Multi-scale cortical bone traits vary in females and males from two mouse models of genetic diversity.

Understanding the genetic basis of cortical bone traits can allow for the discovery of novel genes or biological pathways regulating bone health. Mice are the most widely used mammalian model for skeletal biology and allow for the quantification of traits that cannot easily be evaluated in humans, such as osteocyte lacunar morphology. The goal of our study was to investigate the effect of genetic diversity on multi-scale cortical bone traits of 3 long bones in skeletally-mature mice. We measured bone morphology, mechanical properties, material properties, lacunar morphology, and mineral composition of mouse bones from 2 populations of genetic diversity. Additionally, we compared how intrabone relationships varied in the 2 populations. Our first population of genetic diversity included 72 females and 72 males from the 8 inbred founder strains used to create the Diversity Outbred (DO) population. These 8 strains together span almost 90% of the genetic diversity found in mice (Mus musculus). Our second population of genetic diversity included 25 genetically unique, outbred females and 25 males from the DO population. We show that multi-scale cortical bone traits vary significantly with genetic background; heritability values range from 21% to 99% indicating genetic control of bone traits across length scales. We show for the first time that lacunar shape and number are highly heritable. Comparing the 2 populations of genetic diversity, we show that each DO mouse does not resemble a single inbred founder, but instead the outbred mice display hybrid phenotypes with the elimination of extreme values. Additionally, intrabone relationships (eg, ultimate force vs. cortical area) were mainly conserved in our 2 populations. Overall, this work supports future use of these genetically diverse populations to discover novel genes contributing to cortical bone traits, especially at the lacunar length scale.

Multi-Scale Cortical Bone Traits Vary in Two Mouse Models of Genetic Diversity.

Understanding the genetic basis of cortical bone traits can allow for the discovery of novel genes or biological pathways regulating bone health. Mice are the most widely used mammalian model for skeletal biology and allow for the quantification of traits that can't easily be evaluated in humans, such as osteocyte lacunar morphology. The goal of our study was to investigate the effect of genetic diversity on multi-scale cortical bone traits of three long bones in skeletally-mature mice. We measured bone morphology, mechanical properties, material properties, lacunar morphology, and mineral composition of mouse bones from two populations of genetic diversity. Additionally, we compared how intra-bone relationships varied in the two populations. Our first population of genetic diversity included 72 females and 72 males from the eight Inbred Founder strains used to create the Diversity Outbred (DO) population. These eight strains together span almost 90% of the genetic diversity found in mice (Mus musculus). Our second population of genetic diversity included 25 genetically unique, outbred females and 25 males from the DO population. We show that multi-scale cortical bone traits vary significantly with genetic background; heritability values range from 21% to 99% indicating genetic control of bone traits across length scales. We show for the first time that lacunar shape and number are highly heritable. Comparing the two populations of genetic diversity, we show each DO mouse does not resemble a single Inbred Founder but instead the outbred mice display hybrid phenotypes with the elimination of extreme values. Additionally, intra-bone relationships (e.g., ultimate force vs. cortical area) were mainly conserved in our two populations. Overall, this work supports future use of these genetically diverse populations to discover novel genes contributing to cortical bone traits, especially at the lacunar length scale.

Loading-induced bone formation is mediated by Wnt1 induction in osteoblast-lineage cells.

Mechanical loading on the skeleton stimulates bone formation. Although the exact mechanism underlying this process remains unknown, a growing body of evidence indicates that the Wnt signaling pathway is necessary for the skeletal response to loading. Recently, we showed that Wnts produced by osteoblast lineage cells mediate the osteo-anabolic response to tibial loading in adult mice. Here, we report that Wnt1 specifically plays a crucial role in mediating the mechano-adaptive response to loading. Independent of loading, short-term loss of Wnt1 in the Osx-lineage resulted in a decreased cortical bone area in the tibias of 5-month-old mice. In females, strain-matched loading enhanced periosteal bone formation in Wnt1F/F controls, but not in Wnt1F/F; OsxCreERT2 knockouts. In males, strain-matched loading increased periosteal bone formation in both control and knockout mice; however, the periosteal relative bone formation rate was 65% lower in Wnt1 knockouts versus controls. Together, these findings show that Wnt1 supports adult bone homeostasis and mediates the bone anabolic response to mechanical loading.

Implementation of Telehealth for Psychiatric Care in VA Emergency Departments and Urgent Care Clinics.

