Building Resilience within Institutions Together with Employees (BRITE): Preliminary experience with implementation in an academic cancer centre.

Resilience is defined as the capacity to bounce back and respond to pressure, unpredictability, or adversity in an adaptive and effective manner that leads to learning and positive outcomes. BRITE, Building Resilience within Institutions Together with Employees, the focus of this article, is a program designed to equip healthcare workers with skills to foster their resilience as they work; herein, we describe the context, development, and preliminary implementation results.

Evaluation of the efficacy, safety and glycaemic effects of evolocumab (AMG 145) in hypercholesterolaemic patients stratified by glycaemic status and metabolic syndrome.

AIM: To examine the lipid and glycaemic effects of 52 weeks of treatment with evolocumab. MATERIALS AND METHODS: The Durable Effect of PCSK9 Antibody Compared with Placebo Study (DESCARTES) was a 52-week placebo-controlled trial of evolocumab that randomized 905 patients from 88 study centres in 9 countries, with 901 receiving at least one dose of study drug. For this post-hoc analysis, DESCARTES patients were categorized by baseline glycaemic status: type 2 diabetes, impaired fasting glucose (IFG), metabolic syndrome (MetS) or none of these. Monthly subcutaneous evolocumab (420 mg) or placebo was administered. The main outcomes measured were percentage change in LDL-cholesterol (LDL-C) at week 52 and safety. RESULTS: A total of 413 patients had dysglycaemia (120, type 2 diabetes; 293, IFG), 289 had MetS (194 also had IFG) and 393 had none of these conditions. At week 52, evolocumab reduced LDL-C by >50% in all subgroups, with favourable effects on other lipids. No significant differences in fasting plasma glucose, HbA1c, insulin, C-peptide or HOMA indices were seen in any subgroup between evolocumab and placebo at week 52. The overall incidence of new-onset diabetes mellitus did not differ between placebo (6.6%) and evolocumab (5.6%); in those with baseline normoglycaemia, the incidences were 1.9% and 2.7%, respectively. Incidences of AEs were similar in evolocumab- and placebo-treated patients. CONCLUSIONS: Evolocumab showed encouraging safety and efficacy at 52 weeks in patients with or without dysglycaemia or MetS. Changes in glycaemic parameters did not differ between evolocumab- and placebo-treated patients within the glycaemic subgroups examined.

Efficacy and Tolerability of Evolocumab vs Ezetimibe in Patients With Muscle-Related Statin Intolerance: The GAUSS-3 Randomized Clinical Trial.

