Out-of-Sequence Vaccinations With Measles Vaccine and Diphtheria-Tetanus-Pertussis Vaccine: A Reanalysis of Demographic Surveillance Data From Rural Bangladesh

Abstract Background Due to delays in vaccinations, diphtheria-tetanus-whole-cell-pertussis (DTP) is often given with or after measles vaccine (MV)—out of sequence. We reanalyzed data from Matlab, Bangladesh, to examine how administration of MV and DTP out-of-sequence was associated with child survival. Methods In sum, 36 650 children born between 1986 and 1999 were followed with registration of vaccinations and survival. Controlling for background factors using Cox proportional hazards models, survival was analyzed between 9 and 24 months of age. We measured the mortality rate ratio (MRR) to compare vaccination groups. Oral polio vaccine (OPV) campaigns, which started in 1995, reduced the mortality rate and reduced the difference between vaccination groups. In the main analysis, we therefore censored for OPV campaigns; there were 151 nonaccident deaths before the OPV campaigns. Results Compared with MV administered alone (MV-only), DTP administered with or after MV had MRR 2.20 (1.31–3.70), and DTP-only had MRR 1.78 (1.01–3.11). Compared with MV-only, DTP administered with MV had a female-male MRR 0.56 (0.13–2.38), significantly different to DTP administered after MV, which had MRR 14.83 (1.88–117.1), test of interaction P = .011. Compared with having DTP (no MV) as most recent vaccination, MV-only had a nonaccident MRR of 0.56 (0.32–0.99). Conclusion The negative effects of non-live DTP with or after live MV are not explained merely by selection bias. These observations support a live-vaccine-last policy where DTP should not be given with or after MV.

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Out-of-sequence DTP and measles vaccinations and child mortality in Guinea-Bissau: a reanalysis

BMJ Open ◽

10.1136/bmjopen-2018-024893 ◽

2019 ◽

Vol 9 (9) ◽

pp. e024893 ◽

Cited By ~ 1

Author(s):

Sanne M Thysen ◽

Amabelia Rodrigues ◽

Peter Aaby ◽

Ane B Fisker

Keyword(s):

Mortality Rate ◽

Child Mortality ◽

Proportional Hazards ◽

Child Survival ◽

Secondary Analysis ◽

Oral Polio Vaccine ◽

Vaccination Schedule ◽

Cox Proportional Hazards ◽

Vaccination Status ◽

Guinea Bissau

ObjectivesTo assess whether the sequence of diphtheria-tetanus-pertussis vaccine (DTP) and measles vaccine (MV) was associated with child survival in a dataset previously used to assess non-specific effects of vaccines with no consideration of vaccination sequence.DesignProspective cohort study analysed using the landmark approach.SettingBandim Health Project’s Health and Demographic Surveillance System covering 100 village clusters in rural Guinea-Bissau. The recommended vaccination schedule was BCG and oral polio vaccine (OPV) at birth, DTP and OPV at 6, 10 and 14 weeks, MV at 9 months and booster DTP and OPV at 18 months of age.ParticipantsChildren aged 9–17 months (main analysis) and 18–35 months (secondary analysis: age of booster DTP) with vaccination status assessed between April 1991 and April 1996.MethodsSurvival during the 6 months after assessing vaccination status was compared by vaccination sequence in Cox-proportional hazards models with age as underlying time. Analyses were stratified by sex and village cluster.Main outcome measureMortality rate ratio (MRR) for out-of-sequence vaccinations compared with in-sequence vaccinations.ResultsAmong children aged 9–17 months, 60% of observations (3574/5937) were from children who had received both MV and DTP. Among these, 1590 observations were classified as in-sequence vaccinations (last DTP before MV), and 1984 observations were out-of-sequence vaccinations (1491: MV with DTP and 493: MV before DTP). Out-of-sequence vaccinations were associated with higher mortality than in-sequence vaccinations (MRR 2.10, 95% CI 1.07 to 4.11); the MRR was 2.30 (95% CI 1.15 to 4.58) for MV with DTP and 1.45 (95% CI 0.50 to 4.22) for DTP after MV. Associations were similar for boys and girls (p=0.77). Between 18 and 35 months the mortality rate increased among children vaccinated in-sequence and the differential effect of out-of-sequence vaccinations disappeared.ConclusionOut-of-sequence vaccinations may increase child mortality. Hence, sequence of vaccinations should be considered when planning vaccination programmes or introducing new vaccines into the current vaccination schedule.

