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Undesirable behaviors of dogs and cats may reduce their quality of life and may cause harm to their owners. Such behaviors have been treated with medications as well as behavioral training and environmental modifications. Finnish veterinarians answered a web-based questionnaire to characterize the treatment of undesirable behaviors in dogs and cats by medications. Fourteen indications related to undesirable behaviors were defined in the questionnaire. Most psychoactive medications authorized for veterinary or human use in Finland and allowed to be prescribed for animal use according to the national legislation were listed. In addition, some sedative and analgesic agents were included. Canine and feline undesirable behaviors were treated by the respondents with a wide variety of medications. In many cases, none of the remedies used could be demonstrated to be a clear favorite for a certain indication. Off-label use of psychoactive medications was common. Many medications were used without research-based evidence of their efficacy for the indication in those species in question. Treatment of dogs was more often associated with advice for behavioral training in addition to medications than treatment of cats. Both the common off-label use of medications and the wide variety of substances used for the particular behavioral problem reveal the need for further clinical evidence of the efficacy of medications to treat various canine and feline undesirable behaviors. • Undesirable behaviors of dogs and cats were treated with a wide variety of medicines. • Off-label use of psychoactive medicinal substances was common. • Some drugs were used with no evidence of their efficacy for the indication. • Dog owners were advised for behavioural training more often than cat owners. [ABSTRACT FROM AUTHOR]

Criminality rates are higher among persons with attention-deficit/hyperactivity disorder (ADHD), and evidence that medication reduces crime is limited. Medication rates between clinics vary widely even within universal health care systems, partly because of providers' treatment preferences. We used this variation to estimate causal effects of pharmacological treatment of ADHD on 4-year criminal outcomes. We used Norwegian population-level registry data to identify all unique patients aged 10 to 18 years diagnosed with ADHD between 2009 and 2011 (n = 5,624), their use of ADHD medication, and subsequent criminal charges. An instrumental variable design, exploiting variation in provider preference for ADHD medication between clinics, was used to identify causal effects of ADHD medication on crime among patients on the margin of treatment, that is, patients who receive treatment because of their provider's preference. Criminality was higher in patients with ADHD relative to the general population. Medication preference varied between clinics and strongly affected patients' treatment. Instrumental variable analyses supported a protective effect of pharmacological treatment on violence-related and public-order−related charges with numbers needed to treat of 14 and 8, respectively. There was no evidence for effects on drug-, traffic-, sexual-, or property-related charges. This is the first study to demonstrate causal effects of pharmacological treatment of ADHD on some types of crimes in a population-based natural experiment. Pharmacological treatment of ADHD reduced crime related to impulsive-reactive behavior in patients with ADHD on the margin of treatment. No effects were found on crimes requiring criminal intent, conspiracy, and planning. The ADHD controversy project: Long-term effects of ADHD medication; https://www.isrctn.com/ ; 11891971. [ABSTRACT FROM AUTHOR]

Both depression and rheumatoid arthritis (RA) have a very high comorbidity rate. A bilateral association is estimated to increase the mutual risk and the common denominator is inflammation being observed in both diseases. Previous studies have mainly focused on assessing peripheral blood's inflammatory and pro-inflammatory cytokines levels. We aimed to extend insights into the molecular mechanisms of depression based on hub RA genes. To do so, we prioritized RA-related genes using in-silico tools. We then investigated whether RA-related genes undergo altered expression in patients with unipolar and bipolar depression without a concurrent RA diagnosis and any exponents of active inflammation. In addition, we selected a homogeneous group of patients treated with lithium (Li), which has immunomodulatory properties. The study was performed on patients with bipolar depression (BD, n = 45; Li, n = 20), unipolar depression (UD, n = 27), and healthy controls (HC, n = 22) of both sexes. To identify DEGs in peripheral blood mononuclear cells (PBMCs), we used the SurePrint G3 Microarray and GeneSpring software. We selected a list of 180 hub genes whose altered expression we analyzed using the expression microarray results. In the entire study group, we identified altered expression of 93 of the 180 genes, including 35 down-regulated (OPRM1 gene with highest FC > 3) and 58 up-regulated (TLR4 gene with highest FC > 3). In UD patients, we observed maximally up-regulated expression of the TEK gene (FC > 3), and in BD of the CXCL8 gene (FC > 5). On the other hand, in lithium-treated patients, the gene with the most reduced expression was the TRPV1 gene. The study proved that depression and RA are produced by a partially shared "inflammatory interactome" in which the opioid and angiogenesis pathways are important. [ABSTRACT FROM AUTHOR]

Pharmacotherapy remains crucial for treating bipolar disorder (BD), but knowledge on the treatments actually used by newly diagnosed patients in real-world settings is sparse. Individuals newly diagnosed with BD during 1996–2018, aged 15–65 years, were identified from national Finnish registers. The patients' use of different drug classes (mood stabilizers, antipsychotics and antidepressants) or combinations of these drug classes were followed from initial pharmacotherapy (first line) after BD diagnosis until the fifth line of treatment or until the two-year follow-up time ended. Clinical and sociodemographic factors associated with antidepressants-only as the first treatment line were assessed with logistic regression. 82.6 % of all patients used BD medication during the follow-up. 33.9 % had antidepressants-only as the first, 22.9 % as the second and 19.7 % as the third treatment line. Use of combinations of mood stabilizers, antipsychotics and antidepressants increased by successive treatment lines. Factors associated with antidepressants-only as the first treatment line included older age (>45 years aOR 2.20, 95% CI: 2.01–2.40, 25–45 years: 1.55, 1.42–1.68, compared with those aged <25), diabetes (1.35, 1.17–1.55) and female sex (1.29, 1.21–1.37). BD diagnosis registered in 2016–2018 (0.48, 0.42–0.55) and substance abuse (0.77, 0.71–0.83) were associated with decreased odds. Due to the register-based nature of this study, not all potentially important clinical factors influencing medication use could be controlled for. A large proportion of patients with bipolar disorder are not treated according to treatment guidelines, as use of antidepressants alone is common. Reasons for not following evidence-based recommendations need to be further researched. • Despite clinical guidelines, use of antidepressants alone was frequent among persons with incident BD. • Older age, female sex and comorbid diabetes were associated with antidepressant use. • Use of mood stabilizers, such as lithium was observed to be remarkably low. • Findings support the need for increasing the use of evidence-based treatments for BD. [ABSTRACT FROM AUTHOR]

Macrophages are major host cells for the protozoan Leishmania parasite. Depending on their activation state, they either contribute to the detection and elimination of Leishmania spp. or promote parasite resilience. Here, we report that the activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in macrophages plays a pivotal role in the progression of Leishmania infantum infection by controlling inflammation and redox balance of macrophages. We also highlight the involvement of the NOX2/reactive oxygen species (ROS) axis in early Nrf2 activation and, subsequently, prostaglandin E2 (PGE2)/EP2r signaling in the sustenance of Nrf2 activation upon infection. Moreover, we establish a ferroptosis-like process within macrophages as a cell death program of L. infantum and the protective effect of Nrf2 in macrophages against L. infantum death. Altogether, these results identify Nrf2 as a critical factor for the susceptibility of L. infantum infection, highlighting Nrf2 as a promising pharmacological target for the development of therapeutic approaches for the treatment of visceral leishmaniasis. [Display omitted] • ROS and the PGE2/EP2 axis mediate Nrf2 activation in MΦs to promote L.i. growth • Nrf2 promotes L.i. infection via an anti-oxidant and anti-inflammatory profile of MΦs • Nrf2 in MΦs protects L.i. from lipid peroxidation, preventing its death by ferroptosis Blot et al. demonstrate that Nrf2 is a critical transcription factor that protects Leishmania infantum from lipid peroxidation and death by a ferroptosis-like process through the induction of an anti-oxidant and anti-inflammatory profile of macrophages. Hence, pharmacological inhibition of Nrf2 constitutes a promising target for the treatment of visceral leishmaniasis. [ABSTRACT FROM AUTHOR]