IMPORTANCE: Muscle-related statin intolerance is reported by 5% to 20% of patients. OBJECTIVE: To identify patients with muscle symptoms confirmed by statin rechallenge and compare lipid-lowering efficacy for 2 nonstatin therapies, ezetimibe and evolocumab. DESIGN, SETTING, AND PARTICIPANTS: Two-stage randomized clinical trial including 511 adult patients with uncontrolled low-density lipoprotein cholesterol (LDL-C) levels and history of intolerance to 2 or more statins enrolled in 2013 and 2014 globally. Phase A used a 24-week crossover procedure with atorvastatin or placebo to identify patients having symptoms only with atorvastatin but not placebo. In phase B, after a 2-week washout, patients were randomized to ezetimibe or evolocumab for 24 weeks. INTERVENTIONS: Phase A: atorvastatin (20 mg) vs placebo. Phase B: randomization 2:1 to subcutaneous evolocumab (420 mg monthly) or oral ezetimibe (10 mg daily). MAIN OUTCOME AND MEASURES: Coprimary end points were the mean percent change in LDL-C level from baseline to the mean of weeks 22 and 24 levels and from baseline to week 24 levels. RESULTS: Of the 491 patients who entered phase A (mean age, 60.7 [SD, 10.2] years; 246 women [50.1%]; 170 with coronary heart disease [34.6%]; entry mean LDL-C level, 212.3 [SD, 67.9] mg/dL), muscle symptoms occurred in 209 of 491 (42.6%) while taking atorvastatin but not while taking placebo. Of these, 199 entered phase B, along with 19 who proceeded directly to phase B for elevated creatine kinase (N = 218, with 73 randomized to ezetimibe and 145 to evolocumab; entry mean LDL-C level, 219.9 [SD, 72] mg/dL). For the mean of weeks 22 and 24, LDL-C level with ezetimibe was 183.0 mg/dL; mean percent LDL-C change, -16.7% (95% CI, -20.5% to -12.9%), absolute change, -31.0 mg/dL and with evolocumab was 103.6 mg/dL; mean percent change, -54.5% (95% CI, -57.2% to -51.8%); absolute change, -106.8 mg/dL (P < .001). LDL-C level at week 24 with ezetimibe was 181.5 mg/dL; mean percent change, -16.7% (95% CI, -20.8% to -12.5%); absolute change, -31.2 mg/dL and with evolocumab was 104.1 mg/dL; mean percent change, -52.8% (95% CI, -55.8% to -49.8%); absolute change, -102.9 mg/dL (P < .001). For the mean of weeks 22 and 24, between-group difference in LDL-C was -37.8%; absolute difference, -75.8 mg/dL. For week 24, between-group difference in LDL-C was -36.1%; absolute difference, -71.7 mg/dL. Muscle symptoms were reported in 28.8% of ezetimibe-treated patients and 20.7% of evolocumab-treated patients (log-rank P = .17). Active study drug was stopped for muscle symptoms in 5 of 73 ezetimibe-treated patients (6.8%) and 1 of 145 evolocumab-treated patients (0.7%). CONCLUSIONS AND RELEVANCE: Among patients with statin intolerance related to muscle-related adverse effects, the use of evolocumab compared with ezetimibe resulted in a significantly greater reduction in LDL-C levels after 24 weeks. Further studies are needed to assess long-term efficacy and safety. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01984424.

DOCK2 is critical for CD8(+) TCR(-) graft facilitating cells to enhance engraftment of hematopoietic stem and progenitor cells.

CD8(+) TCR(-) graft facilitating cells (FCs) enhance engraftment of hematopoietic stem cells (HSCs) in allogeneic and syngeneic recipients. The mechanisms by which FCs promote HSC engraftment and tolerance induction have not been fully elucidated. Here, we provide data to support a critical role for dedicator of cytokinesis 2 (DOCK2) in multiple aspects of FCs function. DOCK2(-/-) FCs exhibit compromised facilitative function in vivo as evidenced by the loss of engraftment-enhancing capability for c-Kit(+) Sca-1(+) lineage(-) (KSL) cells, and compromised ability to promote KSL cell homing and lodgment in hematopoietic niche. Deletion of DOCK2 abrogates the ability of FCs to induce differentiation of naïve CD4(+) CD25(-) T cells into FoxP3(+) regulatory T cells and interleukin-10-producing type 1 regulatory T cells in vitro. Moreover, DOCK2(-/-) FCs are unable to promote survival of KSL cells when cocultured with KSL cells. DOCK2(-/-) FCs also exhibit compromised migration to stroma-derived factor-1 in vitro and impaired homing to the bone marrow in vivo. In conclusion, our results demonstrate that DOCK2 is critical for FCs to maintain its immunomodulatory function and exert its trophic effects on KSL cells. These findings may have direct clinical relevance to promote HSC engraftment for treatment of autoimmunity, hemoglobinopathies, and to induce transplantation tolerance.

Oxytocin levels are lower in premenopausal women with type 1 diabetes mellitus compared with matched controls.

