A Mathematical Relationship for Hydromorphone Loading into Liposomes with Trans-Membrane Ammonium Sulfate Gradients

We have studied the loading of the opioid hydromorphone into liposomes using ammonium sulfate gradients. Unlike other drugs loaded with this technique, hydromorphone is freely soluble as the sulfate salt, and, consequently, does not precipitate in the liposomes after loading. We have derived a mathematical relationship that can predict the extent of loading based on the ammonium ion content of the liposomes and the amount of drug added for loading. We have adapted and used the Berthelot indophenol assay to measure the amount of ammonium ions in the liposomes. Plots of the inverse of the fraction of hydromorphone loaded versus the amount of hydromorphone added are linear, and the slope should be the inverse of the amount of ammonium ions present in the liposomes. The inverse of the slopes obtained closely correspond to the amount of ammonium ions in the liposomes measured with the Berthelot indophenol assay. We also show that loading can be less than optimal under conditions where osmotically driven loss of ammonium ions or leakage of drug after loading may occur.     

Pharmacotherapeutic strategies for standard treatment-resistant psoriasis

Introduction: Psoriasis management includes a variety of treatments including localized therapies and systemic treatments; however, many patients report inadequate clinical response and resistance to therapy. Currently there is no treatment algorithm that incorporates effective strategies to tackle the various barriers leading to resistance.

Areas covered: The authors evaluate the scope of resistance, the reasons it occurs, and provide the reader with strategies for overcoming resistance in both localized and systemic therapies for psoriasis.

Expert opinion: Refractory psoriasis involves modifiable and non-modifiable factors that warrant different approaches to maximize clinical response. Treatment-resistance to topical therapies may be due to poor adherence. Improving adherence involves incorporating patients’ treatment preferences, improving the physician-patient relationship, and simplifying treatment regimens. Treatment-resistance to systemic therapies can be due to non-adherence but can also be due to ineffective dosing, development of anti-drug antibodies, and severe disease that necessitates multiple drugs. After addressing non-adherence, strategies to maximize systemic therapies include increasing the dosage, combining treatments, drug switching and incorporating pharmacogenetics.     

Tibial tuberosity fractures in adolescents

Background  Tibial tuberosity fractures in adolescents are uncommon. We retrospectively reviewed all tibial tuberosity fractures in adolescents (10–19) who presented to our level 1 pediatric trauma center over a 7-year period to review fracture morphology, mechanism of injury, fracture management including return to play, as well as complications. Additionally, we present a review of the literature and treatment algorithm. Methods  We reviewed the clinical charts and radiographs of consecutive patients with tibial tuberosity fractures between 01 January 2000 and 01 January 2007. Data parameters included the following: patients age and gender, involved side, injury classification, co-morbidities, mechanism of injury, treatment, return to activity and complications. Data were extracted and reviewed, and a treatment algorithm is proposed with some additional insights into the epidemiology of the injury. Nineteen patients met the inclusion criteria. Results  There were 19 patients with 20 tibial tuberosity fractures. The mean age was 13.7 years. There were 18 males and 1 female patient. There were nine left-sided injuries and eleven right-sided including one patient with bilateral fractures. Mechanism of injuries included basketball injury (8), running injury (5), football injury (3), fall from a scooter (2), high jump (1) and fall (1). Co-morbidities included three patients with concurrent Osgood–Schlatter disease and one with osteogenesis imperfecta. All were treated with ORIF, including arthroscopic-assisted techniques in two cases. Complications included four patients with pre-operative presentation of compartment syndrome all requiring fasciotomy, one post-operative stiffness and one painful hardware requiring removal. Range of motion was started an average of 4.3 weeks post-operatively and return to play was an average of 3.9 months post-operatively. Conclusion  Although uncommon, tibial tuberosity fractures in adolescents are clinically important injuries. Early recognition and treatment (closed or open as appropriate) gives good results. All the patients in our series had surgical fixation as per different indications that have been elaborated. It is important for clinicians to recognize that compartment syndrome remains a significant concern post-injury and in the perioperative period. Close monitoring and timely intervention is recommended. A simple treatment algorithm is presented for clinicians to help manage these injuries.     