• The most effective management strategy for alcohol use disorder is the combination of psychosocial interventions and pharmacological therapy. • Several medications have been tested for the treatment of alcohol use disorder over the years and some of them have been approved, even if the exact panel of approved drugs may vary across. countries. • The currently available medications for the treatment of AUD have shown good overall efficacy. • At present, drugs for AUD are markedly underutilized in clinical practice. Increasing the training of clinicians may increase familiarity with the medications, reducing the lack of confidence in their efficacy, which is an important barrier for their prescription. In the last decades, many medications have been tested for the treatment of Alcohol Use Disorder (AUD). Among them, disulfiram, acamprosate, naltrexone, nalmefene, sodium oxybate and baclofen have been approved in different countries, with different specific indications. Topiramate is not approved for the treatment of AUD, however, it is suggested as a therapeutic option by the American Psychiatric Association for patients who do not tolerate or respond to approved therapies. In this narrative review we have analyzed the main studies available in literature, investigating the efficacy and safety of these medications, distinguishing whether they were oriented towards abstinence or not. Randomized controlled studies, analyzing larger populations for longer periods were the main focus of our analysis. The medications currently available for the treatment of AUD are quite effective, yet further progress can still be achieved through the personalized strategies. Also, these medications are still markedly underutilized in clinical practice and many patients do not have access to specialized treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

To evaluate cost-effective pharmacological treatment in adult kidney transplant recipients from the perspective of the Colombian health system. A decision tree model for the induction phase and a Markov model for the maintenance phase were built. A review of the clinical literature was conducted to extract probabilities, and the life-years were used as the outcome. Costs were calculated using the administrative databases. The evaluating treatment schemes are organized by groups of evidence with direct comparisons. In the induction phase, anti-thymocyte immunoglobulin+ methylprednisolone is dominant, more effective, and less expensive, compared with basiliximab+methylprednisolone. In the maintenance phase, azathioprine (AZA) is dominant in contrast to mycophenolate mofetil (MFM) both with cyclosporine (CIC)+ corticosteroids (CE); CIC is dominant relative to sirolimus (SIR) and tacrolimus (TAC) (both with MFM+CE or AZA+CE), and TAC is dominant compared with SIR (in addition with MFM+CE or mycophenolate sodium [MFS]+CE); MFM is dominant in relation to MFS and everolimus, and SIR is more effective MFM but it does not exceed the threshold (in sum with TAC+CE); MFS and MFM are dominant relative to everolimus, and SIR is more effective than MFM, but it does not exceed the threshold (in addiction with CIC+CE); MFM is dominant in relation to TAC (in sum with SIR+CE), and CIC+AZA+CE is dominant in relation to TAC+MFM+CE. The base-case results for all evidence groups are consistent with the different sensitivity analyses. • The result of this research shows the economic and clinical benefits of the use of different pharmacological treatments for adult kidney transplant recipients in Colombia, considering the years of life gained and organ rejection avoided. • Tacrolimus and cyclosporine are the most used options in clinical practice for maintenance therapy and are included in the cost-effective schemes. • Across the different sets of evidence, tacrolimus+mycophenolate mofetil+corticosteroids, cyclosporine + mycophenolate mofetil+corticosteroids, and cyclosporine+ azathioprine+corticosteroids proved to be the cost-effective strategies in most comparisons. [ABSTRACT FROM AUTHOR]

• VPA use during pre and/or post-natal can cause deficits consistent with ASD. • Valproic acid prenatal and postnatal exposure in animal is a useful model for ASD. • ASD treatment is efficient in core and associated symptoms in animal models. • Peptides and bioinspired compounds are a possible future treatment of ASD. Over the past 70 years, the understanding of Autism Spectrum Disorder (ASD) improved greatly and is characterized as a heterogeneous neuropsychiatric syndrome. ASD is characterized by difficulties in social communication, restricted and repetitive behavior, interests, or activities. And it is often described as a combination of genetic predisposition and environmental factors. There are many treatments and approaches to ASD, including pharmacological therapies with antipsychotics, antidepressants, mood regulators, stimulants, and behavioral ones. However, no treatment is capable of reverting ASD. This review provides an overview of animal models of autism. We summarized genetic and environmental models and then valproic acid treatment as a useful model for ASD. As well as the main therapies and approaches used in the treatment, relating them to the neurochemical pathways altered in ASD, emphasizing the pharmacological potential of peptides and bioinspired compounds found in animal venoms as a possible future treatment for ASD. [ABSTRACT FROM AUTHOR]

To assess the impact of a rooming-in program for babies at risk of Neonatal Abstinence Syndrome (NAS) in one community hospital centre, in Belleville, Ontario. This retrospective chart review was conducted at Belleville General Hospital. The hospital developed a rooming-in program for newborns at risk of NAS in July 2015. Charts on all infants born to mothers using opioids in the 24 months prior to and after the implementation of our program, who met the inclusion criteria, were examined. The study consisted of 15 babies in the Special Care Nursery (SCN) group and 19 babies in the rooming-in group. Rooming-in is associated with a reduction in the need for treatment with morphine [rooming-in group (1/19, 5.3%), SCN group (14/15, 93.3%), p < 0.01], shorter length of stay in hospital [rooming-in group (days = 5), SCN group (days = 20), p < 0.01], improved exclusive breast and/or breast milk-feeding rates [rooming-in group (17/19,89.5%), SCN group (1/15,6.7%), p < 0.01] and lower total hospital cost [rooming-in group ($6458.00), SCN group ($17,851.00), p < 0.01]. Our study demonstrates that rooming-in programs for babies born to mothers using opioids has benefits in terms of quality of care and health care resource utilization. These findings show that rooming-in can be successfully implemented in a community hospital. • Rooming-in can be successfully implemented in a community hospital • Rooming-in is associated with a reduction in the need for treatment with morphine • Rooming-in is associated with a shorter length of stay in hospital • Rooming-in is associated with improved exclusive breast and/or breast milk-feeding rates • Rooming-in is associated with lower total hospital cost [ABSTRACT FROM AUTHOR]

Background: As the burden of treatment-resistant schizophrenia (TRS) on patients and society is high it is important to identify predictors of response to medications in TRS. The aim was to analyse whether baseline patient and study characteristics predict treatment response in TRS in drug trials.Methods: A comprehensive search strategy completed in PubMed, Cochrane and Web of Science helped identify relevant studies. The studies had to meet the following criteria: English language clinical trial of pharmacological treatment of TRS, clear definition of TRS and response, percentage of response reported, at least one baseline characteristic presented, and total sample size of at least 15. Meta-regression techniques served to explore whether baseline characteristics predict response to medication in TRS.Results: 77 articles were included in the systematic review. The overall sample included 7546 patients, of which 41% achieved response. Higher positive symptom score at baseline predicted higher response percentage. None of the other baseline patient or study characteristics achieved statistical significance at predicting response. When analysed in groups divided by antipsychotic drugs, studies of clozapine and other atypical antipsychotics produced the highest response rate.Conclusions: This meta-analytic review identified surprisingly few baseline characteristics that predicted treatment response. However, higher positive symptoms and the use of atypical antipsychotics - particularly clozapine -was associated with the greatest likelihood of response. The difficulty involved in the prediction of medication response in TRS necessitates careful monitoring and personalised medication management. There is a need for more investigations of the predictors of treatment response in TRS. [ABSTRACT FROM AUTHOR]

Insomnia in the elderly is a prevalent condition that poses treatment challenges to practitioners across medical fields. There are many behavioral and other nonpharmacological therapies, 18 Food and Drug Administration-approved pharmacotherapies, and numerous off-label, over the counter and alternative treatments. Most reviews on this subject focus either on pharmacological treatments or behavioral treatments. The authors provide a combined review of available pharmacological and nonpharmacological treatments. The authors narratively reviewed each treatment from our literature search, tabled results with the highest level of available evidence on 5 major sleep outcomes and evaluated these results for clinical significance. The authors also evaluated the safety of pharmacotherapies within the context of the 2019 Beers Criteria for Potentially Inappropriate Medications in the Elderly. The authors found the most rigorous evidence supporting Cognitive Behavioral Therapy for Insomnia as a first-line treatment option, with longer lasting therapeutic effects than treatment with pharmacologic agents alone. The authors also found evidence of similar outcomes from other behavioral interventions, such as Brief Behavioral Therapy for Insomnia and relaxation training. The authors found 4 studies, 2 on relaxation training, 1 on sleep restriction, and 1 on stimulus control limited to the elderly with clinically significant results. The authors found no pharmacological studies limited to the elderly on treatments not contraindicated by Beers criteria with clinically significant results. The authors discussed the challenges of determining clinical significance in sleep studies, the lack of studies restricted to the elderly, and the role of placebo effect. [ABSTRACT FROM AUTHOR]

