High red blood cell folate is associated with an increased risk of diabetes death among a hypertensive cohort.

The relationship between folate and diabetes remains inconclusive, possibly because of folate measured differentially between studies. Interference from mandatory folic acid fortification (FAF) has also been blamed. With both folate intake and circulating concentration measured, we assessed the relationship between folate and the risk of diabetes death in a hypertensive cohort established before FAF. We hypothesized that the association between folate and diabetes death is measurement dependent. We analyzed the data of 3133 hypertensive adults aged ≥19 years who participated in the Third National Health and Nutrition Examination Survey (1991-1994) and were followed up through December 31, 2010. Hazard ratios of diabetes death were estimated for participants with high (4th quarter) folate compared with those with moderate (2nd and 3rd quarters) or low (1st quarter) concentrations of folate. Dietary folate intake, total folate intake (including folate from supplements), serum, and red blood cell (RBC) folate were measured. After 42,025 person-years of follow-up, 165 diabetes deaths were recorded, and a dose-response positive association was observed between diabetes death and RBC folate. The adjusted hazard ratios of diabetes death were 1.00 (reference), 1.42 (95% CI. 1.20-1.68), and 2.21 (1.73-2.82), respectively, for hypertensive adults with low, moderate, and high RBC folate. No association was detected between diabetes death and serum folate concentration, folate intake, or either dietary intake or total intake. With minimized interference from FAF, neither dietary nor serum folate was associated with diabetes death, but elevated RBC folate was associated with a high risk of diabetes deaths among hypertensive patients.

Enhancing Opiorphin's Metabolic Stability and Preserving its Potent Analgesic Effect: A Systematic Review.

BACKGROUND: Opiorphin has been reported to show a stronger analgesic effect than morphine without causing side effects brought about by morphine-like drugs. Functional opiorphin analogs have been created to enhance its metabolic stability and preserve its potent analgesic effect. OBJECTIVE: We conducted a systematic review to summarize all opiorphin analogs and identify those with the strongest metabolic stability and antinociceptive effect. METHODS: From a total of 122 articles, 11 made it to the quantitative synthesis phase. The included articles were categorized into the type of modifications used to improve the metabolic stability of the peptide, metabolism and toxicity profile, drug absorption and in vitro cytotoxicity, anti-nociceptive effect, the opiorphin analogs' administration in animals or humans, and the type of the test used to test the antinociceptive effect. RESULTS: The substitution of natural amino acid with a non-natural amino acid, side-chain modifications, or D-aminoacid substitution were the most used type of peptide modification to create opiorphin analogs. STR-324 and PEGylated liposomes loaded with opiorphin showed the best metabolism and toxicity performance. [C]-[(CH2)6]-QRF-[S-O-(CH2)8]-R showed high stability in human plasma and stronger inhibitory potency. YQRFSR and PEGylated liposomes loaded with opiorphin showed a stronger antinociceptive effect than the parent opiorphin or morphine, with an analgesic effect of PEGylated liposomes lasting more than 50%. Intravenous administration was the preferred method of opiorphin analog administration, and different tests were used to test the antinociceptive effect. CONCLUSION: This paper presents the first systematic review discussing opiorphin and opiorphin analogs and identifies the most promising candidates for future research.

Effects of Educational Interventions in Facilitating Mammography Screening Among Asian American Women: A Meta-Analysis.

PROBLEM IDENTIFICATION: This meta-analysis evaluated the effects of various types of educational interventions on increasing breast cancer screening uptake among Asian American women. LITERATURE SEARCH: Web of Science, MEDLINE®, PubMed®, and Cochrane Library were searched for randomized controlled trials published from 2010 to 2020 of interventions developed to promote mammography uptake among Asian American women. DATA EVALUATION: A random-effects model was used to estimate pooled effect sizes using relative risk measures. A funnel plot was used to assess publication bias. SYNTHESIS: Seven studies were included in this review. Educational interventions identified were primarily culturally sensitive approaches combined with access-enhancing, individually tailored, or group-based approaches. The interventions were effective at increasing the receipt of mammography. IMPLICATIONS FOR NURSING: This review provides insight into the importance of combining other approaches with educational interventions to increase their effectiveness for Asian American women. Future interventions can incorporate various approaches to enhance the ability of Asian American women to overcome barriers to breast cancer screening.

