Analysis of Concomitant Medications Prescribed with Antipsychotics to Patients with Dementia.

INTRODUCTION: Antipsychotics are still commonly prescribed to patients with dementia, despite the many issues that have been identified. This study aimed to quantify antipsychotic prescription in patients with dementia and the types of concomitant medications prescribed with antipsychotics. METHODS: A total of 1,512 outpatients with dementia who visited our department between April 1, 2013 and March 31, 2021, were included in this study. Demographic data, dementia subtypes, and regular medication use at the time of the first outpatient visit were investigated. The association between antipsychotic prescriptions and referral sources, dementia subtypes, antidementia drug use, polypharmacy, and prescription of potentially inappropriate medications (PIMs) was evaluated. RESULTS: The antipsychotic prescription rate for patients with dementia was 11.5%. In a comparison of dementia subtypes, the antipsychotic prescription rate was significantly higher for patients with dementia with Lewy bodies (DLB) than for those with all other dementia subtypes. In terms of concomitant medications, patients taking antidementia drugs, polypharmacy, and PIMs were more likely to receive antipsychotic prescriptions than those who were not taking these medications. Multivariate logistic regression analysis showed that referrals from psychiatric institutions, DLB, N-methyl-d-aspartate (NMDA) receptor antagonists, polypharmacy, and benzodiazepine were associated with antipsychotic prescriptions. CONCLUSIONS: Referrals from psychiatric institutions, DLB, NMDA receptor antagonist, polypharmacy, and benzodiazepine were associated with antipsychotic prescriptions for patients with dementia. To optimise prescription of antipsychotics, it is necessary to improve cooperation between local and specialised medical institutions for accurate diagnosis, evaluate the effects of concomitant medication administration, and solve the prescribing cascade.

Influence of Psychotropic Pro Re Nata Drug Use on Outcomes in Hospitalized Patients with Schizophrenia.

Objective: In the treatment of patients with schizophrenia, pro re nata (PRN) drugs are commonly prescribed for medical indications such as agitation, acute psychiatric symptoms, insomnia, and anxiety. However, high-quality evidence supporting the use of PRN medications is lacking, and these drugs are administered on the basis of clinical experience and habits. Therefore, the actual use of psychotropic PRN drugs and its influence on the patients' outcomes need to be investigated. Methods: This study included 205 patients who underwent inpatient treatment for schizophrenia. We investigated the prescription of psychotropic drugs before admission and at discharge, as well as the dosing frequency of PRN drugs during hospitalization. We also examined the influence of psychotropic PRN drug use on hospitalization days, antipsychotic polypharmacy, and readmission rates. Results: Patients who used psychotropic PRN drugs during hospitalization had significantly longer hospitalization days (p = 7.5 × 10-4) and significantly higher rates of antipsychotic polypharmacy (p = 2.4 × 10-4) at discharge than those who did not use psychotropic PRN drugs. Moreover, a higher number of psychotropic PRN drugs used per day was associated with higher readmission rates within 3 months of discharge (p = 4.4 × 10-3). Conclusion: Psychotropic PRN drug use is associated with prolonged hospitalization, antipsychotic polypharmacy, and increased readmission rates in inpatients with schizophrenia. Therefore, psychiatric symptoms should be stabilized with regularly prescribed medications without the extensive use of psychotropic PRN drugs. Moreover, a system for monitoring and reexamining PRN drug use needs to be established.

Spontaneous Shrinkage of isocitrate dehydrogenase (IDH)-mutant astrocytoma caused by intra-tumoural cyst rupture: a case report.

