Evidence of Reduced Virulence and Increased Colonization among Pneumococcal Isolates of Serotype 3 Clade II Lineage in Mice.

Recent phylogenetic profiling of pneumococcal serotype 3 (Pn3) isolates revealed a dynamic interplay among major lineages with the emergence and global spread of a variant termed Clade II. The cause of Pn3 clade II dissemination along with epidemiological and clinical ramifications are currently unknown. Here, we sought to explore biological characteristics of dominant Pn3 clades in a mouse model of pneumococcal invasive disease and carriage. Carriage and virulence potential were strain dependent with marked differences among clades. We found that clinical isolates from Pn3 clade II are less virulent and less invasive in mice compared to clade I isolates. We also observed that clade II isolates are carried for longer and at higher bacterial densities in mice compared to clade I isolates. Taken together, our data suggest that the epidemiological success of Pn3 clade II could be related to alterations in the pathogen's ability to cause invasive disease and to establish a robust carriage episode.

Factors influencing the indication of coronary angiography in patients presenting with chest pain unspecified: an analysis of two decades (1994-2014).

Guidelines for cardiac catheterization in patients with non-specific chest pain (NSCP) provide significant room for provider discretion, which has resulted in variability in the utilization of invasive coronary angiograms (CAs) and a high rate of normal angiograms. The overutilization of CAs in patients with NSCP and discharged without a diagnosis of coronary artery disease is an important issue in medical care quality. As a result, we sought to identify patient demographic, socioeconomic, and geographic factors that influenced the performance of a CA in patients with NSCP who were discharged without a diagnosis of coronary artery disease. We intended to establish reference data points for gauging the success of new initiatives for the evaluation of this patient population. In this 20-year retrospective cohort study (1994-2014), we examined 107 796 patients with NSCP from the Myocardial Infarction Data Acquisition System, a large statewide validated database that contains discharge data for all patients with cardiovascular disease admitted to every non-federal hospital in NJ. Patients were partitioned into two groups: those offered a CA (CA group; n = 12 541) and those that were not (No-CA group; n = 95 255). Geographic, demographic, and socioeconomic variables were compared between the two groups using multivariable logistic regression, which determined the predictive value of each categorical variable on the odds of receiving a CA. Whites were more likely than Blacks and other racial counterparts (19.7% vs. 5.6% and 16.5%, respectively; P < .001) to receive a CA. Geographically, patients who received a CA were more likely admitted to a large hospital compared to small- or medium-sized ones (12.5% vs. 8.9% and 9.7%, respectively; P < .05), a primary teaching institution rather than a teaching affiliate or community center (16.1 % vs. 14.3% and 9.1%, respectively; P < .001), and at a non-rural facility compared to a rural one (12.1% vs. 6.5%; P < .001). Lastly from a socioeconomic standpoint, patients with commercial insurance more often received a CA compared to those having Medicare or Medicaid/self-pay (13.7% vs. 9.5% and 6.0%, respectively; P < .001). The utilization of CA in patients with NSCP discharged without a diagnosis of coronary artery disease in NJ during the study period may be explained by differences in geographic, demographic, and socioeconomic factors. Patients with NSCP should be well scrutinized for CA eligibility, and reliable strategies are needed to reduce discretionary medical decisions and improve quality of care.

Does One's Socioeconomic Status Predispose to the Development of Stress-Induced Cardiomyopathy?

