Giant T waves and QT interval prolongation associated with guanfacine toxicity.

INTRODUCTION: Guanfacine is a central α2-adrenergic receptor agonist that produces drowsiness, bradycardia, hypotension, and occasionally QT interval prolongation. We discuss giant T waves associated with guanfacine toxicity. CASE SUMMARIES: Three patients presented to the hospital with histories and physical findings compatible with guanfacine toxicity. Supratherapeutic concentrations were confirmed in two of them. All three developed QT interval prolongation and giant T waves on the electrocardiogram. Giant T waves occur commonly in patients with acute myocardial infarct and hyperkalemia, as well as rarely with a number of other cardiac and non-cardiac causes. CONCLUSION: Guanfacine toxicity may cause the novel electrocardiographic finding of 'giant T wave with QT interval prolongation'. Further studies are warranted to investigate the association between the novel electrocardiographic finding and guanfacine toxicity, as well as its diagnostic utility in such cases.

A Case Report of Under-Recognized Conditions in Pulmonary Embolism: Patent Foramen Ovale and Right Ventricular Thrombus.

Pulmonary embolism (PE) is a potentially life-threatening condition that presents with a spectrum of clinical symptoms ranging from asymptomatic to hemodynamic instability. The early diagnosis in the emergency department is often challenging. Although the association between patent foramen ovale (PFO) and thromboembolic events in patients with PE is well-documented, the significance of the presence of PFO in patients with PE may be underrecognized. In addition, the occurrence of right ventricular thrombus (RVT) in PE is a rare but significant complication with implications for disease management. We report a case of acute-on-chronic PE with concurrent bilateral renal infarction due to a paradoxical embolus, alongside RVT. A 35-year-old male presented at our emergency department with complaints of sudden onset abdominal pain. Bilateral renal infarction was identified on a contrast-enhanced computed tomography (CT). Point-of-care ultrasound showed suggestive findings of PE and RVT. Subsequently, a pulmonary CT angiography confirmed bilateral PE, a PFO, and RVT. The patient was effectively managed with thrombolytic therapy, with extracorporeal membrane oxygenation on standby. This case highlights the need to recognize the diverse clinical manifestations of PE and the importance of considering coexisting PFO and RVT in affected patients. The diagnosis of PE can be complex when symptoms overlap with arterial thrombosis, such as renal infarction secondary to a PFO. In addition, RVT, although uncommon, is a serious complication in patients with PE that may require careful evaluation for thrombolytic or anticoagulant therapy. It is critical to consider the possibility of a PFO in all cases of PE, even in the absence of arterial embolism, and to promptly evaluate for RVT prior to initiating treatment.

QT-Interval Prolongation Associated with Supratherapeutic Guanfacine Concentration: A Case Report.

INTRODUCTION: Guanfacine, an alpha-2 adrenergic agonist, is used to treat attention deficit hyperactivity disorder (ADHD). Although cardiovascular effects including hypotension and bradycardia are common adverse effects of guanfacine, the effect of guanfacine on QT intervals remains unclear. The association between the serum concentration of guanfacine and its toxicity has also not been fully investigated. CASE REPORT: This is a case of a 21-year-old woman with ADHD who developed repeated presyncope 1 day before admission. She was taking 3 mg of extended-release guanfacine and 50 mg of sertraline. On admission, she had bradycardia and hypotension. An electrocardiogram (ECG) showed a QT interval of 0.68 s and a QTcF interval of 0.648 s. The QT intervals were manually measured and corrected by the Fridericia formula (QTcF = QT/RR1/3). Although she denied taking an overdose of guanfacine and other drugs, we suspected guanfacine toxicity. The serum guanfacine concentration was 13.0 ng/mL on admission and decreased to 3.2 ng/mL on day 1 and 0.4 ng/mL on day 2. Changes in QTcF intervals and her vital signs correlated with serum guanfacine concentrations. CONCLUSION: Supratherapeutic serum guanfacine concentrations may induce QT prolongation.

Severe Recurrence of Neuroleptic Malignant Syndrome: Usefulness of Dexmedetomidine for Antipsychotic Withdrawal.

