Publications by authors named "Al Ozonoff"

170 Publications

Pediatric Hospital Readmissions for Infants With Neonatal Opioid Withdrawal Syndrome, 2016-2019.

Hosp Pediatr 2021 Sep;11(9):979-988

Division of Infectious Diseases, Boston Children's Hospital, Boston, Massachusetts.

Background And Objectives: Neonatal opioid withdrawal syndrome (NOWS) is associated with long and costly birth hospitalization and increased readmission risk. Our objective was to examine readmissions in the first year of life for infants diagnosed with NOWS compared with infants without NOWS, adjusting for sociodemographic and clinical factors, and to describe use during readmissions in this population.

Methods: Using data from the Pediatric Health Information System, we identified singleton term infants with NOWS and without NOWS or other major condition (by diagnosis codes and All Patient Refined Diagnosis Related Groups coding, respectively) discharged from 2016 to 2019. We predicted time to first readmission within the first year of life using Cox regression analysis. Predictors included NOWS diagnosis, sociodemographic factors, birth NICU use, and birth weight.

Results: We included 155 885 birth discharges from 17 hospitals ( = 1467 NOWS) with 10 087 readmissions. Unadjusted 1-year readmission rates were 9.9% among NOWS infants versus 6.2% among those without NOWS. The adjusted hazard ratio for readmission within the first year was 1.76 (95% confidence interval: 1.40-2.22) for infants with NOWS versus those without. Readmissions for infants with NOWS were longer and costlier and more likely to require intensive care and mechanical ventilation. Readmissions among infants without NOWS were most commonly for jaundice and respiratory and other infections, whereas respiratory infections were the leading cause of readmissions among NOWS infants.

Conclusions: Infants with a NOWS diagnosis were more likely to be readmitted within the first year of life. In future work, researchers should explore potential interventions to prevent readmissions and provide resources to families affected by opioid dependence.
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http://dx.doi.org/10.1542/hpeds.2021-005904DOI Listing
September 2021

Testing the Use of Data Drawn from the Electronic Health Record to Compare Quality.

Pediatr Qual Saf 2021 Jul-Aug;6(4):e432. Epub 2021 Jul 28.

Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pa.

Introduction: Health systems spend $1.5 billion annually reporting data on quality, but efficacy and utility for benchmarking are limited due, in part, to limitations of data sources. Our objective was to implement and evaluate measures of pediatric quality for three conditions using electronic health record (EHR)-derived data.

Methods: PCORnet networks standardized EHR-derived data to a common data model. In 13 health systems from 2 networks for 2015, we implemented the National Quality Forum measures: % children with sickle cell anemia who received a transcranial Doppler; % children on antipsychotics who had metabolic screening; and % pediatric acute otitis media with amoxicillin prescribed. Manual chart review assessed measure accuracy.

Results: Only 39% (N = 2,923) of 7,278 children on antipsychotics received metabolic screening (range: 20%-54%). If the measure indicated screening was performed, the chart agreed 88% of the time [95% confidence interval (CI): 81%-94%]; if it indicated screening was not done, the chart agreed 86% (95% CI: 78%-93%). Only 69% (N = 793) of 1,144 children received transcranial Doppler screening (range across sites: 49%-88%). If the measure indicated screening was performed, the chart agreed 98% of the time (95% CI: 94%-100%); if it indicated screening was not performed, the chart agreed 89% (95% CI: 82%-95%). For acute otitis media, chart review identified many qualifying cases missed by the National Quality Forum measure, which excluded a common diagnostic code.

Conclusions: Measures of healthcare quality developed using EHR-derived data were valid and identified wide variation among network sites. This data can facilitate the identification and spread of best practices.
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http://dx.doi.org/10.1097/pq9.0000000000000432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322494PMC
July 2021

Variation in hospital performance measures from the Turkey Ministry of Health.

Int J Qual Health Care 2021 Aug;33(3)

Precision Vaccines Program, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.

Background: The Turkish healthcare system has seen broad population-based improvements in expanded health insurance coverage and access to healthcare services. Hospital performance in this national system is understudied. We aimed to identify trends in hospital performance over time following implementation of the Health Transformation Program and describe how regional outcomes correlate with regional vital statistics.

Objective: We examine hospital performance data collected by the PHA from 2013 to 2015. We aim to identify the temporal variation in hospital performance for nearly 30 individual measures and to describe the relationship between hospital-level performance measures and regional vital statistics.

Methods: We conducted a retrospective cohort study of 674 public hospitals in Turkey using baseline data from 2013 and follow-up data from 2014-15 collected by the Turkish Statistical Institution and the Public Hospital Agency. We report demographic and socioeconomic data across 12 geographic regions and analyze 29 hospital-level performance measures across four domains: (i) health services; (ii) administrative services; (iii) financial services and (iv) quality measures. We examine temporal variation, and study correlation between performance measures and regional vital statistics. We fit mixed-effects linear regression models to estimate linear trend over time accounting for within-hospital residual correlation. We prepared our manuscript in accordance with guidelines set by the STROBE statement for cohort studies.

Results: During the 3 years of study period, 21 of 29 measures improved and 8 measures worsened. All but three measures demonstrated significant differences across regions of the country. Several measures, including inpatient efficiency, patient satisfaction and audit score, are associated with regional infant mortality and life expectancy.

Conclusions: Evidence of temporal improvement in hospital-level performance may suggest some positive changes within the Turkish national healthcare system. Correlation of some measures with regional level health outcomes suggests a quality measurement strategy to monitor performance changes in the future. Although hospital-level functions have improved performance, the results of our study may help achieve further improvement for the health of the country's citizens.
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http://dx.doi.org/10.1093/intqhc/mzab109DOI Listing
August 2021

Human Newborn Monocytes Demonstrate Distinct BCG-Induced Primary and Trained Innate Cytokine Production and Metabolic Activation .

Front Immunol 2021 13;12:674334. Epub 2021 Jul 13.

Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, United States.

Background: Newborns exhibit distinct immune responses and are at high risk of infection. Neonatal immunization with BCG, the live attenuated vaccine against tuberculosis (TB), is associated with broad protection against a range of unrelated pathogens, possibly reflecting vaccine-induced training of innate immune cells ("innate memory"). However, little is known regarding the impact of age on BCG-induced innate responses.

Objective: Establish an age-specific human monocyte training platform to characterize and compare BCG-induced primary and memory cytokine responses and immunometabolic shifts.

