Search

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. In other words, the functional and cognitive decline in vulnerable patients may be influenced by the choice of treatments for other medical conditions. Despite the importance of these questions, very little research is available. The Alzheimer's Drug Discovery Foundation convened an advisory panel to discuss the existing evidence and to recommend strategies to accelerate the development of comparative effectiveness research on how choices in the clinical care of common chronic diseases may protect from cognitive decline and dementia.

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. In other words, the functional and cognitive decline in vulnerable patients may be influenced by the choice of treatments for other medical conditions. Despite the importance of these questions, very little research is available. The Alzheimer’s Drug Discovery Foundation convened an advisory panel to discuss the existing evidence and to recommend strategies to accelerate the development of comparative effectiveness research on how choices in the clinical care of common chronic diseases may protect from cognitive decline and dementia., Version of Record

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 Streptococcus pneumoniae , 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. Therefore, it is important to understand whether cross-reactive antibodies offer clinical protection against pneumococcal disease. This review explores available evidence of cross-reactivity and cross-protection associated with pneumococcal vaccines, the challenges associated with the assessment of cross-reactivity and cross-protection, and implications for vaccine design and development.

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. Novel conjugation processes, carriers, adjuvants, and vaccine platforms are approaches that could help maintain or improve immunogenicity and subsequent vaccine effectiveness while achieving broader protection with increasing valency in pneumococcal vaccines., Competing Interests: Potential conflicts of interest. K. F., U. K. B., N. B., P. V., and T. J. C. are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc., Rahway, New Jersey, USA (MSD), and may own stock and/or hold stock options in Merck & Co, Inc., Rahway, New Jersey, USA. J. G. J. is a former employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc., Rahway, New Jersey, USA, and may own stock and/or hold stock options in Merck & Co, Inc., Rahway, New Jersey, USA. I. Y. reports no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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., Methods and Findings: We explored design innovations, operational challenges, and infrastructure needs within a multi-stakeholder consortium to evaluate the potential of an APoC platform trial for studying chronic disease treatment regimens using rheumatoid arthritis as a case study. The concept integrates elements from adaptive clinical trials (dynamic treatment regimen strategies) and point-of-care trials (research embedded into routine clinical care) under a perpetual platform infrastructure. The necessary components to implement an APoC platform trial within outpatient settings exist, and present an opportunity for a cross-disciplinary, multi-stakeholder approach. Effective engagement of key stakeholders involved in and impacted by the platform is critical to success. Our collaborative design process identified three high-impact stakeholder-engagement areas: (1) focus on research question(s), (2) design and implementation planning such that it is feasible and fit-for-purpose, and (3) measurement, or meaningful metrics for both clinical (patient outcomes) and system (operational efficiencies) impact., Conclusions: An APoC platform trial for rheumatoid arthritis integrating innovative design elements in a scalable infrastructure has the potential to reduce important uncertainties about the real-world performance of biomedical innovations and improve clinical decisions., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Hirsch reported receiving support for the present manuscript from the NEWDIGS initiative under MIT's Center for Biomedical Innovation (CBI) and from the NEWDIGS initiative under Tufts Medical Center's Center for Biomedical System Design (CBSD). Dr. Velentgas reported receiving support for the present manuscript from IQVIA (past position). Dr. Curtis reported receiving grants from Abbvie, Amgen, GHLF, BMS, CorEvitas, GSK, Janssen, Lilly, Myriad, Novartis, Pfizer, Sanofi, UCB, consulting fees from Abbvie, Amgen, GHLF, BMS, CorEvitas, GSK, Illumination Health, Janssen, Lilly, Myriad, Novartis, Pfizer, Sanofi, Scipher, UCB, and other financial or non-financial interests in Illumination Health. Dr. Larholt reported receiving support for the present manuscript from the NEWDIGS initiative under MIT's Center for Biomedical Innovation (CBI) and reported receiving stock options from Johnson & Johnson. Dr. Park reported being an employee of Core Clinical Sciences, Inc. No other disclosures were reported., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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)., Methods: Adult patients with T2D entered the cohort if they met the criteria for CKD, defined as 2 laboratory test results 90 to 365 days apart (January 2014-September 2017) indicating CKD. Included were patients with no prior use of ACEis or ARBs or evidence of kidney disease in the 365 days prior to cohort entry (baseline). Patients were followed for a maximum of 365 days and were censored on death, disenrollment, or end of data. Patient demographics, comorbidities, and medication use were assessed at baseline, and treatments were assessed over a 1-year followup period. Multivariate logistic regression was used to identify factors associated with ACEi or ARB initiation., Results: Among 15,400 eligible patients without prior ACEi or ARB treatment, only 17% initiated such therapy within a year after meeting CKD criteria. Patients who were White, resided in the northeastern United States, had more comorbidities, had less advanced albuminuria, or used sodium-glucose cotransporter 2 inhibitors were less likely to initiate treatment., Conclusions: A large proportion of patients with T2D meeting criteria for CKD do not initiate the recommended therapy within 1 year of CKD diagnosis, highlighting a need for new therapies that can slow the progression of CKD.

