Impact of Psychiatric and Related Somatic Medications on the Duration and Severity of COVID-19: A Retrospective Explorative Multi-center Study from the German Metropolitan Ruhr-area

2021 ◽  
Author(s):  
Udo Bonnet ◽  
BenediktBernd Claus ◽  
Martin Schaefer ◽  
Jens Kuhn ◽  
Peter Nyhuis ◽  
...  
Keyword(s):  
Multiple Testing ◽  
P Value ◽  
Nasopharyngeal Swab ◽  
Residual Symptom ◽  
Old Patients ◽  
Residual Symptoms ◽  
Ruhr Area ◽  
Symptom Load ◽  
Raas Inhibitors ◽  
Multi Center Study

Abstract Introduction Several psychiatric and somatic medications are assumed to improve COVID-19-symptoms. These include antidepressants, antipsychotics, and anticonvulsants as well as anticoagulants, statins, and renin-angiotensin-aldosterone-system (RAAS)-inhibitors for somatic comorbid conditions. All these agents may reduce the hyperinflammatory response to SARS/CoV-2 or the related negative cardio-cerebrovascular outcomes. Methods In a retrospective longitudinal, multi-center inpatient study, we sought to explore the influence of psychiatric medications on COVID-19, comprising the period from diagnosing SARS/CoV-2-infection via PCR (nasopharyngeal swab) up to the next 21 days. Ninety-six psychiatric inpatients (mean age [SD] 65.5 (20.1), 54% females) were included. The primary outcome was the COVID-19-duration. Secondary outcomes included symptom severity and the presence of residual symptoms. Results COVID-19-related symptoms emerged in 60 (62.5%) patients, lasting 6.5 days on average. Six (6.3%) 56–95 years old patients died from or with COVID-19. COVID-19-duration and residual symptom-presence (n=22, 18%) were not significantly related to any substance. Respiratory and neuro-psychiatric symptom-load was significantly and negatively related to prescription of antidepressants and anticoagulants, respectively. Fatigue was negatively and positively related to RAAS-inhibitors and proton-pump-inhibitors, respectively. These significant relationships disappeared with p-value adjustment owed to multiple testing. The mean total psychiatric burden was not worsened across the study. Discussion None of the tested medications was significantly associated with the COVID-19-duration and -severity up to the end of post-diagnosing week 3. However, there were a few biologically plausible and promising relationships with antidepressants, anticoagulants, and RAAS-inhibitors before p-value adjustment. These should encourage larger and prospective studies to re-evaluate the influence of somatic and psychiatric routine medications on COVID-19-related health outcomes.

scholarly journals AB0132 THE STUDY OF SUBCLINICAL SYNOVITIS DETECTED BY ULTRASONOGRAPHY AND MRI IN RA PATIENTS AFTER REACHING CLINICAL REMISSION ON PATIENT’S SUBJECTIVE SYMPTOMS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1094.2-1094
Author(s):  
M. Nawata ◽  
K. Someya ◽  
T. Aritomi ◽  
M. Funada ◽  
K. Nakamura ◽  
...  
Keyword(s):  
Clinical Remission ◽  
Research Funding ◽  
Morning Stiffness ◽  
Univariate Analysis ◽  
P Value ◽  
Research Support ◽  
Residual Symptoms ◽  
Logistic Analysis ◽  
Significant Difference ◽  
Multivariate Logistic Analysis

