964. Impact of Doxycycline as Malaria Prophylaxis on Risk of Influenza Like Illness Among International Travelers

Abstract Background International travelers are often at risk for both influenza like illness (ILI) and malaria. Doxycycline is active against many pathogens causing ILI and is routinely used for malaria prophylaxis. We evaluated the incidence of and risk factors for ILI, and whether the choice of malaria prophylaxis was associated with ILI. Methods TravMil is a prospective observational study enrolling subjects presenting to 6 military travel clinics. We analyzed pre- and post-travel surveys from travelers to regions outside of the continental United States, Western or Northern Europe, Canada, or New Zealand between July 2010 and August 2018. ILI was defined as subjective fever associated with either a sore throat or cough. Characteristics of trip and traveler and the use of malaria prophylaxis were analyzed to determine association with development of ILI. Poisson regression models with robust error variance were used to estimate relative risk of ILI. Results A total of 3,227 travelers were enrolled: 62.1% male, median age of 39 (IQR 27, 59), median travel duration 19 days (IQR 12, 49). 32% traveled to Africa, 40% to Asia, and 27% to the Caribbean, Mexico, and Central or South America. Military travel (46%) and vacation (40%) were most common reasons for travel. Twenty percent took doxycycline for malaria prophylaxis, 50% other prophylaxis (89% atovaquone–proguanil), and 30% took none. 8.7% developed ILI. Compared with those on no or other prophylaxis, doxycycline was associated with decreased risk of ILI [RR 0.65 (0.43–0.99), P = 0.046], as was military travel [RR 0.30 (0.21–0.43), P < 0.01]. Increased risk of ILI was associated with female gender [RR 1.57 (1.24–1.98), P < 0.01], travel to Asia [RR 1.37 (1.08–1.75), P = 0.01], cruises [RR 2.21 (1.73–2.83), P < 0.01], and longer duration of travel [RR 1.01 (1.00–1.01, P < 0.01]. Conclusion The use of doxycycline is associated with a decreased risk of ILI compared with taking no or other malaria prophylaxis. The reasons for this are unclear but may be related to anti-inflammatory effects, activity against bacterial respiratory pathogens, effects on disease transmission in closed populations (e.g., military deploying groups), or other unmeasured factors. With few proven strategies for decreasing ILI risk in travelers, these findings bear further investigation. Disclosures All authors: No reported disclosures.

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Doxorubicin, cardiac risk factors and cardiac toxicity in elderly patients with diffuse b-cell non-Hodgkin's lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.9050 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 9050-9050

Author(s):

D. L. Hershman ◽

A. Eisenberger ◽

J. Wang ◽

J. Jacobson ◽

V. Grann ◽

...

Keyword(s):