BACKGROUND: Oxytocin, a hormone most commonly associated with parturition and lactation, may have additional roles in diabetes complications. We determined oxytocin levels in premenopausal women with type 1 diabetes mellitus (T1DM) compared with non-diabetic controls and examined associations of oxytocin with health behaviours, clinical factors, biomarkers, kidney function and bone health. Lower oxytocin was hypothesized for T1DM. METHODS: A cross-sectional study of premenopausal women with T1DM (n = 88) from the Wisconsin Diabetes Registry Study, a population-based cohort of incident T1DM cases, and matched non-diabetic controls (n = 74) was conducted. RESULTS: Women with T1DM had lower oxytocin levels than controls adjusting for caffeine and alcohol use (p = 0.03). Health behaviours associated with oxytocin differed between women with and without T1DM: oxytocin was negatively associated with hormonal contraceptive use (quantified as lifetime contraceptive oestrogen exposure) in women with T1DM (p = 0.003), whereas positively related to hormonal contraceptive use (quantified as never/former/current) in controls (p < 0.001). Oxytocin had a positive association with adiposity (waist-to-hip ratio and leptin) in women with T1DM and a negative relationship with adiposity (weight gain) in controls. In T1DM only, oxytocin was positively associated with caffeine intake (p = 0.01) and negatively associated with alcohol use (p = 0.01). Oxytocin was not related to glycemic control, kidney function or bone health in T1DM. CONCLUSIONS: Oxytocin levels are lower in women with T1DM than matched controls. Oxytocin also has opposing associations with hormonal contraceptives and adiposity in women with and without T1DM. Research is needed to determine if the altered oxytocin milieu in T1DM is associated with oxytocinher health outcomes.

Different health behaviours and clinical factors associated with bone mineral density and bone turnover in premenopausal women with and without type 1 diabetes.

BACKGROUND: Women with type 1 diabetes (T1DM) have an elevated fracture risk. We therefore compared the associations of health behaviours and clinical factors with bone mineral density (BMD) and bone remodelling between premenopausal women with and without T1DM to inform potential interventions. METHODS: Participants included women with T1DM (n = 89) from the Wisconsin Diabetes Registry Study and age-matched and race-matched controls without diabetes (n = 76). Peripheral (heel and forearm) and central (hip and spine) BMD, markers of bone resorption and formation, bone cell signalling, glycaemic control, and kidney function were assessed. Health behaviours and medical history were self-reported. RESULTS: In controls, but not in women with T1DM, older age was associated with lower bone resorption (p ≤ 0.006) and formation (p = 0.0007). Body mass index was positively associated with heel and forearm BMD in both controls and T1DM women (all p < 0.0001), but with hip and spine BMD only in controls (p ≤ 0.005). Worse glycaemic control during the previous 10 years, greater alcohol intake, history of smoking, and lack of physical activity were associated with poorer bone outcomes only in women with T1DM (all p ≤ 0.002), whereas use of hormonal contraceptives was related to low bone formation in both women with and without T1DM (all p ≤ 0.006). Diabetes duration, insulin dose, residual C-peptide, and kidney function were not associated with bone in T1DM. CONCLUSIONS: Age and body mass index may not predict bone health in T1DM women. However, modifiable behaviours such as optimizing glycaemic control, limiting substance and hormonal contraceptive use, and increasing physical activity may improve bone health in T1DM women.

Bone health evaluation in a veteran population: a need for the Fracture Risk Assessment Tool (FRAX).

BACKGROUND: Approximately 2 million men in the United States have osteoporosis, but men are seldom evaluated or treated to prevent fracture. In the expanding veteran population, the fracture risk assessment tool, FRAX, could help reduce fracture risk. However, it is unknown how many veterans would meet the FRAX treatment threshold. OBJECTIVE: To determine the proportion of untreated veterans who should be considered for osteoporosis treatment according to the Fracture Risk Assessment Tool (FRAX) among a randomly selected sample of older veterans receiving care at one Veterans Hospital and to determine the proportion of veterans in the sample who had received treatment. METHODS: A retrospective review of 150 randomly selected charts from male veterans at least 70 years of age and female veterans at least 65 years of age receiving primary care at the William S. Middleton Memorial Veterans Hospital, Madison, WI, between January 1, 2007, and October 1, 2010. This study focused on men, but women were included per institutional review board policy. RESULTS: Charts from 147 men and 3 women were reviewed; 25 men had received osteoporosis treatment. Of 122 untreated men, 74 (61%) met FRAX treatment criteria, including 14 who had fractured. Although bone density testing is recommended by the National Osteoporosis Foundation for men at least 70 years old, only 21 (17%) untreated men had been tested. CONCLUSIONS: Most veterans who met FRAX criteria were not treated, including some who had had fractures. The VA should consider recommending FRAX to identify veterans at high risk for fracture.

