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.

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.

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.

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.

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.

Effect of the Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Evolocumab on Glycemia, Body Weight, and New-Onset Diabetes Mellitus.

Statin therapy modestly increases new-onset diabetes risk. The effect of proprotein convertase subtilisin/kexin type 9 inhibition on new-onset diabetes, glycemia, and weight remains unclear. We studied the effects of the proprotein convertase subtilisin/kexin type 9 inhibitor evolocumab on fasting plasma glucose, glycated hemoglobin, weight, and new-onset diabetes mellitus. We pooled 1-year (48-week) data for participants who had completed an evolocumab parent study before entering an open-label extension (OLE) trial. Data were available for 4,802 participants (1,602 on standard of care [SOC]; 3,200 on evolocumab plus SOC) in 2 OLE trials. Evolocumab lowered low-density lipoprotein cholesterol by approximately 60% compared with SOC alone. Over the first year of the OLE trials, there was no difference in median (Q1, Q3) change in glycated hemoglobin (0.1% [-0.1, 0.2] for both SOC and evolocumab plus SOC) and fasting plasma glucose (0.06 mmol/L [-0.28, 0.38 mmol/L] for SOC and 0.06 mmol/L [-0.28, 0.44 mmol/L] for evolocumab plus SOC). Mean weight change (standard error) at 1 year was -0.1 kg (0.2) on SOC compared with 0.3 kg (0.1) on evolocumab plus SOC. The exposure-adjusted incidence rate (95% confidence intervals) for new-onset diabetes per 100 patient years was 3.7 (2.9 to 4.7) on control/SOC alone and 3.9 (3.2 to 4.6) on evolocumab/evolocumab plus SOC treatment. Glycemic changes observed in 6,430 participants at week 12 in the parent studies were comparable with OLE trial findings. In conclusion, evolocumab therapy has no effect on glucose homeostasis over 1 year of open-label treatment.

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.

Evolocumab lowers LDL-C safely and effectively when self-administered in the at-home setting.

Evolocumab has been shown to consistently reduce low-density lipoprotein cholesterol (LDL-C) across populations. The phase 3 studies included administration in the home-use and in-clinic settings but did not specifically evaluate the feasibility of home-use administration. Two clinical studies enrolled patients with hypercholesterolemia or mixed dyslipidemia on statin therapy and with/without ezetimibe received evolocumab in the home-use setting. Patients were randomized to self-administer evolocumab using one of two injection devices biweekly over 6 weeks (autoinjector or prefilled syringe; n = 149; ClinicalTrials.gov, NCT01849497) or monthly over 12 weeks (autoinjector or automated minidoser; n = 164; NCT01879319). The first self-administration occurred in the in-clinic setting, and two more were performed in the at-home setting. Patients were successful in self-administering evolocumab in the home-use setting in approximately 95 % of attempts and experienced LDL-C reductions from baseline to week 6 or the mean of weeks 10 and 12 of approximately 65 %. Rates of successful self-administration and LDL-C reduction were similar across dosing schedules and study devices. Adverse events were similar between randomized groups and generally mild in severity. In two clinical studies, therefore, patients were able to successfully self-administer evolocumab in both the in-clinic and at-home settings regardless of which dosing schedule or device they used.

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.

Lipid-lowering efficacy of the PCSK9 inhibitor evolocumab (AMG 145) in patients with type 2 diabetes: a meta-analysis of individual patient data.

BACKGROUND: Patients with type 2 diabetes have increased cardiovascular risk. PCSK9 monoclonal antibodies have been shown to reduce LDL cholesterol and other lipids, but specific efficacy for patients with diabetes is unknown. We compared the effect of the PCSK9 inhibitor evolocumab on lipid parameters in patients with and without type 2 diabetes. METHODS: We did a random-effects meta-analysis of randomised clinical trials comparing the efficacy of evolocumab, placebo, and ezetimibe to improve lipid parameters in adult patients (age 18-80 years) with or without type 2 diabetes. We searched MEDLINE and Embase to identify eligible 12-week, phase 3 trials published between Jan 1, 2012, and Feb 28, 2015. We excluded trials that included patients who had homozygous familial hypercholesterolaemia. All analyses were based on individual participant data. We used DerSimonian and Laird random-effects meta-analyses to compare the mean changes from baseline in concentrations of LDL cholesterol, non-HDL cholesterol, total cholesterol, triglycerides, lipoprotein(a), and HDL cholesterol at 12 weeks for evolocumab, placebo, and ezetimibe. We also assessed the effect of evolocumab therapy compared with placebo across subgroups of patients based on glycaemia, insulin use, renal function, and cardiovascular disease status at baseline. RESULTS: Three trials met our inclusion criteria, and included 413 patients with type 2 diabetes and 2119 patients without type 2 diabetes. In patients with type 2 diabetes evolocumab caused mean reductions in LDL cholesterol concentration that were 60% (95% CI 51-69) versus placebo and 39% (32-47) versus ezetimibe. In patients without type 2 diabetes, evolocumab caused mean reductions in LDL cholesterol that were 66% (62-70) versus placebo and 40% (36-45) versus ezetimibe. In patients with type 2 diabetes, evolocumab was associated with reductions in non-HDL cholesterol (55% [47-63] vs placebo and 34% [26-41] vs ezetimibe), total cholesterol (38% [32-44] vs placebo and 24% [16-31] vs ezetimibe), and lipoprotein(a) (31% [25-37] vs placebo and 26% [16-35] vs ezetimibe), and an increase in HDL cholesterol (7% [4-11] vs placebo and 8% [4-13] vs ezetimibe). Findings were similar across diabetes subgroups based on glycaemia, insulin use, renal function, and cardiovascular disease status. INTERPRETATION: Evolocumab markedly reduces atherogenic lipoproteins in patients with type 2 diabetes, an effect that is consistent across subgroups and similar to that seen in patients without type 2 diabetes. Results from ongoing cardiovascular outcome trials of PCSK9 inhibitors will provide additional data to inform the use of these drugs in patients with type 2 diabetes. FUNDING: Amgen.

