Pooled Analysis Of Individual Data Research Articles

Utility of waist-to-height ratio, waist circumference and body mass index in predicting clustered cardiometabolic risk factors and subclinical vascular phenotypes in children and adolescents: A pooled analysis of individual data from 14 countries

AimsThe clinical utility of waist-to-height ratio (WHtR) in predicting cardiometabolic risk factors (CMRFs) and subclinical markers of cardiovascular disease remains controversial. We aimed to compare the utility of WHtR with waist circumference (WC) and body mass index (BMI) in identifying children and adolescents (youths) at risk for cardiometabolic outcomes, including clustered CMRFs, high carotid intima-media thickness (cIMT), and arterial stiffness (assessed as high pulse wave velocity, PWV). MethodsWe analyzed data from 34,224 youths (51.0 % boys, aged 6–18 years) with CMRFs, 5004 (49.5 % boys, aged 6–18 years) with cIMT measurement, and 3100 (56.4 % boys, aged 6–17 years) with PWV measurement from 20 pediatric samples across 14 countries. ResultsWHtR, WC, and BMI z-scores had similar performance in discriminating youths with ≥3 CMRFs, with the area under the curve (AUC) (95 % confidence interval, CI)) ranging from 0.77 (0.75–0.78) to 0.78 (0.76–0.80) using the modified National Cholesterol Education Program (NCEP) definition, and from 0.77 (0.74–0.79) to 0.77 (0.74–0.80) using the International Diabetes Federation (IDF) definition. Similarly, all three measures showed similar performance in discriminating youths with subclinical vascular outcomes, with AUC (95 % CI) ranging from 0.67 (0.64–0.71) to 0.70 (0.66–0.73) for high cIMT (≥P95 values) and from 0.60 (0.58–0.66) to 0.62 (0.58–0.66) for high PWV (≥P95 values). ConclusionsOur findings suggest that WHtR, WC, and BMI are equally effective in identifying at-risk youths across diverse pediatric populations worldwide. Given its simplicity and ease of use, WHtR could be a preferable option for quickly screening youths with increased cardiometabolic risk in clinical settings.

The Rate of Asystolic Reflex Syncope Is Not Influenced by Age

BackgroundThe head-up tilt test (HUT) and other evidence suggest that the vagal effect on the heart decreases with age. ObjectivesThe main aim of the study was to assess whether this age effect also affects the rate of asystole in spontaneous reflex syncope (RS). MethodWe performed an analysis of pooled individual data from 4 studies that recruited patients ≥40 years of age affected by certain or suspected RS who received an implantable loop recorder (ILR) and reported follow-up data on syncope recurrence. We assessed the presence of asystolic syncope of >3 seconds or nonsyncopal asystole of >6 seconds recorded by ILR and compared the findings to tilt test results on the same patients. ResultsA total of 1,046 patients received ILR because of unexplained syncope. Of these, 201 (19.2%) had a documentation of an asystolic event of 10-second (Q1-Q3: 6- to 15-second) duration. They were subdivided in 3 age tertiles: ≤60 years (n = 64), 61 to 72 years (n = 72), and ≥73 years (n = 65). The rate of asystolic events was similar in the 3 subgroups (50.1%, 50.1%, and 49.2%, respectively; P = 0.99). Conversely, the rate of asystolic syncope induced during HUT (performed in 169 of 201) was greatly age dependent (31.0%, 12.1%, and 11.1% in increasing age tertiles, respectively; P = 0.009). ConclusionsThe rate of the spontaneous asystolic form of RS documented by ILR is constant at any age >40 years. Conversely, the rate of asystolic syncope induced by HUT is higher in younger patients and decreases with age. The contrasting results between spontaneous and tilt-induced events cast doubt on the concept that asystole in RS is less common in older patients.

Comparison of Different Types of Drug-Eluting Stents for De Novo Long Coronary Artery Lesions.

Outcomes of percutaneous coronary intervention for diffuse long lesions remain relatively unfavorable. Prior clinical trials investigated the relative efficacy and safety of different types of drug-eluting stents (DES) in long lesions. This study sought to compare the relative performance of different types of DES for de novo long (≥25mm) coronary artery lesions. Using a pooled analysis of individual data of 1,450 patients from 3 randomized clinical trials, we compared angiographic and clinical outcomes of 5 different types of DES: 224 patients with cobalt-chromium everolimus-eluting stents (EES), 255 with platinum-chromium EES, 250 with Resolute zotarolimus-eluting stents, 245 with biodegradable polymer biolimus-eluting stents, and 476 with first-generation sirolimus-eluting stents (SES). The primary endpoint was in-segment late lumen loss at 9months. The primary endpoint was not significantly different between 4 second-generation DES and 1 first-generation SES (0.17 ± 0.41mm in cobalt-chromium EES; 0.11 ± 0.37 in platinum-chromium EES: 0.14 ± 0.38 in Resolute zotarolimus-eluting stents; 0.14 ± 0.38 in biodegradable polymer biolimus-eluting stents; or 0.10 ± 0.37 in SES, respectively, overall P = 0.38). Also, there were no significant between-group differences with respect to death, myocardial infarction, target-vessel revascularization, or stent thrombosis at 12months. In the multiple treatment propensity-score analysis, the risk of angiographic and clinical outcomes was also similar among several types of DES. In this patient-level pooled analysis, several second-generation DES showed similar angiographic and clinical outcomes in patients with de novo long coronary lesions. (Percutaneous Treatment of LONG Native Coronary Lesions With Drug-Eluting Stent-III [LONG-DES-III]; NCT01078038; Percutaneous Treatment of LONG Native Coronary Lesions With Drug-Eluting Stent-IV [LONG-DES-IV]; NCT01186094; and Everolimus-eluting [PROMUS-ELEMENT] vs. Biolimus A9-Eluting [NOBORI] Stents for Long-Coronary Lesions [LONG-DES-V]; NCT01186120).

