Changing Trends of Invasive Pneumococcal Disease in the Era of Conjugate Pneumococcal Vaccination in Olmsted County: A Population-Based Study

ObjectiveTo estimate the incidence of invasive pneumococcal disease (IPD) in the pre–13-valent pneumococcal conjugate vaccine (pre-PCV13; 7-valent pneumococcal conjugate vaccine era, 2002-2010) and post-PCV13 (2011-2018) time periods.Patients and MethodsUsing the Rochester Epidemiology Project, we conducted a population-based cohort study of all IPD cases in Olmsted County, Minnesota, from January 1, 2002, to December 31, 2018.ResultsOverall, 187 cases of IPD were identified. The incidence of IPD decreased significantly from 11.1 (95% CI, 9.1 to 13.2) to 5.6 (95% CI, 4.3 to 6.9) per 100,000 person-years when the pre- and post-PCV13 periods (2002-2010 vs 2011-2018) were compared (P<.001). Of the 187 patients with IPD, 112 (59.9%) had previously received at least 1 dose of pneumococcal vaccine. Among the IPD cases in the post-PCV13 period, there was an increase in non-PCV13 serotypes, mainly 11A (from 1.0% [1 of 105] to 6.2% [4 of 64]) and 33F (from 2.9% [3 of 105] to 15.6% [10 of 64]), while PCV13/non–7-valent pneumococcal conjugate vaccine serotypes declined from 38.1% (40 of 105) to 15.6% (10 of 64). At 30 days after an IPD diagnosis, the survival rate was 88.8% (95% CI, 84.4% to 93.4%).ConclusionA marked decline in IPD incidence occurred during the post-PCV13 era. Because of the observed increase in non-PCV13 serotypes, coupled with multiple factors that impact the epidemiology of IPD, ongoing surveillance of patients with IPD, particularly due to non-PCV13 serotypes, is warranted.     

Alcohol,Tobacco and Psychotropic Drugs Use Among a Population with Chronic Pain in Southern Spain. A Cross-Sectional Study

BackgroundSubstance use seems to be higher among populations with chronic pain.AimThe aim of this study is to examine the relationship between the quantity of alcohol, tobacco, and psychotropic drugs consumed and chronic pain among women and men.MethodLinear and logistic regression analyses were carried out using data from the 2015-2016 adults’ version of the Andalusian Health Survey which is a representative cross-sectional population-based study (n = 6,569 adults aged >16 years; 50.8% women; 49.2% men).ResultsDisabling chronic pain was statistically associated with higher tobacco consumption among men (β = –30.0, 95% confidenct interval [CI] –59.5 to –0.60; t = –2.0; p < .05). Regarding alcohol, non-disabling chronic pain and a higher quantity of alcohol consumed are statistically associated for both sexes (women: β = 30.4, 95% CI 2.3-58.6; t = 2.12; p < .05 vs. men: β = 164.2, 95% CI 24.3-340.1); t = 2.30; p < .05). For women and men, both disabling chronic pain (women: odds ratio [OR] = 8.7, 95% CI 6.0-12.7); p < .05 vs. men: OR = 3.5, 95% CI 1.5-8.2); p < .05) and non-disabling chronic pain (women: OR = 3.7, 95% CI 2.0-7.0); p <.05 vs. men: OR = 4.7, 95% CI 95% CI 1.5-14.9); p < .05) were statistically significantly associated with a higher consumption of psychotropic drugs.ConclusionsChronic pain may be related to the quantity of alcohol, tobacco, and psychotropic drugs consumed, and disability appears to be one of the factors that modulates this relationship.     

Age-Related 2-Year Mortality After Transcatheter Aortic Valve Replacement: the YOUNG TAVR Registry

