Asymptomatic Visceral Leishmania infantum Infection in US Soldiers Deployed to Iraq

Abstract Background Visceral leishmaniasis (VL), due to Leishmania infantum, is a persistent intracellular parasitic infection transmitted by the bite of infected sand flies. Symptomatic VL has been reported in U.S. soldiers with Iraq deployment. Untreated symptomatic VL can be fatal; asymptomatic VL (AVL) may establish a lifelong risk of reactivation. We report prevalence and AVL risk factors in Operation Iraqi Freedom (OIF) deployers during 2002–11. Methods Healthy soldiers exposed to VL endemic areas in Iraq and 50 controls who never traveled to endemic regions were recruited through military healthcare facilities (2015–17). Responses to a risk factor survey and blood samples were obtained. Leishmania research diagnostics utilized included enzyme-linked immunosorbent assay (ELISA), rk39 test strips, quantitative polymerase chain reaction (PCR), and interferon gamma release (IGRA) assays. Statistical analyses included Fisher exact test, Pearson χ2 test, Mann-Whitney U test, and logistic regression. Results 200 deployed subjects were enrolled, mostly males (84.0%), of white ethnicity (79.0%), and median age 41 (range 24–61) years. 64% were seropositive for Phlebotomus alexandri saliva antibodies. Prevalence of AVL (any positive test result) was 39/200 (19.5%, 95% confidence interval 14.4%–25.8%). Two (1.0%) PCR, 10 (5%) ELISA, and 28 (14%) IGRA samples were positive. Travel to Ninewa governorate increased risk for AVL (P = .01). Conclusion AVL was identified in 19.5% of OIF deployers; travel to northwest Iraq correlated with infection. Further studies are needed to inform risk for reactivation VL in US veterans and to target additional blood safety and surveillance measures.

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Foodborne Snow Mountain Agent Gastroenteritis in a School Cafeteria

PEDIATRICS ◽

10.1542/peds.79.4.559 ◽

1987 ◽

Vol 79 (4) ◽

pp. 559-563

Author(s):

Charles Guest ◽

Kenneth C. Spitalny ◽

H. Paul Madore ◽

Katherine Pray ◽

Raphael Dolin ◽

...

Keyword(s):

Relative Risk ◽

Strong Association ◽

Case Definition ◽

Enzyme Linked Immunosorbent Assay ◽

Fisher Exact Test ◽

Confidence Limits ◽

Serum Samples ◽

Exact Test ◽

Relative Risks ◽

The Mean

In 1984, an outbreak of gastroenteritis occurred at a school with 1,860 students in Brooklyn, NY. In a single-stage cluster sample of 375 students, 129 (34%) had illnesses that met our case definition of vomiting or diarrhea. The mean incubation period was 26 hours, and the mean illness duration was 24 hours. All case students had eaten in the cafeteria on at least one day between Nov 13 and 16, compared with 174/214 (81%) noncase students (P = 10-8, Fisher exact test). Foods implicated were french fries (relative risk 1.7, 95% confidence limits 1.4, 2.0) and hamburgers (relative risk 1.6, 95%, confidence limits 1.2, 2.1). Two cafeteria employees had served those foods while affected by diarrhea. By a recently developed blocking enzyme-linked immunosorbent assay, six of 11 (55%) case students showed fourfold antibody increases between acute-and convalescent-phase serum samples for Snow Mountain agent, a Norwalk-like virus, compared with one of ten (10%) noncase students (P = .04, Fisher exact test). We strongly suspect, but cannot document conclusively, that the Snow Mountain agent was spread to students on a vector of hot foods contaminated by ill food handlers. Implicated foods conferred low relative risks and could only have accounted for 74% of cases of illness. The strong association between cafeteria exposure and illness, therefore, suggests that additional modes of spread occurred.

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Determination of Clopidogrel Resistance by Whole Blood Platelet Aggregometry and Inhibitors of the P2Y12 Receptor

Clinical Chemistry ◽

10.1373/clinchem.2005.059535 ◽

2006 ◽

Vol 52 (3) ◽

pp. 383-388 ◽

Cited By ~ 57

Author(s):

Boris T Ivandic ◽

Philipp Schlick ◽

Peter Staritz ◽

Kerstin Kurz ◽

Hugo A Katus ◽

...

