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1.
Genes Cells ; 28(1): 5-14, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36318474

RESUMEN

AMP-activated protein kinase (AMPK) inactivation in chronic kidney disease (CKD) leads to energy status deterioration in the kidney, constituting the vicious cycle of CKD exacerbation. Unc-51-like kinase 1 (ULK1) is considered a downstream molecule of AMPK; however, it was recently reported that the activity of AMPK could be regulated by ULK1 conversely. We demonstrated that AMPK and ULK1 activities were decreased in the kidneys of CKD mice. However, whether and how ULK1 is involved in the underlying mechanism of CKD exacerbation remains unknown. In this study, we investigated the ULK1 involvement in CKD, using ULK1 knockout mice. The CKD model of Ulk1-/- mice exhibited significantly exacerbated renal function and worsening renal fibrosis. In the kidneys of the CKD model of Ulk1-/- mice, reduced AMPK and its downstream ß-oxidation could be observed, leading to an energy deficit of increased AMP/ATP ratio. In addition, AMPK signaling in the kidney was reduced in control Ulk1-/- mice with normal renal function compared to control wild-type mice, suggesting that ULK1 deficiency suppressed AMPK activity in the kidney. This study is the first to present ULK1 as a novel therapeutic target for CKD treatment, which regulates AMPK activity in the kidney.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Insuficiencia Renal Crónica , Ratones , Animales , Homólogo de la Proteína 1 Relacionada con la Autofagia/genética , Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Riñón/metabolismo , Insuficiencia Renal Crónica/metabolismo , Fosforilación , Autofagia
2.
Pharmacopsychiatry ; 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38917847

RESUMEN

INTRODUCTION: While antipsychotics are often prescribed for behavioral and psychological symptoms of dementia (BPSD), typically on an off-label basis, these medications have serious adverse effects. This study investigated the long-term use of antipsychotics among inpatients with dementia displaying severe BPSD, focusing on how prescriptions change over time. METHODS: Medical charts at Kusakabe Memorial Hospital were retrospectively reviewed from October 2012 to September 2021. The study included patients diagnosed with dementia, admitted for BPSD, and were continuing antipsychotics at 3 months of their admission. Antipsychotic dosages were categorized as high (≥300 mg/d), medium (100-300 mg/d), and low (<100 mg/d) based on chlorpromazine equivalents and tracked until 15 months during hospitalization. Binary logistic regression was used to identify factors associated with dosage reductions between months 3 and 6. RESULTS: This study involved 188 patients, with an average age of 81.2 years, 67% of whom were diagnosed with Alzheimer's dementia. At 3 months, 15.4% were taking high, 44.1% on medium, and 40.4% on low dosages of antipsychotics. The highest average dosage was observed at 3 months, with a subsequent decrease over time. By the 12th month, 20-30% of patients in all dosage categories had stopped their antipsychotic medication. Significant factors for dosage reduction included higher initial doses (OR 1.003, 95%Cl: 1.001-1.006, P=0.01) and male gender (OR 2.481, 95%Cl: 1.251-4.918, P=0.009). DISCUSSION: A trajectory of antipsychotic dosage in inpatients with severe BPSD has rarely been reported. This research emphasizes the need for personalized strategies in managing long-term pharmacotherapy for this vulnerable group of patients.

3.
Mol Psychiatry ; 27(7): 2950-2967, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35444257

RESUMEN

Antipsychotic drugs are the mainstay in the treatment of schizophrenia. However, one-third of patients do not show adequate improvement in positive symptoms with non-clozapine antipsychotics. Additionally, approximately half of them show poor response to clozapine, electroconvulsive therapy, or other augmentation strategies. However, the development of novel treatment for these conditions is difficult due to the complex and heterogenous pathophysiology of treatment-resistant schizophrenia (TRS). Therefore, this review provides key findings, potential treatments, and a roadmap for future research in this area. First, we review the neurobiological pathophysiology of TRS, particularly the dopaminergic, glutamatergic, and GABAergic pathways. Next, the limitations of existing and promising treatments are presented. Specifically, this article focuses on the therapeutic potential of neuromodulation, including electroconvulsive therapy, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and deep brain stimulation. Finally, we propose multivariate analyses that integrate various perspectives of the pathogenesis, such as dopaminergic dysfunction and excitatory/inhibitory imbalance, thereby elucidating the heterogeneity of TRS that could not be obtained by conventional statistics. These analyses can in turn lead to a precision medicine approach with closed-loop neuromodulation targeting the detected pathophysiology of TRS.


