Central Texas Veterans Health Care System

Insulin resistance is a major underlying mechanism responsible for the 'metabolic syndrome', which is also known as insulin resistance syndrome. The incidence of the metabolic syndrome is increasing at an alarming rate, becoming a major public and clinical problem worldwide. The metabolic syndrome is represented by a group of interrelated disorders, including obesity, hyperglycemia, hyperlipidemia, and hypertension. It is also a significant risk factor for cardiovascular disease and increased morbidity and mortality. Animal studies have demonstrated that insulin and its signaling cascade normally control cell growth, metabolism, and survival through the activation of MAPKs and activation of phosphatidylinositide-3-kinase (PI3K), in which the activation of PI3K associated with insulin receptor substrate 1 (IRS1) and IRS2 and subsequent Akt→Foxo1 phosphorylation cascade has a central role in the control of nutrient homeostasis and organ survival. The inactivation of Akt and activation of Foxo1, through the suppression IRS1 and IRS2 in different organs following hyperinsulinemia, metabolic inflammation, and overnutrition, may act as the underlying mechanisms for the metabolic syndrome in humans. Targeting the IRS→Akt→Foxo1 signaling cascade will probably provide a strategy for therapeutic intervention in the treatment of type 2 diabetes and its complications. This review discusses the basis of insulin signaling, insulin resistance in different mouse models, and how a deficiency of insulin signaling components in different organs contributes to the features of the metabolic syndrome. Emphasis is placed on the role of IRS1, IRS2, and associated signaling pathways that are coupled to Akt and the forkhead/winged helix transcription factor Foxo1.

Ductular reaction (DR) is characterized by the proliferation of reactive bile ducts induced by liver injuries. DR is pathologically recognized as bile duct hyperplasia and is commonly observed in biliary disorders. It can also be identified in various liver disorders including nonalcoholic fatty liver disease. DR is associated with liver fibrosis and damage, and the extent of DR parallels to patient mortality. DR raises scientific interests because it is associated with transdifferentiation of liver cells and may play an important role in hepatic regeneration. The origin of active cells during DR can be cholangiocytes, hepatocytes, or hepatic progenitor cells, and associated signaling pathways could differ depending on the specific liver injury or animal models used in the study. Although further studies are needed to elucidate detailed mechanisms and the functional roles in liver diseases, DR can be a therapeutic target to inhibit liver fibrosis and to promote liver regeneration. This review summarizes previous studies of DR identified in patients and animal models as well as currently understood mechanisms of DR.

OBJECTIVE: The author 1) reassesses the case against a neuronal degeneration hypothesis for schizophrenia; 2) demonstrates that the hypothesis that schizophrenia is a disorder caused by early (i.e., pre- or perinatal) and static (i.e., fixed, nonprogressive) damage to the brain is unsatisfactory because it cannot readily account for brain imaging results from schizophrenic patients and lacks both satisfactory clinical examples and experimental models of early, static developmental disorders resulting in the late spontaneous functional deterioration that characterizes schizophrenia; and 3) offers an alternative pathogenetic hypothesis for schizophrenia that is consistent with the available imaging and neuropathological data. METHOD: Published data on schizophrenia and relevant clinical and experimental studies of neurodevelopment and its disorders are reviewed. RESULTS: The neuropathological studies provide strong evidence against a classic neurodegenerative pathogenesis of schizophrenia and moderate support for prenatal developmental abnormalities. The imaging data provide strong evidence that excessive brain volume loss occurs after maximum brain volume expansion and equivocal evidence that it continues after onset of overt illness. The available clinical and experimental models of late deterioration after static, early brain lesions are unconvincing. A progressive developmental mechanism can reconcile the neuropathological and imaging data, while being compatible with both early onset and late deterioration. CONCLUSIONS: It matters whether the pathogenetic agent in schizophrenia is static or progressive, since if it is the latter it is worthwhile to search not only for means of prevention but also for interventions that will arrest progression as early as possible.

