Associations Between Family-Assessed Quality-of-Dying-and-Death Latent Classes and Bereavement Outcomes for Family Surrogates of ICU Decedents.

OBJECTIVES: To examine associations between family surrogates' bereavement outcomes and four previously determined quality of dying and death (QODD) latent classes (high, moderate, poor-to-uncertain, and worst). DESIGN: Prospective, longitudinal, observational study. SETTING: Medical ICUs at two academically affiliated medical centers in Taiwan. PATIENTS/PARTICIPANTS: Three hundred nine family surrogates responsible for decision-making for critically ill patients at high risk of death (Acute Physiology and Chronic Health Evaluation II scores > 20) from a disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Participants were assessed by the depression and anxiety subscales of the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised, 11 items of the Prolonged Grief Disorder (PGD) scale, and the Medical Outcomes Study 36-Item Short-Form Health Survey at 1, 3, 6, 13, 18, and 24 months post-loss. We simultaneously examined associations of four QODD latent classes with physical and mental health-related quality of life (HRQOL) and symptoms of anxiety, depression, post-traumatic stress disorder (PTSD), and PGD assessed over 24 bereavement months using multivariate hierarchical linear modeling. Surrogates' distinct QODD latent classes assessed at 1-month post-loss were significantly associated with bereavement outcomes, except for physical HRQOL and PGD symptoms. Significantly more depressive symptoms and worse mental HRQOL (ß [95% CI]) were reported by bereaved surrogates in the moderate (1.958 [1.144-2.772], -2.245 [-3.961 to -0.529]), poor-to-uncertain (2.224 [1.438-3.010], -7.026 [-8.683 to -5.369]), and worst (2.081 [1.215-2.964], -4.268 [-6.096 to -2.440]) QODD classes than those in the high QODD class. Bereaved surrogates in the moderate (2.095 [1.392-2.798]) and poor-to-uncertain (0.801 [0.123-1.480]) QODD classes reported more anxiety symptoms, whereas those in the poor-to-uncertain QODD class suffered more PTSD symptoms (2.889 [1.005-4.774]) than those in the high QODD class. CONCLUSIONS: The four distinct QODD latent classes were significantly associated with ICU family surrogates' bereavement outcomes, suggesting targets to improve end-of-life care quality in ICUs.

Quality of dying and death in intensive care units: family satisfaction.

OBJECTIVE: This cohort study identified patterns/classes of surrogates' assessment of their relative's quality of dying and death (QODD) and to evaluate their associations with family satisfaction with intensive care unit (ICU) care. METHODS: We identified QODD classes through latent class analysis of the frequency component of the QODD questionnaire and examined their differences in summary questions on the QODD and scores of the Family Satisfaction in the ICU questionnaire among 309 bereaved surrogates of ICU decedents. RESULTS: Four distinct classes (prevalence) were identified: high (41.3%), moderate (20.1%), poor-to-uncertain (21.7%) and worst (16.9%) QODD classes. Characteristics differentiate these QODD classes including physical symptom control, emotional preparedness for death, and amount of life-sustaining treatments (LSTs) received. Patients in the high QODD class had optimal physical symptom control, moderate-to-sufficient emotional preparedness for death and few LSTs received. Patients in the moderate QODD class had adequate physical symptom control, moderate-to-sufficient emotional preparedness for death and the least LSTs received. Patients in the poor-to-uncertain QODD class had inadequate physical symptom control, insufficient-uncertain emotional preparedness for death and some LSTs received. Patients in the worst QODD class had poorest physical symptom control, insufficient-to-moderate emotional preparedness for death and substantial LSTs received. Bereaved surrogates in the worst QODD class scored significantly lower in evaluations of the patient's overall QODD, and satisfaction with ICU care and decision-making process than those in the other classes. CONCLUSIONS: The identified distinct QODD classes offer potential actionable direction for improving quality of end-of-life ICU care.

