Long-term outcomes of APBI via multicatheter interstitial HDR brachytherapy: Results of a prospective single-institutional registry

PurposeLong-term outcome reports of accelerated partial-breast irradiation (APBI) are limited. Here, we report the 10-year outcomes of APBI delivered using multicatheter interstitial implant (ISI) brachytherapy.Methods and materialsPatients with early-stage breast cancer treated with APBI via ISI brachytherapy were enrolled in a prospective registry. Selection criteria included age ≥40 years, ductal carcinoma in situ or invasive tumor ≤3 cm, negative margins (≥2 mm), and negative axillary nodes. 34 Gy in 10 twice-daily fractions was administered to 2 cm of breast tissue surrounding the surgical bed. Toxicity and cosmetic outcomes were collected prospectively.ResultsA total of 175 patients were included. The median followup time was 10.0 years. Ten-year ipsilateral breast tumor control, regional control, freedom from distant metastasis, breast cancer–specific survival, and overall survival were 92.1%, 96.9%, 97.4%, 97.1%, and 81.2%, respectively. High-grade disease was correlated with increase in the rate of ipsilateral breast tumor recurrence. Grade 1 or 2 skin toxicity was present in 44 patients, and Grade 3 skin toxicity was present in only 1 patient. There were no Grade 4 or higher toxicities observed. Thirty-seven patients developed fat necrosis. Dose Homogeneity Index of ≤0.85 and integrated reference air-kerma of >3400 cGycm²/h correlated with higher rates of fat necrosis. There were 115 (66%), 51 (29%), 8 (5%), and 0 (0%) patients having excellent, good, fair, and poor cosmetic outcomes, respectively.ConclusionsAPBI using ISI brachytherapy offers excellent clinical outcomes in appropriately selected patients with excellent cosmetic outcomes and low rates of toxicities such as symptomatic fat necrosis.     

Evaluation of alternative statistical models for crossover studies to demonstrate caffeine adjuvancy in the treatment of tension headache

This paper discusses alternative statistical models for the analysis of six crossover studies to determine whether better relief of tension headache occurs from treatment with an analgesic plus caffeine (C) than with the analgesic alone (A) or with placebo (P). Each patient in these crossover studies randomly received a pair of distinct medications in such a way as to treat the first two of four headaches with the initial medication in the pair and to treat the third and fourth headaches with the last medication in the pair. In order to have greater power for the C versus A comparison, three times as many patients were randomly assigned to the A:C and C:A sequence groups as to the A:P, C:P, P:A, and P:C sequence groups.

An issue of statistical interest for these crossover studies is the extent to which the possibility of unequal carryover effects of the three medications influences the roles of alternative models for data analysis and the interpretation of results. When carryover effects for all three medications are equal, univariate analysis of variance for the difference scores between the average response for the first two headaches and the average response for the third and fourth headaches for each patient provides nearly the same power for pairwise treatment comparisons as more comprehensive multivariate methods for all four headaches. However, for comparisons concerning carryover effects and for treatment comparisons with adjustment for carryover effects, multivariate methods encompassing all four headaches jointly can provide greater power than univariate analysis for difference scores, particularly when there is low intraclass correlation for responses within the same patient. Another noteworthy role for multivariate methods in situations with potentially unequal carryover effects is their capacity to clarify whether multiple types of carryover effects occur across the second, third, and fourth headaches in the respective sequence groups.

Multivariate models with alternative specifications of carryover effects are fit to the data from the six crossover studies to compare C, A, and P by weighted least squares. The role of potential variation among centers is addressed in these analyses by the use of stratified proportional means over centers, means of center means, and means ignoring centers. The primary focus of attention in the respective analyses is the evaluation of treatment comparisons with and without adjustment for potential differences among carryover effects of the treatments. Comparisons among carryover effects are assessed as well, but they mainly serve a background purpose since the principal issue is the extent to which findings for treatment comparisons are similar across alternative ways of accounting for potential carryover effects.

For all models, the average predicted response across all headaches treated with C was significantly better than that for A or P. For models that adjusted treatment effects for carryover effects in a statistically efficient way, the adjusted direct treatment effect of C was significantly better than that of A or P. Thus, the superiority of C over A found robust support from models both with and without adjustment for potential differences among carryover effects of the treatments.     

广义估计方程与准最小二乘在社区纵向数据分析中的应用

目的 应用广义估计方程和准最小二乘方法分析社区卫生服务中心纵向数据,探讨纵向数据分析的问题,为社区的随访的纵向数据的分析提供科学的方法. 方法 对收集的社区卫生服务中心的糖尿病病人血糖的纵向数据,分别使用广义估计方程和准最小二乘方法以及传统的线性回归模型进行分析并比较结果.同时比较三种方法的标准化残差图. 结果 广义估计方程不收敛时与传统线性模型的结果相同,显示糖尿病人血糖与教育水平相关,而广义估计方程收敛时与准最小二乘的结果相同,显示教育无统计学意义.从标准化残差图看广义估计方程和准最小二乘法对数据的拟合比传统回归好. 结论 广义估计方程和准最小二乘法都能有效的处理纵向数据.与广义估计方程相比,准最小二乘法有一些优势.     