BACKGROUND: T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign is a specific imaging finding of isocitrate dehydrogenase (IDH)-mutant astrocytomas. Histologically, a hypointense area on FLAIR images indicates the presence of microcysts. Here we report a case of IDH-mutant astrocytoma that shrunk spontaneously. CASE DESCRIPTION: A 26-year-old woman presented with a complaint of headache. Her magnetic resonance (MR) images revealed a lesion mass with a T2-FLAIR mismatch sign in the left frontal lobe. Subsequently, after 1 month, she was referred to our department, and we found that the lesion had unexpectedly shrunk; however, no further shrinkage was observed in the next 3 months. Furthermore, a biopsy was performed, and the results indicated a diagnosis of astrocytoma, IDH-mutant CNS WHO grade 3. Thus, she underwent subtotal resection. We found no neurological deficits in the patient, and she received 60 Gy of radiotherapy at the local site and chemotherapy with nimustine hydrochloride (ACNU), followed by the administration of ACNU every 8 weeks for 2 years. Overall, after 36 months of tumour resection, she was in good health and exhibited no recurrence. Notably, her histological and MR image findings suggested that the macroscopic cyst was formed by the fusion of microcysts, which is a characteristic feature of IDH-mutant astrocytoma with a T2-FLAIR mismatch sign, and that the tumour shrunk because of the rupture of the cyst in the Sylvian cistern. CONCLUSION: The present case report suggests that IDH-mutant astrocytoma cannot be ruled out even when the lesion shrinks spontaneously.

Comparison of gene expression profiles among caste differentiations in the termite Reticulitermes speratus.

Termite castes express specialized phenotypes for their own tasks and are a good example of insect polyphenism. To understand the comprehensive gene expression profiles during caste differentiation, RNA-seq analysis based on the genome data was performed during the worker, presoldier, and nymphoid molts in Reticulitermes speratus. In this species, artificial induction methods for each molt have already been established, and the time scale has been clarified. Three different periods (before the gut purge (GP), during the GP, and after the molt) were discriminated in each molt, and two body parts (head and other body regions) were separately sampled. The results revealed that many differentially expressed genes (head: 2884, body: 2579) were identified in each molt. Based on the independent real-time quantitative PCR analysis, we confirmed the different expression patterns of seven out of eight genes in the presoldier molt. Based on the GO and KEGG enrichment analyses, the expressions of genes related to juvenile hormone titer changes (e.g., JH acid methyltransferase), nutrition status (e.g., Acyl-CoA Delta desaturase), and cell proliferation (e.g., insulin receptor), were shown to specifically fluctuate in each molt. These differences may have a crucial impact on caste differentiation. These data are important resources for future termite sociogenomics.

Genomic and transcriptomic analyses of the subterranean termite Reticulitermes speratus: Gene duplication facilitates social evolution.

Termites are model social organisms characterized by a polyphenic caste system. Subterranean termites (Rhinotermitidae) are ecologically and economically important species, including acting as destructive pests. Rhinotermitidae occupies an important evolutionary position within the clade representing a transitional taxon between the higher (Termitidae) and lower (other families) termites. Here, we report the genome, transcriptome, and methylome of the Japanese subterranean termite Reticulitermes speratus Our analyses highlight the significance of gene duplication in social evolution in this termite. Gene duplication associated with caste-biased gene expression was prevalent in the R. speratus genome. The duplicated genes comprised diverse categories related to social functions, including lipocalins (chemical communication), cellulases (wood digestion and social interaction), lysozymes (social immunity), geranylgeranyl diphosphate synthase (social defense), and a novel class of termite lineage-specific genes with unknown functions. Paralogous genes were often observed in tandem in the genome, but their expression patterns were highly variable, exhibiting caste biases. Some of the assayed duplicated genes were expressed in caste-specific organs, such as the accessory glands of the queen ovary and the frontal glands of soldier heads. We propose that gene duplication facilitates social evolution through regulatory diversification, leading to caste-biased expression and subfunctionalization and/or neofunctionalization conferring caste-specialized functions.

Unilateral nephrectomy for young infants with congenital nephrotic syndrome of the Finnish type.

BACKGROUND: The management of congenital nephrotic syndrome of the Finnish type (CNF) is challenging. It is difficult to withdraw intravenous albumin infusions, resulting in long-term hospitalization. In addition, fatal hypotension after bilateral nephrectomy has been reported. In our center, we have performed unilateral nephrectomy during early infancy. METHODS: Infants diagnosed with CNF between 2011 and 2020 in our institution were enrolled. We examined the clinical course before and after unilateral nephrectomy and evaluated the effectiveness of this strategy. RESULTS: Seven patients (all showing NPHS1 mutations) were enrolled. All required daily intravenous albumin infusion via central venous catheter (CVC). Unilateral nephrectomy was performed at a median of 76 days of age (59-208 days). Surgical complications did not occur in any of patients. The mean albumin dose was decreased after unilateral nephrectomy (2.0 vs 0.4 g/kg/day; p = 0.02). Intravenous albumin infusion could be withdrawn at a median of 17 days, the CVC removed at a median of 21 days, and they discharged at a median of 82 days after unilateral nephrectomy. Although bacterial infections were noted seven times before unilateral nephrectomy, only one episode occurred after surgery. Four patients initiated peritoneal dialysis at two to three years of age and all of them underwent kidney transplantation thereafter. CONCLUSIONS: Unilateral nephrectomy during early infancy may be an effective treatment allowing for withdrawal from albumin infusion, prevention of complications, withdrawal from CVCs and shortening hospital stay for patients with CNF.