Recommended assessment and management of sleep disordered breathing in patients with atrial fibrillation, hypertension and heart failure: Taiwan Society of Cardiology/Taiwan Society of sleep Medicine/Taiwan Society of pulmonary and Critical Care Medicine joint consensus statement.

Sleep disordered breathing (SDB) is highly prevalent and may be linked to cardiovascular disease in a bidirectional manner. The Taiwan Society of Cardiology, Taiwan Society of Sleep Medicine and Taiwan Society of Pulmonary and Critical Care Medicine established a task force of experts to evaluate the evidence regarding the assessment and management of SDB in patients with atrial fibrillation (AF), hypertension and heart failure with reduced ejection fraction (HFrEF). The GRADE process was used to assess the evidence associated with 15 formulated questions. The task force developed recommendations and determined strength (Strong, Weak) and direction (For, Against) based on the quality of evidence, balance of benefits and harms, patient values and preferences, and resource use. The resulting 11 recommendations are intended to guide clinicians in determining which the specific patient-care strategy should be utilized by clinicians based on the needs of individual patients.

Comorbid Prolonged Grief, PTSD, and Depression Trajectories for Bereaved Family Surrogates.

Importance: Family surrogates of patients who die in an intensive care unit (ICU) are at risk of cooccurring prolonged grief disorder (PGD), posttraumatic stress disorder (PTSD), and depressive disorder during bereavement, but symptom trajectories are often explored individually. Objectives: To simultaneously examine and determine co-occurrence of PGD, PTSD, and depressive symptom trajectories. Design, Setting, and Participants: This cohort study was conducted in ICUs of 2 Taiwanese medical centers from January 2018 to March 2020, with follow-up through July 2022. Participants included surrogates responsible for decision-making who provided data 6 to 24 months after the death of their loved one. Data were analyzed from August to December 2022. Main Outcomes and Measures: PGD was assessed with the 11 grief symptom items of the PG-13; PTSD, the Impact of Event Scale-Revised; and depressive symptoms, the depression subscale of the Hospital Anxiety and Depression Scale at 6, 13, 18, and 24 months after the death. Latent growth mixture modeling was conducted to identify distinct trajectories, and joint latent class analysis was used to assess joint patterns of trajectories. Results: A total of 303 participants were included, with most younger than 56 years (207 participants [68.3%]), female (177 participants [58.4%]), and married (228 participants [75.2%]), and their relationship with the patient was mostly spouse (88 participants [29.0%]) or adult child (166 participants [54.8%]). Three trajectories were identified each for PGD, PTSD, and depressive symptoms. A resilience trajectory was predominant across PGD (253 participants [83.5%]), PTSD (250 participants [82.5%]), and depressive (200 participants [66.0%]) symptoms. Second most common was a recovery trajectory identified for PGD (36 participants [11.9%]) and PTSD (41 participants [13.5%]) symptoms, while for depressive symptoms, a moderate trajectory (72 participants [23.8%]) signified persistent moderate distress. A chronic trajectory characterized by persistently high distress was identified for PGD (14 participants [4.6%]) and depressive (31 participants [10.2%]) symptoms, whereas a unique delayed-onset trajectory (12 participants [4.0%]) was identified for PTSD symptoms. Most family surrogates (228 participants [75.2%]) experienced cooccurring PGD, PTSD, and depressive symptom trajectories, but multiple patterns were discordant. Symptom trajectories cooccurred in joint patterns: resilient (247 participants [81.5%]), recovered (43 participants [14.1%]), and distressed (14 participants [4.5%]). These patterns were characterized by high conditional probabilities for the resilience (PGD, 0.999; PTSD, 0.999; depressive, 0.804), recovery (PGD, 0.854; PTSD, 0.890; depressive, 0.588), and chronic (PGD, 0.921; PTSD, 0.789; depressive, 0.980) symptom trajectories. Conclusions and Relevance: In this cohort study, grief-related psychological symptoms evolved in complex ways during ICU bereavement, as characterized by heterogeneous trajectories. Some ICU bereaved surrogates experienced persistent elevated PGD, PTSD, and depressive symptoms individually or conjointly, underscoring the importance of early screening to identify this population at high risk of comorbid psychological distress trajectories.

