Development of Learning Objectives to Guide Enhancement of Chronic Disease Prevention and Management Curricula in Undergraduate Medical Education

Phenomenon: Chronic disease is a leading cause of death and disability in the United States. With an increase in the demand for healthcare and rising costs related to chronic care, physicians need to be better trained to address chronic disease at various stages of illness in a collaborative and cost-effective manner. Specific and measurable learning objectives are key to the design and evaluation of effective training, but there has been no consensus on chronic disease learning objectives appropriate to medical student education. Approach: Wagner’sChronic Care Model (CCM) was selected as a theoretical framework to guide development of an enhanced chronic dis-ease prevention and management (CDPM) curriculum. Findings of a literature review of CDPM competencies, objectives, and topical statements were mapped to each of the six domains of the CCM to understand the breadth of existing learning topics within each domain. At an in-person meeting, medical educators prepared a survey for the modified Delphi approach. Attendees iden-tified 51 possible learning objectives from the literature review mapping, rephrased the CCM domains as competencies, constructed possible CDPM learning objectives for each competency with the goal of reaching multi-institutional consensus on a limited number of CDPM learning objectives that would be feasible for institutions to use to guide enhancement of medical student curricula related to CDPM. After the meeting, the group developed a survey which included 39 learning objectives. In the study phase of the modified Delphi approach, 32 physician CDPM experts and educators completed an online survey to prioritize the top 20 objectives. The next step occurred at a CDPM interest group in-person meeting with the goal of identifying the top 10 objectives. Findings: The CCM domains were reframed as the following competencies for medical student education: patient self-care management, decision support, clinical information systems, community resources, delivery systems and teams, and health system practice and improvement. Eleven CDPM learning objectives were identified within the six competencies that were most important in developing curriculum for medical students. Insights: These learning objectives cut across education on the prevention and management of individual chronic diseases and frame chronic disease care as requiring the health system science competencies identified in the CCM. They are intended to be used in combination with traditional disease-specific pathophysiology and treatment objectives. Additional efforts are needed to identify specific curricular strategies and assessment tools for each learning objective

The cost-effectiveness of exercise-based cardiac rehabilitation:a systematic review of the characteristics and methodological quality of published literature

Aim: This descriptive review aimed to assess the characteristics and methodological quality of economic evaluations of cardiac rehabilitation (CR) programs according to updated economic guidelines for healthcare interventions. Recommendations will be made to inform future research addressing the impact of a physical exercise component on cost-effectiveness. Methods: Electronic databases were searched for economic evaluations of exercise-based CR programs published in English between 2000 and 2014. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement was used to review the methodological quality of included economic evaluations. Results: Fifteen economic evaluations met the review inclusion criteria. Assessed study characteristics exhibited wide variability, particularly in their economic perspective, time horizon, setting, comparators and included costs, with significant heterogeneity in exercise dose across interventions. Ten evaluations were based on randomised controlled trials (RCTs) spanning 6-24 months but often with weak or inconclusive results; two were modelling studies; and the final three utilised longer time horizons of 3.5-5 years from which findings suggest that long-term exercise-based CR results in lower costs, reduced hospitalisations and a longer cumulative patient lifetime. None of the 15 articles met all the CHEERS quality criteria, with the majority either fully or partially meeting a selection of the assessed variables. Conclusion: Evidence exists supporting the cost-effectiveness of exercise-based CR for cardiovascular disease patients. However, variability in CR program delivery and weak consistency between study perspective and design limits study comparability and therefore the accumulation of evidence in support of a particular exercise regime. The generalisability of study findings was limited due to the exclusion of patients with comorbidities as would typically be found in a real-world setting. The use of longer time-horizons would be more comparable with a chronic condition and enable economic assessments of the long-term effects of CR. As none of the articles met recent reporting standards for the economic assessment of healthcare interventions, it is recommended that future studies adhere to such guidelines

