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In this study, we evaluated brain perfusion in patients with first-episode medicated schizophrenia using the new analytical method, statistical parametric mapping (SPM) applied to single photon emission computed tomography (SPECT).
We performed SPECT with 99-Tc-ethyl cysteinate dimer (99mTc-ECD) of the brain and magnetic resonance imaging (MRI) in patients with schizophrenia (n = 30) and control subjects matched for age and gender (n = 37). A voxel-by-voxel group analysis was performed using SPM2 (Z > 3.0, P < 0.001, uncorrected for multiple comparisons).
In comparison with control subjects, the volumes of the bilateral frontal areas were found to be decreased on MRI. Blood flow was found to be reduced in the bilateral temporal areas in the patients with schizophrenia on SPECT.
In this study, patients with first-episode schizophrenia appeared to have significant bilateral temporal hypoperfusion, although temporal volumes were not significantly decreased in comparison with control subjects. Abnormality of temporal lobe blood flow in schizophrenia may show that functional changes occur earlier than structural changes, and may assist in the diagnosis of schizophrenia.
Patients with schizophrenia show a significantly higher frequency of hyperbilirubinemia the patients suffering from other psychiatric disorders and the general healthy population. The objective of the current study was to determine whether patients with schizophrenia-associated idiopathic unconjugated hyperbilirubinemia (Gilbert's syndrome, GS) have specific changes in signal intensities on fluid-attenuated inversion-recovery (FLAIR) magnetic resonance (MR) images.
Axial 5-mm-thick FLAIR MR images from schizophrenia patients with GS (n = 18) and schizophrenia patients without GS (n = 18), all diagnosed according to DSM-IV criteria, were compared with age- and sex-matched non-psychiatric controls (n = 18). Signal intensities in the hippocampus, amygdala, caudate, putamen, thalamus, cingulate gyrus, and insula were graded relative to cortical signal intensity in the frontal lobe.
Compared to both schizophrenia patients without GS and normal controls, the schizophrenia patients with GS showed significantly increased signal intensities in almost all regions studied.
Patients with schizophrenia-associated GS have specific changes of signal intensities on FLAIR MR images, suggesting that schizophrenia with GS produces changes in the fronto-temporal cortex, limbic system, and basal ganglia.
Growing evidence indicated that the glutamatergic neurotransmitter system is central to the neurobiology and treatment of mood and anxiety disorders. Riluzole, a drug currently used to slow the progression of amyotrophic lateral sclerosis, is one of the candidate drugs that modulate glutamatergic neurotransmission in the central nervous system. Recently, several open-label clinical trials have suggested that riluzole reduces symptoms of treatment-resistant major depression, obsessive-compulsive disorder and generalized anxiety disorder. Previously, we reported that riluzole rapidly attenuates the hyperemotional responses found in the olfactory bulbectomized rats. This animal model exhibits hyperemotional behavior that may mimic anxiety, aggression and irritability found in depressed patients, suggesting the possible use of riluzole in combating the symptoms of anxiety and depression. Interestingly, we first found that a single riluzole treatment had rapid anti-hyperemotional effects in the rats. In addition, we demonstrated that single riluzole treatment significantly decreased extracellular glutamate levels in medial prefrontal cortex of the rats by in vivo microdialysis examination. Our results propose a hypothesis that riluzole rapidly improve symptoms in depressed patients, as a non-monoamine-based antidepressant. In conclusion, our results suggest that a glutamate-modulating drug, riluzole, is one of the candidate drugs for new generation antidepressants and/or anxiolytics.
The primary goal of this study is to examine the effectiveness of a community-based multimodal intervention program for suicide prevention in regions where the suicide rate was relatively high compared to control regions. The secondary goal was to explore the effectiveness of a community-based multimodal intervention program for suicide prevention in highly populated regions.