Status epilepticus (SE), a medical emergency that is typically terminated through antiepileptic drug treatment, leads to hippocampus dysfunction typified by neurodegeneration, inflammation, altered neurogenesis, as well as cognitive and memory deficits. Here, we examined the effects of intranasal (IN) administration of extracellular vesicles (EVs) secreted from human bone marrow-derived mesenchymal stem cells (MSCs) on SE-induced adverse changes. The EVs used in this study are referred to as A1-exosomes because of their robust antiinflammatory properties. We subjected young mice to pilocarpine-induced SE for 2 h and then administered A1-exosomes or vehicle IN twice over 24 h. The A1-exosomes reached the hippocampus within 6 h of administration, and animals receiving them exhibited diminished loss of glutamatergic and GABAergic neurons and greatly reduced inflammation in the hippocampus. Moreover, the neuroprotective and antiinflammatory effects of A1-exosomes were coupled with long-term preservation of normal hippocampal neurogenesis and cognitive and memory function, in contrast to waned and abnormal neurogenesis, persistent inflammation, and functional deficits in animals receiving vehicle. These results provide evidence that IN administration of A1-exosomes is efficient for minimizing the adverse effects of SE in the hippocampus and preventing SE-induced cognitive and memory impairments.

The COVID-19 pandemic has altered mental health care delivery like no other event in modern history. The purpose of this study was to document the magnitude of that effect by examining (a) the amount of psychologists' telepsychology use before the COVID-19 pandemic, during the pandemic, and anticipated use after the pandemic; as well as (b) the demographic, training, policy, and clinical practice predictors of these changes. This study used a cross-sectional, national online design to recruit 2,619 licensed psychologists practicing in the United States. Prior to the COVID-19 pandemic, psychologists performed 7.07% of their clinical work with telepsychology, which increased 12-fold to 85.53% during the pandemic, with 67.32% of psychologists conducting all of their clinical work with telepsychology. Psychologists projected that they would perform 34.96% of their clinical work via telepsychology after the pandemic. Psychologists working in outpatient treatment facilities reported over a 26-fold increase in telepsychology use during the pandemic, while those in Veterans Affairs medical centers only reported a sevenfold increase. A larger increase in percentage telepsychology use occurred in women, in psychologists who reported an increase in telepsychology training and supportive organizational telepsychology policies, and in psychologists who treated relationship issues, anxiety, and women's issues. The lowest increases in percentage telepsychology use were reported by psychologists working in rural areas, treating antisocial personality disorder, performing testing and evaluation, and treating rehabilitation populations. Although there was a remarkable increase in telepsychology use during the COVID-19 pandemic, individual and practice characteristics affected psychologists' ability to adopt telepsychology. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A great deal of emphasis, clinical and financial, is placed on limb salvage efforts in diabetic patients suffering from lower extremity ulceration. This is because of the impression that amputation in such patients may be a proximal cause of death. While amputation is certainly a negative clinical outcome, it is not entirely clear that it causes death. In this systematic review, we examine the available literature to attempt to understand the role that the ulceration itself may play in mortality. In brief, we searched for human studies in OVID, CINAHL and the COCHRANE CENTRAL DATABASE from 1980 to 2013, looking for articles related to ulcer or wound of the foot, in patients with diabetes or peripheral vascular disease, and death. We looked for articles with 5 years of follow-up, or Kaplan-Meier estimates of 5-year mortality, and excluded reviews and letters. Articles were assessed for quality and potential bias using the Newcastle-Ottawa scale. We find that while the patient populations studied varied widely in terms of demographics and comorbidities, limiting generalisability, 5-year mortality rates after ulceration were around 40%. Risk factors for death commonly identified were increased age, male gender, peripheral vascular disease and renal disease.

