Valery A. Danilack

Association between sclerostin and bone density in chronic spinal cord injury.

Spinal cord injury (SCI) results in profound bone loss due to muscle paralysis and the inability to ambulate. Sclerostin, a Wnt signaling pathway antagonist produced by osteocytes, is a potent inhibitor of bone formation. Short‐term studies in rodent models have shown increased sclerostin in response to mechanical unloading that is reversed with reloading. These studies suggest that complete spinal cord injury, a condition resulting in mechanical unloading of the paralyzed lower extremities, will be associated with high sclerostin levels. We assessed the relationship between circulating sclerostin and bone density in 39 subjects with chronic SCI and 10 without SCI. We found that greater total limb bone mineral content was significantly associated with greater circulating levels of sclerostin. Sclerostin levels were reduced, not elevated, in subjects with SCI who use a wheelchair compared with those with SCI who walk regularly. Similarly, sclerostin levels were lower in subjects with SCI who use a wheelchair compared with persons without SCI who walk regularly. These findings suggest that circulating sclerostin is a biomarker of osteoporosis severity, not a mediator of ongoing bone loss, in long‐term, chronic paraplegia. This is in contrast to the acute sclerostin‐mediated bone loss shown in animal models of mechanical unloading in which high sclerostin levels suppress bone formation. Because these data indicate important differences in the relationship between mechanical unloading, sclerostin, and bone in chronic SCI compared with short‐term rodent models, it is likely that sclerostin is not a good therapeutic target to treat chronic SCI‐induced osteoporosis.

Daily step counts in a US cohort with COPD

BACKGROUND Baseline values for daily step counts in US adults with COPD and knowledge of its accurate measurement, natural change over time, and independent relationships with measures of COPD severity are limited. METHODS 127 persons with stable COPD wore the StepWatch Activity Monitor (SAM) for 14 days, and 102 of them wore it a median 3.9 months later. SAM counts were compared to manual counts in the clinic. We assessed change over time, the effect of season, and relationships with forced expiratory volume in 1 s (FEV(1)) % predicted, 6-min walk test (6MWT) distance, the modified Medical Research Council (MMRC) dyspnea score, and the St. Georges Respiratory Questionnaire Total Score (SGRQ-TS). RESULTS 98% of subjects were males, with mean age 71 ± 8 years and FEV(1) 1.48 ± 0.54 L (52 ± 19% predicted). All 4 GOLD stages were represented, with the most subjects in GOLD II (44%) and GOLD III (37%). The SAM had >90% accuracy in 99% of subjects. Average step count was 5680 steps/day, which decreased with increasing GOLD stage (p = 0.0046). Subjects walked 645 fewer steps/day at follow-up, which was partly explained by season of monitoring (p = 0.013). In a multivariate model, FEV(1) % predicted, 6MWT distance and MMRC score were weakly associated with daily step counts, while SGRQ-TS was not. CONCLUSIONS These findings will aid the design of future studies using daily step counts in COPD. Accurately measured, daily step counts decline over time partly due to season and capture unique information about COPD status.

Pregnancy-Induced Hypertension and Diabetes and the Risk of Cardiovascular Disease, Stroke, and Diabetes Hospitalization in the Year Following Delivery

Although pregnancy events predict the long-term risk of chronic disease, little is known about their short-term impact because of the rarity of clinical events. We examined hospital discharge diagnoses linked to birth certificate data in the year following delivery for 849,639 births during 1995-2004 in New York City, New York. Adjusted odds ratios characterized the relationship between pregnancy complications and subsequent hospitalization for cardiovascular disease, stroke, and diabetes. Gestational hypertension was related to heart failure (adjusted odds ratio = 2.6, 95% confidence interval: 1.5, 4.5). Preeclampsia was related to all of the outcomes considered except type 1 diabetes, with adjusted odds ratios ranging from 2.0 to 4.1. Gestational diabetes was strongly related to the risk of subsequent diabetes (for type 1 diabetes, adjusted odds ratio = 40.4, 95% confidence interval: 23.8, 68.5; for type 2 diabetes, adjusted odds ratio = 22.6, 95% confidence interval: 16.9, 30.4) but to no other outcomes. The relationship of pregnancy complications to future chronic disease is apparent as early as the year following delivery. Moreover, elucidating short-term clinical outcomes offers the potential for etiological insights into the relationship between pregnancy events and chronic disease over the life course.