Design/methods: Human neonatal and adult CD33-selected monocytes were stimulated for 24h with RPMI (control) or BCG (Danish strain) in 10% autologous serum, washed and cultured for 5 additional days, prior to re-stimulation with the TLR4 agonist LPS for another 24h. Supernatants were collected at Day 1 (D1) to measure innate responses and at Day 7 (D7) to assess innate responses by ELISA and multiplex cytokine and chemokine assays. Lactate, a signature metabolite increased during trained immunity, was measured by colorimetric assay.

Results: Cytokine production by human monocytes differed significantly by age at D1 (primary, BCG 1:750 and 1:100 vol/vol, p<0.0001) and D7 (innate memory response, BCG 1:100 vol/vol, p<0.05). Compared to RPMI control, newborn monocytes demonstrated greater TNF (1:100, 1:10 vol/vol, p<0.01) and IL-12p40 (1:100 vol/vol, p<0.05) production than adult monocytes (1:100, p<0.05). At D7, while BCG-trained adult monocytes, as previously reported, demonstrated enhanced LPS-induced TNF production, BCG-trained newborn monocytes demonstrated tolerization, as evidenced by significantly diminished subsequent LPS-induced TNF (RPMI vs. BCG 1:10, p <0.01), IL-10 and CCL5 production (p<0.05). With the exception of IL-1RA production by newborn monocytes, BCG-induced monocyte production of D1 cytokines/chemokines was inversely correlated with D7 LPS-induced TNF in both age groups (p<0.0001). Compared to BCG-trained adult monocytes, newborn monocytes demonstrated markedly impaired BCG-induced production of lactate, a metabolite implicated in immune training in adults.

Conclusions: BCG-induced human monocyte primary- and memory-innate cytokine responses were age-dependent and accompanied by distinct immunometabolic shifts that impact both glycolysis and training. Our results suggest that immune ontogeny may shape innate responses to live attenuated vaccines, suggesting age-specific approaches to leverage innate training for broad protection against infection.
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http://dx.doi.org/10.3389/fimmu.2021.674334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315003PMC
July 2021

Health-related quality of life among colorectal cancer survivors of diverse sexual orientations.

Cancer 2021 Jul 8. Epub 2021 Jul 8.

Department of Population and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts.

Background: The purpose of this study was to examine the health-related quality of life of sexual minority survivors in comparison with heterosexual survivors.

Methods: Four hundred eighty eligible survivors participated in a telephone survey that measured survivors' outcomes, which consisted of physical and mental quality of life and self-rated fair or poor health. These survivors were diagnosed with stage I, II, or III colorectal cancer an average of 3 years before the survey and were recruited from 4 cancer registries. Using forward selection with generalized linear models or logistic regression models, the authors considered 4 domains-personal factors, environmental factors, health condition characteristics, and body function and structure-as correlates for each survivorship outcome.

Results: The authors found that unadjusted physical quality of life and self-rated fair/poor health were similar for all survivors. Sexual minority survivors had poorer unadjusted mental quality of life in comparison with heterosexual survivors. After adjustments for covariates, this difference was no longer statistically significant. Three domains (personal factors, health condition characteristics, and body function and structure) explained colorectal cancer survivors' fair/poor health and 46% of the variance in physical quality of life, whereas 56% of the variance in mental quality of life was explained by personal factors, body function and structure, and environmental factors.

Conclusions: This study has identified modifiable factors that can be used to improve cancer survivors' quality of life and are, therefore, relevant to ongoing efforts to improve the survivorship experience.
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http://dx.doi.org/10.1002/cncr.33762DOI Listing
July 2021

Plasma Adenosine Deaminase (ADA)-1 and -2 Demonstrate Robust Ontogeny Across the First Four Months of Human Life.

Front Immunol 2021 27;12:578700. Epub 2021 May 27.

Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, United States.

Background: Human adenosine deaminases (ADAs) modulate the immune response: ADA1 metabolizing adenosine, a purine metabolite that inhibits pro-inflammatory and Th1 cytokine production, and the multi-functional ADA2, by enhancing T-cell proliferation and monocyte differentiation. Newborns are relatively deficient in ADA1 resulting in elevated plasma adenosine concentrations and a Th2/anti-inflammatory bias compared to adults. Despite the growing recognition of the role of ADAs in immune regulation, little is known about the ontogeny of ADA concentrations.

Methods: In a subgroup of the EPIC002-study, clinical data and plasma samples were collected from 540 Gambian infants at four time-points: day of birth; first week of life; one month of age; and four months of age. Concentrations of total extracellular ADA, ADA1, and ADA2 were measured by chromogenic assay and evaluated in relation to clinical data. Plasma cytokines/chemokine were measured across the first week of life and correlated to ADA concentrations.

Results: ADA2 demonstrated a steady rise across the first months of life, while ADA1 concentration significantly decreased 0.79-fold across the first week then increased 1.4-fold by four months of life. Males demonstrated significantly higher concentrations of ADA2 (1.1-fold) than females at four months; newborns with early-term (37 to <39 weeks) and late-term (≥41 weeks) gestational age demonstrated significantly higher ADA1 at birth (1.1-fold), and those born to mothers with advanced maternal age (≥35 years) had lower plasma concentrations of ADA2 at one month (0.93-fold). Plasma ADA1 concentrations were positively correlated with plasma CXCL8 during the first week of life, while ADA2 concentrations correlated positively with TNFα, IFNγ and CXCL10, and negatively with IL-6 and CXCL8.

Conclusions: The ratio of plasma ADA2/ADA1 concentration increased during the first week of life, after which both ADA1 and ADA2 increased across the first four months of life suggesting a gradual development of Th1/Th2 balanced immunity. Furthermore, ADA1 and ADA2 were positively correlated with cytokines/chemokines during the first week of life. Overall, ADA isoforms demonstrate robust ontogeny in newborns and infants but further mechanistic studies are needed to clarify their roles in early life immune development and the correlations with sex, gestational age, and maternal age that were observed.
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http://dx.doi.org/10.3389/fimmu.2021.578700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190399PMC
June 2021

Bell's palsy and SARS-CoV-2 vaccines-an unfolding story - Authors' reply.

Lancet Infect Dis 2021 09 7;21(9):1211-1212. Epub 2021 Jun 7.

Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.

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http://dx.doi.org/10.1016/S1473-3099(21)00323-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184123PMC
September 2021

Alum:CpG adjuvant enables SARS-CoV-2 RBD-induced protection in aged mice and synergistic activation of human elder type 1 immunity.

bioRxiv 2021 May 21. Epub 2021 May 21.