INTRODUCTION: Stress-induced cardiomyopathy (SIC) has a higher incidence in Caucasians (CAUCs) compared to African-Americans (AAs). Whether this is due to racial predisposition, selection bias, or environmental factors remains unclear. HYPOTHESIS: We hypothesize that people from lower socioeconomic strata (SES) have a lower incidence of SIC. It is possible that the incidence of SIC could be similar among CAUCs and AAs at the same SES. Stress preconditioning maybe protective in preventing SIC. METHODS: Data of patients with the discharge diagnosis of SIC were extracted from the Myocardial Infarction Data Acquisition System spanning the period from 2006 through 2015. The incidence of SIC among CAUCs and AAs was compared per 100,000 New Jersey population and examined across income brackets. CAUCs and AAs data were compared using two-sample proportion tests. RESULTS: During the study period, CAUCs had an overall higher incidence of SIC compared to AAs, 0.017% versus 0.0084% per 100,000 population (p value <0.0001). This difference persisted after a logistic regression adjustment (p = 0.0064). CAUCs in the income brackets of 30-40k had lower incidence of SIC than those in the 60-80k income bracket (p = 0.0156). Those with an income of 60-80k had lower incidence of SIC compared to those with an income of 80-100k. AAs with income between 30 and 60k had a lower incidence of SIC than CAUCs (p = 0.0330). CONCLUSIONS: CAUCs exhibited a trend towards less SIC as a function of lower income. This was not observed among AAs. AAs had a lower incidence of SIC. Our study suggests that SES has a protective effect among CAUCs.

Stroke Recovery Program with Modified Cardiac Rehabilitation Improves Mortality, Functional & Cardiovascular Performance.

BACKGROUND: Physical activity and exercise after stroke is strongly recommended, providing many positive influences on function and secondary stroke prevention. The purpose of this study was to investigate the effect of a stroke recovery program (SRP) integrating modified cardiac rehabilitation on mortality and functional outcomes for stroke survivors. METHODS: This study used a retrospective analysis of data from a prospectively collected stroke rehabilitation database which followed 449 acute stroke survivors discharged from an inpatient rehabilitation facility between 2015 and 2020. For 1-year post-stroke, 246 SRP-participants and 203 nonparticipants were compared. The association of the SRP including modified cardiac rehabilitation with all-cause mortality and functional performance was assessed using the following statistical techniques: log rank test, Cox proportional hazard model and linear mixed effect models. Cardiovascular performance over 36 sessions of modified cardiac rehabilitation was assessed using linear effect model with Tukey procedure. The primary outcome measure was 1-year all-cause mortality rate. Secondary outcomes were functional performance measured in Activity Measure of Post-Acute Care scores and cardiovascular performance measured in metabolic equivalent of tasks times minutes. RESULTS: The SRP-participants had: (1) a significantly reduced 1-year post-stroke mortality rate from hospital admission corresponding to a four-fold reduction in mortality (P = 0.005, CI for risk ratio = [0.08, 0.71]), (2) statistically and clinically significant improvement of function in all Activity Measure of Post-Acute Care domains (P < 0.001 for all, 95% CI for differences in Basic Mobility [5.9, 10.1], Daily Activity [6.2, 11.8], and Applied Cognitive [3.0, 6.8]) compared to the matched cohort and (3) an improvement in cardiovascular performance over 36 sessions with an increase of 78% metabolic equivalent of tasks times minutes (P < 0.001, 95% CI [70.6, 85.9%]) compared to baseline. CONCLUSIONS: Stroke survivors who participated in a comprehensive stroke recovery program incorporating modified cardiac rehabilitation had decreased all-cause mortality, improved overall function, and improved cardiovascular performance.

US Initiative to Eliminate Racial and Ethnic Disparities in Health: The Impact on the Outcomes of ST-Segment-Elevation Myocardial Infarction in New Jersey.

Background In 1998, President Clinton launched a federal initiative to eliminate racial and ethnic health disparities. The impact on the outcomes of ST-segment-elevation myocardial infarction has not been well studied. Methods and Results ST-segment-elevation myocardial infarction outcomes from 1994 to 2015 were studied in 7942 Black, 27 665 Hispanic, and 88 727 White patients with first admission of ST-segment-elevation myocardial infarction using the Myocardial Infarction Data Acquisition System. Logistic regressions were used to assess mortality adjusting for demographics, comorbidities, and interventional procedures. There was an overall rise from 1994 to 2015 in the use of percutaneous coronary interventions in all 3 groups. Before 1998, White patients received more percutaneous coronary interventions compared with Black and Hispanic patients (P<0.05). After 1998, the disparity in use of percutaneous coronary interventions in Black and Hispanic patients was greatly reduced compared with White patients, and the difference reversed in favor of Hispanic patients after 2005 (P<0.05). There was an overall downward trend of in-hospital mortality without evidence of disparity among Black, Hispanic, and White patients. A linear regression model was used with a change point in 1998. Before 1998, the slope of 1-year all-cause and cardiovascular mortality was not statistically significant. After 1998, the mortality showed negative slopes for all 3 groups, however, with lower overall crude mortality for Hispanic patients compared with Black and White patients (P<0.0001). Conclusions The initiative launched in 1998 may have contributed to a reduction in percutaneous coronary intervention usage disparity in patients with ST-segment-elevation myocardial infarction. Short- and long-term mortality decreased in all 3 groups, but more in the Hispanic population.

