FRAX without BMD can be used to risk-stratify Veterans who recently sustained a low trauma non-vertebral/non-hip fracture.

We evaluated the fracture risk assessment tool (FRAX) without bone mineral density (BMD) in predicting treatment recommendations for patients with a recent low trauma fracture other than hip or vertebral. The concordance, sensitivity, and specificity were 75.6%, 67.3%, and 78.2%, respectively. FRAX without BMD can be used after a fracture to expedite treatment. INTRODUCTION: The objective of this study was to evaluate the performance of the fracture risk assessment tool (FRAX) without bone mineral density (BMD) in predicting treatment recommendations for patients who recently sustained a low trauma fracture other than hip or vertebral. METHODS: We utilized a clinical database established by the Fracture Liaison Service at the Durham Veterans Affairs Medical Center to identify male and female Veterans age ≥ 50 years who sustained a low trauma non-hip/non-vertebral fracture and underwent dual-energy x-ray absorptiometry (DXA) between October 2013 and April 2018. FRAX without BMD (FRAX-BMI) and FRAX with BMD (FRAX-BMD) were calculated for the 229 patients identified, and whether or not they met the National Osteoporosis Foundation (NOF) guideline treatment thresholds was compared. RESULTS: There were 55 (24.0%) patients that met criteria for treatment based on NOF guideline established FRAX-BMD thresholds including 27 (11.8%) patients with osteoporosis by DXA. The concordance of FRAX-BMI in predicting treatment recommendations was 75.6% with a sensitivity of 67.3% and a specificity of 78.2%. The area under the curve (AUC) of FRAX-BMI hip fracture risk was 0.79. Assessment/treatment thresholds for hip fracture risk of 1% < FRAX-BMI < 4% were proposed to maximize sensitivity and specificity. CONCLUSION: Among patients who sustained a low trauma non-hip/non-vertebral fracture, FRAX-BMI can be used to stratify risk and identify high-risk patients who could be treated without DXA, low-risk patients who may not need treatment, and intermediate-risk patients to undergo DXA testing.

Influence of personality traits on college women's appraisals of intimate partner violence.

Intimate partner violence (IPV) is a common traumatic stressor for young adult women and results in a number of problems for those who experience it. The appraisals women make of IPV influence the degree of distress they experience in the aftermath of IPV. Research suggests that personality traits may influence IPV appraisals, although there are relatively few studies of this. In this study, we examine the association between Five Factor Model personality traits (i.e., Agreeableness, Conscientiousness, Extraversion, Neuroticism, and Openness) and appraisals of IPV in a sample of young adult women in college who experienced IPV (N = 241) using a Bayesian approach to multiple regression. Results suggest that Agreeableness, Extraversion, and Neuroticism predicted different styles of appraisals over and above the effect of IPV severity. Study findings clarify previous research on the role of personality traits in the response to IPV and suggest directions for future research.

AZD3514, an oral selective androgen receptor down-regulator in patients with castration-resistant prostate cancer - results of two parallel first-in-human phase I studies.

BACKGROUND: AZD3514 is a first-in-class, orally bio-available, androgen-dependent and -independent androgen receptor inhibitor and selective androgen-receptor down-regulator (SARD). METHODS: In study 1 and 2, castration-resistant prostate cancer (CRPC) patients (pts) were initially recruited into a once daily (QD) oral schedule (A). In study 1, pharmacokinetic assessments led to twice daily (BID) dosing (schedule B) to increase exposure. Study 2 explored a once daily schedule. RESULTS: In study 1, 49 pts were treated with escalating doses of AZD3514 (A 35 pts, B 14 pts). Starting doses were 100 mg (A) and 1000 mg (B). The AZD3514 formulation was switched from capsules to tablets at 1000 mg QD. 2000 mg BID was considered non-tolerable due to grade (G) 2 toxicities (nausea [N], vomiting [V]). No adverse events (AEs) met the dose-limiting toxicity (DLT) definition. Thirteen pts received AZD3514 in study 2, with starting doses of 250 mg QD. The most frequent drug-related AEs were N: G1/2 in 55/70 pts (79 %); G3 in 1 pt (1.4 %); & V: G1/2 in 34/70 pts (49 %) & G3 in 1 pt (1.4 %). PSA declines (≥50 %) were documented in 9/70 patients (13 %). Objective soft tissue responses per RECIST1.1 were observed in 4/24 (17 %) pts in study 1. CONCLUSION: AZD3514 has moderate anti-tumour activity in pts with advanced CRPC but with significant levels of nausea and vomiting. However, anti-tumour activity as judged by significant PSA declines, objective responses and durable disease stabilisations, provides the rationale for future development of SARD compounds.