Costs of epilepsy care in referral centers in Italy

This study evaluated the costs of diagnosis and treatment of epilepsy by prognostic group in referral centers for epilepsy. Data were collected in a multicenter retrospective observational study analyzing individual costs in a sample of 708 patients from 16 Italian centers. Patients were classified into five prognostic groups: remission, occasional seizure, active non-drug-resistant, drug-resistant seizures, and surgical candidates. The total cost per patient was 81.4 euros for the remission group, 227.6 euros for the occasional seizures group, 316.6 euros for the active non-drugresistant group, 415.6 euros for the drug-resistant seizures group, and 581.8 euros for surgical candidates. Despite the limitations related to the short observation period (2 months) and the inclusion only of referral centers, this study provides some interesting information about the cost of treatment of epilepsy in Italy, underlining the wide differences between the single cost components for the various prognostic groups.     

Endocytoscopic classification of preneoplastic lesions in the colorectum

Purpose  

The aim of this study is to assess the capability of endocytoscopy (ECS) in differentiating neoplastic from nonneoplastic lesions in the colorectum and to validate an ECS classification.     

Effects of Training on Controllability Attributions of Behavioural Excesses and Deficits Shown by adults with Down Syndrome and Dementia

Background Whereas there is a knowledge base on staff attributions of challenging behaviour, there has been little research on the effects of training, type of behaviour and biological context on staff attributions of controllability in the context of people with intellectual disabilities and dementia. Methods A mixed design was used to investigate the effects of three factors on care staff attributions of the controllability of challenging behaviour. Pre‐ and post‐training measures were administered to participants (n = 97) attending training on ageing, dementia and people with intellectual disabilities. Results No significant effects of diagnosis or type of behaviour on attributions were found. There was a significant increase in knowledge after training (P < 0.001) and training was found to significantly decrease the attribution of controllability (P < 0.001). Conclusion These results suggest that training that focuses on aspects of change relevant to behaviour can favourably influence care staff's knowledge and attributions of controllability within the context of people with Down syndrome and dementia.     

Genetic and environmental influences on externalizing behavior and alcohol problems in adolescence: A female twin study

Genetic and environmental contributions to the observed correlations among DSM-IV ADHD problems [inattentive (INATT) and hyperactive/impulsive (HYP/IMP) behaviors], conduct problems (CDP) and alcohol problems (AlcProb) were examined by fitting multivariate structural equation models to data from the Missouri Adolescent Female Twin Study [N = 2892 twins (831 monozygotic pairs, 615 dizygotic pairs)]. Based on results of preliminary regression models, we modified the structural model to jointly estimate (i) the regression of each phenotype on significant familial/prenatal predictors, and (ii) genetic and environmental contributions to the residual variance and covariance. Results suggested that (i) parental risk factors, such as parental alcohol dependence and regular smoking, increase risk for externalizing behavior; (ii) prenatal exposures predicted increased symptomatology for HYP/IMP (smoking during pregnancy), INATT and CDP (prenatal alcohol exposure); (iii) after adjusting for measured familial/prenatal risk factors, genetic influences were significant for HYP/IMP, INATT, and CDP; however, similar to earlier reports, genetic effects on alcohol dependence symptoms were negligible; and (iv) in adolescence, correlated liabilities for conduct and alcohol problems are found in environmental factors common to both phenotypes, while covariation among impulsivity, inattention, and conduct problems is primarily due to genetic influences common to these three behaviors. Thus, while a variety of adolescent problem behaviors are significantly correlated, the structure of that association may differ as a function of phenotype (e.g., comorbid HYP/IMP and CDP vs. comorbid CDP and AlcProb), a finding that could inform different approaches to treatment and prevention.