Duchenne muscular dystrophy is a devastating neuromuscular disorder characterized by the loss of dystrophin, inevitably leading to cardiomyopathy. Despite publications on prophylaxis and treatment with cardiac medications to mitigate cardiomyopathy progression, gaps remain in the specifics of medication initiation and optimization.

This document is an expert opinion statement, addressing a critical gap in cardiac care for Duchenne muscular dystrophy. It provides thorough recommendations for the initiation and titration of cardiac medications based on disease progression and patient response. Recommendations are derived from the expertise of the Advance Cardiac Therapies Improving Outcomes Network and are informed by established guidelines from the American Heart Association, American College of Cardiology, and Duchenne Muscular Dystrophy Care Considerations. These expert-derived recommendations aim to navigate the complexities of Duchenne muscular dystrophy-related cardiac care.

Comprehensive recommendations for initiation, titration, and optimization of critical cardiac medications are provided to address Duchenne muscular dystrophy-associated cardiomyopathy.

The management of Duchenne muscular dystrophy requires a multidisciplinary approach. However, the diversity of healthcare providers involved in Duchenne muscular dystrophy can result in variations in cardiac care, complicating treatment standardization and patient outcomes. The aim of this report is to provide a roadmap for managing Duchenne muscular dystrophy-associated cardiomyopathy, by elucidating timing and dosage nuances crucial for optimal therapeutic efficacy, ultimately improving cardiac outcomes, and improving the quality of life for individuals with Duchenne muscular dystrophy.

This document seeks to establish a standardized framework for cardiac care in Duchenne muscular dystrophy, aiming to improve cardiac prognosis.

Patients with unbalanced common atrioventricular canal can be difficult to manage. Surgical planning often depends on pre-operative echocardiographic measurements. We aimed to determine the added utility of cardiac MRI in predicting successful biventricular repair in common atrioventricular canal.

We conducted a retrospective cohort study of children with common atrioventricular canal who underwent MRI prior to repair. Associations between MRI and echocardiographic measures and surgical outcome were tested using logistic regression, and models were compared using area under the receiver operator characteristic curve.

We included 28 patients (median age at MRI: 5.2 months). The optimal MRI model included the novel end-diastolic volume index (using the ratio of left ventricular end-diastolic volume to total end-diastolic volume) and the left ventricle–right ventricle angle in diastole (area under the curve 0.83, p = 0.041). End-diastolic volume index ≤ 0.18 and left ventricle–right ventricle angle in diastole ≤ 72° yield a sensitivity of 83% and specificity of 81% for successful biventricular repair. The optimal multimodality model included the end-diastolic volume index and the echocardiographic atrioventricular valve index with an area under the curve of 0.87 (p = 0.026).

Cardiac MRI can successfully predict successful biventricular repair in patients with unbalanced common atrioventricular canal utilising the end-diastolic volume index alone or in combination with the MRI left ventricle–right ventricle angle in diastole or the echocardiographic atrioventricular valve index. A prospective cardiac MRI study is warranted to better define the multimodality characteristic predictive of successful biventricular surgery.

The National Institute for Health and Care Excellence (NICE) interventional procedures programme (IPP) issues guidance on the safety and efficacy of new interventional procedures (IPS). The IPP considers a range of evidence from randomized controlled trials (RCTs) to case series to make final recommendations. Real-world evidence (RWE) can provide additional information on long-term outcomes and patient population characteristics that are not easily captured by RCTs. This study explores the impact of RWE in complementing RCTs on long-term safety and efficacy for national guidance development.

We review the impact of RWE in IPS guidance (IPG) updates and change in guidance recommendations in the last 5 years. This is done by analyzing NICE guidance updates and supporting evidence. A range of RWE was considered in the supporting evidence, for example, registries and clinical audits.

The addition of RWE evidence to IPP guidance update has led to significant changes in the recommendations. For example, in one recent IPG, standard arrangements recommendation based on short-term RCT evidence was changed to a research recommendation when RWE showed an increase in long-term adverse effects. In another recent IPG update, special arrangements recommendation based on short-term RCT evidence was changed to a research recommendation when RWE reported long-term inferior efficacy and safety for the new intervention compared to current standard of care. A complete overview of results of the last 5 years will also be presented at the meeting.