Neuroleptic malignant syndrome (NMS) is a potentially fatal side effect that occurs in patients taking antipsychotics. Patients with NMS are often forced to rechallenge antipsychotic medications to control the underlying psychiatric symptoms. We present a case of severe recurrence of NMS in a patient in whom the administration of antipsychotics was restarted two days after NMS resolution. A 19-year-old man with somatic symptom disorder had been transported for fever, tachycardia, rigidity, and disturbance of consciousness. He was taking atypical antipsychotics with poor medication compliance. A diagnosis of NMS was made, and he was treated with administration of dantrolene sodium and benzodiazepines under tracheal intubation. On day 2, he was extubated. On day 4, his symptoms of NMS improved, but psychiatric symptoms rapidly exacerbated. He and his family strongly insisted on discharge, and we therefore unavoidably restarted the administration of antipsychotics. On day 37, he was retransported, and a diagnosis of recurrence of NMS was made. Blood examination showed marked deterioration of acute kidney injury and disseminated intravascular coagulation compared to those at the first admission. Without the administration of antipsychotics, his psychiatric symptoms were poorly controlled. Administration of dexmedetomidine helped his agitation to be well controlled without antipsychotics for two weeks. Short-term restart of antipsychotic drugs in patients with NMS may result in more severe NMS relapse. Dexmedetomidine may be useful for NMS patients when the administration of antipsychotics cannot be restarted. When antipsychotics are unavoidably rechallenged in patients with NMS, the risk of severe relapse should be taken into consideration, and dexmedetomidine may be used for prolongation of the withdrawal period.

Improving taxonomic classification of marine zooplankton by molecular approach: registration of taxonomically verified 18S and 28S rRNA gene sequences.

Background: Zooplankton plays an important role in the marine ecosystem. A high level of taxonomic expertise is necessary for accurate species identification based on morphological characteristics. As an alternative method to morphological classification, we focused on a molecular approach using 18S and 28S ribosomal RNA (rRNA) gene sequences. This study investigates how the accuracy of species identification by metabarcoding improves when taxonomically verified sequences of dominant zooplankton species are added to the public database. The improvement was tested by using natural zooplankton samples. Methods: rRNA gene sequences were obtained from dominant zooplankton species from six sea areas around Japan and registered in the public database for improving the accuracy of taxonomic classifications. Two reference databases with and without newly registered sequences were created. Comparison of detected OTUs associated with single species between the two references was done using field-collected zooplankton samples from the Sea of Okhotsk for metabarcoding analysis to verify whether or not the newly registered sequences improved the accuracy of taxonomic classifications. Results: A total of 166 sequences in 96 species based on the 18S marker and 165 sequences in 95 species based on the 28S marker belonging to Arthropoda (mostly Copepoda) and Chaetognatha were registered in the public database. The newly registered sequences were mainly composed of small non-calanoid copepods, such as species belonging to Oithona and Oncaea. Based on the metabarcoding analysis of field samples, a total of 18 out of 92 OTUs were identified at the species level based on newly registered sequences in the data obtained by the 18S marker. Based on the 28S marker, 42 out of 89 OTUs were classified at the species level based on taxonomically verified sequences. Thanks to the newly registered sequences, the number of OTUs associated with a single species based on the 18S marker increased by 16% in total and by 10% per sample. Based on the 28S marker, the number of OTUs associated with a single species increased by 39% in total and by 15% per sample. The improved accuracy of species identification was confirmed by comparing different sequences obtained from the same species. The newly registered sequences had higher similarity values (mean >0.003) than the pre-existing sequences based on both rRNA genes. These OTUs were identified at the species level based on sequences not only present in the Sea of Okhotsk but also in other areas. Discussion: The results of the registration of new taxonomically verified sequences and the subsequent comparison of databases based on metabarcoding data of natural zooplankton samples clearly showed an increase in accuracy in species identification. Continuous registration of sequence data covering various environmental conditions is necessary for further improvement of metabarcoding analysis of zooplankton for monitoring marine ecosystems.

Increased care-need in older long-term care insurance users after the 2018 Japan Floods: a retrospective cohort study based on the Japanese long-term care insurance claims.

