Search

BACKGROUND: Chest low-dose computed tomography (LDCT) is a promising technology for population-based screening because it is non-invasive, relatively inexpensive, associated with low radiation and highly sensitive to lung cancer. To improve the cost-effectiveness of lung cancer screening, simultaneous screening for other diseases could be considered. This systematic review was conducted to analyse studies that published evidence on the cost-effectiveness of chest LDCT screening programs for different diseases.METHODS: Scopus and PubMed were searched for English publications (1 January 2011-22 July 2022) using search terms related to screening, computed tomography and cost-effectiveness. An additional search specifically searched for the cost-effectiveness of screening for lung cancer, chronic obstructive pulmonary disease or cardiovascular disease. Included publications should present a full health economic evaluation of population screening with chest LDCT. The extracted data included the disease screened for, model type, country context of screening, inclusion of comorbidities or incidental findings, incremental costs, incremental effects and the resulting cost-effectiveness ratio amongst others. Reporting quality was assessed using the 2022 Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist.RESULTS: The search yielded 1799 unique papers, of which 43 were included. Most papers focused on lung cancer screening (n = 40), and three were on coronary calcium scoring. Microsimulation was the most commonly applied modelling type (n = 16), followed by life table analysis (n = 10) and Markov cohort models (n = 10). Studies reflected the healthcare context of the US (n = 15), Canada (n = 4), the UK (n = 3) and 13 other countries. The reported incremental cost-effectiveness ratio ranged from US$10,000 to US$90,000/quality-adjusted life year (QALY) for lung cancer screening compared to no screening and was US$15,900/QALY-US$45,300/QALY for coronary calcium scoring compared to no screening.DISCUSSION: Almost all health economic evaluations of LDCT screening focused on lung cancer. Literature regarding the health economic benefits of simultaneous LDCT screening for multiple diseases is absent. Most studies suggest LDCT screening is cost-effective for current and former smokers aged 55-74 with a minimum of 30 pack-years of smoking history. Consequently, more evidence on LDCT is needed to support further cost-effectiveness analyses. Preferably evidence on simultaneous screening for multiple diseases is needed, but alternatively, on single-disease screening.REGISTRATION OF SYSTEMATIC REVIEW: Prospective Register of Ongoing Systematic Reviews registration CRD42021290228 can be accessed https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=290228 .

Objectives: Molecular biomarker tests can inform the clinical management of genomic heterogeneous hematological malignancies, yet their availability in routine care largely depends on the supporting health economic evidence. This study aims to systematically review the economic evidence for recent molecular biomarker tests in hematological malignancies. Methods: We conducted a systematic search in five electronic databases for studies published between January 2010 and October 2020. Publications were independently screened by two reviewers. Clinical study characteristics, economic methodology, and results were extracted, and reporting quality was assessed. Results: Fourteen studies were identified, of which half (n = 7; 50%) were full economic evaluations examining both health and economic outcomes. Studies were predominantly conducted in a first-line treatment setting (n = 7; 50%) and adopted a non-lifetime time horizon to measure health outcomes and costs (n = 7; 50%). Five studies reported that companion diagnostics for associated therapies were likely cost-effective for acute myeloid leukemia, chronic myeloid leukemia, diffuse large B-cell lymphoma, and multiple myeloma. Four studies suggested molecular biomarker tests for treatment monitoring in chronic myeloid leukemia were likely cost-saving. Conclusions: Although there is initial confirmation of the promising health economic results, the present research for molecular biomarker tests in hematological malignancies is sparse with many applications of technological advances yet to be evaluated.

Objective To investigate medication prescription patterns among children with JIA, including duration, sequence and reasons for medication discontinuation. Methods This study is a single-centre, retrospective analysis of prospective data from the electronic medical records of JIA patients receiving systemic therapy aged 0–18 years between 1 April 2011 and 31 March 2019. Patient characteristics (age, gender, JIA subtype) and medication prescriptions were extracted and analysed using descriptive statistics, Sankey diagrams and Kaplan–Meier survival methods. Results Over a median of 4.2 years follow-up, the 20 different medicines analysed were prescribed as monotherapy (n = 15) or combination therapy (n = 48 unique combinations) among 236 patients. In non-systemic JIA, synthetic DMARDs were prescribed to almost all patients (99.5%), and always included MTX. In contrast, 43.9% of non-systemic JIA patients received a biologic DMARD (mostly adalimumab or etanercept), ranging from 30.9% for oligoarticular persistent ANA-positive JIA, to 90.9% for polyarticular RF-positive JIA. Among systemic JIA, 91.7% received a biologic DMARD (always including anakinra). When analysing medication prescriptions according to their class, 32.6% involved combination therapy. In 56.8% of patients, subsequent treatment lines were initiated after unsuccessful first-line treatment, resulting in 68 unique sequences. Remission was the most common reason for DMARD discontinuation (44.7%), followed by adverse events (28.9%) and ineffectiveness (22.1%). Conclusion This paper reveals the complexity of pharmacological treatment in JIA, as indicated by: the variety of mono- and combination therapies prescribed, substantial variation in medication prescriptions between subtypes, most patients receiving two or more treatment lines, and the large number of unique treatment sequences.

