Contradictory mortality results in early 2-dose measles vaccine trials: Interactions with oral polio vaccine may explain differences.

OBJECTIVES: Between 2003-2019, three trials (RCTs) in Guinea-Bissau randomised infants to an early 2-dose measles vaccine (MV) schedule at 4 and 9 months vs. standard MV at 9 months. The RCTs produced contradictory mortality results; the effect being beneficial in the 2-dose group in the first but tending to have higher mortality in the last two RCTs. We hypothesised that increased frequency of campaigns with oral polio vaccine (C-OPV) explained the pattern. METHODS: We performed per-protocol analysis of individual-level survival data from the three RCTs in Cox proportional hazards models yielding hazards ratios (HR) for the 2-dose vs. the 1-dose MV group. We examined whether timing of C-OPVs, and early administration of OPV0 (birth to day 14) affected the HRs for 2-dose/1-dose MV. RESULTS: The combined HR(2-dose/1-dose) was 0.79 (95% confidence interval: 0.62-1.00) for children receiving no C-OPV-before-enrolment, but 1.39 (0.97-1.99) for those receiving C-OPV-before-enrolment (homogeneity, p=0.01). C-OPV-before-enrolment had a beneficial effect in the 1-dose group, but tended to have a negative effect in the 2-dose group especially in females. These effects were amplified further by early administration of OPV0. CONCLUSIONS: In the absence of C-OPVs, an early 2-dose MV strategy had beneficial effects on mortality, but frequent C-OPVs may have benefitted the 1-dose group more than the 2-dose MV group, leading to varying results depending on the intensity of C-OPVs.

Effect of early two-dose measles vaccination on childhood mortality and modification by maternal measles antibody in Guinea-Bissau, West Africa: A single-centre open-label randomised controlled trial.

Background: Early 2-dose measles vaccine (MV) at 4 and 9 months of age vs. the WHO strategy of MV at 9 months of age reduced all-cause child mortality in a previous trial. We aimed to test two hypotheses: 1) a 2-dose strategy reduces child mortality between 4 and 60 months of age by 30%; 2) receiving early MV at 4 months in the presence versus absence of maternal measles antibodies (MatAb) reduces child mortality by 35%. Methods: Single-centre open-label community-based randomised controlled trial in Guinea-Bissau, with 2:1 block-randomisation by sex to a 2-dose (4 + 9 months) vs. 1-dose (9 months) MV strategy. Healthy children were eligible 4 weeks after the 3rd diphtheria-tetanus-pertussis-containing vaccine. Before randomisation a blood sample was collected to determine MatAb level. The primary outcome was all-cause mortality. Hazard ratios (HR) were derived from Cox regression in the per protocol population. We tested for interactions with national campaigns with oral polio vaccine (C-OPV). Trial registration: NCT01486355. Findings: Between August 2011-April 17th 2015, 6,636 children were enroled, 6,598[n2-dose=4,397; n1-dose=2,201] were included in the analysis of the primary outcome, The HR(2-dose/1-dose) between 4 and 60 months was 1.38 (95%CI: 0.92-2.06) [deaths: n2-dose=90; n1-dose=33]. Before the 9-month MV and the HR(1-dose/no dose) was 0.94 (0.45-1.96) [deaths: n2-dose=21; n1-dose=11]. The HR(2-dose/1-dose) was 0.81 (0.29-2.22) for children, who received no C-OPV [deaths/children: n2-dose=10/2,801; n1-dose=6/1,365], and 4.73 (1.44-15.6) for children, who received C-OPV before and after enrolment (p for interaction=0.027) [deaths/children: n2-dose=27/1,602; n1-dose=3/837]. In the 2-dose group receiving early MV at 4 months, mortality was 50% (20-68%) lower for those vaccinated in the presence of MatAb vs. the absence of MatAb [deaths/children: nMatAb=51/3,132; nnoMatAb=31/1,028]. Interpretation: The main result contrasts with previous findings but may, though based on a small number of events, be explained by frequent OPV campaigns that reduced the mortality rate, but apparently interacted negatively with early MV. The beneficial non-specific effects of MV in the presence of MatAb should be investigated further. Funding: ERC, Danish National Research Foundation, the Danish Council for Development Research, Ministry of Foreign Affairs, Novo Nordisk Foundation, European Union and the Lundbeck Foundation.

Regional longitudinal strain patterns according to left ventricular hypertrophy in the general population.