Novel Web-Based Drop-In Mindfulness Sessions (Pause-4-Providers) to Enhance Well-Being Among Health Care Workers During the COVID-19 Pandemic: Descriptive and Qualitative Study.

BACKGROUND: The COVID-19 pandemic exerted extraordinary pressure on health care workers (HCWs), imperiling their well-being and mental health. In response to the urgent demand to provide barrier-free support for the health care workforce, Pause-4-Providers implemented 30-minute live web-based drop-in mindfulness sessions for HCWs. OBJECTIVE: This study aims to evaluate the use, feasibility, satisfaction, and acceptability of a novel mindfulness program aimed at enhancing the well-being of HCWs during the COVID-19 pandemic. METHODS: Accrual for the study continued throughout the first 3 pandemic waves, and attendees of ≥1 session were invited to participate. The evaluation framework included descriptive characteristics, including participant demographics, resilience at work, and single-item burnout scores; feedback questionnaires on reasons attended, benefits, and satisfaction; qualitative interviews to further understand participant experience, satisfaction, benefits, enablers, and barriers; and the number of participants in each session summarized according to the pandemic wave. RESULTS: We collected descriptive statistics from 50 consenting HCWs. Approximately half of the participants (24/50, 48%) attended >1 session. The study participants were predominantly female individuals (40/50, 80%) and comprised physicians (17/50, 34%), nurses (9/50, 18%), and other HCWs (24/50, 48%), who were largely from Ontario (41/50, 82%). Of 50 attendees, 26 (52%) endorsed feeling burned out. The highest attendance was in May 2020 and January 2021, corresponding to the first and second pandemic waves. The participants endorsed high levels of satisfaction (43/47, 92%). The most cited reasons for attending the program were to relax (38/48, 79%), manage stress or anxiety (36/48, 75%), wish for loving kindness or self-compassion (30/48, 64%), learn mindfulness (30/48, 64%), and seek help with emotional reactivity (25/48, 53%). Qualitative interviews with 15 out of 50 (30%) participants identified positive personal and professional impacts. Personal impacts revealed that participation helped HCWs to relax, manage stress, care for themselves, sleep better, reduce isolation, and feel recognized. Professional impacts included having a toolbox of mindfulness techniques, using mindfulness moments, and being calmer at work. Some participants noted that they shared techniques with their colleagues. The reported barriers included participants' needing time to prioritize themselves, fatigue, forgetting to apply skills on the job, and finding a private place to participate. CONCLUSIONS: The Pause-4-Providers participants reported that the web-based groups were accessible; appreciated the format, content, and faculty; and had high levels of satisfaction with the program. Both novel format (eg, drop-in, live, web-based, anonymous, brief, and shared activity with other HCWs) and content (eg, themed mindfulness practices including micropractices, with workplace applications) were enablers to participation. This study of HCW support sessions was limited by the low number of consenting participants and the rolling enrollment project design; however, the findings suggest that a drop-in web-based mindfulness program has the potential to support the well-being of HCWs.

Characteristics associated with bone mineral density responses to alendronate in men.