Elderly Patients ◽

B Cell ◽

Regression Models ◽

Proportional Hazards ◽

Cardiac Toxicity ◽

B Cell Lymphoma ◽

Female Gender ◽

Cox Proportional Hazards ◽

Black Race ◽

Increased Risk

9050 Background: Anthracyclines are known to cause acute and chronic cardiotoxicity. In a population-based sample of elderly patients with diffuse large B-cell lymphoma (DLBCL), we studied the cardiac effects of doxorubicin (DOX)-containing regimens and of pre-existing diabetes (DM), hypertension (HTN), and heart disease (HD). Methods: Patients aged =65 years diagnosed with DLBCL 1/1/1992–12/31/2000 in the SEER/Medicare database were grouped by treatment: no chemotherapy, doxorubicin-based chemotherapy, or other chemotherapy. We developed multivariable logistic regression models of the associations of DOX-based chemotherapy with demographic and clinical variables and pre-diagnosis DM, HTN, and HD. We then developed Cox proportional hazards regression models of the association between treatment and subsequent congestive heart failure (CHF) taking the predictors of treatment into account. Results: Of 6,413 patients with DLBCL, 2,536 (39%) received doxorubicin-based chemotherapy. DOX use was associated with later year of diagnosis, female gender, younger age, and being married. Black race (HR 0.50, 95% CI 0.33–0.75), comorbidities, preexisting CHF, HD, and DM (HR 0.73, 95% CI 0.62–0.86) were associated with decreased DOX use. The post-treatment HR for CHF following DOX treatment vs. no chemotherapy was 1.39 (95% CI 1.15–1.67); CHF risk increased with duration of DOX use. It was also associated with increasing age, comorbidities, black race, DM, HTN, and HD. There was a significant interaction between race and DOX (P=0.01); For black patients treated with DOX the HR for CHF was 3.4, as compared to a HR of 1.3 for white patients. Conclusions: Among patients with DLBCL, black race, CRFs and pre-existing HD are all associated with both a reduced likelihood of receiving anthracyclines, and an increased risk of CHF. We have previously found a powerful effect of DOX on survival in this patient population; thus, for most patients, the benefits of treatment would appear to outweigh the risks of cardiac toxicity. However, as the number of long-term survivors grows, the need for research on the side effects of treatment, on host factors that may increase the risk of adverse effects, and on ways to minimize such risks will also grow. No significant financial relationships to disclose.

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Morbidity Associated with Fetal Macrosomia among Women with Diabetes Mellitus

American Journal of Perinatology ◽

10.1055/s-0037-1608811 ◽

2017 ◽

Vol 35 (05) ◽

pp. 515-520 ◽

Cited By ~ 6

Author(s):

Amy O'Neil Dudley ◽

Hector Mendez-Figueroa ◽

Viviana Ellis ◽

Han-Yang Chen ◽

Suneet Chauhan ◽

...

Keyword(s):

Diabetes Mellitus ◽

Regression Models ◽

Neonatal Intensive Care ◽

Distress Syndrome ◽

Error Variance ◽

Outcome Data ◽

Adjusted Relative Risk ◽

Increased Risk ◽

Study Population ◽

Nicu Admission

Objective This article aims to compare the composite maternal and neonatal morbidities (CMM and CNM, respectively) between macrosomic (≥4,000 g) and nonmacrosomic (<4,000 g) newborns among women with diabetes mellitus (DM). Methods Maternal demographic and peripartum outcome data (N = 1,260) were collected from a retrospective cohort. CMM included chorioamnionitis/endometritis, wound infection, shoulder dystocia, eclampsia, pulmonary edema, admission for hypoglycemia, 3rd/4th degree perineal laceration, and death. CNM included 5-minute Appearance, Pulse, Grimace, Activity and Respiration (APGAR) score of <4, neonatal intensive care unit (NICU) admission, respiratory distress syndrome, mechanical ventilation, intraventricular hemorrhage grade III/IV, necrotizing enterocolitis stage II/III, hypoglycemia, hypocalcemia, bronchopulmonary dysplasia, sepsis, seizures, hyperbilirubinemia, and death. Multivariable Poisson regression models with robust error variance were used to calculate adjusted relative risk (aRR) and 95% confidence interval (CI). Results The study population consisted of 967 subjects, including 854 (88.3%) nonmacrosomic and 113 (11.7%) macrosomic infants. After adjustment, the risk of CMM was higher among macrosomic deliveries (aRR = 4.08, 95% CI = 2.45–6.80). The risk of CNM was also higher among macrosomic deliveries (aRR = 1.77, 95% CI = 1.39–2.24). Macrosomia was associated with an increased risk in NICU admission, hypoglycemia, and hyperbilirubinemia. Conclusion Among DM deliveries, macrosomia was associated with a fourfold higher risk of CMM and almost twofold higher risk of CNM.

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Household presentation of influenza and acute respiratory illnesses to a primary care sentinel network: retrospective database studies (2013–2018)

BMC Public Health ◽

10.1186/s12889-020-09790-3 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Simon de Lusignan ◽

Julian Sherlock ◽

Oluwafunmi Akinyemi ◽

Richard Pebody ◽

Alex Elliot ◽

...