Background:The goal of treatment in rheumatoid arthritis (RA) is to achieve remission. There is the patient with residual symptoms in the Japanese RA patient who achieved clinical remission. There are not many studies to examine the relation between everyday life, social activity and evaluation of disease activities using high-sensitivity image examinations (musculoskeletal ultrasound (MSKUS) and MRI).Objectives:To examine the relationship between subjective residual symptoms and imaging examinations in RA patients who have achieved clinical remission.Methods:30 RA patients who achieved SDAI remission during RA treatment. Age, sex, disease duration, physical findings, serological markers, disease activity, HAQ, EQ-5D-5L, FACIT-F, Patient Reported Outcomes (PROs), EGA and medications were evaluated. 44 joints were assessed by MSKUS with gray scale (GS) and power doppler (PD) and contrast-enhanced bilateral joint MRI scoring with OMERACT-RAMRIS scoring.Results:1. The mean SDAI of the 30 RA patients was 1.3. 2.In the analysis of the presence or absence of subjective residual symptoms that led to remission of SDAI (Table 1).Table 1.Subjective residual symptoms/presence (N=17)Subjective residual symptoms/absence (N=13)Univariate analysisp valueMultivariate logistic analysisp valueTJC0.0±0.00.3±0.50.0173HAQ0.4±0.40.05±0.10.00950.00181EQ5D-5L0.8±0.10.9±0.00.0001FACIT-F14.5±9.84.6±4.30.0233Morning stiffness (min)256.5±564.80.0±0.00.0210Pain (VAS) (mm)9.2±9.50.9±1.50.00440.0455PGA (mm)7.7±9.00.5±1.10.0013(1). In the univariate analysis, the number of tender joints, HAQ, EQ-5D-5L, FACIT-F, morning stiffness, and pain VAS were extracted with significant differences.(2). In multivariate logistic analysis, HAQ and pain VAS were extracted as independent factors with significant differences. 3.In univariate analysis of the association between HAQ and pain VAS extracted in multivariate logistic analysis and imaging examinations (MSKUS/MRI), MRI-synovitis was extracted with a significant difference in HAQ.Conclusion:1. It was suggested that Pain VAS and HAQ due to RA could be identified in patients reaching SDAI remission. 2. In patients reaching SDAI remission, Pain VAS ≤10 or HAQ ≤0.5 suggested that subjective residual symptoms may be eliminated. 3. HAQ ≤ 0.5 suggests that synovitis is less likely to be detected on MRI. 4. In patients who have reached SDAI remission, little residual inflammation was observed on US, suggesting that induction of remission is important not only to prevent joint destruction, but also to improve and maintain long-term QoL.Disclosure of Interests:MASAO NAWATA Grant/research support from: I have received research funding from Eli Lilly Japan K.K., Kazuki Someya: None declared, Takafumi Aritomi: None declared, Masashi funada: None declared, Katsumi Nakamura: None declared, SAITO KAZUYOSHI Grant/research support from: I have received research funding from Eli Lilly Japan K.K., Yoshiya Tanaka Speakers bureau: I have received speaking fees from Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, and Santen, Consultant of: I have received consulting fees from Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, and Santen, Grant/research support from: I have received research grants from Mitsubishi-Tanabe, Takeda, Chugai, Astellas, Eisai, Taisho-Toyama, Kyowa-Kirin, Abbvie, and Bristol-Myers

scholarly journals Genetic polymorphisms associated with carotid artery intima-media thickness and coronary artery calcification in women of the Kronos Early Estrogen Prevention Study

2013 ◽  
Vol 45 (2) ◽  
pp. 79-88 ◽  
Author(s):  
Virginia M. Miller ◽  
Tanya M. Petterson ◽  
Elysia N. Jeavons ◽  
Abhinita S. Lnu ◽  
David N. Rider ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Carotid Artery ◽  
Coronary Artery Calcification ◽  
Multiple Testing ◽  
Intima Media Thickness ◽  
Chromosome 17 ◽  
European Ancestry ◽  
P Value ◽  
Prevention Study ◽  
Media Thickness

Menopausal hormone treatment (MHT) may limit progression of cardiovascular disease (CVD) but poses a thrombosis risk. To test targeted candidate gene variation for association with subclinical CVD defined by carotid artery intima-media thickness (CIMT) and coronary artery calcification (CAC), 610 women participating in the Kronos Early Estrogen Prevention Study (KEEPS), a clinical trial of MHT to prevent progression of CVD, were genotyped for 13,229 single nucleotide polymorphisms (SNPs) within 764 genes from anticoagulant, procoagulant, fibrinolytic, or innate immunity pathways. According to linear regression, proportion of European ancestry correlated negatively, but age at enrollment and pulse pressure correlated positively with CIMT. Adjusting for these variables, two SNPs, one on chromosome 2 for MAP4K4 gene (rs2236935, β = 0.037, P value = 2.36 × 10−06) and one on chromosome 5 for IL5 gene (rs739318, β = 0.051, P value = 5.02 × 10−05), associated positively with CIMT; two SNPs on chromosome 17 for CCL5 (rs4796119, β = −0.043, P value = 3.59 × 10−05; rs2291299, β = −0.032, P value = 5.59 × 10−05) correlated negatively with CIMT; only rs2236935 remained significant after correcting for multiple testing. Using logistic regression, when we adjusted for waist circumference, two SNPs (rs11465886, IRAK2, chromosome 3, OR = 3.91, P value = 1.10 × 10−04; and rs17751769, SERPINA1, chromosome 14, OR = 1.96, P value = 2.42 × 10−04) associated positively with a CAC score of >0 Agatston unit; one SNP (rs630014, ABO, OR = 0.51, P value = 2.51 × 10−04) associated negatively; none remained significant after correcting for multiple testing. Whether these SNPs associate with CIMT and CAC in women randomized to MHT remains to be determined.