Long-term exposure to low-level ambient air pollution and incidence of stroke and coronary heart disease: a pooled analysis of six European cohorts within the ELAPSE project

Long-term exposure to outdoor air pollution increases the risk of cardiovascular disease, but evidence is unclear on the health effects of exposure to pollutant concentrations lower than current EU and US standards and WHO guideline limits. Within the multicentre study Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), we investigated the associations of long-term exposures to fine particulate matter (PM2·5), nitrogen dioxide (NO2), black carbon, and warm-season ozone (O3) with the incidence of stroke and acute coronary heart disease. We did a pooled analysis of individual data from six population-based cohort studies within ELAPSE, from Sweden, Denmark, the Netherlands, and Germany (recruited 1992-2004), and harmonised individual and area-level variables between cohorts. Participants (all adults) were followed up until migration from the study area, death, or incident stroke or coronary heart disease, or end of follow-up (2011-15). Mean 2010 air pollution concentrations from centrally developed European-wide land use regression models were assigned to participants' baseline residential addresses. We used Cox proportional hazards models with increasing levels of covariate adjustment to investigate the association of air pollution exposure with incidence of stroke and coronary heart disease. We assessed the shape of the concentration-response function and did subset analyses of participants living at pollutant concentrations lower than predefined values. From the pooled ELAPSE cohorts, data on 137 148 participants were analysed in our fully adjusted model. During a median follow-up of 17·2 years (IQR 13·8-19·5), we observed 6950 incident events of stroke and 10 071 incident events of coronary heart disease. Incidence of stroke was associated with PM2·5 (hazard ratio 1·10 [95% CI 1·01-1·21] per 5 μg/m3 increase), NO2 (1·08 [1·04-1·12] per 10 μg/m3 increase), and black carbon (1·06 [1·02-1·10] per 0·5 10-5/m increase), whereas coronary heart disease incidence was only associated with NO2 (1·04 [1·01-1·07]). Warm-season O3 was not associated with an increase in either outcome. Concentration-response curves indicated no evidence of a threshold below which air pollutant concentrations are not harmful for cardiovascular health. Effect estimates for PM2·5 and NO2 remained elevated even when restricting analyses to participants exposed to pollutant concentrations lower than the EU limit values of 25 μg/m3 for PM2·5 and 40 μg/m3 for NO2. Long-term air pollution exposure was associated with incidence of stroke and coronary heart disease, even at pollutant concentrations lower than current limit values. Health Effects Institute.

Effect of intra-arrest trans-nasal evaporative cooling in out-of-hospital cardiac arrest: a pooled individual participant data analysis

BackgroundRandomized trials have shown that trans-nasal evaporative cooling initiated during CPR (i.e. intra-arrest) effectively lower core body temperature in out-of-hospital cardiac arrest patients. However, these trials may have been underpowered to detect significant differences in neurologic outcome, especially in patients with initial shockable rhythm.MethodsWe conducted a post hoc pooled analysis of individual data from two randomized trials including 851 patients who eventually received the allocated intervention and with available outcome (“as-treated” analysis). Primary outcome was survival with favourable neurological outcome at hospital discharge (Cerebral Performance Category [CPC] of 1–2) according to the initial rhythm (shockable vs. non-shockable). Secondary outcomes included complete neurological recovery (CPC 1) at hospital discharge.ResultsAmong the 325 patients with initial shockable rhythms, favourable neurological outcome was observed in 54/158 (34.2%) patients in the intervention and 40/167 (24.0%) in the control group (RR 1.43 [confidence intervals, CIs 1.01–2.02]). Complete neurological recovery was observed in 40/158 (25.3%) in the intervention and 27/167 (16.2%) in the control group (RR 1.57 [CIs 1.01–2.42]). Among the 526 patients with initial non-shockable rhythms, favourable neurological outcome was in 10/259 (3.8%) in the intervention and 13/267 (4.9%) in the control group (RR 0.88 [CIs 0.52–1.29]; p = 0.67); survival and complete neurological recovery were also similar between groups. No significant benefit was observed for the intervention in the entire population.ConclusionsIn this pooled analysis of individual data, intra-arrest cooling was associated with a significant increase in favourable neurological outcome in out-of-hospital cardiac arrest patients with initial shockable rhythms. Future studies are needed to confirm the potential benefits of this intervention in this subgroup of patients.

