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Behavioural and psychological symptoms of dementia (BPSD) are a clinical challenge for the lack of a sound taxonomy, frequent presentation with comorbid BPSD, lack of specific pharmacologic interventions, poor base of methodologically sound evidence with randomized clinical trials, contamination from the treatment of behavioural disturbances of young and adult psychiatric conditions, and small efficacy window of psychotropic drugs. We present here a treatment workflow based on a concept‐driven literature review based on the notions that (i) the aetiology of BPSD can be mainly neurobiological (so‐called 'primary' symptoms) or mainly environmental and functional ('secondary' symptoms) and that this drives treatment; (ii) the clinical efficacy of psychotropic drugs is driven by their specific profile of receptor affinity; (iii) drug treatment should follow the rules of 'start low–go slow, prescribe and revise'. This article argues in support of the distinction between primary and secondary BPSD, as well as their characteristics, which until now have been just sketchily described in the literature. It also offers comprehensive and pragmatic clinician‐oriented recommendations for the treatment of BPSD. [ABSTRACT FROM AUTHOR]

Trichotillomania (TTM) is an intractable and chronic mental disorder that causes significant distress or functional impairments in various life domains. Most individuals with trichotillomania have other comorbid diagnoses. Bipolar disorder (BD) is one of the most common comorbid conditions. Up to date, no FDA-approved drugs for TTM are available, not to mention children and adolescent patients with TTM and BD. Here, we present a case of an 8-year-old child with a long history of episodic TTM and bipolar disorder who was effectively treated with topiramate in a 3-year follow-up. [ABSTRACT FROM AUTHOR]

Background: Bipolar depression accounts for most of the disease duration in type I and type II bipolar disorder (BD), with few treatment options, often poorly tolerated. Many individuals do not respond to first‐line therapeutic options, resulting in treatment‐resistant bipolar depression (B‐TRD). Esketamine, the S‐enantiomer of ketamine, has recently been approved for treatment‐resistant depression (TRD), but no data are available on its use in B‐TRD. Objectives: To compare the efficacy of esketamine in two samples of unipolar and bipolar TRD, providing preliminary indications of its effectiveness in B‐TRD. Secondary outcomes included the evaluation of the safety and tolerability of esketamine in B‐TRD, focusing on the average risk of an affective switch. Methods: Thirty‐five B‐TRD subjects treated with esketamine nasal spray were enrolled and compared with 35 TRD patients. Anamnestic data and psychometric assessments (Montgomery‐Asberg Depression Rating Scale/MADRS, Hamilton‐depression scale/HAM‐D, Hamilton‐anxiety scale/HAM‐A) were collected at baseline (T0), at one month (T1), and three months (T2) follow up. Results: A significant reduction in depressive symptoms was found at T1 and T2 compared to T0, with no significant differences in response or remission rates between subjects with B‐TRD and TRD. Esketamine showed a greater anxiolytic action in subjects with B‐TRD than in those with TRD. Improvement in depressive symptoms was not associated with treatment‐emergent affective switch. Conclusions: Our results supported the effectiveness and tolerability of esketamine in a real‐world population of subjects with B‐TRD. The low risk of manic switch in B‐TRD patients confirmed the safety of this treatment. [ABSTRACT FROM AUTHOR]

The article informs about the study of neuropsychiatric symptoms (NPSs) in dementia patients during hospitalization in a dementia ward. Topic include discusses the challenges of pharmacological treatments for NPSs and explores the trajectory of these symptoms in patients during a 12-week hospitalization, finding that while some symptoms improved, apathy worsened.

The aim of this debate article is to discuss whether effective treatments are available for mixed urinary incontinence (MUI). Because patients with MUI have both stress and urgency urinary incontinence (SUI and UUI) episodes and current treatment guidelines currently recommend treating the predominant symptom first, this article presents standard and emerging treatments for both SUI and UUI before discussing how well these treatments meet the medical needs of patients with MUI. Standard treatments presented include noninvasive options such as lifestyle changes and pelvic floor exercises, pharmacological agents, and surgery. Treatment of all three types of urinary incontinence (UI) is usually initiated with noninvasive options, after which treatment options diverge based on UI subtype. Multiple pharmacological agents have been developed for the treatment of UUI and overactive bladder, whereas surgery remains the standard option for SUI and stress‐predominant MUI. The divide between UUI and SUI options seems to be propagated in emerging treatments, with most novel pharmacological agents still targeting UUI and even having SUI and stress‐predominant MUI as exclusion criteria for participation in clinical trials. Considering that current treatment options focus almost exclusively on treating the predominant symptom of MUI and that emerging pharmacological treatments exclude patients with stress‐predominant MUI during the development phase, effective treatments for MUI are lacking both in standard and emerging practice. Ideally, agents with dual mechanisms of action could provide symptom benefit for both the stress and urgency components of MUI. [ABSTRACT FROM AUTHOR]

Key content: Bladder pain syndrome (BPS) presents as a spectrum of urological symptoms with poorly understood pathophysiology. Bladder mucosal injury secondary to low grade sub‐clinical infection is a possible trigger, leading to nociceptive upregulation and, subsequently, central sensitisation.Brain abnormalities associated with BPS suggest that neuropathological brain alterations exist, which may contribute to the perceived pain.Central sensitisation plays a role in the disease pathophysiology via an augmentation in the responsiveness of the central pain signalling neurons.The urinary microbiome is implicated as a trigger for the development and maintenance of BPS.Future directions to improve treatment strategies include stratification of patients with BPS into subtypes such as peripheral or central disease and investigation of the urinary microbiome and bladder barrier replacement. Learning objectives: To update clinicians' knowledge of current research into the urinary microbiome and pain sensitisation in BPS pathophysiology.To understand the biodiversity and abundance of urinary microbes and the role of peripheral and central pain sensitisation, which will help identify future management techniques for BPS. Ethical issues: What are the consequences of long‐term antibiotics use for BPS management on bacterial resistance? [ABSTRACT FROM AUTHOR]

Introduction: Rapid cycling bipolar disorder (RCBD) is defined as four or more affective episodes (depression, mania or hypomania) within 1 year. RCBD has a high point of prevalence (from 10% to 20% among clinical bipolar samples) and is associated with greater severity, longer illness duration, worse global functioning and higher suicidal risk, but there is no consensus on treatment option. The use of several pharmacological agents has been reported (levothyroxine, antipsychotics, antidepressants and mood stabilizers). Objective: The main objective of this review was to propose a critical review of the literature and to rank the pharmacological agent using a level of evidence (LEO) adapted from the Center for Evidence‐Based Medicine, and to illustrate it with a case report on off‐label intravenous ketamine. Method: We conducted a review using the MeSH terms and keywords (bipolar [Title/Abstract]) AND (rapid [Title/Abstract]) AND (cycling [Title/Abstract]) AND (treatment [Title/Abstract]). Alexis Bourla and Stéphane Mouchabac screened 638 documents identified through literature search in Medline (PubMed) or by bibliographic references and 164 abstracts were then analyzed. Nonpharmacological treatments were excluded. Result: Seventy articles were included in the review and divided into six categories: mood stabilizers, antipsychotics, hormonal treatments, ketamine and other pharmacological treatments. Discussion: Our review highlights the heterogeneity of the pharmacological treatment of RCBD and no clear consensus can emerge. [ABSTRACT FROM AUTHOR]

