Rigid Inclusion Criteria Research Articles

MIRO study: Do the results of a randomized controlled trial apply in a real population?

BackgroundThe aim of our study was to evaluate the external validity of the MIRO randomized controlled trial findings in a similar nationwide setting “real life” population, especially the benefit of a hybrid approach in esophageal resection for pulmonary complication. The external validity of randomized controlled trial findings to the general population with the same condition remains problematic because of the inherent selection bias and rigid inclusion criteria. MethodsThis study was a cohort study from a National Health Database (Programme de Medicalisation des Systemes d’Informations) between 2010 and 2022. All adult patients operated on using Ivor Lewis resection for esophageal cancer were included. We first validated the detection algorithm of postoperative complications in the health database. Then, we assessed the primary outcome, which was the comparison of postoperative severe pulmonary complications, leak rate, and 30-day mortality between the 2 surgical approaches (hybrid versus open) over a decade. ResultsBetween 2010 and 2012, 162 of 205 patients in the MIRO trial were anonymously identified in the health care database. No difference between randomized controlled trials and healthcare database measurements was found within severe respiratory complications (24% vs 22%, respectively) nor within leak rate (10% vs 9%, respectively). After application of selection criteria according to the MIRO trial, 3,852 patients were included between 2013 and 2022. The hybrid approach was a protective factor against respiratory complications after adjustment for confounding variables (odds ratio = 0.83; 95% confidence interval = 0.71–0.98, P = .025). No significant difference in the 30-day mortality rate or 30-day leakage rate between the types of approach was reported. ConclusionThis national cohort study demonstrates the external validity of the MIRO randomized controlled trial findings in a real-life population within France.

Homoeopathy in the management of chronic kidney disease – A narrative review

Background: Chronic kidney disease (CKD) is the third fastest-growing cause of death around the world and is projected to become the fifth most common cause of years of life lost worldwide by 2040. Objective: This review was done to explore the strengths of homoeopathy in the management of CKD through pre-clinical, clinical and anecdotal evidence. Methods: A search was made for homoeopathic management of CKD in PubMed, Central Council for Research in Homoeopathy e-library, AYUSH Research Portal, EMBASE and Google Scholar. The basic search terms included ‘Homoeopathy’ or ‘homoeopathic drugs’, ‘ESRD’, ‘CRF’, ‘CKD’ and ‘Bright’s disease’. No rigid inclusion criteria was kept due to the paucity of literature on this subject concerning homoeopathy; hence, all studies were included in this review. Further, literature review, through homoeopathic repertories, was also conducted for the anecdotal evidence of frequently used homoeopathic drugs used in the management of CKD. Results: Through an online search, 11 studies were found related to the subject which included two randomised controlled trials (RCTs), eight case series/case reports and one pre-clinical study. Two RCTs focussed on symptoms/signs due to CKD such as pruritus, asthenia, lethargy and headache with positive effects. The evidence generated through case series/reports, though useful for hypothesis-generating studies, was found to have poor reporting quality. Conclusion: At present, the available evidence towards the benefits of homoeopathy in CKD is weak. Further well-designed studies are warranted.

A Meta-Analysis of Facebook-Assisted Learning Outcomes and Their Gender Differences

Social media applications such as Facebook have received wide attention in their use in education. However, it is still hard to arrive at a conclusion regarding whether a Facebook-assisted approach is effective in education and whether there are any significant gender differences in the learning outcomes. Based on rigid inclusion criteria, this study included 21 peer-reviewed high-quality journal articles. Through a meta-analysis using Reviewer Manager 5.3, the authors concluded that a Facebook-assisted approach could obtain significantly higher learning outcomes than the non-Facebook-assisted one with a medium effect size (d = 0.42) and that females could achieve significantly better learning outcomes than males with a very small effect size (d = -0.21) in the Facebook-assisted education. Future research could examine the effect of educational use of other social media applications, as well as in sociological, psychological, or educational dimensions.

Personalized-medicine on carotid endarterectomy and stenting.

