Antipsychotic polypharmacy remains prevalent; it has probably increased for the treatment of schizophrenia in real-world clinical settings. The current evidence suggests some clinical benefits of ...antipsychotic polypharmacy, such as better symptom control with clozapine plus another antipsychotic, and a reversal of metabolic side-effects with a concomitant use of aripiprazole. On the other hand, the interpretation of findings in the literature should be made conservatively in light of the paucity of good studies and potentially serious side-effects. Also, although the available data are still limited, two smaller-scale clinical trials provide preliminary evidence that converting antipsychotic polypharmacy to monotherapy could be a valid and reasonable treatment option. Several studies have explored strategies to change physicians’ antipsychotic polypharmacy prescribing behaviours. These have revealed that, while the impact of purely educational interventions may be limited, more aggressive procedures such as directly notifying physicians by letters or phone calls can be more effective in reducing antipsychotic polypharmacy. In conclusion, antipsychotic polypharmacy can work for some clinically difficult conditions; however, it should be the exception rather than the rule and may be avoidable in many patients. More importantly, the paucity of the data clearly emphasizes the need for further investigations on not only advantages and disadvantages of antipsychotic polypharmacy, but also regarding effective interventions in already prescribed polypharmacy regimens.
•We conducted the first meta-analysis on metabolite levels of kynurenine pathway in patients with depression.•Out of 899 initial records, 22 articles were identified.•Kynurenic acid and kynurenine ...levels are decreased in patients with depression.•Quinolinic acid levels are increased in unmedicated patients with depression.•Future research should examine relationships between treatment and kynurenine pathway.
Abnormalities of the kynurenine (KYN) pathway may be implicated in the pathophysiology of depression. However, the relationships between depression and each metabolite of the KYN pathway remain uncertain. Therefore, we conducted a meta-analysis about the levels of the metabolites of KYN pathway between patients with depression and controls. Out of 899 initial records, we identified 22 articles to form the empirical basis. Seventeen, 10, and 18 studies examined levels of kynurenic acid (KYNA), quinolinic acid (QUIN), and KYN, respectively. KYNA and KYN levels were lower in patients with depression in comparison to controls, while QUIN levels did not differ between the two groups. Antidepressant-free patients showed decreased KYNA levels and increased QUIN levels compared with controls. Male ratios of the samples were negatively associated with study SMDs for KYNA. In conclusion, this meta-analysis revealed that patients with depression had decreased level of KYNA and KYN, whereas antidepressant-free patients showed increased level of QUIN. Nevertheless, given the heterogeneity among their sample characteristics, further research is clearly needed.
We investigated the effects of short-side-chain (SSC) perfluorosulfonic acid ionomers on the electrochemical properties, fuel cell performance and ionomer distribution of a highly dispersed Pt/GCB ...catalyst with a low Pt loading, 0.05 mg cm−2. The SSC ionomers in the cathode catalyst layers (CLs) resulted in an improvement of the Pt utilization (UPt) and Pt effectiveness (EfPt) values compared with those for the conventional long-side-chain (LSC) ionomer. Furthermore, the SSC ionomers with high ion exchange capacity (IEC), e.g., SSC-1.43 and SSC-1.80 ionomers, exhibited significantly enhanced cell performance under low to medium relative humidity (RH) conditions. This result is ascribed to the higher proton conductivity of the SSC ionomers and more effective trapping of water that is produced during the oxygen reduction reaction (ORR) than those of the LSC ionomer. It was also found that the SSC ionomers showed better continuity and uniformity on the Pt and carbon particles than the LSC ionomer, which might have led to improvement of both the mass transport and the proton-conducting network in the CLs. The application of the SSC ionomers as binders demonstrated an increase of the performance at the low Pt loading fuel cell cathode over a wide range of humidity.
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•Pt utilization and effectiveness improve in cathodes with short side chain ionomers.•Short side chain (SSC) ionomer-based cathodes perform better at low humidity.•This is due to higher proton conductivity because of more effective water trapping.•The SSC ionomer covered the Pt and GCB particles more uniformly and continuously.•This leads to improvement of mass transport and proton-conducting networks.