Keyword(s):

Primary Care ◽

Disease Transmission ◽

Negative Binomial ◽

Respiratory Infections ◽

Routine Data ◽

Female Gender ◽

Household Size ◽

Cross Sectional ◽

Sentinel Network ◽

Influenza Like Illness

Abstract Background Direct observation of the household spread of influenza and respiratory infections is limited; much of our understanding comes from mathematical models. The study aims to determine household incidence of influenza-like illness (ILI), lower (LRTI) and upper (URTI) respiratory infections within a primary care routine data and identify factors associated with the diseases’ incidence. Methods We conducted two five-year retrospective analyses of influenza-like illness (ILI), lower (LRTI) and upper (URTI) respiratory infections using the England Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care sentinel network database; a cross-sectional study reporting incident rate ratio (IRR) from a negative binomial model and a retrospective cohort study, using a shared gamma frailty survival model, reporting hazard ratios (HR). We reported the following household characteristics: children < 5 years old, each extra household member, gender, ethnicity (reference white), chronic disease, pregnancy, and rurality. Results The IRR where there was a child < 5 years were 1·62 (1·38–1·89, p < 0·0001), 2·40 (2.04–2.83, p < 0·0001) and 4·46 (3.79–5.255, p < 0·0001) for ILI, LRTI and URTI respectively. IRR also increased with household size, rurality and presentations and by female gender, compared to male. Household incidence of URTI and LRTI changed little between years whereas influenza did and were greater in years with lower vaccine effectiveness. The HR where there was a child < 5 years were 2·34 (95%CI 1·88–2·90, p < 0·0001), 2·97 (95%CI 2·76–3·2, p < 0·0001) and 10·32 (95%CI 10.04–10.62, p < 0·0001) for ILI, LRTI and URTI respectively. HR were increased with female gender, rurality, and increasing household size. Conclusions Patterns of household incidence can be measured from routine data and may provide insights for the modelling of disease transmission and public health policy.

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Prosthesis-Patient Mismatch Causes a Significantly Increased Risk of Operative Mortality in Aortic Valve Replacement

The Heart Surgery Forum ◽

10.1532/hsf98.2013304 ◽

2014 ◽

Vol 17 (3) ◽

pp. 127 ◽

Cited By ~ 1

Author(s):

Muhammad Shahzeb Khan ◽

Faizan Imran Bawany ◽

Asadullah Khan ◽

Mehwish Hussain

Keyword(s):

Aortic Valve ◽

Aortic Valve Replacement ◽

Valve Replacement ◽

Operative Mortality ◽

Univariate Analysis ◽

Female Gender ◽

Valve Prosthesis ◽

Predictors Of Mortality ◽

Increased Risk ◽

Urgent Operation

Background: Small aortic prosthesis can lead to prosthesis-patient mismatch (PPM). Implanting such small prosthesis remains a controversial issue. This study was done to investigate whether or not PPM causes an increased operative mortality in aortic valve replacement (AVR).Methods: Two-hundred-two consecutive patients undergoing primary AVR in a tertiary hospital were included. The sample was grouped according to the aortic valve prosthesis size: ?21 mm (small) and >21 mm (standard). The effect of variables on outcomes was determined by univariate and multivariable regression analyses.Results: PPM was found significantly more among patients with AVR ? 21mm (P < 0.0001). Moreover, the likelihood of mortality also was significantly higher in these patients (P < 0.0001). Univariate analysis demonstrated small prosthesis size, urgent operation, PPM, female gender, and NYHA Class IV as significant predictors of mortality. Multivariate regression identified female gender, PPM, and urgent operation as the key independent predictors of mortality.Conclusion: PPM and female gender are significant predictors of mortality. Care should be taken to prevent PPM by implanting larger prosthesis especially in females.