• Mechanical ventilation is a double-edged sword for pulmonary fibrosis. • The ACE/Ang-2/AT1R axis plays an important role in the process of MVPF. • rACE2, AT1R inhibitor, AGTR1-directed shRNA or ACE inhibitor attenuates MVPF via inhibiting the ACE/Ang-2/AT1R axis. • Pharmacological inhibition of the ACE/Ang-2/AT1R axis might be a promising strategy for the treatment of MVPF. Mechanical ventilation (MV) is an essential therapy for acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. However, it can also induce mechanical ventilation-induced pulmonary fibrosis (MVPF) and the underlying mechanism remains unknown. Based on a mouse model of MVPF, the present study aimed to explore the role of the angiotensin-converting enzyme/angiotensin II/angiotensin type 1 receptor (ACE/Ang-2/AT1R) axis in the process of MVPF. In addition, recombinant angiotensin-converting enzyme 2(rACE2), AT1R inhibitor valsartan, AGTR1-directed shRNA and ACE inhibitor perindopril were applied to verify the effect of inhibiting ACE/Ang-2/AT1R axis in the treatment of MVPF. Our study found MV induced an inflammatory reaction and collagen deposition in mouse lung tissue accompanied by the activation of ACE in lung tissue, increased concentration of Ang-2 in bronchoalveolar lavage fluid (BALF), and upregulation of AT1R in alveolar epithelial cells. The process of pulmonary fibrosis could be alleviated by the application of the ACE inhibitor perindopril, ATIR inhibitor valsartan and AGTR1-directed shRNA. Meanwhile, rACE2 could also alleviate MVPF through the degradation of Ang-2. Our finding indicated the ACE/Ang-2/AT1R axis played an essential role in the pathogenesis of MVPF. Pharmacological inhibition of the ACE/Ang-2/AT1R axis might be a promising strategy for the treatment of MVPF. [ABSTRACT FROM AUTHOR]

The list of available treatment options for managing blood glucose in patients with type 2 diabetes (T2D) has grown over recent years making the task of choosing between traditional and newer glucose-lowering agents a difficult one for healthcare providers. We summarize treatment algorithms developed by popular professional societies and propose a patient-centered and culture-driven recommendations for selecting diabetes medications for people with T2D in Saudi Arabia. Though most professional societies recognize patient's adherence to medications as an important factor in achieving glycemic targets, published algorithms schemes do not formally enlist adherence to medication as a deciding factor in the choice of glucose - lowering agents. Medication appeal to patients, an important determinant of medication adherence, is influenced by several factors including lifestyle, common beliefs, customs and traditions, health literacy, perception of health and disease, socioeconomic and cultural backgrounds, and religious commitments and obligations. In Saudi Arabia, poor adherence to therapy is a major obstacle to effective management of local people with T2D. The Saudi population has a unique socioeconomic and cultural background that widely respect adherence to religion and culture; and the applicability of international guidelines for the management of T2D to the Saudi population has been called into question. In this consensus statement, we propose patient-centered and culture-driven recommendations that integrate medication-adherence and medication-cost into overall selection of diabetes medications for people with T2D in Saudi Arabia. • Poor adherence to medications among people with T2D has been linked to lower attainment of treatment targets. • Professional societies do not prioritize patients' preferences as a deciding factor in selecting glucose - lowering agents. • We propose a patient-centered therapeutic algorithm for the management of T2D in Saudi Arabia. [ABSTRACT FROM AUTHOR]

• There are individual differences in stimulant response among children with attention-deficit/hyperactivity disorder (ADHD). • Scalp electrophysiology may be used to predict ADHD treatment response. • Stimulants appear to normalize the action preparation phase of attention processing. Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder associated with considerable impairment in psychiatric and functional domains. Although stimulant medication can reduce core symptoms of inattention, hyperactivity, and impulsivity, a subgroup of patients does not respond to this intervention. A precision medicine approach has been proposed, whereby biomarkers are used to identify an effective treatment approach for a given individual. This review synthesizes the existing literature on event-related potential (ERP) correlates of stimulant response in children diagnosed with ADHD, with the goal of evaluating the potential for ERP to inform precision medicine care in this population. Forty-three articles were examined and results tentatively suggest that stimulant medications normalize the amplitude of the P300 component, and this is also associated with behavioral improvement. In contrast, results generally indicate that stimulants do not significantly alter early processing components, although there are some exceptions to this finding. Implications for research, theory, and clinical work are considered and concrete recommendations for future directions are provided. While recognizing limitations of existing literature (e.g., homogenous samples, variable methodologies), we conclude that ERP methods represent a promising approach for precision medicine care of patients with ADHD. [ABSTRACT FROM AUTHOR]

Narcolepsy is a rare, chronic, and disabling central nervous system hypersomnia; two forms can be recognized: narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2). Its etiology is still largely unknown, but studies have reported a strong association between NT1 and HLA, as well as a pathogenic association with the deficiency of cerebrospinal hypocretin-1. Thus, the most reliable pathogenic hypothesis is an autoimmune process destroying hypothalamic hypocretin-producing cells. A definitive cure for narcolepsy is not available to date, and although the research in the field is highly promising, up to now, current treatments have aimed to reduce the symptoms by means of different pharmacological approaches. Moreover, overall narcolepsy symptoms management can also benefit from non-pharmacological approaches such as cognitive behavioral therapies (CBTs) and psychosocial interventions to improve the patients' quality of life in both adult and pediatric-affected individuals as well as the well-being of their families. In this review, we summarize the available therapeutic options for narcolepsy, including the pharmacological, behavioral, and psychosocial interventions. [ABSTRACT FROM AUTHOR]

Background: Knowledge on the comparative effectiveness of pharmacological treatments to prevent suicide mortality in bipolar disorder is still lacking.Methods: We studied the risk of suicide mortality during 1996-2012 among all patients who had been hospitalized due to bipolar disorder in Finland (n = 18,018; mean follow-up time 7.2 years) using nation-wide databases. We used a Cox proportional hazards model. Analyses were adjusted for the effects of time since diagnosis, order of treatments, current use of other treatments, polypharmacy, number of suicidal hospitalizations within 2 year (indicator of inherent risk of relapse), age at index date, sex, and calendar year of index date. In secondary analysis, the first 30 days were omitted from analysis after initiation of a psychopharmacological treatment to control for protopathic bias.Results: In comparison between use and no use among specific agents, only lithium (HR 0.33, 95%CI 0.24-0.47, p<0.0001) and valproic acid (HR 0.61, 95%CI 0.48-0.79, p=0.0002) were associated with a significantly decreased risk of suicide in bipolar disorder. Lithium showed a 42% lower risk for suicide mortality compared to valproic acid (HR 0.58, 95% CI 0.39-0.86, p = 0.007). Hypnotics were associated with a significantly (HR 1.52, 95%CI 1.22-1.90, p=0.0002) higher risk of suicide.Limitations: Only hospitalized patients were included.Conclusions: Lithium should be considered as treatment of choice for patients with bipolar disorder who are at high risk for suicide. Hypnotic use among suicidal patients indicates need for close monitoring of these patients. [ABSTRACT FROM AUTHOR]

Background: Patients with reduced left ventricular ejection fraction (EF<40%) are at high risk for adverse outcomes and benefit from evidence based doses of angiotensin converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB) and beta blockers. Our aim was to investigate the dispensing and uptitration of these medications following acute coronary syndrome (ACS), according to left ventricular ejection fraction.Methods: Patients presenting with ACS who underwent coronary angiography during 2015 were recorded in the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry. Medication dispensing data on discharge and at 1-year follow-up were obtained using anonymised linkage to the national pharmaceutical dataset. Doses of medications dispensed were compared to target doses recommended in clinical guidelines.Results: 4,082 patients were included in the study, of whom 602 (15%) had reduced ejection fraction (rEF). More patients with rEF were prescribed ACEi/ARB on discharge compared to those with preserved ejection fraction (pEF) (89% vs. 68%). Beta blocker dispensing on discharge was also higher in the rEF group (94% vs. 83%). In the rEF subgroup, 76% were maintained on ACEi/ARB and 85% on beta blockers by 1 year of follow-up. However, at discharge only 31% and 29% were on ≥50% of target doses of ACEi/ARB and beta blocker doses respectively, and by 1 year this increased only slightly to 34% and 35% respectively.Conclusions: There is suboptimal dispensing of evidence-based medications in the year following ACS. Further intervention is required to improve medication uptitration and adherence, particularly of beta blockers and ACEI/ARBs in those with reduced ejection fraction. [ABSTRACT FROM AUTHOR]