scholarly journals Memory and Spatial Cognition in Breast Cancer Patients Undergoing Adjuvant Endocrine Therapy

Breast Care ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. 240-246 ◽  
Author(s):  
Ute Berndt ◽  
Bernd Leplow ◽  
Robby Schoenfeld ◽  
Tilmann Lantzsch ◽  
Regina Grosse ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Spatial Cognition ◽  
Verbal Memory ◽  
Multiple Testing ◽  
Local Therapy ◽  
Protective Role ◽  
P Value ◽  
Breast Cancer Patients ◽  
Cross Sectional ◽  
Switch Group

Introduction: It is generally accepted that estrogens play a protective role in cognitive function. Therefore, it can be expected that subtotal estrogen deprivation following aromatase inhibition will alter cognitive performance. Methods: In a cross-sectional study we investigated 80 postmenopausal women with breast cancer. Memory and spatial cognition were compared across 4 treatment groups: tamoxifen only (TAM, n = 22), aromatase inhibitor only (AI, n = 22), TAM followed by AI (‘SWITCH group', n = 15), and patients with local therapy (LT) only (surgery and radiation, n = 21). Duration of the 2 endocrine monotherapy arms prior to the assessment ranged from 1 to 3 years. The ‘SWITCH group' received 2-3 years TAM followed by at least 1 year and at most 3 years of AI. Memory and spatial cognition were investigated as planned comparisons. Investigations of processing speed, attention, executive function, visuoconstruction and self-perception of memory were exploratory. Results: With regard to general memory, AI patients performed significantly worse than the LT group (p = 0.013). Significant differences in verbal memory did not remain significant after p-value correction for multiple testing. We found no significant differences concerning spatial cognition between the groups. Conclusion: AI treatment alone significantly impairs general memory compared to the LT group.

Comparison of Human Thymus Gland between Young and Old Age

2021 ◽  
Vol 15 (6) ◽  
pp. 1907-1909
Author(s):  
Faiza Mehboob ◽  
Ponum Mirani ◽  
M. Kamran Ameer ◽  
Khurram Shabeer ◽  
Muhammad Ali Qamar ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Old Age ◽  
Age Groups ◽  
Young Age ◽  
University Hospital ◽  
P Value ◽  
Old Patients ◽  
Human Thymus ◽  
Group I ◽  
Significant Difference

Aim: Study was conducted to examine the different parameters of human thymus glands of young and old patients and compare the findings between both age groups. Study Design: Comparative/observational study Place and Study: Study was conducted at Anatomy department of Nishtar Medical University Hospital, Multan for duration of six months from 15th January 2020 to 15th July 2020. Methods: Total 54 specimens of human thymus of 54 patients were enrolled in this study. All specimens were divided in to two groups I and II, Group I contains 27 patients with ages <30 years and group II with 27 patients having ages 45 to 60 years. All specimens were fixed in 10% formalin solution and then processed for paraffin embedding. Compare the different parameters such as thickness of interlobular connective tissue and thymic capsule, length and number of Hassal’s corpuscles between both groups. Data was analyzed by SPSS 24.0. Results: In group I 12 (44.44%) patients were ages <15 years and 15 (55.56%) patients were ages >15 years. In group 13 (48.15%) and 14 (51.85%) patients were ages <50 years and >50 years. There was a significant difference observed between both groups regarding thickness of interlobular connective tissue and thymic capsule, quantity and length of Hassal’s corpuscles with p-value <0.05. Conclusion: It is to be concluded that patients with young age had significantly less thickness of thymic capsule and interlobular connective tissue with more in number and decreasing size of Hassal’s corpuscles as compared to old age patients. Keywords: Human Thymus Glands, Young Age, Old Age

Abstract MP11: Circulating Plasma Biomarkers Associated With Brain Arteriovenous Malformations