Pharmacotherapy for obstructive sleep apnea - A systematic review and meta-analysis of randomized controlled trials.

Continuous positive airway pressure is the first-line and gold-standard treatment for obstructive sleep apnea (OSA). Pharmacotherapy is not commonly used in treating OSA until recently. Combined noradrenergic and antimuscarinic agents have been clinically applied for OSA patients with variable results. This meta-analysis study aimed to investigate the efficacy of the combined regimen on OSA. A systematic literature search was performed up to November 2022 for the effects of the combined regimen on OSA. Eight randomized controlled trials were identified and systematically reviewed for meta-analysis. There were significant mean differences between OSA patients taking a combined regimen and placebo in apnea-hypopnea index (AHI) [mean difference (MD) -9.03 events/h, 95%CI (-16.22, -1.83 events/h; P = 0.01] and lowest oxygen saturation [MD 5.61%, 95% CI % (3.43, 7.80); P < 0.01]. Meta-regression showed that a higher proportion of male participants was associated with a greater reduction of AHI (p = 0.04). This study showed a positive but modest effect of pharmacotherapy in the reduction of OSA severity. The combination drugs are most applicable to male OSA patients based on their efficacy and pharmacological susceptibility. Pharmacotherapy may be applied as an alternative, adjunctive or synergistic treatment under careful consideration of its side effects.

Temporal reciprocal relationships among anxiety, depression, and posttraumatic stress disorder for family surrogates from intensive care units over their first two bereavement years.

BACKGROUND/OBJECTIVE: Bereaved family surrogates from intensive care units (ICU) are at risk of comorbid anxiety, depression, and post-traumatic stress disorder (PTSD), but the temporal reciprocal relationships among them have only been examined once among veterans. This study aimed to longitudinally investigate these never-before-examined temporal reciprocal relationships for ICU family members over their first two bereavement years. METHODS: In this prospective, longitudinal, observational study, symptoms of anxiety, depression, and PTSD were assessed among 321 family surrogates of ICU decedents from 2 academically affiliated hospitals in Taiwan by the anxiety and depression subscales of the Hospital Anxiety and Depression Scale, and the Impact of Event Scale-Revised, respectively at 1, 3, 6, 13, 18, and 24 months postloss. Cross-lagged panel modeling was conducted to longitudinally examine the temporal reciprocal relationships among anxiety, depression, and PTSD. RESULTS: Examined psychological-distress levels were markedly stable over the first 2 bereavement years: autoregressive coefficients for symptoms of anxiety, depression, and PTSD were 0.585-0.770, 0.546-0.780, and 0.440-0.780, respectively. Cross-lag coefficients showed depressive symptoms predicted PTSD symptoms in the first bereavement year, whereas PTSD symptoms predicted depressive symptoms in the second bereavement year. Anxiety symptoms predicted symptoms of depression and PTSD at 13 and 24 months postloss, whereas depressive symptoms predicted anxiety symptoms at 3 and 6 months postloss while PTSD symptoms predicted anxiety symptoms during the second bereavement year. CONCLUSIONS: Different patterns of temporal relationships among symptoms of anxiety, depression, and PTSD over the first 2 bereavement years present important opportunities to target symptoms of specific psychological distress at different points during bereavement to prevent the onset, exacerbation, or maintenance of subsequent psychological distress.

Dietary profile of pediatric obstructive sleep apnea patients, effects of routine educational counseling, and predictors for outcomes.

