Occupational physical activity, all-cause, cardiovascular disease, and cancer mortality in 349,248 adults: Prospective and longitudinal analyses of the MJ Cohort.

BACKGROUND: Evidence on the health benefits of occupational physical activity (OPA) is inconclusive. We examined the associations of baseline OPA and OPA changes with all-cause, cardiovascular disease (CVD), and cancer mortality and survival times. METHODS: This study included prospective and longitudinal data from the MJ Cohort, comprising adults over 18 years recruited in 1998-2016, 349,248 adults (177,314 women) with baseline OPA, of whom 105,715 (52,503 women) had 2 OPA measures at 6.3 ± 4.2 years (mean ± SD) apart. Exposures were baseline OPA, OPA changes, and baseline leisure-time physical activity. RESULTS: Over a mean mortality follow-up of 16.2 ± 5.5 years for men and 16.4 ± 5.4 years for women, 11,696 deaths (2033 of CVD and 4631 of cancer causes) in men and 8980 deaths (1475 of CVD and 3689 of cancer causes) in women occurred. Combined moderately heavy/heavy baseline OPA was beneficially associated with all-cause mortality in men (multivariable-adjusted hazard ratio (HR) = 0.93, 95% confidence interval (95%CI): 0.89-0.98 compared to light OPA) and women (HR = 0.86, 95%CI: 0.79-0.93). Over a mean mortality follow-up of 12.5 ± 4.6 years for men and 12.6 ± 4.6 years for women, OPA decreases in men were detrimentally associated (HR = 1.16, 95%CI: 1.01-1.33) with all-cause mortality, while OPA increases in women were beneficially (HR = 0.83, 95%CI: 0.70-0.97) associated with the same outcome. Baseline or changes in OPA showed no associations with CVD or cancer mortality. CONCLUSION: Higher baseline OPA was beneficially associated with all-cause mortality risk in both men and women. Our longitudinal OPA analyses partly confirmed the prospective findings, with some discordance between sex groups.

A singleton pregnancy with placental chorioangioma and hydrops fetalis complicated with mirror syndrome and ritodrine-induced side effects: a case report.

BACKGROUND: Ritodrine hydrochloride is a widely used beta-adrenergic agonist used to stop preterm labor in Taiwan. Many side effects causing maternal morbidity and mortality have been reported. We report a case complicated with ritodrine-induced side effects and mirror syndrome that was associated with placental chorioangioma. CASE PRESENTATION: A 36-year-old singleton pregnant woman at 25 6/7 weeks of gestation, with an undiagnosed placental chorioangioma, underwent tocolysis due to preterm uterine contractions. Her clinical condition deteriorated, attributed to mirror syndrome and adverse events induced by ritodrine. An emergency cesarean section was performed at 27 1/7 weeks of gestation, delivering an infant with generalized subcutaneous edema. A placental tumor measuring 8.5 cm was discovered during the operation, and pathology confirmed chorioangioma. Gradual improvement in her symptoms and laboratory data was observed during the postpartum period. Identifying mirror syndrome and ritodrine-induced side effects poses challenges. Therefore, this case is educational and warrants discussion. CONCLUSION: Our case demonstrates mirror syndrome induced by chorioangioma, which is rare, and ritodrine-induced side effects. The cessation of intravenous ritodrine and delivery are the best methods to treat maternal critical status due to fluid overload.

Post-translational Modification of PD-1: Potential Targets for Cancer Immunotherapy.

Activation of effector T cells leads to upregulation of PD-1, which can inhibit T-cell activity following engagement with its ligand PD-L1. Post-translational modifications (PTM), including glycosylation, phosphorylation, ubiquitination, and palmitoylation, play a significant role in regulating PD-1 protein stability, localization, and interprotein interactions. Targeting PTM of PD-1 in T cells has emerged as a potential strategy to overcome PD-1-mediated immunosuppression in cancer and enhances antitumor immunity. The regulatory signaling pathways that induce PTM of PD-1 can be suppressed with small-molecule inhibitors, and mAbs can directly target PD-1 PTMs. Preliminary outcomes from exploratory studies suggest that focusing on the PTM of PD-1 has strong therapeutic potential and can enhance the response to anti-PD-1.