Aim: To compare the prevalence and trends of antipsychotic drug use during pregnancy between countries across four continents.Methods: Individually linked health data in Denmark (2000-2012), Finland (2005-2014), Iceland (2004-2017), Norway (2005-2015), Sweden (2006-2015), Germany (2006-2015), Australia (New South Wales, 2004-2012), Hong Kong (2001-2015), UK (2006-2016), and the US (Medicaid, 2000-2013, and IBM MarketScan, 2012-2015) were used. Using a uniformed approach, we estimated the prevalence of antipsychotic use as the proportion of pregnancies where a woman filled at least one antipsychotic prescription within three months before pregnancy until birth. For the Nordic countries, data were meta-analyzed to investigate maternal characteristics associated with the use of antipsychotics.Results: We included 8,394,343 pregnancies. Typical antipsychotic use was highest in the UK (4.4%) whereas atypical antipsychotic use was highest in the US Medicaid (1.5%). Atypical antipsychotic use increased over time in most populations, reaching 2% in Australia (2012) and US Medicaid (2013). In most countries, prochlorperazine was the most commonly used typical antipsychotic and quetiapine the most commonly used atypical antipsychotic. Use of antipsychotics decreased across the trimesters of pregnancy in all populations except Finland. Antipsychotic use was elevated among smokers and those with parity ≥4 in the Nordic countries.Conclusion: Antipsychotic use during pregnancy varied considerably between populations, partly explained by varying use of the typical antipsychotic prochlorperazine, which is often used for nausea and vomiting in early pregnancy. Increasing usage of atypical antipsychotics among pregnant women reflects the pattern that was previously reported for the general population. [ABSTRACT FROM AUTHOR]

Evidence suggests that cathepsin S (CTSS), a potent mammalian elastase, participates in abdominal aortic aneurysm (AAA) formation. This study examines the hypothesis that pharmacological inhibition of CTSS with an α-ketoamide based compound 6r might suppress AAA in mice. Experimental study of the CaCl 2 induced AAA model in B6 mice and angiotensin II (AngII) infused AAA model in ApoE−/- mice. The effects of intraperitoneal administration of 6r (25 mg/kg) and vehicle every three days since one day after AAA induction were evaluated at 28 days using CaCl 2 induced (n = 12 per group) and AngII infused (n = 8 per group) models. Additionally, the effects of post-treatment with 6r and vehicle from seven days or 14 days after AAA induction were evaluated at 28 days using the CaCl 2 induced model (n = 6 per group). Aortic samples were harvested for histological and biochemical analyses, including cathepsin levels, Verhoeff Van Gieson staining, TUNEL assay, and immunostaining for macrophages. In the CaCl 2 induced model, treatment with 6r suppressed aortic dilatation observed in vehicle treated controls (median: 0.58 vs. 0.92 mm; p <.001), along with reduced CTSS and cathepsin K (CTSK) levels (both p <.001), preserved elastin integrity (p <.001), fewer medial apoptotic cells (p =.012) and less macrophage infiltration (p =.041). In the AngII infused model, the aortic diameter was smaller in 6r treated mice than in vehicle treated controls (median: 0.95 vs. 1.84 mm; p =.047). The levels of CTSS (p <.001) and CTSK (p =.033) and the numbers of elastin breaks (p <.001), medial apoptotic cells (p <.001) and infiltrating macrophages (p =.030) were attenuated under 6r treatment. Finally, post-treatment with 6r from seven days (p =.046) or 14 days (p =.012) after AAA induction limited CaCl 2 induced AAA. Pharmacological inhibition of CTSS by 6r suppresses AAA formation in mice. Also, post-treatment with 6r retards mouse AAA progression. These findings provide proof of concept validation for CTSS as a potential therapeutic target in AAA. Image 1 [ABSTRACT FROM AUTHOR]

Chagas disease (CD) is a tropical neglected illness, affecting mainly populations of low socioeconomic status in Latin America. An estimated 6 to 8 million people worldwide are infected with Trypanosoma cruzi , the etiological agent of CD. Despite being one of the main global health problems, this disease continues without effective treatment during the chronic phase of the infection. The limitation of therapeutic strategies has been one of the biggest challenges on the fight against CD. Nifurtimox and benznidazole, developed in the 1970s, are still the only commercial options with established efficacy on CD. However, the efficacy of these drugs have a proven efficacy only during early infection and the benefits in the chronic phase are questionable. Consequently, there is a growing need for new pharmacological alternatives, either by optimization of existing drugs or by the formulation of new compounds. In the present study, a literature review of the currently adopted therapy, its concomitant combination with other drugs, and potential future treatments for CD was performed, considering articles published from 2012. The revised articles were selected according to the protocol of treatment: evaluation of drug association, drug repositioning and research of new drugs. As a result of the present revision, it was possible to conclude that the use of benznidazole in combination with other compounds showed better results when compared with its use as a single therapy. The search of new drugs has been the strategy most used in pursuing more effective forms of treatment for CD. However, studies have still focused on basic research, that is, they are still in a pre-clinical stage, using methodologies based on in vitro or in animal studies. • There is no effective treatment for chronic Chagas disease. • Association of benznidazole with other drugs is more efficient than benznidazole alone. • Nowadays, most researches focus on the development of new drugs to combat Chagas disease. • Current studies are still in a pre-clinical stage. [ABSTRACT FROM AUTHOR]

Germinal activity persists throughout life within the ventricular-subventricular zone (V-SVZ) of the postnatal forebrain due to the presence of neural stem cells (NSCs). Accumulating evidence points to a recruitment for these cells following early brain injuries and suggests their amenability to manipulations. We used chronic hypoxia as a rodent model of early brain injury to investigate the reactivation of cortical progenitors at postnatal times. Our results reveal an increased proliferation and production of glutamatergic progenitors within the dorsal V-SVZ. Fate mapping of V-SVZ NSCs demonstrates their contribution to de novo cortical neurogenesis. Transcriptional analysis of glutamatergic progenitors shows parallel changes in methyltransferase 14 (Mettl14) and Wnt/β-catenin signaling. In agreement, manipulations through genetic and pharmacological activation of Mettl14 and the Wnt/β-catenin pathway, respectively, induce neurogenesis and promote newly-formed cell maturation. Finally, labeling of young adult NSCs demonstrates that pharmacological NSC activation has no adverse effects on the reservoir of V-SVZ NSCs and on their germinal activity. [Display omitted] • dV-SVZ NSCs reactivate following hypoxia to produce cortical oligodendrocytes and neurons • Hypoxia reactivates embryonic transcriptional programs in glutamatergic progenitors • m6a methylation and Wnt/ꞵ-catenin activation parallel glutamatergic progenitor reactivation • Wnt/ꞵ-catenin activation does not affect young adult forebrain germinal activity Foucault et al. point out the reactivation of postnatal NSC embryonic competences within a specific context, such as chronic neonatal hypoxia. They show reactivation of m6a methylation and Wnt/β-catenin within glutamatergic progenitors, which parallels cortical neurogenesis. Moreover, postnatal NSC activation does not lead to germinal activity dysregulation at young adult ages. [ABSTRACT FROM AUTHOR]