OBJECTIVES: Care for JIA patients has been transformed in the biologics era; however, biologics carry important (although rare) risks and are costly. Flares after biological withdrawal are seen frequently, yet there is little clinical guidance to identify which patients in clinical remission can safely have their biologic discontinued (by stopping or tapering). We examined what characteristics of the child or their context are important to pediatric rheumatologists when making the decision to discuss withdrawal of biologics.METHODS: We conducted a survey including a best-worst scaling (BWS) exercise in pediatric rheumatologists who are part of the UCAN CAN-DU network to assess the relative importance of 14 previously identified characteristics. A balanced incomplete block design was used to generate choice tasks. Respondents evaluated 14 choice sets of 5 characteristics of a child with JIA and identified for each set which was the most and least important in the decision to offer withdrawal. Results were analyzed using conditional logit regression.RESULTS: Fifty-one (out of 79) pediatric rheumatologists participated (response rate 65%). The three most important characteristics were how challenging it was to achieve remission, history of established joint damage, and time spent in remission. The three least important characteristics were history of temporomandibular joint involvement, accessibility of biologics, and the patient's age.CONCLUSIONS: These findings give quantitative insight about factors important to pediatric rheumatologists' decision-making about biologic withdrawal. In addition to high quality clinical evidence, further research is needed to understand the perspective of patients and families to inform shared decision-making about biologic withdrawal for JIA patients with clinically inactive disease. Key Points ● What is already known on this topic-there is limited clinical guidance for pediatric rheumatologists in making decisions about biologic withdrawal for patients with juvenile idiopathic arthritis who are in clinical remission. ● What this study adds-this study quantitatively examined what characteristic of the child in clinical remission, or of their context, are most important to pediatric rheumatologists in deciding whether to offer withdrawal of biologics. ● How this study might affect research, practice or policy-understanding of these characteristics can provide useful information to other pediatric rheumatologists in making their decisions, and may guide areas to focus on for future research.

Research focusing on timely diagnosis and treatment of colorectal cancer is necessary to improve outcomes for people with cancer. Previous attempts to consolidate research on time to diagnosis and treatment have noted varied methodological approaches and quality, limiting the comparability of findings. This systematic review was conducted to comprehensively assess the scope of methodological issues in this field and provide recommendations for future research. Eligible articles had to assess the role of any interval up to treatment, on any outcome in colorectal cancer, in English, with no limits on publication time. Four databases were searched (Ovid Medline, EMBASE, EMCARE and PsycInfo). Papers were screened by two independent reviewers using a two-stage process of title and abstract followed by full text review. In total, 130 papers were included and had data extracted on specific methodological and statistical features. Several methodological problems were identified across the evidence base. Common issues included arbitrary categorisation of intervals (n = 107, 83%), no adjustment for potential confounders (n = 65, 50%), and lack of justification for included covariates where there was adjustment (n = 40 of 65 papers that performed an adjusted analysis, 62%). Many articles introduced epidemiological biases such as immortal time bias (n = 37 of 80 papers that used survival as an outcome, 46%) and confounding by indication (n = 73, 56%), as well as other biases arising from inclusion of factors outside of their temporal sequence. However, determination of the full extent of these problems was hampered by insufficient reporting. Recommendations include avoiding artificial categorisation of intervals, ensuring bias has not been introduced due to out-of-sequence use of key events and increased use of theoretical frameworks to detect and reduce bias. The development of reporting guidelines and domain-specific risk of bias tools may aid in ensuring future research can reliably contribute to recommendations regarding optimal timing and strengthen the evidence base.

BACKGROUND: The early COVID-19 literature suggested that people with cancer may be more likely to be infected with SARS-CoV-2 or develop COVID-19 than people without cancer, due to increased health services contact and/or immunocompromise. While some studies were criticised due to small patient numbers and methodological limitations, they created or reinforced concerns of clinicians and people with cancer. These risks are also important in COVID-19 vaccine prioritisation decisions. We performed a systematic review to critically assess and summarise the early literature. METHODS AND FINDINGS: We conducted a systematic search of Medline/Embase/BioRxiv/MedRxiv/SSRN databases including peer-reviewed journal articles, letters/commentaries, and non-peer-reviewed pre-print articles for 1 January-1 July 2020. The primary endpoints were diagnosis of COVID-19 and positive SARS-CoV-2 test. We assessed risk of bias using a tool adapted from the Newcastle-Ottawa Scale. Twelve studies were included in the quantitative synthesis. All four studies of COVID-19 incidence (including 24,181,727 individuals, 125,649 with pre-existing cancer) reported that people with cancer had higher COVID-19 incidence rates. Eight studies reported SARS-CoV-2 test positivity for > 472,000 individuals, 48,370 with pre-existing cancer. Seven of these studies comparing people with any and without cancer, were pooled using random effects [pooled odds ratio 0.91, 95 %CI: 0.57-1.47; unadjusted for age, sex, or comorbidities]. Two studies suggested people with active or haematological cancer had lower risk of a positive test. All 12 studies had high risk of bias; none included universal or random COVID-19/SARS-CoV-2 testing. CONCLUSIONS: The early literature on susceptibility to SARS-CoV-2/COVID-19 for people with cancer is characterised by pervasive biases and limited data. To provide high-quality evidence to inform decision-making, studies of risk of SARS-CoV-2/COVID-19 for people with cancer should control for other potential modifiers of infection risk, including age, sex, comorbidities, exposure to the virus, protective measures taken, and vaccination, in addition to stratifying analyses by cancer type, stage at diagnosis, and treatment received.