BACKGROUND: Level of care-need (LOC) is an indicator of elderly person's disability level and is officially used to determine the care services provided in Japan's long-term care insurance (LTCI) system. The 2018 Japan Floods, which struck western Japan in July 2018, were the country's second largest water disaster. This study determined the extent to which the disaster affected the LOC of victims and compared it with that of non-victims. METHODS: This is a retrospective cohort study, based on the Japanese long-term care insurance claims from two months before (May 2018) to five months after the disaster (December 2018) in Hiroshima, Okayama, and Ehime prefectures, which were the most severely damaged areas in the country. A code indicating victim status, certified by a residential municipality, was used to distinguish between victims and non-victims. Those aged 64 years or younger, those who had the most severe LOC before the disaster, and those whose LOC increased even before the disaster were excluded. The primary endpoint was the augmentation of pre-disaster LOC after the disaster, which was evaluated using the survival time analysis. Age, gender, and type of care service were used as covariates. RESULTS: Of the total 193,723 participants, 1,407 (0.7%) were certified disaster victims. Five months after the disaster, 135 (9.6%) of victims and 14,817 (7.7%) of non-victims experienced the rise of LOC. The victim group was significantly more likely to experience an augmentation of LOC than the non-victim group (adjusted hazard ratio 1.24; 95% confidence interval 1.06-1.45). CONCLUSIONS: Older people who were affected by the disaster needed more care than before and the degree of care-need increase was substantially more than non-victims. The result suggests that natural disasters generate more demand for care services among the older people, and incur more resources and cost for society than before.

CT chest-cerebral angiography for basilar artery occlusion caused by pulmonary arteriovenous malformation.

Early diagnosis of basilar artery occlusion (BAO) based only on clinical findings is challenging. We present a fully recovered case of BAO caused by pulmonary arteriovenous malformation (PAVM) that was diagnosed early using a protocol for CT angiography (CTA) and promptly treated with endovascular therapy (EVT). A woman in her 50s complained of vertigo with normal level of consciousness (LOC). On arrival, her LOC decreased to a Grass Coma Scale score of 12, and we performed a CT chest-cerebral angiography protocol. Head CTA showed BAO, and an intravenous tissue plasminogen activator was administered, followed by EVT. Chest contrast-enhanced CT showed PAVM in segment 10 of the left lung, which was treated with coil embolisation. For patients with a complaint of vertigo, BAO should be suspected, even if they have an initially normal LOC. A CT chest-cerebral angiography protocol is useful for prompt diagnosis and treatment of BAO and can reveal undetermined causes.

Unusual cause of retroperitoneal hemorrhage: Acute deep vein thrombosis.

Retroperitoneal hemorrhage is rarely associated with acute deep vein thrombosis (DVT). We present a case of retroperitoneal hemorrhage due to disruption of the external iliac vein associated with acute DVT, which was carefully treated with an anticoagulant. A 78-year-old woman complained of acute abdominal pain. Contrast-enhanced computed tomography (CT) showed left retroperitoneal hematoma and venous thrombosis from just above the bifurcation of the inferior vena cava to the left femoral vein. She was admitted for conservative treatment without an anticoagulant. The next day, she developed pulmonary embolism (PE), but administration of an anticoagulant was not started because of the possibility of rebleeding. Forty-four hours after the onset of PE, unfractionated heparin was administrated intravenously. After initiation of anticoagulation, retroperitoneal hemorrhage did not expand and PE did not get worse. Follow-up contrast-enhanced CT suggested May-Thurner syndrome (MTS). She was uneventfully discharged home on the 35th day with oral warfarin. Retroperitoneal hemorrhage is rarely caused by acute DVT in the case of potential causes such as MTS. In such cases, the timing of initiation of anticoagulation is difficult considering the possibility of rebleeding from retroperitoneal hemorrhage. We should start anticoagulation based on both the state of hemostatic and preventive procedures for PE. Learning objective: Retroperitoneal hemorrhage is rarely caused by acute deep vein thrombosis because of the iliac vein rupture. The subsequent occurrence of pulmonary embolism (PE) makes it more complicated and critical because treatment strategies for these two conditions are the opposite: hemostasis versus anticoagulation. The initiation of administration of an anticoagulant should be determined based on status of patients, the procedures of hemostasis, and prevention of PE.

Understanding the Trajectory to a Diagnosis of Tetanus: A Descriptive Study.