Global deployment of vaccines that can provide protection across several age groups is still urgently needed to end the COVID-19 pandemic especially for low- and middle-income countries. While vaccines against SARS-CoV-2 based on mRNA and adenoviral-vector technologies have been rapidly developed, additional practical and scalable SARS-CoV-2 vaccines are needed to meet global demand. In this context, protein subunit vaccines formulated with appropriate adjuvants represent a promising approach to address this urgent need. Receptor-binding domain (RBD) is a key target of neutralizing antibodies (Abs) but is poorly immunogenic. We therefore compared pattern recognition receptor (PRR) agonists, including those activating STING, TLR3, TLR4 and TLR9, alone or formulated with aluminum hydroxide (AH), and benchmarked them to AS01B and AS03-like emulsion-based adjuvants for their potential to enhance RBD immunogenicity in young and aged mice. We found that the AH and CpG adjuvant formulation (AH:CpG) demonstrated the highest enhancement of anti-RBD neutralizing Ab titers in both age groups (∼80-fold over AH), and protected aged mice from the SARS-CoV-2 challenge. Notably, AH:CpG-adjuvanted RBD vaccine elicited neutralizing Abs against both wild-type SARS-CoV-2 and B.1.351 variant at serum concentrations comparable to those induced by the authorized mRNA BNT162b2 vaccine. AH:CpG induced similar cytokine and chemokine gene enrichment patterns in the draining lymph nodes of both young adult and aged mice and synergistically enhanced cytokine and chemokine production in human young adult and elderly mononuclear cells. These data support further development of AH:CpG-adjuvanted RBD as an affordable vaccine that may be effective across multiple age groups.

One Sentence Summary: Alum and CpG enhance SARS-CoV-2 RBD protective immunity, variant neutralization in aged mice and Th1-polarizing cytokine production by human elder leukocytes.
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http://dx.doi.org/10.1101/2021.05.20.444848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142652PMC
May 2021

A cloud-based bioinformatic analytic infrastructure and Data Management Core for the Expanded Program on Immunization Consortium.

J Clin Transl Sci 2020 Sep 22;5(1):e52. Epub 2020 Sep 22.

Precision Vaccines Program, Boston Children's Hospital, Boston, MA, USA.

The Expanded Program for Immunization Consortium - Human Immunology Project Consortium study aims to employ systems biology to identify and characterize vaccine-induced biomarkers that predict immunogenicity in newborns. Key to this effort is the establishment of the Data Management Core (DMC) to provide reliable data and bioinformatic infrastructure for centralized curation, storage, and analysis of multiple de-identified "omic" datasets. The DMC established a cloud-based architecture using Amazon Web Services to track, store, and share data according to National Institutes of Health standards. The DMC tracks biological samples during collection, shipping, and processing while capturing sample metadata and associated clinical data. Multi-omic datasets are stored in access-controlled Amazon Simple Storage Service (S3) for data security and file version control. All data undergo quality control processes at the generating site followed by DMC validation for quality assurance. The DMC maintains a controlled computing environment for data analysis and integration. Upon publication, the DMC deposits finalized datasets to public repositories. The DMC architecture provides resources and scientific expertise to accelerate translational discovery. Robust operations allow rapid sharing of results across the project team. Maintenance of data quality standards and public data deposition will further benefit the scientific community.
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http://dx.doi.org/10.1017/cts.2020.546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057481PMC
September 2020

Human Blood Plasma Shapes Distinct Neonatal TLR-Mediated Dendritic Cell Activation via Expression of the MicroRNA Let-7g.

Immunohorizons 2021 Apr 30;5(4):246-256. Epub 2021 Apr 30.

Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA;

The newborn innate immune system is characterized as functionally distinct, resulting in impaired proinflammatory responses to many stimuli and a bias toward Th2 development. Although the magnitude of impairment can be partially overcome, for instance through activation of TLR7/8 in newborn dendritic cells, the newborn innate response remains distinct from that of adults. Using human in vitro modeling of newborn and adult dendritic cells, we investigated the role of extracellular and intracellular regulators in driving age-specific responses to TLR7/8 stimulation. MicroRNA expression profiling and plasma switch experiments identified Let-7g as a novel regulator of newborn innate immunity. Activation-induced expression of Let-7g in monocyte-derived dendritic cells (MoDCs) is driven by newborn plasma and reduces expression of costimulatory receptors CD86, MHC class I, and CCR7 and secretion of IFN-α and sCD40L. Conversely, an increase in secretion of the Th2-polarizing cytokine IL-12p40 is observed. Overexpression of Let-7g in adult MoDCs resulted in the same observations. Small interfering RNA-mediated ablation of Let-7g levels in newborn MoDCs resulted in an adult-like phenotype. In conclusion, this study reveals for the first time (to our knowledge) that age-specific differences in human plasma induce the microRNA Let-7g as a key mediator of the newborn innate immune phenotype. These observations shed new light on the mechanisms of immune ontogeny and may inform approaches to discover age-specific immunomodulators, such as adjuvants.
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http://dx.doi.org/10.4049/immunohorizons.2000081DOI Listing
April 2021

Follow-up surveillance among colorectal cancer survivors of different sexual orientations.

J Cancer Surviv 2021 Apr 14. Epub 2021 Apr 14.

Harvard Medical School, Boston, MA, USA.

Purpose: The purpose of this study was to examine receipt of follow-up surveillance among sexual minority and heterosexual survivors and identify survivor-, physician-, and practice-level characteristics associated with follow-up surveillance.

Methods: An average of 3 years after their stage I-III colorectal cancer diagnosis, we recruited survivors from four cancer registries. A questionnaire, which queried about sexual orientation and other eligibility criteria, was mailed to all cancer survivors. Subsequently, 418 eligible survivors without recurrent disease participated in a telephone survey. Colorectal cancer-specific follow-up surveillance was defined as colonoscopy, carcinoembryonic antigen (CEA) test, or imaging test. We used logistic regression with forward selection to obtain models that best explained each follow-up test.

Results: About 10% of survivors received no follow-up surveillance, while 70% had colonoscopies. While survivors irrespective of sexual orientation received follow-up surveillance, sexual minority survivors had 3 times the odds of receiving imaging tests compared to heterosexual survivors. Having a designated provider of any specialty was most salient for the receipt of surveillance.

Conclusions: Sexual minority survivors' greater receipt of imaging tests may indicate providers perceive them at greater risk for recurrence than heterosexual survivors. Future studies need to examine provider behaviors towards monitoring colorectal cancer survivors of diverse sexual orientations.

Implications For Cancer Survivors: Guidelines recommend surveillance of colorectal cancer survivors to improve survival. This study showed that having a designated provider for follow-up is most salient for the receipt of surveillance, most survivors receive surveillance, and sexual minority survivors had more imaging tests compared to heterosexual survivors.
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http://dx.doi.org/10.1007/s11764-021-01039-1DOI Listing
April 2021

Assessing the relationship between symptoms and health care utilization in colorectal cancer survivors of different sexual orientations.

