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PurposeTo evaluate the efficacy and safety of transdermal electrical stimulation (TdES) using skin electrodes in patients with central retinal artery occlusion (CRAO).MethodsFive eyes of five patients with CRAO underwent TdES (10-ms biphasic pulses, 20 Hz, 30 min) six times at 2-week intervals. Only the affected eye was stimulated with 1.0-mA pulses in all patients. The primary endpoint was the best-corrected logMAR visual acuity. The secondary endpoints were changes in the best-corrected logMAR visual acuity, Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity, mean deviation of the Humphrey field analyzer (HFA) 10-2, and HFA Esterman test score. We also evaluated its safety.ResultsThe logMAR visual acuity at 12 weeks was improved by 0.1 or more in two patients and was maintained in two patients compared to the baseline. No obvious changes in the mean logMAR visual acuity, ETDRS visual acuity, mean deviation, and HFA Esterman score were observed at 12 weeks compared to the baseline. All five enrolled patients completed the study according to the protocol. No treatment-related adverse events were observed during this study.ConclusionIn this study, logMAR visual acuity was slightly improved in two patients, confirming the safety of TdES. Since CRAO has no established treatment method, further research into the effects of TdES treatment in CRAO patients may be beneficial.

BackgroundCytotoxic effects of radiation play an important role in the treatment of head and neck cancer. However, irradiation is known to lead to the migration of various cancer cells, including those of head and neck cancer. Recently, fibroblasts in the cancer microenvironment have been reported to be involved in this mechanism. Nevertheless, the mechanism underlying migration of head and neck cancer cells remains unclear. Herein, we aimed to elucidate this migration mechanism induced by irradiation in terms of the interaction of head and neck cancer cells with fibroblasts.MethodsWe used the head and neck squamous cell carcinoma (HNSCC) cell lines SAS and FaDu as well as fibroblast cell lines. These cells were irradiated and their viability was compared. In fibroblasts, changes in interleukin-6 (IL-6) secretion caused by irradiation were measured by enzyme-linked immunosorbent assay (ELISA). The cell migration ability of cancer cells was evaluated via a migration assay using a semipermeable membrane. HNSCC cells were cocultured with irradiated and nonirradiated fibroblasts, and their migration ability under each condition was compared. We also examined the effect of IL-6 on the migration of HNSCC cells. Furthermore, to investigate the effect of fibroblast-derived IL-6 on the migration ability of HNSCC cells, we conducted a coculture study using IL-6 neutralizing antibody.ResultsIrradiation reduced the survival of HNSCC cells, whereas fibroblasts were resistant to irradiation. Irradiation also increased IL-6 secretion by fibroblasts. Migration of HNSCC cells was enhanced by coculture with fibroblasts and further enhanced by coculture with irradiated fibroblasts. We also confirmed that the migration of HNSCC cells was induced by IL-6. The enhanced migration of cancer cells caused by coculturing with fibroblasts was canceled by the IL-6 neutralizing antibody.ConclusionThese results show that fibroblasts survive irradiation and induce the migration ability of HNSCC cells through increased secretion of IL-6.

BackgroundAlthough current guidelines recommend admission to the intensive/coronary care unit (ICU/CCU) for patients with ST-segment elevation myocardial infarction (MI), routine use of the CCU in uncomplicated patients with acute MI remains controversial. We aimed to evaluate the safety of management in the general ward (GW) of hemodynamically stable patients with acute MI after primary percutaneous coronary intervention (PCI).MethodsUsing a large nationwide administrative database, a cohort of 19426 patients diagnosed with acute MI in 52 hospitals where a CCU was available were retrospectively analyzed. Patients with mechanical cardiac support and Killip classification 4, and those without primary PCI on admission were excluded. A total of 5736 patients were included and divided into the CCU (n = 3488) and GW (n = 2248) groups according to the type of hospitalization room after primary PCI. Propensity score matching was performed, and 1644 pairs were matched. The primary endpoint was in-hospital mortality at 30 days.ResultsThe CCU group had a higher rate of Killip classification 3 and ambulance use than the GW group. There was no significant difference in the incidence of in-hospital mortality within 30 days among the matched subjects. Multivariable Cox proportional hazard model analysis among unmatched patients supported the findings (hazard ratio 1.12, 95% confidence interval 0.66-1.91, p = 0.67).ConclusionsThe use of the GW was not associated with higher in-hospital mortality in hemodynamically stable patients with acute MI after primary PCI. It may be feasible for the selected patients to be directly admitted to the GW after primary PCI.

BACKGROUND:Previous studies have shown that item responses and total scores on depression screening scales follow characteristic distribution patterns in the United States and Japanese general populations. However, the degree to which these findings, especially in terms of item responses, can be generalized to a European population is unknown. Thus, we analyzed the item responses and total score distribution for the Center for Epidemiologic Studies Depression Scale (CES-D) in a representative Irish cohort from a large, recent study-the Irish Longitudinal Study on Ageing (TILDA). METHODS:We used CES-D data from the 2009-2011 TILDA (8504 individuals). Responses for the 16 depressive symptoms included "rarely," "some of the time," "occasionally," and "all of the time." Item response patterns and total score distribution across these 16 depressive symptom items were examined using graphical analyses and exponential regression modeling. RESULTS:Lines for item responses followed the same pattern across the 16 items. These lines were characterized by intersections in the vicinity of a single point between "rarely" and "some of the time" and parallel patterns from "some of the time" to "all of the time" on a log-normal scale. Total scores for the 16 items exhibited an exponential pattern, except for at the lower end of the distribution. CONCLUSIONS:The present findings suggest that item responses and total scores on depression screening scales among the general population follow the same characteristic patterns across populations from multiple nations.

