An evaluation of the epidemiology of medication discrepancies and clinical significance of medicines reconciliation in children admitted to hospital.

To determine the incidence of unintended medication discrepancies in paediatric patients at the time of hospital admission; evaluate the process of medicines reconciliation; assess the benefit of medicines reconciliation in preventing clinical harm

Associations between childhood deaths and adverse childhood experiences: An audit of data from a child death overview panel

Background: Despite strong associations between adverse childhood experiences (ACEs) and poor health, few studies have examined the cumulative impact of ACEs on causes of childhood mortality. Methods: This study explored if data routinely collected by child death overview panels (CDOPs) could be used to measure ACE exposure and examined associations between ACEs and child death categories. Data covering four years (2012–2016) of cases from a CDOP in North West England were examined. Results: Of 489 cases, 20% were identified as having ≥4 ACEs. Deaths of children with ≥4 ACEs were 22.26 (5.72–86.59) times more likely (than those with 0 ACEs) to be classified as ‘avoidable and non-natural’ causes (e.g., injury, abuse, suicide; compared with ‘genetic and medical conditions’). Such children were also 3.44 (1.75–6.73) times more likely to have their deaths classified as ‘chronic and acute conditions’. Conclusions: This study evidences that a history of ACEs can be compiled from CDOP records. Measurements of ACE prevalence in retrospective studies will miss individuals who died in childhood and may underestimate the impacts of ACEs on lifetime health. Strong associations between ACEs and deaths from ‘chronic and acute conditions’ suggest that ACEs may be important factors in child deaths in addition to those classified as ‘avoidable and non-natural’. Results add to an already compelling case for ACE prevention in the general population and families affected by child health problems. Broader use of routinely collected child death records could play an important role in improving multi-agency awareness of ACEs and their negative health and mortality risks as well in the development of ACE informed responses

The clinical significance of medicines reconciliation in children admitted to hospital

published_or_final_versio

Evaluation of educational needs in patients with diabetes mellitus in respect of medication use in Austria

Effective control of diabetes mellitus type 1 (DM1) and type 2 (DM2) can reduce the development and progression of diabetic complications. Therefore, patient education should be considered as an integral part of diabetes management. Objective The aim of the study was to assess DM patients’ perception of knowledge for their medication and attitude towards self management and pharmacist’s role. Setting The study was conducted at the diabetes out-patient clinic at the Vienna General Hospital (AKH), Division of Endocrinology and Metabolism, Department of Internal Medicine III, Austria. The study was a cross sectional survey using patient data from a validated patient questionnaire and medical records. Medical records were evaluated by applying a medication assessment tool. Main outcome measure To assess the quality of diabetes self management the following outcome measures are considered: HbA1c levels, pre- and post-prandial blood glucose levels, prevention of acute episodes of hypo- and hyperglycaemia, reduction of macrovascular risk factors, short term quality of life, adverse effects and treatment tolerance. Results The present study comprised 225 patients with DM1 and 201 patients with DM2, respectively. In comparison to DM2 patients, cardio- and cerebrovascular diseases were diagnosed very rarely in patients with DM1. The risk for these diseases was higher in patients with other factors of the metabolic syndrome, in addition. Overall, 118 of these patients participated in the questionnaire. The level of positive response on diabetes self-care and knowledge with respect to medication for the prevention of diabetes complications, glycaemic control, and treatment goals in diabetes was 81.8 %. The comparison of patients’ perceptions of diabetes self-care and knowledge showed differences among subgroups. Higher perceived knowledge and selfcare apparently was associated with DM1. Additional findings of this study indicate that patients do not expect community pharmacists to be integrated in a multidisciplinary diabetes care team. Although the level of positive response was found to be high there is still a minority of patients whose level of comprehension appears to be insufficient. Intense pharmaceutical care including patients’ education within a multidisciplinary team could contribute to improvements in those patients

Relationships between adverse childhood experiences and adult mental well-being: results from an English national household survey.