ObjectiveTo comparatively assess the natural history of patients of different ages undergoing transcatheter aortic valve replacement (TAVR).Patients and MethodsFor this study, we used the YOUNG TAVR, an international, multicenter registry investigating mortality trends up to 2 years in patients with aortic valve stenosis treated by TAVR, classified according to 3 prespecified age groups: 75 years or younger (n=179), 76 to 86 years (n=602), and older than 86 years (n=221). A total of 1002 patients undergoing TAVR were included. Demographic, clinical, and outcome data in the youngest group were compared with those of patients 76 to 86 years and older than 86 years. Patients were followed up for up to 2 years.ResultsCompared with patients 75 years or younger (reference group), patients aged 76 to 86 years and older than 86 years had nonsignificantly different 30-day mortality (odds ratio, 0.76; 95% CI, 0.41-1.38; P=.37 and odds ratio, 1.27; 95% CI, 0.62-2.60; P=.51, respectively) and 1-year mortality (hazard ratio (HR), 0.72; 95% CI, 0.48-1.09; P=.12 and HR, 1.11; 95% CI, 0.88-1.40; P=.34, respectively). Mortality at 2 years was significantly lower among patients aged 76 to 86 years (HR, 0.62; 95% CI, 0.42-0.90; P=.01) but not among the older group (HR, 1.06; 95% CI, 0.68-1.67; P=.79). The Society of Thoracic Surgeons 30-day mortality score was lower in younger patients who, however, had a significantly higher prevalence of chronic obstructive pulmonary disease (P=.005 vs the intermediate group and P=.02 vs the older group) and bicuspid aortic valves (P=.02 vs both older groups), larger left ventricles, and lower ejection fractions.ConclusionIn the present registry, mortality at 2 years after TAVR among patients 75 years or younger was higher compared with that of patients aged 75 to 86 years and was not markedly different from that of patients older than 86 years. The findings are attributable at least in part to a greater burden of comorbidities in the younger age group that are not entirely captured by current risk assessment tools.     

Artificial Intelligence Application in Graves Disease: Atrial Fibrillation,Heart Failure and Menstrual Changes

ObjectiveTo study the utility of artificial intelligence (AI)–enabled electrocardiograms (ECGs) in patients with Graves disease (GD) in identifying patients at high risk of atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF), and to study whether AI-ECG can reflect hormonal changes and the resulting menstrual changes in GD.Patients and MethodsPatients diagnosed with GD between January 1, 2009, and December 31, 2019, were included. We considered AF diagnosed at 30 days or fewer before or any time after GD and de novo HFrEF not explained by ischemia, valve disorder, or other cardiomyopathy at/after GD diagnosis. Electrocardiograms at/after index condition were excluded. A subset analysis included females younger than 45 years of age to study the association between ECG-derived female probability and menstrual changes (shorter, lighter, or newly irregular cycles).ResultsAmong 430 patients (mean age, 50±17 years; 337 (78.4%) female), independent risk factors for AF included ECG probability of AF (hazard ratio [HR], 1.5; 95% CI, 1.2 to 1.6 per 10%; P<.001), older age (HR, 1.05; 95% CI, 1.03 to 1.07 per year; P<.001), and overt hyperthyroidism (HR, 3.9; 95% CI, 1.2 to 12.7; P=.03). The C-statistic was 0.85 for the combined model. Among 495 patients (mean age, 52±17 years; 374 (75.6%) female), independent risk factors for HFrEF were ECG probability of low ejection fraction (HR, 1.4; 95% CI, 1.1 to 1.6 per 10%; P=.001) and presence of AF (HR, 8.3; 95% CI, 2.2 to 30.9; P=.002), and a C-statistic of 0.89 for the combined model. Lastly, of 72 females younger than 45 years, 30 had menstrual changes at time of GD and had a significantly lower AI ECG–derived female probability [median 77.3; (IQR 57.9 to 94.4)% vs. median 97.7 (IQR 92.4 to 99.5)%, P<.001].ConclusionAI-enabled ECG identifies patients at risk for GD-related AF and HFrEF and was associated with menstrual changes in women with GD.     

The prevalence and antimicrobial susceptibility of Streptococcus pneumoniae isolated from patients at Jikei University Hospitals after the implementation of the pneumococcal vaccination program in Japan

Studies have shown that pneumococcal vaccination reduces the incidence of Streptococcus pneumoniae infections but does not change the prevalence of S. pneumoniae nasopharyngeal colonization. To comprehensively and longitudinally assess the epidemiology of S. pneumoniae after the introduction of pneumococcal vaccination, we monitored the prevalence and antimicrobial susceptibility of S. pneumoniae, irrespective of its serotypes or pathogenicity, by analyzing specimens collected from a large number of patients at Jikei University Hospitals from 2009 to 2017. A total of 5763 S. pneumoniae isolates were identified out of 375,435 specimens from various sources of patients in different age groups. The prevalence of S. pneumoniae isolated only from patients <5 years old was significantly reduced with the widespread use of pneumococcal vaccines, although this reduction differed by areas where patients resided. The incidence of pneumococcal infections, including bacteremia and otitis media, clearly decreased among patients <5 years old after the introduction of pneumococcal vaccination, while the prevalence of S. pneumoniae isolated from blood specimens of patients 15–64 years old increased, suggesting the involvement of non-vaccine serotypes in the incidence of invasive pneumococcal infections. The antimicrobial susceptibility of S. pneumoniae improved after the introduction of pneumococcal vaccination. Our results show that pneumococcal vaccination has a suppressive effect on the prevalence of S. pneumoniae and the incidence of pneumococcal infections, at least for children <5 years old, in association with an improvement in the antimicrobial susceptibility of S. pneumoniae. However, further measures will be needed to control invasive pneumococcal infections caused by non-vaccine serotypes.     

