Category: Statistics

Cancer Prev Res (Phila). 2021 Apr 13:canprevres.0581.2020. doi: 10.1158/1940-6207.CAPR-20-0581. Online ahead of print.

ABSTRACT

Current therapies for breast cancer prevention only prevent estrogen receptor positive (Er+) disease and toxicity limits use of these agents. Vitamin D is a potential prevention therapy for both Er+ and Er- disease and is safe with few side effects. This study evaluates the effect of one-year of vitamin D supplementation on mammographic density (MD), a biomarker of breast cancer risk in a multicenter randomized controlled trial. Premenopausal women with > 25% MD and no history of cancer, were randomly assigned to 2000IU of vitamin D or placebo orally daily for 1-year. Change in percent MD was evaluated using Cumulus software after all participants completed treatment. Three hundred women enrolled between 1/2011 and 12/2013 with a mean age of 43 and diverse ethnicity (14% Hispanic, 12% African American [AA]). Supplementation significantly increased vitamin D levels compared to placebo (14.5 ng/mL vs -1.6 ng/mL; p<0.0001) with all participants on the Vitamin D arm achieving vitamin D sufficiency at 12 months. Vitamin D was safe and well tolerated. After adjustment for baseline MD, the mean between-arm difference (vitamin D vs placebo) at 1 year was -0.75 [-.26, 1.76 p=0.56]. A greater effect was seen for women with >50% MD and AA women, although neither reached significance. This randomized controlled trial demonstrated significant improvement in vitamin D levels with 2000 IU for one year, with 100% of supplemented women achieving sufficiency. However, a null effect was seen regarding change in MD for premenopausal women (the primary outcome of the study).

PMID:33849913 | DOI:10.1158/1940-6207.CAPR-20-0581

BMJ Open. 2021 Apr 13;11(4):e044949. doi: 10.1136/bmjopen-2020-044949.

ABSTRACT

INTRODUCTION: Surgical interventions can elicit neuroendocrine responses and sympathovagal imbalance, ultimately affecting cardiac autonomic function. Cardiac complications account for 30% of postoperative complications and are the leading cause of morbidity and mortality following non-cardiac surgery. One cardiovascular parameter, heart rate variability (HRV), has been found to be predictive of postoperative morbidity and mortality. HRV is defined as variation in time intervals between heartbeats and is affected by cardiac autonomic balance. Furthermore, altered HRV has been shown to predict cardiovascular events in non-surgical settings. In multiple studies, experimentally induced pain in healthy humans leads to reduced HRV suggesting a causal relationship. In a different studies, chronic pain has been associated with altered HRV, however, in the setting of clinical pain conditions, it remains unclear how much HRV impairment is due to pain itself versus autonomic changes related to analgesia. We aim to review the available evidence describing the association between postsurgical pain and HRV alterations in the early postoperative period.

METHODS AND ANALYSIS: We will conduct a scoping review of relevant studies using detailed searches of MEDLINE and EMBASE, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Included studies will involve participants undergoing non-cardiac surgery and investigate outcomes of (1) measures of pain intensity; (2) measures of HRV and (3) statistical assessment of association between #1 and #2. As secondary review outcomes included studies will also be examined for other cardiovascular events and for their attempts to control for analgesic treatment and presurgical HRV differences among treatment groups in the analysis. This work aims to synthesise available evidence to inform future research questions related to postsurgical pain and cardiac complications.

ETHICS AND DISSEMINATION: Ethics review and approval is not required for this review. The results will be submitted for publication in peer-reviewed journals.

PMID:33849852 | DOI:10.1136/bmjopen-2020-044949

BMJ Open. 2021 Apr 13;11(4):e047134. doi: 10.1136/bmjopen-2020-047134.

ABSTRACT

BACKGROUND: Cardiac rehabilitation (CR) decreases the morbidity and mortality risk among patients with cardiac diseases; however, the impact of CR on patients with diabetes remains underexplored. This is a protocol for a systematic review and meta-analysis methodology to explore if the effect of CR on mortality and morbidity is the same in patients with type 2 diabetes compared with patients without diabetes.