AIMS: A pattern of reduced basal longitudinal strain (BLS) is often observed with left ventricular (LV) hypertrophy (LVH). Whether this pattern is associated with poor outcome is unclear. We aimed to evaluate the prognostic value of regional longitudinal strain according to LV geometry. METHODS AND RESULTS: We investigated participants in the 4th Copenhagen City Heart Study who had an echocardiogram with speckle tracking performed. Participants were stratified according to the presence of LVH (LV mass index ≥116 g/m2 for men and ≥96 g/m2 for women). The outcome was major adverse cardiovascular events (MACE) defined as a composite of myocardial infarction, heart failure, and/or cardiovascular death. The study population consisted of 1090 participants. Mean LVEF was 60% and 160 (15%) had LVH. During a median follow-up of 14.7 years, there were 137 events. Both BLS and midventricular strain, but not apical strain, became incrementally impaired in the spectrum from normal to hypertensives subjects without LVH, and to participants with hypertension and LVH. After multivariable adjustment, BLS and midventricular strain were independently associated with MACE in participants with LVH (BLS: HR 1.08, 95% CI 1.00-1.17, P = 0.041; midventricular strain: HR 1.10, 95% CI 1.00-1.21, P = 0.041) but not in participants without LVH (BLS: HR 0.96, 95% CI 0.90-1.01, P = 0.13; midventricular strain: HR 0.97, 95% CI 0.91-1.03, P = 0.36). CONCLUSION: BLS and midventricular strain, but not apical strain, become incrementally impaired in the spectrum from normal geometry to LVH, and are independently associated with MACE in participants with LVH.

Usefulness of left atrial strain for predicting incident atrial fibrillation and ischaemic stroke in the general population.

AIMS: Left atrial enlargement predicts incident atrial fibrillation (AF). However, the prognostic value of peak atrial longitudinal strain (PALS) for predicting incident AF in participants from the general population is currently unknown. Our aim was to investigate if PALS can be used to predict AF and ischaemic stroke in the general population. METHODS AND RESULTS: A total of 400 participants from the general population underwent a health examination, including two-dimensional speckle tracking echocardiography of the left atrium. The primary endpoint was incident AF at follow-up. All participants with known AF and prior stroke at baseline were excluded (n = 54). The secondary endpoint consisted of the composite of AF and ischaemic stroke. During a median follow-up of 16 years, 36 participants (9%) were diagnosed with incident AF and 30 (7%) experienced an ischaemic stroke, resulting in 66 (16%) experiencing the composite outcome. PALS was a univariable predictor of AF [per 5% decrease: hazard ratio (HR) 1.42; 95% confidence interval (CI) (1.19-1.69), P < 0.001]. However, the prognostic value of PALS was modified by age (P = 0.002 for interaction). After multivariable adjustment PALS predicted AF in participants aged <65 years [per 5% decrease: HR 1.46; 95% CI (1.06-2.02), P = 0.021]. In contrast, PALS did not predict AF in participants aged ≥65 years after multivariable adjustment [per 5% decrease: HR 1.05; 95% CI (0.81-1.35), P = 0.72]. PALS also predicted the secondary endpoint in participants aged <65 years and the association remained significant after multivariable adjustment. CONCLUSION: In a low-risk general population, PALS provides novel prognostic information on the long-term risk of AF and ischaemic stroke in participants aged <65 years.

Global longitudinal strain predicts atrial fibrillation in individuals without hypertension: A Community-based cohort study.

BACKGROUND: Global longitudinal strain (GLS) is a sensitive marker of myocardial dysfunction and atrial reservoir function. We sought to evaluate its value for predicting atrial fibrillation (AF) in the general population. METHODS: Participants from the Copenhagen City Heart Study examined with echocardiography, including speckle tracking analyses, were included. The endpoint was AF obtained through national registries. Proportional hazards Cox regression was applied, including multivariable adjustments made for CHADS2 and CHARGE-AF risk factors. Abnormal GLS was defined as >-18%. RESULTS: The data from 1,309 participants were analyzed. Of those, 153 (12%) developed AF during a median follow-up time of 15.9 years. The follow-up was 100%. The mean age was 57 years, 38% had hypertension, and GLS was  - 18%. In unadjusted analysis, GLS was a univariable predictor of outcome (1.08 (1.04-1.13), p < 0.001, per 1% absolute decrease), but did not remain an independent predictor after adjusting for neither CHADS2 nor CHARGE-AF risk factors. However, hypertension modified the relationship between GLS and AF (p for interaction = 0.010), such that GLS only predicted AF in subjects without hypertension. In participants without hypertension, GLS remained an independent predictor of AF after adjusting for CHADS2 and CHARGE-AF (HR = 1.11 (1.03-1.20) and HR = 1.09 (1.01-1.19), respectively). In these participants, an abnormal GLS was associated with a more than twofold increased risk of AF (HR = 2.16 (1.26-3.72). The incidence rate was 3.17 and 6.81 per 1000 person-years for normal vs. abnormal GLS, respectively. CONCLUSION: Global longitudinal strain predicts AF in individuals without hypertension from the general population, independently of common risk scores.

