Perception of a New Prolonged-Release Buprenorphine Formulation in Patients with Opioid Use Disorder: The PREDEPO Study.

AIM: The aim of the study was to assess the acceptance of patients with opioid use disorder (OUD) to switching their opioid dependence treatment (ODT) for a prolonged-release buprenorphine (PRB) injection according to their prior ODT (buprenorphine/naloxone [B/N] or methadone). METHODS: This was an observational, retrospective/cross-sectional, multicentre study of adult patients diagnosed with OUD on ODT. Data collected from diaries were analysed to know their interest and opinion on PRB. Questions with fixed response options were included, and several Likert scales were used. RESULTS: A total of 98 patients were enrolled (B/N: 50.0%, methadone: 50.0%). The mean age was 46.9 ± 8.43 years and 79.6% were males. PRB was similarly perceived by both groups in most variables analysed, receiving a mean score of 7.2/10 (B/N: 7.4, methadone: 7.0; p = 0.520), and approximately 65% of patients said they were willing to switch to PRB (B/N: 63.3%, methadone: 65.3%; p = 0.833). Of these, a higher percentage in the B/N group considered that switching would be easy/very easy (B/N: 90.3%, methadone: 46.9%; p < 0.001) and that they would start PRB when available (B/N: 64.5%, methadone: 34.3%; p = 0.005). More than 90% would prefer the monthly injection (B/N: 93.6%, methadone: 100%; p = 0.514). One-third of patients in both groups were unsure/would not switch their ODT to PRB (B/N: 36.7%, methadone: 34.7%; p = 0.833). The main reason was administration by injection. CONCLUSION: Two-thirds of patients would switch their treatment for PRB, and most patients on B/N considered that switching would be easy. PRB could be a suitable alternative for OUD management.

Patients'satisfaction and experience in treatment with opioid substitution therapy in Spain. The PREDEPO study. / Satisfacción y experiencia de pacientes en tratamiento con sustitutivos opioides en España. Estudio PREDEPO.

The aim of this study was to compare patients' satisfaction, experience, objectives, and opinion based on their current opioid substitution therapy (OST) (buprenorphine/naloxone (B/N) or methadone). The PREDEPO study is an observational, cross-sectional, multicentric study performed in Spain. Adult patients diagnosed with opioid use disorder (OUD) receiving OST were included. They were asked to fill in a questionnaire regarding their current OST. A total of 98 patients were enrolled (B/N: 50%, methadone: 50%). Mean age was 47 ± 8 years old and 80% were male. Treatment satisfaction was similar between groups. The most frequently reported factor for being "very/quite satisfied" was "being able to distribute the dose at different times throughout the day" (44% B/N vs. 63% methadone; p = .122). A significantly lower proportion of patients in the B/N group versus the methadone group reported that having to collect the medication daily was "very/quite annoying" (19% vs. 52%, p = .032). Treatment objectives reported by the majority of patients were similar between groups ("not feeling in withdrawal anymore", "reduce/definitely stop drug use", "improve my health", and "stop thinking about using daily") except for "not having money problems anymore" (73% B/N vs. 92% methadone; p = .012).  These results suggest there are several unmet expectations regarding current OST. There is a need for new treatments that reduce the burden of OUD, avoid the need for daily dosing, and are less stigmatizing which in turn could improve patient management, adherence and, quality of life.

El objetivo es comparar la satisfacción, experiencia, objetivos y opinión de los pacientes con trastorno por consumo de opioides (TCO) en base a su tratamiento sustitutivo de opioides (TSO) actual (metadona o buprenorfina/naloxona (B/N)). El estudio PREDEPO es un estudio observacional, transversal, multicéntrico desarrollado en España que incluyó pacientes adultos, diagnosticados de TCO y en TSO, quienes contestaron una encuesta sobre su tratamiento actual. Se incluyeron 98 pacientes (B/N:50%, metadona:50%): edad media de 47 ± 8 años y el 80% varones. A nivel de la satisfacción con su tratamiento, los resultados fueron similares entre grupos. El factor "muy/bastante satisfactorio" que se reportó con mayor frecuencia fue "poder repartir las dosis en varios momentos del día" (44% B/N vs. 63% metadona; p = ,122). Se encontraron diferencias significativas en "tener que recoger la medicación diariamente" donde una menor proporción en el grupo B/N contestaron "muy/bastante molesto" versus el grupo metadona (19% vs. 52%, p = ,032). Los objetivos reportados por la mayoría de los pacientes fueron similares entre grupos ("no sentir más síndrome de abstinencia", "disminuir o dejar definitivamente mi consumo de drogas", "mejorar mi estado de salud" y "dejar de pensar en consumir todos los días") excepto en "no tener más problemas de dinero" (72% B/N vs. 92% metadona; p = ,012). Estos resultados evidencian que existen expectativas no cubiertas con los TSO actuales y la necesidad de nuevos tratamientos que disminuyan la carga de la enfermedad, eviten la necesidad de una dosificación diaria y reduzcan el estigma, mejorando así el manejo del paciente, su adherencia y calidad de vida.