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Center-Specific Risk-Adjusted Standardized Mortality Rates on Continuous Ambulatory Peritoneal Dialysis in China

Peritoneal Dialysis International ◽

10.3747/pdi.2018.00085 ◽

2018 ◽

Vol 38 (2_suppl) ◽

pp. 36-44 ◽

Cited By ~ 2

Author(s):

Xueqing Yu ◽

Menghua Chen ◽

Jie Dong ◽

Hong Liu ◽

Zhangsuo Liu ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Mortality Rate ◽

Continuous Ambulatory Peritoneal Dialysis ◽

Fixed Effects ◽

Proportional Hazards ◽

Significant Proportion ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Standardized Mortality Ratios ◽

Expected Mortality

Background The aim of this study was to determine if there were centers in China with unusually high levels of risk-adjusted mortality in continuous ambulatory peritoneal dialysis (CAPD) patients. Methods We analyzed an inception cohort commencing CAPD between 1 January 2005 and 13 August 2015, followed until death, dropout defined as discontinuation of Baxter products, loss to follow-up, or 13 November 2015, whichever occurred first. We calculated standardized mortality ratios (SMRs) from Cox proportional hazards models, adjusting for age, gender, employment status, insurance status, primary renal disease, size of peritoneal dialysis (PD) program, and year of dialysis inception. We calculated 2 SMRs, 1 from models including a fixed effect for center of treatment, and 1 from stratified models. Results In this study, there was a 9.9% annual mortality rate in China, with decreasing mortality risk over time. There was significant variation of outcomes between Chinese centers, with up to 20% of facilities having SMRs indicating a higher risk-adjusted mortality rate than average. In particular, larger centers had better than expected mortality than smaller ones. There was significant misclassification of SMRs calculated using stratification versus fixed-effects models, although both showed directionally similar results. Conclusion Despite overall satisfactory and improving outcomes, our study showed a significant proportion of PD centers with higher than expected mortality. This is a signal for further assessment of these centers in China, after which there might be a range of actions taken depending on the results of the assessment and context, bearing in mind that the variation seen may be driven by factors unrelated to quality of care or beyond the control of hospital.

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Pre-ESRD Dementia and Post-ESRD Mortality in a Large Cohort of Incident Dialysis Patients

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000471761 ◽

2017 ◽

Vol 43 (5-6) ◽

pp. 281-293 ◽

Cited By ~ 5

Author(s):

Miklos Z. Molnar ◽

Keiichi Sumida ◽

Abduzhappar Gaipov ◽

Praveen K. Potukuchi ◽

Tibor Fülöp ◽

...

Keyword(s):

Mortality Rate ◽

Proportional Hazards ◽

International Classification Of Diseases ◽

Cox Proportional Hazards ◽

Dialysis Initiation ◽

Entire Cohort ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

All Cause Mortality ◽

Stage Renal Disease

Background: Conservative management may be a desirable option for elderly, fragile, or demented patients who reach end-stage renal disease (ESRD), yet some patients with dementia are placed on renal replacement therapy nonetheless. Methods: From a nationwide cohort of 45,076 US veterans who transitioned to ESRD over 4 contemporary years (October 1, 2007 to September 30, 2011), we identified 1,336 (3.0%) patients with International Classification of Diseases, Ninth Revision, Clinical Modification code-based dementia diagnosis during the prelude (predialysis) period. We examined the association of prelude dementia with all-cause mortality within the first 6 months following transition to dialysis, using a propensity-matched cohort and Cox proportional hazards models. Results: In the entire cohort, the overall mean ± standard deviation age at baseline was 72 ± 11 years, 95% were male, 23% were African-American, and 66% were diabetic. There were 8,080 (18.5%) deaths (mortality rate, 412; 95% confidence interval [CI], 403-421/1,000 patient-years) in the dementia-negative group, and 396 (29.6%) deaths (mortality rate, 708; 95% CI, 642-782/1,000 patient-years) in the dementia-positive group in the entire cohort in the first 6 months after dialysis initiation. Presence of dementia was associated with higher risk of all-cause mortality (adjusted hazard ratio, 1.25; 95% CI, 1.12-1.38) compared to dementia-free patients in the first 6 months after dialysis initiation. Conclusion: Pre-ESRD dementia is associated with increased risk of early post-ESRD mortality in veterans transitioning to dialysis.

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Neonatal BCG vaccination and child survival in TB-exposed and TB-unexposed children: a prospective cohort study

BMJ Open ◽

10.1136/bmjopen-2019-035595 ◽

2020 ◽

Vol 10 (2) ◽

pp. e035595 ◽

Cited By ~ 3

Author(s):

Sanne M Thysen ◽

Christine Stabell Benn ◽

Victor Francisco Gomes ◽

Frauke Rudolf ◽

Christian Wejse ◽

...