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. Among women with endometriosis, we evaluated factors associated with higher risk of chronic opioid use and quantified the risk of complications associated with the use of opioids., Results: Women with endometriosis were at greater risk for chronic opioid use (OR: 3.76; 95%CI: 3.57-3.96), dependence (OR: 2.73, 95%CI: 2.38-3.13) and overdose (OR: 4.34, 95%CI: 3.06-6.15) compared to women without. Chronic users displayed dose escalation and increase in days supplied over time, as well as co-prescribing with benzodiazepines and sedatives. Approximately 34% of chronic users developed constipation, 20% experienced falls, and 8% reported dizziness. Among endometriosis patients, women in younger age groups, those with other comorbidities associated with pain symptoms, as well as those with depression or anxiety were at a higher risk of developing chronic opioid use., Conclusions: Women with endometriosis had a four times greater risk of chronic opioid use compared to women without. Multimorbidity among these patients was associated with the elevated risk of chronic opioid use and should be taken into account during treatment selection., (© 2021 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

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., Methods: This retrospective, population-based cohort study assessed CKD progression among adults with T2D and with newly recognized CKD identified from US administrative claims data between 1 January 2008 and 30 September 2018. Included were patients with T2D and laboratory evidence of CKD as indicated by the established estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (UACR) criteria. Disease progression was described as transitions across the eGFR- and UACR-based stages., Results: A total of 65 731 and 23 035 patients with T2D contributed to the analysis of eGFR- and UACR-based CKD stage progression, respectively. CKD worsening was observed in approximately 10-17% of patients over a median follow-up of 2 years. Approximately one-third of patients experienced an increase in eGFR values or a decrease in UACR values during follow-up., Conclusions: A relatively high proportion of patients were observed with disease progression over a short period of time, highlighting the need for better identification of patients at risk of rapidly progressive CKD. Future studies are needed to determine the clinical characteristics of these patients to inform earlier diagnostic and therapeutic interventions aimed at slowing disease progression., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

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., Design, Setting, and Participants: Prospective cohort study of the GARFIELD-AF registry, an international, multicenter, observational study of adults aged 18 years and older with recently diagnosed nonvalvular atrial fibrillation and at least 1 risk factor for stroke enrolled between March 2010 and August 2016. Data were extracted for analysis in October 2017 and analyzed from April 2018 to June 2019., Exposure: Participants received either OAC plus AP or OAC alone., Main Outcomes and Measures: Clinical outcomes were measured over 3 and 12 months. Outcomes were adjusted for 40 covariates, including baseline conditions and medications., Results: A total of 24 436 patients (13 438 [55.0%] male; median [interquartile range] age, 71 [64-78] years) were analyzed. Among eligible patients, those receiving OAC plus AP therapy had a greater prevalence of cardiovascular indications for AP, including acute coronary syndromes (22.0% vs 4.3%), coronary artery disease (39.1% vs 9.8%), and carotid occlusive disease (4.8% vs 2.0%). Over 1 year, patients treated with OAC plus AP had significantly higher incidence rates of stroke (adjusted hazard ratio [aHR], 1.49; 95% CI, 1.01-2.20) and any bleeding event (aHR, 1.41; 95% CI, 1.17-1.70) than those treated with OAC alone. These patients did not show evidence of reduced all-cause mortality (aHR, 1.22; 95% CI, 0.98-1.51). Risk of acute coronary syndrome was not reduced in patients taking OAC plus AP compared with OAC alone (aHR, 1.16; 95% CI, 0.70-1.94). Patients treated with OAC plus AP also had higher rates of all clinical outcomes than those treated with OAC alone over the short term (3 months)., Conclusions and Relevance: This study challenges the practice of coprescribing OAC plus AP unless there is a clear indication for adding AP to OAC therapy in newly diagnosed atrial fibrillation.

