedicaSafe, New York, NY, USA; 3Department of Psychiatry, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, Cleveland, OH, USA Objective: As poor medication adherence is common in bipolar disorder (BD), technology-assisted approaches may help to monitor and enhance adherence. This study evaluated preliminary feasibility, patient satisfaction and effects on adherence, BD knowledge, and BD symptoms associated with the use of a multicomponent technology-assisted adherence enhancement system. Methods: This prospective study tested the system in five BD patients over a 15-day period. System components included: 1) an automated pill cap with remote monitoring sensor; 2) a multimedia adherence enhancement program; and 3) a treatment incentive program. This study evaluated system usability, patient satisfaction and effects on adherence (Morisky scale), knowledge (treatment knowledge test [TKT]), and symptoms (internal state scale [ISS]). Results: Mean age of the sample was 62 years, 4/5 (80%) Caucasian, and 4/5 (80%) single/divorced or widowed. Most participants (4/5, 80%) were on a single BD medication. Participants had BD for an average of 21 years. Challenges included attaching the pill sensor to standard pharmacy bottles for individuals using very large pill containers or those with multiday pill boxes. Three of five (60%) individuals completed the full 15-day period. Usability scores were high overall. Mean Morisky scores improved. Means on all four subscales of the ISS were all in the direction of improvement. On the TKT, there was a 40% increase in mean scores. Conclusion: A multicomponent technology-assisted BD adherence enhancement system is feasible. Challenges include accommodating multiple types of pill containers and monitoring multiple drugs simultaneously. The system can also generate adherence information that is potentially useful for treatment planning. Keywords: adherence, compliance, bipolar disorder, manic depressive disorder, mood stabilizers

Martha Sajatovic,1,2 Curtis Tatsuoka,2 Philipp Dines,1 Christopher S Bialko,1 Melanie Athey,1 Tiffany Williams,1 Kristin A Cassidy11Department of Psychiatry, 2Department of Neurology, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, Cleveland, OH, USAObjective: Psychotropic-related weight gain is a common concern among patients with bipolar disorder (BD). This concern affects satisfaction with treatment and may lead to non-adherence and relapse. This was a 12-week, uncontrolled prospective trial of patient-choice–facilitated ziprasidone switching among non-adherent BD patients with weight concerns. This study was conducted from January 2011 to July 2012.Method: Patients were asked to identify the “offending” BD medication which they believed was causing weight problems, and this agent was replaced with ziprasidone. The primary outcome was change in adherence as measured with the Tablets Routine Questionnaire (TRQ). Secondary outcomes included medication attitudes, BD symptoms, global psychopathology, social functioning, and quality of life.Results: The most common agents causing weight concerns were quetiapine (N=7, 23%), aripiprazole (N=4, 13%), olanzapine, lithium, and divalproex (all N=3, 10%). Adherence improved from a baseline of missing 48.6% of prescribed BD medication in the past week (44.9% in the past month) to missing 25.3% (P=0.002) of prescribed BD medication in the past week (P

Objective: Bipolar disorder is a chronic mental illness associated with substantial impairment in quality of life and function. Although there has been tremendous growth in understanding bipolar disorder with respect to treatments, very little study has focused on the viewpoint of affected individuals. The purpose of this study was to examine the subjective experience of illness among 19 men and women with rapid cycling bipolar disorder receiving treatment at an academic psychiatry clinic.Methods: Personal constructs of illness with respect to life-trajectory and societal reaction to the individual, specifically the issue of stigma, were evaluated using a semistructured, open-ended anthropological interview.Results: Participants perceived bipolar disorder as a disease with biologic underpinnings. Stigma was a major issue for all individuals. In common with individuals without serious mental illness, individuals with bipolar disorder work at mastering developmental tasks appropriate for their life stage. At times, younger individuals appeared to have difficulty separating their own identity from the effects of illness. For older individuals with bipolar disorder, life was perceived to be disrupted by bipolar disorder, with early plans and dreams often "derailed."Conclusion: Although bipolar disorder may severely alter an individual's planned life trajectory, accomplishment of life goals can at least partially offset the sense of loss that is often seen in bipolar illness. [ABSTRACT FROM AUTHOR]

For species of management concern, accurate estimates of inbreeding and associated consequences on reproduction are crucial for predicting their future viability. However, few studies have partitioned this aspect of genetic viability with respect to reproduction in a group-living social mammal. We investigated the contributions of foundation stock lineages, putative fitness consequences of inbreeding, and genetic diversity of the breeding versus nonreproductive segment of the Yellowstone National Park gray wolf population. Our dataset spans 25 years and seven generations since reintroduction, encompassing 152 nuclear families and 329 litters. We found more than 87% of the pedigree foundation genomes persisted and report influxes of allelic diversity from two translocated wolves from a divergent source in Montana. As expected for group-living species, mean kinship significantly increased over time but with minimal loss of observed heterozygosity. Strikingly, the reproductive portion of the population carried a significantly lower genome-wide inbreeding coefficients, autozygosity, and more rapid decay for linkage disequilibrium relative to the nonbreeding population. Breeding wolves had significantly longer lifespans and lower inbreeding coefficients than nonbreeding wolves. Our model revealed that the number of litters was negatively significantly associated with heterozygosity (R = -0.11). Our findings highlight genetic contributions to fitness, and the importance of the reproductively active individuals in a population to counteract loss of genetic variation in a wild, free-ranging social carnivore. It is crucial for managers to mitigate factors that significantly reduce effective population size and genetic connectivity, which supports the dispersion of genetic variation that aids in rapid evolutionary responses to environmental challenges., (© The Author(s) 2023. Published by Oxford University Press on behalf of The American Genetic Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The mammalian mouth is colonized by complex microbial communities, adapted to specific niches, and in homeostasis with the host. Individual microbes interact metabolically and rely primarily on nutrients provided by the host, with which they have potentially co-evolved along the mammalian lineages. The oral environment is similar across mammals, but the diversity, specificity, and evolution of community structure in related or interacting mammals are little understood. Here, we compared the oral microbiomes of dogs with those of wild wolves and humans. In dogs, we found an increased microbial diversity relative to wolves, possibly related to the transition to omnivorous nutrition following domestication. This includes a larger diversity of Patescibacteria than previously reported in any other oral microbiota. The oral microbes are most distinct at bacterial species or strain levels, with few if any shared between humans and canids, while the close evolutionary relationship between wolves and dogs is reflected by numerous shared taxa. More taxa are shared at higher taxonomic levels including with humans, supporting their more ancestral common mammalian colonization followed by diversification. Phylogenies of selected oral bacterial lineages do not support stable human-dog microbial transfers but suggest diversification along mammalian lineages (apes and canids). Therefore, despite millennia of cohabitation and close interaction, the host and its native community controls and limits the assimilation of new microbes, even if closely related. Higher resolution metagenomic and microbial physiological studies, covering a larger mammalian diversity, should help understand how oral communities assemble, adapt, and interact with their hosts.IMPORTANCENumerous types of microbes colonize the mouth after birth and play important roles in maintaining oral health. When the microbiota-host homeostasis is perturbed, proliferation of some bacteria leads to diseases such as caries and periodontitis. Unlike the gut microbiome, the diversity of oral microbes across the mammalian evolutionary space is not understood. Our study compared the oral microbiomes of wild wolves, dogs, and apes (humans, chimpanzees, and bonobos), with the aim of identifying if microbes have been potentially exchanged between humans and dogs as a result of domestication and cohabitation. We found little if any evidence for such exchanges. The significance of our research is in finding that the oral microbiota and/or the host limit the acquisition of exogenous microbes, which is important in the context of natural exclusion of potential novel pathogens. We provide a framework for expanded higher-resolution studies across domestic and wild animals to understand resistance/resilience., Competing Interests: The authors declare no conflict of interest.

