Summary Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder; however, it remains underdiagnosed and undertreated. Although screening tools such as the Berlin questionnaire (BQ), ...STOP-BANG questionnaire (SBQ), STOP questionnaire (STOP), and Epworth sleepiness scale (ESS) are widely used for OSA, the findings regarding their diagnostic accuracy are controversial. Therefore, this meta-analysis investigated and compared the summary sensitivity, specificity, and diagnostic odds ratio (DOR) among the BQ, SBQ, STOP, and ESS according to the severity of OSA. Electronic databases, namely the Embase, PubMed, PsycINFO, ProQuest dissertations and theses A&I databases, and China knowledge resource integrated database, were searched from their inception to July 15, 2016. We included studies examining the sensitivity and specificity of the BQ, SBQ, STOP, and ESS against the apnea–hypopnea index (AHI) or respiratory disturbance index (RDI). The revised quality assessment of diagnostic accuracy studies was used to evaluate the methodological quality of studies. A random-effects bivariate model was used to estimate the summary sensitivity, specificity, and DOR of the tools. We identified 108 studies including a total of 47 989 participants. The summary estimates were calculated for the BQ, SBQ, STOP, and ESS in detecting mild (AHI/RDI ≥ 5 events/h), moderate (AHI/RDI ≥ 15 events/h), and severe OSA (AHI/RDI ≥ 30 events/h). The performance levels of the BQ, SBQ, STOP, and ESS in detecting OSA of various severity levels are outlined as follows: for mild OSA, the pooled sensitivity levels were 76%, 88%, 87%, and 54%; pooled specificity levels were 59%, 42%, 42%, and 65%; and pooled DORs were 4.30, 5.13, 4.85, and 2.18, respectively. For moderate OSA, the pooled sensitivity levels were 77%, 90%, 89%, and 47%; pooled specificity levels were 44%, 36%, 32%, and 621%; and pooled DORs were 2.68, 5.05, 3.71, and 1.45, respectively. For severe OSA, the pooled sensitivity levels were 84%, 93%, 90%, and 58%; pooled specificity levels were 38%, 35%, 28%, and 60%; and pooled DORs were 3.10, 6.51, 3.37, and 2.10, respectively. Therefore, for mild, moderate, and severe OSA, the pooled sensitivity and DOR of the SBQ were significantly higher than those of other screening tools ( P < .05); however, the specificity of the SBQ was lower than that of the ESS ( P < .05). Moreover, age, sex, body mass index, study sample size, study populations, presence of comorbidities, PSG or portable monitoring performance, and risk of bias in the domains of the index test and reference standard were significant moderators of sensitivity and specificity ( P < .05). Compared with the BQ, STOP, and ESS, the SBQ is a more accurate tool for detecting mild, moderate, and severe OSA. Sleep specialists should use the SBQ to conduct patient interviews for the early diagnosis of OSA in clinical settings, particularly in resource-poor countries and sleep clinics where PSG is unavailable.
Objective
To assess the risk of Alzheimer's disease (AD) in patients with obstructive sleep apnea (OSA) with or without treatment based on real‐world evidence.
Study Design
Retrospective cohort ...study.
Methods
Patients newly diagnosed with OSA during 1997–2012 were identified using the National Health Insurance Research Database of Taiwan. Patients without OSA were randomly selected and matched in a 1:4 ratio by age, sex, urbanization level, and income. All patients were followed up until death or the end of 2013. The primary outcome was AD occurrence.
Results
This study included 3,978 OSA patients and 15,912 non‐OSA patients. OSA was independently and significantly associated with a higher incidence of AD in an adjusted Cox proportional hazard model (adjusted hazard ratio: 2.12; 95% confidence interval CI, 1.27–3.56). The average period of AD detection from the time of OSA occurrence was 5.44 years (standard deviation: 2.96). Subgroup analyses revealed that the effect of OSA remained significant in patients aged ≥60 years, male subgroups, patients without CPAP or surgical treatment, and patients without pharmacological therapies. Patients with OSA who received treatment (continuous positive airway pressure or surgery) exhibited a significantly reduced risk of AD compared with those without treatment (incidence rate ratio 0.23, 95% CI, 0.06–0.98).
Conclusion
OSA is independently associated with an increased risk of AD. Treatment for OSA reduces the AD risk in OSA patients. AD irreversibility renders OSA as a potential modifiable target for slowing or preventing the process of AD development.