Evidence based medicine (EBM) is the core of current clinical guidelines and is considered as the gold standard of clinical practice. Despite this, a number of limitations and criticisms are moved to EBM. The major one is that this method privileges randomized controlled trials (RCTs), in which the selection of patients is often based on rigid inclusion criteria. The lack of “pragmatism” of some RCTs sometimes makes it difficult to apply guidelines that derive from them to patients observed in clinical practice, who are often affected by comorbidities and disabilities. The new paradigm to overcome this limitation is personalized medicine (PM), which aims to take into account the particular characteristics displayed by the individual. In order to tailor the best treatment for the patient, PM uses EBM but emphasizes the person's specific information from the assessment of the clinic, lifestyle and risk/benefit scores. This narrative review tries to find the best evidence by analysing subgroups and risk scores of patients from meta-analysis and RCTs in order to try to apply PM and to provide good practice points (GPP) on grey aspects and open questions not fully covered by current guidelines on carotid endarterectomy (CEA) and stenting for stroke prevention.

Digital epidemiological and citizen science methodology to capture prospective physical activity in free-living conditions: a SMART Platform study

ObjectivesThe purpose of this study was to develop a replicable methodology of mobile ecological momentary assessments (EMAs) to capture prospective physical activity (PA) within free-living social and physical contexts by...

Exoskeletons for all: The interplay between exoskeletons, inclusion, gender, and intersectionality

AbstractIn this article, we investigate the relation between gender and exoskeleton development through the lens of intersectionality theory. Exoskeleton users come in a wide variety of shapes, sizes, and genders. However, it is often the case that wearable robot engineers do not develop such devices primarily on the premise that the product should fit as many end users as possible. Instead, designers tend to use the one-size-fits-all approach – a design choice that seems legitimate from the return of an investment viewpoint but that may not do as much justice to end users. Intended users of exoskeletons have a series of user criteria, including height, weight, and health condition, in the case of rehabilitation. By having rigid inclusion criteria for whom the intended user of the technology can be, the exclusion criteria will grow in parallel. The implications and deep-rootedness of gender and diversity considerations in practices and structural systems have been largely disregarded. Mechanical and robot technology were historically seen as part of a distinct male sphere, and the criteria used today to develop new technology may reflect the biases that existed in another time that should no longer be valid. To make this technology available for all, we suggest some tools to designers and manufacturers to help them think beyond their target market and be more inclusive.

Journal Club: High-dose methylprednisolone for acute traumatic spinal cord injury: A meta-analysis.

Methylprednisolone is a corticosteroid medication used in acute traumatic spinal cord injury (SCI) to tackle secondary injury cascades. Its use in acute SCI has been the subject of controversy for over 30 years. The second National Acute Spinal Cord Injury Study (NASCIS-2) demonstrated a small benefit of methylprednisolone,1 though this conclusion was derived from a post hoc subgroup analysis.2 Studies that followed did not reach the same conclusion and reported potential adverse effects of the drug.3 However, the 2017 AOSpine guideline continues to recommend high-dose methylprednisolone within 8 hours postinjury,4 based on a meta-analysis with rigid inclusion criteria.5 This Journal Club article reports on a study from Liu et al.,6 who have attempted to resolve this controversy. The study provides an elegant example of meta-analytic methods and has important implications for neurologic clinical practice.

NIMG-73. NEUROLOGICAL ASSESSMENT IN NEURO-ONCOLOGY (NANO) CORRELATES WITH INTEGRATED PREDICTIVE RADIOGRAPHIC BIOMARKERS OF PROGRESSED HIGH GRADE ASTROCYTIC TUMORS (IPROMPT): A PROPOSED SUPPLEMENT TO RANO

