Controlled pilot test of a translated cardiac rehabilitation education curriculum in percutaneous coronary intervention patients in a middle-income country delivered using WeChat: acceptability, engagement, satisfaction and preliminary outcomes.

In China, despite the rapid increase in percutaneous coronary interventions (PCIs), cardiac rehabilitation (CR) is just burgeoning, leaving a need for comprehensive evidence-based education curricula. This pilot study assessed the acceptability of Simplified Chinese CR education delivered via booklets and videos on WeChat asynchronously and the impact on improving knowledge, risk factors, health behaviors and quality of life. In this pre-post, controlled, observational study, interested PCI patients received the 12-week intervention or usual care and WeChat without education. Participants completed validated surveys, including the Coronary Artery Disease Education-Questionnaire and Self-Management Scale. Acceptability (14 Likert-type items), engagement (minutes per week) and satisfaction were assessed in intervention participants. Ninety-six patients consented to participate (n = 49 intervention), of which 66 (68.8%) completed the follow-up assessments. Twenty-seven (77.1%) retained intervention participants engaged with the materials, rating content as highly acceptable (all means ≥4/5) and satisfactory (2.19 ± 0.48/3); those engaging more with the intervention were significantly more satisfied (P = 0.03). While participants in both groups achieved some improvements, only intervention participants had significant increases in disease-related knowledge, reductions in body mass index and triglycerides, as well as improvements in diet (all P < 0.05). In this first study validating the recently translated CR patient education intervention, acceptability and benefits have been supported.

Depressive symptoms predict non-completion of a structured exercise intervention for people with Type 2 diabetes.

AIM: To quantify the impact of depressive symptoms on completion of exercise-based rehabilitation for Type 2 diabetes management. METHODS: Depressive symptoms were assessed using the Center for Epidemiological Studies Depression scale in a prospective cohort of consecutive patients with Type 2 diabetes entering a 6-month hybrid (home- and clinic-based) exercise rehabilitation programme. Attendance at exercise sessions was monitored and programme completion/non-completion was ascertained. RESULTS: Of the programme participants (n=624, mean age 55.6±10.5 years, 47% male), 26.8% endorsed significant depressive symptoms (depression score ≥16) and 68.1% completed the intervention, attending 54.6±30.0% of supervised exercise sessions. Baseline depressive symptoms (depression scale score ≥16) increased the risk of non-completion [hazard ratio 1.49 (95% CI 1.10-2.03); P = 0.010], and predicted fewer sessions attended (ß=-2.1, P= 0.002) in adjusted models. A depression score threshold of ≥10 (48.4% of participants) predicted non-completion [hazard ratio 1.60 (95% CI 1.19-2.17); P= 0.002) with optimum accuracy. Non-completions resulting from lack of interest (18.9 vs. 11.0%; P= 0.026) and medical complications (14.6 vs. 6.6%; P= 0.006) were more common among participants with depression scores ≥10. Greater hazard ratios for depression scores ≥10 were observed in subgroups not currently using insulin [hazard ratio 1.70 (95% CI 1.24-2.33); P= 0.001), or an antidepressant [hazard ratio 1.83 (95% CI 1.32-2.54); P<0.001]. CONCLUSIONS: Depressive symptoms were highly prevalent among participants with Type 2 diabetes entering exercise-based rehabilitation, and even mild depressive symptoms posed a significant barrier to completion. Depression screening may help target additional supports to facilitate completion of exercise interventions for people with Type 2 diabetes.

Comparison of Total Arch and Partial Arch Transposition During Hybrid Endovascular Repair for Aortic Arch Disease.