Asunto(s)
Antipsicóticos , Clozapina , Esquizofrenia , Estimulación Transcraneal de Corriente Directa , Antipsicóticos/uso terapéutico , Clozapina/uso terapéutico , Humanos , Esquizofrenia Resistente al Tratamiento
4.
Compr Psychiatry ; 127: 152425, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37774551

RESUMEN

BACKGROUND: Early medical residents are expected to have a higher prevalence of burnout due to physical and psychological stressors. However psychological distress associated with burnout has not been adequately investigated in a longitudinal manner. We therefore examined the longitudinal trajectory of depression and its associated factors among early medical residents. METHODS: In this cohort study, medical residents (n = 215) who started rotation at the University of Yamanashi Hospital during 2012 to 2018 were recruited and asked to complete the Brief Job Stress Questionnaire (BJSQ), Center for Epidemiologic Studies Depression Scale (CESD), Brief Scale for Coping Profile (BSCP) and Athens Insomnia Scale (AIS) at the time of exit from each clinical department for up to two years over seven years. Factors associated with the CES-D scores were statistically explored, with a cutoff score of 16 to denote depression. RESULTS: The CES-D was completed by 205 residents. The average CES-D score was 10.3 ± 8.0 and the scores were lower in the 2nd versus 1st year of residency (11.3 ± 6.7 versus 9.2 ± 7.0). Multiple regression analysis of BJSQ/BSCP/AIS on CES-D revealed that insomnia had a significant impact on the CES-D scores. Apart from insomnia, avoidance and suppression and peer support had significant effects. Resilient residents, who showed the maximum CES-D score of under 16 consistently throughout the residency, was better in terms of changing a point of view, active solution and changing mood. Women were more likely to express emotions to others, while they reported more job control in the first year. CONCLUSIONS: Our results have high clinical relevance to challenge psychological burnout among early medical residents, offering some possible clues for prevention such as reduced burden, more flexibility during the first year and strengthening coworker support. Insomnia exerted moderate to strong effects on depression and monitoring of sleep appears indispensable in this specific population.


Asunto(s)
Internado y Residencia , Distrés Psicológico , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Femenino , Estudios de Cohortes , Estudios Longitudinales , Depresión/diagnóstico , Depresión/epidemiología , Depresión/psicología , Japón/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/diagnóstico , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Estrés Psicológico/epidemiología , Estrés Psicológico/psicología , Encuestas y Cuestionarios
5.
J ECT ; 39(2): 71-73, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-35536991

RESUMEN

ABSTRACT: Evidence on electroconvulsive therapy (ECT) for people receiving chronic hemodialysis has been rather scarce in the literature. We report the case of a 74-year-old male patient with major depressive disorder on chronic hemodialysis for 14 years with numerous physical complications including abdominal aortic aneurysm, ossification of the posterior longitudinal ligament, and cerebral stroke. Several antidepressant drugs failed to improve the patient, but judicious implementation of a total of 6 ECT sessions under a close liaison with medical experts brought him into remission without any notable adverse effects. In particular, flumazenil, as well as rocuronium and sugammadex, was used together with a strict control of blood pressure. We thoroughly discuss the case and provide a literature review on such topics as assessment of physical complications, medications used for anesthesia, electrode placement, and timing of hemodialysis during ECT sessions, which identified a clear need for more research on this medically challenging issue.


Asunto(s)
Trastorno Depresivo Mayor , Terapia Electroconvulsiva , Masculino , Humanos , Anciano , Terapia Electroconvulsiva/efectos adversos , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/terapia , Depresión/terapia , Rocuronio , Sugammadex
6.
Br J Clin Pharmacol ; 88(7): 3341-3350, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35112390

RESUMEN

AIMS: Develop a robust and user-friendly software tool for the prediction of dopamine D2 receptor occupancy (RO) in patients with schizophrenia treated with either olanzapine or risperidone, in order to facilitate clinician exploration of the impact of treatment strategies on RO using sparse plasma concentration measurements. METHODS: Previously developed population pharmacokinetic models for olanzapine and risperidone were combined with a pharmacodynamic model for D2 RO and implemented in the R programming language. Maximum a posteriori Bayesian estimation was used to provide predictions of plasma concentration and RO based on sparse concentration sampling. These predictions were then compared to observed plasma concentration and RO. RESULTS: The average (standard deviation) response times of the tools, defined as the time required for the application to predict parameter values and display the output, were 2.8 (3.1) and 5.3 (4.3) seconds for olanzapine and risperidone, respectively. The mean error (95% confidence interval) and root mean squared error (95% confidence interval) of predicted vs. observed concentrations were 3.73 ng/mL (-2.42-9.87) and 10.816 ng/mL (6.71-14.93) for olanzapine, and 0.46 ng/mL (-4.56-5.47) and 6.68 ng/mL (3.57-9.78) for risperidone and its active metabolite (9-OH risperidone). Mean error and root mean squared error of RO were -1.47% (-4.65-1.69) and 5.80% (3.89-7.72) for olanzapine and -0.91% (-7.68-5.85) and 8.87% (4.56-13.17) for risperidone. CONCLUSION: Our monitoring software predicts concentration-time profiles and the corresponding D2 RO from sparsely sampled concentration measurements in an accessible and accurate form.


