Evidence-based implementation practices applied to the intensive treatment of eating disorders: Summary of research and illustration of principles using a case example

Implementation of evidence‐based practices (EBPs) in intensive treatment settings poses a major challenge in the field of psychology. This is particularly true for eating disorder (ED) treatment, where multidisciplinary care is provided to a severe and complex patient population; almost no data exist concerning best practices in these settings. We summarize the research on EBP implementation science organized by existing frameworks and illustrate how these practices may be applied using a case example. We describe the recent successful implementation of EBPs in a community‐based intensive ED treatment network, which recently adapted and implemented transdiagnostic, empirically supported treatment for emotional disorders across its system of residential and day‐hospital programs. The research summary, implementation frameworks, and case example may inform future efforts to implement evidence‐based practice in intensive treatment settings.Published versio

'A hard-won capability': the experiences of parents managing their babies' medicines after discharge from a neonatal unit.:'A hard-won capability'

IntroductionParents of babies who required neonatal care are responsible for managing their medicines after they are discharged home. There is wide variation in the information and amount of preparation given to parents prior to assuming this challenging task. The aim of the Parent co-Designed Drug Information for parents and Guardians Taking Neonates home (PADDINGToN) study was to explore parents' experiences of managing their babies' medicines post discharge from a neonatal unit and to use this information to develop suitable resources for future families.MethodsA qualitative participatory interpretative approach using a mixture of remote and face-to-face small group interviews or one-to-one interviews was used. Parents were recruited using social media advertisements and convenience sampling from five study sites (four neonatal units in England and one in Ireland). Parents from other neonatal units were invited to take part through social media advertisement. The interviews were audio-recorded and inductive reflexive thematic analysis was used to analyze the data.Results17 parents (14 mothers, 3 fathers) participated. One over-arching theme, 'A hard won capability', and four major interpretive themes were generated from the analysis of the data: Being in NICU and the prospect of going home: emotional and practical challenges; Living the reality of being at home: the uncertainty associated with giving medicines; Being at home: battling the system and a lack of support/knowledge; and Suggesting ways forward: parents' lived insights into improving information and resources.ConclusionDespite the challenges they faced, parents developed strategies for safely and reliably managing medicines administration and they assimilated knowledge, built their confidence and achieved a capability in medicines administration. Their experiences have been used to build a suite of medicines administration resources to support future parents.</jats:sec

Hepatitis C virus transmission between eight high-income countries among men who have sex with men: a whole-genome analysis.

BACKGROUND Microelimination of the hepatitis C virus (HCV) among men who have sex with men (MSM) could be complicated by continuous external introductions and the emergence of phylogenetic clusters harbouring clinically significant resistance-associated substitutions (RAS). To investigate international clustering and the prevalence and transmission of RAS, we aimed to analyse whole-genome HCV sequences from MSM with a recently acquired infection who participated in a large, international HCV treatment trial. METHODS For this whole-genome analysis, we obtained HCV sequences from 128 MSM who had acquired HCV within the past 12 months and were participating in the REACT trial. The participants from whom sequences were obtained were recruited at 24 sites in eight countries. We inferred maximum-likelihood phylogenies and identified transmission clusters for HCV genotypes separately. We constructed time-scaled phylogenies to estimate cluster introduction dates and used a Bayesian Skygrid approach to estimate the effective population size over the past 50 years. We calculated the prevalence of RAS and the extent of RAS transmission in the study population. FINDINGS The majority of recent HCV infections were part of international networks that arose in the late 1990s and early 2000s. Sequences obtained in the same country clustered frequently, and in 36% of subclusters since 2015 we found evidence of international transmission. European MSM were more likely than non-European MSM to be in a cluster (odds ratio 11·9 [95% CI 3·6-43·4], p<0·0001). The effective population size decreased rapidly since around 2015 in Europe. RAS associated with substantially diminished cure rates were infrequently detected and transmission of highly resistant viruses was not observed. INTERPRETATION Despite antiviral treatment becoming widely available, international transmission of HCV among MSM has still occurred over the past 8 years, which could complicate microelimination of the virus in this population. RAS-enriched clusters and widespread RAS transmission are currently not a threat to elimination goals. These findings support an international approach for HCV microelimination among MSM. FUNDING National Institutes of Health and Dr. C.J. Vaillant Fonds

Retreatment for hepatitis C virus direct-acting antiviral therapy virological failure in primary and tertiary settings: The REACH-C cohort