Epithelial-mesenchymal transitions (EMTs) play an important role in tissue construction during embryogenesis, and evidence suggests that this process may also help to remodel some adult tissues after injury. Activation of the hedgehog (Hh) signaling pathway regulates EMT during development. This pathway is also induced by chronic biliary injury, a condition in which EMT has been suggested to have a role. We evaluated the hypothesis that Hh signaling promotes EMT in adult bile ductular cells (cholangiocytes). In liver sections from patients with chronic biliary injury and in primary cholangiocytes isolated from rats that had undergone bile duct ligation (BDL), an experimental model of biliary fibrosis, EMT was localized to cholangiocytes with Hh pathway activity. Relief of ductal obstruction in BDL rats reduced Hh pathway activity, EMT, and biliary fibrosis. In mouse cholangiocytes, coculture with myofibroblastic hepatic stellate cells, a source of soluble Hh ligands, promoted EMT and cell migration. Addition of Hh-neutralizing antibodies to cocultures blocked these effects. Finally, we found that EMT responses to BDL were enhanced in patched-deficient mice, which display excessive activation of the Hh pathway. Together, these data suggest that activation of Hh signaling promotes EMT and contributes to the evolution of biliary fibrosis during chronic cholestasis.

OBJECTIVE: Many of the effects of angiotensin (Ang) II are mediated through specific plasma membrane receptors. However, Ang II also elicits biological effects from the interior of the cell (intracrine), some of which are not inhibited by Ang receptor blockers (ARBs). Recent in vitro studies have identified high glucose as a potent stimulus for the intracellular synthesis of Ang II, the production of which is mainly chymase dependent. In the present study, we determined whether hyperglycemia activates the cardiac intracellular renin-Ang system (RAS) in vivo and whether ARBs, ACE, or renin inhibitors block synthesis and effects of intracellular Ang II (iAng II). RESEARCH DESIGN AND METHODS: Diabetes was induced in adult male rats by streptozotocin. Diabetic rats were treated with insulin, candesartan (ARB), benazepril (ACE inhibitor), or aliskiren (renin inhibitor). RESULTS: One week of diabetes significantly increased iAng II levels in cardiac myocytes, which were not normalized by candesartan, suggesting that Ang II was synthesized intracellularly, not internalized through AT(1) receptor. Increased intracellular levels of Ang II, angiotensinogen, and renin were observed by confocal microscopy. iAng II synthesis was blocked by aliskiren but not by benazepril. Diabetes-induced superoxide production and cardiac fibrosis were partially inhibited by candesartan and benazepril, whereas aliskiren produced complete inhibition. Myocyte apoptosis was partially inhibited by all three agents. CONCLUSIONS: Diabetes activates the cardiac intracellular RAS, which increases oxidative stress and cardiac fibrosis. Renin inhibition has a more pronounced effect than ARBs and ACE inhibitors on these diabetes complications and may be clinically more efficacious.

BACKGROUND: Depression frequently occurs in combination with diabetes mellitus, adversely affecting the course of illness. OBJECTIVE: To determine whether enhancing care for depression improves affective and diabetic outcomes in older adults with diabetes and depression. DESIGN: Preplanned subgroup analysis of the Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) randomized, controlled trial. SETTING: 18 primary care clinics from 8 health care organizations in 5 states. PATIENTS: 1801 patients 60 years of age or older with depression; 417 had coexisting diabetes mellitus. INTERVENTION: A care manager offered education, problem-solving treatment, or support for antidepressant management by the patient's primary care physician; diabetes care was not specifically enhanced. MEASUREMENTS: Assessments at baseline and at 3, 6, and 12 months for depression, functional impairment, and diabetes self-care behaviors. Hemoglobin A(1c) levels were obtained for 293 patients at baseline and at 6 and 12 months. RESULTS: At 12 months, diabetic patients who were assigned to intervention had less severe depression (range, 0 to 4 on a checklist of 20 depression items; between-group difference, -0.43 [95% CI, -0.57 to -0.29]; P < 0.001) and greater improvement in overall functioning (range, 0 [none] to 10 [unable to perform activities]; between-group difference, -0.89 [CI, -1.46 to -0.32]) than did participants who received usual care. In the intervention group, weekly exercise days increased (between-group difference, 0.50 day [CI, 0.12 to 0.89 day]; P = 0.001); other self-care behaviors were not affected. At baseline, mean (+/-SD) hemoglobin A1c levels were 7.28% +/- 1.43%; follow-up values were unaffected by the intervention (P > 0.2). LIMITATIONS: Because patients had good glycemic control at baseline, power to detect small but clinically important improvements in glycemic control was limited. CONCLUSIONS: Collaborative care improves affective and functional status in older patients with depression and diabetes; however, among patients with good glycemic control, such care minimally affects diabetes-specific outcomes.