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. Twenty-two volunteers from academia, pharmaceutical companies, and government agencies applied the GRACE Checklist to those articles, providing 56 assessments. Ten senior academic and industry experts provided assessments of overall article quality for the purpose of decision support. We also rated each article based on the number of annual citations and impact factor of the journal in which the article was published. To identify checklist items that were most predictive of quality, classification and regression tree (CART) analysis, a binary, recursive, partitioning methodology, was used to create 3 decision trees, which compared the 56 article assessments with 3 external quality outcomes: (1) expert assessment of overall quality, (2) citation frequency, and (3) impact factor. A fourth tree looked at the composite outcome of all 3 quality indicators., Results: The best predictors of quality included the following: use of concurrent comparators, limiting the study to new initiators of the study drug, equivalent measurement of outcomes in study groups, collecting data on most if not all known confounders or effect modifiers, accounting for immortal time bias in the analysis, and use of sensitivity analyses to test how much effect estimates depended on various assumptions. Only sensitivity analyses appeared consistently as a predictor of quality in all 4 trees. When a composite outcome of the 3 quality measures was used, the GRACE Checklist showed high sensitivity and specificity (71.43% and 80.95%, respectively)., Conclusions: The GRACE Checklist stands out from other consensus-driven and expert guidance documents because of its extensive validation efforts. This most recent work shows that the checklist has strong sensitivity and specificity, increasing its utility as a screening tool to identify high-quality observational comparative effectiveness research worthy of in-depth review and applicability for decision support., Disclosures: No outside funding supported this research. All authors are full-time employees of Quintiles, which provides research and consulting services to the biopharmaceutical industry. The authors have no other disclosures to report. Two of the 3 CART trees were presented at the International Society of Pharmacepidemiology in 2015 ("Article Citations per Year" and "Journal Impact Factor"). The original validation study was published in the March 2014 issue of the Journal of Managed Care & Specialty Pharmacy. The checklist questions and scoring were included using a table that was originally published by this journal in 2014. Study concept and design were primarily contributed by Dreyer and Velentgas, along with Bryant. Bryant took the lead in data collection and analysis, along with Dreyer and Velentgas, and data interpretation was performed by Dreyer, Velentgas, and Bryant. The manuscript was written and revised primarily by Dreyer, along with Bryant and Velentgas.

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. Among patients with unclassified CFTR genotype, sweat chloride was an independent predictor of survival (<60 HR 0.53 [0.37, 0.77], 60-<80 0.51 [0.42, 0.63])., Conclusions: Sweat chloride concentration may be a useful predictor of mortality and clinical phenotype when CFTR genotype functional class is unclassified., (Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