An Electronic Health Record–Compatible Model to Predict Personalized Treatment Effects From the Diabetes Prevention Program: A Cross-Evidence Synthesis Approach Using Clinical Trial and Real-World Data

ObjectiveTo develop an electronic health record (EHR)-based risk tool that provides point-of-care estimates of diabetes risk to support targeting interventions to patients most likely to benefit.Patients and MethodsA risk prediction model was developed and validated in a large observational database of patients with an index visit date between January 1, 2012, and December 31, 2016, with treatment effect estimates from risk-based reanalysis of clinical trial data. The risk model development cohort included 1.1 million patients with prediabetes from the OptumLabs Data Warehouse (OLDW); the validation cohort included a distinct sample of 1.1 million patients in OLDW. The randomly assigned clinical trial cohort included 3081 people from the Diabetes Prevention Program (DPP) study.ResultsEleven variables reliably obtainable from the EHR were used to predict diabetes risk. This model validated well in the OLDW (C statistic = 0.76; observed 3-year diabetes rate was 1.8% (95% confidence interval [CI], 1.7 to 1.9) in the lowest-risk quarter and 19.6% (19.4 to 19.8) in the highest-risk quarter). In the DPP, the hazard ratio (HR) for lifestyle modification was constant across all levels of risk (HR, 0.43; 95% CI, 0.35 to 0.53), whereas the HR for metformin was highly risk dependent (HR, 1.1; 95% CI, 0.61 to 2.0 in the lowest-risk quarter vs HR, 0.45; 95% CI, 0.35 to 0.59 in the highest-risk quarter). Fifty-three percent of the benefits of population-wide dissemination of the DPP lifestyle modification and 73% of the benefits of population-wide metformin therapy can be obtained by targeting the highest-risk quarter of patients.ConclusionThe Tufts–Predictive Analytics and Comparative Effectiveness DPP Risk model is an EHR-compatible tool that might support targeted diabetes prevention to more efficiently realize the benefits of the DPP interventions.     

Pneumococcal vaccination reduces in-hospital mortality,length of stay and medical expenditure in hospitalized elderly patients

Pneumococcal vaccination has been shown to reduce occurrence of invasive pneumococcal diseases in elderly patients. In this study, we investigated the real-world efficacy of pneumococcal vaccination implemented in elderly individuals in Japan. We reviewed the in-patient database of Juntendo University Hospital and selected elderly patients (≥65 years-old) who had received in-patient care in the general medicine department during 2014–2018. A total of 1355 patients were retrospectively enrolled and comprised of 1045 unvaccinated and 315 vaccinated elderly individuals. Prior vaccination was found associated with all-cause shorter hospital stays (adjusted RR = 0.66, 95% CI = 0.57 to 0.76) and less medical expenditure (adjusted RR = 0.76, 95% CI = 0.66 to 0.87) compared with no vaccination, as well as protection for all-cause in-hospital mortality (adjusted OR = 0.42, 95% CI = 0.22 to 0.83). The association of shorter hospital stays and less medical expenditure with vaccination was also observed in the context of pneumonia, although no altered risk in mortality was observed. In conclusion, this study is one of the first reporting real-world data after the initiation of pneumococcal vaccination program in 2014 in Japan. The national PPV23 vaccination program contributed to the reduction of all-cause in-patient days, mortality, and medical expenses in the elderly aged ≥65 years. Further data is warranted to evaluate the contribution from influenza vaccination and protein-conjugate based pneumococcal vaccine.     