Background: Dietary behavior is a main contributing yet modifiable factor to the body weight status of children and may be involved in the pathophysiology of childhood obstructive sleep apnea (OSA). This study aimed to investigate the dietary profile of pediatric OSA patients, effects of educational counseling after adenotonsillectomy, and predictor for disease resolution. Methods: This observational study included 50 pediatric OSA patients undergoing adenotonsillectomy with routine educational counseling (Group 1), 50 pediatric OSA patients undergoing adenotonsillectomy without formal educational counseling (Group 2), and 303 healthy children without OSA (Control). The three groups were matched by age. The consumption frequency of 25 food items/groups was assessed by the Short Food Frequency Questionnaire. Quality of life was evaluated by the OSA-18 questionnaire. Sleep architecture and OSA severity were measured by standard polysomnography. Between- and within-group comparisons were analyzed by non-parametric approaches and generalized estimating equations. Prediction of disease recovery was performed by multivariable logistic regression models. Results: Group 1 children consumed fruit drinks with sugar, vegetables, sweets, chocolate, rice, and noodles more frequently than Control Group children. At baseline, the distributions of sex, weight status, OSA-18 scores, and polysomnographic variables were comparable between Group 1 and Group 2. After a 12-month follow-up, Group 1 had better improvements in physical suffering, caregiver concerns, sleep architecture, and mean peripheral oxygen saturation compared to Group 2. Furthermore, Group 1 no longer had excessive consumption of fruit drinks with sugar, chocolate, and noodles; however, food consumption frequencies did not change significantly. Notably, younger age and reduced intake of butter/margarine on bread and noodles were independent predictors of cured OSA in Group 1. Conclusion: The present study preliminarily characterized an unhealthy dietary profile among pediatric OSA patients and suggested that routine educational counseling in addition to adenotonsillectomy yielded some clinical benefits. Certain items/groups of food frequencies may be associated with disease recovery and further investigations are warranted.

ICU Bereaved Surrogates' Transition Through States of Co-Occurring Prolonged Grief Disorder, Posttraumatic Stress Disorder, and Depression Symptoms.

OBJECTIVES: Grief-related psychological distress often co-occurs to conjointly impair function during bereavement. Knowledge of comorbid grief-related psychological distress is limited: no longitudinal study has examined dynamic patterns of co-occurring prolonged grief disorder (PGD), posttraumatic stress disorder (PTSD), and depression, and previous assessment time frames have been variable and potentially inadequate given the duration criterion for PGD. Therefore, the purpose of this study was to investigate the transition of distinct symptom states based on the co-occurrence of PGD, PTSD, and depression symptoms for ICU bereaved surrogates over their first two bereavement years. DESIGN: Prospective, longitudinal, observational study. SETTING: Medical ICUs at two academically affiliated medical centers in Taiwan. PATIENTS/PARTICIPANTS: Three hundred three family surrogates responsible for decision-making for critically ill patients at high risk of death (Acute Physiology and Chronic Evaluation II scores > 20) from a disease. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Participants were assessed by 11 items of the Prolonged Grief Disorder (PG-13) scale, the Impact of Event Scale-Revised, and the depression subscale of the Hospital Anxiety and Depression Scale at 6, 13, 18, and 24 months postloss. PGD-PTSD-depression-symptom states and their evolution were examined by latent transition analysis. The following four distinct PGD-PTSD-depression-symptom states (prevalence) were initially identified: resilient (62.3%), subthreshold depression-dominant (19.9%), PGD-dominant (12.9%), and PGD-PTSD-depression comorbid (4.9%) states. These PGD-PTSD-depression-symptom states remained highly stable during the first two bereavement years, with transitions predominantly toward resilience. Prevalence for each state at 24 months postloss was 82.1%, 11.4%, 4.0%, and 2.5%, respectively. CONCLUSIONS: Four highly stable PGD-PTSD-depression-symptom states were identified, highlighting the importance of screening for subgroups of ICU bereaved surrogates with increased PGD or comorbid PGD, PTSD, and depression symptoms during early bereavement.

Adenotonsillectomy-related changes in systemic inflammation among children with obstructive sleep apnea.

