Mastitis and Mammary Abscess Management Audit (MAMMA) in the UK and Ireland.

BACKGROUND: The aim of this multicentre prospective audit was to describe the current practice in the management of mastitis and breast abscesses in the UK and Ireland, with a specific focus on rates of surgical intervention. METHODS: This audit was conducted in two phases from August 2020 to August 2021; a phase 1 practice survey and a phase 2 prospective audit. Primary outcome measurements for phase 2 included patient management pathway characteristics and treatment type (medical/radiological/surgical). RESULTS: A total of 69 hospitals participated in phase 2 (1312 patients). The key findings were a high overall rate of incision and drainage (21.0 per cent) and a lower than anticipated proportion of ultrasound-guided aspiration of breast abscesses (61.0 per cent). Significant variations were observed regarding the rate of incision and drainage (range 0-100 per cent; P < 0.001) and the rate of needle aspiration (range 12.5-100 per cent; P < 0.001) between individual units. Overall, 22.5 per cent of patients were admitted for inpatient treatment, out of whom which 72.9 per cent were commenced on intravenous antibiotics. The odds of undergoing incision and drainage for a breast abscess or being admitted for inpatient treatment were significantly higher if patients presented at the weekend compared with a weekday (P ≤ 0.023). Breast specialists reviewed 40.9 per cent of all patients directly, despite the majority of patients (74.2 per cent) presenting within working hours on weekdays. CONCLUSIONS: Variation in practice exists in the management of mastitis and breast abscesses, with high rates of incision and drainage in certain regions of the UK. There is an urgent need for a national best-practice toolbox to minimize practice variation and standardize patient care.

Mastitis and breast abscess is a painful infection of the breast. It is an extremely common breast problem. One in three women can get this condition at some stage in their life. To treat a breast abscess, the pus inside should be drained out of the body. This can be done either by cutting into the breast using surgery or by inserting a fine needle using an ultrasonography scan (which uses ultrasound). Fine-needle drainage has the benefit that it does not require admission to hospital. Surgery can cause the breast to look misshapen. It is unknown which method is used more often in the UK and Ireland. The aim of this study was to describe how mastitis and breast abscesses are treated in the UK and Ireland. This study involved a survey of practice (phase 1) and collection of data, which are routinely recorded for these patients (phase 2). This study involved 69 hospitals and 1312 patient records. One in five women had an operation for a breast abscess. This was higher than expected. Six in 10 women had a pus drainage using a fine needle. The chance of having an operation depended on the hospital. Women that came to hospital at the weekend were almost twice as likely to have an operation. One in five women were admitted to hospital. The chances of that more than doubled if a woman came to hospital at the weekend. There are differences in treatment of mastitis and breast abscesses across the UK and Ireland. Changes need to be put in place to make access to treatment more equal.

DECO: a framework for jointly analyzing de novo and rare case/control variants, and biological pathways.

MOTIVATION: Rare variant-based analyses are beginning to identify risk genes for neuropsychiatric disorders and other diseases. However, the identified genes only account for a fraction of predicted causal genes. Recent studies have shown that rare damaging variants are significantly enriched in specific gene-sets. Methods which are able to jointly model rare variants and gene-sets to identify enriched gene-sets and use these enriched gene-sets to prioritize additional risk genes could improve understanding of the genetic architecture of diseases. RESULTS: We propose DECO (Integrated analysis of de novo mutations, rare case/control variants and omics information via gene-sets), an integrated method for rare-variant and gene-set analysis. The method can (i) test the enrichment of gene-sets directly within the statistical model, and (ii) use enriched gene-sets to rank existing genes and prioritize additional risk genes for tested disorders. In simulations, DECO performs better than a homologous method that uses only variant data. To demonstrate the application of the proposed protocol, we have applied this approach to rare-variant datasets of schizophrenia. Compared with a method which only uses variant information, DECO is able to prioritize additional risk genes. AVAILABILITY: DECO can be used to analyze rare-variants and biological pathways or cell types for any disease. The package is available on Github https://github.com/hoangtn/DECO.