Keyword(s):

Cohort Study ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Proportional Hazards ◽

Child Survival ◽

Observation Time ◽

Cox Proportional Hazards ◽

Lower Mortality ◽

Bcg Vaccination ◽

Cox Proportional Hazards Models

ObjectivesTo assess the association between neonatal BCG vaccination and mortality between 28 days and 3 years of age among tuberculosis (TB)-exposed and TB-unexposed children.DesignProspective cohort study.SettingBandim Health Project runs an urban Health and Demographic Surveillance site in Guinea-Bissau with registration of mortality, vaccination status and TB cases.ParticipantsChildren entered the analysis when their vaccination card was inspected after 28 days of age and remained under surveillance to 3 years of age. Children residing in the same house as a TB case were classified as TB-exposed from 3 months prior to case registration to the end of follow-up.MethodsUsing Cox-proportional hazards models with age as underlying time scale, we compared mortality of children with and without neonatal BCG between October 2003 and September 2017.Main outcome measureHR for neonatal BCG compared with no neonatal BCG by TB-exposure status.ResultsAmong the 39 421 children who entered the analyses, 3022 (8%) had observation time as TB-exposed. In total, 84% of children received neonatal BCG. Children with neonatal BCG had lower mortality both in TB-exposed (adjusted HR: 0.57 (0.26 to 1.27)) and in TB-unexposed children (HR: 0.57 (95% CI 0.47 to 0.69)) than children without neonatal BCG. Children exposed to TB had higher mortality than TB-unexposed children if they had not received neonatal BCG.ConclusionNeonatal BCG vaccination was associated with lower mortality among both TB-exposed and TB-unexposed children, consistent with neonatal BCG vaccination having beneficial non-specific effects. Interventions to increase timely BCG vaccination are urgently warranted.

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Models to Assess the Association of a Semiquantitative Exposure With Outcomes

American Journal of Epidemiology ◽

10.1093/aje/kwaa071 ◽

2020 ◽

Vol 189 (12) ◽

pp. 1573-1582 ◽

Cited By ~ 1

Author(s):

John M Lachin ◽

Ionut Bebu ◽

Barbara Braffett

Keyword(s):

Risk Factor ◽

Proportional Hazards ◽

Factor Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Factor Effect ◽

The Mean ◽

The Difference ◽

Using Data ◽

Biased Estimates

Abstract A semiquantitative risk factor has 2 components: any exposure (yes/no) and the quantitative amount of exposure (if exposed). We describe the statistical properties of alternative analyses with such a risk factor using linear, logistic, or Cox proportional hazards models. Often analyses employ the amount exposed as a single quantitative covariate, including the nonexposed with value zero. However, this analysis provides a biased estimate of the exposure coefficient (slope) and we describe the magnitude of the bias. This bias can be eliminated by adding a binary covariate for exposed versus not to the model. This 2-factor analysis captures the full risk-factor effect on the outcome. However, the coefficient for any exposure versus not does not have a meaningful interpretation. Alternatively, when exposure values among those exposed are centered (by subtracting the mean), the estimate of this coefficient represents the difference in the outcome between those exposed versus not in aggregate. We also show that the biased model provides biased estimates of the coefficients for other covariates added to the model. Proper analysis of a semiquantitative risk factor should start with a 2-factor model, with centering, to assess the joint contributions of the 2 components of the risk-factor exposure. Properties of models were illustrated using data from a multisite study in North America (1983–2019).

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Regional differences in time off work after injury: a comparison of Australian states and territories within a single workers compensation system

10.1101/2020.07.23.20160416 ◽

2020 ◽

Cited By ~ 2

Author(s):

Tyler J Lane ◽

Luke R Sheehan ◽

Shannon E Gray ◽

Alex Collie

Keyword(s):

Proportional Hazards ◽

Reference Group ◽

Cox Proportional Hazards ◽

Compensation System ◽

Workers Compensation ◽

South Wales ◽

Compensation Systems ◽

Cox Proportional Hazards Models ◽

Regional Factors ◽

The Difference

Background Time off work after workplace injury varies by compensation system. While often attributed to features of the compensation system, unaccounted regional factors may drive much of the effect. In this study, we compare disability durations by state and territory of residence within a single national workers compensation system. Large differences would indicate that factors other than compensation system settings are responsible for system effects observed in previous studies. Methods We applied crude and adjusted Cox proportional hazards models to compare disability durations by state and territory of residence. Confounders included factors known to influence disability duration. Durations were left-censored at two weeks and right-censored at 104 weeks. Results We analysed N = 38,686 claims. In both crude and adjusted models, three of the seven states and territories significantly differed from the reference group, New South Wales. However, two of the three were different between crude and adjusted models. Regional effects were relatively small compared to other factors including insurer type, age, and type of injury. Conclusions Regional factors influence disability duration, which persist with adjustment for demographic, work, insurer type, and injury confounders. However, the effects are inconsistently significant and fairly small, especially when compared to the effect of confounders and system effects found in previous studies. Regional factors likely only account for a small share of the difference in disability duration between compensation systems.