A Pharmacoepidemiological Study of Myocarditis and Pericarditis Following the First Dose of mRNA COVID-19 Vaccine in Europe.

This study assessed the myocarditis and pericarditis reporting rate of the first dose of mRNA COVID-19 vaccines in Europe. Myocarditis and pericarditis data pertinent to mRNA COVID-19 vaccines (1 January 2021-11 February 2022) from EudraVigilance database were combined with European Centre for Disease Prevention and Control (ECDC)'s vaccination tracker data. The reporting rate was expressed as events (occurring within 28 days of the first dose) per 1 million individuals vaccinated. An observed-to-expected (OE) analysis quantified excess risk for myocarditis or pericarditis following the first mRNA COVID-19 vaccination. The reporting rate of myocarditis per 1 million individuals vaccinated was 17.27 (95% CI, 16.34-18.26) for CX-024414 and 8.44 (95% CI, 8.18-8.70) for TOZINAMERAN; and of pericarditis, 9.76 (95% CI, 9.06-10.51) for CX-024414 and 5.79 (95% CI, 5.56-6.01) for TOZINAMERAN. Both vaccines produced a myocarditis standardized morbidity ratio (SMR) > 1, with the CX-024414 vaccine having a greater SMR than TOZINAMERAN. Regarding TOZINAMERAN, SMR for pericarditis was >1 when considering the lowest background incidence, but <1 when considering the highest background incidence. Our results suggest an excess risk of myocarditis following the first dose of the mRNA COVID-19 vaccine, but the relationship between pericarditis and the mRNA COVID-19 vaccine remains unclear.

Changes in physical activity and risk of ischemic stroke: The ARIC study.

BACKGROUND: Limited data exist regarding the impact of changes in physical activity (PA) over time on ischemic stroke risk. Exploring this understudied area could help improve stroke prevention strategies and promote PA during the lifespan. METHODS: We evaluated 11,089 Atherosclerosis Risk in Communities (ARIC) participants recruited in 1987-1989 who completed Visit 3 (1993-1995). We classified PA as meeting recommendations, not meeting recommendations, or no PA. Categories of increased, decreased, stable high, and stable low PA and a continuous PA variable were also evaluated. Crude and adjusted Cox regression models were used to characterize the association of 6-year changes in PA and ischemic stroke risk. RESULTS: Participants had a mean age of 60 years. During a median of 21 years, 762 ischemic stroke events occurred. Compared to the participants with recommended PA at both visits, those with no PA had 46% higher hazards of ischemic stroke (hazard ratio (HR) = 1.46 (95% confidence interval (CI) = 1.17, 1.82)), and those with recommended PA at Visit 1 and no PA at Visit 3 also had 37% higher hazards (HR = 1.37 (95% CI = 1.02, 1.83)). Participants who increased their PA from Visit 1 to Visit 3 had 23% lower hazard than those with stable low PA at both visits (HR = 0.77 (95% CI = 0.63, 0.94)), while those who decreased their PA had 25% higher hazards compared to those with stable high PA at both visits (HR = 1.25 (95% CI = 1.01, 1.54)). CONCLUSION: Physical inactivity during midlife increases ischemic stroke risk, while meeting PA recommendations reduces it.

OSA and Subsequent Risk of Hospitalization With Pneumonia, Respiratory Infection, and Total Infection: The Atherosclerosis Risk in Communities Study.