Successful endoscopic surgical treatment of pleuroperitoneal communication in two infant cases.

BACKGROUND: Pleuroperitoneal communication (PPC) is an uncommon, but potentially life-threatening complication of peritoneal dialysis (PD). If a fistula does not close with conservative treatment, surgical repair is required. However, approximately half of these patients are forced to shift from PD to hemodialysis. Although it is important to confirm the site of the fistula to achieve a successful surgical treatment, this identification is more difficult in pediatric patients than in adults. CASE PRESENTATION: We report two infantile cases of severe PPC associated with PD. In both cases, the age at onset was less than 2 years, and right-sided pleural effusion with dyspnea was observed. PPC was diagnosed by the change in color of the pleural fluid after the injection of a dye into the peritoneal cavity. Peritoneal scintigraphy and single-photon emission computed tomography and computed tomography (SPECT/CT) were performed, and these were effective in locating the fistula site. Endoscopic surgery (video-assisted thoracic surgery (VATS) and laparoscopic surgery) was performed. Indocyanine green (ICG), which was injected into the abdominal cavity, showed the exact site of the fistula. The fistula was successfully closed by attaching an absorbable sheet to it from the thoracic side and an autograft (the falciform ligament) to it from the abdominal side in one patient. In the other patient, the fistula site was resected and sutured, and reinforced with an absorbable sheet. In both cases, PD was resumed without any complication. CONCLUSION: We successfully treated two infants of PPC by endoscopic surgery. To identify the fistula site, the ICG navigation method was useful. Even in small infants, PPC can be treated successfully by endoscopic surgical repair if the site of the fistula is identified.

Eosinophilic peritonitis in children on chronic peritoneal dialysis.

BACKGROUND: Eosinophilic peritonitis (EP) is sometimes difficult to distinguish from bacterial peritonitis (BP) at onset, as they are often overlapping. Previous reports show EP occurs more frequently in infants, although the reason is unknown. METHODS: The study population was 77 pediatric patients receiving chronic peritoneal dialysis (PD) in our center. We compared clinical and laboratory data at onset of EP with those of BP. We also investigated age distribution at onset of EP and PD-related surgery. RESULTS: Eleven patients developed EP (18 episodes) and 19 patients developed BP (38 episodes). EP patients showed lower rate of cloudy dialysate (44.4% vs. 74.4%; p = 0.04), lower rate of fever (38.9% vs. 56.4%), lower frequency of abdominal pain (16.7% vs. 38.5%), higher peripheral blood eosinophil counts (/µL) (514 vs. 160; p < 0.001), and lower serum C-reactive protein level (mg/dL) (0.4 vs. 4.7; p < 0.001) than BP patients. Thirteen EP events were observed after 169 surgical interventions. Age at surgery-related EP was similar to age at surgery without EP (2.6 vs. 2.1; p = 0.65). There was no significant difference in postoperative EP occurrence between groups <2 years and ≥ 2 years (6.2% vs. 9.1%; p = 0.48). However, infants received more operations than older children. CONCLUSION: Clinical symptoms in children and laboratory data of EP in children were less severe than those of BP. As incidence of postoperative EP did not differ by age, we speculate that higher incidence of EP in infants might be associated with higher incidence of surgery, although further validation is necessary.

Investigating interest in orthopedic surgery within an entire medical faculty: A cross-sectional study.