Livers are comprised of maturational lineages of cells beginning extrahepatically in the hepato-pancreatic common duct near the duodenum and intrahepatically in zone 1 by the portal triads. The extrahepatic stem cell niches are the peribiliary glands deep within the walls of the bile ducts; those intrahepatically are the canals of Hering in postnatal livers and that derive from ductal plates in fetal livers. Intrahepatically, there are at least eight maturational lineage stages from the stem cells in zone 1 (periportal), through the midacinar region (zone 2), to the most mature cells and apoptotic cells found pericentrally in zone 3. Those found in the biliary tree are still being defined. Parenchymal cells are closely associated with lineages of mesenchymal cells, and their maturation is coordinated. Each lineage stage consists of parenchymal and mesenchymal cell partners distinguishable by their morphology, ploidy, antigens, biochemical traits, gene expression, and ability to divide. They are governed by changes in chromatin (e.g., methylation), gradients of paracrine signals (soluble factors and insoluble extracellular matrix components), mechanical forces, and feedback loop signals derived from late lineage cells. Feedback loop signals, secreted by late lineage stage cells into bile, flow back to the periportal area and regulate the stem cells and other early lineage stage cells in mechanisms dictating the size of the liver mass. Recognition of maturational lineage biology and its regulation by these multiple mechanisms offers new understandings of liver biology, pathologies, and strategies for regenerative medicine and treatment of liver cancers.

Previously, we reported that chronic stroke subjects had significant improvements in isometric strength, free reaching extent, and clinical evaluations of function after training in the mirror-image movement enabler (MIME) robotic device. Our primary goal in this analysis was to investigate the hypothesis that the robotic training promoted improved muscle activation patterns. To this end, we examined the interaction forces, kinematics, and electromyograms recorded during training of eight different movement patterns in active-constrained mode. In this mode, the robot constrained the reaching movements to be toward the target, and the movement velocity was proportional to the force produced along the trajectory. Thirteen chronic stroke subjects trained in MIME for 24 1-h sessions over an eight-week period. Work output was significantly increased by week five in all eight movement patterns. Low-level subjects increased their extent of reach, while high-level subjects increased their speed. Directional errors in force production were reduced in six of eight movement patterns. Electromyographic data provided evidence for improved muscle activation patterns in the four movement patterns that started at tabletop level and ended at shoulder level. In contrast, there was no evidence of improved muscle activation patterns in any of the tabletop movements, with increased activation of antagonists in two movement patterns. This dichotomy may have been related to compensation at the shoulder girdle during movements that remained at tabletop level. A simple biomechanical model will be introduced to demonstrate the likelihood of this possibility.

PURPOSE: This article is a descriptive analysis of rural nurses' perceived readiness to manage disaster situations. DESIGN AND METHODS: The 58-item Disaster Readiness Questionnaire was used to survey hospital-based nurses from rural communities in Texas during the summer of 2011. The data were collected by emailing a link through the various hospital intranet sites, resulting in a sample size of 620 nurses. RESULTS: Findings revealed that most nurses are not confident in their abilities to respond to major disaster events. The nurses who were confident were more likely to have had actual prior experience in disasters or shelters. Self-regulation of behavior (motivation) was a significant predictor of perceived nurse competence to manage disasters only in regard to the nurse's willingness to assume the risk of involvement in a disaster situation. Healthcare climate (job satisfaction) was not a determinant of disaster preparedness. CONCLUSIONS: Global increases in natural and human-induced disasters have called attention to the part that health providers play in mitigation and recovery. Since nurses are involved in planning, mitigation, response, and recovery aspects of disasters, they should actively seek opportunities to participate in actual disaster events, mock drills, and further educational opportunities specific to disaster preparedness. Administrators must support and encourage disaster preparedness education of nurses to promote hospital readiness to provide community care delivery in the event of a disaster situation. CLINICAL RELEVANCE: Nursing comprises the largest healthcare workforce, and yet there is very little research examining nurses' readiness for disaster.