Influence of maladaptive personality traits on women's posttraumatic cognitions of IPV.

OBJECTIVE: Intimate partner violence (IPV) is a problem for women worldwide. One factor that affects the severity of women's distress in the aftermath of IPV is how they make meaning of the violence they experienced. Posttraumatic meaning-making takes the form of 3 distinct posttraumatic cognitions: self-blame, other negative thoughts about oneself, and negative thoughts about the world. Women's posttraumatic cognitions in the aftermath of IPV are in part a function of personality. Research on personality and posttraumatic cognitions has focused primarily on the influence of normative personality traits, although maladaptive personality traits are more common in clinical assessment. One of the most common models of maladaptive traits is DSM-5's Alternative Model of Personality Disorder (AMPD), which contains 5 maladaptive variants of normative personality traits (Antagonism, Detachment, Disinhibition, Negative Affect, and Psychoticism). Although there is increasing research on the AMPD traits in general, there is limited research on the influence of these traits on women's response to IPV specifically. METHOD: In this study we examine the association between AMPD traits and posttraumatic cognitions of IPV in a sample of women exposed to IPV (N = 199) using a Bayesian approach to multiple regressions. RESULTS: Results suggest that IPV and Negative Affect were the primary influences on all 3 IPV-related posttraumatic cognitions and that other traits had differential effects depending on the type of posttraumatic cognition under analysis. CONCLUSIONS: These findings clarify our understanding of individual differences in posttraumatic response and have implications for the treatment of women exposed to IPV. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A pilot study to explore circulating tumour cells in pancreatic cancer as a novel biomarker.

BACKGROUND: Obtaining tissue for pancreatic carcinoma diagnosis and biomarker assessment to aid drug development is challenging. Circulating tumour cells (CTCs) may represent a potential biomarker to address these unmet needs. We compared prospectively the utility of two platforms for CTC enumeration and characterisation in pancreatic cancer patients in a pilot exploratory study. PATIENTS AND METHODS: Blood samples were obtained prospectively from 54 consenting patients and analysed by CellSearch and isolation by size of epithelial tumour cells (ISET). CellSearch exploits immunomagnetic capture of CTCs-expressing epithelial markers, whereas ISET is a marker independent, blood filtration device. Circulating tumour cell expression of epithelial and mesenchymal markers was assessed to explore any discrepancy in CTC number between the two platforms. RESULTS: ISET detected CTCs in more patients than CellSearch (93% vs 40%) and in higher numbers (median CTCs/7.5 ml, 9 (range 0-240) vs 0 (range 0-144)). Heterogeneity observed for epithelial cell adhesion molecule, pan-cytokeratin (CK), E-Cadherin, Vimentin and CK 7 expression in CTCs may account for discrepancy in CTC number between platforms. CONCLUSION: ISET detects more CTCs than CellSearch and offers flexible CTC characterisation with potential to investigate CTC biology and develop biomarkers for pancreatic cancer patient management.

Association Between Intimate Partner Violence Subtypes and Post-traumatic Stress Disorder Symptoms and Hazardous Substance Use.