Gray Wolves (Canis lupus) are territorial, group living carnivores that live in packs typically consisting of a dominant breeding pair and their offspring. Breeding tenures are relatively short and competitive, with vacancies usually occurring following a breeder's death, and are often filled by unrelated immigrants or by relatives of the previous breeder. The frequency and conditions of active breeder displacements are poorly understood. Position changes in the dominance hierarchy are common yet rarely documented in detail. We describe a male breeding position turnover in a wolf pack by males from a neighboring pack in mid-summer 2016 in Yellowstone National Park. Over the course of two months, three males from the Mollie's pack displaced the breeding male of the neighboring Wapiti Lake pack, joined the pack's two adult females, and subsequently raised the previous male's four approximately three-month old pups. In the five years following the displacement (2017 to 2021), at least one of the intruding males has successfully bred with the dominant female and most years with a subordinate female (who was one of the pups at the time of displacement). The pack reared pups to adulthood each year. Male breeding displacements are likely influenced by male-male competition and female mate choice. These changes are the result of individuals competing to improve breeding position and may lead to increased pack stability and greater reproductive success. We report in detail on the behavior of a closely observed breeding displacement and we discuss the adaptive benefits of the change., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Toxoplasma gondii is a protozoan parasite capable of infecting any warm-blooded species and can increase risk-taking in intermediate hosts. Despite extensive laboratory research on the effects of T. gondii infection on behaviour, little is understood about the effects of toxoplasmosis on wild intermediate host behavior. Yellowstone National Park, Wyoming, USA, has a diverse carnivore community including gray wolves (Canis lupus) and cougars (Puma concolor), intermediate and definitive hosts of T. gondii, respectively. Here, we used 26 years of wolf behavioural, spatial, and serological data to show that wolf territory overlap with areas of high cougar density was an important predictor of infection. In addition, seropositive wolves were more likely to make high-risk decisions such as dispersing and becoming a pack leader, both factors critical to individual fitness and wolf vital rates. Due to the social hierarchy within a wolf pack, we hypothesize that the behavioural effects of toxoplasmosis may create a feedback loop that increases spatial overlap and disease transmission between wolves and cougars. These findings demonstrate that parasites have important implications for intermediate hosts, beyond acute infections, through behavioural impacts. Particularly in a social species, these impacts can surge beyond individuals to affect groups, populations, and even ecosystem processes., (© 2022. The Author(s).)

Background: Mood-stabilizing medications are a cornerstone of treatment for people with bipolar disorder, though approximately half of these individuals are poorly adherent with their medication, leading to negative and even severe health consequences. While a variety of approaches can lead to some improvement in medication adherence, there is no single approach that has superior adherence enhancement and limited data on how these approaches can be implemented in clinical settings. Existing data have shown an increasing need for virtual delivery of care and interactive telemedicine interventions may be effective in improving adherence to long-term medication., Methods: Customized adherence enhancement (CAE) is a brief, practical bipolar-specific approach that identifies and targets individual patient adherence barriers for intervention using a flexibly administered modular format that can be delivered via telehealth communications. CAE is comprised of up to four standard treatment modules including Psychoeducation, Communication with Providers, Medication Routines, and Modified Motivational Interviewing. Participants will attend assigned module sessions with an interventionist based on their reasons for non-adherence and will be assessed for adherence, functioning, bipolar symptoms, and health resource use across a 12-month period. Qualitative and quantitative data will also be collected to assess barriers and facilitators to CAE implementation and reach and adoption of CAE among clinicians in the community., Discussion: The proposed study addresses the need for practical adherence interventions that are effective, flexible, and designed to adapt to different settings and patients. By focusing on a high-risk, vulnerable group of people with bipolar disorder, and refining an evidence-based approach that will integrate into workflow of public-sector care and community mental health clinics, there is substantial potential for improving bipolar medication adherence and overall health outcomes on a broad level., Trial Registration: The study was registered on ClinicalTrials.gov NCT04622150 on November 9, 2020., (© 2022. The Author(s).)

Background: Chronic psychotic disorders (CPD) impose a particularly significant burden in resource-limited settings. Combining long-acting antipsychotic medication (LAI) with a customized adherence enhancement intervention (CAE-L) has potential to advance care., Methods: Nineteen adults ≥ age 18 with CPD who self-reported missing ≥20% of antipsychotic medication within the last month were stabilized on oral haloperidol prior to transitioning to monthly haloperidol decanote for 25 weeks. Outcome evaluations were conducted at baseline and Week 25. Primary outcomes were oral medication adherence assessed via the Tablet Routines Questionnaire (TRQ) and LAI injection frequency. Secondary outcomes included CPD symptoms measured by the Brief Psychiatric Rating Scale and Clinical Global Impressions, functioning evaluated using the Social and Occupational Functioning Scale, and medication attitudes assessed with the Drug Attitudes Inventory., Results: Mean sample age was 38.79 (SD = 9.31) with 18 individuals completing the study. There was one serious adverse event, a relapse into substance use, not deemed study-related. Mean endpoint LAI dosage was 65.79 mg (SD = 22.38). TRQ mean scores were 21.84 (SD =13.83) and 12.94 (SD = 11.93) at screen and baseline respectively. For only two individuals who were on concomitant oral medication at 25 weeks, TRQ change was not calculated. LAI injection frequency was 100%. Medication attitudes scores significantly improved from 7.89 (SD = 2.72) to 9.83 (SD = 0.52) (p = .001.) Changes in CPD symptoms and functioning were non-significant., Conclusions: CAE-L appears to be preliminarily feasible and acceptable in Tanzanians with CPD., Trial Registration: The study was registered on ClinicalTrials.gov (NCT04327843) on March 31, 2020., (© 2022. The Author(s).)

Objective: People with bipolar disorder (BD) often have difficulty with medication adherence. This pilot trial combined a behavioral customized adherence enhancement (CAE) approach with long-acting injectable (LAI) antipsychotic medication and assessed effects on adherence, BD symptoms, and functional status., Methods: This 6-month prospective, uncontrolled trial of the intervention (CAE with LAI) in 30 poorly adherent individuals with BD assessed adherence using the Tablets Routine Questionnaire (TRQ) and symptoms using the Brief Psychiatric Rating Scale (BPRS), Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), and Clinical Global Impressions (CGI). Functioning was assessed via the Social and Occupational Functioning Assessment Scale (SOFAS) and Global Assessment of Functioning (GAF). Assessments were conducted at screening, baseline, week 12, and week 24 (6 months). The LAI was aripiprazole once monthly. The study was conducted between April 2018 and May 2020., Results: The mean age of the sample was 49.5 years (SD = 9.3), and 56.7% were Black. Nine individuals (30%) terminated the study prematurely, 1 due to side effects (tremor). The mean LAI dose was 314.3 mg (SD = 96.4). The proportion of missed medications in the past week (mean TRQ) from screen to 24 weeks significantly improved from 50.1% (SD 24.8) to 16.9% (SD = 27.0) ( P  < .001), and past month TRQ improved from 40.6% (SD = 23.8) to 19.2% (SD = 24.0) (a trend for significance, P  = .0599). TRQ change from baseline to 24 weeks was not significant. There were significant improvements on the BPRS ( P  < .001), MADRS ( P  = .01), YMRS ( P  < .001), CGI ( P  < .001), SOFAS ( P  < .001), and GAF ( P  < .001)., Conclusion: A personalized intervention to address adherence barriers combined with LAI can improve recovery outcomes in high-risk individuals with BD., Trial Registration: ClinicalTrials.gov Identifier: NCT03408873., (© Copyright 2021 Physicians Postgraduate Press, Inc.)

Objective: The Multilevel Facilitation of Long-Acting Antipsychotic Medication Program (MAP) is a novel intervention to increase the appropriate use of long-acting injectable (LAI) antipsychotics in community mental health clinics. The authors investigated the feasibility of MAP, facilitators and barriers to use, and preliminary impact on LAI medication use., Methods: Two clinics in Texas and two in Ohio serving 750 and 617 individuals with schizophrenia receiving oral antipsychotics, respectively, were asked to change clinical procedures for 1 year by using either the not receiving optimum benefit (NOB) checklist or the checklist plus MAP. Providers used the NOB checklist to identify individuals who could benefit from switching to LAI antipsychotics. MAP clinics used the NOB checklist plus nonbranded academic detailing for providers and a shared-decision-making video and tool for consumers. Use of MAP components was tracked, and barriers and facilitators were collected quarterly. Antipsychotic prescription counts were provided by participating clinics., Results: Barriers to use of MAP included loss of local champions and administrators, difficulty with provider buy-in, limited availability of peer specialists, and a lack of infrastructural support to integrate MAP into clinic flow. Higher scores on the NOB checklist were associated with more provider LAI medication offers and greater patient acceptance of LAI antipsychotics. LAI medication use increased in clinics over time, but it is unclear whether this increase was due to MAP., Conclusions: Changing MAP components to fit local procedures and to circumvent unique barriers could aid implementation. Further research should investigate the potential impact of MAP components on LAI medication use.

