Lumbo-sacral loads and pelvis -trunk coordination in runners with chronic and resolved acute low back pain

The purpose of this dissertation was to investigate, in vivo, the effect of low back pain status on lumbo-sacral (L5S1) joint reaction force and moment profiles, and also on pelvis-trunk coordination during locomotion. We studied three groups of runners: runners with low to moderate LBP (LBP), runners who had recovered from a single bout of acute LBP (RES), and runners who never had LBP (CTRL). We developed an inverse dynamics model to investigate L5S1 mechanics. Results indicated that L5S1 reaction forces increased as stride length increased (p\u3c0.024) in healthy runners, as did peak sagittal L5S1 moments (p=0.078). Subsequently, we used this model to examine L5S1 differences between our three experimental groups at their preferred running speed and at 3.8 m/s. While differences were observed between speeds for many L5S1 variables, and between groups for peak vertical GRF, no differences were found between groups for lumbar angle ROM, peak L5S1 joint reaction force, or L5S1 joint moment. In a further study, pelvis and trunk range of motion (ROM), relative phase coordination (CRP) and coordination variability (CRPvar) were compared between our groups over a range of locomotor speeds. We found increased pelvis-trunk CRP in the frontal plane for the LBP group as compared to the CTRL group during walking (p=0.029). During running, we observed increased pelvis axial ROM for the LBP group as compared to CTRL (p=0.010), and increased CRP for CTRL as compared to both RES (p=0.021) and LBP group (p=0.025), and increased CRPvar for CTRL as compared to LBP group (p=0.019). Findings from the second and third studies demonstrated differences between clinical groups despite the relative low levels of disability (mean Modified Oswestry Disability Questionnaire score = 7.9±6.2%), and suggest that mechanical and coordinative differences exist between those with and without LBP. Further, our RES group demonstrated characteristics common to both extreme groups (CTRL and LBP), supporting previous literature regarding residual performance effects. Our findings further suggest that the RES group represented a transition stage between the CTRL and LBP groups

A history of low back pain affects pelvis and trunk coordination during a sustained manual materials handling task

Purpose: The purpose of this study was to compare the coordination between the trunk and the pelvis during a sustained asymmetric repetitive lifting task between a group with a history of low back pain (LBP; HBP) and a group with no history of LBP (NBP). Methods: Volunteers lifted a 11-kg box from ankle height in front to a shelf 45° off-center at waist height, and lowered it to the start position at 12 cycles/min for 10 min. Lifting side was alternated during the trial. Continuous relative phase was used to calculate coordination between the pelvis and trunk rotation at the beginning (Min 1), middle (Min 5), and end of the bout (Min 9). Results: While there were no main effects for group, a significant interaction between time and group indicated that, in the frontal plane, the NBP group coordination was more anti-phase toward the end of the bout, with no such differences for the HBP group. Analysis of sagittal-axial (bend and twist) coordination revealed the HBP group coordination was more in-phase at the end of the bout over the entire cycle and for the lifting phase alone, with no such differences for the NBP group. Conclusion: Differences between groups demonstrate residual consequences of LBP in an occupational scenario, even though the HBP group was pain-free for >6 months prior to data collection. More in-phase coordination in the HBP group may represent a coordination pattern analogous to “guarded gait” which has been observed in other studies, and may lend insight as to why these individuals are at increased risk for re-injury

Anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind, phase 3 clinical trial

