Educational challenges for 22q11.2 deletion syndrome in Japan: Findings from a mixed methods survey.

BACKGROUND: The 22q11.2 deletion syndrome (22q11DS) is characterised by a changing pattern of overlapping intellectual, physical, and mental disabilities along the course of one's life. However, the impact of overlapping disorders (multimorbidity) on educational challenges remains unclear. METHOD: A survey was conducted with 88 caregivers of individuals with 22q11DS. A quantitative analysis of educational challenges and support needs divided into age groups (7-12, 13-15, 16-18, and 19 years and over) and a qualitative analysis of the free-text items in the questionnaire was conducted. RESULTS: Caregivers were more interested in comprehensive developmental support when their children were younger, and the emphasis shifted to concerns regarding environments that matched individual characteristics at older ages. Furthermore, when there are multiple disabilities or disorders, support is concentrated on the more obvious disabilities, and the lack of support for the less superficially obvious disabilities associated with multiple difficulties, including mental health problems, can be a challenge for people with 22q11DS and their families. CONCLUSIONS: This study suggests a need for increased focus on multimorbidity and associated disabilities in school education that are difficult to observe because of their mildness or borderline levels if present alone.

Medical, welfare, and educational challenges and psychological distress in parents caring for an individual with 22q11.2 deletion syndrome: A cross-sectional survey in Japan.

Parents of children with 22q11.2 deletion syndrome (22q11DS) experience distress not only due to multimorbidity in the patients, but also due to professionals' lack of understanding about 22q11DS and insufficient support systems. This study investigated relationships between medical, welfare, and educational challenges and parental psychological distress. A cross-sectional survey was conducted on primary caregivers of children with 22q11DS. Participants included 125 parents (114 mothers, 91.2%; average age = 44.3 years) who reported their challenges, psychological distress, and child's comorbidities of 22q11DS. Results showed that the difficulty in going to multiple medical institutions (ß = 0.181, p < 0.05) and lack of understanding by welfare staff and insufficient welfare support systems for 22q11DS (ß = 0.220-0.316, all p < 0.05) were associated with parental psychological distress, even after adjusting for child's comorbidities. In the subsample of parents whose child attended an educational institution, inadequate management in classroom and mismatch between service and users in educational settings were associated with psychological distress (ß = 0.222-0.296, all p < 0.05). This study reveals the importance of assessing not only severity of comorbidities in 22q11DS, but also the medical, welfare, and educational challenges for parental mental health.

Cefepime-induced encephalopathy: Neural mass modeling of triphasic wave-like generalized periodic discharges with a high negative component (Tri-HNC).

AIM: Cefepime, a fourth-generation cephalosporin, acts as a GABAA receptor antagonist. Cefepime-induced encephalopathy (CIE) is frequently overlooked. We aimed to clarify the clinical features, characteristic electroencephalography (EEG), and mechanisms of CIE to aid in its early recognition. METHODS: CIE cases documented by a single-center consultation-liaison team between April 2015 and March 2017 were retrospectively reviewed. For further investigation, neural mass modeling was performed in silico. RESULTS: Three patients with CIE refused medication/examination and showed overt pain, palilalia, and much greater deterioration of eye and verbal response than the motor response, which was possibly related to GABAergic dysfunction. Triphasic wave-like generalized periodic discharges with a high negative component (Tri-HNC) were identified on the EEG of all three cases. The simulation reproduced the characteristic feature of 2-3 Hz Tri-HNC and recovery course on EEG, and a possible involvement of individual differences in pharmacological intervention. It also suggested that auto-inhibition (synaptic inputs from interneuron to interneuron) dysregulation contributed to generating Tri-HNC in CIE. CONCLUSION: As CIE is iatrogenic and continues unless cefepime is stopped, early recognition is crucial. Physicians should be vigilant about altered mental status, pain, and verbal changes in patients taking cefepime. Tri-HNC on EEG can expedite the diagnosis of CIE, and the association between Tri-HNC and CIE suggests that an excitatory and inhibitory imbalance due to the dysfunction of GABAergic interneurons is the underlying mechanism. This modeling may offer a new method of investigating disorders related to GABAergic dysfunction.

Does This Adult Patient With Jolt Accentuation of Headache Have Acute Meningitis?