IMpact of flash glucose Monitoring in pEople with type 2 Diabetes Inadequately controlled with non-insulin Antihyperglycaemic ThErapy (IMMEDIATE): A randomized controlled trial.

AIM: To examine the efficacy and patient satisfaction of intermittently scanned continuous glucose monitoring (isCGM) in adults using non-insulin therapies for the management of type 2 diabetes. MATERIALS AND METHODS: The IMMEDIATE study was a multisite, open label, randomized controlled trial with follow-up at 16 weeks. Adults with type 2 diabetes using at least one non-insulin therapy, with an HbA1c of 7.5% or higher (≥ 58 mmol/mol), were randomized 1:1 to receive an isCGM device plus diabetes self-management education (isCGM + DSME) or DSME alone. Enrolment occurred from 8 September 2020 to 24 December 2021. The primary outcome was percentage mean time in range (TIR), in the final 2-week period, measured via blinded CGM. RESULTS: One hundred and sixteen participants were randomized (mean age, 58 years; diabetes duration, 10 years; mean HbA1c, 8.6% [70 mmol/mol]). At 16 weeks of follow-up, the isCGM and DSME arm had a significantly greater mean TIR by 9.9% (2.4 hours) (95% CI, -17.3% to -2.5%; P < .01), significantly less time above range by 8.1% (1.9 hours) (95% CI, 0.5% to 15.7%; P = .037), and a greater reduction in mean HbA1c by 0.3% (3 mmol/mol) (95% CI, 0% to 0.7%; P = .048) versus the DSME arm. Time below range was low and not significantly different between groups and hypoglycaemic events were few in both groups. Glucose monitoring satisfaction was higher among isCGM users (adjusted difference -0.5 [95% CI, -0.7 to -0.3], P < .01). CONCLUSIONS: The IMMEDIATE study has shown that among non-insulin-treated individuals with type 2 diabetes, use of isCGM is associated with an improvement in glycaemic outcomes.

Predicting Participation Willingness in Ecological Momentary Assessment of General Population Health and Behavior: Machine Learning Study.

BACKGROUND: Ecological momentary assessment (EMA) is widely used in health research to capture individuals' experiences in the flow of daily life. The majority of EMA studies, however, rely on nonprobability sampling approaches, leaving open the possibility of nonrandom participation concerning the individual characteristics of interest in EMA research. Knowledge of the factors that predict participation in EMA research is required to evaluate this possibility and can also inform optimal recruitment strategies. OBJECTIVE: This study aimed to examine the extent to which being willing to participate in EMA research is related to respondent characteristics and to identify the most critical predictors of participation. METHODS: We leveraged the availability of comprehensive data on a general young adult population pool of potential EMA participants and used and compared logistic regression, classification and regression trees, and random forest approaches to evaluate respondents' characteristic predictors of willingness to participate in the Decades-to-Minutes EMA study. RESULTS: In unadjusted logistic regression models, gender, migration background, anxiety, attention deficit hyperactivity disorder symptoms, stress, and prosociality were significant predictors of participation willingness; in logistic regression models, mutually adjusting for all predictors, migration background, tobacco use, and social exclusion were significant predictors. Tree-based approaches also identified migration status, tobacco use, and prosociality as prominent predictors. However, overall, willingness to participate in the Decades-to-Minutes EMA study was only weakly predictable from respondent characteristics. Cross-validation areas under the curve for the best models were only in the range of 0.56 to 0.57. CONCLUSIONS: Results suggest that migration background is the single most promising target for improving EMA participation and sample representativeness; however, more research is needed to improve prediction of participation in EMA studies in health.

Exploring the effect of ADHD traits on the moment-to-moment interplay between provocation and aggression: Evidence from dynamic structural equation modeling.