Neonatal Bacille Calmette-Guérin vaccination and tuberculin skin test reactions at 2- and 6-months: Effects on mortality up to 1 year of age.

BACKGROUND: In randomized trials, Bacille Calmette-Guérin (BCG) vaccine has been associated with reduced all-cause mortality. BCG-induced Tuberculin Skin Test (TST) reactions have also been associated with reduced all-cause mortality. We aimed to assess the association between TST responses and subsequent mortality in three birth cohorts and conducted a meta-analysis of existing studies. METHODS: Observational study within three Guinea-Bissau BCG trial birth cohorts (conducted 2002-04, 2009-2013 and 2014-18) that encompassed children who were BCG-vaccinated within 28 days with TSTs performed at 2- (n = 1389) and 6-months (n = 2635) of age. We evaluated TST reaction determinants by binomial regression and assessed the association between TSTs > 1 mm (reactors) vs. ≤ 1 mm (non-reactors) and subsequent mortality risk up to age 12 months in Cox-models providing Mortality Rate Ratios (MRRs). We searched PubMed for studies to calculate meta-estimates of the association between TST reactivity by age 2- and 6-months and all-cause mortality. RESULTS: Large post-vaccination wheal size was associated with 6-month TST positivity and so was receiving BCG-Denmark or BCG-Japan, compared with BCG-Russia. By age 2 months, 22% (302/1389) of infants were TST reactors with a 2-12-month mortality risk of 1.7% (5/302) vs. 3.3% (36/1087) for non-reactors, the corresponding reactor/non-reactor MRR = 0.49 (0.19-1.26). By age 6 months, 44% (1149/2635) of infants were reactors and the 6-12-month mortality risk was 0.4% (4/1149) vs. 0.6% (9/1486) for non-reactors, the MRR = 0.87 (0.27-2.86). The literature search provided 3 studies. The meta-analysis revealed a uniform pattern of reduced mortality associated with TST reactivity, a TST response by 2 months being associated with an MRR of 0.59 (0.39-0.90); for 6-month TST responses the MRR was 0.65 (0.43-1.00). CONCLUSION: Among BCG-vaccinated infants, TST reactions were associated with markedly reduced mortality. Improved vaccination technique and using certain BCG strains could lead to a higher TST reaction prevalence, which would enhance BCG's beneficial non-specific effects.

Diastolic function assessed with speckle tracking over a decade and its prognostic value: The Copenhagen City Heart Study.

BACKGROUND: The ratio of transmitral early filling velocity to early diastolic strain rate (E/e'sr) may be a more accurate measure of LV filling pressure then ratio of early filling pressure to early tissue velocity. The aim of the study was to investigate the impact of age, sex, obesity, smoking, hypertension, hypercholesterolemia, diabetes, physical activity level, socioeconomic, and psychosocial status on E/e'sr over a decade. Additionally, the predictive value of ΔE/e'sr on future major adverse cardiovascular events (MACE) has never been explored. METHOD: The study included 623 participants from the general population, who participated in the 4th and 5th Copenhagen City Heart Study (CCHS4 and CCHS5). Examinations were median 10 years apart. MACE was the composite endpoint of heart failure, myocardial infarction, and all-cause death. RESULTS: Follow-up time was median 5.7 years, and 43 (7%) experienced MACE. Mean age was 51 ± 14 years, and 43% were male. Mean ΔE/e'sr was 2.1 ± 23.0 cm. After multivariable adjustment for demographic, clinical, and biochemistry variables, high age (stand. ß-coef. = .24, P < .001) and mean arterial blood pressure (MAP) (stand. ß-coef. = .17, P < .001) were significantly associated with an accelerated increase in E/e'sr In multivariable Cox regression, E/e'sr at CCHS5 and ΔE/e'sr were independent predictors of MACE (HR = 1.20, 95% CI [1.01; 1.42] per 10 cm increase for both). ΔE/e'sr did only provide incremental prognostic value to change in left atrial volume index of the conventional diastolic measurements. CONCLUSION: In the general population, age and MAP were predictors of an accelerated increase in E/e'sr over a decade. E/e'sr at CCHS5 and ΔE/e'sr were independent predictors of future MACE.

