Pre-emptive ice pack cryotherapy for reducing pain caused by long-acting deltoid injectable antipsychotic treatment: A single-center open-label study.

PURPOSE: This empirical study aims to investigate the efficacy of pre-emptive cryotherapy in reducing pain that is caused by the deltoid intramuscular (IM) injection of long-acting injectable (LAI) antipsychotics in clinical settings. PATIENTS AND METHODS: This study included 29 outpatients receiving LAI antipsychotic treatment. The evaluations of pain during (1) the usual procedure (control), (2) pre-emptive use of ice pack cryotherapy (pre-cooling), and (3) pre-emptive use of a room-temperature ice pack (pre-touching) were conducted using a numerical rating scale (NRS) for comparison. All patients were administered with LAI antipsychotics via deltoid IM. Furthermore, the results of the Positive and Negative Symptom Scale (PANSS), clinical global impressions (CGI) scale, and Global Assessment of Functioning (GAF) scale that were administered during the control procedure were evaluated. RESULTS: The median NRS pain scores during the IM injection of LAI antipsychotics were 4.0 (3.0-5.0), 2.0 (1.0-3.0), and 3.0 (2.5-6.0) for the control, pre-cooling, and pre-touching conditions, indicating a significant difference (p = 6.0 × 10-6). The NRS pain scores for the pre-cooling condition were significantly lower than those for the control and pre-touching conditions (p = 2.5 × 10-5 and 6.7 × 10-5, respectively). No significant correlation was observed between the NRS pain scores for the control condition and the PANSS, CGI scale, or GAF scale scores. Furthermore, no adverse events were recorded during the study period. CONCLUSION: Pain during the deltoid IM injection of LAI antipsychotics was found to be reduced by pre-emptive skin cooling. To date, this is the first study to confirm the effectiveness of pre-emptive cryotherapy for relieving such pain in clinical situations.

Potential of TAK-593 Ophthalmic Emulsion for the Treatment of Age-Related Macular Degeneration.

Intravitreal injection therapy of anti-vascular endothelial growth factor (VEGF) antibody or steroids is the mainstream for patients with age-related macular degeneration (AMD). However, since intravitreal injection is invasive administration, side effects such as endophthalmitis are major problems. In this study, we selected eye drops as a non-invasive treatment method, and aimed to develop eye drops that can deliver TAK-593 (VEGF receptor tyrosine kinase inhibitor) to the posterior segment of the eye. Since TAK-593 is a poorly water-soluble drug, the TAK-593 emulsion was formulated. The solubility of TAK-593 in various oils was measured, and the oil used for the emulsion was selected. Furthermore, viscosity enhancers were added to the emulsion in order to improve the drug delivery into the eye. As viscosity enhancer, xanthan gum was selected based on the properties and the viscosity of the emulsion. The delivery of TAK-593 to the posterior eye was increased by the formulation concentration and the addition of viscosity enhancers. In the laser-induced choroidal neovascularization model, TAK-593 emulsion eye drops showed the same angiogenesis-suppression efficacy as anti-VEGF antibody intravitreal injection. From these results, it was revealed that TAK-593 with an effective drug concentration can be delivered to the posterior eye by non-invasive eye drop administration.

Pathophysiology, prognosis and treatment of tardive dyskinesia.

Tardive dyskinesia (TD), a movement disorder associated with antipsychotics, most frequently affects the lower face and jaw muscles, but can also affect walking, breathing and use of the hands and limbs. Knowledge of TD among physicians may be limited, and the pathophysiology of TD is poorly understood. We conducted this review to summarise the current knowledge surrounding the pathophysiology of TD and present recommendations for prevention and treatment based on a literature search and roundtable discussion attended by psychiatrists in Japan. It has been suggested that dopamine hypersensitivity, damaged gamma-aminobutyric acidergic neurons and/or increased production of reactive oxygen species may contribute to development of TD. Symptoms can profoundly affect everyday life; patients who develop TD have poorer prognoses, worse health-related quality of life, greater social withdrawal and higher mortality than patients without TD. Traditional treatment options include dietary supplements, although evidence for their effectiveness is low. Among pharmaceutical interventions, there is moderate evidence that switching to the second-generation antipsychotic clozapine, which has a lower affinity for dopamine D2 receptors than other antipsychotics, may improve symptoms. Vesicular monoamine transporter 2 (VMAT-2) inhibitors, which oppose the increased dopaminergic activity associated with prolonged antipsychotic use by interfering with dopamine uptake and storage, have the strongest evidence for efficacy. VMAT-2 inhibitors are approved in the United States for the treatment of TD, and the first VMAT-2 inhibitor was approved in Japan for this indication in March 2022. Most guidelines recommend treating TD by first reducing the dose of antipsychotics or switching to clozapine or other second-generation antipsychotics, which have a lower association with TD than first-generation antipsychotics. We recommend focusing on prevention and monitoring for TD when prescribing antipsychotics, given that TD is often irreversible. Physicians should treat with antipsychotics only when necessary and at the lowest effective dose, and frequently monitor for TD symptoms. Plain Language Summary: Plain Language Summary (In Japanese). Visual Summary: Visual Summary (In Japanese).