OBJECTIVE: Total arch transposition (TAT) during hybrid endovascular repair for aortic arch disease is believed to allow a better landing zone, but also to be associated with higher peri-operative mortality than partial arch transposition (PAT). Information on this issue is limited. METHOD: This study was a retrospective analysis. All 53 consecutive patients with aortic arch disease (41 males, mean age 65.0 years) who underwent hybrid endovascular repair with TAT (zone 0, n=20) or PAT (zone 1 or 2, n=33) from 2008 to 2014 were analyzed retrospectively. The peri-operative and late outcomes of these two groups were compared. RESULTS: Baseline characteristics, including EuroSCORE II results, were similar in the two groups. After procedures, peri-operative mortalities and stroke rates were similar in the two groups (5.0% vs. 9.1%, p=1.000, and 10.0% vs. 6.1%, p=.627). Interestingly, all four strokes occurred in patients with a type III aortic arch irrespective of transposition type. Primary success rates (80.0% vs. 69.7%, p=.527) and type I endoleak incidences (20.0% vs. 27.3%, p=.744) were not significantly different. During follow up (mean duration 36.9 months), overall survival (89.7% vs. 87.4% at 1 year and 89.7% vs. 79.3% at 3 years; p=.375) and re-intervention free survival rates (78.6% vs. 92.0% at 1 year; 72.0% vs. 62.2% at 3 years, p=.872) were similar in the two groups. CONCLUSION: Morbidity and mortality were high within the first year of hybrid endovascular therapy for aortic arch disease, implying that candidates for hybrid procedures need to be selected carefully. Hybrid endovascular repair with TAT was found to have peri-operative mortality, stroke, and long-term survival rates comparable with PAT, so hybrid endovascular repair may be considered, irrespective of type of arch reconstruction, when clinically indicated.

Predictors of low bone mineral density of the stroke-affected hip among ambulatory individuals with chronic stroke.

UNLABELLED: Risk of hip fracture is greater poststroke than in an age-matched healthy population, in part because of declining hip BMD. We found that individuals may be at risk of loss of hip BMD from muscle atrophy, asymmetrical gait, and poor affected-side ankle dorsiflexor strength. These impairments may be targeted during rehabilitation. INTRODUCTION: This study aimed to determine predictors of low hip BMD on the stroke-affected side in people living in the community. METHODS: Forty-three participants (female; 27.9%), mean age 62.4 ± 13.5 and 17.9 ± 32.8 months, poststroke with motor impairments underwent dual energy X-ray absorptiometry scans. Gait characteristics, isometric strength, body composition, and fasting plasma lipids were measured. RESULTS: At entry, 34.9% (15/43) of the participants had low total hip BMD on the stroke-affected side. Of those with low BMD, 93.3% (14/15) had a step length symmetry ratio >1, indicating greater reliance on the non-paretic leg for weight bearing. Logistic regression analysis revealed that lower affected-side ankle dorsiflexor strength (ß = 0.700, p = 0.02), lower total body fat-free mass index (ß = 0.437, p = 0.02), and greater step length symmetry ratio during walking (ß = 1.135 × 10(3), p = 0.03) were predictors of low hip BMD. CONCLUSION: Low BMD of the stroke-affected side hip is prevalent in over a third of individuals with lower limb motor impairments. These individuals may be at particular risk of accelerated loss of BMD at the hip from asymmetrical gait pattern and poor affected-side ankle dorsiflexor strength. These impairments are intervention targets that may be addressed during rehabilitation which includes resistance training and addresses gait impairments.

Pediatric Mental Health Emergencies During 5 COVID-19 Waves in New York City.

OBJECTIVES: To describe the proportion of pediatric mental health emergency department (MH-ED) visits across 5 COVID-19 waves in New York City (NYC) and to examine the relationship between MH-ED visits, COVID-19 prevalence, and societal restrictions. METHODS: We conducted a time-series analysis of MH-ED visits among patients ages 5 to 17 years using the INSIGHT Clinical Research Network, a database from 5 medical centers in NYC from January 1, 2016, to June 12, 2022. We estimated seasonally adjusted changes in MH-ED visit rates during the COVID-19 pandemic, compared with predicted prepandemic levels, specific to each COVID-19 wave and stratified by mental health diagnoses and sociodemographic characteristics. We estimated associations between MH-ED visit rates, COVID-19 prevalence, and societal restrictions measured by the Stringency Index. RESULTS: Of 686 500 ED visits in the cohort, 27 168 (4.0%) were MH-ED visits. The proportion of MH-ED visits was higher during each COVID-19 wave compared with predicted prepandemic trends. Increased MH-ED visits were seen for eating disorders across all waves; anxiety disorders in all except wave 3; depressive disorders and suicidality/self-harm in wave 2; and substance use disorders in waves 2, 4, and 5. MH-ED visits were increased from expected among female, adolescent, Asian race, high Child Opportunity Index patients. There was no association between MH-ED visits and NYC COVID-19 prevalence or NY State Stringency Index. CONCLUSIONS: The proportion of pediatric MH-ED visits during the COVID-19 pandemic was higher during each wave compared with the predicted prepandemic period, with varied increases among diagnostic and sociodemographic subgroups. Enhanced pediatric mental health resources are essential to address these findings.