METHODS AND ANALYSIS: Interventional and non-interventional studies comparing the effect of CR, for at least 1 month, on all-cause mortality and cardiovascular outcomes including fatal and non-fatal myocardial infarction, revascularisation and rehospitalisation in adults with cardiac diseases will be deemed eligible for inclusion. Studies published between 1990 and 2020 will be searched in PubMed, Embase, Cochrane, CINAHL, Scopus and in registries for randomised controlled trials. Eligible studies will be selected using the Covidence software, and their salient details regarding the design, population, tested interventions and outcomes of interest will be gathered. The quality of studies to be deemed eligible and reviewed will be assessed using the Cochrane Collaboration and National Heart, Lung, and Blood Institute’s tools. The appraisal process will be based on the study design (interventional and non-interventional). In the meta-analysis step, the pooled effect of CR on the outcomes will be estimated. All meta-analyses will be done using the random-effects model approach (inverse-variance method). I ² and p value of χ² statistics will guide the heterogeneity assessment. Subgroup analyses will also be performed. The small study effect will be investigated by generating the funnel plots. The symmetry of the latter will be tested by performing Egger’s test.

ETHICS AND DISSEMINATION: The systematic review will use data from published literature; hence, no ethical approval will be required. Findings of the systematic review and meta-analysis will be published in peer-reviewed international journals and will be disseminated in local and international scientific meetings.

PROSPERO REGISTRATION NUMBER: CRD42020148832.

PMID:33849857 | DOI:10.1136/bmjopen-2020-047134

Nan Fang Yi Ke Da Xue Xue Bao. 2021 Mar 25;41(3):424-429. doi: 10.12122/j.issn.1673-4254.2021.03.16.

ABSTRACT

OBJECTIVE: To explore the changes of small-world network properties in patients with primary insomnia based on resting-state functional magnetic resonance imaging (rs-fMRI).

OBJECTIVE: The rs-MRI data and neurological scale data of 65 patients and 60 matched healthy controls were collected. The brain network was constructed using GRENTA software. SPSS software and network-based statistical analysis methods were used for statistical analysis.

OBJECTIVE: There was no significant difference between the two groups in terms of age, gender or education level (P > 0.05), but PSQI, HAMA and HAMD scale scores differed significantly between the two groups (P < 0.05). Both of the groups showed attributes of the small-world network. Compared with the control group, the patients with insomnia showed lower Cp, γ, Eloc, λ, connectivity, and σ of the small world network (P < 0.05).

OBJECTIVE: Patients with primary insomnia have lower global and local efficiencies than healthy individuals, and their ability to transmit information on the surface topology is impaired. Our data provide objective imaging evidences for the neuropathological mechanism of patients with primary insomnia.

PMID:33849835 | DOI:10.12122/j.issn.1673-4254.2021.03.16

BMJ Open. 2021 Apr 13;11(4):e040912. doi: 10.1136/bmjopen-2020-040912.

ABSTRACT

OBJECTIVE: To assess a possible interaction effect between physical activity and air pollution on first incidence of ischaemic heart disease (IHD).

DESIGN: Prospective cohort study.

SETTING: Umeå, Northern Sweden.

PARTICIPANTS: We studied 34 748 adult participants of Västerbotten Intervention Programme cohort from 1990 to January 2014. Annual particulate matter concentrations (PM_2.5 and PM₁₀) at the participants’ residential addresses were modelled and a questionnaire on frequency of exercise and active commuting was completed at baseline. Cox proportional hazards modelling was used to estimate (1) association with physical activity at different levels of air pollution and (2) the association with particulate matter at different levels of physical activity.

OUTCOME: First incidence of IHD.

RESULTS: Over a mean follow-up of 12.4 years, there were 1148 IHD cases. Overall, we observed an increased risk of IHD among individuals with higher concentrations of particles at their home address. Exercise at least twice a week was associated with a lower risk of IHD among participants with high residential PM_2.5 (hazard ratio (HR) 0.60; 95% CI: 0.44 to 0.82) and PM₁₀ (HR 0.55; 95% CI: 0.4 to 0.76). The same beneficial effect was not observed with low residential PM_2.5 (HR 0.94; 95% CI: 0.72 to 1.22) and PM₁₀ (HR 0.99; 95% CI: 0.76 to 1.29). An increased risk associated with higher long-term exposure to particles was only observed among participants that exercised in training clothes at most one a week and among those not performing any active commuting. However, only the interaction effect on HRs for exercise was statistically significant.

CONCLUSION: Exercise was associated with a lower risk of first incidence of IHD among individuals with higher residential particle concentrations. An air pollution-associated risk was only observed among those who exercised less. The findings support the promotion of physical activity and a mitigation of air pollution.

PMID:33849846 | DOI:10.1136/bmjopen-2020-040912

Cytokine. 2021 Apr 10:155522. doi: 10.1016/j.cyto.2021.155522. Online ahead of print.