Long-lasting leukocytosis in patients with schizophrenia treated with clozapine after electroconvulsive therapy : ECT stabilizes white blood cell count.

INTRODUCTION: The present study was conducted to investigate the possible hematologic impact of long-term electroconvulsive therapy (ECT) in patients with drug-resistant schizophrenia and receiving clozapine therapy. SUBJECTS AND METHODS: In this retrospective study, clinical charts of 57 hospitalized patients with schizophrenia who required clozapine therapy because of active psychotic symptoms resistant to other antipsychotics were examined. For 18 who underwent ECT, the first assessment was conducted at the end of that therapy (average two months after start, 7.68 sessions) and the second two months later. As for the 39 patients who did not undergo ECT, the first and second assessment points were at two and four months, respectively, after a randomly chosen time point. RESULTS: Multiple regression analysis revealed that modified ECT (m-ECT) (ß = 0.346, p = 0.005), gender (males showed greater increase) (ß = 0.273, p = 0.023), and disease duration (longer associated with greater increase) (ß = 0.258, p = 0.033) were correlated with a change in white blood cell (WBC) count (ΔR2 = 0.277, p < 0.001) at the first assessment point. At the second assessment point, multiple regression analysis showed that m-ECT (ß = 0.262, p = 0.039), gender (males showed greater increase) (ß = 0.264, p = 0.036), and disease duration (longer associated with greater increase) (ß = 0.234, p = 0.068) were again correlated with changed WBC count (ΔR2 = 0.203, p < 0.007). DISCUSSION: An increase in leukocytes may have a protective influence against the adverse myelosuppressive effects of clozapine. However, a simple mobilization of leukocytes from bone marrow to peripheral circulation may not enhance the immune system, leading to only a masking of the effects of a potential immuno-insufficient state in the treated patient. In either case, should leukocytosis be induced and then remain for an extended period, hematologists, as well as psychiatrists involved in electroconvulsive intervention for clozapine-treated patients, must keep this factor in mind.

Current perspectives on the epidemiology and burden of tardive dyskinesia: a focused review of the clinical situation in Japan.

Tardive dyskinesia (TD) is a movement disorder that can develop with the use of dopamine receptor-blocking agents and is most commonly caused by antipsychotics. The use of antipsychotics is expanding, which may lead to an increased number of patients experiencing TD. To summarise the current knowledge of the epidemiology and risk factors for TD in Japan, we reviewed articles related to the current state of knowledge around TD identified through a PubMed search, and held a roundtable discussion of experts in Japan on 9 September 2021 to form the basis of the opinion presented within this review. The true prevalence of TD among patients treated with antipsychotics is not well characterised; it is reported to be between 15% and 50% globally and between 6.5% and 7.7% in Japan. Potential barriers to timely treatment of TD include the stigma surrounding mental health issues and the lack of data regarding TD in Asian patients. This review summarises the current knowledge of the epidemiology, challenges to TD diagnosis and risk factors for TD in Japan. Recent strategies for symptom monitoring and early diagnosis, as well as consensus recommendations are included. Achieving a high level of awareness of TD among physicians who treat patients with psychiatric disorders is of great importance and physicians should ensure that patients with psychiatric disorders receiving antipsychotics are proactively monitored for signs of TD. Plain Language Summary: Plain Language Summary (In Japanese). Visual Summary: Visual Summary (In Japanese).