Characterization of the ileal microbiota in rejecting and nonrejecting recipients of small bowel transplants.

Small bowel transplantation can be a life-preserving procedure for patients with irreversible intestinal failure. Allograft rejection remains a major source of morbidity and mortality and its accurate diagnosis and treatment are critical. In this study, we used pyrosequencing of 16S ribosomal RNA gene tags to compare the composition of the ileal microbiota present during nonrejection, prerejection and active rejection states in small bowel transplant patients. During episodes of rejection, the proportions of phylum Firmicutes (p < 0.001) and the order Lactobacillales (p < 0.01) were significantly decreased, while those of the phylum Proteobacteria, especially the family Enterobacteriaceae, were significantly increased (p < 0.005). Receiver-operating characteristic analysis revealed that relative proportions of several bacterial taxa in ileal effluents and especially Firmicutes, could be used to discriminate between nonrejection and active rejection. In conclusion, the findings obtained during this study suggest that small bowel transplant rejection is associated with changes in the microbial populations in ileal effluents and support microbiota profiling as a potential diagnostic biomarker of rejection. Future studies should investigate if the dysbiosis that we observed is a cause or a consequence of the rejection process.

Variability in pediatric appendectomy: The association between disposable supply cost and procedure duration.

BACKGROUND: Pediatric appendicitis accounts for a notable proportion of health care use and cost in the United States. To identify opportunities for cost savings during pediatric laparoscopic appendectomy, this study assessed whether surgeons' use of costlier disposable supplies correlated with procedure duration and patient outcomes. METHODS: This retrospective cross-sectional study assessed laparoscopic appendectomy for uncomplicated pediatric appendicitis at 2 tertiary-care academic hospitals. The cost of disposable surgical supplies, procedure duration, and patient outcomes were obtained from medical records. The correlation between average supply cost and procedure duration among surgeons was assessed using Pearson's correlation coefficient. Associations between use of specific disposable supplies and supply cost or procedure duration were assessed using Student's t tests. RESULTS: A total of 380 laparoscopic appendectomies were performed by 11 surgeons. Mean normalized supply cost varied between surgeons (range: 60.6%-151.1%) and was not correlated with procedure duration (R = 0.2951, P = .378). The use of energy-based sealing devices (76.7% increase, P < .001), staplers (38.4% increase, P < .001), endoscopic specimen pouches (45.3% increase, P < .001), and disposable ports (43.6% increase, P < .001) increased overall disposable supply cost. None of the disposable supplies in this analysis were associated with shorter procedures. Based on Medicaid reimbursement, the interquartile range of supply cost was 9.2% and 6.0% of hospital revenue at each site. CONCLUSION: Surgeons varied in their use of disposable supplies for pediatric laparoscopic appendectomy, but the cost of supplies used did not influence outcomes. Incentivizing more judicious supply use may reduce costs related to pediatric appendicitis.

Feasibility and preliminary efficacy of the LEAD trial: a cluster randomized controlled lifestyle intervention to improve hippocampal volume in older adults at-risk for dementia.

BACKGROUND: Healthy diet and exercise are associated with reduced risk of dementia in older adults. The impact of diet and exercise interventions on brain health is less consistent, especially with dietary interventions which rely on varying approaches. Our objective was to evaluate the feasibility and preliminary efficacy of a 6-month intervention combining exercise with a novel dietary counseling approach to improve hippocampal volume among older adults at-risk for dementia. METHODS: Participants with vascular risk factors and subjective cognitive decline or early mild cognitive impairment were cluster randomized in groups of 3-4 to the diet intervention (DIET) or control education (ED) group. All participants engaged in 1 h of supervised exercise per week and additional exercise at home. DIET involved 1 h per week of group-based dietary counseling comprising education, goal setting, and strategy training. ED involved 1 h per week of group-based brain health education classes. Our primary outcome was change in hippocampal volume from baseline to 6 months. Secondary outcomes included changes in cognitive function, blood biomarkers, diet, and fitness. Recruitment challenges and early discontinuation of the trial due to COVID-19 necessitated a revised focus on feasibility and preliminary efficacy. RESULTS: Of 190 older adults contacted, 14 (7%) were eligible and enrolled, constituting 21% of our recruitment target. All participants completed the intervention and attended 90% of exercise and DIET/ED sessions on average. All 6-month assessments prior to COVID-19 were completed but disruptions to in-person testing resulted in incomplete data collection. No serious adverse events occurred and all participants expressed positive feedback about the study. Preliminary findings did not identify any significant changes in hippocampal volume; however, substantial improvements in diet and HbA1c were observed with DIET compared to ED (d = 1.75 and 1.07, respectively). CONCLUSIONS: High adherence and retention rates were observed among participants and preliminary findings illustrate improvements in diet quality and HbA1c. These results indicate that a larger trial is feasible if difficulties surrounding recruitment can be mitigated. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03056508 .

