The randomized controlled trial (RCT) is the gold standard study design allowing critical comparison of clinical outcomes while minimizing bias. Traditionally clinical trials are evaluated through ...statistical significance, expressed by P-values and confidence intervals. However, until recently, the robustness of a study's conclusions has been given little attention. A new metric, the fragility index, quantifies the number of patients theoretically required to switch outcomes in order to reverse the study conclusions. The primary aim of our work was to determine the fragility index of RCTs in the pediatric orthopaedic literature. The secondary aim was to determine study factors associated with lower fragility index.
Pubmed and Embase were systematically searched for pediatric orthopaedic RCTs published September 1, 2006 to September 1, 2016. Two independent reviewers screened titles, abstracts, and manuscripts to identify studies published in English involving 2 treatment arms. Trials without dichotomous primary or secondary outcomes or with patients >18 years were excluded. Data were extracted from each eligible article in duplicate and the fragility index was determined using Fisher exact test, with previously published methods. Univariate analysis was used to determine factors associated with lower fragility index.
Seventeen trials were eligible for inclusion. The median treatment arm size was 58 and overall sample size was 116 patients. The median fragility index was 3 (range, 0 to 18). A fragility index of 3 means that just 3 patients would need to switch treatment outcomes in order for the trial results to become statistically nonsignificant. In 1 study, the number of patients lost to follow-up exceeded the fragility index, such that the study conclusions could be completely reversed purely depending on the outcomes of the patients lost to follow-up. Lower fragility index was associated with smaller patient sample sizes and greater P-values.
The fragility index is a useful adjunct metric to the P-value and confidence intervals, allowing analysis of the robustness of study conclusions. RCTs in pediatric orthopaedics often have small sample sizes, many with low fragility indices. Future efforts could focus on encouraging institutional collaboration and patient recruitment with the ultimate goal of improving RCT sample sizes, and potentially improving the robustness of RCT results.
Level I.
The gene regulatory networks that coordinate the development of the cardiac and pulmonary systems are essential for terrestrial life but poorly understood. The T-box transcription factor Tbx5 is ...critical for both pulmonary specification and heart development, but how these activities are mechanistically integrated remains unclear. Here using
and mouse embryos, we establish molecular links between Tbx5 and retinoic acid (RA) signaling in the mesoderm and between RA signaling and sonic hedgehog expression in the endoderm to unveil a conserved RA-Hedgehog-Wnt signaling cascade coordinating cardiopulmonary (CP) development. We demonstrate that Tbx5 directly maintains expression of
the RA-synthesizing enzyme, in the foregut lateral plate mesoderm via an evolutionarily conserved intronic enhancer. Tbx5 promotes posterior second heart field identity in a positive feedback loop with RA, antagonizing a Fgf8-Cyp regulatory module to restrict FGF activity to the anterior. We find that Tbx5/Aldh1a2-dependent RA signaling directly activates
transcription in the adjacent foregut endoderm through a conserved MACS1 enhancer. Hedgehog signaling coordinates with Tbx5 in the mesoderm to activate expression of
which induces pulmonary fate in the foregut endoderm. These results provide mechanistic insight into the interrelationship between heart and lung development informing CP evolution and birth defects.
Unstable slipped capital femoral epiphysis (SCFE) may lead to avascular necrosis (AVN) in up to 60% of patients. The aim of this study was to assess the best clinical evidence to determine the effect ...of capsular decompression (CD) on odds of AVN in unstable SCFE.
Medline, Embase, and Cochrane databases were systematically searched for comparative studies investigating AVN rates in unstable SCFE treated with or without CD (aspiration, percutaneous, or open). Quality was evaluated by the Newcastle Ottawa Scale. A comparative analysis with pooled effect estimates using random-effects modeling was calculated. Secondary analysis pooled AVN rates from both comparative studies and case series.
Comparative analysis included 17 retrospective studies with 453 hips (201 with CD, 252 without CD). Thirty-four of 201 (17%) hips with CD developed AVN, while 67 of 252 (27%) hips without CD developed AVN. The odds of AVN for patients treated with or without CD odds ratio=0.80, 95% confidence interval (CI): 0.48-1.35 was not statistically different. Subanalysis on patients treated with in situ pinning or positional reduction and pinning showed no difference in AVN rates with or without CD (odds ratio=0.97, 95% CI: 0.44-2.10). In the secondary analysis of 17 comparative studies and 23 case series, the average rate of AVN was 17%, 0.17 (95% CI: 0.13-0.23) for patients treated with CD (60/447 hips) and 28%, 0.28 (95% CI: 0.22-0.35) for patients treated without CD (129/464 hips).
There was no statistically significant decrease in odds of AVN with CD. However, studies were limited by their retrospective nature and inadequate documentation of CD techniques; the majority lacked femoral head blood flow monitoring to demonstrate adequate decompression. Future prospective studies with carefully documented complete decompression may help to elucidate the effect of CD on AVN risk. Although there was no statistically different odds of AVN with or without CD, even this large meta-analysis was underpowered, and one cannot conclude that there was truly no difference in odds of AVN without an appropriately powered study. Therefore, we recommend routine CD for all unstable SCFEs pending additional research, as CD adds little to the surgical procedure and may minimize the risk of a devastating insult to the femoral head.