Background: The prevalence of alcohol use disorder (AUD) is estimated to be 10 times higher amongst individuals in the criminal justice system than the general population. Alcohol use is also one of the strongest modifiable risk factors for recidivism. One intervention that has been shown to be effective in reducing alcohol consumption in the general population is medication‐assisted treatment (MAT), and this systematic review synthesized the existing evidence on MAT for AUD in correctional settings. Methods: Empirical, peer‐reviewed studies on approved medications for AUD in correctional populations were searched in major databases. One hundred sixty‐two articles were initially screened and 14 eligible articles were included in the final review. Four articles examined disulfiram, and 10 articles examined naltrexone. Results: The studies on disulfiram were considerably older than those on naltrexone, predating contemporary scientific standards. Disulfiram in combination with substantial contingencies in a supervised setting significantly reduced alcohol‐related measures of consumption and recidivism and had acceptable safety and tolerability. All naltrexone studies showed significant reductions in alcohol‐related measures, but effects on recidivism were mixed. The naltrexone studies indicated that it was highly acceptable and well tolerated. In addition, offenders receiving naltrexone had significantly greater medication adherence, treatment attendance, and treatment duration than with placebo. Conclusions: A small number of studies on pharmacological interventions for AUD in the correctional population suggest that MAT is effective in reducing alcohol consumption, although results on recidivism are mixed. On balance, the evidence was more supportive of naltrexone in reducing alcohol‐related outcomes than disulfiram and it may also be a more feasible intervention in correctional settings. Further research on MAT to address AUD in correctional populations with larger sample sizes, longer duration, and in combination with behavioral interventions is warranted. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate the effectiveness of pain neuroscience education (PNE) in addition to usual treatment in patients with fibromyalgia syndrome. Methods: Forty patients were randomized into 2 groups. The experimental group underwent PNE sessions over 6 weeks in addition to pharmacological treatment, and the control group was given only pharmacological treatment. The primary outcome measure was functional status and the secondary outcome measures were widespread pain pressure threshold and kinesiophobia level. All assessments were conducted before the intervention and at the end of the 6th and 12th weeks by the same blinded researcher. Results: The intervention group had significantly greater improvement than the control group in terms of the mean total scores in the Fibromyalgia Impact Questionnaire (P =.001) and the Tampa Scale of Kinesiophobia (P =.001) with large effect sizes. The intervention group also had significantly greater improvement in the pain pressure threshold values of the cervical (P =.040), thoracic (P =.001), lumbar (P <.001), elbow (P =.005) and calf (P =.006) regions with moderate‐to‐large effect sizes. Conclusion: This study showed that the addition of 6‐week PNE sessions to pharmacological treatment was successful in improving functional status, widespread pain pressure threshold, and level of kinesiophobia in patients with fibromyalgia syndrome during a 12‐week follow‐up period. [ABSTRACT FROM AUTHOR]

Esophagectomy for esophageal cancer is one of the most invasive procedures in gastrointestinal surgery. An invasive surgical procedure causes postoperative lung injury through the surgical procedure and one‐lung ventilation during anesthesia. Lung injury developed by inflammatory response to surgical insults and oxidative stress is associated with pulmonary morbidity after esophagectomy. Postoperative pulmonary complications negatively affect the long‐term outcomes; therefore, an effort to reduce lung injury improves overall survival after esophagectomy. Although significant evidence has not been established, various pharmacological treatments for reducing lung injury, such as administration of a corticosteroid, neutrophil elastase inhibitor, and vitamins are considered to have efficacy for pulmonary morbidity. In this review we survey the following topics: mediators during the perioperative periods of esophagectomy and the efficacy of pharmacological therapies for patients with esophagectomy on pulmonary complications. [ABSTRACT FROM AUTHOR]

Objective: This study examined the feasibility, safety, and potential efficacy of lisdexamfetamine (LDX) as a treatment for adults with bulimia nervosa (BN). Method: An open‐label 8‐week feasibility study was conducted in participants with BN. Enrollment rate, dropout rate, safety outcomes, and eating disorder symptom change were examined. Results: Eighteen of 23 participants completed the study per protocol. There was no participant‐initiated dropout due to adverse drug reactions and no severe and unexpected adverse drug reactions. An average increase in heart rate of 12.1 beats/min was observed. There was a mean weight reduction of 2.1 kg and one participant was withdrawn for clinically significant weight loss. In the intent‐to‐treat sample, there were reductions in objective binge episodes and compensatory behaviors from Baseline to Post/End‐of‐Treatment (mean difference = −29.83, 95% confidence interval: −43.38 to −16.27; and mean difference = −33.78, 95% confidence interval: −48.74 to −18.82, respectively). Discussion: Results of this study indicate that a randomized controlled trial would be feasible with close monitoring of certain safety parameters (especially over a longer time period as long‐term safety is unknown). However, the results should not be used as evidence for clinicians to prescribe LDX to individuals with BN before its efficacy and safety are properly tested. Trial Registration Number: NCT03397446. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are known to be the most fatal diseases worldwide. Ischaemia/reperfusion (I/R) injury is at the centre of the pathology of the most common cardiovascular diseases. According to the World Health Organization estimates, ischaemic heart disease is the leading global cause of death, causing more than 9 million deaths in 2016. After cardiovascular events, thrombolysis, percutaneous transluminal coronary angioplasty or coronary bypass surgery are applied as treatment. However, after restoring coronary blood flow, myocardial I/R injury may occur. It is known that this damage occurs due to many pathophysiological mechanisms, especially increasing reactive oxygen types. Besides causing cardiomyocyte death through multiple mechanisms, it may be an important reason for affecting other cell types such as platelets, fibroblasts, endothelial and smooth muscle cells and immune cells. Also, polymorphonuclear leukocytes are associated with myocardial I/R damage during reperfusion. This damage may be insufficient in patients with co‐morbidity, as it is demonstrated that it can be prevented by various endogenous antioxidant systems. In this context, the resulting data suggest that optimal cardioprotection may require a combination of additional or synergistic multi‐target treatments. In this review, we discussed the pathophysiology, experimental models, biomarkers, treatment and its relationship with genetics in myocardial I/R injury. Significance of the study: This review summarized current information on myocardial ischaemia/reperfusion injury (pathophysiology, experimental models, biomarkers, genetics and pharmacological therapy) for researchers and reveals guiding data for researchers, especially in the field of cardiovascular system and pharmacology. [ABSTRACT FROM AUTHOR]

Objective: To investigate the application of treatment modalities for patients with osteonecrosis of the femoral head (ONFH) in mainland China. Methods: This cross‐sectional study was based on the online application of China Osteonecrosis of the Femoral Head Database (CONFHD). Between July 2016 to December 2018, the CONFHD program planned to recruit ONFH patients from 12 administrative areas across mainland China. Real‐world medical records of treatment regimens for these patients, including surgeries and prescriptions, were approved to upload to the CONFHD application for further analysis. The surgeries performed on these patients were classified into total hip arthroplasty and hip‐preserving procedures, and the latter was further classified into core decompression, bone grafting, and tantalum rod implantation. Prescription medications were classified into chemical medicine and Chinese herbal medicine (CHM); chemical medicine was further classified according to their chemical compounds, and CHM was classified according to therapeutic functions based on traditional Chinese medicine theory. Descriptive analysis was performed to summarize the application of different treatment regimens on the overall sample. Results: A total of 1491 patients (2381 hips) who fulfilled the protocol criteria were included. There were 1039 males and 452 females with a mean age of 47.29 ± 12.69 years. The causes of ONFH were alcoholism in 642 patients (43%), corticosteroid in 439 patients (29%), trauma in 239 patients (16%), and idiopathic ONFH in 171 patients (11%). Operative treatments (including total hip arthroplasty and hip‐preserving procedures) were performed on 49% of patients (43% of hips), chemical medicine therapy (including bisphosphonate, statins, and prostacyclin) was given to 37% of patients (37% of hips), and CHM was administrated to 72% of patients (75% of hips). The aforementioned interventions were not always used alone, since 47% of patients (52% of hips) received combined regimens with multiple interventions. Among hips treated by surgery, all hips with ARCO stage IV ONFH received THA (305 hips), and THA was also performed on 63 hips with stage II ONFH. Over half of hips with stage I (81%), II (91%), and III (92%) ONFH had received pharmacological treatments. Prostacyclin and bisphosphonate were the top two most prescribed medicines used alone. CHM therapies with multiple CHM functions were more commonly prescribed. Conclusion: Current treatment modalities for ONFH patients in mainland China include operative treatment, chemical medicine, and CHM. Combined regimens with different treatment modalities are common in real‐world clinical practices. [ABSTRACT FROM AUTHOR]

