Eculizumab in Pregnant Patients with Paroxysmal Nocturnal Hemoglobinuria.

BACKGROUND: Eculizumab, a humanized monoclonal antibody against complement protein C5 that inhibits terminal complement activation, has been shown to prevent complications of paroxysmal nocturnal hemoglobinuria (PNH) and improve quality of life and overall survival, but data on the use of eculizumab in women during pregnancy are scarce. METHODS: We designed a questionnaire to solicit data on pregnancies in women with PNH and sent it to the members of the International PNH Interest Group and to the physicians participating in the International PNH Registry. We assessed the safety and efficacy of eculizumab in pregnant patients with PNH by examining the birth and developmental records of the children born and adverse events in the mothers. RESULTS: Of the 94 questionnaires that were sent out, 75 were returned, representing a response rate of 80%. Data on 75 pregnancies in 61 women with PNH were evaluated. There were no maternal deaths and three fetal deaths (4%). Six miscarriages (8%) occurred during the first trimester. Requirements for transfusion of red cells increased during pregnancy, from a mean of 0.14 units per month in the 6 months before pregnancy to 0.92 units per month during pregnancy. Platelet transfusions were given in 16 pregnancies. In 54% of pregnancies that progressed past the first trimester, the dose or the frequency of use of eculizumab had to be increased. Low-molecular-weight heparin was used in 88% of the pregnancies. Ten hemorrhagic events and 2 thrombotic events were documented; both thrombotic events occurred during the postpartum period. A total of 22 births (29%) were premature. Twenty cord-blood samples were examined for the presence of eculizumab; the drug was detected in 7 of the samples. A total of 25 babies were breast-fed, and in 10 of these cases, breast milk was examined for the presence of eculizumab; the drug was not detected in any of the 10 breast-milk samples. CONCLUSIONS: Eculizumab provided benefit for women with PNH during pregnancy, as evidenced by a high rate of fetal survival and a low rate of maternal complications. (ClinicalTrials.gov number, NCT01374360.).

Association of the 12-Gene Breast DCIS Score® Assay With Local Recurrence in Patients With Ductal Carcinoma In Situ Treated on Accelerated Partial Breast Radiotherapy Protocols.

BACKGROUND: The following analysis explores clinicopathologic factors and the 12-gene Breast DCIS Score test result in order to better define an appropriate DCIS (ductal carcinoma in situ) population eligible for APBI (accelerated partial breast radiotherapy). METHODS: This exploratory analysis aimed to retrospectively measure the association between the 12-gene Oncotype DX Breast DCIS Score® assay (Redwood City, CA) and relevant clinicopathologic factors with locoregional recurrence in a pooled cohort of women treated with local excision and APBI on prospective phase II (NCT01185145) and phase III (NCT01185132) clinical trials. Univariable Cox proportional hazards regression was used to determine whether there was an association between local recurrence and DCIS Score result risk group (≥ 39 vs < 39) and clinicopathologic factors. RESULTS: This analysis included 104 evaluable patients (n = 18 from NCT01185145 and n = 86 from NCT01185132). The median age was 60 years (range: 40-79). Seventy-nine percent of patients were postmenopausal. The median span of DCIS was 10 mm (range 2-45 mm). Two-thirds of the cohort presented with necrosis (71%). The distribution of DCIS Score® results ranged from 0 to 82, with 69% of patients having a DCIS Score result < 39. The median follow-up time was 8.2 years in NCT01185145 versus 3.0 years in NCT01185132. There were 6 local ipsilateral breast recurrences. DCIS Score result was significantly associated with local recurrence in univariable modeling, hazard ratio = 10.3 (95% CI 1.7, 198.4); p = 0.010. None of the clinicopathologic characteristics resulted in any significant association with locoregional recurrence. CONCLUSION: The Breast DCIS Score assay demonstrated risk stratification in this cohort of patients treated with local excision and APBI pooled from two clinical trials. These results are consistent with those recently published utilizing whole breast radiotherapy. Due to the small number of local recurrence events and limited follow-up time, further investigations are needed to confirm findings.

Psychometric evaluation of the FACT Colorectal Cancer Symptom Index (FCSI-9): reliability, validity, responsiveness, and clinical meaningfulness.

BACKGROUND: Patient-reported outcomes (PROs) are essential for evaluating treatment effects on health-related quality of life and symptoms from the patient's perspective. This study sought to evaluate the psychometric properties of the nine-item Functional Assessment of Cancer Therapy/National Comprehensive Cancer Network Colorectal Cancer Symptom Index (FCSI-9) in a metastatic colorectal cancer (mCRC) population. METHODS: The FCSI-9 and EQ-5D were administered every 2-4 weeks to mCRC subjects in a phase III clinical trial. Three hundred ninety-one mCRC subjects completed the questionnaires at baseline and at least one follow-up assessment. Internal consistency reliability, test-retest reliability, construct validity, known groups validity, responsiveness, and the minimum important difference (MID) of the FCSI-9 were evaluated. RESULTS: The internal consistency and test-retest reliability of the FCSI-9 were acceptable (0.81 and 0.76, respectively). Construct validity was supported based on moderate correlations with the EQ-5D. Known groups validity was evaluated by examining the FCSI-9 scores of subjects categorized by their Eastern Cooperative Oncology Group performance status (PS) score. Subjects with better PS scores reported significantly higher FCSI-9 scores than those with lower PS scores at both baseline and week 8. Responsiveness, as measured by Guyatt's statistic, was 0.77 from baseline to week 8 and 0.60 from week 4 to week 12. Considering all data together, the MID of the FCSI-9 is estimated to be in the range of 1.5-3.0 points. CONCLUSION: Results provide preliminary evidence of the reliability, validity, and responsiveness of the FCSI-9.