Neuroepithelial cell competition triggers loss of cellular juvenescence.

Cell competition is a cell-cell interaction mechanism which maintains tissue homeostasis through selective elimination of unfit cells. During early brain development, cells are eliminated through apoptosis. How cells are selected to undergo elimination remains unclear. Here we aimed to identify a role for cell competition in the elimination of suboptimal cells using an in vitro neuroepithelial model. Cell competition was observed when neural progenitor HypoE-N1 cells expressing RASV12 were surrounded by normal cells in the co-culture. The elimination through apoptosis was observed by cellular changes of RASV12 cells with rounding/fragmented morphology, by SYTOX blue-positivity, and by expression of apoptotic markers active caspase-3 and cleaved PARP. In this model, expression of juvenility-associated genes Srsf7 and Ezh2 were suppressed under cell-competitive conditions. Srsf7 depletion led to loss of cellular juvenescence characterized by suppression of Ezh2, cell growth impairment and enhancement of senescence-associated proteins. The cell bodies of eliminated cells were engulfed by the surrounding cells through phagocytosis. Our data indicates that neuroepithelial cell competition may have an important role for maintaining homeostasis in the neuroepithelium by eliminating suboptimal cells through loss of cellular juvenescence.

Geolocation data of irrigation network in water user association's operation area under community-based and provider-based network governance.

Massive irrigation development has influenced the way farmers govern water user associations (WUAs) in Klambu Wilalung Irrigation District in Central Java, Indonesia. Recently, farmers adopt community-based (swakelola) and provider-based (lelang) network governance to manage the WUAs. The physical conditions of the irrigation network have become the primary driver of WUA's governance selection. This article provides geolocation data of irrigation network in the operation area of WUAs under community-based and provider-based network governance. The irrigation network consisted of two components, irrigation canal, and structure. Irrigation canal divided into the primary and secondary canal. The data cover GPS Tracks coordinates for 75 secondary canals and seven primary canals. Meanwhile, irrigation structures were grouped into main and support structures and consists of 12 types of structure. The data covers the GPS waypoint coordinates for 194 irrigation structures. The data also provide basic information of 34 WUAs applying community-based (11 WUAs) and provider-based (23 WUAs) network governance. WUAs basic information obtained from a survey conducted in 2016 and covers information on the type of governance, number of board, number of member farmers, size of operation area, and administrative location of each WUAs. Finally, the data is useful in planning research aimed to explain the role of irrigation infrastructure in shaping WUAs governance. Also, the information is crucial to planning a field survey in the area of the Klambu Wilalung Irrigation District in Central Java.

Risk Factors for Skin Toxicities Associated with Bendamustine-Based Chemotherapy in Patients with Non-Hodgkin Lymphoma.

Bendamustine plays an especially important role as a treatment for non-Hodgkin lymphoma (NHL). However, patients administered bendamustine alone or in combination with rituximab (BR) may experience drug-associated skin toxicities that can profoundly impact their health-related QOL through both physical discomfort and psychological distress. Moreover, worsening skin symptoms may lead to dose reduction or termination in the management of cancer chemotherapy. We retrospectively investigated patient backgrounds and pretreatment characteristics from medical records of NHL patients treated with bendamustine alone or BR therapy and identified predictive factors for skin toxicities at the start of chemotherapy. Patients were eligible for the study if they were 20 years older, diagnosed with NHL, and received bendamustine alone or BR therapy at the Department of Hematology, Kobe City Medical Center General Hospital, between April 1, 2011, and March 31, 2018. This study included 95 patients with newly diagnosed or refractory or relapsed NHL. Multivariate stepwise logistic regression analysis with backward selection revealed that baseline non-prior chemotherapy (odds ratio (OR), 15.72; 95% confidence interval (CI), 4.24-83.13, p < 0.001) was a significant factor influencing the occurrence of skin toxicity. Our results demonstrated that non-prior chemotherapy was a significant risk factor for skin toxicities in patients with NHL receiving bendamustine alone or BR therapy. No patient experience serious side effects of grade 3 or higher and that bendamustine is very useful as a first-line treatment.

Risk Factors for Febrile Neutropenia Induced by Docetaxel Chemotherapy in Patients with Non-small Cell Lung Cancer.