Physical Activity and Mortality Across Levels of Adiposity: A Prospective Cohort Study From the UK Biobank

ObjectiveTo examine the combined and stratified associations of physical activity and adiposity measures, modelled as body mass index (BMI), abdominal adiposity (waist circumference), and body fat percentage (BF) with all-cause mortality.Patients and MethodsUsing the UK Biobank cohort, we extracted quintiles of self-reported weekly physical activity. Categories of measured BMI, waist circumference, and BF were generated. Joint associations between physical activity-adiposity categories and mortality were examined using Cox proportional hazards models adjusted for demographic, behavioral, and clinical covariates. Physical activity-mortality associations were also examined within adiposity strata. Participants were followed from baseline (2006 to 2010) through January 31, 2018.ResultsA total of 295,917 participants (median follow-up, 8.9 years, during which 6684 deaths occurred) were included. High physical activity was associated with lower risk of premature mortality in all strata of adiposity except for those with BMI ≥35 kg/m². Highest risk (HR, 1.54; 95% CI; 1.33 to 1.79) was observed in individuals with low physical activity and high BF as compared with the high physical activity–low BF referent. High physical activity attenuated the risk of high adiposity when using BF (HR, 1.24; 95% CI; 1.04 to 1.49), but the association was weaker with BMI (HR, 1.45; 95% CI; 1.21 to 1.73). Physical activity also attenuated the association between mortality and high waist circumference.ConclusionLow physical activity and adiposity were both associated with a higher risk of premature mortality, but high physical activity attenuated the increased risk with adiposity irrespective of adiposity metric, except in those with a BMI ≥35 kg/m².     

What are the risk factors for recurrent UTI with repeated ESBL-producing Enterobacteriaceae? A retrospective cohort study

IntroductionA previous study has shown that two-thirds of patients with urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae experience recurrence with the same bacteria on subsequent UTI episodes. However, little is known about which patients suffer from UTI due to ESBL-producing Enterobacteriaceae repeatedly. This study aimed to investigate the risk factors for recurrent UTI due to repeated ESBL-producing organism infections.MethodsThis retrospective, single-center, observational cohort study screened all patients with UTI caused by ESBL-producing strains between January 2012 and April 2019. Among the patients who were followed up, patients who experienced UTI recurrence were enrolled and divided into two groups: ESBL recurrence group and non-ESBL recurrence group. Multivariable Cox proportional hazards regression analyses were performed to evaluate the association between patient characteristics and the development of recurrent UTI caused by ESBL-producing Enterobacteriaceae.ResultsA total of 330 patients were followed up after the diagnosis of UTI caused by ESBL-producing organisms. Among the patients, 115 (34.8%) experienced UTI recurrence, and 71 (61.7%) of them experienced subsequent recurrent UTI due to ESBL-producing organisms. Patient's age (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.00–1.04; P = 0.046) and recurrent UTI history (HR, 1.69; 95% CI, 1.05–2.72; P = 0.031) were significantly associated with an increased risk of recurrence with ESBL-producing Enterobacteriaceae.ConclusionThese findings showed that a history of previous frequent UTI recurrence is the risk factor for recurrence of UTI due to repeated ESBL producing Enterobacteriaceae infections.     

Effect of the Renin-Angiotensin System Inhibitors on Inflammatory Markers: A Systematic Review and Meta-analysis of Randomized Controlled Trials

ObjectiveTo synthesize more conclusive evidence on the anti-inflammatory effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs).MethodsPubMed, Scopus, and Embase were searched from inception until March 1, 2021. We included randomized controlled trials (RCTs) that assessed the effect of ACEIs or ARBs, compared with placebo, on any of the following markers: C-reactive protein (CRP), interleukin 6 (IL-6), or tumor necrosis factor α (TNF-α). Mean changes in the levels of these markers were pooled as a weighted mean difference (WMD) with a 95% CI.ResultsThirty-two RCTs (n=3489 patients) were included in the final analysis. Overall pooled analysis suggested that ACEIs significantly reduced plasma levels of CRP (WMD, ?0.54 [95% CI, ?0.88 to ?0.21]; P=.002; I²=96%), IL-6 (WMD, ?0.84 [95% CI, ?1.03 to ?0.64]; P<.001; I²=0%), and TNF-α (WMD, ?12.75 [95% CI, ?17.20 to ?8.29]; P<.001; I²=99%). Moreover, ARBs showed a significant reduction only in IL-6 (WMD, ?1.34 [95% CI, ?2.65 to ?0.04]; P=.04; I²=85%) and did not significantly affect CRP (P=.15) or TNF-α (P=.97) levels. The lowering effect of ACEIs on CRP levels remained significant with enalapril (P=.006) and perindopril (P=.01) as well as with a treatment duration of less than 24 weeks (WMD, -0.67 [95% CI, ?1.07 to -0.27]; P=.001; I²=94%) and in patients with coronary artery disease (WMD, ?0.75 [95% CI, ?1.17 to ?0.33]; P<.001; I²=96%).ConclusionBased on this meta-analysis, ACEIs showed a beneficial lowering effect on CRP, IL-6, and TNF-α, whereas ARBs were effective as a class in reduction of IL-6 only.     