Abstract This year nearly 86,000 persons in the US will be diagnosed with a primary brain tumor. Glioblastoma (GBM) is the deadliest and most common of these tumors in adults with overall survival around 15mos. Disease progression is inevitable, and effective second-line therapies are few. Delays in identifying progressed GBM risks neurologic decline, continuation of ineffective therapies, and increased tumor-mutational-burden, potentially rendering treatment less-effective. Brain tumor imaging can be ambiguous and is an active topic in neuro-oncology as there are currently no validated approaches to assessment of tumor treatment response. We present a single institution database including 622 gross-totally-resected GBMs (2006–2018) to evaluate changes in T2/FLAIR signal intensity (T2FSI), diffusion restriction, and contrast enhancement both in and around the resection cavity (RC) to determine earliest indicators of tumor progression. Analysis of NANO score was completed to correlate with predicted tumor progression. This is an early data release of an ongoing two-phased retrospective/prospective study with findings that support a novel integration of radiographic sequences and NANO to supplement established RANO criteria in earlier detection of GBM progression. Of 622 confirmed GBMs, 158 fit the rigorous criteria – included here are 58 cases. We report 70% (n=41) of patients show RC T2FSI correlating with restricted diffusion and increasing NANO score (0.5–1.4) as early as 3.8mos prior to and at time of radiographic progression, respectively. Previous studies have reported similar T2FSI but without associated NANO, less rigid inclusion criteria, and limited MRI sequences. We also report imaging phenomena, not previously described, such as FLAIR migration and FLAIR coring timed closely with progression. The proposed technique uses routine MRI, therefore readily standardized in clinical practice. With further validation, this novel integration of imaging and neurologic assessment might serve to supplement existing response criteria in GBM and improve clinician confidence in earlier detection of progression.

Impressive response of CD30‐negative, treatment‐refractory mycosis fungoides to brentuximab vedotin

Brentuximab vedotin is a CD30-antibody/drug conjugate which has demonstrated excellent response in treating CD30-positive mycosis fungoides (MF) and anaplastic large cell lymphoma (ALCL). In this report, we present a patient with CD30-negative MF refractory to multiple other lines of therapy who demonstrated a dramatic response to brentuximab. This paradoxical response may be due to inadequate detection of CD30 expression by immunohistochemical techniques. From this case we see that even in the setting of apparent CD30 negativity, brentuximab may be a viable treatment option for patients who require bridging to stem cell transplant or seek successful palliation. This case highlights the point that rigid inclusion criteria for MF trials without use of more sensitive techniques to confirm lack of CD30 expression may inappropriate.

Maxillary Sinus Floor Elevation Techniques with Recent Advances: A Literature Review

Background: In the rehabilitation of atrophic posterior maxilla, factors such as age, extraction of teeth result in loss of alveolar bone height together with increased pneumatization of sinus contradicting the implant surgery. Although adequate bone height can be achieved using various maxillary sinus augmentation techniques, these procedures have been practiced successfully. However, significant complications occur such as perforations or tearing. To maintain the integrity of Schneiderian membrane subsequently increasing the success rate a retrospective analysis is carried out on various techniques with complications which occur during and after treatment.Methods: A systematic online and manual review of the literature identified articles dealing with SFE. Applying rigid inclusion criteria, screening and data abstraction were performed independently by two reviewers. The follow-up of was a minimum of 6 months. The articles selected were carefully read and data of interest were tabulated. The identified articles were analyzed regarding implant outcome, with or without graft using different surgical techniques with complication rates using random-effects Poisson regression models to obtain summary estimates/ year proportions. This article reviews various sinus lift techniques for intact elevation of Schneiderian membrane based on advanced PUBMED, Medline, Cochrane database system search of English-language literature from the year 2004 to present in order to compare and evaluate the success rate with minimal complications selecting the most suitable which can fulfill the criteria of being non-invasive, less time-consuming, more reliable and less traumatic.Result:After reviewing various sinus elevation techniques; nasal suction technique(NaSucT), balloon antral elevation technique(BAOSFE), and Hydraulic Sinus Lift technique(HySiLift) emerges as more favourable among all these and can efficiently lift the Schneiderian membrane with minimal trauma. We must emphasize that these are new techniques and cannot replace the conventional techniques as a whole.

An Advanced Protocol‐Driven Transition from Parenteral Prostanoids to Inhaled Trepostinil in Pulmonary Arterial Hypertension

