Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February–May 2020). Patients’ characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction ( p < 0.001 ). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.

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Disentangling the association of hydroxychloroquine treatment with mortality in Covid-19 hospitalized patients through Hierarchical Clustering

10.1101/2021.01.27.21250238 ◽

2021 ◽

Author(s):

Licia Iacoviello ◽

Keyword(s):

Hierarchical Clustering ◽

Intervention Studies ◽

Smoking Status ◽

Blood Parameters ◽

Low Risk ◽

Inverse Association ◽

Current Controversy ◽

Chronic Pulmonary Diseases ◽

History Of

AbstractThe efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and intervention studies reporting contrasting results.To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February-May 2020). Patients’ characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ.We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster*HCQ interaction (p<0.001). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome.These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute clarifying the current controversy on HCQ efficacy in Covid-19 treatment.

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Risk Factors for Olfactory and Gustatory Dysfunctions in Patients with SARS-CoV-2 Infection

Neuroepidemiology ◽

10.1159/000514888 ◽

2021 ◽

pp. 1-8

Author(s):

Francesca Galluzzi ◽

Veronica Rossi ◽

Cristina Bosetti ◽

Werner Garavello

Keyword(s):

Risk Factors ◽

Smoking Status ◽

Inverse Association ◽

Current Smoking ◽

Logistic Regression Models ◽

Respiratory Allergies ◽

History Of ◽

Never Smokers ◽

Smell Loss ◽

Relevant Covariates

Introduction: Smell and taste loss are characteristic symptoms of SARS-CoV-2 infection. The aim of this study is to investigate the prevalence and risk factors associated with olfactory and gustatory dysfunctions in coronavirus disease (COVID-19) patients. Methods: We conducted an observational, retrospective study on 376 patients with documented SARS-CoV-2 infection admitted to the San Gerardo Hospital in Monza, Italy, from March to July 2020. All patients answered a phone questionnaire providing information on age, sex, smoking status, and clinical characteristics. Adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated through logistic regression models including relevant covariates. Results: The prevalence of olfactory and gustatory dysfunctions in COVID-19 patients was 33.5 and 35.6%, respectively. Olfactory dysfunctions were significantly directly associated with current smoking and history of allergy, the multivariable ORs being 6.53 (95% CI 1.16–36.86) for current smokers versus never smokers, and 1.89 (95% CI 1.05–3.39) for those with an allergy compared to those without any allergy. Respiratory allergy in particular was significantly associated with olfactory dysfunctions (multivariable OR 2.30, 95% CI 1.02–5.17). Significant inverse associations were observed for patients aged 60 years or more (multivariable OR 0.33, 95% CI 0.19–0.57) and hospitalization (multivariable OR 0.22, 95% CI 0.06–0.89). Considering gustatory dysfunctions, after allowance of other variables a significant direct association was found for respiratory allergies (OR 2.24, 95% CI 1.03–4.86), and an inverse association was found only for hospitalization (OR 0.21, 95% CI 0.06–0.76). Conclusion: Our study indicates that current smoking and history of allergy (particularly respiratory) significantly increase the risk for smell loss in COVID-19 patients; the latter is also significantly associated to taste loss. Hospitalization has an inverse association with the risk of olfactory and gustatory dysfunctions, suggesting that these may be symptoms characteristics of less severe SARS-CoV-2 infection.

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P2-13 Family history of cancer: the role of smoking status of affected relatives

Journal of Epidemiology & Community Health ◽

10.1136/jech.2011.142976h.50 ◽

2011 ◽

Vol 65 (Suppl 1) ◽

pp. A223-A223

Author(s):

T. N. Toporcov ◽

J. L. F. Antunes ◽

M. B. de Carvalho ◽

D. L. Figueiredo ◽

J. F. Gois-Filho ◽

...

Keyword(s):

Family History ◽

Smoking Status ◽

Family History Of Cancer ◽

History Of ◽

History Of Cancer

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Plasma alkylresorcinol metabolite, a biomarker of whole-grain wheat and rye intake, and risk of ischemic stroke: a case-control study

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqy323 ◽

2019 ◽

Vol 109 (2) ◽

pp. 1-7 ◽

Cited By ~ 7

Author(s):

Taoping Sun ◽

Yanwei Zhang ◽

Hao Huang ◽

Xiaoqian Wang ◽

Li Zhou ◽

...