The relation between attention deficit hyperactivity disorder (ADHD) symptoms and aggression is well documented; however, the processes that account for higher levels of aggression associated with ADHD in the course of daily life are little understood. The current study used ecological momentary assessment to explore how ADHD traits relate to individual differences in perceiving provocation from others and the resultant aggressive behaviors; and the strengths of the links between provocation and aggression in the flow of daily life. A dynamic structural equation model was fit using data from a subpopulation of young adults involved in the longitudinal z-proso study (n = 259, median-age 20). Data on provocation and aggression was collected at four quasi-random time periods per day over a 14-day period. Individuals with higher ADHD trait levels reported higher instances of provocation and aggression, with ADHD traits significantly moderating aggression inertia such that those with higher levels of ADHD traits showed greater persistence of aggressive behavior over time. However, ADHD trait levels did not significantly moderate any of the observed cross-lagged effects. Our findings suggest that individuals with higher levels of ADHD traits are at greater risk of exposure to interpersonal interactions involving interpersonal provocation, show higher levels of aggressive behavior in daily life, and find it more difficult to reduce their aggression once triggered. These findings support the importance of targeting factors such as social skills and emotion regulation that may underpin the increased difficulties in interpersonal interactions often experienced by individuals with high levels of ADHD symptoms.

Real-world glycaemic outcomes in adult persons with type 1 diabetes using a real-time continuous glucose monitor compared to an intermittently scanned glucose monitor: A retrospective observational study from the Canadian LMC diabetes registry (REAL-CGM-T1D).

Real-time continuous glucose monitoring (rtCGM) and intermittently scanned CGM (isCGM) have both been shown to improve glycaemic outcomes in people with T1D. The aim of this study was to compare real-world glycaemic outcomes at 6-12 months in a propensity score matched cohort of CGM naïve adults with T1D who initiated a rtCGM or an isCGM. Among the matched rtCGM and isCGM cohorts (n = 143/cohort), rtCGM users had a significantly greater HbA1c benefit compared to isCGM users (adjusted difference, -3 mmol/mol [95% CI, -5 to -1]; -0.3% [95% CI, -0.5 to -0.1]; p = 0.01). There was a significantly greater lowering of HbA1c for rtCGM compared to isCGM when baseline HbA1c was <69 mmol/mol (8.5%) (adjusted difference, -4 mmol/mol [95% CI, -7 mmol/mol to -2 mmol/mol]; -0.4% [95% CI, -0.6% to -0.2%]; p < 0.001), and in MDI users (adjusted difference, -3 mmol/mol [95% CI, -6 mmol/mol to -0 mmol/mol]; -0.3% [95% CI -0.5% to 0.0%], p = 0.04). The rtCGM cohort had significantly greater time in range (58.3 ± 16.1% vs. 54.5 ± 17.1%, p = 0.03), lower time below range (2.1 ± 2.7% vs. 6.1 ± 5.0%, p < 0.001) and lower glycaemic variability compared to the isCGM cohort. In this real-world analysis of adults with T1D, rtCGM users had a significantly greater reduction in HbA1c at 6-12 months compared to isCGM, and significantly greater time in range, lower time below range and lower glycaemic variability, compared to a matched cohort of isCGM users.

International comparison of glycaemic control in people with type 1 diabetes: an update and extension.

AIMS: To update and extend a previous cross-sectional international comparison of glycaemic control in people with type 1 diabetes. METHODS: Data were obtained for 520,392 children and adults with type 1 diabetes from 17 population and five clinic-based data sources in countries or regions between 2016 and 2020. Median HbA1c (IQR) and proportions of individuals with HbA1c < 58 mmol/mol (<7.5%), 58-74 mmol/mol (7.5-8.9%) and ≥75 mmol/mol (≥9.0%) were compared between populations for individuals aged <15, 15-24 and ≥25 years. Logistic regression was used to estimate the odds ratio (OR) of HbA1c < 58 mmol/mol (<7.5%) relative to ≥58 mmol/mol (≥7.5%), stratified and adjusted for sex, age and data source. Where possible, changes in the proportion of individuals in each HbA1c category compared to previous estimates were calculated. RESULTS: Median HbA1c varied from 55 to 79 mmol/mol (7.2 to 9.4%) across data sources and age groups so a pooled estimate was deemed inappropriate. OR (95% CI) for HbA1c < 58 mmol/mol (<7.5%) were 0.91 (0.90-0.92) for women compared to men, 1.68 (1.65-1.71) for people aged <15 years and 0.81 (0.79-0.82) aged15-24 years compared to those aged ≥25 years. Differences between populations persisted after adjusting for sex, age and data source. In general, compared to our previous analysis, the proportion of people with an HbA1c  < 58 mmol/l (<7.5%) increased and proportions of people with HbA1c ≥ 75 mmol/mol (≥9.0%) decreased. CONCLUSIONS: Glycaemic control of type 1 diabetes continues to vary substantially between age groups and data sources. While some improvement over time has been observed, glycaemic control remains sub-optimal for most people with Type 1 diabetes.