N-Methyl- D -aspartate glutamate receptors (NMDARs) are involved in multiple physiopathological processes, including synaptic plasticity, neuronal network activities, excitotoxic events, and cognitive impairment. Abnormalities in NMDARs can initiate a cascade of pathological events, notably in Alzheimer's disease (AD) and even other neuropsychiatric disorders. The subunit composition of NMDARs is plastic, giving rise to a diverse array of receptor subtypes. While they are primarily found in neurons, NMDAR complexes, comprising both traditional and atypical subunits, are also present in non-neuronal cells, influencing the functions of various peripheral tissues. Furthermore, protein-protein interactions within NMDAR complexes has been linked with Aβ accumulation, tau phosphorylation, neuroinflammation, and mitochondrial dysfunction, all of which potentially served as an obligatory relay of cognitive impairment. Nonetheless, the precise mechanistic link remains to be fully elucidated. In this review, we provided an in-depth analysis of the structure and function of NMDAR, investigated their interactions with various pathogenic proteins, discussed the current landscape of NMDAR-based therapeutics, and highlighted the remaining challenges during drug development. • Imbalance in synaptic and extrasynaptic NMDARs activity links to AD pathology. • Non-neuronal NMDARs influence a range of physiological and pathological processes. • NMDAR-associated protein interactionsmay enable the development of innovative means to disrupt NMDAR-dependent death signaling. • We overview current NMDAR-based therapeutics, highlighting the prospects and challenges of NMDAR-based drug development for AD. [ABSTRACT FROM AUTHOR]

Treatment strategies for NFPA include surgery, radiotherapy, medical treatment, or follow-up. The treatment of NFPAs with compressive symptoms is surgical. However, in case of post-surgical tumor remnants, there may be treatment strategies that include observation and radiotherapy. Recently, medical treatment with cabergoline (CAB) has been recommended to contain and/or reduce the size of the tumor remnant. Based on the findings that many NFPAs show a dopamine receptor (DR) and somatostatin receptor (SR) expression, medical therapy with dopamine agonists (DAs) and somatostatin receptor ligands (SSRLs) has been tested as an alternative to prevent recurrence after surgery. The DAs have been the most extensively studied, showing some potential in terms of tumor shrinkage. SSRLs and other emerging medical options are much less studied. We will review and critically evaluate the current data on the medical therapy of NFPAs to elucidate their role in the management of this tumor type. In the case of actively growing remnants (more than 10% growth per year) and high-risk pituitary adenomas, treatment with CAB at a dose of 1.5–3.0 mg is indicated for tumor containment and/or reduction. In relation to combined chemotherapy with CAB, there is little information in the literature to support its use. In our experience, CAB treatment can be used after radiotherapy as an adjuvant treatment. [ABSTRACT FROM AUTHOR]

Pharmacological treatment can play an important role in the successful management of chronic pain and should be prescribed as part of a biopsychosocial approach. When planning a pharmacological strategy for chronic pain it is important to consider the nature and likely source of the pain. This article will summarize common pharmacological options in current clinical use for the management of chronic pain. [ABSTRACT FROM AUTHOR]

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Abstract Background The use of cocaine as a recreational drug has increased over recent years. In this study, we aimed to analyze the prevalence, and in-hospital and long-term outcomes of acute coronary syndrome (ACS) associated with cocaine consumption (ACS-ACC). Methods A prospective observational registry of young patients hospitalised with ACS from 2001 through 2015, we analysed ACS-ACC temporal trends, clinical characteristics, and major adverse cardiovascular events (MACE) during long-term follow-up. Results There were 8153 admissions with ACS, of whom 864 patients were ≤50-years-old; 59 patients (6.8%) presented with ACS-ACC. The prevalence of patients with a history of cocaine consumption increased to maximum of 18% in 2008 with no variations thereafter (r = 0.74, p < 0.001). The ACS-ACC incidence increased over time from 5% to 9% (r = 0.25, p = 0.07). Compared to patients with ACS not associated with cocaine consumption, the ACS-ACC exhibited a higher incidence of in-hospital ventricular tachycardia (16.9% vs 4.7%, p < 0.001) and trends to in-hospital mortality (3.4% vs 1.0%, p = 0.097); during a median follow-up of 5.6 years, ACS-ACC had higher risk of MACE (HR 1.83; 95% CI 1.04–3.25, p = 0.038), higher risk of myocardial infarction (HR 2.39, 95% CI 1.02–5.60, p = 0.045), and higher risk of cardiovascular mortality (HR 6.26; 95% CI 1.67–23.43, p = 0.006). Conclusion Young patients with ACS-ACC carry a high risk of short and long-term major adverse cardiovascular events. Over the 15-year study period, we observed an increasing prevalence of this entity. This trend and its outcomes underscore the need for increased awareness and improved management strategies. Highlights • Cocaine consumption has increased in Europe recently. • Cocaine increases risk of acute coronary syndrome (ACS). • ACS-ACC carry high risk of major adverse cardiovascular events. [ABSTRACT FROM AUTHOR]

Background: The aim of this naturalistic longitudinal study was to add evidence regarding the potential of Cloninger's temperament traits (novelty seeking, harm avoidance, reward dependence and persistence) for predicting the effect of pharmacological treatment on the rates of therapeutic response and remission.Methods: The study was based on 200 outpatients with unipolar depressive disorders of different severity and course of illness, and extended up to 6 months of follow-up. Patients were assessed in their temperament with the Tridimensional Personality Questionnaire (TPQ) and their condition was classified (in course and severity) according to the International Classification of Diseases, Tenth revision (ICD-10) diagnostic criteria for research. Patients were blindly rated (concerning other predicting variables) on the improved Clinical Global Impression-Severity scale for depression (iCGI-S) at baseline, 6 weeks, 3 months and 6 months. Outcome measures at the last observation carried forward were therapeutic response (reduction of ≥50% in the last iCGI-S) and remission (last iCGI-S = 0), which were available for 187 patients.Results: Remission was independently and directly associated with length of follow-up, and inversely with the baseline iCGI-S score and harm avoidance (patients in the high tertile had a 2.7 likelihood of non-remission in comparison with those in the low tertile); persistence was found to have a complex, V-shape relationship with remission. Within a sub-sample of more severe cases (n = 118), having higher harm avoidance scores, a more favorable outcome was associated with higher reward dependence and the non-smoking condition.Limitations: With a naturalistic, non-experimental design, the sample may not be representative of the general population.Conclusions: Temperament traits may help predict outcome in patients treated for depression. [ABSTRACT FROM AUTHOR]

Background: Current intervention strategies have been slow in reducing suicide rates, particularly in mood disorders. Thus, for intervention and prevention, a new approach is necessary. Investigating the effects of a medication known for its anti-suicidal properties on neurobiological and neurocognitive substrates of suicidal thinking may provide a deeper and more meaningful understanding of suicide.Method: A literature search of recognised databases was conducted to examine the intersection of suicide, mood disorders, and the mechanisms of lithium.Results: This review synthesises the extant evidence of putative suicide biomarkers and endophenotypes and melds these with known actions of lithium to provide a comprehensive picture of processes underlying suicide. Specifically, the central importance of glycogen synthase kinase-3β (GSK3β) is discussed in detail because it modulates multiple systems that have been repeatedly implicated in suicide, and which lithium also exerts effects on.Limitations: Suicide also occurs outside of mood disorders but we limited our discussion to mood because of our focus on lithium and extending our existing model of suicidal thinking and behaviour that is contextualised within mood disorders.Conclusions: Focusing on the neurobiological mechanisms underpinning suicidal thinking and behaviours through a lithium lens identifies important targets for assessment and intervention. The use of objective measures is critical and using these within a framework that integrates findings from different perspectives and domains of research is likely to yield replicable and validated markers that can be employed both clinically and for further investigation of this complex phenomenon. [ABSTRACT FROM AUTHOR]

