Miracle-dz/UniFAR-FTUs huggingface dataset:
Blinding and bias in randomized controlled trials: when to measure the effectiveness of blinding

EDITOR–A recent letter by Hastings‐Ison and Graham1 considered three randomized controlled trials (RCTs) that report the outcome of botulinum neurotoxin A (BoNT‐A) injections in children with cerebral palsy (CP), and asserted that they were not effectively blinded. This assertation is made because, at follow‐up, parents and researchers were able to identify which group (BoNT‐A or placebo) the child was allocated to. However, a question such as ‘Do you think your child received BoNT‐A or placebo? ’ can only be used to assess the effectiveness of blinding if it is answered before any effect due to the treatment occurs. If the same question is asked after the treatment has taken effect, then it becomes an outcome measure – a measure of the parent's expectation of the intervention's success.
Combined intravenous immunoglobulin and methylprednisolone as induction treatment in chronic inflammatory demyelinating polyneuropathy (OPTIC protocol): a prospective pilot study

We hypothesized that combining intravenous immunoglobulin (IVIg) and intravenous methylprednisolone (IVMP) leads to more frequent remission compared with IVIg alone while maintaining the fast efficacy of IVIg. In this uncontrolled pilot study, we evaluated remission, rate of improvement and safety in patients with chronic inflammatory demyelinating polyradiculoneuropathy receiving induction treatment with combined IVIg and IVMP.
Noise Adaptation Generative Adversarial Network for Medical Image Analysis

Machine learning has been widely used in medical image analysis under an assumption that the training and test data are under the same feature distributions. However, medical images from difference devices or the same device with different parameter settings are often contaminated with different amount and types of noises, which violate the above assumption. Therefore, the models trained using data from one device or setting often fail to work for that from another. Moreover, it is very expensive and tedious to label data and re-train models for all different devices or settings. To overcome this noise adaptation issue, it is necessary to leverage on the models trained with data from one device or setting for new data. In this paper, we reformulate this noise adaptation task as an image-to-image translation task such that the noise patterns from the test data are modified to be similar to those from the training data while the contents of the data are unchanged. In this paper, we propose a novel Noise Adaptation Generative Adversarial Network (NAGAN), which contains a generator and two discriminators. The generator aims to map the data from source domain to target domain. Among the two discriminators, one discriminator enforces the generated images to have the same noise patterns as those from the target domain, and the second discriminator enforces the content to be preserved in the generated images. We apply the proposed NAGAN on both optical coherence tomography (OCT) images and ultrasound images. Results show that the method is able to translate the noise style. In addition, we also evaluate our proposed method with segmentation task in OCT and classification task in ultrasound. The experimental results show that the proposed NAGAN improves the analysis outcome.
Low miR-150-5p and miR-320b Expression Predicts Reduced Survival of COPD Patients

Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of death, reducing life expectancy on average between 5 and 7 years. The survival time after diagnosis, however, varies considerably as a result of the heterogeneity of COPD. Therefore, markers that predict individual survival of COPD patients are of great value. We analyzed baseline molecular profiles and collected 54 months of follow-up data of the cohort study “COPD and SYstemic consequences-COmorbidities NETwork” (COSYCONET). Genome-wide microRNA signatures from whole blood collected at time of the inclusion in the study were generated for 533 COPD patients including patients that deceased during the 54-month follow-up period (n = 53) and patients that survived this period (n = 480). We identified two blood-born microRNAs (miR-150-5p and miR-320b) that were highly predictive for survival of COPD patients. The expression change was then confirmed by RT-qPCR in 245 individuals. Ninety percent of patients with highest expression of miR-150-5p survived the 54-month period in contrast to only 50% of patients with lowest expression intensity. Moreover, the abundance of the oncogenic miR-150-5p in blood of COPD patients was predictive for the development of cancer. Thus, molecular profiles measured at the time of a COPD diagnosis have a high predictive power for the survival of patients.
Improved Accuracy of Cervical Spinal Surgery With Robot-Assisted Screw Insertion: A Prospective, Randomized, Controlled Study.