Patients with pulmonary arterial hypertension (PAH) often require parenteral prostanoids to improve symptoms and signs of PAH. Complications of parenteral prostanoids-such as catheter-related infections and intolerable adverse effects-may develop, prompting transition to inhaled prostanoids. We report a prospective, protocol-driven transition from parenteral prostanoids to inhaled prostanoids with monitoring of exercise gas exchange and acute hemodynamics. Three PAH centers recruited patients transitioning from parenteral prostanoids to inhaled trepostinil. Rigid inclusion criteria were used, including parenteral prostanoid dose < 30 ng/kg/min, New York Heart Association functional class (FC) < 3, and pulmonary vascular resistance (PVR) < 6 Wood units. Of the 9 patients meeting initial inclusion criteria, 3 were excluded. In the remaining patients, the parenteral prostanoid was reduced and the inhaled prostanoid was increased over 24-36 hours with continuous hemodynamic monitoring. Exercise capacity and FC were measured at baseline and weeks 1, 4, and 12. All patients were successfully weaned from parenteral prostanoids. An acute PVR decrease was seen with most inhaled prostanoid doses, but PVR varied throughout the transition. Patients tolerated inhaled prostanoids for 9-12 breaths 4 times a day with no treatment-limiting adverse events. At week 12, FC was unchanged, and all patients continued to receive inhaled prostanoids without serious adverse events or additional PAH therapy. In 5 of 6 patients, 6-minute walk distance and peak [Formula: see text] were within 10% of baseline. Using a strict transition protocol and rigid patient selection criteria, the parenteral prostanoid to inhaled prostanoid transition appeared safe and well tolerated and did not result in clinical deterioration over 12 weeks. Hemodynamic variability noted acutely during transition in our study did not adversely affect successful transition. (Trial registration: ClinicalTrials.gov identifier: NCT01268553).

Response to “Weight Loss, Blood Pressure Reduction, and Aortic Stiffness: An Old Dilemma Revisited”

While we thank Cockroft and colleagues for their interest in our paper, it is evident that several points need clarification in their letter titled “Weight Loss, Blood Pressure Reduction, and Aortic Stiffness: An Old Dilemma Revisited” (1). As the authors state, Wildman and colleagues have previously established that weight change is a determinant of pulse wave velocity (PWV) (2). However, significant differences exist between their study and ours, making comparison impossible. While recruitment to our study was based on rigid inclusion criteria including BMI, fasting blood glucose, cholesterol, and blood pressure at the point of entry, the Wildman study inclusion was irrespective of BMI and had no specific blood glucose, cholesterol or blood pressure exclusion levels. Perhaps, most importantly, over 20% of their subjects were also smokers. In addition, their cohort was on average overweight and not obese with a BMI of 27 (±5.4), and as a group gained 1.2kg (0.4 kg/m

Retinal nerve fibre layer attenuation: clinical indicator for vigabatrin toxicity

To investigate whether persistent visual field defects among patients exposed once to the antiepileptic drug vigabatrin (VGB) were associated with peripapillary retinal nerve fibre layer thickness (RNFLT) attenuation. Nine individuals with partial epilepsy and VGB-attributed visual field loss (group 1; 18 eyes) and seven age- and gender-matched individuals with epilepsy and no previous VGB exposure (group 2; 14 eyes) were included in the study. Full-field 120 point screening perimetry out to 60 degrees from central fixation using the Humphrey Field Analyzer was performed. RNFLT was quantified by optical coherence tomography (OCT) using Fast RNFLT protocol, Stratus OCT (3.0) after pupillary dilation. The results from the right eye are presented in this article. Among the patients with VGB-attributed visual field loss, five patients had only peripheral field defect (group 1a) and the remaining four had advanced field defects both in the periphery and within 30° from central fixation (group 1b). None of the patients in the control group had manifest visual field loss. The mean RNFLT among the patients with VGB-attributed visual field loss was significantly attenuated compared to the controls [mean total RNFLT: group 1: 75.6 ± 12.7 μm, group 2: 103.5 ± 9.7 μm, mean difference 27.9 μm, (CI 15.9-39.9; p < 0.001)]. RNFLT values classified as borderline according to normative database (Stratus OCT) occurred more frequently among individuals with VGB-attributed visual field loss than in controls (frequency in group 1: 6/9; group 2: 0/7, p = 0.011). The nasal, superior and inferior quadrants of RNFLT in individuals with VGB-attributed visual field loss were significantly attenuated, while no difference was detected in temporal quadrants compared to controls. Both individuals with peripheral and those with advanced visual field losses in the VGB group had attenuated mean total RNFLT compared to controls (p = 0.006, p = 0.002, respectively). Occurrence of borderline classification of total RNFLT ≤5th percentile was more frequent among individuals with advanced visual field loss than among controls (p = 0.048). Persistent visual field loss attributed to VGB is associated with reduced peripapillary RNFLT and was detected both among patients with advanced and among patients with only peripheral visual field defects. Measurements of RNFLT with OCT might be considered as a diagnostic supplement in the follow-up of patients exposed to vigabatrin.