Keyword(s):

Whole Blood ◽

Adenosine Monophosphate ◽

Blood Platelet ◽

P2y12 Receptor ◽

Fisher Exact Test ◽

Exact Test ◽

Clopidogrel Resistance ◽

Impedance Aggregometry ◽

Platelet Aggregometry ◽

Increased Risk

Abstract Background: Inhibition of platelet aggregation by clopidogrel may be insufficient in up to 30% of users. These nonresponders carry an increased risk of cardiovascular events. We reported here a simple assay to study clopidogrel responsiveness. Methods: Electrical impedance aggregometry was performed in diluted whole blood in the presence of 5 and 20 μmol/L ADP. Some samples were incubated with 0.1 mmol/L methyl-S-adenosine monophosphate (MeSAMP), a P2Y12 receptor blocker, to maximize inhibition of aggregation before aggregometry. To validate the assay, we analyzed 6-min impedance in 21 healthy probands and 244 patients with coronary artery disease (CAD). Results: At 5 μmol/L ADP, the imprecision of the assay was 11%. Mean (SD) impedance of the healthy cohort was 12.2 (2.2) Ω. The mean − 3 SD was used to define the cutoff for clopidogrel responsiveness: responders and nonresponders exhibited a 6-min impedance ≤5 Ω and >5 Ω, respectively. Samples from nonresponders were incubated with MeSAMP and analyzed again to distinguish pharmacokinetic and pharmacodynamic types of resistance. Sixteen percent of CAD patients were classified as nonresponders (38 and 2 cases of pharmacokinetic and pharmacodynamic resistance, respectively). Female sex was strongly associated with clopidogrel resistance (P = 0.0002, Fisher exact test). A higher clopidogrel loading dose (P = 0.0353, Mann–Whitney U-test) was given to responders (median, 450 mg) than nonresponders (median, 300 mg). Age and cardiovascular diagnosis showed no significant associations. Conclusions: Impedance aggregometry using 5 μmol/L ADP is a useful tool for studying clopidogrel responsiveness. MeSAMP allows characterization of responsiveness “on treatment” and may be useful for optimizing clopidogrel dosing.

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Increased risk for abnormalities on perioperative colon screening in patients with microsatellite instability–positive endometrial carcinoma

International Journal of Gynecological Cancer ◽

10.1111/j.1525-1438.2006.00735.x ◽

2006 ◽

Vol 16 (6) ◽

pp. 1980-1986 ◽

Cited By ~ 2

Author(s):

B. M. Buttin ◽

M. A. Powell ◽

P. J. Goodfellow ◽

S. N. Lewin ◽

R. K. Gibb ◽

...

Keyword(s):

Regression Analysis ◽

Microsatellite Instability ◽

Medical Records ◽

Fisher Exact Test ◽

Exact Test ◽

Molecular Stratification ◽

Colon Cancers ◽

Increased Risk ◽

Primary Colon ◽

Endometrial Cancers

Microsatellite instability (MSI) is a feature of certain hereditary and sporadic endometrial and colon cancers. We set out to determine whether molecular stratification of endometrial cancers based on tumor MSI status could help identify patients at increased risk for abnormalities found on perioperative colon screening. From a prospectively accrued series of 413 patients, medical records were reviewed from 94 patients with MSI positive (MSI+) and 94 patients with MSI negative (MSI−) endometrial cancers, matched by year of diagnosis. We reviewed clinicopathologic data and results of perioperative colon screening. Differences were analyzed using Fisher exact test and logistic regression analysis. There were no significant clinicopathologic differences between the two cohorts. Sixty-five percent of patients in each group underwent perioperative colon screening. However, patients with MSI+ cancers had a twofold increase in the frequency of colonic abnormalities (30% versus 14.8%, P= 0.044) over those with MSI− cancers. Furthermore, the only primary colon cancers (N= 2) were found in women with MSI+ endometrial cancers that were unmethylated at the MLH1 promoter. Our data suggest that patients with MSI+ endometrial cancers are at increased risk for abnormalities on perioperative colon screening. Those with MSI+MLH1 unmethylated cancers appear to be at highest risk.