Asunto(s)
Antipsicóticos , Antipsicóticos/uso terapéutico , Teorema de Bayes , Benzodiazepinas , Humanos , Olanzapina , Receptores de Dopamina D2/metabolismo , Risperidona/uso terapéutico
7.
Gan To Kagaku Ryoho ; 49(2): 205-207, 2022 Feb.
Artículo en Japonés | MEDLINE | ID: mdl-35249062

RESUMEN

A 64-year-old man with gastric tumor in the antrum had been diagnosed with gastric neuroendocrine carcinoma(NEC) by biopsy and multiple lymph node metastases(#3 and #6)by abdominal computed tomography. After staging laparoscopy showed that there were no non-curative factors, neoadjuvant chemotherapy(S-1/cisplatin[CDDP]: 2 courses)and distal gastrectomy and D2 lymph node dissection were performed. The pathological diagnosis was shown as pathological complete response(pCR). After adjuvant chemotherapy(S-1/CDDP: 2 courses, S-1: 6 courses)was administered, the patient is alive at 8 years without recurrence.


Asunto(s)
Carcinoma Neuroendocrino , Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Neuroendocrino/tratamiento farmacológico , Carcinoma Neuroendocrino/cirugía , Cisplatino , Combinación de Medicamentos , Gastrectomía , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Ácido Oxónico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Tegafur
8.
Gan To Kagaku Ryoho ; 49(13): 1992-1994, 2022 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-36733068

RESUMEN

A 78-year-old man with advanced thoracic esophageal cancer underwent radical esophagectomy after neoadjuvant chemotherapy with cisplatin plus 5-FU. He had left adrenal metastasis 10 months after surgery and removed it, but 3 months later he had liver metastases. After 2 courses of chemotherapy with nedaplatin plus 5-FU, resection was performed. One course of nedaplatin plus 5-FU for adjuvant chemotherapy was added, but the patient was followed up without another chemotherapy after surgery because of intestinal obstruction due to infection and increase of the lymphatic cyst in the abdominal cavity. Six months after the liver resection, nodules appeared in the right lung, and 4 months later, multiple nodules extending to both lungs were observed. Therefore, it was judged that there were multiple lung metastases, and administration of nivolumab was started. He has been 3 years since the recurrence of esophageal cancer and 17 months after the start of nivolumab administration, but the recurrence lesion is only progressing to lung metastasis.


Asunto(s)
Neoplasias Esofágicas , Neoplasias Pulmonares , Masculino , Humanos , Anciano , Nivolumab/uso terapéutico , Fluorouracilo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/secundario , Esofagectomía
9.
Pharmacopsychiatry ; 54(2): 60-67, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33434943

RESUMEN

INTRODUCTION: Conventional treatment guidelines of schizophrenia do not necessarily provide solutions on clinically important issues. METHODS: A total of 141 certified psychiatrists of the Japanese Society of Clinical Neuropsychopharmacology evaluated treatment options regarding 19 clinically relevant situations in the treatment of schizophrenia with a 9-point scale (1="disagree" and 9="agree"). RESULTS: First-line antipsychotics varied depending on predominant symptoms: risperidone (mean±standard deviation score, 7.9±1.4), olanzapine (7.5±1.6), and aripiprazole (6.9±1.9) were more likely selected for positive symptoms; aripiprazole (7.6±1.6) for negative symptoms; aripiprazole (7.3±1.9), olanzapine (7.2±1.9), and quetiapine (6.9±1.9) for depression and anxiety; and olanzapine (7.9±1.5) and risperidone (7.5±1.5) for excitement and aggression. While only aripiprazole was categorized as a first-line treatment for relapse prevention (7.6±1.0) in patients without noticeable symptoms, aripiprazole (8.0±1.6) and brexpiprazole (6.9±2.3) were categorized as such for social integration. First-line treatments in patients who are vulnerable to extrapyramidal symptoms include quetiapine (7.5±2.0) and aripiprazole (6.9±2.1). DISCUSSION: These clinical recommendations represent the expert consensus on the use of a particular antipsychotic medication for a particular situation, filling a current gap in the literature.


