Background Epidemiologic studies link short sleep duration to obesity and weight gain. Insufficient sleep appears to alter circulating levels of the hormones leptin and ghrelin, which may promote ...appetite, although the effects of sleep restriction on caloric intake and energy expenditure are unclear. We sought to determine the effect of 8 days/8 nights of sleep restriction on caloric intake, activity energy expenditure, and circulating levels of leptin and ghrelin. Methods We conducted a randomized study of usual sleep vs a sleep restriction of two-thirds of normal sleep time for 8 days/8 nights in a hospital-based clinical research unit. The main outcomes were caloric intake, activity energy expenditure, and circulating levels of leptin and ghrelin. Results Caloric intake in the sleep-restricted group increased by +559 kcal/d (SD, 706 kcal/d, P = .006) and decreased in the control group by −118 kcal/d (SD, 386 kcal/d, P = .51) for a net change of +677 kcal/d (95% CI, 148-1,206 kcal/d; P = .014). Sleep restriction was not associated with changes in activity energy expenditure ( P = .62). No change was seen in levels of leptin ( P = .27) or ghrelin ( P = .21). Conclusions Sleep restriction was associated with an increase in caloric consumption with no change in activity energy expenditure or leptin and ghrelin concentrations. Increased caloric intake without any accompanying increase in energy expenditure may contribute to obesity in people who are exposed to long-term sleep restriction. Trial Registration ClinicalTrials.gov ; No.: NCT01334788 ; URL: www.clinicaltrials.gov
Measurement of bone mineral density is the most common method of diagnosing and assessing osteoporosis. We sought to estimate the average rate of change in bone mineral density as a function of age ...among Canadians aged 25-85, stratified by sex and use of antiresorptive agents.
We examined a longitudinal cohort of 9423 participants. We measured the bone mineral density in the lumbar spine, total hip and femoral neck at baseline in 1995-1997, and at 3-year (participants aged 40-60 years only) and 5-year follow-up visits. We used the measurements to compute individual rates of change.
Bone loss in all 3 skeletal sites began among women at age 40-44. Bone loss was particularly rapid in the total hip and was greatest among women aged 50-54 who were transitioning from premenopause to postmenopause, with a change from baseline of -6.8% (95% confidence interval CI -7.5% to -4.9%) over 5 years. The rate of decline, particularly in the total hip, increased again among women older than 70 years. Bone loss in all 3 skeletal sites began at an earlier age (25-39) among men than among women. The rate of decline of bone density in the total hip was nearly constant among men 35 and older and then increased among men older than 65. Use of antiresorptive agents was associated with attenuated bone loss in both sexes among participants aged 50-79.
The period of accelerated loss of bone mineral density in the hip bones occurring among women and men older than 65 may be an important contributor to the increased incidence of hip fracture among patients in that age group. The extent of bone loss that we observed in both sexes indicates that, in the absence of additional risk factors or therapy, repeat testing of bone mineral density to diagnose osteoporosis could be delayed to every 5 years.
Abstract The amino-bisphosphonates are first-line therapy for the treatment of most patients with osteoporosis, with proven efficacy to reduce fracture risk at the spine, hip, and other nonvertebral ...skeletal sites. Further, bisphosphonates have been associated with a significant decrease in morbidity and increase in survival. Following the use of bisphosphonates in millions of patients in clinical practice, some unexpected possible adverse effects have been reported, including osteonecrosis of the jaw, atypical femur fractures, atrial fibrillation, and esophageal cancer. Because bisphosphonates are incorporated into the skeleton and continue to exert an antiresorptive effect for a period of time after dosing is discontinued, the concept of a drug holiday has emerged, whereby the risk of adverse effects might be decreased while the patient still benefits from antifracture efficacy. Patients receiving bisphosphonates who are not at high risk for fracture are potential candidates for a drug holiday, while for those with bone mineral density in the osteoporosis range or previous history of fragility fracture, the benefits of continuing therapy probably far outweigh the risk of harm.
Abstract Vertebral fractures are common and can result in acute and chronic pain, decreases in quality of life, and diminished lifespan. The identification of vertebral fractures is important because ...they are robust predictors of future fractures. The majority of vertebral fractures do not come to clinical attention. Numerous modalities exist for visualizing suspected vertebral fracture. Although differing definitions of vertebral fracture may present challenges in comparing data between different investigations, at least 1 in 5 men and women aged >50 years have one or more vertebral fractures. There is clinical guidance to target spine imaging to individuals with a high probability of vertebral fracture. Radiology reports of vertebral fracture need to clearly state that the patient has a “fracture,” with further pertinent details such as the number, recency, and severity of vertebral fracture, each of which is associated with risk of future fractures. Patients with vertebral fracture should be considered for antifracture therapy. Physical and pharmacologic modalities of pain control and exercises or physiotherapy to maintain spinal movement and strength are important components in the care of vertebral fracture patients.