BACKGROUND:Rapid dissemination of information regarding adverse drug reactions is a key aspect for improving pharmacovigilance. There is a possibility that unknown adverse drug reactions will become apparent through post-marketing administration. Currently, although there have been studies evaluating the relationships between a drug and adverse drug reactions using the JADER database which collects reported spontaneous adverse drug reactions, an efficient approach to assess the association between adverse drug reactions of drugs with the same indications as well as the influence of demographics (e.g. gender) has not been proposed. METHODS AND FINDINGS:We utilized the REAC and DEMO tables from the May 2015 version of JADER for patients taking antidepressant drugs (SSRI, SNRI, and NaSSA). We evaluated the associations using association analyses with an apriori algorithm. Support, confidence, lift, and conviction were used as indicators for associations. The highest score in adverse drug reactions for SSRI was obtained for "aspartate aminotransferase increased", "alanine aminotransferase increased", with values of 0.0059, 0.93, 135.5, and 13.9 for support, confidence, lift and conviction, respectively. For SNRI, "international normalized ratio increased", "drug interaction" were observed with 0.0064, 1.00, 71.9, and NA. For NaSSA, "anxiety", "irritability" were observed with 0.0058, 0.80, 49.9, and 4.9. For female taking SSRI, the highest support scores were observed in "twenties", "suicide attempt", whereas "thirties", "neuroleptic malignant syndrome" were observed for male. Second, for SNRI, "eighties", "inappropriate antidiuretic hormone secretion" were observed for female, whereas "interstitial lung disease" and "hepatitis fulminant" were for male. Finally, for NaSSA, "suicidal ideation" was for female, and "rhabdomyolysis" was for male. CONCLUSIONS:Different combinations of adverse drug reactions were noted between the antidepressants. In addition, the reported adverse drug reactions differed by gender. This approach using a large database for examining the associations can improve safety monitoring during the post-marketing phase.

BACKGROUND:In a previous study, we reported that the distribution of total depressive symptoms scores according to the Center for Epidemiologic Studies Depression Scale (CES-D) in a general population is stable throughout middle adulthood and follows an exponential pattern except for at the lowest end of the symptom score. Furthermore, the individual distributions of 16 negative symptom items of the CES-D exhibit a common mathematical pattern. To confirm the reproducibility of these findings, we investigated the distribution of total depressive symptoms scores and 16 negative symptom items in a sample of Japanese employees. METHODS:We analyzed 7624 employees aged 20-59 years who had participated in the Northern Japan Occupational Health Promotion Centers Collaboration Study for Mental Health. Depressive symptoms were assessed using the CES-D. The CES-D contains 20 items, each of which is scored in four grades: "rarely," "some," "much," and "most of the time." The descriptive statistics and frequency curves of the distributions were then compared according to age group. RESULTS:The distribution of total depressive symptoms scores appeared to be stable from 30-59 years. The right tail of the distribution for ages 30-59 years exhibited a linear pattern with a log-normal scale. The distributions of the 16 individual negative symptom items of the CES-D exhibited a common mathematical pattern which displayed different distributions with a boundary at "some." The distributions of the 16 negative symptom items from "some" to "most" followed a linear pattern with a log-normal scale. CONCLUSIONS:The distributions of the total depressive symptoms scores and individual negative symptom items in a Japanese occupational setting show the same patterns as those observed in a general population. These results show that the specific mathematical patterns of the distributions of total depressive symptoms scores and individual negative symptom items can be reproduced in an occupational population.

BACKGROUND:Several studies have shown that total depressive symptom scores in the general population approximate an exponential pattern, except for the lower end of the distribution. The Center for Epidemiologic Studies Depression Scale (CES-D) consists of 20 items, each of which may take on four scores: "rarely," "some," "occasionally," and "most of the time." Recently, we reported that the item responses for 16 negative affect items commonly exhibit exponential patterns, except for the level of "rarely," leading us to hypothesize that the item responses at the level of "rarely" may be related to the non-exponential pattern typical of the lower end of the distribution. To verify this hypothesis, we investigated how the item responses contribute to the distribution of the sum of the item scores. METHODS:Data collected from 21,040 subjects who had completed the CES-D questionnaire as part of a Japanese national survey were analyzed. To assess the item responses of negative affect items, we used a parameter r, which denotes the ratio of "rarely" to "some" in each item response. The distributions of the sum of negative affect items in various combinations were analyzed using log-normal scales and curve fitting. RESULTS:The sum of the item scores approximated an exponential pattern regardless of the combination of items, whereas, at the lower end of the distributions, there was a clear divergence between the actual data and the predicted exponential pattern. At the lower end of the distributions, the sum of the item scores with high values of r exhibited higher scores compared to those predicted from the exponential pattern, whereas the sum of the item scores with low values of r exhibited lower scores compared to those predicted. CONCLUSIONS:The distributional pattern of the sum of the item scores could be predicted from the item responses of such items.

Previous research has reported that the mean of depressive symptoms is stable in the general population through middle adulthood. To understand the stability of depressive symptoms during middle adulthood, we investigated the nature of the distribution of depressive symptoms.We analyzed 24,890 subjects aged 15 to 84 years who participated in the Active Survey of Health and Welfare, Japan. Depressive symptoms were assessed using the Japanese version of the Center for Epidemiologic Studies Depression Scale (CES-D). The descriptive statistics and frequency curves of the distributions were then compared according to age group.The distribution of depressive symptoms was stable through middle adulthood. The right tail which covers clinical depression was more stable than the left tail or peak of the distributions. The right tail of the distribution during middle adulthood exhibited a linear pattern with a log-normal scale.The right tail of the distribution of depressive symptoms is stable and exhibits an exponential pattern during middle adulthood.