NOCOMIT-J is a community-based large-scale non-randomized controlled trial, involving seven intervention regions with accompanying control regions, all with populations of statistically sufficient size. The program consists of
1) Establishing social support networks in the public health system for suicide prevention and mental health promotion;
2) A primary prevention measures of awareness campaign for the public and key personnel;
3) Secondary prevention measures for screening, counseling and outreach services for high-risk individuals;
4) After-care for individuals bereaved by suicide;
5) Suicide prevention measures especially for individuals with mental illness and work-related problems.
This study protocol was reviewed and approved by the Central Ethics Committee of the J-MISP. Additionally, the regional leaders obtained written authorization from the local governors.
The intervention started in July 2006, and continued for 3.5 years. Participants are Japanese and foreign residents living in the intervention and control regions, a total of population of 2,120,000 individuals.
Because treatment and prevention of suicide are complex and encompass many factors, success will need multi-sector collaboration. We hope that the results of NOCOMIT-J will help to develop effective strategies to reduce future suicide rate. (ClinicalTrials.gov: NCT00737165)
A history of previous suicide attempt is a potent risk factor for suicide later on. Crisis intervention initiated at emergency medical facilities for suicide attempters are considered important components for suicide prevention. The primary aim of this trial is to examine the effectiveness of an extensive intervention for suicide attempters in prevention of recurrent suicidal behavior, as compared with standard intervention.
ACTION-J is a single blinded randomized controlled trial. In this trial, case management intervention were provided at 19 emergency medical facilities in Japan. After psychiatric evaluation and psychological education, subjects were randomly assigned to either a group receiving continuous case management or standard care. Suicidal ideation, depressive symptoms, and general health condition were evaluated as secondary measures. The stratified logrank test based on allocation factors will be performed for all eligible participants in the intent-to-treat analysis. The study protocol was reviewed and approved by the Central Ethics Committee of the J-MISP. The protocol was also reviewed and approved by the On-site Research Ethics Committee at each participating hospital.
The intervention was initiated in July 2006. By December 2009, 914 subjects were randomized. Subject follow-up continued for 1.5 to 5 years, till the end of June 2011. ACTION-J would provide valuable information on suicide attempters and may develop effective case management to reduce future risk for suicide attempters. (ClinicalTrials.gov: NCT00736918.)
Copper is a candidate for use as an overpack material in deep underground nuclear waste disposal. Copper, however, is susceptible to corrosion following closure of the repository and migration of the corrosion products through the buffer material may affect the migration of redox-sensitive radionuclides. Electromigration experiments were performed whereby a copper coupon, which was in contact with compacted bentonite, served as the working electrode and was held at a constant potential of between +100 to +400 mV vs. Ag/AgCl electrode for up to 48 h. The amounts of copper that migrated into the bentonite specimens were found to be in good agreement with the calculated values based on the corrosion current flow for the assumption that copper underwent anodic dissolution as Cu(II). A model based on dispersion and electromigration was able to explain the measured copper profiles in the bentonite specimens. The fitted values of the dispersion coefficient did not depend on the applied potential and were about 10-12 m2/s.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
The apparent diffusion coefficients of strontium in compacted bentonites were investigated at various concentrations of NaHCO3. Purified sodium bentonite Kunipia-F® was compacted with a jig into cylindrical pellets 10 mm in diameter and 10 mm high with dry densities of 1.0 to 1.6 Mg/m3. Each bentonite pellet was inserted into an acrylic resin column and saturated with carbonated water containing 0.1 to 1.0 M NaHCO3 for more than 1 month. The face of the bentonite specimen was spiked with 5 μL of 1.0 M SrCl2 tracer solution. After a few weeks, the strontium diffusion profiles were measured by inductively coupled plasma-mass spectrometry. The apparent diffusion coefficients of strontium decreased slightly with increasing dry density. NaHCO3 concentrations of 0.5 M decreased the apparent diffusion coefficients of strontium by half at a dry density of 1.0 Mg/m3 and quarter at 1.6 Mg/m3. At a higher NaHCO3 concentration of 1.0 M, no strontium diffusion profile was observed, whereas white precipitate was observed on the face of the bentonite specimen where it was spiked with strontium. This white precipitate could be strontianite, which is strontium carbonate. Diffusion experiments using cesium were carried out for comparison, and the presence of carbonate had no effect on the apparent diffusion coefficient.