OBJECTIVE: In order to identify appropriate candidates with suspected meningitis for lumbar puncture (LP), study designs and diagnostic values of jolt accentuation of headache (JA) were reviewed. BACKGROUND: Acute meningitis is a life-threatening disease that requires LP for accurate diagnosis. JA was reported the most sensitive indicator of cerebrospinal fluid pleocytosis; however, subsequent studies have failed to confirm this claim. METHODS: We reviewed articles concerning JA, published prior to December 2017, using MEDLINE and Japanese medical databases. Seven original articles based on independent cohorts were eligible for inclusion and articles citing these 7 were thoroughly searched (11 in total). Additionally, all medical records of our previously reported cohort were reviewed again to explore how the patients' background influenced diagnostic values of JA. RESULTS: We hypothesized that an oversimplified dichotomy of JA findings, pleocytosis, and meningitis created a misconception that JA is a universal indicator of meningitis. We clarify the difference between them and present altered mental status (AMS) as a key to decrease the sensitivity of JA. Notably, the sensitivity and specificity of JA were relatively low in unselected groups, while they tended to be high in the selected sub-groups with acute onset of headache and fever, without AMS or neurological deficits. Unselected populations included etiologies of pleocytosis other than acute meningitis, which might weaken the association between JA and pleocytosis. CONCLUSION: JA is not a universal, stand-alone, indicator of meningitis in febrile patients with headache. Therefore, we propose a stepwise approach for patients with suspected acute meningitis. AMS or neurological deficits suggest an intracranial pathology, which may necessitate a lumbar puncture. JA seems a useful tool for distinguishing acute aseptic meningitis from upper respiratory infection when used in the selected cohort of febrile patients (≥37°C) with recent-onset headache (within 2 weeks before presentation) and normal mental status. This approach and diagnostic values of JA should be further investigated by prospective studies using operationally sorted candidates.

Accuracy of oncologist assessments of psychiatric problems in cancer inpatients.

OBJECTIVE: Our objective was to examine the accuracy of non-psychiatrist assessments of psychiatric problems in cancer patients. METHOD: We conducted a retrospective chart review of cancer patients who were admitted and referred to the consultation-liaison (C-L) team between January of 2011 and December of 2012. The agreement between non-psychiatrist assessments and final diagnoses by attending C-L psychiatrists was estimated for every category of referral assessment using codes from the International Classification of Mental and Behavioral Disorders (10th revision). The data were obtained from the consultation records of 240 cancer inpatients who were referred to the C-L service at a tertiary care center in Tokyo. RESULTS: The agreement ratio between referring oncologists and psychiatrists differed according to the evaluation categories. The degrees of agreement for the categories of "delirious," "depressive," "dyssomnia," "anxious," "demented," "psychotic," and "other" were 0.87, 0.43, 0.51, 0.50, 0.27, 0.55, and 0.57, respectively. The agreement for all patients was 0.65. Significant differences were observed among seven categories (chi-squared value = 42.454 at p < 0.001 and df = 6). The analysis of means for proportions showed that the degree of agreement for the "delirious" category was significantly higher and that that for the "depressive" category was lower than that for all patients, while for the "demented" category it was close to the lower decision limit but barely significant. One half of the 20 cases who were referred as depressive were diagnosed with delirium, with one quarter of those having continuously impaired consciousness. Some 7 of the 11 cases who were referred as demented were diagnosed as having delirium. SIGNIFICANCE OF RESULTS: The accuracy of non-psychiatrist assessments for psychiatric problems in cancer patients differs by presumed diagnosis. Oncologists should consider unrecognized delirium in cancer inpatients who appear depressed or demented.

How can we identify patients with delirium in the emergency department?: A review of available screening and diagnostic tools.

Delirium is a widespread and serious but under-recognized problem. Increasing evidence argues that emergency health care providers need to assess the mental status of the patient as the "sixth vital sign". A simple, sensitive, time-efficient, and cost-effective tool is needed to identify delirium in patients in the emergency department (ED); however, a stand-alone measurement has not yet been established despite previous studies partly because the differential diagnosis of dementia and delirium superimposed on dementia (DSD) is too difficult to achieve using a single indicator. To fill up the gap, multiple aspects of a case should be assessed including inattention and arousal. For instance, we proposed the 100 countdown test as an effective means of detecting inattention. Further dedicated studies are warranted to shed light on the pathophysiology and better management of dementia, delirium and/or "altered mental status". We reviewed herein the clinical questions and controversies concerning delirium in an ED setting.

