Category: Statistics

Lymphat Res Biol. 2022 Jun 10. doi: 10.1089/lrb.2021.0076. Online ahead of print.

ABSTRACT

Background: Lymphatic endothelial cells production or modification were closely related to the extracellular matrix (ECM) molecules. The serum hyaluronic acid (HA), laminin (LN), procollagen type III N-peptide (PIIINP), and collagen type IV (CGIV) levels were researched to explore the clinical significance of serum ECM proteins in the diagnosis and differentiation of lymphedema. Methods: Fifty-five patients were enrolled. They were divided into primary lymphedema (PLE), secondary lymphedema (SLE), and venous edema (VE) groups. Twenty-two healthy controls were also recruited as normal control (NC). Serum HA, LN, PIIINP, and CGIV levels of all subjects were assessed using chemiluminescence immunoassay. Statistical analysis and receiver operating characteristic (ROC) curves were used to data analysis. Results: The serum levels of CGIV were significantly decreased in both PLE and SLE groups compared with those in the NC group. Reduced serum CGIV levels were associated with the severity of lymphedema. The serum levels of CGIV and PIIINP were identified decreased in both PLE and SLE groups compared with those in the VE group. However, the levels of serum HA and LN were not observed significantly changed in both PLE and SLE groups than those in NC or VE group. Furthermore, ROC curve indicated that serum CGIV and PIIINP were capable of providing good diagnostic and differential diagnostic efficacy at the most appropriate cutoff point value. Conclusion: The serum levels of CGIV may have clinical significance in the diagnosis of lymphedema. CGIV and PIIINP may play a role in the differentiation of lymphedema from VE.

PMID:35687386 | DOI:10.1089/lrb.2021.0076

JMIR Form Res. 2022 Jun 10;6(6):e36052. doi: 10.2196/36052.

ABSTRACT

BACKGROUND: We piloted a web-based, provider-driven mobile app (DialysisConnect) to fill the communication and care coordination gap between hospitals and dialysis facilities.

OBJECTIVE: This study aimed to describe the development and pilot implementation of DialysisConnect.

METHODS: DialysisConnect was developed iteratively with focus group and user testing feedback and was made available to 120 potential users at 1 hospital (hospitalists, advanced practice providers [APPs], and care coordinators) and 4 affiliated dialysis facilities (nephrologists, APPs, nurses and nurse managers, social workers, and administrative personnel) before the start of the pilot (November 1, 2020, to May 31, 2021). Midpilot and end-of-pilot web-based surveys of potential users were also conducted. Descriptive statistics were used to describe system use patterns, ratings of multiple satisfaction items (1=not at all; 3=to a great extent), and provider-selected motivators of and barriers to using DialysisConnect.

RESULTS: The pilot version of DialysisConnect included clinical information that was automatically uploaded from dialysis facilities, forms for entering critical admission and discharge information, and a direct communication channel. Although physicians comprised most of the potential users of DialysisConnect, APPs and dialysis nurses were the most active users. Activities were unevenly distributed; for example, 1 hospital-based APP recorded most of the admissions (280/309, 90.6%) among patients treated at the pilot dialysis facilities. End-of-pilot ratings of DialysisConnect were generally higher for users versus nonusers (eg, “I can see the potential value of DialysisConnect for my work with dialysis patients”: mean 2.8, SD 0.4, vs mean 2.3, SD 0.6; P=.02). Providers most commonly selected reduced time and energy spent gathering information as a motivator (11/26, 42%) and a lack of time to use the system as a barrier (8/26, 31%) at the end of the pilot.

CONCLUSIONS: This pilot study found that APPs and nurses were most likely to engage with the system. Survey participants generally viewed the system favorably while identifying substantial barriers to its use. These results inform how best to motivate providers to use this system and similar systems and inform future pragmatic research in care coordination among this and other populations.

PMID:35687405 | DOI:10.2196/36052

Pain Med. 2022 Jun 10;23(Supplement_1):S1-S53. doi: 10.1093/pm/pnac046.

ABSTRACT

There have been some modest recent advancements in the research of Complex Regional Pain Syndrome, yet the amount and quality of the work in this complicated multifactorial disease remains low (with some notable exceptions; e.g., the recent work on the dorsal root ganglion stimulation). The semi-systematic (though in some cases narrative) approach to review is necessary so that we might treat our patients while waiting for “better research.” This semi-systematic review was conducted by experts in the field, (deliberately) some of whom are promising young researchers supplemented by the experience of “elder statesman” researchers, who all mention the system they have used to examine the literature. What we found is generally low- to medium-quality research with small numbers of subjects; however, there are some recent exceptions to this. The primary reason for this paucity of research is the fact that this is a rare disease, and it is very difficult to acquire a sufficient sample size for statistical significance using traditional statistical approaches. Several larger trials have failed, probably due to using the broad general diagnostic criteria (the “Budapest” criteria) in a multifactorial/multi-mechanism disease. Responsive subsets can often be identified in these larger trials, but not sufficient to achieve statistically significant results in the general diagnostic grouping. This being the case the authors have necessarily included data from less compelling protocols, including trials such as case series and even in some instances case reports/empirical information. In the humanitarian spirit of treating our often desperate patients with this rare syndrome, without great evidence, we must take what data we can find (as in this work) and tailor a treatment regime for each patient.

