Evaluation of molecular inversion probe versus TruSeq® custom methods for targeted next-generation sequencing.

Resolving the genetic architecture of painful neuropathy will lead to better disease management strategies. We aimed to develop a reliable method to re-sequence multiple genes in a large cohort of painful neuropathy patients at low cost. In this study, we compared sensitivity, specificity, targeting efficiency, performance and cost effectiveness of Molecular Inversion Probes-Next generation sequencing (MIPs-NGS) and TruSeq® Custom Amplicon-Next generation sequencing (TSCA-NGS). Capture probes were designed to target nine sodium channel genes (SCN3A, SCN8A-SCN11A, and SCN1B-SCN4B). One hundred sixty-six patients with diabetic and idiopathic neuropathy were tested by both methods, 70 patients were validated by Sanger sequencing. Sensitivity, specificity and performance of both techniques were comparable, and in agreement with Sanger sequencing. The average targeted regions coverage for MIPs-NGS was 97.3% versus 93.9% for TSCA-NGS. MIPs-NGS has a more versatile assay design and is more flexible than TSCA-NGS. The cost of MIPs-NGS is >5 times cheaper than TSCA-NGS when 500 or more samples are tested. In conclusion, MIPs-NGS is a reliable, flexible, and relatively inexpensive method to detect genetic variations in a large cohort of patients. In our centers, MIPs-NGS is currently implemented as a routine diagnostic tool for screening of sodium channel genes in painful neuropathy patients.

Medication review using a Systematic Tool to Reduce Inappropriate Prescribing (STRIP) in adults with an intellectual disability: A pilot study.

A Systematic Tool to Reduce Inappropriate Prescribing (STRIP), which includes the Screening Tool to Alert doctors to Right Treatment (START) and the Screening Tool of Older Peoples' Prescriptions (STOPP), has recently been developed in the Netherlands for older patients with polypharmacy in the general population. Active involvement of the patient is part of this systematic multidisciplinary medication review. Although annual review of pharmacotherapy is recommended for people with an intellectual disability (ID), a specific tool for this population is not yet available. Besides, active involvement can be compromised by ID. Therefore, the objective of this observational pilot study was to evaluate the process of medication review using STRIP in adults with an ID living in a centralized or dependent setting and the identification of drug-related problems using this tool. The study was performed in three residential care organizations for ID. In each organization nine clients with polypharmacy were selected by an investigator (a physician in training to become a specialized physician for individuals with an ID) for a review using STRIP. Clients as well as their legal representatives (usually a family member) and professional caregivers were invited to participate. Reviews were performed by an investigator together with a pharmacist. First, to evaluate the process time-investments of the investigator and the pharmacist were described. Besides, the proportion of reviews in which a client and/or his legal representative participated was calculated as well as the proportion of professional caregivers that participated. Second, to evaluate the identification of drug-related problems using STRIP, the proportion of clients with at least one drug-related problem was calculated. Mean time investment was 130minutes for the investigator and 90minutes for the pharmacist. The client and/or a legal representatives were present during 25 of 27 reviews (93%). All 27 professional caregivers (100%) were involved. For every client included at least one drug-related problem was identified. In total 127 drug-related problems were detected, mainly potentially inappropriate or unnecessary drugs. After six months, 15.7% of the interventions were actually implemented. Medication review using STRIP seems feasible in adults with an ID and identifies drug-related problems. However, in this pilot study the implementation rate of suggested interventions was low. To improve the implementation rate, the treating physician should be involved in the review process. Besides, specific adaptations to STRIP to address drug-related problems specific for this population are required.