Tia L. Kauffman

Effectiveness of Seasonal Trivalent Influenza Vaccine for Preventing Influenza Virus Illness Among Pregnant Women: A Population-Based Case-Control Study During the 2010–2011 and 2011–2012 Influenza Seasons

BACKGROUND Although vaccination with trivalent inactivated influenza vaccine (TIV) is recommended for all pregnant women, no vaccine effectiveness (VE) studies of TIV in pregnant women have assessed laboratory-confirmed influenza outcomes. METHODS We conducted a case-control study over 2 influenza seasons (2010-2011 and 2011-2012) among Kaiser Permanente health plan members in 2 metropolitan areas in California and Oregon. We compared the proportion vaccinated among 100 influenza cases (confirmed by reverse transcription polymerase chain reaction) with the proportions vaccinated among 192 controls with acute respiratory illness (ARI) who tested negative for influenza and 200 controls without ARI (matched by season, site, and trimester). RESULTS Among influenza cases, 42% were vaccinated during the study season compared to 58% and 63% vaccinated among influenza-negative controls and matched ARI-negative controls, respectively. The adjusted VE of the current season vaccine against influenza A and B was 44% (95% confidence interval [CI], 5%-67%) using the influenza-negative controls and 53% (95% CI, 24%-72%) using the ARI-negative controls. Receipt of the prior seasons vaccine, however, had an effect similar to receipt of the current seasons vaccine. As such, vaccination in either or both seasons had statistically similar adjusted VE using influenza-negative controls (VE point estimates range = 51%-76%) and ARI-negative controls (48%-76%). CONCLUSIONS Influenza vaccination reduced the risk of ARI associated with laboratory-confirmed influenza among pregnant women by about one-half, similar to VE observed among all adults during these seasons.

Systematic review of the predictive effect of MSI status in colorectal cancer patients undergoing 5FU-based chemotherapy

BackgroundWe systematically reviewed the evidence for the interaction of microsatellite instability status (MSI) and treatment with 5FU in colorectal cancer to determine how well MSI status predicts health outcomes in patients undergoing 5FU-based chemotherapy.MethodsWe conducted a search of four electronic databases through June 2013. We considered studies that included both colorectal cancer patients treated with 5FU-based chemotherapy and untreated patients with survival outcomes presented by MSI status.ResultsWe identified 16 studies for qualitative analysis (9,212 patients) with 14 studies eligible for meta-analysis. The microsatellite stable (MSS) group showed an effect of 5FU treatment on disease-free survival (HR of 0.62 [95% CI: 0.54, 0.71]) and overall survival (HR of 0.65 [95% CI: 0.54, 0.79]), indicating that MSS patients who received 5FU treatment had longer survival than MSS patients who were untreated. The effect of 5FU treatment was not statistically significant for microsatellite high (MSI-H) patients for disease-free survival (HR of 0.84 [95% CI: 0.53, 1.32]) or overall survival (HR 0.66 [95% CI: 0.43, 1.03]). However, the summarized point estimates of the effects of 5FU treatment for the MSS and MSI-H groups were not different at a statistically significant level.ConclusionsOur analyses indicate that treatment with 5FU-based chemotherapy improves disease-free and overall survival in CRC patients, but that there is no difference in the effect of treatment based on MSI status. Therefore, the use of MSI status to guide treatment decisions about the use of 5FU treatment for CRC has no significant benefits for patients.

“Is It Worth Knowing?” Focus Group Participants’ Perceived Utility of Genomic Preconception Carrier Screening

As genome sequencing technology advances, research is needed to guide decision-making about what results can or should be offered to patients in different clinical settings. We conducted three focus groups with individuals who had prior preconception genetic testing experience to explore perceived advantages and disadvantages of genome sequencing for preconception carrier screening, compared to usual care. Using a discussion guide, a trained qualitative moderator facilitated the audio-recorded focus groups. Sixteen individuals participated. Thematic analysis of transcripts started with a grounded approach and subsequently focused on participants’ perceptions of the value of genetic information. Analysis uncovered two orientations toward genomic preconception carrier screening: “certain” individuals desiring all possible screening information; and “hesitant” individuals who were more cautious about its value. Participants revealed valuable information about barriers to screening: fear/anxiety about results; concerns about the method of returning results; concerns about screening necessity; and concerns about partner participation. All participants recommended offering choice to patients to enhance the value of screening and reduce barriers. Overall, two groups of likely users of genome sequencing for preconception carrier screening demonstrated different perceptions of the advantages or disadvantages of screening, suggesting tailored approaches to education, consent, and counseling may be warranted with each group.