The prognostic value of left atrial dyssynchrony measured by speckle tracking echocardiography in the general population.

LA dyssynchrony is a predictor of cardiovascular morbidity in various patient populations. However, the prognostic value of LA dyssynchrony as evaluated by two-dimensional speckle tracking (2D-STE) in the general population is unknown. A cohort of 375 participants without atrial fibrillation (AF), ischemic heart disease (IHD), heart failure (HF) or previous ischemic stroke (IS) had an echocardiogram, including LA 2D-STE, performed. LA dyssynchrony was defined as the standard deviation of the time to peak regional LA reservoir strain values. The endpoints were all-cause mortality, a combined endpoint of AF and IS, and a combined endpoint of major adverse cardiovascular events (MACE) comprised of acute myocardial infarction (AMI), HF or cardiovascular death (CVD). During a median follow up of 16.1 years (IQR 15.0-16.3 years), 83 (22%) participants died, 60 (15%) reached the composite endpoint of AF and IS, and 38 (10%) reached the composite MACE endpoint. LA dyssynchrony was a univariable predictor of all-cause mortality (HR 1.07, 95% CI 1.02-1.11, p = 0.001) but was not significantly associated with the combined endpoint of AF and IS (HR 1.05, p = 0.064) nor MACE (HR 1.04, p = 0.22). However, when adjusted for age, LA dyssynchrony did not predict all-cause mortality (HR 1.03, p = 0.28). Similarly, after further adjustments for clinical and echocardiographic parameters LA dyssynchrony did not predict any of the study outcomes. In this general population study, LA dyssynchrony was not an independent predictor of all-cause mortality and did not predict MACE nor a composite outcome consisting of AF and IS.

Penta is associated with an increased female-male mortality ratio: cohort study from Bangladesh.

Diphtheria-tetanus-pertussis (DTP) vaccine may be associated with excess female deaths. There are few studies of possible nonspecific effects of the DTP-containing vaccine Penta (DTP-hepatitis B-Haemophilus influenzae type b). We therefore investigated whether Penta vaccinations were associated with excess female deaths in rural Bangladesh. Between June 29, 2011 and April 20, 2016, we examined the mortality rates of 7644 children followed between 6 weeks and 9 months of age. We analyzed mortality using crude mortality rate ratio (MRR) and age-adjusted MRR (aMRR) from a Cox proportional hazards model. Mortality was analyzed according to sex, number of doses of Penta, and the order in which BCG and Penta were administered. During follow-up, 43 children died. For children who were only BCG vaccinated (BCG-only), the adjusted F/M MRR was 0.47 (0.09-2.48). However, among children who had Penta as their most recent vaccination, the adjusted F/M MRR was 9.91 (1.16-84.44). Hence, the adjusted F/M MRR differed significantly for BCG-only and for Penta as the most recent administered vaccination. Although the mortality rate was low in rural Bangladesh, there was a marked difference between adjusted F/M MRR's for children vaccinated with BCG-only compared with children where Penta was the most recent administered vaccination. Although usually ascribed to differential treatment and access to care, DTP-containing vaccines may be part of the explanation for the excessive female mortality reported in some regions.

The impact of cardiovascular risk factors on global longitudinal strain over a decade in the general population: the copenhagen city heart study.

Global longitudinal strain (GLS) declines throughout adult-life as the LV remodels and adapts. Information on the impact of cardiac risk factors such as male sex, obesity, smoking status, hypertension, hypercholesterolemia, and diabetes on GLS. over time has not yet been investigated. The present prospective longitudinal study included 689 participants of the 4th and 5th Copenhagen City Heart Study who had GLS measured at both timepoints. Mean age was 51 years and 45% were male. All participants underwent two echocardiographic examinations median 10.4 (IQR: 10.2, 10.9) years apart. Average decline in GLS during follow-up was -0.7%. High age, male sex, high body mass index, and mean arterial blood pressure (MAP) proved to be significantly associated with an accelerated decline in GLS. In a multivariable regression model including all the investigated cardiovascular risk factors, age (stand. ß-coef. = -0.10, P = 0.005), male sex (stand. ß-coef. = -0.16, P < 0.001), and MAP (stand. ß-coef. = -0.07, P = 0.009) were independent predictors of an accelerated decline in GLS during a 10-year period. Finally, the investigated risk factors had different regional impact after the same multivariable adjustments. Male sex had a significant impact on changes in longitudinal strain at the apical, mid-wall and basal segments, meanwhile MAP and age only accelerated changes in the mid-wall and basal longitudinal strain. In the general population age, male sex, and MAP are independent predictors of an accelerated decline in GLS over a 10-year period. Furthermore, MAP, male sex and age had different regional impact.