Stratifying computer literacy: a competency measurement strategy.

Institutions using a clinical information system which feeds an electronic medical record system must consider evaluation programs that measure the nurse's ability to use and understand the clinical data in the clinical information system. By measuring and tracking the nurse's level of computer literacy, training programs and system enhancements can be better designed. A well-designed system will lead to improved system acceptance and higher adoption rates. There is a need for a defined system implementation strategy that includes nursing staff assessment and system training formulated to fit the specific literacy levels of the majority users of the clinical information system, the nursing staff. Computer literacy in relation to the use of clinical information systems and electronic medical record adoption is the focus of this article. If a strategy based on Benner's novice to expert theory is implemented, computer literacy among frontline users could be assessed, and appropriate education and training programs can be developed. Ultimately, these programs would promote positive perception of the clinical information system, which would result in a better adoption rate of the electronic medical record.

Clinical relevance of the 21-gene Recurrence Score® assay in treatment decisions for patients with node-positive breast cancer in the genomic era.

In contemporary management of early-stage breast cancer, clinical decisions regarding adjuvant systemic therapy are increasingly made after considering both genomic assay results and clinico-pathologic features. Genomic information augments the prognostic information gleaned from clinico-pathologic features by providing risk estimates for distant recurrence and/or breast cancer-specific survival based on individual tumor biology. The 21-gene Oncotype DX Breast Recurrence Score® (RS) assay is validated to be prognostic and predictive of chemotherapy benefit in patients with hormone receptor-positive (HR+), HER2-negative early-stage breast cancer, regardless of nodal status. Because patients frequently are recommended to receive adjuvant chemotherapy based on the perceived poor prognosis related to a positive nodal status, inconsistent use of any prognostic genomic assay in the node-positive (N+) setting likely results in overtreatment of some patients, particularly those with a low genomic risk as defined by the RS test. This comprehensive review of the evidence for the RS assay in patients with N+, HR+, HER2-negative early-stage breast cancer focuses on outcomes of patients with low RS results treated with hormonal therapy alone. Aggregate findings show that the RS assay consistently identifies patients with low genomic risk N+ breast cancer, in whom adjuvant chemotherapy can be avoided without adversely affecting outcomes. This evidence suggests that HR+ patients with limited nodal involvement and low RS results should discuss with their physicians the pros and cons of adjuvant chemotherapy at the time their treatment plans are being decided.

Systemic BP and heart rate as prognostic indicators in pulmonary arterial hypertension.

BACKGROUND: Heart rate (HR) and systolic BP (SBP) are significant multivariate predictors of survival in patients with pulmonary arterial hypertension (PAH) as part of a 19-element formula. To what extent HR and BP alone predict survival and future hospitalization in patients with PAH is unknown. METHODS: We analyzed data from the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry), a prospective, observational study of patients with PAH. Patients were analyzed by quintile (Q) according to values of HR, SBP, and SBP/HR. Kaplan-Meier curves were calculated by Q for survival and freedom from hospitalization. RESULTS: For patients in the worst Q, 1-year survival after enrollment was 85% ± 2% for SBP, 86% ± 2% for HR, and 84% ± 2% for SBP/HR vs 91% ± 1% for the middle three Qs (P < .001). Hospitalization occurred more frequently than mortality but with a similar pattern among Qs. One-year survival after first follow-up of patients in the worst Q for change (Δ) in SBP since enrollment was 85% ± 2% (P = .004), 86% ± 2% for ΔHR (P = .12), and 84% ± 2% for ΔSBP/HR (P = .024) vs the middle three Qs (ΔSBP: 91% ± 1%; ΔHR: 90% ± 1%; ΔSBP/HR: 90% ± 1%). CONCLUSIONS: Changes in vital signs from enrollment to first follow-up were less predictive of mortality than the values of vital-sign parameters at either enrollment or first follow-up. HR, SBP, and SBP/HR at enrollment identified high-risk groups with survival differences of 5% to 7% and freedom from hospitalization differences of 9% to 11% vs lower-risk groups. SBP/HR defines the highest-risk group, including most of the high-risk patients defined by HR and SBP separately. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov.

Modified Severity of Dyspepsia Assessment pain scale: a new tool for measuring upper abdominal pain in osteoarthritis patients taking NSAIDs.

BACKGROUND: This study evaluated the electronically administered modified Severity of Dyspepsia Assessment (mSODA) pain scale, a six-item measure of upper abdominal pain intensity, for daily use in osteoarthritis patients taking nonsteroidal anti-inflammatory drugs. METHODS: Once the mSODA pain scale was isolated, cognitive debriefing interviews (n = 30) were used to examine its appropriateness in the target population. Following administration of the instrument in two Phase III pivotal trials, the data were analyzed to examine reliability, validity, responsiveness, and the minimal important difference. RESULTS: Using a subset of trial data (n = 90 patients), the mSODA pain scale proved to be a unidimensional, highly internally consistent instrument (α = 0.93) with good test-retest reliability (intraclass correlation coefficient 0.77). Construct validity was established via moderate correlations with other similar patient-reported outcomes. Additionally, known-groups validity demonstrated that the mSODA pain scale could distinguish between subjects who did and did not report gastrointestinal symptoms and antacid use (both P values ≤ 0.05). The mSODA pain scale was also responsive to change in heartburn at weeks 6 and 12 (Guyatt's statistic = 1.7 and 2.6, respectively), and the minimal important difference obtained via ½ SD was 5.7 (range 2-47). CONCLUSION: This research suggests that the mSODA pain scale is both feasible and valid for assessing dyspepsia in patients taking nonsteroidal anti-inflammatory drugs for relief of symptoms of osteoarthritis.