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Sarah E Wetzel-Strong ◽  
Shantel M Weinsheimer ◽  
Jeffrey Nelson ◽  
Ludmila Pawlikowska ◽  
Dewi Clark ◽  
...  
Keyword(s):  
Multiple Testing ◽  
Statistical Significance ◽  
Protein Profiling ◽  
P Value ◽  
P Values ◽  
Plasma Biomarkers ◽  
Standard Curve ◽  
Disease States ◽  
Heparin Plasma ◽  
Circulating Levels

Objective: Circulating plasma protein profiling may aid in the identification of cerebrovascular disease signatures. This study aimed to identify circulating angiogenic and inflammatory biomarkers that may serve as biomarkers to differentiate sporadic brain arteriovenous malformation (bAVM) patients from other conditions with brain AVMs, including hereditary hemorrhagic telangiectasia (HHT) patients. Methods: The Quantibody Human Angiogenesis Array 1000 (Raybiotech) is an ELISA multiplex panel that was used to assess the levels of 60 proteins related to angiogenesis and inflammation in heparin plasma samples from 13 sporadic unruptured bAVM patients (69% male, mean age 51 years) and 37 patients with HHT (40% male, mean age 47 years, n=19 (51%) with bAVM). The Quantibody Q-Analyzer tool was used to calculate biomarker concentrations based on the standard curve for each marker and log-transformed marker levels were evaluated for associations between disease states using a multivariable interval regression model adjusted for age, sex, ethnicity and collection site. Statistical significance was based on Bonferroni correction for multiple testing of 60 biomarkers (P< 8.3x10 - 4 ). Results: Circulating levels of two plasma proteins differed significantly between sporadic bAVM and HHT patients: PDGF-BB (P=2.6x10 -4 , PI= 3.37, 95% CI:1.76-6.46) and CCL5 (P=6.0x10 -6 , PI=3.50, 95% CI=2.04-6.03). When considering markers with a nominal p-value of less than 0.01, MMP1 and angiostatin levels also differed between patients with sporadic bAVM and HHT. Markers with nominal p-values less than 0.05 when comparing sporadic brain AVM and HHT patients also included angiostatin, IL2, VEGF, GRO, CXCL16, ITAC, and TGFB3. Among HHT patients, the circulating levels of UPAR and IL6 were elevated in patients with documented bAVMs when considering markers with nominal p-values less than 0.05. Conclusions: This study identified differential expression of two promising plasma biomarkers that differentiate sporadic bAVMs from patients with HHT. Furthermore, this study allowed us to evaluate markers that are associated with the presence of bAVMs in HHT patients, which may offer insight into mechanisms underlying bAVM pathophysiology.

scholarly journals Cardiometabolic health during early adulthood and risk of miscarriage: a prospective study

2021 ◽  
Vol 5 ◽  
pp. 205
Author(s):  
Maria C. Magnus ◽  
Diana D. S. Ferreira ◽  
Maria Carolina Borges ◽  
Kate Tilling ◽  
Deborah A. Lawlor ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Multiple Testing ◽  
Early Adulthood ◽  
Hdl Cholesterol ◽  
Female Offspring ◽  
Cardiometabolic Health ◽  
P Value ◽  
Relative Risks ◽  
Parents And Children ◽  
Increased Risk

Background: Several studies have found that women who are overweight or obese have an increased risk of miscarriage. There is also some evidence of associations of other aspects of cardiometabolic health, including blood pressure and lipids, with miscarriage risk, although these have not been examined to the same extent as body-mass index (BMI). Methods: Our objective was to investigate the risk of miscarriage according to pre-pregnancy cardiometabolic health. We examined pre-pregnancy levels of BMI, blood pressure, fasting insulin and metabolites profile at age 18 and risk of miscarriage by age 24. The study included adult female offspring in the Avon Longitudinal Study of Parents and Children with a pregnancy between 18 and 24 years of age (n=434 for BMI and blood pressure; n=265 for metabolites). We used log-binomial regression to calculate adjusted associations between cardiometabolic health measures and miscarriage. Results: The overall risk of miscarriage was 22%.  The adjusted relative risks for miscarriage were 0.96 (95% CI: 0.92-1.00) for BMI (per unit increase), 0.98 (0.96-1.00) for systolic blood pressure, and 1.00 (0.97-1.04) for diastolic blood pressure (per 1 mmHg increase).  Total cholesterol, total lipids and phospholipids in HDL-cholesterol were associated with increased likelihood of miscarriage, but none of the p-values for the metabolites were below the corrected threshold for multiple testing (p-value ≤0.003). Conclusions: Our findings indicate no strong evidence to support a relationship between pre-pregnancy cardiometabolic health and risk of miscarriage in young, healthy women who became pregnant before age 24. Future studies are necessary that are able to evaluate this question in samples with a wider age range.