An Index of Daily Step Count and Systemic Inflammation Predicts Clinical Outcomes in Chronic Obstructive Pulmonary Disease

BACKGROUND Identification of persons with chronic obstructive pulmonary disease (COPD) at risk for acute exacerbations (AEs) targets them for close monitoring. OBJECTIVES We examined the ability of a novel index combining physical activity and systemic inflammation to identify persons at risk for AEs. METHODS In an observational cohort study of 167 persons with COPD, we assessed daily step count, a direct measure of physical activity, with the StepWatch Activity Monitor and measured plasma C-reactive protein (CRP) and IL-6 levels. AEs and COPD-related hospitalizations were assessed prospectively over a median of 16 months. Predictors of AEs and COPD-related hospitalizations were assessed using negative binomial models. MEASUREMENTS AND MAIN RESULTS Median daily step count was 5,203 steps (interquartile range, 3,627-7,024). Subjects with daily step count ≤ 5,203 and CRP > 3 mg/l had an increased rate of AEs (rate ratio [RR], 2.06; 95% confidence interval [CI], 1.30-3.27) and COPD-related hospitalizations (RR, 3.51; 95% CI, 1.73-7.11) compared with subjects with daily step count > 5,203 and CRP ≤ 3 mg/l, adjusting for FEV1% predicted and prednisone use for AE in the previous year. Similarly, subjects with daily step count ≤ 5,203 and IL-6 > 2 pg/ml had an increased rate of AEs (RR, 2.04; 95% CI, 1.14-3.63) and COPD-related hospitalizations (RR, 4.27; 95% CI, 1.56-11.7) compared with subjects with daily step count > 5,203 and IL-6 ≤ 2 pg/ml. CONCLUSIONS An index combining daily step count and systemic inflammation can predict AEs and COPD-related hospitalizations. A validation study in a separate cohort is needed to confirm the utility of the proposed index as a clinical tool to risk stratify persons with COPD.

Daily Step Count Is Associated With Plasma C-Reactive Protein and IL-6 in a US Cohort With COPD

BACKGROUND Physical activity is an important clinical marker of disease status in COPD. COPD is also characterized by low-grade systemic inflammation. However, the relationship between physical activity and systemic inflammation in COPD is unclear. METHODS We monitored daily step count, a directly measured physical activity, using the StepWatch Activity Monitor, an ankle-worn accelerometer, in 171 people with stable COPD. Exercise capacity was assessed with the 6-min walk test (6MWT). We measured plasma C-reactive protein (CRP) and IL-6 levels. Linear regression models examined the cross-sectional associations of daily step count and 6MWT distance with CRP and IL-6 levels. RESULTS Subjects had a mean age 72±8 years and mean FEV1 1.5±0.57 L (54±20% predicted). Median daily step count was 5,203 (interquartile range [IQR], 3,627-7,024], CRP level was 2.4 mg/L (IQR, 1.2-5.0), and IL-6 level was 2.9 pg/mL (IQR, 2.0-5.1). Each 1,000-step increase in daily step count was associated with a 0.94 mg/L and 0.96 pg/mL decrease in CRP (P=.020) and IL-6 (P=.044) levels, respectively, adjusting for age, FEV1 % predicted, pack-years smoked, cardiac disease, current statin use, history of acute exacerbations, and season. There was a significant linear trend of increasing daily step count by quartiles and decreasing CRP (P=.0007) and IL-6 (P=.023) levels. Higher 6MWT distance was also significantly associated with lower CRP and IL-6 values. CONCLUSION People with COPD who walked the most had the lowest plasma CRP and IL-6 levels. These results provide the conceptual basis to study whether an intervention to promote walking will reduce systemic inflammation in people with COPD.

Unexpected complications of low-risk pregnancies in the United States

OBJECTIVE Determining appropriate sites of care for any type of medical issue assumes successful matching of patient risks to facility capabilities and resources. In obstetrics, predicting patients who will have a need for additional resources beyond routine obstetric and neonatal care is difficult. Women without prenatal risk factors and their newborns may experience unexpected complications during delivery or postpartum. In this study, we report the risk of unexpected maternal and newborn complications among pregnancies without identified prenatal risk factors. STUDY DESIGN We conducted a cross-sectional investigation utilizing US natality data to analyze 10 million birth certificate records from 2011 through 2013. We categorized pregnancies as low risk (no prenatal risk factors) or high risk (at least 1 prenatal risk factor) according to 19 demographic, medical, and pregnancy characteristics. We evaluated 21 individual unexpected or adverse intrapartum and postpartum outcomes in addition to a composite indicator of any adverse outcome. RESULTS Among 10,458,616 pregnancies, 38% were identified as low risk and 62% were identified as high risk for unexpected complications. At least 1 unexpected complication was indicated on the birth certificate for 46% of all pregnancies, 29% of low-risk pregnancies, and 57% of high-risk pregnancies. While the risk for unexpected or adverse outcomes was greatly reduced for the low-risk group compared to the high-risk group overall and for several of the individual outcomes, low-risk pregnancies had higher risks of vacuum delivery, forceps delivery, meconium staining, and chorioamnionitis compared to high-risk pregnancies. CONCLUSION Of births, 29% identified to be low risk had an unexpected complication that would require nonroutine obstetric or neonatal care. Additionally, for select outcomes, risks were higher in the low-risk group compared to the group with identified risk factors. This information is important for planning location of birth and evaluating birthing centers and hospitals for necessary resources to ensure quality care and patient safety.

