The need for a liquid biopsy in non‐small cell lung cancer (NSCLC) patients is rapidly increasing. We studied the relation between overall survival (OS) and the presence of four cancer biomarkers ...from a single blood draw in advanced NSCLC patients: EpCAMhigh circulating tumor cells (CTC), EpCAMlow CTC, tumor‐derived extracellular vesicles (tdEV) and cell‐free circulating tumor DNA (ctDNA). EpCAMhigh CTC were detected with CellSearch, tdEV in the CellSearch images and EpCAMlow CTC with filtration after CellSearch. ctDNA was isolated from plasma and mutations present in the primary tumor were tracked with deep sequencing methods. In 97 patients, 21% had ≥2 EpCAMhigh CTC, 15% had ≥2 EpCAMlow CTC, 27% had ≥18 tdEV and 19% had ctDNA with ≥10% mutant allele frequency. Either one of these four biomarkers could be detected in 45% of the patients and all biomarkers were present in 2%. In 11 out of 16 patients (69%) mutations were detected in the ctDNA. Two or more unfavorable biomarkers were associated with poor OS. The presence of EpCAMhigh CTC and elevated levels of tdEV and ctDNA was associated with a poor OS; however, the presence of EpCAMlow CTC was not. This single tube approach enables simultaneous analysis of multiple biomarkers to explore their potential as a liquid biopsy.
What's new?
Liquid biopsies may provide a convenient and patient‐friendly approach to inform prognosis and prediction of the best treatment management. Here, the authors studied the relation between overall survival and the presence of four different cancer biomarkers from a single blood draw in 97 advanced non‐small cell lung cancer (NSCLC) patients. The presence of EpCAM high‐expressing circulating tumour cells and elevated levels of tumour vesicles and tumour DNA were associated with a poor clinical outcome, but not the presence of EpCAM low‐expressing CTC. This single tube approach enables simultaneous analysis of several biomarkers to explore their potential as a liquid biopsy.
Postpartum depression often remains unaddressed. Screening in well-child care (WCC) may improve early detection, promote maternal recovery, and reduce effects on child development. We assessed the ...effectiveness of screening for postpartum depression in WCC compared with care as usual (CAU) on outcomes at mother and child levels.
In a prospective, quasiexperimental, comparative design, mothers visiting Dutch WCC centers were exposed either to screening at 1, 3, and 6 months postpartum (
= 1843) or to CAU (
= 1246). Assessments were at 3 weeks (baseline), 9 months (the Mini International Neuropsychiatric Interview), and 12 months (the Spielberger State-Trait Anxiety Inventory, the Short-Form 12-Item Health Survey, the Maternal Self-Efficacy in the Nurturing Role questionnaire, and the Ages and Stages Questionnaire-Social Emotional) postpartum.
Significantly fewer mothers in the intervention group were depressed at 9 months postpartum compared with the CAU group (0.6% vs 2.5% for major depression). The adjusted odds ratio was 0.28 (95% confidence interval, 0.12 to 0.63; Cohen's d, 0.70). For minor and major depression, figures were 3.0% vs 8.4%, and the adjusted odds ratio was 0.40 (95% confidence interval, 0.27 to 0.58; Cohen's d, 0.51). For parenting, anxiety symptoms, and mental health functioning, the intervention resulted in effect sizes ranging from 0.23 to 0.27. The effect on the child's socioemotional development was negligible.
Implementation of screening for postpartum depression in WCC should be seriously considered given its positive effects on maternal mental health. The benefits of optimizing the trajectory after screening on maternal and child outcomes need further attention.
Little is known about how patients weigh benefits and harms of available treatments for Parkinson's Disease (oral medication, deep brain stimulation, infusion therapy). In this study we have (1) ...elicited patient preferences for benefits, side effects and process characteristics of treatments and (2) measured patients' preferred and perceived involvement in decision-making about treatment.
Preferences were elicited using a best-worst scaling case 2 experiment. Attributes were selected based on 18 patient-interviews: treatment modality, tremor, slowness of movement, posture and balance problems, drowsiness, dizziness, and dyskinesia. Subsequently, a questionnaire was distributed in which patients were asked to indicate the most and least desirable attribute in nine possible treatment scenarios. Conditional logistic analysis and latent class analysis were used to estimate preference weights and identify subgroups. Patients also indicated their preferred and perceived degree of involvement in treatment decision-making (ranging from active to collaborative to passive).
