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Inconsistent results regarding the risk of relapse and better subjective outcomes of previous antipsychotic dose reduction trials in patients with remitted psychosis have not been verified using therapeutic drug monitoring (TDM). This study examined plasma drug concentrations of a dose-tapering trial which exhibited the potential of successful maintenance under lower antipsychotic dosages.
Methods
A 2-year open-label randomized prospective trial recruited remitted patients to undergo guided antipsychotic tapering. Blood samples were collected at baseline, annually, and after each dose reduction. Plasma aripiprazole/dehydroaripiprazole concentrations were determined using LC–MS/MS. The relationship between the dose and serum drug levels was examined using Spearman's correlation. Divided at 120 ng/mL, relapse rate, global function, quality of life, and psychopathology were compared between high- and low- drug level groups.
Results
A total of 126 blood samples were collected, after excluding13 samples due of non-adherence. The correlation coefficients between dosage and drug level were 0.853 (aripiprazole) and 0.864 (dehydroaripiprazole), and the dose and concentration plots were parallel along the tapering trajectories, except patients with non-adherence. The concentration-to-dose ratio of aripiprazole in this cohort, 17.79 ± 7.23 ng/mL/mg, was higher than that in Caucasian populations. No significant differences were observed in the clinical outcomes between the high- and low-level groups. Remarkably, 12 of 15 patients maintained remission at plasma aripiprazole concentrations of <120 ng/mL.
Conclusions
The lower-than-expected doses reached in our antipsychotic tapering trial were substantiated to provide adequate prophylactic effects by TDM results in a subset of patients treated with aripiprazole, even considering the differences in pharmacogenomics between ethnicities.
The right inferior frontal gyrus (RIFG) is a potential beneficial brain stimulation target for autism. This randomized, double-blind, two-arm, parallel-group, sham-controlled clinical trial assessed the efficacy of intermittent theta burst stimulation (iTBS) over the RIFG in reducing autistic symptoms (NCT04987749).
Methods
Conducted at a single medical center, the trial enrolled 60 intellectually able autistic individuals (aged 8–30 years; 30 active iTBS). The intervention comprised 16 sessions (two stimulations per week for eight weeks) of neuro-navigated iTBS or sham over the RIFG. Fifty-seven participants (28 active) completed the intervention and assessments at Week 8 (the primary endpoint) and follow-up at Week 12.
Results
Autistic symptoms (primary outcome) based on the Social Responsiveness Scale decreased in both groups (significant time effect), but there was no significant difference between groups (null time-by-treatment interaction). Likewise, there was no significant between-group difference in changes in repetitive behaviors and exploratory outcomes of adaptive function and emotion dysregulation. Changes in social cognition (secondary outcome) differed between groups in feeling scores on the Frith-Happe Animations (Week 8, p = 0.026; Week 12, p = 0.025). Post-hoc analysis showed that the active group improved better on this social cognition than the sham group. Dropout rates did not vary between groups; the most common adverse event in both groups was local pain. Notably, our findings would not survive stringent multiple comparison corrections.
Conclusions
Our findings suggest that iTBS over the RIFG is not different from sham in reducing autistic symptoms and emotion dysregulation. Nonetheless, RIFG iTBS may improve social cognition of mentalizing others' feelings in autistic individuals.
Patients with remitted psychosis wish to reduce antipsychotic doses yet facing increased risks of relapse. Examining dose-tapering processes may provide insights to re-evaluate the risk-to-benefit balance. We aimed to depict and subgroup tapering trajectories, and explore factors associated with different dose-reduction patterns.
Methods
A 2-year open-label randomized prospective comparative trial from August 2017 to September 2022 in Taiwan. Patients with a history of schizophrenia-related psychotic disorders under stable medications and symptoms were eligible, randomizing a proportion to conduct guided dose reduction. We depicted the trajectories of individual patients and named subgroups based on dose-tapering patterns. Predictors of baseline characteristics for designated subgroups were examined by logistic regression analysis; changes in outcomes were compared by paired t-test.