Support Care Cancer 2021 Oct 19;29(10):5821-5830. Epub 2021 Mar 19.

Section of Hematology Oncology, Boston University School of Medicine, Boston, MA, USA.

Objective: The purpose of this study was to determine the association of physical and psychological symptoms with health care utilization in sexual minority and heterosexual colorectal cancer survivors.

Methods: Four hundred eighteen colorectal cancer survivors who were in remission an average of 3 years after their diagnosis were surveyed about their non-emergency health care visits during the preceding 3 months. Survivors reported whether they had experienced any of 21 symptoms common among colorectal cancer survivors in the past week. The relation between having had two or more health care visits in the preceding 3 months and symptoms experienced was assessed using logistic regression, controlling for cancer registry, sexual orientation, sex, age, race/ethnicity, income, and comorbidities.

Results: Of the survivors, 12% reported no symptoms, while 12% reported six or more symptoms. Sexual minority survivors reported significantly more weight concerns and more health-related and general anxiety as well as worse body image than heterosexual survivors. Frequent worrying about weight and experiencing sore skin around the anal area or stoma were the two symptoms that significantly contributed towards explaining survivors' increased health care utilization.

Conclusion: Weight concerns, which are more common among the heaviest survivors, may prompt survivors to seek help from health care providers, which may lead to more frequent visits. On the other hand, some symptoms, despite their prevalence, had no relationship with the frequency of health care visits, raising questions about whether survivors share these concerns with providers.
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http://dx.doi.org/10.1007/s00520-021-06157-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410628PMC
October 2021

Multicohort Retrospective Validation of a Predictive Biomarker for Topoisomerase I Inhibitors.

Clin Colorectal Cancer 2021 06 10;20(2):e129-e138. Epub 2020 Dec 10.

Division of Hematology Oncology, Department of Medicine, Boston University School of Medicine, Boston, MA. Electronic address:

Purpose: The camptothecin (CPT) analogs topotecan and irinotecan specifically target topoisomerase I (topoI) and are used to treat colorectal, gastric, and pancreatic cancer. Response rate for this class of drug varies from 10% to 30%, and there is no predictive biomarker for patient stratification by response. On the basis of our understanding of CPT drug resistance mechanisms, we developed an immunohistochemistry-based predictive test, P-topoI-Dx, to stratify the patient population into those who did and did not experience a response.

Patients And Methods: The retrospective validation studies included a training set (n = 79) and a validation cohort (n = 27) of gastric cancer (GC) patients, and 8 cohorts of colorectal cancer (CRC) patient tissue (n = 176). Progression-free survival for 6 months was considered a positive response to CPT-based therapy. Formalin-fixed, paraffin-embedded slides were immunohistochemically stained with anti-phospho-specific topoI-Serine10 (topoI-pS10), quantitated, and analyzed statistically.

Results: We determined a threshold of 35% positive staining to offer optimal test characteristics in GC. The GC (n = 79) training set demonstrated 76.6% (95% confidence interval, 64-86) sensitivity; 68.8% (41-88) specificity; positive predictive value (PPV) 92.5% (81-98); and negative predictive value (NPV) 42.3% (24-62). The GC validation set (n = 27) demonstrated 82.4% (56-95) sensitivity and 70.0% (35-92) specificity. Estimated PPV and NPV were 82.4% (56-95) and 70.0% (35-92) respectively. In the CRC validation set (n = 176), the 40% threshold demonstrated 87.5% (78-94) sensitivity; 70.0% (59-79) specificity; PPV 70.7% (61-79); and NPV 87.0 % (77-93).

Conclusion: The analysis of retrospective data from patients (n = 282) provides clinical validity to our P-topoI-Dx immunohistochemical test to identify patients with disease that is most likely to respond to topoI inhibitors.
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http://dx.doi.org/10.1016/j.clcc.2020.11.005DOI Listing
June 2021

Predictive Value of Direct Disk Diffusion Testing from Positive Blood Cultures in a Children's Hospital and Its Utility in Antimicrobial Stewardship.

J Clin Microbiol 2021 05 19;59(6). Epub 2021 May 19.

Division of Infectious Diseases, Boston Children's Hospital, Boston, Massachusetts, USA.

Accurate and early susceptibility results could reduce overuse of broad-spectrum antibiotics for empirical treatment of bacteremia. Direct disk diffusion testing (dDD) using nonstandardized inocula directly from blood cultures could facilitate earlier narrowing of antibiotics. To determine the predictive value of dDD compared with standardized antimicrobial susceptibility testing (AST), we performed a retrospective cohort study of 582 blood cultures from 495 pediatric patients with bacteremia. Positive and negative predictive value (PPV: number of isolates susceptible by both dDD and AST divided by the total number of isolates susceptible by dDD; NPV: number of isolates not susceptible [either intermediate or resistant] by both dDD and AST divided by the total number of isolates not susceptible by dDD), sensitivity, specificity, and 95% confidence interval were calculated for each bacterium-antibiotic combination. We evaluated the Antibiotic Spectrum Index of prescribed antibiotics to assess change in antibiotic prescribing after availability of Gram stain, dDD, and AST results. dDD results were available a median of 21 h before AST results. dDD had PPVs of ≥96% for most organism-antibiotic pairs, including 100% (CI 96 to 100%) for with oxacillin and 99% (CI 93 to 100%) for with ceftriaxone. NPVs of dDD were variable and frequently lower than the PPV. Very major errors and major errors occurred in 31/5,454 (0.6%) and 231/5,454 (4.2%) organism-antibiotic combinations, respectively. Antibiotics were narrowed in 30% of cases after a dDD result and a further 25% of cases after AST result. dDD is highly predictive of susceptibility for many common organism-antibiotic combinations and provides actionable information one day earlier than standard susceptibility approaches. dDD has the potential to facilitate earlier deescalation to narrow-spectrum antibiotic treatment.
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http://dx.doi.org/10.1128/JCM.02445-20DOI Listing
May 2021

Bell's palsy and SARS-CoV-2 vaccines.

Lancet Infect Dis 2021 04 24;21(4):450-452. Epub 2021 Feb 24.

Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address:

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http://dx.doi.org/10.1016/S1473-3099(21)00076-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906673PMC
April 2021

Ethical climate in contemporary paediatric intensive care.

J Med Ethics 2021 Jan 11. Epub 2021 Jan 11.