BACKGROUND: Discrepancies exist between the magnitude of musculoskeletal problems and the competency of physicians practicing musculoskeletal medicine, which likely stems from medical school-level educational deficiencies. Therefore, inadequate orthopedic surgery education during medical school may affect the number of students aspiring to practice orthopedic surgery. However, the motivating factors underlying medical students' selection of a career specialty are largely unknown. This study aims to use a survey to examine the motivations of medical students who consider orthopedic surgery as a potential career specialty. METHODS: A questionnaire survey was administered to medical students in our medical faculty. The results were stratified on the basis of gender, year, and experience as a patient; results were then compared between students who wished to practice orthopedic surgery and those who did not consider it a potential specialty. RESULTS: Of the 499 students who responded to the questionnaire, 47% considered orthopedic surgery as their career specialty. Being male and having experienced orthopedic surgery as a patient were significant factors influencing the aspiration to practice orthopedic surgery (p < 0.001). In addition, the motivation for choosing orthopedic surgery was academic interest for 55% of students. In the first and fifth years, more than half of the students preferred an orthopedic surgery specialty. The percentage of fifth-year students who were candidates for orthopedic surgery as their career specialty significantly exceeded that of students in other years (p = 0.03). However, the percentage of students considering orthopedic surgery decreased in the sixth year. CONCLUSION: Our findings suggest that orthopedic surgeons should provide a clearer, more informative job description to attract female medical students' attention and change their negative perception of orthopedic surgery. Furthermore, including education that incorporates experiences closer to clinical practice at the medical-school level is important for increasing the number of candidates for orthopedics.

Refractory Hypertension in Infantile-Onset Denys-Drash Syndrome.

Denys-Drash syndrome is characterized by progressive nephropathy, gonadal dysgenesis, and Wilms tumor caused by a WT1 gene mutation. Infants with Denys-Drash syndrome frequently experience severe hypertension, but detailed clinical manifestations have yet to be clarified. Cases of infantile-onset Denys-Drash syndrome with severe hypertension at our hospital were retrospectively analyzed and the pathogenesis of hypertension was investigated. Six infants who received the diagnosis of Denys-Drash syndrome at the median age of 10 days (range: 2-182 days) were enrolled. Five infants had the complication of severe hypertension within a few days of diagnosis. All the patients showed rapid progression to end-stage renal disease and urgently required dialysis due to anuria/oliguria and hypervolemia with a median duration of 7.5 days (range: 0-17 days) on the day after diagnosis. Even under dialysis, all the patients continued to need antihypertensive treatment. Five patients underwent a preventive nephrectomy for Wilms tumor, and one patient underwent a nephrectomy due to progression to Wilms tumor. Two patients developed hypotension after a nephrectomy. The main causes of hypertension were hypervolemia in the predialysis stage, renin-associated hypertension in the dialysis stage, and multiple factors, including increased plasma catecholamine-associated hypertension in the postnephrectomy dialysis stage. At last the follow-up after bilateral nephrectomy, four of the five patients required antihypertensive treatment. Not all the patients showed target organ complications caused by hypertension. Severe hypertension is a common complication of infantile-onset Denys-Drash syndrome. The possibility of hypotension after nephrectomy should be considered in patients with Denys-Drash syndrome.

Histone modifying genes are involved in the molting period during soldier differentiation in Zootermopsis nevadensis.

Caste differentiation in eusocial insects is an outstanding example of phenotypic plasticity. Recent studies indicate that epigenetic regulation, including DNA methylation and histone modification, play a role in the morphological and behavioral polyphenism observed in the caste differentiation of hymenopteran insects. The role of epigenetic regulation in termite caste differentiation, however, is still obscure. In this study, we performed a functional analysis of epigenetic-related genes during soldier differentiation in Zootermopsis nevadensis, for which the entire genome sequence is available. In an incipient colony of this species, the oldest 3rd instar larva (No. 1 larva) always differentiates into a presoldier (intermediate stage of soldier), and the next-oldest 3rd instar larva (No. 2 larva) molts into a 4th instar (which functions as a worker). First, we detected seven epigenetic-related genes with significantly increased expression levels in the soldier-destined No. 1 larvae using RNA-seq data. Second, RNA interference (RNAi) of these seven genes was performed in the No. 1 larvae. RNAi of three histone modifying genes extended the presoldier molting period. Furthermore, these RNAi treatments reduced the expression levels of genes involved in juvenile hormone (JH) synthesis, binding and signaling. These results indicate that epigenetic-related genes do not directly affect termite soldier differentiation; nonetheless, some histone modifying genes have an effect on molting periods, possibly due to the regulation of JH action during soldier differentiation.