• Half of the Malaysian stroke patients had at least one risk factor not treated. • Atrial fibrillation was the most untreated risk factor before a stroke. • Patients with untreated risk factors had triple the odds of in-hospital death. • Untreated hypertension and atrial fibrillation were associated with more death. • Untreated prior stroke was associated with more disability. The study aimed to determine the prevalence of untreated pharmacologically modifiable cardiovascular risk factors (PMRF) among patients with ischaemic stroke and the association with in-hospital mortality and functional outcome. We analysed the data from ischaemic stroke cases admitted to Sarawak General Hospital between June 2013 and June 2021. We matched the underlying PMRFs with prior medications and categorised them as treated, untreated, or no PMRF. We calculated the prevalence and assessed the association between untreated PMRFs and in-hospital mortality or favourable functional outcome (FFO) at discharge, which was adjusted for age, sex, and other covariates in multivariable models. We included 1963 patients [65.4% male, 59.8 (SD 13.4) years]; 43.8% who had at least one untreated PMRF had triple the odds of in-hospital mortality [adjusted OR (aOR) 2.86, (95%CI 1.44, 5.70)], whereas 30.2% who had all PMRFs treated showed no significant association. Untreated hypertension [aOR 2.19 (95%CI 1.21, 3.98)], treated [aOR 3.02 (95%CI 1.32, 6.92)], and untreated atrial fibrillation [aOR 1.89 (95%CI 1.18, 3.03)] were significantly associated with more in-hospital death, whereas treated prior stroke was associated with fewer in-hospital death [aOR 0.31 (95%CI 0.11, 0.84)]. Treated diabetes [aOR 0.66 (95%CI 0.49, 0.88)] and untreated prior stroke [aOR 0.53 (95%CI 0.33, 0.83)] were associated with fewer FFO. The high prevalence of untreated underlying PMRFs was significantly associated with poorer outcomes among Malaysian patients with ischaemic stroke in Sarawak. Efforts are needed to promote early screening and treatment of cardiovascular risk factors to reduce the burdens and improve stroke outcomes in this region. [ABSTRACT FROM AUTHOR]

Several hypnotic agents commonly recommended for improving sleep at sea level are discouraged at high altitude. We aimed to evaluate the efficacy and safety of drugs prescribed for improving sleep quality in patients with acute exposure to high altitudes by conducting a systematic review and meta-analysis. An electronic search was executed for randomized controlled trials comparing drug treatments with placebo and no-treatment conditions, which used objective sleep parameters or subjective sleep quality evaluations. Eight studies (152 participants) were included in the meta-analysis and involved trials using acetazolamide, temazepam, zolpidem, zaleplon, and theophylline. Generally, the nonbenzodiazepines were reported to be superior and safe in improving sleep quality. Participants who were administered zaleplon or zolpidem reported a significant improvement in subjective sleep quality. As measured by polysomnography, both zaleplon and zolpidem improved the total sleep time, sleep efficiency index, and stage 4 sleep duration, whereas they decreased the wake-after-sleep onset without impairing ventilation. In contrast, temazepam was not superior to placebo in terms of quicker onset of sleep and better sleep quality. On the other hand, acetazolamide and theophylline both reduced the sleep efficiency index. The present results favored zaleplon and zolpidem in improving both the objective and subjective quality of sleep without impairing ventilation. [ABSTRACT FROM AUTHOR]

Background: Disturbance of gait is a key feature of Parkinson's disease (PD) and has a negative impact on quality of life. Deficits in cognition and sensorimotor processing impair the ability of people with PD to walk quickly, efficiently and safely. Recent evidence suggests that emotional disturbances may also affect gait in PD.Research Question: We explored if there were relationships between walking ability, emotion and cognitive impairment in people with PD.Methods: The literature was firstly reviewed for unimpaired individuals. The recent experimental evidence for the influence of emotion on gait in people with PD was then explored. The contribution of affective disorders to continuous gait disorders was investigated, particularly for bradykinetic and hypokinetic gait. In addition, we investigated the influence of emotional processing on episodic gait disturbances, such as freezing of gait. Potential effects of pharmacological, surgical and physical therapy interventions were also considered.Results: Emerging evidence showed that emotional disturbances arising from affective disorders such as anxiety and depression, in addition to cognitive impairment, could contribute to gait disorders in some people with PD. An analysis of the literature indicated mixed evidence that improvements in affective disorders induced by physical therapy, pharmacological management or surgery improve locomotion in PD.Significance: When assessing and treating gait disorders in people with PD, it is important to take into the account non-motor symptoms such as anxiety, depression and cognitive impairment, in addition to the motor sequalae of this progressive neurological condition. [ABSTRACT FROM AUTHOR]

The anti-inflammatory and immunomodulatory effects of nanoparticles in several chronic diseases have been extensively researched. The aim of this review is to examine how nanoparticles modulate the inflammatory pathways that characterize the most prevalent forms of microcrystal-induced arthritis, including gout, pseudogout, and BCP-induced arthritis. The nanoparticles of chitosan-coated calcium phosphate, uricase, aceclofenac, and gold have been investigated in crystal-inducedarthritis. The most important results of the studies outlined in this review show that nanoparticles can inhibit the expression and the release of some pro-inflammatory mediators and proteolytic enzymes, and the activity of different transcriptional factors in vitro, as well as decrease the uric acid levels in several studies of in vitro and in vivo models of gout, which show interesting results in terms of decreasing the amount of crystals and tissue damage, respectively. In view of their multiple beneficial effects, nanoparticles can be considered a valuable therapy that contributes to the pharmacological treatment in crystalinduced arthritis. [ABSTRACT FROM AUTHOR]

Objectives To gather expert opinion on the conduct of clinical trials that will facilitate regulatory review and approval of appropriate efficacious pharmacological treatments for hand osteoarthritis (OA), an area of high unmet clinical need. Methods The European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal diseases (ESCEO) organized a working group under the auspices of the International Osteoporosis Foundation (IOF) and the World Health Organization (WHO). Results This consensus guideline is intended to provide a reference tool for practice, and should allow for better standardization of the conduct of clinical trials in hand OA. Hand OA is a heterogeneous disease affecting different, and often multiple, joints of the thumb and fingers. It was recognized that the various phenotypes and limitations of diagnostic criteria may make the results of hand OA trials difficult to interpret. Nonetheless, practical recommendations for the conduct of clinical trials of both symptom and structure modifying drugs are outlined in this consensus statement, including guidance on study design, execution, and analysis. Conclusions While the working group acknowledges that the methodology for performing clinical trials in hand OA will evolve as knowledge of the disease increases, it is hoped that this guidance will support the development of new pharmacological treatments targeting hand OA. [ABSTRACT FROM AUTHOR]

Antidepressant medications are the most common treatment for major depression and related disorders. Pharmacogenetic studies have demonstrated that response to these medications is associated with genetic variation. While these studies have been invaluable they have yet to explain why a significant number of patients do not respond to their initial medication. The epigenetic modification known as DNA methylation has recently been studied in the context of antidepressant treatment response. As such, the purpose of this article is to review the advances made in the relatively new field of pharmaco-epigenetics of antidepressant response. We included all published articles examining DNA methylation in association with antidepressant treatment response in Major Depressive Disorder from April 2006 to June 2016 using the PubMed, Medline, PsychInfo and Web of Science databases. At the present time, although original articles are limited, epigenetic modifications of SLC6A4 , BDNF , and IL11 genes are showing promising results as biomarkers for prediction of antidepressant response. However, research methods and results are heterogeneous and additional studies are required before results are generalizable. At the end of this review we provide recommendations for study design and analytic approaches. [ABSTRACT FROM AUTHOR]

Aim We examined the first- and second-line pharmacological treatment for delirium to determine which drugs were chosen, how and when second-line drugs were started, and the effectiveness and tolerability of those treatments. Methods A retrospective medical chart review was performed for delirium inpatients referred to the Department of Psychiatry, Hiroshima Citizens Hospital, from October 2011 to September 2012. Clinical diagnoses were based on ICD-10. We compared the baseline severity of delirium, duration needed for improvement, and rescue with antipsychotics between subjects given only first-line drugs and those switched to second-line drugs. Results We studied 194 consecutive patients including 127 men and 67 women whose average age was 76.5 ± 9.8 years. For first-line drugs, trazodone was most frequently prescribed (n = 100, 51.5%), followed by quetiapine (n = 57, 29.4%). Among patients treated with trazodone or quetiapine as first line treatment, 59 of 100 (59%) continued trazodone and 52 of 57 (91.2%) continued quetiapine. Duration needed for improvement did not differ significantly between patients treated with trazodone as a first line drug and those with quetiapine as same. Conclusion Trazodone can be a candidate drug as one of the first line drugs for delirium. [ABSTRACT FROM AUTHOR]