STUDY DESIGN Prospective, randomized, controlled trial. OBJECTIVE To compare robot-assisted and conventional implantation techniques by evaluating the accuracy and safety of implanting screws in cervical vertebrae. SUMMARY OF BACKGROUND DATA Cervical spinal surgery is difficult and dangerous as screw misplacement might lead not only to decreased stability but also neurological, vascular, and visceral injuries. A new robot-assisted surgical procedure has been introduced to improve the accuracy of implant screw positioning. METHODS We randomly assigned 135 patients with newly diagnosed cervical spinal disease and who required screw fixation using either robot-assisted or conventional fluoroscopy-assisted cervical spinal surgery. The primary outcomes were the discrepancies between the planned trajectories and the actual screw positions. RESULTS Altogether, 127 patients underwent the assigned intervention (61 robot-assisted and 66 conventional fluoroscopy-assisted). The baseline characteristics including the screw types, were similar in the two groups. Altogether, 390 screws were planed and placed in the cervical vertebrae, and 94.9% were acceptable. The robot-assisted group had a better screw placement accuracy than the conventional fluoroscopy-assisted group with associated p values <0.001 [0.83 (0.44, 1.29) vs 1.79 (1.41, 2.50) mm]. The Gertzbein and Robbins scales also showed a significant difference between the two groups (p < 0.001). Furthermore, the robot-assisted group experienced significantly less blood loss during surgery than the conventional fluoroscopy-assisted group [200 (50, 375) vs 350 (100, 500) ml; p=0.002] and shorter length of stay after surgery (p = 0.021). These two groups did not differ significantly regarding the duration of the operation (p = 0.525). Neurological injury occurred in one case in the conventional fluoroscopy-assisted group. CONCLUSIONS The accuracy and clinical outcomes of cervical spinal surgery using the robot-assisted technique tended to be superior to those with the conventional fluoroscopy-assisted technique in this prospective, randomized, controlled trial. LEVEL OF EVIDENCE 2.
Making Causal Inference More Social and (Social) Epidemiology More Causal.

A society's social structure and the interactions of its members determine when key drivers of health occur, for how long they last, and how they operate. Yet, it has been unclear whether causal inference methods can help us find meaningful interventions on these fundamental social drivers of health. Galea and Hernán propose that we place hypothetical interventions on a spectrum and estimate their effects by emulating trials, either through individual-level data analysis or systems science modeling (Galea & Hernán. Am J Epidemiol. 2019;XX(XX):XXXX-XXXX)). In this commentary, by way of example in health disparities research, we probe this "closer engagement of social epidemiology with formal causal inference approaches. " The formidable, but not insurmountable, tensions call for causal reasoning and effect estimation in social epidemiology that should always be enveloped by a thorough understanding of how systems and the social exposome shape risk factor and health distributions. We argue that one way towards progress is a true partnership of social epidemiology and causal inference with bilateral feedback aimed at integrating social epidemiologic theory, causal identification and modeling methods, systems thinking, and improved study design and data. To produce consequential work, we must make social epidemiology more causal and causal inference more social.
Nivolumab-associated bullous pemphigoid reactions involving multiple epitopes

Figure 1. Clinical and histopathological features. A, B) Various sizes of flaccid blisters/pustules with crusts and tense bullae on the lower extremities. C) Macular erythema with crusts and brown pigmentation on the abdomen. D) Intraepidermal neutrophilic abscesses with acantholysis (hematoxylin and eosin stain [H&E]; original magnification: ×200). E) In some lesions, subepidermal clefts with marked oedema are observed (H&E; original magnification: ×200). F) A number of eosinophils have infiltrated the upper and mid-dermis (H&E; original magnification: ×400). G) Intercellular IgA deposition shown by direct immunofluorescence staining.
The use of allergen-specific IgE tests in general practice.