Two preference patterns were found in the patient sample (N = 192). One class of patients focused largely on optimising the process of care, while the other class focused more on controlling motor-symptoms. Patients who had experienced advanced treatments, had a shorter disease duration, or were still employed were more likely to belong to the latter class. For both classes, the benefits of treatment were more influential than the described side effects. Furthermore, many patients (45%) preferred to take the lead in treatment decisions, however 10.8% perceived a more passive or collaborative role instead.
Patients weighted the benefits and side effects of treatment differently, indicating there is no "one-size-fits-all" approach to choosing treatments. Moreover, many patients preferred an active role in decision-making about treatment. Both results stress the need for physicians to know what is important to patients and to share treatment decisions to ensure that patients receive the treatment that aligns with their preferences.
In The Netherlands, helmet therapy is a commonly used treatment in infants with skull deformation (deformational plagiocephaly or deformational brachycephaly). However, evidence of the effectiveness ...of this treatment remains lacking. The HEADS study (HElmet therapy Assessment in Deformed Skulls) aims to determine the effects and costs of helmet therapy compared to no helmet therapy in infants with moderate to severe skull deformation.
Pragmatic randomised controlled trial (RCT) nested in a cohort study. The cohort study included infants with a positional preference and/or skull deformation at two to four months (first assessment). At 5 months of age, all children were assessed again and infants meeting the criteria for helmet therapy were asked to participate in the RCT. Participants were randomly allocated to either helmet therapy or no helmet therapy. Parents of eligible infants that do not agree with enrolment in the RCT were invited to stay enrolled for follow up in a non-randomisedrandomised controlled trial (nRCT); they were then free to make the decision to start helmet therapy or not. Follow-up assessments took place at 8, 12 and 24 months of age. The main outcome will be head shape at 24 months that is measured using plagiocephalometry. Secondary outcomes will be satisfaction of parents and professionals with the appearance of the child, parental concerns about the future, anxiety level and satisfaction with the treatment, motor development and quality of life of the infant. Finally, compliance and costs will also be determined.
HEADS will be the first study presenting data from an RCT on the effectiveness of helmet therapy. Outcomes will be important for affected children and their parents, health care professionals and future treatment policies. Our findings are likely to influence the reimbursement policies of health insurance companies.Besides these health outcomes, we will be able to address several methodological questions, e.g. do participants in an RCT represent the eligible target population and do outcomes of the RCT differ from outcomes found in the nRCT?
ISRCTN18473161.
Patient-centered design that addresses patients' preferences and needs is considered an important aim for improving health care systems. At present, within the field of pain rehabilitation, patients' ...preferences regarding telerehabilitation remain scarcely explored and little is known about the optimal combination between human and electronic contact from the patients' perspective. In addition, limited evidence is available about the best way to explore patients' preferences. Therefore, the assessment of patients' preferences regarding telemedicine is an important step toward the design of effective patient-centered care.
To identify which telerehabilitation treatment options patients with chronic pain are most likely to accept as alternatives to conventional rehabilitation and assess which treatment attributes are most important to them.
A discrete choice experiment with 15 choice tasks, combining 6 telerehabilitation treatment characteristics, was designed. Each choice task consisted of 2 hypothetical treatment scenarios and 1 opt-out scenario. Relative attribute importance was estimated using a bivariate probit regression analysis. One hundred and thirty surveys were received, of which 104 were usable questionnaires; thus, resulting in a total of 1547 observations.
Physician communication mode, the use of feedback and monitoring technology (FMT), and exercise location were key drivers of patients' treatment preferences (P<.001). Patients were willing to accept less frequent physician consultation offered mainly through video communication, provided that they were offered FMT and some face-to-face consultation and could exercise outside their home environment at flexible exercise hours. Home-based telerehabilitation scenarios with minimal physician supervision were the least preferred. A reduction in health care premiums would make these telerehabilitation scenarios as attractive as conventional clinic-based rehabilitation.
"Intermediate" telerehabilitation treatments offering FMT, some face-to-face consulting, and a gym-based exercise location should be pursued as promising alternatives to conventional chronic pain rehabilitation. Further research is necessary to explore whether strategies other than health care premium reductions could also increase the value of home telerehabilitation treatment.
Most preference-based instruments producing overall values for health states are devised on the simplifying assumption that the overall effect of distinct health-related quality of life domains ...(attributes) of the instrument equals the sum of the attributes. Nevertheless, health attributes are often inter-related and depend on each other.
To investigate whether inclusion of second-order interactions in the three-level EuroQol five-dimensional questionnaire (EQ-5D-3L) value function would result in better fit and lead to different health state values than a model with main effects only.