ABSTRACT

Complement is an important branch of innate immunity; however, its biological significance goes far beyond the scope of simple nonspecific defense and involves a variety of physiological functions, including the adaptive immune response. In this review, to unravel the complex relationship between complement and tumors, we reviewed the high diversity of complement components in cancer and the heterogeneity of their production and activation pathways. In the tumor microenvironment, complement plays a dual regulatory role in the occurrence and development of tumors, affecting the outcomes of the immune response. We explored the differential expression levels of various complement components in human cancers via the Oncomine database. The gene expression profiling interactive analysis (GEPIA) tool and Kaplan-Meier plotter (K-M plotter) confirmed the correlation between differentially expressed complement genes and tumor prognosis. The tumor immune estimation resource (TIMER) database was used to statistically analyze the effect of complement on tumor immune infiltration. Finally, with a view to the role of complement in regulating T cell metabolism, complement could be a potential target for immunotherapies. Targeting complement to regulate the antitumor immune response seems to have potential for future treatment strategies. However, there are still many complex problems, such as who will benefit from this therapy and how to select the right therapeutic target and determine the appropriate drug concentration. The solutions to these problems depend on a deeper understanding of complement generation, activation, and regulatory and control mechanisms.

PMID:33849765 | DOI:10.1016/j.cyto.2021.155522

J Pediatr Urol. 2021 Mar 19:S1477-5131(21)00126-1. doi: 10.1016/j.jpurol.2021.03.010. Online ahead of print.

ABSTRACT

INTRODUCTION: Minimally-invasive surgery (MIS) has been adopted slowly in pediatric oncology. We attempted to describe contemporary national trends in MIS use; we hypothesized that adolescents (who are more likely to have relatively small renal cell carcinomas) would have a higher proportion of MIS than younger children (who are more likely to have relatively large Wilms tumors) and that this relationship would vary by region.

OBJECTIVE: To explore whether pediatric urologic oncology outcomes vary by patient age or by surgical technique.

METHODS: We queried the 1998-2014 National Inpatient Sample (NIS) and included encounters in children aged ≤ 18 y, ICD-9 diagnostic code for renal tumor, and procedure code for open or MIS partial or radical nephrectomy. All analyses used weighted descriptive statistics and outcomes are compared based on age group (</>10 y) or surgery type; Wald-Chi square test was used for differences in proportions and unadjusted weighted ANOVA was used to test for differences in means.

RESULTS: 9259 weighted encounters were included; 91% were <10 years old and 50.7% were female. MIS surgery accounted for 1.8% of encounters; there was a difference in proportions by age group (1% <9 y vs. 9.9% >9 y, p < 0.01). The proportion of surgery type was similar across regions within age groups, however. Complications occurred in 13.3% of encounters; mean inpatient length of stay was 8.9 days (SD: 0.3); mean cost was $ 34,457.68 (SD: $1197.00). There was no evidence of a difference between surgery type and proportion of post-operative complications, mean inpatient length of stay or mean inpatient cost.

DISCUSSION: The admission-based, retrospective design of NIS left us unable to assess long-term outcomes, repeated admissions, or to track a particular patient across time; this is particularly relevant for oncologic variables on interest such as tumor stage or event-free survival. We were similarly limited in evaluating the effect of pre-surgical referral patterns on patient distributions.

CONCLUSION: In this preliminary descriptive analysis, MIS techniques were infrequently used in children, but there was a higher proportion of MIS use among adolescents. There were similar proportions of surgery type across geographic regions within the United States. Whether this infrequent usage is appropriate is as yet unclear given the lack of Level I evidence regarding the relative merits of MIS and open surgery for pediatric and adolescent renal tumors.

PMID:33849794 | DOI:10.1016/j.jpurol.2021.03.010

Z Evid Fortbild Qual Gesundhwes. 2021 Apr 10:S1865-9217(21)00037-4. doi: 10.1016/j.zefq.2021.02.009. Online ahead of print.

ABSTRACT

INTRODUCTION: Examinations are a central element of the medical curriculum: they contribute significantly to the quality assurance of medical training and subsequent medical care. In order to meet the high expectations placed on examinations in terms of content, legal and organizational aspects, continuous quality assurance measures are necessary. The aim of this paper was to record and analyze the quality assurance measures implemented at the medical faculty of Heidelberg.

METHODS: We investigated quality indicators that are relevant to medical examinations -adequate choice of examination formats, blueprint/validity, reliability and distribution of grades, feedback to students, consequences of examinations – within the faculty examinations in the decentrally organized Heidelberg Curriculum Medicinale (HeiCuMed). In addition, the organizational structures in examination management were examined. For this purpose, interviews were conducted with teaching staff, students and the technical examination administration.

