Implications of Cross-Reactivity and Cross-Protection for Pneumococcal Vaccine Development.

Pneumococcal vaccines are a cornerstone for the prevention of pneumococcal diseases, reducing morbidity and mortality in children and adults worldwide. Pneumococcal vaccine composition is based on the polysaccharide capsule of , which is one of the most important identified contributors to the pathogen's virulence. Similarities in the structural composition of polysaccharides included in licensed pneumococcal vaccines may result in cross-reactivity of immune response against closely related serotypes, including serotypes not included in the vaccine.

Immunogenicity of Current and Next-Generation Pneumococcal Conjugate Vaccines in Children: Current Challenges and Upcoming Opportunities.

Global use of pneumococcal conjugate vaccines (PCVs) with increasingly broader serotype coverage has helped to reduce the burden of pneumococcal disease in children and adults. In clinical studies comparing PCVs, higher-valency PCVs have met noninferiority criteria (based on immunoglobulin G geometric mean concentrations and response rates) for most shared serotypes. A numeric trend of declining immunogenicity against shared serotypes with higher-valency PCVs has also been observed; however, the clinical relevance is uncertain, warranting additional research to evaluate the effectiveness of new vaccines.

Extending the vision of adaptive point-of-care platform trials to improve targeted use of drug therapy regimens: An agile approach in the learning healthcare system toolkit.

Objectives: Improving the targeted use of drug regimens requires robust real-world evidence (RWE) to address the uncertainties that remain regarding their real-world performance following market entry. However, challenges in the current state of RWE production limit its impact on clinical decisions, as well as its operational scalability and sustainability. We propose an adaptive point-of-care (APoC) platform trial as an approach to RWE production that improves both clinical and operational efficiencies.

ACE inhibitor or ARB treatment among patients with diabetes and chronic kidney disease.

Objectives: Many patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) experience a delay in treatment or fail to initiate treatment with guideline-recommended angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) after CKD diagnosis. This study aimed to describe treatment patterns and treatment initiation after initial CKD diagnosis among patients with T2D.

Study Design: Retrospective analysis using data from the Optum Clinformatics Data Mart administrative claims database (January 2014-September 2018).

Chronic kidney disease progression among patients with type 2 diabetes identified in US administrative claims: a population cohort study.

Background: Chronic kidney disease (CKD), one of the most common complications of type 2 diabetes (T2D), is associated with poor health outcomes and high healthcare expenditures. As the CKD population increases, a better understanding of the prevalence and progression of CKD is critical. However, few contemporary studies have explored the progression of CKD relative to its onset in T2D patients using established markers derived from real-world care settings.

Cardiovascular and Renal Outcomes in Patients with Type-2 Diabetes and Chronic Kidney Disease Identified in a United States Administrative Claims Database: A Population Cohort Study.

Introduction: CKD, a common complication of type-2 diabetes (T2D), causes considerable disease burden. Patients with T2D and CKD are considered high-risk for complications; however, studies describing patients with T2D and incident CKD identified from real-world data using the diagnostic gold-standard criteria - estimated glomerular filtration rate and urine albumin-to-creatinine ratio (UACR) - are scarce.

Methods: In this population-based cohort study, we sought to estimate the rates of cardiovascular and renal outcomes among patients with T2D and CKD by comorbidity subgroups and CKD severity.

Chronic opioid use and complication risks in women with endometriosis: A cohort study in US administrative claims.

Background: Women with endometriosis are prescribed opioids for pain relief but may be vulnerable to chronic opioid use given their comorbidity profile.

Methods: A cohort study was conducted in the Clinformatics™ DataMart database between 2006 and 2017 comparing women aged 18-50 years with endometriosis (N = 36 373) to those without (N = 2 172 936) in terms of risk of chronic opioid use, opioid dependence diagnosis, and opioid overdose. Chronic opioid use was defined as ≥120 days' supply dispensed or ≥10 fills of an opioid during any 365-day interval.

Outcomes Associated With Oral Anticoagulants Plus Antiplatelets in Patients With Newly Diagnosed Atrial Fibrillation.

