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1.
Examining variation in the measurement of multimorbidity in research: a systematic review of 566 studies.
Ho, IS, Azcoaga-Lorenzo, A, Akbari, A, Black, C, Davies, J, Hodgins, P, Khunti, K, Kadam, U, Lyons, RA, McCowan, C, et al
The Lancet. Public health. 2021;(8):e587-e597
Abstract
BACKGROUND A systematic understanding of how multimorbidity has been constructed and measured is unavailable. This review aimed to examine the definition and measurement of multimorbidity in peer-reviewed studies internationally. METHODS We systematically reviewed studies on multimorbidity, via a search of nine bibliographic databases (Ovid [PsycINFO, Embase, Global Health, and MEDLINE], Web of Science, the Cochrane Library, CINAHL Plus, Scopus, and ProQuest Dissertations & Theses Global), from inception to Jan 21, 2020. Reference lists and tracked citations of retrieved articles were hand-searched. Eligible studies were full-text articles measuring multimorbidity for any purpose in community, primary care, care home, or hospital populations receiving a non-specialist service. Abstracts, qualitative research, and case series were excluded. Two reviewers independently reviewed the retrieved studies with conflicts resolved by discussion or a third reviewer, and a single researcher extracted data from published papers. To assess our objectives of how multimorbidity has been measured and examine variation in the chronic conditions included (in terms of number and type), we used descriptive analysis (frequencies, cross-tabulation, and negative binomial regression) to summarise the characteristics of multimorbidity studies and measures (study setting, source of morbidity data, study population, primary study purpose, and multimorbidity measure type). This systematic review is registered with PROSPERO, CRD420201724090. FINDINGS 566 studies were included in our review, of which 206 (36·4%) did not report a reference definition for multimorbidity and 73 (12·9%) did not report the conditions their measure included. The number of conditions included in measures ranged from two to 285 (median 17 [IQR 11-23). 452 (79·9%) studies reported types of condition within a single multimorbidity measure; most included at least one cardiovascular condition (441 [97·6%] of 452 studies), metabolic and endocrine condition (440 [97·3%]), respiratory condition (422 [93·4%]), musculoskeletal condition (396 [87·6%]), or mental health condition (355 [78·5%]) in their measure of multimorbidity. Chronic infections (123 [27·2%]), haematological conditions (110 [24·3%]), ear, nose, and throat conditions (107 [23·7%]), skin conditions (70 [15·5%]), oral conditions (19 [4·2%]), and congenital conditions (14 [3·1%]) were uncommonly included. Only eight individual conditions were included by more than half of studies in the multimorbidity measure used (diabetes, stroke, cancer, chronic obstructive pulmonary disease, hypertension, coronary heart disease, chronic kidney disease, and heart failure), with individual mental health conditions under-represented. Of the 566 studies, 419 were rated to be of moderate risk of bias, 107 of high risk of bias, and 40 of low risk of bias according to the Effective Public Health Practice Project quality assessment tool. INTERPRETATION Measurement of multimorbidity is poorly reported and highly variable. Consistent reporting of measure definitions should be required by journals, and consensus studies are needed to define core and study-dependent conditions to include in measures of multimorbidity. FUNDING Health Data Research UK.
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2.
A scoping review of PhotoVoice for people with post-stroke aphasia.
Dietz, A, Mamlekar, CR, Bakas, KL, McCarthy, MJ, Harley, D, Bakas, T
Topics in stroke rehabilitation. 2021;(3):219-235
Abstract
BACKGROUND PhotoVoice is a qualitative research methodology designed to engage and empower marginalized members of a community and/or to understand community needs. PhotoVoice seems aphasia-friendly because it relies on personal photographs to convey opinions regarding prespecified topics. However, PhotoVoice is based on a procedure referred to as the SHOWeD method. Participants are asked to reflect upon their photos by discussing (1) what they See, (2) what is Happening, (3) the relation to Our life, (3) Why the issue or condition exists, and then to (4) explain what can be Done to address the issue(s) at hand. Due to the linguistic demand required to convey complex thoughts and ideas inherent in this methodology, adaptations are likely required to successfully implement with people who have aphasia. AIMS A scoping review was conducted to summarize the current literature regarding the use of PhotoVoice with people who have aphasia, to address two questions:(1) Are people with post-stroke aphasia included in PhotoVoice studies?(2) What, if any, modifications are required to address post-stroke aphasia and motor impairments? MAIN CONTRIBUTION This scoping review revealed that researchers often exclude people with aphasia from post-stroke PhotoVoice research. Three studies outlined adaptations that allowed successful implementation with people who have post-stroke aphasia. CONCLUSIONS Further inquiry regarding how best to adapt PhotoVoice for people with aphasia will facilitate their ability to be included in community-based research. This is an important step in ensuring that all post-stroke stakeholders are involved in projects related to social justice and policy for stroke survivors.