Intimate partner violence (IPV) is a common problem for women in the United States and is associated with symptoms of post-traumatic stress disorder (PTSD) as well as hazardous use of substances like alcohol and drugs. However, not all subtypes of IPV (i.e., physical, sexual, and psychological) are equally predictive of PTSD and hazardous substance use. Although previous research suggests that psychological IPV has the strongest relative effect on PTSD symptoms and substance use, there is less research on IPV subtypes' cumulative effects. In this study, we examined the relative and cumulative effects of physical, sexual, and psychological IPV on PTSD symptoms and hazardous substance use in a sample of women in the United States recruited via Amazon's Mechanical Turk (N = 793) using bootstrapped multiple regression and configural frequency analyses. Results suggest that physical IPV had the most pronounced influence (medium-large effect sizes) on substance use across women, but that the cumulative effects of all three IPV subtypes were most closely associated with diagnostic levels of both PTSD and substance use at the level of groups of women. These findings clarify and extend previous research on the differential effects of IPV subtypes and provide directions for future research and clinical intervention.

Association of knee and ankle osteoarthritis with physical performance.

OBJECTIVE: The direct measurement of the ability to perform physical tasks yields information about factors contributing to poor function and insights into strategies for preventing disability. Our goal was to evaluate the relationship of walking speed and balance tests with specific radiographic features of knee and ankle osteoarthritis (OA). METHODS: A timed eight foot walk and a standing balance test were performed by 138 participants of a longitudinal observational study of knee OA progression. Radiographic features of OA severity, joint space narrowing (JSN), a surrogate for cartilage loss and osteophyte (OST) formation, were assessed for the knee and ankle. The association of these performance measures with radiographic OA was evaluated using correlation analysis, adjusted for age, gender, body mass index (BMI), and number of comorbidities. RESULTS: Knee and ankle JSN, but not OST, was negatively associated with specific performance tests: walking speed was associated with knee JSN (Spearman rho = -0.20, P = 0.02) and balance was associated with ankle (subtalar joint) JSN (Spearman rho = -0.22, P = 0.01). These relationships remained significant upon further control for knee and ankle pain. CONCLUSIONS: Structural joint damage due to OA (JSN in contrast to OST) negatively impacted specific domains of physical performance. These results indicate that targeting specific joints for specific functional outcomes may be indicated, and suggest that prevention of cartilage damage in these joints is a sensible target for OA disease modification to prevent disability.

Incremental effects of betrayal trauma and borderline personality disorder symptoms on suicide risk.

OBJECTIVE: Suicide is a problem on college campuses. One of the strongest predictors of suicide risk is symptoms of borderline personality disorder (BPD). Additional factors, such as trauma, also increase risk for suicide. One type of trauma that is especially insidious is 1 in which people are betrayed by others on whom they depend for support or protection (betrayal traumas). However, there is little research on the incremental effects of BPD symptoms and trauma with varying degrees of betrayal on suicide risk. METHOD: In this study, we examined the relative effects of BPD symptoms and traumatic experiences with varying degrees of betrayal on suicide risk in a sample of college students (N = 915) using a Bayesian approach to multiple linear regression. RESULTS: Results suggest that BPD symptoms and traumas with high and medium degrees of betrayal have incremental effects on suicide risk, although this effect differs by sex. CONCLUSION: These findings highlight the utility of assessing history of trauma over and above BPD symptoms in the prediction of suicide risk and have implications for future research and clinical intervention. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Is diabetes associated with poorer self-efficacy and motivation for physical activity in older adults with arthritis?

