Detailing the effects of polypharmacy in psychiatry: longitudinal study of 320 patients hospitalized for depression or schizophrenia

Current treatment standards in psychiatry are oriented towards polypharmacy, that is, patients receive combinations of several antidepressants, antipsychotics, mood stabilizers, anxiolytics, hypnotics, antihistamines, and anticholinergics, along with other somatic treatments. In tandem with the beneficial effects of psychopharmacological drug treatment, patients experience significant adverse reactions which appear to have become more frequent and more severe with the rise of ubiquitous polypharmacy. In this study, we aimed to assess today's acute inpatient treatment of depressive and schizophrenic disorders with focus on therapeutic strategies, medications, adverse side effects, time course of recovery, and efficacy of treatments. Of particular interest was the weighing of the benefits and drawbacks of polypharmacy regimens. We recruited a total of 320 patients hospitalized at three residential mental health treatment centers with a diagnosis of either schizophrenic (ICD-10: "F2x.x"; n = 94; "F2 patients") or depressive disorders (ICD-10: "F3x.x"; n = 226; "F3 patients"). The study protocol included (1) assessment of previous history by means of the SADS Syndrome Check List SSCL-16 (lifetime version); (2) repeated measurements over 5 weeks assessing the time course of improvement by the Hamilton Depression Scale HAM-D and the Positive and Negative Syndrome Scale PANSS, along with medications and adverse side effects through the Medication and Side Effects Inventory MEDIS; and (3) the collection of blood samples from which DNA and serum were extracted. Polypharmacy was by far the most common treatment regimen (85%) in this study. On average, patients received 4.50 ± 2.68 medications, consisting of 3.30 ± 1.84 psychotropic drugs, plus 0.79 ± 1.13 medications that alleviate adverse side effects, plus 0.41 ± 0.89 other somatic medications. The treating psychiatrists appeared to be the main determining factor in this context, while «previous history» and «severity at baseline» played a minor role, if at all. Adverse drug reactions were found to be an inherent component of polypharmacy and tended to have a 2-3 times higher incidence compared to monotherapy. Severe adverse reactions could not be attributed to a particular drug or drug combination. Rather, the empirical data suggested that severe side effects can be triggered by virtually all combinations of drugs, provided patients have a respective vulnerability. In terms of efficacy, there were no advantages of polypharmacy over monotherapy. The results of this study underlined the fact that polypharmacy regimens are not equally suited for every patient. Specifically, such regimens appeared to have a negative impact on treatment outcome and to obfuscate the "natural" time course of recovery through a multitude of interfering factors. Evidence clearly speaks against starting just every therapeutic intervention in psychiatry with a combination of psychopharmaceuticals. We think that it is time for psychiatry to reconsider its treatment strategies, which are far too one-sidedly fixated on psychopharmacology and pay far too little attention to alternative approaches, especially in mild cases where psychotherapy without concurrent medication should still be an option. Also, regular exercises and sports can definitely be an effective therapeutic means in a considerable number of cases. General practitioners (GPs) are particularly in demand here

Propositional update operators based on formula/literal dependence

International audienceWe present and study a general family of belief update operators in a propositional setting. Its operators are based on formula/literal dependence, which is more fine-grained than the notion of formula/variable dependence that was proposed in the literature: formula/variable dependence is a particular case of formula/literal dependence. Our update operators are defined according to the "forget-then-conjoin" scheme: updating a belief base by an input formula consists in first forgetting in the base every literal on which the input formula has a negative influence, and then conjoining the resulting base with the input formula. The operators of our family differ by the underlying notion of formula/literal dependence, which may be defined syntactically or semantically, and which may or may not exploit further information like known persistent literals and pre-set dependencies. We argue that this allows to handle the frame problem and the ramification problem in a more appropriate way. We evaluate the update operators of our family w.r.t. two important dimensions: the logical dimension, by checking the status of the Katsuno-Mendelzon postulates for update, and the computational dimension, by identifying the complexity of a number of decision problems (including model checking, consistency and inference), both in the general case and in some restricted cases, as well as by studying compactability issues. It follows that several operators of our family are interesting alternatives to previous belief update operators

As a Matter of Factions: The Budgetary Implications of Shifting Factional Control in Japan’s LDP

