近赤外線スペクトロスコピィを用いた覚醒剤精神病と統合失調症の鑑別

Despite some slight differences in symptomatology, differential diagnosis of methamphetamine-induced psychosis (MAP) versus schizophrenia can be challenging because both disorders present a large overlap in their clinical symptoms. However, a recent study has shown that near-infrared spectroscopy (NIRS) performed during a cognitive task can be a powerful tool to differentiate between these two disorders. Here, we evaluated verbal fluency task performance during NIRS in 15 patients diagnosed with MAP and 19 with schizophrenia matched for age and sex. We used prefrontal probes and a 24-channel NIRS machine to measure the relative concentrations of oxyhaemoglobin every 0.1 s during the task. For each patient, the neurocognitive function and clinical psychopathology were evaluated using the Positive and Negative Symptom Scale (PANSS), and the Brief Assessment of Cognition in Schizophrenia (BACS). Oxyhaemoglobin changes in the prefrontal cortex were significantly higher in the MAP group compared to those in the schizophrenia group, particularly in the right dorsolateral prefrontal cortex. In contrast, we found no significant difference in PANSS and BACS scores. Our findings suggest that NIRS measurement could be applied to differentiate patients with MAP from those with schizophrenia, even in cases where clinical symptoms are similar.博士（医学）・甲第645号・平成28年3月15日This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0

Phamacogenomics of Clozapine-Induced Agranulocytosis

Background: Clozapine-induced agranulocytosis (CIA)/clozapine-induced granulocytopenia (CIG) (CIAG) is a life-threatening event for schizophrenic subjects treated with clozapine. Methods: To examine the genetic factor for CIAG, a genome-wide pharmacogenomic analysis was conducted using 50 subjects with CIAG and 2905 control subjects. Results: We identified a significant association in the human leukocyte antigen (HLA) region (rs1800625, p = 3.46 × 10−9, odds ratio [OR] = 3.8); therefore, subsequent HLA typing was performed. We detected a significant association of HLA-B*59:01 with CIAG (p = 3.81 × 10−8, OR = 10.7) and confirmed this association by comparing with an independent clozapine-tolerant control group (n = 380, p = 2.97 × 10−5, OR = 6.3). As we observed that the OR of CIA (OR: 9.3~15.8) was approximately double that in CIG (OR: 4.4~7.4), we hypothesized that the CIG subjects were a mixed population of those who potentially would develop CIA and those who would not develop CIA (non-CIA). This hypothesis allowed the proportion of the CIG who were non-CIA to be calculated, enabling us to estimate the positive predictive value of the nonrisk allele on non-CIA in CIG subjects. Assuming this model, we estimated that 1) ~50% of CIG subjects would be non-CIA; and 2) ~60% of the CIG subjects without the risk allele would be non-CIA and therefore not expected to develop CIA. Conclusions: Our results suggest that HLA-B*59:01 is a risk factor for CIAG in the Japanese population. Furthermore, if our model is true, the results suggest that rechallenging certain CIG subjects with clozapine may not be always contraindicated

Abnormal Liver Function Tests and Long-Term Outcomes in Patients Discharged after Acute Heart Failure

Abnormal liver function tests (LFTs) are known to be associated with impaired clinical outcomes in heart failure (HF) patients. However, this implication varies with each single LFT panel. We aim to evaluate the long-term outcomes of acute HF (AHF) patients by assessing multiple LFT panels in combination. From a prospective multicenter registry in Japan, 1158 AHF patients who were successfully discharged were analyzed (mean age, 73.9 ± 13.5 years; men, 58%). LFTs (i.e., total bilirubin, aspartate aminotransferase or alanine aminotransferase, and alkaline phosphatase) at discharge were assessed; borderline and abnormal LFTs were defined as 1 and ≥2 parameter values above the normal range, respectively. The primary endpoint was composite of all-cause death or HF readmission. At the time of discharge, 28.7% and 8.6% of patients showed borderline and abnormal LFTs, respectively. There were 196 (16.9%) deaths and 298 (25.7%) HF readmissions during a median 12.4-month follow-up period. The abnormal LFTs group had a significantly higher risk of experiencing the composite outcome (adjusted hazard ratio: 1.51, 95% confidence interval: 1.08–2.12, p = 0.017), whereas the borderline LFTs group was not associated with higher risk of adverse events when referenced to the normal LFTs group. Among AHF patients, the combined elevation of ≥2 LFT panels at discharge was associated with long-term adverse outcomes

