Identification of behaviour change techniques in deprescribing interventions: a systematic review and meta-analysis.

AIMS: Deprescribing interventions safely and effectively optimize medication use in older people. However, questions remain about which components of interventions are key to effectively reduce inappropriate medication use. This systematic review examines the behaviour change techniques (BCTs) of deprescribing interventions and summarizes intervention effectiveness on medication use and inappropriate prescribing. METHODS: MEDLINE, EMBASE, Web of Science and Academic Search Complete and grey literature were searched for relevant literature. Randomized controlled trials (RCTs) were included if they reported on interventions in people aged ≥65 years. The BCT taxonomy was used to identify BCTs frequently observed in deprescribing interventions. Effectiveness of interventions on inappropriate medication use was summarized in meta-analyses. Medication appropriateness was assessed in accordance with STOPP criteria, Beers' criteria and national or local guidelines. Between-study heterogeneity was evaluated by I-squared and Chi-squared statistics. Risk of bias was assessed using the Cochrane Collaboration Tool for randomized controlled studies. RESULTS: Of the 1561 records identified, 25 studies were included in the review. Deprescribing interventions were effective in reducing number of drugs and inappropriate prescribing, but a large heterogeneity in effects was observed. BCT clusters including goals and planning; social support; shaping knowledge; natural consequences; comparison of behaviour; comparison of outcomes; regulation; antecedents; and identity had a positive effect on the effectiveness of interventions. CONCLUSIONS: In general, deprescribing interventions effectively reduce medication use and inappropriate prescribing in older people. Successful deprescribing is facilitated by the combination of BCTs involving a range of intervention components.

Teaching Prescribing: Just What the Doctor Ordered? A Thematic Analysis of the Views of Newly Qualified Doctors.

Undergraduate medical education has been criticised for failing to adequately prepare doctors for the task of prescribing. Pharmacists have been shown to improve medication use in hospitals. This study aims to elicit the views of intern doctors on the challenges of prescribing, and to suggest changes in education to enhance prescribing practice and potential role of the pharmacist. Semi-structured, qualitative interviews were conducted with intern doctors in their first year post qualification in an Irish hospital. Data collection was conducted until no new themes emerged and thematic analysis was performed. Thirteen interviews took place. Interns described training in practical prescribing as limited and felt the curriculum failed to convey the reality of actual prescribing. Pharmacists were perceived to be a useful, but underutilised, information source in the prescribing process. They requested an earlier introduction, and repeated exposure, to prescribing, and suggested the involvement of peers and pharmacists in this teaching. Intern doctors reported difficulties in applying knowledge gained in medical school to clinical practice. New strategies are needed to enhance the clinical relevance of the medical curriculum by rethinking the learning outcomes regarding prescribing practice and the involvement of pharmacists in prescribing education.

Improved MS/MS analysis of succinylacetone extracted from dried blood spots when combined with amino acids and acylcarnitine butyl esters.

BACKGROUND: The utilization of succinylacetone (SUAC) as the primary metabolic marker for tyrosinemia Type I is now well known, thus new methods have been developed to analyze SUAC as a first tier test in newborn screening. One approach is to prepare a SUAC hydrazine derivative from the dried blood spots (DBS) previously utilized in the extraction of acylcarnitine (AC) and amino acids (AA). The final derivatized products of SUAC, AA and AC are combined in a single tandem mass spectrometric (MS/MS) analysis. However, butyl esterification techniques may result in contamination of underivatized acylcarnitines by as much as 20%. We have developed a simple wash step to improve the combined analysis of SUAC, AA and AC in DBS by MS/MS. METHODS: AA and AC were extracted with methanol containing labeled internal standard from 3.2mm punches taken from the DBS specimen. The previously extracted blood spot that remains after removal of the methanol extraction solvent was used in the preparation of SUAC with and without additional washing of the blood spot. The butyl ester eluates of AA and AC, and SUAC hydrazine derivatives were recombined and measured by MS/MS. RESULTS: Three additional methanol wash steps of the remaining DBS punches prior to SUAC derivatization reduced the presence of underivatized acylcarnitines, resulting in a 4-fold reduction of underivatized palmitoylcarnitine. Palmitoylcarnitine butyl ester is detected at m/z 456 while the underivatized species is detected at m/z 400, which is also the mass of dodecanoylcarnitine butyl ester. The linearity of the SUAC assay was unchanged by the additional wash steps. For butyl esterification methods, the preferred analytic procedure, the presence of AC can compromise the results of a newborn screen for the actual concentrations of acylcarnitines. It is essential to remove any underivatized acylcarnitines prior to SUAC analysis. CONCLUSION: The additional methanol wash steps did not alter SUAC assay results but did remove underivatized acylcarnitines which could result in the incorrect quantification of acylcarnitines.

Quantification of malonylcarnitine in dried blood spots by use of MS/MS varies by stable isotope internal standard composition.

BACKGROUND: The utilization of MS/MS for the analysis of amino acids and acylcarnitines from dried blood spots (DBS) is routine in many newborn screening (NBS) laboratories. Recently, malonylcarnitine (C3DC) was shown to be elevated in the DBS of affected infants with malonic acidemia. Quantitative features were unknown, so that its measurement was an approximation. Synthesis of malonylcarnitine enabled both a study in the analytical characteristics of C3DC and a survey of its measurement in NBS laboratories. METHODS: Malonylcarnitine was enriched in blood and spotted onto filter paper cards. The DBS were sent to several laboratories for analysis, and the results were returned to the Centers for Disease Control and Prevention (CDC) for evaluation. Reports included a description of the MS/MS method utilized. RESULTS: A pilot proficiency survey shows a bimodal distribution of data from 98 laboratories. Analysis of proficiency data reveals the use of different stable isotope internal standards for quantification. Analysis of standard, labeled or unlabelled ((2)H(3)-octanoylcarnitine (C8), glutarylcarnitine (C5DC) and malonylcarnitine (C3DC) revealed significantly different ion detection values. Quantification in laboratories is based on the ratio of the metabolite in question to a reference stable isotope standard. CONCLUSIONS: Quantification of metabolites depends upon the reference isotope standard utilized. Quantification requires describing the standards used for estimation of concentration (a pseudo-concentration) and a notation that includes a reference to the isotope standard used. This descriptive method will enable harmonization of data in screening laboratories.