Some patients experience reduced bone mineral density (BMD) despite bisphosphonate therapy. We performed a retrospective chart review study to detect factors associated with decreased BMD in men prescribed alendronate. Two investigators reviewed eligible medical records and used a standardized form to record potential characteristics predicting men's response to alendronate. We analyzed patient characteristics associated with annualized change in hip and spine BMD (D-BMD). Among 115 eligible men, 19 (17 %) experienced significantly decreased BMD at the hip or spine, defined as a change exceeding precision error. Eleven men (10 %) fractured during therapy. Spine D-BMD was positively associated with adherence to alendronate (R = 0.23, p = 0.02) and inversely associated with baseline body weight (R = -0.21, p = 0.03). Hip D-BMD was positively associated with annualized weight change (R = 0.19, p = 0.0498) and negatively associated with patient age and number of concomitant medications (R = -0.21, p = 0.03; R = -0.20, p = 0.03, respectively). In stepwise linear models, spine D-BMD was associated positively with alendronate adherence and multivitamin use and negatively with baseline body weight. Hip D-BMD was negatively associated with age. Fracture during treatment was associated with fracture prior to therapy (p = 0.03). In this small study of men prescribed alendronate, BMD response showed a positive association with adherence to therapy, weight gain, and use of a multivitamin. By contrast, older age, higher baseline body weight, and higher number of medications were each associated with a decrease in BMD. Larger studies are needed to confirm and extend these findings.

The Impact of Parent and Family Caregiver Roles Among Canadian Radiation Oncologists.

PURPOSE: Working parents, and a rising number of adults delivering care for aging relatives, experience numerous challenges in their personal, family, professional, and financial lives owing to multiple responsibilities. This study describes the experiences of Canadian radiation oncologist (RO) parents and family caregivers, reporting challenges that may exist in providing family care with clinical and academic work commitments. METHODS AND MATERIALS: Canadian ROs, via RO heads of departments in cancer centers across Canada, and physician members of the Canadian Association of Radiation Oncology were invited to participate in an anonymous online survey between November 2021 and January 2022. The survey focused on demographics, experiences of pregnancy and leave, parenting and adult caregiving responsibilities, and self-care. RESULTS: A total of 103 staff ROs (38%) completed the survey and 78 (75.7%) identified as having a parental (76 [89.7%]) and/or other family caregiver (8 [10.3%]) role; 41% were female and 59% were male, with no difference between genders in the number of children (median, 2; interquartile range, 1-3; P = .17). More female respondents took parental leave for their first child compared with male respondents (mean, 29 vs 6 weeks; P < .001). Of male respondents who started caring for their first child during residency, 27% took parental leave, compared with 77% who started caring for their first child as a staff member (P = .003). The majority of respondents described "always/usually" having collegial support for each pregnancy and parental leave. Both genders described parental responsibilities as negatively affecting attendance at conferences (male, 65%; female, 77%; P = .31) and early or late work-related meetings (male, 76%; female, 79%; P = 1.0). More female respondents described parental responsibilities as negatively affecting their career (50% vs 29%; P = .085). Of female respondents, 52% (vs 26% of male respondents; P = .044) identified a physician mentor or positive role model around parenting issues. CONCLUSIONS: Parental and other family caregiving responsibilities are not gender unique in Canadian ROs, but competing work and family roles may affect genders differently.

Taking control of osteoporosis to cut down on risk of fracture.

This article examines osteoporosis, other risk factors for future fracture and different management approaches. The past few years have seen advances in osteoporosis care with new assessment tools, national guidelines and an increased range of medications. Action by a variety of professionals is needed to improve outcomes for patients and reduce fractures; as well as identification and assessment of high-risk patients, long-term follow up to provide lifestyle advice about the use of bone-sparing medications is vital. Nurses can identify at-risk patients and provide ongoing intervention, education and support.

The benefits of community-based participatory arts activities for people living with dementia: a thematic scoping review.

BACKGROUND: The drive towards living well with dementia has resulted in a growing recognition of the value of community-based participatory arts activities. This review aimed to explore their overall impact and holistic benefits for people with early to moderate stages of dementia. METHODS: Using a scoping review methodology and thematic analysis, this review explored relevant literature published between 2008 and 2019. RESULTS: 26 published papers were identified, comprising visual arts, literary arts, comedy, music and dance. The key themes included person-centred, in-the-moment approaches; participation and communication; attention and cognition; social cohesion and relationships; and the role of space, place and objects. CONCLUSIONS: There is strong evidence in support of using participatory arts for dementia, regardless of art form. In-the-moment and person-centred approaches were deemed impactful. Further research is needed to explore the importance of setting, material culture and the methodological or theoretical perspectives in participatory arts and dementia research.

