Pulmonary embolism and 3-month outcomes in 4036 patients with venous thromboembolism and chronic obstructive pulmonary disease: data from the RIETE registry

Background

Patients with chronic obstructive pulmonary disease (COPD) have a modified clinical presentation of venous thromboembolism (VTE) but also a worse prognosis than non-COPD patients with VTE. As it may induce therapeutic modifications, we evaluated the influence of the initial VTE presentation on the 3-month outcomes in COPD patients.

Methods

COPD patients included in the on-going world-wide RIETE Registry were studied. The rate of pulmonary embolism (PE), major bleeding and death during the first 3 months in COPD patients were compared according to their initial clinical presentation (acute PE or deep vein thrombosis (DVT)).

Results

Of the 4036 COPD patients included, 2452 (61%; 95% CI: 59.2-62.3) initially presented with PE. PE as the first VTE recurrence occurred in 116 patients, major bleeding in 101 patients and mortality in 443 patients (Fatal PE: first cause of death). Multivariate analysis confirmed that presenting with PE was associated with higher risk of VTE recurrence as PE (OR, 2.04; 95% CI: 1.11-3.72) and higher risk of fatal PE (OR, 7.77; 95% CI: 2.92-15.7).

Conclusions

COPD patients presenting with PE have an increased risk for PE recurrences and fatal PE compared with those presenting with DVT alone. More efficient therapy is needed in this subtype of patients.     

无创呼吸机在慢性阻塞性肺疾病急性加重期应用的疗效评价

摘要目的：观察无创呼吸机对不伴有呼吸衰竭的慢性阻塞性肺疾病急性加重期（AECOPD）患者症状、体征、血气分析和肺功能的影响。方法：80例AECOPD患者随机分为对照组和试验组,对照组给予常规治疗,如常规抗感染、化痰、平喘等治疗。试验组在常规治疗的基础上给予无创呼吸机正压通气（NIPPV）治疗。评价两组患者治疗前和治疗一周后临床症状体征、血气分析和肺功能的变化。结果：两组患者治疗后临床症状及体征评分较治疗前均呈下降趋势（P〈0．05）,但试验组下降更为明显（P〈0．05）,并且试验组症状改善时间明显缩短（P〈0．05）;治疗后两组的pH,PO2和SaO2均较治疗前升高,PC02较治疗前下降（P〈0．05）,和对照组相比,治疗后试验组的PO：和PC02改善更明显（P〈0．05）,而pH和Sa02无显著差异（P〉0．05）;治疗后两组的FEV1,FVC,FEV1实测值／预计值和FEVI％均较治疗前升高（P〈0．05）,试验组升高更明显（P〈0．05）。结论：对不伴有呼吸衰竭的AECOPD患者早期应用NIPPV治疗能有效改善临床症状和体征,缩短症状改善时间,改善通气,缓解呼吸肌疲劳,预防呼吸衰竭的发生。     

Exploring the role of circadian clock gene and association with cancer pathophysiology

ABSTRACT

Most of the processes that occur in the mind and body follow natural rhythms. Those with a cycle length of about one day are called circadian rhythms. These rhythms are driven by a system of self-sustained clocks and are entrained by environmental cues such as light-dark cycles as well as food intake. In mammals, the circadian clock system is hierarchically organized such that the master clock in the suprachiasmatic nuclei of the hypothalamus integrates environmental information and synchronizes the phase of oscillators in peripheral tissues.

The circadian system is responsible for regulating a variety of physiological and behavioral processes, including feeding behavior and energy metabolism. Studies revealed that the circadian clock system consists primarily of a set of clock genes. Several genes control the biological clock, including BMAL1, CLOCK (positive regulators), CRY1, CRY2, PER1, PER2, and PER3 (negative regulators) as indicators of the peripheral clock.

Circadian has increasingly become an important area of medical research, with hundreds of studies pointing to the body’s internal clocks as a factor in both health and disease. Thousands of biochemical processes from sleep and wakefulness to DNA repair are scheduled and dictated by these internal clocks. Cancer is an example of health problems where chronotherapy can be used to improve outcomes and deliver a higher quality of care to patients.

In this article, we will discuss knowledge about molecular mechanisms of the circadian clock and the role of clocks in physiology and pathophysiology of concerns.     

