Association between insomnia severity and presenteeism among Japanese daytime workers.

Presenteeism is the loss of productivity due to a worker's health problems, despite the worker being present at the workplace. Although the association between presenteeism and insomnia complaints is well known, few studies have examined the association between insomnia severity and presenteeism. This study aimed to explore the association between insomnia severity and presenteeism. This study included 1925 participants (1543 males, 379 females, and three of other genders) in total. The mean age of the participants was 49.94 ± 9.82 years. The inclusion criteria were full-time employment, working 8 hr per day and 5 days per week, and having no night shifts. The insomnia severity was classified based on the Insomnia Severity Index and Athens Insomnia Scale criteria. Logistic regression analysis showed that moderate and severe insomnia severity were associated to a greater magnitude with presenteeism than mild insomnia severity. Severe insomnia severity was associated to a greater magnitude with presenteeism than moderate insomnia severity. In summary, logistic regression analysis showed that increased insomnia severity based on Insomnia Severity Index classification was associated with increased odds of presenteeism, but increased insomnia severity based on Athens Insomnia Scale classification was not fully consistent with increased odds of presenteeism. Because increased insomnia severity is associated with worsening of presenteeism, early detection of and early intervention against insomnia complaints are important for reducing presenteeism. This study was the first to examine the associations between presenteeism and insomnia severity classification of no insomnia, mild, moderate, and severe insomnia severity.

Clinical outcome and prognostic factors in hepatocellular carcinoma patients with bone metastases medicated with zoledronic acid.

AIMS: We retrospectively analyzed the clinical outcome and prognostic parameters in patients with hepatocellular carcinoma (HCC) and bone metastases who had received treatment with zoledronic acid (ZOL). METHODS: Ninety-nine HCC patients with bone metastases who had been treated with ZOL were enrolled in this retrospective cohort study. We analyzed the prognostic factors, including serum N-telopeptide of type I collagen (NTX) levels, as bone metabolism markers. RESULTS: The median overall survival (OS) time was 11.5 months. Child-Pugh grade A (P = 0.004) and intrahepatic tumor stage (IHTS) T0-3 (P = 0.010) correlated significantly with favorable OS. In 46 patients with grade A and T0-3, receiver operating characteristic curve analysis defined 16 nmol BCE/L serum NTX as the cut-off level for median OS. Multivariate analysis identified baseline serum NTX <16 nmol BCE/L (P = 0.045) as the only significant and independent determinant of OS. CONCLUSION: Low baseline serum NTX level correlated with favorable outcome in bone metastatic HCC patients with Child-Pugh grade A and IHTS T0-3 treated with ZOL.

Complete response to short-term sorafenib treatment alone for hepatocellular carcinoma with bone, lymph node, and peritoneum metastases.

We report a 60-year-old male patient who developed extrahepatic metastases in bone, peritoneum, and lymph nodes (confirmed by computed tomography and positron emission tomography-computed tomography) after hepatectomy for hepatocellular carcinoma. He was treated with sorafenib (800 mg/day) but developed grade 3 hand-foot syndrome. He continued to be treated with sorafenib but at a lower dose (400 mg/week). The response to sorafenib therapy was graded as complete response at 6 months by the Response Evaluation Criteria in Solid Tumors. Sorafenib was continued for 8 months and the patient remained in complete response for 11 months. Further reporting of similar cases should help design treatment strategies and evaluate predictors of the response to sorafenib therapy.

Improvement of renal dysfunction in a patient with hepatitis C virus-related liver cirrhosis by daclatasvir and asunaprevir combination therapy: A case report.

Recently, treatments for chronic hepatitis C virus (HCV) infection have been drastically improved by the development of direct-acting antiviral agents. In September 2014, dual oral therapy using daclatasvir (DCV) and asunaprevir (ASV) was approved for the treatment of chronic HCV infection in Japan. We treated a patient with HCV-related liver cirrhosis with severe leg edema due to chronic renal dysfunction using this dual oral therapy. Although serum alanine aminotransferase increased rapidly during the first week of treatment, the antiviral therapy was able to continue, and liver function recovered spontaneously. After 1 month of treatment, serum HCV RNA became continuously undetectable, and serum albumin level gradually increased. Throughout the therapy, serum creatinine level nearly normalized, and leg edema gradually improved. These improvements continued after the combination therapy was completed. HCV RNA remained undetectable following the end of therapy, and sustained virological response at 12 weeks was achieved. It has been reported that chronic HCV infection is associated with renal dysfunction and that HCV eradication can improve it. DCV and ASV combination therapy is safe for patients who have renal dysfunction and may be a suitable therapy for chronic hepatitis C patients with renal dysfunction.

Development of hepatocellular carcinoma in patients with hepatitis C virus infection who achieved sustained virological response following interferon therapy: A large-scale, long-term cohort study.

