Online Supplementary File Research Articles

Development of a new health-related quality of life measure for people with diabetes who experience hypoglycaemia: the Hypo-RESOLVE QoL

Aims/hypothesisValid and reliable patient-reported outcome measures are vital for assessing disease impact, responsiveness to healthcare and the cost-effectiveness of interventions. A recent review has questioned the ability of existing measures to assess hypoglycaemia-related impacts on health-related quality of life for people with diabetes. This mixed-methods project was designed to produce a novel health-related quality of life patient-reported outcome measure in hypoglycaemia: the Hypo-RESOLVE QoL.MethodsThree studies were conducted with people with diabetes who experience hypoglycaemia. In Stage 1, a comprehensive health-related quality of life framework for hypoglycaemia was elicited from semi-structured interviews (N=31). In Stage 2, the content validity and acceptability of draft measure content were tested via three waves of cognitive debriefing interviews (N=70 people with diabetes; N=14 clinicians). In Stage 3, revised measure content was administered alongside existing generic and diabetes-related measures in a large cross-sectional observational survey to assess psychometric performance (N=1246). The final measure was developed using multiple evidence sources, incorporating stakeholder engagement.ResultsA novel conceptual model of hypoglycaemia-related health-related quality of life was generated, featuring 19 themes, organised by physical, social and psychological aspects. From a draft version of 76 items, a final 14-item measure was produced with satisfactory structural (χ2=472.27, df=74, p<0.001; comparative fit index =0.943; root mean square error of approximation =0.069) and convergent validity with related constructs (r=0.46–0.59), internal consistency (α=0.91) and test–retest reliability (intraclass correlation coefficient =0.87).Conclusions/interpretationThe Hypo-RESOLVE QoL is a rigorously developed patient-reported outcome measure assessing the health-related quality of life impacts of hypoglycaemia. The Hypo-RESOLVE QoL has demonstrable validity and reliability and has value for use in clinical decision-making and as a clinical trial endpoint.Data availabilityAll data generated or analysed during this study are included in the published article and its online supplementary files (https://doi.org/10.15131/shef.data.23295284.v2).Graphical

Optimal Oracle Inequalities for Projected Fixed-Point Equations, with Applications to Policy Evaluation

Linear fixed-point equations in Hilbert spaces arise in a variety of settings, including reinforcement learning, and computational methods for solving differential and integral equations. We study methods that use a collection of random observations to compute approximate solutions by searching over a known low-dimensional subspace of the Hilbert space. First, we prove an instance-dependent upper bound on the mean-squared error for a linear stochastic approximation scheme that exploits Polyak–Ruppert averaging. This bound consists of two terms: an approximation error term with an instance-dependent approximation factor and a statistical error term that captures the instance-specific complexity of the noise when projected onto the low-dimensional subspace. Using information-theoretic methods, we also establish lower bounds showing that both of these terms cannot be improved, again in an instance-dependent sense. A concrete consequence of our characterization is that the optimal approximation factor in this problem can be much larger than a universal constant. We show how our results precisely characterize the error of a class of temporal difference learning methods for the policy evaluation problem with linear function approximation, establishing their optimality. Funding: This work was partially supported by grants from the Office of Naval Research [Grant DOD-ONRN00014-18-1-2640] and the National Science Foundation (NSF) [NSF-IIS Grant 1909365, NSF-DMS Grant 2015454, and NSF-CCF Grant 1955450] to M. J. Wainwright. Part of this work was performed when A. Pananjady was visiting the Simons Institute for the Theory of Computing, where he was supported by a Swiss Re Research Fellowship. Supplemental Material: The online supplementary file is available at https://doi.org/10.1287/moor.2022.1341 .

The reporting and handling of missing data in longitudinal studies of older adults is suboptimal: a methodological survey of geriatric journals