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Cerebral small vessel disease or intracranial large vessel atherosclerosis may carry different risk for future strokes

Stroke and Vascular Neurology ◽

10.1136/svn-2019-000305 ◽

2020 ◽

Vol 5 (2) ◽

pp. 128-137

Author(s):

Huimin Chen ◽

Yuesong Pan ◽

Lixia Zong ◽

Jing Jing ◽

Xia Meng ◽

...

Keyword(s):

Regression Models ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Arterial Stenosis ◽

Small Vessel ◽

Minor Stroke ◽

Bleeding Events ◽

Stroke Outcomes ◽

Vessel Disease ◽

Increased Risk

BackgroundThe effect of cerebral small vessel disease (CSVD) and intracranial arterial stenosis (ICAS) on stroke outcomes remains unclear.MethodsData of 1045 patients with minor stroke or transient ischaemic attack (TIA) were obtained from 45 sites of the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. We assessed the associations of burdens of CSVD and ICAS with new strokes and bleeding events using multivariate Cox regression models and those with modified Rankin Scale (mRS) scores using ordinal logistic regression models.ResultsAmong the 1045 patients, CSVD was present in 830 cases (79.4%) and ICAS in 460 (44.0%). Patients with >1 ICAS segment showed the highest risk of new strokes (HR 2.03, 95% CI 1.15 to 3.56, p=0.01). No association between CSVD and the occurrence of new strokes was found. The presence of severe CSVD (common OR (cOR) 2.01, 95% CI 1.40 to 2.89, p<0.001) and >1 ICAS segment (cOR 2.15, 95% CI 1.57 to 2.93, p<0.001) was associated with higher mRS scores. Severe CSVD (HR 10.70, 95% CI 1.16 to 99.04, p=0.04), but not ICAS, was associated with a higher risk of bleeding events. Six-point modified CSVD score improved the predictive power for bleeding events and disability.InterpretationCSVD is associated with more disability and bleeding events, and ICAS is associated with an increased risk of stroke and disability in patients with minor stroke and TIA at 3 months. CSVD and ICAS may represent different vascular pathologies and play distinct roles in stroke outcomes.Trial registration numberNCT00979589

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Low HbA1c levels and all-cause or cardiovascular mortality among people without diabetes: the US National Health and Nutrition Examination Survey 1999–2015

International Journal of Epidemiology ◽

10.1093/ije/dyaa263 ◽

2020 ◽

Author(s):

Kosuke Inoue ◽

Roch Nianogo ◽

Donatello Telesca ◽

Atsushi Goto ◽

Vahe Khachadourian ◽

...

Keyword(s):

Cardiovascular Mortality ◽

Regression Models ◽

Machine Learning Algorithms ◽

Logistic Regression Models ◽

Health And Nutrition ◽

Increased Risk ◽

The Us ◽

All Cause Mortality ◽

Hba1c Levels

Abstract Objective It is unclear whether relatively low glycated haemoglobin (HbA1c) levels are beneficial or harmful for the long-term health outcomes among people without diabetes. We aimed to investigate the association between low HbA1c levels and mortality among the US general population. Methods This study includes a nationally representative sample of 39 453 US adults from the National Health and Nutrition Examination Surveys 1999–2014, linked to mortality data through 2015. We employed the parametric g-formula with pooled logistic regression models and the ensemble machine learning algorithms to estimate the time-varying risk of all-cause and cardiovascular mortality by HbA1c categories (low, 4.0 to <5.0%; mid-level, 5.0 to <5.7%; prediabetes, 5.7 to <6.5%; and diabetes, ≥6.5% or taking antidiabetic medication), adjusting for 72 potential confounders including demographic characteristics, lifestyle, biomarkers, comorbidities and medications. Results Over a median follow-up of 7.5 years, 5118 (13%) all-cause deaths, and 1116 (3%) cardiovascular deaths were observed. Logistic regression models and machine learning algorithms showed nearly identical predictive performance of death and risk estimates. Compared with mid-level HbA1c, low HbA1c was associated with a 30% (95% CI, 16 to 48) and a 12% (95% CI, 3 to 22) increased risk of all-cause mortality at 5 years and 10 years of follow-up, respectively. We found no evidence that low HbA1c levels were associated with cardiovascular mortality risk. The diabetes group, but not the prediabetes group, also showed an increased risk of all-cause mortality. Conclusions Using the US national database and adjusting for an extensive set of potential confounders with flexible modelling, we found that adults with low HbA1c were at increased risk of all-cause mortality. Further evaluation and careful monitoring of low HbA1c levels need to be considered.