Modification of incident cancer risk with changes in metabolic syndrome status: A prospective cohort study in Taiwan.

PURPOSE: We aimed to investigate the effect of altered metabolic syndrome (MetS) status on cancer risk. METHODS: From 2002 through 2008 of the Taiwan MJ cohort, there were 111,616 adults who had repeated MetS measurements performed 3.3 years apart and were followed up for cancer incidence over 11.8 years. Cancer was confirmed based on histopathological reports. RESULTS: Participants were categorized as MetS-free (n = 80,409; no MetS at the first or last health screening), MetS-developed (n = 9833; MetS absence at the first screening and presence at the last screening), MetS-recovered (n = 8958; MetS presence at the first screening and absence at the last screening), and MetS-persisted (n = 12,416; MetS presence at the first and last screenings). We used the Fine-Gray sub-distribution method, with death as competing risk, to determine the association between MetS changes and incident cancer risk. During 1320,796 person-years of follow-up, 5862 individuals developed cancer. The incidence rate of cancer per 1000 person-years was 3.89 in the MetS-free, 5.26 in MetS-developed, 4.61 in MetS-recovered, and 7.33 in MetS-persisted groups (P < .001). Compared with the MetS-free group, MetS-persisted individuals had a higher risk of incident cancer. CONCLUSIONS: Persistent MetS was found to be associated with a high risk of incident cancer.

Iron overload induces cerebral endothelial senescence in aged mice and in primary culture in a sex-dependent manner.

Iron imbalance in the brain negatively affects brain function. With aging, iron levels increase in the brain and contribute to brain damage and neurological disorders. Changes in the cerebral vasculature with aging may enhance iron entry into the brain parenchyma, leading to iron overload and its deleterious consequences. Endothelial senescence has emerged as an important contributor to age-related changes in the cerebral vasculature. Evidence indicates that iron overload may induce senescence in cultured cell lines. Importantly, cells derived from female human and mice generally show enhanced senescence-associated phenotype, compared with males. Thus, we hypothesize that cerebral endothelial cells (CEC) derived from aged female mice are more susceptible to iron-induced senescence, compared with CEC from aged males. We found that aged female mice, but not males, showed cognitive deficits when chronically treated with ferric citrate (FC), and their brains and the brain vasculature showed senescence-associated phenotype. We also found that primary culture of CEC derived from aged female mice, but not male-derived CEC, exhibited senescence-associated phenotype when treated with FC. We identified that the transmembrane receptor Robo4 was downregulated in the brain vasculature and in cultured primary CEC derived from aged female mice, compared with those from male mice. We discovered that Robo4 downregulation contributed to enhanced vulnerability to FC-induced senescence. Thus, our study identifies Robo4 downregulation as a driver of senescence induced by iron overload in primary culture of CEC and a potential risk factor of brain vasculature impairment and brain dysfunction.

Piperic acid derivative as a molecular modulator to accelerate the IAPP aggregation process and alter its antimicrobial activity.

Piperic acid derivatives were found to affect the islet amyloid polypeptide (IAPP) aggregation process. Structure-activity relationship studies revealed that PAD-13 was an efficient molecular modulator to accelerate IAPP fibril formation by promoting primary and secondary nucleation and reducing its antimicrobial activity.

Treatment and mortality risk of older adults with non-small cell cancer in Taiwan: A population-based cohort study.