Genetics, recombination and clinical features of human rhinovirus species C (HRV-C) infections; interactions of HRV-C with other respiratory viruses

To estimate the frequency, molecular epidemiological and clinical associations of infection with the newly described species C variants of human rhinoviruses (HRV), 3243 diagnostic respiratory samples referred for diagnostic testing in Edinburgh were screened using a VP4-encoding region-based selective polymerase chain reaction (PCR) for HRV-C along with parallel PCR testing for 13 other respiratory viruses. HRV-C was the third most frequently detected behind respiratory syncytial virus (RSV) and adenovirus, with 141 infection episodes detected among 1885 subjects over 13 months (7.5%). Infections predominantly targeted the very young (median age 6–12 months; 80% of infections in those <2 years), occurred throughout the year but with peak incidence in early winter months. HRV-C was detected significantly more frequently among subjects with lower (LRT) and upper respiratory tract (URT) disease than controls without respiratory symptoms; HRV-C mono-infections were the second most frequently detected virus (behind RSV) in both disease presentations (6.9% and 7.8% of all cases respectively). HRV variants were classified by VP4/VP2 sequencing into 39 genotypically defined types, increasing the current total worldwide to 60. Through sequence comparisons of the 5′untranslated region (5′UTR), the majority grouped with species A (n = 96; 68%, described as HRV-Ca), the remainder forming a phylogenetically distinct 5′UTR group (HRV-Cc). Multiple and bidirectional recombination events between HRV-Ca and HRV-Cc variants and with HRV species A represents the most parsimonious explanation for their interspersed phylogeny relationships in the VP4/VP2-encoding region. No difference in age distribution, seasonality or disease associations was identified between HRV-Ca and HRV-Cc variants. HRV-C-infected subjects showed markedly reduced detection frequencies of RSV and other respiratory viruses, providing evidence for a major interfering effect of HRV-C on susceptibility to other respiratory virus infections. HRV-C's disease associations, its prevalence and evidence for interfering effects on other respiratory viruses mandates incorporation of rhinoviruses into future diagnostic virology screening

Replication of Associations of Genetic Loci Outside the HLA Region With Susceptibility to Anti-Cyclic Citrullinated Peptide-Negative Rheumatoid Arthritis

OBJECTIVE: Genetic polymorphisms within the HLA region explain only a modest proportion of anti-cyclic citrullinated peptide (anti-CCP)-negative rheumatoid arthritis (RA) heritability. However, few non-HLA markers have been identified so far. This study was undertaken to replicate the associations of anti-CCP-negative RA with non-HLA genetic polymorphisms demonstrated in a previous study. METHODS: The Rheumatoid Arthritis Consortium International densely genotyped 186 autoimmune-related regions in 3,339 anti-CCP-negative RA patients and 15,870 controls across 6 different populations using the Illumina ImmunoChip array. We performed a case-control replication study of the anti-CCP-negative markers with the strongest associations in that discovery study, in an independent cohort of anti-CCP-negative UK RA patients. Individuals from the arcOGEN Consortium and Wellcome Trust Case Control Consortium were used as controls. Genotyping in cases was performed using Sequenom MassArray technology. Genome-wide data from controls were imputed using the 1000 Genomes Phase I integrated variant call set release version 3 as a reference panel. RESULTS: After genotyping and imputation quality control procedures, data were available for 15 non-HLA single-nucleotide polymorphisms in 1,024 cases and 6,348 controls. We confirmed the known markers ANKRD55 (meta-analysis odds ratio [OR] 0.80; P = 2.8 × 10(-13) ) and BLK (OR 1.13; P = 7.0 × 10(-6) ) and identified new and specific markers of anti-CCP-negative RA (prolactin [PRL] [OR 1.13; P = 2.1 × 10(-6) ] and NFIA [OR 0.85; P = 2.5 × 10(-6) ]). Neither of these loci is associated with other common, complex autoimmune diseases. CONCLUSION: Anti-CCP-negative RA and anti-CCP-positive RA are genetically different disease subsets that only partially share susceptibility factors. Genetic polymorphisms located near the PRL and NFIA genes represent examples of genetic susceptibility factors specific for anti-CCP-negative RA

How do men in the United Kingdom decide to dispose of banked sperm following cancer treatment?