Background: Few studies have examined pediatric rheumatologists’ approaches to treatment decision making for biologic therapy for patients with juvenile idiopathic arthritis (JIA). This study presents the qualitative research undertaken to support the development of a Best–Worst Scaling (BWS) survey for tapering in JIA. The study objectives were to (1) describe the treatment decision-making process of pediatric rheumatologists to initiate and taper biologics; and (2) select attributes for a BWS survey. Methods: Pediatric rheumatologists across Canada were recruited to participate in interviews using purposeful sampling. Interviews were conducted until saturation was achieved. Interview recordings were transcribed verbatim and transcripts were analyzed using deductive thematic analysis. Initial codes were organized into themes and subthemes using an iterative process. Attributes for the BWS survey were developed from these themes and a literature review was conducted in parallel to inform survey development. Further refinement of the attributes was done through consultation with the research team. Results: Five pediatric rheumatologists participated in the interviews. Shared decision making was part of the approach to initiating and tapering biologics in their practice. Tapering approaches differed; some pediatric rheumatologists preferred to stop biologics immediately, while others tapered by reducing dose and/or increasing the dose interval over time. A total of 14 attributes were developed for the BWS. Thirteen attributes were selected from the themes that emerged from the qualitative interviews and one attribute was included after review with the research team. Attributes related to patient characteristics included JIA subtype, time in remission, history or presence of joint damage or erosive disease, how challenging it was to achieve remission, and history of flares. Contextual attributes included accessibility of biologics and willingness to taper biologics. Conclusion: This study contributes to the limited literature on pediatric rheumatologists’ approaches to treatment decision making for biologics in JIA and identifies attributes that affect the decision to both initiate and taper. Further research is planned to implement the BWS survey to understand the importance of the attributes identified. Additional investigation is required to determine if these characteristics align with patient and parent preferences.

Few studies have examined pediatric rheumatologists' approaches to treatment decision making for biologic therapy for patients with juvenile idiopathic arthritis (JIA). This study presents the qualitative research undertaken to support the development of a Best-Worst Scaling (BWS) survey for tapering in JIA. The study objectives were to (1) describe the treatment decision-making process of pediatric rheumatologists to initiate and taper biologics; and (2) select attributes for a BWS survey.Pediatric rheumatologists across Canada were recruited to participate in interviews using purposeful sampling. Interviews were conducted until saturation was achieved. Interview recordings were transcribed verbatim and transcripts were analyzed using deductive thematic analysis. Initial codes were organized into themes and subthemes using an iterative process. Attributes for the BWS survey were developed from these themes and a literature review was conducted in parallel to inform survey development. Further refinement of the attributes was done through consultation with the research team.Five pediatric rheumatologists participated in the interviews. Shared decision making was part of the approach to initiating and tapering biologics in their practice. Tapering approaches differed; some pediatric rheumatologists preferred to stop biologics immediately, while others tapered by reducing dose and/or increasing the dose interval over time. A total of 14 attributes were developed for the BWS. Thirteen attributes were selected from the themes that emerged from the qualitative interviews and one attribute was included after review with the research team. Attributes related to patient characteristics included JIA subtype, time in remission, history or presence of joint damage or erosive disease, how challenging it was to achieve remission, and history of flares. Contextual attributes included accessibility of biologics and willingness to taper biologics.This study contributes to the limited literature on pediatric rheumatologists' approaches to treatment decision making for biologics in JIA and identifies attributes that affect the decision to both initiate and taper. Further research is planned to implement the BWS survey to understand the importance of the attributes identified. Additional investigation is required to determine if these characteristics align with patient and parent preferences.

Over half of patients with lung cancer are diagnosed at a stage when curative treatment is not possible, suggesting an earlier diagnosis could improve outcomes. This comprehensive overview summarises the evidence on 1) times to diagnosis and treatment, 2) their impact on patient outcomes, 3) risk factors and 4) interventions to reduce time intervals, and 5) key methodological issues in such studies. Eligible articles were relevant systematic or scoping reviews and meta-analyses, searched via PubMed, Embase, Web of Science, and Cochrane Library; published from database inception to 6 August 2020 (PROSPERO identifier: CRD42020203530). A total of 18 systematic and scoping reviews were included. Times to diagnosis and treatment significantly varied and were often longer than recommended in international guidelines. Results regarding the impact of time intervals on survival or tumour stage indicated mixed associations (positive, negative, or no); in each review, however, more studies reported either no or negative association. Risk factors were considerable, categorized at the disease, patient, healthcare provider and system levels. Interventions including fast-access diagnosis programs, patient navigation and multidisciplinary strategies were effective in reducing times to diagnosis and treatment. Methodological issues included large variations in interval definitions and summary measures, lack of addressing an important potential source of bias-the "waiting time paradox"-and few studies of trends over time of these intervals. The current evidence indicates that patients with lung cancer experience diagnosis and treatment delays given guidelines' recommendations, but there are inconsistent findings about the association between times to diagnosis and treatment and patient outcomes. This is partially due to variations in definitions of time intervals, and limitations in analytic approaches that fail to account for a potential waiting time paradox. The identified risk factors and effective interventions demonstrate the potential for improvements in addressing diagnostic and treatment delays, regionally and globally.