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3.
Towards the standardization of the absorbed dose report mode in high energy photon beams.
Younes, T, Chauvin, M, Delbaere, A, Labour, J, Fonteny, V, Simon, L, Fares, G, Vieillevigne, L
Physics in medicine and biology. 2021;(4):045009
Abstract
The benefits of using an algorithm that reports absorbed dose-to-medium have been jeopardized by the clinical experience and the experimental protocols that have mainly relied on absorbed dose-to-water. The aim of the present work was to investigate the physical aspects that govern the dosimetry in heterogeneous media using Monte Carlo method and to introduce a formalism for the experimental validation of absorbed dose-to-medium reporting algorithms. Particle fluence spectra computed within the sensitive volume of two simulated detectors (T31016 Pinpoint 3D ionization chamber and EBT3 radiochromic film) placed in different media (water, RW3, lung and bone) were compared to those in the undisturbed media for 6 MV photon beams. A heterogeneity correction factor that takes into account the difference between the detector perturbation in medium and under reference conditions as well as the stopping-power ratios was then derived for all media using cema calculations. Furthermore, the different conversion approaches and Eclipse treatment planning system algorithms were compared against the Monte Carlo absorbed dose reports. The detectors electron fluence perturbation in RW3 and lung media were close to that in water (≤1.5%). However, the perturbation was greater in bone (∼4%) and impacted the spectral shape. It was emphasized that detectors readings should be corrected by the heterogeneity correction factor that ranged from 0.932 in bone to 0.985 in lung. Significant discrepancies were observed between all the absorbed dose reports and conversions, especially in bone (exceeding 10%) and to a lesser extent in RW3. Given the ongoing advances in dose calculation algorithms, it is essential to standardize the absorbed dose report mode with absorbed dose-to-medium as a favoured choice. It was concluded that a retrospective conversion should be avoided and switching from absorbed dose-to-water to absorbed dose-to-medium reporting algorithm should be carried out by a direct comparison of both algorithms.
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4.
Consensus for experimental design in electromyography (CEDE) project: Amplitude normalization matrix.
Besomi, M, Hodges, PW, Clancy, EA, Van Dieën, J, Hug, F, Lowery, M, Merletti, R, Søgaard, K, Wrigley, T, Besier, T, et al
Journal of electromyography and kinesiology : official journal of the International Society of Electrophysiological Kinesiology. 2020;:102438
Abstract
The general purpose of normalization of EMG amplitude is to enable comparisons between participants, muscles, measurement sessions or electrode positions. Normalization is necessary to reduce the impact of differences in physiological and anatomical characteristics of muscles and surrounding tissues. Normalization of the EMG amplitude provides information about the magnitude of muscle activation relative to a reference value. It is essential to select an appropriate method for normalization with specific reference to how the EMG signal will be interpreted, and to consider how the normalized EMG amplitude may change when interpreting it under specific conditions. This matrix, developed by the Consensus for Experimental Design in Electromyography (CEDE) project, presents six approaches to EMG normalization: (1) Maximal voluntary contraction (MVC) in same task/context as the task of interest, (2) Standardized isometric MVC (which is not necessarily matched to the contraction type in the task of interest), (3) Standardized submaximal task (isometric/dynamic) that can be task-specific, (4) Peak/mean EMG amplitude in task, (5) Non-normalized, and (6) Maximal M-wave. General considerations for normalization, features that should be reported, definitions, and "pros and cons" of each normalization approach are presented first. This information is followed by recommendations for specific experimental contexts, along with an explanation of the factors that determine the suitability of a method, and frequently asked questions. This matrix is intended to help researchers when selecting, reporting and interpreting EMG amplitude data.
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5.
Comparison of two treatments on a covariate variable.
Lin, TY, Liao, CT, Li, CR, Tsai, JR, Liu, YT
Journal of biopharmaceutical statistics. 2020;(4):649-661
Abstract
In clinical trials, the efficacy of treatment might be dependent on the value of a covariate variable. Therefore, it might be possible to detect the region over the covariate variable where the two treatments under investigation do not have significantly different efficacy or the region of superiority of one treatment. The non-significant region can be verified to be a confidence interval for the abscissa of the intersection point of two regression lines, and each of the complementary regions of the confidence interval corresponds to a region of superiority. In this study, we develop a method of constructing the confidence interval based on the concept of a generalized pivotal quantity, so as to perform the task of detecting the possible three regions for a clinical trial. Two real-world examples are given to illustrate the application of our proposed method, and a simulation study is conducted to evaluate its performance.