Personalized Target Heart Rate for Patients with Heart Failure and Reduced Ejection Fraction

The optimal heart rate (HR) in patients with heart failure with reduced ejection fraction (HFrEF) has been ill-defined. Recently, a formula was proposed for estimating the target heart rate (THR), which eliminates the overlap between the E and A wave (E-A overlap). We aim to validate its prognostic significance in the multicenter WET-HF registry. This study used data from 647 patients with HFrEF hospitalized for acute decompensated HF (ADHF). The patients were divided into the 2 groups by THR. The primary endpoint was defined as the composite of all-cause death and ADHF readmission. The THR successfully discriminated the incidence of the primary endpoint, whereas no significant difference was observed in the primary endpoint when dividing the patients by uniform cutoff 70 bpm. HR at discharge ≤ THR was inversely associated with the primary endpoint. Restricted cubic spline analysis demonstrated the difference between HR at discharge, and THR (ΔHR) from −10 to ±0 was associated with a lower risk of primary endpoint and ΔHR from ±0 to +15 was associated with a higher risk. THR discriminated long-term outcomes in patients with HFrEF more efficiently than the uniform cutoff, suggesting that it may aid in tailored HR reduction strategies

Low-Density Lipoprotein Cholesterol Levels on Statins and Cardiovascular Event Risk in Stable Coronary Artery Disease --An Observation From the REAL-CAD Study--

BACKGROUND: The relationship between very low on-treatment low-density lipoprotein cholesterol (LDL-C) level and cardiovascular event risk is still unclear in patients receiving the same doses of statins.Methods and Results: From the REAL-CAD study comparing high-dose (4 mg/day) with low-dose (1 mg/day) pitavastatin therapy in patients with stable coronary artery disease, 11, 105 patients with acceptable statin adherence were divided into 3 groups according to the on-treatment LDL-C level at 6 months (<70 mg/dL, 70-100 mg/dL, and ≥100 mg/dL). The primary outcome measure was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina requiring emergent admission. The adjusted risks of the LDL-C <70 mg/dL group relative to the LDL-C 70-100 mg/dL group (reference) was not significantly different for the primary outcome measure in both 1 mg/day and 4 mg/day strata (HR 0.84, 95% CI 0.58-1.18, P=0.32, and HR 1.25, 95% CI 0.88-1.79, P=0.22). The adjusted risk of the LDL-C ≥100 mg/dL group relative to the reference group was not significant for the primary outcome measure in the 1 mg/day stratum (HR 0.82, 95% CI 0.60-1.11, P=0.21), whereas it was highly significant in the 4 mg/day stratum (HR 3.32, 95% CI 2.08-5.17, P<0.001). CONCLUSIONS: A very low on-treatment LDL-C level (<70 mg/dL) was not associated with lower cardiovascular event risk compared with moderately low on-treatment LDL-C level (70-100 mg/dL) in patients receiving the same doses of statins

Association of Non-Invasive Positive Pressure Ventilation with Short-Term Clinical Outcomes in Patients Hospitalized for Acute Decompensated Heart Failure

The real-world evidence has been sparse on the impact of non-invasive positive pressure ventilation (NPPV) on the outcomes in acute decompensated heart failure (ADHF) patients. We aim to explore this issue in the prospective multicenter WET-HF registry. Among 3927 patients (77 (67–84) years, male 60%), the NPPV was used in 775 patients (19.7%). The association of NPPV use with in-hospital outcome and length of hospital stay (LOS) was examined by two methods, propensity score (PS) matching and multivariable analysis with adjustment for PS. In these analyses the NPPV group exhibited a lower endotracheal intubation (ETI) rate and a comparable in-hospital mortality, but longer LOS compared to the non-NPPV group. In the stratified analysis, the NPPV group exhibited a significantly lower ETI rate in patients with ischemic etiology, systolic blood pressure (sBP) &gt; 140 mmHg and the Controlling Nutritional Status (CONUT) score ≤ 3, indicating better nutritional status. On the contrary, NPPV use was associated with longer LOS in patients with non-ischemic etiology, sBP &lt; 100 mmHg and CONUT score &gt; 3. In conclusion, NPPV use was associated with a lower incidence of ETI. Particularly, patients with ischemic etiology, high sBP, and better nutritional status might benefit from NPPV use