These findings indicate that increased availability of RWE in HTA has the potential to impact national guidance recommendations. In addition, it shows how RWE can fill the evidence base gaps created by RCTs. Such data can confirm or contradict the findings of RCTs, or generate questions needing further research, or support disinvestment in non-effective technologies.

Accounts of patient experiences are increasingly used in health technology assessment (HTA) processes. However, we know little about their impact on the decision-making process. This study aims to assess the level and the type of impact of patient input to highly specialised technologies (HSTs) and interventional procedures (IPs) guidance at the National Institute for Health and Care Excellence (NICE).

A questionnaire was developed to capture quantitative and qualitative data on the amount and type of impact of patient input into NICE HTAs. It was completed by committee members of the guidance-producing programs after a discussion of the considered topics. The data were analyzed by topic and overall, for each program, and compared across programs.

Patient input was assessed on ten pieces of HST guidance published between January 2015 and November 2019, and on twenty-six pieces of IP guidance scoped between February 2016 and October 2018. A total of 96 responses were collected for HST and 440 for IP. The level of impact of patient input was higher for HST than for IP. For HST, no respondents stated that it had no impact, whereas in IP, 35 percent of respondents did. The most common types of impact found for HST and IP were that it helped interpret the other evidence and that it provided new evidence.

The impact of patient input is not necessarily explicit in changing recommendations, but it provides context, reassurance, and new information to the committee for the decision-making process in HTAs.

Secure forensic mental health services treat patients with high rates of treatment-resistant psychoses. High rates of obesity and medical comorbidities are common. Population-based studies have identified high-risk groups in the event of SARS-CoV-2 infection, including those with problems such as obesity, lung disease and immune-compromising conditions. Structured assessment tools exist to ascertain the risk of adverse outcome in the event of SARS-CoV-2 infection.

To assess risk of adverse outcome in the event of SARS-CoV-2 infection in a complete population of forensic psychiatry patients using structured assessment tools.

All patients of a national forensic mental health service (n = 141) were rated for risk of adverse outcome in the event of SARS-CoV-2 infection, using two structured tools, the COVID-Age tool and the COVID-Risk tool.

We found high rates of relevant physical comorbidities. Mean chronological age was 45.5 years (s.d. = 11.4, median 44.1), mean score on the COVID-Age tool was 59.1 years (s.d. = 19.4, median 58.0), mean difference was 13.6 years (s.d. = 15.6), paired t = 10.9, d.f. = 140, P < 0.001. Three patients (2.1%) were chronologically over 70 years of age, compared with 43 (30.5%) with a COVID-Age over 70 (χ2 = 6.99, d.f. = 1, P = 0.008, Fisher's exact test P = 0.027).

Patients in secure forensic psychiatric services represent a high-risk group for adverse outcomes in the event of SARS-COV-2 infection. Population-based guidance on self-isolation and other precautions based on chronological age may not be sufficient. There is an urgent need for better physical health research and treatment in this group.

Dialysis patients may not have access to conventional renal replacement therapy (RRT) following disasters. We hypothesized that improvised renal replacement therapy (ImpRRT) would be comparable to continuous renal replacement therapy (CRRT) in a porcine acute kidney injury model.

Following bilateral nephrectomies and 2 hours of caudal aortic occlusion, 12 pigs were randomized to 4 hours of ImpRRT or CRRT. In the ImpRRT group, blood was circulated through a dialysis filter using a rapid infuser to collect the ultrafiltrate. Improvised replacement fluid, made with stock solutions, was infused pre-pump. In the CRRT group, commercial replacement fluid was used. During RRT, animals received isotonic crystalloids and norepinephrine.

There were no differences in serum creatinine, calcium, magnesium, or phosphorus concentrations. While there was a difference between groups in serum potassium concentration over time (P < 0.001), significance was lost in pairwise comparison at specific time points. Replacement fluids or ultrafiltrate flows did not differ between groups. There were no differences in lactate concentration, isotonic crystalloid requirement, or norepinephrine doses. No difference was found in electrolyte concentrations between the commercial and improvised replacement solutions.