I-PV: a CIRCOS module for interactive protein sequence visualization.

SUMMARY: Today's genome browsers and protein databanks supply vast amounts of information about proteins. The challenge is to concisely bring together this information in an interactive and easy to generate format. AVAILABILITY AND IMPLEMENTATION: We have developed an interactive CIRCOS module called i-PV to visualize user supplied protein sequence, conservation and SNV data in a live presentable format. I-PV can be downloaded from http://www.i-pv.org. CONTACT: ibrahim.tanyalcin@i-pv.org, itanyalc@vub.ac.be or support@i-pv.org SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Convert your favorite protein modeling program into a mutation predictor: "MODICT".

BACKGROUND: Predict whether a mutation is deleterious based on the custom 3D model of a protein. RESULTS: We have developed MODICT, a mutation prediction tool which is based on per residue RMSD (root mean square deviation) values of superimposed 3D protein models. Our mathematical algorithm was tested for 42 described mutations in multiple genes including renin (REN), beta-tubulin (TUBB2B), biotinidase (BTD), sphingomyelin phosphodiesterase-1 (SMPD1), phenylalanine hydroxylase (PAH) and medium chain Acyl-Coa dehydrogenase (ACADM). Moreover, MODICT scores corresponded to experimentally verified residual enzyme activities in mutated biotinidase, phenylalanine hydroxylase and medium chain Acyl-CoA dehydrogenase. Several commercially available prediction algorithms were tested and results were compared. The MODICT PERL package and the manual can be downloaded from https://github.com/IbrahimTanyalcin/MODICT . CONCLUSIONS: We show here that MODICT is capable tool for mutation effect prediction at the protein level, using superimposed 3D protein models instead of sequence based algorithms used by POLYPHEN and SIFT.

Analysis of phenotype and outcome in essential thrombocythemia with CALR or JAK2 mutations.

The JAK2 V617F mutation, the thrombopoietin receptor MPL W515K/L mutation and calreticulin (CALR) mutations are mutually exclusive in essential thrombocythemia and support a novel molecular categorization of essential thrombocythemia. CALR mutations account for approximately 30% of cases of essential thrombocythemia. In a retrospective study, we examined the frequency of MPL and CALR mutations in JAK2 V617F-negative cases of essential thrombocythemia (n=103). In addition, we compared the clinical phenotype and outcome of CALR mutant cases of essential thrombocythemia with a cohort of JAK2 V617F-positive essential thrombocythemia (n=57). CALR-positive cases represented 63.7% of double-negative cases of essential thrombocythemia, and most carried CALR type 1 or type 2 indels. However, we also identified one patient who was positive for both the JAK2 V617F and the CALR mutations. This study revealed that CALR mutant essential thrombocythemia is associated with younger age, higher platelet counts, lower erythrocyte counts, leukocyte counts, hemoglobin, and hematocrit, and increased risk of progression to myelofibrosis in comparison with JAK2 V617F-positive essential thrombocythemia. Analysis of the CALR mutant group according to indel type showed that CALR type 1 deletion is strongly associated with male gender. CALR mutant patients had a better overall survival than JAK2 V617F-positive patients, in particular patients of age 60 years or younger. In conclusion, this study in a Belgian cohort of patients supports and extends the growing body of evidence that CALR mutant cases of essential thrombocythemia are phenotypically distinct from JAK2 V617F-positive cases, with regards to clinical and hematologic presentation as well as overall survival.