Impact of Modified Cardiac Rehabilitation Within a Stroke Recovery Program on All-Cause Hospital Readmissions.

OBJECTIVE: A Stroke Recovery Program (SRP) including cardiac rehabilitation demonstrated lower all-cause mortality rates, improved cardiovascular function, and overall functional ability among stroke survivors. Neither an effect of SRP on acute care hospital readmission rates nor cost savings have been reported. DESIGN: This prospective matched cohort study included 193 acute stroke survivors admitted to an inpatient rehabilitation facility between 2015 and 2017. The 105 SRP participants and 88 nonparticipants were matched exactly for stroke type, sex, and race and approximately for age, baseline functional scores, and medical complexity scores. Primary outcome measured acute care hospital readmission rate up to 1 yr post-stroke. Secondary outcomes measured costs. RESULTS: A 22% absolute reduction (P = 0.006) in hospital readmissions was observed between the SRP participant (n = 47, or 45%) and nonparticipant (n = 59, or 67%) groups. This resulted in significant cost savings. The conventional care cost to the Center for Medicare and Medicaid Services for stroke patients for both readmissions and outpatient therapy is estimated at $9.67 billion annually. The yearly cost for these services with utilization of the SRP is $8.55 billion. CONCLUSION: Acute care hospital readmissions were reduced in stroke survivors who participated in SRP. Future study is warranted to examine whether widespread application of a similar program may improve quality of life and decrease cost.

Monotherapy treatment with chlorthalidone or amlodipine in the systolic blood pressure intervention trial (SPRINT).

This post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) examined the performance of chlorthalidone (C) versus amlodipine (A) monotherapies. ANOVA was used to analyze the differences in systolic blood pressure (SBP) response between C and A. Logistic regression was used to examine monotherapy failure (adding a second antihypertensive agent or switching to a different antihypertensive agent) rates. Four hundred ninety-one participants were treated with C monotherapy (n = 210, mean dose = 22 mg/day) or A monotherapy (n = 281, mean dose = 7 mg/day). There was a significant difference in mean SBP reduction between the C and A monotherapies at the third visit (higher reduction with A, adjusted p = .018). Unadjusted analysis showed a higher failure with C in the standard treatment group. Although the average SBP at failure was higher and above the 140 mm Hg cutoff that indicated monotherapy failure with A (142.60) compared with C (138.40), more participants on C failed despite having SBP below the 140 cutoff. This was probably due to decisions made by the investigative teams to change the antihypertensive regimen, because, in their opinion, the clinical picture required it. After adjusting for baseline characteristics, C had higher failure than A only in the standard treatment group (1.64 odds ratio [OR], 95% CI 1.06-2.56, p = .028). A sub-analysis including participants who had never used antihypertensive treatment before randomization had similar results (2.57 OR, 95% CI 1.34-5.02, p = .004). Overall, in SPRINT chlorthalidone was associated with higher monotherapy failure than amlodipine in the standard treatment group because of decisions of the investigative teams.

A Twenty-Year Analysis of Demographics, Surgical Management, and Outcomes of Aortic Stenosis in New Jersey.