BACKGROUND: OSA has been linked to microaspiration, systemic inflammation, and suboptimal immune function. RESEARCH QUESTION: Is OSA prospectively associated with risk of hospitalization for pneumonia, respiratory, and total infections? STUDY DESIGN AND METHODS: Prospective cohort. Participants in the Atherosclerosis Risk in Communities (ARIC) study (N = 1,586) underwent polysomnography in 1996-1998 and were followed up through 2018 for infection-related hospitalizations. The apnea-hypopnea index (AHI; events/h) was used to categorize participants as having severe OSA (≥ 30), moderate OSA (15-29), mild OSA (5-14), or a normal breathing pattern (< 5). Cox regression was used to calculate hazard ratios (HRs) and 95% CIs. RESULTS: ARIC participants were on average 62.7 (SD = 5.5) years of age, and 52.8% were female. Severe OSA was present in 6.0%, moderate OSA in 12.7%, mild OSA in 30.0%, and normal breathing in 51.3%. A total of 253 hospitalizations with pneumonia occurred over a median 20.4 (max, 22.9) years' follow-up. Participants with severe OSA were at 1.87 times (95% CI, 1.19-2.95) higher risk of hospitalization with pneumonia compared with those with a normal breathing pattern after adjustment for demographics and lifestyle behaviors. Results were attenuated modestly after adjustment for BMI (1.62 [0.99-2.63]), and prevalent asthma and COPD (1.62 [0.99-2.63]). A similar pattern existed for hospitalization with respiratory infection and composite infection (demographic and behavior-adjusted HRs: 1.47 [0.96-2.25] and 1.48 [1.07-2.04], respectively). INTERPRETATION: Severe OSA was associated with increased risk of hospitalizations with pneumonia in this community-based cohort. OSA patients may benefit from more aggressive efforts to prevent pneumonia and other infectious conditions.

Proteomic profiling identifies novel proteins for genetic risk of severe COVID-19: the Atherosclerosis Risk in Communities Study.

BACKGROUND: Genome-wide association studies have identified six genetic variants associated with severe COVID-19, yet the mechanisms through which they may affect disease remains unclear. We investigated proteomic signatures related to COVID-19 risk variants rs657152 (ABO), rs10735079 (OAS1/OAS2/OAS3), rs2109069 (DPP9), rs74956615 (TYK2), rs2236757 (IFNAR2) and rs11385942 (SLC6A20/LZTFL1/CCR9/FYCO1/CXCR6/XCR1) as well as their corresponding downstream pathways that may promote severe COVID-19 in risk allele carriers and their potential relevancies to other infection outcomes. METHODS: A DNA aptamer-based array measured 4870 plasma proteins among 11 471 participants. Linear regression estimated associations between the COVID-19 risk variants and proteins with correction for multiple comparisons, and canonical pathway analysis was conducted. Cox regression assessed associations between proteins identified in the main analysis and risk of incident hospitalized respiratory infections (2570 events) over a 20.7-year follow-up. RESULTS: The ABO variant rs657152 was associated with 84 proteins in 7241 white participants with 24 replicated in 1671 Black participants. The TYK2 variant rs74956615 was associated with ICAM-1 and -5 in white participants with ICAM-5 replicated in Black participants. Of the 84 proteins identified in the main analysis, seven were significantly associated with incident hospitalized respiratory infections including Ephrin type-A receptor 4 (hazard ratio (HR): 0.87; P = 2.3 × 10-11) and von Willebrand factor type A (HR: 1.17; P = 1.6x10-13). CONCLUSIONS: Novel proteomics signatures and pathways for COVID-19-related risk variants TYK2 and ABO were identified. A subset of these proteins predicted greater risk of incident hospitalized pneumonia and respiratory infections. Further studies to examine these proteins in COVID-19 patients are warranted.

Time-varying Reproduction Numbers of COVID-19 in Georgia, USA, March 2, 2020 to November 20, 2020.