Level of Evidence
IV Laryngoscope, 130:2292–2298, 2020
Death in intensive care units (ICUs) may increase bereaved family members' risk for posttraumatic stress disorder (PTSD). However, posttraumatic stress-related symptoms (hereafter as PTSD symptoms) ...and their precipitating factors were seldom examined among bereaved family members and primarily focused on associations between PTSD symptoms and patient/family characteristics. We aimed to investigate the course and predictors of clinically significant PTSD symptoms among family members of deceased ICU patients by focusing on modifiable quality indicators for end-of-life ICU care.
In this longitudinal observational study, 319 family members of deceased ICU patients were consecutively recruited from medical ICUs from two Taiwanese medical centers. PTSD symptoms were assessed at 1, 3, 6, and 13 months post-loss using the Impact of Event Scale-Revised (IES-R). Family satisfaction with end-of-life care in ICUs was assessed at 1 month post-loss. End-of-life care received in ICUs was documented over the patient's ICU stay. Predictors for developing clinically significant PTSD symptoms (IES-R score ≥ 33) were identified by multivariate logistic regression with generalized estimating equation modeling.
The prevalence of clinically significant PTSD symptoms decreased significantly over time (from 11.0% at 1 month to 1.6% at 13 months post-loss). Longer ICU stays (adjusted odds ratio 95% confidence interval = 1.036 1.006, 1.066), financial insufficiency (3.166 1.159, 8.647), and reported use of pain medications (3.408 1.230, 9.441) by family members were associated with a higher likelihood of clinically significant PTSD symptoms among family members during bereavement. Stronger perceived social support (0.937 0.911, 0.965) and having a Do-Not-Resuscitate (DNR) order issued before the patient's death (0.073 0.011, 0.490) were associated with a lower likelihood of clinically significant PTSD symptoms. No significant association was observed for family members' satisfaction with end-of-life care (0.988 0.944, 1.034) or decision-making in ICUs (0.980 0.944, 1.018).
The likelihood of clinically significant PTSD symptoms among family members decreased significantly over the first bereavement year and was lower when a DNR order was issued before death. Enhancing social support and facilitating a DNR order may reduce the trauma of ICU death of a beloved for family members at risk for developing clinically significant PTSD symptoms.
Mechanical power (MP) refers to the energy delivered by a ventilator to the respiratory system per unit of time. MP referenced to predicted body weight (PBW) or respiratory system compliance have ...better predictive value for mortality than MP alone in acute respiratory distress syndrome (ARDS). Our objective was to assess the potential impact of consecutive changes of MP on hospital mortality among ARDS patients receiving extracorporeal membrane oxygenation (ECMO).
We performed a retrospective analysis of patients with severe ARDS receiving ECMO in a tertiary care referral center in Taiwan between May 2006 and October 2015. Serial changes of MP during ECMO were recorded.
A total of 152 patients with severe ARDS rescued with ECMO were analyzed. Overall hospital mortality was 53.3%. There were no significant differences between survivors and nonsurvivors in terms of baseline values of MP or other ventilator settings. Cox regression models demonstrated that mean MP alone, MP referenced to PBW, and MP referenced to compliance during the first 3 days of ECMO were all independently associated with hospital mortality. Higher MP referenced to compliance (HR 2.289 95% CI 1.214-4.314, p = 0.010) was associated with a higher risk of death than MP itself (HR 1.060 95% CI 1.018-1.104, p = 0.005) or MP referenced to PBW (HR 1.004 95% CI 1.002-1.007, p < 0.001). The 90-day hospital mortality of patients with high MP (> 14.4 J/min) during the first 3 days of ECMO was significantly higher than that of patients with low MP (≦ 14.4 J/min) (70.7% vs. 46.8%, p = 0.004), and the 90-day hospital mortality of patients with high MP referenced to compliance (> 0.53 J/min/ml/cm H
O) during the first 3 days of ECMO was significantly higher than that of patients with low MP referenced to compliance (≦ 0.53 J/min/ml/cm H
O) (63.6% vs. 29.7%, p < 0.001).
MP during the first 3 days of ECMO was the only ventilatory variable independently associated with 90-day hospital mortality, and MP referenced to compliance during ECMO was more predictive for mortality than was MP alone.
Abstract
Background
Bereaved ICU family surrogates are at risk of comorbid prolonged grief disorder (PGD), posttraumatic stress disorder (PTSD), and depression. Knowledge about temporal relationships ...between PGD, PTSD, and depression is limited by a lack of relevant studies and diverse or inappropriate assessment time frames given the duration criterion for PGD. We aimed to determine the temporal reciprocal relationships between PGD, PTSD, and depressive symptoms among ICU decedents’ family surrogates during their first 2 bereavement years with an assessment time frame reflecting the PGD duration criterion.