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Higher Intake of Sulfur Amino Acids Is Associated with Greater Mortality Among US Adults: NHANESIII Cohort Study (P18-061-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz039.p18-061-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Zhen Dong ◽

Xiang Gao ◽

Vernon Chinchilli ◽

Joshua Muscat ◽

John Richie

Keyword(s):

Amino Acids ◽

Proportional Hazards ◽

The United States ◽

Cox Proportional Hazards ◽

Dietary Factors ◽

Sulfur Amino Acids ◽

Negative Effects ◽

Diabetes Mortality ◽

Cox Proportional Hazards Models ◽

Protein Density

Abstract Objectives Preclinical evidence has suggested that low consumptions of sulfur amino acids (SAA) methionine (Met) and cysteine (Cys) are associated with a variety of health benefits including delayed aging and lower incidence of aging-related diseases including diabetes. Further, in the United States, the average person consumes SAA at levels far in excess of the Recommended Dietary Allowance (RDA) and a variety of negative effects of excess SAA intake have been reported. However, there is little data regarding the relationship between SAA intake and health status in humans. We thus prospectively analyzed the associations between SAA intake and all-cause and disease-specific mortality rates in a large cohort of US adults participating in the Third National Examination and Nutritional Health Survey (NHANES III) Study. Methods Dietary intake of SAA was assessed via a 24-h recall questionnaire. Mortality cases were assessed via search in the National Death Index. Hazard ratios (HR) were calculated from Cox proportional hazards models to evaluate associations between intakes of SAAs intake (in quintiles) and risk of mortality. Models were adjusted for age, sex, body mass index (BMI), smoking, alcohol intake, dietary factors, and disease history. Results A total of 3594 mortality events out of 12,395 eligible participants occurred during 23 years of follow-up. After full adjustment, absolute intake of higher Met, Cys, and total SAA were associated with increases in all-cause mortality (HR = 1.13 (1.00–1.13), 1.15 (1.01–1.30), 1.13 (1.00–1.27), respectively), and in diabetes mortality (HR = 3.00 (1.53–5.70), 3.26(1.65–6.46), 3.81(1.87–7.77), respectively). No associations were found with other causes of mortality. When SAA intake was expressed as protein density, only Cys and total SAA intake were positively associated with increased diabetes mortality (P < 0.02). Conclusions Overall, these data support our hypothesis that higher consumption of SAA is associated with increased mortality. Given the high intake of SAA among the US population, our findings may have important public health implications. Funding Sources This study was not externally funded. Supporting Tables, Images and/or Graphs

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PETCO2 gradient: a novel prognostic parameter in cardiopulmonary exercise testing

European Heart Journal ◽

10.1093/ehjci/ehaa946.1077 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

I.D Poveda Pinedo ◽

I Marco Clement ◽

O Gonzalez ◽

I Ponz ◽

A.M Iniesta ◽

...

Keyword(s):

Exercise Testing ◽

Proportional Hazards ◽

Cardiopulmonary Exercise Testing ◽

Cox Proportional Hazards ◽

Prognostic Parameter ◽

Cardiopulmonary Exercise ◽

Proportional Hazards Regression ◽

Kaplan Meier ◽

Baseline Characteristics ◽

The Difference

Abstract Background Previous parameters such as peak VO2, VE/VCO2 slope and OUES have been described to be prognostic in heart failure (HF). The aim of this study was to identify further prognostic factors of cardiopulmonary exercise testing (CPET) in HF patients. Methods A retrospective analysis of HF patients who underwent CPET from January to November 2019 in a single centre was performed. PETCO2 gradient was defined by the difference between final PETCO2 and baseline PETCO2. HF events were defined as decompensated HF requiring hospital admission or IV diuretics, or decompensated HF resulting in death. Results A total of 64 HF patients were assessed by CPET, HF events occurred in 8 (12.5%) patients. Baseline characteristics are shown in table 1. Patients having HF events had a negative PETCO2 gradient while patients not having events showed a positive PETCO2 gradient (−1.5 [IQR −4.8, 2.3] vs 3 [IQR 1, 5] mmHg; p=0.004). A multivariate Cox proportional-hazards regression analysis revealed that PETCO2 gradient was an independent predictor of HF events (HR 0.74, 95% CI [0.61–0.89]; p=0.002). Kaplan-Meier curves showed a significantly higher incidence of HF events in patients having negative gradients, p=0.002 (figure 1). Conclusion PETCO2 gradient was demonstrated to be a prognostic parameter of CPET in HF patients in our study. Patients having negative gradients had worse outcomes by having more HF events. Time to first event, decompensated heart Funding Acknowledgement Type of funding source: None