Results
Fifty-one patients undergoing guided dose reduction, 18 (35.3%) reduced 4 steps consecutively (sequential reducers, SR), 14 (27.5%) reduced 1 to 3 steps (modest reducers, MR), 3 (5.9%) re-escalated to previous level (alert reducers, AR), 7 (13.7%) returned to baseline level (baseline returners, BR), 6 (11.7%) relapsed (failed reducers, FR) and 3 (5.9%) withdrew without relapse (early exits, EE). Patients with a history of relapse assumed a conservative dose-tapering pace; only the SR subgroup exhibited significant improvements in functioning and quality of life while failing to identify variables for predicting who would become SR or FR.
Conclusions
Guided dose reduction comprises dynamic processes with differences between individual trajectories. The proposed naming of dose-tapering patterns/subgroups provides a framework depicting patients undergoing dose-tapering. Longer-term observation and more flexible tapering approaches are anticipated to reveal favorable outcomes.
Patients with remitted psychosis face a dilemma between the wish to discontinue antipsychotics and the risk of relapse. We test if an operationalized guided-dose-reduction algorithm can help reach a lower effective dose without increased risks of relapse.
Methods
A 2-year open-label randomized prospective comparative cohort trial from Aug 2017 to Sep 2022. Patients with a history of schizophrenia-related psychotic disorders under stable medications and symptoms were eligible, randomized 2:1 into guided dose reduction group (GDR) v. maintenance treatment group (MT1), together with a group of naturalistic maintenance controls (MT2). We observed if the relapse rates would be different between 3 groups, to what extent the dose could be reduced, and if GDR patients could have improved functioning and quality of life.
Results
A total of 96 patients, comprised 51, 24, and 21 patients in GDR, MT1, and MT2 groups, respectively. During follow-up, 14 patients (14.6%) relapsed, including 6, 4, and 4 from GDR, MT1, and MT2, statistically no difference between groups. In total, 74.5% of GDR patients could stay well under a lower dose, including 18 patients (35.3%) conducting 4 consecutive dose-tapering and staying well after reducing 58.5% of their baseline dose. The GDR group exhibited improved clinical outcomes and endorsed better quality of life.
Conclusions
GDR is a feasible approach as the majority of patients had a chance to taper antipsychotics to certain extents. Still, 25.5% of GDR patients could not successfully decrease any dose, including 11.8% experienced relapse, a risk comparable to their maintenance counterparts.
A proportion of patients with bipolar disorder (BD) manifests with only unipolar mania (UM). This study examined relevant clinical features and psychosocial characteristics in UM compared with depressive-manic (D-M) subgroups. Moreover, comorbidity patterns of physical conditions and psychiatric disorders were evaluated between the UM and D-M groups.
Methods
This clinical retrospective study (N = 1015) analyzed cases with an average of 10 years of illness duration and a nationwide population-based cohort (N = 8343) followed up for 10 years in the Taiwanese population. UM was defined as patients who did not experience depressive episodes and were not prescribed adequate antidepressant treatment during the disease course of BD. Logistic regression models adjusted for relevant covariates were used to evaluate the characteristics and lifetime comorbidities in the two groups.
Results
The proportion of UM ranged from 12.91% to 14.87% in the two datasets. Compared with the D-M group, the UM group had more psychotic symptoms, fewer suicidal behaviors, a higher proportion of morningness chronotype, better sleep quality, higher extraversion, lower neuroticism, and less harm avoidance personality traits. Substantially different lifetime comorbidity patterns were observed between the two groups.
Conclusions
Patients with UM exhibited distinct clinical and psychosocial features compared with patients with the D-M subtype. In particular, a higher risk of comorbid cardiovascular diseases and anxiety disorders is apparent in patients with D-M. Further studies are warranted to investigate the underlying mechanisms for diverse presentations in subgroups of BDs.
The Brain Health Test-7 (BHT-7) is a revised tool from the original BHT, containing more tests about frontal lobe function. It was developed with theaim of identifying patients with mild cognitive impairment (MCI) and early dementia.
Research objective
Here we report the validity of the BHT-7 versus the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) in differentpsychiatry or neurology clinics.
Methods
Patients with memory complaints were recruited in this study from the outpatient clinic of psychiatry or neurology in 3 different kinds of hospitals. Allpatients underwent the evaluation of the BHT-7, MMSE, MoCA, and clinical dementia rating (CDR). The clinical diagnosis (normal, MCI, dementia) was made by consensus meeting, taking into account all available data.