Patterns of adverse childhood experiences and associations with prenatal substance use and poor infant outcomes in a multi-country cohort of mothers: a latent class analysis.

BACKGROUND: This paper enumerates and characterizes latent classes of adverse childhood experiences and investigates how they relate to prenatal substance use (i.e., smoking, alcohol, and other drugs) and poor infant outcomes (i.e., infant prematurity and low birthweight) across eight low- and middle-income countries (LMICs). METHODS: A total of 1189 mother-infant dyads from the Evidence for Better Lives Study cohort were recruited. Latent class analysis using the Bolck, Croon, and Hagenaars (BCH) 3-step method with auxiliary multilevel logistic regressions was performed. RESULTS: Three high-risk classes and one low-risk class emerged: (1) highly maltreated (7%, n = 89), (2) emotionally and physically abused with intra-familial violence exposure (13%, n = 152), (3), emotionally abused (40%, n = 474), and (4) low household dysfunction and abuse (40%, n = 474). Pairwise comparisons between classes indicate higher probabilities of prenatal drug use in the highly maltreated and emotionally abused classes compared with the low household dysfunction and abuse class. Additionally, the emotionally and physically abused with intra-familial violence exposure class had higher probability of low birthweight than the three remaining classes. CONCLUSION: Our results highlight the multifaceted nature of ACEs and underline the potential importance of exposure to childhood adversities on behaviors and outcomes in the perinatal period. This can inform the design of antenatal support to better address these challenges.

Sleep Quality Moderates the Relationship between Anxiety Sensitivity and PTSD Symptoms in Combat-exposed Veterans.

Objective/Background: Posttraumatic stress disorder (PTSD) and related conditions (e.g., depression) are common in Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn (OEF/OIF/OND) veterans. High anxiety sensitivity (AS), defined as fear of anxiety and anxiety-related consequences, is related to greater PTSD and depressive symptoms; however, few studies have identified possible modifiers of these associations. The current study examined the moderating role of sleep quality in the associations between AS and PTSD and depressive symptoms. Participants: Participants were 155 OEF/OIF/OND community veterans ages 21-40 (12.3% women). Methods: Participants completed a semi-structured clinical interview for DSM-IV PTSD symptoms (Clinician Administered PTSD Scale; CAPS) and self-report measures of anxiety sensitivity (Anxiety Sensitivity Index), sleep quality (Pittsburgh Sleep Quality Index global score; PSQI), and depressive symptoms (Beck Depression Inventory-II; BDI-II). Results: Results of hierarchical linear regression models indicated that the main effects of AS and global PSQI score were significantly associated with greater PTSD and depressive symptoms (both with sleep items removed), above and beyond the covariates of trauma load and military rank. Sleep quality moderated the relationship between AS and PTSD symptoms (but not depressive symptoms), such that greater AS was associated with greater PTSD symptoms for individuals with good sleep quality, but not poor sleep quality. Conclusions: Sleep quality and AS account for unique variance in PTSD and depressive symptoms in combat-exposed veterans. AS may be less relevant to understanding risk for PTSD among combat-exposed veterans experiencing poor sleep quality.

An Update on Precision Medicine Advances In Neurodevelopmental Disorders.

Neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention-deficit/hyper-activity disorder (ADHD), represent a group of conditions that manifest early in child development and produce impairments across multiple domains of functioning. Although a number of pharmacological and psychosocial treatments exist to improve the symptoms associated with these syndromes, treatment advances have lagged. The Precision Medicine Initiative was launched with the goal of revolutionizing medicine by progressing beyond the historical one-size-fits-all approach. In this review, we evaluate current research efforts to personalize treatments for ASD and ADHD. Most pharmacogenetic testing has focused on the cytochrome P450 enzyme family with a particular focus on CYP2D6 and CYP2C19, which are genes that produce an enzyme that acts as a key metabolizer of many prescribed medications. This article provides an update on the state of the field of pharmacogenetics and "therapy-genetics" in the context of ASD and ADHD, and it also encourages clinicians to follow US Food and Drug Administration recommendations regarding pharmacogenetic testing.

Semaglutide once weekly in people with type 2 diabetes: Real-world analysis of the Canadian LMC diabetes registry (SPARE study).

AIMS: To investigate real-world short-term clinical outcomes in adults with type 2 diabetes (T2D) who initiated semaglutide in a specialist endocrinology practice in Canada. MATERIALS AND METHODS: This study was a retrospective observational study using data from the Canadian LMC Diabetes Registry. Adults with T2D who were naïve to glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy, initiated semaglutide therapy as usual standard of care between February 2018 and February 2019, and maintained semaglutide therapy during follow-up, were eligible for analysis. The primary outcome was mean change in glycated haemoglobin (HbA1c) at 3- to 6-month follow-up. RESULTS: In the final analytical cohort (n = 937), there was a statistically significant mean ± SD reduction in HbA1c of -1.03 ± 1.24% (11.3 ± 13.6 mmol/mol, P < 0.001) and weight of -3.9 ± 4.0 kg (P < 0.001), with no significant change in self-reported incidence of hypoglycaemia. There was a significant reduction in HbA1c and weight regardless of number of co-therapies or semaglutide dose. However, adults using the 1.0-mg dose had a significantly greater reduction in HbA1c compared to adults using the 0.25- to 0.5-mg dose (between-group difference - 0.24 ± 0.06%, 2.6 ± 0.7 mmol/mol; P < 0.001). Adults using basal-bolus therapy required a significantly lower median total daily dose of insulin after adding semaglutide (0.82 vs. 0.93 U/kg; P < 0.001). CONCLUSIONS: This retrospective observational study demonstrated that GLP-1RA-naïve adults with T2D initiating semaglutide in a real-world clinical practice had a statistically and clinically significant reduction in HbA1c and body weight after 3 to 6 months, regardless of semaglutide dose or order of semaglutide therapy, with no significant change in reported incidence of hypoglycaemia.

Goal achievement of HbA1c and LDL-cholesterol in a randomized trial comparing colesevelam with ezetimibe: GOAL-RCT.

AIM: To compare the efficacy and safety of colesevelam and ezetimibe as second-line low density lipoprotein-cholesterol (LDL-c)-lowering options in type 2 diabetes (T2D). MATERIALS AND METHODS: GOAL-RCT is a 24-week, open-label, randomized, pragmatic clinical trial. Subjects with T2D with uncontrolled HbA1c (7.1%-10%) and LDL-c (>2.0 mmol/L) were randomized 1:1 to colesevelam 3.75 g or ezetimibe 10 mg daily. The primary composite outcome was the proportion of participants achieving an LDL-c target of ≤2.0 mmol/L and HbA1c target of ≤7.0%. Intention to treat analysis was performed. RESULTS: Two hundred subjects were enrolled: mean age 59 ± 10 years; mean HbA1c 8.0%; mean LDL-c 2.5 mmol/L; 97% on statin therapy. The primary composite outcome was achieved by similar proportions of participants with colesevelam (14.6%) and ezetimibe (10.5%) (Pnon-inferiority < .001, Psuperiority = .41). LDL-c reduction from baseline was less with colesevelam compared with ezetimibe (14.0% vs. 23.2%, P < .01), as was the proportion of subjects achieving an LDL-c target of ≤2.0 mmol/L (47.6% and 67.0%, respectively; P = .007). Mean HbA1c was reduced with colesevelam (-0.26 ± 0.10%), while no change was observed with ezetimibe (difference P = .06). Adverse events and discontinuation rates were higher for colesevelam (20.2% and 31.1%) compared with ezetimibe (7.2% and 6.2%), respectively. CONCLUSIONS: Among subjects with T2D, the initiation of colesevelam or ezetimibe led to similar achievement of primary composite outcome (LDL-c and HbA1c within target), with ezetimibe recording a greater LDL-c reduction and better tolerability than colesevelam.