Objectives The aim of this study was to determine the impact of fat gain and its distribution on endothelial function in lean healthy humans. Background Endothelial dysfunction has been identified as ...an independent predictor of cardiovascular events. Whether fat gain impairs endothelial function is unknown. Methods A randomized controlled study was conducted to assess the effects of fat gain on endothelial function. Forty-three normal-weight healthy volunteers were recruited (mean age 29 years; 18 women). Subjects were assigned to gain weight (approximately 4 kg) (n = 35) or to maintain weight (n = 8). Endothelial function (brachial artery flow-mediated dilation FMD) was measured at baseline, after fat gain (8 weeks), and after weight loss (16 weeks) for fat gainers and at baseline and follow-up (8 weeks) for weight maintainers. Body composition was measured by dual-energy X-ray absorptiometry and abdominal computed tomographic scans. Results After an average weight gain of 4.1 kg, fat gainers significantly increased their total, visceral, and subcutaneous fat. Blood pressure and overnight polysomnography did not change after fat gain or loss. FMD remained unchanged in weight maintainers. FMD decreased in fat gainers (9.1 ± 3% vs. 7.8 ± 3.2%, p = 0.003) but recovered to baseline when subjects shed the gained weight. There was a significant correlation between the decrease in FMD and the increase in visceral fat gain (rho = −0.42, p = 0.004), but not with subcutaneous fat gain (rho = −0.22, p = 0.15). Conclusions In normal-weight healthy young subjects, modest fat gain results in impaired endothelial function, even in the absence of changes in blood pressure. Endothelial function recovers after weight loss. Increased visceral rather than subcutaneous fat predicts endothelial dysfunction. (Fat Gain and Cardiovascular Disease Mechanisms; NCT00589498 )
Driven largely by international declines in rates of walking and bicycling to school and the noted health benefits of physical activity for children, research on children's active commuting to school ...has expanded rapidly during the past 5 years. We summarize research on predictors and health consequences of active commuting to school and outline and evaluate programs specific to children's walking and bicycling to school.
Literature on children's active commuting to school published before June 2007 was compiled by searching PubMed, PsycINFO, and the National Transportation Library databases; conducting Internet searches on program-based activities; and reviewing relevant transportation journals published during the last 4 years.
Children who walk or bicycle to school have higher daily levels of physical activity and better cardiovascular fitness than do children who do not actively commute to school. A wide range of predictors of children's active commuting behaviors was identified, including demographic factors, individual and family factors, school factors (including the immediate area surrounding schools), and social and physical environmental factors. Safe Routes to School and the Walking School Bus are 2 public health efforts that promote walking and bicycling to school. Although evaluations of these programs are limited, evidence exists that these activities are viewed positively by key stakeholders and have positive effects on children's active commuting to school.
Future efforts to promote walking and bicycling to school will be facilitated by building on current research, combining the strengths of scientific rigor with the predesign and postdesign provided by intervention activities, and disseminating results broadly and rapidly.
Fathers’ engagement in infant caregiving is linked with positive social, emotional, and developmental outcomes in children; however, its relationship with fathers’ own health is largely unknown. This ...longitudinal study examined associations between fathers’ caregiving engagement with their 6-month-old infants and their physical activity, sugar-sweetened beverage (SSB) consumption, nighttime sleep duration, and depressive symptoms 6 months later when infants were 12 months old. Participants were 143 fathers of infants (62.7% non-Hispanic White, 82.3% with a bachelor’s degree). Fathers reported their frequency of engagement in seven caregiving activities when infants were 6 months old. Fathers’ physical activity, SSB consumption, nighttime sleep duration, and depressive symptoms were assessed when infants were 6 and 12 months old. Multivariate logistic regression analysis was used to assess if fathers who reported higher infant caregiving at 6 months had more positive health outcomes at 12 months, controlling for fathers’ age, race/ethnicity, education, employment, household income, and the outcome at 6 months. Fathers who reported higher caregiving engagement when infants were 6 months old had increased odds of being sufficiently physically active 6 months later (unadjusted odds ratio OR = 1.19, 95% confidence interval CI = 1.00, 1.41; adjusted OR = 1.47, 95% CI = 1.11, 1.96). No links were identified between fathers’ caregiving engagement and their SSB consumption, nighttime sleep duration, or depressive symptoms. In summary, fathers’ engagement in infant caregiving may be beneficial to their physical activity in the first year after birth. There was insufficient evidence in this study that the benefits of caregiving engagement were experienced broadly across multiple health outcomes.