The ImpRRT system achieved similar performance to CRRT and may represent a potential option for temporary RRT following disasters.

The IDEAL (Idea, Development, Exploration, Assessment, Learning) Framework measures the maturity of evidence base behind surgical innovation. The NICE Interventional Procedures (IP) programme issues guidance for the United Kingdom National Health Service (NHS) on use of surgical innovation. One of four recommendations can be made: (a) standard arrangements, (b) special arrangements, (c) research only, and (d) do not use. This study aimed to investigate whether the recommendation of NICE IP guidance corresponded with the stage of innovation as determined by IDEAL, thus IDEAL's role in informing future guidance production.

A retrospective sample of 103 pieces of guidance issued between 2015 and 2018 was analysed. One researcher examined the evidence base and determined the corresponding stage of the IDEAL framework, numbered 1, 2, 2a, 3 and 4. The primary outcome measure was the association between stage of evidence on IDEAL framework and the recommendation of published NICE IP guidance.

There were twenty-one (20 percent), thirty-three (32 percent), three (3 percent), forty (39 percent) and six (6 percent) procedures at IDEAL stages 1, 2, 2a, 3 and 4, respectively. Of those at stage 1 (idea), 48 percent were given research only arrangements, 43 percent special arrangements, and 10 percent standard. Many of the procedures at stages 2 (development) and 2a (exploration) were given standard arrangements (39 percent and 67 percent respectively). Forty-three percent of stage 3 (assessment) and 67 percent of stage 4 (learning) guidance were identified standard. At stage 4 none were given a ‘research only’ recommendation.

Procedures given ‘standard’ arrangements guidance are more likely have a mature and robust evidence base as determined by IDEAL. Those with limited evidence are more likely to be given a more cautious ‘research only’ guidance. Routine use of this framework could help inform future guidance production however cannot replace the decision-making function of the NICE committee which also involves patient experiences, population characteristics, risk of serious safety events, and equity issues.

Failure of the Fontan circulation is not a well-understood clinical phenomena.For some patients, a gradual increase in pulmonary vascular resistance (PVR) and structural changes in the pulmonary artery may be an important causative factor. To further investigate this issue, we employed optical coherence tomography (OCT) to evaluate structural changes within the pulmonary arteries of Fontan patients and compared to those with a normal pulmonary circulation.

Pulmonary artery OCT was performed, without complications, in 12 Fontan and 11 control patients. Wall thickness and wall:vessel cross-sectional area (CSA) ratio were calculated after image acquisition, using digital planimetry.

There was no difference in wall thickness between both groups. Median wall thickness for Fontan patients was 0.12 mm (IQR, 0.10–0.14) and for controls was 0.11 mm (IQR, 0.10–0.12; p = 0.62). Wall:vessel CSA ratio for Fontan patients was 0.13 (IQR, 0.12–0.16) and for controls was 0.13 (IQR, 0.11–0.15) (p = 0.73). There was no association between wall thickness and ventricle morphology, age at catheterisation, age at Fontan, years since Fontan completion, pulmonary artery pressure, and PVR. The vessel media was more readily visualised in control patients.

OCT of the pulmonary arteries in Fontan patients is safe and feasible. Our OCT findings suggest that during childhood, pulmonary artery wall dimensions are normal in Fontan children with reassuring hemodynamics. Further evaluation of Fontan patients with abnormal hemodynamics and serial evaluation into adulthood are required to conclude on the utility of OCT for identifying early pulmonary artery structural changes.

Cognitive behavioral therapy (CBT) is an effective treatment for many patients suffering from major depressive disorder (MDD), but predictors of treatment outcome are lacking, and little is known about its neural mechanisms. We recently identified longitudinal changes in neural correlates of conscious emotion regulation that scaled with clinical responses to CBT for MDD, using a negative autobiographical memory-based task.