Minimally invasive treatment of laryngoceles: a systematic review and pooled analysis.

Laryngoceles are best treated with surgery. The goal of this study is to compare patient outcomes and complications in patients undergoing removal of laryngoceles with either transoral endoscopic/microlaryngoscopic or robotic approaches. A systematic review of the published literature was conducted using Pubmed, Web of Science, and the Cochrane Clinical Trials databases. A pooled analysis of individual data was used to compare outcomes between robotic and endoscopic approaches. A total of 30 studies were included. Nine studies with 95 patients were included in the final analysis. Eighty-one (85.26%) were treated with microlaryngoscopic surgery and 14 (14.74%) were treated with robotic-assisted surgery. The rates of tracheostomy (RR = 1.44, 95% CI = 0.389-5.332), complications (RR = 0.329, 95% CI = 0.047-2.294) and recurrence (RR = 0.354, 95% CI = 0.021-5.897) were not statistically different between groups. Within the endoscopic subgroup, 66 laryngoceles (78.57%) were completely excised, while 18 (21.43%) laryngoceles were treated with marsupialization. Marsupialization was associated with an increased risk of recurrence (RR = 4.889, 95% CI = 1.202-19.891). In the robotic subgroup, there was an increased risk of nasogastric tube use (RR = 103.867, 95% CI = 6.379-1619.214) and a longer mean length of hospital stay (p = 0.0001). Transoral treatment of laryngoceles has complication and recurrence rates of 18.95% and 7.37%, respectively. Robotic approaches are associated with higher rates of NGT use and increased hospital stay, however much of this is due to one robotic surgeon's preference for routine NGT placement and higher rates of combined laryngocele removal via robotic approach. Complete excision of combined laryngoceles is possible with transoral approaches. Marsupialization, reported in traditional endoscopic approaches, is associated with a significantly higher rate of recurrence (22.22% vs. 4.76%).

Characteristics of intracerebral haemorrhage associated with COVID-19: a systematic review and pooled analysis of individual patient and aggregate data

Background and purposeThere are very few studies of the characteristics and causes of ICH in COVID-19, yet such data are essential to guide clinicians in clinical management, including challenging anticoagulation decisions. We aimed to describe the characteristics of spontaneous symptomatic intracerebral haemorrhage (ICH) associated with COVID-19.MethodsWe systematically searched PubMed, Embase and the Cochrane Central Database for data from patients with SARS-CoV-2 detected prior to or within 7 days after symptomatic ICH. We did a pooled analysis of individual patient data, then combined data from this pooled analysis with aggregate-level data.ResultsWe included data from 139 patients (98 with individual data and 41 with aggregate-level data). In our pooled individual data analysis, the median age (IQR) was 60 (53–67) years and 64% (95% CI 54–73.7%) were male; 79% (95% CI 70.0–86.9%) had critically severe COVID-19. The pooled prevalence of lobar ICH was 67% (95% CI 56.3–76.0%), and of multifocal ICH was 36% (95% CI 26.4–47.0%). 71% (95% CI 61.0–80.4%) of patients were treated with anticoagulation (58% (95% CI 48–67.8%) therapeutic). The median NIHSS was 28 (IQR 15–28); mortality was 54% (95% CI 43.7–64.2%). Our combined analysis of individual and aggregate data showed similar findings. The pooled incidence of ICH across 12 cohort studies of inpatients with COVID-19 (n = 63,390) was 0.38% (95% CI 0.22–0.58%).ConclusionsOur data suggest that ICH associated with COVID-19 has different characteristics compared to ICH not associated with COVID-19, including frequent lobar location and multifocality, a high rate of anticoagulation, and high mortality. These observations suggest different underlying mechanisms of ICH in COVID-19 with potential implications for clinical treatment and trials.

Association between initial and residual pulmonary vascular obstruction and pulmonary embolism recurrence, a pooled analysis