Using an efficient design, 400 pairs of EQ-5D-3L health states were generated in a pairwise choice format. We analyzed responses of 4000 people from the general population using a conditional logit model, and we tested goodness of fit using pseudo R2, Akaike information criterion, differences in log-likelihood, and likelihood ratio. We compared accuracies of models’ predictions based on root mean square error and mean absolute error.
The interaction-effects model showed systematically lower values than the main-effects model. Inclusion of interactions resulted only in a slightly better model fit. Interactions comprising mobility and self-care were the most salient.
For the EQ-5D-3L, a value function based on interactions produces systematically lower values than a main-effects model, meaning that the effect of two or more health problems combined is stronger than the sum of the individual main effects.
The purpose of this study was to investigate to what extent the outcomes of a discrete choice experiment (DCE) differ based on respondents' psychological distance to the decision at hand.
A DCE ...questionnaire regarding individuals' preferences for genetic screening for colorectal cancer (CRC) within the Dutch national CRC screening program was created. The DCE contained nine D-efficient designed choice tasks and was distributed among two populations that differ in their psychological distance to the decision at hand: 1) a representative sample of the Dutch general population aged 55-65 years, and 2) a sample of Dutch individuals who attended an information appointment regarding colonoscopies following the detection of blood in their stool sample in the CRC screening program. The DCE consisted of four attributes related to the decision whether to participate in genetic screening for CRC: 1) risk of being genetically predisposed, 2) risk of developing CRC, 3) frequency of follow-up colonoscopies, and 4) survival. Direct attribute ranking, dominant decision-making behavior, and relative importance scores (based on panel MIXL) were compared between the two populations. Attribute level estimates were compared with the Swait and Louviere test.
The proportion of respondents who both ranked survival as the most important attribute, and showed dominant decision-making behavior for this attribute, was significantly higher in the screened population compared to the general population. The relative importance scores of the attributes significantly differed between populations. Finally, the Swait and Louviere test also revealed significant differences in attribute level estimates in both the populations.
The study outcomes differed between populations depending on their psychological distance to the decision. This study shows the importance of adequate sample selection; therefore, it is advocated to increase attention to study sample selection and reporting in DCE studies.
To identify which specifications and approaches to model selection better predict health preferences, the International Academy of Health Preference Research (IAHPR) hosted a predictive modeling ...competition including 18 teams from around the world.
In April 2016, an exploratory survey was fielded: 4074 US respondents completed 20 out of 1560 paired comparisons by choosing between two health descriptions (e.g., longer life span vs. better health). The exploratory data were distributed to all teams. By July, eight teams had submitted their predictions for 1600 additional pairs and described their analytical approach. After these predictions had been posted online, a confirmatory survey was fielded (4148 additional respondents).
The victorious team, “Discreetly Charming Econometricians,” led by Michał Jakubczyk, achieved the smallest χ2, 4391.54 (a predefined criterion). Its primary scientific findings were that different models performed better with different pairs, that the value of life span is not constant proportional, and that logit models have poor predictive validity in health valuation.
The results demonstrated the diversity and potential of new analytical approaches in health preference research and highlighted the importance of predictive validity in health valuation.
Lung cancer screening can reduce cancer mortality. Most implementation studies focus only on low-dose computed tomography (LDCT) and clinical attributes of screening and do not include preferences of ...potential participants. In this study we evaluated the perceived value of screening programs based on LDCT, breath analysis (BA), or blood biomarkers (BB) according to the perspective of the target population.
A multi-criteria decision analysis framework was adopted. The weights of seven attributes of screening (sensitivity, specificity, radiation burden, duration of screening process, waiting time until results are communicated, location of screening, and mode of screening) were obtained from an earlier study that included a broad sample from the Netherlands. Performance data for the screening modalities was obtained from clinical trials and expert opinion. Parameter uncertainty about clinical performances was incorporated probabilistically, while heterogeneity in preferences was analyzed through subgroup analyses.
The mean overall values were 0.58 (CI: 0.57 to 0.59), 0.57 (CI: 0.56 to 0.59), and 0.44 (CI: 0.43 to 0.45) for BB, BA, and LDCT, respectively. Seventy-seven per cent of respondents preferred BB or BA. For most subgroups, the overall values were similar to those of the entire sample. BA had the highest value for respondents who would have been eligible for earlier screening trials.
BB and BA seem valuable to participants because they can be applied in a primary care setting. Although LDCT still seems preferable given its strong and positive evidence base, it is important to take non-clinical attributes into account to maximize attendance.
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