BACKGROUND: We assessed the risk factors for the development of hepatocellular carcinoma (HCC) following successful eradication of hepatitis C virus (HCV) with interferon (IFN) therapy in a long-term, large-scale cohort study. METHODS: We reviewed 1094 consecutive patients with HCV who achieved sustained virological response (SVR) following IFN therapy between January 1995 and September 2013. RESULTS: During the observation period (median 50 months: range 13-224), 36 (3%) of 1094 patients developed HCC after SVR. The median period from SVR to diagnosis of HCC was 37 months (range 17-141), and the cumulative rates of HCC at 5, 10, and 15 years were 4%, 6%, and 12%, respectively. Multivariate analysis identified old age (≥60 years, HR, 3.1: 95%CI, 1.3-6.6: P = 0.009), male sex (HR, 12.0: 95%CI, 2.8-50.0: P < 0.0001), advanced fibrosis stage (F3/4, HR, 3.2: 95%CI, 1.6-7.2: P < 0.0001), and alpha-fetoprotein ≥10 ng/mL at 1 year after SVR (HR, 7.8: 95%CI, 2.9-16.8: P < 0.0001) as significant and independent risk factors for post-SVR HCC. CONCLUSIONS: Older age and male sex (host factors), advanced fibrosis stage (pre-IFN treatment factor), and higher alpha-fetoprotein values (post-treatment factor) were significantly associated with HCC development after HCV eradication.

Preoperative Fluorine 18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Prediction of Microvascular Invasion in Small Hepatocellular Carcinoma.

OBJECTIVES: This study aimed to assess the value of preoperative fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET-CT) for predicting microvascular invasion (MVI) in small hepatocellular carcinoma (HCC). METHODS: We retrospectively examined 60 patients who received F-FDG PET-CT prior to hepatic resection for small HCC (≤30 mm) with subsequent MVI confirmation by histopathology. The associations between PET-positive status and tumor factors were assessed. Furthermore, independent predictors for MVI and diagnostic utility of each MVI predictor were assessed. RESULTS: Multivariate analysis revealed the presence of MVI as an independent predictor of PET-positive status (P = 0.023). Maximum standardized uptake value (SUVmax) of 3.2 or greater (P = 0.017) and lens culinaris agglutinin a-reactive α-fetoprotein (AFP-L3) 19% or greater (P = 0.010) were independent predictors of MVI. Areas under the receiver operating characteristic curves for SUVmax of 3.2 or greater, AFP-L3 19% or greater, and both factors combined for predicting MVI were 0.712 (0.493-0.932), 0.755 (0.563-0.947), and 0.856 (0.721-0.991), respectively. The sensitivity and specificity for predicting MVI were 77.8% and 74.5% for SUVmax of 3.2 or greater, 66.7% and 84.3% for AFP-L3 19% or greater, and 88.9% and 82.4% for the combination. CONCLUSIONS: F-FDG PET-CT and AFP-L3 may be useful for predicting MVI in small HCC, and the combination of the 2 factors provided reliable assessment for selection of suitable hepatic resection and liver transplantation candidates.

Assessment of Outcome of Hepatic Arterial Infusion Chemotherapy in Patients with Advanced Hepatocellular Carcinoma by the Combination of RECIST and Tumor Markers.

To assess the outcome of stable disease (SD) patients with advanced hepatocellular carcinoma (HCC) by tumor markers after the first course of hepatic arterial infusion chemotherapy (HAIC). The study subjects were 156 HCC patients treated with HAIC and classified as Child Pugh A, with no extrahepatic metastasis, and no history of sorafenib treatment. In the study and validation cohorts, the AFP and DCP ratios of patients who were considered SD to the first course of HAIC were analyzed by AUROC for a prediction of response to the second course of HAIC. The imaging response to the first course of HAIC was classified as partial response (PR), SD and progressive disease (PD) in 29 (18.8%), 80 (51.9%), and 44 (28.6%) patients respectively. For SD patients, the a-fetoprotein (AFP) and des-y-carboxy prothrombin (DCP) ratios of patients who were considered SD to the first course of HAIC were analyzed by the receiver operating characteristic curve for prediction of response to the second course of HAIC in the study cohorts. The area under the curve of AFP ratio was 0.743. The area under the curve of DCP ratio was 0.695. The cut-off values of AFP and DCP ratios were 1.3 and 1.0, respectively. In the validation cohort, the accuracy of the prediction of response in this validation cohort (71.4%) showed no significant difference compared to that in the study cohort (72.4%) (p = 1.0). The results suggested that patients with a high tumor marker ratio could be switched to alternative therapeutic regimens despite the SD response to HAIC.

Network analysis to estimate central insomnia symptoms among daytime workers at-risk for insomnia.