School of Medicine, University of Queensland, Brisbane, Queensland, Australia.

Ethical climate (EC) has been broadly described as how well institutions respond to ethical issues. Developing a tool to study and evaluate EC that aims to achieve sustained improvements requires a contemporary framework with identified relevant drivers. An extensive literature review was performed, reviewing existing EC definitions, tools and areas where EC has been studied; ethical challenges and relevance of EC in contemporary paediatric intensive care (PIC); and relevant ethical theories. We surmised that existing EC definitions and tools designed to measure it fail to capture nuances of the PIC environment, and sought to address existing gaps by developing an EC framework for PIC founded on ethical theory. In this article, we propose a Paediatric Intensive Care Ethical Climate (PICEC) conceptual framework and four measurable domains to be captured by an assessment tool. We define PICEC as the collective felt experience of interdisciplinary team members arising from those factors that enable or constrain their ability to navigate ethical aspects of their work. PICEC both results from and is influenced by how well ethical issues are understood, identified, explored, reflected on, responded to and addressed in the workplace. PICEC encompasses four, core inter-related domains representing drivers of EC including: (1) organisational culture and leadership; (2) interdisciplinary team relationships and dynamics; (3) integrated child and family-centred care; and (4) ethics literacy. Future directions involve developing a PICEC measurement tool, with implications for benchmarking as well as guidance for, and evaluation of, targeted interventions to foster a healthy EC.
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http://dx.doi.org/10.1136/medethics-2020-106818DOI Listing
January 2021

Preparing for Life: Plasma Proteome Changes and Immune System Development During the First Week of Human Life.

Front Immunol 2020 20;11:578505. Epub 2020 Oct 20.

Department of Pathology, Boston Children's Hospital, Boston, MA, United States.

Neonates have heightened susceptibility to infections. The biological mechanisms are incompletely understood but thought to be related to age-specific adaptations in immunity due to resource constraints during immune system development and growth. We present here an extended analysis of our proteomics study of peripheral blood-plasma from a study of healthy full-term newborns delivered vaginally, collected at the day of birth and on day of life (DOL) 1, 3, or 7, to cover the first week of life. The plasma proteome was characterized by LC-MS using our established 96-well plate format plasma proteomics platform. We found increasing acute phase proteins and a reduction of respective inhibitors on DOL1. Focusing on the complement system, we found increased plasma concentrations of all major components of the classical complement pathway and the membrane attack complex (MAC) from birth onward, except C7 which seems to have near adult levels at birth. In contrast, components of the lectin and alternative complement pathways mainly decreased. A comparison to whole blood messenger RNA (mRNA) levels enabled characterization of mRNA and protein levels in parallel, and for 23 of the 30 monitored complement proteins, the whole blood transcript information by itself was not reflective of the plasma protein levels or dynamics during the first week of life. Analysis of immunoglobulin (Ig) mRNA and protein levels revealed that IgM levels and synthesis increased, while the plasma concentrations of maternally transferred IgG1-4 decreased in accordance with their half-lives. The neonatal plasma ratio of IgG1 to IgG2-4 was increased compared to adult values, demonstrating a highly efficient IgG1 transplacental transfer process. Partial compensation for maternal IgG degradation was achieved by endogenous synthesis of the IgG1 subtype which increased with DOL. The findings were validated in a geographically distinct cohort, demonstrating a consistent developmental trajectory of the newborn's immune system over the first week of human life across continents. Our findings indicate that the classical complement pathway is central for newborn immunity and our approach to characterize the plasma proteome in parallel with the transcriptome will provide crucial insight in immune ontogeny and inform new approaches to prevent and treat diseases.
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http://dx.doi.org/10.3389/fimmu.2020.578505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732455PMC
June 2021

COVID-19 Misinformation Spread in Eight Countries: Exponential Growth Modeling Study.

J Med Internet Res 2020 12 15;22(12):e24425. Epub 2020 Dec 15.

Department of Pediatrics, Harvard Medical School, Boston, MA, United States.

Background: The epidemic of misinformation about COVID-19 transmission, prevention, and treatment has been going on since the start of the pandemic. However, data on the exposure and impact of misinformation is not readily available.

Objective: We aim to characterize and compare the start, peak, and doubling time of COVID-19 misinformation topics across 8 countries using an exponential growth model usually employed to study infectious disease epidemics.

Methods: COVID-19 misinformation topics were selected from the World Health Organization Mythbusters website. Data representing exposure was obtained from the Google Trends application programming interface for 8 English-speaking countries. Exponential growth models were used in modeling trends for each country.

Results: Searches for "coronavirus AND 5G" started at different times but peaked in the same week for 6 countries. Searches for 5G also had the shortest doubling time across all misinformation topics, with the shortest time in Nigeria and South Africa (approximately 4-5 days). Searches for "coronavirus AND ginger" started at the same time (the week of January 19, 2020) for several countries, but peaks were incongruent, and searches did not always grow exponentially after the initial week. Searches for "coronavirus AND sun" had different start times across countries but peaked at the same time for multiple countries.

Conclusions: Patterns in the start, peak, and doubling time for "coronavirus AND 5G" were different from the other misinformation topics and were mostly consistent across countries assessed, which might be attributable to a lack of public understanding of 5G technology. Understanding the spread of misinformation, similarities and differences across different contexts can help in the development of appropriate interventions for limiting its impact similar to how we address infectious disease epidemics. Furthermore, the rapid proliferation of misinformation that discourages adherence to public health interventions could be predictive of future increases in disease cases.
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http://dx.doi.org/10.2196/24425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744144PMC
December 2020

Treadmill injuries in children.

Am J Emerg Med 2021 08 18;46:495-498. Epub 2020 Nov 18.

Boston Children's Hospital, Department of Emergency Medicine, Boston, USA. Electronic address:

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http://dx.doi.org/10.1016/j.ajem.2020.10.066DOI Listing
August 2021

Bacteriology of pediatric breast abscesses beyond the neonatal period.

Am J Emerg Med 2021 03 11;41:193-196. Epub 2020 Nov 11.

Boston Children's Hospital, Department of Emergency Medicine, United States of America; Boston Children's Hospital, Clinical Informatics Fellowship Program, United States of America. Electronic address:

Background: Limited data exist regarding the presentation and bacteriology of nonneonatal pediatric breast abscess.

Objective: To determine the bacteriology and characteristic presentation of pediatric breast abscesses in a tertiary care center.

Methods: Cross-sectional study of patients age 1 month to 21 years admitted to a pediatric Emergency Department (ED) between 1996 and 2018 with a breast abscess. Patients with pre-existing conditions were excluded. Records were reviewed to determine demographics, history, physical exam findings, wound culture results, imaging and ED disposition. We used descriptive statistics to describe prevalence of different bacteria.