Short-term effects of low-dose tolvaptan in acute decompensated heart failure patients with severe aortic stenosis: The LOHAS registry

Background: Tolvaptan exerts potent diuretic effects in heart failure patients without hemodynamic instability. Nonetheless, its clinical efficacy for acute decompensated heart failure (ADHF) due to severe aortic stenosis (AS) remains unclear. This study aimed to evaluate the short-term effects of tolvaptan in ADHF patients with severe AS. Methods: The LOw-Dose Tolvaptan (7.5 mg) in Decompensated Heart Failure Patients with Severe Aortic Stenosis (LOHAS) registry is a multicenter (7 centers) prospective registry that assessed the short-term effects of tolvaptan in subjects hospitalized for ADHF with severe AS. A total of 59 subjects were enrolled between September 2014 and December 2017. The primary endpoints were changes in body weight and fluid balance measured daily from baseline up to 4 days. Results: The median [interquartile range] patient age and aortic valve area were 85.0 [81.0–89.0] years and 0.58 [0.42–0.74] cm2, respectively. Body weight continuously decreased, and fluid balance was maintained from baseline to day 4 (p 150 mEq/L) and worsening renal function occurred in 2 (3.4%) and 4 (6.8%) patients, respectively. Conclusions: Short-term treatment with low-dose tolvaptan is safe and effective, providing stable hemodynamic parameters in patients with ADHF and severe AS

Multimorbidity, guideline‐directed medical therapies, and associated outcomes among hospitalized heart failure patients

Abstract Aims Multimorbidity is common among heart failure (HF) patients and may attenuate guideline‐directed medical therapy (GDMT). Multimorbid patients are under‐represented in clinical trials; therefore, the effect of multimorbidity clustering on the prognosis of HF patients remains unknown. We evaluated the prevalence of multimorbidity clusters among consecutively registered hospitalized HF patients and assessed whether GDMT attenuated outcomes. Methods and results We examined 1924 hospitalized HF patients with reduced left ventricular ejection fraction (<50%) in a multicentre registry (West Tokyo HF Registry: WET‐HF). Ten comorbid conditions in the WET‐HF were abstracted: coronary artery disease, atrial fibrillation, stroke, anaemia, chronic obstructive pulmonary disease, renal dysfunction, obesity, hypertension, dyslipidaemia, and diabetes. Patients were divided into three groups (0–2: n = 451; 3–4: n = 787; and ≥5: n = 686) based on the number of comorbid conditions. The primary composite endpoint was all‐cause mortality and HF rehospitalization. The most prevalent comorbidities were renal dysfunction (67.9%), hypertension (66.0%), and anaemia (53.8%). Increased comorbidity was associated with increased adverse outcomes [3–4: hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.13–1.77, P = 0.003; ≥5: HR 2.12, 95%CI 1.69–2.65, P < 0.001; and reference: 0–2] and lower GDMT prescription rate (0–2: 69.2%; 3–4: 57.7%; and ≥5: 57.6%). GDMT was associated with decreased adverse outcomes; this association was maintained even as the comorbidity burden increased but tended to weaken (0–2: HR 0.53, 95%CI 0.35–0.78; P = 0.001; 3–4: HR 0.82, 95%CI 0.65–1.04, P = 0.095; and ≥5: HR 0.81, 95%CI 0.65–1.00, P = 0.053; P for interaction = 0.156). Conclusions Comorbidity clusters were prevalent and associated with poorer outcomes. GDMT remained beneficial regardless of the comorbidity burden but tended to weaken with increasing comorbidity burden. Further research is required to optimize medical care in these patients