The EQUATOR Network and reporting guidelines: Helping to achieve high standards in reporting health research studies

Poorly reported research seriously undermines the usability of reported findings and misleads clinicians, researchers, policy makers and, ultimately, patients. Guidelines for reporting health research are available but they are not widely used. The EQUATOR Network is an international initiative that aims to systematically tackle the problems of poor reporting. The main goals of the EQUATOR Network are to improve the clarity, completeness and transparency of scientific publications by providing resources and education relating to the reporting of health research and assisting in the development, dissemination and implementation of robust reporting guidelines.     

Consensus guidelines for the uniform reporting of study ethics in anatomical research within the framework of the anatomical quality assurance (AQUA) checklist

Unambiguous reporting of a study's compliance with ethical guidelines in anatomical research is imperative. As such, clear, universal, and uniform reporting guidelines for study ethics are essential. In 2016, the International Evidence‐Based Anatomy Working group in collaboration with international partners established reporting guidelines for anatomical studies, the Anatomical Quality Assurance (AQUA) Checklist. In this elaboration of the AQUA Checklist, consensus guidelines for reporting study ethics in anatomical studies are provided with in the framework of the AQUA Checklist. The new guidelines are aimed to be applicable to research across the spectrum of the anatomical sciences, including studies on both living and deceased donors. The authors hope the established guidelines will improve ethical compliance and reporting in anatomical research. Clin. Anat. 31:521–524, 2018. © 2018 Wiley Periodicals, Inc.     

Guidelines for clinical trials using artificial intelligence – SPIRIT‐AI and CONSORT‐AI†

The rapidly growing use of artificial intelligence in pathology presents a challenge in terms of study reporting and methodology. The existing guidelines for the design (SPIRIT) and reporting (CONSORT) of clinical trials have been extended with the aim of ensuring production of the highest quality evidence in this field. We explore these new guidelines and their relevance and application to pathology as a specialty. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.     

Methodological reporting behavior,sample sizes,and statistical power in studies of event‐related potentials: Barriers to reproducibility and replicability

Methodological reporting guidelines for studies of ERPs were updated in Psychophysiology in 2014. These guidelines facilitate the communication of key methodological parameters (e.g., preprocessing steps). Failing to report key parameters represents a barrier to replication efforts, and difficulty with replicability increases in the presence of small sample sizes and low statistical power. We assessed whether guidelines are followed and estimated the average sample size and power in recent research. Reporting behavior, sample sizes, and statistical designs were coded for 150 randomly sampled articles from five high‐impact journals that frequently published ERP research from 2011 to 2017. An average of 63% of guidelines were reported, and reporting behavior was similar across journals, suggesting that gaps in reporting is a shortcoming of the field rather than any specific journal. Publication of the guidelines article had no impact on reporting behavior, suggesting that editors and peer reviewers are not enforcing these recommendations. The average sample size per group was 21. Statistical power was conservatively estimated as .72?.98 for a large effect size, .35?.73 for a medium effect, and .10?.18 for a small effect. These findings indicate that failing to report key guidelines is ubiquitous and that ERP studies are primarily powered to detect large effects. Such low power and insufficient following of reporting guidelines represent substantial barriers to replication efforts. The methodological transparency and replicability of studies can be improved by the open sharing of processing code and experimental tasks and by a priori sample size calculations to ensure adequately powered studies.     

An international unified approach to reporting and grading invasive breast cancer. An overview of the International Collaboration on Cancer Reporting (ICCR) initiative

Standardised reporting of breast cancer key pathology data has become the norm in some parts of the world, but are based on national or regional guidelines that differ in certain aspects, resulting in divergent reporting practices and a lack of comparability of data internationally. The International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organizations, have recently produced a new international dataset for the pathology reporting of breast cancer, including resection specimens with invasive cancer and ductal carcinoma in situ (DCIS) of the breast. This initiative aims at providing an international unified approach to reporting cancer. The guidance was prepared by an international expert panel consisting of experienced breast pathologists, a surgeon, and an oncologist. The dataset includes core (essential) and noncore (optional) data items based on a critical review and discussion of current evidence. Commentary is provided for each data item to explain the rationale for selection, its clinical relevance, and to highlight potential areas of disagreement or lack of evidence, in which case a consensus position was formulated. The process concludes with international public consultation, before ratification and publication on the free open access ICCR website, with a synoptic reporting guide. The key aim is to promote high-quality, standardised pathology reporting that can be used worldwide. Histological grade, tumour size, and oestrogen receptor status are used in this article to illustrate this process and the detail provided to support its inclusion.     