Results: We identified 210 patients who met study criteria. Median age was 13.6 years [IQR 6.6, 17.4], and 91% (191/210) were females. Ninety-two patients (43.8%) were 'pre-treated' with antibiotics prior to ED visit, and 33/210 (16%) were febrile. Ultrasound was obtained in 85 patients (40.5%), 69 patients had a single abscess and 16 had multiple abscesses. Most patients were treated with antibiotics and 100 had a surgical intervention, of these 89 had I&D and 11 a needle aspiration. Admission rate was 45%. Culture results were available for 75 (75%). Thirty-three (44%) had a negative culture, or grew non-aureus staphylococci or other skin flora. Culture were positive for MSSA 21 (28%), MRSA 13 (17%), Proteus mirabilis 2 (2.6%), Serratia 1 (1.3%). Other organisms include Gram-negative bacilli, group A Streptococcus and enterococcus.

Conclusions: Non-neonatal pediatric breast abscess bacteriology is no different than data published on other skin abscesses. MRSA coverage should be considered based on local prevalence in skin infections.
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http://dx.doi.org/10.1016/j.ajem.2020.11.018DOI Listing
March 2021

Survivors' Perceptions of Quality of Colorectal Cancer Care by Sexual Orientation.

Am J Clin Oncol 2020 09;43(9):660-666

Harvard Medical School.

Objective: The objective of this study was to assess sexual minority and heterosexual survivors' perceived quality of cancer care and identify demographic, clinical, and psychosocial characteristics associated with patient-centered quality of care.

Materials And Methods: Four cancer registries provided data on 17,849 individuals who were diagnosed with stage I, II, or III colorectal cancer an average of 3 years prior and resided in predetermined diverse geographic areas. A questionnaire, which queried about sexual orientation and other eligibility criteria was mailed to all cancer survivors. Of these, 480 eligible survivors participated in a telephone survey. Quality of cancer care was defined by 3 measures of interpersonal care (physician communication, nursing care, and coordination of care) and by rating cancer care as excellent. We used generalized linear models and logistic regression with forward selection to obtain models that best explained each quality of care measure.

Results: Sexual minority survivors rated physician communication, nursing care, and coordination of care similarly to heterosexual survivors, yet a significantly higher percentage of sexual minority survivors rated the overall quality of their cancer care as excellent (59% vs. 49%). Sexual minority survivors' greater likelihood of reporting excellent care remained unchanged after adjusting for demographic, clinical, and psychosocial characteristics.

Conclusions: Sexual minority survivors' ratings of quality of colorectal cancer care were comparable or even higher than heterosexual survivors. Sexual minority survivors' reports of excellent care were not explained by their interpersonal care experiences.
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http://dx.doi.org/10.1097/COC.0000000000000732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011297PMC
September 2020

Clinician Perceptions of Timing and Presentation of Drug-Drug Interaction Alerts.

Appl Clin Inform 2020 05 22;11(3):487-496. Epub 2020 Jul 22.

Emergency Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States.

Objective: Alert presentation of clinical decision support recommendations is a common method for providing information; however, many alerts are overridden suggesting presentation design improvements can be made. This study attempts to assess pediatric prescriber information needs for drug-drug interactions (DDIs) alerts and to evaluate the optimal presentation timing and presentation in the medication ordering process.

Methods: Six case scenarios presented interactions between medications used in pediatric specialties of general medicine, infectious disease, cardiology, and neurology. Timing varied to include alert interruption at medication selection versus order submission; or was noninterruptive. Interviews were audiotaped, transcribed, and independently analyzed to derive central themes.

Results: Fourteen trainee and attending clinicians trained in pediatrics, cardiology, and neurology participated. Coders derived 8 central themes from 929 quotes. Discordance exists between medication prescribing frequency and DDI knowledge; providers may commonly prescribe medications for which they do not recognize DDIs. Providers wanted alerts at medication selection rather than at order signature. Alert presentation themes included standardizing text, providing interaction-specific incidence/risk information, DDI rating scales, consolidating alerts, and providing alternative therapies. Providers want alerts to be actionable, for example, allowing medication discontinuation and color visual cues for essential information. Despite alert volume, participants did not "mind being reminded because there is always the chance that at that particular moment (they) do not remember it" and acknowledged the importance of alerts as "essential in terms of patient safety."

Conclusion: Clinicians unanimously agreed on the importance of receiving DDI alerts to improve patient safety. The perceived alert value can be improved by incorporating clinician preferences for timing and presentation.
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http://dx.doi.org/10.1055/s-0040-1714276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383060PMC
May 2020

Clinical Protocol for a Longitudinal Cohort Study Employing Systems Biology to Identify Markers of Vaccine Immunogenicity in Newborn Infants in The Gambia and Papua New Guinea.

Front Pediatr 2020 30;8:197. Epub 2020 Apr 30.

Vaccines and Immunity Theme, Medical Research Council Unit the Gambia at London School of Hygiene and Tropical Medicine, Fajara, Gambia.

Infection contributes to significant morbidity and mortality particularly in the very young and in low- and middle-income countries. While vaccines are a highly cost-effective tool against infectious disease little is known regarding the cellular and molecular pathways by which vaccines induce protection at an early age. Immunity is distinct in early life and greater precision is required in our understanding of mechanisms of early life protection to inform development of new pediatric vaccines. We will apply transcriptomic, proteomic, metabolomic, multiplex cytokine/chemokine, adenosine deaminase, and flow cytometry immune cell phenotyping to delineate early cellular and molecular signatures that correspond to vaccine immunogenicity. This approach will be applied to a neonatal cohort in The Gambia ( ~ 720) receiving at birth: (1) Hepatitis B (HepB) vaccine alone, (2) Bacille Calmette Guerin (BCG) vaccine alone, or (3) HepB and BCG vaccines, (4) HepB and BCG vaccines delayed till day 10 at the latest. Each study participant will have a baseline peripheral blood sample drawn at DOL0 and a second blood sample at DOL1,-3, or-7 as well as late timepoints to assess HepB vaccine immunogenicity. Blood will be fractionated via a "small sample big data" standard operating procedure that enables multiple downstream systems biology assays. We will apply both univariate and multivariate frameworks and multi-OMIC data integration to identify features associated with anti-Hepatitis B (anti-HB) titer, an established correlate of protection. Cord blood sample collection from a subset of participants will enable human modeling to test mechanistic hypotheses identified regarding vaccine action. Maternal anti-HB titer and the infant microbiome will also be correlated with our findings which will be validated in a smaller cohort in Papua New Guinea ( ~ 80). The study has been approved by The Gambia Government/MRCG Joint Ethics Committee and The Boston Children's Hospital Institutional Review Board. Ethics review is ongoing with the Papua New Guinea Medical Research Advisory Committee. All de-identified data will be uploaded to public repositories following submission of study output for publication. Feedback meetings will be organized to disseminate output to the study communities. : Clinicaltrials.gov Registration Number: NCT03246230.
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http://dx.doi.org/10.3389/fped.2020.00197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205022PMC
April 2020

Utility of Blood Cultures and Empiric Antibiotics in Febrile Pediatric Hemophilia Patients With Central Venous Access Devices.

