Characterization of the novel HLA‐DQB1*06:48 allele by group‐specific sequencing

HLA‐DQB1*06:48 has single nucleotide polymorphisms within codons 70 and 62 of exon 2 (GGG>AGG and AAG>AAC) relative to HLA‐DQB1*06:02:01 and HLA‐DQB1*06:37. This results in amino acid differences (G>R and K>N) that will change the polarity and charge of the encoded antigen and may therefore affect its peptide repertoire.     

Improving evidence‐based practice in rehabilitation: Introducing PsycBITETM

Background: Clinicians face significant obstacles in their access to evidence for the efficacy of different communicative and cognitive treatments after brain impairment. These include the need to search across diverse journals and different clinical conditions to find potential treatments and the lack of easily accessible standards by which to evaluate the methodological rigour of treatment studies once found.

Aims: We aimed to address these issues by developing a freely available, user‐friendly database of all relevant treatment trials for psychologically based disorders that arise from brain impairment.

Methods & Procedures: PsycBITE^TM (http://www.psycbite.com) was developed as an internet‐based database and was officially launched in 2004. Included on PsycBITE^TM are all trials that have been published that evaluate treatment for any communication, cognitive, or psychological disorder arising from any form of acquired brain impairment in children (above the age of 5 years) and adults. PsycBITE^TM also provides a rating for the methodological rigour of each trial using the previously established PEDro scale (Maher, Sherrington, Herbert, Moseley, & Elkins, 2003 Maher, C. G., Sherrington, C., Herbert, R. D., Moseley, A. M. and Elkins, M. 2003. Reliability of the PEDro scale for rating quality of randomized controlled trials.. Physical Therapy, 83: 713–721. [PubMed], [Web of Science ®] , [Google Scholar]) for randomised controlled trials (RCT) and non‐RCT group comparisons. A PsycBITE^TM rating scale for single case experimental studies is still under development. This report overviews the database, its contents, and the methodology by which papers are selected for inclusion.

Outcomes & Results: As of June 2005 there are 1167 treatment studies listed on PsycBITE^TM with prospective searches being conducted on a regular basis. The highest proportion of studies report treatments for communication disorders followed by behavioural problems and memory. Ratings of the randomised controlled trials, group comparisons, and single case studies are available for a proportion of papers and are being updated continuously.

Conclusions: PsycBITE^TM is an invaluable resource for clinicians and researchers interested in an evidence‐based practice approach to treatment. It is a free, fast, and effective way of accessing and evaluating treatments for communicative and cognitive disorders following brain impairment.     

Measuring the social interactions of people with traumatic brain injury and their communication partners: The adapted Kagan scales

Background: Considerable attention has been given to the nature of communication impairments of individuals with TBI (Coelho, 2007 Coelho, C. A. 2007. Management of discourse deficits following traumatic brain injury: Progress, caveats, and needs. Seminars in Speech & Language, 28(2): 122–135.  [Google Scholar]; Ylvisaker, Turkstra, & Coelho, 2005 Ylvisaker, M., Turkstra, L. S. and Coelho, C. 2005. Behavioral and social interventions for individuals with traumatic brain injury: A summary of the research with clinical implications. Seminars in Speech & Language, 26: 256–267. [Crossref], [PubMed] , [Google Scholar]). However, there have been few data focusing on the way communication partners deal with the often distressing sequelae of TBI.

Aims: This study reports inter- and intra-rater reliability of the Adapted Measure of Support in Conversation (MSC) and Measure of Participation in Conversation (MPC) for TBI interactions.

Method & Procedures: The MSC and MPC were adapted to reflect theoretical models of cognitive-communication support for people with TBI. A total of 10 casual and 10 purposeful TBI interactions were independently rated by two raters to establish inter-rater reliability and by one rater on two separate occasions to determine intra-rater reliability.

Outcomes & Results: Excellent inter-rater agreement was established on the MSC (ICC?=?0.85–0.97) and the MPC (ICC?=?0.84–0.89). Intra-rater agreement was also strong (MSC: ICC?=?0.80–0.90; MPC: ICC?=?0.81–0.92). Over 90% of all ratings scored within 0.5 on a 9-point scale.