[An Adult Case of 22q11.2 Deletion Syndrome with Congenital Abnormalities and Neurodevelopmental Disorders, Which Remained Undiagnosed Until Presentation of Auditory Hallucinations].

22q11.2 deletion syndrome (22q11.2 DS) is characterized by cardiac defects, abnormal facial features, thymic hypoplasia, cleft palate, and hypocalcemia, including DiGeorge syndrome (DGS), velocardiofacial syndrome (VCFS), and conotruncal anomaly face (CTAF) syndrome. Psychiatric symptoms were recently shown to be very common in patients with 22q11.2 DS, prompting greater interest in this syndrome. Early diagnosis during childhood based on a con- stellation of physical features is optimal ; however, as some patients remain undiagnosed until the presentation of other symptoms in adult life, psychiatrists are well advised to familiarize themselves with basic information concerning 22q11.2 DS. A 25-year-old woman presenting with auditory hallucinations was referred to A hospital for examination and treatment. Her family history revealed both paternal and maternal rela- tives with schizophrenia. At birth, she presented a cleft palate and ventricular septum defect. She first became ambulatory at age 4 and became verbal a year later. Her intelligence quotient was estimated at around 40 and mental retardation (DSM-IV) with autistic features was diag- nosed at age 7. After graduating from a special high school, she obtained fulltime employment in a workshop. However, auditory hallucinations began disrupting her life from 22 years of age. Although olanzapine temporarily alleviated her symptoms, the resultant extrapyramidal symp- toms worsened and she was referred to A hospital again at age 25. The patient presented with micrognathia and a flat nasal root and spoke a maximum of 3 words per sentence in a very high and indistinct tone. A cardiac defect (ventricular septal defect), scoliosis, and low platelets were also observed. The diagnosis of 22qll.2 DS was confirmed using fluorescence in situ hybridization (FISH). The patient and her family were subsequently introduced to a 22q11.2 DS patients' support group. Careful genetic counseling is paramount, but the diagnosis of 22q11.2 DS can make updated information, official aid, and access to support groups available to patients and their family. Emergency complications such as seizures due to hypocalcemia can also be anticipated. The comparatively late diagnosis of 22q11.2 DS in our patient, which went undetected until the presentation of auditory hallucinations, in the context of mental retardation with autis- tic features (DSM-IV) underscores the importance of detailed clinical observation. "One rare variant" possibly points out the essence of psychiatric pathophysiology. Moreover, 22q11.2 DS has been listed as an intractable disease in Japan since 2015. When patients present with neurodevelopmental disorders and schizophrenic symptoms, we should carefully observe their physical features for clues to the possible diagnosis of 22q11.2 DS.

Cerebrospinal fluid/blood glucose ratio as an indicator for bacterial meningitis.

BACKGROUND: Bacterial meningitis is an emergent disease requiring prompt diagnosis and treatment with appropriate antimicrobials. Although the lumbar puncture is widely used as a diagnostic tool for bacterial meningitis, it remains unclear which value in cerebrospinal fluid (CSF) analysis in emergency laboratory tests precisely predicts the presence of bacterial meningitis. METHODS: This is a single-center, retrospective review of medical records to determine which emergency laboratory CSF test results are useful for predicting bacterial meningitis. The diagnosis of meningitis is made when the white blood cell count in CSF exceeds 5 cells/µL, while the diagnosis of bacterial meningitis additionally requires the growth of a pathogen from a CSF culture or the identification of a pathogen in Gram staining of CSF specimen. RESULTS: We identified 15 patients with bacterial meningitis and 129 patients with aseptic meningitis. While neutrophil-predominant pleocytosis and a decreased glucose level in CSF can predict the presence of bacterial meningitis, the CSF/blood glucose ratio is more precise (optimal cut-off=0.36, sensitivity=92.9%, specificity=92.9%, area under the curve=.97) even after administration of antimicrobials prior to examination in the emergency department. CONCLUSION: This study suggests that the CSF/blood glucose ratio may be a better single indicator for bacterial meningitis. Since the CSF glucose and blood glucose values are promptly and easily obtained from a lumbar puncture, the CSF/blood glucose ratio should be considered as a timely diagnostic indicator of bacterial meningitis. It may also help exclude the diagnosis of bacterial meningitis especially in cases in which no microorganisms can be cultured.