BackgroundMissing data are common in longitudinal studies, and more so, in studies of older adults, who are susceptible to health and functional decline that limit completion of assessments. We assessed the extent, current reporting, and handling of missing data in longitudinal studies of older adults.MethodsMedline and Embase databases were searched from 2015 to 2019 for publications on longitudinal observational studies conducted among persons ≥55 years old. The search was restricted to 10 general geriatric journals published in English. Reporting and handling of missing data were assessed using questions developed from the recommended standards. Data were summarised descriptively as frequencies and proportions.ResultsA total of 165 studies were included in the review from 7032 identified records. In approximately half of the studies 97 (62.5%), there was either no comment on missing data or unclear descriptions. The percentage of missing data varied from 0.1 to 55%, with a 14% average among the studies that reported having missing data. Complete case analysis was the most common method for handling missing data with nearly 75% of the studies (n = 52) excluding individual observations due to missing data, at the initial phase of study inclusion or at the analysis stage. Of the 10 studies where multiple imputation was used, only 1 (10.0%) study followed the guideline for reporting the procedure fully using online supplementary documents.ConclusionThe current reporting and handling of missing data in longitudinal observational studies of older adults are inadequate. Journal endorsement and implementation of guidelines may potentially improve the quality of missing data reporting. Further, authors should be encouraged to use online supplementary files to provide additional details on how missing data were addressed, to allow for more transparency and comprehensive appraisal of studies.

Introduction to corrigendum to ‘Level of MFAP4 in ascites independently predicts 1-year transplant-free survival in patients with cirrhosis’ [JHEP Reports 3 (2021) 100287

It has come to our attention that the units for both serum MFAP4 and ascites MFAP4 were erroneously reported as U/L in our article rather than the correct units, U/ml. Please see the corrected version of the article here. This error has also been corrected in the online supplementary file. We apologise for this error and any inconvenience caused.

Study protocol of the global Effisayil 1 Phase II, multicentre, randomised, double-blind, placebo-controlled trial of spesolimab in patients with generalized pustular psoriasis presenting with an acute flare

IntroductionGeneralized pustular psoriasis (GPP) is a rare, potentially life-threatening disease characterised by recurrent flares of widespread neutrophilic aseptic skin pustular eruption. Despite the availability of approved biologics for GPP in...

A multi-centre, randomized, non-inferiority trial to compare ulipristal with standard surgical treatment in women with symptomatic uterine fibroids: Protocol of the MYOMEX-2 trial

ObjectivesFibroids are the most common benign tumours found in the uterus and can cause various symptoms. In 20–50 % of the women, an intervention is required. When conservative options fail, invasive options such as hysterectomy, uterine artery embolization or myomectomy are eligible options. Ulipristal acetate (UPA) was launched as the sole available long term pharmaceutical treatment, with the potential to avoid surgery. It is suggested that UPA improves quality of life, reduces symptoms and fibroid volumes. However, UPA is an expensive medicine, is possibly associated with liver injury and has never been directly compared to surgical treatment. The aim of this trial is to compare UPA to surgical treatment on both effectiveness and cost-effectiveness. Primary outcome is the reduction in symptom severity scores (part of the Uterine Fibroid Symptom and Quality of Life questionnaire) at 24 months of follow-up compared to baseline. Secondary outcomes include quality of life, societal costs, societal participation, liver function variation, patient satisfaction and preference. Outcomes will be analysed according to intention-to-treat principle. Study DesignThe MYOMEX-2 trial is an open-label, multicentre, non-inferiority randomized controlled trial. Patients are pre-menopausal women with symptomatic fibroids eligible for surgical treatment (hysterectomy, myomectomy or UAE). Fibroid symptoms may comprise (but are not limited to) heavy menstrual bleeding, bulk symptoms or pain. Patients are randomised 2:1 in a parallel group design between two treatment arms: 119 patients in the UPA group and 60 patients in the surgery group. Follow up comprises of online questionnaires, outpatient visits and phone appointments on several follow up moments, up to 24 months after surgery or start UPA. Registration detailsMYOMEX-2 trial; protocol version 4, date 22−02-2019; NTR6860; NL62638.029.18. All items from the World Health Organization Trial Registration Data Set are provided in the online supplementary file (Appendix-B).

Prospective evaluation of improving fluoroquinolone exposure using centralised therapeutic drug monitoring (TDM) in patients with tuberculosis (PERFECT): a study protocol of a prospective multicentre cohort study

IntroductionGlobal multidrug-resistant tuberculosis (MDR-TB) treatment success rates remain suboptimal. Highly active WHO group A drugs moxifloxacin and levofloxacin show intraindividual and interindividual pharmacokinetic variability which can cause low drug exposure....