Although insomnia complaints are associated with mental health problems and reduced work productivity, the central insomnia symptoms in workers at-risk for insomnia remain unclear. This study aimed to identify the central insomnia symptoms among daytime workers at risk for insomnia. The participants were 881 Japanese daytime workers at-risk for insomnia with a mean age of 49.33 ± 9.92 years. At-risk for insomnia was defined as an Athens Insomnia Scale score of six or higher. The Athens Insomnia Scale was used as a screening for at-risk insomnia because it has higher sensitivity and specificity than other insomnia screening scales. The Insomnia Severity Index is recommended as a mechanism of insomnia and an outcome measure; therefore, a network analysis was conducted with the seven items of the Insomnia Severity Index. The important variables in the connections between insomnia symptoms were estimated from centrality indices, which were interpretable only for strength. The strength value results suggest that difficulty staying asleep and worry about sleep problems were the central insomnia symptoms. The connections were stronger for difficulty staying asleep and problem waking up too early, difficulty staying asleep and difficulty falling asleep, and interference with daytime functions and noticeable to others. Worry about sleep problems was strongly associated with variables other than nocturnal insomnia symptoms. Therefore, difficulty staying asleep and worry about sleep problems are important variables in daytime workers at-risk for insomnia and are key points for improvement or exacerbation of insomnia symptoms.

Impact of sleep debt, social jetlag, and insomnia symptoms on presenteeism and psychological distress of workers in Japan: a cross-sectional study.

BACKGROUND: Presenteeism is an indicator of productivity loss and the risk of absence from work due to mental health problems. The purpose of this study was to determine the impact of sleep debt, social jetlag, and insomnia symptoms on presenteeism and psychological distress. METHODS: The participants were 351 Japanese workers (271 males, 79 females, and one of other gender, with a mean age of 49 ± 9.49 years). The eligibility criteria for this study were full-time employment, working eight hours per day, five days per week, and no night shifts. The participants answered questionnaires measuring sleep debt, social jetlag, insomnia symptoms, presenteeism, and psychological distress. RESULTS: Insomnia symptoms had the greatest impact on presenteeism and psychological distress when compared with sleep debt and social jetlag (adjusted odds ratio (OR) = 5.61, 95% confidence interval (CI) = 2.88-10.91; adjusted OR = 7.29, 95%CI = 3.06-17.35). Sleep debt had a greater impact on presenteeism and psychological distress than did social jetlag (adjusted OR = 1.61, 95%CI = 1.14-2.27; adjusted OR = 1.68, 95%CI = 1.11-2.54), which had no impact on these variables (adjusted OR = 1.04, 95%CI = 0.91-1.20; adjusted OR = 0.96, 95%CI = 0.76-1.22). CONCLUSIONS: The findings of this study indicated that insomnia symptoms had a more significant impact on presenteeism and psychological distress than social jetlag and sleep debt. Although sleep debt might have an independent impact on presenteeism and psychological distress, social jetlag did not.

A systematic review of the effect of sleep interventions on presenteeism.

BACKGROUND: Sleep problems interfere with work performance. Decreased work productivity due to health problems is defined as presenteeism. Although empirical data on the improvement of presenteeism by sleep interventions have been published, a systematic review elucidating whether there is a difference in the improvement of presenteeism across various types of sleep interventions has not yet been published. This systematic review of studies aimed to clarify which sleep interventions are more likely to be effective in improving presenteeism. METHODS: The electronic databases PubMed, PsycINFO, and MEDLINE were used to perform a literature search (the start and end search dates were October 20, 2019, and March 11, 2020, respectively). A combination of terms such as "employee*," "sleep," "insomnia," and "presenteeism" was used for the search. Both randomized and non-randomized control trials were included in this systematic review. RESULTS: Six types of sleep interventions were identified, including cognitive behavioral therapy for insomnia (CBT-I), sleep hygiene education, yoga, mindfulness, weight loss program, and changing the color temperature of fluorescent lights in the workplace. Only CBT-I improved both sleep problems and presenteeism compared with a control group. The results of this review also show that there is heterogeneity in the measurement of presenteeism. CONCLUSIONS: The results of this systematic review suggested that CBT-I could be adapted for workers with sleep problems and presenteeism. We discussed whether CBT-I improved both sleep problems and presenteeism compared with other interventions. In addition, methods for measuring presenteeism in future research are proposed.

Advanced glycation end products (AGE) and their receptor (RAGE) in the brain of patients with Creutzfeldt-Jakob disease with prion plaques.

The objective of this study was to assess the pathological role of advanced glycation end products (AGE) and the receptor for AGE (RAGE) in Creutzfeldt-Jakob disease (CJD). We immunohistochemically investigated the occipital lobe of three patients with CJD containing with prion protein (PrP) plaques using anti-AGE and RAGE antibodies. Many PrP-positive plaques were observed in these patients, and the PrP-positive prion plaques also showed immunoreactivity for the anti-AGE antibody. Furthermore, many astrocytes contained-PrP positive granules, and the same astrocytes also contained many AGE- and RAGE-immunopositive granules. The staining pattern of these granules showed good concordance with that of PrP. These findings suggest that there may be a RAGE-mediated PrP degradation pathway in CJD as is the case for beta-amyloid protein in Alzheimer's disease.