EEG and video documentation of benzodiazepine challenge in catatonic stupor: A case report.

INTRODUCTION: Catatonia, a psychomotor disorder characterized by diverse clinical signs, including stupor and mutism, remains elusive in its causes and a challenge to diagnose. Moreover, it is often underrecognized due to its resemblance to disorders of consciousness. However, when diagnosing catatonia, an antipsychotic medication may exacerbate the condition. The first-line treatment typically includes benzodiazepines and/or electroconvulsive therapy (ECT). CASE REPORT: A 60-year-old woman with systemic lupus erythematosus (SLE) and epilepsy presented with catatonic stupor. Despite stable treatment, she experienced an acute deterioration in consciousness, requiring hospitalization. Her condition improved markedly following a benzodiazepine challenge, as documented on EEG. This improvement was short-lived, but a second benzodiazepine challenge restored her from E1V1M1 (stupor) to E4V5M6 within minutes, as documented by a video recording. The patient was treated with lorazepam 1.5 mg/day orally and did not experience further relapses. DISCUSSION: The diagnosis of catatonia had been based on her scores on the Bush-Francis Catatonia Rating Scale (BFCRS; Screening, 6/14; Severity, 19), despite meeting only two DSM-5 criteria for catatonia (stupor and mutism). The diagnosis was supported by EEG and video documentation, excluding other potential differential diagnoses such as nonconvulsive status epilepticus and encephalopathy. Additional quantitative EEG analyses indicated that benzodiazepine administration increased brainwide alpha and beta band power significantly, suggesting that the benzodiazepine normalized attention, consciousness, and long-range synchronization. This report additionally emphasizes the significance of video recordings in managing catatonia, and it helps in accurately tracking symptoms, documenting comprehensively, and improving patient understanding, which is crucial for treatment adherence.

Integrating psychiatry into basic clinical skills: A three-year nationwide quantitative assessment of postgraduate training programs.

Aim: The aim of this study was to develop quantitative outcome indicators for psychiatric training programs integrated into the General Medicine In-Training Examination (GM-ITE) and to investigate which characteristics correlate with high scores in psychiatry. Methods: A nationwide cross-sectional study was conducted over 3 fiscal years (2021-2023). An anonymous online questionnaire was distributed to postgraduate year 1 and 2 residents who completed the GM-ITE. The primary outcome was GM-ITE score, with a particular focus on psychiatry. Multiple-choice questions for the psychiatry field were created by board-certified psychiatrists with various subspecialties, then reviewed and piloted. Multiple regression analysis examined correlations between GM-ITE score and various resident and facility characteristics. Results: A total of 18,226 residents participated over the 3 years, of whom 5%-6% aspired to specialize in psychiatry. Quantitative scores were effective in the psychiatry field across all 3 years. Psychiatry aspirants had lower scores in internal medicine, emergency, and total scores but higher scores in psychiatry. Residents from university hospitals had lower psychiatry scores, while the number of psychiatry beds and supervising psychiatrists did not correlate with higher psychiatry scores. These findings indicate the need for psychiatric training programs distinct from general internal medicine and emergency training. Conclusion: Based on these quantitative psychiatry scores, this study highlights the necessity of improving physical assessment skills during residency for psychiatry aspirants, who score higher in psychiatry. Future research should identify effective training programs and facility practices that lead to higher psychiatry scores among residents, and thereby better integrate psychiatry into basic clinical skills.

Absence of jolt accentuation of headache cannot accurately rule out meningitis in adults.