Evening chronotype is associated with poor cardiovascular health and adverse health behaviors in a diverse population of women

ABSTRACT

Chronotype reflects time of day preferences for performing daily activities. Previous research within Asian and European cohorts indicates evening chronotype is associated with elevated cardiometabolic risk. However, evidence is limited from population-based US cohorts, particularly among women in whom evening chronotype prevalence may become higher after middle-age, coinciding with life stages associated with higher cardiovascular disease (CVD) risk. This cross-sectional study evaluated associations of chronotype with overall cardiovascular health (CVH), health behaviors, and cardiometabolic risk factors among 506 women (mean age = 37 ± 16y, 62% racial/ethnic minority) in the American Heart Association (AHA)’s Go Red for Women Strategically-Focused Research Network cohort at Columbia University (New York City, NY, USA). Chronotype was assessed using the validated Morningness-Eveningness Questionnaire (MEQ) and categorized as “evening”, “intermediate”, and “morning” chronotypes. Health behaviors (diet, physical activity, and sleep) were assessed using validated questionnaires. Anthropometrics, clinical blood pressure, and blood biomarkers were assessed at the clinic visit. CVH was evaluated using the AHA Life’s Simple 7 (LS7) metrics; LS7 scores of 0–8 and 9–14 were considered indicative of poor and moderate-to-high CVH, respectively. Linear and logistic regression models adjusted for age, race/ethnicity, education, health insurance, and menopausal status were used to examine associations of MEQ scores and chronotype categories with overall CVH, clinical cardiometabolic risk factors, and health behaviors. Overall, 13% of women identified as evening chronotypes, while 55% and 32% reported being intermediate and morning types. In linear models, higher MEQ scores were associated with higher AHA LS7 scores (β(SE) = 0.02(0.01); p = .014), indicative of more favorable CVH, and with health behaviors not included in the LS7. Higher MEQ scores were also associated with lower Pittsburgh Sleep Quality Index, i.e. better sleep quality, (β(SE) = ?0.07(0.02), p < .0001), lower insomnia severity (β(SE) = ?0.14(0.01), p < .0001), shorter time to fall asleep (β(SE) = ?0.28(0.14), p = .044), and less sedentary time (β(SE) = ?0.11(0.03), p = .001). In logistic regression models, evening chronotype, compared to intermediate/morning type, was associated with higher odds of having poor CVH (OR(95%CI):2.41(1.20–4.85)), not meeting AHA diet (OR(95%CI):2.89(1.59–5.23)) and physical activity guidelines (OR(95%CI):1.78(1.03–3.07)), and having short sleep (OR(95%CI):2.15(1.24–3.73)) or insomnia (OR(95%CI):2.69(1.53–4.75)). The evening type compared to morning type was also associated with being a current smoker (OR(95%CI):2.14(1.02–4.52)) and having poor sleep quality (OR(95%CI:2.35(1.27–4.37)) and long sleep onset latency (OR(95%CI:1.89(1.00–3.56)). In our cohort of women, evening chronotype was related to poor CVH, likely driven by its influence on health behaviors. These findings, although warranting confirmation prospectively in other populations, suggest chronotype is an important factor to consider and possibly target when designing lifestyle interventions for CVD prevention.     

Social and environmental impacts on sleep in captive Asian elephants (Elephas maximus)

Modern zoos strive to improve standards of animal management, husbandry and welfare of their animals as part of a continual evaluation process. Elephants (Elephantidae) have received particular attention in recent years due to the challenge of providing environments which promote natural behavior and opportunities for social interaction. A number of measures have been proposed to measure wellbeing, with sleep quality increasingly being used. Sleep is a vital aspect of life for cell replenishment as well as optimal development of young. Sleep deprivation can lead to immunosuppression and illness; therefore animal managers have a responsibility to ensure they reduce the potential for disturbance through noise, light, or other environmental factors. The social environment also plays an essential role in wellbeing, particularly for species that live in multi-generational family units. In this study the nocturnal behavior of a multi-generational captive herd was observed to determine impacts of husbandry changes on sleep duration and bout length (measured as recumbent rest). As expected, average total duration of sleep was higher in younger elephants and rates were comparable to those reported in other studies of Asian elephants. Overnight access to an outdoor paddock in warmer weather increased overall average bout length of sleep in the herd. Average total duration of sleep also increased for the herd following the movement of an unrelated adult female who had previously shown weak bonds with other herd members. This indicates that social compatibility is a vital component of elephant welfare, impacting not only behavioral interactions but sleep quality and duration.     

