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B3 lesions comprise different histopathological entities that are considered benign but ‘of unknown biological potential’. These entities may act as risk indicators (for both breasts) or as non-obligatory precursors of malignancy. Being diagnosed at percutaneous breast biopsy, an additional risk of underestimate exists. Imaging appearances, histopathological appearance and risk of associated malignancy are presented. B3 lesions of high risk, which thus should usually be excised, include atypical ductal hyperplasia (ADH), pleomorphic or necrotic type of lobular neoplasia (LIN 3), and papillary lesions with atypias. Intermediate risk may be associated with classic lobular carcinoma in situ (LIN 2) or flat epithelial atypia (FEA), and low risk with radial sclerosing lesions (RSLs) and papillary lesions without atypias. LIN 1 is mostly an incidental finding acting as risk indicator. Follow-up is adequate if the initial diagnostic problem is solved. According to international guidelines, risk and subsequent recommendations should be discussed for each individual patient, taking into account biological risk, representative sampling, lesion size, lesion extent, percentage of lesion removal, other individual risks, and the possibility of surveillance. With vacuumassisted breast biopsy (VABB), surgery may be avoided for more of the small lesions at low risk. Further data collection and diligent evaluation may help to better assess the individual risk, to better adapt treatment recommendations and avoid overtreatment. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

BACKGROUND: Health benefits associated with diets rich in vegetables and fruit (VF) are often attributed to the antioxidant activity of their constituent phytochemicals. However, in vivo evidence that VF actually reduce markers of oxidative stress is limited. OBJECTIVE: An 8-wk dietary intervention was conducted to test the hypothesis that increased VF consumption decreases oxidative stress. Urinary excretion of 8-isoprostane F2alpha (8-iso-PGF2alpha) was used as an index of whole-body lipid peroxidation. DESIGN: The diets evaluated had comparable amounts of all macronutrients but varied in their content of VF. After a 2-wk low-VF (3.0 servings/d) run-in diet, 246 women were randomly assigned to receive either 3.6 (low) or 9.2 (high) servings VF/d. The low-VF group was switched to the high-VF diet during the final 2 wk of the study. Blood and first-void urine specimens were obtained at baseline and at 2-wk intervals thereafter. RESULTS: The run-in diet reduced 8-iso-PGF2alpha concentrations by 33% (P < 0.0001). The excretion of 8-iso-PGF2alpha with the low-VF diet remained the same as that with the run-in diet, whereas urinary concentrations of 8-iso-PGF2alpha were further reduced (P < 0.01) by the high-VF diet, either fed throughout the study or when the diet was switched from low to high VF (P = 0.05). The greatest reductions in 8-iso-PGF2alpha were observed in subjects in the highest quartile of baseline concentrations of 8-iso-PGF2alpha. CONCLUSIONS: A significant reduction in the excretion of 8-iso-PGF2alpha was induced by the run-in diet and the high-VF diet. The degree of reduction was related to the subject's baseline urinary concentration of 8-iso-PGF2alpha. Copyright © 2005 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Abstract Background Weight loss in overweight or obese breast cancer patients is associated with an improved prognosis for long term survival. However, it is not clear whether the macronutrient composition of the chosen weight loss dietary plan imparts further prognostic benefit. A study protocol is presented for a dietary intervention to investigate the effects of weight loss dietary patterns that vary markedly in fat and carbohydrate contents on biomarkers of exposure to metabolic processes that may promote tumorigenesis and that are predictive of long term survival. The study will also determine how much weight must be lost for biomarkers to change in a favorable direction. Methods/Design Approximately 370 overweight or obese postmenopausal breast cancer survivors (body mass index: 25.0 to 34.9 kg/m2) will be accrued and assigned to one of two weight loss intervention programs or a non-intervention control group. The dietary intervention is implemented in a free living population to test the two extremes of popular weight loss dietary patterns: a high carbohydrate, low fat diet versus a low carbohydrate, high fat diet. The effects of these dietary patterns on biomarkers for glucose homeostasis, chronic inflammation, cellular oxidation, and steroid sex hormone metabolism will be measured. Participants will attend 3 screening and dietary education visits, and 7 monthly one-on-one dietary counseling and clinical data measurement visits in addition to 5 group visits in the intervention arms. Participants in the control arm will attend two clinical data measurement visits at baseline and 6 months. The primary outcome is high sensitivity C-reactive protein. Secondary outcomes include interleukin-6, tumor necrosis factor-α, insulin-like growth factor-1 (IGF), IGF binding protein-3, 8-isoprostane-F2-alpha, estrone, estradiol, progesterone, sex hormone binding globulin, adiponectin, and leptin. Discussion While clinical data indicate that excess weight for height is associated with poor prognosis for long term survival, little attention is paid to weight control in the clinical management of breast cancer. This study will provide information that can be used to answer important patient questions about the effects of dietary pattern and magnitude of weight loss on long term survival following breast cancer treatment. Clinical Trial Registration CA125243

The article studies the significance of natural killer (NK) cell activity on tumor directed B cell immunity. It demonstrates an important NK cell regulatory function on the development of tumor directed B cell responses. The article discusses the need for tumor vaccination strategies to pay attention on the NK cell status of patients.