Predicting the long-term impact of rotavirus vaccination in 112 countries from 2006 to 2034: A transmission modeling analysis

Rotavirus vaccination has been shown to reduce rotavirus burden in many countries, but the long-term magnitude of vaccine impacts is unclear, particularly in low-income countries. We use a transmission model to estimate the long-term impact of rotavirus vaccination on deaths and disability adjusted life years (DALYs) from 2006 to 2034 for 112 low- and middle-income countries. We also explore the predicted effectiveness of a one- vs two- dose series and the relative contribution of direct vs indirect effects to overall impacts. To validate the model, we compare predicted percent reductions in severe rotavirus cases with the percent reduction in rotavirus positivity among gastroenteritis hospital admissions for 10 countries with pre- and post-vaccine introduction data. We estimate that vaccination would reduce deaths from rotavirus by 49.1 % (95 % UI: 46.6–54.3 %) by 2034 under realistic coverage scenarios, compared to a scenario without vaccination. Most of this benefit is due to direct benefit to vaccinated individuals (explaining 69–97 % of the overall impact), but indirect protection also appears to enhance impacts. We find that a one-dose schedule would only be about 57 % as effective as a two-dose schedule 12 years after vaccine introduction. Our model closely reproduced observed reductions in rotavirus positivity in the first few years after vaccine introduction in select countries. Rotavirus vaccination is likely to have a substantial impact on rotavirus gastroenteritis and its mortality burden. To sustain this benefit, the complete series of doses is needed.     

Accelerated partial breast irradiation with interstitial multicatheter brachytherapy after breast-conserving surgery for low-risk early breast cancer

Patients with low-risk invasive ductal carcinoma treated with breast-conserving surgery (BCS) were included in a multicatheter brachytherapy APBI protocol. The primary endpoint was ipsilateral breast recurrence. Between December 2008–December 2017, 186 low-risk breast cancer patients were treated with APBI using interstitial multicatheter brachytherapy and followed prospectively. At 5-years of follow-up, cumulative local recurrence (LR) and cause-specific survival was 1.1% (95% CI 0.3–1.9) and 98.3% (95% CI 97.3–99.3%) respectively. No grade 3 adverse effects were observed. Postoperative APBI using multicatheter brachytherapy after BCS in early breast cancer patients have excellent rates of local control and survival, without significant toxicity.     

Partial medial meniscectomy leads to altered walking mechanics two years after anterior cruciate ligament reconstruction: Meniscal repair does not

BackgroundPartial meniscectomy dramatically increases the risk for post-traumatic, tibiofemoral osteoarthritis after anterior cruciate ligament reconstruction (ACLR). Concomitant medial meniscus surgery influences walking biomechanics (e.g., medial tibiofemoral joint loading) early after ACLR; whether medial meniscus surgery continues to influence walking biomechanics two years after ACLR is unknown.Research questionDoes medial meniscus treatment at the time of ACLR influence walking biomechanics two years after surgery?MethodsThis is a secondary analysis of prospectively collected data from a clinical trial (NCT01773317). Fifty-six athletes (age 24 ± 8 years) with operative reports, two-year biomechanical analyses, and no second injury prior to two-year testing participated after primary ACLR. Participants were classified by concomitant medial meniscal status: no medial meniscus involvement (n = 36), partial medial meniscectomy (n = 9), and medial meniscus repair (n = 11). Participants underwent biomechanical analyses during over-ground walking including surface electromyography; a validated musculoskeletal model estimated medial compartment tibiofemoral contact forces. Gait variables were analyzed using 3 × 2 ANOVAs with group (medial meniscus treatment) and limb (involved versus uninvolved) comparisons.ResultsThere was a main effect of group (p = .039) for peak knee flexion angle (PKFA). Participants after partial medial meniscectomy walked with clinically meaningfully smaller PKFAs in both the involved and uninvolved limbs compared to the no medial meniscus involvement group (group mean difference [95%CI]; involved: −4.9°[−8.7°, −1.0°], p = .015; uninvolved: −3.9°[−7.6°, −0.3°], p = .035) and medial meniscus repair group (involved: −5.2°[−9.9°, −0.6°], p = .029; uninvolved: −4.7°[−9.0°, −0.3°], p = .038). The partial medial meniscectomy group walked with higher involved versus uninvolved limb medial tibiofemoral contact forces (0.45 body weights, 95% CI: −0.01, 0.91 BW, p = 0.053) and truncated sagittal plane knee excursions, which were not present in the other two groups.SignificanceAberrant gait biomechanics may concentrate high forces in the antero-medial tibiofemoral cartilage among patients two years after ACLR plus partial medial meniscectomy, perhaps explaining the higher osteoarthritis rates and offering an opportunity for targeted interventions.Level of EvidenceLevel III.