Introduction The best treatment option (short-term or extended anticoagulant treatment) after a first unprovoked pulmonary embolism (PE) is debated. Pulmonary vascular obstruction, measured by the pulmonary vascular obstruction index (PVOI) at diagnosis or during the follow-up, has been associated with an increased risk of venous thromboembolism (VTE) recurrence when anticoagulants are stopped [1] . But results are not entirely consistent [2] , and PVOI classification cut-offs vary among studies. We therefore conducted a pooled analysis of 3 studies of the F-CRIN INNOVTE network. The primary objective of this work is to assess if elevated PVOI at the time of PE diagnosis and after months of anticoagulation are independent risk factors of VTE recurrence after a first episode of PE, and if so, to estimate which PVOI cut-off values would be the most discriminating for predicting VTE recurrence. Method We performed a pooled analysis of individual data from 3 French studies conducted within the F-CRIN INNOVTE network: a randomised double-blind controlled clinical trial and two observational longitudinal cohort studies. PVOI was measured by ventilation/perfusion lung scan during two periods; one at the time of index PE (initial PVOI), and one several months later, after anticoagulation treatment of the acute phase (post-treatment PVOI). PVOI was expressed in percentage of vascular obstruction. VTE recurrence was defined as objectively confirmed PE episode or deep vein thrombosis. The associations between PVOI (both initial and post-treatment) and VTE recurrence were jointly estimated using a multivariate Cox proportional hazards regression model. To manage confounding, the model was further stratified on the study, as well as adjusted on anticoagulant treatment duration, which could have been affected by PVOI measurement in the two observational cohort studies. By this means, the direct effect of PVOI on VTE recurrence may be estimated. Optimal PVOI thresholds were estimated by 10-fold cross-validation, using areas under curve (AUC) computed from time-dependant receiver-operating characteristic (ROC) curves. Results The total number of patients was 922. The median duration of follow-up was 42 months (IQR: 38–60). Mean age was 60 ± 18 years, 56% of patients were female. VTE recurrences occurred in 149 patients (4.2 events per 100 person-years). The most discriminating cut-offs were > 35% for initial PVOI (AUC: 0.71, 95% CI: 0.71–0.71), and > 5% for post-treatment PVOI (AUC: 0.69, 95% CI: 0.68–0.69). Initial PVOI > 35% and post-treatment PVOI > 5% were significantly associated with the risk of VTE recurrences (HR 1.61, 95% CI: 1.07–2.43 and HR 1.63, 95% CI: 1.06–2.50, respectively). Conclusion After a first episode of PE, initial PVOI > 35% and post-treatment PVOI > 5% were found to be independent predictors of VTE recurrence. Those results could in the future help detect more accurately patients with high-risk of VTE recurrence, and thus provide help in clinical decision-making for adapting anticoagulation therapy.

Instant rule-out of suspected non-ST-segment elevation myocardial infarction using high-sensitivity cardiac troponin T with Copeptin versus a single low high-sensitivity cardiac troponin T: findings from a large pooled individual data analysis on 10,329 patients

BackgroundEvidence is sparse and inconsistent on the role of a dual marker strategy (DMS) combining Copeptin with cardiac troponin T (cTnT) for instant rule-out of a non-ST-segment myocardial infarction (NSTEMI) when high sensitivity cardiac troponin T (hs-cTnT) is used.MethodsData on 10,329 patients from 5 trials were pooled to evaluate initial Copeptin in combination with hs-cTnT against a single marker strategy (SMS) based on hs-cTnT < limit of detection. Endpoints were sensitivities and negative predictive values (NPV) for rule-out of NSTEMI, 30-day all-cause mortality and rates of applicability for DMS or SMS.ResultsNPV for rule-out of NSTEMI was high, exceeding 99.0% for the lower limits of the 95% confidence intervals (99.0% vs 99.2%) for DMS and SMS, and NPV for all cause death at 30 days was similar with very low mortality after rule-out [0.07% (0.0–0.4%) vs 0.0% (0.0–1.2%), p = 1.0], but applicability was 2.4-fold higher [64.6% (63.0–66.2%) vs 27.9% (26.2%—29.7%), p < 0.001] with DMS than SMS. In a secondary analysis on DMS after inclusion of high risk patients, performance and applicability were similar.ConclusionFindings corroborate the 2015 European Society of Cardiology recommendation to use dual marker strategy for instant rule-out of NSTEMI, extending evidence to hs-cTnT. Novel data demonstrate a comparably safe and effective instant rule-out with Copeptin in combination with hs-cTnT versus a single marker strategy based on very low hs-cTnT but a more than twofold higher applicability of the dual marker strategy without the need to exclude very early presenters or other important subgroups.Graphic abstractDual marker strategy using hs-cTnT at 99th percentile and Copeptin versus ESC 0-h immediate rule-out based on hs-cTnT < limit of detection

Impact of hypertension stratified by diabetes on the lifetime risk of cardiovascular disease mortality in Japan: a pooled analysis of data from the Evidence for Cardiovascular Prevention from Observational Cohorts in Japan study.

Lifetime risk is an informative estimate to motivate people to change lifestyle behaviors, especially from a younger age, in public health education. The impact of the combination of hypertension and diabetes on the lifetime risk of cardiovascular mortality has not been investigated in Asian populations. A pooled analysis of individual data from nine cohorts was performed. A total of 57,339 Japanese men and women were eligible for the analysis. We used the modified Kaplan-Meier approach and estimated the remaining lifetime risk of cardiovascular mortality starting from the index age of 35 years. Participants were classified into four categories defined by hypertension and diabetes. The lifetime risk was increased in the order of those without either risk, those without hypertension but with diabetes, those with hypertension but without diabetes, and those with both risks. The lifetime risk of cardiovascular mortality at the 35-year index age was as follows: 7.8% in men and 6.2% in women for those without either hypertension or diabetes, 13.2% in men and 9.5% in women for those without hypertension but with diabetes, 17.2% in men and 11.7% in women for those with hypertension but without diabetes, and 19.4% in men and 15% in women for those with both risks. These findings reinforce the need for a life-course perspective in the management of hypertension and diabetes from a younger age.