Validation of an innovative method,based on tilt sensing,for the assessment of activity and body position

Since there is less movement during sleep than during wake, the recording of body movements by actigraphy has been used to indirectly evaluate the sleep–wake cycle. In general, most actigraphic devices are placed on the wrist and their measures are based on acceleration detection. Here, we propose an alternative way of measuring actigraphy at the level of the arm for joint evaluation of activity and body position. This method analyzes the tilt of three axes, scoring activity as the cumulative change of degrees per minute with respect to the previous sampling, and measuring arm tilt for the body position inference. In this study, subjects (N?=?13) went about their daily routine for 7 days, kept daily sleep logs, wore three ambulatory monitoring devices and collected sequential saliva samples during evenings for the measurement of dim light melatonin onset (DLMO). These devices measured motor activity (arm activity, AA) and body position (P) using the tilt sensing of the arm, with acceleration (wrist acceleration, WA) and skin temperature at wrist level (WT). Cosinor, Fourier and non-parametric rhythmic analyses were performed for the different variables, and the results were compared by the ANOVA test. Linear correlations were also performed between actimetry methods (AA and WA) and WT. The AA and WA suitability for circadian phase prediction and for evaluating the sleep–wake cycle was assessed by comparison with the DLMO and sleep logs, respectively. All correlations between rhythmic parameters obtained from AA and WA were highly significant. Only parameters related to activity levels, such as mesor, RA (relative amplitude), VL5 and VM10 (value for the 5 and 10 consecutive hours of minimum and maximum activity, respectively) showed significant differences between AA and WA records. However, when a correlation analysis was performed on the phase markers acrophase, mid-time for the 10 consecutive hours of highest (M10) and mid-time for the five consecutive hours of lowest activity (L5) with DLMO, all of them showed a significant correlation for AA (R?=?0.607, p?=?0.028; R?=?0.582, p?=?0.037; R?=?0.620, p?=?0.031, respectively), while for WA, only acrophase did (R?=?0.621, p?=?0.031). Regarding sleep detection, WA showed higher specificity than AA (0.95?±?0.01 versus 0.86?±?0.02), while the agreement rate and sensitivity were higher for AA (0.76?±?0.02 versus 0.66?±?0.02 and 0.71?±?0.03 versus 0.53?±?0.03, respectively). Cohen’s kappa coefficient also presented the highest values for AA (0.49?±?0.04) and AP (0.64?±?0.04), followed by WT (0.45?±?0.06) and WA (0.37?±?0.04). The findings demonstrate that this alternative actigraphy method (AA), based on tilt sensing of the arm, can be used to reliably evaluate the activity and sleep–wake rhythm, since it presents a higher agreement rate and sensitivity for detecting sleep, at the same time allows the detection of body position and improves circadian phase assessment compared to the classical actigraphic method based on wrist acceleration.     

Heat tolerance after total and partial acute sleep deprivation

Sleep deprivation (SD) is suggested to be associated with reduced thermo-regulatory functions. This study aimed to quantify the effect of partial (PSD) and total (TSD) 24?h SD using a standard heat tolerance test (HTT). Eleven participants underwent HTT after well-rested state, PSD and TSD. No significant physiological differences were found between the exposures but subjective discomfort was higher after TSD. Evening chronotypes' temperature during HTT was higher after TSD compared with PSD (p = 0.017). After TSD, evening chronotypes compared to intermediate chronotypes' temperature was higher during the first hour of the HTT (p?<?0.05), suggesting that thermo-regulatory function during exercise in the heat is influenced by chronotype.     

Chronotype and sleep duration: The influence of season of assessment

Little is known about human entrainment under natural conditions, partly due to the complexity of human behavior, torn between biological and social time and influenced by zeitgebers (light–dark cycles) that are progressively “polluted” (and thereby weakened) by artificial light. In addition, data about seasonal variations in sleep parameters are scarce. We, therefore, investigated seasonal variation in cross-sectional assessments of sleep/wake times of 9765 subjects from four European populations (EGCUT?=?Estonian Genome Centre, University of Tartu in Estonia; KORA?=?Cooperative Health Research in the Region of Augsburg in Germany; KORCULA?=?The Korcula study in Croatia; and ORCADES?=?The Orkney Complex Disease Study in Scotland). We identified time-of-year dependencies for the distribution of chronotype (phase of entrainment assessed as the mid-sleep time point on free days adjusted for sleep deficit of workdays) in cohorts from Estonia (EGCUT) and Germany (KORA). Our results indicate that season (defined as daylight saving time – DST and standard zonetime periods – SZT) specifications of photoperiod influence the distribution of chronotype (adjusted for age and sex). Second, in the largest investigated sample, from Estonia (EGCUT; N?=?5878), we could detect that seasonal variation in weekly average sleep duration was dependent on individual chronotype. Later chronotypes in this cohort showed significant variation in their average sleep duration across the year, especially during DST (1?h advance in social time from the end of March to end of October), while earlier chronotypes did not. Later chronotypes not only slept less during the DST period but the average chronotype of the population assessed during this period was earlier than during the SZT (local time for a respective time zone) period. More in detail, hierarchical multiple regression analyses showed that, beyond season of assessment (DST or SZT), social jetlag (SJl; the discrepancy between the mid sleep on free and work days – which varied with age and sex) contributed to a greater extent to the variation in sleep duration than chronotype (after taking into account factors that are known to influence sleep duration, i.e. age, sex and body mass index). Variation in chronotype was also dependent on age, sex, season of assessment and SJl (which is highly correlated with chronotype – SJl was larger among later chronotypes). In summary, subjective assessments of sleep/wake times are very reliable to assess internal time and sleep duration (e.g. reproducing sleep duration and timing tendencies related to age and sex across the investigated populations), but season of assessment should be regarded as a potential confounder. We identified in this study photoperiod (seasonal adaptation) and SJl as two main factors influencing seasonal variation in chronotype and sleep duration. In conclusion, season of assessment, sex and age have an effect on epidemiological variation in sleep duration, chronotype and SJl, and should be included in studies investigating associations between these phenotypes and health parameters, and on the development of optimal prevention strategies.     