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Polymorphisms in Phase I (CYP450) Genes CYP1A1 (rs4646421), CYP1B1 (rs1056836), CYP19A1 (rs749292) and CYP2C8 (rs1058930) and Their Relation to Risk of Breast Cancer: A Case-Control Study in Mazandaran Province in North of Iran

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2019.667 ◽

2019 ◽

Vol 7 (15) ◽

pp. 2488-2496 ◽

Cited By ~ 2

Author(s):

Golpar Golmohammadzadeh ◽

Abbas Mohammadpour ◽

Nematollah Ahangar ◽

Mohammad Shokrzadeh

Keyword(s):

Breast Cancer ◽

Case Control Study ◽

Control Group ◽

Fisher Exact Test ◽

Mazandaran Province ◽

Chi Square ◽

Exact Test ◽

Cyp1b1 Gene ◽

Increased Risk ◽

Control Study

BACKGROUND: The second leading cause of cancer-related death in women is breast cancer. Xenobiotic Metabolizing Enzymes (XMEs) contribute to the detoxification of numerous cancer therapy-induced products. In the metabolism of xenobiotic, cytochrome P450s or monooxygenases perform an important function by catalysing the hydroxylation reaction. In this study, the susceptibility and genetic polymorphisms of CYP450 isoenzymes was investigated that may have an etiological role in breast cancer. AIM: The main purpose of this study was to evaluate the association of CYP1A1 (rs4646421), CYP1B1 (rs1056836), CYP2C8 (rs1058930), and CYP19A1 (rs749292) polymorphisms with the risk of breast cancer in Mazandaran province. MATERIAL AND METHODS: This cross-sectional case-control study were recruited 72 patients and 51 healthy individuals and was performed between March 2018 to May 2018 in the Oncology Department at Imam Hospital in Sari city, Iran. Peripheral blood samples were collected in EDTA tube, and DNA extraction was performed using the salting-out method and WizPrep extraction kits. Breast cancer patients with known clinicopathological characters and healthy women as control group were genotyped for genes polymorphisms by PCR-RFLP technique, using restriction enzymes. Chi-square, Fisher exact test and Logistic regression model, were applied for statistical analysis. RESULTS: The results of the experiments showed that there was a significant relationship between two groups and the age of the patients is significantly higher than the control group (p = 0.044). According to the chi-square and Fisher exact test, education, pregnancy, menopause status and oppose were significant between the two groups. Based on using a logistic regression model in two normalized and age-adjusted models to finding relationship between the genotypes of each gene and breast cancer risk, it was determined that in the CYP2C8 genotype, those who have the CG allele have a 7.74 degree increased risk of breast cancer (CI = 95% 0.95-62.5) and in the CYP19A1 gene, individuals with GA genotype, increased risk of breast cancer (CI = %95 1.52-27.21), about the CYP1B1 gene, people with two genotypes of CG + GG had higher risk of breast cancer (CI = %95 1.19-5.71) and allele G has decreased risk of breast cancer in this gene (P = 0.0271), also allele G in CYP2C8 gene had the protective effect (P = 0.02). In the age-adjusted model, for the CYP2C8 gene, GG genotype increased risk of breast cancer (CI = %95 1.11-75.84) as well as, the CG + GG genotype in CYP1B1 gene (CI = %95 1.31-6.57). CONCLUSION: Our results confirm the association between CYP2C8 (rs1058930), CYP19A1 (rs749292) and CYP1B1 (rs1056836) gene polymorphisms and increased risk of breast cancer in women in Mazandaran province.