BACKGROUND: In 2020, Severe Acute Respiratory Syndrome Coronavirus 2 impacted Georgia, USA. Georgia announced a state-wide shelter-in-place on April 2 and partially lifted restrictions on April 27. We estimated the time-varying reproduction numbers (Rt) of COVID-19 in Georgia, Metro Atlanta, and Dougherty County and environs from March 2, 2020, to November 20, 2020. METHODS: We analyzed the daily incidence of confirmed COVID-19 cases in Georgia, Metro Atlanta, and Dougherty County and its surrounding counties, and estimated Rt using the R package EpiEstim. We used a 9-day correction for the date of report to analyze the data by assumed date of infection. RESULTS: The median Rt estimate in Georgia dropped from between 2 and 4 in mid-March to < 2 in late March to around 1 from mid-April to November. Regarding Metro Atlanta, Rt fluctuated above 1.5 in March and around 1 since April. In Dougherty County, the median Rt declined from around 2 in late March to 0.32 on April 26. Then, Rt fluctuated around 1 in May through November. Counties surrounding Dougherty County registered an increase in Rt estimates days after a superspreading event occurred in the area. CONCLUSIONS: In Spring 2020, Severe Acute Respiratory Syndrome Coronavirus 2 transmission in Georgia declined likely because of social distancing measures. However, because restrictions were relaxed in late April and elections were conducted in November, community transmission continued, with Rt fluctuating around 1 across Georgia, Metro Atlanta, and Dougherty County as of November 2020. The superspreading event in Dougherty County affected surrounding areas, indicating the possibility of local transmission in neighboring counties.

Effective Practices and Recommendations for Drive-Through Clinic Points of Dispensing: A Systematic Review.

OBJECTIVE: Drive-through clinics (DTCs) are a novel type of point of dispensing where participants drive to a designated location and receive prophylaxis while remaining inside their vehicle. The objective of this review was to identify effective practices and recommendations for implementing DTCs for mass prophylaxis dispensing during emergency events. METHODS: A systematic review was conducted for articles covering DTCs published between 1990 and 2019. Inclusion criteria were peer-reviewed, written in English, and addressed DTCs sufficiently. Effective practices and recommendations identified in the literature were presented by theme. RESULTS: A total of 13 articles met inclusion criteria. The themes identified were (1) optimal DTC design and planning via decision support systems and decision support tools; (2) clinic layouts, locations, and design aspects; (3) staffing, training, and DTC communication; (4) throughput time; (5) community outreach methods; (6) DTC equipment; (7) infection prevention and personal protective equipment; and (8) adverse events prevention and traffic management. CONCLUSIONS: DTCs are an essential component of emergency preparedness and must be optimally designed and implemented to successfully dispense mass prophylaxis to a community within 48 hours. The effective practices and recommendations presented can be used for the development, implementation, and improvement of DTCs for their target populations.

Triggering of cardiovascular disease by infection type: The Atherosclerosis Risk in Communities study (ARIC).

INTRODUCTION: Acute infections are known triggers of cardiovascular disease (CVD) but how this association varies across infection types is unknown. We hypothesized while acute infections increase CVD risk, the strength of this association varies across infection types. METHOD: Acute coronary heart disease (CHD) and ischemic stroke cases were identified in the Atherosclerosis Risk in Communities Study (ARIC). ICD-9 codes from Medicare claims were used to identify cellulitis, pneumonia, urinary tract infections (UTI), and bloodstream infections. A case-crossover design and conditional logistic regression were used to compare infection types among acute CHD and stroke cases 14, 30, 42, and 90 days before the event with two corresponding control periods (1 and 2 years prior). RESULTS: Of the 1312 acute CHD cases, 116 had a UTI, 102 had pneumonia, 43 had cellulitis, and 28 had a bloodstream infection 90 days before the CHD event. Pneumonia (OR = 25.53 (9.21,70.78)), UTI (OR = 3.32 (1.93, 5.71)), bloodstream infections (OR = 5.93 (2.07, 17.00)), and cellulitis (OR = 2.58 (1.09, 6.13)) were associated with higher acute CHD risk within 14 days of infection. Of the 727 ischemic stroke cases, 12 had cellulitis, 27 had pneumonia, 56 had a UTI, and 5 had a bloodstream infection within 90 days of the stroke. Pneumonia (OR = 5.59 (1.77, 17.67)) and UTI (OR = 3.16 (1.68, 5.94)) were associated with higher stroke risk within 14 days of infection. CONCLUSIONS: Patients with pneumonia, UTI, or bloodstream infection appear to be at a 2.5 to 25.5 fold elevated CVD risk following infection. Preventive therapies during this high-risk period should be considered.

Hospitalization With Major Infection and Incidence of End-Stage Renal Disease: The Atherosclerosis Risk in Communities (ARIC) Study.