BACKGROUND: Adenotonsillar hypertrophy is the most common cause of pediatric obstructive sleep apnea (OSA). Although adenotonsillectomy considerably reduces OSA and systemic inflammation, whether and how systemic inflammation influences the effects of adenotonsillectomy on OSA has yet to be determined. METHODS: This study investigated the associations between changes in anatomical variables, % changes in subjective OSA-18 questionnaire scores, % changes in 11 polysomnographic parameters, and % changes in 27 systemic inflammatory biomarkers in 74 children with OSA. RESULTS: Fifty-six (75.6%) boys and 18 (24.4%) girls with the mean age of 7.4 ± 2.2 years and apnea-hypopnea index (AHI) of 14.2 ± 15.9 events/h were included in the statistical analysis. The mean period between before and after adenotonsillectomy was 5.6 ± 2.6 months. After adenotonsillectomy, the OSA-18 score, eight of 11 polysomnographic parameters, and 20 of 27 inflammatory biomarkers significantly improved (all p < 0.005). Notably, there were significant associations between change in tonsil size and % change in AHI ( r = 0.23), change in tonsil size and % changes in interleukin-8 (IL-8) ( r = 0.34), change in tonsil size and % change in and IL-10 ( r = -0.36), % change in IL-8 and % change in C-C chemokine ligand 5 (CCL5) ( r = 0.30), and % change in CCL5 and % change in AHI ( r = 0.38) (all p < 0.005). Interestingly, % change in IL-8 and % change in CCL5 serially mediated the relationship between change in tonsil size and % change in AHI (total effect: ß = 16.672, standard error = 8.274, p = 0.048). CONCLUSION: These preliminary findings suggest that systemic inflammation is not only a complication of OSA but also that it mediates the surgical effects, which may open avenues for potential interventions to reduce tonsil size and OSA severity through the regulation of IL-8 and CCL5.

Using sleep heart rate variability to investigate the sleep quality in children with obstructive sleep apnea.

Background: Obstructive sleep apnea (OSA) is associated with impaired sleep quality and autonomic dysfunction. Adenotonsillectomy significantly improves subjective and objective sleep quality in children with OSA. However, the postoperative changes in heart rate variability (HRV) indices (indicators of cardiac autonomic function) and their importance remain inconclusive in childhood OSA. This retrospective case series aimed to investigate the association of sleep HRV indices, total OSA-18 questionnaire score (a subjective indicator of sleep quality) and polysomnographic parameters (objective indicators of sleep quality), and effects of adenotonsillectomy on HRV indices, total OSA-18 questionnaire score and polysomnographic parameters in children with OSA. Methods: Seventy-six children with OSA were included in baseline analysis, of whom 64 (84%) completed at least 3 months follow-up examinations after adenotonsillectomy and were included in outcome analysis. Associations between baseline variables, and relationships with treatment-related changes were examined. Results: Multivariable linear regression models in the baseline analysis revealed independent relationships between tonsil size and obstructive apnea-hypopnea index (OAHI), adenoidal-nasopharyngeal ratio and very low frequency (VLF) power of HRV (an indicator of sympathetic activity), and normalized low frequency power (an indicator of sympathetic activity) and OAHI. The outcome analysis showed that adenotonsillectomy significantly improved standard deviation of all normal-to-normal intervals, and high frequency power, QoL (in terms of reduced total OSA-18 questionnaire score), OAHI and hypoxemia. Using a conceptual serial multiple mediation model, % change in OSA-18 questionnaire score and % change in VLF power serially mediated the relationships between change in tonsil size and % change in OAHI. Conclusions: The improvement in OAHI after adenotonsillectomy was serially mediated by reductions in total OSA-18 questionnaire score and VLF power. These preliminary findings are novel and provide a direction for future research to investigate the effects of VLF power-guided interventions on childhood OSA.

Effect of Preoperative Weight Status and Disease Presentation on Postoperative Elevated Blood Pressure After Childhood Adenotonsillectomy.