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Improving Ambulatory Health Care Proxy Completion Rates: Implementing an Interdisciplinary Clinic-Based Process

American Journal of Medical Quality ◽

10.1177/1062860620915280 ◽

2020 ◽

Vol 35 (6) ◽

pp. 491-499

Author(s):

Lauge Sokol-Hessner ◽

Griffen Allen ◽

Jennifer Cluett

Keyword(s):

Primary Care ◽

Health Care ◽

Care Practice ◽

Fisher Exact Test ◽

Health Care Proxy ◽

Exact Test ◽

The North ◽

Increased Risk ◽

Physician Leaders ◽

Interdisciplinary Process

All adults should complete a health care proxy (HCP), especially those who are seriously ill or otherwise at increased risk of losing capacity. This study describes the implementation of an interdisciplinary process for helping patients complete HCPs during nonurgent visits at a large urban academic primary care practice between July 2014 and May 2017. The process was mapped using direct observations. Pre- and post-implementation measurement of the percent of patients who completed HCPs during their visit revealed significant improvement (1.4% vs 26.1% in the North Suite, special cause variation). Over the study period, the percentage of patients with HCP information rose significantly across the entire clinic (eg, 37% to 80% in the North Suite, Fisher exact test P < .0001; similar findings in other suites). Key facilitators and barriers to implementation were identified by physician leaders. An interdisciplinary process can sustainably improve the percentage of primary care patients with a completed HCP.

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Abstract 537: Higher Prevalence of Risk Alleles for Hyperuricemia Parallels Elevated Incidence of Gout and Growing Risk for Cardiovascular Diseases in a Hmong Population

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.34.suppl_1.537 ◽

2014 ◽

Vol 34 (suppl_1) ◽

Author(s):

Youssef M Roman ◽

Jenny D Xiong ◽

Jeremiah S Menk ◽

Kathleen Culhane-Pera ◽

Robert J Straka

Keyword(s):

Elevated Serum ◽

Asian Population ◽

Allele Frequencies ◽

Fisher Exact Test ◽

Snp Analysis ◽

Cvd Risk ◽

Significance Level ◽

Exact Test ◽

Risk Alleles ◽

Increased Risk

Introduction: Hyperuricemia (HU) is the strongest predictor of gout and highly associated with major CVD including hypertension, HF, and CKD. The Hmong, a unique Asian population numbering > 60,000 in Minnesota, have a two-fold increased risk of gout compared to non-Hmong, rising prevalence of CVD, and may differ from other Asian populations in these regards. A genetic predisposition to elevated Serum Uric Acid (SUA) may help identify individuals at risk for gout and CVD. We quantified the Minor Allele Frequencies (MAFs) of known genetic variants (SNPs) associated with HU and compared the MAFs between our Hmong sample and both a reference (HapMap) population of Caucasian (CEU) as well as Han-Chinese (CHB). Methods: Salivary DNA from 235 self-identified Hmong was genotyped using either a Sequenom (iPLEX Gold) or TaqMan approach. MAFs for seven SNPs within candidate genes ( SLC2A9, SLC22A12, PDZK1, and ABCG2 ) identified by GWAS, were determined in our Hmong sample. Associations between HU and genotype were examined for 57/235 Hmong with known SUA levels. A Chi-Square or Fisher exact test with a Bonferroni corrected significance level (<0.007) was used to evaluate MAF differences. Mean SUA concentrations were compared by genotype using one-way ANOVA. Results: Our Hmong participant's age [mean (±SD)] was 30.2 (15.4) years, with >61% overweight or obese and a mean (±SD) SUA of 6.3 (1.7) mg/dL. Although the frequency of risk alleles in the Hmong were significantly higher compared to CEU (6/7) and CHB (3/7) populations, independent SNP by SNP analysis did not show a clear association with SUA. Risk allele frequencies were always more frequent in the Hmong versus comparator groups. Conclusion: MAFs of selected SNPs for HU are not independent of race. The higher prevalence of risk alleles for HU in the Hmong versus CEU and CHB populations may partly explain the clinically observed higher prevalence of gout and CVD risk in the Hmong. Although sample size precludes a robust assessment of an association between genotype and SUA, to our knowledge this is the first study to examine the genetic basis of HU in the Hmong.

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Morphological Features and Prognostic Significance of ARID1A-Deficient Esophageal Adenocarcinomas

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2016-0318-oa ◽

2017 ◽

Vol 141 (7) ◽

pp. 970-977 ◽

Cited By ~ 8

Author(s):

Michael G. Drage ◽

Mingkhwan Tippayawong ◽

Agoston T. Agoston ◽

Yifan Zheng ◽

Raphael Bueno ◽

...