BACKGROUND: Older patients tend to have decreased physical functions and more comorbidities than younger patients. At present, the best management for very elderly patients with lung cancer is not known. In this study, we aimed to investigate treatment and mortality risk of older adults with non-small cell cancer (NSCLC) in Taiwan. METHODS: This study analyzed data from the Taiwan Cancer Registry database. Patients aged ≥80 years with newly diagnosed NSCLC between 2010 and 2017 were included. Treatment options were categorized as curative, palliative, and no treatment. Patients were followed up until death or December 31, 2020. Univariable and multivariable Cox proportional hazards models were used to estimate mortality risk, and Kaplan-Meier survival curves were drawn. RESULTS: A total of 11 941 patients, aged ≥80 years, with newly diagnosed NSCLC between 2010 and 2017 were identified from the Taiwan Cancer Registry and followed up until 2020. The mean age was 84.4 ± 3.7 years old, and 7468 (62.54%) were men. The Kaplan-Meier survival curves showed significant differences across the three treatment options (log-rank p < 0.001). Results from multivariate Cox regression demonstrated that patients on palliative treatment (adjusted HR: 0.52, 95% CI: 0.48-0.56, p < 0.001) and curative treatment (adjusted HR: 0.45, 95% CI: 0.42-0.48, p < 0.001) had a significantly lower mortality risk than those with no treatment. The subgroup analyses stratified by cancer stages also showed consistent findings. CONCLUSION: Elderly patients with NSCLC had significantly decreased mortality risk when receiving curative or palliative treatment compared with those without treatment. In the future, further studies are warranted to investigate complications and quality of life of elderly patients with NSCLC during palliative or curative treatment.

The abundances of LTF and SOD2 in amniotic fluid are potential biomarkers of gestational age and preterm birth.

Neonates who are born preterm (PT) are usually characterized by immature physiological development, and preterm birth (PTB) is the leading cause of neonatal morbidity and mortality if intensive medical care is not available to PTB neonates. Early prediction of a PTB enables medical personnel to make preparations in advance, protecting the neonate from the subsequent health risks. Therefore, many studies have worked on identifying invasive or noninvasive PT biomarkers. In this study, we collected amniocentesis-derived (at the second trimester of gestation) amniotic fluid (AF) samples. At delivery, AF samples were classified into PTB or full-term birth (FTB). We first applied protein mass spectrometry technology to globally screen AF proteins, followed by specific protein validation with ELISA. We identified four protein biomarkers of PTB, including lactotransferrin (LTF), glutathione-disulfide reductase (GSR), myeloperoxidase (MPO) and superoxide dismutase 2 (SOD2). Further analyses demonstrated that their abundances were negatively correlated with neonatal weight and gestational age. In addition, by mimicking survival rate analysis widely used in tumor biology, we found that LTF and SOD2 were prognostic factors of gestational age, with higher levels denoting shorter gestational age. Finally, using the abundances of the four protein biomarkers, we developed a prediction model of PTB with an auROC value of 0.935 (sensitivity = 0.94, specificity = 0.89, p value = 0.0001). This study demonstrated that the abundances of specific proteins in amniotic fluid were not only the prognostic factors of gestational age but also the predictive biomarkers of PTB. These four AF proteins enable identification of PTB early in the second trimester of gestation, facilitating medical intervention to be applied in advance.

Biomarkers in long COVID-19: A systematic review.