Seasonal variation in the non-specific effects of BCG vaccination on neonatal mortality: three randomised controlled trials in Guinea-Bissau.

The BCG vaccine protects non-specifically against other diseases than tuberculosis. Three randomised controlled trials of early BCG in Guinea-Bissau found a 38% reduction in all-cause neonatal mortality. Little is known about the underlying mechanisms. In Guinea-Bissau, prevalent infectious diseases display distinct seasonality. Revisiting the three trials (>6500 infants) comparing early BCG versus no early BCG in low weight infants on all-cause neonatal mortality over 12 consecutive years, we explored the seasonal variation in BCG's effect on mortality. In a subgroup of participants, adaptive and innate cytokine responses were measured 4 weeks after randomisation. Consistently over the course of the three trials and 12 years, the effect of BCG on all-cause neonatal mortality was particularly beneficial when administered in November to January, coincident with peaking malaria infections. During these months, BCG was also associated with stronger proinflammatory responses to heterologous challenge. Recent studies have suggested a protective effect of BCG against malaria. BCG may also ameliorate immune-compromising fatal effects of placental malaria in the newborn.

Duration of early systolic lengthening: prognostic potential in the general population.

BACKGROUND: When the left ventricle pressure rises during early systole, myocardial fibres with reduced contractility tend to stretch instead of shortening. This interval is known as duration of early systolic lengthening (DESL). We sought to investigate if DESL provides prognostic information on cardiovascular events. METHODS AND RESULTS: In this prospective study we included 1210 participants from a low-risk general population who underwent speckle tracking echocardiography (men 41%, mean age 56 years, SD 16). Primary endpoints were incident heart failure (HF), myocardial infarction (MI), and cardiovascular death (CVD). We defined DESL as time from onset of Q-wave on the electrocardiogram to peak positive systolic strain. In addition, we assessed the ratio between DESL and duration of cardiac systole, DESLsystole.During median follow-up of 16 years, 90 (7%) developed HF, 50 (4%) MI, and 70 (6%) experienced CVD. Both DESL [hazard ratio (HR) 1.58 95%CI 1.16-2.15, P = 0.004 per 10 ms increase] and DESLsystole (HR 1.74 95%CI 1.24-2.47, P = 0.001 per 1% increase) were predictors of HF. Similarly, DESL (HR 1.40 95%CI 1.09-1.78, P = 0.007 per 10 ms increase) and DESLsystole (HR 1.58 95%CI 1.01-2.49, P = 0.047 per 1% increase) were predictors of MI. No associations were found with CVD. After adjusting for clinical and echocardiographic parameters, the associations remained significant. DESLsystole was superior to systolic echocardiographic parameters for predicting HF (P = 0.012). CONCLUSION: DESL and the novel index of DESLsystole provide independent and novel prognostic information on the risk of HF and MI in the general population. Evaluation of DESL should be explored in future echocardiographic studies.

Ratio of transmitral early filling velocity to early diastolic strain rate predicts long-term risk of cardiovascular morbidity and mortality in the general population.