Keyword(s):

Microsatellite Instability ◽

Proportional Hazards ◽

Prognostic Significance ◽

Nodal Metastasis ◽

Cox Proportional Hazards ◽

Barrett Esophagus ◽

Fisher Exact Test ◽

Exact Test ◽

Increased Risk ◽

Primary Driver

Context.— The clinicopathologic and prognostic significance of ARID1A mutation in esophageal adenocarcinoma (EAC) is unknown. Objective.— To determine the morphological correlates and prognostic significance of ARID1A-deficient EAC. Design.— One hundred twenty cases of primary EAC were evaluated for a predetermined set of histologic features and immunohistochemistry for ARID1A, p53, and MLH1 performed on EAC, as well as adjacent Barrett esophagus and Barrett esophagus–associated dysplasia, when feasible. Associations between categorical clinicopathologic variables were analyzed by Fisher exact test, and survival analysis was performed by a Cox proportional hazards analysis. Results.— The study group included 97 men and 23 women (mean age, 66 years). Loss of ARID1A expression was seen in 12 of 120 EACs (10%). ARID1A-deficient tumors showed a strong correlation with a medullary and mucinous phenotype, and 8 of 12 (67%) had at least one feature reminiscent of high microsatellite instability colon carcinomas (mucinous or medullary differentiation, marked intratumoral or peritumoral lymphoid infiltrate). A mutant p53 pattern was present in 52 of 120 EACs (43%) and showed no correlation with ARID1A deficiency (P > .05). MLH1 loss was present in only 2 of 120 EACs (2%); both of which were also deficient in ARID1A. ARID1A-deficient EACs showed a trend toward increased risk of nodal metastasis but had no effect on overall patient survival. Conclusions.— ARID1A-deficient EACs show a phenotype similar to colon cancer with high microsatellite instability but do not appear to have any prognostic significance. Concurrent MLH1 loss is not seen in most ARID1A-deficient tumors, suggesting that ARID1A may be a primary driver of carcinogenesis in a subset of EACs.

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Increased rate of venous thrombosis may be associated with inpatient dihydroergotamine treatment

Neurology ◽

10.1212/wnl.0000000000004108 ◽

2017 ◽

Vol 89 (3) ◽

pp. 279-283 ◽

Cited By ~ 5

Author(s):

Amy R. Tso ◽

Irene R. Patniyot ◽

Amy A. Gelfand ◽

Peter J. Goadsby

Keyword(s):

Venous Thrombosis ◽

San Francisco ◽

Thrombotic Event ◽

Anticoagulation Therapy ◽

Fisher Exact Test ◽

Exact Test ◽

Increased Risk ◽

Treatment Dose ◽

Low Threshold ◽

The University

Objective:To review whether the incidence of catheter-associated venous thromboses was higher in patients receiving IV dihydroergotamine compared to lidocaine.Methods:We retrospectively reviewed all admissions at the University of California, San Francisco Headache Center from February 25, 2008, through October 31, 2014, for age, sex, diagnosis, aura, treatment dose, type of IV line used, days with line, superficial (SVT) or deep venous thrombosis (DVT), and pulmonary embolism (PE).Results:A peripherally inserted central catheter (PICC) or midline catheter was placed in 315 of 589 (53%) admissions. Mean age was 38 years with a range of 6 to 79 years; 121 patients (21%) were ≤18 years old. Seventy-four percent (433 of 589) of patients were female. Of 263 dihydroergotamine admissions using a PICC or midline catheter, 19 (7.2%) had either an SVT or DVT or a PE; 2 patients were diagnosed with both DVT and PE. Of 52 lidocaine admissions using a PICC or midline catheter, none had a thrombotic event (p = 0.05, Fisher exact test). Age, sex, aura, total dihydroergotamine dose, and number of days with line were not significant predictors of venous thrombosis.Conclusions:IV dihydroergotamine treatment may be associated with an increased risk of catheter-associated venous thrombosis. A low threshold for diagnostic ultrasound investigation is appropriate because anticoagulation therapy was frequently required.