Objective: To conduct a mixed-methods evaluation of an emergency telehealth intervention in unscheduled settings (emergency department [ED] and urgent care clinic [UCC]) within the Veterans Health Administration (VHA). Materials and Methods: We used the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework to conduct a mixed-methods evaluation of a novel telehealth program implemented in the VHA (Hospital System) in March 2020. We compared the 3 months preimplementation (December 1, 2019 through February 29, 2020) with the 3 months postimplementation (April 1, 2020 through June 30, 2020), then followed sustainability through January 31, 2021. Qualitative data were obtained from surveys and semistructured interviews of staff and providers and analyzed with thematic analysis. Results: Patient demographics and dispositions were similar pre- and postimplementation. The telemental health intervention was used in 319 (83%) unscheduled mental health consultations in the postimplementation phase. After implementation, we did not detect adverse trends in length of stay, 7-day revisits, or 30-day mortality. Use remained high with 82% (n = 1,010) of all unscheduled mental health consultations performed by telemental health in the sustainability phase. Staff and clinician interviews identified the following themes in the use of telemental health: (1) enhanced efficiency without compromising quality and safety, (2) initial apprehension, (3) the COVID-19 pandemic, and (4) sustainability after resolution of the COVID-19 pandemic. Conclusions: This mixed-methods evaluation of unscheduled telemental health implementation found that its use was feasible, did not impact the safety and efficacy of mental health consultations, and was highly acceptable and sustainable in unscheduled settings.

Identifying and Addressing the Hidden Reasons Why Patients Refuse Discharge From the Hospital.

BACKGROUND: Consultation-liaison psychiatrists are often asked to evaluate patients who refuse discharge from a medical facility. Literature to guide clinicians on the management of these patients is very limited. OBJECTIVE: This article seeks to explain this phenomenon through a case series, provide a differential diagnosis of patients who request to stay in the hospital, as well as provide clinicians with direction in the management of these difficult situations. METHODS: We discuss a case series of 3 patients treated at a large academic medical center, who refused discharge, discuss potential differential diagnoses, and provide management recommendations to guide clinicians. DISCUSSION: Providing care for a patient who refuses discharge can present several dilemmas for the treatment provider. Additionally, patients who refuse discharge may face emotional, physical, and financial costs secondary to continued unnecessary medical hospitalization. A variety of psychiatric conditions may contribute to a patient׳s desire to stay in the hospital. CONCLUSIONS: Patients who refuse medical discharge can present unique challenges for hospital-based medical providers as well as consultation psychiatrists who care for these patients. Careful consideration of diagnostic etiologies as well as coordination of care across the treatment team may be required to manage these unique and challenging cases.

Readings on psychosomatic medicine: survey of resources for trainees.

BACKGROUND: As systems of care become more complex and comorbid medical and psychiatric illness becomes more evident, it is essential to prepare psychiatric trainees for practice in more integrated models of care. OBJECTIVE: We sought to identify readings available for residency training in consultation-liaison (C-L) psychiatry/psychosomatic medicine with the intent to help educators and trainees identify appropriate and essential learning resources within the field. METHODS: We reviewed readings available to the residents (including commonly used textbooks in C-L psychiatry and C-L training programs' required reading lists) and identified areas of consensus regarding the topics germane to the care of patients with comorbid medical and psychiatric illness (namely depression, dementia, and delirium) and the education of trainees. RESULTS: There was considerable variation in the references cited by well-regarded textbooks and by reading lists created for trainees in C-L psychiatry. In the 4 textbooks reviewed, there were 83 shared citations on delirium (including 10 citations that were common to all 4 textbooks and 17 citations shared by 3 textbooks). Markedly less overlap was noted in the chapters on depression (only 2 references cited in all of the textbooks with relevant content) and dementia (only 7 shared references). CONCLUSION: Given the paucity of overlap of citations in commonly used textbooks, we recommend that practical topical reviews or textbook chapters be used as core (required) or recommended readings for residents on C-L psychiatry rotations, supplemented by a small number of studies or case series that illustrate key teaching points on each essential topic.

Hepatotoxicity from antituberculous therapy in the elderly: a systematic review.