Mycoplasma pneumoniae Encephalitis and Reactivation of Herpes Simplex Virus: In Reply

We thank Dr Eisenhut for his interest in our prospective 12-year study of herpes simplex encephalitis in children.1 Because of the standardized comprehensive prospective microbiologic investigations performed on all children who were admitted to our institution with acute encephalitis, evidence of infection with >1 potential pathogen is often observed. This approach is very different from retrospective reviews of cases in which the final diagnosis is the point of entry into the study. In a recent review of our data, approximately one fourth of the cases showed evidence of infection (of variable strength) with ≥2 pathogens.2 In situations such as this, it is often not possible to determine with certainty which pathogen is the causative agent. Furthermore, in some cases, >1 of the potential pathogens may be playing a role.In regard to the specific cases mentioned by Dr Eisenhut, we disagree with his conclusion that Mycoplasma pneumoniae is the more likely pathogen. We believe that most experts would consider the detection of herpes simplex virus (HSV) in the cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) as strong evidence of causality irrespective of HSV serologic results or microbiologic evidence of infection with other potential pathogens. The failure to detect a rise in complement fixation titer to HSV (cases 7 and 8) between acute and convalescent sera could be a result of the well-known limited sensitivity of this assay.3,4 In regard to case 9, it is possible that the convalescent sample was obtained too early (51 days) for HSV seroconversion to have occurred. In 1 prospective study of HSV seroconversion, the median time between onset of genital tract symptoms and seroconversion was 56 days (interquartile range: 16–121 days).5 In addition, there is a paucity of data on the sensitivity of HSV serology in the setting of HSV encephalitis. We acknowledge that when both HSV and M pneumoniae are detected by PCR in the CSF (cases 7 and 9), it is difficult to assign causality solely to 1 pathogen. To avoid subjective assignment of causality, we set rigid inclusion criteria for herpes simplex encephalitis; these criteria are detailed in the methods section of our article.1Dr Eisenhut refers to “local reactivation” of HSV as a possible explanation for the delayed detection of HSV in the CSF of case patient 9. We do recognize that local reactivation (not causally related to the encephalitis) may be an explanation for some patients with positive HSV CSF PCR results but believe this to be unlikely in this case because of the aforementioned stringent criteria used to define HSV encephalitis. We did exclude several cases in which HSV was detected in the CSF by PCR because of a clear alternative diagnosis or absence of typical CSF, electroencephalographic, or neuroimaging findings, again in accordance with preselected exclusion criteria. As discussed in our article, we support a full course of therapy for possible HSV encephalitis for children in whom HSV is detected in the CSF by PCR irrespective of the suspected cause of the encephalitic process. In addition, it has been shown that the detection of HSV in the CSF by PCR of patients with HSV encephalitis can be delayed.6 Hence, HSV should not be excluded as a possible cause of encephalitis solely on the basis of a single negative CSF PCR assay, particularly if the lumbar puncture was performed during the first 48 to 72 hours of illness.We agree that M pneumoniae is an important cause of acute encephalitis in children and that additional research into the role of this pathogen in neurologic disease is needed. In a previous publication pertaining to M pneumoniae and acute childhood encephalitis, we stratified cases into probable, possible, and indeterminate categories in accordance with the strength of microbiologic evidence implicating M pneumoniae as the cause.7 Accordingly, M pneumoniae was considered to be the probable cause of 6.9% of the acute childhood encephalitis cases. As indicated in that article, cases in which the only evidence of M pneumoniae infection was serologic were often associated with more compelling evidence of infection with other potential pathogens. This observation suggests that many of the positive immunoglobulin M assays for M pneumoniae were probably falsely positive, perhaps as a result of cross-reactivity of M pneumoniae antigens and human brain antigens8–10 or other inherent limitations in the specificity of serologic tests for M pneumoniae.11Determining the etiology and pathogenesis of acute childhood encephalitis remains a major hurdle to the appropriate management of this condition. Ultimately, new innovative diagnostic and treatment strategies will be needed to improve the outcome of this often devastating entity.