Demographic data and the scores of the MMSE, MoCA, and BHT-7 between groups were compared. Logistic regression was adopted for analysis of optimal cutoff values, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), receiver operating characteristic (ROC) curve,and the area under the ROC curve (AUC).
Results
We enrolled a total of 1090 subjects (normal 402, MCI 317, dementia 371); of them, 705 (64.7%) were female. There was a statistically significant differencein age, years of education, and 3 cognitive test scores among the 3 groups.
Compared with the MMSE and MoCA, the BHT-7 performed slightly betterthan MMSE and MoCA in differentiating MCI or dementia from the normalcontrols (Table 1). For BHT- 7, the cutoff point was 17 between normal andMCI, and 14 between normal and dementia. These cutoff points for BHT-7were consistent through 3 different clinical settings, but inconsistent for MMSE and MoCA. The testing time for the BHT-7 was about 5-7 minutes, shorter than that of the MMSE and MoCA.
Conclusion
Compared with MMSE and MoCA, the BHT-7 showed slightly better performance in differentiating normal from MCI or dementia subjects. The testing time for the BHT-7 was shorter, and its cutoff points were consistent through different outpatient clinic settings. The results support that BHT-7 is auseful cognitive screening tool for MCI or early dementia in various hospital settings.
Table 1
Comparisons of the performance of BHT-7, MMSE, MoCA
Patients with COVID-19 may present with respiratory syndromes indistinguishable from those caused by common viruses. Early isolation and containment is challenging. Although screening all patients with respiratory symptoms for COVID-19 has been recommended, the practicality of such an effort has yet to be assessed.
Methods:
Over a 6-week period during a SARS-CoV-2 outbreak, our institution introduced a “respiratory surveillance ward” (RSW) to segregate all patients with respiratory symptoms in designated areas, where appropriate personal protective equipment (PPE) could be utilized until SARS-CoV-2 testing was done. Patients could be transferred when SARS-CoV-2 tests were negative on 2 consecutive occasions, 24 hours apart.
Results:
Over the study period, 1,178 patients were admitted to the RSWs. The mean length-of-stay (LOS) was 1.89 days (SD, 1.23). Among confirmed cases of pneumonia admitted to the RSW, 5 of 310 patients (1.61%) tested positive for SARS-CoV-2. This finding was comparable to the pickup rate from our isolation ward. In total, 126 HCWs were potentially exposed to these cases; however, only 3 (2.38%) required quarantine because most used appropriate PPE. In addition, 13 inpatients overlapped with the index cases during their stay in the RSW; of these 13 exposed inpatients, 1 patient subsequently developed COVID-19 after exposure. No patient–HCW transmission was detected despite intensive surveillance.
Conclusions:
Our institution successfully utilized the strategy of an RSW over a 6-week period to contain a cluster of COVID-19 cases and to prevent patient–HCW transmission. However, this method was resource-intensive in terms of testing and bed capacity.
The synthesis of aluminum nitride (AlN) powders from aluminum (Al) particles via a thermal nitridation process was carried out at high temperature (>900 °C) with a long reaction time (∼several hours). This study proposes a two-stage plasma-chemical synthesis process to efficiently minimize the agglomeration of Al particles, reduce the reaction time and temperature, and promote the formation of AlN powders. In the first stage, partially nitrided Al powders were produced at temperatures lower than 600 °C in atmospheric-pressure microwave N2 plasma. The particle size of the as-prepared powders was similar to that of the original Al powders. In the second stage, the reaction temperature was increased to 700–800 °C and the reaction time was less than 5 min in N2 plasma. Well-dispersed AlN powders with almost no agglomeration were produced. Moreover, the particle size was lower than that of the original Al.
