The effect of physical activity on sleep disturbance in various populations: a scoping review of randomized clinical trials.

BACKGROUND: Promoting physical activity (PA) in different populations experiencing sleep disturbance may increase population PA levels and improve sleep. This scoping review aimed to examine the effect of various PA intervention strategies on sleep across different populations, identify key sleep outcomes, and analyze knowledge gaps by mapping the relevant literature. METHODS: For this study, we systematically searched articles published till March 2022 from PubMed, Web of Science, Cochrane Library, and Embase databases for randomized clinical trials (RCTs) regarding the effect of physical activity on sleep. Two authors extracted key data and descriptively analyzed the data. Thematic analysis was used to categorize the results into themes by all authors. Arksey and O'Malley's scoping review framework was used to present the findings. RESULTS: Twenty-one randomized controlled trials out of 3052 studies were finally included with 3677 participants (2852 females (78%)). Five trials were conducted in healthy working-age adults with sleep disturbance but without the diagnosis of insomnia, five in healthy older adults, two in perinatal women, four in patients with cancer, three in mental illness related subjects, and another two in other disease-related areas. PA interventions were diverse, including walking, resistance training, aerobic exercise, housework, water exercise, basketball, smartphone/tablet "apps", web, online videos or wearable actigraphy, and self-determined exercise. Three major themes were identified: (1) Sleep environment may be important to address prior to instituting PA interventions, (2) All types of PA were effective for improving sleep in all populations studied, (3) Self-tolerated PA is safe for improving sleep in the elderly and in co-morbid or perinatal populations. CONCLUSIONS: PA is effective and safe for improving sleep in both healthy and co-morbid populations with sleep disturbance by increasing daily activity levels using a variety of strategies, even low intensity, such as housekeeping, sit-to-stand repetitions, along with encouraging PA through web pages, videos, and self-goal setting apps. In addition, this scoping review identifies the need for further therapeutic research and future exploration in populations with sleep initiation or sleep maintenance disturbance.

Comparison between simple triage and rapid treatment and Taiwan Triage and Acuity Scale for the emergency department triage of victims following an earthquake-related mass casualty incident: a retrospective cohort study.

BACKGROUND: Triage plays a crucial role in the emergency department (ED) management of mass casualty incidents (MCIs) when resources are limited. This study aimed to compare the performance of simple triage and rapid treatment (START) with that of the Taiwan Triage and Acuity Scale (TTAS) for the ED triage of victims following an earthquake-related MCI. METHODS: We retrospectively reviewed the records of victims presenting at our ED with earthquake-related injuries within 24 h of a large-scale earthquake. TTAS was initially used at our ED for this event, and START was performed by retrospectively reviewing the patient records in a blinded manner. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of START and TTAS were determined for predicting ED discharge. RESULTS: We enrolled 105 patients (predominantly women, 60.0%; median age, 45.0 years) in this study; most of them presented with traumatic injuries and were initially triaged as TTAS level III (78.1%), followed by TTAS level II (11.4%). Although the majority of the victims (81.0%) were discharged, four deaths occurred. A moderate agreement in differentiating emergency from nonemergency patients was observed between START and TTAS. Furthermore, both the triage systems showed similar predictions for ED disposition (START AUC/sensitivity/specificity: 0.709/82.35%/55.00%; TTAS AUC/sensitivity/specificity: 0.709/90.59%/45.00%). CONCLUSIONS: The present study demonstrated that START and TTAS have similar triage accuracy and ability to predict ED disposition. Our findings demonstrate that START may be used as an alternative to TTAS for the ED triage of victims following earthquake-related MCIs.

Effects of HER2 status on the prognosis of male breast cancer: a population-based study.

