Interrupting Endocrine Therapy to Attempt Pregnancy after Breast Cancer.

BACKGROUND: Prospective data on the risk of recurrence among women with hormone receptor-positive early breast cancer who temporarily discontinue endocrine therapy to attempt pregnancy are lacking. METHODS: We conducted a single-group trial in which we evaluated the temporary interruption of adjuvant endocrine therapy to attempt pregnancy in young women with previous breast cancer. Eligible women were 42 years of age or younger; had had stage I, II, or III disease; had received adjuvant endocrine therapy for 18 to 30 months; and desired pregnancy. The primary end point was the number of breast cancer events (defined as local, regional, or distant recurrence of invasive breast cancer or new contralateral invasive breast cancer) during follow-up. The primary analysis was planned to be performed after 1600 patient-years of follow-up. The prespecified safety threshold was the occurrence of 46 breast cancer events during this period. Breast cancer outcomes in this treatment-interruption group were compared with those in an external control cohort consisting of women who would have met the entry criteria for the current trial. RESULTS: Among 516 women, the median age was 37 years, the median time from breast cancer diagnosis to enrollment was 29 months, and 93.4% had stage I or II disease. Among 497 women who were followed for pregnancy status, 368 (74.0%) had at least one pregnancy and 317 (63.8%) had at least one live birth. In total, 365 babies were born. At 1638 patient-years of follow-up (median follow-up, 41 months), 44 patients had a breast cancer event, a result that did not exceed the safety threshold. The 3-year incidence of breast cancer events was 8.9% (95% confidence interval [CI], 6.3 to 11.6) in the treatment-interruption group and 9.2% (95% CI, 7.6 to 10.8) in the control cohort. CONCLUSIONS: Among select women with previous hormone receptor-positive early breast cancer, temporary interruption of endocrine therapy to attempt pregnancy did not confer a greater short-term risk of breast cancer events, including distant recurrence, than that in the external control cohort. Further follow-up is critical to inform longer-term safety. (Funded by ETOP IBCSG Partners Foundation and others; POSITIVE ClinicalTrials.gov number, NCT02308085.).

Influence of Resisted Sled-Pull Training on the Sprint Force-Velocity Profile of Male High-School Athletes.

Cahill, MJ, Oliver, JL, Cronin, JB, Clark, K, Cross, MR, Lloyd, RS, and Lee, JE. Influence of resisted sled-pull training on the sprint force-velocity profile of male high-school athletes. J Strength Cond Res 34(10): 2751-2759, 2020-Although resisted sled towing is a commonly used method of sprint-specific training, little uniformity exists around training guidelines for practitioners. The aim of this study was to assess the effectiveness of unresisted and resisted sled-pull training across multiple loads. Fifty-three male high-school athletes were assigned to an unresisted (n = 12) or 1 of 3 resisted groups: light (n = 15), moderate (n = 14), and heavy (n = 12) corresponding to loads of 44 ± 4 %BM, 89 ± 8 %BM, and 133 ± 12 %BM that caused a 25, 50, and 75% velocity decrement in maximum sprint speed, respectively. All subjects performed 2 sled-pull training sessions twice weekly for 8 weeks. Split times of 5, 10, and 20 m improved across all resisted groups (d = 0.40-1.04, p < 0.01) but did not improve with unresisted sprinting. However, the magnitude of the gains increased most within the heavy group, with the greatest improvement observed over the first 10 m (d ≥ 1.04). Changes in preintervention to postintervention force-velocity profiles were specific to the loading prescribed during training. Specifically, F0 increased most in moderate to heavy groups (d = 1.08-1.19); Vmax significantly decreased in the heavy group but increased in the unresisted group (d = 012-0.44); whereas, Pmax increased across all resisted groups (d = 0.39-1.03). The results of this study suggest that the greatest gains in short distance sprint performance, especially initial acceleration, are achieved using much heavier sled loads than previously studied in young athletes.