Differential phenotypic expression of a novel PDHA1 mutation in a female monozygotic twin pair.

Pyruvate dehydrogenase complex (PDC) deficiency caused by mutations in the X-linked PDHA1 gene has a broad clinical presentation, and the pattern of X-chromosome inactivation has been proposed as a major factor contributing to its variable expressivity in heterozygous females. Here, we report the first set of monozygotic twin females with PDC deficiency, caused by a novel, de novo heterozygous missense mutation in exon 11 of PDHA1 (NM_000284.3: c.1100A>T). Both twins presented in infancy with a similar clinical phenotype including developmental delay, episodes of hypotonia or encephalopathy, epilepsy, and slowly progressive motor impairment due to pyramidal, extrapyramidal, and cerebellar involvement. However, they exhibited clear differences in disease severity that correlated well with residual PDC activities (approximately 60% and 20% of mean control values, respectively) and levels of immunoreactive E1α subunit in cultured skin fibroblasts. To address whether the observed clinical and biochemical differences could be explained by the pattern of X-chromosome inactivation, we undertook an androgen receptor assay in peripheral blood. In the less severely affected twin, a significant bias in the relative activity of the two X chromosomes with a ratio of approximately 75:25 was detected, while the ratio was close to 50:50 in the other twin. Although it may be difficult to extrapolate these results to other tissues, our observation provides further support to the hypothesis that the pattern of X-chromosome inactivation may influence the phenotypic expression of the same mutation in heterozygous females and broadens the clinical and genetic spectrum of PDC deficiency.

The Nomological Network of a Behavioral Distress Tolerance Task in Veterans.

There is a relative lack of research on distress tolerance (DT) in veteran samples. The aims of the study were to (a) evaluate convergent and discriminant validity of a behavioral measure of DT compared to theoretically similar (i.e., self-report DT, negative urgency) and dissimilar (i.e., risk-taking) constructs and (b) evaluate the concurrent validity of DT in relation to posttraumatic stress disorder (PTSD) and depressive symptoms in a veteran sample. A sample of U.S. veterans who served after the September 11, 2001 terror attacks (N = 306, 89.9% male; M age 30.2 years, SD = 4.5, range: 21-40 years) completed self-report and behavioral measures of DT, risk-taking, impulsivity, and depressive symptoms, and completed a clinical interview for PTSD. Results of a multitrait-multimethod matrix found significant yet minimal shared variance, r2 = .01-.03, ps = .002-.055, between the self-report and behavioral measures of DT. We used a series of multiple regressions to examine the relative contribution of the behavioral and self-report DT measures in the prediction of PTSD and depressive symptoms. Self-reported, but not behavioral, DT accounted for unique variance in PTSD, r2 = .12, p < .001, and depressive symptoms, r2 = .23, p < .001. Participants with PTSD or higher scores on measures of depression were more likely to report greater increases in frustration and irritability after completing the behavioral task. Results indicate that DT is not a unidimensional construct and must be considered in the context of specific emotions (e.g., tolerance of irritability vs. fear) and contexts (e.g., behavioral, affective).

Does Parenting Influence the Enduring Impact of Severe Childhood Sexual Abuse on Psychiatric Resilience in Adulthood?

This study examined the effect of parenting on the association between childhood sexual abuse (CSA) and psychiatric resilience in adulthood in a large female twin sample (n = 1423) assessed for severe CSA (i.e., attempted or completed intercourse before age 16). Severe CSA was associated with lower resilience to recent stressors in adulthood (defined as the difference between their internalizing symptoms and their predicted level of symptoms based on cumulative exposure to stressful life events). Subscales of the Parental Bonding Instrument were significantly associated with resilience. Specifically, parental warmth was associated with increased resilience while parental protectiveness was associated with decreased resilience. The interaction between severe CSA and parental authoritarianism was significant, such that individuals with CSA history and higher authoritarianism scores had lower resilience. Results suggest that CSA assessment remains important for therapeutic work in adulthood and that addressing parenting may be useful for interventions in children with a CSA history.