OBJECTIVE: This study was designed to analyze the effects of human epidermal growth factor receptor-2 (HER2) status on the prognosis of male breast cancer (MBC). METHODS: The SEER database was used to identify MBC patients diagnosed between 2010 and 2015. Patients were divided into HER2-negative and HER2-positive groups and chi-square test was used to compare the demographics. Propensity score matching (PSM) was used to remove confounding factors. The log-rank test was used to compare the overall survival (OS) and disease-specific survival (DSS) between the two groups. Univariate and multivariate Cox regression analyses were used to evaluate the effects of different variables on the prognosis of MBC patients. Subgroup analysis was conducted by using R software to explore the benefit of OS and DSS in the subgroup of MBC patients. RESULTS: In the matched cohort, the log-rank test showed that there was a longer OS (P=0.044) in the HER2-negative group, and the 4-year OS rate in HER2-negative patients was significantly improved (P=0.008), but there was no difference in the DSS (P=0.408) and the 4-year DSS rates (P=0.198) between the two groups. Univariate and multivariate Cox regression also showed that the HER2 status did not independently associate with DSS (P=0.444). Subgroup analysis showed that HER2-negative patients experienced a longer OS in the subgroup of tumors 2-4 cm in size, no distant metastasis and who had received radiotherapy, but none of subgroup was found a significant difference in DSS between different HER2 status. CONCLUSION: This study identified that HER2 status had a clear influence on OS in patients with MBC, and there was a longer OS and a higher 4-year OS rate in the HER2-negative group. In addition, we observed that HER2 status had no significant effect on DSS in patients with MBC.

The efficacy and safety of immune checkpoint inhibitor combination therapy in lung cancer: a systematic review and meta-analysis.

The value of immune checkpoint inhibitor (ICI) combination therapy for patients with lung cancer remains unclear. We conducted a meta-analysis using PubMed, Embase, and ClinicalTrials.gov databases to identify eligible randomized controlled trials (RCTs) that might provide a reference for clinical practice. The selection criteria were defined according to the population, intervention, comparison, outcome and study design (PICOS) framework. In all, 12 RCTs with 5,989 patients were included in this meta-analysis. Our results showed that ICI combination therapy was significantly associated with the improvement of overall response rate (ORR) (RR =1.44 [95% CI 1.19, 1.74], P=0.0002), progression-free survival (PFS) (HR =0.67 [95% CI 0.59, 0.77], P<0.00001), and OS (HR =0.81 [95% CI 0.70, 0.95], P=0.008) in lung cancer. In subgroup analyses, combination ICI therapy significantly prolonged OS in non-small-cell lung cancer (NSCLC) patients (HR =0.80 [95% CI 0.73, 0.88], P<0.00001) but not in SCLC (HR =0.94 [95% CI 0.82, 1.08], P=0.40) patients. Data suggested that PD-1 inhibitors had higher efficacy and safety profiles than PD-L1 and CTLA-4 inhibitors in combination ICI therapy for lung cancer patients. Furthermore, tolerability analysis revealed higher incidences of grade ≥3 AEs, fatigue, and increased transaminases from combination ICI therapy. In conclusion, our meta-analysis indicated that combination ICI therapy should be considered in clinical practice and future study designs for NSCLC patients. However, the current data do not support the large-scale clinical application of combination ICI therapy in SCLC patients.

Clinical and molecular characteristics associated with the efficacy of PD-1/PD-L1 inhibitors for solid tumors: a meta-analysis.

We conducted a meta-analysis to estimate the impact of different clinical and molecular characteristics on the efficacy of programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors. PubMed and Web of Science were searched for related trials. Eleven eligible studies, comprising 5,663 patients, were included in this meta-analysis. We found that the PD-1/PD-L1 inhibitor was associated with a 31% reduction in the risk of death (hazard ratio [HR]=0.69; 95% CI 0.64-0.74; P<0.00001) for patients with melanoma, non-small-cell lung cancer (NSCLC), urothelial carcinoma, head and neck carcinoma, and renal cell carcinoma. In subgroup analyses, all the patients with PD-L1-positive tumors had overall survival (OS) benefits from PD-1/PD-L1 inhibitors regardless of PD-L1 expression level, and a dose-effect relationship between the expression of PD-L1 and OS benefit from PD-1/PD-L1 inhibitors was observed. There was an OS improvement for patients with a smoking history (P<0.00001), but no OS benefit was observed for nonsmokers (P=0.28). In addition, first-line therapy had better OS than second-line or later treatment (P=0.02). No significant improvement of OS was observed (P=0.70) in patients aged ≥75 years. The relative treatment efficacy was similar according to sex (male vs female, P=0.60), performance status (0 vs ≥1, P=0.68), tumor histology (squamous NSCLC vs non-squamous NSCLC vs melanoma vs urothelial carcinoma vs head and neck carcinoma vs renal cell carcinoma, P=0.64), and treatment type (PD-1 inhibitor vs PD-L1 inhibitor, P=0.36). In conclusion, PD-L1-positive tumors, smoking history, and first-line treatment were potential factors for the efficacy of PD-1/PD-L1 inhibitors. Patients with higher PD-L1 expression might achieve greater OS benefits. In addition, sex, performance status, tumor histology, and treatment type could not predict the efficacy of this therapy. In contrast, patients aged >75 years and nonsmokers might not get OS benefits from this treatment. These results may improve treatment strategies and patient selection for PD-1/PD-L1 inhibitors.