Current policy in the UK recommends that men bank sperm prior to cancer treatment, but very few return to use it for reproductive purposes or agree to elective disposal even when their fertility recovers and their families are complete. We assessed the demographic, medical and psychological variables that influence the decision to dispose by contacting men (n = 499) who banked sperm more than five years previously, and asked them to complete questionnaires about their views on sperm banking, fertility and disposal. From 193 responses (38.7% response rate), 19 men (9.8%) requested disposal within four months of completing the questionnaire. Compared with men who wanted their sperm to remain in storage, they were significantly more confident that their fertility had recovered (OR = 1.78, 95% CI = 1.05-3.03, p = 0.034), saw fertility monitoring (semen analysis) as less important (OR = 0.61, 95% CI = 0.39-0.94, p = 0.026), held more positive attitudes to disposal (OR = 5.71, 95% CI = 2.89-11.27, p < 0.001), were more likely to have experienced adverse treatment side-effects (OR = 4.37, CI = 1.61-11.85, p = 0.004) and had less desire for children in the future (OR = 0.41, 95% CI = 0.26-0.64, p < 0.001). Information about men's reasons to dispose of banked sperm may be helpful in devising new strategies to encourage men to engage with sperm banking clinics and make timely decisions about the fate of their samples

Negative-feedback regulation of FGF signalling by DUSP6/MKP-3 is driven by ERK1/2 and mediated by Ets factor binding to a conserved site within the DUSP6/MKP-3 gene promoter

DUSP6 (dual-specificity phosphatase 6), also known as MKP-3 [MAPK (mitogen-activated protein kinase) phosphatase-3] specifically inactivates ERK1/2 (extracellular-signal-regulated kinase 1/2) in vitro and in vivo. DUSP6/MKP-3 is inducible by FGF (fibroblast growth factor) signalling and acts as a negative regulator of ERK activity in key and discrete signalling centres that direct outgrowth and patterning in early vertebrate embryos. However, the molecular mechanism by which FGFs induce DUSP6/MKP-3 expression and hence help to set ERK1/2 signalling levels is unknown. In the present study, we demonstrate, using pharmacological inhibitors and analysis of the murine DUSP6/MKP-3 gene promoter, that the ERK pathway is critical for FGF-induced DUSP6/MKP-3 transcription. Furthermore, we show that this response is mediated by a conserved binding site for the Ets (E twenty-six) family of transcriptional regulators and that the Ets2 protein, a known target of ERK signalling, binds to the endogenous DUSP6/MKP-3 promoter. Finally, the murine DUSP6/MKP-3 promoter coupled to EGFP (enhanced green fluorescent protein) recapitulates the specific pattern of endogenous DUSP6/MKP-3 mRNA expression in the chicken neural plate, where its activity depends on FGFR (FGF receptor) and MAPK signalling and an intact Ets-binding site. These findings identify a conserved Ets-factor-dependent mechanism by which ERK signalling activates DUSP6/MKP-3 transcription to deliver ERK1/2-specific negative-feedback control of FGF signalling

Why don't some men with banked sperm respond to letters about their stored samples?