We retrospectively obtained data of patient background and pretreatment characteristics from medical records and identified the predictive factors of febrile neutropenia (FN) in patients with non-small cell lung cancer (NSCLC) treated with docetaxel alone or in combination with the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab. Patients were eligible for inclusion in the study if they were 20 years or older, diagnosed with NSCLC, and received docetaxel monotherapy alone or in combination with bevacizumab at the Department of Respiratory Medicine, Kobe City Medical Center General Hospital, between July 1, 2011, and March 31, 2018. Eighty-one patients with recurrent or advanced NSCLC were included. Multivariate stepwise logistic regression analysis with backward selection revealed that lower baseline Eastern Cooperative Oncology Group performance status (ECOG-PS) scores of 1 and 2 (odds ratio (OR), 5.098; 95% confidence interval (CI), 1.045-24.879, p = 0.021) and baseline platelet count below 18.8 × 104/µL (OR, 3.861; 95% CI, 1.211-12.311, p = 0.022) were significant factors influencing the FN occurrence rate. Our results demonstrated that ECOG-PS 1-2 and lower baseline platelet count were significant risk factors of FN in patients with NSCLC receiving docetaxel-based chemotherapy. Moreover, the combination of anti-VEGF antibodies and docetaxel might be associated with increased FN frequency. Despite the limitations of this study including its retrospective design, single-center site, and small sample size, baseline ECOG-PS score and platelet count may be regarded as important indices to identify patients for prophylactic granulocyte-colony stimulating factor (G-CSF) treatment before docetaxel-based chemotherapy.

Evaluation of adverse events focusing on infection associated with infliximab originator and biosimilar using a spontaneous reporting system database.

BACKGROUND: Infliximab (IFX) has changed the management of many life-threatening immune-mediated diseases. The high cost of IFX and its patent expiry have led to pharmaceutical companies developing a biosimilar; however, its safety profile remains unknown in the real world. The purpose of this study was to clarify the adverse events associated with IFX originator and its biosimilar using the Japanese Adverse Drug Event Report (JADER) database. METHODS: Adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency between the third quarter of 2014 and the fourth quarter of 2018. We calculated the reporting odds ratio and 95% confidence interval for each adverse event. RESULTS: We obtained 2771 reports of adverse events associated with IFX originator and 402 reports with IFX biosimilar. Signals were detected for pneumonia, interstitial lung disease, tuberculosis, and sepsis with both IFX originator and its biosimilar, whereas there was no signal for infection with the biosimilar. CONCLUSIONS: The strength of the association between IFX originator and its biosimilar with adverse events is partly different, but reports were quite limited for the biosimilar compared with originator. It is recommended that research be continued in order to accumulate a wide variety of information, and that newly reported data be placed in the multifaceted viewpoints for improvement of care levels.

Evaluation of medication-related osteonecrosis of the jaw using the Japanese Adverse Drug Event Report database.

BACKGROUND: Bisphosphonates (BPs) and denosumab are widely used to treat osteoporosis and complications associated with bone metastases. However, medication-related osteonecrosis of the jaw (MRONJ) is a serious problem. OBJECTIVE: The objective of this study was to evaluate the frequency, outcome, and characteristics of patients with drug-induced MRONJ. METHODS: Retrospective pharmacovigilance disproportionality analysis was conducted using the Japanese Adverse Drug Event Report (JADER) database from the Pharmaceuticals and Medical Devices Agency. Adverse event reports submitted to JADER between 2004 and 2017 were analyzed, and the reporting odds ratio (ROR) was calculated. RESULTS: Among the BPs that cause MRONJ, zoledronate was the most common; therefore, we compared the characteristics of cases of MRONJ induced by zoledronate with those induced by denosumab. Among the 3,875 (68.1% women) cases of MRONJ, zoledronate-related MRONJ accounted for 1,283 (56.0% women) and denosumab-related MRONJ accounted for 322 (55.3% women). MRONJ was more frequent after 70 years of age regardless of the use of either zoledronate or denosumab; onset occurred after 1 year from the denosumab treatment, but it is unknown when onset occurred after zoledronate treatment. The outcomes for MRONJ were poor, with 406 reports on zoledronate (31.6%) and 152 reports on denosumab (47.2%) demonstrating nonrecovery. Zoledronate (ROR: 319.3, 95% CI: 296.0-344.4) had the highest ROR among BP agents. Denosumab had a high ROR (ROR: 155.2, 95% CI: 136.5-176.3). Zoledronate and denosumab were used in similar patient backgrounds, and their use resulted in a similar frequency of MRONJ. CONCLUSION: The findings of this comprehensive evaluation of MRONJ using the JADER database will be helpful for prescribing medications to elderly patients.