Introduction of a mass burn casualty triage system in a hospital during a powder explosion disaster: a retrospective cohort study.

Background: The triage system used during an actual mass burn casualty (MBC) incident is a major focus of concern. This study introduces a MBC triage system that was used by a burn center during an actual MBC incident following a powder explosion in New Taipei City, Taiwan. Methods: This study retrospectively analyzed data from patients who were sent to the study hospital during a MBC incident. The patient list was retrieved from a national online management system. A MBC triage system was developed at the study hospital using the following modifiers: consciousness, breathing, and burn size. Medical records were retrieved from electronic records for analysis. Patient outcomes consisted of emergency department (ED) disposition and intervention. Results: The patient population was predominantly female (56.3%), with an average age of 24.9 years. Mean burn sizes relative to the TBSA of triage level I, II, and III patients were 57.9%, 40.5%, and 8.7%, respectively. ICU length of stay differed markedly according to triage level (mean days for levels I vs II vs III: 57.9 vs 39.9 vs 2.5 days; p < 0.001). Triage system levels I and II indicate ICU admission with a sensitivity of 93.9% (95%CI 80.4-98.3%) and a specificity of 86.7% (62.1-96.3%).Overall, 3 (6.3%) patients were under-triaged. Two (4.2%) patients were over-triaged. Sixteen (48.5%) and 21 (63.6%) patients of triage levels I and II received endotracheal intubation and central venous catheterization, respectively. Sorting of the study population with simple triage and rapid treatment (START) showed great sensitivity (100.0%) but poor specificity (53.3%). The Taiwan Triage and Acuity Scale (TTAS) presented 87.9% sensitivity and 93.9% specificity. Conclusions: The current MBC triage algorithm served as a good indicator of ED disposition but might have raised excessive immediate attention and had the potential to exhaust the available resources. These findings add to our knowledge of the MBC triage system and should help future researchers in adjusting the triage criteria to fit actual disasters.

One-year survival rate and healthcare costs after cardiac arrest in Taiwan, 2006-2012.

OBJECTIVES: The annual increase in costs and the quality of life of survivors of cardiac arrest are major concerns. This study used National Health Insurance Research Database (NHIRD) of Taiwan to evaluate the 1-year survival rate and the annual healthcare costs of survivors after cardiac arrest. METHODS: This retrospective, fixed-cohort study conducted from 2006 to 2012, involved 2 million individuals randomly selected from the NHIRD of Taiwan. Adult patients at least 18 years old who were diagnosed with cardiac arrest were enrolled. Survival was followed up for 1 year. RESULTS: In total, 2,256 patients were enrolled. The survivor cohort accounted for 4% (89/2256) of the study population. There were no significant differences in the demographic characteristics of the survival and non-survival cohorts, with the exceptions of gender (male: survival vs. non-survival, 50.6% vs. 64.5%, p = 0.007), diabetes mellitus (49.4% vs. 35.8%, p = 0.009), and acute coronary syndrome (44.9% vs. 31.9%, p = 0.010). Only 38 (1.7%) patients survived for > 1 year. The mean re-admission to hospital during the 1-year follow up was 73.5 (SD: 110.2) days. The mean healthcare cost during the 1-year follow up was $12,953. Factors associated with total healthcare costs during the 1-year follow up were as follows: city or county of residence, being widowed, and Chronic Obstructive Pulmonary Disease (city or county of residence, ß: -23,604, p < 0.001; being widowed, ß: 25,588, p = 0.049; COPD, ß: 14,438, p = 0.024). CONCLUSIONS: There was a great burden of the annual healthcare costs of survivors of cardiac arrest. Socioeconomic status and comorbidity were major confounders of costs. The outcome measures of cardiac arrest should extend beyond the death, and encompass destitution. These findings add to our knowledge of the health economics and indicate future research about healthcare of cardiac arrest survivors.