Alcohol use disorder (AUD) is characterized by dysfunction in motivational, mood‐stress regulation, and sleep systems that interact in complex ways to heighten the risk of relapse during abstinence. Emerging data suggest that excessive and chronic alcohol use disrupts sleep homeostasis and, in abstinence, subjects with AUD are known to experience insomnia that may persist for weeks to years, which we propose to refer to as insomnia associated with alcohol cessation (IAAC). The purpose of this review is to provide an update of pharmacological approaches to therapy including compounds in development, to raise awareness of the prevalence of and unmet need in IAAC and highlight differences in treatment consideration for IAAC as compared to insomnia disorder. We performed a search of select electronic databases to identify studies of pharmacological agents used to treat sleep disturbances in abstinent or treatment‐seeking patients with alcohol use disorder. The search, conducted in June 2019 and updated in December 2019, yielded 1,188 abstracts after duplicates were removed, of which 36 full‐text articles were assessed for eligibility. Eighteen studies were included, 15 randomized controlled trials and three open‐label studies. Several classes of medications including antidepressants, anticonvulsants, and antipsychotics have been evaluated for their effectiveness in treating sleep disturbances in abstinent or treatment‐seeking patients with AUD. None of these medications are approved by the FDA for the treatment of IAAC, and the currently available evidence for these agents is limited. Randomized, controlled clinical trials are warranted to evaluate the efficacy and safety of medications in the treatment of IAAC. [ABSTRACT FROM AUTHOR]

Aims: Sacubitril/Valsartan (Sac/Val) was proven more effective than enalapril for symptomatic patients with heart failure (HF) with reduced ejection fraction (HFrEF). This study aimed to investigate eligibility, titration, and tolerability for Sac/Val in a real‐world clinical setting. Methods and results: This retrospective cohort study consists of two parts. In Part 1 (eligibility study), all patients discharged from Sahlgrenska University Hospital due to HF were consecutively included during 1 year. Data from the patients' medical records were collected. Patients were adjudicated to be eligible based on European Society of Cardiology (ESC) criteria for angiotensin receptor neprilysin inhibitor (ARNI) with the exception of N‐terminal (NT)‐proBNP levels. Patients who received <50% of target dose angiotensin‐converting enzyme/angiotensin receptor blocker and otherwise fulfilled ESC criteria were adjudicated to be potentially eligible. In Part 2 (tolerability study), all patients receiving Sac/Val during the same period were included. Medical data regarding dose, titration, and adverse effects and events were registered. A total of 1355 patients (mean age 78 ± 13 years) were hospitalized for HF and 619 patients had an EF ≤40%. Twenty percent were eligible for initiation of ARNI, and additionally 8% were potentially eligible. In all 95 patients (mean age 65 ± 12 years) were initiated with Sac/Val, which correlates to 13%. The patients who were initiated were younger (65 years), more often had dilated cardiomyopathy (31%), more often were on guideline‐directed medical therapy, and had a higher frequency of cardiac resynchronization therapy and implantable cardioverter–defibrillator compared with the patients who did not receive Sac/Val. Of the initiated patients, 59% reached target dose of Sac/Val, and 15% discontinued due to adverse effects. The most common cause of discontinuation was benign gastrointestinal adverse effects, followed by elevated creatinine, malaise, and vertigo. Female gender [odds ratio (OR) 3.58; 95% CI 1.07–2.00; P = 0.038] and NT‐proBNP ≥ median level (OR 0.48; 95% CI 0.26–0.90; P = 0.021) was associated with termination of the medication. Conclusions: Among HFrEF patients in this real‐world cohort, 20% were eligible for ARNI; however, only 13% received the treatment. Sac/Val was well tolerated, but 41% of the patients did not reach target dose. How this affects outcome is not known and needs further investigation. [ABSTRACT FROM AUTHOR]

Background: Spasticity is a frequent multifactorial manifestation of multiple sclerosis (MS), affecting mostly the chronic courses of the disease. Its impact on patient functioning and quality of life is profound. Treatment of spasticity includes oral and intrathecal anti‐spastic drugs, muscle injections with relaxant agents, physical therapy, electrical and magnetic stimulation and peripheral nerve stimulation, alone or in various combinations. Methods: This Italian consensus on the treatment of spasticity in MS was produced by a large group of Italian MS experts in collaboration with neurophysiologists, experts in the production of guidelines and patients' representatives operating under the umbrella of the Italian Neurological Society, the Associazione Italiana Sclerosi Multipla and the European Charcot Foundation. This guideline was developed in accordance with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A total of 11 questions were formulated following the PICO framework (patients, intervention, comparator, outcome). Controlled studies only were included in the analysis. Results: Despite some consistent limitations due to the poor methodological quality of most studies, there was a consensus on a strong recommendation for the use of intrathecal baclofen, oromucosal spray of nabiximols and intramuscular injection of botulinum toxin. The level of recommendation was weak for oral baclofen, tizanidine, gabapentin, benzodiazepines and transcranial magnetic stimulation. Conclusions: There is a clear need for new larger multicentre well‐designed clinical trials with a duration that allows the persistence of the effects and the long‐term safety of the interventions to be evaluated. [ABSTRACT FROM AUTHOR]

ABSTRACT: The implementation of potential new step‐up or step‐down treatment recommendations in response to current guidelines is one of the main challenges currently faced in actual daily practice settings. In the present narrative review, we aim to discuss the relevance of these step‐up and step‐down proposals at the patient level in daily clinical practice. In particular, we aim to review the challenges associated with inhaled maintenance therapy for chronic obstructive pulmonary disease (COPD) in four clinical scenarios. First, we discuss the step up from single to double bronchodilation, including current controversies regarding the addition of a second bronchodilator versus initial treatment with two bronchodilators. Second, we discuss the step up from double bronchodilation to triple therapy while challenging current indications for inhaled steroid therapy and discussing triple therapy designs. Third, we discuss the step down from triple therapy to double bronchodilation while evaluating the effect of this downshift in risk categories on the patient according to the new classifications. Finally, we discuss the step down from double to single bronchodilation, with a special focus on safety. We believe this review will help to highlight the most relevant discussion points regarding the treatment of COPD in a manner that will stimulate and guide related clinical research. [ABSTRACT FROM AUTHOR]

Abstract: Background: The Italian severe/uncontrolled asthma (SUA) web‐based registry encompasses demographic, clinical, functional, and inflammatory data; it aims to raise SUA awareness, identifying specific phenotypes and promoting optimal care. Methods: Four hundred and ninety three adult patients from 27 Italian centers (recruited in 2011‐2014) were analyzed. Results: Mean age was 53.8 years. SUA patients were more frequently female (60.6%), with allergic asthma (83.1%). About 30% showed late onset of asthma diagnosis/symptoms (>40 years); the mean age for asthma symptoms onset was 30.2 years and for asthma diagnosis 34.4 years. 97.1% used ICS (dose 2000 BDP), 93.6% LABA in association with ICS, 53.3% LTRAs, 64.1% anti‐IgE, 10.7% theophylline, and 16.0% oral corticosteroids. Mean FEV1% pred of 75.1%, median values of 300/mm3 of blood eosinophil count, 323 kU/L of serum total IgE, and 24 ppb of FENO were shown. Most common comorbidities were allergic rhinitis (62.4%), gastroesophageal reflux (42.1%), sinusitis (37.9%), nasal polyposis (30.2%), and allergic conjunctivitis (30.2%). 55.7% of SUA patients had exacerbations in the last 12 months, 9.7% emergency department visits, and 7.3% hospitalizations. Factors associated with exacerbation risk were obesity (OR, 95% CI 2.46, 1.11‐5.41), psychic disorders (2.87, 0.89‐9.30—borderline), nasal polyps (1.86, 0.88‐3.89—borderline), partial/poor asthma treatment adherence (2.54, 0.97‐6.67—borderline), and anti‐IgE use in a protective way (0.26, 0.12‐0.53). Comparisons to severe asthma multicenter studies and available registries showed data consistency across European and American populations. Conclusions: An international effort in the implementation of SUA patients’ registries could help to better understand the clinical features and to manage severe asthma, representing a non‐negligible socioeconomic burden for health services. [ABSTRACT FROM AUTHOR]