Impaired regulation of blood glucose levels in diabetes mellitus (DM) patients and the associated elevation of blood glucose levels are known to increase the risk of diabetic cardiomyopathy (DC). In the present study, a probiotic bacterium, Lactobacillus reuteri GMN-32, was evaluated for its potential to reduce blood glucose levels and to provide protection against DC risks in streptozotocin (STZ)-induced DM rats. The blood glucose levels of the STZ-induced DM rats when treated with L. reuteri GMN-32 decreased from 4480 to 3620 mg/l (with 107 colony-forming units (cfu)/d) and 3040 mg/l (with 109 cfu/d). Probiotic treatment also reduced the changes in the heart caused by the effects of DM. Furthermore, the Fas/Fas-associated protein with death domain pathway-induced caspase 8-mediated apoptosis that was observed in the cardiomyocytes of the STZ-induced DM rats was also found to be controlled in the probiotic-treated rats. The results highlight that L. reuteri GMN-32 treatment reduces blood glucose levels, inhibits caspase 8-mediated apoptosis and promotes cardiac function in DM rats as observed from their ejection fraction and fractional shortening values. In conclusion, the administration of L. reuteri GMN-32 probiotics can regulate blood glucose levels, protect cardiomyocytes and prevent DC in DM rats.
Owing to energy conservation of waste heat, Lead telluride, PbTe, based materials have promising good thermoelectric properties around a range of middle temperature (Fig. 1, from 300 to 600°C), due to their high melting point, fine chemical stability, and the high figure of merit Z. The general physical properties and factors affecting the figure of merit have been reviewed. This research is focused on the n-type of PbTe materials and collocated with analysis of densities, hardness, elastic modulus, and thermoelectric properties thermoelectric figure of merit ZT=GS2T/κ (where G is electrical conductivity, S is Seebeck coefficient , T is absolute temperature, and κ is thermal conductivity). Room temperature hardness and Young’s modulus are measured by nano-indentation. In this study, the hot-press compacts under the pressure of 4 ton/cm2 can reach the maximum density about 8.2 g/cm3, and hardness and elastic modulus are 0.6 GPa and 70 GPa, respectively. The figure of merit value (ZT) of PbTe in low temperature (around 340°C) was found about 1 with carrier concentration above 1019 cm−3. These results also indicate that the powder metallurgy parameters provide potentialities for further increase of the high efficiency of energy conversion in PbTe materials.
Various topics related to reverse logistics have been discussed over the years. Most of them have assumed that facilities are kept open once they are established, and no returned products or recovery parts are stocked in intermediate recycling stations. However, firms may have the right to repeatedly open or close their facilities according to their economic benefits if they can acquire their facilities by lease. It also turns out that intermediate recycling stations like collection centers and disassembly centers usually stock returned products or parts in their facilities. By simultaneously relaxing these two assumptions, this study explores a logistics system with multiple items, each of which consists of some components among a variety of spare parts. The purpose is to maximize the total logistics costs by establishing a production schedule and reverse logistics framework over finite time periods for a logistics system. The mathematical model established in this study is a constrained linear integer programming problem. A genetic based algorithm is developed with the help of linear programming to find solutions to this problem. Limited computational experiments show that the proposed approach can produce better feasible solutions than the well-known CPLEX 10.0 software.
Fluorescent nanodiamonds (FNDs) with a size in the range of 10 – 100 nm have been produced by ion irradiation and annealing, and isolated by differential centrifugation. Single particle spectroscopic characterization with confocal fluorescence microscopy and fluorescence correlation spectroscopy indicates that they are photostable and useful as an alternative to far-red fluorescent proteins for bioimaging applications. We demonstrate the application by performing in vivo imaging of bare and bioconjugated FND particles (100 nm in diameter) in C. elegans and zebrafishes and exploring the interactions between this novel nanomaterial and the model organisms. Our results indicate that FNDs can be delivered to the embryos of both organisms by microinjection and eventually into the hatched larvae in the next generation. No deleterious effects have been observed for the carbon-based nanoparticles in vivo. The high fluorescence brightness, excellent photostability, and nontoxic nature of the nanomaterial have allowed long-term imaging and tracking of embryogenesis in the organisms.
To evaluate the effect on decrease in blood pressure of modifying risk factors for stroke, such as blood lipid profiles, diet habits and indices of body weight, through a family-based nutrition health education programme among hypertensive patients and pre-hypertensive subjects without taking any antihypertensive drugs.
Design and setting
This was a community-based prospective study. The study population was randomly selected from communities in Taipei; potential subjects were invited by telephone to participate.
Subjects
After excluding subjects whose blood pressure was normal and those using antihypertensive drugs, there were 390 participants included in the study. Subjects in the intervention group (n 293) received nutrition health education on blood pressure control and stroke-related risk factor modification at each visit. Non-intervention subjects (n 97) only acquired a general education sheet available in clinics. The blood pressure of study subjects was measured at baseline and 6-month follow-up to evaluate the intervention’s effect on decrease in blood pressure.