Superiority of high sensitivity cardiac troponin T vs. I for long-term prognostic value in patients with chest pain; data from the Akershus cardiac Examination (ACE) 3 study

BackgroundCardiac troponins (cTn) are essential in the diagnostic assessment of non-ST-segment-elevation acute coronary syndrome (NSTE-ACS). Elevated concentrations of cTnT and cTnI predict cardiovascular events in non-acute settings, but the individual troponin isotype association with long-term mortality in patients with suspected unstable angina pectoris (UAP) is less clear.MethodsPatients hospitalized with chest pain between June 2009 and December 2010 were included in the Akershus Cardiac Examination 3 Study and followed for median 6.6 (IQR 6.2-7.1) years. The index diagnosis was adjudicated by an independent committee as NSTE-myocardial infarction (NSTEMI), UAP or non-ACS. Blood samples were collected within 24 h of admission and analyzed with high sensitivity assays for cTnT (hs-cTnT, Roche) and cTnI (hs-cTnI, Singulex).ResultsOf 402 patients included, 74 (18%) were classified as NSTEMI, 88 (22%) UAP and 240 (60%) non-ACS. hs-cTnI concentrations were detectable in all patients (median 3 [IQR 1–11] ng/L), while hs-cTnT concentrations were above the level of blank in 205 (51%) (median 3 [IQR 3–16] ng/L). In patients with UAP, both log₂-transformed hs-cTnT and hs-cTnI were associated with all-cause mortality in analyses that adjusted for other risk factors: HR 2.40 [95% CI 1.75–3.30], p < 0.001 and HR 1.44 [1.14–1.81], p = 0.002. There were no significant sex-dependent differences in the association between hs-cTnT or hs-cTnI and outcome. Time dependent receiver-operating characteristics area under the curve was 0.85 (95% CI 0.79–0.92) for hs-cTnT and 0.74 (0.64–0.84) for hs-cTnI, p = 0.008 for difference between values.ConclusionsHigher concentrations of hs-cTnT and hs-cTnI were both associated with all-cause mortality in patients with UAP, but the association with outcome was stronger for hs-cTnT than for hs-cTnI.     

Geographic Inequalities in Cardiovascular Mortality in the United States: 1999 to 2018

ObjectiveTo evaluate the trends in cardiovascular, ischemic heart disease (IHD), stroke, and heart failure mortality in the stroke belt in comparison with the rest of the United States.Patients and MethodsWe evaluated the nationwide mortality data of all Americans from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database from 1999 to 2018. Cause-specific deaths were identified in the stroke belt and nonstroke belt populations using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. The relative percentage gap was estimated as the absolute difference computed relative to nonstroke belt mortality. Piecewise linear regression and age-period-cohort modeling were used to assess, respectively, the trends and to forecast mortality across the 2 regions.ResultsThe cardiovascular mortality rate (per 100,000 persons) was 288.3 (95% CI, 288.0 to 288.6; 3,684,273 deaths) in the stroke belt region and 251.2 (95% CI, 251.0 to 251.3; 13,296,164 deaths) in the nonstroke belt region. In the stroke belt region, age-adjusted mortality rates due to all cardiovascular causes (average annual percentage change [AAPC] in mortality rates, ?2.4; 95% CI, ?2.8 to ?2.0), IHD (AAPC, ?3.8; 95% CI, ?4.2 to ?3.5), and stroke (AAPC, ?2.8; 95% CI, ?3.4 to ?2.1) declined from 1999 to 2018. A similar decline in cardiovascular (AAPC, ?2.5; 95% CI, ?3.0 to ?2.0), IHD (AAPC, ?4.0; 95% CI, ?4.3 to ?3.7), and stroke (AAPC, ?2.9; 95% CI, ?3.2 to ?2.2) mortality was seen in the nonstroke belt region. There was no overall change in heart failure mortality in both regions (P_AAPC>.05). The cardiovascular mortality gap was 11.8% in 1999 and 15.9% in 2018, with a modest reduction in absolute mortality rate difference (~7 deaths per 100,000 persons). These patterns were consistent across subgroups of age, sex, race, and urbanization status. An estimated 101,953 additional cardiovascular deaths need to be prevented from 2020 to 2025 in the stroke belt to ameliorate the gap between the 2 regions.ConclusionDespite the overall decline, substantial geographic disparities in cardiovascular mortality persist. Novel approaches are needed to attenuate the long-standing geographic inequalities in cardiovascular mortality in the United States, which are projected to increase.     