Depression is increasingly recognized as a chronic and relapsing disorder. However, an important minority of patients who start treatment for their major depressive episode recover to euthymia. It is clinically important to be able to predict such individuals.
The study is a secondary analysis of a recently completed pragmatic megatrial examining first- and second-line treatments for hitherto untreated episodes of non-psychotic unipolar major depression (n = 2011). Using the first half of the cohort as the derivation set, we applied multiply-imputed stepwise logistic regression with backward selection to build a prediction model to predict remission, defined as scoring 4 or less on the Patient Health Quetionnaire-9 at week 9. We used three successively richer sets of predictors at baseline only, up to week 1, and up to week 3. We examined the external validity of the derived prediction models with the second half of the cohort.
In total, 37.0% (95% confidence interval 34.8–39.1%) were in remission at week 9. Only the models using data up to week 1 or 3 showed reasonable performance. Age, education, length of episode and depression severity remained in the multivariable prediction models. In the validation set, the discrimination of the prediction model was satisfactory with the area under the curve of 0.73 (0.70–0.77) and 0.82 (0.79–0.85), while the calibration was excellent with non-significant goodness-of-fit χ2 values (p = 0.41 and p = 0.29), respectively.
Patients and clinicians can use these prediction models to estimate their predicted probability of achieving remission after acute antidepressant therapy.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Recently, rehabilitation therapists have become involved in cancer rehabilitation; however, no communication skills training that increases the ability to provide emotional support for cancer patients has been developed for rehabilitation therapists. In addition, no study has examined associations between rehabilitation therapists’ communication skills and their level of autistic-like traits (ALT), which are in-born characteristics including specific communication styles and difficulty communicating with patients. In this study, we aimed to investigate whether confidence in communicating with patients mitigates communication difficulties experienced by rehabilitation therapists who have high levels of ALT.
Rehabilitation therapists who treat patients with cancer completed self-administered postal questionnaires anonymously. Scores were obtained on the Autism-Spectrum Quotient short form, confidence in communication, and communication difficulties. We used covariance structure analyses to test hypothetical models, and confirmed that confidence in communication mediates the relationship between ALT and perceived communication difficulties.
Participants included 1,343 respondents (49.6%). Autism-Spectrum Quotient scores were positively correlated with communication difficulties (r = 0.16, p < 0.001). The correlation was mitigated by confidence in communication in the fit model. However, higher confidence in creating a supportive atmosphere was associated with more difficulty in communication (r = 0.16, p < 0.001).
Significance of results
Communication difficulty was linked to rehabilitation therapists’ ALTs. By increasing confidence in areas of communication other than creation of a supportive atmosphere, ALT-related difficulties in communication may be ameliorated. Confidence to create supportive environments correlated positively with difficulty. Communication skills training to increase confidence in communication for rehabilitation therapists should be developed with vigilance regarding ALT levels.
The apparent diffusion coefficients of La, Nd, Eu, Dy, Er, and Lu in compacted bentonites were investigated at various bicarbonate concentrations. The apparent diffusion coefficients of these lanthanides tended to decrease with increasing dry density. At bicarbonate concentrations below 0.25 M, lanthanum had the largest diffusion coefficient (ca. 10-13 m2/s) at 1.0 Mg/m3, and the diffusion coefficient decreased with increasing atomic number. On the other hand, at bicarbonate concentrations above 0.25 M, lutetium had the largest diffusion coefficient, and the diffusion coefficient decreased with decreasing atomic number. In particular, lanthanum and neodymium had diffusion coefficients below 10-14 m2/s, even at 1.0 Mg/m3. The diffusion coefficient of europium was around 10-13 m2/s at 1.0 Mg/m3 and was influenced less by the bicarbonate concentration. The diffusion coefficient of lutetium increased from 2 × 10-14 to 10-12 m2/s as the bicarbonate concentration was increased to 1.0 M. The concentration of carbonate ion in the pore water of bentonite is estimated to be much lower than that in solutions in contact with bentonite from the viewpoints of solubility and chemical species of lanthanides.