Purpose: Long COVID, also known as post-acute sequelae of COVID-19, refers to the constellation of long-term symptoms experienced by people suffering persistent symptoms for one or more months after SARS-CoV-2 infection. Blood biomarkers can be altered in long COVID patients; however, biomarkers associated with long COVID symptoms and their roles in disease progression remain undetermined. This study aims to systematically evaluate blood biomarkers that may act as indicators or therapeutic targets for long COVID. Methods: A systematic literature review in PubMed, Embase, and CINAHL was performed on 18 August 2022. The search keywords long COVID-19 symptoms and biomarkers were used to filter out the eligible studies, which were then carefully evaluated. Results: Identified from 28 studies and representing six biological classifications, 113 biomarkers were significantly associated with long COVID: (1) Cytokine/Chemokine (38, 33.6%); (2) Biochemical markers (24, 21.2%); (3) Vascular markers (20, 17.7%); (4) Neurological markers (6, 5.3%); (5) Acute phase protein (5, 4.4%); and (6) Others (20, 17.7%). Compared with healthy control or recovered patients without long COVID symptoms, 79 biomarkers were increased, 29 were decreased, and 5 required further determination in the long COVID patients. Of these, up-regulated Interleukin 6, C-reactive protein, and tumor necrosis factor alpha might serve as the potential diagnostic biomarkers for long COVID. Moreover, long COVID patients with neurological symptoms exhibited higher levels of neurofilament light chain and glial fibrillary acidic protein whereas those with pulmonary symptoms exhibited a higher level of transforming growth factor beta. Conclusion: Long COVID patients present elevated inflammatory biomarkers after initial infection. Our study found significant associations between specific biomarkers and long COVID symptoms. Further investigations are warranted to identify a core set of blood biomarkers that can be used to diagnose and manage long COVID patients in clinical practice.

Gonadotropin-releasing hormone agonist treatment and ischemic heart disease among female patients with breast cancer: A cohort study.

BACKGROUND: The risk of ischemic heart disease (IHD) due to the impact of gonadotropin-releasing hormone (GnRH) agonists among female patients with breast cancer remains a controversy. METHODS: Information from the Registry for Catastrophic Illness, the National Health Insurance Research Database (NHIRD), and the Death Registry Database in Taiwan were analyzed. Female patients with breast cancer were selected from the Registry for Catastrophic Illness from January 1, 2000, to December 31, 2018. All the breast cancer patients were followed until new-onset IHD diagnosis, death, or December 31, 2018. A Kaplan-Meier survival curve was drawn to show the difference between patients treated with and without GnRH agonists. The Cox regression analysis was used to investigate the effects of GnRH agonists and the incidence of IHD. RESULTS: A total of 172,850 female patients with breast cancer were recognized with a mean age of 52.6 years. Among them, 6071(3.5%) had received GnRH agonist therapy. Kaplan-Meier survival curves showed a significant difference between patients with and without GnRH therapy (log-rank p < 0.0001). Patients who received GnRH therapy had a significantly decreased risk of developing IHD than those without GnRH therapy (HR = 0.18; 95% CI = 0.14-0.23). After adjusting for age, treatment, and comorbidity, patients who received GnRH therapy still had a significantly lower risk of developing IHD (AHR = 0.5, 95% CI = 0.39-0.64). CONCLUSION: The study showed that the use of GnRH agonists for breast cancer treatment was significantly associated with a reduced risk of IHD. Further research is required to investigate the possible protective effect of GnRH on IHD.

Deglycosylation of SLAMF7 in breast cancers enhances phagocytosis.

N-linked glycosylation of proteins is one of the post-translational modifications (PTMs) that shield tumor antigens from immune attack. Signaling lymphocytic activation molecule family 7 (SLAMF7) suppresses cancer cell phagocytosis and is an ideal target under clinical development. PTM of SLAMF7, however, remains less understood. In this study, we investigated the role of N-glycans on SLAMF7 in breast cancer progression. We identified seven N-linked glycosylation motifs on SLAMF7, which are majorly occupied by complex structures. Evolutionally conserved N98 residue is enriched with high mannose and sialylated glycans. Hyperglycosylated SLAMF7 was associated with STT3A expression in breast cancer cells. Inhibition of STT3A by a small molecule inhibitor, N-linked glycosylation inhibitor-1 (NGI-1), reduced glycosylation of SLAMF7, resulting in enhancing antibody affinity and phagocytosis. To provide an on-target effect, we developed an antibody-drug conjugate (ADC) by coupling the anti-SLAMF7 antibody with NGI-1. Deglycosylation of SLAMF7 increases antibody recognition and promotes macrophage engulfment of breast cancer cells. Our work suggests deglycosylation by ADC is a potential strategy to enhance the response of immunotherapeutic agents.