BACKGROUND: Elderly persons have the highest rates of tuberculosis (TB) in the United States compared to all other age groups. A systematic literature review was conducted to determine if older age was a risk factor for hepatotoxicity resulting from treatment with first-line drugs used to treat active (TB) and latent tuberculosis (LTBI). METHODS: A systematic review of MEDLINE, Cochrane Controlled Trial Registry, CINAHL(®), and Science Citation Index Expanded (from 1970 to 2011) was performed to determine the risk of hepatotoxicity, comparing those over 60 with those under 60. A meta-analysis was performed using a random effects model along with log odds ratios and the chi-square test. FINDINGS: Thirty-eight studies (40,034 participants; 1208 cases of hepatotoxicity) met the selection criteria. For active TB, an overall mean effect of 0.277 (p = 0.024, 95% CI: 0.037-0.517) was observed, which is equivalent to an odds ratio of 1.32 (95% CI: 1.04-1.68). For LTBI, an overall mean effect of 1.42 (p < 0.001, 95% CI: 0.794-2.05) was observed, which translates to an odds ratio of 4.14 (95% CI: 2.21-7.74). INTERPRETATION: Our analysis revealed that patients older than 60 had significantly more risk of hepatotoxicity. These studies suggest that a gentler regimen of treatment for older individuals could benefit health outcomes in this population of TB patients and minimize risks to the public's health.

Diagnosing delirium in older emergency department patients: validity and reliability of the delirium triage screen and the brief confusion assessment method.

STUDY OBJECTIVE: Delirium is a common form of acute brain dysfunction with prognostic significance. Health care professionals caring for older emergency department (ED) patients miss delirium in approximately 75% of cases. This error results from a lack of available measures that can be performed rapidly enough to be incorporated into clinical practice. Therefore, we developed and evaluated a novel 2-step approach to delirium surveillance for the ED. METHODS: This prospective observational study was conducted at an academic ED in patients aged 65 years or older. A research assistant and physician performed the Delirium Triage Screen (DTS), designed to be a highly sensitive rule-out test, and the Brief Confusion Assessment Method (bCAM), designed to be a highly specific rule-in test for delirium. The reference standard for delirium was a comprehensive psychiatrist assessment using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. All assessments were independently conducted within 3 hours of one another. Sensitivities, specificities, and likelihood ratios with their 95% confidence intervals (95% CIs) were calculated. RESULTS: Of 406 enrolled patients, 50 (12.3%) had delirium diagnosed by the psychiatrist reference standard. The DTS was 98.0% sensitive (95% CI 89.5% to 99.5%), with an expected specificity of approximately 55% for both raters. The DTS's negative likelihood ratio was 0.04 (95% CI 0.01 to 0.25) for both raters. As the complement, the bCAM had a specificity of 95.8% (95% CI 93.2% to 97.4%) and 96.9% (95% CI 94.6% to 98.3%) and a sensitivity of 84.0% (95% CI 71.5% to 91.7%) and 78.0% (95% CI 64.8% to 87.2%) when performed by the physician and research assistant, respectively. The positive likelihood ratios for the bCAM were 19.9 (95% CI 12.0 to 33.2) and 25.2 (95% CI 13.9 to 46.0), respectively. If the research assistant DTS was followed by the physician bCAM, the sensitivity of this combination was 84.0% (95% CI 71.5% to 91.7%) and specificity was 95.8% (95% CI 93.2% to 97.4%). If the research assistant performed both the DTS and bCAM, this combination was 78.0% sensitive (95% CI 64.8% to 87.2%) and 97.2% specific (95% CI 94.9% to 98.5%). If the physician performed both the DTS and bCAM, this combination was 82.0% sensitive (95% CI 69.2% to 90.2%) and 95.8% specific (95% CI 93.2% to 97.4%). CONCLUSION: In older ED patients, this 2-step approach (highly sensitive DTS followed by highly specific bCAM) may enable health care professionals, regardless of clinical background, to efficiently screen for delirium. Larger, multicenter trials are needed to confirm these findings and to determine the effect of these assessments on delirium recognition in the ED.

Antidepressant drugs.

Therapeutic Reviews aim to provide essential independent information for health professionals about drugs used in palliative and hospice care. Additional content is available on www.palliativedrugs.com. Country-specific books (Hospice and Palliative Care Formulary USA, and Palliative Care Formulary, British and Canadian editions) are also available and can be ordered from www.palliativedrugs.com. The series editors welcome feedback on the articles (hq@palliativedrugs.com).

Delirium in patients with head and neck cancer in the outpatient treatment setting.