In Canada, reimbursement recommendations on drugs for common and rare indications (for example, orphan drugs) are made through the pan-Canadian Oncology Drug Review (pCODR) and the Common Drug Review (CDR). However, some stakeholders have called for a separate mechanism for orphan drugs, arguing that existing processes place too much weight on their high price tags. The purpose of this study was to examine factors associated with positive recommendations on drugs for rare diseases.
Information was extracted from CDR and pCODR recommendations on drugs for diseases (prevalence of less than 1 in 2,000) up to April 2018. Univariate and multivariate logistic regression models were applied to explore the influence of the following variables on recommendations: year; prevalence; clinical safety and effectiveness (safety, quality of life, symptoms, surrogate outcomes, and survival); quality of evidence (availability of comparative data, external validity, and bias); unmet need; treatment cost; and incremental cost-effective ratio (ICER). Two-way interactions were also tested.
Of 128 recommendations, fifty-four (77 percent) and forty (69 percent) were positive for cancer and non-cancer indications, respectively. For cancer indications, all submissions reporting meaningful improvements in surrogate, quality of life, and survival outcomes were significantly more likely to have a positive recommendation. Submissions showing a lack of external validity were significantly less likely to receive a positive recommendation. For non-cancer indications, more recent submissions and those presenting no safety issues were associated with positive recommendations. Prevalence, treatment cost, and ICER were not determinants of positive or negative recommendations.
For both cancer and non-cancer orphan drugs, impact on clinical safety and effectiveness, rather than cost, appears to be a key factor in the formulation of recommendations.
Many population-based studies identify surgical complications using hospital discharge abstract databases (DAD). With DAD, however, complications occurring after the discharge date cannot be followed up. This study used physician claims data to identify the complications of partial nephrectomy, and to compare the rates of complications of open, laparoscopic, and robot-assisted nephrectomies.
Physician claims, DAD, and ambulatory care data from April 2003 to March 2016 were provided by Alberta Health. DAD and ambulatory care data were used to extract information on patients with kidney cancer who underwent partial nephrectomy. All physician claims within 30 days before and after surgery for the cohort were extracted. The numbers of the same International Classification of Diseases, Ninth Revision (ICD-9), codes before and after surgery were compared. If a number increased after surgery, this diagnosis was initially identified as a complication. All diagnoses with neoplasms were excluded. The incidence rates of complications for the three surgery groups were calculated. Chi-squared tests were conducted for the following nephrectomy comparisons: laparoscopic versus open; robot-assisted versus open; and robot-assisted versus laparoscopic.
A total of 1,890 kidney cancer patients had partial nephrectomies. Among them, 1,080, 411, and 399 had open, laparoscopic, and robot-assisted nephrectomies, respectively. One patient who had two different nephrectomies on the same day was excluded from analysis. The robot-assisted group had lower rates of digestive complications (ICD-9: 537–578, 787, 789, 998.6) and infections (ICD-9: 004–041, 998.5) than the open group, and higher rates of genitourinary complications (ICD-9: 584–599, 788, 997.5) than the laparoscopy group. The robot-assisted group had lower rates than the open group for most of the complication categories, but the differences were not statistically significant.
Robot-assisted surgery appears to be superior to open surgery, but no better than laparoscopic surgery, in terms of minimizing the risk of complications following partial nephrectomy.