Type of menopause, age of menopause and variations in the risk of incident cardiovascular disease: pooled analysis of individual data from 10 international studies.

How does the risk of cardiovascular disease (CVD) vary with type and age of menopause? Earlier surgical menopause (e.g. <45 years) poses additional increased risk of incident CVD events, compared to women with natural menopause at the same age, and HRT use reduced the risk of CVD in women with early surgical menopause. Earlier age at menopause has been linked to an increased risk of CVD mortality and all-cause mortality, but the extent that this risk of CVD varies by type of menopause and the role of postmenopausal HRT use in reducing this risk is unclear. Pooled individual-level data of 203767 postmenopausal women from 10 observational studies that contribute to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE) consortium were included in the analysis. Postmenopausal women who had reported menopause (type and age of menopause) and information on non-fatal CVD events were included. Type of menopause (natural menopause and surgical menopause) and age at menopause (categorised as <35, 35-39, 40-44, 45-49, 50-54 and ≥55 years) were exposures of interest. Natural menopause was defined as absence of menstruation over a period of 12 months (no hysterectomy and/or oophorectomy) and surgical menopause as removal of both ovaries. The study outcome was the first non-fatal CVD (defined as either incident coronary heart disease (CHD) or stroke) event ascertained from hospital medical records or self-reported. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CI for non-fatal CVD events associated with natural menopause and surgical menopause. Compared with natural menopause, surgical menopause was associated with over 20% higher risk of CVD (HR 1.22, 95% CI 1.16-1.28). After the stratified analysis by age at menopause, a graded relationship for incident CVD was observed with lower age at menopause in both types of natural and surgical menopause. There was also a significant interaction between type of menopause and age at menopause (P < 0.001). Compared with natural menopause at 50-54 years, women with surgical menopause before 35 (2.55, 2.22-2.94) and 35-39 years (1.91, 1.71-2.14) had higher risk of CVD than those with natural menopause (1.59, 1.23-2.05 and 1.51, 1.33-1.72, respectively). Women who experienced surgical menopause at earlier age (<50 years) and took HRT had lower risk of incident CHD than those who were not users of HRT. Self-reported data on type and age of menopause, no information on indication for the surgery (e.g. endometriosis and fibroids) and the exclusion of fatal CVD events may bias our results. In clinical practice, women who experienced natural menopause or had surgical menopause at an earlier age need close monitoring and engagement for preventive health measures and early diagnosis of CVD. Our findings also suggested that timing of menopause should be considered as an important factor in risk assessment of CVD for women. The findings on CVD lend some support to the position that elective bilateral oophorectomy (surgical menopause) at hysterectomy for benign diseases should be discouraged based on an increased risk of CVD. InterLACE project is funded by the Australian National Health and Medical Research Council project grant (APP1027196). GDM is supported by Australian National Health and Medical Research Council Principal Research Fellowship (APP1121844). There are no competing interests.

A Pooled Individual Participant Data Analysis of Trans-Nasal Cooling in Out-of-Hospital Cardiac Arrest

Background: Randomized trials have shown that trans-nasal evaporative cooling initiated during CPR (i.e. intra-arrest) effectively lower core body temperature in out-of-hospital cardiac arrest patients. However, these trials may have been underpowered to detect significant differences in neurologic outcome, especially in patients with initial shockable rhythm. Methods: We conducted a pooled analysis of individual data from two randomised trials including 843 patients who eventually received the allocated intervention and with available outcome. Primary outcome was survival with favourable neurological outcome at hospital discharge (Cerebral Performance Category [CPC] of 1-2) according to the initial rhythm (shockable vs. non-shockable). Secondary outcomes included complete neurological recovery (CPC 1) at hospital discharge. Findings: Among the 325 patients with initial shockable rhythms, favourable neurological outcome was observed in 54/158 (34.2%) patients in the intervention and 40/167 (24.0%) in the control group (RR 1.43 [confidence intervals, CIs 1.01-2.02]). Complete neurological recovery was observed in 40/158 (25.3%) in the intervention and 27/167 (16.2%) in the control group (RR 1.57 [CIs 1.01-2.42]. Among the 518 patients with initial non-shockable rhythms, favourable neurological outcome was observed in 10/250 (4.0%) patients in the intervention and 13/267 (4.9%) in the control group (RR 0.82 [CIs 0.37-1.84]; complete neurological recovery was observed in 4/250 (1.6%) and 5/267 (1.9%) patients, respectively (RR 0.85 [CIs 0.23-3.15]. Interpretation: In this pooled analysis of individual data, intra-arrest cooling was associated with a significant increase in favourable neurological outcome in out-of-hospital cardiac arrest patients with initial shockable rhythms. No effects were observed in patients with initial non-shockable rhythms. Funding Statement: No funding has been received for this study. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: Ethics and institutional committees in each participating country approved the study protocols and written consent was obtained from closest relative or a legal representative of each patient after hospital admission and, at a later stage, from each patient who showed neurological recovery. Both studies were conducted according to the requirements of the Declaration of Helsinki.