Methods
This prospective, longitudinal, observational study examined PGD, PTSD, and depressive symptoms among 303 family surrogates of ICU decedents from two academic hospitals using 11 items of the Prolonged Grief Disorder-13, the Impact of Event Scale—Revised, and the depression subscale of the Hospital Anxiety and Depression Scale, respectively, at 6, 13, 18, and 24 months post-loss. Cross-lagged panel modeling was conducted: autoregressive coefficients indicate variable stability, and cross-lagged coefficients indicate the strength of reciprocal relationships among variables between time points.
Results
Symptoms (autoregressive coefficients) of PGD (0.570–0.673), PTSD (0.375–0.687), and depression (0.591–0.655) were stable over time. Cross-lagged standardized coefficients showed that depressive symptoms measured at 6 months post-loss predicted subsequent symptoms of PGD (0.146) and PTSD (0.208) at 13 months post-loss. PGD symptoms did not predict depressive symptoms. PTSD symptoms predicted subsequent depressive symptoms in the second bereavement year (0.175–0.278). PGD symptoms consistently predicted subsequent PTSD symptoms in the first 2 bereavement years (0.180–0.263), whereas PTSD symptoms predicted subsequent PGD symptoms in the second bereavement year only (0.190–0.214). PGD and PTSD symptoms are bidirectionally related in the second bereavement year.
Conclusions
PGD, PTSD, and depressive symptoms can persist for 2 bereavement years. Higher PGD symptoms at 6 months post-loss contributed to the exacerbation of PTSD symptoms over time, whereas long-lasting PTSD symptoms were associated with prolonged depression and PGD symptoms beyond the first bereavement year. Identification and alleviation of depression and PGD symptoms as early as 6 months post-loss enables bereaved surrogates to grieve effectively and avoid the evolution of those symptoms into long-lasting PGD, PTSD, and depression.
Bereaved ICU family surrogates' psychological distress, e.g., anxiety, depression, and post-traumatic stress disorder (PTSD), is usually examined independently, despite the well-recognized ...comorbidity of these symptoms. Furthermore, the few studies exploring impact of psychological distress on development of prolonged grief disorder (PGD) did not consider the dynamic impact of symptom evolution. We identified surrogates' distinct patterns/states of comorbid psychological distress and their evolution over the first 3 months of bereavement and evaluated their associations with PGD at 6-month postloss.
A longitudinal observational study was conducted on 319 bereaved surrogates. Symptoms of anxiety, depression, PTSD, and PGD were measured by the anxiety and depression subscales of the Hospital Anxiety and Depression Scale, Impact of Event Scale-Revised scale, and the PGD-13, respectively. Distinct psychological-distress states and their evolution were examined by latent transition analysis. Association between psychological-distress states and PGD symptoms was examined by logistic regression.
Three distinct comorbid psychological-distress states (prevalence) were initially identified: no distress (56.3%), severe-depressive/borderline-anxiety distress (30.5%), and severe-anxiety/depressive/PTSD distress (13.3%). Except for those in the stable no-distress state, surrogates tended to regress to states of less psychological distress at the subsequent assessment. The proportion of participants in each psychological-distress state changed to no distress (76.8%), severe-depressive/borderline-anxiety distress (18.6%), and severe-anxiety/depressive/PTSD distress (4.6%) at 3-month postloss. Surrogates in the severe-depressive/borderline-anxiety distress and severe-anxiety/depressive/PTSD-distress state at 3-month postloss were more likely to develop PGD at 6-month postloss (OR 95% = 14.58 1.48, 143.54 and 104.50 10.45, 1044.66, respectively).
A minority of family surrogates of ICU decedents suffered comorbid severe-depressive/borderline-anxiety distress and severe-anxiety/depressive/PTSD symptoms during early bereavement, but they were more likely to progress into PGD at 6-month postloss.
Obstructive sleep apnea (OSA) is a disease with great cardiovascular risk. Interleukin-8 (IL-8), an important chemokine for monocyte chemotactic migration, was studied under intermittent hypoxia ...condition and in OSA patients. Monocytic THP-1 cells were used to investigate the effect of intermittent hypoxia on the regulation of IL-8 by an intermittent hypoxic culture system. The secreted protein and mRNA levels were studied by means of enzyme-linked immunosorbent assay and RT/real-time PCR. The chemotactic migration of monocytes toward a conditioned medium containing IL-8 was performed by means of the transwell filter migration assay. Peripheral venous blood was collected from 31 adult OSA patients and RNA was extracted from the monocytes for the analysis of IL-8 expression. The result revealed that intermittent hypoxia enhanced the monocytic THP-1 cells to actively express IL-8 at both the secreted protein and mRNA levels, which subsequently increased the migration ability of monocytes toward IL-8. The ERK, PI3K and PKC pathways were demonstrated to contribute to the activation of IL-8 expression by intermittent hypoxia. In addition, increased monocytic IL-8 expression was found in OSA patients, with disease severity dependence and diurnal changes. This study concluded the monocytic IL-8 gene expression can be activated by intermittent hypoxia and increased in OSA patients.