The host-associated microbiome is an important player in the ecology and evolution of species. Despite growing interest in the medical, veterinary, and conservation communities, there remain numerous questions about the primary factors underlying microbiota, particularly in wildlife. We bridged this knowledge gap by leveraging microbial, genetic, and observational data collected in a wild, pedigreed population of gray wolves ( Canis lupus ) inhabiting Yellowstone National Park. We characterized body site-specific microbes across six haired and mucosal body sites (and two fecal samples) using 16S rRNA amplicon sequencing. At the phylum level, we found that the microbiome of gray wolves primarily consists of Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria, and Proteobacteria, consistent with previous studies within Mammalia and Canidae. At the genus level, we documented body site-specific microbiota with functions relevant to microenvironment and local physiological processes. We additionally employed observational and RAD sequencing data to examine genetic, demographic, and environmental correlates of skin and gut microbiota. We surveyed individuals across several levels of pedigree relationships, generations, and social groups, and found that social environment (i.e., pack) and genetic relatedness were two primary factors associated with microbial community composition to differing degrees between body sites. We additionally reported body condition and coat color as secondary factors underlying gut and skin microbiomes, respectively. We concluded that gray wolf microbiota resemble similar host species, differ between body sites, and are shaped by numerous endogenous and exogenous factors. These results provide baseline information for this long-term study population and yield important insights into the evolutionary history, ecology, and conservation of wild wolves and their associated microbes., Competing Interests: None declared., (© 2021 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Aggression is a quantitative trait deeply entwined with individual fitness. Mapping the genomic architecture underlying such traits is complicated by complex inheritance patterns, social structure, pedigree information and gene pleiotropy. Here, we leveraged the pedigree of a reintroduced population of grey wolves (Canis lupus) in Yellowstone National Park, Wyoming, USA, to examine the heritability of and the genetic variation associated with aggression. Since their reintroduction, many ecological and behavioural aspects have been documented, providing unmatched records of aggressive behaviour across multiple generations of a wild population of wolves. Using a linear mixed model, a robust genetic relationship matrix, 12,288 single nucleotide polymorphisms (SNPs) and 111 wolves, we estimated the SNP-based heritability of aggression to be 37% and an additional 14% of the phenotypic variation explained by shared environmental exposures. We identified 598 SNP genotypes from 425 grey wolves to resolve a consensus pedigree that was included in a heritability analysis of 141 individuals with SNP genotype, metadata and aggression data. The pedigree-based heritability estimate for aggression is 14%, and an additional 16% of the phenotypic variation was explained by shared environmental exposures. We find strong effects of breeding status and relative pack size on aggression. Through an integrative approach, these results provide a framework for understanding the genetic architecture of a complex trait that influences individual fitness, with linkages to reproduction, in a social carnivore. Along with a few other studies, we show here the incredible utility of a pedigreed natural population for dissecting a complex, fitness-related behavioural trait., (© 2020 John Wiley & Sons Ltd.)

The relationship between medication attitudes and adherence as well as reliable measures of medication attitudes need further study. This study examined the psychometric properties of the Attitudes Toward Mood Stabilizers Questionnaire (AMSQ) in bipolar participants and the relationship between medication attitudes and adherence, measured by the self-reported Tablets Routine Questionnaire (TRQ). Inclusion criteria included mood stabilizer treatment and 20% or more medication nonadherence. Measures were given pretreatment and posttreatment. Average age was 47 years; majority were female (69%), African American (67%), and unmarried (53%). AMSQ's test-retest reliability was ρ = 0.73 (p < 0.001). AMSQ correlated with TRQ (rs = 0.20, p < 0.01) at baseline. Factor analysis identified three factors: positive/favorable attitudes, negative/critical attitudes, and unintentional nonadherence. Change in AMSQ across time correlated with change in TRQ. The AMSQ is valid psychometrically and is sensitive to change. Medication attitudes are related to adherence behavior. Interventions should include targeting specific domains of medication attitudes, such as illness knowledge.

Objective: To assess depressive symptom outcomes in a pooled sample of epilepsy self-management randomized controlled trials (RCTs) from the Managing Epilepsy Well (MEW) Network integrated research database (MEW DB)., Methods: Five prospective RCTs involving 453 adults with epilepsy compared self-management intervention (n = 232) versus treatment as usual or wait-list control outcomes (n = 221). Depression was assessed with the nine-item Patient Health Questionnaire. Other variables included age, gender, race, ethnicity, education, income, marital status, seizure frequency, and quality of life. Follow-up assessments were collapsed into a visit 2 and a visit 3; these were conducted postbaseline., Results: Mean age was 43.5 years (SD = 12.6), nearly two-thirds were women, and nearly one-third were African American. Baseline sample characteristics were mostly similar in the self-management intervention group versus controls. At follow-up, the self-management group had a significantly greater reduction in depression compared to controls at visit 2 (P < .0001) and visit 3 (P = .0002). Quality of life also significantly improved in the self-management group at visit 2 (P = .001) and visit 3 (P = .005)., Significance: Aggregate MEW DB analysis of five RCTs found depressive symptom severity and quality of life significantly improved in individuals randomized to self-management intervention versus controls. Evidence-based epilepsy self-management programs should be made more broadly available in neurology practices., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

Objective: This study evaluated the feasibility, acceptability, and preliminary efficacy of psychoeducation plus an automated text messaging intervention (Individualized Texting for Adherence Building-Cardiovascular [iTAB-CV]) to improve adherence to antihypertensives and bipolar disorder medication., Methods: After a psychoeducation program, iTAB-CV was administered for 2 months. In month 1, participants received one educational-motivational and one mood rating text daily. In month 2, medication reminders were added., Results: The sample (N=38) was 74% African American and 53% women, with a mean±SD age of 51.53±9.06. Antihypertensive nonadherence decreased from a mean of 43%±23% to 21%±18% at 12 weeks (χ 2 =34.6, df=3, p<0.001). Systolic blood pressure decreased from a mean of 144.8±15.5 mmHg to 136.0±17.8 mmHg (χ 2 =17.6, df=3, p<.001). Retention was 100%., Conclusions: In this uncontrolled trial, participants were highly engaged and medication adherence and reduced systolic blood pressure were sustained after psychoeducation plus iTAB-CV. Because iTAB-CV is automated and delivered remotely, it has the potential to reach a large and challenging population.