OBJECTIVE: To evaluate whether the incidence of infectious diseases increases the long-term risk for incident end-stage renal disease (ESRD) in the general population. PATIENTS AND METHODS: In 10,290 participants of the Atherosclerosis Risk in Communities Study who attended visit 4 (1996-1998), we evaluated the association of incident hospitalization with major infections (pneumonia, urinary tract infection, bloodstream infection, and cellulitis and osteomyelitis) with subsequent risk for ESRD through September 30, 2015. Hospitalization with major infection was entered into multivariable Cox models as a time-varying exposure to estimate the hazard ratios. RESULTS: Mean age was 63 years, and of 10,290 individuals, 56% (n=5781) were women, 22% (n=2252) were black, and 7% (n=666) had an estimated glomerular filtration rate less than 60 mL/min/1.73 m2. During a median follow-up of 17.4 years, there were 2642 incident hospitalizations with major infection and 281 cases of ESRD (132 cases after hospitalization with major infection). The risk for ESRD was higher following major infection compared with while free of major infection (crude incidence rate, 10.9 vs 1.0 per 1000 person-years). In multivariable time-varying Cox analysis, hospitalization with major infection was associated with a 3.3-fold increased risk for ESRD (hazard ratio, 3.34; 95% CI, 2.56-4.37). The association was similar across pneumonia, urinary tract infection, bloodstream infection, and cellulitis and osteomyelitis, and remained significant across subgroups of age, sex, race, diabetes, history of cardiovascular disease, and chronic kidney disease. CONCLUSION: Hospitalization with major infection was independently and robustly associated with subsequent risk for ESRD. Whether preventive approaches against infection have beneficial effects on kidney outcomes may deserve future investigations.

Endodontic therapy and incident cardiovascular disease: The Atherosclerosis Risk in Communities (ARIC) study.

OBJECTIVES: Previous studies on a potential association between endodontic infection (EI) and cardiovascular disease (CVD) produced mixed results. Endodontic treatment (ET) may also be linked to cardiovascular risk, as a marker for prior chronic dental infection and subclinical EI in other teeth. We tested the hypothesis that ET is associated with elevated risk of coronary heart disease (CHD), ischemic stroke (IS), heart failure (HF), or venous thromboembolism (VTE). METHODS: ARIC participants who completed the dental ancillary study exam 4 (1996-1998; n = 6,638) were included in the analyses. Participants were followed through 2013 for CHD, stroke, and HF and 2011 for VTE. Cox-proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for CHD, IS, HF, and VTE across ET classifications adjusting for age, sex, race/center, education, income, smoking, alcohol consumption, BMI, statin use, family history of CHD, physical activity, diet quality, insurance status, last dental visit, dental visit frequency, having a current dentist, and tooth loss due to gum disease. RESULTS: Among participants, 21.0% reported a single ET, while 28.5% reported multiple ETs. Over a median of 15.8 years of follow-up, there were 506 incident CHD events, 311 IS events, 739 HF events, and 219 VTE events. There were no significant associations between self-reported history of ET and any of our outcomes (HR (95%CI): CHD = 1.16 (0.87,1.44), IS = 0.77 (0.55,1.09), HF = 1.00 (0.81,1.24), VTE = 0.98 (0.67,1.43)) after adjustment. CONCLUSIONS: Our results do not support an independent association between ET and development of CHD, IS, HF, or VTE.

Incident Hospitalization with Major Cardiovascular Diseases and Subsequent Risk of ESKD: Implications for Cardiorenal Syndrome.

