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Background CONSORT guidelines call for precise reporting of behavior change interventions: we need rigorous methods of characterizing active content of interventions with precision and specificity. Objectives The objective of this study is to develop an extensive, consensually agreed hierarchically structured taxonomy of techniques [behavior change techniques (BCTs)] used in behavior change interventions. Methods In a Delphi-type exercise, 14 experts rated labels and definitions of 124 BCTs from six published classification systems. Another 18 experts grouped BCTs according to similarity of active ingredients in an open-sort task. Inter-rater agreement amongst six researchers coding 85 intervention descriptions by BCTs was assessed. Results This resulted in 93 BCTs clustered into 16 groups. Of the 26 BCTs occurring at least five times, 23 had adjusted kappas of 0.60 or above. Conclusions “BCT taxonomy v1,” an extensive taxonomy of 93 consensually agreed, distinct BCTs, offers a step change as a method for specifying interventions, but we anticipate further development and evaluation based on international, interdisciplinary consensus.

ObjectiveSynthesis that can filter the evidence from multiple sources to inform the choice of intervention components is highly desirable yet, at present, there are few examples of systematic reviews that explicitly define this type of synthesis using behaviour change frameworks. Here, we demonstrate how using the Theoretical Domains Framework (TDF) and the Behaviour Change Wheel (BCW) made it possible to bring together the findings from a series of three interconnected systematic reviews on the self-care of minor ailments (MAs) to inform the choice of intervention components.MethodThe TDF and the capability, opportunity, motivation model of behaviour at the hub of the BCW were used to synthesise the findings from the three reviews, including syntheses of service-user views in interviews (review 1, 20 studies) and surveys (review 2, 13 studies), and evaluations of a range of interventions and services (review 3, 21 studies).ResultsThe TDF and BCW approach provided a systematic, structured and replicable methodology for retrospectively integrating different types of evidence within a series of systematic reviews. Several intervention strategies, grounded in theory and discussed with key stakeholders, were suggested, which can be implemented and tested.ConclusionsThis novel application of the TDF/BCW approach illustrates how it can be used to bring together quantitative and qualitative evidence to better understand self-care behaviour for MAs within a systematic review context. The TDF/BCW approach facilitated exploration of the contradictions and gaps between the separate review syntheses, and supported the identification of possible intervention strategies, grounded in theory. The ongoing development and refinement of this method is supported.PROSPERO registration numberCRD42017071515

Microviridins and other ω-ester-linked peptides, collectively known as graspetides, are characterized by side-chain–side-chain linkages installed by ATP-grasp enzymes. Here we report the discovery of a family of graspetides, the gene clusters of which also encode an O -methyltransferase with homology to the protein repair catalyst protein l -isoaspartyl methyltransferase. Using heterologous expression, we produced fuscimiditide, a ribosomally synthesized and post-translationally modified peptide (RiPP). NMR analysis of fuscimiditide revealed that the peptide contains two ester cross-links forming a stem–loop macrocycle. Furthermore, an unusually stable aspartimide moiety is found within the loop macrocycle. We fully reconstituted fuscimiditide biosynthesis in vitro including formation of the ester and aspartimide moieties. The aspartimide moiety embedded in fuscimiditide hydrolyses regioselectively to isoaspartate. Surprisingly, this isoaspartate-containing peptide is also a substrate for the l -isoaspartyl methyltransferase homologue, thus driving any hydrolysis products back to the aspartimide form. Whereas an aspartimide is often considered a nuisance product in protein formulations, our data suggest that some RiPPs have aspartimide residues intentionally installed via enzymatic activity. The biosynthesis of fuscimiditide, a ribosomally synthesized post-translationally modified peptide, has now been reported. Heterologous expression and analysis of fuscimiditide showed it contained two side-chain–side-chain ester linkages and an aspartimide in its backbone. The aspartimide moiety is unexpectedly stable, suggesting this structure is the intended natural product.

Research teams report challenges in conducting overviews and many of these relate to the synthesis of outcome data from multiple reviews that lead to unclear evidence. This limits research from being used by policymakers and other review users who need accessible robust evidence. In this commentary, we present a case study on creating a toolkit of interventions for preventing violence against women and girls (VAWG). This toolkit is underpinned by systematic methods and a priori criteria that identify a single best up-to-date systematic review of each subtopic. The best evidence toolkit approach does not require the synthesis of multiple reviews and produces clear, standardised evidence across subtopics efficiently. This approach offers a pragmatic alternative to overviews when presenting a broad spectrum of intervention approaches, populations or outcomes. This approach may be particularly beneficial when the primary aim is to communicate with policymakers.