Associations of long-term exposure to ambient PM2.5 with mortality in Chinese adults: A pooled analysis of cohorts in the China-PAR project

BackgroundThe concentration-response relationship between mortality and long-term exposure to fine particulate matter (PM2.5) has not been fully elucidated, especially at high levels of PM2.5 concentrations. ObjectiveWe aimed to evaluate chronic effects of ambient PM2.5 exposure on deaths among Chinese adults in high-exposure settings. MethodsParticipants of the Prediction for Atherosclerotic cardiovascular disease Risk in China (China-PAR) project were included from four prospective cohorts among Chinese adults aged ≥18 years old. The overall follow-up rate of the four cohorts was 93.4% until the recent follow-up survey that ended in 2015. The average of satellite-based PM2.5 concentrations during 2000–2015 at 1-km spatial resolution was assigned to each participant according to individual residence addresses. Based on the pooled analysis of individual data from the four cohorts, a Cox proportional hazards model was used to estimate the hazard ratio (HR) and corresponding 95% confidence intervals (95% CIs) for the association of PM2.5 exposure with mortality after multivariate adjustment. ResultsA total of 116,821 participants were eligible in the final analysis. During a mean of 7.7 years of follow-up, 6,395 non-accidental deaths and 2,507 cardio-metabolic deaths occurred. The mean of PM2.5 concentration was 64.9 μg/m3 ranging from 31.2 μg/m3 to 97.0 μg/m3. For each 10 μg/m3 increment in PM2.5, the HR was 1.11 (95% CI: 1.08–1.14) for non-accidental mortality and 1.22 (95% CI: 1.16–1.27) for cardio-metabolic mortality. In addition, a weak exponential curve for the concentration-response association between mortality and PM2.5 was observed among Chinese adults. ConclusionsOur study provided important evidence of the long-term effects of PM2.5 exposure on deaths among Chinese adults. The findings expand our knowledge on concentration-response relationship in high-exposure environments, which is essential to address the urgent challenge of reducing the disease burden attributable to PM2.5 exposure in rapidly industrializing countries such as China.

Long-term survival outcomes of undifferentiated embryonal sarcoma of the liver: a pooled analysis of 308 patients.

Treatment of undifferentiated embryonal sarcoma of the liver (UESL) is a great clinical challenge due to its rarity. This study aims to examine the long-term survival of UESL patients after treatment using different therapeutic modalities. A pooled analysis of individual data was performed on all UESL patients obtained from literature search (n = 307) and our institution (n = 1). The 5-year overall survival rate of the 308 patients was 65.8%, 70% for partial hepatectomy group (n = 271), 78.9% for liver transplantation group (n = 14) and 6.6% for nonsurgical treatment group (n = 23). For patients receiving partial hepatectomy, paediatric patients, radical resection and combined chemotherapy were independent predictors for improved survival. Radical hepatectomy combined chemotherapy should be considered as the preferred treatment option for USEL. Liver transplantation appears to be a reasonable alternative for unresectable disease.

Holistic services for people with advanced disease and chronic or refractory breathlessness: a mixed-methods evidence synthesis

BackgroundBreathlessness is a common and distressing symptom of many advanced diseases, affecting around 2 million people in the UK. Breathlessness increases with disease progression and often becomes chronic or refractory. Breathlessness-triggered services that integrate holistic assessment and specialist palliative care input as part of a multiprofessional approach have been developed for this group, offering tailored interventions to support self-management and reduce distress.ObjectivesThe aim was to synthesise evidence on holistic breathlessness services for people with advanced disease and chronic or refractory breathlessness. The objectives were to describe the structure, organisation and delivery of services, determine clinical effectiveness, cost-effectiveness and acceptability, identify predictors of treatment response, and elicit stakeholders’ evidence-based priorities for clinical practice, policy and research.DesignThe mixed-methods evidence synthesis comprised three components: (1) a systematic review to determine the clinical effectiveness, cost-effectiveness and acceptability of holistic breathlessness services; (2) a secondary analysis of pooled individual data from three trials to determine predictors of clinical response; and (3) a transparent expert consultation (TEC), comprising a stakeholder workshop and an online consensus survey, to identify stakeholders’ priorities.ResultsThirty-seven papers reporting on 18 holistic breathlessness services were included in the systematic review. Most studies enrolled people with thoracic cancer, were delivered over 4–6 weeks, and included breathing training, relaxation techniques and psychological support. Meta-analysis demonstrated significant reductions in the Numeric Rating Scale (NRS) distress due to breathlessness, significant reductions in the Hospital Anxiety and Depressions Scale (HADS) depression scores, and non-significant reductions in the Chronic Respiratory Disease Questionnaire (CRQ) mastery and HADS anxiety, favouring the intervention. Recipients valued education, self-management interventions, and expertise of the staff in breathlessness and person-centred care. Evidence for cost-effectiveness was limited and inconclusive. The responder analysis (n = 259) revealed baseline CRQ mastery and NRS distress to be strong predictors of the response to breathlessness services assessed by these same measures, and no significant influence from baseline breathlessness intensity, patient diagnosis, lung function, health status, anxiety or depression. The TEC elicited 34 priorities from stakeholders. Seven priorities received high agreement and consensus, reflecting stakeholders’ (n = 74) views that services should be person-centred and multiprofessional, share their breathlessness management skills with others, and recognise the roles and support needs of informal carers.LimitationsThe evidence synthesis draws predominantly from UK services and may not be generalisable to other settings. Some meta-analyses were restricted by reporting biases and statistical heterogeneity.ConclusionsDespite heterogeneity in composition and delivery, holistic breathlessness services are highly valued by recipients and can lead to significant improvements in the distress caused by breathlessness and depression. Outcomes of improved mastery and reduced distress caused by breathlessness are not influenced by patient diagnosis, lung function or health status. Stakeholders highlighted the need for improved access to person-centred, multiprofessional breathlessness services and support for informal carers.Future workOur research suggests that key therapeutic components of holistic breathlessness services be considered in clinical practice and models of delivery and educational strategies to address stakeholders’ priorities tested.Study registrationThis study is registered as PROSPERO CRD42017057508.FundingThe National Institute for Health Research (NIHR) Health Services and Delivery programme. Matthew Maddocks, Wei Gao and Irene J Higginson are supported by the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) South London; Matthew Maddocks is supported by a NIHR Career Development Fellowship (CDF-2017-009), William D-C Man is supported by the NIHR CLAHRC Northwest London and Irene J Higginson holds a NIHR Emeritus Senior Investigator Award.