PMID:35687369 | DOI:10.1093/pm/pnac046

J Obstet Gynaecol. 2022 Jun 10:1-6. doi: 10.1080/01443615.2022.2074787. Online ahead of print.

ABSTRACT

Maternity statistics of England in 2020 showed rise in Caesarean Section (CS) rate to 31%. Some studies correlated adverse gynaecological symptoms e.g. menstrual irregularities and pelvic pain to ‘niche’ formation at CS scar site. Niche formation was speculated to cause myometrial hypertrophy aggravating these symptoms. This was a prospective comparative histological study including 52 consecutive benign hysterectomy specimens which were categorised into 2 groups: (i) specimens with CS scar (n = 22), (ii) specimens with no CS scar (n = 30). Median (IQ range) uteri weight was 97.2grms (43.5-226) and 91.7grms (35.7-201.7) in study and control groups, respectively (p = .991). Mean (±SD) thickness of anterior myometrial wall was 18.7 mm (±3.6) and 19.4 mm (±4.5) in study and control groups, respectively (p = .58). Mean (±SD) thickness of posterior myometrial wall was 19.1 mm (±3.7) and 18.7 mm (±3.9) in study and control groups, respectively (p = .78). The assumption that CS scar causes myometrial hypertrophy was not demonstrated in this study.IMPACT STATEMENTWhat is already known on this subject? Maternity statistics world-wide show a continuous rise in the rate of Caesarean Section (CS) operation. The CS scar is assumed to be related to adverse clinical gynaecological symptoms such as intermenstrual bleeding, dysmenorrhoea, dyspareunia and chronic pelvic pain; however, the mechanism of this association is not clear. Further, little is known about the effects of CS scar on uterine wall morphology and function.What do the results of this study add? This study was the first prospective series in the literature to compare the uteri with scar with those without in respect of weight and myometrial wall thickness. It was not able to demonstrate the association between having CS scar and myometrial hypertrophy which was hypothesised to be the cause of adverse gynaecological symptoms. However, the microscopic examination of the CS scar revealed adenomyosis, haemorrhage and/or chronic inflammation in most cases.What are the implications of these findings for clinical practice and/or future research? The clinical implication of the histological changes shown in the CS scar requires large comparative clinical studies.

PMID:35687352 | DOI:10.1080/01443615.2022.2074787

JAMA Netw Open. 2022 Jun 1;5(6):e2216183. doi: 10.1001/jamanetworkopen.2022.16183.

ABSTRACT

IMPORTANCE: Ensuring patients have access to safe and efficacious medicines in a timely manner is an essential goal for regulatory agencies, one which has particular importance in oncology because of the substantial unmet need for new therapies. The 2 largest regulatory agencies, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), have pivotal global roles, and their recommendations and approvals are frequently followed by other national regulators.

OBJECTIVE: To compare market authorization dates for new oncology therapies approved in the US and Europe over the past decade and to examine and contrast the regulatory activities of the FDA and EMA in the approval of new cancer medicines.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study reviewed the FDA and EMA regulatory databases to identify new oncology therapies approved in both the US and Europe from 2010 to 2019, and characterization of the timings of regulatory activities. Statistical analysis was performed from January to April 2022.

MAIN OUTCOMES AND MEASURES: Regulatory approval date, review time, submission of market authorization application, accelerated approval or conditional marketing authorization status and proportion of approvals prior to peer-reviewed publication of pivotal trial results.

RESULTS: In total, 89 new concomitant oncology therapies were approved in the US and Europe from 2010 to 2019. The FDA approved 85 oncology therapies (95%) before European authorization and 4 therapies (5%) after. The median (IQR) delay in market authorization for new oncology therapies in Europe was 241 (150-370) days compared with the US. The median (IQR) review time was 200 (155-277) days for the FDA and 426 (358-480) days for the EMA. Sixty-four new licensing applications (72%) were submitted to the FDA first, compared with 21 (23%) to the EMA. Thirty-five oncology therapies (39%) were approved by the FDA prior to pivotal study publication, whereas only 8 (9%) by the EMA.