To assess the added prognostic value of serial monitoring of urinary C-C motif chemokine ligand 14 (uCCL14) over that of single measurements, which have been shown to be prognostic for development of ...persistent severe acute kidney injury (AKI) in critically ill patients.
Retrospective observational study.
Data derived from two multinational ICU studies (Ruby and Sapphire).
Critically ill patients with early stage 2-3 AKI.
None.
We analyzed three consecutive uCCL14 measurements at 12-hour intervals after diagnosis of stage 2-3 AKI by Kidney Disease Improving Global Outcomes criteria. Primary outcome was persistent severe AKI, defined as 72 consecutive hours of stage 3 AKI, death, or receipt of dialysis prior to 72 hours. uCCL14 was measured using the NEPHROCLEAR uCCL14 Test on the Astute 140 Meter (Astute Medical, San Diego, CA). Based on predefined, validated cutoffs, we categorized uCCL14 as: low (≤ 1.3 ng/mL), medium (> 1.3 to ≤ 13 ng/mL), or high (> 13 ng/mL). Seventy-five of 417 patients with three consecutive uCCL14 measurements developed persistent severe AKI. Initial uCCL14 category strongly correlated with primary endpoint and, in most cases (66%), uCCL14 category was unchanged over the first 24 hours. Compared with no change and accounting for baseline category, decrease in category was associated with decreased odds of persistent severe AKI (odds ratio OR, 0.20; 95% CI, 0.08-0.45;
< 0.001) and an increase in category with increased odds (OR, 4.04; 95% CI, 1.75-9.46;
= 0.001).
In one-third of patients with moderate to severe AKI uCCL14 risk category altered over three serial measurements and such changes were associated with altered risk for persistent severe AKI. Serial CCL-14 measurement may detect progression or resolution of underlying kidney pathology and help refine AKI prognosis.
Abstract Osteoporosis is a chronic disease that requires life-long strategies to reduce fracture risk. Few trials have investigated the balance of benefits and risk with long-term use of osteoporosis ...therapies and fewer still have investigated the consequences of treatment discontinuation. The best available evidence suggests that up to 10 years of treatment with an oral bisphosphonate maintains the degree of fracture risk reduction observed in the three-year registration trials. With denosumab, 10 years of therapy appears to provide fracture risk reduction similar to or better than that observed in the three-year registration trial. Available data suggest an increasing but low risk of fractures with atypical features with increasing duration of bisphosphonate therapy. Published data linking duration of therapy to osteonecrosis of the jaw are lacking for bisphosphonates and denosumab. Other side effects associated with denosumab or bisphosphonates do not appear to be related to therapy duration. The anti-fracture benefits of long-term therapy with bisphosphonates and denosumab in appropriately selected patients outweigh the low risk of serious side effects.
Summary We analyzed a series of 55 disseminated appendiceal mucinous neoplasms treated at our institution for GNAS and KRAS mutations in an attempt to correlate mutation status with ...clinicopathological findings and patient survival. GNAS mutations (p.R201H, c.602G>A and p.R201C, and c.602C>T) were identified in 17 (31%) of 55 of disseminated mucinous neoplasms and were found in 8 (35%) of 23 low-grade mucinous neoplasms, 7 (37%) of 19 high-grade mucinous adenocarcinomas lacking a signet ring cell component, and 2 (15%) of 13 high-grade mucinous adenocarcinomas with a signet ring cell component. All 7 mucinous adenocarcinomas composed of pure (>95%) signet ring cells harbored wild-type GNAS . There was no significant association between GNAS mutations and sex and age (both with P > .05) or between GNAS mutations and individual adverse histologic features including cytologic grade, destructive invasion, tumor cellularity, angiolymphatic invasion, perineural invasion, and signet ring cells (all with P > .05). KRAS mutations were identified in 22 (40%) of 55 disseminated mucinous neoplasms. GNAS- mutated disseminated appendiceal mucinous neoplasms more frequently harbored concurrent KRAS mutations compared with GNAS wild-type tumors (65% versus 29%, P = .018). GNAS mutations were not significantly associated with overall survival (both with P > .05). Only overall tumor grade was an independent predictor of overall survival in the multivariate analysis ( P = .01). Our results indicate that GNAS mutations are frequently identified in both low-grade and high-grade disseminated appendiceal mucinous neoplasms indicating that GNAS mutation status cannot be used to distinguish between low-grade from high-grade appendiceal mucinous neoplasms.
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