Gambling disorder (GD) is a topical problem in developed countries and may be present in 1-3% of the general population. The pathophysiology of this disorder is largely unknown but it shares similarities to other behavioral addictions. Multiple neurotransmitter systems, including dopaminergic, serotonergic, noradrenergic, glutamatergic, and opioidergic, have been implicated in GD. Based on available articles, only the opioid antagonist naltrexone has been documented to demonstrate clinical efficacy in multiple studies including double-blind studies. Nalmefene, another opioid antagonist, may be active as well but its dose-response effect remains unclear. Contrarily, current test results do not support the therapeutic use of any antidepressant drug. Some positive data has been made available supporting the use of N-acetylcystein, but more studies are needed to confirm this. No clear or definite information is currently available for other drugs. [ABSTRACT FROM AUTHOR]

Non-alcoholic steatohepatitis ( NASH) is characterized by lobular inflammation and hepatocellular ballooning, and may be associated with liver fibrosis leading to cirrhosis and its complications. A pharmacological approach is necessary to treat NASH because of failure to change dietary habits and lifestyle in most patients. Insulin resistance with an increased release of free fatty acids, oxidative stress and activation of inflammatory cytokines seem to be key features for disease progression. Thiazolidinediones, such as pioglitazone and antioxidant agents, such as vitamin E, were the first pharmacological options to be evaluated for NASH. In recent years, several new molecules that target different pathways related to NASH pathogenesis, such as liver metabolic homeostasis, inflammation, oxidative stress and fibrosis, have been developed. Obeticholic acid ( INT-747) and elafibranor ( GFT-505) have provided promising results in phase IIb, randomized, placebo-controlled clinical trials and they are being evaluated in ongoing phase III studies. Most of the potential treatments for NASH are under investigation in phase II studies, with some at phase I. This diversity in possible treatments calls for a better understanding of NASH in order to enrich trial populations with patients more susceptible to progress and to respond. This manuscript aims to review the pharmacological NASH treatment landscape. [ABSTRACT FROM AUTHOR]

Background Primary tic disorders, notably Tourette syndrome, are very common movement disorders in childhood. However, the management of such patients still poses great therapeutic challenges to medical professionals. Methods Based on a synthesis of the available guidelines published in Europe, Canada, and the United States, coupled with more recent therapeutic developments, the authors provide a pragmatic guide to aid clinicians in deciding when and how to treat patients who have primary tic disorders. Results After a systematic assessment of tics and common neuropsychiatric comorbidities (primarily attention-deficit hyperactivity disorder [ ADHD] and obsessive-compulsive disorder [ OCD]), the first step in treatment is a comprehensive psychoeducation of patients and families that addresses the protean phenomenology of tics and associated behaviors, coping mechanisms, prognosis, and treatment options. When more active intervention beyond watchful monitoring is indicated, hierarchical evaluation of treatment targets (i.e., tics vs. comorbid behavioral symptoms) is crucial. Behavioral treatments for tics are restricted to older children and are not readily available to all centers, mainly due to the paucity of well-trained therapists. Pharmacological treatments, such as antipsychotics for tics, stimulants and atomoxetine for ADHD, and α2A-agonists for children with tics plus ADHD, represent widely available and effective treatment options, but safety monitoring must be provided. Combined polypharmacological and behavioral/pharmacological approaches, as well as neuromodulation strategies, remain under-investigated in this population of patients. Conclusions The treatment of children with tics and Tourette syndrome is multifaceted. Multidisciplinary teams with expertise in neurology, psychiatry, psychology, and pediatrics may be helpful to address the complex needs of these children. [ABSTRACT FROM AUTHOR]

Aim: There are few long-term studies of adaptive functions as an outcome measure of pharmacological treatment in attention-deficit/hyperactivity disorder (ADHD). This study assessed the adaptive abilities of children with ADHD before and after several years of pharmacological treatment.Method: We studied 12 children with a mean age of 15 years - seven boys and five girls - who had continued pharmacological treatment for ADHD for more than four years. The Adaptive Behaviour Assessment Scales - Second Edition ratings by their teachers were compared before and after they had received treatment for ADHD.Results: On a group level, the conceptual, practical and general adaptive composite domains improved significantly between the baseline and follow-up study. There were clear individual variations: more than half of the group increased from an adaptive level far below average to average, a minority displayed no major changes, and one individual deteriorated. The girls tended to have better outcomes than the boys.Conclusion: This study was nonrandomised and only analysed within-group changes in a small number of participants. However, the findings suggest that four to five years of stimulant treatment had markedly positive effects on adaptive functioning in more than half of the school-age children with ADHD. [ABSTRACT FROM AUTHOR]

Purpose This article is a standardization document of the International Children's Continence Society (ICCS); it represent a consensus of ICCS on the management of pediatric daytime urine incontinence (DUI). Materials and Methods This document was designed and written by a multi-disciplinary core group of authors appointed by the ICCS' board. Results Based on evidence of studies and the experience of experts, the treatment guideline of DUI is assembled in this standardization document. Guidelines and the algorithm of management include non-pharmacological treatment (urotherapy), as well as the pharmacological therapy and other modalities that are presented for DUI in general, as along with recommendations for individual conditions. Conclusion The final document is not a systematic literature review. It includes relevant research when available as well as experts' opinion on the current understanding of daytime incontinence in children. This document illustrates that specific treatment of DUI based on an exact diagnosis is effective. The mainstay of treatment is urotherapy, but a combination of treatment modalities is often necessary. Neurourol. Urodynam. 36:43-50, 2017. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy (HCM) is entering a phase of intense translational research that holds promise for major advances in disease-specific pharmacological therapy. For over 50 years, however, HCM has largely remained an orphan disease, and patients are still treated with old drugs developed for other conditions. While judicious use of the available armamentarium may control the clinical manifestations of HCM in most patients, specific experience is required in challenging situations, including deciding when not to treat. The present review revisits the time-honoured therapies available for HCM, in a practical perspective reflecting real-world scenarios. Specific agents are presented with doses, titration strategies, pros and cons. Peculiar HCM dilemmas such as treatment of dynamic outflow obstruction, heart failure caused by end-stage progression and prevention of atrial fibrillation and ventricular arrhythmias are assessed. In the near future, the field of HCM drug therapy will rapidly expand, based on ongoing efforts. Approaches such as myocardial metabolic modulation, late sodium current inhibition and allosteric myosin inhibition have moved from pre-clinical to clinical research, and reflect a surge of scientific as well as economic interest by academia and industry alike. These exciting developments, and their implications for future research, are discussed. [ABSTRACT FROM AUTHOR]

