Runt-related transcription factor 1 (RUNX1) is essential for normal hematopoiesis. RUNX1 mutations have rarely been reported in chronic myelomonocytic leukemia (CMML). We examined RUNX1 mutations in 81 patients with CMML at initial diagnosis. Mutational analysis was performed on bone marrow samples by direct sequencing of all reverse transcription PCR products amplified with three primer pairs that cover the entire coding sequences of RUNX1b. Thirty-two RUNX1 mutations were detected in 30 patients (37%); 23 mutants were located in the N-terminal part and 9 in the C-terminal region. The mutations consisted of 9 missense, 1 silent, 7 nonsense and 15 frameshift mutations. Two patients had biallelic heterozygous mutations. There was no difference in overall survival between patients with and without RUNX1 mutations, but a trend of higher risk of acute myeloid leukemia (AML) progression was observed in mutation-positive patients (16/30 vs 17/51, P ¼ 0.102), especially in patients with C-terminal mutations (P ¼ 0.023). The median time to AML progression was 6.8 months in patients with C-terminal mutations compared with 28.3 months in those without mutations (P ¼ 0.022). This study showed for the first time a high frequency of RUNX1 mutations in CMML. C-terminal mutations might be associated with a more frequent and rapid AML transformation.

The role of internal tandem duplication of fms-like tyrosine kinase 3 (FLT3/ITD), mutations at tyrosine kinase domain (FLT3/ TKD) and N-ras mutations in the transformation of myelodysplastic syndrome (MDS) to AML was investigated in 82 MDS patients who later progressed to AML; 70 of them had paired marrow samples at diagnosis of MDS and AML available for comparative analysis. Five of the 82 patients had FLT3/ITD at presentation. Of the 70 paired samples, seven patients acquired FLT3/ITD during AML evolution. The incidence of FLT3/ITD at diagnosis of MDS was significantly lower than that at AML transformation (3/70 vs 10/70, Po0.001). FLT3/ITD( þ ) patients progressed to AML more rapidly than FLT3/ITD(À) patients (2.570.5 vs 11.971.5 months, P ¼ 0.114). FLT3/ITD( þ ) patients had a significantly shorter survival than FLT3/ITD(À) patients (5.671.3 vs 18.071.7 months, P ¼ 0.0008). After AML transformation, FLT3/ITD was also associated with an adverse prognosis. One patient had FLT3/TKD mutation (D835Y) at both MDS and AML stages. Additional three acquired FLT3/TKD (one each with D835 H, D835F and I836S) at AML transformation. Five of the 70 matched samples had N-ras mutation at diagnosis of MDS compared to 15 at AML transformation (Po0.001), one lost and 11 gained N-ras mutations at AML progression. Coexistence of FLT3/TKD and N-ras mutations was found in two AML samples. N-ras mutations had no prognostic impact either at the MDS or AML stage. Our results show that one-third of MDS patients acquire activating mutations of FLT3 or N-ras gene during AML evolution and FLT3/ITD predicts a poor outcome in MDS.

No abstract

Background: Medication-related adverse events, or adverse drug reactions (ADRs) are harmful events caused by medication. ADRs could have profound effects on the patients' quality of life, as well as creating an increased burden on the healthcare system. ADRs are one of the rising causes of morbidity and mortality internationally, and will continue to be a significant public health issue with the increased complexity in medication, to treat various diseases in an aging society. This scoping review aims to provide a detailed map of the most common adverse drug reactions experienced in primary healthcare setting, the drug classes that are most commonly associated with different levels/types of adverse drug reactions, causes of ADRs, their prevalence and consequences of experiencing ADRs. Methods: We systematically reviewed electronic databases Ovid MEDLINE, Embase, CINAHL Plus, Cochrane Central Register of Controlled Trials, PsycINFO and Scopus. In addition, the National Patient Safety Foundation Bibliography and the Agency for Health Care Research and Quality and Patient Safety Net Bibliography were searched. Studies published from 1990 onwards until December 7, 2018 were included as the incidence of reporting drug reactions were not prevalent before 1990. We only include studies published in English. Results: The final search yielded a total of 19 citations for inclusion published over a 15-year period that primarily focused on investigating the different types of adverse drug reactions in primary healthcare. The most causes of adverse events were related to drug related and allergies. Idiosyncratic adverse reactions were not very commonly reported. The most common adverse drug reactions reported in the studies included in this review were those that are associated with the central nervous system, gastrointestinal system and cardiovascular system. Several classes of medications were reported to be associated with adverse events. Conclusion: This scoping review identified that the most causes of ADRs were drug related and due to allergies. Idiosyncratic adverse reactions were not very commonly reported in the literature. This is mainly because it is hard to predict and these reactions are not associated with drug doses or routes of administration. The most common ADRs reported in the studies included in this review were those that are associated with the central nervous system, gastrointestinal system and cardiovascular system. Several classes of medications were reported to be associated with ADRs.

Accessible Summary What is known about shared decision‐making? There is increasing evidence of the positive impact of shared decision‐making on health outcomes. There has been little exploration of shared decision‐making regarding people diagnosed with serious mental illness from the perspectives of key stakeholders including consumers, families and mental health professionals. What this paper adds to existing knowledge? Consumers show variability in the preference for their involvement. Most stakeholders acknowledge the importance of family involvement. MHPs should share the responsibility and right to facilitate consumer involvement. There is bidirectional association between shared decision‐making and therapeutic relationships. The practice of shared decision‐making is related to multiple factors, and one main perceived barrier is time. The majority of studies are from Western countries. What are the implications for practice? Elicit consumer preferences and establish a collaborative therapeutic relationship. Encourage and engage families in treatment decision‐making. Inter‐professional collaboration should be integrated into shared decision‐making. It might require lengthier consultation time. Studies in non‐Western countries are needed to fully understand the impact of culture on shared decision‐making. AbstractIntroductionShared decision‐making (SDM) has been broadly advocated in health services and constitutes an important component of patient‐centred care and relationship‐based care.AimTo review available literature related to perceptions of key stakeholders about shared decision‐making in serious mental illness.MethodAn integrative review was conducted through a search of four online databases from January 2012 to June 2019.ResultsForty‐six articles were included. Six themes were generated from the data analysis: (a) dynamic preferences for SDM, (b) various stakeholders are rarely involved, (c) SDM is not routinely implemented, (d) multiple facilitators and barriers to SDM, (e) SDM and therapeutic relationships interact, (f) SDM has a promising impact on health outcomes.DiscussionOverall, most stakeholders have recognized the importance and flexibility of SDM in serious mental illness, although it is not routine in mental health service. Consumer preferences show variability in their involvement. Most stakeholders acknowledged the importance of family involvement to treatment decision‐making. There are several significant challenges to practice SDM. It may require extended consultation times and increasing empirical evidence regarding the SDM outcomes, as well as integrating inter‐professional collaboration into SDM. Most studies were conducted in Western culture.Implications for practiceMental health nurses should elicit consumer preferences and establish a collaborative therapeutic relationship. Encourage and engage families in treatment decision‐making when consumers prefer their families to be involved. Inter‐professional collaboration should be integrated into shared decision‐making. The...