Background Early reports suggested that COVID-19 patients with cancer were at higher risk of COVID-19-related death. We conducted a systematic review with risk of bias assessment and synthesis of the early evidence on the risk of COVID-19-related death for COVID-19 patients with and without cancer. Methods and Findings We searched Medline/Embase/BioRxiv/MedRxiv/SSRN databases to 1 July 2020. We included cohort or case-control studies published in English that reported on the risk of dying after developing COVID-19 for people with a pre-existing diagnosis of any cancer, lung cancer, or haematological cancers. We assessed risk of bias using tools adapted from the Newcastle-Ottawa Scale. We used the generic inverse-variance random-effects method for meta-analysis. Pooled odds ratios (ORs) and hazard ratios (HRs) were calculated separately. Of 96 included studies, 54 had sufficient non-overlapping data to be included in meta-analyses (>500,000 people with COVID-19, >8,000 with cancer; 52 studies of any cancer, three of lung and six of haematological cancers). All studies had high risk of bias. Accounting for at least age consistently led to lower estimated ORs and HRs for COVID-19-related death in cancer patients (e.g. any cancer versus no cancer; six studies, unadjusted OR=3.30,95%CI:2.59-4.20, adjusted OR=1.37,95%CI:1.16-1.61). Adjusted effect estimates were not reported for people with lung or haematological cancers. Of 18 studies that adjusted for at least age, 17 reported positive associations between pre-existing cancer diagnosis and COVID-19-related death (e.g. any cancer versus no cancer; nine studies, adjusted OR=1.66,95%CI:1.33-2.08; five studies, adjusted HR=1.19,95%CI:1.02-1.38). Conclusions The initial evidence (published to 1 July 2020) on COVID-19-related death in people with cancer is characterised by multiple sources of bias and substantial overlap between data included in different studies. Pooled analyses of non-overlapping early data with adjustment for at least age indicated a significantly increased risk of COVID-19-related death for those with a pre-existing cancer diagnosis. Data availability All the original data of this study were available upon reasonable request to the corresponding authors (KC or JS).

Purpose To examine how socio-demographic, comorbidities and information needs influence quality of life (QoL) outcomes of survivors of breast, colorectal, or prostate cancer, non-Hodgkin lymphoma or melanoma. Methods Cross-sectional postal survey with eligible participants identified through a population-based cancer registry. QoL outcomes were assessed by EQ-5D-5L, social difficulties index (SDI) and, for those employed at diagnosis, current employment. Regression analyses explored associations between outcome variables and cancer type, age, time since diagnosis, residential location, socio-economic disadvantage, comorbidities and unmet information needs. Mediation analyses examined whether comorbidities and information needs explained relationships between outcome variables and socio-economic disadvantage. Results 2115 survivors participated. Mean EQ-5D-5L scores (mean = 0.84) were similar to population averages and SDI scores were low for the entire sample (mean = 3.80). In multivariate analyses, being aged over 80, greater socio-economic disadvantage, comorbidities and unmet information needs decreased EQ-5D-5L scores. Higher SDI scores were associated with socio-economic disadvantage, comorbidities and unmet information needs. Not being employed was associated with being aged over 50, more comorbidities and socio-economic disadvantage. Comorbidities but not information needs partially mediated the impact of socio-economic disadvantage on EQ-5D-5L and SDI accounting for 17% and 14% of the total effect of socio-economic disadvantage respectively. Neither comorbidities nor information needs mediated the association between socio-economic disadvantage and employment outcomes. Conclusions To improve quality of life, survivorship care should be better tailored to address the needs of individuals given their overall health and impact of comorbidities, their age and type of cancer and not simply time since diagnosis.

Background Diabetes mellitus, cardiovascular diseases, chronic kidney disease, and thyroid diseases are chronic diseases that require regular monitoring through blood tests. This paper first investigates the experiences of chronic care patients with venipuncture and their expectations of an at-home blood-sampling device, and then assesses the impact on societal costs of implementing such a device in current practice. Methods An online survey was distributed among chronic care patients to gain insight into their experience of blood sampling in current practice, and their expectations of an at-home blood-sampling device. The survey results were used as input parameters in a patient-level monte carlo analysis developed to represent a hypothetical cohort of Dutch chronically ill patients to investigate the impact on societal costs compared to usual care. Results In total, 1311 patients participated in the survey, of which 31% experience the time spent on the phlebotomy appointment as a burden. Of all respondents, 71% prefer to use an at-home blood-sampling device to monitor their chronic disease. The cost analysis indicated that implementing an at-home blood-sampling device increases the cost of phlebotomy itself by €27.25 per patient per year, but it reduces the overall societal costs by €24.86 per patient per year, mainly due to limiting productivity loss. Conclusions Patients consider an at-home blood-sampling device to be more user-friendly than venous phlebotomy on location. Long waiting times and crowded locations can be avoided by using an at-home blood-sampling device. Implementing such a device is likely cost-saving as it is expected to reduce societal costs.

BACKGROUND The emergence of genetic and genomic sequencing approaches for pediatric patients has raised questions about the genomic health literacy levels, attitudes toward receiving genomic information, and use of this information to inform treatment decisions by pediatric patients and their parents. However, the methods to educate pediatric patients and their parents about genomic concepts through digital health interventions have not been well-established. OBJECTIVE The primary objective of this scoping review is to investigate the current levels of genomic health literacy and the attitudes toward receiving genomic information among pediatric patients and their parents. The secondary aim is to investigate patient education interventions that aim to measure and increase genomic health literacy among pediatric patients and their parents. The findings from this review will be used to inform future digital health interventions for patient education. METHODS A scoping review using PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines and protocols was completed using the following databases: MEDLINE, Embase, CINAHL, and Scopus. Our search strategy included genomic information inclusive of all genetic and genomic terms, pediatrics, and patient education. Inclusion criteria included the following: the study included genetic, genomic, or a combination of genetic and genomic information; the study population was pediatric (children and adolescents RESULTS Of the 4618 studies, 14 studies (n=6, 43% qualitative, n=6, 43% mixed methods, and n=2, 14% quantitative) were included. Key findings were based on the following 6 themes: knowledge of genomic concepts, use of the internet and social media for genomic information, use of genomic information for decision-making, hopes and attitudes toward receiving genomic information, experiences with genetic counseling, and interventions to improve genomic knowledge. CONCLUSIONS This review identified that older age is related to the capacity of understanding genomic concepts, increased genomic health literacy levels, and the perceived ability to participate in decision-making related to genomic information. In addition, internet-searching plays a major role in obtaining genomic information and filling gaps in communication with health care providers. However, little is known about the capacity of pediatric patients and their parents to understand genomic information and make informed decisions based on the genomic information obtained. More research is required to inform digital health interventions and to leverage the leading best practices to educate these genomic concepts.