Asunto(s)
Antipsicóticos , Esquizofrenia , Antipsicóticos/efectos adversos , Aripiprazol/efectos adversos , Benzodiazepinas/uso terapéutico , Consenso , Humanos , Japón , Fumarato de Quetiapina/efectos adversos , Esquizofrenia/tratamiento farmacológico
10.
Gan To Kagaku Ryoho ; 48(13): 1895-1897, 2021 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-35045439

RESUMEN

A 75-year-old man with a Type 3 advanced gastric cancer in the middle gastric body and paraaortic lymph node swelling was treated chemotherapy. After treatment, we performed an exploratory laparotomy and curative total gastrectomy. As adjuvant chemotherapy, S-1 treatment was administrated for 4 courses but multiple metastases from left supraclavicular to paraaortic lymph nodes. First, Cape plus CDDP plus T-mab therapy treated. Because of acute renal failure, Cape plus L-OHP plus T-mab was administrated but response evaluation was PD. In the second-line therapy, Ramucirumab plus paclitaxel was performed 4 courses. Third, we administrated Nivolumab. After 6 courses, response evaluation was PR and we continued 24 courses. At the same time, there was acute-onset Nivolumab-induced organizing pneumonia and we treated steroid pulse, azithromycin and introduced home oxygen therapy. At the present, 47 months long-term survival achieved after Nivolumab treatment.


Asunto(s)
Nivolumab , Neoplasias Gástricas , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Gastrectomía , Humanos , Metástasis Linfática , Masculino , Nivolumab/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía
11.
Bipolar Disord ; 22(8): 822-830, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32558145

RESUMEN

OBJECTIVES: The aim of this study was to develop a consensus guideline by certified experts of the Japanese Society of Clinical Neuropsychopharmacology on the psychopharmacological treatment for bipolar disorders I and II (BP-I and BP-II), in order to fill the gap in the literature and provide more concrete guidance for challenging and controversial real-world situations. METHODS: Experts were asked to assess treatment options regarding 19 clinical situations of bipolar disorder with a nine-point Likert scale (one = "disagree" and nine = "agree"). According to the responses from 119 experts, the options were categorized into the first-, second-, and third-line treatments. RESULTS: For the treatment of BP-I, lithium monotherapy was categorized as a first-line treatment for manic episodes (mean ± standard deviation score, 7.0 ± 2.2), depressive episodes (7.1 ± 2.0), and the maintenance phase (7.8 ± 1.8). Combination therapy of lithium and an atypical antipsychotic was endorsed for manic episodes (7.7 ± 1.7), depressive episodes with (7.1 ± 2.0) and without mixed features (6.9 ± 2.2), and the maintenance phase (6.9 ± 2.1). Similarly, in BP-II, lithium monotherapy was categorized as a first-line treatment for hypomanic episodes (7.3 ± 2.2), depressive episodes (7.0 ± 2.2), and the maintenance phase (7.3 ± 2.3), while combination therapy of lithium and an atypical antipsychotic was recommended for hypomanic episodes (6.9 ± 2.4).No antipsychotic monotherapy or antidepressant treatment was categorized as a first-line treatment for any type of episode. CONCLUSIONS: These recommendations reflect the current evidence and represent the experts' consensus on using lithium for the treatment of bipolar disorder. Clinicians should consider the effectiveness and adverse effects of antipsychotic and antidepressant medications for the treatment of bipolar disorder.


Asunto(s)
Antidepresivos/uso terapéutico , Antipsicóticos/uso terapéutico , Trastorno Bipolar/tratamiento farmacológico , Litio/uso terapéutico , Consenso , Quimioterapia Combinada , Femenino , Humanos , Japón
12.
Psychosomatics ; 61(1): 24-30, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31607503

