The role of epidemiology in informing United States childhood immunization policy and practice.

One of the ten greatest public health achievements is childhood vaccination because of its impact on controlling and eliminating vaccine-preventable diseases (VPDs). Evidence-based immunization policies and practices are responsible for this success and are supported by epidemiology that has generated scientific evidence for informing policy and practice. The purpose of this report is to highlight the role of epidemiology in the development of immunization policy and successful intervention in public health practice that has resulted in a measurable public health impact: the control and elimination of VPDs in the United States. Examples in which epidemiology informed immunization policy were collected from a literature review and consultation with experts who have been working in this field for the past 30 years. Epidemiologic examples (e.g., thimerosal-containing vaccines and the alleged association between the measles, mumps, and rubella (MMR) vaccine and autism) are presented to describe challenges that epidemiologists have addressed. Finally, we describe ongoing challenges to the nation's ability to sustain high vaccination coverage, particularly with concerns about vaccine safety and effectiveness, increasing use of religious and philosophical belief exemptions to vaccination, and vaccine hesitancy. Learning from past and current experiences may help epidemiologists anticipate and address current and future challenges to respond to emerging infectious diseases, such as COVID-19, with new vaccines and enhance the public health impact of immunization programs for years to come.

An unusual case of alpha-1-antitrypsin deficiency: SZ/Z.

A female patient was first seen at age 65 due to a diagnosis of alpha-1-antitrypsin deficiency (AATD). She was a lifelong non-smoker, with no significant history of second hand smoke exposure. There was no prior family history of AATD or liver disease. Her serum AAT concentration was measured on two occasions and in both cases, concentration was <0.21 g/L. The patient was referred for genetic testing to determine her SERPINA1 (the gene responsible for AATD) genotype. Three deficiency alleles were identified: she was heterozygous for S, a mild deficiency allele, and homozygous for Z, a severe deficiency allele. This case represents unusual convergence of three pathogenic SERPINA1 variants in a single individual. We report the investigations used to clarify her unusual genotype and propose non-crossover gene conversion as the likely mechanism.

Pre-Kidney Transplant Lower Extremity Impairment and Post-Kidney Transplant Mortality.

Prediction models for post-kidney transplantation mortality have had limited success (C-statistics ≤0.70). Adding objective measures of potentially modifiable factors may improve prediction and, consequently, kidney transplant (KT) survival through intervention. The Short Physical Performance Battery (SPPB) is an easily administered objective test of lower extremity function consisting of three parts (balance, walking speed, chair stands), each with scores of 0-4, for a composite score of 0-12, with higher scores indicating better function. SPPB performance and frailty (Fried frailty phenotype) were assessed at admission for KT in a prospective cohort of 719 KT recipients at Johns Hopkins Hospital (8/2009 to 6/2016) and University of Michigan (2/2013 to 12/2016). The independent associations between SPPB impairment (SPPB composite score ≤10) and composite score with post-KT mortality were tested using adjusted competing risks models treating graft failure as a competing risk. The 5-year posttransplantation mortality for impaired recipients was 20.6% compared to 4.5% for unimpaired recipients (p < 0.001). Impaired recipients had a 2.30-fold (adjusted hazard ratio [aHR] 2.30, 95% confidence interval [CI] 1.12-4.74, p = 0.02) increased risk of postkidney transplantation mortality compared to unimpaired recipients. Each one-point decrease in SPPB score was independently associated with a 1.19-fold (95% CI 1.09-1.30, p < 0.001) higher risk of post-KT mortality. SPPB-derived lower extremity function is a potentially highly useful and modifiable objective measure for pre-KT risk prediction.

Induction Immunosuppression and Clinical Outcomes in Kidney Transplant Recipients Infected With Human Immunodeficiency Virus.

There is an increased risk of acute rejection (AR) in human immunodeficiency virus-positive (HIV+) kidney transplant (KT) recipients. Induction immunosuppression is standard of care for those at high risk of AR; however, use in HIV+ patients is controversial, given fears of increased infection rates. We sought to compare clinical outcomes between HIV+ KT recipients who were treated with (i) anti-thymocyte globulin (ATG), (ii) IL-2 receptor blocker, and (iii) no induction. We studied 830 HIV+ KT recipients between 2000 and 2014, as captured in the Scientific Registry of Transplant Recipients, and compared rates of delayed graft function (DGF), AR, graft loss and death. Infections and hospitalizations were ascertained by International Classification of Diseases, Ninth Revision codes in a subset of 308 patients with Medicare. Compared with no induction, neither induction agent was associated with an increased risk of infection (weighted hazard ratio [wHR] 0.80, 95% confidence interval [CI] 0.55-1.18). HIV+ recipients who received induction spent fewer days in the hospital (weighted relative risk [wRR] 0.70, 95% CI 0.52-0.95), had lower rates of DGF (wRR 0.66, 95% CI 0.51-0.84), less graft loss (wHR 0.47, 95% CI 0.24-0.89) and a trend toward lower mortality (wHR 0.60, 95% CI 0.24-1.28). Those who received induction with ATG had lower rates of AR (wRR 0.59, 95% CI 0.35-0.99). Induction in HIV+ KT recipients was not associated with increased infections; in fact, those receiving ATG, the most potent agent, had the lowest rates. In light of the high risk of AR in this population, induction therapy should be strongly considered.