Clinical Characteristics and Survival Outcomes for Non-Small-Cell Lung Cancer Patients with Epidermal Growth Factor Receptor Double Mutations.

Multiple randomized clinical trials have demonstrated that epidermal growth factor receptor (EGFR) exon 19 deletion (19Del) and exon 21 L858R mutation (L858R) are highly correlated with sensitivity to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in non-small-cell lung cancer (NSCLC). A mutation in exon 20 (T790M) is reportedly associated with resistance to EGFR-TKIs. However, few studies have focused on patients harboring double mutations in these 3 mutation sites. In this retrospective study, forty-five patients (45/2546, 1.7%) harbored double mutations of 19Del, L858R, and T790M. Twenty-four patients with EGFR double mutations received EGFR-TKI therapy. Clinical characteristics of these patients, including the response to EGFR-TKIs and progression-free survival outcome for EGFR-TKI treatment (PFS-TKI), were analyzed. Patients with EGFR double mutations were more likely to be nonsmokers, have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1, have adenocarcinoma, and be at stage III-IV. The ORR, DCR, and median PFS-TKI in patients harboring EGFR double mutations were lower than in patients with a single EGFR-activating mutation. The differences in ORR and DCR were statistically insignificant between the 3 groups. Patients with double mutations of 19Del and T790M had longer PFS-TKIs than patients in the other 2 groups.

Efficacy of EGFR tyrosine kinase inhibitors in non-small cell lung cancer patients harboring different types of EGFR mutations: A retrospective analysis.

With the development of molecular pathology, many types of epidermal growth factor receptor (EGFR) mutations have been identified. The efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) patients with different types of EGFR mutations, especially in patients with single rare mutations or complex mutations (co-occurrence of two or more different mutations), has not been fully understood. This study aimed to examine the efficacy of EGFR-TKIs in NSCLC patients with different types of EGFR mutations. Clinical data of 809 NSCLC patients who harbored different types of EGFR mutations and treated from January 2012 to October 2016 at Renmin Hospital and Zhongnan Hospital, Wuhan, were retrospectively reviewed. The clinical characteristics of these patients and the efficacy of EGFR-TKIs were analyzed. Among these patients, 377 patients had only the EGFR del-19 mutation, 362 patients the EGFR L858R mutation in exon 21, 33 patients single rare mutations and 37 patients complex mutations. Among these 809 patients, 239 patients were treated with EGFR-TKIs. In all the 239 patients, the disease control rate (DCR) was 93.7% with two patients (0.2%) achieving complete response (CR), the median progression free survival (PFS) was 13.0 months (95% confidence interval [CI], 11.6-14.4 months), and the median overall survival (OS) was 55.0 months (95% CI, 26.3-83.7 months). Subgroup analysis revealed that the DCR in patients harboring single rare or complex mutations of EGFR was significantly lower than in those with del-19 or L858R mutation (P<0.001). Patients with classic mutations (del-19 and/or L858R mutations) demonstrated longer PFS (P<0.001) and OS (P=0.017) than those with uncommon mutations (single rare and/or complex mutations). Furthermore, the patients with single rare mutations had shorter median OS than in those with other mutations. Multivariate Cox regression analysis identified that the type of EGFR mutations was an independent risk factor for PFS (hazard ratio [HR]=0.308, 95% CI, 0.191-0.494, P<0.001) and OS (HR=0.221, 95% CI, 0.101-0.480, P<0.001). The results suggest that the single rare or complex EGFR mutations confer inferior efficacy of EGFR-TKIs treatment to the classic mutations. The prognosis of the single rare EGFR mutations is depressing. EGFR-TKIs may be not a good choice for NSCLC patients with single rare mutations of EGFR. Further studies in these patients with uncommon mutations (especially for the patients with single rare mutations) are needed to determine a better precision treatment.