Objective: "Self-management for people with epilepsy and a history of negative health events" (SMART) is a novel group-format epilepsy self-management intervention demonstrated to reduce negative health events (NHEs) such as accidents, emergency department visits, and seizures in adults with epilepsy in a 6-month prospective randomized controlled trial (RCT); SMART also reduced depressive symptoms and improved health functioning and quality of life. This report describes the longer-term (12-month) post-efficacy RCT outcomes in adults with epilepsy who received SMART., Methods: After completing a 6-month, prospective RCT that demonstrated efficacy of SMART vs 6-month waitlist control (WL), adults ≥18 years of age with epilepsy were followed for an additional 12 months. Individuals originally randomized to WL received the 8-week SMART intervention immediately following the conclusion of the RCT. For this long-term extension analysis, assessments were conducted at 24 weeks (the 6-month primary outcome time-point of the efficacy RCT), at 32 weeks for individuals originally randomized to WL, and at 48 weeks and 72 weeks for all individuals. Outcomes assessed included past 6-month NHE counts, depressive symptoms assessed with the 9-item Patient Health Questionnaire (PHQ-9) and Montgomery-Asberg Depression Rating Scale (MADRS), and quality of life assessed with the 10-item Quality of Life in Epilepsy (QOLIE-10)., Results: At the beginning of this long-term observational period (24-week follow-up time point for the original RCT), there were 50 individuals in the group originally randomized to SMART and 52 originally randomized to WL. Mean age was 41.4 years, 70% women (N = 71), 64% (N = 65) African-American, and 8% Hispanic (N = 8). Study attrition from week 24 to week 72 was 8% in the arm originally randomized to SMART and 17% in the arm originally randomized to WL. During the 12-month observation period (24 weeks to 72 weeks), there were a total of 44 serious adverse events and 4 deaths, none related to study participation. There was no significant change in total past 6-month NHE counts in the group originally randomized to SMART, although the group had significantly reduced 6-month seizure counts. The group originally randomized to WL, who received SMART during this observational period, had a reduction in total NHE counts. The group originally randomized to SMART had relatively stable levels on other outcome variables except for a trend for improved MADRS (p = 0.08). In the group originally randomized to WL, there were significant improvements in PHQ-9 (p = 0.01), MADRS (p ≤ 0.01), and QOLIE-10 (p = 0.004)., Conclusions: This post-RCT extension study suggests that adults with epilepsy who participate in the SMART intervention sustain clinical effects at 1-year follow-up and may have incremental improvements in seizure frequency and mood. Future research needs to identify opportunities for scale-up and outreach to other high-risk groups with epilepsy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Chronic psychotic disorders (CPDs) occur worldwide and cause significant burden including reduced quality of life and functional impairment. Care for CPD includes psychosocial and pharmacologic interventions (i.e. antipsychotic drugs) and ongoing health monitoring. This is challenging in resource-limited settings where staff are sparse and/or undertrained. Importantly, mental health human resource needs predict continued deficits compounded by increasing disease burden. A U.S. team recently developed and tested a CPD treatment approach that combines the use of long-acting antipsychotic medication (LAI) with a brief and practical customized adherence enhancement behavioral intervention (CAE-L). This report describes the methodological details of an ongoing, first-ever refinement and preliminary testing of CAE-L in poorly adherent patients with CPD in Tanzania. Additional innovative elements include: 1) a manualized curriculum that targets specific barriers and facilitators to medication adherence in Tanzanians with CPD, and 2) targeting known, high-risk individuals with CPD (those who miss ≥20% of prescribed antipsychotic medication). The study procedures are intended to pave the way for implementing a large-scale intervention trial for CPD in the Tanzanian setting. An important component of this project is capacity building to help form the next generation of care providers. Visit exchanges modeled on a successful NIH-funded Medical Education Partnership Initiative (MEPI) template will also use the U.S. and Tanzanian teams to share expertise, problem-solve, and plan iterative refinements of project deliverables. Taken together, this project has potential to advance the care of people with CPD in Tanzania and has high generalizability to Sub-Saharan Africa and other lower-resource settings.

Objective: Nonadherence in bipolar disorder (BD) ranges from 20% to 60%. Customized adherence enhancement (CAE) is a brief, BD-specific approach that targets individual adherence barriers. This prospective, 6-month, randomized controlled trial conducted from October 2012 to July 2017 compared CAE versus a rigorous BD-specific educational program (EDU) on adherence, symptoms, and functional outcomes in poorly adherent individuals., Methods: One hundred eighty-four participants with DSM-IV BD were randomized to CAE (n = 92) or EDU (n = 92). Primary outcome was adherence change measured by the Tablets Routine Questionnaire (TRQ) and BD symptoms measured by the Brief Psychiatric Rating Scale. Other outcomes were scores on the Global Assessment of Functioning, Montgomery-Asberg Depression Rating Scale, Young Mania Rating Scale, and Clinical Global Impressions Scale. Assessments were conducted at screening, baseline, 10 weeks, 14 weeks, and 6 months., Results: The sample mean (SD) age was 47.40 (10.46) years; 68.5% were female, and 63.0% were African American. At screening, individuals missed a mean (SD) of 55.15% (28.22%) of prescribed BD drugs within the past week and 48.01% (28.46%) in the past month. Study attrition was < 20%. At 6 months, individuals in CAE had significantly improved past-week (P = .001) and past-month (P = .048) TRQ scores versus those in EDU. Past-week TRQ score improvement remained significant after adjustment for multiple comparisons. There were no treatment arm differences in BPRS scores or other symptoms, possibly related to low symptom baseline values. Baseline-to-6-month comparison showed significantly higher GAF scores (P = .036) for CAE versus EDU. Although both groups used more mental health services at 6 months compared to baseline, increase for CAE was significantly less than that for EDU (P = .046)., Conclusions: Whereas both CAE and EDU were associated with improved outcomes, CAE had additional positive effects on adherence, functioning, and mental health resource use compared to EDU., Trial Registration: ClinicalTrials.gov identifier: NCT00183495., (© Copyright 2018 Physicians Postgraduate Press, Inc.)

Objective: Despite advances in care, many people with epilepsy have negative health events (NHEs) such as accidents, emergency department visits, and poor quality of life. "Self-management for people with epilepsy and a history of negative health events" (SMART) is a novel group format epilepsy self-management intervention. A community participatory approach informed the refinement of SMART, which was then tested in a 6-month randomized controlled trial of SMART (n = 60) versus waitlist control (WL, n = 60)., Methods: Participants were adults aged ≥18 years with epilepsy and an NHE within the past 6 months (seizure, accident, self-harm attempt, emergency department visit, or hospitalization). Assessments were conducted at screening, baseline, 10 weeks, and 24 weeks (6 months). Primary outcome was 6-month change in total NHE count. Additional outcomes included depression on the nine-item Patient Health Questionnaire and Montgomery-Asberg Depression Rating Scale, quality of life on the 10-item Quality of Life in Epilepsy, functioning on the 36-item Short-Form Health Survey, and seizure severity on the Liverpool Seizure Severity Scale., Results: Mean age was 41.3 years (SD = 11.82), 69.9% were African American, 74.2% were unemployed, and 87.4% had an annual income < US$25 000; 57.5% had a seizure within 30 days of enrollment. Most NHEs were seizures. Six-month study attrition was 14.2% overall and similar between arms. Individuals randomized to SMART had greater reduction in total median NHEs from baseline to 6 months compared to WL (P = 0.04). SMART was also associated with improved nine-item Patient Health Questionnaire (P = 0.032), Montgomery-Asberg Depression Rating Scale (P = 0.002), 10-item Quality of Life in Epilepsy (P < 0.001), and 36-item Short-Form Health Survey (P = 0.015 physical health, P = 0.003 mental health) versus WL. There was no difference in seizure severity., Significance: SMART is associated with reduced health complications and improved mood, quality of life, and health functioning in high-risk people with epilepsy. Additional efforts are needed to investigate potential for scale-up., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

Objectives: Targeted Training in Illness Management (TTIM) focuses on enhancing care engagement for people living with serious mental illness and diabetes. This secondary analysis from a 60-week, randomized controlled trial of TTIM versus treatment as usual evaluated racial subgroup outcomes., Method: Demographics, clinical characteristics, and diabetes status were evaluated for those self-identifying as non-Hispanic White, African American, and Hispanic. Longitudinal response to TTIM was evaluated using a multiple domain risk index. Due to their small sample size; those identifying as Hispanic were excluded from this analysis., Results: Non-Hispanic White participants had greater baseline socioeconomic advantages. Baseline risk scores, glycosylated hemoglobin (HbA1c) values, and HbA1c differences over time were similar for African American and non-Hispanic White participants., Conclusions and Implications for Practice: African American participants living with serious mental illness and diabetes receiving TTIM did as well as non-Hispanic White participants. Inclusive approaches that feature peer support and are situated in safety-net health care settings need to be further investigated with respect to potentially impacting health disparities. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