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Association of ADH1B polymorphism and alcohol consumption with increased risk of intracerebral hemorrhagic stroke

Journal of Translational Medicine ◽

10.1186/s12967-021-02904-4 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Chun-Hsiang Lin ◽

Oswald Ndi Nfor ◽

Chien-Chang Ho ◽

Shu-Yi Hsu ◽

Disline Manli Tantoh ◽

...

Keyword(s):

Ischemic Stroke ◽

Alcohol Consumption ◽

Genetic Variants ◽

Regression Models ◽

Hemorrhagic Stroke ◽

Alcohol Exposure ◽

Modifiable Risk Factors ◽

Aldehyde Dehydrogenase 2 ◽

Logistic Regression Models ◽

Increased Risk

Abstract Background Alcohol consumption is one of the modifiable risk factors for intracerebral hemorrhage, which accounts for approximately 10–20% of all strokes worldwide. We evaluated the association of stroke with genetic polymorphisms in the alcohol metabolizing genes, alcohol dehydrogenase 1B (ADH1B, rs1229984) and aldehyde dehydrogenase 2 (ALDH2, rs671) genes based on alcohol consumption. Methods Data were available for 19,500 Taiwan Biobank (TWB) participants. We used logistic regression models to test for associations between genetic variants and stroke. Overall, there were 890 individuals with ischemic stroke, 70 with hemorrhagic stroke, and 16,837 control individuals. Participants with ischemic but not hemorrhagic stroke were older than their control individuals (mean ± SE, 58.47 ± 8.17 vs. 48.33 ± 10.90 years, p < 0.0001). ALDH2 rs671 was not associated with either hemorrhagic or ischemic stroke among alcohol drinkers. However, the risk of developing hemorrhagic stroke was significantly higher among ADH1B rs1229984 TC + CC individuals who drank alcohol (odds ratio (OR), 4.85; 95% confidence interval (CI) 1.92–12.21). We found that the test for interaction was significant for alcohol exposure and rs1229984 genotypes (p for interaction = 0.016). Stratification by alcohol exposure and ADH1B rs1229984 genotypes showed that the risk of developing hemorrhagic stroke remained significantly higher among alcohol drinkers with TC + CC genotype relative to those with the TT genotype (OR, 4.43, 95% CI 1.19–16.52). Conclusions Our study suggests that the ADH1B rs1229984 TC + CC genotype and alcohol exposure of at least 150 ml/week may increase the risk of developing hemorrhagic stroke among Taiwanese adults.

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The association of bullous pemphigoid with dipeptidyl-peptidase 4 inhibitors: a ten-year prospective observational study

BMC Endocrine Disorders ◽

10.1186/s12902-021-00689-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Vaia Lambadiari ◽

Aikaterini Kountouri ◽

Foteini Kousathana ◽

Emmanouil Korakas ◽

Georgios Kokkalis ◽

...