Secondary review reduced inpatient MRI orders and avoidable hospital days.

INTRODUCTION: Medical centers have dramatically increased the use of magnetic resonance imaging (MRI). At 2 large academic tertiary care centers in New York City, nearly half of inpatient MRI orders took more than 12 h to complete, delaying patient discharge and increasing avoidable hospital days. We posited that transitioning inpatient MRIs to outpatient facilities, when safe and appropriate, could reduce inpatient MRI orders and avoidable hospital days. METHODS: We manually reviewed 59 inpatient MRI orders delayed on the estimated date of discharge (EDD). These orders were often delayed due to no standard process to escalate orders for medical reasons or no system to coordinate outpatient orders. We developed a revised workflow involving an automation platform that flagged inpatient MRI orders requested within 24 h of the EDD and emailed the care team to request a second review of the order. The care team reconsidered whether the order was (1) required for discharge, (2) non-urgent and could be converted to an outpatient order, or (3) unnecessary and could be canceled. RESULTS: Over 9 months, the automation platform flagged 618 inpatient MRI orders, of which 53.9% (333/618) were reviewed by the care team. Among the orders, 24.0% (80/333) of reviewed orders and 12.9% (80/618) of all orders were transitioned to either outpatient or canceled orders. These transitioned orders were associated with 267 fewer avoidable hospital days and a cost savings of $199,194. CONCLUSION: A standardized process and second review of inpatient MRI orders on the EDD can reduce inappropriate orders and more effectively use inpatient imaging resources. PRECIS: A standardized workflow and automation platform encouraged a second review of inpatient MRI orders to reduce inappropriate orders, avoidable hospital days, and hospital costs.

Brain derived neurotrophic factor, cardiopulmonary fitness and cognition in patients with coronary artery disease.

OBJECTIVE: To assess serum brain derived neurotrophic factor (BDNF) concentrations as a correlate of cardiopulmonary fitness and as a predictor of cognitive performance in subjects with coronary artery disease (CAD). METHODS: Serum BDNF concentrations were assayed by ELISA and fitness was assessed using a standardized exercise stress test. The Mini Mental Status Examination (MMSE), California Verbal Learning Test 2nd Ed., Stroop, Trail Making Test B and the Digit Symbol-Coding task were administered. The val66met BDNF genotype and serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations were determined as potential confounders. RESULTS: In subjects with CAD (n=88; 85.2% male, mean age 62.8±10.5 yr), cardiopulmonary fitness was associated with higher serum BDNF concentrations (ß=.305, p=.013). Higher serum BDNF concentrations were associated with higher MMSE scores (F(1,87)=15.406, p<.0005) and better performance on the Digit Symbol-Coding task (F(1,87)=9.620, p=.003). IL-6, TNF-α and the val66met genotype did not influence these results. CONCLUSION: Serum BDNF concentrations were associated with cardiopulmonary fitness, psychomotor processing speed and overall cognition in subjects with CAD.

LSD use in the United States: Trends, correlates, and a typology of us.