Pediatr Emerg Care 2020 Apr 28. Epub 2020 Apr 28.

Harvard Medical School.

Background: Children with hemophilia frequently require long-term central venous access devices (CVADs) for regular infusion of factor products. Hemophilia patients are not immunocompromised, but the presence and use of CVADs are associated with infections including bacteremia. Currently, the utility of blood cultures in evaluation of the febrile hemophilia patient with an indwelling CVAD is unknown, nor is optimal empiric antibiotic use.

Methods: We performed a retrospective cross-sectional study of febrile immunocompetent hemophilia patients with CVADs presenting to a large academic urban pediatric emergency department from 1995 to 2017. We used a natural language processing electronic search, followed by manual chart review to construct the cohort. We analyzed rate of pathogen recovery from cultures of blood in subgroups of hemophilia patients, the pathogen profile, and the reported pathogen susceptibilities to ceftriaxone.

Results: Natural language processing electronic search identified 181 visits for fever among hemophilia patients with indwelling CVADs of which 147 cases from 44 unique patients met study criteria. Cultures of blood were positive in 56 (38%) of 147 patients (95% confidence interval, 30%-47%). Seventeen different organisms were isolated (10 pathogens and 7 possible pathogens) with Staphylococcus aureus and coagulase-negative Staphylococcus species as the most common. Thirty-four percent of isolates were reported as susceptible to ceftriaxone. Positive blood cultures were more common in cases involving patients with inhibitors (n = 71) versus those without (n = 76), odds ratio, 7.4 (95% confidence interval, 3.5-15.9). This was observed irrespective of hemophilia type.

Conclusions: Febrile immunocompetent hemophilia patients with indwelling CVADs have high rates of bacteremia. Empiric antimicrobial therapy should be targeted to anticipated pathogens and take into consideration local susceptibility patterns for Staphylococcus aureus.
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http://dx.doi.org/10.1097/PEC.0000000000002106DOI Listing
April 2020

Transgender individuals' cancer survivorship: Results of a cross-sectional study.

Cancer 2020 06 5;126(12):2829-2836. Epub 2020 Mar 5.

National LGBT Cancer Network, Providence, Rhode Island.

Background: Transgender individuals' cancer prevalence and transgender cancer survivors' health needs have received scarce attention. The current study compared transgender and cisgender individuals' cancer prevalence and described the health needs of transgender cancer survivors.

Methods: The authors used Behavioral Risk Factor Surveillance System data on 95,800 cisgender and transgender individuals who self-reported a cancer diagnosis. Using multiple logistic regression, they estimated cancer prevalence and calculated odds ratios with 95% confidence intervals of physical, psychological, overall health, and health behaviors of transgender survivors compared with cisgender survivors.

Results: After adjusting for confounders, transgender men had a significantly higher (>2-fold) number of cancer diagnoses compared with cisgender men, but not cisgender women. Cancer prevalence among gender nonconforming individuals and transgender women was not significantly different from that of cisgender men and cisgender women. Gender nonconforming survivors had significantly greater physical inactivity, heavy episodic alcohol use, and depression compared with cisgender men and cisgender women. Transgender men survivors were significantly more likely to report poor physical health and greater medical comorbidities and were less likely to report smoking compared with cisgender men and cisgender women. Transgender women survivors were significantly more likely to report diabetes compared with cisgender men and cisgender women and were more likely to report cardiovascular disease compared with cisgender women.

Conclusions: Clinicians should be aware of the higher prevalence of cancer among transgender men and a potential survivorship bias among transgender individuals. Transgender survivors have considerable variation in their risk profile. Clinicians and health services can target gender nonconforming survivors' depression and health behaviors to improve survival and should address the complex comorbidities of transgender men and transgender women.
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http://dx.doi.org/10.1002/cncr.32784DOI Listing
June 2020

A Primary Care-Based Quality Improvement Initiative to Increase Identification of Pediatric International Travelers.

Am J Trop Med Hyg 2020 05;102(5):1016-1021

Boston Children's Hospital, Boston, Massachusetts.

Children who travel internationally to visit friends and relatives (VFRs) are at risk for travel-related illness, but underuse pretravel health services. Although primary care clinics can identify travelers and address pretravel health needs, to date, there are few published reports on effective primary care-based pretravel interventions. We developed a quality improvement initiative to increase traveler identification at a primary care clinic serving families that frequently travel to VFRs. Interventions included a screening question asked at all clinic visits, provider and staff training, travel fliers, and health recommendation sheets for families. Interventions were implemented during 2017 and 2018 peak travel seasons. Travel visit rates and characteristics during the intervention period were compared with pre-intervention baseline periods (April-August, 2015-16). Surveys with providers were conducted to assess disruptiveness of the interventions, and rates of duplicate travel visits were assessed. A total of 738 unique travel events were identified during peak travel seasons from 2015 to 2018, encompassing travel to 29 countries across five continents. Overall, there were 428 unique travel events (3.0% of all clinic visits) during peak seasons 2017-18, compared with 310 unique travel events (2.2% of all clinic visits) during peak seasons 2015-16 (rate ratio 1.34 [95% CI: 1.16-1.56], < 0.001). None of the 18 healthcare providers or staff surveyed found new travel screening processes to be disruptive or bothersome. Implementation of a primary care-based multimodal travel screening and education initiative was associated with a significantly increased rate of travel visits.
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http://dx.doi.org/10.4269/ajtmh.19-0636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204565PMC
May 2020

Licensed Bacille Calmette-Guérin (BCG) formulations differ markedly in bacterial viability, RNA content and innate immune activation.

Vaccine 2020 02 28;38(9):2229-2240. Epub 2020 Jan 28.

Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT & Harvard, Cambridge, MA 02142, USA. Electronic address:

Background: Bacille Calmette-Guérin (BCG), the live attenuated tuberculosis vaccine, is manufactured under different conditions across the globe generating formulations that may differ in clinical efficacy. Innate immune recognition of live BCG contributes to immunogenicity suggesting that differences in BCG viability may contribute to divergent activity of licensed formulations.