Virological failure occurs in a small proportion of people treated for hepatitis C virus (HCV) with direct-acting antiviral (DAA) therapies. This study assessed retreatment for virological failure in a large real-world cohort. REACH-C is an Australian observational study (n = 10,843) evaluating treatment outcomes of sequential DAA initiations across 33 health services between March 2016 to June 2019. Virological failure retreatment data were collected until October 2020. Of 408 people with virological failure (81% male; median age 53; 38% cirrhosis; 56% genotype 3), 213 (54%) were retreated once; 15 were retreated twice. A range of genotype specific and pangenotypic DAAs were used to retreat virological failure in primary (n = 56) and tertiary (n = 157) settings. Following sofosbuvir/velpatasvir/voxilaprevir availability in 2019, the proportion retreated in primary care increased from 21% to 40% and median time to retreatment initiation declined from 294 to 152 days. Per protocol (PP) sustained virological response (SVR12) was similar for people retreated in primary and tertiary settings (80% vs 81%; p = 1.000). In regression analysis, sofosbuvir/velpatasvir/voxilaprevir (vs. other regimens) significantly decreased likelihood of second virological failure (PP SVR12 88% vs. 77%; adjusted odds ratio [AOR] 0.29; 95%CI 0.11–0.81); cirrhosis increased likelihood (PP SVR12 69% vs. 91%; AOR 4.26; 95%CI 1.64–11.09). Indigenous Australians had lower likelihood of retreatment initiation (AOR 0.36; 95%CI 0.15–0.81). Treatment setting and prescriber type were not associated with retreatment initiation or outcome. Virological failure can be effectively retreated in primary care. Expanded access to simplified retreatment regimens through decentralized models may increase retreatment uptake and reduce HCV-related mortality

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Combination of Serum Free Light Chain Analysis with Capillary Zone Electrophoresis Improves Screening for Monoclonal Gammopathies.

Abstract Introduction: Screening for multiple myeloma requires both serum and urine protein electrophoresis, because in about 20% of patients with myeloma, monoclonal free light chain (FLC) is the only paraprotein found, and it is commonly missed by serum protein electrophoresis. However, many requests for testing do not include a urine sample (&gt;80% of requests in our experience). This risks missing clinically significant disease. Recent availability of serum FLC assays has raised the possibility that these assays may replace testing for urinary FLC in screening for monoclonal gammopathies, and that the serum kappa:lambda light chain ratio (LCR) may be more sensitive for detecting monoclonal FLC than serum and urine protein gel electrophoresis. Aims: To identify how many additional patients with monoclonal gammopathies would be detected if serum FLC assays were incorporated into the routine myeloma screen. To evaluate the ability of serum FLC assays to identify all patients identified by urine protein electrophoresis. Method and Setting: We analysed data from a consecutive cohort of 753 serum blood samples submitted for myeloma screening to Hull Royal Infirmary Immunology Laboratory between 03/23/07 and 05/31/07. During this period all myeloma screen requests received serum capillary zone protein electrophoresis (CE) (SEBIA Capillarys 2, Analytical Technologies) and serum FLC analysis using a latex-enhanced immunoassay (The Binding Site, Birmingham, UK on a Beckman-Coulter IMMAGE nephelometric analyzer). When available, urine protein CE was also perfomed (SEBIA Capillarys 2). Samples with an abnormal serum CE or serum LCR were tested by immunofixation (SEBIA Hydrasys, Analytical Technologies). Repeat samples were requested from patients with LCR outside the reference interval (0.26–1.65) before referral, but an immediate hematology referral was recommended if LCR &gt;3.5 sd from the mean (ie 0.18–2.01). Results: Of 753 patients, 118 had features on serum CE requiring immunofixation. Of these, 76 had a monoclonal paraprotein identified. A further 46 samples had normal serum CE with abnormal LCR and 25 of these had LCR outide mean±3.5 sd. Of 6 patients so far referred as a result of abnormal LCR but normal serum CE, 4 (67%) had a lymphoproliferative disease (free kappa myeloma, free kappa MGUS, free lambda MGUS, and a chronic lymphocytic leukaemia). Urine samples were received from 128 (17%) patients, of whom 8 (6%) had a monoclonal FLC identified in the urine. All of these patients had an abnormal serum LCR, though in one patient with acute renal failure and raised kappa and lambda results the LCR was borderline abnormal (1.75), with a very small band in the urine, visible only by agarose gel immunofixation. For the 2 patients with normal serum CE, but with urinary monoclonal FLC present, serum LCR was abnormal (LCR= 33 and 1.75). Discussion and Conclusions: Use of serum FLC assays increased the detection of monoclonal paraproteins (by 5% so far but further follow up is required to quantify this exactly). Serum FLC analysis had a sensitivity of 100% for identifying patients with urinary FLC.</jats:p