Positive affect, depressive symptoms, and arthritis pain of elderly people over time.

BACKGROUND: Older adults frequently experience physical symptoms of arthritis pain. We examined the dynamic change of arthritis pain and depressive symptoms over time. We also addressed the influence of time varying arthritis pain on depressive symptoms and positive affect among community dwelling older individuals. METHODS: Analyses were based on data from 4 annual follow-ups in a sample of 299 elderly residents (M=83.78) of Florida retirement communities. We estimated a hierarchical growth curve model that related the effects of time varying pain and characteristics of participants such as age, gender, cognitive functioning, emotional support and health. Growth curve modeling was used to assess changes in emotional well-being as a function of arthritis pain over time. RESULTS: We found that depressive symptoms increased over 4 years whereas positive affect declined over 4 years with significant between-person differences in levels and slopes. As predicted, changes in arthritis pain co-varied with both depressive symptoms and positive affect over time. Gender, cognitive functioning, health conditions and emotional support from others were associated with between person differences in level of emotional well-being. CONCLUSIONS: Our findings suggest that conceptualization of emotional well-being of older adults as a dynamic, changing construct applies both depressive symptoms and positive affect. Findings also suggest that arthritis pain as well as emotional support contribute to depressive symptoms and to positive affect among older adults with arthritis.

Fidelity and acceptability of an adaptive intervention for caregivers: an exploratory study.

OBJECTIVE: There has been growing interest in providing tailored or adaptive interventions to family caregivers as a way of addressing their heterogeneity of risk factors and other needs. A particular challenge in an adaptive study is to implement the individualized intervention protocol as planned (program fidelity). This study explores the fidelity of implementation of an adaptive intervention for family caregivers of persons with dementia and its acceptability to caregivers. METHOD: Using a sample of 35 caregivers of person with dementia who participated in a program development study, we gathered information on acceptability and fidelity of the program from multiple sources, including caregiver and counselor reports and ratings of recordings of sessions. RESULTS: Findings show that caregivers have high levels of acceptance of the intervention plan and high ratings of satisfaction with the program. Ratings of satisfaction and counselor competence were not associated with the amount of treatment provided. Ratings by counselors and independent raters found good fidelity for two of the three program domains. DISCUSSION: The results demonstrate that trained counselors can follow a tailored intervention plan and that caregivers' experience of the program did not differ depending on how much intervention was provided. A next step is to determine how an adaptive protocol would affect caregiver outcomes.

Positive association between striatal serotonin level and abnormal involuntary movements in chronic L-DOPA-treated hemiparkinsonian rats.

Although l-DOPA represents the standard of care in Parkinson's disease, long-term treatment may be compromised by l-DOPA-induced dyskinesia (LID), with adverse fluctuations in motor responsiveness and progressive loss of control. Here we show that in rats with 6-hydroxydopamine-induced lesions of the median forebrain bundle, LID correlates with 5-HT levels. Rats were treated with l-DOPA (6 mg/kg) and benserazide (15 mg/kg) daily for 3 weeks to induce the development of abnormal involuntary movements (AIMs). After this chronic l-DOPA treatment, the lesion side of the rats displayed significant changes in striatal dopamine (DA) and 5-HT levels. Striatal DA and 5-hydroxytryptamine (5-HT) levels were inversely correlated, and AIMs were strongly positively correlated with DA levels and negatively correlated with 5-HT levels. Axial AIMs were more strongly correlated with DA and 5-HT levels than were the other AIMs subtypes, while locomotive AIMs showed no significant correlation at all. In addition, striatal 5-HT was more strongly (negatively) correlated with the AIMs than striatal DA levels. These results demonstrate that 5-HT contributes to LID and that both striatal DA (positively) and 5-HT (negatively) affect the severity of LID. We suggest that by strategic modification of the serotonin system it may be possible to attenuate the adverse effects of chronic l-DOPA therapy.