Injection of hope.

A new drug or the prevention of osteoporosis is both effective and convenient, only requiring an injection every six months.

Mindfulness-Based Cognitive Therapy Intervention for Young Adults with Cancer: A Pilot Mixed-Method Study.

Purpose: Group mindfulness-based interventions are emerging as a promising, nonstigmatizing, and cost-effective strategy that may improve the well-being of individuals living with cancer. This study is a pilot pre-post mixed-method study to examine the feasibility, acceptability, and effects of an 8-week Mindfulness-based Cognitive Therapy group for Young Adults with Cancer (YA-MBCT). Methods: We approached young adults with cancer, who enrolled in YA-MBCT groups, offered at a large cancer hospital in Toronto, Ontario, Canada. Feasibility and acceptability were assessed through attendance rate and a postintervention satisfaction scale. Psychosocial outcomes were evaluated with a pre-post questionnaire package, with validated self-report measures, assessing depression, anxiety, perceived stress, quality of life, mindfulness, and self-compassion. Qualitative interviews were completed among a subset of participants to gain additional feedback. Results: Participants were 70 young adults with cancer, recruited from five YA-MBCT groups. Sixty participants (85%) attended a minimum of six of eight sessions, and overall satisfaction rates were high. All psychosocial outcomes demonstrated statistically significant changes (p < 0.01), with medium to large effect sizes (Cohen's d > 0.5). Qualitative interviews (n = 14) demonstrated overall positive views about the intervention, and provided insight into unique age-specific benefits, including reducing fear of cancer recurrence, improving body image, and creating a sense of belonging. Conclusion: The YA-MBCT is feasible and acceptable among young adults with cancer, with the potential to improve psychosocial outcomes. Our preliminary results should be replicated with larger studies with an active control group.

A Qualitative Study of a Compassion, Presence, and Resilience Training for Oncology Interprofessional Teams.

The well-being of health care providers may be challenged by their work, with evidence that oncology health care providers are a high-risk group for burnout. The present qualitative pilot study evaluated a mindfulness-based group intervention, referred to as Compassion, Presence, and Resilience Training (CPR-T), for oncology interprofessional teams. The purpose of this study was to elucidate the subjective experience of oncology health care providers receiving CPR-T and their perceptions of its benefits, risks, or challenges. The CPR-T was delivered to providers from two oncology teams in a large cancer center in Canada. Ten of these providers participated in semistructured interviews 1 to 5 months after completing the CPR-T. The interview transcripts were coded using a thematic analysis strategy. Five benefits of the CPR-T were identified: learning to pause, acquiring a working definition of stress and self-care, becoming fully present, building self-compassion, and receiving organizational acknowledgment and recognition of stress. In addition, two participant-identified challenges were recognized: sharing vulnerability within interprofessional teams and committing to a sitting meditation practice. These findings demonstrate positive transformations as a result of the CPR-T, as well as important challenges, and have important implications for holistic health care practice in oncology. Further research is necessary to validate the findings of this explorative study.

Serotonin Differentially Regulates L5 Pyramidal Cell Classes of the Medial Prefrontal Cortex in Rats and Mice.