OBJECTIVES: The primary aim was to explore whether arthritis is associated with poorer self-efficacy and motivation for, and participation in, two specific types of physical activity (PA): endurance training (ET) and strength training (ST). A further objective was to determine whether the added burden of diabetes contributes to a further reduction in these PA determinants and types. METHODS: Self-efficacy and motivation for exercise and minutes per week of ET and ST were measured in 347 older veterans enrolled in a home-based PA counselling intervention. Regression analyses were used to compare high versus low self-efficacy and motivation and PA minutes in persons without arthritis, with arthritis alone, and with arthritis plus diabetes. RESULTS: Persons with arthritis alone reported lower self-efficacy for ET and ST than those without arthritis [odds ratio (OR)ET 0.71, 95% confidence interval (CI) 0.39­1.20; ORST 0.69, 95% CI 0.39­1.20]. A further reduction in self-efficacy for these two types of PA was observed for those with both arthritis and diabetes (ORET 0.65, 95% CI 0.44­0.92; ORST 0.64, 95% CI 0.44­0.93; trend p < 0.001). There was no trend towards a reduction in motivation for PA in those with arthritis alone or with arthritis and diabetes. Persons with arthritis exhibited higher motivation for ET than those without arthritis (ORET 1.85, 95% CI 1.12­3.33). There were no significant differences between the three groups in minutes of ET (p = 0.93), but persons with arthritis plus diabetes reported significantly less ST compared to individuals with arthritis only (p = 0.03). CONCLUSIONS: Despite reduced self-efficacy for ET and ST and less ST in older persons with arthritis, motivation for both PA types remains high, even in the presence of diabetes.

The impact of self-reported arthritis and diabetes on response to a home-based physical activity counselling intervention.

OBJECTIVES: Physical activity (PA) has the potential to improve outcomes in both arthritis and diabetes, but these conditions are rarely examined together. Our objective was to explore whether persons with arthritis alone or those with both arthritis and diabetes could improve amounts of PA with a home-based counselling intervention. METHODS: As part of the Veterans LIFE (Learning to Improve Fitness and Function in Elders) Study, veterans aged 70-92 were randomized to usual care or a 12-month PA counselling programme. Arthritis and diabetes were assessed by self-report. Mixed models were used to compare trajectories for minutes of endurance and strength training PA for persons with no arthritis (n = 85), arthritis (n = 178), and arthritis plus diabetes (n = 84). RESULTS: Recipients of PA counselling increased minutes of PA per week independent of disease status (treatment arm by time interaction p < 0.05 for both; endurance training time p = 0.0006 and strength training time p < 0.0001). Although PA was lower at each wave among persons with arthritis, and even more so among persons with arthritis plus diabetes, the presence of these conditions did not significantly influence response to the intervention (arthritis/diabetes group x time interactions p > 0.05 for both outcomes) as each group experienced a nearly twofold or greater increase in PA. CONCLUSIONS: A home-based PA intervention was effective in increasing minutes of weekly moderate intensity endurance and strength training PA in older veterans, even among those with arthritis or arthritis plus diabetes. This programme may serve as a useful model to improve outcomes in older persons with these pervasive diseases.

Point-of-care Hepatitis C virus testing and linkage to treatment in an Australian inner-city emergency department.

BACKGROUND: In Australia, Hepatitis C Virus (HCV) treatment is declining, despite broad access to direct-acting antiviral medication. People who inject drugs are proportionally over-represented in emergency department presentations. Emergency department assessment of people who have injected drugs for HCV presents an opportunity to engage this marginalised population with treatment. We describe the outcomes of risk-based screening and point-of-care anti-HCV testing for emergency department patients, and linkage to outpatient antiviral treatment. METHODS: During the three-month study period, consecutive adult patients who presented to the emergency department during the study times were screened for risk factors and offered the OraQuick oral HCV antibody test. Those with reactive results were offered venepuncture in the emergency department for confirmatory testing and direct-acting antiviral treatment in clinic. The main outcome measures were the number and proportion of viremic participants that were linked to the hepatitis clinic, commenced treatment and achieved a sustained viral response. Secondary outcome measures were the proportion (%) of presentations screened that were oral antibody reactive, and the prevalence and type of HCV risk factors. RESULTS: During the study period, 2408 of the 3931 (61%) presentations to the emergency department were eligible for screening. Of these 2408 patients, 1122 (47%) participated, 307 (13%) declined participation and 977 (41%) could not be approached during their time in the emergency department. Among the 1122 participants, 378 (34%) reported at least one risk factor. Subsequently, 368 (97%) of the 378 participants underwent OraQuick anti-HCV test, and 50 (14%) had a reactive result. A risk factor of ever having injected drugs was present in 44 (88%) of participants who were sero-positive. Of the 45 that had blood tested, 30 (67%) were HCV ribonucleic acid (RNA) positive. Three participants died. Of the 27 remaining participants, 10 (37%) commenced treatment and 7 of these 10 (70%) obtained a cure. There was a high rate of homelessness (24%) among anti-HCV positive participants. CONCLUSION: Among emergency department participants with a risk factor for HCV, positive serology was common using a rapid point-of-care test. A history of injecting drug use was identified as the risk factor with highest yield for positive HCV serology, and is suitable as a single screening question. However, linkage to care post ED presentation was low in this marginalised population. There is a need for new pathways to improve the care cascade for marginalised individuals living with HCV infection.

Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.

Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.

In vivo formation of N-nitrosomorpholine in CD-1 mice exposed by inhalation to nitrogen dioxide and by gavage to morpholine.

Male CD-1 mice were exposed to approximately 20 ppm nitrogen dioxide (NO2) for 5-6 hours, to 1 g morpholine/kg body weight by gavage, or to both. Treatments were repeated daily for 5 consecutive days. N-nitrosomorpholine (NMOR) was found in whole carcasses (16-146 ng NMOR/mouse) in all animals that had been exposed to both NO2 and to morpholine, but NMOR was not found in tissues from animals that had been exposed to either chemical alone. Approximately one-third of the NMOR was found in the gastrointestinal tract, mainly in the stomach. The coadministration of 2 g sodium ascorbate/kg body weight or 1 g alpha-tocopheryl acetate/kg body weight had no effect on the amount of NMOR that was found in any tissue. Another possible product of the interaction of NO2 and morpholine, N-nitromorpholine, was not detected in any tissue. We concluded that the repeated, concurrent exposures of mice to NO2 by inhalation and to morpholine by gavage resulted in the in vivo formation of significant quantities of NMOR. The biological significance of the observation remains unknown.

The safety and efficacy of combined amitriptyline and tranylcypromine antidepressant treatment. A controlled trial.

Sixty patients meeting DSM-III criteria for major depression were assigned randomly to double-blind treatment for four weeks according to fixed-dosage steps with (1) amitriptyline hydrochloride alone, up to a maximum dosage of 300 mg/day; (2) tranylcypromine alone, up to 40 mg/day; or (3) the combination of amitriptyline hydrochloride, up to 150 mg/day, and tranylcypromine, up to 20 mg/day. The conditions of patients in all three treatment groups improved equally. The combined treatment did not produce a higher frequency of side effects, and no side effects, such as hypertensive or hyperthermic crises, occurred in any patient. Both amitriptyline alone and combined treatment produced substantially more anticholinergic side effects than did tranylcypromine. These results support the safety and efficacy of the combined treatment, although claims for superior efficacy over single-antidepressant treatments in this heterogenous population were not supported.

Differences between behavior therapists and psychotherapists.

Patient-therapist interaction patterns of three experienced behavior therapists and three matched analytically oriented therapists were compared. Each therapist saw ten patients in short-term individual therapy. The more active behavior therapists dominated the conversation in terms of speech time, more frequently offered explicit advice and instructions, gave more direct information, presented their own value judgments, and exerted greater control over the content of the interaction than did psychotherapists. Although both groups provided a warm and accepting atmosphere, behavior therapists showed higher levels of accurate empathy, interpersonal contact, and therapist self-congruence. Patients viewed behavior therapists as more authoritarian and believed that psychotherapists encourage greater independence. It was concluded that the two therapy approaches to patients were consistent with theoretical models of each.