BACKGROUND: Meningitis is a common emergency disease. Signs and symptoms easily observed at the bedside are needed because early recognition of the possibility of meningitis is necessary for the decision to perform lumbar puncture. Jolt accentuation of headache has been reported to be the most sensitive diagnostic test; however, limited articles have reproduced its sensitivity. METHODS: This is a single-center retrospective medical record review between 2007 and 2012. We diagnosed meningitis based on the criterion standard that cerebrospinal fluid total cells is more than 5/mm(3), in accordance with previous studies. All diagnostic and management decisions including Kernig sign, nuchal rigidity, and jolt accentuation of headache were at the physician's discretion. We calculated the sensitivity and specificity of well-known signs and symptoms of meningitis and, especially, compared the efficacy of jolt accentuation of headache with previous studies. RESULTS: We investigated 531 adult patients who were suspected of meningitis and had lumbar puncture performed. Of these patients, 139 had meningitis. Background characteristics and vital signs were not clinically different between the 2 groups, although classic tetralogy of bacterial meningitis (fever, nuchal rigidity, mental disturbance, and headache) was worth investigated. The sensitivity and specificity of jolt accentuation of headache were 63.9% (95% confidence interval, 51.9%-76.0%) and 43.2% (34.7%-51.6%), respectively. CONCLUSION: The absence of jolt accentuation of headache test cannot, on its own, accurately rule out meningitis in adults. Further studies are warranted to reproduce this result and to discover better bedside diagnostic tests.

Are hospitals with both medical/surgical and psychiatric services associated with decreased difficulty in ambulance transfer for patients with self-harm behaviour? A nationwide retrospective observational study using ambulance transfer data in Japan.

OBJECTIVES: Ambulance diversion and prolonged prehospital transfer time have a significant impact on patient care outcomes. Self-harm behaviour in particular is associated with difficulty in hospital acceptance and longer prehospital transfer time. This study aimed to determine if hospitals with both medical/surgical and psychiatric inpatient beds and high-level emergency care centres are associated with a decreased rate of difficulty in hospital acceptance and shorter prehospital transfer time for patients seeking medical care after self-harm behaviour. DESIGN AND SETTING: A retrospective observational study using the database of Japanese ambulance dispatch data in 2015. PARTICIPANTS: Patients who were transferred by ambulances after self-harm behaviour. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Multivariable logistic regression analysis and multivariable linear regression analysis were performed to assess whether the presence of hospitals with both medical/surgical and psychiatric inpatient beds and high-level emergency care centres in the city were associated with a decreased rate of difficulty in hospital acceptance and shorter prehospital transfer time. RESULTS: The number of transfers due to self-harm behaviour in 2015 was 32 849. There was an association between decreased difficulty in hospital acceptance and the presence of high-level emergency care centres (OR 0.63, 95% CI 0.55 to 0.71, p<0.01) and hospitals with both medical/surgical and psychiatric inpatient beds (OR 0.50, 95% CI 0.38 to 0.66, p<0.01). There was a significant reduction in prehospital transfer time in the city with high-level emergency care centres (4.21 min, 95% CI 3.53 to 4.89, p<0.01) and hospitals with medical/surgical and psychiatric inpatient beds (3.46 min, 95% CI 2.15 to 4.77, p<0.01). CONCLUSION: Hospitals with both medical/surgical and psychiatric inpatient beds and high-level emergency care centres were associated with significant decrease in difficulty in hospital acceptance and shorter prehospital transfer time.

Relationship between high trait anxiety in 22q11.2 deletion syndrome and the difficulties in medical, welfare, and educational services.

Aim: The 22q11.2 deletion syndrome (22q11DS) is associated with a high prevalence of mental health comorbidities. However, not enough attention has been paid to the elevated prevalence of high trait anxiety that begins early in life and may be enduring. We sought to identify specific medical, welfare, or educational difficulties associated with high trait anxiety in 22q11DS. Methods: A questionnaire-based survey was conducted for the parents of 22q11DS individuals (N = 125). First, a multiple regression analysis was conducted to confirm the hypothesis that high trait anxiety in individuals with 22q11DS would be associated with parents' psychological distress. This was based on 19 questionnaire options regarding what difficulties the parents currently face about their child's disease, characteristics, and traits. Next, we explored what challenges faced in medical, welfare, and educational services would be associated with the trait anxiety in their child. Results: The multiple regression analysis confirmed that the high trait anxiety was significantly associated with parental psychological distress (ß = 0.265, p = 0.018) among the 19 clinical/personal characteristics of 22q11DS. Furthermore, this characteristic was associated with various difficulties faced in the medical care, welfare, and education services, and the parent-child relationship. Conclusion: To our knowledge, this is the first study to clarify quantitatively how the characteristic of high anxiety level in 22q11DS individuals is related to the caregivers' perceived difficulties in medical, welfare, and educational services. These results suggest the necessity of designing service structures informed of the fact that high trait anxiety is an important clinical feature of the syndrome.