Background The In-Center Hemodialysis Consumer Assessment of Healthcare Providers and Systems (ICH CAHPS) Survey is the first patient reported outcome measure included in the U.S. Medicare End Stage Renal Disease Quality Incentive Program. Administered twice yearly, it assesses in-center dialysis experience and survey responses are tied to dialysis facility payments. Low response rates, currently approximately 35%, raise concern for possible underrepresentation of patient groups. Methods Cross-sectional analysis of survey administration in 2012 to all in-center hemodialysis patients in Dialysis Clinic, Inc. (DCI) facilities nationally over 18 years old who received hemodialysis at their facility for at least 3 months. Patient-level covariates included demographic, clinical, laboratory, and functional characteristics. Random effects multivariable logistic regression was used to assess survey non-response. Results Among 11,055 eligible patients 6541 (59%) were non-responders. Of the remaining 4514 responders, 549 (14%) surveys were not usable due to presence of proxy help or incomplete responses. Non-responders were more likely to be men, non-white, younger, single, dual Medicare/Medicaid eligible, less educated, non-English speaking, and not active on the transplant list; non-responders had longer ESRD vintage, lower body mass index, lower serum albumin, worse functional status, and more hospitalizations, missed treatments, and shortened treatments. Similar associations were found using more parsimonious multivariable analyses and after imputing missing data. Conclusions Non-responders to the ICH CAHPS significantly differed from responders, broadly spanning individuals with fewer socioeconomic advantages and greater illness burden, raising limitations in interpreting facility survey results. Future research should assess reasons for non-response to improve ICH CAHPS generalizability and utility.

Introduction: The world-wide lockdown caused by Coronavirus Disease 2019 (COVID-19) has upended the trajectories of lives everywhere. The medical profession has been on the front lines of this rapidly developing situation, which in turn has called for unprecedented changes in the medical school curriculum. These changes have severe implications for medical students interested in applying to competitive surgical specialties like orthopedics. Methods: As medical students in 3 different class years pursuing orthopedic surgery, we provide our perspectives on the impact that COVID-19 has had on medical student orthopedic education. Results: With the removal of away rotations and a shift to virtual interviews, rising fourth year medical students are arguably the most impacted as they prepare for the orthopedic residency application process. Third year students, who are in the exploratory phase of choosing a specialty, also face uncertainties in the shift to a “new” clerkship experience that may (1) be of shorter duration, (2) implement shifts to limit overcrowding of clinical space, and (3) increase the use of telehealth over direct patient contact. Discussion: The COVID-19 pandemic has altered the course of medical students’ orthopedic education in unprecedented ways. We believe the following suggestions may be helpful for students seeking alternative, supplemental ways of learning: (1) read up on major orthopedic journals, (2) reach out to orthopedic surgeons in areas of interest, (3) reach out to program directors/medical clerkship directors/program coordinators for opportunities to attend their educational curriculum virtually, (4) attend online lectures and hospital grand rounds, and (5) practice suturing technique with a practice kit. Conclusions: While the medical education landscape remains uncertain amid the evolving conditions of COVID-19, as medical students we strive to learn from this pandemic and respond to future unforeseen challenges with resilience, dedication, and compassion: all qualities we admire in orthopedic surgeons.

Background Clinical practice guidelines emphasize shared decision-making for kidney replacement treatment, yet little is known about the influence of cultural differences on that process. We undertook a retrospective chart review to explore the process and timing of dialysis decision making and initiation in Chinese American patients to provide quality kidney care for this population. Design Participants received outpatient care at Tufts Medical Center and dialysis at Dialysis Clinic, Inc. Boston or Somerville, MA from 2001–2021. Clinic chart review sourced demographic, clinical, and end-of-life care information from 180 participants (82 Chinese American, 98 other) from stage 4 chronic kidney disease (CKD) and dialysis initiation. Results Chinese American participants were older (mean 70 vs. 59, p  < 0.0001), less likely to speak English (12% vs. 87%, p  < 0.0001), and used interpreter services more (80% vs. 11%, p  < 0.0001). Chinese American participants had more visits (median 14 vs. 10, p  = 0.005); were more often accompanied by family members (75% vs. 40%, p  < 0.001); and had significantly lower rates of healthcare proxy documentation (35% vs. 55%, p  = 0.006). There was no statistical difference in months between first CKD 4 visit and first dialysis. Both groups started dialysis at the same average eGFR and with similar rates of permanent dialysis access. Chinese American participants had significantly lower serum albumin at dialysis initiation (mean 3.3 g/dL vs 3.7 g/dL, p  = 0.0003). Documentation reflected a low number of conversations about non-dialytic care, end-of-life planning, or palliative care in both groups across all visits. Conclusion The time between CKD 4 and dialysis initiation was the same in both groups, suggesting a similar overall outcome of care. Chart documentation suggests that Chinese American participants had a significantly higher number of visits with nephrologists where discussion about dialysis was noted and were more likely to have a family member present at the visit. Fewer Chinese American participants completed healthcare proxies. Among all study participants, healthcare proxy, code status, and palliative care discussions were reported less frequently than expected. These findings highlight opportunities for collaboration between palliative care clinicians and nephrologists.