Underutilization of Lynch syndrome screening in a multisite study of patients with colorectal cancer

Purpose:The aim of this study was to examine Lynch syndrome screening of patients with metastatic colorectal cancer in integrated health-care-delivery organizations.Methods:We determined the availability of Lynch syndrome screening criteria and actual Lynch syndrome screening in the medical records of 1,188 patients diagnosed with metastatic colorectal cancer between 2004 and 2009 at seven institutions in the Cancer Research Network.Results:We found infrequent use of Lynch syndrome screening (41/1,188). Family history was available for 937 of the 1,188 patients (79%). There was sufficient information to assess Lynch syndrome risk using family history–based criteria in 719 of the 937 patients (77%) with family history documentation. In 391 individuals with a family history of a Lynch syndrome–associated cancer, 107 (27%) could not be evaluated due to missing information such as age of cancer onset. Eleven percent of patients who met the Bethesda criteria and 25% of individuals who met the Amsterdam II criteria were screened for Lynch syndrome. Recommended guidelines were adhered to during screening, but no testing method was preferred.Conclusion:The information required for Lynch syndrome screening decisions is routinely collected but seldom used. There is a critical gap between collection of family history and its use to guide Lynch syndrome screening, which may support a case for implementation of universal screening guidelines.Genet Med 15 12, 933–940.Genetics in Medicine (2013); 15 12, 933–940. doi:10.1038/gim.2013.43

Genome sequencing and carrier testing: decisions on categorization and whether to disclose results of carrier testing

Purpose:We investigated the use of genome sequencing for preconception carrier testing. Genome sequencing could identify one or more of thousands of X-linked or autosomal recessive conditions that could be disclosed during preconception or prenatal counseling. Therefore, a framework that helps both clinicians and patients understand the possible range of findings is needed to respect patient preferences by ensuring that information about only the desired types of genetic conditions are provided to a given patient.Methods:We categorized gene–condition pairs into groups using a previously developed taxonomy of genetic conditions. Patients could elect to receive results from these categories. A Return of Results Committee (RORC) developed inclusion and exclusion criteria for each category.Results:To date, the RORC has categorized 728 gene–condition pairs: 177 are categorized as life span–limiting, 406 are categorized as serious, 93 are categorized as mild, 41 are categorized as unpredictable, and 11 are categorized as adult-onset. An additional 64 gene–condition pairs were excluded from reporting to patients or put on a watch list, generally because evidence that a gene and condition were associated was limited.Conclusion:Categorization of gene–condition pairs using our taxonomy simplifies communication regarding patient preferences for carrier information from a genomic test.Genet Med advance online publication 12 January 2017

KRAS Testing and Epidermal Growth Factor Receptor Inhibitor Treatment for Colorectal Cancer in Community Settings

Background: In metastatic colorectal cancer (mCRC), mutations in the KRAS gene predict poor response to EGF receptor (EGFR) inhibitors. Clinical treatment guidelines now recommend KRAS testing if EGFR inhibitors are considered. Our study investigates the clinical uptake and utilization of KRAS testing. Methods: We included 1,188 patients with mCRCs diagnosed from 2004 to 2009, from seven integrated health care delivery systems with a combined membership of 5.5 million. We used electronic medical records and targeted manual chart review to capture the complexity and breadth of real-world clinical oncology care. Results: Overall, 428 patients (36%) received KRAS testing during their clinical care, and 266 (22%) were treated with EGFR inhibitors. Age at diagnosis (P = 0.0034), comorbid conditions (P = 0.0316), and survival time from diagnosis (P < 0.0001) influence KRAS testing and EGFR inhibitor prescribing. The proportion who received KRAS testing increased from 7% to 97% for those treated in 2006 and 2010, respectively, and 83% of all treated patients had a KRAS wild-type genotype. Most patients with a KRAS mutation (86%) were not treated with EGFR inhibitors. The interval between mCRC diagnosis and receipt of KRAS testing decreased from 26 months (2006) to 10 months (2009). Conclusions: These findings show rapid uptake and incorporation of this predictive biomarker into clinical oncology care. Impact: In this delivery setting, KRAS testing is widely used to guide treatment decisions with EGFR inhibitors in patients with mCRCs. An important future research goal is to evaluate utilization of KRAS testing in other delivery settings in the United States. Cancer Epidemiol Biomarkers Prev; 22(1); 91–101. ©2012 AACR.