RESUMEN

BACKGROUND: Sudden unexpected deaths occur more frequently among patients with severe mental illness (SMI), but direct evidence on the causes is still scarce. OBJECTIVE: The objective of this study is to investigate initial rhythms and characteristics of out-of-hospital cardiac arrest among patients with SMI. METHODS: We conducted a systematic chart review of adult patients who suffered from out-of-hospital cardiac arrest and transferred to Tokyo Metropolitan Bokutoh Hospital in Japan between January 2011 and December 2017. The initial rhythms, clinical characteristics, and outcomes were compared between patients with schizophrenia or mood disorders (i.e., SMI) and nonpsychiatric control patients. Values of interest were compared using Fisher's exact test or Mann-Whitney U-test, as appropriate. Multiple regression analysis was also conducted to investigate the effect of SMI on the initial rhythms. RESULTS: A total of 2631 patients were included in this study. Of these, 157 patients had SMI. Fatal arrhythmias (i.e., ventricular fibrillation and ventricular tachycardia) were less frequently noted as the initial rhythms among patients with SMI than among controls (5.7% vs. 18.8%, adjusted odds ratio = 0.27, 95% confidence interval = 0.13-0.55, P < 0.001). Patients with SMI were significantly younger (median [range], 58 years [22-85] vs. 72 years [18-108], P < 0.001) and less frequently had comorbid physical illnesses than controls (the proportion of patients without comorbidities; 58.6% vs. 37.1%, P < 0.001). Survival and neurological function at discharge were not different between the 2 groups. CONCLUSION: Fatal arrhythmia may account for a relatively small portion in excess of sudden death among patients with SMI. Furthermore, appropriate medical checkups for the patients with SMI at earlier ages would be important to prevent sudden cardiac death.


Asunto(s)
Trastornos del Humor/epidemiología , Paro Cardíaco Extrahospitalario/epidemiología , Esquizofrenia/epidemiología , Taquicardia Ventricular/epidemiología , Fibrilación Ventricular/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Arritmias Cardíacas/epidemiología , Estudios de Casos y Controles , Comorbilidad , Muerte Súbita Cardíaca/epidemiología , Femenino , Paro Cardíaco/epidemiología , Humanos , Japón/epidemiología , Masculino , Trastornos Mentales/epidemiología , Persona de Mediana Edad , Oportunidad Relativa , Tasa de Supervivencia , Adulto Joven
13.
Surg Radiol Anat ; 42(12): 1509-1515, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32500228

RESUMEN

PURPOSE: In the present study, we focused on the accessory middle colic artery and aimed to increase the safety and curative value of colorectal cancer surgery by investigating the artery course and branching patterns. METHODS: We included 143 cases (mean age, 70.4 ± 11.2 years; 86 males) that had undergone surgery for neoplastic large intestinal lesions at the First Department of Surgery at Yamagata University Hospital between August 2015 and July 2018. We constructed three-dimensional (3D) computed tomography (CT) angiograms and fused them with reconstructions of the large intestines. We investigated the prevalence of the accessory middle colic artery, the variability of its origin, and the prevalence and anatomy of the arteries accompanying the inferior mesenteric vein at the same level as the origin of the inferior mesenteric artery. RESULTS: Accessory middle colic artery was observed in 48.9% (70/143) cases. This arose from the superior mesenteric artery in 47, from the inferior mesenteric artery in 21, and from the celiac artery in two cases. In 78.2% (112/143) cases, an artery accompanying the inferior mesenteric vein was present at the same level as the origin of the inferior mesenteric artery; this artery was the left colic artery in 92, the accessory middle colic artery in 11, and it divided and became the left colic artery and the accessory middle colic artery in 10 cases. CONCLUSION: 3D CT angiograms are useful for preoperative evaluation. Accessory middle colic arteries exist and were observed in 14.9% of cases.


Asunto(s)
Variación Anatómica , Intestino Grueso/irrigación sanguínea , Anciano , Anciano de 80 o más Años , Arterias/anatomía & histología , Neoplasias Colorrectales/cirugía , Angiografía por Tomografía Computarizada , Femenino , Humanos , Imagenología Tridimensional , Intestino Grueso/cirugía , Masculino , Venas Mesentéricas/anatomía & histología , Persona de Mediana Edad
14.
Ophthalmology ; 126(11): 1557-1566, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31257036