Rationale: Up to 30-50% of individuals with epilepsy have depressive symptoms, which often complicate seizure management and reduce overall quality of life. To identify and manage depressive symptoms appropriately, clinicians need standardized instruments that can accurately identify and monitor those with clinically significant depression. The self-reported 9-item Patient Health Questionnaire (PHQ-9) has been used relatively widely to screen and monitor depression in epilepsy. The rater-administered Montgomery-Asberg Depression Rating Scale (MADRS) is a rater-administered instrument widely used in depression treatment trials but less widely applied in epilepsy. This secondary analysis from 2 epilepsy self-management clinical trials compared depression severity ratings using the PHQ-9 and the MADRS instruments., Methods: Data for this analysis were derived from pooled baseline and longitudinal data from 2 prospective epilepsy self-management randomized controlled trials (RCTs). Both RCTs assessed depression with the PHQ-9 and the MADRS. For this analysis, total depression severity scores and case classification of individuals with no/minimal, mild, moderate/moderately severe, and severe depression were assessed using both PHQ-9 and MADRS., Results: The sample contained 164 individuals with epilepsy. Demographic and clinical variables between the 2 studies were generally similar. There were 107 women (64.8%), 106 African-Americans (64.2%), and 51 Whites (30.9%). Individuals had epilepsy for an average of 22.1 (SD: 15.5). Mean past 30-day seizure frequency at baseline was 3.1 (SD: 11.6). Baseline mean PHQ-9 was 10.7 (SD: 6.80) with depression severity of 32 (19.6%) not or minimally depressed, 47 (28.8%) mildly depressed, 37 (22.7%) moderately depressed, 27 (16.6%) moderately severely depressed, and 20 (12.3%) severely depressed. Baseline mean MADRS severity was 18.5 (SD: 11.3) with 30 (18.8%) not or minimally depressed, 27 (16.9%) mildly depressed, 92 (56.1%) moderately depressed, and 11 (6.9%) severely depressed. The correlation between total PHQ-9 and total MADRS was 0.843 (p < .01) although case classification by depression severity varied somewhat between the two instruments., Conclusions: Standardized measures to evaluate depression severity in people with epilepsy can help identify cases and monitor treatment. The PHQ-9 and MADRS both perform well in assessing depression in people with epilepsy although administration burden is less with PHQ-9 thus making it likely preferable for settings where time and epilepsy specialty resources are limited., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aims: In spite of advances in care, people with epilepsy experience negative health events (NHEs), such as seizures, emergency department (ED) visits, and hospitalizations. Being able to identify characteristics that are associated with NHE risk can help inform care approaches that reduce complications and burden. This analysis using baseline data from a larger randomized epilepsy self-management clinical trial assessed the relationship between demographic and clinical variables vs. seizure-related complications among people with epilepsy., Methods: Data were derived from a baseline sample of a larger prospective study of 120 individuals with epilepsy who experienced an NHE within the last 6months. Demographic characteristics, depression assessed with the 9-item Patient Health Questionnaire (PHQ-9) and the Montgomery-Asberg Depression rating scale (MADRS), quality of life assessed with the 10-item Quality of Life in Epilepsy Inventory (QOLIE-10), self-efficacy assessed the Epilepsy Self-Efficacy Scale (ESES), social support assessed with the Multidimensional Scale of Perceived Social Support (MSPSS), self-management assessed with the Epilepsy Self-Management Scale (ESMS), and stigma assessed with the Epilepsy Stigma Scale (ESS) were all examined in association with past 6-month NHE frequency and 30-day seizure frequency., Results: Except for lower levels of education and lower levels of income being associated with higher 30-day and 6-month seizure frequency, demographic variables were generally not significantly associated with NHEs. Higher 30-day seizure frequency was associated with greater depression severity on PHQ-9 (p<0.01) and MADRS (p<0.01). Higher 6-month seizure frequency was also associated with greater depression severity on PHQ-9 (p<.001) and MADRS (p=0.03). Both 30-day and 6-month seizure frequency were significantly negatively associated with QOLIE-10 (p<0.001). Both 30day (p=0.01) and 6-month (p=0.03) seizure frequency were associated with worse stigma on ESS. Total NHE count was associated with more severe depression on PHQ-9 (p=0.02), and MADRS (p=0.04), worse quality of life on QOLIE-10 (p<0.01), and more stigma on ESS (p=0.03)., Conclusions: Consistent with previous literature, more frequent seizures were associated with worse depression severity and quality of life. A finding that is less established is that higher seizure frequency is also associated with worse epilepsy-related stigma. Epilepsy self-management approaches need to address depression and stigma as well as seizure control., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Long-acting injectable antipsychotics (LAI) can optimize adherence for high-risk serious mental illness (SMI). This customized adherence-enhancement approach delivered by social worker interventionists was combined with LAI (CAE-L) of paliperidone palmitate for homeless, poorly adherent individuals with SMI., Methods: This 6-month prospective, uncontrolled trial of CAE-L in 30 recently homeless individuals with SMI assessed adherence using the Tablets Routine Questionnaire, injection frequency, and SMI symptoms measured by the Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, and Clinical Global Impressions. The Social and Occupational Functioning Assessment Scale measured social function. Standardized scales assessed extrapyramidal effects., Findings: Patients' mean age was 43.6 (SD, 9.53) years, and they were mainly minorities (86.7% African American) and single/never married (72.4%). Rate of substance abuse within the past year was 40.0%, and rate of incarceration within the past 6 months was 32.1%. Four participants (13.3%) terminated the study prematurely. Customized adherence enhancement + LAI was associated with good adherence to LAI (92.9%) and improved adherence with oral drug as measured by Tablets Routine Questionnaire (P = 0.02). There were significant improvements in Positive and Negative Syndrome Scale (P < 0.01), Brief Psychiatric Rating Scale (P < 0.001), Clinical Global Impressions (P = 0.003), and Social and Occupational Functioning Assessment Scale (P = 0.005). There were no significant extrapyramidal effects., Implications: While findings must be tempered by the methodological limitations, CAE-L seems associated with multiple domains of improvement in homeless/recently homeless individuals with SMI. Adverse effects limit tolerability in some individuals, and not all will remain engaged. However, LAI combined with a patient-centered behavioral approach can improve outcomes for some high-risk individuals with SMI.

Objectives: We assessed characteristics that may predict outpatient appointment attendance in outpatient medical clinics among patients comorbid for serious mental illness (SMI) and type 2 diabetes (DM)., Methods: Baseline covariate data from 200 individuals with SMI-DM enrolled in a randomized controlled trial (RCT) were used to examine characteristics associated with electronic health record-identified clinic appointment attendance using a generalized estimating equations approach. The analyses evaluated the relationship between clinic attendance and potentially modifiable factors including disease knowledge, self-efficacy, social support, physical health, and mental health, as well as demographic information., Results: Demographic and mental health characteristics were most associated with clinic attendance in adults with SMI-DM. Physical health was not associated with clinic attendance., Conclusions: Information on clinical and demographic characteristics and factors potentially modifiable by psychological interventions may be useful in improving adherence to treatment among SMI-DM patients. It is our hope that clinicians and researchers will use these results to help tailor adherence-facilitating interventions among people at particular risk for poor engagement in care.

Objectives: A 60-week randomized controlled trial assessed the effects of targeted training in illness management (TTIM) versus treatment as usual among 200 individuals with serious mental illness and diabetes mellitus., Methods: The study used the Clinical Global Impression (CGI), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Brief Psychiatric Rating Scale (BPRS) to assess psychiatric symptoms; the Global Assessment of Functioning (GAF) and the Sheehan Disability Scale (SDS) to assess functioning; the 36-Item Short-Form Health Survey (SF-36) to assess general health, and serum glycosylated hemoglobin (HbA1c) to assess diabetes control., Results: Participants' mean±SD age was 52.7±9.5 years, and 54% were African American. They were diagnosed as having depression (48%), schizophrenia (25%), and bipolar disorder (28%). At baseline, depression severity was substantial but psychosis severity was modest. At 60 weeks, there was greater improvement among TTIM participants versus treatment-as-usual recipients on the CGI (p<.001), the MADRS (p=.016), and the GAF (p=.003). Diabetes knowledge was significantly improved among TTIM participants but not in the treatment-as-usual group. In post hoc analyses among participants whose HbA1c levels at baseline met recommendations set by the American Diabetes Association for persons with high comorbidity (53%), TTIM participants had minimal change in HbA1c over the 60-week follow-up, whereas HbA1c levels worsened in the treatment-as-usual group., Conclusions: TTIM was associated with improved psychiatric symptoms, functioning, and diabetes knowledge compared with treatment as usual. Among participants with better diabetes control at baseline, TTIM participants had better diabetes control at 60 weeks compared with recipients of treatment as usual.