To evaluate the resource implications of different delivery models for the provision of additional findings (AF) in genomics from a health-care purchaser perspective.Data from the Additional Findings study were used to develop and validate a discrete event simulation model that represented the pathway of delivering AF. Resource implications were estimated by microcosting the consultations, sample verifications, bioinformatics, curation, and multidisciplinary case review meetings. A proof-of-concept model was used to generate costing, and then the simulation model was varied to assess the impact of an automated analysis pipeline, use of telehealth consultation, full automation with electronic decision support, and prioritizing case review for cases with pathogenic variants.For the proof-of-concept delivery model, the average total cost to report AF was US$430 per patient irrespective of result pathogenicity (95% confidence interval [CI] US$375-US$489). However, the cost of per AF diagnosis was US$4349 (95% CI US$3794-US$4953). Alternative approaches to genetic counseling (telehealth, decision support materials) and to multidisciplinary case review (pathogenic AF cases only) lowered the total per patient cost of AF analysis and reporting by 41-51%.Resources required to provide AF can be reduced substantially by implementing alternative approaches to counseling and multidisciplinary case review.

Background The emergence of genetic and genomic sequencing approaches for pediatric patients has raised questions about the genomic health literacy levels, attitudes toward receiving genomic information, and use of this information to inform treatment decisions by pediatric patients and their parents. However, the methods to educate pediatric patients and their parents about genomic concepts through digital health interventions have not been well-established. Objective The primary objective of this scoping review is to investigate the current levels of genomic health literacy and the attitudes toward receiving genomic information among pediatric patients and their parents. The secondary aim is to investigate patient education interventions that aim to measure and increase genomic health literacy among pediatric patients and their parents. The findings from this review will be used to inform future digital health interventions for patient education. Methods A scoping review using PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines and protocols was completed using the following databases: MEDLINE, Embase, CINAHL, and Scopus. Our search strategy included genomic information inclusive of all genetic and genomic terms, pediatrics, and patient education. Inclusion criteria included the following: the study included genetic, genomic, or a combination of genetic and genomic information; the study population was pediatric (children and adolescents Results Of the 4618 studies, 14 studies (n=6, 43% qualitative, n=6, 43% mixed methods, and n=2, 14% quantitative) were included. Key findings were based on the following 6 themes: knowledge of genomic concepts, use of the internet and social media for genomic information, use of genomic information for decision-making, hopes and attitudes toward receiving genomic information, experiences with genetic counseling, and interventions to improve genomic knowledge. Conclusions This review identified that older age is related to the capacity of understanding genomic concepts, increased genomic health literacy levels, and the perceived ability to participate in decision-making related to genomic information. In addition, internet-searching plays a major role in obtaining genomic information and filling gaps in communication with health care providers. However, little is known about the capacity of pediatric patients and their parents to understand genomic information and make informed decisions based on the genomic information obtained. More research is required to inform digital health interventions and to leverage the leading best practices to educate these genomic concepts.

Data on medium-term outcome of patients with acute coronary syndrome (ACS), treated with newer-generation durable polymer drug-eluting stents (DES) in severely calcified coronary lesions, are scarce. We aimed to assess the impact of severe coronary lesion calcification on clinical outcome of patients with ACS, treated with newer-generation DES.The TWENTE and DUTCH PEERS randomized trials comprise 1779 ACS patients, who were categorized into patients with versus without severe target lesion calcification. We performed a patient-level pooled analysis to assess 2-year outcome, including target vessel failure (TVF), a composite of cardiac death, target vessel-related myocardial infarction (MI), or target vessel revascularization (TVR).Patients with severe target lesion calcification (n=340, 19.1%) were older (66.8±10.6 years vs. 62.8±11.5 years, p0.001) and had more often diabetes (22.1% vs. 16.8%, p=0.02) and hypercholesterolemia (51.5% vs. 42.9%, p=0.005) than other patients (n=1439, 79.9%). In addition they showed a higher TVF rate (12.4% vs.7.0%, p=0.001), mainly related to a difference in TVR (6.8% vs. 3.3%, p=0.003). There was a borderline significant between-group difference in cardiac death (3.6% vs. 1.8%, p=0.05), but not in target vessel MI (3.8% vs.2.6%, p=0.23) and definite stent thrombosis (0.9% vs. 0.6%, p=0.71). Multivariate analysis demonstrated that severe lesion calcification was an independent risk factor of TVF (adjusted HR; 1.58, 95% CI: 1.23-2.03; p0.001).In patients with ACS, treatment of severely calcified lesions with newer-generation DES was associated with an overall higher clinical event risk - related in particular to a higher TVR rate, while the risk of MI was low.