INTRODUCTION In Denmark, diagnosing and treating allergy is mainly performed by general practitioners (GPs), but precise expectations of the GPs are not described in guidelines. Furthermore, very little is known about GPs' use of allergen-specific immunoglobulin E (sIgE) tests. The aim of this study was to describe the use of these tests in the Central Denmark Region. METHODS We performed analyses on data from all sIgE tests ordered by GPs in the Central Denmark Region in 2015. A test was considered positive if the serum level of IgE was ≥ 0.35 kU/l. RESULTS Serum levels of sIgE were determined in 26,129 patients, equivalent to 2% of the Danish population. A total of 106,237 tests were performed, the majority as part of screening algorithms for inhalant and food allergens. Screening was ordered 20,697 times for inhalation allergens and 12,999 times for food allergens. Additionally, a considerable number of tests for antibiotics (n = 4,407), insect venom (n = 748) and other allergens were performed (n = 824). Positive rates were determined for various allergens in relation to gender and age. The rates were generally higher than rates known to be present in the background population. A higher percentage of females than males was tested. However, positive rates were generally lower in females than in males. CONCLUSIONS This is the first descriptive analysis of the use of testing for sIgE in general practice. Results from this study may be used to optimise how GPs order and interpret sIgE tests in the future. FUNDING none. TRIAL REGISTRATION not relevant.
Visualizing the Complexity of the Athlete-Monitoring Cycle Through Principal-Component Analysis.

PURPOSE To discuss the use of principal-component analysis (PCA) as a dimension-reduction and visualization tool to assist in decision making and communication when analyzing complex multivariate data sets associated with the training of athletes. CONCLUSIONS Using PCA, it is possible to transform a data matrix into a set of orthogonal composite variables called principal components (PCs), with each PC being a linear weighted combination of the observed variables and with all PCs uncorrelated to each other. The benefit of transforming the data using PCA is that the first few PCs generally capture the majority of the information (ie, variance) contained in the observed data, with the first PC accounting for the highest amount of variance and each subsequent PC capturing less of the total information. Consequently, through PCA, it is possible to visualize complex data sets containing multiple variables on simple 2D scatterplots without any great loss of information, thereby making it much easier to convey complex information to coaches. In the future, athlete-monitoring companies should integrate PCA into their client packages to better support practitioners trying to overcome the challenges associated with multivariate data analysis and interpretation. In the interim, the authors present here an overview of PCA and associated R code to assist practitioners working in the field to integrate PCA into their athlete-monitoring process.
Racial and Gender Differences in the Presentation of Pruritus

Background: Pruritus is a common disease symptom with a variety of etiologies known to reduce patient quality of life. We aimed to characterize the racial and gender differences in the presentation of pruritus for itch-related patient visits both within a single institution and nationally. Methods: Cross sectional study of patients ≥ 18 years old seen at Johns Hopkins Health System between 1/1/12 and 1/1/18. Results were compared to data from 2005–2011 from the National Ambulatory Medical Care Survey (NAMCS) and the National Health Ambulatory Medical Care Survey (NHAMCS). Results: Our findings indicate that itch patients at JHHS (n = 18,753) were more likely to be black compared to white patients (37% vs. 19%, p < 0.01) when compared to patients without itch—a trend also noted nationally based on data from NAMCS/NHAMCS (26% vs. 21%, p = 0.05). Black itch patients are also more likely to be diagnosed with prurigo nodularis (OR 2.37, p < 0.0001), lichen planus (OR 1.22, p < 0.0001), and atopic dermatitis OR 1.51, p < 0.0001). Female itch patients are more likely to be diagnosed with autoimmune (OR 1.66, p < 0.0001) and psychiatric comorbidities (OR 1.2–1.8, p < 0.0001) than male itch patients. When compared to black itch patients nationally, white itch patients were more likely to visit a dermatologist (29% vs. 18%, p = 0.028). Our data can identify associated conditions and demographic differences but are unable to support a causal relationship. Conclusions: Black and female patients are more likely to present with pruritus, a symptom associated with comorbidities such as prurigo nodularis, lichen planus, atopic dermatitis, and psychiatric conditions.
Antiretroviral therapy adherence among treatment-naive HIV-infected patients: A retrospective cohort study.