BACKGROUND: Cardiorenal syndrome is a well known concept, bolstered by extensive investigations of CKD as a risk factor of cardiovascular disease. However, data on whether cardiovascular disease increases long-term risk of ESKD are sparse. METHODS: We assessed the association of incident hospitalization with major cardiovascular diseases (heart failure, atrial fibrillation, coronary heart disease, and stroke) with subsequent risk of ESKD among individuals enrolled in the Atherosclerosis Risk in Communities study; the analysis included 9047 individuals without prevalent cardiovascular disease at their fourth study visit. Each relevant incident cardiovascular disease event was entered into multivariable Cox proportional hazard models as a time-varying exposure to estimate hazard ratios. RESULTS: During a median follow-up of 17.5 years, there were 2598 cases of hospitalization with cardiovascular disease (heart failure, n=1269; atrial fibrillation, n=1337; coronary heart disease, n=696; and stroke, n=559) and 210 cases of incident ESKD. The incidence of major cardiovascular disease was associated with increased risk of ESKD, with the highest risk for heart failure (hazard ratio, 11.40; 95% confidence interval, 8.38 to 15.50), followed by coronary heart disease, atrial fibrillation, and stroke. When we analyzed heart failure with preserved ejection fraction and heart failure with reduced ejection fraction separately, the risk was nominally higher for heart failure with preserved ejection fraction. CONCLUSIONS: Major incident cardiovascular disease events were associated with ESKD, independent of kidney risk factors. In particular, heart failure showed a very strong association with ESKD. Our findings highlight the importance of monitoring and managing kidney disease in patients with cardiovascular disease. The potentially distinct contribution to ESKD of heart failure with preserved versus reduced ejection fraction deserves future investigation.

Association between serum folate and cardiovascular deaths among adults with hypertension.

BACKGROUND: A significant shift toward high folate concentrations has been taking place following the mandatory folate fortification. Yet the relationship between folate and health outcomes beyond neural tube defects remains understudied. We longitudinally examined relationships between serum folate and risk of cardiovascular death. METHODS: We analyzed data of 3116 adults aged ≥19 who participated in the Third National Health and Nutrition Examination Survey, 1991-1994 and were diagnosed with hypertension. Vital status was followed through December 31, 2010. Cox regression was used to estimate hazard ratios (HRs) of cardiovascular deaths for individuals with serum folate in the first quartile and fourth quartile compared with the patients with interquartile folate. RESULTS: After 33627 person years (p*ys) of follow-up, 1298 deaths were recorded with 638 cardiovascular disease (CVD) deaths (109 strokes and 529 heart diseases). A U-shaped association appeared after multivariable adjustment for heart disease, acute myocardial infarction, and overall CVD deaths. The mortality rate for heart disease in patients with low, moderate, and high folate were 12.18/1000 p*ys, 14.12/1000 p*ys, and 23.80/1000 p*ys, respectively, and the corresponding adjusted HRs were 1.79 (95% confidence interval, CI = 1.63-1.98), 1.00 (reference), and 1.31 (1.17-1.46). The HRs of acute myocardial infarction were 2.28 (1.80-2.88), 1.00 (reference), and 1.77 (1.42-2.20) for hypertensive patients with serum folate in low quartile, interquartile, and high quartile, respectively. CONCLUSIONS: Among hypertensive adults, both low and high folate were associated with an elevated risk of dying from cardiovascular diseases compared with adults with moderate serum folate concentration.

Association of Testosterone Therapy With Risk of Venous Thromboembolism Among Men With and Without Hypogonadism.

Importance: Testosterone therapy is increasingly prescribed in patients without a diagnosis of hypogonadism. This therapy may be associated with increased risk of venous thromboembolism (VTE) through several mechanisms, including elevated hematocrit levels, which increase blood viscosity. Objective: To assess whether short-term testosterone therapy exposure is associated with increased short-term risk of VTE in men with and without evidence of hypogonadism. Design, Setting, and Participants: This case-crossover study analyzed data on 39 622 men from the IBM MarketScan Commercial Claims and Encounter Database and the Medicare Supplemental Database from January 1, 2011, to December 31, 2017, with 12 months of follow-up. Men with VTE cases who were free of cancer at baseline and had 12 months of continuous enrollment before the VTE event were identified by International Classification of Diseases codes. Men in the case period were matched with themselves in the control period. Case periods of 6 months, 3 months, and 1 month before the VTE events were defined, with equivalent control periods (6 months, 3 months, and 1 month) in the 6 months before the case period. Exposures: National drug codes were used to identify billed testosterone therapy prescriptions in the case period (0-6 months before the VTE) and the control period (6-12 months before the VTE). Main Outcomes and Measures: The main outcome in this case-only experiment was first VTE event stratified by the presence or absence of hypogonadism. Results: A total of 39 622 men (mean [SD] age, 57.4 [14.2] years) were enrolled in the study, and 3110 men (7.8%) had evidence of hypogonadism. In age-adjusted models, testosterone therapy use in all case periods was associated with a higher risk of VTE in men with (odds ratio [OR], 2.32; 95% CI, 1.97-2.74) and without (OR, 2.02; 95% CI, 1.47-2.77) hypogonadism. Among men without hypogonadism, the point estimate for testosterone therapy and VTE risk in the 3-month case period was higher for men younger than 65 years (OR, 2.99; 95% CI, 1.91-4.68) than for older men (OR, 1.68; 95% CI, 0.90-3.14), although this interaction was not statistically significant (P = .14). Conclusions and Relevance: Testosterone therapy was associated with an increase in short-term risk for VTE among men with and without hypogonadism, with some evidence that the association was more pronounced among younger men. These findings suggest that caution should be used when prescribing testosterone therapy.