Background:Background: With growing emphasis on patient involvement in health technology assessment, there is a need for scientific methods that formally elicit patient preferences. Analytic hierarchy process (AHP) and conjoint analysis (CA) are two established scientific methods - albeit with very different objectives. Abstract: Objective:Objective: The objective of this study was to compare the performance of AHP and CA in eliciting patient preferences for treatment alternatives for stroke rehabilitation. Abstract: Methods:Methods: Five competing treatments for drop-foot impairment in stroke were identified. One survey, including the AHP and CA questions, was sent to 142 patients, resulting in 89 patients for final analysis (response rate 63%). Standard software was used to calculate attribute weights from both AHP and CA. Performance weights for the treatments were obtained from an expert panel using AHP. Subsequently, the mean predicted preference for each of the five treatments was calculated using the AHP and CA weights. Differences were tested using non-parametric tests. Furthermore, all treatments were rank ordered for each individual patient, using the AHP and CA weights. Abstract: Results:Results: Important attributes in both AHP and CA were the clinical outcome (0.3 in AHP and 0.33 in CA) and risk of complications (about 0.2 in both AHP and CA). Main differences between the methods were found for the attributes 'impact of treatment' (0.06 for AHP and 0.28 for two combined attributes in CA) and 'cosmetics and comfort' (0.28 for two combined attributes in AHP and 0.05 for CA). On a group level, the most preferred treatments were soft tissue surgery (STS) and orthopedic shoes (OS). However, STS was most preferred using AHP weights versus OS using CA weights (p < 0.001). This difference was even more obvious when interpreting the individual treatment ranks. Nearly all patients preferred STS according to the AHP predictions, while >50% of the patients chose OS instead of STS, as most preferred treatment using CA weights. Abstract: Conclusion:Conclusion: While we found differences between AHP and CA, these differences were most likely caused by the labeling of the attributes and the elicitation of performance judgments. CA scenarios are built using the level descriptions, and hence provide realistic treatment scenarios. In AHP, patients only compared less concrete attributes such as 'impact of treatment.' This led to less realistic choices, and thus overestimation of the preference for the surgical scenarios. Several recommendations are given on how to use AHP and CA in assessing patient preferences.

The outcome of percutaneous coronary intervention with newer generation permanent polymer-coated drug-eluting stents (DES) in patients with severely calcified lesions is greatly unknown. We assessed the impact of severe lesion calcification on clinical outcome in patients with stable angina who underwent percutaneous coronary intervention with newer generation DES.TWENTE and DUTCH PEERS randomized trials enrolled 1423 patients with stable angina, who were categorized into patients with versus without severe target lesion calcification. A patient-level pooled analysis assessed clinical outcome, including target vessel failure (TVF), a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization (TVR).Patients with severe calcification (n = 342) were older (66.6 ± 9.1 vs 64.2 ± 9.8 years, P.001) and had more diabetes (25.7% vs 20.4%, P = .04) than other patients (n = 1081). Patients with calcified lesions had higher rates of TVF (16.4% vs 9.8%, pLogrank = .001), cardiac death (4.4% vs 1.5%, P = .03), target vessel myocardial infarction (7.6% vs 3.4%, P = .001), and definite stent thrombosis (1.8% vs 0.4%, P = .02). Multivariate analysis demonstrated that severe calcification was an independent risk factor of 2-year TVF (HR 1.42, 95% CI: 1.02-1.99, pLogrank = .04); landmark analysis showed that this was based on a difference during the first year (periprocedural: 5.8% vs. 3.1%, pLogrank = .02; first year: 7.5% vs. 3.8%, pLogrank = .007; second year: 4.1% vs. 3.3%, pLogrank = .54).In patients with stable angina, severe target lesion calcification is associated with an increased risk of adverse cardiovascular events following treatment with newer generation permanent polymer-coated DES. This increase in risk is restricted to the first year of follow-up, which is an encouraging finding.

This study sought to assess sex differences in chest pain after percutaneous coronary intervention (PCI) with newer generation drug-eluting stents (DES).Sex-based data on chest pain after PCI with DES are scarce.The authors performed a patient-level pooled analysis of the TWENTE and DUTCH PEERS randomized trials, in which patients were treated with newer generation permanent polymer-coated DES. At 1 and 2 years, clinical follow-up was available in 99.8% and patient-reported chest pain data in 94.1% and 93.6%, respectively.Among all 3,202 patients, the 871 (27.2%) women were older (67.5 ± 10.2 years vs. 62.8 ± 10.6 years; p0.001) and had more cardiovascular risk factors: diabetes (24.2% vs. 17.8%; p0.001), hypertension (63.6% vs. 51.6%; p0.001), and positive family history (54.5% vs. 50.1%; p = 0.03). At 1- and 2-year follow-up, women reported more clinically relevant chest pain (16.3% vs. 10.5%; p0.001, and 17.2% vs. 11.1%; p0.001, respectively). Multivariate analysis demonstrated that female sex independently predicted clinically relevant chest pain at 1- and 2-year follow-up both during daily activities and at minimum physical exertion/at rest (1 year adjusted odds ratio [OR]: 1.7; 95% confidence interval [CI]: 1.2 to 2.4; p = 0.002; and adjusted OR: 1.8; 95% CI: 1.3 to 2.5; p0.001; 2-year adjusted OR: 1.8; 95% CI: 1.3 to 2.6; p0.001; and adjusted OR: 1.7; 95% CI: 1.3 to 2.3; p = 0.001). Nevertheless, the 2-year rates of death, myocardial infarction, revascularization, stent thrombosis, and various composite clinical endpoints were similar for both sexes.Although the incidence of adverse cardiovascular events was low and similar for both sexes, women showed a statistically significantly higher prevalence of clinically relevant chest pain, which might be largely related to mechanisms other than epicardial coronary obstruction.