Apatinib in refractory radiation-induced brain edema: A case report.

RATIONALE: Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has observed to be effective and safe in refractory radiation-induced brain edema, like Avastin did. Till now, there is no case report after apatinib came in the market. PATIENT CONCERNS: Two patients who received brain radiotherapy developed clinical manifestations of brain edema, including dizziness, headache, limb activity disorder, and so on. DIAGNOSES: Two patients were both diagnosed as refractory radiation-induced brain edema. INTERVENTIONS: Two patients received apatinib (500 mg/day) for 2 and 4 weeks. OUTCOMES: Two patients got symptomatic improvements from apatinib in different degrees. Magnetic resonance imaging after apatinib treatments showed that compared with pre-treatment imaging, the perilesional edema reduced dramatically. However, the toxicity of apatinib was controllable and tolerable. LESSONS: Apatinib can obviously relieve the symptoms of refractory radiation-induced brain edema and improve the quality of life, which offers a new method for refractory radiation-induced brain edema in clinical practices. But that still warrants further investigation in the prospective study.

Pneumocystis Pneumonia Infection in a Survivor of Paraquat Intoxication.

Patients who survived recent paraquat intoxication might be treated with glucocorticoid andcyclophosphamide to avoid further lung fi brosis. Such patients might be susceptible to opportunistic infections. Pneumocystis pneumonia (PCP) is an important opportunistic lung infection in hematologic malignancy patients on chemotherapy. We report a patient who recently survived paraquat intoxication and presented with acute respiratory insuffi ciency post glucocorticoid and cyclosporine treatment. A fulminant clinical course, and a clear medical history of immunocompromised state draw physician's attention to the possible opportunistic lung infection. PCP infection was confi rmed by a PCP deoxyribonucleic acid test. The symptoms improved markedly after appropriate antibiotics treatment. This report suggests that clinicians should consider PCP infection in patients who develop secondary pneumonia after paraquat intoxication. PCP treatment as part of empirical antibiotics should be added, especially in such patients presented with rapidly progressive course.

The association of leptin and homocysteine with renal function impairment in a population of Taiwanese adults.

BACKGROUND & AIMS: Higher levels of leptin and homocysteine (Hcy) have been evaluated as risk factors of chronic kidney disease in patients and general population. The aim of this study was to examine gender differences in the associations of leptin and Hcy levels and renal function a representative healthy young population in Taiwan. METHODS: The participants aged ≥18 years who underwent health examinations were included and categorized into three groups by gender-specific tertiles of leptin and Hcy levels. Estimated glomerular filtration rates (eGFR) were estimated according to the modified equation of Modification of Diet in Renal Disease (MDRD). RESULTS: A higher mean Hcy level was found in male subjects than females. Mean values of metabolic syndrome risk factors significantly elevated with increasing leptin levels in both genders. Both male and female subjects with higher plasma Hcy levels were more likely to have a lower eGFR. Plasma Hcy levels were significantly negatively correlated with eGFR in linear regression models adjusted for age and smoking. The associations persisted even after mean arterial pressure and fasting plasma glucose were included for adjustments both genders. Plasma Hcy level was negatively associated eGFR and the association was more profound for females. CONCLUSIONS: Leptin levels did not reveal strong or consistent evidence to support a significant association with eGFR. Hcy had a more decisive effect on renal function impairment than leptin and may be considered a more sensitive biomarker for Taiwanese adults.

Risk factors associated with complications in patients with chemotherapy-induced febrile neutropenia in emergency department.