Keyword(s):

Ischemic Stroke ◽

Stroke Risk ◽

Case Control Study ◽

Smoking Status ◽

Case Control ◽

Inverse Association ◽

Whole Grain ◽

History Of ◽

Ischemic Stroke Risk ◽

Control Study

ABSTRACT Background Epidemiologic studies on whole grains and risk of stroke have reported inconsistent results, with some suggesting a protective effect but others showing a null association. Objectives The aim of this study was to examine whether plasma 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), a biomarker of whole-grain wheat and rye intake, is associated with risk of ischemic stroke. Methods A hospital-based case-control study was conducted between March 2011 and May 2016. Cases (n = 990) with first ischemic stroke were matched to controls (n = 990) by sex and age. Concentrations of plasma DHPPA were determined by high-performance liquid chromatography–tandem mass spectrometry. We calculated ORs for the association of plasma DHPPA concentrations with ischemic stroke risk through the use of logistic regression. Results Plasma DHPPA was inversely associated with ischemic stroke risk. After adjustment for potential confounding factors, the ORs for ischemic stroke across increasing quartiles of plasma DHPPA concentrations were 1 (referent), 0.76 (95% CI: 0.58, 0.99), 0.71 (95% CI: 0.54, 0.92), and 0.59 (95% CI: 0.45, 0.77), respectively (P-trend = 0.001). The inverse association was also observed in all subgroups of participants according to sex, age, body mass index, smoking status, alcohol consumption, history of hypertension, and history of diabetes. Conclusions Our study showed that higher plasma DHPPA concentrations were associated with lower risk of ischemic stroke. This finding provides further evidence to support the health benefits of whole-grain consumption.

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Cooperation in primates

Interaction Studies ◽

10.1075/is.16.3.02alb ◽

2015 ◽

Vol 16 (3) ◽

pp. 361-382 ◽

Cited By ~ 8

Author(s):

Anna Albiach-Serrano

Keyword(s):

Observational Studies ◽

Evolutionary History ◽

Nonhuman Primates ◽

Cooperative Behavior ◽

Experimental Studies ◽

Primate Species ◽

Future Studies ◽

History Of ◽

Methodological Difficulties

Observational studies have suggested that some nonhuman primates’ cooperative behavior may rely on their capacity to share goals and understand the role of their partners. Experimental studies have tried to find evidence for this under controlled conditions, investigating aspects like the degree of organization in different primate species and the individuals’ capacity to recognize and choose good partners, switch roles with them, and care about their outcomes. Often, the results have been mixed. Partly, this is because of the methodological difficulties inherent to empirical research. In this paper, I offer a critical, methodological review of the experimental studies done in the last years on nonhuman primates’ cooperation, I discuss their findings, and suggest possible solutions to some of the procedural problems. Hopefully, this will contribute to improve the design of future studies and therefore our knowledge about the evolutionary history of cooperation.

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The role of gastrointestinal pathogens in inflammatory bowel disease: a systematic review

Therapeutic Advances in Gastroenterology ◽

10.1177/17562848211004493 ◽

2021 ◽

Vol 14 ◽

pp. 175628482110044

Author(s):

Jordan E. Axelrad ◽

Ken H. Cadwell ◽

Jean-Frederic Colombel ◽

Shailja C. Shah

Keyword(s):