Aims: It has previously been demonstrated that the ratio of early mitral inflow velocity to global diastolic strain rate (E/e'sr) is a significant predictor of cardiac events in specific patient populations. The utility of this measurement to predict cardiovascular events in a general population has not been evaluated. Methods and results: A total of 1238 participants in a general population study underwent a health examination including echocardiography where global longitudinal strain (GLS) and E/e'sr were determined. The primary endpoint was the composite of incident heart failure (HF), acute myocardial infarction (AMI) or cardiovascular death (CVD). During follow-up (median 11 years), 140 (11.3%) participants reached the composite endpoint. E/e'sr was associated with adverse outcome [HR 1.17 95% CI (1.13-1.21); P < 0.001, per 10 cm increase]. After multivariable adjustment for echocardiographic and clinical parameters, E/e'sr remained an independent predictor of the composite endpoint [HR 1.08, 95% CI (1.02-1.13); P = 0.003] as opposed to E/e' [HR 1.03, 95% CI (0.99-1.06); P = 0.11 per 1 unit increase]. Global longitudinal strain modified the relationship between E/e'sr and outcome (P for interaction = 0.015). E/e'sr was a stronger predictor in participants with good systolic function as determined by GLS (GLS > 18%) after multivariable adjustment, when compared to participants with reduced systolic function (GLS < 18%) [HR 1.28 95% CI (1.06-1.54); P = 0.011, and HR 1.08 95% CI (1.02-1.14); P = 0.012, respectively). E/e'sr provided incremental information [Harrell's C-index: 0.839 (0.81-0.87) vs. 0.844 (0.82-0.87); P = 0.045] beyond the SCORE risk chart. Conclusion: In the general population, E/e'sr provides independent and incremental prognostic information regarding cardiovascular morbidity and mortality. Additionally, E/e'sr is a stronger predictor of cardiac events than E/e'.

Post-systolic shortening: normal values and association with validated echocardiographic and invasive measures of cardiac function.

Post-systolic shortening (PSS) does not contribute to the ejection of blood and may inhibit diastolic filling. We determined normal values of PSS in healthy subjects and investigated associations with echocardiographic and invasive measures of systolic and diastolic function. We prospectively analyzed participants from the general population (n = 620, mean age 47 ± 14 years) with no cardiovascular disease. Participants underwent echocardiography, including speckle tracking assessment of the post-systolic index (PSI), strain and time. We defined the PSI as: 100 × [(peak global longitudinal strain - peak systolic longitudinal strain)/(peak global longitudinal strain)]. We also included stable patients (n = 44) referred for left ventricle (LV) catheterization and echocardiography. Normal values: median PSI 2.0% (IQR 0.7, 4.8), post-systolic strain 0.4% (IQR 0.2, 0.8) and post-systolic time 22.6 ms (IQR 10.7, 40.8). Sex modified the relationship between PSI and age (P interaction = 0.037), such that PSI increased with age in women but not in men. PSI was associated with diastolic function (e', E/e' and E/A) (P < 0.05 for all), but not with LV ejection fraction (P = 0.08). PSI was associated with invasively measured LV pressure decline in early diastole, dP/dt min ([Formula: see text] = 0.12, P = 0.010), but not with LV pressure rise in early systole, dP/dt max ([Formula: see text]= - 0.05, P = 0.30). A PSI > 5% had 82% specificity and 99% sensitivity for identifying impaired LV systolic and/or diastolic function. Normal values of PSS are modified by sex. The PSI is associated with most validated echocardiographic and invasive measures of cardiac systolic and diastolic function.

Prognostic value of left atrial strain in predicting cardiovascular morbidity and mortality in the general population.

AIMS: Left atrial (LA) enlargement predicts cardiovascular risk. The prognostic value of left atrial peak reservoir strain (LA RS) by two-dimensional speckle tracking in the general population is currently unknown. This study sought to determine the prognostic value of LA RS in the general population. METHODS AND RESULTS: A total of 385 participants without atrial fibrillation, heart failure (HF), and ischaemic heart disease (IHD) had an echocardiogram including left ventricular and LA speckle-tracking analysis performed. LA RS was averaged from the three apical views. The endpoint was a composite of incident IHD, HF, or cardiovascular death. Median follow-up was 12.6 years (interquartile-range 11.5-12.8 years). Follow-up was 100%. Fifty-one participants (13.3%) reached the composite outcome. LA RS was a univariable predictor of outcome [hazard ratio (HR) 1.25, 95% confidence interval (95% CI) 1.09-1.43; P = 0.002]. However, LA RS did not remain an independent predictor of outcome after adjustment for clinical parameters. The prognostic value was modified by sex (P = 0.011). LA RS predicted the composite outcome in women but not in men when adjusting for clinical parameters (women: HR 1.46, 95% CI 1.05-2.02; P = 0.025) (men: HR 0.96, 95% CI 0.81-1.14; P = 0.65). Further adjustment for echocardiographic parameters did not significantly alter the results. LA RS added incremental prognostic information in addition to SCORE and the American Heart Association/American College of Cardiology Pooled Cohort Equation in women only. CONCLUSION: LA RS is a univariable predictor of cardiovascular morbidity and mortality in the general population. However, the prognostic value of LA RS is modified by sex. LA RS is an independent predictor of outcome in women but not in men.