OBJECTIVE To determine the incidence of antiretroviral therapy (ART) adherence among treatment-naive HIV infected patients and to evaluate the impact of single-tablet regimen (STR) on ART adherence among this population. DESIGN Retrospective cohort study. METHODS We used a nationally representative sample of IQVIA LRx Lifelink individual level pharmacy claims database during 2011-16, and defined adult patients with index date (first complete ART regimen prescription fill date) after June 30, 2011 as treatment-naive. We estimated ART adherence, measured as the proportion of days covered (PDC) during one year following the index date. We conducted multivariable analysis to identify the factors associated with optimum adherence (≥90% PDC). We also compared adherence between patients prescribed STR and multiple-tablet regimens (MTR) among those prescribed integrase strand transfer inhibitor (INSTI)- or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. RESULTS Overall 42.9% of the patients were optimally adherent. Adherence was significantly lower among blacks, Hispanics and patients in low income communities. Adjusting for the covariates, patients on STR had higher incidence of optimum adherence compared to those on MTR among patients on INSTI-based regimens [49% vs 24%, Relative Risk (RR), 2.16 (95% CI: 1.96-2.26)], but no significant difference was observed among those on NNRTI-based regimen [45% vs 45%, RR, 1.12 (95% CI: 0.99-1.26)]. CONCLUSION Low ART adherence observed among treatment naïve patients in this nationally representative study suggests the need for public health interventions to improve adherence among this population.
Adult attachment anxiety moderates the relation between self-reported childhood maltreatment and borderline personality disorder features.

Childhood maltreatment is one of many risk factors for borderline personality disorder (BPD). However, not all individuals with BPD report histories of childhood maltreatment. Therefore, it is necessary to identify factors that contextualize the relation between childhood maltreatment and BPD features. With its emphasis on the developmental origins of emotion regulation, attachment theory provides a useful framework to understand how people are differentially affected by early life stress. The present study examined self-reported adult attachment as a moderator in the relation between childhood maltreatment and BPD features in a large undergraduate sample (n = 1 033). Attachment anxiety, but not attachment avoidance, moderated the relation between childhood maltreatment and BPD features, and this relation was non-significant among participants low (-1 standard deviation) in attachment anxiety. These results support the hypothesis that secure attachment in adulthood may buffer against the otherwise deleterious effects of distal risk factors on personality pathology. Future research should continue to examine this question across risk factors and across disorders. Furthermore, we suggest that researchers who have historically examined attachment as a mediator cross-sectionally should re-examine their data for evidence of a moderation effect. © 2019 John Wiley & Sons, Ltd.
Influence of Storage Conditions and Preservatives on Metabolite Fingerprints in Urine

Human urine, which is rich in metabolites, provides valuable approaches for biomarker measurement. Maintaining the stability of metabolites in urine is critical for accurate and reliable research results and subsequent interpretation. In this study, the effect of storage temperature (4, 22, and 40 °C), storage time (24 and 48 h), and use of preservatives (boric acid (BA), thymol) and para-aminobenzoic acid (PABA) on urinary metabolites in the pooled urine samples from 20 participants was systematically investigated using large-scale targeted liquid chromatography tandem mass spectrometry (LC-MS/MS)-based metabolomics. Statistical analysis of 158 reliably detected metabolites showed that metabolites in urine with no preservative remained stable at 4 °C for 24 and 48 h as well as at 22 °C for 24 h, but significant metabolite differences were observed in urine stored at 22 °C for 48 h and at 40 °C. The mere addition of BA caused metabolite changes. Thymol was observed to be effective in maintaining metabolite stability in urine in all the conditions designed, most likely due to the inhibitory effect of thymol on urine microbiota. Our results provide valuable urine preservation guidance during sample storage, which is essential for obtaining reliable, accurate, and reproducible analytical results from urine samples.
A critical appraisal of vasomotor symptom assessment tools used in clinical trials evaluating hormone therapy compared to placebo.