Light Exposure Among Adolescents With Delayed Sleep Phase Disorder: A Prospective Cohort Study

The objective of this study was to compare light exposure and sleep parameters between adolescents with delayed sleep phase disorder (DSPD; n?=?16, 15.3?±?1.8 yrs) and unaffected controls (n?=?22, 13.7?±?2.4 yrs) using a prospective cohort design. Participants wore wrist actigraphs with photosensors for 14 days. Mean hourly lux levels from 20:00 to 05:00?h and 05:00 to 14:00?h were examined, in addition to the 9-h intervals prior to sleep onset and after sleep offset. Sleep parameters were compared separately, and were also included as covariates within models that analyzed associations with specified light intervals. Additional covariates included group and school night status. Adolescent delayed sleep phase subjects received more evening (p?<?.02, 22:00–02:00?h) and less morning (p?<?.05, 08:00–09:00?h and 10:00–12:00?h) light than controls, but had less pre-sleep exposure with adjustments for the time of sleep onset (p?<?.03, 5–7?h prior to onset hour). No differences were identified with respect to the sleep offset interval. Increased total sleep time and later sleep offset times were associated with decreased evening (p?<?.001 and p?=?.02, respectively) and morning (p?=?.01 and p?<?.001, respectively) light exposure, and later sleep onset times were associated with increased evening exposure (p?<?.001). Increased total sleep time also correlated with increased exposure during the 9?h before sleep onset (p?=?.01), and a later sleep onset time corresponded with decreased light exposure during the same interval (p?<?.001). Outcomes persisted regardless of school night status. In conclusion, light exposure interpretation requires adjustments for sleep timing among adolescents with DSPD. Pre- and post-sleep light exposures do not appear to contribute directly to phase delays. Sensitivity to morning light may be reduced among adolescents with DSPD. (Author correspondence: auger.raymond1@mayo.edu)     

Relationships among sleep timing,sleep duration and glycemic control in Type 2 diabetes in Thailand

There is evidence that the sleep and circadian systems play a role in glucose metabolism. In addition to physiological factors, sleep is also affected by behavioral, environmental, cultural and social factors. In this study, we examined whether morning or evening preference, sleep timing and sleep duration are associated with glycemic control in patients with type 2 diabetes residing in Thailand. Two hundred and ten type 2 diabetes patients who were not shift workers completed an interview and questionnaires to collect information on diabetes history, habitual sleep duration and sleep timing. Chronotype, an individual’s tendency for being a “morning” or “evening” person, was assessed using the Composite Score of Morningness (CSM), which reflects an individual’s subjective preference for activities in the morning or evening, as well as mid-sleep time on weekend nights (MSF), which reflects their actual sleep behavior. Most recent hemoglobin A1c (HbA1c) values were retrieved from medical records. Evening preference (as indicated by lower CSM), later bedtime on weekends, and shorter sleep duration correlated with higher HbA1c (r?=??0.18, p?=?0.01; r?=?0.17, p?=?0.01 and r?=??0.17, p?=?0.01, respectively), while there was no association between MSF or wake up time and glycemic control. In addition, later bedtime on weekends significantly correlated with shorter sleep duration (r?=??0.34, p?<?0.001). Hierarchical regression analyses adjusting for age, sex, body mass index, insulin use and diabetes duration revealed that later bedtime on weekends was significantly associated with poorer glycemic control (B?=?0.018, p?=?0.02), while CSM was not. Mediation analysis revealed that this association was fully mediated by sleep duration. In summary, later bedtime on weekends was associated with shorter sleep duration and poorer glycemic control in patients with type 2 diabetes. It is likely that patients with later weekend bedtimes curtail their sleep by waking up earlier. Exploring the potential reasons for this phenomenon (e.g. cultural influences, metropolitan lifestyle, environmental factors, family and social obligations) specific to a Thai population may help identify behavioral modifications (i.e. earlier bedtime and/or sleep duration extension) that could possibly lead to improved glycemic control in this population.