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Toxicity of PD-1/CTLA-4 inhibitor immunotherapy among elderly patients.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e14139 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e14139-e14139 ◽

Cited By ~ 1

Author(s):

Vidit Kapoor ◽

Olivier Rixe

Keyword(s):

Side Effects ◽

Metastatic Melanoma ◽

Population Group ◽

The Elderly ◽

Fisher Exact Test ◽

Check Point ◽

Exact Test ◽

Increased Risk ◽

Significant Difference ◽

Check Point Inhibitors

e14139 Background: The use of Immune check point inhibitors in advanced metastatic melanoma is becoming increasingly common especially in the elderly population. With metastatic melanoma being mostly a disease of the elderly, the safety and toxicity profile of immune check point inhibitors in this population group continues to remain controversial. Prior studies have hypothesized that due to reduced immune responses in the elderly, toxicity to immune check point inhibitors is expected to be low. In this study we aim to analyze the association of check point inhibitor induced immuno-toxicity with age. Methods: We analyzed 108 patients with stage 4 metastatic melanoma who were treated with anti-PD1 and/or anti-CTLA-4 immunotherapy. Out of these patients, 58 (53.7%) were 65 or more years old and 50 (46.3%) were < 65 years old. Overall, 64 (59.3%) patients had autoimmune side effects; 35 (60.3%) were 65 years or older and 29 (48%) were < 65 years old. The most common side effects were dermatitis (n = 22, 20.4%) and colitis (n = 21, 19.4%). Incidences of various autoimmune side effects were calculated in both groups (65 years or older and < 65 years old). Fisher exact test was used to calculate p values Results: There was a significant difference between the incidence of dermatitis between the two groups. (51.4% in 65 years or older and 24.1% in < 65 years old group, p = 0.04). The incidence of colitis was more in the 65 years or older group (37.1%) as compared to < 65 years group (31.1%) however results were not statistically significant (p = 0.79). Similarly, there was no significant difference in other autoimmune side effects including hepatitis, arthritis, pneumonitis, thyroiditis, hypophysitis, adrenalitis, anemia and thrombocytopenia between the two groups. Also, there was no significant difference in the incidence of different grades of side effects (1 to 4) between the two groups. Conclusions: Patients who are 65 years or older can safely tolerate immunotherapy as compared to patients < 65 years old but with an increased risk of dermatitis. These data should be validated by a larger study population.

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Factors associated with abnormalities of the cytopathological uterine cervix test in South of Brazil

Revista Brasileira de Saúde Materno Infantil ◽

10.1590/1806-93042017000400002 ◽

2017 ◽

Vol 17 (4) ◽

pp. 637-643

Author(s):

Willian Augusto de Melo ◽

Sandra Marisa Pelloso ◽

Aline Alvarenga ◽

Maria Dalva de Barros Carvalho

Keyword(s):

Uterine Cervix ◽

Education Level ◽

Fisher Exact Test ◽

Low Grade ◽

Cervical Lesions ◽

Significance Level ◽

Exact Test ◽

White Ethnicity ◽

Factors Associated ◽

South Of Brazil

Abstract Objectives: to identify factors associated with abnormal cytopathological test uterine cervix. Methods: it is a analytical study with the participation of 390 women who presented abnormal cytopathological from a city in the state of Paraná in 2012. They were randomly selected through sampling plan. Sociodemographic information such as age, marital status, education level and ethnicity were considered independent variables while the high or low-grade cytological lesions as dependent variable. We analyzed the data statistically by Yates Corrected test, Fisher exact test and measures of association by odds ratio. For all analyzes was considered significance level of 5% and 95% confidence interval. Results: the mean age was 38.8 years, 72.9% were married or common-law marriage, 49.7% with low education level and 87.4% race/color white. HPV contamination was detected in 49.7% of women and high-grade cytological lesions in 18.2%. The low educa-tional level (95%OR=4.07) and non-white ethnicity (95%OR=2.22) were strongly associated with the development to cervical lesions (p<0.05). Conclusions: sociodemoghaphic characteristics were crucial to high-risk lesions and development of cervical cancer, especially in women with low educational level and race/color black or brown. These results confirm the persistence of diseases related to preventable and avoidable causes in the country.

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