BACKGROUND: Recent years have witnessed an increased interest in LSD. This study investigates current information on the trends and correlates of LSD use from years 2002-2018 and seeks to develop an initial typology of use and misuse. METHODS: Data is taken from the NSDUH (National Survey on Drug Use and Health) collected between 2002 and 2018 and trends and correlates of LSD use were analyzed with a survey adjusted logistic regression. RESULTS: Our findings indicate that LSD use has increased 200 % over the study period (.23 % 2002-2005 to .72 % 2015-2018, AOR = 1.10, 95 % CI = 1.08, 1.12). Our findings also indicate several correlates of LSD use including higher levels of education (college degrees: AOR = 1.62, 95 % CI = 1.23, 2.13), not being married (divorced or separated, AOR = 2.31, 95 % CI = 1.44, 3.73, and have never been married, AOR = 5.67, f 95 % CI = 4.09, 7.86), as well as higher levels of antisocial behavior (having been arrested AOR = 3.20, 95 % CI = 2.50, 4.09) and comorbid mental health and substance abuse disorders (serious psychological distress, AOR = 2.39, 95 % CI = 2.05, 2.80). Further, four distinct subclasses were also discovered within LSD users and two of these subtypes of LSD users contained comorbid mental health disturbances and heavy involvement in the criminal justice system. CONCLUSION: LSD use has been on the rise within the last decades, particularly among those who are well educated. Two subclasses of LSD use (those with severe comorbid mental health disorders and those with criminal justice involvement) may require further interventions.

Interferons and bacterial lipopolysaccharide protect macrophages from productive infection by human immunodeficiency virus in vitro.

To determine the effects of immunomodulatory agents upon HIV replication in macrophages, cultured monocyte-derived macrophages were treated with various substances and then infected with a macrophage-tropic strain of HIV-1. Pretreatment with rIFN-alpha, IFN-beta, and IFN-gamma, or bacterial LPS prevented viral replication in macrophages. In treated cultures, little or no infectious HIV or p24 core antigen was released into the supernatant, no virions were seen by electron microscopy, no viral RNA or DNA was detectable in the cell lysates, and no cytopathology (as determined by multinucleated giant cell formation) occurred. In contrast, pretreatment with a wide dose range of recombinant IL-1 beta, IL-2, IL-4, IL-6, M-CSF, TNF, or lymphotoxin failed to protect macrophages from productive infection by HIV. A consistent effect of granulocyte/macrophage-CSF on HIV replication in macrophages was not observed. In dose response studies, pretreatment with approximately 100 U/ml of IFN-alpha, approximately 10 U/ml of IFN-beta, or approximately 100 U/ml of IFN-gamma was sufficient to prevent virion release maximally and to prevent cytopathology completely. In kinetic studies, IFN-alpha, IFN-gamma, or LPS were added to the macrophage cultures either before or after infection with HIV. Even when added 3 d after infection with a multiplicity of 1 50% tissue-culture infectious dose per cell, all three treatments markedly reduced virion release, suggesting that these agents act at a point in the viral life cycle beyond the early events of virus binding, penetration, and uncoating. These data indicate that HIV replication in previously uninfected macrophages may be regulated by an inducible host cell mechanism. These findings may explain the restricted replication of HIV in macrophages in vivo and suggest an antiviral role for interferons in the therapy of HIV infection.

Dynamin at the neck of caveolae mediates their budding to form transport vesicles by GTP-driven fission from the plasma membrane of endothelium.

The molecular mechanisms mediating cell surface trafficking of caveolae are unknown. Caveolae bud from plasma membranes to form free carrier vesicles through a "pinching off" or fission process requiring cytosol and driven by GTP hydrolysis (Schnitzer, J.E., P. Oh, and D.P. McIntosh. 1996. Science. 274:239-242). Here, we use several independent techniques and functional assays ranging from cell-free to intact cell systems to establish a function for dynamin in the formation of transport vesicles from the endothelial cell plasma membrane by mediating fission at the neck of caveolae. This caveolar fission requires interaction with cytosolic dynamin as well as its hydrolysis of GTP. Expression of dynamin in cytosol as well as purified recombinant dynamin alone supports GTP-induced caveolar fission in a cell-free assay whereas its removal from cytosol or the addition to the cytosol of specific antibodies for dynamin inhibits this fission. Overexpression of mutant dynamin lacking normal GTPase activity not only inhibits GTP-induced fission and budding of caveolae but also prevents caveolae-mediated internalization of cholera toxin B chain in intact and permeabilized endothelial cells. Analysis of endothelium in vivo by subcellular fractionation and immunomicroscopy shows that dynamin is concentrated on caveolae, primarily at the expected site of action, their necks. Thus, through its ability to oligomerize, dynamin appears to form a structural collar around the neck of caveolae that hydrolyzes GTP to mediate internalization via the fission of caveolae from the plasma membrane to form free transport vesicles.