Background. Apoptosis is one of the causes of immune depression in sepsis. Pyroptosis also occurs in sepsis. The toll-like receptor (TLR) 4 and receptor for advanced glycation end products (RAGE) ...have been shown to play important roles in apoptosis and pyroptosis. However, it is still unknown whether TLR4 inhibition decreases apoptosis in sepsis. Methods. Stimulated peripheral blood mononuclear cells (PBMCs) with or without lipopolysaccharides (LPS) and high-mobility group box 1 (HMGB1) were cultured with or without TLR4 inhibition using monoclonal antibodies from 20 patients with sepsis. Caspase-3, caspase-8, and caspase-9 activities were measured. The expression of B cell lymphoma 2 (Bcl2) and Bcl2-associated X (Bax) was measured. The cell death of PBMCs was detected using a flow cytofluorimeter. Results. After TLR4 inhibition, Bcl2 to Bax ratio elevated both in LPS and HMGB1-stimulated PBMCs. The activities of caspase-3, caspase-8, and caspase-9 did not change in LPS or HMGB1-stimulated PBMCs. The cell death of LPS and HMGB1-stimulated CD8 lymphocytes and monocytes increased after TLR4 inhibition. The cell death of CD4 lymphocytes was unchanged. Conclusion. The apoptosis did not decrease, while TLR4 was inhibited. After TLR4 inhibition, there was an unknown mechanism to keep cell death in stimulated PBMCs in patients with sepsis.
To investigate the risk factors of postoperative elevated blood pressure (BP) in children with childhood obstructive sleep apnea syndrome (OSAS) after adenotonsillectomy (AT).
Case series with ...planned data collection.
Tertiary referral center.
Two hundred forty-five consecutive children (180 boys and 65 girls, median age 6.6 years) with polysomnography-diagnosed OSAS who underwent AT between January 2010 and August 2019. Clinical, polysomnographic, and evening BP data were assessed preoperatively and postoperatively (≥3 months after AT). Changes in the variables before and after AT and between individuals with and without hypertension were compared.
Postoperatively, the median (interquartile range) apnea-hypopnea index significantly decreased from 10.4 (5.3-22.6) to 2.2 (1.0-3.8) events/h. In addition, the mean (standard deviation) evening diastolic BP z-score significantly decreased from 0.7 (0.94) to 0.5 (0.81) in the overall cohort, and both systolic (2.1 0.94-1.0 1.31) and diastolic BP z-scores (1.6 0.98-0.7 0.85) significantly decreased in the preoperative elevated BP subgroup. Multivariate logistic regression analysis showed that preoperative obesity (adjusted odds ratio = 4.36, 95% confidence interval = 2.24-8.49) and mean peripheral oxygen saturation <95% during sleep (adjusted odds ratio = 2.73, 95% confidence interval = 1.29-5.79) were independently associated with postoperative elevated BP.
Preoperative obesity and mean peripheral oxygen saturation <95% during sleep were significantly associated with postoperative elevated BP in the children with OSAS, further indicating the importance of careful BP monitoring in this subgroup despite AT treatment.
Background and objectives: Acute kidney injury (AKI) is common in critically ill patients, especially those with sepsis. Persistently low human leukocyte antigen (HLA)-DR expression in monocytes ...reflects the decreased function of antigen-presenting cells, contributing to poor outcomes in sepsis. This study aimed to establish an association between AKI and HLA-DR expression in monocytes of patients with sepsis. Materials and Methods: We detected HLA-DR expression in monocytes and measured plasma levels of S100A12, high-mobility group box 1 (HMGB1), advanced glycation end products (AGE), and soluble receptor for AGE (sRAGE) from septic patients and healthy controls. Results: HLA-DR expression in monocytes was decreased in patients with AKI than in those without AKI (29.8 ± 5.0% vs. 53.1 ± 5.8%, p = 0.005). Compared with AKI patients, the mean monocyte HLA-DR expression in patients with end-stage renal disease was increased without statistical significance. There were no differences in the AGE/sRAGE ratio and plasma levels of S100A12, HMGB1, AGE, and sRAGE between patients with and without AKI. Conclusions: Compared with septic patients without AKI, patients with AKI had significantly lower HLA-DR expression in monocytes. The role of hemodialysis in monocyte HLA-DR expression needs further studies to explore.