Bye Bye By-Line, Hello Contributors

Bye Bye By-Line, Hello Contributors

Sinus Floor Elevation Using Osteotomes: A Systematic Review and Meta‐Analysis

Various techniques of sinus floor elevation (SFE) are described. The elevation with osteotomes (OSFE) from a crestal approach is a relatively new technique. The aim of this systematic review and meta-analysis was to evaluate the clinical outcome of implants placed into the maxillary sinus augmented with an OSFE technique. A systematic online and manual review of the literature identified articles dealing with OSFE. Applying rigid inclusion criteria, screening and data abstraction were performed independently by two reviewers. The follow-up of loaded implants was a minimum of 6 months. The identified articles were analyzed regarding implant outcome and defined surgical aspects. Survival and success rates were estimated by Kaplan-Meier curves. Eight out of 44 articles dealing with osteotome sinus floor elevation met the inclusion criteria. Five of the studies met established success criteria. The survival and success rates were 95.7% and 96.0% after 24 months and 36 months, respectively. The median and mean follow-up periods were 24 and 18.73 months for the survival rate and 24 and 19.7 months for the success rate. Regarding different surgical elements, i.e., osteotome techniques, implant types, and augmentation materials, the database was multivariate. Thus, no statistical analysis could be performed on these parameters. Short-term clinical success/survival (<or years) of implants placed with an osteotome sinus floor elevation technique seems to be similar to that of implants conventionally placed in the partially edentulous maxilla. Controlled prospective clinical studies are needed to evaluate the long-term outcome and various surgical modifications of OSFE.

A Surface Electromyography Assessment of Patients Subsequent to Motor Vehicle Crash (MVC) and Controls to Establish Presence of Soft-Tissue Injury

Introduction. The consequences of motor vehicle crashes (MVC) is broad, involving medical care, time lost from work, insurance claims, and even disability. Despite copious research, no one method has provided both dynamic evaluation and treatment direction. While many studies have been done, none have included comprehensive dynamic muscle imaging with spectral analysis.This pilot study was designed to determine if surface EMG (sEMG) data of cervico-scapular muscles during functional tasks could be used to accurately discriminate between healthy subjects and patients using an automated system of multivariate analyses.Method. Twenty subjects included ten patients in treatment post (recent) whiplash resulting from a MVC and ten controls who met rigid inclusion criteria. The PAC (Physiological Analysis Compilation) sEMG software system, using the Neck-PAC protocol, collected the data. Eliminating human interpretation for complete standardization, the file was then subjected to an automated system of data analysis with multiple clusters of data. This report format produces six scales related to various areas of function and a Physiological Total. One trained evaluator collected data from all twenty subjects. The evaluator then removed all identification and provided them to the author for segregation into the two groups tagged only with a random file number. The author performed the automated analysis on the files with no knowledge of symptoms or group status.Results. The author reviewed the results of the automated report generated and correctly placed all subjects in the appropriate “patient” or “control” group with 100% accuracy. For the patients, the report identified the severity, the major area of faults with specific findings. While this information is valuable for treatment, for the purpose of this study it was not utilized by the treating from which the data was collected.Conclusions. This study suggests that a high technology sEMG system, with multiple combinations of algorithms producing data analysis, can distinguish soft tissue injuries in patients with a whiplash injury from healthy controls.

A multidimensional approach to the assessment of clinical validity in a study on CCVD treatment: dihydroergocristine versus placebo

An example of multidimensional assessment procedure applied to the study of treatment effects in a type of pathological aging is presented in this paper. Data discussed here come from a clinical trial performed to evaluate the effects of an ergot derivate, dihydroergocristine, in CCVD memory deficits. The multidimensional assessment procedure consisted of behavioral, clinical, and psychometric measures aimed to identify both the results related to drug activity (experimental validity), and the implications that these eventual drug-induced changes have on the everyday life patients' competence (clinical validity). 97 out-patients (both sexes were represented), with a mean age of 61.21 y (SD 7.29), who suffered from mild to moderate chronic cerebro-vascular disturbances were included in this double-blind study only when they met rigid inclusion criteria. The experimental period was 12 weeks. Results indicate a pattern of convergent, statistically significant, changes which evidence how treatment-associated memory changes are accompanied by an improvement of emotional and physical well being and by a modification of behavioral structure which is characterized by greater efficiency and greater responsiveness to stimuli.