OBJECTIVE: To investigate the risk factors of postoperative elevated blood pressure (BP) in children with childhood obstructive sleep apnea syndrome (OSAS) after adenotonsillectomy (AT). STUDY DESIGN: Case series with planned data collection. SETTING: Tertiary referral center. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Combined Airway and Bariatric Surgery (CABS) for Obstructive Sleep Apnea Patients with Morbid Obesity: A Comprehensive Alternative Preliminary Study.

Although continuous positive airway pressure is the gold standard for obstructive sleep apnea (OSA), it does not improve obesity. By contrast, bariatric surgery significantly improves obesity but with sustained OSA in the majority of patients. This study proposes a comprehensive technique­combined airway and bariatric surgery (CABS)­to improve both obesity and OSA. The aims of the study are to evaluate the feasibility, safety and efficacy of CABS in morbidly obese OSA patients. The retrospective study enrolled 20 morbidly obese OSA patients (13 males; median age, 44 years; median apnea−hypopnea index (AHI), 63.2 event/h; median body mass index (BMI), 41.4 kg/m2). The study population was divided into two groups based on patients' volition after shared decision making. The bariatric surgery (BS) group included laparoscopic sleeve gastrectomy (LSG, n = 8) and laparoscopic Roux-en-Y gastric bypass (LRYGB, n = 2). CABS involved bariatric surgery­LSG (n = 8) and LRYGB (n = 2) in conjunction with airway surgery (concurrent nasal/palatal/lingual surgery [n = 8], concurrent palatal/lingual surgery [n = 2]). Patients received a home sleep apnea test at baseline and one year after surgery. The two patient groups were not different in age, sex, preoperative AHI or preoperative BMI. There was no airway compromise, wound bleeding or infection throughout the postoperative period. One year after surgery, patients in both groups achieved significant improvement in AHI and BMI. Furthermore, the improvement in AHI was significantly higher (p = 0.04) in the CABS group than in the BS group despite the insignificant change in BMI reduction (p = 0.63) between the two groups. In the CABS group, the BMI dropped from 40.4 to 28.4 kg/m2 (p < 0.0001) and the AHI decreased from 75.1 to 4.5 event/h (p = 0.0004). The classic success rate for OSA was 90% and the cure rate was 60% in the CABS group. A perioperative assessment of CABS group patients also revealed a significant improvement in the Epworth sleepiness scale, minimal O2 saturation, snoring index and heart rate. CABS is feasible and safe in treating OSA with morbid obesity. CABS achieves more reduction in AHI than BS alone with high success and cure rates for OSA. CABS can also significantly improve quality of life and general health and offers a comprehensive alternative for morbidly obese OSA patients.

How symptoms of prolonged grief disorder, posttraumatic stress disorder, and depression relate to each other for grieving ICU families during the first two years of bereavement.

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.

Decreased Monocyte HLA-DR Expression in Patients with Sepsis and Acute Kidney Injury.

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.

Alterations in Gut Microbiota and Upregulations of VPAC2 and Intestinal Tight Junctions Correlate with Anti-Inflammatory Effects of Electroacupuncture in Colitis Mice with Sleep Fragmentation.

The relationship between inflammatory bowel disease and sleep disturbances is complicated and of increasing interest. We investigated the inflammatory and immunological consequences of EA in sleep-deprived colitis and found that dextran sulfate sodium (DSS)-induced colitis in sleep-fragmented (SF) mice was more severe than that in mice with normal sleep. This increase in the severity of colitis was accompanied by reduced body weight, shortened colon length, and deteriorated disease activity index. DSS with SF mice presented obvious diminished intestinal tight junction proteins (claudin-1 and occludin), elevated proinflammatory cytokines (CRP, IFN-γ, IL-6), lowered melatonin and adiponectin levels, downregulated vasoactive intestinal peptide (VIP) type 1 and 2 receptor (VPAC1, VPAC2) expression, and decreased diversity of gut bacteria. EA ameliorated colitis severity and preserved the performance of the epithelial tight junction proteins and VIP receptors, especially VPAC2. Meanwhile, the innate lymphoid cells-derived cytokines in both group 2 (IL-4, IL5, IL-9, IL-13) and group 3 (IL-22, GM-CSF) were elevated in mice colon tissue. Furthermore, dysbiosis was confirmed in the DSS group with and without SF, and EA could maintain the species diversity. Firmicutes could be restored, such as Lachnospiraceae, and Proteobacteria become rebalanced, mainly Enterobacteriaceae, after EA intervention. On the other hand, SF plays different roles in physiological and pathological conditions. In normal mice, interrupted sleep did not affect the expression of claudin-1 and occludin. But VPAC1, VPAC2, and gut microbiota diversity, including Burkholderiaceae and Rhodococcus, were opposite to mice in an inflamed state.