Results
Significant decreases of 2·0 mmHg and 5·9 mmHg in systolic blood pressure were observed both in pre-hypertensive and hypertensive subjects in the intervention group. Additionally, intervention subjects with improvement of total cholesterol and LDL cholesterol, decrease in indices of body weight and increase in consumption of fruit and vegetables also had significant lowering of blood pressure.
Conclusions
The present study provided evidence that the blood pressure of pre-hypertensive and hypertensive subjects could decrease significantly, without taking antihypertensive drugs, after modifying blood lipid profiles and waist by dietary habits changed through a family-based nutrition heath education programme, resulting in a significant effect on stroke risk reduction.
To evaluate the effects of a hand hygiene program on compliance with hand hygiene and the rate of nosocomial infections in a neonatal intensive care unit (NICU).
Design:
Open trial.
Setting:
A level-III NICU in a teaching hospital.
Participants:
Nurses, physicians, and other healthcare workers in the NICU.
Interventions:
A multimodal campaign for hand hygiene promotion was conducted beginning in September 1998. This program consisted of formal lectures, written instructions and posted reminders regarding hand hygiene and proper handwashing techniques, covert observation, financial incentives, and regular group feedback on compliance. Surveillance of handwashing compliance and nosocomial infections before and during the program was analyzed.
Results:
Overall compliance with hand hygiene improved from 43% at baseline to 80% during the promotion program. The rate of nosocomial infections decreased from 15.13 to 10.69 per 1,000 patient-days (P = .003) with improved handwashing compliance. In particular, respiratory tract infections decreased from 3.35 to 1.06 per 1,000 patient-days during the handwashing campaign (P = .002). Furthermore, the correlation between nosocomial infection of the respiratory tract and handwashing compliance also reached statistical significance (r = -0.385; P = .014).
Conclusions:
Improved compliance with handwashing was associated with a significant decrease in overall rates of nosocomial infection and respiratory infections in particular. Washing hands is a simple, economical, and effective method for preventing nosocomial infections in the NICU
The sudden emergence of severe acute respiratory syndrome (SARS) caused international anxiety owing to its highly contagious and pandemic transmission. Health workers are vulnerable and are at high risk of infection.
Aims
To assess SARS-related stress and its immediate psychological impact and responses among health workers.
Method
Health workers in a tertiary hospital affected by SARS were invited to complete a questionnaire designed to evaluate exposure experience, psychological impact and psychiatric morbidity. The risk and rates of psychiatric morbidity were estimated for exposure experience.
Results
Altogether, 1257 health workers successfully completed the survey. In the initial phase of the outbreak, when the infection was spreading rapidly, feelings of extreme vulnerability, uncertainty and threat to life were perceived, dominated by somatic and cognitive symptoms of anxiety. During the ‘repair’ phase, when the infection was being brought under control, depression and avoidance were evident. The estimated prevalence of psychiatric morbidity measured by the Chinese Health Questionnaire was about 75%.
Conclusions
The outbreak of SARS could be regarded as an acute episode of a bio-disaster, leading to a significantly high rate of psychiatric morbidity.
We have developed a fabrication procedure for growing photonic crystals in the lithographic defined microchannels, which enables easy integration with other planar optical components. This technique is based on the directed evaporation induced self-assembly of nanoparticles in the microchannels. Substrates with pre-patterned microchannels (30-100 μm wide) were dipped into solution of nanoparticles for several days. By controlling the evaporation rate, the meniscus contacting the microchannels will undergo evaporation-induced self-assembly. The capillary forces cause nanospheres to crystallize within the microchannels forming colloidal photonic crystals in the microchannels. Two types of colloidal particles, polystyrene and silica, have been employed to fabricate colloidal photonic crystals in the microchannels. Both types of colloidal particles were found to form large-area well-ordered colloidal single crystals in the microchannels. The optical reflection spectra from the (111) surfaces of the colloidal crystals formed by various sizes of nanoparticles have been measured. And the measured reflection peaks agree with the photonic bandgap calculated by the plane wave expansion method.
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