This systematic review and meta-analysis examined predictors of successful antipsychotic dose reduction in schizophrenia. Prospective clinical trials and randomized controlled trials (RCTs) ...investigating antipsychotic dose reduction in schizophrenia were selected for systematic review and meta-analysis, respectively. In total, 37 trials were identified. Only 8 studies focused on second-generation antipsychotics (SGAs); no studies investigated long-acting injectable SGAs. Of 24 studies evaluating relapse or symptom changes, 20 (83.3%) met the criteria for successful dose reduction. Factors associated with successful dose reduction were study duration < 1 year, age > 40 years, duration of illness > 10 years, and post-reduction chlorpromazine equivalent (CPZE) dose > 200 mg/day. Clinical deterioration was mostly re-stabilized by increasing the dose to the baseline level (N = 7/8, 87.5%). A meta-analysis of 18 RCTs revealed that relapse rate was significantly higher in the reduction group than the maintenance group (risk ratio RR = 1.96; 95% confidence interval CI, 1.23-3.12), whereas neurocognition was significantly improved (standardized mean difference = 0.69; 95% CI, 0.25-1.12). A subgroup analysis indicated that only a post-reduction CPZE dose ≤ 200 mg/day was associated with an increased risk of relapse (RR = 2.79; 95% CI, 1.29-6.03). Thus, when reducing antipsychotic doses, clinicians should consider the long-term risk of relapse in younger patients with a relatively short illness duration and keep the final doses higher than CPZE 200 mg/day. Further studies, particularly those involving SGAs, are warranted to determine the optimal strategies for successful antipsychotic dose reduction in schizophrenia.
Segregation is a key theme of this film: Poly(arylene ether sulfone ketone) multiblock membranes containing highly sulfonated hydrophilic blocks were prepared by postsulfonation. High local ...concentrations of sulfonic acid groups within the hydrophilic blocks enhanced the phase separation of the two block types (see picture), and the high interconnectivity of the rodlike hydrophilic aggregates led to high proton conductivity even at low humidity.
We updated our previous systematic review regarding clinical guidelines and algorithms on antipsychotic treatment in the maintenance phase of schizophrenia (doi: 10.1016/j.schres.2011.11.021) to ...incorporate and synthesize more recent findings to guide clinical practice.
We conducted a systematic literature search to identify clinical guidelines and algorithms describing antipsychotic treatment in the maintenance phase of schizophrenia using MEDLINE and Embase. We assessed overall quality of the guidelines/algorithms according to the AGREE II instrument and extracted information on treatment recommendations.
We identified 20 guidelines/algorithms from various regions, including 11 updated or newly launched ones after the previous systematic review in 2012. All of the guidelines/algorithms satisfied a certain level of quality. Where mentioned, endorsements were sorted into “recommended”, “partially recommended”, or “not recommended”. As for antipsychotic discontinuation strategy, a majority of guidelines/algorithms that mentioned this strategy did not recommend it for multiple-episode schizophrenia (N = 5/6). On the other hand, the guidelines/algorithms tended to shift from “not recommended” to “partially recommended” both for schizophrenia in general (N = 7/13, N = 7/8 for those published after 2013) and first-episode schizophrenia (N = 10/11, N = 7/7 for those published after 2013) regarding this strategy. All guidelines/algorithms (N = 9/9) converged to discourage antipsychotic intermittent/targeted strategy. Similar to antipsychotic discontinuation strategy, all of the updated or new guidelines/algorithms (N = 6/6) endorsed antipsychotic dose reduction/lower dose strategy.
Recent clinical guidelines and algorithms on antipsychotic maintenance treatment in schizophrenia shifted more toward a possibility of antipsychotic discontinuation and dose reduction/lower dose strategies. Nonetheless, clinicians need to contemplate on the risk-benefit balance of these strategies for individual patients.