Early Hospital Readmission After Simultaneous Pancreas-Kidney Transplantation: Patient and Center-Level Factors.

Early hospital readmission is associated with increased morbidity, mortality, and cost. Following simultaneous pancreas-kidney transplantation, rates of readmission and risk factors for readmission are unknown. We used United States Renal Data System data to study 3643 adult primary first-time simultaneous pancreas-kidney recipients from December 1, 1999 to October 31, 2011. Early hospital readmission was any hospitalization within 30 days of discharge. Modified Poisson regression was used to determine the association between readmission and patient-level factors. Empirical Bayes statistics were used to determine the variation attributable to center-level factors. The incidence of readmission was 55.5%. Each decade increase in age was associated with an 11% lower risk of readmission to age 40, beyond which there was no association. Donor African-American race was associated with a 13% higher risk of readmission. Each day increase in length of stay was associated with a 2% higher risk of readmission until 14 days, beyond which each day increase was associated with a 1% reduction in the risk of readmission. Center-level factors were not associated with readmission. The high incidence of early hospital readmission following simultaneous pancreas-kidney transplant may reflect clinical complexity rather than poor quality of care.

Frailty and Health-Related Quality of Life in End Stage Renal Disease Patients of All Ages.

BACKGROUND: Frailty is associated with worse health-related quality of life (HRQOL) in older adults and worse clinical outcomes in adults of all ages with end stage renal disease (ESRD). It is unclear whether frail adults of all ages with ESRD are more likely to experience worse HRQOL. OBJECTIVE: The goal of this study was to identify factors associated with worsening HRQOL in this population. DESIGN, SETTING AND MEASUREMENTS: We studied 233 adults of all ages with ESRD enrolled (11/2009-11/2013) in a longitudinal cohort study. Frailty status was measured at enrollment and HRQOL was reported (Excellent, Very Good, Good, Fair or Poor) at the initial assessment and follow-up (median follow-up 9.4 months). We studied factors associated with Fair/Poor HRQOL at follow-up using logistic regression and factors associated with HRQOL change using multinomial regression. All models were adjusted for age, sex, race, education, BMI, diabetes status, history of a previous transplant, type of dialysis and time between assessments. RESULTS: Fair/Poor HRQOL was reported by 28% at initial assessment and 33% at follow-up. 47.2% of participants had stable HRQOL, 22.8% better HRQOL, and 30.0% worse HRQOL at follow-up (P<0.001). In adjusted models, only frailty was associated with Fair/Poor HRQOL at follow-up (OR: 2.79, 95% CI: 1.32-5.90) and worsening HRQOL at follow-up (RR: 2.91, 95%CI: 1.08-7.80). CONCLUSIONS: Frail adults of all ages with ESRD are more likely to experience fair/poor HRQOL and worsening HRQOL over time. Frailty represents a state of decreased physiologic reserve that impacts not only clinical outcomes but also the patient-centered outcome of HRQOL.

Frailty and mortality in kidney transplant recipients.

We have previously described strong associations between frailty, a measure of physiologic reserve initially described and validated in geriatrics, and early hospital readmission as well as delayed graft function. The goal of this study was to estimate its association with postkidney transplantation (post-KT) mortality. Frailty was prospectively measured in 537 KT recipients at the time of transplantation between November 2008 and August 2013. Cox proportional hazards models were adjusted for confounders using a novel approach to substantially improve model efficiency and generalizability in single-center studies. We precisely estimated the confounder coefficients using the large sample size of the Scientific Registry of Transplantation Recipients (n = 37 858) and introduced these into the single-center model, which then estimated the adjusted frailty coefficient. At 5 years, the survivals were 91.5%, 86.0% and 77.5% for nonfrail, intermediately frail and frail KT recipients, respectively. Frailty was independently associated with a 2.17-fold (95% CI: 1.01-4.65, p = 0.047) higher risk of death. In conclusion, regardless of age, frailty is a strong, independent risk factor for post-KT mortality, even after carefully adjusting for many confounders using a novel, efficient statistical approach.

Sequelae of early hospital readmission after kidney transplantation.