scholarly journals The Characterization of Disease Severity Associated IgG Subclasses Response in COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Huanle Luo ◽  
Tingting Jia ◽  
Jiamin Chen ◽  
Shike Zeng ◽  
Zengzhao Qiu ◽  
...  
Keyword(s):  
Viral Load ◽  
Disease Severity ◽  
Young Patients ◽  
Neutralizing Antibody ◽  
Igg Subclasses ◽  
Nasopharyngeal Swab ◽  
Obvious Effect ◽  
Old Patients ◽  
Biological Sex ◽  
Specific Igg

Increasing evidence suggests that dysregulated immune responses are associated with the clinical outcome of coronavirus disease 2019 (COVID-19). Nucleocapsid protein (NP)-, spike (S)-, receptor binding domain (RBD)- specific immunoglobulin (Ig) isotypes, IgG subclasses and neutralizing antibody (NAb) were analyzed in 123 serum from 63 hospitalized patients with severe, moderate, mild or asymptomatic COVID-19. Mild to modest correlations were found between disease severity and antigen specific IgG subclasses in serum, of which IgG1 and IgG3 were negatively associated with viral load in nasopharyngeal swab. Multiple cytokines were significantly related with antigen-specific Ig isotypes and IgG subclasses, and IL-1β was positively correlated with most antibodies. Furthermore, the old patients (≥ 60 years old) had higher levels of chemokines, increased NAb activities and SARS-CoV-2 specific IgG1, and IgG3 responses and compromised T cell responses compared to the young patients (≤ 18 years old), which are related with more severe cases. Higher IgG1 and IgG3 were found in COVID-19 patients with comorbidities while biological sex had no effect on IgG subclasses. Overall, we have identified diseases severity was related to higher antibodies, of which IgG subclasses had weakly negative correlation with viral load, and cytokines were significantly associated with antibody response. Further, advancing age and comorbidities had obvious effect on IgG1 and IgG3.

scholarly journals An approach to gene-based testing accounting for dependence of tests among nearby genes

2021 ◽  
Author(s):  
Ronald J Yurko ◽  
Kathryn Roeder ◽  
Bernie Devlin ◽  
Max G'Sell
Keyword(s):  
Multiple Testing ◽  
Association Studies ◽  
Autism Spectrum ◽  
P Value ◽  
Genome Wide Association Studies ◽  
Strongly Correlated ◽  
Test Statistics ◽  
Test Statistic ◽  
Genome Wide ◽  
Insight Into

In genome-wide association studies (GWAS), it has become commonplace to test millions of SNPs for phenotypic association. Gene-based testing can improve power to detect weak signal by reducing multiple testing and pooling signal strength. While such tests account for linkage disequilibrium (LD) structure of SNP alleles within each gene, current approaches do not capture LD of SNPs falling in different nearby genes, which can induce correlation of gene-based test statistics. We introduce an algorithm to account for this correlation. When a gene's test statistic is independent of others, it is assessed separately; when test statistics for nearby genes are strongly correlated, their SNPs are agglomerated and tested as a locus. To provide insight into SNPs and genes driving association within loci, we develop an interactive visualization tool to explore localized signal. We demonstrate our approach in the context of weakly powered GWAS for autism spectrum disorder, which is contrasted to more highly powered GWAS for schizophrenia and educational attainment. To increase power for these analyses, especially those for autism, we use adaptive p-value thresholding (AdaPT), guided by high-dimensional metadata modeled with gradient boosted trees, highlighting when and how it can be most useful. Notably our workflow is based on summary statistics.