Objective. To determine the effect of electrical stimulation of hamstrings and L3/4 dermatome on the swing phase of gait. Materials and Methods. Five subjects with incomplete spinal cord injury (SCI) with spasticity were included. Two electrical stimulation methods were investigated, i.e., hamstrings and L3/4 dermatome stimulation. Both interventions were applied during the swing phase of gait. The main outcome measures were step length, maximum hip, and knee flexion during the swing phase of gait. In three subjects changes of spinal inhibition during gait were evaluated using the Hoffman reflex/m (motor)-wave (H/M) ratio at mid swing. Results. The hip flexion decreased 4.6 degrees (p < 0.05) when the hamstrings were stimulated during the swing phase, whereas the knee flexion was not changed. The step length did not change significantly. One subject showed a decrease of the H/M ratio to a nonpathologic level during hamstrings stimulation. Conclusion. It was concluded that hamstrings stimulation during the swing phase results in a reduction of the hip flexion in all five SCI subjects. The H/M ratio of the vastus lateralis was normalized using hamstrings stimulation in one of three subjects. Stimulation of the L3/4 dermatome provides no significant changes in gait performance, but in one subject the H/M ratio increased.

299 Background: The need for validated circulating biomarkers is well recognised in advanced prostate cancer (PCa). Circulating biomarkers evaluating plasma cell-free nucleic acids and circulating tumour cells are being investigated for their clinical utility. There has been a lack of consensus with regards to analyses, reporting and clinical effectiveness of these biomarkers. A consensus meeting was held to address these issues. Methods: A multi-disciplinary panel comprising 18 international prostate cancer experts (including surgeons, medical and radiation oncologists) were consulted prior to the consensus meeting. Four key areas relating to the field of circulating biomarkers were deemed important for discussion: 1) The current utility of circulating biomarkers in 2017; 2) The clinical needs for circulating biomarkers in PCa; 3) The most pressing blood-based molecular assays required; and 4) The steps necessary for developing circulating biomarkers. Using a modified Delphi process, 50 consensus questions were pre-defined for the panel to answer by voting anonymously but publicly at the consensus meeting. Results: A consensus was declared (i.e. ≥ 75% of panellists who did not vote ‘unqualified’ or ‘abstain’ chose the same opinion) in 12/50 (24%) questions. A further 8/50 (16%) of replies were close to reaching consensus (≥ 60% of panellists choosing the same answer). The panel agreed that there is a very high and urgent unmet need for predictive biomarkers, with consensus that DNA repair biomarkers in particular are needed urgently. Metastatic PCa was identified as having the highest clinical need for development of biomarkers to measure response and as surrogate endpoints. Panellists unanimously voted that reproducibility validation studies are of paramount importance. The consensus panel also predicted that cfDNA will impact practice by 2020. Conclusions: This expert consensus identified the need for clinical trials of validated circulating biomarkers to develop predictive, response and surrogacy assays. These could have major clinical and healthcare economic implications, minimizing over-treatment and allowing the delivery of more precise patient care.

Both the complexity of clinically applied tissue engineering techniques for articular cartilage repair - such as autologous chondrocyte implantation (ACI) - plus increasing healthcare costs, and market competition, are forcing a shift in focus from two-stage to single-stage interventions that are more cost-effective. Early health economic models are expected to provide essential insight in the parameters driving the cost-effectiveness of new interventions before they are introduced into clinical practice. The present study estimated the likely incremental cost-effectiveness ratio (ICER) of a new investigator-driven single-stage procedure (IMPACT) compared with both microfracture and ACI, and identified those parameters that affect the cost-effectiveness. A decision tree with clinical health states was constructed. The ICER was calculated by dividing the incremental societal costs by the incremental Quality Adjusted Life Years (QALYs). Costs were determined from a societal perspective. A headroom analysis was performed to determine the maximum price of IMPACT compared with both ACI and microfracture, assuming a societal willingness to pay (WTP) of €30 000/QALY. One-way sensitivity analysis was performed to identify those parameters that drive the cost-effectiveness. The societal costs of IMPACT, ACI and microfracture were found to be €11 797, €29 741 and €6081, respectively. An 8% increase in all utilities after IMPACT changes the ICER of IMPACT vs. microfracture from €147 513/QALY to €28 588/QALY. Compared with ACI, IMPACT is less costly, which is largely attributable to the cell expansion procedure that has been rendered redundant. While microfracture can be considered the most cost-effective treatment option for smaller defects, a single-stage tissue engineering procedure can replace ACI to improve the cost-effectiveness for treating larger defects, especially if clinical non-inferiority can be achieved. Copyright © 2016 John WileySons, Ltd.

This study assessed clinical events and patient-reported chest pain 2 years after treatment of all-comers with Resolute Integrity zotarolimus-eluting stents (Medtronic Vascular, Santa Rosa, California) and Promus Element everolimus-eluting stents (Boston Scientific, Natick, Massachusetts).For both drug-eluting stents (DES), no all-comer outcome data from12 months of follow-up have been published. Although there is increasing interest in patient-reported chest pain following stenting, data with novel DES are scarce.The DUTCH PEERS multicenter trial (TWENTE II) (DUrable Polymer-Based STent CHallenge of Promus ElemEnt Versus ReSolute Integrity) Randomized Trial [TWENTE II]) randomized 1,811 all-comer patients to treatment with 1 type of DES. Monitoring and event adjudication were performed by independent contract research organizations.The 2-year follow-up of 1,810 patients (99.9%) was available. The primary composite endpoint target vessel failure occurred in 8.6% and 7.8% of patients treated with zotarolimus- and everolimus-eluting stents, respectively (p = 0.55). Rates of components of target vessel failure were: cardiac death (2.4% vs. 1.9%, p = 0.42); target vessel-related myocardial infarction (2.4% vs. 1.8%, p = 0.33); clinically-indicated target vessel revascularization (4.6% vs. 4.9%, p = 0.83). At 1- and 2-year follow-up,80% of patients were free from chest pain (no between-stent difference). In addition,87% of patients were either free from chest pain or experienced pain only at maximal physical exertion, but not during normal daily activities. Patients with chest pain after 12 months at no more than moderate physical effort had a higher risk of target vessel revascularization during the following year (hazard ratio: 1.89 [95% confidence interval: 1.05 to 3.39], p = 0.03).During the second year of follow-up, the incidence of adverse clinical endpoints remained similar and low for both DES. The vast majority of patients were free from chest pain.