We investigated the incidence and characteristics of 14,996 patients with aortic stenosis (AS) who were hospitalized in New Jersey between the years 1995 to 2015. The average age was 72, the majority were Caucasian males and common co-morbidities were hypertension, coronary artery disease and hypercholesterolemia. Hospital admission for AS declined between 1995 to 2007, to 10/100,000 patients, and increased to 15/100,000 patients in 2015 (p for trend <0.001). During the study period, the percentage of patients who received aortic valve replacement (AVR) increased (p <0.001). All-cause and cardiovascular mortality were higher among patients who did not undergo AVR at 1-year (HR 1.98 CI 1.75 to 2.23, p <0.001 and HR 1.82 CI 1.57 to 2.11, p <0.001, respectively) and 3-years (HR 2.16 CI 1.96 to 2.38, p <0.001 and HR 2.16 CI 1.90 to 2.45, p <0.001, respectively). The probability for readmission for AS was higher in patients who did not receive AVR compared to patients who had AVR at 1 year (HR 92.95 CI 57.85 to 149.35, p <0.001) and 3 years (HR 70.36 CI 47.18 to 104.95, p <0.001). These data imply that earlier diagnosis of AS and AVR when indicated will improve outcomes.

Constrictive Pericarditis after Open Heart Surgery: A 20-Year Case Controlled Study.

BACKGROUND: Constrictive pericarditis is a rare complication of open heart surgery (OHS), but little is known regarding the etiologic determinants, and prognostic factors. The purpose of this study was to investigate clinical predictors and long term prognosis of post-operative constrictive pericarditis (CP). METHODS: Using the Myocardial Infarction Data Acquisition System database, we analyzed records of 142,837 patients who were admitted for OHS in New Jersey hospitals between 1995 and 2015. Ninety-one patients were hospitalized with CP 30 days or longer after discharge from OHS. Differences in proportions were analyzed using Chi square tests. Controls were matched to cases for demographics, surgical procedure type, history of OHS, and propensity score. Cox proportional hazard models were used to evaluate the risk of all-cause death. Log-rank tests and Cox models were used to assess differences in the Kaplan-Meier survival curves with and without adjustments for comorbidities. RESULTS: Patients with CP were more likely to have history of valve disease (VD, p < 0.001), atrial fibrillation (AF, p = 0.024) renal disease (CKD, p = 0.028), hemodialysis (HD, p = 0.008), previous OHS (p < 0.001). Patients with CP compared to matched controls had a higher 7-year mortality (p < 0.001). This difference became statistically significant at 1-year after surgery. CONCLUSION: CP is a rare complication of OHS that occurs more frequently in patients with VD, AF, CKD, HD, multiple OHS, and it is associated with an unfavorable long-term prognosis. Given the large number of OHS performed every year, the results highlight the need for clinicians to recognize and properly manage this complication of OHS.

Uses and opportunities for machine learning in hypertension research.

BACKGROUND: Artificial intelligence (AI) promises to provide useful information to clinicians specializing in hypertension. Already, there are some significant AI applications on large validated data sets. METHODS AND RESULTS: This review presents the use of AI to predict clinical outcomes in big data i.e. data with high volume, variety, veracity, velocity and value. Four examples are included in this review. In the first example, deep learning and support vector machine (SVM) predicted the occurrence of cardiovascular events with 56%-57% accuracy. In the second example, in a data base of 378,256 patients, a neural network algorithm predicted the occurrence of cardiovascular events during 10 year follow up with sensitivity (68%) and specificity (71%). In the third example, a machine learning algorithm classified 1,504,437 patients on the presence or absence of hypertension with 51% sensitivity, 99% specificity and area under the curve 87%. In example four, wearable biosensors and portable devices were used in assessing a person's risk of developing hypertension using photoplethysmography to separate persons who were at risk of developing hypertension with sensitivity higher than 80% and positive predictive value higher than 90%. The results of the above studies were adjusted for demographics and the traditional risk factors for atherosclerotic disease. CONCLUSION: These examples describe the use of artificial intelligence methods in the field of hypertension.

Meta-Analysis of Usefulness of Treatment of Hypercholesterolemia With Statins for Primary Prevention in Patients Older Than 75 Years.