Prognostic Importance of Left Ventricular Mechanical Dyssynchrony in Predicting Cardiovascular Death in the General Population.

BACKGROUND: Cardiovascular death (CVD) is a leading cause of death and constitutes a major burden on society. Left ventricular mechanical dyssynchrony (LVMD), evaluated as SD of time to peak regional longitudinal strain, is a capable predictor of many cardiovascular outcomes related to CVD, including ventricular arrhythmias, but the prognostic utility of LVMD in the general population is unknown. Hence, this study sought to determine the prognostic value of LVMD in the general population in predicting CVD. METHODS AND RESULTS: A total of 1138 participants underwent a general health examination and an echocardiographic examination including speckle tracking analysis with subsequent calculation of LVMD from time-to-peak regional strain. Primary end point was CVD, and secondary end point was noncardiovascular death. Follow-up was 100%. During a median follow-up of 11.1 years (interquartile range: 10.2-11.3 years), 62 participants suffered CVD (5.5%) while 131 participants experienced noncardiovascular death (11.5%). LVMD was an independent predictor of CVD (subdistribution hazard ratio, 1.04; 95% CI, 1.01-1.06; P=0.004, per 10-ms increase) in competing risk regression treating noncardiovascular death as a competing risk and retained prognostic capability after extensive multivariable adjustment. LVMD was not a significant predictor of noncardiovascular death. LVMD added incremental prognostic information in predicting CVD beyond the Systematic Coronary Risk Evaluation risk chart and a modified version of the American College of Cardiology/American Heart Association Pooled Cohort Equation. CONCLUSIONS: Left ventricular mechanical dyssynchrony adds incremental prognostic information in addition to established risk factors in prediction of CVD in individuals from the general population without atrial fibrillation and significant valvular disease.

Admission and mortality at the main neonatal intensive care unit in Guinea-Bissau.

Background: The authors assessed the risk of admission and mortality at the main neonatal intensive care unit (NICU) at the National Hospital Simão Mendes (NHSM) in Guinea-Bissau. Methods: The Bandim Health Project (BHP) maintains a health and demographic surveillance system (HDSS) in the capital Bissau, including at the NHSM. Data from January 2008 to August 2013 was used to assess NICU incubator admissions and mortality. Results: The overall NICU admission rate was 4.8% (1575/33,005); the lowest rate in 2012 (4.0% (214/5293)) and the highest rate in 2009 (6.0% (369/6134)). The overall mortality among admitted children was 19.6% (289/1476), declining from 26.7% (68/255) in 2008 to 13.0% (16/123) in 2013. Birth weight <1500 g (OR=353, (95% CI: 244-510) compared with normal birth weight 2500 g-4000 g), Apgar score≤3 (OR=13.2 (9.72-18.0) compared with Apgar score 7-10) and single motherhood (OR=1.44 (1.20-1.74)) were associated with NICU admission. Low Apgar score was a risk factor for NICU mortality (OR=6.21 (2.05-18.81)) and females (OR=0.55 (0.38-0.79) had a lower mortality than males. Conclusion: Approximately 5% of the hospital-born children were admitted to an incubator and among those almost 20% died, although mortality did decline. Male sex, very low birth weight and low Apgar score were strongly associated with NICU admissions and mortality.

Postsystolic Shortening by Speckle Tracking Echocardiography Is an Independent Predictor of Cardiovascular Events and Mortality in the General Population.