Adipose stem cells preincubated with theanine exert liver regeneration through increase of stem cell paracrine VEGF and suppression of ROS, pyroptosis as well as autophagy markers in liver damage induced by N-nitrosodiethylamine.

AIMS: Liver diseases induce a severe decrease in quality of life. Stem cell based therapy shows therapeutic potential in the treatment of liver injury. Theanine is a unique amino acid found in green tea and could confer beneficial effects on cell protection. This study investigates if protective effect on the liver by stem cells preincubated with theanine is better than that from stem cells without preincubated theanine. METHODS: We transplanted theanine preincubated adipose-derived stem cells (ADSC) to male Wistar rats with liver dysfunction induced by N-nitrosodiethylamine. The viability, migration and antioxidant capabilities were performed in the ADSC pre-incubated with theanine. Hepatic functional, structural and molecular assays were determined in the animals with or without theanine preincubated ADSC. KEY FINDINGS: Cell model revealed that ADSC preincubated with green tea theanine (T-ADSC) increased cell capabilities including viability, migration and paracrine secretion. In vivo results indicated that several pathological conditions were observed in rats with liver injury induced by DEN including structural changes and expression of pyroptosis as well as autophagy markers. The above pathological conditions were improved when the rats received both ADSC and T-ADSC treatment. Furthermore, T-ADSC showed better therapeutic effect on rats with liver injury than ADSC due to significant suppression of pyroptosis markers caspase-1 and IL-1ß as well as autophagy marker LC3-II accompanied with intensive paracrine VEGF from T-ADSC. SIGNIFICANCE: Increased paracrine VEGF secretion from T-ADSC plays a crucial role in liver regeneration. A future clinical study may be designed for further verification of these experimental in vivo findings.

L-Theanine-Treated Adipose-Derived Mesenchymal Stem Cells Alleviate the Cytotoxicity Induced by N-Nitrosodiethylamine in Liver.

BACKGROUND: Liver inflammation is the main cause of severe liver diseases, including liver fibrosis, steatohepatitis, cirrhosis and hepatocellular carcinoma. Cell therapy topics are receiving increasingly more attention. The therapeutic applications of mesenchymal stem cells (MSC) have become one of the most discussed issues. While other stem cells have therapeutic effects, they have only one or two clinical applications. MSCs are responsible for repairing a variety of tissue injuries. Moreover, MSCs could be derived from several sources, including adipose tissue. MSCs are usually more abundant and easier to obtain compared to other stem cells. METHODS: To prove the concept that MSCs have homing ability to the injured tissue and assist in tissue repair, we examined the effects of intravenous injected adipose-derived mesenchymal stem cells (ADSCs) in a N-nitrosodiethylamine (DEN)-induced liver injury rat model. RESULTS: The significant repairing ability of ADSCs was observed. The levels of fibrosis, apoptosis, and tumorigenesis in the DEN-injured liver tissues all decreased after ADSC treatment. Furthermore, to enhance the therapeutic effects of ADSCs, we pretreated them with L-theanine, which promotes the hepatocyte growth factor secretion of ADSC, and therefore improved the healing effects on injured liver tissue. CONCLUSION: ADSCs, especially L-theanine-pretreated ADSCs, have anti-inflammation, anti-apoptosis, and anti-tumorigenesis effects on the N-nitrosodiethylamine-induced liver injury rat model.

Changes in physical activity and adiposity with all-cause, cardiovascular disease, and cancer mortality.