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6.
Problems lowering the study quality in traditional medicine, introspection from an example of meta-analysis of acupuncture.
Chen, Q, Wang, Q, Ding, S, Li, S, Zhang, Y, Chen, S, Lin, X, Li, C, Asakawa, T
BMC complementary medicine and therapies. 2020;(1):41
Abstract
BACKGROUND Most randomized controlled trials (RCTs) of traditional medicine (such as traditional Chinese medicine (TCM), psychotherapy or behavioral therapy, and dietary interventions, etc.) have reported that they could not provide convincing evidence to support the efficacy because of the low quality of their studies. Here, we aimed to determine the underlying problems of the study quality using standards of evidence-based medicine (EBM) to evaluate the efficacy of traditional medicine. METHODS We conducted an example of meta-analysis to evaluate the efficacy of acupuncture, a classical treatment of TCM, for treatment of intracerebral hemorrhage (ICH). The quality of the included studies was evaluated by using a Jadad score. RESULTS A total of 24 Chinese RCTs that enrolled 1815 patients with ICH were included. Although the results suggested that acupuncture had good efficacy for relief of neurological deficits and improvement of the activities of daily living despite the high heterogeneity of the included studies, the low quality of the included literature reduced the worthiness of the evidence. Two systematic problems (lack of blinding and allocation concealment and high heterogeneity) and one non-systematic problem (lack of reports on adverse events and follow-up) of the TCM studies were found in this illustrational meta-analysis. We believed that other interventions of traditional medicine also suffer from these problems. CONCLUSIONS Non-systematic problems can be improved by perfecting the experimental design, educating the researcher, and improving the reporting system. However, systematic problems are derived from the characteristics of traditional medicine that are difficult to be corrected. We propose that adoption of objective indexes might be a better solution to improve the systematic problems of traditional medicine. We summarized the problems and the underlying solutions, which may contribute to improve the study quality of systematic review in traditional medicine, strictly complying with the principles of EBM.
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7.
Pharmacokinetic/pharmacodynamic data extrapolation models for improved pediatric efficacy and toxicity estimation, with application to secondary hyperparathyroidism.
Basu, C, Ma, X, Mo, M, Xia, HA, Brundage, R, Al-Kofahi, M, Carlin, BP
Pharmaceutical statistics. 2020;(6):882-896
Abstract
In most drug development settings, the regulatory approval process is accompanied by extensive studies performed to understand the drug's pharmacokinetic (PK) and pharmacodynamic (PD) properties. In this article, we attempt to utilize the rich PK/PD data to inform the borrowing of information from adults during pediatric drug development. In pediatric settings, it is especially crucial that we are parsimonious with the patients recruited for experimentation. We illustrate our approaches in the context of clinical trials of cinacalcet for treating secondary hyperparathyroidism in pediatric and adult patients with chronic kidney disease, where we model both parathyroid hormone (efficacy endpoint) and corrected calcium levels (safety endpoint). We use population PK/PD modeling of the cinacalcet data to quantitatively assess the similarity between adults and children, and use this information in various hierarchical Bayesian adult borrowing rules whose statistical properties can then be evaluated. In particular, we simulate the bias and mean square error performance of our approaches in settings where borrowing is and is not warranted to inform guidelines for the future use of our methods.
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8.
Identification and evaluation of risk of generalizability biases in pilot versus efficacy/effectiveness trials: a systematic review and meta-analysis.