Febrile neutropenia caused by chemotherapy is a frequent medical emergency associated with severe complications in the emergency department (ED). Timely administration of antibiotics is believed to improve patient outcomes for several infectious diseases such as pneumonia and sepsis but has not been thoroughly evaluated for reducing risk of complications in chemotherapy-induced febrile neutropenia. The aim of this study was to evaluate associations between the risk factors and serious complications in patients presenting to the ED with febrile neutropenia. We reviewed the health information system database to identify a retrospective cohort of patients with febrile neutropenia who visited the ED of a tertiary medical hospital from January to December 2008. Only episodes of febrile neutropenia caused by chemotherapy for underlying cancer were included. Serious complications during hospitalization were defined as unstable hemodynamic status, respiratory distress, altered mental status, newly developed arrhythmia that required intervention, and death during hospitalization. Univariate and multivariate logistic regression analysis was performed to determine potential factors associated with serious complications. We further use decision tree approach to help analyze variables. Among a total of 81 febrile neutropenic episodes in 78 patients, 25 (30.8%) episodes of serious complications were identified. Latency of the first dose of antibiotics, pneumonia and platelet counts ≤ 50,000/mm(3) were identified as independent factors associated with serious complications of febrile neutropenia. Earlier administration of antibiotics is associated with fewer complications in patients presenting to the ED with febrile neutropenia.

Pituitary apoplexy associated with cortisol-induced hyperglycemia and acute delirium.

Pituitary apoplexy indicates pituitary adenoma hemorrhage, which could result in acute pituitary insufficiency and mortality. The typical symptoms are headache, visual disturbance, nausea, vomiting, altered mental status, and panhypopituitarism. However, cortisol-induced hyperglycemia and acute delirium could be an initial presentation of a pituitary adenoma hemorrhage with stormy release of the adrenocorticotrophic hormone. A 28-year-old woman presented with severe vomiting, irritable state, and delusion. She had medical history of irregular menstrual cycles and marked body weight gain after her second childbirth 8 years ago. She was diagnosed of diabetic ketoacidosis 2 days before this visiting at local medical department. On physical examination, Cushing appearance without definite neurological deficit was disclosed. Further blood tests revealed high blood sugar, cortisol, and adrenocorticotrophic hormone levels without evidence of diabetic ketoacidosis. The brain computed tomography and magnetic resonance imaging showed pituitary macroadenoma and pituitary hemorrhage. Cushing disease with pituitary apoplexy was then diagnosed. Conservative management with delayed neurosurgery was applied. The patient became clear with normalized cortisol and blood sugar levels soon after. Follow-up computed tomography scan of the brain revealed no progression of tumor bleeding or mass effect. To our knowledge, pituitary apoplexy associated with cortisol-induced hyperglycemia and acute delirium has never been reported before. This case reminds us of pituitary apoplexy and its rare manifestations.

Acquired hemophilia A associated with therapeutic cupping.

Acquired hemophilia A is defined as the development of factor VIII inhibitors in a nonhemophilic patient. The inhibitors can develop in association with autoimmune disease, allergic drug reactions [1,2], malignancies [2], and pregnancy [3]. It is rare, but frequently complicated by severe bleeding and compartment syndrome [1,4]. Therapeutic cupping is a traditional remedy done by applying heated cup over the back and limbs to cause congestion. This procedure is mostly used by South Asian and Middle Eastern countries. We report a 58-year-old woman who presented with extensive and compressive bruising which led to pending compartment syndrome of her left thigh in 2 days after cupping. The coagulopathy was first considered owing to new-onset severe deep tissue bleeding. Acquired hemophilia A was diagnosed with prolonged activated partial thromboplastin time (83 seconds) and incorrectable mixing plasma test. Quantitative assays revealed reduced level of factor VIII (b0.1%) and the presence of factor VIII inhibitors (20 BU) in the serum. Fresh frozen plasma transfusion, coagulation factor supply, and immunosuppressive therapy with steroid began immediately after diagnosis was made. Her activated partial thromboplastin time was gradually normalized. She was discharged home with improving symptoms and minimized bruises 1 week later. To our knowledge, acquired hemophilia A associated with therapeutic cupping has never been mentioned before in the literature.