Aggression directed at conspecific groups is common among gregarious, territorial species, and for some species such as gray wolves (Canis lupus) intraspecific strife is the leading cause of natural mortality. Each individual in a group likely has different measures of the costs and benefits associated with a group task, such as an aggressive attack on another group, which can alter motivation and behavior. We observed 292 inter-pack aggressive interactions in Yellowstone National Park between 1 April 1995 and 1 April 2011 (>5300days of observation) in order to determine the role of both sexes, and the influence of pack, age, and other traits on aggression. We recorded the behaviors and characteristics of all individuals present during the interactions (n=534 individuals) and which individuals participated in each step (i.e. chase, attack, kill, flight) of the interaction. Overall, all wolves were more likely to chase rivals if they outnumbered their opponent, suggesting packs accurately assess their opponent's size during encounters and individuals adjust their behavior based on relative pack size. Males were more likely than females to chase rival packs and gray-colored wolves were more aggressive than black-colored wolves. Male wolves and gray-colored wolves also recorded higher cortisol levels than females and black-colored wolves, indicating hormonal support for more intense aggressive behavior. Further, we found a positive correlation between male age and probability of chasing, while age-specific participation for females remained constant. Chasing behavior was influenced by the sex of lone intruders, with males more likely to chase male intruders. This difference in behavior suggests male and female wolves may have different strategies and motivations during inter-pack aggressive interactions related to gray wolf mating systems. A division of labor between pack members concerning resource and territory defense suggests selection for specific traits related to aggression is an adaptive response to intense competition between groups of conspecifics., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Individuals with bipolar disorder (BD) have high rates of nonadherence, medical illness, and premature mortality. This analysis reexamined correlates of poor adherence to nonpsychiatric medication in 73 patients with BD and medical comorbidities. The majority was female (74%) and African American (77%) with mean age of 48.08 (SD, 8.04) years, mean BD duration of 28.67 (SD, 10.24) years, mean years of education of 12.01 (SD, 1.87), and mean proportion of days with missed doses in past week of 43.25 (SD, 31.14). Sex, age, education, race, and living alone did not correlate with adherence. More BD medications and more severe psychiatric symptoms correlated with worse adherence. Specifically, poor adherence correlated with the retardation and vegetative factors of Montgomery-Åsberg Depression Rating Scale and affect factor of the Brief Psychiatric Rating Scale. Among poorly adherent patients with BD and medical comorbidities, the number of BD medications, tension/anxiety, and somatic symptoms of depression related to worse nonpsychiatric medication adherence.

Objective: Care for people with serious mental illness and diabetes is complicated by clinical heterogeneity. This cross-sectional analysis of 200 individuals with comorbid serious mental illness and diabetes explored differentiation between patient subgroups that were characterized on the basis of selected dimensions within a biopsychosocial framework., Methods: Relationships between self-efficacy, treatment expectation, social support, and depression were first assessed via bivariate Spearman correlations among 200 individuals participating in a randomized controlled trial who had diabetes along with major depression, bipolar disorder, or schizophrenia. Next, latent profile analyses were conducted to determine underlying subgroups on the basis of these variables. The resultant groups were compared on diabetes control, function, and symptoms., Results: Two subgroups emerged. One had more severe psychiatric symptoms, low scores on other psychosocial variables, and worse diabetes control. The other had low levels of psychiatric symptoms, better scores on other variables, and better diabetes control., Conclusions: Symptom presentation and internal and external resources appeared to be related to diabetes control for people with comorbid diabetes and serious mental illness. Care approaches need to go beyond standard education and consider biopsychosocial variables.

Background: Femoral stem fracture following total hip arthroplasty is an uncommon event that requires immediate revision surgery., Questions/purposes: We report on four patients who experienced stem fractures of one design and a review of the US Food and Drug Administration adverse event reports on this design., Methods: Fracture surfaces of four EMPERION™ (Smith & Nephew, Memphis, TN) femoral stems were analyzed under optical and scanning electron microscopy. A search of the FDA's Manufacturer and User Facility Device Experience (MAUDE) that reports on all EMPERION™ adverse events was completed., Results: Fracture surfaces exhibited characteristics consistent with a fatigue fracture mechanism. Sixteen MAUDE reports claimed stem fracture or breakage of EMPERION™ stems., Conclusion: The four cases of EMPERION™ stem fractures were likely driven by small stem diameter, high offset, and high patient weight. Modular stem-sleeve femoral systems are susceptible to fatigue failure under high stress and should only be used in appropriate patients, whom are not considered obese., Competing Interests: Compliance with Ethical Standard Conflict of Interest Chelsea N. Koch, BS, Laura Serrano Mateo, MD, and Kevin A. Cassidy, MD have declared that they have no conflict of interest. Stephen Kayiaros, MD reports personal fee from Depuy and other from Pfizer, outside the work. Seth A. Jerabek, MD reports personal fees from Stryker, outside the work. Alejandro Gonzalez Della Valle, MD reports personal fees from OrthoSensor, Ortho Development, and Link Bio, outside the work. Human/Animal Rights All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5). Informed Consent Informed consent was obtained from all patients for being included in the study. Required Author Forms Disclosure forms provided by the authors are available with the online version of this article.

For group-living mammals, social coordination increases success in everything from hunting and foraging (Crofoot and Wrangham in Mind the Gap, Springer, Berlin, 2010; Bailey et al. in Behav Ecol Sociobiol 67:1-17, 2013) to agonism (Mosser and Packer in Anim Behav 78:359-370, 2009; Wilson et al. in Anim Behav 83:277-291, 2012; Cassidy et al. in Behav Ecol 26:1352-1360, 2015). Cooperation is found in many species and, due to its low costs, likely is a determining factor in the evolution of living in social groups (Smith in Anim Behav 92:291-304, 2014). Beyond cooperation, many mammals perform costly behaviors for the benefit of group mates (e.g., parental care, food sharing, grooming). Altruism is considered the most extreme case of cooperation where the altruist increases the fitness of the recipient while decreasing its own fitness (Bell in Selection: the mechanism of evolution. Oxford University Press, Oxford 2008). Gray wolf life history requires intra-pack familiarity, communication, and cooperation in order to succeed in hunting (MacNulty et al. in Behav Ecol doi: 10.1093/beheco/arr159 2011) and protecting group resources (Stahler et al. in J Anim Ecol 82: 222-234, 2013; Cassidy et al. in Behav Ecol 26:1352-1360, 2015). Here, we report 121 territorial aggressive inter-pack interactions in Yellowstone National Park between 1 April 1995 and 1 April 2011 (>5300 days of observation) and examine each interaction where one wolf interferes when its pack mate is being attacked by a rival group. This behavior was recorded six times (17.6 % of interactions involving an attack) and often occurred between dyads of closely related individuals. We discuss this behavior as it relates to the evolution of cooperation, sociality, and altruism.

Recruitment and retention of individuals with serious mental illness (SMI) and comorbid diabetes mellitus (DM) in research studies can be challenging with major impediments being difficulties reaching participants via telephone contact, logistic difficulties due to lack of transportation, ongoing psychiatric symptoms, and significant medical complications. Research staff directly involved in recruitment and retention processes of this study reviewed their experiences. The largest barriers at the macro, mediator, and micro levels identified in this study were inclement weather, transportation difficulties, and intermittent and inaccessible telephone contact. Barrier work-around practices included using the health system's EHR to obtain current phone numbers, providing transportation assistance (bus passes or parking reimbursement), and flexible scheduling of appointments. Suggestions are intended to assist in planning for recruitment and retention strategies.