Filipin-sensitive caveolae-mediated transport in endothelium: reduced transcytosis, scavenger endocytosis, and capillary permeability of select macromolecules.

Caveolae or noncoated plasmalemmal vesicles found in a variety of cells have been implicated in a number of important cellular functions including endocytosis, transcytosis, and potocytosis. Their function in transport across endothelium has been especially controversial, at least in part because there has not been any way to selectively inhibit this putative pathway. We now show that the ability of sterol binding agents such as filipin to disassemble endothelial noncoated but not coated plasmalemmal vesicles selectively inhibits caveolae-mediated intracellular and transcellular transport of select macromolecules in endothelium. Filipin significantly reduces the transcellular transport of insulin and albumin across cultured endothelial cell monolayers. Rat lung microvascular permeability to albumin in situ is significantly decreased after filipin perfusion. Conversely, paracellular transport of the small solute inulin is not inhibited in vitro or in situ. In addition, we show that caveolae mediate the scavenger endocytosis of conformationally modified albumins for delivery to endosomes and lysosomes for degradation. This intracellular transport is inhibited by filipin both in vitro and in situ. Other sterol binding agents including nystatin and digitonin also inhibit this degradative process. Conversely, the endocytosis and degradation of activated alpha 2-macroglobulin, a known ligand of the clathrin-dependent pathway, is not affected. Interestingly, filipin appears to inhibit insulin uptake by endothelium for transcytosis, a caveolae-mediated process, but not endocytosis for degradation, apparently mediated by the clathrin-coated pathway. Such selective inhibition of caveolae not only provides critical evidence for the role of caveolae in the intracellular and transcellular transport of select macromolecules in endothelium but also may be useful for distinguishing transport mediated by coated versus noncoated vesicles.

Role of GTP hydrolysis in fission of caveolae directly from plasma membranes.

Caveolae are specialized invaginated cell surface microdomains of undefined function. A cell-free system that reconstituted fission of caveolae from lung endothelial plasma membranes was developed. Addition of cytosol and the hydrolysis of guanosine triphosphate (GTP) induced caveolar fission. The budded caveolae were isolated as vesicles rich in caveolin and the sialoglycolipid GM1 but not glycosyl-phosphatidylinositol (GPI)-anchored proteins. These vesicles contained the molecular machinery for endocytosis and transcytosis. In permeabilized endothelial cells, GTP stimulated, whereas GTPgammaS prevented, caveolar budding and endocytosis of the cholera toxin B chain to endosomes. Thus, caveolae may bud to form discrete carrier vesicles that participate in membrane trafficking.

Separation of caveolae from associated microdomains of GPI-anchored proteins.

In situ coating of the surface of endothelial cells in rat lung with cationic colloidal silica particles was used to separate caveolae from detergent-insoluble membranes rich in glycosyl phosphatidylinositol (GPI)-anchored proteins but devoid of caveolin. Immunogold electron microscopy showed that ganglioside GM1-enriched caveolae associated with an annular plasmalemmal domain enriched in GPI-anchored proteins. The purified caveolae contained molecular components required for regulated transport, including various lipid-anchored signaling molecules. Such specialized distinct microdomains may exist separately or together in the plasma membrane to organize signaling molecules and to process surface-bound ligands differentially.

Lower serum osteocalcin concentrations in patients with type 2 diabetes and relationships with vascular risk factors among patients with coronary artery disease.