Oxytocin is gaining traction in the treatment of various substance use disorders (SUD). We performed a systematic review assessing the efficacy of oxytocin for treating different SUD. The electronic databases MEDLINE, EMBASE, CENTRAL, and the Cochrane Database of Systematic Reviews were searched for randomized controlled trials examining the effects of oxytocin vs. placebo in SUD samples. Quality assessment was conducted using a Cochrane validated checklist. A total of 17 trials with unique samples were identified. These were conducted on participants with SUD involving alcohol (n = 5), opioids (n = 3), opioids and/or cocaine/other stimulants (n = 3), cannabis (n = 2), or nicotine (n = 4). Across the SUD-groups, oxytocin reduced withdrawal symptoms (3/5 trials), negative emotional states (4/11 trials), cravings (4/11 trials), cue-induced cravings (4/7 trials), and consumption (4/8 trials). Sixteen trials had an overall considerable risk of bias. In conclusion, although oxytocin showed some promising therapeutic effects, the findings are too inconsistent and the trials too heterogeneous to derive any firm conclusions. Sounder methodological and well-powered trials are warranted. • Oxytocin is a possible candidate for the treatment of substance use disorders (SUD). • This is the first systematic review to examine the effects of oxytocin on SUD. • Oxytocin showed some promising effects on certain types of SUD. • The most consistent finding was reduced withdrawal symptoms after opioid cessation. • Sounder methodological and well-powered trials are needed to derive firm conclusions. [ABSTRACT FROM AUTHOR]

[Display omitted] Osteogenesis imperfecta (OI) is a genetically heterogeneous connective tissue disorder characterized by bone fragility and different extra-skeletal manifestations. The severity of these manifestations makes it possible to classify OI into different subtypes based on the main clinical features. This review aims to outline and describe the current pharmacological alternatives for treating OI, grounded on clinical and preclinical reports, such as antiresorptive agents, anabolic agents, growth hormone, and anti-TGFβ antibody, among other less used agents. The different options and their pharmacokinetic and pharmacodynamic properties will be reviewed and discussed, focusing on the variability of their response and the molecular mechanisms involved to attain the main clinical goals, which include decreasing fracture incidence, improving pain, and promoting growth, mobility, and functional independence. [ABSTRACT FROM AUTHOR]

Background Cardiac resynchronization therapy (CRT) is associated with improved morbidity and mortality in patients with chronic heart failure (HF) on optimal medical therapy. We aimed to evaluate changes of medical therapy during CRT and its influence on the CRT response. Methods We evaluated 85 HF patients' pharmacological treatment changes during 1-year follow-up of CRT. Statistical analysis was performed using IBM SPSS statistical software (SPSS v.21.0 for Mac OS X). Results Beta-blockers (BAB) were used in 81.2% of patients before CRT, and consumption increased after CRT implantation (96.5% at 1-year follow-up visit) ( p < 0.002). Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) consumption and dose didn’t significantly change statistically during the study. 55.3% of patients were taking spironolactone before CRT, and this number increased at discharge till 76.5% ( p < 0.001) and till 70.6% ( p = 0.01) at 1-year follow-up visit. The average dose of spironolactone during the study significantly decreased statistically. The use of diuretics was higher after CRT device implantation, compared with the period before CRT 80% to 84.7% ( p < 0.001), but torasemide dose hadn't significantly changed statistically and remained almost the same. Cardiovascular medication consumption was significantly lower before CRT, compared with discharge ( p < 0.001) and follow-up ( p < 0.001) periods. However, no statistically significant relation between pharmacological treatment and echocardiographic response was found. Conclusions The present study confirmed that pharmacological treatment has changed during the period before and after CRT. But no statistically significant relation between pharmacological treatment and echocardiographic response was found. [ABSTRACT FROM AUTHOR]

Objectives: The aims of the current review were (1) to give an overview of human studies investigating pharmacotherapy to ameliorate visuospatial neglect and (2) to evaluate the quality of those studies.Methods: A systematic literature search using PubMed, Scopus, and ResearchGate was conducted in regard to studies that evaluated pharmacological interventions aiming to ameliorate poststroke visuospatial neglect. The search was limited in the following features: species (human), adults (≥18 years of age), language (English), and type of neglect (visuospatial). Two independent authors extracted data on study content and effectiveness and evaluated the quality of studies and methods.Results: A total of 11 studies were identified. Three studies were considered to be of moderate quality, the others of low quality. Seven studies represented dopaminergic treatment; 3 studies represented cholinergic treatment; and 1 study represented noradrenergic treatment. Three dopaminergic studies showed primarily positive effects of dopaminergic stimulation on visuospatial neglect, whereas three others showed adverse effects. All 3 cholinergic studies found positive effects in some outcome measures concerning visuospatial neglect. Noradrenergic stimulation improved maintenance of attention when exploring space.Conclusions: Currently, cholinergic therapy might be the best option for future research. However, we must emphasize the explorative nature and the limited quality of the reviewed studies. [ABSTRACT FROM AUTHOR]

The World Health Organization essential medications list for hospice/palliative care reflects that, with the judicious use of currently available medications, the majority of symptoms can be lessened, and some controlled completely. Even with optimal use of current medications, symptom control is still unacceptable for many people. Currently available medications offer great benefit to a minority of patients, some benefit to an additional group, and no benefit or harms to others. In symptom control, development of new drugs is advancing at a glacial pace, contrasting to the rapid advances seen in many other disciplines. Specialists in palliative care should agree on several principles consequently: 1) Access to symptom-control drugs codified in the World Health Organization Essential Medicines list deserves the strongest support from national policies and professional guidelines, especially in resource-challenged countries. 2) The optimal use of currently available symptom-control drugs cannot yield acceptably high rates of net benefits. 3) There is a compelling need to identify patient subgroups that are likely to benefit from available medications and provide rigorous empirical support for indications, dosing, and route of administration for clinical practice. 4) New therapies are needed requiring an accelerated effort to investigate further the pathophysiology, neurobiology, and pharmacogenetics of distressing symptoms, and factors contributing to variations in drug response. This development requires a lengthy lead time. 5) Smarter ways to promote new knowledge into practice are needed as no drug will be suitable for all patients. We need to improve clinical characterization and biomarker technology to bring the best drugs to the right patients every time. [ABSTRACT FROM AUTHOR]

Bipolar disorder is a mood dysregulation characterized by recurrent symptoms and episodes of mania, hypomania, depression, and mixed mood. The complexity of treating patients with bipolar disorder prompted the Taiwanese Society of Biological Psychiatry and Neuropsychopharmacology (TSBPN) to publish the first Taiwan consensus on pharmacological treatment of bipolar disorders in 2012. This paper presents the updated consensus, with changes in diagnostic criteria (i.e., mixed features) and emerging pharmacological evidence published up to April 2022. Our working group systemically reviewed the clinical research evidence and international guidelines and determined the levels of evidence for each pharmacological treatment on the basis of the most recent World Federation of Societies of Biological Psychiatry grading system. Four clinical-specific issues were proposed. The current TSBPN Bipolar Taskforce then discussed research evidence and clinical experience related to each treatment option in terms of efficacy and acceptability and then appraised final recommendation grades through anonymous voting. In the updated consensus, we include the pharmacological recommendations for bipolar disorder with mixed features considering its high prevalence, the severe clinical prognosis, and the absence of approved medications. Cariprazine, lurasidone, repetitive transcranial magnetic stimulation, and ketamine are incorporated as treatment options. In the maintenance phase, the application of long-acting injectable antipsychotics is emphasized, and the hazards of using antidepressants and conventional antipsychotics are proposed. This updated Taiwan consensus on pharmacological treatment for bipolar disorder provides concise evidence-based and empirical recommendations for clinical psychiatric practice. It may facilitate treatment outcome improvement in patients with bipolar disorder. • 2012 Taiwan bipolar treatment consensus needs to be renewed based on new evidence and criteria changes. • 34 expert psychiatrists with mean 26 years of clinical experience were organized. • Novel treatments such as ketamine and rTMS and four critical issues are included. • The updated consensus may boost bipolar treatment and international collaboration. [ABSTRACT FROM AUTHOR]