P532 Safety and efficacy of endoscopic dilation of small bowel Crohn’s disease strictures by balloon-assisted enteroscopy: pooled analysis of individual data from 210 patients

P532 Safety and efficacy of endoscopic dilation of small bowel Crohn’s disease strictures by balloon-assisted enteroscopy: pooled analysis of individual data from 210 patients

Relationships between intensity, duration, cumulative dose, and timing of smoking with age at menopause: A pooled analysis of individual data from 17 observational studies.

BackgroundCigarette smoking is associated with earlier menopause, but the impact of being a former smoker and any dose-response relationships on the degree of smoking and age at menopause have been less clear. If the toxic impact of cigarette smoking on ovarian function is irreversible, we hypothesized that even former smokers might experience earlier menopause, and variations in intensity, duration, cumulative dose, and age at start/quit of smoking might have varying impacts on the risk of experiencing earlier menopause.Methods and findingsA total of 207,231 and 27,580 postmenopausal women were included in the cross-sectional and prospective analyses, respectively. They were from 17 studies in 7 countries (Australia, Denmark, France, Japan, Sweden, United Kingdom, United States) that contributed data to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on smoking status, cigarettes smoked per day (intensity), smoking duration, pack-years (cumulative dose), age started, and years since quitting smoking was collected at baseline. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CIs) for the associations between each smoking measure and categorised age at menopause (<40 (premature), 40–44 (early), 45–49, 50–51 (reference), and ≥52 years). The association with current and former smokers was analysed separately. Sensitivity analyses and two-step meta-analyses were also conducted to test the results. The Bayesian information criterion (BIC) was used to compare the fit of the models of smoking measures.Overall, 1.9% and 7.3% of women experienced premature and early menopause, respectively. Compared with never smokers, current smokers had around twice the risk of experiencing premature (RRR 2.05; 95% CI 1.73–2.44) (p < 0.001) and early menopause (1.80; 1.66–1.95) (p < 0.001). The corresponding RRRs in former smokers were attenuated to 1.13 (1.04–1.23; p = 0.006) and 1.15 (1.05–1.27; p = 0.005). In both current and former smokers, dose-response relationships were observed, i.e., higher intensity, longer duration, higher cumulative dose, earlier age at start smoking, and shorter time since quitting smoking were significantly associated with higher risk of premature and early menopause, as well as earlier menopause at 45–49 years. Duration of smoking was a strong predictor of age at natural menopause. Among current smokers with duration of 15–20 years, the risk was markedly higher for premature (15.58; 11.29–19.86; p < 0.001) and early (6.55; 5.04–8.52; p < 0.001) menopause. Also, current smokers with 11–15 pack-years had over 4-fold (4.35; 2.78–5.92; p < 0.001) and 3-fold (3.01; 2.15–4.21; p < 0.001) risk of premature and early menopause, respectively. Smokers who had quit smoking for more than 10 years had similar risk as never smokers (1.04; 0.98–1.10; p = 0.176). A limitation of the study is the measurement errors that may have arisen due to recall bias.ConclusionsThe probability of earlier menopause is positively associated with intensity, duration, cumulative dose, and earlier initiation of smoking. Smoking duration is a much stronger predictor of premature and early menopause than others. Our findings highlight the clear benefits for women of early smoking cessation to lower their excess risk of earlier menopause.

Efficacy of zofenopril in combination with thiazide diuretics in patients with acute myocardial infarction: a pooled individual data analysis of four randomized, double-blind, controlled, prospective studies.