Background and objective Tetanus is a rare but potentially fatal disease in developed countries, including Japan. It is very difficult to diagnose this condition early because of its broad symptomatology and the lack of familiarity with tetanus among both physicians and patients. In this study, we aimed to describe the clinical manifestations of tetanus and to examine as to which departments/branches of medicine patients consult in order to provide helpful information for diagnosing this challenging condition. Materials and methods This was a descriptive, retrospective study conducted at a single tertiary hospital from January 2011 to December 2021. Patients with generalized tetanus, cephalic tetanus, and local tetanus presenting to our emergency department were included in the study. We examined the clinical manifestations and departments that patients with tetanus visited first. Additionally, the initial diagnosis and diagnostic evaluation before the diagnosis were examined. Results Of the total 10 patients included in the study, nine had generalized tetanus and one had cephalic tetanus; the common initial manifestations were neck stiffness (30%), dysarthria (20%), and trismus (20%). Of note, 80% of patients also complained of dysphagia before the diagnosis. Patients first visited various departments, including a dental clinic (30%) and the department of otorhinolaryngology (20%). Only two patients were accurately diagnosed with tetanus at the first department they visited. Physicians performed head imaging for all the patients. Conclusions Based on our findings, in Japan, patients with tetanus present with symptoms that physicians interpret or suspect to be associated with disorders of the central nervous system. Meanwhile, patients themselves tend to consider the symptoms as indicative of oral or dental issues. Further prospective studies involving a larger number of participants are needed to investigate the clinical course of tetanus until the establishment of a diagnosis.

Effects of 2018 Japan floods on healthcare costs and service utilization in Japan: a retrospective cohort study.

BACKGROUND: Floods and torrential rains are natural disasters caused by climate change. Unfortunately, such events are more frequent and are increasingly severe in recent times. The 2018 Japan Floods in western Japan were one of the largest such disasters. This study aimed to evaluate the effect of the 2018 Japan Floods on healthcare costs and service utilization. METHODS: This retrospective cohort study included all patients whose receipts accrued between July 2017 and June 2019 in Hiroshima, Okayama, and Ehime prefectures using the National Database of Health Insurance Claims. We used Generalized Estimating Equations (GEEs) to investigate yearly healthcare costs during the pre-and post-disaster periods, quarterly high-cost patients (top 10%), and service utilization (outpatient care, inpatient care, and dispensing pharmacy) during the post-disaster period. After the GEEs, we estimated the average marginal effects as the attributable disaster effect. RESULTS: The total number of participants was 5,534,276. Victims accounted for 0.65% of the total number of participants (n = 36,032). Although there was no significant difference in pre-disaster healthcare costs (p = 0.63), post-disaster costs were $3,382 (95% CI: 3,254-3,510) for victims and $3,027 (95% CI: 3,015-3,038) for non-victims (p < 0.001). The highest risk difference among high-cost patients was 0.8% (95% CI: 0.6-1.1) in the fourth quarter. In contrast, the highest risk difference of service utilization was in the first quarter (outpatient care: 7.0% (95% CI: 6.7-7.4), inpatient care: 1.3% (95% CI: 1.1-1.5), and dispensing pharmacy: 5.9% (95% CI: 5.5-6.4)). CONCLUSION: Victims of the 2018 Japan Floods had higher medical costs and used more healthcare services than non-victims. In addition, the risk of higher medical costs was highest at the end of the observation period. It is necessary to estimate the increase in healthcare costs according to the disaster scale and plan for appropriate post-disaster healthcare service delivery.

A case of colonic fecal impaction caused by excessive dietary fiber intake that was endoscopically treated with intra-fecal injection of a bowel-cleansing agent.

Background and Aim: A 75-year-old man who had eaten half a head of chopped raw cabbage (approximately 600 g) daily was suffering from the left lower pain, abdominal fullness, and constipation. He was diagnosed with colonic ileus and obstructive colitis due to a fecal impaction in the sigmoid-descending junction. During colonoscopy, a tapered catheter was repeatedly inserted into the impacted feces to inject a bowel-cleansing agent. Finally, the feces were broken to be fragmented enough to path the endoscope through. After the procedure, his symptoms were immediately relieved. Relevance for Patients: Excessive dietary fiber intake can induce fecal ileus. Endoscopic treatment with intra-fecal injection of a bowel-cleansing agent is useful and worth attempting for disimpaction of feces.