Drug-induced tubulointerstitial nephritis in a retrospective study using spontaneous reporting system database.

INTRODUCTION: Tubulointerstitial nephritis (TIN) is a problem in clinical settings because drug therapy is the cause in most cases. Patients often present with nonspecific symptoms, which can lead to delays in the diagnosis and treatment of the disease. The purpose of this study was to clarify the rank-order of the association of TIN with the causative drugs using a spontaneous reporting system database. MATERIALS AND METHODS: Data were extracted from the Japanese Adverse Drug Event Report database of the Pharmaceuticals and Medical Devices Agency (Japan). Based on 5,195,890 reports of all adverse reactions, we obtained 3,088 reports of TIN caused by all drugs and calculated the reporting odds ratio (ROR) and 95% CI for TIN. RESULTS: The 5 drugs with the highest RORs were gliclazide (ROR, 30.5; 95% CI, 17.4-53.2), tosufloxacin tosilate hydrate (ROR, 29.5; 95% CI, 21.3-41.0), piperacillin-tazobactam (ROR, 24.3; 95% CI, 19.4-30.5), cefteram pivoxil (ROR, 23.5; 95% CI, 12.5-44.2), and mefenamic acid (ROR, 22.5; 95% CI, 13.4-37.7). No sex-related difference was observed in drug-induced TIN. Most of the reports about TIN onset following the administration of culprit drugs were recorded within 12 weeks. CONCLUSION: Based on the results, a comprehensive study using a pharmacovigilance database enabled us to identify the dugs that most frequently induced TIN, so these drugs should be used carefully in clinical practice to avoid TIN.

Differential profiles of adverse events associated with mycophenolate mofetil between adult and pediatric renal transplant patients.

OBJECTIVE: Immunosuppressive regimens after renal transplantation usually include a combination of calcineurin inhibitors, corticosteroids, and a proliferation inhibitor, either azathioprine or mycophenolate mofetil (MMF), to prevent rejection and maintain graft function. MMF has a stronger immunosuppressive effect than does azathioprine. This study aimed to examine MMF-associated adverse events in renal transplant patients. METHODS: Retrospective pharmacovigilance disproportionality analysis was conducted using the Japanese Adverse Drug Event Report database. RESULTS: A total of 11,594 adverse drug events were reported in renal transplant patients; 10,272 (88.6%) involved adults and 1322 (11.4%) involved children. In adult patients, the most frequent adverse events induced by MMF were cytomegalovirus infection (272 reports), urinary tract infection (69 reports), and polyomavirus-associated nephropathy (61 reports). Among adverse events, the highest reporting odds ratio (ROR) was found for cytomegalovirus infection (ROR, 1.58; 95% confidence interval, 1.36-1.83). In pediatric patients, the rank order for MMF-associated adverse events was cytomegalovirus infection (27 reports), bronchitis (23 reports), and cytomegalovirus viremia (19 reports), but these adverse events were not detected as a signal. CONCLUSION: Our results show the safety profile of MMF in pediatric renal transplant patients. These findings can be used to update information used for prescriptions for pediatric patients.

Changes in content of triterpenoids and polysaccharides in Ganoderma lingzhi at different growth stages.

Ganoderma lingzhi is a traditional medicinal mushroom, and its extract contains many bioactive compounds. Triterpenoids and polysaccharides are the primary bioactive components that contribute to its medicinal properties. In this study, we quantified 18 triterpenoids, total triterpenoid content and total polysaccharide content in the ethanol and water extracts of G. lingzhi at different growth stages. Triterpenoids were quantified by liquid chromatograph-tandem mass spectrometry in the multiple-reaction-monitoring mode. Total triterpenoid and total polysaccharide content were determined by colorimetric analysis. The results indicated that the fruit bodies at an early growth stage had a higher content of ganoderic acid A, C2, I and LM2, as well as of ganoderenic acid C and D, than those at a later growth stage. In contrast, ganoderic acid K, TN and T-Q contents were higher in mature fruit bodies (maturation stage). The highest total triterpenoid and total polysaccharide contents were found in fruit bodies before maturity (stipe elongation stage or early stage of pileus formation). Our results provide information which will contribute to the establishment of an efficient cultivation system for G. lingzhi with a higher content of triterpenoids.