The desire to see free ranging large carnivores in their natural habitat is a driver of tourism in protected areas around the globe. However, large carnivores are wide-ranging and subject to human-caused mortality outside protected area boundaries. The impact of harvest (trapping or hunting) on wildlife viewing opportunities has been the subject of intense debate and speculation, but quantitative analyses have been lacking. We examined the effect of legal harvest of wolves (Canis lupus) along the boundaries of two North American National Parks, Denali (DNPP) and Yellowstone (YNP), on wolf viewing opportunities within the parks during peak tourist season. We used data on wolf sightings, pack sizes, den site locations, and harvest adjacent to DNPP from 1997-2013 and YNP from 2008-2013 to evaluate the relationship between harvest and wolf viewing opportunities. Although sightings were largely driven by wolf population size and proximity of den sites to roads, sightings in both parks were significantly reduced by harvest. Sightings in YNP increased by 45% following years with no harvest of a wolf from a pack, and sightings in DNPP were more than twice as likely during a period with a harvest buffer zone than in years without the buffer. These findings show that harvest of wolves adjacent to protected areas can reduce sightings within those areas despite minimal impacts on the size of protected wolf populations. Consumptive use of carnivores adjacent to protected areas may therefore reduce their potential for non-consumptive use, and these tradeoffs should be considered when developing regional wildlife management policies.

Objective: To understand factors related to managing illness in older individuals with serious mental illness (SMI)., Methods: Baseline data from 200 individuals with SMI and diabetes enrolled in a study were used to compare characteristics between older (age >55) vs. younger (age ≤55) individuals., Results: Older individuals had better diabetes control compared to younger individuals, those with major depressive disorder had diabetes for a longer duration, worse diabetic control, and more emergency department encounters., Conclusions: Helping younger individuals with SMI learn to manage their mental and physical health early-on might minimize the negative and cumulative effect of diabetes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: This study assessed the relationship between nonadherence to psychotropic and nonpsychotropic medications for 88 patients nonadherent to medication treatment for bipolar disorder., Methods: This descriptive study was part of a clinical trial promoting medication adherence. Nonadherence was defined as ≥ 20% of days with missed doses., Results: A majority of the sample was female and had type I bipolar disorder; 49% had hypertension, 39% had hyperlipidemia, and 69% smoked; average body mass index was 34, and 65% were obese. The median proportion of days with missed doses was 53.6% (interquartile ratio [IQR]=38.10%-73.40%) for psychotropic medications and 33.93% (IQR=13.81%-51.91%) for nonpsychotropic medications. There was a significant difference between nonadherence to psychotropic and nonpsychotropic medication for the past week (z=-4.11, p<.001) and past month (z=-4.19, p<.001). More global psychopathology was associated with nonpsychotropic nonadherence., Conclusions: Psychotropic adherence was worse than nonpsychotropic adherence, yet both were poor. Improving adherence to cardiovascular medications is a reasonable pathway to improve cardiovascular health in this population.

Introduction: Progression of osteoarthritis in the unreplaced compartment following unicondylar knee arthroplasty (UKA) may be hastened if kinematics is disturbed following UKA implantation. The purpose of this study was to analyze tibiofemoral kinematics of the balanced and overstuffed UKA in comparison with the native knee during passive flexion since this is a common clinical assessment., Methods: Ten cadaveric knees were mounted to robotic manipulator and underwent passive flexion from 0 to 90°. The kinematic pathway was recorded in the native knee and in the balanced, fixed bearing UKA. The medial UKA was implanted using a measured resection technique. Additionally, a one millimeter thicker tibial insert was installed to simulate the effects of overstuffing. Tibial kinematics in relation to the femur was recorded., Results: Following UKA the tibia was externally rotated, and in valgus relative to the native knee near extension. In flexion, installing the UKA caused the knee to be translated medially and anteriorly. The tibia was translated distally through the entire range of flexion after UKA. Compared to the balanced UKA, overstuffing further increased valgus at full extension and distal translation of the tibia from full extension to 45° flexion., Conclusions: UKA implantation altered tibiofemoral kinematics in all planes. Differences were small; nevertheless, they may affect tibiofemoral loading patterns., Clinical Relevance: Alterations in tibiofemoral kinematics following UKA might have implications for prosthesis failure and progression of osteoarthritis in the remaining compartment. Overstuffing should be avoided as it further increased valgus and did not improve the remaining kinematics., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objectives: This analysis of screening and baseline data from an ongoing trial examined self-report versus automated adherence monitoring and assessed the relationship between bipolar disorder (BD) symptoms and adherence in 104 poorly adherent individuals., Methods: Adherence was measured with the Tablets Routine Questionnaire (TRQ) and the Medication Event Monitoring System (MEMS). Symptoms were measured with the Montgomery-Åsberg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS), and the Brief Psychiatric Rating Scale (BPRS)., Results: The mean age of the sample was 46.3 years [standard deviation (SD) = 9.41 years], with 72% (n = 75) women and 71% (n = 74) African American subjects. Adherence improved from screening to baseline, with a mean missed drug proportion measured by TRQ of 61.43% (SD = 26.48%) versus a baseline mean of 46.61% (SD = 30.55%). The mean proportion of missed medication using MEMS at baseline was 66.43% (SD = 30.40%). The correlation between TRQ and MEMS was 0.47. The correlation between a single index drug and all BD medications was 0.95. Symptoms were generally positively correlated with TRQ (worse adherence = more severe symptoms), but in most instances was only at a trend level (p > 0.05), with the exception of the correlations between baseline TRQ and MADRS and BPRS, which were positive (r = 0.20 and r = 0.21, respectively) and significant (p ≤ 0.05)., Conclusions: In patients with BD, monitoring increased adherence by 15%. MEMS identified 20% more non-adherence than self-report. Using a standard procedure to identify a single index drug for adherence monitoring may be one way to assess global adherence in patients with BD receiving polypharmacy treatment. Greater BD symptom severity may be a clinical indicator to assess for adherence problems., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: In spite of growing numbers of older people, there are few treatment studies on late-life bipolar disorder (BD). This was a 12-week prospective, open-label trial to assess efficacy and tolerability of adjunct asenapine in non-demented older adults (≥ 60 years) with sub-optimal previous response to BD treatments., Methods: Asenapine was initiated at 5 mg/day and titrated as tolerated. Effects on global psychopathology were measured with Clinical Global Impression, bipolar version (CGI-BP), and the Brief Psychiatric Rating Scale (BPRS). Mood polarity severity was measured with the Hamilton Depression Rating Scale, Montgomery Asberg Depression Rating Scale, and Young Mania Rating Scale. Other outcomes included the World Health Organization Disability Assessment Schedule II., Results: Fifteen individuals were enrolled (mean age 68.6, SD 6.12; 53% female; 73% Caucasian, 13% African American, and 7% Asian). There were 4/15 (27%) individuals who prematurely terminated the study, whereas 11/15 (73%) completed the study. There were significant improvements from baseline on the BPRS (p < 0.05), on CGI-BP overall (p < 0.01), and on CGI-BP mania (p < 0.05) and depression (p < 0.01) subscales. The mean dose of asenapine was 11.2 (SD 6.2) mg/day. The most common reported side effects were gastrointestinal discomfort (n = 5, 33%), restlessness (n = 2, 13%), tremors (n = 2, 13%), cognitive difficulties (n = 2, 13%), and sluggishness (n = 2, 13%)., Conclusions: Older people with BD had global improvements on asenapine. Most reported adverse effects were mild and transient, but adverse effects prompted drug discontinuation in just over one quarter of patients. Although risks versus benefits in older people must always be carefully considered, asenapine may be a treatment consideration for some non-demented geriatric BD patients., (Copyright © 2014 John Wiley & Sons, Ltd.)

Objectives: Medication nonadherence occurs in 20-60% of persons with bipolar disorder (BD) and is associated with serious negative outcomes, including relapse, hospitalization, incarceration, suicide and high healthcare costs. Various strategies have been developed to measure adherence in BD. This descriptive paper summarizes challenges and workable strategies using electronic medication monitoring in a randomized clinical trial (RCT) in patients with BD., Methods: Descriptive data from 57 nonadherent individuals with BD enrolled in a prospective RCT evaluating a novel customized adherence intervention versus control were analyzed. Analyses focused on whole group data and did not assess intervention effects. Adherence was assessed with the self-reported Tablets Routine Questionnaire and the Medication Event Monitoring System (MEMS)., Results: The majority of participants were women (74%), African American (69%), with type I BD (77%). Practical limitations of MEMS included misuse in conjunction with pill minders, polypharmacy, cost, failure to bring to research visits, losing the device, and the device impacting baseline measurement. The advantages were more precise measurement, less biased recall, and collecting data from past time periods for missed interim visits., Conclusions: Automated devices such as MEMS can assist investigators in evaluating adherence in patients with BD. Knowing the anticipated pitfalls allows study teams to implement preemptive procedures for successful implementation in BD adherence studies and can help pave the way for future refinements as automated adherence assessment technologies become more sophisticated and readily available.