The unpredictability and uncertainty of the COVID-19 pandemic; the associated lockdowns, physical distancing, and other containment strategies; and the resulting economic breakdown could increase the ...risk of mental health problems and exacerbate health inequalities. Preliminary findings suggest adverse mental health effects in previously healthy people and especially in people with pre-existing mental health disorders. Despite the heterogeneity of worldwide health systems, efforts have been made to adapt the delivery of mental health care to the demands of COVID-19. Mental health concerns have been addressed via the public mental health response and by adapting mental health services, mostly focusing on infection control, modifying access to diagnosis and treatment, ensuring continuity of care for mental health service users, and paying attention to new cases of mental ill health and populations at high risk of mental health problems. Sustainable adaptations of delivery systems for mental health care should be developed by experts, clinicians, and service users, and should be specifically designed to mitigate disparities in health-care provision. Thorough and continuous assessment of health and service-use outcomes in mental health clinical practice will be crucial for defining which practices should be further developed and which discontinued. For this Position Paper, an international group of clinicians, mental health experts, and users of mental health services has come together to reflect on the challenges for mental health that COVID-19 poses. The interconnectedness of the world made society vulnerable to this infection, but it also provides the infrastructure to address previous system failings by disseminating good practices that can result in sustained, efficient, and equitable delivery of mental health-care delivery. Thus, the COVID-19 pandemic could be an opportunity to improve mental health services.
The purpose of this study was to compare prefrontal cortex (PFC) activity among subjects with differing social anxiety (SA) severity levels to identify a possible biomarker for severe SA. Further, SA ...is generally under-diagnosed, so we examined if such measurements could be acquired conveniently, non-invasively, and at low cost using a portable near-infrared spectroscopy (NIRS) system. We classified 96 participants into three groups based on Liebowitz Social Anxiety Scale (LSAS) total score: Low SA (LSA,
n
= 40), Moderate SA (MSA,
n
= 39), and High SA (HSA,
n
= 17). We compared the prefrontal hemodynamic responses among LSAS severity groups during a verbal fluency task using a palm-sized NIRS system. The HSA group exhibited a significantly lower hemodynamic response in the left PFC compared to LSA and MSA groups, whereas there was no significant difference between LSA and MSA groups. There was also no significant difference in the right PFC hemodynamic response among groups. Differences in the severity of SA symptoms may be related to the left PFC function. Low PFC activity during specific cognitive tasks may provide a biomarker for distinguishing severe from mild/moderate SA symptoms to guide subsequent therapeutic decisions.
We have examined the durability of a double-layer hydrogen electrode, consisting of a samaria-doped ceria (SDC) scaffold with highly dispersed Ni-Co nanoparticles as the catalyst layer and a thin ...current collecting layer of Ni-yttria-stabilized zirconia (YSZ) cermet for a reversible solid oxide cell (R-SOC). When steam electrolysis was performed continuously (solid oxide electrolysis cell, SOEC) at 800 °C, a rapid, large increase in the ohmic resistance of the hydrogen electrode side was observed. In contrast, the durability of the hydrogen electrode was found to be improved remarkably by reversible cycling operation between SOEC and solid oxide fuel cell (SOFC) modes, i.e., virtually no degradation over 1200 h. This could be ascribed to a stabilization of the microstructure of the hydrogen electrode. It was also found that the durability of the oxygen electrode, which was based on a composite of La0.6Sr0.4Co0.2Fe0.8O3−δ (LSCF) and SDC with an SDC interlayer, was also improved by the reversible cycling operation, compared with a slight degradation in the continuous SOEC operation.
Abstract The kinematics of shocks, ejecta knots, and the compact remnant of a supernova remnant give insights into the nature of the progenitor and the surrounding environment. We report on a ...measurement of the proper motion of X-ray knots and rims of the magnetar-hosting supernova remnant RCW 103. Chandra data obtained in three epochs, 1999, 2010, and 2016, are used. We find a global deceleration of 12 knots and rims in both northern and southern regions within the last ∼24 yr, even though the age of the remnant is thought to be greater than 2 kyr. Some of them even changed their directions of motion from outward (∼1000 km s −1 ) to inward (∼−2000 km s −1 ). Our findings can be explained by a collision with a high-density medium at both the northern and southern edges of the remnant, although the remnant may still be expanding in the windblown cavity. The proper motion of the associated magnetar 1E 161348−5055 is possibly detected with a velocity of ≈500 km s −1 .
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