Experimental Studies ◽

Inverse Association ◽

Inflammatory Conditions ◽

Gastrointestinal Pathogens ◽

Bowel Diseases ◽

Environmental Trigger ◽

Inflammatory Bowel ◽

Gut Microbial Community ◽

New Onset

The inflammatory bowel diseases (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, progressive, inflammatory conditions of the gastrointestinal tract. Imbalance in the gut microbial community, or dysbiosis, and the subsequent immune response, represent the critical relationship between genetic susceptibility, microbes, and environment factors, that result in IBD. Gastrointestinal pathogens – a common cause of dysbiosis – have been implicated as an environmental trigger in new onset IBD, as well as flare of existing IBD. In this article, we systematically review clinical data regarding the association between specific gastrointestinal pathogens and IBD. Numerous bacteria, viruses, fungi, and parasites have been implicated in the pathogenesis of IBD, and exacerbations of existing disease. In this article, we will also specifically discuss the less recognized microbes that have an inverse association with IBD, including certain bacterial pathogens, such as Helicobacter pylori, and parasites, such as Trichuris species. Future prospective and experimental studies are required to establish causality and clarify potential mechanisms of enteric pathogens in modifying the risk and course of IBD.

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Antibodies against phosphorylcholine in hospitalized versus non-hospitalized obese subjects

Scientific Reports ◽

10.1038/s41598-021-99615-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Amra Jujić ◽

J. Korduner ◽

H. Holm ◽

G. Engström ◽

E. Bachus ◽

...

Keyword(s):

Metabolic Syndrome ◽

Smoking Status ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Glucose Levels ◽

History Of ◽

Obese Subjects ◽

Anti Inflammatory

AbstractObesity associates with reduced life expectancy, type 2 diabetes, hypertension and cardiovascular disease, and is characterized by chronic inflammation. Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein, dead cells and some microorganisms. Antibodies against PC (anti-PC) have anti-inflammatory properties. Here, we explored the role of anti-PC in hospitalized versus non-hospitalized obese. One-hundred-and-twenty-eight obese (BMI ≥ 30 kg/m2) individuals (59.8 (± 5.5) years, 53.9% women) from the Malmö Diet and Cancer Cardiovascular Cohort were examined and IgM, IgG1 and IgG2 anti-PC were analyzed by ELISA. Individuals with at least one recorded history of hospitalization prior to study baseline were considered hospitalized obese (HO). Associations between IgM, IgG1 and IgG2 anti-PC and HO (n = 32)/non-hospitalized obese (NHO) (n = 96), but also with metabolic syndrome and diabetes were analysed using logistic regressions. Both IgM and IgG1 anti-PC were inversely associated with HO, also after controlling for age and sex. When further adjusted for waist circumference, systolic blood pressure, glucose levels and smoking status, only IgG1 anti-PC remained significantly associated with HO. In multivariate models, each 1 standard deviation of increment in anti-PC IgG1 levels was inversely associated with prevalence of HO (odds ratio 0.57; CI 95% 0.33–0.98; p = 0.044). IgG2 anti-PC did not show any associations with HO. Low levels of IgM and IgG1 anti-PC are associated with higher risk of being a HO individual independent of sex and age, IgG1 anti-PC also independently of diabetes and metabolic syndrome. The anti-inflammatory properties of these antibodies may be related to inflammation in obesity and its complications.

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Vitamin B6 and Diabetes: Relationship and Molecular Mechanisms

International Journal of Molecular Sciences ◽

10.3390/ijms21103669 ◽

2020 ◽

Vol 21 (10) ◽

pp. 3669 ◽

Cited By ~ 2

Author(s):

Elisa Mascolo ◽

Fiammetta Vernì

Keyword(s):

Vitamin B6 ◽

Molecular Mechanisms ◽

Experimental Studies ◽

Protective Role ◽

Genome Integrity ◽

Inverse Association ◽

Cellular Mechanisms ◽

Glycation End Products ◽

The Relationship

Vitamin B6 is a cofactor for approximately 150 reactions that regulate the metabolism of glucose, lipids, amino acids, DNA, and neurotransmitters. In addition, it plays the role of antioxidant by counteracting the formation of reactive oxygen species (ROS) and advanced glycation end-products (AGEs). Epidemiological and experimental studies indicated an evident inverse association between vitamin B6 levels and diabetes, as well as a clear protective effect of vitamin B6 on diabetic complications. Interestingly, by exploring the mechanisms that govern the relationship between this vitamin and diabetes, vitamin B6 can be considered both a cause and effect of diabetes. This review aims to report the main evidence concerning the role of vitamin B6 in diabetes and to examine the underlying molecular and cellular mechanisms. In addition, the relationship between vitamin B6, genome integrity, and diabetes is examined. The protective role of this vitamin against diabetes and cancer is discussed.