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. Since no single gold standard exists for validation, checklist item responses were compared with 3 different types of external quality ratings (N=88 articles). The articles compared treatment effectiveness and/or safety of drugs, medical devices, and medical procedures. We validated checklist item responses 3 ways against external quality ratings, using published articles of observational CE or safety studies: (a) Systematic Review-quality assessment from a published systematic review; (b) Single Expert Review-quality assessment made according to the solicited "expert opinion" of a senior researcher; and (c) Concordant Expert Review-quality assessments from 2 experts for which there was concordance. Volunteers (N=113) from 5 continents completed 280 article assessments using the checklist. Positive and negative predictive values (PPV, NPV, respectively) of individual items were estimated to compare testers' assessments with those of experts., Results: Taken as a whole, the scale had better NPV than PPV, for both data and methods. The most consistent predictor of quality relates to the validity of the primary outcomes measurement for the study purpose. Other consistent markers of quality relate to using concurrent comparators, minimizing the effects of bias by prudent choice of covariates, and using sensitivity analysis to test robustness of results. Concordance of expert opinion on the quality of the rated articles was 52%; most checklist items performed better., Conclusions: The 11-item GRACE checklist provides guidance to help determine which observational studies of CE have used strong scientific methods and good data that are fit for purpose and merit consideration for decision making. The checklist contains a parsimonious set of elements that can be objectively assessed in published studies, and user testing shows that it can be successfully applied to studies of drugs, medical devices, and clinical and surgical interventions. Although no scoring is provided, study reports that rate relatively well across checklist items merit in-depth examination to understand applicability, effect size, and likelihood of residual bias. The current testing and validation efforts did not achieve clear discrimination between studies fit for purpose and those not, but we have identified a critical, though remediable, limitation in our approach. Not specifying a specific granular decision for evaluation, or not identifying a single study objective in reports that included more than one, left reviewers with too broad an assessment challenge. We believe that future efforts will be more successful if reviewers are asked to focus on a specific objective or question. Despite the challenges encountered in this testing, an agreed upon set of assessment elements, checklists, or score cards is critical for the maturation of this field. Substantial resources will be expended on studies of real-world effectiveness, and if the rigor of these observational assessments cannot be assessed, then the impact of the studies will be suboptimal. Similarly, agreement on key elements of quality will ensure that budgets are appropriately directed toward those elements. Given the importance of this task and the lessons learned from these extensive efforts at validation and user testing, we are optimistic about the potential for improved assessments that can be used for diverse situations by people with a wide range of experience and training. Future testing would benefit by directing reviewers to address a single, granular research question, which would avoid problems that arose by using the checklist to evaluate multiple objectives, by using other types of validation test sets, and by employing further multivariate analysis to see if any combination or sequence of item responses has particularly high predictive validity.

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 357.0). Medical record reviews by a panel of 3 neurologists were conducted for case confirmation. Claims data considered for inclusion in the case-ascertainment algorithm included coding position, physician specialty, visit type, diagnostic tests. PPVs were used to assess the contribution of study factors in predicting case status., Results: Among 361 individuals with a GBS diagnosis code, 106 were confirmed overall (PPV=0.29), varying from 0.24 to 0.56 across the 4 sites. Requiring the GBS code to be associated with a neurologist visit (PPV=0.53) or to be in a primary position on an inpatient claim (0.56) improved the performance. A composite algorithm including a primary inpatient GBS code and a neurologist visit associated with any GBS code gave the highest PPV (0.70). Incorporating claims for diagnostic testing had little impact on the PPV. Findings were generally similar across study sites., Conclusions: Algorithms were able to identify GBS cases better than the single occurrence of the diagnostic code for GBS, and these algorithms may perform similarly in different claims environments., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

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. We conducted a study to assess the risk of GBS after MCV4 vaccination using health plan administrative and claims data together with the review of primary medical records of potential cases., Methods: Retrospective cohort study among 12.6 million 11- to 21-year-old members of five US health plans with a total membership of 50 million. Automated enrollment and medical claims data from March 2005 through August 2008 were used to identify the population, the vaccinations administered, and the medical services associated with possible GBS. Medical records were reviewed and adjudicated by a neurologist panel to confirm cases of GBS. The study used distributed data analysis methods that minimized sharing of protected health information., Results: We confirmed 99 GBS cases during 18,322,800 person-years (5.4/1,000,000 person-years). More than 1.4 million MCV4 vaccinations were observed. No confirmed cases of GBS occurred within 6 weeks after vaccination. The upper 95% CI for the attributable risk of GBS associated with MCV4 is estimated as 1.5 cases per 1,000,000 doses., Conclusions: Among members of five US health plans, MCV4 vaccination was not associated with increased GBS risk., (Copyright © 2012 John Wiley & Sons, Ltd.)