Long-term storage of banked sperm, especially when it is not needed, for reproductive purposes, is costly and poses practical problems for sperm banks. For sperm banks to function efficiently, men must understand the implications of unnecessary storage, and make timely decisions about disposal of their own samples. Men who bank sperm prior to cancer treatment are routinely offered follow-up consultations to test their fertility, update consent and, where necessary, expedite referral for Assisted Conception. Yet sperm banks report that men do not respond to letters, suggesting samples are stored needlessly. We conducted semi-structured interviews with six men with a history of not responding to letters, to document reasons for non-response. Interviews were transcribed and analysed using Interpretive Phenomenological Analysis. Men's reasons for not responding are a complex interplay between past, present and future perspectives. In terms of their past, information is important on diagnosis, because men must understand that fertility can change after treatment. Present and future concerns focus on fears of being told fertility has not recovered and being pressured to dispose of banked sperm. The challenge is to devise invitation letters that address men's concerns while offering them tangible benefits and peace of mind

Safety of disinvestment in mid- to late-term follow-up post primary hip and knee replacement: The UK SAFE evidence synthesis and recommendations

Background: Joint replacement surgery has revolutionised the management of degenerative joint disease. Increasing demand for surgery and post-surgical reviews has overwhelmed orthopaedic services and, consequently, many centres have reduced or stopped follow-up. Such disinvestment is without an evidence base and raises questions regarding the consequences to patients.Objectives: To produce evidence- and consensus-based recommendations as to how, when and on whom follow-up should be conducted. Our research question was ‘Is it safe to disinvest in mid- to late-term follow-up of hip and knee replacement?’.MethodsThe study comprised three complementary evidence synthesis work packages to inform a final consensus process. Work package 1 was a systematic review of the clinical effectiveness and cost-effectiveness literature. Work package 2 used routine national data sets (i.e. the Clinical Practice Research Datalink–Hospital Episode Statistics, Hospital Episode Statistics–National Joint Registry–patient-reported outcome measures) to identify pre, peri and postoperative predictors of mid- to late-term revision, and prospective data from 560 patients to understand how patients present for revision surgery. Work package 3 used a Markov model to simulate the survival, health-related quality of life and NHS costs of patients following hip or knee replacement surgery. Finally, evidence from work packages 1–3 informed a face-to-face consensus panel, which involved 32 stakeholders.Results: Our overarching statements are as follows: (1) these recommendations apply to post primary hip and knee replacement follow-up; (2) the 10-year time point in these recommendations is based on a lack of robust evidence beyond 10 years; and (3) in these recommendations, the term ‘complex cases’ refers to individual patient and surgical factors that may increase the risk of replacement failure. Our recommendations are as follows: for Orthopaedic Data Evaluation Panel 10A* (ODEP-10A*) minimum implants, it is safe to disinvest in routine follow-up from 1 to 10 years post non-complex hip and knee replacement provided that there is rapid access to orthopaedic review; (2) for ODEP-10A* minimum implants in complex cases or non-ODEP-10A* minimum implants, periodic follow-up post hip and knee replacement may be required from 1 to 10 years; (3) at 10 years post hip and knee replacement, clinical and radiographic evaluation is recommended; and (4) after 10 years post hip and knee replacement, frequency of further follow-up should be based on the 10-year assessment (note that ongoing rapid access to orthopaedic review is still required) [Stone M, Smith L, Kingsbury S, Czoski-Murray C, Judge A, Pinedo-Villanueva R, et al. Evidence-based follow-up recommendations following primary hip and knee arthroplasty (UK SAFE). Orthop Proc 2020;102–B:13. https://doi.org/10.1302/1358-992X.2020.5.013].Limitations: The current absence of data beyond 10 years restricted the evidence base.Conclusions: For ODEP-10A* prostheses, the UK SAFE programme demonstrated that it is safe to disinvest in routine follow-up in the 1- to 10-year period after non-complex hip and knee replacement. At 10 years, clinical and radiographic review is recommended. Complex cases, implants not meeting the 10A* criteria and follow-up after revision surgery are not covered by this recommendation.Future work: The evidence base for follow-up after 10 years requires further evaluation. Further work should establish the most clinically effective and cost-effective model of delivering a rapid access service and evaluate alternative models for follow-up services, such as virtual clinics. Finally, the needs and outcomes of patients who are symptomatic but do not have appropriate follow-up should be investigated