BACKGROUND: Lower serum concentrations of the osteoblast-derived protein, osteocalcin, have been associated with poorer glycemic control, insulin resistance and atherosclerosis, and with the development of type 2 diabetes (T2DM). METHODS: This study compares concentrations of two physiological forms of osteocalcin, carboxylated (cOCN) and uncarboxylated (unOCN), between participants with T2DM (n = 20) and age-, gender- and body mass index (BMI)-matched participants without T2DM (n = 40) among patients with coronary artery disease (CAD), and it explores relationships between osteocalcin concentrations and cardiovascular risk factors. RESULTS: Concentrations of unOCN (2.71 ±â€¯1.86 vs. 4.70 ±â€¯2.03 ng/mL; t = -3.635, p = 0.001) and cOCN (8.70 ±â€¯2.27 vs. 10.77 ±â€¯3.69 ng/mL; t = -2.30, p = 0.025) were lower in participants with T2DM. In participants without T2DM, concentrations of cOCN were associated with fitness (VO2Peak rho = 0.317, p = 0.047) and lower body fat (rho = -0.324, p = 0.041). In participants with T2DM, lower unOCN was associated with HbA1c (rho = -0.516, p = 0.020). Higher body mass was associated with higher unOCN (rho = 0.423, p = 0.009) in participants without T2DM, but with lower concentrations of both unOCN (rho = -0.590, p = 0.006) and cOCN (rho = -0.632, p = 0.003) in participants with T2DM. CONCLUSION: In patients with CAD, lower osteocalcin concentrations were related to type 2 diabetes, and to adverse fitness, metabolic and obesity profiles.

Cost-utility analysis of Canadian tailored prophylaxis, primary prophylaxis and on-demand therapy in young children with severe haemophilia A.

Primary prophylaxis is the emerging standard treatment for boys with severe haemophilia. Tailored (escalating-dose) prophylaxis (EscDose), beginning at a low frequency and escalating with repeated bleeding may prevent arthropathy at a lower cost than standard prophylaxis (SP). From a societal perspective, we compared the incremental cost per joint-haemorrhage that is avoided and quality-adjusted-life-year (QALY) gained of SP and EscDose to on-demand (Demand) therapy in severe haemophilia A boys treated to age 6 using a decision analytic model. Costs included factor VIII (FVIII), professional visits and tests, central venous placement/complications, hospitalization, home programmes and parents' lost work-days. Resource utilization was estimated by surveying 17 Canadian clinics. The natural history of bleeding and other probabilities were determined from a longitudinal chart review (n = 24) and published literature. EscDose costs an additional $3192 per joint-haemorrhage that was avoided compared with Demand whereas SP costs an additional $9046 per joint-haemorrhage that was avoided compared with EscDose. Clinic costs and lost wages were reduced by 60-80% for EscDose and SP compared with Demand. EscDose attained more QALYs than SP and Demand on account of less bleeding than Demand and lower need for ports than SP. The incremental cost per QALY for EscDose vs. Demand was $542 938. EscDose was less expensive with similar QALYs compared to SP. Sensitivity analysis was performed on all probability- and cost-estimates, and showed the model was sensitive to the cost of FVIII and the SP and target joint utilities. In conclusion, prophylaxis will substantially improve clinical outcomes and quality of life compared to Demand treatment, but with substantial cost.

A prospective study examining the influence of cardiac rehabilitation on the sedentary time of highly sedentary, physically inactive patients.

OBJECTIVES: Prolonged sedentary time is recognized as a distinct health risk, and mortality risks are expected to be greatest for individuals with low exercise levels. It is unknown whether participation in exercise-based cardiac rehabilitation (CR) programs influences sedentary behaviour particularly among those patients expected to be at greatest mortality risk. This study examined the influence of CR participation on sedentary behaviour and identified the proportion and characteristics (socio-demographic and clinical) of patients who do not meet exercise recommendations and have prolonged sedentary times. METHODS: A prospective study was conducted among patients of an exercise-based CR program and assessments performed at baseline and 3 months. Physical activity and sedentary behaviour information were collected by self-report, and convergent validity was examined on an accelerometer-wearing subsample. RESULTS: Of 468 CR patients approached, 130 participants were recruited with an average sedentary time of 8hours/day. Sedentary behaviour remained consistent at follow-up (relative change= -2.4%, P=0.07) notwithstanding a greater proportion meeting exercise recommendations (relative change= 57.4%). 19.2% of participants were classified to have prolonged sedentary time and not meet exercise recommendations at baseline. No significant differences were found between the characteristics of high-risk individuals and lower risk subgroups. Findings were consistent among the accelerometer-derived subgroup and the overall sample despite poor to moderate convergent validity. CONCLUSIONS: These results suggest that the exercise-focus of CR may not reduce sedentary behaviours. Future studies are needed to determine whether sedentary behaviour-specific reduction strategies are more effective than traditional exercise-based strategies and lead to meaningful improvements in clinical outcomes.