Stylized versus voxel phantoms: a juxtaposition of organ depth distributions

For external irradiation, the variability in organ dose estimation found between computational phantom generations arises particularly from the differences in organ positioning. This work represents the first effort to quantify the differences in organ depth below the body surface between a stylized and voxel phantom series. Herein, the revised Oak Ridge National Laboratory stylized phantom series and the University of Florida/National Cancer Institute voxel phantom series were compared. Both series include whole-body models of the newborn; the 1-, 5-, 10-, and 15-year-old; and the adult human. Organ depths from eight different directions applicable to external irradiation geometries were computed: antero-posterior, postero-anterior, left and right lateral, rotational, isotropic, cranial and caudal directions. Organ depths in the stylized phantoms were computed using a ray-tracing technique available through Monte Carlo radiation transport simulations in MCNP6. Organ depths in the voxel phantom were found using phantom matrix manipulation. Resultant organ depths for both series were plotted as distributions; available are twenty-four organs and two bone tissue distributions for each of six phantom ages and in each of the eight directional geometries. Quantitative data descriptors (e.g. mean and median depths) were also tabulated. For demonstration purposes, a literature review of relevant stylized versus voxel comparison works was performed to explore where the quantification of organ depth differences can provide further insight or evidence to study conclusions. The entire dataset of organ depth distributions and their data descriptors can be found in online supplementary files.

Optimus BONUS: open access simulation-based education packages on paediatric resuscitation using spaced repetition and deliberate practice

Open access paediatric healthcare simulations are relatively scarce.1 2 In addition, freely available scenarios are packaged as isolated educational experiences separate from the broader educational needs of individuals and institutions....

Phenotypic alterations in pancreatic lymph node stromal cells from human donors with type 1 diabetes and NOD mice.

Tolerance induction in lymph nodes can be mediated by both haematopoietic cells (e.g. specific dendritic cells subsets) and by non-haematopoietic cells (e.g. lymph node stromal cells [LNSCs]) when they present peripheral tissue antigens to autoreactive T cells. LNSCs normally regulate T cell trafficking and survival and help to maintain peripheral tolerance by exerting immunosuppressive effects. However, whether autoimmunity can be associated with defective tolerogenic functions of LNSCs is unknown and studies aimed at characterising LNSCs in humans are lacking. We hypothesised that dysregulated T cell responses in pancreatic lymph nodes (PLNs) from donors with type 1 diabetes and from NOD mice may be associated with altered LNSC function. We analysed PLNs from donors with type 1 diabetes and NOD mice for LNSC distribution and phenotype using flow cytometry. We assessed the expression of tolerance-related genes in different subsets of LNSCs from human donors, as well as in a population of dendritic cells enriched in autoimmune regulator (AIRE)+ cells and identified as HLA-DRhigh CD45low. The relative frequency of different LNSC subsets was altered in both donors with type 1 diabetes and NOD mice, and both MHC class II and programmed death-ligand 1 (PD-L1) expression were upregulated in human type 1 diabetes. Tolerance-related genes showed similar expression profiles between mouse and human LNSCs at steady state but were generally upregulated in the context of human type 1 diabetes, while, at the same time, many such genes were downregulated in the AIRE-enriched dendritic cell population. Our study shows that LNSCs are substantially altered in type 1 diabetes, but, surprisingly, they exhibit an enhanced tolerogenic phenotype along with increased antigen-presenting potential, which may indicate an attempt to offset dendritic cell-related tolerogenic defects in tolerance. Thus, LNSCs could constitute alternative therapeutic targets in which to deliver antigens to help re-establish tolerance and prevent or treat type 1 diabetes. All data generated or analysed during this study are included in the published article (and its online supplementary files). Biomark gene expression data were deposited on the Mendeley repository at https://data.mendeley.com/datasets/d9rdzdmvyf/1 . Any other raw datasets are available from the corresponding author on reasonable request. No applicable resources were generated or analysed during the current study.

Should this systematic review and meta-analysis change my practice? Part 2: exploring the role of the comparator, diversity, risk of bias and confidence

Systematic review and meta-analyses (SRMA) represent the highest quality of evidence of the effects of interventions and have the capacity to usefully inform clinical decisions, reduce research waste and direct...

Correction to: A systematic review of patient perspectives on surveillance after colorectal cancer treatment.

The original version of this article unfortunately contained a mistake. The online supplementary files are missing. The complete version of online supplementary materials are published with this erratum.

Standard admission order sets promote ordering of unnecessary investigations: a quasi-randomised evaluation in a simulated setting

Standard admission order sets have become ubiquitous across hospitals to promote adherence to practice guidelines and increase ordering efficiency.1 2 This standardisation arose in part out of a need to...