Clinical guidelines from the United States and Europe do not recommend treatment with statins for primary prevention in patients with hypercholesterolemia who are older than 75 years. Data from 35 randomized controlled trials in this age group where statin therapy for primary prevention was compared with placebo or usual care were analyzed. Using all-cause death as the outcome, we performed 2 types of analyses: frequentist and Bayesian. Frequentist analysis indicated no significant difference in mortality between cases (on statins) and controls (on placebo or usual care, p = 0.16). However, in the Bayesian analysis, patients >75 years had lower mortality from treatment with statins (p = 0.03). In conclusion, Bayesian analysis indicates a definite, statistically significant and clinically relevant benefit of statin treatment for primary prevention in patients >75 years of age.

Use of advanced statistical techniques to predict all-cause mortality in the Systolic Blood Pressure Intervention Trial.

BACKGROUND: The Systolic Blood Pressure Intervention Trial (SPRINT) was conducted in patients with hypertension and additional risk for cardiovascular disease who were randomized to the intensive blood pressure group targeting systolic blood pressure (SBP) less than 120 mm Hg and to the standard group where the target was less than 140 mm Hg. Analyses were done in the matched group of participants with the same gender, same age (±2 years) and same SBP (±3 mm Hg) at three months of treatment regardless of initial randomization to intensive or standard group (shaded area in Figure 1). METHODS AND RESULTS: During 3.26 years of follow-up, intensive group participants had 14.8 mm Hg lower SBP and received on average one more (2.8 vs. 1.8) blood pressure lowering medications. This was associated with lower all-cause mortality in the intensive treatment group (hazard ratio, 0.73; 95% CI, 0.60 to 0.90, p = 0.003). The effect on SBP was achieved at 3 months and remained unchanged thereafter. This paper addresses two questions with respect to all-cause mortality in SPRINT in the matched set. 1) What is the effect of receiving more than one drug on all-cause mortality. Conditional logistic regression for all-cause mortality with respect to number of drugs indicated that during the 3.26 years of follow-up persons who received more than one drug were more likely to die (coefficient = 0.5039, OR = 1.6552, p = 0.0322) than patients who received one drug. 2) Was there a U curve relationship between on treatment SBP and all-cause mortality? A U curve fitting a quadratic equation (parabola) of SBP and all-cause death was observed. This was seen in the patients randomized to the standard target group in unadjusted analyses as well as in analyses adjusted for demographics or all covariates (p < 0.001 for all). The U curves in the combined group and the intensive treatment group were less pronounced. CONCLUSION: SPRINT participants who were matched for gender, age, and SBP at 3 months, and received more than one drug had higher all-cause mortality during the 3.26 years of follow-up. Those who were randomized to standard treatment target had a U curve relationship between SBP at three months and all-cause mortality. The U curves in the combined group and the intensive treatment group were less pronounced.

Preeclamptic Women Are at Significantly Higher Risk of Future Cardiovascular Outcomes Over a 15-Year Period.

Background: Preeclampsia (PE) may lead to maternal and infant mortality and severe medical complications. Understanding future short- and long-term cardiovascular (CV) outcomes of PE is important to women's health. Materials and Methods: A retrospective matched case-control study assessed the risks of CV outcomes over a 15-year period (1999-2013) in pregnant case women, with gravidity and parity of one, diagnosed with PE, compared to pregnant primiparous control women who were not diagnosed with PE. The New Jersey Electronic Birth Certificate (EBC) database and the Myocardial Infarction Data Acquisition System (MIDAS), a database of all hospital admissions in New Jersey with longitudinal follow-up, were used to conduct the analysis. Participants were 18 years and older with demographics consistent with New Jersey, a state with a range of racial and ethnic diversity. Main outcome measures postpregnancy and over this 15-year period were myocardial infarction (MI), stroke, CV death, and all-cause death. Results: Women with PE (N = 6,360) were more likely to suffer MI, stroke, CV death, and all-cause death than controls (N = 325,347). After matching cases to controls for demographics and comorbidities, hazard ratios of PE cases for the outcomes of MI (p adjusted for comorbidities and demographics = 0.0196), CV death (adjusted p = 0.007), and all-cause death (adjusted p = 0.0026) were significantly higher than 1 compared to matched controls. Women with PE had 3.94 (95% CI: 1.25-12.4) times higher hazard for MI, 4.66 (95% CI: 1.52-14.26) times higher hazard of CV death, and 2.32 (95% CI: 1.34-4.02) times higher hazard for all-cause death than matched controls. Conclusions: This 15-year study indicates that women who have PE with their first pregnancy have a significantly higher risk of adverse CV outcomes compared to controls and suggest a heightened and continued CV monitoring after birth for this population of women.