Inflammatory cytokines and distant recurrence in HER2-negative early breast cancer in the ECOG-ACRIN 5103 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 520-520
Author(s):  
Joseph A. Sparano ◽  
Anne M. O'Neill ◽  
Noah Graham ◽  
Donald W. Northfelt ◽  
Chau T. Dang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Early Breast Cancer ◽  
Inflammatory Cytokines ◽  
Multiple Testing ◽  
Distant Recurrence ◽  
Stage Ii ◽  
P Value

520 Background: Systemic inflammation may contribute to cancer progression (PMC2803035), including recurrence of early breast cancer (PMC4828958). We hypothesized that inflammatory cytokines and/or chemokines may be associated with distant recurrence (DR). Methods: We performed a case:control study in women with stage II-III Her2-negative breast cancer, all of whom had surgery and adjuvant chemotherapy (doxorubicin/cyclophosphamide, then weekly paclitaxel) with/without bevacizumab, plus endocrine therapy if ER-positive (PMC6118403). Propensity score matching was used to identify approximately 250 case:control pairs (with/without DR). Serum samples obtained before adjuvant chemotherapy were analyzed using the MSD V-Plex Human Cytokine 36-Plex Kit for detection of human cytokines and chemokines involved in the Th1/Th2 pathway, chemotaxis, the Th17 pathway, angiogenesis, and immune system regulation. Conditional logistic regression analysis, with models fit via maximum likelihood, were used to estimate hazard ratios (HRs) and test for associations. Due to skewed nature of cytokines, HRs are reported on log base 2 scale. If adjusted for multiple testing including 36 markers, a p value of < 0.0014 would be required for statistical significance. Results: A total 249 matched pairs (498 patients) were identified. Covariates used for propensity score matching included age, menopausal status (post 54% vs. pre/peri 46%), ER/PR status (one/both pos 64% vs. both neg 36%) tumor size ( < = 2cm 17%, > 2-5cm 67%, > 5cm 16%) nodal status (neg 15%,1-3+ 32%, 4+ 53%), and grade (low 3%, int. 31%, high 66%). The only biomarker associated with a significantly increased DR risk when adjusted for multiple testing was the proinflammatory cytokine IL-6 (HR 1.37, 95% confidence intervals [CI] 1.15, 1.65, p = 0.0006). Others associated with a 2-sided p value < 0.05 included the chemokine MDC(macrophage-derived chemokine/CCL22) (1.90, 95% CI 1.17, 3.1, p = 0.0098), the T helper cell inflammatory cytokine IL-17A (HR 1.36, 95% CI 1.10, 1.67, p = 0.0052), and the cytokine VEGF-A (HR 1.13 for, 95% CI 1.01, 1.27, p = 0.037). There was no statistical interaction between VEGF-A and bevacizumab benefit. The median and mean value for IL-6 was 0.95 and 7.5 pg/ml (range 0.04-2761.24 pg/ml). Conclusions: This analysis provides level 1B evidence indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher DR risk in high-risk stage II-III breast cancer despite optimal adjuvant systemic therapy. This provides a foundation for confirmatory validation of IL-6 as a prognostic biomarker, and potentially as a predictive biomarker for testing therapeutic interventions targeting the IL-6/JAK/STAT3 pathway. Supported by NCI U10CA180820,180794,180821; UG1CA189859,232760,233290, 233196; Komen Foundation; Breast Cancer Research Foundation. Clinical trial information: NCT00433511.

scholarly journals The harmonic mean p-value for combining dependent tests

2019 ◽  
Vol 116 (4) ◽  
pp. 1195-1200 ◽  
Author(s):  
Daniel J. Wilson
Keyword(s):  
Multiple Testing ◽  
Statistical Power ◽  
Scientific Discovery ◽  
Association Studies ◽  
Harmonic Mean ◽  
P Value ◽  
Genome Wide Association Studies ◽  
Familywise Error Rate ◽  
Significance Threshold ◽  
Genome Wide

Analysis of “big data” frequently involves statistical comparison of millions of competing hypotheses to discover hidden processes underlying observed patterns of data, for example, in the search for genetic determinants of disease in genome-wide association studies (GWAS). Controlling the familywise error rate (FWER) is considered the strongest protection against false positives but makes it difficult to reach the multiple testing-corrected significance threshold. Here, I introduce the harmonic mean p-value (HMP), which controls the FWER while greatly improving statistical power by combining dependent tests using generalized central limit theorem. I show that the HMP effortlessly combines information to detect statistically significant signals among groups of individually nonsignificant hypotheses in examples of a human GWAS for neuroticism and a joint human–pathogen GWAS for hepatitis C viral load. The HMP simultaneously tests all ways to group hypotheses, allowing the smallest groups of hypotheses that retain significance to be sought. The power of the HMP to detect significant hypothesis groups is greater than the power of the Benjamini–Hochberg procedure to detect significant hypotheses, although the latter only controls the weaker false discovery rate (FDR). The HMP has broad implications for the analysis of large datasets, because it enhances the potential for scientific discovery.

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