BACKGROUND: The relationship between joint changes in physical activity and adiposity with mortality is not well understood. We examined the association of changes in these two established risk factors with all-cause (ACM), cardiovascular disease (CVD), and cancer mortality. METHODS: We used longitudinal data from Taiwan's MJ Cohort, comprising 116,228 general population adults recruited from 1998-2013 with repeated measures 4.6 y (2.5) apart and followed up for mortality for 11.9 y (3.5). Physical activity, body mass index (BMI), waist circumference (WC), and body fat percentage (BF%) groups and changes were based on public health and clinical guidelines. RESULTS: Compared to stable-insufficient physical activity, increasing physical activity from any baseline level was associated with lower ACM (HR [95%CI]): 0.85 [0.74, 0.96]) and CVD mortality (0.72 [0.55, 0.93]) risk. This was approximately equal to meeting physical activity guidelines at both timepoints (eg: 0.71 [0.58, 0.88] for CVD mortality). Compared to stable-overweight/moderate adiposity, decreasing adiposity level attenuated but did not offset mortality risk for all three outcomes (eg: BMI = 0.95 [0.76, 1.16] for CVD mortality). Only maintaining a healthy adiposity level at both timepoints offset mortality risk (BMI = 0.75 [0.61, 0.89]) for CVD mortality). In the joint changes analyses, lower mortality risk was a consequence of increases in physical activity across adiposity change groups (eg: WC decrease = 0.57 [0.48, 0.67]; WC stability = 0.73 [0.66, 0.80], WC increase = 0.83 [0.72, 0.97] for ACM). Decreasing adiposity attenuated the negative associations of decreased physical activity (BF% = 1.13 [0.95, 1.35] for ACM). CONCLUSIONS: We found a lower risk for ACM, CVD, and cancer mortality from increasing physical activity and an attenuation from decreasing adiposity regardless of baseline levels. The beneficial associations of joint changes were primarily driven by physical activity, suggesting lower mortality risk may be more immediate through physical activity improvements compared to adiposity improvements alone.

Prognostic serum biomarkers in cancer patients with COVID-19: A systematic review.

PURPOSE: Cancer patients with COVID-19 likely express biomarker changes in circulation. However, the biomarkers used in SARS-CoV-2 infected cancer patients for COVID-19 severity and prognosis are largely unclear. Therefore, this systematic review aims to determine what biomarkers were measured in cancer patients with COVID-19 and their prognostic utility. METHODS: A systematic literature review in PubMed, Embase, and Scopus was performed on June 16th, 2021. The search keywords coronavirus, neoplasm, biomarkers, and disease progression were used to filter out 17 eligible studies, which were then carefully evaluated. RESULTS: A total of 4,168 patients, 16 types of cancer, and 60 biomarkers were included. Seven up-regulated markers, including CRP, d-dimer, ferritin, IL-2R, IL-6, LDH, and PCT, were identified in eligible studies. Albumin and hemoglobin were significantly down-regulated in cancer patients with COVID-19. Moreover, we observed that the SARS-CoV-2 infected cancer patients with lower CRP, ferritin, and LDH levels successfully survived from COVID-19 treatments. CONCLUSION: Several important clinical biomarkers, such as CRP, ferritin, and LDH, may serve as the prognostic markers to predict the outcomes following COVID-19 treatment and monitor the deterioration of COVID-19 in cancer patients.

End-of-life discussions reduce the utilization of life-sustaining treatments during the last three months of life in cancer patients.

Studies to examine the impact of end-of-life (EOL) discussions on the utilization of life-sustaining treatments near death are limited and have inconsistent findings. This nationwide population-based cohort study determined the impact of EOL discussions on the utilization of life-sustaining treatments in the last three months of life in Taiwanese cancer patients. From 2012 to 2018, this cohort study included adult cancer patients, which were confirmed by pathohistological reports. Life-sustaining treatments during the last three months of life included cardiopulmonary resuscitation, intubation, and defibrillation. EOL discussions in cancer patients were confirmed by their medical records. Association of EOL discussions with utilization of life-sustaining treatments were assessed using multiple logistic regression. Of 381,207 patients, the mean age was 70.5 years and 19.4% of the subjects received life-sustaining treatments during the last three months of life. After adjusting for other covariates, those who underwent EOL discussions were less likely to receive life-sustaining treatments during the last three months of life compared to those who did not (Adjusted odds ratio [AOR] 0.87; 95% confidence interval [CI] 0.85-0.89). Considering the type of treatments, EOL discussions correlated with a lower likelihood of receiving cardiopulmonary resuscitation (AOR = 0.45, 95% CI 0.43-0.47), endotracheal intubation (AOR = 0.92, 95%CI 0.90-0.95), and defibrillation (AOR = 0.54, 95%CI 0.49-0.59). Since EOL discussions are associated with less aggressive care, our study supports the importance of providing these discussions to cancer patients during the EOL treatment.