Periodontal disease and incident venous thromboembolism: The Atherosclerosis Risk in Communities study.

AIM: Periodontal disease is a cardiovascular disease (CVD) risk factor but few studies have considered the relationship between periodontal disease and venous thromboembolism (VTE). We hypothesized that periodontal disease is independently associated with increased risk of incident VTE. MATERIALS AND METHODS: We used data from 8,092 participants of the Atherosclerosis Risk in Communities (ARIC) study to examine periodontal disease in 1996-1998 and incident VTE through 2011. Periodontal disease was determined using self-reported tooth loss due to gum disease and dental examinations. Cox proportional hazards regression models were used to estimate hazard ratios for VTE and 95% confidence intervals adjusted for relevant confounders. RESULTS AND CONCLUSIONS: Participants were on average 62.7 years old at baseline and 13.9% self-reported tooth loss from gum disease. Over a mean of 12.9 years of follow-up, there were 313 incident VTE events. Self-reported tooth loss due to gum disease was associated with 30% higher VTE risk (HR = 1.29 (0.96, 1.73) after adjusting demographic factors, SES, periodontal risk factors, oral hygiene, and access to dental care variables. No statistically significant associations between clinical measures of periodontitis and VTE were observed after adjustment. Further research is needed to elucidate whether a relationship between periodontal disease and VTE exists.

Inpatient and Outpatient Infection as a Trigger of Cardiovascular Disease: The ARIC Study.

Background Acute infections are known cardiovascular disease ( CVD ) triggers, but little is known regarding how CVD risk varies following inpatient versus outpatient infections. We hypothesized that in- and outpatient infections are associated with CVD risk and that the association is stronger for inpatient infections. Methods and Results Coronary heart disease (CHD) and ischemic stroke cases were identified and adjudicated in the ARIC (Atherosclerosis Risk in Communities Study). Hospital discharge diagnosis codes and Medicare claims data were used to identify infections diagnosed in in- and outpatient settings. A case-crossover design and conditional logistic regression were used to compare in- and outpatient infections among CHD and ischemic stroke cases (14, 30, 42, and 90 days before the event) with corresponding control periods 1 and 2 years previously. A total of 1312 incident CHD cases and 727 incident stroke cases were analyzed. Inpatient infections (14-day odds ratio [ OR ]=12.83 [5.74, 28.68], 30-day OR =8.39 [4.92, 14.31], 42-day OR =6.24 [4.02, 9.67], and 90-day OR =4.48 [3.18, 6.33]) and outpatient infections (14-day OR =3.29 [2.50, 4.32], 30-day OR =2.69 [2.14, 3.37], 42-day OR =2.45 [1.97, 3.05], and 90-day OR =1.99 [1.64, 2.42]) were more common in all CHD case periods compared with control periods and inpatient infection was a stronger CHD trigger for all time periods ( P<0.05). Inpatient infection was also a stronger stroke trigger with the difference borderline statistically significant ( P<0.10) for the 42- and 90-day time periods. Conclusions In- and outpatient infections are associated with CVD risk. Patients with an inpatient infection may be at particularly elevated CVD risk and should be considered potential candidates for CVD prophylaxis.

Hospitalization with infection and incident venous thromboembolism: The ARIC study.