Methods: We compared BCG-Denmark (DEN), -Japan (JPN), -India (IND), -Bulgaria (BUL) and -USA in vitro with respect to a) viability as measured by colony-forming units (CFU), mycobacterial membrane integrity, and RNA content, and b) cytokine/chemokine production in newborn cord and adult peripheral blood.

Results: Upon culture, relative growth was BCG-USA > JPN ≫ DEN > BUL = IND. BCG-IND and -BUL demonstrated >1000-fold lower growth than BCG-JPN in 7H9 medium and >10-fold lower growth in commercial Middlebrook 7H11 medium. BCG-IND demonstrated significantly decreased membrane integrity, lower RNA content, and weaker IFN-γ inducing activity in whole blood compared to other BCGs. BCG-induced whole blood cytokines differed significantly by age, vaccine formulation and concentration. BCG-induced cytokine production correlated with CFU, suggesting that mycobacterial viability may contribute to BCG-induced immune responses.

Conclusions: Licensed BCG vaccines differ markedly in their content of viable mycobacteria possibly contributing to formulation-dependent activation of innate and adaptive immunity and distinct protective effects.
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http://dx.doi.org/10.1016/j.vaccine.2019.11.060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556328PMC
February 2020

Neighborhood Characteristics and Colorectal Cancer Survivors' Quality of Care.

Health Equity 2019 13;3(1):619-627. Epub 2019 Dec 13.

Boston University School of Medicine, Boston, Massachusetts.

Quality cancer care entails receipt of a Survivorship Care Plan (SCP). The purpose of this study was to determine differences in SCP delivery by patient-level and neighborhood characteristics. We obtained California cancer registry data on individuals who were diagnosed with stage I, II, or III colorectal cancer (CRC) between 2012 and 2015 and resided in predetermined geographic areas. We then mailed them a questionnaire, which queried about receipt of a SCP and its content. SCP was defined by content, as summary of cancer treatment, cancer surveillance recommendations, and/or an individualized preventive care. Using logistic regression modeling, each measure of SCP, as well as the summary measure (none vs. any), was evaluated by person-level characteristics. Subsequently, neighborhood-level characteristics were added to the model to explore their additional value. Overall 80% of CRC survivors received a SCP. Receipt of SCPs was associated with person-level characteristics, while neighborhood characteristics did not make an additional contribution. Young, male employed survivors and those with more recent diagnoses or later cancer stages had greater odds of receiving a SCP. When providing SCPs, health care providers prioritize patient groups who they may perceive as vulnerable or likely to benefit from SCPs.
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http://dx.doi.org/10.1089/heq.2019.0062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918517PMC
December 2019

The power of peers: an effectiveness evaluation of a cluster-controlled trial of group antenatal care in rural Nepal.

Reprod Health 2019 Oct 22;16(1):150. Epub 2019 Oct 22.

Nyaya Health Nepal, Kathmandu, Nepal.

Background: Reducing the maternal mortality ratio to less than 70 per 100,000 live births globally is one of the Sustainable Development Goals. Approximately 830 women die from pregnancy- or childbirth-related complications every day. Almost 99% of these deaths occur in developing countries. Increasing antenatal care quality and completion, and institutional delivery are key strategies to reduce maternal mortality, however there are many implementation challenges in rural and resource-limited settings. In Nepal, 43% of deliveries do not take place in an institution and 31% of women have insufficient antenatal care. Context-specific and evidence-based strategies are needed to improve antenatal care completion and institutional birth. We present an assessment of effectiveness outcomes for an adaptation of a group antenatal care model delivered by community health workers and midwives in close collaboration with government staff in rural Nepal.

Methods: The study was conducted in Achham, Nepal, via a public private partnership between the Nepali non-profit, Nyaya Health Nepal, and the Ministry of Health and Population, with financial and technical assistance from the American non-profit, Possible. We implemented group antenatal care as a prospective non-randomized, cluster-controlled, type I hybrid effectiveness-implementation study in six village clusters. The implementation approach allowed for iterative improvement in design by making changes to improve the quality of the intervention. We evaluated effectiveness through a difference in difference analysis of institutional birth rates between groups prior to implementation of the intervention and 1 year after implementation. Additionally, we assessed the change in knowledge of key danger signs and the acceptability of the group model compared with individual visits in a nested cohort of women receiving home visit care and home visit care plus group antenatal care. Using a directed content and thematic approach, we analyzed qualitative interviews to identify major themes related to implementation.

Results: At baseline, there were 457 recently-delivered women in the six village clusters receiving home visit care and 214 in the seven village clusters receiving home visit care plus group antenatal care. At endline, there were 336 and 201, respectively. The difference in difference analysis did not show a significant change in institutional birth rates nor antenatal care visit completion rates between the groups. There was, however, a significant increase in both institutional birth and antenatal care completion in each group from baseline to endline. We enrolled a nested cohort of 52 participants receiving home visit care and 62 participants receiving home visit care plus group antenatal care. There was high acceptability of the group antenatal care intervention and home visit care, with no significant differences between groups. A significantly higher percentage of women who participated in group antenatal care found their visits to be 'very enjoyable' (83.9% vs 59.6%, p = 0.0056). In the nested cohort, knowledge of key danger signs during pregnancy significantly improved from baseline to endline in the intervention clusters only (2 to 31%, p < 0.001), while knowledge of key danger signs related to labor and childbirth, the postpartum period, and the newborn did not in either intervention or control groups. Qualitative analysis revealed that women found that the groups provided an opportunity for learning and discussion, and the groups were a source of social support and empowerment. They also reported an improvement in services available at their village clinic. Providers noted the importance of the community health workers in identifying pregnant women in the community and linking them to the village clinics. Challenges in birth planning were brought up by both participants and providers.

Conclusion: While there was no significant change in institutional birth and antenatal care completion at the population level between groups, there was an increase of these outcomes in both groups. This may be secondary to the primary importance of community health worker involvement in both of these groups. Knowledge of key pregnancy danger signs was significantly improved in the home visit plus group antenatal care cohort compared with the home visit care only group. This initial study of Nyaya Health Nepal's adapted group care model demonstrates the potential for impacting women's antenatal care experience and should be studied over a longer period as an intervention embedded within a community health worker program.

Trial Registration: ClinicalTrials.gov Identifier: NCT02330887 , registered 01/05/2015, retroactively registered.
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http://dx.doi.org/10.1186/s12978-019-0820-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805428PMC
October 2019
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