Congenital tracheomalacia, resulting from incomplete tracheal cartilage development, is a relatively common birth defect that severely impairs breathing in neonates. Mutations in the Hedgehog (HH) ...pathway and downstream Gli transcription factors are associated with tracheomalacia in patients and mouse models; however, the underlying molecular mechanisms are unclear. Using multiple
mouse mutants including one that mimics Pallister-Hall Syndrome, we show that excessive Gli repressor activity prevents specification of tracheal chondrocytes. Lineage tracing experiments show that Sox9+ chondrocytes arise from HH-responsive splanchnic mesoderm in the fetal foregut that expresses the transcription factor Foxf1. Disrupted HH/Gli signaling results in 1) loss of Foxf1 which in turn is required to support Sox9+ chondrocyte progenitors and 2) a dramatic reduction in
, a secreted ligand that potentiates Wnt signaling known to be required for chondrogenesis. These results reveal a HH-Foxf1-Rspo2 signaling axis that governs tracheal cartilage development and informs the etiology of tracheomalacia.
This study aimed to determine the prevalence and quality of endodontic treatment, by radiographically assessing the periapical periodontitis and endodontic treatment status in patients with ...cardiovascular disease (CVD) and cardiovascular risk (CVR) factors. Patients who visited the Out Patient Department of Institute of Dental Sciences and Department of Cardiology, Institute of Medical Sciences and SUM Hospital, Siksha ‘O’ Anusandhan University, Bhubaneswar, from August 2021 to February 2022, for a check-up or dental problem were considered as participants in this study. After obtaining informed consent, the participants were enrolled on the Oral Infections and Vascular Disease Epidemiology Study (INVEST) IDS, BHUBANESWAR. After testing negative for COVID-19, patients’ demographic details, such as age and gender were recorded, followed by a panoramic radiographic examination (OPG). A total sample of 408 patients were divided into three groups: Group 1/control (without any cardiovascular manifestation) consisting of 102 samples, group 2 of 222 CVR patients, and group 3 of 84 CVD cases. The CVR and CVD groups had a preponderance of elderly age groups between 60 to 70 years, with a significantly higher proportion of males. Co-morbidities such as diabetes mellitus, hypertension, and dyslipidemia were significantly associated with the CVR and CVD groups. From OPG interpretation, it was observed that the periapical radiolucency was greater in the CVR and CVD groups than in the control group (p = 0.009). The prevalence of endodontically treated teeth was higher in CVR and CVD than in the control group (p = 0.028). A high prevalence of dental caries, about 70%, was reported in all three groups (p = 0.356). The presence of dental restoration among all the groups was low (p = 0.079). The proportion of periodontal bone loss in the control group was significantly lower than CVR and CVD (p = 0.000). There was a strong association between periapical radiolucency, endodontically treated teeth, and periodontal bone loss in CVR and CVD patients. Notably, the associations reported herein do not reflect a cause-effect relationship; however, individuals with endodontic pathologies may accumulate additional risk factors predisposing them to hypertension or other CVDs. The results emphasize that eliminating local infections may decrease the systemic infection burden.
Existing visualization recommendation systems commonly rely on a single snapshot of a dataset to suggest visualizations to users. However, exploratory data analysis involves a series of related ...interactions with a dataset over time rather than one‐off analytical steps. We present Solas, a tool that tracks the history of a user's data analysis, models their interest in each column, and uses this information to provide visualization recommendations, all within the user's native analytical environment. Recommending with analysis history improves visualizations in three primary ways: task‐specific visualizations use the provenance of data to provide sensible encodings for common analysis functions, aggregated history is used to rank visualizations by our model of a user's interest in each column, and column data types are inferred based on applied operations. We present a usage scenario and a user evaluation demonstrating how leveraging analysis history improves in situ visualization recommendations on real‐world analysis tasks.
Radiographic examination forms an integral part of clinical dentistry, with some form of radiographs necessary on the majority of patients. Intra-oral periapical (IOPA) radiographs form the backbone ...of imaging for diagnosis and follow-up of various dento-facial pathologies. However, certain patient populations are unable to tolerate intra-oral films/sensors due to various reasons. A not-so recent development called extra-oral periapical (EOPA) radiography may be a useful adjuvant to such a situation, at least in the near future. It is essentially a technique where the film is placed extra-orally overlying the tooth of interest. The following manuscript is an attempt to throw light on this technique and the impact it may have on various disciplines of dental practices. The advantages and disadvantages of EOPA radiography and it′s comparison to IOPA radiography has been discussed.
In a world where technology has bridged the gap
between people communicating to reducing human efforts and
improving efficiency, the problem that major hospitals &
pharmacies face is i.e. lack of ...staff & resources. As per the survey
conducted by LANCET1, India faces a significant shortage in
medical staff which leads to patients being unattended for several
hours. This problem can be solved if the tasks per staff member is
reduced and one such way is by reducing their repetitive
movement from the patient's room to the pharmacy for giving the
medicines to the patient. This effort can be reduced by creating a
remotely located machine which can be placed at the right place to
dispense medicines automatically. This reduces the extra
movements and hence provides them the time to do tasks that are
of more importance. Although the concept of an automated
medicine dispensing unit is not new, it is something that if built
and implemented, can provide aid to patients in developing
countries.
A Seawall requires reflecting and dissipating entire wave energy with zero transmission. The permeability would significantly affect its hydraulic stability under wave loads. Thus, the permeability ...of a structure changes with the material and consequently a variation in the composite structure may give a different perspective on the hydraulic performance of a seawall altogether. As a first step towards establishing the composite seawall, a comprehensive permeability test is performed as a preliminary assessment of hydraulic conductivity. In the current research, a bag made of non-woven geotextile polymer filled with sand and a roll of non-woven needle punched coir geotextile is investigated. A total number of 20 model tests were performed by varying the orientation and positions of the material composites and thereby the gaps in the structure. The results are noted and future research possibilities into the design and development of a composite seawall as an alternative to traditional seawall are thus presented.
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