Productivity loss of caregivers of schizophrenia patients: a cross-sectional survey in Japan.

BACKGROUND: When a family member is diagnosed with schizophrenia, it causes stress to the caregiver that can eventually result in missed work days and lower work performance. AIM: This study aims at revealing productivity costs for caregivers of schizophrenia patients in Japan. METHOD: A cross-sectional survey of caregivers was conducted and resulted in 171 respondents. The assessment of work productivity included calculating the costs of absenteeism, presenteeism and total productivity costs. This was accomplished using the "Work Productivity and Activity Impairment Questionnaire" (WPAI). RESULTS: A relative majority of caregivers in the sample provided care for their spouse (47%), 18% cared for their brother or sister and 16% provided care for their child. Per capita productivity costs totaled JPY 2.42 million, with JPY 2.36 million (97%) of that amount being due to presenteeism. CONCLUSIONS: The burden on caregivers is substantial enough to warrant structured support programs aimed at maintaining careers' physical and mental health, helping them provide more effective care to schizophrenia patients and eventually increase productivity at work.

Pharmaceutical properties of a low-substituted hydroxypropyl cellulose (L-HPC) hydrogel as a novel external dressing.

Controlling the moisture balance between exudates and their transpiration from the surface of wounded skin is important for healing. Low-substituted hydroxypropyl cellulose (L-HPC) hydrogel sheets (HGSs) possessing high water retention and water vapor transmission properties were prepared by neutralizing the highly viscous alkaline liquid of 7-10% L-HPC. Glycerol-impregnated L-HPC hydrogel sheets (L-HPC G-HGSs) were obtained by exchanging aqueous liquid in L-HPC HGSs. The physical characteristics required for wound dressings, i.e., mechanical strength, adhesive strength, and water retention properties, as well as the water vapor transmission (WVT) properties of L-HPC HGSs and L-HPC G-HGSs were evaluated. The mechanical strengths of L-HPC HGSs were enhanced with increases in the L-HPC content. The impregnation of glycerol in L-HPC HGSs yielded a significantly elasticated sheet. The adhesive strengths of L-HPC HGSs were significantly lower than those of commercial medical dressings. Water retention in L-HPC HGSs after being stored for 2h at 37°C was approximately 50%. The WVT rate of 7% L-HPC HGS was approximately 40g/m(2)/h, which was markedly higher than that of silicone gel type medical dressings. In conclusion, L-HPC HGSs are promising dressings that maintain an adequate moisture balance by transpiring excessive wound exudates with less damage to the healing wound.

Biological activities and phytochemical profiles of extracts from different parts of bamboo (Phyllostachys pubescens).

Besides being a useful building material, bamboo also is a potential source of bioactive substances. Although some studies have been performed to examine its use in terms of the biological activity, only certain parts of bamboo, especially the leaves or shoots, have been studied. Comprehensive and comparative studies among different parts of bamboo would contribute to a better understanding and application of this knowledge. In this study, the biological activities of ethanol and water extracts from the leaves, branches, outer culm, inner culm, knots, rhizomes and roots of Phyllostachys pubescens, the major species of bamboo in Japan, were comparatively evaluated. The phytochemical profiles of these extracts were tentatively determined by liquid chromatography-mass spectrometry (LC-MS) analysis. The results showed that extracts from different parts of bamboo had different chemical compositions and different antioxidative, antibacterial and antiallergic activities, as well as on on melanin biosynthesis. Outer culm and inner culm were found to be the most important sources of active compounds. 8-C-Glucosylapigenin, luteolin derivatives and chlorogenic acid were the most probable compounds responsible for the anti-allergy activity of these bamboo extracts. Our study suggests the potential use of bamboo as a functional ingredient in cosmetics or other health-related products.

Imidapril and enalapril similarly inhibit plasma matrix metalloproteinase activities and attenuate left ventricular remodeling in patients with acute myocardial infarction.