Importance: Patients with nonvalvular atrial fibrillation at risk of stroke should receive oral anticoagulants (OAC). However, approximately 1 in 8 patients in the Global Anticoagulant Registry in the Field (GARFIELD-AF) registry are treated with antiplatelet (AP) drugs in addition to OAC, with or without documented vascular disease or other indications for AP therapy.

Objective: To investigate baseline characteristics and outcomes of patients who were prescribed OAC plus AP therapy vs OAC alone.

Implementation of the uterine fibroids Option Grid patient decision aids across five organizational settings: a randomized stepped-wedge study protocol.

Background: Uterine fibroids are non-cancerous overgrowths of the smooth muscle in the uterus. As they grow, some cause problems such as heavy menstrual bleeding, pelvic pain, discomfort during sexual intercourse, and rarely pregnancy complications or difficulty becoming pregnant. Multiple treatment options are available.

Comparative effectiveness of uterine fibroids procedures using linked medical record and claims data.

Aims: To compare durability of uterus-conserving procedures for symptomatic fibroids in terms of incidence and time to subsequent procedures.

Patients & Methods: We conducted a retrospective database study of 2648 patients having a uterus-conserving procedure for uterine fibroids from 2005 to 2011 with a minimum of 2 years follow-up.

Results: Patients with myomectomy or uterine artery embolization as their index procedure had lower risk of a subsequent procedure during the study compared with patients who underwent endometrial ablation.

The GRACE Checklist: A Validated Assessment Tool for High Quality Observational Studies of Comparative Effectiveness.

Background: Recognizing the growing need for robust evidence about treatment effectiveness in real-world populations, the Good Research for Comparative Effectiveness (GRACE) guidelines have been developed for noninterventional studies of comparative effectiveness to determine which studies are sufficiently rigorous to be reliable enough for use in health technology assessments.

Objective: To evaluate which aspects of the GRACE Checklist contribute most strongly to recognition of quality.

Methods: We assembled 28 observational comparative effectiveness articles published from 2001 to 2010 that compared treatment effectiveness and/or safety of drugs, medical devices, and medical procedures.

A call for comparative effectiveness research to learn whether routine clinical care decisions can protect from dementia and cognitive decline.

Common diseases like diabetes, hypertension, and atrial fibrillation are probable risk factors for dementia, suggesting that their treatments may influence the risk and rate of cognitive and functional decline. Moreover, specific therapies and medications may affect long-term brain health through mechanisms that are independent of their primary indication. While surgery, benzodiazepines, and anti-cholinergic drugs may accelerate decline or even raise the risk of dementia, other medications act directly on the brain to potentially slow the pathology that underlies Alzheimer's and other dementia.

Quality of life and visual acuity outcomes in the Registry in Glaucoma Outcomes Research study.

Aims: The RiGOR study evaluated the association of treatment and patient-reported outcomes for open-angle glaucoma patients.

Methods: The Glaucoma Symptom Scale (National Eye Institute-Visual Function Questionnaire (NEI-VFQ) and visual acuity (VA) were collected as quality of life measures.

Results: The proportion of patients with improvement of at least two lines of vision was highest in the incisional surgery group (14.

Impact of treatment strategies for open angle glaucoma on intraocular pressure: the RiGOR study.

Aims: The RiGOR study's primary outcome measure was a 15% reduction in intraocular pressure (IOP) for patients with open-angle glaucoma at 1 year.

Methods: Patients received treatment according to the ophthalmologist's usual practice.

Results: A higher proportion of patients in the incisional and other surgery group achieved a 15% reduction in IOP than in the laser surgery or additional medication groups (82, 57, and 57% respectively).

Practice patterns and treatment changes for open-angle glaucoma: the RiGOR study.

Aims: The RiGOR study provides a current picture of the types of glaucoma treatment over 12 months.

Methods: Patients were identified and enrolled at the time of decision to proceed with laser surgery procedure or other procedure such as incisional surgery or drainage device implantation, or initiation of a new or additional course of therapy with medication for glaucoma treatment.

Results: The most frequent type of treatments were prostaglandin analogues (60%) among patients with additional medication, selective laser trabeculoplasty (87%) among patients with laser surgery and trabeculectomy (57%) among patients with incisional surgery.

RiGOR: a prospective observational study comparing the effectiveness of treatment strategies for open-angle glaucoma.