Comparison of intuitive assessment and palliative care screening tool in the early identification of patients needing palliative care.

The intuitive assessment of palliative care (PC) needs and Palliative Care Screening Tool (PCST) are the assessment tools used in the early detection of patients requiring PC. However, the comparison of their prognostic accuracies has not been extensively studied. This cohort study aimed to compare the validity of intuitive assessment and PCST in terms of recognizing patients nearing end-of-life (EOL) and those appropriate for PC. All adult patients admitted to Taipei City Hospital from 2016 through 2019 were included in this prospective study. We used both the intuitive assessment of PC and PCST to predict patients' 6-month mortality and identified those appropriate for PC. The c-statistic value was calculated to indicate the predictive accuracies of the intuition and PCST. Of 111,483 patients, 4.5% needed PC by the healthcare workers' intuitive assessment, and 6.7% had a PCST score ≥ 4. After controlling for other covariates, a positive response 'yes' to intuitive assessment of PC needs [adjusted odds ratio (AOR) = 9.89; 95% confidence interval (CI) 914-10.71] and a PCST score ≥ 4 (AOR = 6.59; 95%CI 6.17-7.00) were the independent predictors of 6-month mortality. Kappa statistics showed moderate concordance between intuitive assessment and PCST in predicting patients' 6-month mortality (k = 0.49). The c-statistic values of the PCST at recognizing patients' 6-month mortality was significantly higher than intuition (0.723 vs. 0.679; p < 0.001). As early identification of patients in need of PC could improve the quality of EOL care, our results suggest that it is imperative to screen patients' palliative needs by using a highly accurate screening tool of PCST.

Hospice Care Services Associated With a Lower Utilization of Life-Sustaining Treatments During End-Of-Life Care Among People Living With HIV/AIDS: A Population-Based Cohort Study.

Background: Hospice care involves improving quality of end-of-life (EOL) care and respecting patients' preferences regarding EOL treatment. However, the impact of hospice care services on the utilization of life-sustaining treatments during EOL care in patients with life-limiting diseases has not been extensively studied. Objectives: This nationwide cohort study aimed to determine the impact of hospice care services on the utilization of life-sustaining treatments during the last 3 months of life among people living with HIV/AIDS (PLWHA) in Taiwan. Methods: From 2000 to 2018, we identified adult PLWHA from Taiwan centers for disease control HIV Surveillance System. HIV-infected individuals were defined as positive HIV-1 Western blot. Life-sustaining treatments included cardiopulmonary resuscitation, intubation, mechanical ventilation support, and defibrillation. The association of hospice care services with the utilization of life-sustaining treatments was determined using multiple logistic regression. Results: Of 5691 PLWHA, 2595 (45.9%) subjects utilized life-sustaining treatments during the last 3 months of life. After adjusting for other covariates, PLWHA with hospice care services were less likely to receive life-sustaining treatments during the last 3 months of life than those without the services (adjusted odds ratio [AOR] = .50, 95% confidence interval [CI]: .37-.66). Considering the type of life-sustaining treatments, hospice care services were associated with lower likelihood of receiving cardiopulmonary resuscitation (AOR = .22, 95% CI: .13-.39), endotracheal intubation (AOR = .48, 95% CI: .35-.65), and mechanical ventilation support (AOR = .56, 95% CI: .42-.75). Conclusion: Hospice care services were associated with a lower utilization of life-sustaining treatments during the last 3 months of life among PLWHA.