Trends in Hospitalization for Infective Endocarditis as a Reason for Admission or a Secondary Diagnosis.

We postulate that the trends for infective endocarditis (IE) are different for patients admitted for this condition compared with those admitted for a different reason with IE as a secondary diagnosis. Using the Myocardial Infarction Data Acquisition System (MIDAS) database, we analyzed 21,443 records of patients hospitalized with diagnosis of IE from 1994 to 2015. There were 9,191 patients hospitalized with IE as the primary diagnosis, and 12,252 patients with IE as a secondary diagnosis. Piecewise linear models were used to detect changes in trends. A bootstrap method was used to assess the statistical significance of the slopes and break point of each model. Differences in co-morbidities and microbiological patterns were analyzed. Trend analysis showed a significant decrease in IE as the primary diagnosis starting in the year 2004 (p <0.01). Hospitalizations with IE as a secondary diagnosis showed a linear increase in incidence (p <0.001), without any change points. In primary diagnosis IE, the proportion of streptococci as a causative microorganism was higher compared with staphylococci (p <0.001). On the contrary, in secondary diagnosis IE, the proportion of staphylococci was higher than streptococci (p <0.001). The proportion of gram-negative and other organism IE was similar in both groups. In conclusion, this study showed 2 divergent temporal trends in hospitalizations for IE as a primary or secondary diagnosis starting in 2004. The profile of the microorganisms reveals a steady higher proportion of staphylococcal infection in secondary diagnosis IE compared with streptococcal infection. Different strategies are needed for the prevention of IE.

Effect of cholesterol lowering with statins or proprotein convertase subtilisin/kexin type 9 antibodies on cataracts: A meta-analysis.

BACKGROUND: It is not known whether statins or proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies are associated with cataract and whether very low achieved low-density lipoprotein cholesterol (LDL-C) lowering may cause cataract. OBJECTIVE: To examine two questions: whether statins and/or PCSK9 antibodies cause or prevent cataracts and whether very low LDL-C is associated with increased risk of cataract. METHODS: Systematic searches of PubMed, ClinicalTrials.gov, Web of Science, The Cochrane Library, and an Federal Drug Administration report were used to perform random effects meta-analyses on the relationship of statins and/or PCSK9 antibodies with cataract. These meta-analyses were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULTS: Prespecified analyses indicated no significant effect of statins or PCSK9 antibodies (odds ratio [OR] 0.99, 95% confidence interval [CI] 0.83-1.17, P = .8889) or differences between the effects of statins (OR 0.89, 95% CI 0.66-1.19, P = .4349) and PCSK9 antibodies (OR 1.04, 95% CI 0.85-1.28, P = .7042) on the development of cataract. Also, there was no significant effect of LDL-C lowering to different levels with respect to cataract (OR 1.06, 95% CI 0.92-1.22, P = .4317). Meta-regression of the log OR for cataract vs LDL-C during treatment did not show a statistically significant relationship (P for slope = .3972). CONCLUSION: There was no significant effect of cholesterol lowering with statins or PCSK9 antibodies or differences between these two medication classes in causing or preventing cataracts. However, it is difficult to make definitive statements regarding PCSK9 antibodies because there is no long-term experience with these agents. Very low LDL-C was not associated with higher risk of cataract.