BACKGROUND AND OBJECTIVES: Acute triggers for VTE, which may include infection, are understudied, as is the timing and duration of VTE risk after infection. We hypothesized that there is an association between hospitalization with infection and short-term VTE risk that exceeds the known association between hospitalization and VTE. METHODS: VTE cases and infections were identified in the Atherosclerosis Risk in Communities (ARIC) cohort. A case-crossover design and conditional logistic regression were used to compare hospitalized infections among VTE cases (14, 30, 42, and 90days before VTE) with corresponding control periods 1year and 2years prior. Since hospitalization is a known VTE trigger, study design and analytical techniques were used to isolate the impact of infection. RESULTS: There were 845 adjudicated incident VTE cases. Hospitalization with infection was more common in all case periods compared to equivalent control periods: 14day OR (95% CI)=1.7 (0.5, 5.8), 30day OR (95% CI)=2.7 (1.1, 6.4), 42day OR (95% CI)=2.2 (1.1, 4.7), and 90day OR (95% CI)=1.2 (0.7, 2.0). The association was generally strongest in exposure periods closest to the VTE event and decreased as the time window before VTE increased. CONCLUSIONS: These results support the hypothesis that hospitalized infection is a trigger of VTE. VTE preventive measures may prevent VTE events if used in the peri-infection period but clinical trials are needed.

Hospitalized Infection as a Trigger for Acute Ischemic Stroke: The Atherosclerosis Risk in Communities Study.

BACKGROUND AND PURPOSE: Acute triggers for ischemic stroke, which may include infection, are understudied, as is whether background cardiovascular disease (CVD) risk modifies such triggering. We hypothesized that infection increases acute stroke risk, especially among those with low CVD risk. METHODS: Hospitalized strokes and infections were identified in the Atherosclerosis Risk in Communities (ARIC) cohort. A case-crossover design and conditional logistic regression were used to compare hospitalized infections among patients with stroke (14, 30, 42, and 90 days before stroke) with corresponding control periods 1 year and 2 years before stroke. Background CVD risk was assessed at both visit 1 and the visit most proximal to stroke, with risk dichotomized at the median. RESULTS: A total of 1008 adjudicated incident ischemic strokes were included. Compared with control periods, hospitalized infection was more common within 2 weeks before stroke (14-day odds ratio [OR], 7.7; 95% CI, 2.1-27.3); the strength of association declined with increasing time in the exposure window before stroke (30-day OR, 5.7 [95% CI, 2.3-14.3]; 42-day OR, 4.5 [95% CI, 2.0-10.2]; and 90-day OR, 3.6 [95% CI, 2.1-6.5]). Stroke risk was higher among those with low compared with high CVD risk, with this interaction reaching statistical significance for some exposure periods. CONCLUSIONS: These results support the hypothesis that hospitalized infection is a trigger of ischemic stroke and may explain some cryptogenic strokes. Infection control efforts may prevent strokes. CVD preventive therapies may prevent strokes if used in the peri-infection period, but clinical trials are needed.

Twenty Years of Neighborhood Effect Research: An Assessment.

This paper reviews the magnitude and empirical findings of social epidemiological neighborhood effects research. An electronic keyword literature search identified 1369 empirical and methodological neighborhood effects papers published in 112 relevant journals between 1990 and 2014. Analyses of temporal trends were conducted by focus, journal type (e.g., epidemiology, public health, or social science), and specific epidemiologic journal. Select papers were then critically reviewed. Results show an ever-increasing number of papers published, notably since the year 2000, with the majority published in public health journals. The variety of health outcomes analyzed is extensive, ranging from infectious disease to obesity to criminal behavior. Papers relying on data from experimental designs are thought to yield the most credible results, but such studies are few and findings are inconsistent. Papers relying on data from observational designs and multilevel models typically show small statistically significant effects, but most fail to appreciate fundamental identification problems. Ultimately, of the 1170 empirically focused neighborhood effects papers published in the last 24 years, only a handful have clearly advanced our understanding of the phenomena. The independent impact of neighborhood contexts on health remains unclear. It is time to expand the social epidemiological imagination.