CONCLUSION AND RELEVANCE: In this cross-sectional study, new oncology therapies were approved earlier in the US than Europe. The FDA received licensing applications sooner and had shorter review times. However, more therapies were approved prior to licensing study publication, leaving uncertainty for practitioners regarding clinical utility and safety of newly approved therapies.

PMID:35687337 | DOI:10.1001/jamanetworkopen.2022.16183

JAMA Netw Open. 2022 Jun 1;5(6):e2216393. doi: 10.1001/jamanetworkopen.2022.16393.

ABSTRACT

IMPORTANCE: An adequate system for triaging patients with head trauma in prehospital settings and choosing optimal medical institutions is essential for improving the prognosis of these patients. To our knowledge, there has been no established way to stratify these patients based on their head trauma severity that can be used by ambulance crews at an injury site.

OBJECTIVES: To develop a prehospital triage system to stratify patients with head trauma according to trauma severity by using several machine learning techniques and to evaluate the predictive accuracy of these techniques.

DESIGN, SETTING, AND PARTICIPANTS: This single-center retrospective cohort study was conducted by reviewing the electronic medical records of consecutive patients who were transported to Tokyo Medical and Dental University Hospital in Japan from April 1, 2018, to March 31, 2021. Patients younger than 16 years with cardiopulmonary arrest on arrival or with a significant amount of missing data were excluded.

MAIN OUTCOMES AND MEASURES: Machine learning-based prediction models to detect the presence of traumatic intracranial hemorrhage were constructed. The predictive accuracy of the models was evaluated with the area under the receiver operating curve (ROC-AUC), area under the precision recall curve (PR-AUC), sensitivity, specificity, and other representative statistics.

RESULTS: A total of 2123 patients (1527 male patients [71.9%]; mean [SD] age, 57.6 [19.8] years) with head trauma were enrolled in this study. Traumatic intracranial hemorrhage was detected in 258 patients (12.2%). Among several machine learning algorithms, extreme gradient boosting (XGBoost) achieved the mean (SD) highest ROC-AUC (0.78 [0.02]) and PR-AUC (0.46 [0.01]) in cross-validation studies. In the testing set, the ROC-AUC was 0.80, the sensitivity was 74.0% (95% CI, 59.7%-85.4%), and the specificity was 74.9% (95% CI, 70.2%-79.3%). The prediction model using the National Institute for Health and Care Excellence (NICE) guidelines, which was calculated after consultation with physicians, had a sensitivity of 72.0% (95% CI, 57.5%-83.8%) and a specificity of 73.3% (95% CI, 68.7%-77.7%). The McNemar test revealed no statistically significant differences between the XGBoost algorithm and the NICE guidelines for sensitivity or specificity (P = .80 and P = .55, respectively).

CONCLUSIONS AND RELEVANCE: In this cohort study, the prediction model achieved a comparatively accurate performance in detecting traumatic intracranial hemorrhage using only the simple pretransportation information from the patient. Further validation with a prospective multicenter data set is needed.

PMID:35687335 | DOI:10.1001/jamanetworkopen.2022.16393

Minerva Cardiol Angiol. 2022 Jun 10. doi: 10.23736/S2724-5683.22.05998-1. Online ahead of print.

ABSTRACT

BACKGROUND: Valvular heart disease (VHD) requires optimized outpatient management that is generally considered to be best delivered by a dedicated, multidisciplinary team (Heart Valve Clinic, HVC). Although HVC is promoted by clinical guidelines and organized in many centers, real world outcome assessments are limited. Thus, we evaluated the performance, clinical and management outcomes during a 6-year experience with an original HVC model.

METHODS: By interrogating the local database, 1047 consecutive patients admitted to the HVC from January 2015 to October 2020 were found. Management and mortality were checked for all patients. After 3 years of HVC activity, in order to improve appropriateness and efficiency, access priority criteria were introduced. Thus, the study population was divided in two Period subgroups (before and after access criteria introduction) that were compared.

RESULTS: A total of 1047 consecutive patients admitted to the HVC constituted the study population; 346 patients (33%) were recommended for invasive treatment. After a mean follow up of 25.7 ± 3.1 months, 37 patients (3.5%) died. When comparing study periods, statistically-significant increase inpatients’ complexity and VHD severity was noticed in Period 2, also translating into higher rate of referral to intervention (39.0% vs. 29.4% in Period 1; p = 0.001). Finally, despite higher rate of elderly and frail patients, operative mortality was not jeopardized.

CONCLUSIONS: The present study reports a comprehensive assessment of the characteristics and outcomes achieved through an original HVC model. Standardization of access criteria supports the HVC improvement.

PMID:35687315 | DOI:10.23736/S2724-5683.22.05998-1

Nanoscale. 2022 Jun 10. doi: 10.1039/d2nr01819e. Online ahead of print.