Aims: To assess physicians' adherence to guideline-recommended medications for the treatment of chronic heart failure (CHF) with reduced ejection fraction.Methods and Results: QUALIFY is an international prospective observational longitudinal survey of 7092 CHF outpatients recruited 1-15 months after hospitalization for heart failure from September 2013 to December 2014 in 547 centres in 36 countries. We constructed a five-class guideline adherence score for angiotensin converting enzyme inhibitors (ACEIs), beta-blockers, angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists, and ivabradine. The adherence score was good in 67%, moderate in 25%, and poor in 8% of patients. Adherence was lower in women than men but there were differences in age (65.7 ± 12.5 years women vs. 62.2 ± 12.4 years men, P < 0.001) and the proportion of women at ≥50% target dose of beta-blockers was lower in those >67 years (median) (11% vs. 16.2%, P = 0.005). Geographic variations were observed with lower adherence scores in Central/Eastern European countries. The proportion of patients at target dose and ≥50% of target dose was low (27.9% and 63.3% for ACEIs, 14.8% and 51.8% for beta-blockers, 6.9% and 39.5% for ARBs, and 6.9% and 39.5% for ivabradine, respectively). It was also lower in patients most recently hospitalized (<6  vs. ≥6 months) except for beta-blockers.Conclusion: This international survey shows that adherence to guideline-recommended medications is relatively satisfactory but the dosage of recommended CHF medications is usually suboptimal. Action plans aimed at improving adherence to guidelines are required. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the effectiveness of antipsychotic medications in preventing and treating delirium. Design Systematic review and meta-analysis. Setting PubMed, EMBASE, CINAHL, and ClinicalTrials.gov databases were searched from January 1, 1988, to November 26, 2013. Participants Adult surgical and medical inpatients. Intervention Antipsychotic administration for delirium prevention or treatment in randomized controlled trials or cohort studies. Measurements Two authors independently reviewed all citations, extracted relevant data, and assessed studies for potential bias. Heterogeneity was considered as chi-square P < .1 or I2 > 50%. Using a random-effects model (I2 > 50%) or a fixed-effects model (I2 < 50%), odds ratios ( ORs) were calculated for dichotomous outcomes (delirium incidence and mortality), and mean or standardized mean difference for continuous outcomes (delirium duration, severity, hospital and intensive care unit ( ICU) length of stay ( LOS)). Sensitivity analyses included postoperative prevention studies only, exclusion of studies with high risk of bias, and typical versus atypical antipsychotics. Results Screening of 10,877 eligible records identified 19 studies. In seven studies comparing antipsychotics with placebo or no treatment for delirium prevention after surgery, there was no significant effect on delirium incidence ( OR = 0.56, 95% confidence interval ( CI) = 0.23-1.34, I2 = 93%). Using data reported from all 19 studies, antipsychotic use was not associated with change in delirium duration, severity, or hospital or ICU LOS, with high heterogeneity among studies. No association with mortality was detected ( OR = 0.90, 95% CI = 0.62-1.29, I2 = 0%). Conclusion Current evidence does not support the use of antipsychotics for prevention or treatment of delirium. Additional methodologically rigorous studies using standardized outcome measures are needed. [ABSTRACT FROM AUTHOR]

Objectives The aim of the present study was to describe prescription patterns and changes in these patterns over the last decade for patients diagnosed with bipolar disorder in mental healthcare, using population-based and nationwide data, and to relate the findings to recommendations from international guidelines. Methods A population-based, nationwide study was carried out. It included register-based longitudinal data on all patients with a first-ever contact with mental healthcare with a diagnosis of mania/bipolar disorder from the entire Danish population, and all prescription data for this population during the decade from 2000 to 2011, inclusive. Results A total of 3,205 patients were included in the study. Lithium was prescribed less, and antiepileptic and atypical antipsychotic agents were prescribed substantially more during the study period. Lithium went from being the first drug prescribed to being the last, and was replaced by atypical antipsychotic agents. Antiepileptic agents went from being the fourth to the second drug class prescribed, and the prescription of antidepressants was virtually unchanged, at a high level, during the decade (one-year value 40-60%). The prescription of lamotrigine and quetiapine increased substantially. Combination therapy increased for all drug combinations, except for lithium combined with antidepressants. Conclusions Major changes took place in drug prescriptions during the study period. The decrease in the use of lithium and the constant high use of antidepressants do not align with recommendations from international guidelines. [ABSTRACT FROM AUTHOR]

Aims This study aimed to investigate systematically (i) the appropriate dietary conditions to induce the features of the MetS in APOE* 3Leiden.humanCholesteryl Ester Transfer Protein ( E3L. CETP) mice and (ii) whether the response of this model to different antidiabetic and hypolipidemic drugs is similar as in humans. Methods Male obese, IR and dyslipidemic E3L. CETP mice were treated with antidiabetic drugs rosiglitazone, liraglutide or an experimental 11β-hydroxysteroid-dehydrogenase-1 ( HSD-1) inhibitor, or with hypolipidemic drugs atorvastatin, fenofibrate or niacin for 4-6 weeks. The effects on bw, IR and plasma and liver lipids were assessed. Results Rosiglitazone, liraglutide and HSD-1 inhibitor significantly decreased glucose and insulin levels or IR. Liraglutide and HSD-1 inhibitor also decreased bw. Atorvastatin, fenofibrate and niacin improved the dyslipidemia and fenofibrate and niacin increased high-density lipoprotein ( HDL) cholesterol. In addition, hepatic triglycerides were significantly decreased by treatment with rosiglitazone and liraglutide, while hepatic cholesterol esters were significantly decreased by rosiglitazone and atorvastatin. Conclusions We conclude that the E3L. CETP mouse is a promising novel translational model to investigate the effects of new drugs, alone or in combination, that affect IR, diabetic dyslipidemia and non-alcoholic fatty liver disease ( NAFLD). [ABSTRACT FROM AUTHOR]

Aim To compare survival on different beta-blockers in heart failure. Methods and results We identified all Danish patients ≥35 years of age who were hospitalized with a first admission for heart failure and who initiated treatment with a beta-blocker within 60 days of discharge. The study period was 1995-2011. The main outcome was all-cause mortality and all-cause hospitalization. Cox proportional hazard models were used to compare survival. The study included 58 634 patients of whom 30.121 (51.4%) died and 46.990 (80.1%) were hospitalized during follow-up. The mean follow-up time was 4.1 years. In an unadjusted model carvedilol was associated with a lower mortality [hazard ratio ( HR) 0.737, 0.714-0.761] compared with metoprolol (reference) while bisoprolol was not associated with an increased mortality ( HR 1.020, 0.973-1.069). In a model adjusted for possible confounders and stratified according to beta-blocker dosages, patients that received high-dose carvedilol (≥50 mg daily) had a lower all-cause mortality risk ( HR 0.873, 0.789-0.966) than patients receiving high-dose (≥200 mg daily) metoprolol (reference). High-dose bisoprolol (≥10 mg daily) was associated with a greater risk of death ( HR 1.125, 1.004-1.261). High-dose carvedilol was associated with significantly lower all-cause hospitalization risk ( HR 0.842, 0.774-0.915) than high-dose metoprolol (reference), while high-dose bisoprolol had insignificantly lower risk than high-dose metoprolol ( HR 0.948, 0.850-1.057). Conclusions Heart failure patients receiving high-dose carvedilol (≥50 mg daily) showed significantly lower all-cause mortality risk and hospitalization risk, compared with other beta-blockers. [ABSTRACT FROM AUTHOR]

Background Migraine is a common illness in children associated with a negative impact on the quality of life. In the Netherlands, treatment of migraine is commonly performed by general practitioners (GPs). The migraine guideline of the Dutch College of General Practitioners recommends inactivity and acetaminophen in patients with migraine who are younger than 18 years of age. Objective The aim of our study was to evaluate the pharmacological treatment of migraine in children by GPs before referral to the hospital. Our objective was to answer the following questions. First, are GPs inclined to prescribe medication not listed in the Dutch College of General Practitioners Guideline? Second, which clinical characteristics are associated with the use of medication not listed in this guideline? Methods In this retrospective cross-sectional study, prescribed medication and migraine characteristics were investigated in Dutch migraine patients (age <18 years), using hospital records and a paper-and-pencil questionnaire. Results A total of 223 children were included. Medications not listed in the guideline were used in 41.3% of the patients before referral. In children younger than 12 years, the use of medication not listed in the guideline was associated with an older age, when compared with children who were treated according to the guideline. In the group of patients older than 11 years, the use of medication not listed in the guideline was associated with a longer history of migraine and a longer duration of the migraine attacks. Conclusions Medications not listed in the GPs guideline were used in a large portion of the patients younger than 18 years with migraine who were referred to secondary care. [ABSTRACT FROM AUTHOR]