In disposal of high-level radioactive waste, carbon steel overpack will be corroded after closure of the repository, creating a reducing, low-pH environment around the repository. A plutonium diffusion experiment was performed over 15 years with Kunigel V1, which is a typical Japanese bentonite that contains about 50% montmorillonite, in contact with an iron coupon. A tracer solution (10 µL) containing 1 kBq of 238Pu was applied at the interface between the iron coupon and compacted bentonite that was saturated with deionized water. After the diffusion period, the plutonium distribution in the bentonite specimen was measured with an alpha scintillation counter, and the iron and sodium distributions were obtained by inductively coupled plasma-mass spectrometry. Plutonium penetrated into the bentonite to a depth of 2 mm, and more than 90% of plutonium remained in corrosion product at the interface. The bentonite around the interface was dark green like green rust or magnetite according to visual observation. Iron was detected throughout the bentonite and there was a particularly high iron concentration from the interface to a depth of 2 mm, whereas the sodium concentration decreased slightly from the interface to 2 mm. We proposed that ferrous ions diffused into bentonite as the iron coupon corroded and precipitated such as magnetite. The magnetite precipitation would decrease the bentonite pH, resulting in the dissolution and migration of plutonium. Small cracks were also observed 2 to 6 mm from the interface and could have been formed by the migration of hydrogen generated by corrosion.
To determine the characteristics of acute phase nystagmus in patients with cerebellar lesions, and to identify a useful indicator for differentiating central lesions from peripheral lesions.
Acute phase nystagmus and the appearance of neurological symptoms were retrospectively investigated in 11 patients with cerebellar stroke.
At the initial visit, there were no patients with vertical nystagmus, direction-changing gaze evoked nystagmus or pure rotatory nystagmus. There were four cases with no nystagmus and seven cases with horizontal nystagmus at the initial visit. There were no neurological symptoms, except for vertigo and hearing loss, in any cases at the initial visit. The direction and type of nystagmus changed with time, and neurological symptoms other than vertigo appeared subsequently to admission.
It is important to observe the changes in nystagmus and other neurological findings for the differential diagnosis of central lesions.
NUMO and JAEA have been conducting a joint research since FY2011, which is aimed
to enhance the methodology of repository design and performance assessment in
preliminary investigation stage for the deep geological disposal of high-level
radioactive waste. As a part of this joint research, we have been developing
glass dissolution models which include various processes derived from
glass-overpack-bentonite buffer interaction, considering the precipitation of
Fe-silicates associated with steel overpack corrosion, and Si transport through
altered layer of glass. The objective of this modeling work is to show
comprehensively the lifetime of the vitrified waste due to glass matrix
dissolution timescales through sensitivity analysis, and to identify the
feature/process that most strongly influences the lifetime, and to identify
future R&D issues that would help to improve the nuclide transport
analysis with confidential value and the safety case in future. The sensitivity
analysis suggested that the duration of the glass dissolution might be predicted
in the ranges from 3.8×103 to 1.9×105
years. Also, the results indicated that the precipitation of
Fe–silicate has the strongest influence on the long-team behavior of
In disposing of high-level radioactive waste, the drop in pH in the repository as the iron overpack corrodes must be considered. Plutonium migration behavior may be affected by the pH of pore water in compacted bentonite barriers in high-level waste repositories. To examine the effect of pH on migration behavior, H-bentonite was prepared by treating Japanese Na-bentonite, Kunipia-F, with hydrochloric acid. Diffusion experiments were performed with mixtures of Na- and H-bentonites. The pH value in the pore water of the water-saturated bentonite mixtures decreased from 8 to 3 as the mixing ratio of H-bentonite increased. Diffusion experiments were carried out by using 238Pu then apparent diffusion coefficients were determined from the plutonium distribution in the specimens. The apparent diffusion coefficients were on the order of 10-13 to 10-12 m2/s at pH values lower than 4, whereas they were less than 10-14 m2/s at pH values higher than 6.5. These results indicate that plutonium diffused faster as Pu3+ or PuO22+ due to disproportionation at lower pH while plutonium could be retarded as Pu(OH)40 by sorption on bentonite at higher pH.