Improving Osteoporosis Management in Primary Care: An Audit of the Impact of a Community Based Fracture Liaison Nurse.

BACKGROUND: Osteoporosis and associated fragility fractures are a major health problem; they are more common in women over 50 years old. Fracture liaison nurses have been widely used in secondary care to promote the recognition of fragility fractures and to promote the use of bone-sparing medication to reduce the risk of recurrent facture. OBJECTIVE: Audit the impact of a primary care based fracture liaison nurse on the detection of fragility fractures in people with osteoporosis and their treatment with a bone-sparing medication. METHOD: This audit took place in 12 GP practices using 'before and after' cross-sectional extractions of anonymised routine data. We report, for females 50-74 years and ≥ 75 years old, socio-economic deprivation index, the prevalence of osteoporosis, recording of fragility fractures, dual-energy X-ray absorptiometry (DXA), smoking, and body-mass index (BMI) and use of appropriate bone-sparing medication. We used Altman's test of independent proportions to compare before and after data. RESULTS: Recording of the diagnosis of osteoporosis increased from 1.5% to 1.7% (p = 0.059); the rate of DXA scans fell (1.8% to 1.4%; p = 0.002); recording of fractures and fragility fractures more than doubled (0.8% to 2.0%; p<0.001 and 0.5% to 1.5%; p<0.001, respectively) with approximate doubling of the recording of smoking, and BMI (p<0.001 level). Fragility fracture recording rose from 8.8% to 15% in females aged 50 to 74, and from 0.8% to 2.3% in people aged ≥ 75 years old (p<0.001). There appeared to be inequity in the service, people who were least deprived were more likely to receive DXA scans and the more deprived to be prescribed bone sparing agents. CONCLUSION: A fracture liaison nurse in primary care has been associated with a period of improved management. Liaison nurses based in different parts of the health system should be tested in a prospective trial.

Immune reconstitution/immunocompetence in recipients of kidney plus hematopoietic stem/facilitating cell transplants.

Nineteen subjects have more than 18 months' follow-up in a phase IIb tolerance protocol in HLA-mismatched recipients of living donor kidney plus facilitating cell enriched hematopoietic stem cell allografts (FCRx). Reduced intensity conditioning preceded a kidney allograft, followed the next day by FCRx. Twelve have achieved stable donor chimerism and have been successfully taken off immunosuppression (IS). We prospectively evaluated immune reconstitution and immunocompetence. Return of CD4 and CD8 T central and effector memory cell populations was rapid. T-cell receptor (TCR) Excision Circle analysis showed a significant proportion of chimeric cells produced were being produced de novo. The TCR repertoires posttransplant in chimeric subjects were nearly as diverse as pretransplant donors and recipients, and were comparable to subjects with transient chimerism who underwent autologous reconstitution. Subjects with persistent chimerism developed few serious infections when off IS. The majority of infectious complications occurred while subjects were still on conventional IS. BK viruria and viremia resolved after cessation of IS and no tissue-invasive cytomegalovirus infections occurred. Notably, although 2 of 4 transiently or nonchimeric subjects experienced recurrence of their underlying autoimmune disorders, none of the chimeric subjects have, suggesting that self-tolerance is induced in addition to tolerance to alloantigen. No persistently chimeric subject has developed donor-specific antibody, and renal function has remained within normal limits. Patients were successfully vaccinated per The American Society for Blood and Marrow Transplantation guidelines without loss of chimerism or rejection. Memory for hepatitis vaccination persisted after transplantation. Chimeric subjects generated immune responses to pneumococcal vaccine. These data suggest that immune reconstitution and immunocompetence are maintained in persistently chimeric subjects.

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.

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.