Comparative efficacy of exercise regimens on sleep quality in older adults: A systematic review and network meta-analysis.

The efficacies of various exercise modalities in improving older adults' sleep quality remain unclear. Therefore, in this study, network meta-analysis was performed by comparing the efficacies of various exercise regimens in improving sleep quality in this age group. Six electronic databases were searched for relevant studies between the date of database creation and August 13, 2021. Only randomized controlled trials reporting the effects of exercise on sleep quality in this population were included. Random-effects network meta-analysis based on a frequentist framework was conducted. In total, 35 trials involving 3519 older adults were included. Cognitive behavioral therapy for insomnia, muscle endurance training combined with walking, Tai chi, Baduanjin, resistance training combined with walking, and resistance training significantly improved sleep quality to a greater degree than did usual care (P < 0.05). Muscle endurance training combined with walking led to significantly higher sleep quality than did regimens involving sleep hygiene, Pilates, only walking, health education, resistance training, Taichi, resistance training combined with walking, or yoga. Muscle endurance training combined with walking was identified as the optimal exercise program (88.9%) for enhancing sleep quality in older adults. The results of this study support the claim that exercise can improve sleep quality in this population. PROSPERO registration number: CRD42020178209.

The 3% Oxygen Desaturation Index is an Independent Risk Factor for Hypertension Among Children with Obstructive Sleep Apnea.

Background: Obstructive sleep apnea (OSA) and obesity are both directional risk factors of hypertension. Chronic intermittent hypoxemia (IH) is a commonly observed pathophysiological mechanism involved in multiple comorbidities of OSA. However, their interactions are not well understood in children. This study aimed to investigate the associations of IH indexes (oxygen desaturation index 3% [ODI3], mean peripheral oxygen saturation [SpO2], least SpO2, and time with SpO2 < 85%), apnea-hypopnea index, and weight status with hypertension in a sample of pediatric OSA patients. Methods: The medical records of 365 pediatric OSA patients were retrospectively reviewed in this cross-sectional study. Demographics, anthropometrics, standard in-laboratory polysomnography, and nocturnal blood pressure were collected. Multivariate logistic regression with forward selection was used to identify independent predictors of hypertension. Results: Multivariate logistic regression analysis showed that ODI3 (odds ratio [OR] = 1.02, 95% confidence interval [CI] = 1.01-1.03) and body mass index z-score (OR = 1.34, 95% CI = 1.12-1.60) were independent continuous predictors of pediatric hypertension, whilst severe OSA (OR = 2.62, 95% CI = 1.60-4.29) and overweight/obesity (OR = 2.63, 95% CI = 1.59-4.34) were independent categorical predictors. Traditional risk factors including male sex (OR = 2.33, 95% CI = 1.02-5.33), late childhood/adolescence (OR = 1.98, 95% CI = 1.01-3.88), and overweight/obesity (OR = 2.97, 95% CI = 1.56-5.67) combined with sleep hypoxemia (least SpO2 ≤ 95%) (OR = 2.24, 95% CI = 1.16-4.04) predicted hypertension (R 2 = 0.21) in the severe IH subgroup (n = 205), while the no/mild IH subgroup (n = 160) had an entirely different predictor, severe OSA (OR = 3.81, 95% CI = 1.49-9.74) (R 2 = 0.07). Conclusion: The close relationships among IH, overweight/obesity, and hypertension highlight the importance of reducing IH and body weight in children with OSA.