Beets, MW, Weaver, RG, Ioannidis, JPA, Geraci, M, Brazendale, K, Decker, L, Okely, AD, Lubans, D, van Sluijs, E, Jago, R, et al
The international journal of behavioral nutrition and physical activity. 2020;(1):19
Abstract
BACKGROUND Preliminary evaluations of behavioral interventions, referred to as pilot studies, predate the conduct of many large-scale efficacy/effectiveness trial. The ability of a pilot study to inform an efficacy/effectiveness trial relies on careful considerations in the design, delivery, and interpretation of the pilot results to avoid exaggerated early discoveries that may lead to subsequent failed efficacy/effectiveness trials. "Risk of generalizability biases (RGB)" in pilot studies may reduce the probability of replicating results in a larger efficacy/effectiveness trial. We aimed to generate an operational list of potential RGBs and to evaluate their impact in pairs of published pilot studies and larger, more well-powered trial on the topic of childhood obesity. METHODS We conducted a systematic literature review to identify published pilot studies that had a published larger-scale trial of the same or similar intervention. Searches were updated and completed through December 31st, 2018. Eligible studies were behavioral interventions involving youth (≤18 yrs) on a topic related to childhood obesity (e.g., prevention/treatment, weight reduction, physical activity, diet, sleep, screen time/sedentary behavior). Extracted information included study characteristics and all outcomes. A list of 9 RGBs were defined and coded: intervention intensity bias, implementation support bias, delivery agent bias, target audience bias, duration bias, setting bias, measurement bias, directional conclusion bias, and outcome bias. Three reviewers independently coded for the presence of RGBs. Multi-level random effects meta-analyses were performed to investigate the association of the biases to study outcomes. RESULTS A total of 39 pilot and larger trial pairs were identified. The frequency of the biases varied: delivery agent bias (19/39 pairs), duration bias (15/39), implementation support bias (13/39), outcome bias (6/39), measurement bias (4/39), directional conclusion bias (3/39), target audience bias (3/39), intervention intensity bias (1/39), and setting bias (0/39). In meta-analyses, delivery agent, implementation support, duration, and measurement bias were associated with an attenuation of the effect size of - 0.325 (95CI - 0.556 to - 0.094), - 0.346 (- 0.640 to - 0.052), - 0.342 (- 0.498 to - 0.187), and - 0.360 (- 0.631 to - 0.089), respectively. CONCLUSIONS Pre-emptive avoidance of RGBs during the initial testing of an intervention may diminish the voltage drop between pilot and larger efficacy/effectiveness trials and enhance the odds of successful translation.
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9.
Quality of Lactation Studies Investigating Antidepressants.
den Besten-Bertholee, D, van der Meer, DH, Ter Horst, PGJ
Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine. 2019;(6):359-365
Abstract
Introduction: The aim of this study was to determine the quality of lactation studies investigating antidepressants in breast milk according to the Food and Drug Administration (FDA) draft guidelines and the article by Begg et al., 2002, published in the official journal of the International Lactation Consultant Association (ILCA). Materials and Methods: We used PubMed and LactMed® for the literature search. Furthermore, cross references were searched for additional studies. Results: A total number of 60 articles were included for review. For selective serotonin reuptake inhibitors and venlafaxine, only two studies correctly assessed the absolute infant dose and milk to plasma ratio; one sertraline and one fluoxetine study. Of all tricyclic antidepressants, one study for amitriptyline and one for nortriptyline assessed these endpoints correctly. We found a lack of information on breast milk sampling methods in many studies. Concentrations needed for the calculations were based on single measurements instead of at least five measurements during one dose interval, and the relative infant dose was not normalized by maternal weight, or an average maternal weight of 70 kg was used as a standard. Discussion: We conclude that the quality of the current literature on this topic does not meet the standards of the FDA. Studies of higher quality are needed to determine the extent of drug transfer to breast milk for antidepressants, so an adequate recommendation about use of these drugs during lactation can be given.
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10.
Integrating Clinical and Epidemiologic Data on Allergic Diseases Across Birth Cohorts: A Harmonization Study in the Mechanisms of the Development of Allergy Project.
Benet, M, Albang, R, Pinart, M, Hohmann, C, Tischer, CG, Annesi-Maesano, I, Baïz, N, Bindslev-Jensen, C, Lødrup Carlsen, KC, Carlsen, KH, et al
American journal of epidemiology. 2019;(2):408-417
Abstract
The numbers of international collaborations among birth cohort studies designed to better understand asthma and allergies have increased in the last several years. However, differences in definitions and methods preclude direct pooling of original data on individual participants. As part of the Mechanisms of the Development of Allergy (MeDALL) Project, we harmonized data from 14 birth cohort studies (each with 3-20 follow-up periods) carried out in 9 European countries during 1990-1998 or 2003-2009. The harmonization process followed 6 steps: 1) organization of the harmonization panel; 2) identification of variables relevant to MeDALL objectives (candidate variables); 3) proposal of a definition for each candidate variable (reference definition); 4) assessment of the compatibility of each cohort variable with its reference definition (inferential equivalence) and classification of this inferential equivalence as complete, partial, or impossible; 5) convocation of a workshop to agree on the reference definitions and classifications of inferential equivalence; and 6) preparation and delivery of data through a knowledge management portal. We agreed on 137 reference definitions. The inferential equivalence of 3,551 cohort variables to their corresponding reference definitions was classified as complete, partial, and impossible for 70%, 15%, and 15% of the variables, respectively. A harmonized database was delivered to MeDALL investigators. In asthma and allergy birth cohorts, the harmonization of data for pooled analyses is feasible, and high inferential comparability may be achieved. The MeDALL harmonization approach can be used in other collaborative projects.