Objectives: While medication treatment is necessary for the successful management of bipolar disorder (BD), non-adherence rates are up to 60%. Although medication attitudes are believed to be relevant to adherence behavior, few studies have investigated the trajectories of adherence change. This study evaluated attitudinal correlates of adherence conversion in 86 poorly adherent individuals with BD., Methods: This secondary analysis pooled data from two uncontrolled prospective trials of customized adherence enhancement (CAE), a psychosocial intervention delivered over 4-6 weeks. Poor adherence was defined as missing at least 20% of prescribed BD medication based on the self-reported Tablets Routine Questionnaire (TRQ). The sample was dichotomized into converters who achieved good adherence (N=44) and non-converters who remained poorly adherent (N=21). Converters vs. non-converters were compared on adherence, attitudes, and symptoms at baseline, 6 weeks and 3 months., Results: At baseline, converters and non-converters were similar demographically and clinically, but converters were less non-adherent (32% doses missed) than non-converters (59% missed). At 6 weeks, converters had better attitudes than non-converters. At 3 months, converters maintained improvements, but group differences were less pronounced due to some improvement in non-converters. Converters had better adherence at 3 months and trajectories differed for the groups on attitudes. Symptoms gradually improved for both converters and non-converters., Conclusions: Over two-thirds of poorly adherent BD patients who received CAE converted to good adherence. Improved medication attitudes may be a driver of improved adherence behavior and ultimately reduce BD symptoms., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Data from 157 individuals with serious mental illness and comorbid diabetes enrolled in an ongoing treatment study were used to examine clinical correlates of diabetes control., Methods: Factors assessed included depressive symptoms (Montgomery-Åsberg Depression Rating Scale), global psychopathology severity (Brief Psychiatric Rating Scale), and glycosylated hemoglobin (HbA1c), a biomarker of diabetes control., Results: Seventy-seven participants had depression, 40 had schizophrenia, and 40 had bipolar disorder. Most were moderately to severely depressed with poor diabetes control. No correlation between diagnosis and diabetes control was found after adjustment for gender, race, health literacy, diabetes duration, and diabetes knowledge. Greater depression severity and longer diabetes duration were related to poorer diabetes control. Lower severity of global psychopathology was related to poorer diabetes control, perhaps because of overall low levels of psychosis and mania., Conclusions: People with serious mental illness and diabetes face multiple challenges, which, along with severe depression, may impede diabetes self-management.

Objective: While previous work has demonstrated elevation of both comorbid anxiety disorders and diabetes mellitus type II in individuals with serious mental illness, little is known regarding the impact of comorbid anxiety on diabetes mellitus type II outcomes in serious mental illness populations. We analyzed baseline data from patients with serious mental illness and diabetes mellitus type II to examine relationships between comorbid anxiety, glucose control as measured by hemoglobin A1c score, and overall illness burden., Methods: Using baseline data from an ongoing prospective treatment study involving 157 individuals with serious mental illness and diabetes mellitus type II, we compared individuals with and without a comorbid anxiety disorder and compared hemoglobin A1c levels between these groups to assess the relationship between anxiety and management of diabetes mellitus type II. We conducted a similar analysis using cumulative number of anxiety diagnoses as a proxy for anxiety load. Finally, we searched for associations between anxiety and overall medical illness burden as measured by Charlson score., Results: Anxiety disorders were seen in 33.1% (N=52) of individuals with serious mental illness and diabetes mellitus type II and were associated with increased severity of depressive symptoms and decreased function. Hemoglobin A1c levels were not significantly different in those with or without anxiety, and having multiple anxiety disorders was not associated with differences in diabetes mellitus type II control. However, depressive symptoms were significantly associated with higher hemoglobin A1c levels. Neither comorbid anxiety nor anxiety load was significantly associated with overall medical burden., Conclusion: One in three people with serious mental illness and diabetes mellitus type II had anxiety. Depressive symptoms were significantly associated with Hb1Ac levels while anxiety symptoms had no relation to hemoglobin A1c; this is consistent with previously published work. More studies are needed to better understand the relationship between depression, anxiety, and health management in people with serious mental illness and diabetes mellitus type II., (© The Author(s) 2015.)

This analysis compared medication attitudes and reasons for nonadherence in three distinct groups of patients with serious mental illness (SMI). Cohort 1 had 43 patients with bipolar disorder (BD) treated in a community mental health setting, cohort 2 had 43 patients with BD taking an atypical antipsychotic and treated in an academic medical center, and cohort 3 had 30 patients with schizophrenia or schizoaffective disorder who had been homeless in the last year. Standardized attitudinal scales found generally negative attitudes toward medication and limited illness insight. Although the three cohorts differed with regard to severity of symptoms, age of onset, education, baseline adherence, and race, the groups had similar medication attitudes before and after treatment. Despite group differences in demographic and clinical variables, our analyses found more similarities than differences in medication attitudes among these three discrete groups of poorly adherent, symptomatic patients with SMI. The common attitudinal characteristics have implications for delivery of health care services that can enhance treatment adherence in high-risk SMI patients.

Background: Treatment nonadherence in people with schizophrenia is associated with relapse and homelessness. Building on the usefulness of long-acting medication and our work in psychosocial interventions to enhance adherence, we conducted a prospective uncontrolled trial of customized adherence enhancement (CAE) plus long-acting injectable antipsychotic (LAI) using haloperidol decanoate in 30 homeless or recently homeless individuals with DSM-IV-defined schizophrenia or schizoaffective disorder., Method: Participants received monthly CAE and LAI (CAE-L) for 6 months. Primary outcomes were adherence, as measured by the Tablets Routine Questionnaire, and housing status. Secondary outcomes included psychiatric symptoms, functioning, side effects, and hospitalizations. The study was conducted from July 2010 to December 2012., Results: The mean age of participants was 41.8 years (SD = 8.6); they were mainly minorities (90%, n = 27 African-American) and mainly single/never married (70%, n = 21). Most (97%, n = 29) had past or current substance abuse and had been incarcerated (97%, n = 29). Ten individuals (33%) terminated the study prematurely. CAE-L was associated with good adherence to LAI (at 6 months, 76%) and dramatic improvement in oral medication adherence, which changed from missing 46% of medication at study enrollment to missing only 10% at study end (P = .03). There were significant improvements in psychiatric symptoms (P < .001) and functioning (P < .001). Akathisia was a major side effect with LAI., Conclusions: While interpretation of findings must be tempered by the methodological limitations, CAE-L appears to be associated with improved adherence, symptoms, and functioning in homeless or recently homeless individuals with schizophrenia or schizoaffective disorder. Additional research is needed on effective and practical approaches to improving health outcomes for homeless people with serious mental illness., Trial Registration: ClinicalTrials.gov identifier: NCT01152697., (© Copyright 2013 Physicians Postgraduate Press, Inc.)

Aims To identify clinical factors associated with disability in depressed older adults with bipolar disorder (BPD) receiving lamotrigine. Methods Secondary analysis of a multi-site, 12-week, open-label, uncontrolled study of addon lamotrigine in 57 adults 60 years and older with BD I or II depression. Measures included the Montgomery Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS), Cumulative Illness Rating Scale for Geriatrics (CIRS-G), Dementia Rating Scale (DRS), and WHO-Disability Assessment Scale II (WHO-DAS II). Results Medical comorbidiy in this group of elders was substantial, with roughly 60% of subjects having disorders of the vascular, musculoskeletal/integument, and endodrine/metabolic/breast systems. We found significant relationships among mood (MADRS), medical comorbidity (CIRS-G), cognition (DRS), and disability (WHO-DAS II). More severe BPD depression, more medical comorbidity and more impaired cognition were all associated with lower functioning in BPD elders. Conclusions Our findings fit the paradigm shift that has been occurring in BPD, supporting the notion that BPD is not solely an illness of mood but that it affects multiple domains impacting overall functioning.