Factors associated with bereaved family surrogates' satisfaction with end-of-life care in intensive care units.

OBJECTIVES: Family satisfaction with end-of-life care in the intensive care unit constitutes an important outcome for evaluating end-of-life care quality. Research on this topic focuses on linking end-of-life care processes to family-surrogate satisfaction with the patient's end-of-life care but has seldom examined patient- and family-surrogate-based factors. We aimed to comprehensively and simultaneously examine factors facilitating or deterring family satisfaction with end-of-life care in the intensive care unit from patient- and family-surrogate perspectives. METHODS: For this secondary-analysis study, 278 Taiwanese family surrogates were surveyed one-month post-patient death using the Family Satisfaction in the Intensive Care Unit questionnaire (FS-ICU), which measures care and decision-making. Associations between family satisfaction with end-of-life care and patient and family characteristics, patient disease severity, and length of intensive care stay were examined by multivariate, multilevel linear regression models. RESULTS: Female family surrogates were more satisfied with patients' end-of-life care than male family surrogates when patients had a higher APACHE II but a lower SOFA score. Adult-child surrogates had lower FS-ICU Care scores than other family surrogates. Higher satisfaction with ICU decision-making was associated with patients' higher APACHE II but lower SOFA scores, longer stay and family socio-demographics, including being unmarried, educational attainment above junior high school and reported financial sufficiency to make ends meet. CONCLUSION: Patient disease severity and family-surrogate characteristics are significantly associated with surrogates' satisfaction with patients' end-of-life care in the intensive care unit. Specific interventions should be tailored to the needs of high-risk family surrogates to increase their satisfaction with this care.

ICU bereaved surrogates' comorbid psychological-distress states and their associations with prolonged grief disorder.

BACKGROUND/OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Elevated serum matrix metalloproteinase-2 levels in heart failure patients with reduced ejection fraction and Cheyne-Stokes respiration.

STUDY OBJECTIVES: Cheyne-Stokes respiration (CSR), a kind of central sleep apnea, is referred to as a poor prognostic factor in heart failure patients with reduced ejection fraction (HFrEF). Matrix metalloproteinase (MMP) and B-type natriuretic peptide (BNP) play important roles in HFrEF patients and are markers of poor prognosis. However, there is no literature mentioning the changes in MMP and BNP in HFrEF patients with CSR. METHODS: From June 2018 to June 2019, 41 adult patients with stable heart failure and left ventricular ejection fraction < 50% were enrolled from the cardiology clinic. After history-taking and medication review to exclude possible central nervous system- or medication-related central sleep apnea, an overnight polysomnography study was performed, and CSR was identified. The morning serum MMP-2, MMP-9, and BNP levels were determined using enzyme-linked immunosorbent assay and fluorescence immunoassay techniques. A positive airway pressure device was applied to 7 patients for 3 months. RESULTS: The serum MMP-2 and BNP levels were significantly higher in HFrEF patients with CSR than in patients without CSR. In addition, elevated serum MMP-2 levels correlated well with the severity of sleep apnea and intermittent hypoxia, which were represented as the apnea-hypopnea index and the oxygen desaturation index. No positive correlation was found between those markers and left ventricular ejection fraction. Finally, the treatment of sleep apnea with continuous positive airway pressure for 3 months tended to reduce the elevated serum MMP-2 levels. CONCLUSIONS: Higher serum MMP-2 and BNP levels were found in HFrEF patients with CSR. Elevated MMP-2 levels were correlated with the severity of sleep apnea and intermittent hypoxia. CITATION: Chuang L-P, Pang J-HS, Lin S-W, et al. Elevated serum matrix metalloproteinase-2 levels in heart failure patients with reduced ejection fraction and Cheyne-Stokes respiration. J Clin Sleep Med. 2022;18(5):1365-1373.