Can physical activity eliminate the mortality risk associated with poor sleep? A 15-year follow-up of 341,248 MJ Cohort participants.

BACKGROUND: This study examined the joint associations of sleep patterns and physical activity (PA) with all-cause, cardiovascular disease (CVD), and cancer mortality. METHODS: A total of 341,248 adults (mean age = 39.7 years; men: 48.3%) were included in the study, with a 15-year follow-up. Participants reported sleep duration and disturbances (difficulty falling asleep, easily awakened, or use of sleeping medication). PA was classified into 4 levels: <7.5, 7.5-14.9, 15.0-29.9, and ≥30.0 metabolic equivalent hours per week (MET-h/week). To understand the joint associations of sleep patterns and PA with mortality, Cox proportional hazard models were conducted, with exposure variables combining sleep duration/disturbances and PA. RESULTS: Compared with the reference group (sleeping 6-8 h/day), individuals who slept >8 h/day had higher risk for all-cause mortality (hazard ratio (HR) = 1.307, 95% confidence interval (95%CI): 1.248-1.369), CVD mortality (HR = 1.298, 95%CI: 1.165-1.445), and cancer mortality (HR = 1.128, 95%CI: 1.042-1.220). Short sleep duration was not associated with mortality risk. Increased risk of all-cause and CVD mortality was found in participants who had difficulty falling asleep (HR = 1.120, 95%CI: 1.068-1.175; HR = 1.163, 95%CI: 1.038-1.304, respectively), and used sleeping medication (HR = 1.261, 95%CI: 1.159-1.372; HR = 1.335, 95%CI: 1.102-1.618, respectively) compared with those who slept well. Long sleep duration and sleep disturbances were not associated with risk of all-cause and CVD mortality among individuals achieving a PA level of ≥15 MET-h/week, and in particular among those achieving ≥30 MET-h/week. CONCLUSION: Long sleep duration, difficulty falling asleep, and use of sleeping medication were related to a higher risk of death. Being physically active at a moderate intensity for 25-65 min/day eliminated these detrimental associations.

Increased mortality after intravitreal injections of anti-VEGF for neovascular AMD among patients with prior stroke or acute myocardial infarction.

OBJECTIVES: To evaluate whether intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) in neovascular age-related macular degeneration (nAMD) patients with prior stroke or acute myocardial infarction (AMI) are associated with increased mortality. METHODS: From 2005 to 2013, nAMD patients in the Taiwan National Health Insurance Research Database who received IVI of anti-VEGF and had a diagnosis of stroke/AMI prior to their first injections were defined as the IVI group. The mortality of the IVI group during the study period was compared to that of the non-IVI group, which consisted of nAMD patients who had prior stroke/AMI but were never exposed to anti-VEGF. The IVI group and the non-IVI group were 1-4 matched according to propensity score (PS), which was derived from age, sex, date of stroke/AMI and comorbidities. PS-adjusted Cox regression analyses were used to estimate the hazard ratio (HR) for mortality associated with IVI of anti-VEGF. Subgroup analyses were also performed according to the interval between stroke/AMI and IVI (≤6 months, 6 months to 1 year, 1-2 years, >2 years). RESULTS: There were 3384 individuals in the IVI group and 13,536 individuals in the non-IVI group. The IVI group had a significantly higher mortality risk (adjusted HR = 2.37; 95% confidence interval (CI), 2.14-2.62) than the non-IVI group. Subgroup analyses revealed that elevated mortality was significant when anti-VEGF was injected within 1 year after stroke/AMI. CONCLUSIONS: We found an increased mortality risk associated with IVI of anti-VEGF in nAMD patients with prior stroke/AMI compared to the mortality risk of nAMD patients with prior stroke/AMD but without exposure to anti-VEGF.