The morbidity and mortality from chronic biliary diseases (i.e., the cholangiopathies) remains substantial. End-stage liver disease from biliary causes of cirrhosis (e.g., primary biliary cirrhosis [PBC], and primary sclerosing cholangitis) account for approximately one third of patients referred for liver transplantation. A single-topic conference sponsored by the American Association for the Studies of Liver Diseases entitled "The Pathobiology of Biliary Epithelia" brought together investigators to review the status of the field of cholangiocyte pathobiology, identify new areas of interest, and propose future directions. This information was presented in 6 sessions: "Structural and Functional Characteristics of the Bile Duct System," "Biological Topics from Nonbiliary Epithelia," "Malignant Transformation of Cholangiocytes," "Cholangiocyte Proliferation and Death," "Transport Mechanisms in Bile Duct Epithelia," and "Pathobiology of Biliary Epithelia." In the 7 years since the first symposium on this topic, major advances have been made in our understanding of ductal bile formation, including, greater insight into the hormones, intracellular signaling mechanisms, and effector proteins responsible for bile secretion and absorption. More sophisticated imaging technologies have increased our understanding of the polarity of cholangiocytes, their embryology and ultrastructural anatomy, and in vivo human secretory responses to current medical therapy. Information on mediators of inflammation permeated many sessions, having potentially important roles in malignant transformation of cholangiocytes, cholangiocyte apoptosis, fluid and electrolyte transport, and have begun to be specifically characterized for certain biliary diseases, e.g., acquired immunodeficiency syndrome (AIDS) cholangiopathy and graft-versus-host disease (GVHD).

PURPOSE: Participatory decision making (PDM) is associated with improved diabetes control. We examine a causal model linking PDM to improved clinical outcomes that included patient activation and medication adherence. METHODS: This observational study was conducted in 5 family physician offices. Diabetic patients were recruited by mail and by completing a study interest card at the conclusion of their office visit. Two survey questionnaires, administered 12 months apart, elicited patients' ratings of their physician's PDM style at baseline and their level of activation and medication adherence both at baseline and at follow-up. Measures of glycated hemoglobin (hemoglobin A(1c)), systolic blood pressure, and low-density lipoprotein (LDL) cholesterol were abstracted from the medical record starting 12 months before the baseline survey to 12 months after the follow-up survey. A path analysis using a structural equation model was used to test hypotheses. RESULTS: We mailed questionnaires to 236 participants; 166 (70%) returned the baseline questionnaire, and 141 (80%) returned the follow-up questionnaire. Hemoglobin A(1c) levels, systolic blood pressure, and LDL cholesterol values all declined significantly, and patient activation and medication adherence improved. PDM at baseline was associated with patient activation at follow-up. Patient activation at follow-up was associated with medication adherence at follow-up, and medication adherence at follow-up was associated with change in hemoglobin A(1c) levels and LDL cholesterol values but not with systolic blood pressure. CONCLUSIONS: Participatory decision making during primary care encounters by patients with type 2 diabetes resulted in improvements in hemoglobin A(1c) levels and LDL cholesterol values by improving patient activation, which in turn improved medication adherence.

This paper presents the design, control and performance of a high fidelity four degree-of-freedom wrist exoskeleton robot, RiceWrist, for training and rehabilitation. The RiceWrist is intended to provide kinesthetic feedback during the training of motor skills or rehabilitation of reaching movements. Motivation for such applications is based on findings that show robot-assisted physical therapy aids in the rehabilitation process following neurological injuries. The exoskeleton device accommodates forearm supination and pronation, wrist flexion and extension and radial and ulnar deviation in a compact parallel mechanism design with low friction, zero backlash and high stiffness. As compared to other exoskeleton devices, the RiceWrist allows easy measurement of human joint angles and independent kinesthetic feedback to individual human joints. In this paper, joint-space as well as task-space position controllers and an impedance-based force controller for the device are presented. The kinematic performance of the device is characterized in terms of its workspace, singularities, manipulability, backlash and backdrivability. The dynamic performance of RiceWrist is characterized in terms of motor torque output, joint friction, step responses, behavior under closed loop set-point and trajectory tracking control and display of virtual walls. The device is singularity-free, encompasses most of the natural workspace of the human joints and exhibits low friction, zero-backlash and high manipulability, which are kinematic properties that characterize a high-quality impedance display device. In addition, the device displays fast, accurate response under position control that matches human actuation bandwidth and the capability to display sufficiently hard contact with little coupling between controlled degrees-of-freedom.