ABSTRACT

Structural analysis of metal clusters confined in nanoporous materials is typically performed by X-ray-driven techniques. Although X-ray analysis has proved its strength in the characterization of metal clusters, it provides averaged structural information. Therefore, we here present an alternative workflow for bringing the characterization of confined metal clusters towards the local scale. This workflow is based on the combination of aberration-corrected transmission electron microscopy (TEM), TEM image simulations, and powder X-ray diffraction (XRD) with advanced statistical techniques. In this manner, we were able to characterize the clustering of Pb atoms in Linde Type A (LTA) zeolites with Pb loadings as low as 5 wt%. Moreover, individual Pb clusters could be directly detected. The proposed methodology thus enables a local-scale characterization of confined metal clusters in zeolites. This is important for further elucidation of the connection between the structure and the physicochemical properties of such systems.

PMID:35687327 | DOI:10.1039/d2nr01819e

Environ Sci Pollut Res Int. 2022 Jun 10. doi: 10.1007/s11356-022-21333-4. Online ahead of print.

ABSTRACT

Colloidal particles can attach the contaminants like heavy metals and radionuclides and act as contaminant carriers to provide a faster movement of pollutants through the interconnecting pores of the porous medium. The electrostatic repulsive force between the negatively charged colloids and the solid surface restricts the transport of the mobile colloids to the larger pores of the porous medium and initiates the size exclusion mechanism. The temporal moment analysis is treated as an effective tool to interpret the solute breakthrough curves for analyzing the statistical behavior of the contaminants. In past literature, the temporal moments have not been incorporated with the breakthrough curves of colloids and colloid-facilitated contaminants for statistical interpretation. In this research study, the temporal variations of concentrations of mobile colloids, solute attached to the mobile colloids, and the dissolved solute are obtained numerically in a fully saturated one-dimensional column considering a continuous source for varying size exclusion and colloid attachment coefficient. Utilizing the simulated spatially varying breakthrough curves, the temporal moments are estimated to calculate the mass recovery, average residence time, and the spreading of mobile colloids and dissolved solutes. The temporal moment analysis suggests that the velocity enhancement for higher size exclusion reduces the average residence time of the mobile colloids and the solute adsorbed to the mobile colloids significantly. The mass recovery of mobile colloids and the solute attached to the mobile colloids increases at a specific depth for higher size exclusion. The estimated second central moment attributes that the solute spreading follows the nonlinear trend for low size exclusion. The peaks of the relative concentration of mobile colloids and solute attached to mobile colloids drastically decrease with an increase in attachment coefficient. The peak of the relative concentration of dissolved contaminant enhances with attachment coefficient. The high second temporal moment of the dissolved contaminant at a higher attachment coefficient indicates the slow interaction of dissolved solute and porous medium and that enables a greater spreading of solute through the interconnecting porous medium. The study suggests that the faster movement of mobile colloids and the solute attached to the mobile colloids at higher exclusion imparts a potential risk of groundwater contamination and thorough statistical interpretation is needful to analyze the behavior of colloids and colloid-facilitated contaminants. The research work does not consider the transient flow field and the effect of the presence of air phase in the partially saturated soil column in the groundwater system.

PMID:35687282 | DOI:10.1007/s11356-022-21333-4

Eur Child Adolesc Psychiatry. 2022 Jun 10. doi: 10.1007/s00787-022-01986-9. Online ahead of print.

ABSTRACT

The clinical validity of the distinction between ADHD and ASD is a longstanding discussion. Recent advances in the realm of data-driven analytic techniques now enable us to formally investigate theories aiming to explain the frequent co-occurrence of these neurodevelopmental conditions. In this study, we probe different theoretical positions by means of a pre-registered integrative approach of novel classification, subgrouping, and taxometric techniques in a representative sample (N = 434), and replicate the results in an independent sample (N = 219) of children (ADHD, ASD, and typically developing) aged 7-14 years. First, Random Forest Classification could predict diagnostic groups based on questionnaire data with limited accuracy-suggesting some remaining overlap in behavioral symptoms between them. Second, community detection identified four distinct groups, but none of them showed a symptom profile clearly related to either ADHD or ASD in neither the original sample nor the replication sample. Third, taxometric analyses showed evidence for a categorical distinction between ASD and typically developing children, a dimensional characterization of the difference between ADHD and typically developing children, and mixed results for the distinction between the diagnostic groups. We present a novel framework of cutting-edge statistical techniques which represent recent advances in both the models and the data used for research in psychiatric nosology. Our results suggest that ASD and ADHD cannot be unambiguously characterized as either two separate clinical entities or opposite ends of a spectrum, and highlight the need to study ADHD and ASD traits in tandem.

PMID:35687205 | DOI:10.1007/s00787-022-01986-9