Citations

Background: Existing knee joint–specific outcome questionnaires lack content pertinent to patients with multiligament knee injuries. Purpose: To develop and test the reliability and validity of a novel disease-specific quality of life questionnaire for patients with multiligament knee injuries. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: Participants in this study included patients with multiligament knee injuries and clinician experts. Inclusion criteria were (1) patients with multiligament knee injury (age, 18-60 years), (2) ≥6 months after injury, and (3) operative or nonoperative treatment. Exclusion criteria were (1) preexisting osteoarthritis or inflammatory arthritis and (2) intracerebral/spinal cord injury. In phase I of the study, 85 eligible patients were mailed a questionnaire composed of 132 items from 11 existing knee questionnaires. Items were rated with regard to importance and frequency on a 5-point Likert scale. Criteria for inclusion in the first draft of the Multiligament Quality of Life (MLQOL) questionnaire included mean importance rating ≥3.5 and frequency <30% for the response “never experienced.” In phase II, patient focus groups and expert interviews were conducted until no further new content was generated for the MLQOL, and in phase III, 99 eligible patients across 2 centers were mailed a preliminary MLQOL questionnaire along with the Tegner activity scale, Short Form (SF)–36, and anchor questions. Interitem and item-to-total correlations were used to perform item reduction to generate a final MLQOL instrument, which was tested for internal consistency (Cronbach alpha), test-retest reliability (interclass correlation coefficient [ICC]), and construct validity. Results: At the end of phase III, a final MLQOL instrument was developed that was composed of 4 domains (physical impairments [PI], emotional impairments [EI], activity limitations [AL], and societal involvement [SI]) with 52 items in total. The MLQOL had adequate content validity, as none of the domains had any floor or ceiling effects. The Cronbach alpha was .94 (PI), .93 (EI), .94 (AL), and .91 (SI); ICC values were .89 (PI), .86 (EI), .91 (AL), and .88 (SI). Seven of 8 a priori hypotheses were satisfied, indicating good construct validity. Conclusion: The MLQOL instrument is a novel disease-specific quality of life tool that has demonstrated excellent content validity, reliability, and construct validity.

Significance The major portion of hereditary breast cancer still remains unexplained, and many susceptibility loci are yet to be found. Exome sequencing of 24 high-risk familial BRCA1/2 -negative breast cancer patients and further genotyping of a large sample set of breast/ovarian cancer cases and controls was used to discover previously unidentified susceptibility alleles and genes. A significant association of a FANCM nonsense mutation with breast cancer, especially triple-negative breast cancer, identifies FANCM as a breast cancer susceptibility gene. Identification of such risk alleles is expected to improve cancer risk assessment for breast cancer patients and families, and may lead to improvements in the prevention, early diagnosis, and treatment of cancer.

Abstract Supplemental Digital Content is available in the text.

Abstract Lung cancer has a familial component which suggests a genetic contribution to its etiology. Given the strong evidence linking smoking with lung cancer, we studied miRNA-related loci in genes associated with smoking behavior. CHRNA, CHRNB gene families, CYP2A6, and DRD1 (dopamine receptor D1) were mined for SNPs that fell within the seed region of miRNA binding sites and then tested for associations with risk in a three-stage validation approach. A 3′UTR (untranslated region) SNP in DRD1 was associated with a lower risk of lung cancer among individuals exposed to secondhand smoke during childhood [OR, 0.69; 95% confidence interval (CI), 0.60–0.79; P &lt; 0.0001]. This relationship was evident in both ever (OR, 0.74; 95% CI, 0.62–0.88; P = 0.001) and never smokers (OR, 0.61; 95% CI, 0.47–0.79; P &lt; 0.0001), European American (OR, 0.65; 95% CI, 0.53–0.80; P &lt; 0.0001), and African American (OR, 0.73; 95% CI, 0.62–0.88; P = 0.001) populations. Although much remains undefined about the long-term risks associated with exposure to secondhand smoke and heterogeneity between individuals in regard to their susceptibility to the effects of secondhand smoke, our data show an interaction between an SNP in the 3′UTR of DRD1 and exposure to secondhand smoke during childhood. Further work is needed to explore the mechanistic underpinnings of this SNP and the nature of the interaction between DRD1 and exposure to secondhand smoke during childhood. Cancer Prev Res; 7(12); 1210–8. ©2014 AACR.

Abstract BACKGROUND Anticoagulation protocols used during mechanical circulatory support call for titration of antiplatelet agents. We compared the precision and reliability of 5 platelet function tests in healthy volunteers and donors on daily antiplatelet therapy to distinguish their efficacy for titrating antiplatelet therapy. METHODS We assessed arachidonic acid–induced platelet function by light transmission aggregometry (LTA), Multiplate impedance aggregometry, VerifyNow, and platelet mapping by thromboelastography (TEG PM). We assessed ADP-induced platelet function by the same methods and flow cytometry. Forty healthy volunteers and 10–13 volunteers on daily aspirin and/or clopidogrel therapy were evaluated. We compared tests for intraassay precision, interassay precision (samples from 2 separate blood draws), and reliability coefficient. RESULTS For arachidonic acid–induced platelet aggregation in healthy volunteers, intra- and interassay CVs were ≤10% for all methods. Intra- and interassay precision among donors on daily aspirin was ≤30% for all methods except LTA (38% interassay CV) and TEG PM (95% intraassay and 104% interassay CV). For ADP-induced platelet function, intra- and interassay precision was ≤10% and ≤30% for all methods. Only Multiplate demonstrated moderate or greater (R &gt; 0.40) reliability coefficients for arachidonic acid–induced platelet function among all subjects. All methods of ADP-induced platelet function, except TEG PM, demonstrated substantial or greater (R &gt; 0.60) reliability among all subjects. CONCLUSIONS TEG PM is least suited to monitor effects of antiplatelet agents. Multiplate impedance aggregometry was the only method to demonstrate an acceptable reliability coefficient among healthy volunteers and donors on both aspirin and clopidogrel therapy.

AbstractContext:Exogenous dehydroepiandrosterone (DHEA) therapy has been proposed to replenish the depletion of endogenous DHEA and its sulfate form, which occurs with advancing age and is thought to be associated with loss of libido and menopausal symptoms.Objective:We conducted a systematic review and meta-analysis to summarize the evidence supporting the use of systemic DHEA in postmenopausal women with normal adrenal function.Methods:We searched MEDLINE, EMBASE, PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through January 2014. Pairs of reviewers, working independently, selected studies and extracted data from eligible randomized controlled trials (RCTs). We used the random-effects model to pool across studies and evaluated heterogeneity using the I2 statistic.Results:We included 23 RCTs with moderate to high risk of bias enrolling 1188 women. DHEA use was not associated with significant improvement in libido or sexual function (standardized mean difference, 0.35; 95% confidence interval, −0.02 to 0.73; P value = .06; I2 = 62%). There was also no significant effect of DHEA on serious adverse effects, serum lipids, serum glucose, weight, body mass index, or bone mineral density. This evidence warranted low confidence in the results, mostly due to imprecision, risk of bias, and inconsistency across RCTs.Conclusions:Evidence warranting low confidence suggests that DHEA administration does not significantly impact sexual symptoms or selected metabolic markers in postmenopausal women with normal adrenal function.