BACKGROUND: Postsystolic shortening (PSS) has been proposed as a novel marker of contractile dysfunction in the myocardium. Our objective was to assess the prognostic potential of PSS on cardiovascular events and death in the general population. METHODS AND RESULTS: The study design consisted of a prospective cohort study of 1296 low-risk participants from the general population, who were examined by speckle tracking echocardiography. The primary end point was the composite of heart failure, myocardial infarction, and cardiovascular death, defined as major adverse cardiovascular events (MACEs). The secondary end point was all-cause death. The postsystolic index (PSI) was defined as follows: [(maximum strain in cardiac cycle-peak systolic strain)/(maximum strain in cardiac cycle)]×100. PSS was regarded as present if PSI >20%. During a median follow-up of 11 years, 149 participants (12%) were diagnosed as having MACEs and 236 participants (18%) died. Increasing number of walls with PSS predicted both end points, an association that persisted after adjustment for age, sex, estimated glomerular filtration rate, global longitudinal strain, hypertension, heart rate, left ventricular ejection fraction, LV mass index, pro-B-type natriuretic peptide, previous ischemic heart disease, systolic blood pressure, average peak early diastolic longitudinal mitral annular velocity (e'), ratio between peak transmitral early and late diastolic inflow velocity (E/A), and left atrial volume index: MACEs (hazard ratio, 1.35; 95% confidence interval, 1.09-1.67; P=0.006 per 1 increase in walls displaying PSS) and death (hazard ratio, 1.30; 95% confidence interval, 1.08-1.57; P=0.006 per 1 increase in walls displaying PSS). The strongest predictor of end points was ≥2 walls exhibiting PSS. The PSI also predicted increased risk of the end points, and the associations remained significant in multivariable models: MACEs (per 1% increase in PSI: hazard ratio, 1.18; 95% confidence interval, 1.02-1.36; P=0.024) and death (per 1% increase in PSI: hazard ratio, 1.18; 95% confidence interval, 1.05-1.33; P=0.005). CONCLUSIONS: Presence of PSS in the general population provides independent and long-term prognostic information on the occurrence of MACEs and death.

National Immunization Campaigns with Oral Polio Vaccine Reduce All-Cause Mortality: A Natural Experiment within Seven Randomized Trials.

BACKGROUND: A recent WHO review concluded that live BCG and measles vaccine (MV) may have beneficial non-specific effects (NSEs) reducing mortality from non-targeted diseases. NSEs of oral polio vaccine (OPV) were not examined. If OPV vaccination campaigns reduce the mortality rate, it would suggest beneficial NSEs. SETTING: Between 2002 and 2014, Guinea-Bissau had 15 general OPV campaigns and other campaigns with OPV plus vitamin A supplementation (VAS), VAS-only, MV, and H1N1 vaccine. In this period, we conducted seven randomized controlled trials (RCTs) with mortality as main outcome. METHODS: Within these RCTs, we assessed whether the mortality rate was lower after-campaign than before-campaign. We used Cox models with age as underlying time and further adjusted for low birth-weight, season and time trend in mortality. We calculated the adjusted mortality rate ratio (MRR) for after-campaign vs before-campaign. RESULTS: The mortality rate was lower after OPV-only campaigns than before, the MRR being 0.81 (95% CI = 0.68-0.95). With each additional dose of campaign-OPV the mortality rate declined further (MRR = 0.87 (95% CI: 0.79-0.96) per dose) (test for trend, p = 0.005). No other type of campaign had similar beneficial effects. Depending on initial age and with follow-up to 3 years of age, the number needed to treat with campaign-OPV-only to save one life was between 68 and 230 children. CONCLUSION: Bissau had no case of polio infection so the results suggest that campaign-OPV has beneficial NSEs. Discontinuation of OPV-campaigns in low-income countries may affect general child mortality levels negatively.

Prognostic Value of Echocardiography in Hypertensive Versus Nonhypertensive Participants From the General Population.

Hypertension may be the most significant cardiovascular risk factor. Few studies have assessed the prognostic value of echocardiography in hypertensive individuals. This study examines the incremental prognostic value of adding echocardiographic parameters to established risk factors in individuals from the general population with and without hypertension. A total of 1294 individuals from the general population underwent a health examination and an echocardiogram including 2-dimensional speckle tracking. Outcome was a composite of ischemic heart disease and heart failure. The prevalence of hypertension was 38.3%. During a median follow-up of 12.5 years (interquartile range, 9.4-12.8 years), 222 participants (17.2%) developed the outcome. Out of these 222 events, 145 (65%) occurred in hypertensive participants, whereas 77 (35%) occurred in nonhypertensive individuals, corresponding to an incidence rate of 32/(1000×person-years) and 8/(1000×person-years), respectively. Follow-up was 100%. After multivariable adjustment, only left ventricular mass index predicted the outcome in hypertensive individuals, whereas only global longitudinal strain predicted the outcome in nonhypertensive individuals. In hypertensive individuals the prognostic value of left ventricular mass index was incremental to SCORE and abnormal ECG status. In nonhypertensive individuals the prognostic value of global longitudinal strain was incremental to SCORE and abnormal ECG status. The prognostic value of echocardiography in predicting cardiovascular outcomes in the general population is altered by hypertension. In hypertensive individuals, left ventricular mass index added incremental prognostic value in addition to established risk factors. In nonhypertensive individuals, global longitudinal strain added incremental prognostic value in addition to established risk factors.