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Proactive management of penicillin and other antibiotic allergies

Allergy and Asthma Proceedings ◽

10.2500/aap.2020.41.190024 ◽

2020 ◽

Vol 41 (2) ◽

pp. 82-89 ◽

Cited By ~ 2

Author(s):

David A. Khan

Keyword(s):

Cross Reactivity ◽

Low Risk ◽

Penicillin Allergy ◽

Proactive Management ◽

Patient Morbidity ◽

Life Saving ◽

Inpatient Settings ◽

History Of ◽

Drug Challenge

Background: Antibiotic allergies, especially penicillin, are the most frequent drug allergy listed in the medical record. Proactive evaluations of antibiotic allergies, particularly penicillin allergies, have been recommended by various specialty societies. Objective: To review the history of the discovery of penicillin, implications of the penicillin allergy label, various delabeling strategies as well as a brief overview of the approach to cephalosporin, fluoroquinolone, and macrolide allergy. Methods: Recent studies on penicillin allergy delabeling and on cephalosporin and fluoroquinolone allergies were reviewed. Results: Although Alexander Fleming is often solely credited with the discovery of penicillin, other scientists were critical to the development of penicillin as a life-saving antibiotic. The vast majority of patients with a penicillin allergy label are not allergic; however, this label results in increased morbidities and mortality. A variety of penicillin delabeling strategies can be used in both the outpatient and the inpatient settings. The role of direct penicillin challenge in patients at low risk is emerging and is the method of choice for children. Patients with an unconfirmed penicillin allergy have a low risk of reacting to cephalosporins. The R1 side chain largely dictates cephalosporin allergy and cross-reactivity. Drug challenge is the preferred method for evaluation of both fluoroquinolone and macrolide allergy. Conclusion: Multiple effective methods are available to delabel patients of common antibiotic allergies. Delabeling patients in a proactive manner can reduce patient morbidity.

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Incidence of lung cancer following pneumonia in smokers: a population-based study

QJM ◽

10.1093/qjmed/hcab030 ◽

2021 ◽

Author(s):

D Shepshelovich ◽

N Barda ◽

H Goldvaser ◽

N Dagan ◽

A Zer ◽

...

Keyword(s):

Lung Cancer ◽

Smoking Status ◽

Population Based ◽

Sensitivity Analyses ◽

Smoking History ◽

Study Cohort ◽

Occult Malignancy ◽

History Of ◽

Heavy Smokers

Summary Background Pneumonia is more common in smokers compared with non-smokers. A high 1-year prevalence of lung cancer following hospitalization for pneumonia was demonstrated in heavy smokers. Aim To assess the association between hospitalization for pneumonia among ever-smokers and subsequent lung cancer risk. Design Retrospective analysis. Methods The study cohort included all ever-smokers aged 55–80 hospitalized for pneumonia between the years 2010–15 covered by a large medical insurer in Israel. Controls were matched to cases by age in a 4:1 ratio. The primary outcome was the association between hospitalization for pneumonia and subsequent 1-year incidence of lung cancer, adjusted for gender, smoking status (past/current) and pack years. Pre-specified sensitivity analyses excluded heavy smokers (smoking history of more than 30 pack years) and patients diagnosed with lung cancer within 30 days of hospitalization, as they probably had clinical or radiological findings suggestive of lung cancer, making them ineligible for screening. Results Lung cancer was identified in 275 of 12 807 (2.1%) patients following hospitalization for pneumonia and in 44 of 51 228 (0.1%) controls (adjusted odds ratio 22.46, 95% CI 16.29–30.96, P < 0.001). Among patients hospitalized for pneumonia, 1-year lung cancer incidence remained high after excluding heavy smokers and patients diagnosed within 30 days of the index date (1.3% and 1.4%, respectively). Conclusions Hospitalization for pneumonia is associated with high 1-year incidence of lung cancer in ever-smokers, supporting the important role of the widely used practice of performing follow up imaging post-pneumonia to exclude occult malignancy.

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