We now examine the neural correlates of emotional reactivity and emotion regulation during viewing of emotionally salient images as predictors of treatment outcome with CBT for MDD, and the relationship between longitudinal change in functional magnetic resonance imaging (fMRI) responses and clinical outcomes. Thirty-two participants with current MDD underwent baseline MRI scanning followed by 14 sessions of CBT. The fMRI task measured emotional reactivity and emotion regulation on separate trials using standardized images from the International Affective Pictures System. Twenty-one participants completed post-treatment scanning. Last observation carried forward was used to estimate clinical outcome for non-completers.

Pre-treatment emotional reactivity Blood Oxygen Level-Dependent (BOLD) signal within hippocampus including CA1 predicted worse treatment outcome. In contrast, better treatment outcome was associated with increased down-regulation of BOLD activity during emotion regulation from time 1 to time 2 in precuneus, occipital cortex, and middle frontal gyrus.

CBT may modulate the neural circuitry of emotion regulation. The neural correlates of emotional reactivity may be more strongly predictive of CBT outcome. The finding that treatment outcome was predicted by BOLD signal in CA1 may suggest overgeneralized memory as a negative prognostic factor in CBT outcome.

Emergency physicians play an important role in providing care at the end-of-life as well as identifying patients who may benefit from a palliative approach. Several studies have shown that emergency medicine (EM) residents desire further training in palliative care. We performed a national cross-sectional survey of EM program directors. Our primary objective was to describe the number of Canadian postgraduate EM training programs with palliative and end-of-life care curricula.

A 15-question survey in English and French was sent by email to all program directors of both the Canadian College of Family Physicians emergency medicine (CCFP(EM)) and the Royal College of Physicians and Surgeons of Canada emergency medicine (RCPSC-EM) postgraduate training programs countrywide using FluidSurveys™ with a modified Dillman approach.

We received a total of 26 responses from the 36 (response rate = 72.2%) EM postgraduate programs in Canada. Ten out of 26 (38.5%) programs had a structured educational program pertaining to palliative and end-of-life care. Lectures or seminars were the exclusive choice to teach content. Clinical palliative medicine rotations were mandatory in one out of 26 (3.8%) programs. The top two barriers to implementation of palliative and end-of-life care curricula were lack of time (84.6%) and curriculum development concerns (80.8%).

Palliative and end-of-life care training within EM has been identified as an area of need. This cross-sectional survey demonstrates that a minority of Canadian EM programs have palliative and end-of-life care curricula. It will be important for all EM training programs, RCPSC-EM and CCFP(EM), in Canada, to develop an agreed upon set of competencies and to structure their curricula around them.

The National Institute of Health and Care Excellence (NICE) assesses the efficacy and safety of interventional procedures for use in the National Health Service (NHS). Since 2006, NICE's Public Involvement Programme (PIP) has obtained ‘patient commentary’ to inform committee decisions, using a questionnaire asking patients about their experience of the procedure including benefits, disadvantages and side effects. Commentary is considered by the committee alongside other evidence. The PIP has piloted a project to: capture the impact of the patient commentary on the committee's decision-making; explore patterns of impact; and identify criteria that indicate when patient commentary may not be required.

The pilot included all interventional procedures guidance started between February 2016 and February 2017. Committee members’ views were captured using a form completed whenever patient commentary was considered. Responses were anonymized, entered into an electronic system, analyzed, and correlated against ‘committee comments’ in the published guidance. After twelve months, there was an unrepresentatively narrow spread of conditions, and most topics were updating previously published guidance rather than novel topics. The pilot was therefore extended by six months.

Patient commentary commonly had an impact on decision-making; however, no discernible patterns have yet been identified, nor criteria for when it may not be required. Key findings were: (i) patient commentary is equally useful for guidance updates as novel guidance, and (ii) interpretation and assessment of ‘impact’ varied across committee members but the majority agreed it reinforced the other evidence.

Patient commentary has a measurable impact on committee decision-making. Very occasionally it provides new evidence and routinely provides reassurance that the published evidence is substantiated by real-world patient opinion. Measuring the impact of commentary seems to have raised its profile, with more committee comments about patient issues included in guidance during the pilot than in preceding years. The project needs to be extended to identify which procedures are least likely to benefit from patient commentary and why.