What is the role of timing in the surgical and rehabilitative care of community-dwelling older persons with acute hip fracture?

OBJECTIVE: To determine the relationship of surgical repair of acute hip fracture within 2 days of hospital admission, followed by more than 5 sessions per week of physical and occupational therapy (PT/OT), to outcomes after acute hip fracture. DESIGN: Comparison of hip fracture outcomes via secondary analysis of data obtained by retrospective medical record review according to timing of surgical repair and frequency of PT/OT, adjusted for patient, medical care, and hospital characteristics. SAMPLE: The study included the medical records of 1880 elderly Medicare recipients admitted from the community to 284 acute care hospitals in 5 states during 1981 and 1982 or 1985 and 1986 with a primary diagnosis of acute hip fracture who underwent surgical repair and received PT/OT. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The postoperative day when ambulation first occurred, the length of hospital stay, and return to the community. RESULTS: Earlier surgical repair was associated with a shorter length of hospital stay (5 fewer days, P < .001) without a statistically significant increase in medical complications. High frequency PT/OT was associated with earlier ambulation (odds ratio [OR], 1.76; 95% confidence limits [CL], 1.50, 2.07). Patients who ambulated earlier [corrected] had shorter lengths of stay (6.5 fewer days, P < .001), were more likely to return to the community (OR, 1.45; 95% CL, 1.16, 1.81), and had better 6-month survival (OR, 2.8; 95% CL, 2.06, 3.88), and patients younger than 85 years had fewer in-hospital complications (11% vs 4%, P < .001). CONCLUSION: Surgical repair within the first 2 days of hospitalization and more than 5 PT/OT sessions per week were associated with better health outcomes in a nationally representative sample of elderly patients with hip fracture.

Platelet monoamine oxidase activity in elderly depressed outpatients.

Platelet monoamine oxidase (MAO) activity was assayed in 42 unmedicated, elderly, RDC depressed, unipolar outpatients over 60 years of age, 17 nondepressed controls, and 17 younger volunteers without psychiatric illness. Elderly depressed women (n = 22) had significantly higher MAO activity than sex- and age-comparable controls. No significant relationships between MAO activity and duration of current depressive episode, duration of illness, or family history of affective disorder were obtained. These results extend to elderly female outpatients the finding that depression is associated with increased platelet MAO activity, exceeding the normal age-related increase.

Visual evoked potentials in dementia: a meta-analysis and empirical study of Alzheimer's disease patients.

A meta-analytic review of flash and pattern reversal visual evoked potential research indicates that elderly demented patients have longer P100 latencies than age-matched control subjects. In the present empirical research, patients with research diagnoses of probable Alzheimer's disease were compared with sex- and age-matched control subjects using P100 latencies of visual evoked potentials (VEP) elicited by flash and pattern reversal. As compared to control subjects, Alzheimer's disease patients showed significantly longer P100 latencies of the VEP elicited by pattern reversal; the flash P100 only marginally distinguished them. These findings are discussed within the context of VEP recording practices, patient selection, sex and age matching of control subjects, and the visual system.

Auditory attention in process and reactive schizophrenia.

The present data indicate that, based on level of premorbid adjustment (process-reactive), schizophrenic subjects differ in auditory attention processes. Generally speaking, poor premorbid adjustment is associated with more attention dysfunction. Results also indicate that attentional deficits improve for all schizophrenic subjects after a 28-day period of neuroleptic therapy.

Short-term analytically oriented psychotherapy versus behavior therapy.

Ninety-four outpatients with anxiety neurosis or personality disorder were randomly assigned for four months to a waiting list, behavior therapy, or psychoanalytically oriented therapy. The target symptoms of all three groups improved significantly, but the two treated groups improved equally well and significantly more than those on the waiting list. There were no significant differences among the groups in work or social adjustment; however, the patients who received behavior therapy had a significant overall improvement at four months. One year and two years after the initial assessment, all groups were found to be equally and significantly improved.