The Journal of Pathology's approach to publication ethics and misconduct

This Editorial highlights recent changes at The Journal of Pathology intended to improve our ability to detect, and we hope deter, instances of ethical misconduct among submissions made to the Journal, such as cases of guest authorship and plagiarism. We also discuss our experience to date and describe our policies for dealing with such cases. These changes are all encapsulated in our full online Author Guidelines.     

The Bethesda System for Reporting Thyroid Cytology (TBSRTC): From look‐backs to look‐ahead

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was formalized in October 2007 by experts in thyroidology at the National Institute of Health in Bethesda, Maryland. The first edition of the TBSRTC book was published in 2010 and the second edition in 2018. The TBSRTC is widely employed in cytology practices in the United States and has also served as a model for similar tiered classification schemes for reporting thyroid cytopathology specimens. The tremendous success of TBSRTC cannot be underscored, it has provided a diagnostic framework which is well aligned with the present and the future of thyroid nodule management.     

Ultrasound method applied to characterize healthy femoral diaphysis of Wistar rats in vivo

A simple experimental protocol applying a quantitative ultrasound (QUS)pulse-echo technique was used to measure the acoustic parameters of healthyfemoral diaphyses of Wistar rats in vivo. Five quantitativeparameters [apparent integrated backscatter (AIB), frequency slope of apparentbackscatter (FSAB), time slope of apparent backscatter (TSAB), integratedreflection coefficient (IRC), and frequency slope of integrated reflection(FSIR)] were calculated using the echoes from cortical and trabecular bone inthe femurs of 14 Wistar rats. Signal acquisition was performed three times ineach rat, with the ultrasound signal acquired along the femur''s central regionfrom three positions 1 mm apart from each other. The parameters estimated forthe three positions were averaged to represent the femur diaphysis. The resultsshowed that AIB, FSAB, TSAB, and IRC values were statistically similar, but theFSIR values from Experiments 1 and 3 were different. Furthermore, Pearson''scorrelation coefficient showed, in general, strong correlations among theparameters. The proposed protocol and calculated parameters demonstrated thepotential to characterize the femur diaphysis of rats in vivo.The results are relevant because rats have a bone structure very similar tohumans, and thus are an important step toward preclinical trials and subsequentapplication of QUS in humans.     

Aspirin plus calcium supplementation to prevent superimposed preeclampsia: a randomized trial

Preeclampsia is an important cause of maternal and perinatal morbidity and mortality. Previous studies have tested calcium supplementation and aspirin separately to reduce the incidence of preeclampsia but not the effects of combined supplementation. The objective of this study was to investigate the effectiveness of aspirin combined with calcium supplementation to prevent preeclampsia in women with chronic hypertension. A double-blind, placebo-controlled randomized clinical trial was carried out at the antenatal clinic of a large university hospital in São Paulo, SP, Brazil. A total of 49 women with chronic hypertension and abnormal uterine artery Doppler at 20-27 weeks gestation were randomly assigned to receive placebo (N = 26) or 100 mg aspirin plus 2 g calcium (N = 23) daily until delivery. The main outcome of this pilot study was development of superimposed preeclampsia. Secondary outcomes were fetal growth restriction and preterm birth. The rate of superimposed preeclampsia was 28.6% lower among women receiving aspirin plus calcium than in the placebo group (52.2 vs 73.1%, respectively, P=0.112). The rate of fetal growth restriction was reduced by 80.8% in the supplemented group (25 vs 4.8% in the placebo vs supplemented groups, respectively; P=0.073). The rate of preterm birth was 33.3% in both groups. The combined supplementation of aspirin and calcium starting at 20-27 weeks of gestation produced a nonsignificant decrease in the incidence of superimposed preeclampsia and fetal growth restriction in hypertensive women with abnormal uterine artery Doppler.     

From information processing to behavioral intentions: Exploring cancer patients’ motivations for clinical trial enrollment

Objective

To investigate cancer patients’ motivations for clinical trial enrollment, this study tests the proposition that a model of Risk Information Seeking and Processing (RISP) could serve as an antecedent to the Theory of Planned Behavior (TPB).

Methods

With data from a telephone survey, we examined whether components of the RISP model had significant impact on belief-based attitudes and behavioral intentions.

Results

Risk judgment and affective responses, especially optimistic feelings, consistently related to attitudes and behavioral intentions. Trust in doctors also significantly related to our respondents’ positive attitudes toward clinical trials.

Conclusion

The RISP model might have more constrained applicability as compared to the TPB in explaining cancer patients’ motivations for clinical trial enrollment. However, certain components of the RISP model seemed to contribute to our respondents’ attitude formation as interesting additions to the TPB.

Practice implications

Communication about clinical trials is a balance act between providing sufficient information about the potential risks and benefits involved in a clinical trial and managing emotional responses that cancer patients associate with participation. Both acts contribute to the formation of positive attitudes toward clinical trials among cancer patients, which is the driving force behind their intentions for clinical trial enrollment.     