Aims: The RigOR study was designed to assess comparative effectiveness of medications, laser trabeculoplasty and incisional surgery in patients with open-angle glaucoma (OAG) in the community initiating a new or additional course of therapy as judged necessary by their ophthalmologist. This paper focuses specifically on demographic and clinical characteristics of OAG patients at enrollment.

Patients & Methods: A total of 2597 with OAG already on medical therapy were enrolled from 45 community and academic practices throughout the USA.

Association of sweat chloride concentration at time of diagnosis and CFTR genotype with mortality and cystic fibrosis phenotype.

Background: The extent to which sweat chloride concentration predicts survival and clinical phenotype independently of CFTR genotype in cystic fibrosis is not well understood.

Methods: We analyzed the US Cystic Fibrosis Foundation Patient Registry data using Cox regression to examine the relationship between sweat chloride concentration (<60, 60-<80, ≥80mmol/L), CFTR genotype (high and lower risk for lung function decline), and survival and mixed linear regression to examine the relationship between sweat chloride, CFTR genotype, and measures of lung function and growth.

Results: When included in the same model, CFTR genotype, but not sweat chloride, was independently associated with survival and with lung function, height, and BMI.

Characterization of Missing Data in Clinical Registry Studies.

Patterns of missing data are seldom well-characterized in observational research. This study examined the magnitude of, and factors associated with, missing data across multiple observational studies. Missingness was evaluated for demographic, clinical, and patient-reported outcome (PRO) data from a procedure registry (TOPS), a rare disease (cystic fibrosis) registry (Port-CF), and a comparative effectiveness registry (glaucoma, RiGOR).

The GRACE checklist for rating the quality of observational studies of comparative effectiveness: a tale of hope and caution.

Background: While there is growing demand for information about comparative effectiveness (CE), there is substantial debate about whether and when observational studies have sufficient quality to support decision making.

Objective: To develop and test an item checklist that can be used to qualify those observational CE studies sufficiently rigorous in design and execution to contribute meaningfully to the evidence base for decision support.

Methods: An 11-item checklist about data and methods (the GRACE checklist) was developed through literature review and consultation with experts from professional societies, payer groups, the private sector, and academia.

Algorithms for identification of Guillain-Barré Syndrome among adolescents in claims databases.

Background: Health insurance claims databases can provide data for studies of vaccine-related Guillain-Barre' Syndrome (GBS), but not all patients with a diagnostic ICD-9-CM code for GBS have the disease. The objective of this study was to evaluate the positive predictive values (PPVs) of claims-based algorithms for identifying GBS cases in 4 claims database environments.

Methods: Potential cases were adolescents ages 11-21 with at least one claim for GBS (ICD-9-CM code 357.

A prospective observational safety study on MF59(®) adjuvanted cell culture-derived vaccine, Celtura(®) during the A/H1N1 (2009) influenza pandemic.

Background: The present study was a prospective observational study to evaluate the safety profile of Celtura(®), a monovalent, cell culture-derived, inactivated subunit influenza vaccine prepared from A/California/07/2009(H1N1) with the adjuvant MF59(®). Subjects were enrolled prospectively during the H1N1 2009 influenza pandemic at medical centres in Colombia, Chile, Switzerland, and Germany during the period December 2009 to June 2010.

Methods: Subjects ages 18 and older were followed for the occurrence of adverse events (AEs) for six months after vaccination.

Risk of Guillain-Barré syndrome after meningococcal conjugate vaccination.

Purpose: A new meningococcal conjugate vaccine (MCV4) was introduced in 2005. Shortly after, case reports of Guillain-Barré syndrome (GBS), a serious demyelinating disease, began to be reported to the Vaccine Adverse Event Reporting System. In 2006, the Centers for Disease Control and Prevention and the Food and Drug Administration requested the evaluation of GBS risk after MCV4 vaccination.

Incorporating stakeholder perspectives in developing a translation table framework for comparative effectiveness research.

This project used a stakeholder-driven process to understand the factors that drive the selection of study designs for comparative effectiveness research (CER). The project assembled a diverse stakeholder committee to explore the basis of a translation framework and gathered input through surveys, interviews and an in-person meeting. Stakeholders recommended different study designs for the CER topic areas and identified different outcomes as the most important outcomes to study in each area.