BACKGROUND: Individuals' childhood experiences can strongly influence their future health and well-being. Adverse childhood experiences (ACEs) such as abuse and dysfunctional home environments show strong cumulative relationships with physical and mental illness yet less is known about their effects on mental well-being in the general population. METHODS: A nationally representative household survey of English adults (n = 3,885) measuring current mental well-being (Short Edinburgh-Warwick Mental Well-being Scale SWEMWBS) and life satisfaction and retrospective exposure to nine ACEs. RESULTS: Almost half of participants (46.4 %) had suffered at least one ACE and 8.3 % had suffered four or more. Adjusted odds ratios (AORs) for low life satisfaction and low mental well-being increased with the number of ACEs. AORs for low ratings of all individual SWEMWBS components also increased with ACE count, particularly never or rarely feeling close to others. Of individual ACEs, growing up in a household affected by mental illness and suffering sexual abuse had the most relationships with markers of mental well-being. CONCLUSIONS: Childhood adversity has a strong cumulative relationship with adult mental well-being. Comprehensive mental health strategies should incorporate interventions to prevent ACEs and moderate their impacts from the very earliest stages of life

Unequal allelic expression of wild-type and mutated β-myosin in familial hypertrophic cardiomyopathy

Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease, which in about 30% of the patients is caused by missense mutations in one allele of the β-myosin heavy chain (β-MHC) gene (MYH7). To address potential molecular mechanisms underlying the family-specific prognosis, we determined the relative expression of mutant versus wild-type MYH7-mRNA. We found a hitherto unknown mutation-dependent unequal expression of mutant to wild-type MYH7-mRNA, which is paralleled by similar unequal expression of β-MHC at the protein level. Relative abundance of mutated versus wild-type MYH7-mRNA was determined by a specific restriction digest approach and by real-time PCR (RT-qPCR). Fourteen samples from M. soleus and myocardium of 12 genotyped and clinically well-characterized FHC patients were analyzed. The fraction of mutated MYH7-mRNA in five patients with mutation R723G averaged to 66 and 68% of total MYH7-mRNA in soleus and myocardium, respectively. For mutations I736T, R719W and V606M, fractions of mutated MYH7-mRNA in M. soleus were 39, 57 and 29%, respectively. For all mutations, unequal abundance was similar at the protein level. Importantly, fractions of mutated transcripts were comparable among siblings, in younger relatives and unrelated carriers of the same mutation. Hence, the extent of unequal expression of mutated versus wild-type transcript and protein is characteristic for each mutation, implying cis-acting regulatory mechanisms. Bioinformatics suggest mRNA stability or splicing effectors to be affected by certain mutations. Intriguingly, we observed a correlation between disease expression and fraction of mutated mRNA and protein. This strongly suggests that mutation-specific allelic imbalance represents a new pathogenic factor for FHC

Identification of functional differences between recombinant human α and β cardiac myosin motors

The myosin isoform composition of the heart is dynamic in health and disease and has been shown to affect contractile velocity and force generation. While different mammalian species express different proportions of α and β myosin heavy chain, healthy human heart ventricles express these isoforms in a ratio of about 1:9 (α:β) while failing human ventricles express no detectable α-myosin. We report here fast-kinetic analysis of recombinant human α and β myosin heavy chain motor domains. This represents the first such analysis of any human muscle myosin motor and the first of α-myosin from any species. Our findings reveal substantial isoform differences in individual kinetic parameters, overall contractile character, and predicted cycle times. For these parameters, α-subfragment 1 (S1) is far more similar to adult fast skeletal muscle myosin isoforms than to the slow β isoform despite 91% sequence identity between the motor domains of α- and β-myosin. Among the features that differentiate α- from β-S1: the ATP hydrolysis step of α-S1 is ~ten-fold faster than β-S1, α-S1 exhibits ~five-fold weaker actin affinity than β-S1, and actin·α-S1 exhibits rapid ADP release, which is >ten-fold faster than ADP release for β-S1. Overall, the cycle times are ten-fold faster for α-S1 but the portion of time each myosin spends tightly bound to actin (the duty ratio) is similar. Sequence analysis points to regions that might underlie the basis for this finding