Daily practice and prognostic factors for pneumonia caused by methicillin-resistant Staphylococcus aureus in Japan: A multicenter prospective observational cohort study

Pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) is associated with poor clinical outcomes. We surveyed clinical outcomes of MRSA pneumonia in daily practice to identify risk factors for the clinical failure and mortality in patients with MRSA pneumonia.This multicenter prospective observational study was performed across 48 Japanese medical institutions. Adult patients with culture-positive MRSA pneumonia were recruited and treated with anti-MRSA antibiotics. The relationships between clinical and microbiological characteristics and clinical outcomes at test of cure (TOC) or 30-day all-cause mortality were analyzed.In total, 199 eligible patients, including nursing and healthcare-associated pneumonia (n = 95), hospital-acquired pneumonia (n = 76), and community-acquired pneumonia (n = 25), received initial treatment with anti-MRSA agents such as vancomycin (n = 135), linezolid (n = 36), or teicoplanin (n = 22). Overall clinical failure rate at TOC and the 30-day mortality rate were 51.1% (48/94 patients) and 33.7% (66/196 patients), respectively. Multivariable logistic regression analyses for vancomycin-treated populations revealed that abnormal white blood cell count (odds ratio [OR] 4.34, 95% confidence interval [CI] 1.31–14.39) was a risk factor for clinical failure and that no therapeutic drug monitoring (OR 3.10, 95% CI 1.35–7.12) and abnormally high C-reactive protein level (OR 3.54, 95% CI 1.26–9.92) were risk factors for mortality.In conclusion, this study provides evidence that majority of MRSA pneumonia patients are initially treated with vancomycin in Japan, and the absence of therapeutic drug monitoring for vancomycin is significantly associated with the mortality in patients with MRSA pneumonia.     

Tricuspid Regurgitation Impact on Outcomes (TRIO): A Simple Clinical Risk Score

ObjectiveTo determine which clinical variables infer the highest risk for mortality in patients with notable tricuspid regurgitation (TR) and to develop a clinical assessment tool (the Tricuspid Regurgitation Impact on Outcomes [TRIO] score).Patients and MethodsA single-center retrospective cohort of 13,608 patients with undifferentiated moderate to severe TR at the time of index echocardiography between January 1, 2005, and December 31, 2016, was included. Baseline demographic and clinical data were obtained. Patients were randomly assigned to a training (N=10,205) and a validation (N=3403) cohort. Median follow-up was 6.5 years (interquartile range, 0.8 to 11.0 years). Variables associated with mortality were identified by Cox proportional hazards methods. A geographically distinct cohort of 7138 patients was used for further validation. The primary end point was all-cause mortality over 10 years.ResultsThe 5-year probability of death was 53% for moderate TR, 63% for moderate-severe TR (hazard ratio [HR], 1.24 [95% CI, 1.17 to 1.31]; P<.001 vs moderate), and 71% for severe TR (HR, 1.55 [95% CI, 1.47 to 1.64]; P<.001 vs moderate). Factors associated with all-cause mortality on multivariate analysis included age 70 years or older, male sex, creatinine level greater than 2 mg/dL, congestive heart failure, chronic lung disease, aspartate aminotransferase level of 40 U/L or greater, heart rate of 90 beats/min or greater, and severe TR. Variables were assigned 1 or 2 points (HR, >1.5) and added to compute the TRIO score. The score was associated with all-cause mortality (C statistic = 0.67) and was able to separate patients into risk categories. Findings were similar in the second, independent and geographically distinct cohort.ConclusionThe TRIO score is a simple clinical tool for risk assessment in patients with notable TR. Future prospective studies to validate its use are warranted.     