Background Overuse of antibiotics has contributed to antimicrobial resistance; a growing public health threat. In long-term care facilities, levels of inappropriate prescribing are as high as 75%. Numerous interventions targeting long-term care facilities’ antimicrobial stewardship have been reported with varying, and largely unexplained, effects. Therefore, this review aimed to apply behavioural science frameworks to specify the component behaviour change techniques of stewardship interventions in long-term care facilities and identify those components associated with improved outcomes. Method A systematic review (CRD42018103803) was conducted through electronic database searches. Two behavioural science frameworks, the Behaviour Change Wheel and Behaviour Change Technique Taxonomy were used to classify intervention descriptions into intervention types and component behaviour change techniques used. Study design and outcome heterogeneity prevented meta-analysis and meta-regression. Interventions were categorised as ‘very promising’ (all outcomes statistically significant), ‘quite promising’ (some outcomes statistically significant), or ‘not promising’ (no outcomes statistically significant). ‘Promise ratios’ (PR) were calculated for identified intervention types and behaviour change techniques by dividing the number of (very or quite) promising interventions featuring the intervention type or behaviour change technique by the number of interventions featuring the intervention type or behaviour change technique that were not promising. Promising intervention types and behaviour change techniques were defined as those with a PR ≥ 2. Results Twenty studies (of19 interventions) were included. Seven interventions (37%) were ‘very promising’, eight ‘quite promising’ (42%) and four ‘not promising’ (21%). Most promising intervention types were ‘persuasion’ ( n  = 12; promise ratio (PR) = 5.0), ‘enablement’ ( n  = 16; PR = 4.33) and ‘education’ ( n  = 19; PR = 3.75). Most promising behaviour change techniques were ‘feedback on behaviour’ ( n  = 9; PR = 8.0) and ‘restructuring the social environment’ (e.g. staff role changes; n  = 8; PR = 7.0). Conclusion Systematic identification of the active ingredients of antimicrobial stewardship in long-term care facilities was facilitated through the application of behavioural science frameworks. Incorporating environmental restructuring and performance feedback may be promising intervention strategies for antimicrobial stewardship interventions within long-term care facilities.

Acute myeloid leukemia (AML) is a heterogeneous disease that accounts for ~20% of all childhood leukemias, and more than 40% of children with AML relapse within three years of diagnosis. Although recent efforts have focused on developing a precise medicine-based approach towards treating AML in adults, there remains a critical gap in therapies designed specifically for children. Here, we present ex vivo drug sensitivity profiles for children with de novo AML using an automated flow cytometry platform. Fresh diagnostic blood or bone marrow aspirate samples were screened for sensitivity in response to 78 dose conditions by measuring the reduction in leukemic blasts relative to the control. In pediatric patients treated with conventional chemotherapy, comprising cytarabine, daunorubicin and etoposide (ADE), ex vivo drug sensitivity results correlated with minimal residual disease (r = 0.63) and one year relapse-free survival (r = 0.70; AUROC = 0.94). In the de novo ADE analysis cohort of 13 patients, AML cells showed greater sensitivity to bortezomib/panobinostat compared with ADE, and comparable sensitivity between venetoclax/azacitidine and ADE ex vivo. Two patients showed a differential response between ADE and bortezomib/panobinostat, thus supporting the incorporation of ex vivo drug sensitivity testing in clinical trials to further evaluate the predictive utility of this platform in children with AML.

Background This systematic overview was commissioned by England’s Department of Health and Social Care (DHSC) to assess the evidence on direct (previously ‘novel’) oral anticoagulants (OACs), compared with usual care, in adults, to prevent stroke related to atrial fibrillation (AF), and to prevent and treat venous thromboembolism (VTE). Specifically, to assess efficacy and safety, genotyping, self-monitoring, and patient and clinician experiences of OACs. Methods We searched MEDLINE, Embase, ASSIA, and CINAHL, in October, 2017, updated in November 2021. We included systematic reviews, published from 2014, in English, assessing OACs, in adults. We rated review quality using AMSTAR2 or the JBI checklist. Two reviewers extracted and synthesised the main findings from the included reviews. Results We included 49 systematic reviews; one evaluated efficacy, safety, and cost-effectiveness, 17 assessed genotyping, 23 self-monitoring or adherence, and 15 experiences (seven assessed two topics). Generally, the direct OACs, particularly apixaban (5 mg twice daily), were more effective and safer than warfarin in preventing AF-related stroke. For VTE, there was little evidence of differences in efficacy between direct OACs and low-molecular-weight heparin (prevention), warfarin (treatment), and warfarin or aspirin (secondary prevention). The evidence suggested that some direct OACs may reduce the risk of bleeding, compared with warfarin. One review of genotype-guided warfarin dosing assessed AF patients; no significant differences in stroke prevention were reported. Education about OACs, in patients with AF, could improve adherence. Pharmacist management of coagulation may be better than primary care management. Patients were more adherent to direct OACs than warfarin. Drug efficacy was highly valued by patients and most clinicians, followed by safety. No other factors consistently affected patients’ choice of anticoagulant and adherence to treatment. Patients were more satisfied with direct OACs than warfarin. Conclusions For stroke prevention in AF, direct OACs seem to be more effective and safer than usual care, and apixaban (5 mg twice daily) had the best profile. For VTE, there was no strong evidence that direct OACs were better than usual care. Education and pharmacist management could improve coagulation control. Both clinicians and patients rated efficacy and safety as the most important factors in managing AF and VTE. Systematic review registration PROSPERO CRD42017084263—one deviation; efficacy and safety were from one review.