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A semi-supervised approach for rapidly creating clinical biomarker phenotypes in the UK Biobank using different primary care EHR and clinical terminology systems

JAMIA Open ◽

10.1093/jamiaopen/ooaa047 ◽

2020 ◽

Author(s):

Spiros Denaxas ◽

Anoop D Shah ◽

Bilal A Mateen ◽

Valerie Kuan ◽

Jennifer K Quint ◽

...

Keyword(s):

Primary Care ◽

Proportional Hazards ◽

Biomarker Discovery ◽

Data Extraction ◽

Cox Proportional Hazards ◽

Research Quality ◽

Uk Biobank ◽

Expert Review ◽

Cox Proportional Hazards Models ◽

The Uk

Abstract Objectives The UK Biobank (UKB) is making primary care electronic health records (EHRs) for 500 000 participants available for COVID-19-related research. Data are extracted from four sources, recorded using five clinical terminologies and stored in different schemas. The aims of our research were to: (a) develop a semi-supervised approach for bootstrapping EHR phenotyping algorithms in UKB EHR, and (b) to evaluate our approach by implementing and evaluating phenotypes for 31 common biomarkers. Materials and Methods We describe an algorithmic approach to phenotyping biomarkers in primary care EHR involving (a) bootstrapping definitions using existing phenotypes, (b) excluding generic, rare, or semantically distant terms, (c) forward-mapping terminology terms, (d) expert review, and (e) data extraction. We evaluated the phenotypes by assessing the ability to reproduce known epidemiological associations with all-cause mortality using Cox proportional hazards models. Results We created and evaluated phenotyping algorithms for 31 biomarkers many of which are directly related to COVID-19 complications, for example diabetes, cardiovascular disease, respiratory disease. Our algorithm identified 1651 Read v2 and Clinical Terms Version 3 terms and automatically excluded 1228 terms. Clinical review excluded 103 terms and included 44 terms, resulting in 364 terms for data extraction (sensitivity 0.89, specificity 0.92). We extracted 38 190 682 events and identified 220 978 participants with at least one biomarker measured. Discussion and conclusion Bootstrapping phenotyping algorithms from similar EHR can potentially address pre-existing methodological concerns that undermine the outputs of biomarker discovery pipelines and provide research-quality phenotyping algorithms.

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Changes in Metabolic Syndrome Status and Breast Cancer Risk: A Nationwide Cohort Study

Cancers ◽

10.3390/cancers13051177 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1177

Author(s):

In Young Choi ◽

Sohyun Chun ◽

Dong Wook Shin ◽

Kyungdo Han ◽

Keun Hye Jeon ◽

...

Keyword(s):

Breast Cancer ◽

Metabolic Syndrome ◽

Proportional Hazards ◽

Screening Program ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Increased Risk ◽

Health Screening Program ◽

Design And Methods

Objective: To our knowledge, no studies have yet looked at how the risk of developing breast cancer (BC) varies with changes in metabolic syndrome (MetS) status. This study aimed to investigate the association between changes in MetS and subsequent BC occurrence. Research Design and Methods: We enrolled 930,055 postmenopausal women aged 40–74 years who participated in a biennial National Health Screening Program in 2009–2010 and 2011–2012. Participants were categorized into four groups according to change in MetS status during the two-year interval screening: sustained non-MetS, transition to MetS, transition to non-MetS, and sustained MetS. We calculated multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for BC incidence using the Cox proportional hazards models. Results: At baseline, MetS was associated with a significantly increased risk of BC (aHR 1.11, 95% CI 1.06–1.17) and so were all of its components. The risk of BC increased as the number of the components increased (aHR 1.46, 95% CI 1.26–1.61 for women with all five components). Compared to the sustained non-MetS group, the aHR (95% CI) for BC was 1.11 (1.04–1.19) in the transition to MetS group, 1.05 (0.96–1.14) in the transition to non-MetS group, and 1.18 (1.12–1.25) in the sustained MetS group. Conclusions: Significantly increased BC risk was observed in the sustained MetS and transition to MetS groups. These findings are clinically meaningful in that efforts to recover from MetS may lead to reduced risk of BC.

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