Patients' ratings of genetic conditions validate a taxonomy to simplify decisions about preconception carrier screening via genome sequencing

Advances in genome sequencing and gene discovery have created opportunities to efficiently assess more genetic conditions than ever before. Given the large number of conditions that can be screened, the implementation of expanded carrier screening using genome sequencing will require practical methods of simplifying decisions about the conditions for which patients want to be screened. One method to simplify decision making is to generate a taxonomy based on expert judgment. However, expert perceptions of condition attributes used to classify these conditions may differ from those used by patients. To understand whether expert and patient perceptions differ, we asked women who had received preconception genetic carrier screening in the last 3 years to fill out a survey to rate the attributes (predictability, controllability, visibility, and severity) of several autosomal recessive or X‐linked genetic conditions. These conditions were classified into one of five taxonomy categories developed by subject experts (significantly shortened lifespan, serious medical problems, mild medical problems, unpredictable medical outcomes, and adult‐onset conditions). A total of 193 women provided 739 usable ratings across 20 conditions. The mean ratings and correlations demonstrated that participants made distinctions across both attributes and categories. Aggregated mean attribute ratings across categories demonstrated logical consistency between the key features of each attribute and category, although participants perceived little difference between the mild and serious categories. This study provides empirical evidence for the validity of our proposed taxonomy, which will simplify patient decisions for results they would like to receive from preconception carrier screening via genome sequencing.

Generating a taxonomy for genetic conditions relevant to reproductive planning.

As genome or exome sequencing (hereafter genome‐scale sequencing) becomes more integrated into standard care, carrier testing is an important possible application. Carrier testing using genome‐scale sequencing can identify a large number of conditions, but choosing which conditions/genes to evaluate as well as which results to disclose can be complicated. Carrier testing generally occurs in the context of reproductive decision‐making and involves patient values in a way that other types of genetic testing may not. The Kaiser Permanente Clinical Sequencing Exploratory Research program is conducting a randomized clinical trial of preconception carrier testing that allows participants to select their preferences for results from among broad descriptive categories rather than selecting individual conditions. This paper describes (1) the criteria developed by the research team, the return of results committee (RORC), and stakeholders for defining the categories; (2) the process of refining the categories based on input from patient focus groups and validation through a patient survey; and (3) how the RORC then assigned specific gene–condition pairs to taxonomy categories being piloted in the trial. The development of four categories (serious, moderate/mild, unpredictable, late onset) for sharing results allows patients to select results based on their values without separately deciding their interest in knowing their carrier status for hundreds of conditions. A fifth category, lifespan limiting, was always shared. The lessons learned may be applicable in other results disclosure situations, such as incidental findings.

Design of a randomized controlled trial for genomic carrier screening in healthy patients seeking preconception genetic testing

Population-based carrier screening is limited to well-studied or high-impact genetic conditions for which the benefits may outweigh the associated harms and costs. As the cost of genome sequencing declines and availability increases, the balance of risks and benefits may change for a much larger number of genetic conditions, including medically actionable additional findings. We designed an RCT to evaluate genomic clinical sequencing for women and partners considering a pregnancy. All results are placed into the medical record for use by healthcare providers. Through quantitative and qualitative measures, including baseline and post result disclosure surveys, post result disclosure interviews, 1–2 year follow-up interviews, and team journaling, we are obtaining data about the clinical and personal utility of genomic carrier screening in this population. Key outcomes include the number of reportable carrier and additional findings, and the comparative cost, utilization, and psychosocial impacts of usual care vs. genomic carrier screening. As the study progresses, we will compare the costs of genome sequencing and usual care as well as the cost of screening, pattern of use of genetic or mental health counseling services, number of outpatient visits, and total healthcare costs. This project includes novel investigation into human reactions and responses from would-be parents who are learning information that could both affect a future pregnancy and their own health.

Stakeholder perspectives on implementing a universal Lynch syndrome screening program: a qualitative study of early barriers and facilitators

Purpose:Evidence-based guidelines recommend that all newly diagnosed colon cancer be screened for Lynch syndrome (LS), but best practices for implementing universal tumor screening have not been extensively studied. We interviewed a range of stakeholders in an integrated health-care system to identify initial factors that might promote or hinder the successful implementation of a universal LS screening program.Methods:We conducted interviews with health-plan leaders, managers, and staff. Interviews were audio-recorded and transcribed. Thematic analysis began with a grounded approach and was also guided by the Practical Robust Implementation and Sustainability Model (PRISM).Results:We completed 14 interviews with leaders/managers and staff representing involved clinical and health-plan departments. Although stakeholders supported the concept of universal screening, they identified several internal (organizational) and external (environment) factors that promote or hinder implementation. Facilitating factors included perceived benefits of screening for patients and organization, collaboration between departments, and availability of organizational resources. Barriers were also identified, including: lack of awareness of guidelines, lack of guideline clarity, staffing and program “ownership” concerns, and cost uncertainties. Analysis also revealed nine important infrastructure-type considerations for successful implementation.Conclusion:We found that clinical, laboratory, and administrative departments supported universal tumor screening for LS. Requirements for successful implementation may include interdepartmental collaboration and communication, patient and provider/staff education, and significant infrastructure and resource support related to laboratory processing and systems for electronic ordering and tracking.Genet Med 18 2, 152–161.