Drastic reduction in pneumococcal meningitis in children owing to the introduction of pneumococcal conjugate vaccines: Longitudinal analysis from 2002 to 2016 in Japan

IntroductionThe characteristics of pneumococcal isolates and their associations with outcomes in pediatric meningitis are unclear. This study aimed to clarify serotypes and resistance genotypes of Streptococcus pneumoniae from children with meningitis and evaluate the patient prognoses and backgrounds.MethodsLarge-scale surveillance was conducted from 2002 to 2016 through periods I–V. Serotypes and penicillin (PEN) resistance genotypes were analyzed for pneumococcal isolates (n = 459) and cerebrospinal fluid (CSF) samples (n = 25). Furthermore, underlying diseases (n = 251), prognoses (n = 202), and laboratory data were evaluated.ResultsThe number of meningitis cases decreased drastically after the introduction of 7-valent pneumococcal conjugate vaccine (PCV7) to ?53.6% and after switching to PCV13 to ?70.2%. In particular, this reduction was apparent at ≤3 years of age. The proportion of the PCV7 serotype decreased sharply from 70.1% before introduction to 2.6% during period V; however, the non-vaccine type increased from 17.5% to 87.2%. The PEN resistance rate (gPRSP) was decreased from approximately 49% to 12.2% during period V. Among cases revealed prognosis, sequelae and mortality rates were 16.3% and 5.4%, respectively. The rate of the patients with underlying diseases was 26.3% and relatively high in ≥6 years. Laboratory data associated with a poor prognosis were low white blood cell count (<12.7 × 10³/μL), low platelet count (<28.1 × 10⁴/μL), low CSF-glucose (<36 mg/dL), and high CSF-protein (≥142 mg/dL).ConclusionsChanges in serotype prevalence warrant continuous monitoring to observe future trends of pneumococcal meningitis, and further developments in multivalent conjugate vaccines are required.     

Fitness and Mortality Among Persons 70 Years and Older Across the Spectrum of Cardiovascular Disease Risk Factor Burden: The FIT Project

ObjectiveTo determine whether fitness could improve mortality risk stratification among older adults compared with cardiovascular disease (CVD) risk factors.MethodsWe examined 6509 patients 70 years of age and older without CVD from the Henry Ford ExercIse Testing Project (FIT Project) cohort. Patients performed a physician-referred treadmill stress test between 1991 and 2009. Traditional categorical CVD risk factors (hypertension, hyperlipidemia, diabetes, and smoking) were summed from 0 to 3 or more. Fitness was grouped as low, moderate, and high (<6, 6 to 9.9, and ≥10 metabolic equivalents of task). All-cause mortality was ascertained through US Social Security Death Master files. We calculated age-adjusted mortality rates, multivariable adjusted Cox proportional hazards, and Kaplan-Meier survival models.ResultsPatients had a mean age of 75±4 years, and 3385 (52%) were women; during a mean follow-up of 9.4 years, there were 2526 deaths. A higher fitness level (P<.001), not lower CVD risk factor burden (P=.31), was associated with longer survival. The age-adjusted mortality rate per 1000 person-years was 56.7 for patients with low fitness and 0 risk factors compared with 24.9 for high fitness and 3 or more risk factors. Among patients with 3 or more risk factors, the adjusted mortality hazard was 0.68 (95% CI, 0.61 to 0.76) for moderate and 0.51 (95% CI, 0.44 to 0.60) for high fitness compared with the least fit.ConclusionAmong persons aged 70 years and older, there was no significant difference in survival of patients with 0 vs 3 or more risk factors, but a higher fitness level identified older persons with good long-term survival regardless of CVD risk factor burden.     

Usefulness of β-lactam and macrolide combination therapy for treating community-acquired pneumonia patients hospitalized in the intensive care unit: Propensity score analysis of a prospective cohort study

IntroductionWhether β-lactam and macrolide combination therapy reduces mortality in severe community-acquired pneumonia (SCAP) patients hospitalized in the intensive care unit (ICU) is controversial. The aim of the present study was to evaluate the usefulness of β-lactam and macrolide combination therapy for SCAP patients hospitalized in the ICU.MethodsA prospective, observational, cohort study of hospitalized pneumonia patients was performed. Hospitalized SCAP patients admitted to the ICU within 24 h between October 2010 and October 2017 were included for analysis. The primary outcome was 30-day mortality, and secondary outcomes were 14-day mortality and ICU mortality. Inverse probability of treatment weighting (IPTW) analysis as a propensity score analysis was used to reduce biases, including six covariates: age, sex, C-reactive protein, albumin, Pneumonia Severity Index score, and APACHE II score.ResultsA total of 78 patients were included, with 48 patients in the non-macrolide-containing β-lactam therapy group and 30 patients in the macrolide combination therapy group. β-lactam and macrolide combination therapy significantly decreased 30-day mortality (16.7% vs. 43.8%; P = 0.015) and 14-day mortality (6.7% vs. 31.3%; P = 0.020), but not ICU mortality (10% vs 27.1%, P = 0.08) compared with non-macrolide-containing β-lactam therapy. After adjusting by IPTW, macrolide combination therapy also decreased 30-day mortality (odds ratio, 0.29; 95%CI, 0.09–0.96; P = 0.04) and 14-day mortality (odds ratio, 0.19; 95%CI, 0.04–0.92; P = 0.04), but not ICU mortality (odds ratio, 0.34; 95%CI, 0.08–1.36; P = 0.13).ConclusionsCombination therapy with β-lactam and macrolides significantly improved the prognosis of SCAP patients hospitalized in the ICU compared with a non-macrolide-containing β-lactam regimen.     