RESUMEN

PURPOSE: To present phenotypic features of 22 patients with S-antigen (SAG) mutations. DESIGN: Retrospective cohort study. PARTICIPANTS: Twenty-one Japanese patients from 16 families with a homozygous c.924delA mutation and 1 patient with a homozygous c.636delT mutation in the SAG gene. METHODS: Clinical records on symptoms; best-corrected visual acuity; and Goldmann perimetry, fundus photography, fundus autofluorescence (FAF), OCT, and electroretinography results were reviewed. MAIN OUTCOME MEASURES: Best-corrected visual acuity, Goldmann perimetry results, imaging findings, and electroretinography results. RESULTS: Ten patients had Oguchi disease and 12 had retinitis pigmentosa (RP) with mean follow-up periods of 13.8 and 10.2 years, respectively. Retinitis pigmentosa patients were older (mean age, 56.0 years) than those with Oguchi disease (mean age, 22.1 years; P < 0.001) at the initial visit. Night blindness noted in childhood was the most common initial symptom for both Oguchi disease (80.0%) and RP (91.7%) patients. Best-corrected visual acuity in the logarithm of the minimum angle of resolution (logMAR) was well preserved in Oguchi disease patients (mean, 0.02 logMAR in both eyes) but reduced in most RP patients (mean, 1.32 logMAR [right eye] and 1.35 logMAR [left eye]). Similarly, the visual field in the retinal area was preserved in Oguchi disease patients (mean, 677 mm2 right eye and 667 mm2 left eye) and reduced in RP patients (mean, 369 mm2 right eye and 294 mm2 left eye). Fundus images revealed a characteristic golden sheen with no retinal degeneration in Oguchi disease patients, excluding 2 with macular degeneration detected by FAF, OCT, or both and 1 with mild retinal degeneration confirmed by OCT and fluorescein angiography. Pigmentary retinal degeneration most evident posteriorly was observed in RP patients, accompanied by a characteristic golden sheen in 12 of 14 patients undergoing ultra-widefield fundus imaging. OCT showed disrupted macular structure, and FAF revealed variable hypofluorescence. Electroretinography identified absent rod responses in both diseases, along with relative preservation of cone responses in Oguchi disease patients. Three patients showed progressive loss of the golden sheen based on fundus images, including 1 who demonstrated RP 26 years after the initial diagnosis of Oguchi disease. CONCLUSIONS: Retinitis pigmentosa with SAG mutations often shows a characteristic golden sheen surrounding posterior pigmentary retinal degeneration. Oguchi disease can show progressive degeneration in adulthood, rarely resulting in RP.


Asunto(s)
Arrestina/genética , Enfermedades Hereditarias del Ojo/diagnóstico , Mutación , Ceguera Nocturna/diagnóstico , Retinitis Pigmentosa/diagnóstico , Adolescente , Adulto , Anciano , Niño , Preescolar , Electrorretinografía , Enfermedades Hereditarias del Ojo/genética , Enfermedades Hereditarias del Ojo/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Ceguera Nocturna/genética , Ceguera Nocturna/fisiopatología , Fenotipo , Retina/fisiopatología , Retinitis Pigmentosa/genética , Retinitis Pigmentosa/fisiopatología , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Agudeza Visual/fisiología , Pruebas del Campo Visual , Campos Visuales/fisiología
15.
J Clin Psychopharmacol ; 39(4): 329-335, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31188232

RESUMEN

PURPOSE/BACKGROUND: Patients with schizophrenia as well as their psychiatrists are hesitant to reduce the antipsychotic dose in fear of relapse. To overcome such dilemmas, we developed models to individually calculate an oral dose that corresponds to a given target dopamine D2 receptor occupancy. METHODS/PROCEDURES: In this pilot, 52-week single-blind randomized controlled trial, 35 clinically stable patients with schizophrenia receiving either risperidone or olanzapine monotherapy were randomly assigned to dose reduction (n = 17) or dose maintenance group (n = 18). In the former group, baseline doses were reduced to the doses corresponding to 65% D2 occupancy (the lower end of therapeutic window) at trough that were calculated from randomly collected plasma concentrations using our models. FINDINGS/RESULTS: In the dose reduction group, doses of risperidone and olanzapine were decreased from 4.2 ± 1.9 to 1.4 ± 0.4 and 12.8 ± 3.9 to 6.7 ± 1.8 mg/d, whereas the doses in the dose maintenance group were 4.3 ± 1.9 and 15.8 ± 4.6 mg/d, respectively. Twelve subjects (70.5%) and 13 subjects (72.2%) in the dose reduction and dose maintenance groups completed the study (P = 0.604), whereas 3 subjects (18.8%) and none dropped out because of clinical worsening in the dose reduction and dose maintenance groups, respectively. There were not significant differences in score changes in Positive and Negative Syndrome Scale between the 2 groups but in Positive subscale scores in the Clinical Global Impression-Schizophrenia (0.4 ± 0.7 in the dose reduction group vs -0.1 ± 0.7 in the dose maintenance group, P = 0.029). IMPLICATIONS/CONCLUSIONS: Although our model-guided dose reduction strategy was found to be comparable with no-dose change in terms of dropout rates, safety issues have to be further examined.