Keyword(s):

Bullous Pemphigoid ◽

Prospective Observational Study ◽

Dipeptidyl Peptidase ◽

Dermatology Department ◽

Steroid Administration ◽

Dipeptidyl Peptidase 4 ◽

Increased Risk ◽

Dipeptidyl Peptidase 4 Inhibitors ◽

A Prospective Study

Abstract Background Bullous pemphigoid is the most common bullous chronic autoimmune skin disease. Recent studies have suggested dipeptidyl-peptidase 4 inhibitors as possible predisposing agents of bullous pemphigoid. The objective of our study was to prospectively estimate the association between gliptins and the development of bullous pemphigoid. Methods We conducted a prospective study which included all patients diagnosed with biopsy-proven bullous pemphigoid in the Dermatology Department of our hospital between April 1, 2009 and December 31,2019. The diagnosis of bullous pemphigoid was based on specific clinical, histological and immunological features. Results Overall 113 consecutive patients (age 75 ± 13 years, 62 females) with the diagnosis of bullous pemphigoid were enrolled. Seventy-six patients (67.3%) suffered from type 2 Diabetes and 52 (46%) were treated with dipeptidyl-peptidase 4 inhibitors. The most frequent prescribed gliptin was vildagliptin, being administered to 45 cases (39.8% of total patients enrolled, 86.5% of the patients treated with gliptins). Gliptins were withdrawn immediately after the diagnosis of bullous pemphigoid, which together with steroid administration led to remission of the rash. Conclusions This study revealed that treatment with dipeptidyl-peptidase 4 inhibitors, especially vildagliptin, is significantly associated with an increased risk of bullous pemphigoid development.

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COVID-19 mortality in the UK Biobank cohort: revisiting and evaluating risk factors

European Journal of Epidemiology ◽

10.1007/s10654-021-00722-y ◽

2021 ◽

Vol 36 (3) ◽

pp. 299-309 ◽

Cited By ~ 1

Author(s):

Joshua Elliott ◽

Barbara Bodinier ◽

Matthew Whitaker ◽

Cyrille Delpierre ◽

Roel Vermeulen ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Body Mass Index ◽

Vitamin D ◽

Regression Models ◽

Oral Steroid ◽

Uk Biobank ◽

Steroid Use ◽

Increased Risk ◽

Male Sex

AbstractMost studies of severe/fatal COVID-19 risk have used routine/hospitalisation data without detailed pre-morbid characterisation. Using the community-based UK Biobank cohort, we investigate risk factors for COVID-19 mortality in comparison with non-COVID-19 mortality. We investigated demographic, social (education, income, housing, employment), lifestyle (smoking, drinking, body mass index), biological (lipids, cystatin C, vitamin D), medical (comorbidities, medications) and environmental (air pollution) data from UK Biobank (N = 473,550) in relation to 459 COVID-19 and 2626 non-COVID-19 deaths to 21 September 2020. We used univariate, multivariable and penalised regression models. Age (OR = 2.76 [2.18–3.49] per S.D. [8.1 years], p = 2.6 × 10–17), male sex (OR = 1.47 [1.26–1.73], p = 1.3 × 10–6) and Black versus White ethnicity (OR = 1.21 [1.12–1.29], p = 3.0 × 10–7) were independently associated with and jointly explanatory of (area under receiver operating characteristic curve, AUC = 0.79) increased risk of COVID-19 mortality. In multivariable regression, alongside demographic covariates, being a healthcare worker, current smoker, having cardiovascular disease, hypertension, diabetes, autoimmune disease, and oral steroid use at enrolment were independently associated with COVID-19 mortality. Penalised regression models selected income, cardiovascular disease, hypertension, diabetes, cystatin C, and oral steroid use as jointly contributing to COVID-19 mortality risk; Black ethnicity, hypertension and oral steroid use contributed to COVID-19 but not non-COVID-19 mortality. Age, male sex and Black ethnicity, as well as comorbidities and oral steroid use at enrolment were associated with increased risk of COVID-19 death. Our results suggest that previously reported associations of COVID-19 mortality with body mass index, low vitamin D, air pollutants, renin–angiotensin–aldosterone system inhibitors may be explained by the aforementioned factors.

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