Objective Anxiety disorders are treatable conditions, but many affected individuals neither seek professional help nor adhere to recommended pharmacological treatments. Increasing the health literacy of people with (or at risk of) anxiety disorders may encourage treatment-seeking and adherence to recommended interventions. Aims of this study were to review the literature relating to health literacy in the treatment of anxiety disorders, focusing on results on public opinion on psychotropic medications and its effectiveness in improving access to psychiatric health care and the actual use of medications. Methods A computerized literature search of the published literature on mental health literacy was undertaken, focusing on the question of whether increased mental health literacy led to increased treatment-seeking and pharmacotherapy adherence in individuals with anxiety disorders. Results Twelve relevant articles were identified. All reported that improving mental health literacy leads to raised awareness, and in 10 out of 12 studies, increased help-seeking. However, there is currently no unequivocal evidence to show that increasing health literacy leads to increased use of medication in any psychiatric disorder, including anxiety disorders. Two studies show that knowledge of presumed biological mechanisms can predict use of psychotropic medication, including antidepressants, in psychiatric disorders, however, not specifically in anxiety disorders. Conclusion There have been few investigations of health literacy focused on psychotropic medications. Given the prevalence, burden and sub-optimal recognition, and treatment of anxiety disorders, further work is needed to determine whether increased mental health literacy is associated with treatment-seeking and medication adherence in patients with these disorders. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT It is believed that glycogen synthase kinase-3 (GSK-3) hyperphosphorylates tau protein in progressive supranuclear palsy (PSP). The Tau Restoration on PSP (TAUROS) study was a double-blind, placebo-controlled, randomized trial to assess the efficacy, safety, and tolerability of tideglusib, a GSK-3 inhibitor, as potential treatment for PSP. The study enrolled 146 PSP patients with mild-to-moderate disease who were randomized to receive once-daily 600 mg tideglusib, 800 mg tideglusib, or placebo (ratio, 2:2:1) administered orally over 52 weeks. The primary endpoint was the change from baseline to week 52 on the PSP rating scale. Secondary endpoints were safety and tolerability of tideglusib, changes in motor function (the Timed Up and Go Test), cognition (Dementia Rating Scale-2, Frontal Assessment Battery, verbal fluency), apathy (Starkstein scale), activities of daily living (Schwab and England scale; Unified Parkinson's Disease Rating Scale, part II), quality of life (EuroQol), and Global Clinical Assessment. Brain atrophy on magnetic resonance imaging and several biomarkers in plasma and cerebrospinal fluid also were examined. No significant differences were detected in the primary or secondary endpoints at week 52 between placebo and either dose of tideglusib. Tideglusib was safe, with the exception of some asymptomatic, transient, and reversible transaminase elevations (mainly alanine aminotransferase) in 9% of patients, and diarrhea in 13% of patients. Tideglusib was generally well tolerated but it did not show clinical efficacy in patients with mild-to-moderate PSP. © 2014 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Objectives To systematically review the current literature on the pharmacological treatment of postmeal reductions in blood pressure ( BP). Design A systematic literature search and standardized data collection of randomized controlled trials on the pharmacological prevention of postprandial reductions in BP in adults using MEDLINE (1950-), EMBASE (1980-), and CINAHL databases was conducted up to July 2013. Bibliographies of relevant reports were also hand-searched to identify all potentially eligible studies. Setting Systematic review of randomized controlled trials using PRISMA guidelines. Measurements Articles were assessed using the Critical Appraisal Skills Programme for randomized controlled trials. Results Thirteen articles reporting 12 studies (1 study was reported in 2 articles) demonstrated that caffeine (5 studies); acarbose; 3,4- DL-threo-dihydroxyphenylserine; guar gum (3 studies); and octreotide (2 studies) statistically attenuated the postprandial reduction in BP. One caffeine study did not show this. Most studies did not include individuals with symptomatic postprandial hypotension ( PPH), so interpretation and application of these findings to this patient group should be made with caution. For symptomatic participants, there was improvement with acarbose but none with caffeine. Differences in the way the data were presented in the studies did not allow for quantification of treatment effects using meta-analysis. Conclusion Drug interventions can attenuate postprandial reductions in BP, but they may not necessarily be effective in people with symptomatic PPH. [ABSTRACT FROM AUTHOR]

Obesity dramatically increases the risk of development of cardiovascular and metabolic diseases. Endothelial dysfunction induced by obesity is an important risk factor that impairs blood flow controls in various organs. Impaired endothelial function occurs early in life in obese children. Obesity-induced endothelial dysfunction is associated with decreased nitric oxide (NO) production due to impaired endothelial NO synthase activity and expression and increased production of superoxide anion and the endogenous NOS inhibitor ADMA, together with increased vasoconstrictor factors, such as endothelin-1 and sympathetic nerve activation. Decreased endothelial progenitor cells are also involved in endothelial cell senescence in obese individuals. Insulin resistance and diabetes mellitus augment obesity-induced endothelial dysfunction. Adipokines liberated from adipose tissues play roles in modulating endothelial function; adiponectin and ghrelin have beneficial effects on endothelial cells. Effects of leptin on endothelial function are controversial. Decreased body weight by physical exercise, dietary interventions, and bariatric surgery are effective measures that reverse endothelial dysfunction; however, the weight control is not only the reason for improving of endothelia function. Pharmacological therapies with β-adrenoceptor antagonists, resveratolol, anti-obesity agents, nifedipine, and NADPH oxidase inhibitors may also be effective; however, these treatments have to be utilized under the basis of exercise and dietary controls. [ABSTRACT FROM AUTHOR]

Fear extinction-based exposure treatment is an important component of psychotherapy for anxiety disorders such as posttraumatic stress disorder (PTSD). Recent studies have focused on pharmacological approaches combined with exposure therapy to augment extinction. In this study, we elucidated the therapeutic potential of the serotonin 1A (5-HT1A) receptor agonist tandospirone compared with the effects of the N-methyl- D-aspartate partial agonist D-cycloserine (DCS), focusing on the possible involvement of dopaminergic mechanisms. We used a rat model of juvenile stress [aversive footshock (FS)] exposure during the third postnatal week (3wFS). The 3wFS group exhibited extinction deficit reflected in sustained fear-related behavior and synaptic dysfunction in the hippocampal CA1 field and medial prefrontal cortex (mPFC), which are responsible for extinction processes. Tandospirone administration (5 mg/kg, i.p.) before and after the extinction trials ameliorated both the behavioral deficit and synaptic dysfunction, i.e., synaptic efficacy in the CA1 field and mPFC associated with extinction training and retrieval, respectively, was potentiated in the tandospirone-treated 3wFS group. Extracellular dopamine release in the mPFC was increased by extinction retrieval in the non-FS control group. This facilitation was not observed in the 3wFS group; however, tandospirone treatment increased cortical dopamine levels after extinction retrieval. DCS (15 mg/kg, i.p.) also ameliorated the extinction deficit in the 3wFS group, but impaired extinction in the non-FS control group. These results suggest that tandospirone has therapeutic potential for enhancing synaptic efficacy associated with extinction processes by involving dopaminergic mechanisms. Pharmacological agents that target cortical dopaminergic systems may provide new insights into the development of therapeutic treatments of anxiety disorders, including PTSD. © Synapse, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Aims This paper reviews the published literature regarding outcomes following maternal treatment with buprenorphine in five areas: maternal efficacy, fetal effects, neonatal effects, effects on breast milk and longer-term developmental effects. Methods Within each outcome area, findings are summarized first for the three randomized clinical trials and then for the 44 non-randomized studies (i.e. prospective studies, case reports and series and retrospective chart reviews), only 28 of which involve independent samples. Results Results indicate that maternal treatment with buprenorphine has comparable efficacy to methadone, although difficulties may exist with current buprenorphine induction methods. The available fetal data suggest buprenorphine results in less physiological suppression of fetal heart rate and movements than methadone. Regarding neonatal effects, perhaps the single definitive conclusion is that prenatal buprenorphine treatment results in a clinically significant less severe neonatal abstinence syndrome ( NAS) than treatment with methadone. The limited research suggests that, like methadone, buprenorphine is compatible with breastfeeding. Data available thus far suggest that there are no deleterious effects of in utero buprenorphine exposure on infant development. Conclusions While buprenorphine produces a less severe neonatal abstinence syndrome than methadone, both methadone and buprenorphine are important parts of a complete comprehensive treatment approach for opioid-dependent pregnant women. [ABSTRACT FROM AUTHOR]