BACKGROUND: Cysteinyl leukotrienes are important proinflammatory mediators believed to have a role in allergic rhinitis. OBJECTIVE: This multicentre, randomized, double-blind, placebo- and active-controlled trial evaluated the effectiveness and tolerability of montelukast, a cysteinyl leukotriene receptor antagonist, for treating patients with seasonal allergic rhinitis. METHODS: After a 3- to 5-day, single-blind placebo run-in period, 1302 male and female patients (aged 15-81 years) with active allergic rhinitis symptoms were randomly assigned to receive montelukast 10 mg (n = 348), loratadine 10 mg (n = 602), or placebo (n = 352) administered once daily at bedtime for 2 weeks during the spring allergy season. RESULTS: Mean patient characteristics and symptom scores at baseline were similar for the three treatment groups. The primary end-point, daytime nasal symptoms score (mean of nasal congestion, rhinorrhea, nasal pruritus, and sneezing scores; 0-3 scale), improved from baseline during treatment by (least squares mean, 95% confidence interval) - 0.37 (- 0.43, - 0.31), - 0.47 (- 0.52, - 0.43), and - 0.24 (- 0.29, - 0.18) in the montelukast, loratadine, and placebo groups, respectively (P < or = 0.001 comparing each active treatment with placebo). Mean changes from baseline in all other diary-based scores, including night-time and eye symptom scores, were significantly greater for each active treatment than for placebo. The rhinoconjunctivitis quality of life overall score improved significantly with montelukast and with loratadine as compared with placebo. Montelukast and loratadine showed a safety profile comparable to that of placebo. CONCLUSION: Montelukast is well tolerated and provides improvements in daytime and night-time symptoms, as well as quality of life parameters, for patients with seasonal allergic rhinitis.

OBJECTIVE: To investigate if the widely publicized warnings in 2003 from the US Food and Drug Administration about a possible increased risk of suicidality with antidepressant use in young people were associated with changes in antidepressant use, suicide attempts, and completed suicides among young people. DESIGN: Quasi-experimental study assessing changes in outcomes after the warnings, controlling for pre-existing trends. SETTING: Automated healthcare claims data (2000-10) derived from the virtual data warehouse of 11 health plans in the US Mental Health Research Network. PARTICIPANTS: Study cohorts included adolescents (around 1.1 million), young adults (around 1.4 million), and adults (around 5 million). MAIN OUTCOME MEASURES: Rates of antidepressant dispensings, psychotropic drug poisonings (a validated proxy for suicide attempts), and completed suicides. RESULTS: Trends in antidepressant use and poisonings changed abruptly after the warnings. In the second year after the warnings, relative changes in antidepressant use were -31.0% (95% confidence interval -33.0% to -29.0%) among adolescents, -24.3% (-25.4% to -23.2%) among young adults, and -14.5% (-16.0% to -12.9%) among adults. These reflected absolute reductions of 696, 1216, and 1621 dispensings per 100,000 people among adolescents, young adults, and adults, respectively. Simultaneously, there were significant, relative increases in psychotropic drug poisonings in adolescents (21.7%, 95% confidence interval 4.9% to 38.5%) and young adults (33.7%, 26.9% to 40.4%) but not among adults (5.2%, -6.5% to 16.9%). These reflected absolute increases of 2 and 4 poisonings per 100,000 people among adolescents and young adults, respectively (approximately 77 additional poisonings in our cohort of 2.5 million young people). Completed suicides did not change for any age group. CONCLUSIONS: Safety warnings about antidepressants and widespread media coverage decreased antidepressant use, and there were simultaneous increases in suicide attempts among young people. It is essential to monitor and reduce possible unintended consequences of FDA warnings and media reporting.