Cognitive impairment is a core feature of Major Depressive Disorder (MDD) but treatments targeting cognition are lacking. Numerous pre-clinical and clinical studies have investigated potential cognition treatments, but overall the evidence is conflicting. We conducted a systematic search following the PRISMA guidelines on PubMed and PsychInfo to evaluate the extant evidence and methodological challenges in randomized controlled trials (RCTs) of biological, psychological and behavioural candidate treatments targeting cognition in MDD. Inclusion criteria were RCTs with a placebo control assessing potential pro-cognitive effects of candidate treatments in MDD. Two independent authors reviewed the studies and assessed their risk of bias with the Cochrane Collaboration׳s Risk of Bias tool. Twenty-eight eligible studies (24 biological and four psychological or behavioural studies) were identified. Cognition was the primary treatment target in ten (36%) trials and an additional treatment outcome together with mood symptoms in 18 (64%) trials. The risk of bias was high or unclear in 93% of trials due to potential selective outcome reporting or ‘pseudospecificity’ ( unspecific cognitive improvement due to reduced depression severity), and/or insufficient details on how the allocation sequence was generated or how blinding was maintained. Several promising treatments were identified, including vortioxetine, erythropoietin, transcranial direct current stimulation and cognitive remediation. However, several common methodological challenges may impede advances in the field. In particular, future trials should select one cognitive composite score as primary outcome, screen for cognitive impairment before inclusion of participants and address ‘pseudospecificity’ issues. Together, these strategies may improve the success of future cognition trials in MDD. [ABSTRACT FROM AUTHOR]

Cardiogenic shock is a clinical syndrome of impaired tissue perfusion caused by primary cardiac dysfunction and inadequate cardiac output. It represents one of the most lethal clinical conditions in intensive care medicine with mortality >40%. Management of different clinical presentations of cardiogenic shock includes guidance of cardiac preload, afterload, heart rate and contractility by differential pharmacological modulation of volume, systemic and pulmonary vascular resistance and cardiac output besides reversing the triggering cause. Data from large registries and randomized controlled trials on optimal diagnostic guidance as well as choice of pharmacological agents has accrued significantly in recent years. This state-of-the-art review summarizes the basic concepts of cardiogenic shock, the diagnostic work-up and currently available evidence and guideline recommendations on pharmacological treatment of cardiogenic shock. [ABSTRACT FROM AUTHOR]

Management of chronic pain should be achieved with a biopsychosocial approach and often requires multidisciplinary input. Pharmacological treatment can play an important role in the successful management of chronic pain. When planning a pharmacological strategy for chronic pain it is important to consider the nature and likely source of the pain. This review article will summarize common pharmacological options in current clinical use for the management of chronic pain. [ABSTRACT FROM AUTHOR]

Deficits in social cognition, including emotional processing, are hallmarks of schizophrenia and antipsychotic agents seem to be ineffectual to improve these symptoms. However, oxytocin does seem to have beneficial effects on social cognition. The aim of this study was to examine the effects of four months of treatment with intranasal oxytocin, in 31 patients with schizophrenia, on distinct aspects of social cognition. This was assessed using standardized and experimental tests in a randomized, double-blind, placebo-controlled, cross-over trial. All patients underwent clinical and experimental assessment before treatment, four months after treatment and at the end of treatment. Social cognition abilities were assessed with the Mayer–Salovey–Caruso Emotional Intelligence Test (MSCEIT) and the Reading the Mind in the Eyes task (RMET). Furthermore, an Emotional Priming Paradigm (EPP) was developed to examine the effects of oxytocin on implicit perceptual sensitivity to affective information and explicit facial affect recognition. We found that oxytocin improved performance on MSCEIT compared to placebo in Branch 3-Understanding Emotion ( p -value=0.004; Cohen׳s d =1.12). In the EPP task, we observed a significant reduction of reaction times for facial affect recognition ( p -value=0.021; Cohen׳s d =0.88). No effects were found for implicit priming or for theory of mind abilities. Further study is required in order to highlight the potential for possible integration of oxytocin with antipsychotic agents as well as to evaluate psycho-social treatment as a multi-dimensional approach to increase explicit emotional processing abilities and compensate social cognition deficits related to schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Citicoline is a drug approved for the treatment of acute ischemic stroke. Although evidence of its efficacy has been reported, recently published results of a large placebo-controlled clinical trial did not show differences. This study aims to assess whether starting citicoline treatment within 14 days after stroke onset improves the outcome in patients with acute ischemic stroke, as compared with placebo.Methods: A systematic search was performed to identify all published, unconfounded, randomized, double-blind, and placebo-controlled clinical trials of citicoline in acute ischemic stroke.Results: Ten randomized clinical trials met our inclusion criteria. The administration of citicoline was associated with a significant higher rate of independence, independently of the method of evaluation used (odds ratio [OR] 1.56, 95% confidence interval [CI] = 1.12-2.16 under random effects; OR 1.20, 95% CI = 1.06-1.36 under fixed effects). After studying the cumulative meta-analysis, and with the results obtained with the subgroup of patients who were not treated with recombinant tissue plasminogen activator (rtPA) (OR 1.63, 95% CI = 1.18-2.24 under random effects; OR 1.42, 95% CI = 1.22-1.66 under fixed effects), our hypothesis of dilution of the effect of citicoline was confirmed. When we analyzed the effect of citicoline in patients who were not treated with rtPA and were receiving the highest dose of citicoline started in the first 24 hours after onset, based on more recent trials, there was no heterogeneity, and the size of the effect has an OR of 1.27 (95% CI = 1.05-1.53).Conclusions: This systematic review supports some benefits of citicoline in the treatment of acute ischemic stroke. But, on top of the best treatment available (rtPA), citicoline offers a limited benefit. [ABSTRACT FROM AUTHOR]

Objective While individual trials suggest benefit of interventions for excoriation (skin-picking) disorder (ExD), limited systematic evaluation of treatments, or their collective benefit, exists. Methods The present study examined the current state of treatments for ExD in a systematic review and meta-analysis and explored potential treatment moderators. Twelve trials were identified for review, including five with a control condition. Of these, nine were eligible to be included in the meta-analysis (three with a control). Results A fixed-effects meta-analysis found a large overall treatment effect size ( g = 1.13), comprised of large effects for behavioral treatments ( g = 1.19), lamotrigine ( g = 0.98) and selective serotonin reuptake inhibitors ( g = 1.09). Clinician-rated measures did not significantly differ from self-rated measures; however, larger effects were observed on self-rated measures of severity, as compared to impairment [Q(1) = 4.63, P = .03]. Treatment type, trial length and trial methodological quality were not significant moderators. For controlled trials, the comparative efficacy of treatments for ExD was in the moderate range ( g = 0.47). Conclusion Findings suggest that treatment for ExD has benefit; however, the meta-analysis did not provide strong evidence to support any specific treatment or to suggest its unique clinical benefit over control conditions. Overall, there is a lack of study on treatments for ExD and additional randomized controlled trials with inclusion of multiple informants in assessment is needed. [ABSTRACT FROM AUTHOR]

• Major psychiatric disorders show lower P3B amplitudes than healthy controls. • Use of multiple medications lowers P3B amplitudes. • Psychotic disorders show less MMN than other major psychiatric disorders. • P3A amplitudes are lower in substance use disorders. Attention deficits measured using event-related potentials (ERPs) have been frequently reported in several major psychiatric disorders, e.g. mood disorder (MD), psychotic disorder (PD) and substance use disorder (SUD). However, comparisons between these specific categories are lacking. Here we investigated if electrophysiological parameters of basic information processing are associated with the above-mentioned categories of psychiatric disorders, or instead were associated with general psychopathology. 579 subjects with MD, PD or SUD and healthy controls (HC) were included. Participants were tested in a passive auditory and an active visual oddball paradigm to assess mismatch negativity (MMN), P3A and P3B amplitudes. Additionally, we examined associations between these measures and psychoactive medication treatments. All patients had significantly lower P3B amplitudes compared to healthy controls, while only SUD patients had lower P3A amplitudes than MD, PD and HC. PD patients also produced significantly less MMN than both MD and SUD patients. Additionally, we found significantly higher P3B amplitude in HC compared to patients without psychopharmacological treatment and patients treated with two or more psychoactive compounds (polypharmacy), but no significant associations with medication on P3A and MMN amplitudes. Our results add to the theory that P3B deficits are associated with general psychopathology, whereas P3A and MMN deficits appear to be associated with substance abuse and psychotic disorders respectively. [ABSTRACT FROM AUTHOR]