BackgroundIn the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) studies, early administration of zofenopril after acute myocardial infarction (AMI) was prognostically beneficial as compared to placebo and other angiotensin-converting enzyme inhibitors (ACEIs), such as lisinopril and ramipril. Here, we investigated whether zofenopril efficacy could be affected by a concomitant use of thiazide diuretics (TDs).MethodsThis was a post hoc analysis of pooled individual patient data from the SMILE studies. Patients treated with other diuretics than TDs were excluded. The primary study endpoint was the 1-year combined occurrence of death or hospitalization for CV causes, with or without TD.ResultsAmong 2,995 patients, 263 (8.8%) were treated with a combination including a TD (TD+), whereas 2,732 (91.2%) were not treated with any diuretic (TD−). Proportions of subjects who were treated with TD were equally distributed (p=0.774) within the placebo, zofenopril, and other ACEIs groups. The 1-year risk of major cardiovascular events was similar in TD+ (18.3%) and TD− (16.8%) patients (hazard ratio [HR] 1.04; 95% CI 0.74–1.45; p=0.838). After stratifying per concomitant treatment and TD, the 1-year risk of CV events was significantly lower with zofenopril than with placebo (HR 0.70; 95% CI 0.55–0.88; p=0.002) and other ACEIs (HR 0.58; 95% CI 0.46–0.74; p=0.0001). Treatment with ACEIs and TD as concomitant therapy was associated with a larger blood pressure (BP) reduction (p=0.0001 for systolic BP and p=0.045 for diastolic BP).ConclusionIn post AMI patients, zofenopril maintained its positive impact on prognosis compared to placebo or other ACEIs, regardless concomitant TD administration. In this setting, TD shows advantages in managing the most difficult hypertensive patients.

Overweight is associated to a better prognosis in metastatic colorectal cancer: A pooled analysis of FFCD trials

BackgroundPrevious studies showed that high and low body mass index (BMI) was associated with worse prognosis in early-stage colorectal cancer (CRC), and low BMI was associated with worse prognosis in metastatic CRC (mCRC). We aimed to assess efficacy outcomes according to BMI. Patients and methodsA pooled analysis of individual data from 2085 patients enrolled in eight FFCD first-line mCRC trials from 1991 to 2013 was performed. Comparisons were made according to the BMI cut-off: Obese (BMI ≥30), overweight patients (BMI ≥ 25), normal BMI patients (BMI: 18.5–24) and thin patients (BMI <18.5). Interaction tests were performed between BMI effect and sex, age and the addition of antiangiogenics to chemotherapy. ResultsThe rate of BMI ≥25 patients was 41.5%, ranging from 37.6% (1991–1999 period) to 41.5% (2000–2006 period) and 44.8% (2007–2013 period). Comparison of overweight patients versus normal BMI range patients revealed a significant improvement of median overall survival (OS) (18.5 versus 16.3 months, HR = 0.88 [0.80–0.98] p = 0.02) and objective response rate (ORR) (42% versus 36% OR = 1.23 [1.01–1.50] p = 0.04) but a comparable median progression-free survival (PFS) (7.8 versus 7.2 months, HR = 0.96 [0.87–1.05] p = 0.35). Subgroup analyses revealed that overweight was significantly associated with better OS in men. OS and PFS were significantly shorter in thin patients. ConclusionOverweight patients had a prolonged OS compared with normal weight patients with mCRC. The association of overweight with better OS was only observed in men. The pejorative prognosis of BMI <18.5 was confirmed.

Interaction between cardiovascular risk factors and body mass index and 10-year incidence of cardiovascular disease, cancer death, and overall mortality

The effect of above-normal body mass index (BMI) on health outcomes is controversial because it is difficult to distinguish from the effect due to BMI-associated cardiovascular risk factors. The objective was to analyze the impact on 10-year incidence of cardiovascular disease, cancer deaths and overall mortality of the interaction between cardiovascular risk factors and BMI. We conducted a pooled analysis of individual data from 12 Spanish population cohorts with 10-year follow-up. Participants had no previous history of cardiovascular diseases and were 35–79years old at basal examination. Body mass index was measured at baseline being the outcome measures ten-year cardiovascular disease, cancer and overall mortality. Multivariable analyses were adjusted for potential confounders, considering the significant interactions with cardiovascular risk factors. We included 54,446 individuals (46.5% with overweight and 27.8% with obesity). After considering the significant interactions, the 10-year risk of cardiovascular disease was significantly increased in women with overweight and obesity [Hazard Ratio=2.34 (95% confidence interval: 1.19–4.61) and 5.65 (1.54–20.73), respectively]. Overweight and obesity significantly increased the risk of cancer death in women [3.98 (1.53–10.37) and 11.61 (1.93–69.72)]. Finally, obese men had an increased risk of cancer death and overall mortality [1.62 (1.03–2.54) and 1.34 (1.01–1.76), respectively]. In conclusion, overweight and obesity significantly increased the risk of cancer death and of fatal and non-fatal cardiovascular disease in women; whereas obese men had a significantly higher risk of death for all causes and for cancer. Cardiovascular risk factors may act as effect modifiers in these associations.