OBJECTIVES: To examine patient preferences for incorporating religion and/or spirituality into therapy for anxiety or depression and examine the relations between patient preferences and religious and spiritual coping styles, beliefs and behaviors. METHOD: Participants (66 adults, 55 years or older, from earlier studies of cognitive-behavioral therapy for late-life anxiety and/or depression in primary care) completed these measures by telephone or in-person: Geriatric Anxiety Inventory, Client Attitudes Toward Spirituality in Therapy, Patient Interview, Brief Religious Coping, Religious Problem Solving Scale, Santa Clara Strength of Religious Faith, and Brief Multidimensional Measure of Religiousness and Spirituality. Spearman's rank-order correlations and ordinal logistic regression examined religious/spiritual variables as predictors of preferences for inclusion of religion or spirituality into counseling. RESULTS: Most participants (77-83%) preferred including religion and/or spirituality in therapy for anxiety and depression. Participants who thought it was important to include religion or spirituality in therapy reported more positive religious-based coping, greater strength of religious faith, and greater collaborative and less self-directed problem-solving styles than participants who did not think it was important. CONCLUSION: For individuals like most participants in this study (Christians), incorporating spirituality/religion into counseling for anxiety and depression was desirable.

PURPOSE: Recent results suggests the risk of a new onset of depression increases with longer duration of opioid analgesic use. It is unclear whether new-onset depression related to opioid analgesic use is a function of the dose prescribed or the duration of use or both. METHODS: Using a retrospective cohort design, we collected patient data from 2000 to 2012 from the Veterans Health Administration (VHA), and from 2003 to 2012 from both Baylor Scott & White Health (BSWH) and the Henry Ford Health System (HFHS). Patients (70,997 VHA patients, 13,777 BSWH patients, and 22,981 HFHS patients) were new opioid users, aged 18 to 80 years, without a diagnosis of depression at baseline. Opioid analgesic use duration was defined as 1 to 30, 31 to 90, and more than 90 days, and morphine equivalent dose (MED) was defined as 1 to 50 mg/d, 51 to 100 mg/d, and greater than 100 mg/d of analgesic. Pain and other potential confounders were controlled for by inverse probability of treatment-weighted propensity scores. RESULTS: New-onset depression after opioid analgesic use occurred in 12% of the VHA sample, 9% of the BSWH sample, and 11% of the HFHS sample. Compared with 1- to 30-day users, new-onset depression increased in those with longer opioid analgesic use. Risk of new-onset depression with 31 to 90 days of opioid analgesic use ranged from hazard ratio [HR] = 1.18 (95% CI, 1.10-1.25) in VHA to HR = 1.33 (95% CI, 1.16-1.52) in HFHS; in opioid analgesic use of more than 90 days, it ranged from HR = 1.35 (95% CI, 1.26-1.44) in VHA to HR = 2.05 (95% CI, 1.75-2.40) in HFHS. Dose was not significantly associated with a new onset of depression. CONCLUSIONS: Opioid-related new onset of depression is associated with longer duration of use but not dose. Patients and practitioners should be aware that opioid analgesic use of longer than 30 days imposes risk of new-onset depression. Opioid analgesic use, not just pain, should be considered a potential source when patients report depressed mood.

PURPOSE: The aim of this work is to provide evidence-based guidance on the management of osteoporosis in survivors of adult cancer. METHODS: ASCO convened a multidisciplinary Expert Panel to develop guideline recommendations based on a systematic review of the literature. RESULTS: The literature search of the 2018 systematic review by the US Preventive Services Task Force in the noncancer population was used as the evidentiary base upon which the Expert Panel based many of its recommendations. A total of 61 additional studies on topics and populations not covered in the US Preventive Services Task Force review were also included. Patients with cancer with metastatic disease and cancer survival outcomes related to bone-modifying agents are not included in this guideline. RECOMMENDATIONS: Patients with nonmetastatic cancer may be at risk for osteoporotic fractures due to baseline risks or due to the added risks that are associated with their cancer therapy. Clinicians are advised to assess fracture risk using established tools. For those patients with substantial risk of osteoporotic fracture, the clinician should obtain a bone mineral density test. The bone health of all patients may benefit from optimizing nutrition, exercise, and lifestyle. When a pharmacologic agent is indicated, bisphosphonates or denosumab at osteoporosis-indicated dosages are the preferred interventions.