PURPOSE: Delirium is a common neurocognitive disorder among patients with cancer. In patients with head and neck cancer, delirium has been examined in the postoperative setting. Because no studies have reported on delirium during outpatient cancer treatment, we conducted a prospective study in 69 patients with head and neck cancer to examine neurocognitive function before, during, and after outpatient treatment. We also conducted a retrospective study in a subset of caregivers. In this paper, we report the prevalence and incidence of delirium and subsyndromal delirium (SSD) during outpatient treatment. METHODS: Assessments were conducted before treatment, at scheduled treatment visits, and at a 3-month post-treatment visit. Delirium and SSD were assessed using the Confusion Assessment Method (CAM). Following treatment, we retrospectively asked patients (n = 58) and a subset of caregivers (n = 23) whether patients experienced delirium during treatment. RESULTS: Based on CAM assessments at scheduled treatment visits, six patients (8.6%) developed delirium during treatment. Additionally, 31% of patients and 43.5% of caregivers retrospectively reported delirium. The prevalence and incidence of SSD were 7.2% and 45.3%, respectively. CONCLUSIONS: These data suggest that delirium and SSD are frequent in patients with head and neck cancer undergoing outpatient treatment. Delirium was often associated with medical complications. The potential impact of delirium and SSD on treatment outcomes, recovery, and caregiving are significant clinical concerns.

Anti-epileptic drugs.

Therapeutic Reviews aim to provide essential independent information for health professionals about drugs used in palliative and hospice care. Additional content is available on www.palliativedrugs.com. Country-specific books (Hospice and Palliative Care Formulary USA, and Palliative Care Formulary, British and Canadian editions) are also available and can be ordered from www.palliativedrugs.com. The series editors welcome feedback on the articles (hq@palliativedrugs.com).

An approach to the patient with organ failure: transplantation and end-of-life treatment decisions.

Organ transplantation offers an opportunity for extended survival and enhanced quality of life to patients with end-stage organ disease. Significant challenges are associated with both pre- and post-transplantation care, however, that require awareness of psychiatric issues in this patient population. Ventricular assist devices have added another dimension to patient care and to quality-of-life considerations. Unfortunately, effective incorporation of palliative care and end-of-life discussions is frequently overlooked during caretaking of these patients.

Legacy activities as interventions approaching the end of life.

We examined the efficacy of an innovative family-based intervention designed to decrease caregiving stress and increase family communication among individuals with chronic, life-limiting illnesses and their family caregivers in a randomized, contact control group design. The intervention group received three home visits in which the interventionist actively worked with the family to construct a personal Legacy, usually a scrapbook with photographs or audiotaped stories. Control group families received three supportive telephone calls. Of the 42 families that entered the project, 31 families completed follow-up assessments within 9 to 10 weeks (14 control; 17 intervention; 72% African American) for a retention rate of 74%. Intervention caregivers showed reduced caregiving stress in comparison with control group caregivers, who showed increases in stress. Intervention patients reported decreased breathing difficulty and increased religious meaning. Caregivers and patients reported greater social interaction on the part of the patient. All participants in the intervention group initiated a Legacy activity and reported that Legacy improved family communication. Legacy interventions hold promise and are simple to implement.

Interest in research participation among hospice patients, caregivers, and ambulatory senior citizens: practical barriers or ethical constraints?

OBJECTIVES: The purpose of this survey study was to explore hypothetical interest in research participation among hospice patients and caregivers compared to ambulatory senior citizens. DESIGN: Cross-sectional survey. SETTING: Twenty-one community-based hospice offices, a university medical center geriatric ambulatory care clinic, and 3 community-based senior citizen centers. PARTICIPANTS: Participants were hospice patients, caregivers, and ambulatory senior citizens not enrolled in hospice. MEASUREMENTS: Using a self-administered questionnaire, participants rated their interest in participating in survey/interview and therapeutic studies, identified potential benefits and barriers to research participation, and reported their preferences for who they would want to approach them about research participation. RESULTS: Forty-six percent of hospice patients and 60% of caregivers reported an interest in interview or survey research participation; 45% and 57%, respectively, expressed interest in therapeutic research. Compared to hospice patients, caregivers reported higher rates of personal interest in both survey research (p =< 0.001) and therapeutic research (p=<0.001) and were more likely to report that the hospice patients they cared for would be interested (p = 0.005 and p = 0.027). Younger hospice patients were more favorably disposed toward both survey and therapeutic research participation than hospice patients over the age of 75 (p = 0.063 and 0.011). The proportion of older hospice patients showing interest in research did not differ significantly from ambulatory senior citizens for either type of research (p = 0.56, 0.98). CONCLUSION: This study suggests that many hospice patients are interested in research participation and are able to articulate benefits and barriers, which supports the inclusion of this population in research.