We recently elucidated risk factors for early hospital readmission (EHR) following kidney transplantation (KT). We now sought to quantify the independent associations between EHR and post-KT outcomes, including late hospital readmission (LHR: 1 year after EHR window), death-censored graft loss and mortality, among Medicare-primary KT recipients (2000-2005). Of 32961 KT recipients, 7.7% had at least one readmission within 3 days of discharge, 14.8% within 7 days, 22.4% within 14 days and 30.5% within 30 days of discharge after the initial KT hospitalization. KT recipients who experienced EHR within 30 days of discharge after the initial KT hospitalization were more likely to have experienced LHR (29.6% vs. 9.0%, p<0.001) and were at 3.02 times higher (95% CI: 2.82-3.23, p<0.001) risk of LHR. Additionally, EHR was associated with death-censored graft loss (deceased donor recipients hazard ratio [HR]: 1.43, 95% CI: 1.36-1.51, p<0.001 and live donor recipients HR: 1.54, 95% CI: 1.40-1.70, p<0.001) and mortality (deceased donor recipients HR: 1.50, 95% CI: 1.43-1.58, p<0.001 and live donor recipients HR: 1.45, 95% CI: 1.32-1.60, p<0.001). Thirty days posttransplant represents a high-risk window for KT recipients and the readmissions during this window are strong predictors of adverse sequelae, particularly LHRs. Efforts should be made to implement and improve systems to reduce LHR and subsequent graft loss and mortality among recipients with EHR.

Frailty and early hospital readmission after kidney transplantation.

Early hospital readmission (EHR) after kidney transplantation (KT) is associated with increased morbidity and higher costs. Registry-based recipient, transplant and center-level predictors of EHR are limited, and novel predictors are needed. We hypothesized that frailty, a measure of physiologic reserve initially described and validated in geriatrics and recently associated with early KT outcomes, might serve as a novel, independent predictor of EHR in KT recipients of all ages. We measured frailty in 383 KT recipients at Johns Hopkins Hospital. EHR was ascertained from medical records as ≥1 hospitalization within 30 days of initial post-KT discharge. Frail KT recipients were much more likely to experience EHR (45.8% vs. 28.0%, p = 0.005), regardless of age. After adjusting for previously described registry-based risk factors, frailty independently predicted 61% higher risk of EHR (adjusted RR = 1.61, 95% CI: 1.18-2.19, p = 0.002). In addition, frailty improved EHR risk prediction by improving the area under the receiver operating characteristic curve (p = 0.01) as well as the net reclassification index (p = 0.04). Identifying frail KT recipients for targeted outpatient monitoring and intervention may reduce EHR rates.

Early hospital readmission after kidney transplantation: patient and center-level associations.

Early hospital readmission (EHR) is associated with increased morbidity, costs and transition-of-care errors. We sought to quantify rates of and risk factors for EHR after kidney transplantation (KT). We studied 32 961 Medicare primary KT recipients (2000-2005) linked to Medicare claims through the United States Renal Data System. EHR was defined as at least one hospitalization within 30 days of initial discharge after KT. The association between EHR and recipient and transplant factors was explored using Poisson regression; hierarchical modeling was used to account for study center-level differences. The overall EHR rate was 31%, and 19 independent patient-level factors associated with EHR were identified: recipient factors included older age, African American race and various comorbidities; transplant factors included ECD, length of stay and lack of induction therapy. The unadjusted rate of EHR by center ranged from 18% to 47%, but conventional center-level factors (percent African American, percent age > 60, percent deceased donor and percent expanded criteria donor) were not associated with EHR. However, intermediate total volume and average length of stay were associated with increased EHR risk. Better identification of patients at risk for early hospital readmission following KT may guide discharge planning and early posttransplant outpatient monitoring.

Development of an information management system using a strategic planning process.

This article details the development of an information management system to facilitate the ability of clinicians to identify risk factors present in low-birthweight deliveries and to determine geographic clusters of risk factors. These data would serve as a basis for planning clinical interventions at the community level. The strategic planning process provided a framework for successful design and implementation of the information management system.

Breast cancer estrogen and progesterone receptors.

Data from 2933 consecutive cases of primary breast carcinoma, observed in our Institute from 1984 to 1994, having documented estrogen (ER) and progesterone (PR) receptor levels, were obtained from the Institute's Hospital Tumor Registry and analysed after being categorised as follows: age, less than or equal to 60 vs. >60; menopausal status, pre-menopausal vs. post-menopausal; histology, ductal vs. lobular vs. others; tumor size, T-1 vs. T-2, T-3, T-4; nodal status, N-0, vs. N+; histologic grade, 1-2 vs. 3; focality, unifocal vs. multifocal; ER status, <10 fmol/mg protein vs. greater than or equal to 15. At multivariate analysis, using a logistic model including age, histology, tumor size, nodal status, histologic grade, uni-multifocality and PGF/ER status, significant associations were, for ER status: PGR status (OR = 34.01, 95% CI:20.08-57.80), histology (OR = 3.24, 95% CI:1.85-5.67), histologic grade (OR = 2.18, 95% CI:1.38-3.42), menopausal status (OR = 2.17, 95% CI:1.26-3.74), age (OR = 34.01, 95% CI:20.08-57.80), menopausal status (OR = 5.27, 95% CI:1.43-3.33), age (OR = 1.71, 95% CI:1.13-2.59). The finding that estrogen receptor positivity was more prevalent among tumors with lobular histology seems to suggest the possibility of fundamental differences in tumor biology ductal and lobular cancers.