The prefrontal cortex receives a dense serotonergic innervation that plays an important role in its regulation. However, how serotonin regulates different pyramidal and interneuron cell classes in this area is incompletely understood. Previous work in rats has shown that serotonin differentially regulates two classes of pyramidal cells in layer 5. It excites one class by activating 5-HT2A receptors, whereas it more subtly modulates the integrative properties of the other by co-activating 5-HT1A and 5-HT2A receptors. Here we have used electrophysiological recordings, combined with retrograde labeling and morphological reconstruction, to show that the first cell class corresponds to long range corticofugal neurons and the second corresponds to intratelencephalic neurons. These results suggest that, in rats, serotonin facilitates subcortical output while more subtly modulating cortico-cortical and cortico-striatal output. Interestingly, these results obtained in rats differ from those previously reported for mouse prefrontal cortex. Therefore we reinvestigated the effects of serotonin in mice and confirmed that serotonin predominantly activates inhibitory 5-HT1A receptors on long-range corticofugal cells. Thus serotonin exerts opposite effects on these cells in rats and mice. Finally, we determined whether cortical serotonin responsiveness in mice is regulated during development. Serotonin elicited predominantly depolarizing inward current responses during the early postnatal period, whereas inhibitory 5-HT1A receptor-mediated responses did not become evident until the end of the second postnatal week. These results reveal commonalities as well as unexpected differences in the serotonergic regulation of long-range corticofugal and intratelencephalic neurons of layer 5 in rat and mouse.

Effect of Evolocumab on Lipoprotein Particles.

The level of low-density lipoprotein cholesterol (LDL-C) reflects the cholesterol carried mainly by low-density lipoprotein particles (LDL-P). LDL-C, however, does not always correlate with LDL-P because of the variable amounts of cholesterol per particle. Consideration of LDL-P concentrations in addition to LDL-C may help guide therapeutic decisions in a select number of patients. Evolocumab is a fully human monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9 that lowers both LDL-C and cardiovascular events. To evaluate the effect of evolocumab on serum levels and size of lipoprotein particles, we conducted a post hoc subanalysis of 619 patients from the Durable Effect of PCSK9 Antibody Compared with Placebo Study or DESCARTES trial, a 52-week, randomized, double-blind, placebo-controlled, global study of patients with hyperlipidemia. At baseline, mean LDL-P concentration was 1077 nmol/L for the placebo group and 1100 nmol/L for the evolocumab group. In patients receiving evolocumab, week 52 total LDL-P concentration decreased to 610 nmol/L, a treatment difference of 50% versus placebo. Evolocumab also reduced concentrations of medium very low-density lipoprotein particles (VLDL-P), small VLDL-P, and intermediate-density lipoprotein particle: median (Q1, Q3) changes were -15.2% (-48, 48), -29% (-54, 18), and -36% (-70, 22), respectively. Mean (95% confidence interval) % changes in total LDL particle size in the evolocumab group was -1.7 (-2.0, -1.4); % changes in HDL and VLDL particle sizes were 1.1 (0.7, 1.5) and 8.7 (7.0, 10.5), respectively. Changes in total LDL, HDL, and VLDL particle sizes (vs placebo) were all significant (p <0.001). In conclusion, evolocumab significantly lowers atherogenic lipoprotein particles including low-density and remnant lipoproteins.

Patient assessment in the diagnosis, prevention, and treatment of osteoporosis.

Assessment of the patient with osteoporosis includes history and physical examination, laboratory testing, and imaging studies. Information gathered during this assessment assists clinicians in targeting strategies to prevent fractures. The medical history should contain items such as personal and family history of fractures, lifestyle, intake of substances such as vitamin D, calcium, corticosteroids, and other medications. The physical examination can reveal relevant information such as height loss and risk of falls. Bone mineral density (BMD), most commonly determined by dual-energy x-ray absorptiometry, best predicts fracture risk in patients without previous fracture. BMD testing is most efficient in women over 65 years old but is also helpful for men and women with risk factors. Serial BMD tests can identify individuals losing bone mass, but clinicians should be aware of what constitutes a significant change. Laboratory testing can detect other risk factors and can provide clues to etiology. Selection of laboratory tests should be individualized, as there is no consensus regarding which tests are optimal. Biochemical markers of bone turnover have a potential role in fracture risk assessment and in gauging response to therapy, but are not widely used at present. Clinicians should be aware of problems with vitamin D measurement, including seasonal variation, variability among laboratories, and the desirable therapeutic range. Careful assessment of the osteoporotic patient is essential in developing a comprehensive plan that reduces fracture risk and improves quality of life.