Investigation of the incidence of immunisation stress-related response following COVID-19 vaccination in healthcare workers

IntroductionSafe vaccination worldwide is critical to end the coronavirus disease 2019 (COVID-19) pandemic. We aimed to evaluate adverse reactions to vaccination using a web-based questionnaire and examine the risk factors for the occurrence of immunisation stress-related response (ISRR).MethodsWe conducted a questionnaire survey using Google Form® among the employees of St. Marianna University Hospital who had received the COVID-19 vaccine between April 2021 and May 2021, 1 week after the first and second vaccinations. We developed and used a questionnaire to identify individuals with ISRR according to the World Health Organization diagnostic criteria. A generalised linear mixed model was constructed with ISRR onset as the dependent variable, subjects as the random factor, and each parameter as a fixed factor. A multivariate model was constructed using the forced imputation method with factors that were significant in the univariate analysis.ResultsWe enrolled 2,073 and 1,856 respondents in the first and second questionnaire surveys, respectively. Fifty-five and 33 ISRR cases were identified in the first and second vaccinations, respectively. In the univariate analysis, strong pre-vaccination anxiety (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.30–4.12, p = 0·004) and history of allergy (OR, 1.6; 95% CI, 1.14–2.24, p = 0·007) were significant risk factors. Multivariate analysis also showed that strong pre-vaccination anxiety (OR, 2.1; 95% CI, 1.15–3.80, p = 0.016) and history of allergy (OR, 1.5; 95% CI, 1.09–2.15, p = 0.014) were significant risk factors.ConclusionsConfirmation of allergy prior to vaccination and subsequent action are essential for addressing ISRR.     

Physical Activity,Cardiorespiratory Fitness,and Population-Attributable Risk

ObjectiveTo determine population-attributable risk (PAR) and exposure impact number (EIN) for mortality associated with impaired cardiorespiratory fitness (CRF), physical inactivity, and other risk markers among veteran subjects.MethodsThe sample included 5890 male subjects (mean age 58±15) who underwent a maximal exercise test for clinical reasons between January 1, 1992, and December 31, 2014. All-cause mortality was the end point. Cox multivariable hazard models were performed to determine clinical, demographic, and exercise-test determinants of mortality. Population-attributable risks and EIN for the lowest quartile of CRF and for inactive behavior were analyzed, accounting for competing events.ResultsThere were 2728 deaths during a mean ± standard deviation follow-up period of 9.9±5.8 years. Having low CRF (<5.0 metabolic equivalents [METs]) was associated with an approximate 3-fold higher risk of mortality and a PAR of 12.9%. Each higher MET achieved on the treadmill was associated with a 15% reduction in mortality (hazard ratio [HR]=0.85; 95% confidence interval [CI], 0.83 to 0.88; P<.001). Nearly half the sample was inactive, and these subjects had a 23% higher mortality risk and a PAR of 8.8%. The least fit quartile (<5.0 METs) had relative risks of ≈6.0 compared with the most-fit group (HR=5.99; 95% CI, 4.9 to 7.3). The least-active tertile had ≈2-fold higher risks of mortality vs the most active subjects (HR=1.9; 95% CI, 0.91 to 4.1). The lowest EIN was observed for low fitness (3.8; 95% CI, 3.4 to 4.3, P<.001), followed by diabetes, smoking, hypertension, and physical inactivity (all P<.001 except for diabetes, P=.008).ConclusionBoth higher CRF and physical activity provide protection against all-cause mortality in subjects referred for exercise testing for clinical reasons. Encouraging physical activity with the aim of increasing CRF would have a significant impact on reducing mortality.