Single trial coupling of Purkinje cell activity to speed and error signals during circular manual tracking

The simple spike firing of cerebellar Purkinje cells encodes information on the kinematics of limb movements. However, these conclusions have been primarily based on averaging the discharge of Purkinje cells across trials and time and there is little information on whether Purkinje cell simple spike firing encodes specific motor errors during limb movements. Therefore, this study investigated single-trial correlations between the instantaneous simple spike firing of Purkinje cells with various kinematics and error signals. Purkinje cells (n = 126) were recorded in the intermediate and lateral zones centered on the primary fissure while three monkeys intercepted and tracked a target moving in a circle. Cross-correlation analysis was performed between the instantaneous simple spike firing rate and speed, the directional component of the velocity vector, and error signals during single movement trials. Significant correlations at physiologically relevant lags of ±250 ms were observed with tracking speed for 37% of Purkinje cells, with the velocity component in 39%, with direction error in 6% and speed error in 25%. Simple spike firing of the majority of Purkinje cells with significant correlation showed a negative lag with respect to speed and a positive lag with respect to error signals. We hypothesize that the cerebellum is involved in movement planning and control by continuously monitoring movement errors and making intermittent corrections that are represented as fluctuations in the speed profile.     

Energy system contribution in a maximal incremental test: correlations with pacing and overall performance in a 10-km running trial

This study aimed to verify the association between the contribution of energy systems during an incremental exercise test (IET), pacing, and performance during a 10-km running time trial. Thirteen male recreational runners completed an incremental exercise test on a treadmill to determine the respiratory compensation point (RCP), maximal oxygen uptake (V˙O2max), peak treadmill speed (PTS), and energy systems contribution; and a 10-km running time trial (T10-km) to determine endurance performance. The fractions of the aerobic (W_AER) and glycolytic (W_GLYCOL) contributions were calculated for each stage based on the oxygen uptake and the oxygen energy equivalents derived by blood lactate accumulation, respectively. Total metabolic demand (W_TOTAL) was the sum of these two energy systems. Endurance performance during the T10-km was moderately correlated with RCP, V˙O2maxand PTS (P<@0.05), and moderate-to-highly correlated with W_AER, W_GLYCOL, and W_TOTAL (P<0.05). In addition, W_AER, W_GLYCOL, and W_TOTAL were also significantly correlated with running speed in the middle (P<0.01) and final (P<0.01) sections of the T10-km. These findings suggest that the assessment of energy contribution during IET is potentially useful as an alternative variable in the evaluation of endurance runners, especially because of its relationship with specific parts of a long-distance race.     

EAACI Biologicals Guidelines—Omalizumab for the treatment of chronic spontaneous urticaria in adults and in the paediatric population 12–17 years old

Chronic spontaneous urticaria (CSU) imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity and insufficient efficacy of classical drugs such as H₁R-antihistamines. Better understanding of the mechanisms has enabled a stratified approach to the management of CSU, supporting the use of targeted treatment with omalizumab. However, many practical issues including selection of responders, the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based) and its cost-effectiveness still require further clarification. The EAACI Guidelines on the use of omalizumab in CSU follow the GRADE approach in formulating recommendations for each outcome. In addition, future therapeutic approaches and perspectives as well as research priorities are discussed.     

A novel inborn error of the coenzyme Q10 biosynthesis pathway: cerebellar ataxia and static encephalomyopathy due to COQ5 C‐methyltransferase deficiency

Primary coenzyme Q10 (CoQ₁₀; MIM# 607426) deficiencies are an emerging group of inherited mitochondrial disorders with heterogonous clinical phenotypes. Over a dozen genes are involved in the biosynthesis of CoQ₁₀, and mutations in several of these are associated with human disease. However, mutations in COQ5 (MIM# 616359), catalyzing the only C‐methylation in the CoQ₁₀ synthetic pathway, have not been implicated in human disease. Here, we report three female siblings of Iraqi‐Jewish descent, who had varying degrees of cerebellar ataxia, encephalopathy, generalized tonic‐clonic seizures, and cognitive disability. Whole‐exome and subsequent whole‐genome sequencing identified biallelic duplications in the COQ5 gene, leading to reduced levels of CoQ₁₀ in peripheral white blood cells of all affected individuals and reduced CoQ₁₀ levels in the only muscle tissue available from one affected proband. CoQ₁₀ supplementation led to clinical improvement and increased the concentrations of CoQ₁₀ in blood. This is the first report of primary CoQ₁₀ deficiency caused by loss of function of COQ5, with delineation of the clinical, laboratory, histological, and molecular features, and insights regarding targeted treatment with CoQ₁₀ supplementation.