BackgroundDuctal carcinoma in situ is currently managed with excision, radiotherapy, and adjuvant hormone therapy, usually tamoxifen. We postulated that an aromatase inhibitor would be safer and more effective. We therefore undertook this trial to compare anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy.MethodsThe double-blind, randomised, phase 3 National Surgical Adjuvant Breast and Bowel Project (NSABP) B-35 trial was done in 333 participating NSABP centres in the USA and Canada. Postmenopausal women with hormone-positive ductal carcinoma in situ treated by lumpectomy with clear resection margins and whole-breast irradiation were enrolled and randomly assigned (1:1) to receive either oral tamoxifen 20 mg per day (with matching placebo in place of anastrozole) or oral anastrozole 1 mg per day (with matching placebo in place of tamoxifen) for 5 years. Randomisation was stratified by age (<60 vs ≥60 years) and patients and investigators were masked to treatment allocation. The primary outcome was breast cancer-free interval, defined as time from randomisation to any breast cancer event (local, regional, or distant recurrence, or contralateral breast cancer, invasive disease, or ductal carcinoma in situ), analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00053898, and is complete.FindingsBetween Jan 1, 2003, and June 15, 2006, 3104 eligible patients were enrolled and randomly assigned to the two treatment groups (1552 to tamoxifen and 1552 to anastrozole). As of Feb 28, 2015, follow-up information was available for 3083 patients for overall survival and 3077 for all other disease-free endpoints, with median follow-up of 9·0 years (IQR 8·2-10·0). In total, 212 breast cancer-free interval events occurred: 122 in the tamoxifen group and 90 in the anastrozole group (HR 0·73 [95% CI 0·56-0·96], p=0·0234). A significant time-by-treatment interaction (p=0·0410) became evident later in the study. There was also a significant interaction between treatment and age group (p=0·0379), showing that anastrozole is superior only in women younger than 60 years of age. Adverse events did not differ between the groups, except for thrombosis or embolism--a known side-effect of tamoxifen-for which there were 17 grade 4 or worse events in the tamoxifen group versus four in the anastrozole group.InterpretationCompared with tamoxifen, anastrozole treatment provided a significant improvement in breast cancer-free interval, mainly in women younger than 60 years of age. This finding means that women will benefit from having a choice of effective agents for ductal carcinoma in situ.FundingUS National Cancer Institute and AstraZeneca Pharmaceuticals LP

Patient-reported outcomes with anastrozole versus tamoxifen for postmenopausal patients with ductal carcinoma in situ treated with lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind, phase 3 clinical trial

BackgroundThe NSABP B-35 trial compared 5 years of treatment with anastrozole versus tamoxifen for reducing subsequent occurrence of breast cancer in postmenopausal patients with ductal carcinoma in situ. This report assesses the effect of these drugs on quality of life and symptoms.MethodsThe study was done at 333 hospitals in North America. Postmenopausal women with hormone-positive ductal carcinoma in situ treated by lumpectomy with clear resection margins and whole breast irradiation were randomly assigned to receive either tamoxifen (20 mg/day) or anastrazole (1 mg/day) for 5 years, stratified by age (<60 years vs ≥60 years). Patients and investigators were masked to treatment allocation. Patients completed questionnaires at baseline and every 6 months thereafter for 6 years. The primary outcomes were SF-12 physical and mental health component scale scores, and vasomotor symptoms (as per the BCPT symptom scale). Secondary outcomes were vaginal symptoms and sexual functioning. Exploratory outcomes were musculoskeletal pain, bladder symptoms, gynaecological symptoms, cognitive symptoms, weight problems, vitality, and depression. We did the analyses by intention to treat, including patients who completed questionnaires at baseline and at least once during follow-up. This study is registered with ClinicalTrials.gov, NCT00053898.FindingsBetween Jan 6, 2003, and June 15, 2006, 3104 patients were enrolled in the study, of whom 1193 were included in the quality-of-life substudy: 601 assigned to tamoxifen and 592 assigned to anastrozole. We detected no significant difference between treatment groups for: physical health scores (mean severity score 46·72 for tamoxifen vs 45·85 for anastrozole; p=0·20), mental health scores (52·38 vs 51·48; p=0·38), energy and fatigue (58·34 vs 57·54; p=0·86), or symptoms of depression (6·19 vs 6·39; p=0·46) over 5 years. Vasomotor symptoms (1·33 vs 1·17; p=0·011), difficulty with bladder control (0·96 vs 0·80; p=0·0002), and gynaecological symptoms (0·29 vs 0·18; p<0·0001) were significantly more severe in the tamoxifen group than in the anastrozole group. Musculoskeletal pain (1·50 vs 1·72; p=0·0006) and vaginal symptoms (0·76 vs 0·86; p=0·035) were significantly worse in the anastrozole group than in the tamoxifen group. Sexual functioning did not differ significantly between the two treatments (43·65 vs 45·29; p=0·56). Younger age was significantly associated with more severe vasomotor symptoms (mean severity score 1·45 for age <60 years vs 0·65 for age ≥60 years; p=0·0006), vaginal symptoms (0·98 vs 0·65; p<0·0001), weight problems (1·32 vs 1·02; p<0·0001), and gynaecological symptoms (0·26 vs 0·22; p=0·014).InterpretationGiven the similar efficacy of tamoxifen and anastrozole for women older than age 60 years, decisions about treatment should be informed by the risk for serious adverse health effects and the symptoms associated with each drug. For women younger than 60 years old, treatment decisions might be driven by efficacy (favouring anastrozole); however, if the side-effects of anastrozole are intolerable, then switching to tamoxifen is a good alternative.FundingUS National Cancer Institute, AstraZeneca Pharmaceuticals