Aims The Maternal Opioid Treatment: Human Experimental Research ( MOTHER) project, an eight-site randomized, double-blind, double-dummy, flexible-dosing, parallel-group clinical trial is described. This study is the most current-and single most comprehensive-research effort to investigate the safety and efficacy of maternal and prenatal exposure to methadone and buprenorphine. Methods The MOTHER study design is outlined, and its basic features are presented. Conclusions At least seven important lessons have been learned from the MOTHER study: (i) an interdisciplinary focus improves the design and methods of a randomized clinical trial; (ii) multiple sites in a clinical trial present continuing challenges to the investigative team due to variations in recruitment, patient populations and hospital practices that, in turn, differentially impact recruitment rates, treatment compliance and attrition; (iii) study design and protocols must be flexible in order to meet the unforeseen demands of both research and clinical management; (iv) staff turnover needs to be addressed with a proactive focus on both hiring and training; (v) the implementation of a protocol for the treatment of a particular disorder may identify important ancillary clinical issues worthy of investigation; (vi) timely tracking of data in a multi-site trial is both demanding and unforgiving; and (vii) complex multi-site trials pose unanticipated challenges that complicate the choice of statistical methods, thereby placing added demands on investigators to effectively communicate their results. [ABSTRACT FROM AUTHOR]

Abstract: Levetiracetam is an anticonvulsant which is assumed to act by modulating neurotransmitter release via binding to the vesicle protein SV2A. This could have an impact on signaling in the nociceptive system, and a pilot study indicated relief of neuropathic pain with levetiracetam. Objectives: The aim of this study was to test the analgesic effect of levetiracetam in painful polyneuropathy. Methods: This was a randomized, double-blind, placebo-controlled, cross-over trial with levetiracetam 3000mg/day versus placebo (6-week treatment periods). Patients with diagnosed polyneuropathy and symptoms for more than 6months, age between 20 and 80years, pain intensity of more than 4 on a 0–10-point numeric rating scale, and pain at least 4days a week were included in the study. The primary outcome measure was pain relief at the end of each treatment period as measured on a 6-point verbal scale. Results: Ninety-three patients were screened for participation and 39 patients entered the study. Thirty-five patients were included in the data analysis. There were no differences in the ratings of pain relief (levetiracetam 2.29 versus placebo 2.28, p =0.979), total pain intensity (levetiracetam 5.5 versus placebo 5.3, p =0.293) or any of the other outcome measures (p =0.147–1.00). Conclusion: This study indicates that the anticonvulsant levetiracetam has no clinically relevant effect on painful polyneuropathy. [Copyright &y& Elsevier]

Viral bronchiolitis is common, and about 98-99% of infants are managed in the home. Because about 95% of infants <2 years old are infected with respiratory syncytial virus, however, bronchiolitis is the commonest reason for admission to hospital in the first 6 months of life. It is usually a self-limiting condition lasting around a week in previously well children. About 1% of infants are admitted to hospital, and about 10% of hospitalised infants will require admission to the intensive care unit. Respiratory syncytial virus is isolated from about 70% of infants hospitalised with bronchiolitis. The emphasis of hospital treatment is to ensure adequate hydration and oxygenation. Other than supplemental oxygen, little in the way of pharmacological treatment has been demonstrated to alter the course of the illness or the risk of wheezing in the months following bronchiolitis. [ABSTRACT FROM AUTHOR]

Apathy is defined as a disorder of motivation. There is wide acknowledgement that apathy is an important behavioral syndrome in Alzheimer's disease and in various neuropsychiatric disorders. In light of recent research and the renewed interest in the correlates and impacts of apathy and in its treatments, it is important to develop criteria for apathy that will be widely accepted, have clear operational steps, and be easy to apply in clinical practice and in research settings. Meeting these needs was the focus for a task force that included members of the European Psychiatric Association, the European Alzheimer's Disease Consortium and experts from Europe, Australia and North America. [ABSTRACT FROM AUTHOR]

Background and objectives: This second European Federation of Neurological Societies Task Force aimed at updating the existing evidence about the pharmacological treatment of neuropathic pain since 2005. Methods: Studies were identified using the Cochrane Database and Medline. Trials were classified according to the aetiological condition. All class I and II randomized controlled trials (RCTs) were assessed; lower class studies were considered only in conditions that had no top-level studies. Treatments administered using repeated or single administrations were considered, provided they are feasible in an outpatient setting. Results: Most large RCTs included patients with diabetic polyneuropathies and post-herpetic neuralgia, while an increasing number of smaller studies explored other conditions. Drugs generally have similar efficacy in various conditions, except in trigeminal neuralgia, chronic radiculopathy and HIV neuropathy, with level A evidence in support of tricyclic antidepressants (TCA), pregabalin, gabapentin, tramadol and opioids (in various conditions), duloxetine, venlafaxine, topical lidocaine and capsaicin patches (in restricted conditions). Combination therapy appears useful for TCA-gabapentin and gabapentin-opioids (level A). Conclusions: There are still too few large-scale comparative studies. For future trials, we recommend to assess comorbidities, quality of life, symptoms and signs with standardized tools and attempt to better define responder profiles to specific drug treatments. [ABSTRACT FROM AUTHOR]

J. Neurochem. (2010) 113, 1644–1658. Lesioned axons do not regenerate in the adult mammalian CNS, owing to the over-expression of inhibitory molecules such as myelin-derived proteins or chondroitin sulphate proteoglycans. In order to overcome axon inhibition, strategies based on extrinsic and intrinsic treatments have been developed. For myelin-associated inhibition, blockage with NEP1–40, receptor bodies or IN-1 antibodies has been used. In addition, endogenous blockage of cell signalling mechanisms induced by myelin-associated proteins is a potential tool for overcoming axon inhibitory signals. We examined the participation of glycogen synthase kinase 3β (GSK3β) and extracellular-related kinase (ERK) 1/2 in axon regeneration failure in lesioned cortical neurons. We also investigated whether pharmacological blockage of GSK3β and ERK1/2 activities facilitates regeneration after myelin-directed inhibition in two models: (i) cerebellar granule cells and (ii) lesioned entorhino-hippocampal pathway in slice cultures, and whether the regenerative effects are mediated by Nogo Receptor 1 (NgR1). We demonstrate that, in contrast to ERK1/2 inhibition, the pharmacological treatment of GSK3β inhibition strongly facilitated regrowth of cerebellar granule neurons over myelin independently of NgR1. Finally, these regenerative effects were corroborated in the lesioned entorhino-hippocampal pathway in NgR1−/ − mutant mice. These results provide new findings for the development of new assays and strategies to enhance axon regeneration in injured cortical connections. [ABSTRACT FROM AUTHOR]

Aims: This study evaluated the prevalence of left-ventricular (LV) dysfunction in vascular surgery patients and pharmacological treatment, according ESC guidelines. [ABSTRACT FROM PUBLISHER]

The cardiac action potential can be divided into five distinct phases designated phases 0–4. The exact shape of the action potential comes about primarily as an orchestrated function of ion channels. The present review will give an overview of ion channels involved in generating the cardiac action potential with special emphasis on potassium channels involved in phase 3 repolarization. In humans, these channels are primarily Kv11.1 (hERG1), Kv7.1 (KCNQ1) and Kir2.1 (KCNJ2) being the responsible α-subunits for conducting IKr, IKs and IK1. An account will be given about molecular components, biophysical properties, regulation, interaction with other proteins and involvement in diseases. Both loss and gain of function of these currents are associated with different arrhythmogenic diseases. The second part of this review will therefore elucidate arrhythmias and subsequently focus on newly developed chemical entities having the ability to increase the activity of IKr, IKs and IK1. An evaluation will be given addressing the possibility that this novel class of compounds have the ability to constitute a new anti-arrhythmic principle. Experimental evidence from in vitro, ex vivo and in vivo settings will be included. Furthermore, conceptual differences between the short QT syndrome and IKr activation will be accounted for. [ABSTRACT FROM AUTHOR]