The aim of the present study was to assess the impact on clinical outcome of right coronary artery (RCA) ostial coverage with second-generation drug-eluting stents (DES).Treatment of the aorta-ostial (AO) region of the RCA with bare metal stents and first-generation DES has been associated with a higher risk of target-lesion revascularization (TLR).Of the 1,391 patients of the prospective TWENTE trial, we identified 321 (23%) with single-vessel RCA treatment, who were categorized into stenting with AO stent coverage (AOC) versus stenting without AOC. The AO region was defined as 3 mm from the aortic orifice.The 67 (20.9%) patients with AOC showed more severe lesion calcifications than the 254 patients without AOC (31.3% vs. 12.6%; P 0.01). In the AOC group, there was a higher prevalence of hypercholesterolemia and family history of coronary disease (75.4% vs. 61.6%, and 68.7% vs. 53.5%, respectively; P = 0.03). During 2-year follow-up, patients in the AOC group had a higher incidence of TLR (7.5% vs. 1.6%; P = 0.02). Following adjustment for confounders, AOC independently predicted TLR with an adjusted hazard ratio of 4.1 (95% CI: 1.17-14.39; P = 0.03).AO treatment of the RCA with second-generation DES is feasible, but our data suggest that stent coverage of the right AO segment remains a predictor of TLR.

Adolescent idiopathic scoliosis (AIS) can lead to pain, impaired spinal function, and socio-psychological problems. Conventional surgical treatment of severe forms of AIS fuses the vertebrae, thereby restricting spinal function and growth of the adolescents. Non-fusion surgical treatment (NFS) is being proposed to prevent these drawbacks. To support the further development of NFS, this study aims to predict the health economic performance of the new NFS treatment and compare it with standard AIS treatment. A decision tree was constructed to compare NFS with bracing, possibly followed by posterior fusion surgery. The outcome measures were quality of life, complications, and costs. The Analytic Hierarchy Process (AHP), a technique for multi-criteria decision analysis, supported an expert panel of biomedical engineers and orthopaedic surgeons to predict the missing NFS performance data in the decision tree. The decision tree analysis showed that NFS is the preferred form of treatment in patients prone to disease progression. The advantages are its positive effect on spinal function and the self-esteem of the patient. Future clinical acceptance of NFS can be supported by reduced costs and an optimization of the prediction of progression. As more clinical evidence becomes available over time, these data can be added to the health economic model.

The aim was to determine if the treatment of a drop foot by means of an implantable two-channel peroneal nerve stimulator improves health-related quality of life (HRQoL). All subjects were measured at baseline and after a follow-up period of 12 and 26 weeks. Twenty-nine stroke survivors with chronic hemiplegia with drop foot who fulfilled the predefined inclusion and exclusion criteria were included in the present randomized controlled trial. The intervention group received an implantable two-channel peroneal nerve stimulator for correction of their drop foot. The control group continued using their conventional walking device, consisting of an ankle-foot orthosis, orthopedic shoes, or no device. HRQoL was assessed in two different ways: (i) by taking descriptive measures, that is, the Short Form-36 (SF-36; generic measure) and the Disability Impact Profile (DIP; specific measure); and (ii) by obtaining preference-based utilities both measured with the time trade-off (direct way) and by calculating them from the EuroQol (EQ-5D) and SF-36. A significant positive effect of the implantable device was found on the physical functioning domain, the general health domain, and the physical component summary score of the SF-36. For the DIP, a significant improvement was found on the domains mobility, self-care, and psychological status in the intervention group. Regarding the preference-based utility measures, a significant effect was found for the utility index calculated from the EQ-5D. The implantable two-channel peroneal nerve stimulator seems to be efficient to improve HRQoL, mainly the domains related to physical functioning. A relation was present between the utility indexes calculated from the EQ-5D and SF-36.

This pilot study explores the influence of a single dose of fluoxetine (20 mg) on the muscle activation patterns and functional ability of the muscles in the lower part of the arm in chronic stroke patients.A crossover, placebo-controlled clinical trial was conducted in 10 patients. After administration of either a single dose of fluoxetine (20 mg) or a placebo, muscle activation of the lower arm was measured during maximum (isometric) force of the musculus flexor carpi radialis and musculus extensor carpi radialis. Delay times, grip strength, and Motricity Index were measured to assess functional ability.After fluoxetine intake, a significant increase in activation was found in both agonist and antagonist muscles of the paretic arm (P0.05). This increase did not influence the motor function.In this pilot study, it was found that fluoxetine influences motor output in chronic stroke patients. Therefore, fluoxetine may influence motor recovery after stroke. Additional studies have to be conducted to explore the effects of fluoxetine on motor recovery after stroke.