How the 2018 Japan Floods Impacted Nursing Home Admissions for Older Persons: A Longitudinal Study Using the Long-Term Care Insurance Comprehensive Database.

OBJECTIVES: As disasters become more frequent because of global warming, countries across the world are seeking ways to protect vulnerable older populations. Although these conditions may increase nursing home admission (NHA) rates for older persons, we know of no studies that have directly tested this hypothesis. DESIGN: This was a retrospective cohort study. SETTING AND PARTICIPANTS: We analyzed data from long-term care insurance (LTCI) users in 3 Japanese prefectures that incurred heavy damage from the 2018 Japan Floods, which is the largest recorded flooding disaster in national history. Specifically, we extracted NHA data from the LTCI comprehensive database, both for disaster-affected and unaffected individuals. METHODS: We employed the Cox proportional hazards model to calculate multivariate-adjusted hazard ratios (HRs) for NHAs within a 6-month period following the 2018 Japan Floods, with adjustments for potential confounding factors. RESULTS: Of the 187,861 individuals who used LTCI services during the investigated period, we identified 2156 (1.1%) as disaster affected. The HR for NHA was significantly higher for disaster-affected (vs unaffected) individuals (adjusted HR 3.23: 95% CI 2.88‒3.64), and also higher than the HRs for older age (90-94 years vs 65-69 years: 2.29, CI 1.93‒2.70), cognitive impairment (severe impairment vs normal: 1.40, CI 1.25‒1.57), and physical function (bedridden vs independent: 2.27, CI 1.83‒2.70). According to our subgroup analyses, the adjusted HR for disaster-affected individuals unable to feed themselves was 6.00 (CI 3.68‒9.79), with a significant interaction between the 2 variables (P = .01). CONCLUSIONS AND IMPLICATIONS: Natural disasters increase the risk of NHA for older persons, especially those who are unable to feed themselves. Health care providers and policymakers should understand and prepare for this emerging risk factor.

Diagnostic accuracy of rapid antigen tests in cerebrospinal fluid for pneumococcal meningitis: a systematic review and meta-analysis.

BACKGROUND: Streptococcus pneumoniae is a leading cause of bacterial meningitis worldwide. Conventional microbiological assays take several days and require the use of various drugs for empirical treatment. Rapid antigen tests in cerebrospinal fluid (CSF) may be useful to triage pneumococcal meningitis immediately. OBJECTIVES: To elucidate whether rapid antigen tests in CSF are useful in the triage of pneumococcal meningitis. METHODS: Data sourcesCochrane CENTRAL, MEDLINE, EMBASE, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov databases were searched. Study eligibility criteriaAll types of cohort studies except multiple-group studies, where the sensitivity and specificity of rapid antigen tests in CSF compared with CSF culture can be extracted. ParticipantsPatients with suspected meningitis. TestsRapid antigen tests in CSF. Reference standardsOne or more of the following: blood culture, CSF culture, and polymerase chain reaction in CSF. Assessment of risk of biasThe methodological quality of the included studies was assessed using QUADAS-2. Methods of data synthesisWe used a random-effects bivariate model for the meta-analysis. We conducted a subgroup analysis by dividing studies into types of antigen tests, adults and children, low-income and high-income countries, and with or without exposure to antibiotics before lumbar puncture. RESULTS: Forty-four studies involving 14 791 participants were included. Most studies had a moderate-to-low methodological quality. Summary sensitivity and specificity were 99.5% (95% confidence interval (CI), 92.4-100%) and 98.2% (95% CI, 96.9-98.9%), respectively. Positive predictive values and negative predictive values at the median prevalence (4.2%) in the included studies were 70.8% (95% CI, 56.6-79.9%) and 100% (95% CI, 99.7-100%), respectively. The diagnostic accuracy was consistent across the various subgroups, except for slightly reduced sensitivity in high-income countries. CONCLUSIONS: Rapid antigen tests in CSF would be useful in triaging pneumococcal meningitis. Further studies are warranted to investigate the clinical benefit of ruling out pneumococcal meningitis based on the results of rapid antigen tests.