OBJECTIVE Vasomotor symptoms (VMS) have been consistently reported as the leading predictor of health-related quality of life (HRQOL) among menopausal women, and the strongest indication for treatment. The North American Menopause Society endorses the use of oral estrogen for the treatment of VMS based on a Cochrane meta-analysis. The Cochrane review concludes that oral hormone therapy reduces the frequency and severity of VMS. The objective of this review is to critically appraise the outcome measures used in these clinical trials to evaluate whether there is adequate evidence that oral hormone therapy improves HRQOL. METHODS Each trial in the 2004 Cochrane review of oral hormone therapy for the management of VMS was evaluated with respect to study design, outcome measures, and method of analysis. RESULTS Twenty-four randomized, double-blind, placebo-controlled clinical trials were appraised. Six trials were excluded from the Cochrane meta-analysis due to inadequate reporting of outcome measures. Of the remaining trials, 15 trials assessed only symptom frequency and/or severity. One trial used a subscale of the General Health Questionnaire. Two trials used the Greene Climacteric Scale, a validated outcome measure in menopausal women, to directly assess the impact of hormone therapy on HRQOL. Both studies showed an improvement in HRQOL in the hormone-treated group, although the sample size was small (n = 118) and the effect was modest. CONCLUSION Although oral hormone therapy improves VMS scores, there is a paucity of evidence on whether it improves HRQOL in menopausal women. Future studies using validated, patient-reported outcome measures that directly assess HRQOL are needed.
Clinical value of soluble urokinase type plasminogen activator receptors in chronic kidney disease

Abstract Chronic kidney disease (CKD) will progress to end stage without treatment, the decline off renal function may not linear. A sensitive marker such as soluble urokinase-type plasminogen activator receptors (suPARs) may allow potential intervention and treatment in earlier stages of CKD. Objectives: This study was designed to measure plasma (suPAR) in patients with CKD with different stages and to find its correlation with the disease severity. Methods: This study was conducted on 114 subjects, 84 were patients with different stages and different causes of CKD, and 30 healthy subjects as controls. Blood urea, serum creatinine, serum high-sensitive C-reactive protein, estimated glomerular filtration rate, and 24 hours proteinuria were measured, renal biopsy was done for all patients, and plasma (suPAR) was measured using enzyme-linked immunosorbent assay. Results: suPAR plasma levels were significantly higher in patients with CKD (7.9 ± 3.82 ng/mL) than controls (1.76 ± 0.77 ng/mL, P < .001). suPAR correlated with the disease severity. In stage 1 to 2 group, it was 3.7 ± 1.5 ng/mL, in stage 3 to 4, it was 10.10 ± 1.22 ng/mL, and in stage 5 group, it was 12.34 ± 0.88 ng/mL; the difference between the 3 groups was highly significant (P < .001). A cutoff point 2.5 ng/mL of suPAR was found between controls and stage 1 group. According to the cause of CKD, although patients with obstructive cause and those with focal glomerulosclerosis had the higher levels 9.11 ± 3.32 ng/mL and 8.73 ± 3.19 ng/mL, respectively, but there was no significant difference between patients with CKD according to the cause of the CKD. Conclusion: Plasma (suPAR) increased in patients with CKD and correlated with disease severity.
Combined pulsed and thermal radiofrequency versus thermal radiofrequency alone in the treatment of recurrent trigeminal neuralgia after microvascular decompression: A double blinded comparative study

Recurrent trigeminal neuralgia (RTN) is a common clinical problem and pain recurs in many patients after microvascular decompression (MVD). We evaluated the effect of adding pulsed radiofrequency to radiofrequency thermocoagulation at 60°C compared to radiofrequency thermocoagulation at 70°C alone in the treatment of recurrent trigeminal neuralgia after microvascular decompression.