Asunto(s)
Antipsicóticos/administración & dosificación , Esquizofrenia/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Olanzapina/administración & dosificación , Escalas de Valoración Psiquiátrica , Risperidona/administración & dosificación
16.
Psychosomatics ; 60(4): 402-409, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30503364

RESUMEN

BACKGROUND: Electroconvulsive therapy (ECT) is indicated for critical psychiatric conditions, which themselves constitute a risk for deep venous thrombosis (DVT) owing to prolonged immobility, dehydration, and venous stasis. OBJECTIVE: We describe challenging instances of ECT implementation while taking direct oral anticoagulants (DOACs). METHOD: We report on 8 patients receiving DOACs for DVT who were successfully treated with ECT at the University of Yamanashi Hospital. We also provide a literature review on this topic. RESULTS: There were 6 female patients (the average age was 60.9+/-13.4 y.o.) and diagnoses included major depression, bipolar depression and schizophrenia. DOACs were edoxaban for 4 patients, rivaroxaban for 2, and apixaban for 2. A total of 92 ECT sessions were cautiously and safely completed in collaboration with multidisciplinary medical professionals without problematic adverse events, such as bleeding. A literature search found one case series of warfarin but currently available evidence is confined to sporadic case reports regarding ECT and DOACs for DVT. These reports were represented by successful implementation of ECT to patients receiving treatment with anticoagulants for DVT or thromboembolism. Ours is the first of a successful treatment with ECT while taking apixaban or edoxaban. CONCLUSION: A clinical dilemma is that ECT is indicated for critical conditions that are likely to predispose patients to developing DVT. Paucity of data clearly highlights the need for more studies to support a contention that ECT, when carefully performed in consultation with other medical experts, is a viable treatment for those with DVT receiving oral anticoagulants.


Asunto(s)
Anticoagulantes/uso terapéutico , Terapia Electroconvulsiva/métodos , Trastornos Mentales/complicaciones , Trastornos Mentales/terapia , Trombosis de la Vena/complicaciones , Trombosis de la Vena/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Anticoagulantes/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
17.
Pharmacopsychiatry ; 52(6): 251-260, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29940662

RESUMEN

INTRODUCTION: Kampo is a Japanese traditional medicinal system and is represented by unity of mind and body. It is originally based upon Chinese traditional medicine but has uniquely developed in Japan. METHODS: A narrative review on the use of Kampo for psychiatric conditions is provided. RESULTS: Kampo formula is a combination of several crude ingredients; most derive from natural plants and some from animals and minerals. These Kampo formulae are widely prescribed in almost all medical disciplines, including psychiatry, in Japan; they have been used for various psychiatric disorders such as dementia, schizophrenia spectrum disorders, mood disorders, anxiety disorders, and personality disorders. Kampo is a versatile traditional medicine with a variety of positive effects on mental states with relatively benign side effect profiles. Kampo formulae can be adjunctively combined with or substituted for the Western psychotropic drugs, which will provide more treatment options to patients with psychiatric conditions. DISCUSSION: This review summarizes the current knowledge on Kampo for psychiatric conditions, highlighting a paucity of data and a need for further good-quality evidence on these medications.


Asunto(s)
Medicina Kampo , Trastornos Mentales/tratamiento farmacológico , Humanos , Resultado del Tratamiento
18.
Pharmacopsychiatry ; 52(4): 175-179, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29791934

RESUMEN

INTRODUCTION: While the current nomenclature of psychotropic drugs is disease-based, their approved indications do not always match their classifications. METHODS: Information on approved indications of "second-generation antipsychotics" and "newer antidepressants" that are available in the United States (US), the United Kingdom (UK), France, Germany, and Japan were extracted from their packet inserts. RESULTS: A significant proportion of "atypical antipsychotics" were approved for psychiatric conditions other than psychotic disorders (i. e., bipolar disorder, major depressive disorder, and autistic disorder) as follows: 76.9% in the US, 66.7% in the UK, 66.7% in France, 60.0% in Germany, and 44.4% in Japan. Likewise, more than half of "newer antidepressants" had approved indications for psychiatric conditions other than depression (e. g., panic disorder, obsessive compulsive disorder, social anxiety disorder, general anxiety disorder, and post-traumatic stress disorder): 56.3% in the US, 69.2% in the UK, 69.2% in France, 50.0% in Germany, and 62.5% in Japan. CONCLUSIONS: Our results raise concerns regarding generic terminologies of "antipsychotics" and "antidepressants" since the conventional indication-based nomenclature does not fit well with the official indication.