RESULTS: The surveys show that the quality indicators in HeiCuMed have already been met in many areas. Optimization work remains to be done concerning the criteria “adequate choice of examination formats”, “feedback to students” as well as the documentation of the examination process and the definition of substitution regulations.

DISCUSSION: Training courses, statistical analysis and accompanying research are essential for establishing additional innovative, practice-oriented examination formats. In order to improve feedback to students, formative assessments should be more intensively integrated into the curriculum. As a measure for structured quality-oriented examination management, it is also helpful to document the examination procedure and the staff assigned to it using templates.

CONCLUSION: Especially with decentralized examination management, the internal coordination of individual departments is of great importance in order to guarantee the quality of examinations. Regular surveys of the parties involved can be of support by collecting best-practice examples and deliver the respective information in handouts encouraging interdisciplinary exchange.

PMID:33849803 | DOI:10.1016/j.zefq.2021.02.009

Pediatr Neurosurg. 2021 Apr 13:1-10. doi: 10.1159/000515038. Online ahead of print.

ABSTRACT

OBJECTIVE: We sought to compare our large single-institution cohort of postnatal myelomeningocele closure to the 2 arms of the Management of Myelomeningocele Study (MOMS) trial at the designated trial time points, as well as assess outcomes at long-term follow-up among our postnatal cohort.

METHODS: A single-institutional retrospective review of myelomeningocele cases presenting from 1995 to 2015 at Children’s Hospital of Pittsburgh was performed. We compared outcomes at 12 and 30 months to both arms of the MOMS trial and compared our cohort’s outcomes at those designated time points to our long-term outcomes. Univariate statistical analysis was performed as appropriate.

RESULTS: One-hundred sixty-three patients were included in this study. All patients had at least 2-year follow-up, with a mean follow-up of 10 years (range 2-20 years). There was no difference in the overall distribution of anatomic level of defect. Compared to our cohort, the prenatal cohort had a higher rate of tethering at 12 months of age, 8 versus 1.8%. Conversely, the Chiari II decompression rate was higher in our cohort (10.4 vs. 1.0%). At 30 months, the prenatal cohort had a higher rate of independent ambulation, but our cohort demonstrated the highest rate of ambulation with or without assistive devices among the 3 groups. When comparing our cohort at these early time points to our long-term follow-up data, our cohort’s ambulatory function decreased from 84 to 66%, and the rate of detethering surgery increased almost 10-fold.

CONCLUSIONS: This study demonstrated that overall ambulation and anatomic-functional level were significantly better among our large postnatal cohort, as well as having significantly fewer complications to both fetus and mother, when compared to the postnatal cohort of the MOMS trial. Our finding that ambulatory ability declined significantly with age in this patient population is worrisome for the long-term outcomes of the MOMS cohorts, especially given the high rates of cord tethering at early ages within the prenatal cohort. These findings suggest that the perceived benefits of prenatal closure over postnatal closure may not be as substantial as presented in the original trial, with the durability of results still remaining a concern.

PMID:33849030 | DOI:10.1159/000515038

Cerebrovasc Dis. 2021 Apr 13:1-6. doi: 10.1159/000515320. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Randomized controlled trials have demonstrated the importance of time to endovascular therapy (EVT) in clinical outcomes in large vessel occlusion (LVO) acute ischemic stroke. Delays to treatment are particularly prevalent when patients require a transfer from hospitals without EVT capability onsite. A computer-aided triage system, Viz LVO, has the potential to streamline workflows. This platform includes an image viewer, a communication system, and an artificial intelligence (AI) algorithm that automatically identifies suspected LVO strokes on CTA imaging and rapidly triggers alerts. We hypothesize that the Viz application will decrease time-to-treatment, leading to improved clinical outcomes.

METHODS: A retrospective analysis of a prospectively maintained database was assessed for patients who presented to a stroke center currently utilizing Viz LVO and underwent EVT following transfer for LVO stroke between July 2018 and March 2020. Time intervals and clinical outcomes were compared for 55 patients divided into pre- and post-Viz cohorts.

RESULTS: The median initial door-to-neuroendovascular team (NT) notification time interval was significantly faster (25.0 min [IQR = 12.0] vs. 40.0 min [IQR = 61.0]; p = 0.01) with less variation (p < 0.05) following Viz LVO implementation. The median initial door-to-skin puncture time interval was 25 min shorter in the post-Viz cohort, although this was not statistically significant (p = 0.15).

CONCLUSIONS: Preliminary results have shown that Viz LVO implementation is associated with earlier, more consistent NT notification times. This application can serve as an early warning system and a failsafe to ensure that no LVO is left behind.

PMID:33849032 | DOI:10.1159/000515320