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. Adverse events of special interest (AESIs) were neuritis, convulsion (seizure), anaphylaxis, encephalitis, vasculitis, Guillain-Barre syndrome, demyelinating conditions, Bell's palsy, and laboratory-confirmed vaccination failure., Results: Overall, 7348 AEs were reported in 2296 of 3989 enrolled subjects (57.6%). Only two AEs were considered related to injection site reactions. No laboratory-confirmed cases of influenza were reported. There were 108 medically confirmed serious adverse events (SAEs) reported among 73 subjects with 6 such SAEs described as possibly or probably related to vaccination. Three fatal cases were reported and assessed as not related to vaccination. Two AESIs classified as convulsion were reported and assessed as not related to vaccination. Both AESIs occurred well outside the pre-specified 7 day risk window representing the likely timeframe of the occurrence of seizure following vaccination., Conclusions: The results of this study support the overall good safety profile of MF59 adjuvanted cell culture-derived influenza vaccine as administered in adults during the 2009-2010 H1N1 influenza pandemic. No concern is raised regarding the occurrence of AESIs., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objectives: To assess the predictive value of claims-based outpatient urticaria diagnosis codes to identify potential vaccine-related adverse events (AEs) when recorded on the same day as influenza vaccination., Study Design and Setting: Health plan members with outpatient claims for influenza vaccination and urticaria on the same day between October 1, 2002, and December 31, 2007, were eligible for inclusion. Electronic medical records (EMRs) for 50 eligible patients with the most recent visits of interest occurring at a large group practice were sampled for review., Results: EMRs were available and reviewed for 42 of 50 patients. An influenza vaccination was confirmed in all reviewed medical charts. Urticaria occurring on the day of influenza vaccination was confirmed for 40% of participants (17/42); 3 confirmed urticaria diagnoses were potential AEs and 14 urticaria events occurred before vaccination. Among those with unconfirmed diagnoses, 17 had no evidence of urticaria on physical examination on the day of interest (4 had evidence of a nonurticarial rash and 13 had no evidence of rash on examination) and 8 had insufficient information to make a clinical determination., Conclusion: Outpatient diagnosis codes for urticaria found in health insurance claims data are limited in their predictive value to identify same-day vaccine AEs., (Copyright 2010 Elsevier Inc. All rights reserved.)

We estimated life expectancy at birth for Gaucher disease type 1 (GD1) patients by comparing survival data from GD1 patients enrolled in ICGG Gaucher Registry to the U.S. population using standard life table methods. 2,876 GD1 patients had 102 reported deaths in 13,509 person-years of follow-up. Estimated life expectancy at birth was 68 y, compared with 77 y in reference population; splenectomized patients, 64 y; nonsplenectomized, 72 y. Causes of death for 63/102 patients were malignancy (17/63), cardiovascular (11/63), and cerebrovascular (8/63). Estimated life expectancy at birth for GD1 patients was approximately 9 y less than reference population. Malignancies did not contribute to shortened life expectancy., (Copyright 2008 Wiley-Liss, Inc.)

Purpose: We describe a multi-center post-marketing safety study that uses distributed data methods to minimize the need for covered entities to share protected health information (PHI). Implementation has addressed several issues relevant to creation of a large scale post-marketing drug safety surveillance system envisioned by the FDA's Sentinel Initiative., Methods: This retrospective cohort study of Guillain-Barré syndrome (GBS) following meningococcal conjugate vaccination incorporates the data and analytic expertise of five research organizations closely affiliated with US health insurers. The study uses administrative claims data, plus review of full text medical records to adjudicate the status of individuals with a diagnosis code for GBS (ICD9 357.0). A distributed network approach is used to create the analysis files and to perform most aspects of the analysis, allowing nearly all of the data to remain behind institutional firewalls. Pooled analysis files transferred to a central site will contain one record per person for approximately 0.2% of the study population, and contain PHI limited to the month and year of GBS onset for cases or the index date for matched controls., Results: The first planned data extraction identified over 9 million eligible adolescents in the target age range of 11-21 years. They contributed an average of 14 months of eligible time on study over 27 months of calendar time. MCV4 vaccination coverage levels exceeded 20% among 17-18-year olds and 16% among 11-13 and 14-16-year-old age groups by the second quarter of 2007., Conclusion: This study demonstrates the feasibility of using a distributed data network approach to perform large scale post-marketing safety analyses and is scalable to include additional organizations and data sources. We believe these results can inform the development of a large national surveillance system., (Copyright (c) 2008 John Wiley & Sons, Ltd.)