Conclusions: This is the first scale to measure the communication partner during TBI interactions. It shows promise in evaluating communication partner training programmes.     

Impact of Being a Peer Recovery Specialist on Work and Personal Life: Implications for Training and Supervision

Peer recovery specialists are an important resource in community mental health settings. This study, which was part of a larger statewide assessment, evaluates how the role impacts work and personal lives of peers, with implications for improving the training and supervision of this service. The importance of peer work has been investigated through client outcomes, however less work has investigated outcomes on peers themselves, which impacts the work force and service delivery. Nine focus groups were conducted with peer recovery specialists. A two-stage qualitative analysis led to two overarching themes, work and personal, and six subthemes. Findings suggest being a peer presents unique benefits and challenges in work and personal life. Peers benefit from more training and supervision, consistency within the role, and maintaining boundaries. Additionally, work environment roles may be improved by attention to needs of supervisors in terms of skills for effective supervision and clarification of supervisory roles.

     

Rapid Delivery of Diazepam from Supersaturated Solutions Prepared Using Prodrug/Enzyme Mixtures: Toward Intranasal Treatment of Seizure Emergencies

Current treatments for seizure emergencies, such as status epilepticus, include intravenous or rectal administration of benzodiazepines. While intranasal delivery of these drugs is desirable, the small volume of the nasal cavity and low drug solubility pose significant difficulties. Here, we prepared supersaturated diazepam solutions under physiological conditions and without precipitation, using a prodrug/enzyme system. Avizafone, a peptide prodrug of diazepam, was delivered with—Aspergillus oryzae (A.O.) protease, an enzyme identified from a pool of hydrolytic enzymes in assay buffer, pH 7.4 at 32°C. This enzyme converted avizafone to diazepam at supersaturated concentrations. In vitro permeability studies were performed at various prodrug/enzyme ratios using Madin-Darby canine kidney II-wild type (MDCKII-wt) monolayers, a representative model of the nasal epithelium. Monolayer integrity was examined using TEER measurement and the lucifer yellow permeability assay. Prodrug/drug concentrations were measured using HPLC. Enzyme kinetics with avizafone-protease mixtures revealed K_M = 1,501 ± 232 μM and V_max = 1,369 ± 94 μM/s. Prodrug-protease mixtures, when co-delivered apically onto MDCKII-wt monolayers, showed 2–17.6-fold greater diazepam flux (S = 1.3–15.3) compared to near-saturated diazepam (S = 0.7). Data for prodrug conversion upstream (apical side) and drug permeability downstream (basolateral side) fitted reasonably well to a previously developed in vitro two compartment pharmacokinetic model. Avizafone-protease mixtures resulted in supersaturated diazepam in less than 5 min, with the rate and extent of supersaturation determined by the prodrug/enzyme ratio. Together, these results suggest that an intranasal avizafone-protease system may provide a rapid and alternative means of diazepam delivery.

Electronic supplementary material

The online version of this article (doi:10.1208/s12248-014-9596-5) contains supplementary material, which is available to authorized users.KEY WORDS: avizafone enzyme activation, diazepam delivery, hydrophobic drugs, MDCK monolayers, rapid absorption, seizure emergencies, supersaturation     

The novel use of a biodegradable stent placed by percutaneous transhepatic cholangiography for the treatment of a hepaticojejunostomy biliary leak following an extended left hepatectomy and pancreaticoduodenectomy

A 61-year-old man presented with jaundice, and subsequently underwent an extended left hepatectomy and pancreaticoduodenectomy for a cholangiocarcinoma invading the head of the pancreas. The patient developed sepsis due to a biliary leak at the hepaticojejunostomy. We describe the original use of a biodegradable stent, deployed via percutaneous transhepatic cholangiography into the Roux limb, resulting in good drainage and resolution of sepsis. The chief benefit of this procedure is the lack of need for subsequent removal as well as purported reduced biofilm accumulation. We believe this to be the first reported case of this type and the literature surrounding the subject is also discussed.