For 38 years, the Liberal Democratic Party (LDP) maintained single-party control over the Japanese government. This lack of partisan turnover in government has frustrated attempts to explain Japanese government policy changes using political variables. In this paper, we look for intraparty changes that may have led to changes in Japanese budgetary policy. Using a simple model of agenda-setting, we hypothesize that changes in which intraparty factions “control” the LDP affect the party’s decisions over spending priorities systematically. This runs contrary to the received wisdom in the voluminous literature on LDP factions, which asserts that factions, whatever their raison d’être, do not exhibit different policy preferences. We find that strong correlations do exist between which factions comprise the agenda-setting party “mainstream” and how the government allocates spending across pork-barrel and public goods items

Automating Agential Reasoning: Proof-Calculi and Syntactic Decidability for STIT Logics

This work provides proof-search algorithms and automated counter-model extraction for a class of STIT logics. With this, we answer an open problem concerning syntactic decision procedures and cut-free calculi for STIT logics. A new class of cut-free complete labelled sequent calculi G3LdmL^m_n, for multi-agent STIT with at most n-many choices, is introduced. We refine the calculi G3LdmL^m_n through the use of propagation rules and demonstrate the admissibility of their structural rules, resulting in auxiliary calculi Ldm^m_nL. In the single-agent case, we show that the refined calculi Ldm^m_nL derive theorems within a restricted class of (forestlike) sequents, allowing us to provide proof-search algorithms that decide single-agent STIT logics. We prove that the proof-search algorithms are correct and terminate

Assessing the ecological vulnerability of the shallow steppe Lake Neusiedl (Austria-Hungary) to climate-driven hydrological changes using a palaeolimnological approach

9openInternationalBothLake Neusiedl, the largest steppe lake in Europe, is particularly sensitive to climate variations due to its extreme shallowness (zmax = 1.8 m) and low ratio of catchment to lake area (3.5 : 1). Changes in water budget, salinity and turbidity have key implications for the lake’s ecology and management. Here, we present a multi-proxy palaeolimnological reconstruction of the evolution of Lake Neusiedl since the end of its last complete desiccation (1865–1868), based on an undisturbed radiometrically dated core taken from the open water portion of the lake. Geochemical and biological (algal) proxies outline the succession of three major ecological stages since 1873 ± 16 yrs, with the first major changes appearing already in the 1930s as driven by climate related hydrological variability. Subfossil diatoms proved to be reliable for tracking long-term changes in the trophic conditions of Lake Neusiedl while diatom-inferred lake conductivity revealed to be unreliable due to a combination of lake environmental settings and the absence of a site-specific training set. Nonetheless, multivariate statistical analyses and comparisons with limnological data confirm a great potential of subfossil diatoms for revealing past ecological changes and tipping points of shallow lakes, as long as studies rely on a multi-proxy approach. In agreement with limnological surveys, the sediment record corroborates the high vulnerability of Lake Neusiedl, both in present and past times, towards climate-driven changes in water level and salinity, and allows the prediction, by analogy with the past, of future ecological changes in a context of global warming and increasing nutrient inputs from non-point sources.openTolotti, M.; Guella, G.; Herzig, A.; Rodeghiero, M.; Rose, N.L.; Soja, G.; Zechmeister, T.; Yang, H.; Teubner, K.Tolotti, M.; Guella, G.; Herzig, A.; Rodeghiero, M.; Rose, N.L.; Soja, G.; Zechmeister, T.; Yang, H.; Teubner, K

Stiffness Imaging With a Continuum Appendage: Real-Time Shape and Tip Force Estimation From Base Load Readings

In this paper, we propose benefiting from load readings at the base of a continuum appendage for real-time forward integration of Cosserat rod model with application in configuration and tip load estimation. The application of this method is successfully tested for stiffness imaging of a soft tissue, using a 3-DOF hydraulically actuated braided continuum appendage. Multiple probing runs with different actuation pressures are used for mapping the tissue surface shape and directional linear stiffness, as well as detecting non-homogeneous regions, e.g. a hard nodule embedded in a soft silicon tissue phantom. Readings from a 6-axis force sensor at the tip is used for comparison and verification. As a result, the tip force is estimated with 0.016-0.037 N (7-20%) mean error in the probing and 0.02-0.1 N (6-12%) in the indentation direction, 0.17 mm (14%) mean error is achieved in estimating the surface profile, and 3.4-15 [N/m] (10-16%) mean error is observed in evaluating tissue directional stiffness, depending on the appendage actuation. We observed that if the appendage bends against the slider motion (toward the probing direction), it provides better horizontal stiffness estimation and better estimation in the perpendicular direction is achieved when it bends toward the slider motion (against the probing direction). In comparison with a rigid probe, ≈ 10 times smaller stiffness and ≈ 7 times larger mean standard deviation values were observed, suggesting the importance of a probe stiffness in estimation the tissue stiffness