Effects of kinesiotaping added to a rehabilitation programme for patients with rotator cuff tendinopathy: protocol for a single-blind, randomised controlled trial addressing symptoms, functional limitations and underlying deficits

IntroductionRotator cuff tendinopathy (RCTe) is the most frequent cause of shoulder pain, resulting in considerable losses to society and public resources. Muscle imbalance and inadequate sensorimotor control are deficits often...

The treatment of multidirectional instability of the shoulder with a rehabilitation programme: Part 2.

The most commonly recommended initial treatment for multidirectional instability is a rehabilitation program. Although there is evidence to support the effect of conservative management on this condition, the published literature provides little information on the exercise parameters of such programs. This paper is the second part of a two-part series that outlines a six-stage rehabilitation program for multidirectional instability with a focus on scapula control and exercise drills into functional positions. This paper outlines stages 3 to 6 of this rehabilitation program. This clinical protocol is currently being tested for efficacy as part of a randomized controlled trial (Australian New Zealand Clinical Trials Registry #ACTRN12613001240730). The information in this paper and additional online supplementary files will provide therapists with adequate detail to replicate the rehabilitation program in the clinical setting.

The treatment of multidirectional instability of the shoulder with a rehabilitation program: Part 1.

The most commonly recommended initial treatment for multidirectional instability is a rehabilitation program. Although there is evidence to support the effect of conservative management on this condition, the published literature provides little information on the exercise parameters of such programs. In addition, current published rehabilitation programs for multidirectional instability do not focus on scapula stability or exercise drills into functional and sports-specific positions, which are often important aspects to consider in this patient population. The aim of this paper (Part 1) is to outline the first two stages of a six-stage rehabilitation program for the conservative management of multidirectional instability with a focus on scapula control and exercise drills into functional positions. This clinical protocol is currently being tested for efficacy as part of a randomized controlled trial (Australian New Zealand Clinical Trials Registry #ACTRN12613001240730). The information in this paper and additional online supplementary files will provide therapists with adequate detail to replicate the rehabilitation program in the clinical setting.

Clinical and technical considerations in the analysis of gingival crevicular fluid.

Despite the technical challenges involved when collecting, processing and analyzing gingival crevicular fluid samples, research using gingival crevicular fluid has, and will continue to play, a fundamental role in expanding our understanding of periodontal pathogenesis and healing outcomes following treatment. A review of the literature, however, clearly demonstrates that there is considerable variation in the methods used for collection, processing and analysis of gingival crevicular fluid samples by different research groups around the world. Inconsistent or inadequate reporting impairs interpretation of results, prevents accurate comparison of data between studies and potentially limits the conclusions that can be made from a larger body of evidence. The precise methods used for collection and analysis of gingival crevicular fluid (including calibration studies required before definitive clinical studies) should be reported in detail, either in the methods section of published papers or as an online supplementary file, so that other researchers may reproduce the methodology. Only with clear and transparent reporting will the full impact of future gingival crevicular fluid research be realized. This paper discusses the complexities of gingival crevicular fluid collection and analysis and provides guidance to researchers working in this field.

Potential Dangers with Open Access Data Files in the Expanding Open Data Movement

Scientific papers with large data sets tend to be supported by open access online supplementary files that fortify verification, reproducibility, and accountability. Such files complete the background picture of a scientific manuscript and tend to be presented to the public in a variety of common file formats, such as Word, Excel or PDF. Yet, such files may potentially also present a risk since their content is most often not protected and could be easily mined by dishonest parties. These concerns, as well as the policies in place by seven leading STM publishers, are discussed with a view to increasing awareness. Simple solutions are available to reduce the risk, but surprisingly, these have not been applied widely yet.

Sequential Sufficient Dimension Reduction for Large p, Small n Problems

Summary We propose a new and simple framework for dimension reduction in the large p, small n setting. The framework decomposes the data into pieces, thereby enabling existing approaches for n&amp;gt;p to be adapted to n &amp;lt; p problems. Estimating a large covariance matrix, which is a very difficult task, is avoided. We propose two separate paths to implement the framework. Our paths provide sufficient procedures for identifying informative variables via a sequential approach. We illustrate the paths by using sufficient dimension reduction approaches, but the paths are very general. Empirical evidence demonstrates the efficacy of our paths. Additional simulations and applications are given in an on-line supplementary file.

Conservative treatment of adhesive small bowel obstruction in children: a systematic review

ObjectiveTo assess the effectiveness of conservative treatment for adhesive small bowel obstruction (ASBO) in children.DesignSystematic review of studies involved children with ASBO who received initial conservative/non-operative treatment.SettingThe search was performed...