Process evaluation of a pharmacist-led intervention aimed at deprescribing and appropriate use of cardiometabolic medication among adult people with type 2 diabetes.

BACKGROUND: A quasi-experimental study investigated a pharmacist-led intervention aimed at deprescribing and medication management among adult patients with type 2 diabetes at risk of hypoglycaemia. OBJECTIVE: This study aimed to evaluate the process of implementing the intervention consisting of a tailored clinical medication review (CMR) supported by a training and a toolbox. METHODS: Mixed-methods study based on the Grant framework, including the domains "recruitment," "delivery of intervention" and "response" of pharmacists and patients. Data collected were administrative logs, semi-structured observations of patient consultations (n = 8), interviews with pharmacists (n = 16) and patient-reported experience measure (PREM) questionnaires (n = 66). RESULTS: Tailored CMRs were conducted largely as intended for 90 patients from 14 pharmacies. Although patient selection based on a medication-derived hypoglycaemia risk score was considered useful, pharmacists experienced barriers to proposing deprescribing in patients with recent medication changes, without current hypoglycaemic events, or treated by medical specialists. The training and toolbox were evaluated positively by the pharmacists. Overall, patients were satisfied with the CMR. CONCLUSION: Pharmacists and patients valued the CMR focusing on deprescribing and medication management. To optimize implementation and effectiveness of the intervention, improvements can be made to the patient selection, pharmacist training and the collaboration between healthcare professionals.

Shallow whole-genome sequencing of bone marrow aspirates in myelodysplastic neoplasms: A retrospective comparison with cytogenetics.

Copy number alterations (CNA) are powerful prognostic markers in myelodysplastic neoplasms (MDS) and are routinely analyzed by conventional cytogenetic analysis (CCA) on bone marrow (BM). Although CCA is still the gold standard, it requires extensive hands-on time and highly trained staff for the analysis, making it a laborious technique. To reduce turn-around-time per case, shallow whole genome sequencing (sWGS) technologies offer new perspectives for the diagnostic work-up of this disorder. We compared sWGS with CCA for the detection of CNAs in 33 retrospective BM samples of patients with MDS. Using sWGS, CNAs were detected in all cases and additionally allowed the analysis of three cases for which CCA failed. The prognostic stratification (IPSS-R score) of 27 out of 30 patients was the same with both techniques. In the remaining cases, discrepancies were caused by the presence of balanced translocations escaping sWGS detection in two cases, a subclonal aberration reported with CCA that could not be confirmed by FISH or sWGS, and the presence of an isodicentric chromosome idic(17)(p11) missed by CCA. Since sWGS can almost entirely be automated, our findings indicate that sWGS is valuable in a routine setting validating it as a cost-efficient tool.

Older people's attitudes towards deprescribing cardiometabolic medication.

BACKGROUND: Overtreatment with cardiometabolic medication in older patients can lead to major adverse events. Timely deprescribing of these medications is therefore essential. Self-reported willingness to stop medication is usually high among older people, still overtreatment with cardiometabolic medication is common and deprescribing is rarely initiated. An important barrier for deprescribing reported by general practitioners is the patients' unwillingness to stop the medication. More insights are needed into the influence of patients' characteristics on their attitudes towards deprescribing and differences in these attitudes between cardiometabolic medication groups. METHODS: A survey in older people using cardiometabolic medication using the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire was performed. Participants completed the general rPATD and an adapted version for four medication groups. Linear and ordinal logistic regression were used to assess the influence of age, sex, therapeutic area and number of medications used on the patients' general attitudes towards deprescribing. Univariate analysis was used to compare differences in deprescribing attitudes towards sulfonylureas, insulins, antihypertensive medication and statins. RESULTS: Overall, 314 out of 1143 invited participants completed the survey (median age 76 years, 54% female). Most participants (80%) were satisfied with their medication and willing to stop medications if their doctor said it was possible (88%). Age, sex and therapeutic area had no influence on the general attitudes towards deprescribing. Taking more than ten medicines was significantly associated with a higher perceived medication burden. Antihypertensive medication and insulin were considered more appropriate than statins, and insulin was considered more appropriate than sulfonylureas not favouring deprescribing. CONCLUSIONS: The majority of older people using cardiometabolic medication are willing to stop one of their medicines if their doctor said it was possible. Health care providers should take into account that patients perceive some of their medication as more appropriate than other medication when discussing deprescribing.

Ultra-low coverage whole genome sequencing of ccfDNA in multiple myeloma: A tool for laboratory routine?

Multiple myeloma (MM), is a heterogeneous disease in which chromosomal abnormalities are important for prognostic risk stratification. Cytogenetic profiling with FISH on plasma cells from bone marrow samples (BM-PCs) is the current gold standard, but variable infiltration of plasma cells or failed aspiration can hamper this process. Ultra-low coverage sequencing (ULCS) of circulating cell-free DNA (ccfDNA) may offer a minimally invasive alternative for the work-up of these cases. We compared ULCS, aCGH and FISH on selected BM-PCs in a routine setting with ULCS of ccfDNA for the detection of somatic copy number aberrations (CNAs) in MM. METHODS: Purified CD138+ BM-PCs of 23 MM patients at initiation of their treatment were subjected to aCGH, FISH and ULCS. Paired samples of peripheral blood-ccfDNA obtained at diagnosis were analyzed by ULCS and compared to the results found in BM-PCs. RESULTS: Using ULCS of ccfDNA, cytogenetic markers were identified in 18 out of 23 patients; five cases could not be analyzed due to low (≤3%) tumor fraction (TF). High similarity between CNA profiles of BM-PCs and ccfDNA was found. Moreover, 78% of the ccfDNA profiles resulted in the same risk classification as the routine FISH and/or BM-PCs ULCS and aCGH. Chromothripsis was detected in five patients; these had the highest TF values (range 7.1% to 42%) in our series and their profiles showed other high-risk anomalies. CONCLUSION: This proof-of-principle study indicates that ULCS of ccfDNA can reveal CNAs in MM and should be explored further as a cost-efficient alternative, especially in cases where BM-PC purification fails.

Ultra-low depth sequencing of plasma cell DNA for the detection of copy number aberrations in multiple myeloma.

Cytogenetic abnormalities are powerful prognostic factors in multiple myeloma (MM) and are routinely analyzed by FISH on bone marrow (BM) plasma cells (PC). Although considered the gold standard, FISH experiments can be laborious and expensive. Therefore, array-CGH (aCGH) has been introduced as an alternative approach for detecting copy number aberrations (CNA), reducing the number of FISH experiments per case and yielding genome-wide information. Currently, next generation sequencing (NGS) technologies offer new perspectives for the diagnostic workup of malignant disorders. In this study, we examined ultra-low depth whole genome sequencing (LDS) as a valid alternative for aCGH for the detection of CNA in BM PC in MM. To this end, BM aspirates obtained in a diagnostic setting from 20 MM cases were analyzed. CD138+ cell-sorted samples were subjected to FISH analysis. DNA was extracted for subsequent aCGH and LDS analysis. CNA were detected by aCGH and LDS in all but one case. Importantly, all CNA identified by parallel first generation aCGH analysis were also detected by LDS, along with six additional CNA in five cases. One of these additional aberrations was in a region of prognostic importance in MM and was confirmed using FISH. However, risk stratification in these particular cases was unaffected. Thus, a perfectly concordant prognostication between array-CGH and LDS was observed. This validates LDS as a novel and cost-efficient tool for the detection of CNA in MM.