Asunto(s)
Antidepresivos/clasificación , Antipsicóticos/clasificación , Trastornos Mentales/clasificación , Trastornos Mentales/tratamiento farmacológico , Terminología como Asunto , Antidepresivos/uso terapéutico , Antipsicóticos/uso terapéutico , Aprobación de Drogas , Humanos , Uso Fuera de lo Indicado
19.
Psychiatry Clin Neurosci ; 73(5): 243-247, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30588704

RESUMEN

AIM: Although sudden cardiac deaths are more common in psychiatric patients than the general population, data on their causes are very limited. The aim of this study was to investigate initial rhythms and causes of out-of-hospital cardiac arrest (OHCA) in patients with psychiatric disorders. METHODS: We conducted a systematic chart review of patients resuscitated after OHCA and hospitalized in the Tertiary Emergency Medical Center of Tokyo Metropolitan Bokutoh Hospital in Japan between January 2010 and December 2017. The initial rhythms and causes of OHCA were compared between psychiatric patients and non-psychiatric patients. Parameters of interest were compared using chi-squared test, Fisher's exact test, or the Mann-Whitney U-test, as appropriate. RESULTS: A total of 49 psychiatric and 600 non-psychiatric patients were eligible for this study. Fatal but shockable arrhythmias (i.e. ventricular fibrillation and ventricular tachycardia) were less frequently observed as initial rhythms in patients with psychiatric disorders than the others (22.4% vs 49.7%, P < 0.001). Cardiac origin was less common as the cause of OHCA (26.5% vs 58.5%, P < 0.01), while airway obstruction and pulmonary embolism were more frequent in psychiatric versus non-psychiatric patients (24.5% vs 6.5%, P < 0.01; and 12.2% vs 1.5%, P < 0.01, respectively). The results were similar when psychiatric patients were compared with sex- and age-matched controls selected from the non-psychiatric patient group. CONCLUSION: Although fatal arrhythmias may be less common, non-cardiac causes such as pulmonary embolism and airway obstruction need to be treated with high clinical suspicion in an event of sudden cardiac arrest in psychiatric patients.


Asunto(s)
Obstrucción de las Vías Aéreas/complicaciones , Arritmias Cardíacas/complicaciones , Trastornos Mentales , Paro Cardíaco Extrahospitalario/etiología , Embolia Pulmonar/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Obstrucción de las Vías Aéreas/epidemiología , Arritmias Cardíacas/epidemiología , Comorbilidad , Femenino , Humanos , Masculino , Trastornos Mentales/epidemiología , Persona de Mediana Edad , Paro Cardíaco Extrahospitalario/epidemiología , Embolia Pulmonar/epidemiología , Estudios Retrospectivos , Adulto Joven
20.
J ECT ; 35(4): 279-287, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31764452

RESUMEN

OBJECTIVES: Delirium following electroconvulsive therapy (ECT) has been a clinical challenge, which, however, has not been investigated through a systematic literature review. The objective of this study was to systematically synthesize available evidence regarding factors associated with post-ECT delirium. METHODS: We conducted a systematic literature search for any type of original investigations that reported risk factors of post-ECT delirium, using PubMed. RESULTS: The literature search identified 43 relevant articles. One study found an association between catatonic feature and increased risk of postictal delirium. Five studies reported that the presence of cerebrovascular disease, Parkinson disease, or dementia was related to higher incidence of post-ECT delirium. Incidence of post-ECT course delirium was increased with bitemporal stimulation (3 studies). One study showed that ultrabrief pulse ECT reduced reorientation time following seizure compared with brief pulse ECT. High stimulus intensity resulted in more prolonged reorientation time after ECT than lower stimulus intensity (2 studies). Longer seizure length was significantly associated with post-ECT delirium in 1 study. Eight studies that examined postictal delirium in association with medications used, including lithium, did not show any consistent finding in their relationships. Four studies showed decreased incidence of postictal delirium in those receiving dexmedetomidine. CONCLUSIONS: Limited evidence suggests that catatonic feature, cerebrovascular disease, Parkinson disease, dementia, bitemporal electrode placement, high stimulus intensity, or longer seizure length are associated with an increased risk of post-ECT delirium. Moreover, dexmedetomidine and ultrabrief pulse ECT seem to have preventive effects of post-ECT delirium.


Asunto(s)
Delirio/etiología , Terapia Electroconvulsiva/efectos adversos , Humanos , Factores de Riesgo
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