Abstract: At the Sixth Annual Mild Cognitive Impairment Symposium in Miami Beach, Florida, a multidisciplinary group of experts from the Alzheimer''s disease (AD) community met to discuss the current status of AD intervention trials and future plans for designing trials of prodromal AD and/or mild cognitive impairment. There is no agreement regarding a single pathogenic mechanism to be targeted, although a consensus seems to be emerging that effective treatment will require attacking multiple targets. These targets include beta amyloid (Aß) aggregates (including different isoforms and different aggregation species), neurofibrillary tangles composed of hyperphosphorylated tau, neuronal and synaptic loss, and mechanisms that contribute to Aß deposition–induced inflammation and immune dysregulation. Vascular disease, which is very common in the elderly, also appears to be a contributor to AD pathogenesis and might be modifiable through pharmacologic and lifestyle interventions to reduce the impact of conditions such as hypertension and metabolic syndrome. Potential disease-modifying approaches that were discussed, including pharmacologic agents that target Aβ, immunotherapy to eliminate plaques in the brain, passive immunotherapy, and secretase inhibitors. Nonpharmacologic approaches included stimulation of endogenous bone marrow cells, which can enter the brain and remove amyloid deposits, and cognitive and exercise training. Innovative trial designs are required that will allow a drug''s effectiveness to be determined efficiently in the transition from normal to mild cognitive impairment to probable AD. This might be achieved through the use of various forms of imaging and measurement of biochemical markers in the blood or cerebrospinal fluid, as well as measures that assess very early cognitive and behavioral changes. In the absence of effective treatments for AD, clinicians are faced with a dilemma about why, when, and how to disclose the diagnosis to patients and their family members and/or caregivers. The issues were discussed from multiple perspectives by a panel that included a lay representative, neurologist, psychiatrist, primary care physician, and a psychosocial researcher. [Copyright &y& Elsevier]

Objective: The aim of this paper was to review the association of most commonly used psychopharmacological drugs with weight gain in bipolar disorder. Method: Information was retrieved from a PubMed/Medline literature search reviewing weight gain in pharmacological studies in bipolar disorder. Results: Obesity and overweight in bipolar disorder are partly related to prescribed drugs with a strong effect of clozapine and olanzapine. Lesser but still relevant weight gain is caused by quetiapine, risperidone, lithium, valproate, gabapentin and by some antidepressants. Ziprasidone, aripiprazole, carbamazepine and lamotrigine do not seem to cause significant overweight. Conclusion: Careful monitoring of weight changes in patients before and after drug prescription should be implemented in the clinical routine and drugs which potentially cause weight gain should be avoided in overweight patients with bipolar disorder. Furthermore, eating habits and daily activities should be targeted as they may also have a significant impact on overall health and weight-related issues. [ABSTRACT FROM AUTHOR]

Aim: To study the associations between weight loss with sibutramine and orlistat with psychological aspects that may interact with patients’ response to these drugs. Methods: A total of 478 obese patients with a mean body mass index of 42 ± 12 kg/m2 gave self-reported, retrospective data on different types of previous weight loss treatments (sibutramine and orlistat, and Weight Watchers used as a control condition) including the amount of weight lost with these treatments, eating behaviour (Dutch Eating Behaviour Questionnaire) and personality (NEO Personality Inventory – Revised). Results: Greater weight loss with sibutramine was associated with lower levels of restrained eating and higher levels of ‘neuroticism’, in particular ‘anxiety’ and ‘depression’. Greater weight loss with orlistat was associated with aspects of the personality dimension ‘conscientiousness’ (e.g. ‘order’ and ‘deliberation’). Conclusion: Sibutramine may exert its greatest effect in patients whose eating is a ‘natural’ response to hunger rather than regulated by cognitions and conscious controls. Patients with low levels of restraint could be more sensitive to the satiety-enhancing effect of sibutramine. They may be able to reduce their food intake without cognitive interference and/or start to control their eating most radically in response to enhanced satiety. Enhanced satiety may also help patients withstand a wish to eat triggered by psychological distress. Possible central nervous system effects on mood could also have reduced eating, which was related to distress. The administration regimen of orlistat is more demanding, requiring greater adherence. This can account for the finding that personality attributes such as conscientiousness are important for success. [ABSTRACT FROM AUTHOR]

Objectives.—To determine the clinical status, with respect to pain indices and disability level, of chronic migraine patients with medication overuse who were treated 3 years previously. Background.—Patients who have chronic migraine accompanied by medication overuse are particularly difficult to treat. Investigations are limited in number, few have included follow-up beyond 6 months, and almost none have examined whether treatment leads to concurrent improvements in disability and functional impairment. In a prior report, we described the clinical course of 84 such patients followed for 1 full year after treatment. Methods.—These same 84 patients were followed for 2 additional years to assess longer term maintenance of effects, using measurement procedures identical to those in the original investigation. Results.—Both endpoint and completer analyses revealed significant improvement on all measures studied—headache days per month, analgesic consumption, and MIDAS scores (Total, Headache Frequency, and Headache Intensity)—with some loss of benefits over time for the pain indices. MIDAS total scores, however, were lower at 36 months than at 6 months. Comparisons of those who completed the 3-year follow-up to those who did not revealed few differences at baseline. All of this suggests attrition did not have a bearing on outcome. Discussion.—High levels of maintenance were revealed at 3 years. Even though reports of pain revealed some lessening of effects, this was not accompanied by reports of deterioration in functioning. This suggests that patients have learned to adapt and adjust to headaches in their daily lives. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate duloxetine (a serotonin-noradrenaline reuptake inhibitor) in women with symptoms of overactive bladder (OAB), as it has been shown to increase the bladder capacity in an animal model. PATIENTS AND METHODS In all, 306 women (aged 21–84 years) were recruited and randomly assigned to placebo (153) or duloxetine (80-mg/day for 4 weeks increased to 120-mg/day for 8 weeks; 153). Symptoms of OAB were defined as bothersome urinary urgency and/or urge urinary incontinence (UI) for ≥3 months. Participants were also required to have a mean daytime voiding interval (VI) of ≤2 h and urodynamic observations of either detrusor overactivity (DOA) or urgency which limited bladder capacity to <400 mL, both with no stress UI (SUI). The primary efficacy analysis compared the treatment effects on mean change from baseline to endpoint in the mean number of voiding episodes (VE)/24 h. The secondary efficacy analyses compared the treatment effects on the number of UI episodes (IE)/24 h, in the Incontinence Quality of Life questionnaire (I-QOL) score, and on the mean daytime VI. Safety was assessed with vital signs, adverse event reporting, routine laboratory testing, electrocardiogram, and the measurement of postvoid residual urine volumes (PVR). RESULTS Patients randomized to duloxetine had significant improvements over those randomized to placebo for decreases in VE and IE, for increases in the daytime VI, and for improvements in I-QOL scores at both doses of duloxetine. Urodynamic studies showed no significant increases in maximum cystometric capacity or in the volume threshold for DOA. The most common treatment-emergent adverse events with duloxetine (nausea, 31%; dry mouth, 16%; dizziness, 14%; constipation, 14%; insomnia, 13%; and fatigue, 11%) were the same as those reported by women with SUI and were significantly more common with duloxetine than placebo. Laboratory assessments, vital signs and electrocardiograms were stable relative to baseline, with no relevant differences detected between groups. There was a significant difference in the change in PVR with duloxetine (<5 mL mean increase) but no patient reported hesitancy or retention. CONCLUSION In this trial, duloxetine was better than placebo for treating women with ‘wet’ and ‘dry’ symptoms of OAB associated with DOA or a bladder capacity of <400 mL. [ABSTRACT FROM AUTHOR]

This paper reviews and discusses existing barriers to diagnosis and treatment for patients with dementia in Europe as well as approaches to overcome these barriers. The barriers to care are manifold, being present at all levels in each society and between countries in Europe. Multilevel and multifaceted strategies are needed to improve diagnosis and treatments for all patients with cognitive complaints. A multidisciplinary approach based on close collaboration between GPs and specialised memory clinics may be the ideal model for early accurate diagnosis and subsequently early pharmacological and psychosocial interventions. For all healthcare professionals, there should be specialised training in dementia and frequently updated practice guidelines to provide the framework for standards of care. Culture-sensitive strategies to promote public knowledge and destigmatize dementia are essential. Policy makers and authorities should be made aware of the benefits of early access to diagnosis and treatment. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]