Subjective self-assessment of physical activity is negatively affected by monitoring awareness in subjects with mild cognitive impairment : A crossover randomised controlled trial

Publisher Copyright: © 2021 Verduci Editore s.r.l. All rights reserved.OBJECTIVE: Physical activity plays an important role in maintaining mental and physical health. This study assessed the effect of physical activity monitoring awareness on the physical activity level and subjective self-assessment of physical activity in middle-aged subjects with normal cognitive function (NCF) and mild cognitive impairment (MCI). PATIENTS AND METHODS: Thirty-five subjects aged 50-65 years with NCF and MCI were randomised into two experimental groups, each taking part in two one-week intervention periods. Subjects in group A were not aware that their physical activity was monitored in the first week (phase I) and were aware of the monitoring in the second week (phase II), whereas it was the opposite order for group B. Physical activity was assessed using the ActiGraph GT9X accelerometer and International Physical Activity Questionnaire (IPAQ). RESULTS: A total of 32 subjects (MCI: n = 12, NCF: n = 20) completed both intervention periods, with MCI subjects having significantly lower objectively assessed physical activity than NCF participants. Moreover, subjectively assessed physical activity in the MCI group was significantly higher when the participants were unaware of physical activity monitoring. A significant phase-group interaction was found in total (MET-min/d: P = 0.0072; min/d: P = 0.0194) and moderate (MET-min/d: P = 0.0015; min/d: P = 0.0020) physical activity as well as energy expenditure (p = 0.0366) assessed by the IPAQ and in the percentage of sedentary behaviour (p = 0.0330) and the average number of steps (p = 0.0342) assessed by ActiGraph. CONCLUSIONS: The awareness of physical activity assessment might decrease the ability to subjectively assess physical activity in subjects with MCI.Peer reviewe

Hydrokinetic pancreatic function and insulin secretion are moduled by Cl− uniporter Slc26a9 in mice

Aim: Slc26a9 is a member of the Slc26 multifunctional anion transporter family. Polymorphisms in Slc26a9 are associated with an increased incidence of meconium ileus and diabetes in cystic fibrosis patients. We investigated the expression of Slc26a9 in the murine pancreatic ducts, islets and parenchyma, and elucidated its role in pancreatic ductal electrolyte and fluid secretion and endocrine function. Methods: Pancreatic Slc26a9 and CFTR mRNA expression, fluid and bicarbonate secretion were assessed in slc26a9−/− mice and their age- and sex-matched wild-type (wt) littermates. Glucose and insulin tolerance tests were performed. Results: Compared with stomach, the mRNA expression of Slc26a9 was low in pancreatic parenchyma, 20-fold higher in microdissected pancreatic ducts than parenchyma, and very low in islets. CFTR mRNA was ~10 fold higher than Slc26a9 mRNA expression in each pancreatic cell type. Significantly reduced pancreatic fluid secretory rates and impaired glucose tolerance were observed in female slc26a9−/− mice, whereas alterations in male mice did not reach statistical significance. No significant difference was observed in peripheral insulin resistance in slc26a9−/− compared to sex- and aged-matched wt controls. In contrast, isolated slc26a9−/− islets in short term culture displayed no difference in insulin content, but a significantly reduced glucose-stimulated insulin secretion compared to age- and sex-matched wt islets, suggesting that the impaired glucose tolerance in the absence of Slc26a9 expression these is a pancreatic defect. Conclusions: Deletion of Slc26a9 is associated with a reduction in pancreatic fluid secretion and impaired glucose tolerance in female mice. The results underline the importance of Slc26a9 in pancreatic physiology. © 2021 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society