Priscilla Velentgas

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. 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.

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. Adverse events of special interest (AESIs) were neuritis, convulsion (seizure), anaphylaxis, encephalitis, vasculitis, Guillain-Barre syndrome, demyelinating conditions, Bells 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.

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. During the discussions, stakeholders described a variety of factors that influenced their study design recommendations. The stakeholder activities resulted in the identification of several key themes, including the need to have a highly specific detailed research question before discussing appropriate designs and the need to use multiple studies, potentially of different designs, to address the CER topic areas. The insights and themes from this project may inform efforts to develop a translation table.

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). Generalized linear mixed effects models were fit to assess whether patient characteristics or follow-up methods predicted missingness. Data from 156,707 surgical procedures, 32,118 cystic fibrosis patients, and 2373 glaucoma patients were analyzed. Data were rarely missing for demographics, treatments, and outcomes. Missingness for clinical variables varied by registry and measure and depended on whether a variable was required. Within RiGOR, PRO forms were missing more often when collected by e-mail compared with office-based paper data collection. In Port-CF, missingness varied based on insurance status and sex. Strategic consideration of operational approaches affecting missing data should be performed prior to data collection and assessed periodically during study conduct.

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. CONCLUSION For 36% of patients, a treatment cascade involves two or more therapies over a year. This demonstrates the complex nature of open-angle glaucoma treatment.

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. RESULTS Overall, 784 (30%) patients were treated with laser surgery, 436 with other surgical procedures (17%), and 1377 with additional medication (53%). Patients had mild (35%) or moderate (31%) glaucoma, with 28% with severe glaucoma. CONCLUSION The RiGOR study enrolled a diverse population and will provide valuable information regarding visual function and treatment patterns among different racial/ethnic populations. African-American and Hispanic patients entered the study with poorer visual acuity and more severe glaucoma.

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. 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.

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

AIMS The RiGOR studys 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 ophthalmologists 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). In multivariate regression analyses, incisional surgery patients were 2.7-times as likely as patients treated with additional medication to achieve a 15% reduction in IOP (odds ratio: 2.67; 95% CI: 2.01-3.57). CONCLUSION Incisional and other surgical procedures are effective treatments. There were no differences in treatment response by race or ethnicity.

Comparing Patient-Centered Outcomes after Treatment for Uterine Fibroids

....................................................................................................................... 3 1. BACKGROUND ................................................................................................................. 4 2. METHODS ........................................................................................................................ 6 2.1 Retrospective Cohort Study ............................................................................................................................... 6 2.1.1 Study Design .................................................................................................................................................... 6 2.1.2 Subjects ........................................................................................................................................................... 7 2.1.3 Variables .......................................................................................................................................................... 8 2.1.4 Statistical Methods ........................................................................................................................................ 10 2.2 Stakeholder Engagement ................................................................................................................................ 11 2.2.1 Study Design .................................................................................................................................................. 11 2.2.2 Subjects ......................................................................................................................................................... 12 2.2.3 Analysis Methods .......................................................................................................................................... 12 3. RESULTS ......................................................................................................................... 12 3.1 Retrospective Cohort Study ............................................................................................................................. 12 3.1.1 Descriptive Data ............................................................................................................................................ 12 3.1.2 Main Results .................................................................................................................................................. 17 3.1.3 Sensitivity Analyses ....................................................................................................................................... 28 3.2 Stakeholder Engagement ................................................................................................................................ 29 3.2.1 Main Results .................................................................................................................................................. 29 4. DISCUSSION ................................................................................................................... 31 4.1 Retrospective Cohort Study ...................................................................................................................... 31 4.1.1 Key Results ..................................................................................................................................................... 31 4.1.2 Biases and Limitations ................................................................................................................................... 32 4.2 Stakeholder Engagement ................................................................................................................................ 34 5. CONCLUSION ................................................................................................................. 35 5.1 Retrospective Cohort Study .............................................................................................................................. 35 5.2 Stakeholder Engagement ................................................................................................................................. 36 6. REFERENCES.................................................................................................................... 37 7. APPENDICES ................................................................................................................... 39

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 (14.2% compared with 9.9% for laser surgery and 10.9% for additional medication). CONCLUSION No clinically relevant differences were seen in benefit for the laser surgery or incisional surgery groups compared with additional medications for the Glaucoma Symptom Scale or NEI-VFQ measures or subscales. Differences in quality of life by race need to be explored in further studies.