The global therapist competence scale for youth psychosocial treatment: Development and initial validation.

OBJECTIVE: We describe the development and initial psychometric properties of the observer-rated Global Therapist Competence Scale for Youth Psychosocial Treatment (G-COMP) in the context of cognitive-behavioral treatment (CBT) for youth anxiety disorders. METHOD: Independent coders rated 744 sessions from a sample of 68 youth (mean age = 10.56 years) using the G-COMP and the instruments of alliance, involvement, CBT adherence, CBT competence. RESULTS: Inter-rater reliability coefficients, ICC(2,2), were greater than .60 for the 5 G-COMP domain scores. G-COMP scores yielded small to medium correlations with instruments of alliance (rs = .17-.44) and youth involvement in treatment (rs = .08-.53), and medium to large correlations with instruments of CBT competence and adherence (rs = .26-.63). Therapists in the research setting were rated higher compared to newly trained therapists in community clinics. CONCLUSION: Preliminary reliability and validity of the G-COMP are promising, but future research is needed with non-CBT samples.

The LMC Skills, Confidence & Preparedness Index (SCPI): development and evaluation of a novel tool for assessing self-management in patients with diabetes.

BACKGROUND: Optimal diabetes care requires a specific set of self-management behaviours. The purpose of this study was to present the development and initial psychometric evaluation of a new tool to measure three key aspects of a patient's diabetes self-management: knowledge of the skill, confidence in being able to perform the skill and preparedness to implement the skill. METHODS: A sequential exploratory mixed-methods design was used. A panel of educators, researchers and clinicians established a scale with items that would adequately capture skills, confidence and preparedness in seven core health behaviours central to diabetes care. The psychometric properties of the items were pilot tested on 120 participants with diabetes from a tertiary referral centre, and repeated 6 months later on 70 participants. Item selection was informed by factor analysis, item-total statistics and the need for brevity. RESULTS: Twenty five items from a pool of 36 were retained, with an excellent overall intraclass correlation (ICC) of 0.94 (95% CI 0.92-0.99; p < 0.001). Internal consistency for the subscales (skills-9 items, confidence - 8 items, preparedness - 8 items) was very good (intraclass correlation between 0.83 and 0.88), and retest reliability after 6 months was also good (r = 0.48; p < 0.01). The scale was positively correlated to established scales that assess skill (Michigan Diabetes Knowledge Test) (r = 0.21;p = 0.01), and assess skill and confidence (Diabetes Empowerment Scale) (r = 0.28;p < 0.01). CONCLUSIONS: The Skills, Confidence & Preparedness Index is a brief and easy to administer new scale that is more comprehensive than existing tools. It should be used to assess self-management in patients with diabetes, optimize the resources applied to each patient, and determine educational needs and direct clinical management. The scale should be further evaluated in a broader population of patients with diabetes.

The clinical, biochemical and genetic features associated with RMND1-related mitochondrial disease.

BACKGROUND: Mutations in the RMND1 (Required for Meiotic Nuclear Division protein 1) gene have recently been linked to infantile onset mitochondrial disease characterised by multiple mitochondrial respiratory chain defects. METHODS: We summarised the clinical, biochemical and molecular genetic investigation of an international cohort of affected individuals with RMND1 mutations. In addition, we reviewed all the previously published cases to determine the genotype-phenotype correlates and performed survival analysis to identify prognostic factors. RESULTS: We identified 14 new cases from 11 pedigrees that harbour recessive RMND1 mutations, including 6 novel variants: c.533C>A, p.(Thr178Lys); c.565C>T, p.(Gln189*); c.631G>A, p.(Val211Met); c.1303C>T, p.(Leu435Phe); c.830+1G>A and c.1317+1G>T. Together with all previously published cases (n=32), we show that congenital sensorineural deafness, hypotonia, developmental delay and lactic acidaemia are common clinical manifestations with disease onset under 2 years. Renal involvement is more prevalent than seizures (66% vs 44%). In addition, median survival time was longer in patients with renal involvement compared with those without renal disease (6 years vs 8 months, p=0.009). The neurological phenotype also appears milder in patients with renal involvement. CONCLUSIONS: The clinical phenotypes and prognosis associated with RMND1 mutations are more heterogeneous than that were initially described. Regular monitoring of kidney function is imperative in the clinical practice in light of nephropathy being present in over 60% of cases. Furthermore, renal replacement therapy should be considered particularly in those patients with mild neurological manifestation as shown in our study that four recipients of kidney transplant demonstrate good clinical outcome to date.

