Further Evidence That OPG rs2073618 Is Associated With Increased Risk of Musculoskeletal Symptoms in Patients Receiving Aromatase Inhibitors for Early Breast Cancer

BackgroundAromatase inhibitors (AI) reduce recurrence and death in patients with early-stage hormone receptor-positive (HR +) breast cancer. Treatment-related toxicities, including AI-induced musculoskeletal symptoms (AIMSS), are common and may lead to early AI discontinuation. The objective of this study was to replicate previously reported associations for candidate germline genetic polymorphisms with AIMSS.MethodsWomen with stage 0-III HR + breast cancer initiating adjuvant AI were enrolled in a prospective clinic-based observational cohort. AIMSS were assessed by patient-reported outcomes (PRO) including the PROMIS pain interference and physical function measures plus the FACT-ES joint pain question at baseline and after 3 and 6 months. For the primary analysis, AIMSS were defined as ≥ 4-point increase in the pain interference T-score from baseline. Secondary AIMSS endpoints were defined as ≥ 4-point decrease in the physical function T-score from baseline and as ≥ 1-point increase on the FACT-ES joint pain question from baseline. The primary hypothesis was that TCL1A rs11849538 would be associated with AIMSS. Twelve other germline variants in CYP19A1, VDR, PIRC66, OPG, ESR1, CYP27B1, CYP17A1, and RANKL were also analyzed assuming a dominant genetic effect and prespecified direction of effect on AIMSS using univariate logistic regression with an unadjusted α = 0.05. Significant univariate associations in the expected direction were adjusted for age, race, body mass index (BMI), prior taxane, and the type of AI using multivariable logistic regression.ResultsA total of 143 participants with PRO and genetic data were included in this analysis, most of whom were treated with anastrozole (78%) or letrozole (20%). On primary analysis, participants carrying TCL1A rs11849538 were not more likely to develop AIMSS (odds ratio = 1.29, 95% confidence interval: 0.55–3.07, p = 0.56). In the statistically uncorrected secondary analysis, OPG rs2073618 was associated with AIMSS defined by worsening on the FACT-ES joint pain question (OR = 3.33, p = 0.004), and this association maintained significance after covariate adjustment (OR = 3.98, p = 0.003).ConclusionCarriers of OPG rs2073618 may be at increased risk of AIMSS. If confirmed in other cohorts, OPG genotyping can be used to identify individuals with HR + early breast cancer in whom alternate endocrine therapy or interventions to enhance symptom detection and implement strategies to reduce musculoskeletal symptoms may be needed.

Prevalence of pain and fatigue in post-stroke patients: a study transverse.

Background: Motor and functional recovery in post-stroke individuals is a process of interference from non-motor aspects such as pain and fatigue.The prevalence of these symptoms and their impact on the rehabilitation process need to bebetter understood and studied, mainly in the strategies for the construction of therapeutic approaches. Objectives: To analyze the prevalence of pain and fatigue in individual’s post-stroke. Design and setting: Cross-sectional study that followed the STROBE recommendations. An outpatient clinic at UFRN / FACISA in Santa Cruz-RN institution. Approved by the Research Ethics Committee (Opinion No. 2,622,853). Methods: One sample perconvenience, had 29 post-stroke individuals. The individuals were evaluated using the following clinical instruments: the Mini Mental State Examination (MMSE),Functional Independence (FI), Fulg-Meyer Scale (FMS), Sensory Assessment of Nottingham (SAN), McGill Pain Question (MOQ) and the Severity of Fatigue (SSF). The data were analyzed descriptively. Results: Participants presented the following characteristics clinical: MMSE, 19 (median), (0(1ºQ)/24 (3ºQ)); FI, 80 (0/121); FMS, 36 (36/88); SAN, 108 (0/108); SSF, 9 (0/27). Thus, the prevalence of pain was 28% (8) and the fatigue was present in 76% (22) of the individuals. Conclusions: We found a high prevalence of fatigue in patients with chronic stroke, however we did not find relationship with pain. Further studies are needed to understand these conditions and identify which factors contribute to the prevalence of such symptoms.

Validation of the NARCOMS Registry: pain assessment

The North American Research Committee on Multiple Sclerosis (NARCOMS) Registry is a multiple sclerosis (MS) self-report registry with more than 24 000 participants. Participants report disability status upon enrolment, and semi-annually using Performance Scales (PS), Patient Determined Disease Steps (PDDS) and a pain question. In November 2000 and 2001, we also collected the Pain Effects Scale (PES). Our aim was to validate the NARCOMS pain question using the PES as our criterion measure. We measured correlations between the pain question and age, disease duration, various PS subscales and PDDS to assess construct validity. We correlated pain question responses in participants who reported no change in PDSS or the PS subscales between questionnaires to determine test—retest reliability. We measured responsiveness in participants who reported a substantial change in the sensory, spasticity PS subscales. The correlation between the pain question and PES was r=0.61 in November 2000, and r=0.64 in November 2001 (both P<0.0001). Correlations between the pain question and age, and disease duration were low, indicating divergent validity. Correlations between the pain question and spasticity, sensory PS subscales and PDSS were moderate, indicating convergent validity. Test—retest reliability was r=0.84 (P<0.0001). Responsiveness was 70.7%. The pain question is a valid self-report measure of pain in MS.