Matrix metalloproteinase (MMP) plays a critical role in the development of ventricular remodeling after acute myocardial infarction (AMI). Imidapril, an angiotensin-converting enzyme inhibitor, has been shown to inhibit MMP activity. We investigated whether imidapril inhibits plasma MMP activities and attenuates ventricular remodeling in patients with AMI in comparison with enalapril. We enrolled 70 patients with AMI. All patients underwent primary percutaneous coronary intervention and were randomly assigned either to imidapril (n = 35) or to enalapril (n = 35) treatment. Left ventriculography was performed in acute (day 14) and chronic (6 months) phases, and plasma MMP-2 and MMP-9 activities were measured by zymography. Any changes in left ventricular end-diastolic volume index and ejection fraction from acute to chronic phases did not differ between the 2 groups. The plasma MMP-2 and MMP-9 activities at day 14 were both significantly decreased compared with those at day 1 in both groups (all P < 0.05). At 6 months, MMP-9 activity still remained decreased in both groups (P < 0.05 vs. day 1). Overall, there were no differences between the 2 groups both in plasma MMP-2 and MMP-9 activities. These results demonstrate that imidapril exerts inhibitory effects on plasma MMP activities and attenuates left ventricular remodeling in patients with AMI similar to enalapril.

Anger is a distinctive feature of epilepsy patients with depression.

Controversy exists regarding the similarity between depression as seen in patients with epilepsy and in those with idiopathic major depression. The objective of this study was to examine whether anger is a distinctive feature of depression in epilepsy. Participants included 487 adult patients with epilepsy (study group) and 85 patients with idiopathic major depression according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria, and without other neurological complications (control group). All participants completed the Inventory of Depressive Symptomatology Self-Report (IDS-SR) and the Buss-Perry Aggression Questionnaire (BAQ). The IDS-SR is a self-report questionnaire that measures depression severity and assesses all symptoms of depression as defined by the DSM-IV. The BAQ is a self-rating scale designed for assessing aggression. After examining potential confounding factors (i.e., demographic and clinical variables) using a multivariate linear regression model, BAQ scores were compared between the study (n = 85) and control groups (n = 54) for patients with moderate or severe depression using established cut-off points (IDS-SR score > 25). BAQ scores were significantly higher in the study group (P = 0.009). Among the BAQ subscales, only anger showed a statistically significant difference (P = 0.013). Although a significant correlation was revealed between the IDS-SR and BAQ scores in the study group, no such correlation was found in the control group. Thus, anger might be a constituent component of depression among epilepsy patients, but not among idiopathic major depression patients.

A randomized, double-blind, sham-controlled study of static electric field therapy by high voltage alternating current for active rheumatoid arthritis.

Static electric field therapy by high voltage alternating current (EF-HVAC) is a traditional complementary Japanese medicine used for headache, shoulder stiffness, chronic constipation and insomnia. Open-label studies and clinical experience in Japan have suggested that this electric field therapy is safe and effective in treating chronic arthritis. We evaluated the efficacy of EF-HVAC therapy in a randomized, double-blinded, sham-controlled trial in patients with active rheumatoid arthritis (RA) in community-based general physician centers. Thirty patients fulfilling American College of Rheumatology (ACR) criteria for RA were treated with EF-HVAC therapy with the LEGACIS PLUS System (COCOROCA Corp., Tokyo, Japan) or sham therapy for 12 weeks and followed for 4 weeks without treatment. The disease activity score 28 (DAS28-CRP), visual analogue scale for pain (VAS), modified health assessment questionnaire (MHAQ), and inflammatory parameters were used as the outcome variable. Twenty four patients (n = 12 in each group) were analyzed by a per protocol analysis. Although a significant reduction in DAS28-CRP was observed in EF-HVAC group at 8 and 12 weeks compared to before treatment, there were no significant differences in DAS28-CRP scores during treatment between two groups. The scale of VAS was also significantly decreased by the treatment with EF-HVAC compared to before treatment, in addition, the scale of VAS in EF-HVAC group was significantly lower than sham group at 8 and 12 weeks. Changes in another parameters including MHAQ were not significant between before and after treatment, or by all comparative study between two groups. There were no adverse events related the treatment. In conclusion, the EF-HVAC therapy has a beneficial effect on the improvement to subjective pain of RA.