LRPPRC mutations cause early-onset multisystem mitochondrial disease outside of the French-Canadian population.

Mitochondrial Complex IV [cytochrome c oxidase (COX)] deficiency is one of the most common respiratory chain defects in humans. The clinical phenotypes associated with COX deficiency include liver disease, cardiomyopathy and Leigh syndrome, a neurodegenerative disorder characterized by bilateral high signal lesions in the brainstem and basal ganglia. COX deficiency can result from mutations affecting many different mitochondrial proteins. The French-Canadian variant of COX-deficient Leigh syndrome is unique to the Saguenay-Lac-Saint-Jean region of Québec and is caused by a founder mutation in the LRPPRC gene. This encodes the leucine-rich pentatricopeptide repeat domain protein (LRPPRC), which is involved in post-transcriptional regulation of mitochondrial gene expression. Here, we present the clinical and molecular characterization of novel, recessive LRPPRC gene mutations, identified using whole exome and candidate gene sequencing. The 10 patients come from seven unrelated families of UK-Caucasian, UK-Pakistani, UK-Indian, Turkish and Iraqi origin. They resemble the French-Canadian Leigh syndrome patients in having intermittent severe lactic acidosis and early-onset neurodevelopmental problems with episodes of deterioration. In addition, many of our patients have had neonatal cardiomyopathy or congenital malformations, most commonly affecting the heart and the brain. All patients who were tested had isolated COX deficiency in skeletal muscle. Functional characterization of patients' fibroblasts and skeletal muscle homogenates showed decreased levels of mutant LRPPRC protein and impaired Complex IV enzyme activity, associated with abnormal COX assembly and reduced steady-state levels of numerous oxidative phosphorylation subunits. We also identified a Complex I assembly defect in skeletal muscle, indicating different roles for LRPPRC in post-transcriptional regulation of mitochondrial mRNAs between tissues. Patient fibroblasts showed decreased steady-state levels of mitochondrial mRNAs, although the length of poly(A) tails of mitochondrial transcripts were unaffected. Our study identifies LRPPRC as an important disease-causing gene in an early-onset, multisystem and neurological mitochondrial disease, which should be considered as a cause of COX deficiency even in patients originating outside of the French-Canadian population.

The safety of emergency medicine.

The patient safety movement has been active for over a decade, but the issue of patient safety in emergency care and the emergency department (ED) has only recently been brought into the forefront. The ED environment has traditionally been considered unsafe, but there is little data to support this assertion. This paper reviews the literature on patient safety and highlights the challenges associated with using the current evidence base to inform practice due to the variability in methods of measuring safety. Studies looking at safety in the ED report low rates for adverse events ranging from 3.6 to 32.6 events per 1000 attendances. The wide variation in reported rates on adverse events reflects the significant differences in methods of reporting and classifying safety incidents and harm between departments; standardisation in the ED context is urgently required to allow comparisons to be made between departments and to quantify the impact of specific interventions. We outline the key factors in emergency care which may hinder the provision of safer care and consider solutions which have evolved or been proposed to identify and mitigate against harm. Interventions such as team training, telephone follow-up, ED pharmacist interventions and rounding, all show some evidence of improving safety in the ED. We further highlight the need for a collaborative whole system approach as almost half of safety incidents in the ED are attributable to external factors, particularly those related to information flow, crowding, demand and boarding.