Reasons Persons with COPD Do Not Walk and Relationship with Daily Step Count

Abstract Background: Physical activity (PA) is significantly reduced in persons with COPD. Assessing reasons why persons with COPD do not engage in PA can guide development of effective interventions to promote PA. Methods: We queried 102 participants with stable COPD about disease-related and general reasons why they do not walk more. The StepWatch Activity Monitor (Orthocare Innovations, Mountlake Terrace, WA, USA) assessed daily step count, a direct measure of PA. Regression models assessed daily step count by response categories, adjusting for age and FEV1 % predicted. Results: Subjects had mean age 72 ± 8 years and mean FEV1 1.48 ± 0.55 L (52 ± 19% predicted). COPD-related worries of becoming short of breath (SOB), needing to use inhalers, or oxygen level becoming low were endorsed by 31, 14, and 12 subjects, respectively. Controlling for age and FEV1% predicted, those who worried about becoming SOB walked an average of 1,329 fewer steps per day than those who did not worry (p = 0.020). Those who worried about needing to use inhalers walked an average of 1,806 fewer steps per day than those who did not worry (p = 0.016). Subjects who were the most motivated and confident walked significantly more than those who were the least motivated and confident. Conclusions: Presence of COPD-related reasons and lower motivation and confidence are associated with lower daily step count. Management of dyspnea and education about medication use during exercise, and strategies to increase motivation and confidence could facilitate walking in COPD.

Performance of a pedometer to measure physical activity in a U.S. cohort with chronic obstructive pulmonary disease.

Objective assessment of physical activity (PA) in chronic obstructive pulmonary disease (COPD) is important. We examined the performance of the Omron HJ-720ITC pedometer. A sample of 176 persons with stable COPD wore the Omron and the StepWatch Activity Monitor (SAM) in the clinic and the community. A 4 s step filter in the Omron screens out erroneous intermittent steps; it captures continuous walking that lasts >4 s. The SAM captures all intermittent and continuous steps walked. Omron-steps were compared with manually counted steps in the clinic and with SAM-steps in the community. We calculated the intraclass correlation coefficient for the first 2 d, the first 3 d, etc., up to 14 d. The Omron registered >/= 90% of the manually counted steps from the in-clinic walk in 155 of 176 subjects (88%). In the community, 47 +/- 16% of SAM-steps were continuous ones that were captured by the Omron. For the Omron and the SAM, at least 7 d of monitoring should be used to capture decreases in PA on weekend days and obtain optimum reliability for all Global Initiative for Chronic Obstructive Lung Disease stages. The Omron accurately and reliably measures continuous walking in COPD. The Omron may be ideal for use in PA interventions that promote continuous walking as exercise.

The effect of labour induction on the risk of caesarean delivery: using propensity scores to control confounding by indication.

To use propensity score methods to control for confounding by indication in the association between labour induction and caesarean delivery.

Associations with chest illness and mortality in chronic spinal cord injury

Abstract Objective Identify factors associated with chest illness and describe the relationship between chest illness and mortality in chronic spinal cord injury (SCI). Design Cross-sectional survey assessing chest illness and a prospective assessment of mortality. Methods Between 1994 and 2005, 430 persons with chronic SCI (mean ± SD), 52.0 ± 14.9 years old, and ≥4 years post SCI (20.5 ± 12.5 years) underwent spirometry, completed a health questionnaire, and reported any chest illness resulting in time off work, indoors, or in bed in the preceding 3 years. Deaths through 2007 were identified. Outcome measures Logistic regression assessing relationships with chest illness at baseline and Cox regression assessing the relationship between chest illness and mortality. Results Chest illness was reported by 139 persons (32.3%). Personal characteristics associated with chest illness were current smoking (odds ratio =2.15; 95% confidence interval =1.25–3.70 per each pack per day increase), chronic obstructive pulmonary disease (COPD) (3.52; 1.79–6.92), and heart disease (2.18; 1.14–4.16). Adjusting for age, subjects reporting previous chest illness had a non-significantly increased hazard ratio (HR) for mortality (1.30; 0.88–1.91). In a multivariable model, independent predictors of mortality were greater age, SCI level and completeness of injury, diabetes, a lower %-predicted forced expiratory volume in 1 second, heart disease, and smoking history. Adjusting for these covariates, the effect of a previous chest illness on mortality was attenuated (HR = 1.15; 0.77–1.73). Conclusion In chronic SCI, chest illness in the preceding 3 years was not an independent risk factor for mortality and was not associated with level and completeness of SCI, but was associated with current smoking, physician-diagnosed COPD, and heart disease history.