Introduction: Approximately one-third of HER2+ early stage breast cancer (ESBC) patients have TOP2A-amplified breast cancer, the subpopulation known to benefit from anthracycline use (Press et al, JCO 2011). Data are needed to evaluate whether outcomes in ESBC patients treated with nonanthracycline-based regimens like docetaxel and cyclophosphamide + trastuzumab (HER TC) are affected by TOP2A or cMYC gene copy number. Methods: This was an open-label, phase II study of HER TC in HER2+ breast cancer patients. Outcome data have been previously reported (Jones et al, SABCS 2011, PD07- 03). Tissue was collected to review HER2, cMYC, and TOP2A gene copy number at a central reference laboratory. HER2, cMYC, and TOP2A amplification was defined as FISH ratio >2, and deletion was defined as FISH ratio <1. Every 21 days, patients received T 75mg/m2 IV and C 600mg/m2 IV, plus weekly H 4mg/kg IV (loading dose) and 2mg/kg IV thereafter for a total of 4 cycles. After 4 cycles of TC+H, patients continued on H for 1 year on a 3-week schedule. The primary endpoint was disease-free survival (DFS) at 2 years with continued follow-up for 3 years. Secondary endpoints were overall survival (OS) and safety. Results: 493 patients with HER2+ ESBC were enrolled. From the 493 patients, 438 (89%) tissue samples were available and analyzed at Caris Diagnostics (Phoenix, AZ) to test for TOP2A, cMYC, and HER2 gene copy number by FISH. HER2 status was confirmed as positive in 87% of samples. Results for TOP2A, cMYC, and HER2 were generated in 438, 436, and 438 samples, respectively. TOP2A was classified as amplified in 43%, normal in 30%, deleted in 27%. cMYC was classified as amplified in 99(23%), normal in 246(56%), and deleted in 91(21%). Three-year DFS and OS in TOP2A and cMYC status as well as ER and Nodal status are depicted in Table 1. Multivariate analyses of age, nodal status, ER status, and gene expression shown below in Table 2 indicate that neither cMYC nor TOP2A status had an effect on outcome. Only nodal and ER status affected outcome. Conclusion: Outcome (DFS + OS) in a phase II study of a nonanthracycline regimen (TC) coupled with H was unaffected by cMYC or TOP2A gene copy number status. Only ER and nodal status showed an effect in a multivariate analysis. [ABSTRACT FROM AUTHOR]

The authors describe their experiences as members of an international online study group, initiated before the COVID-19 pandemic to read aloud and discuss Bion's (1965) Transformations . The three separately authored essays and commentary included here reflect the multifaceted phenomena in which images and voices in Zoom rectangles are transformed into shared emotional experience, the O of the group in Bion's language. These observations show how group members translate online experience into a felt sense of being with others, and suggest that oscillations in the sense of being inside or outside the group demonstrate the dialectical and constantly changing nature of the analytic field in an online group.

In this paper the relationship of the analytic pair in treatments with the aid of digital media is investigated as to how it is experienced in a double virtual relationship in which the other is not physically present. The author argues that 'remote analysis' promotes a regression to idealised object imagoes because it is located in a double virtual space-that of the medium and that of psychoanalysis. Both spaces involve an attack on or at least a destabilisation of the defence and so target the domain of the virtually immortal wishful impulses (Freud, 1933, p. 73). With reference to a case example, the author discusses how previously suppressed biographical memories that had only been perceived as physical experience and pain could be lived through in double virtuality and experienced so that they became undeniable for the patient and accessible to working through. As a result emotional insight and deeper understanding were achieved. The psychic reality of the unfulfilled longing became palpable and could be overcome in the virtual space of remote analysis and analysis in person.

The research aim was to use orange essential oil and trehalose in a carrageenan matrix to form edible packaging. The edible packaging experimentally produced by casting from an aqueous solution were evaluated by the following analysis: UV-Vis spectrum, transparency value, transmittance, attenuated total reflectance Fourier-Transform spectroscopy (FTIR), scanning electron microscopy (SEM) and antimicrobial activity. The obtained results showed that the combination of orange essential oil with trehalose decreases the transmittance value in the UV and Vis regions (up to 0.14% ± 0.02% at 356 nm), meaning that produced films can act as a UV protector. Most produced films in the research were resistant to Gram-positive bacteria ( Staphylococcus aureus subsp. aureus ), though most films did not show antibacterial properties against Gram-negative bacteria and yeasts. FTIR and SEM confirmed that both the amount of carrageenan used and the combination with orange essential oil influenced the compatibility of trehalose with the film matrix. The research showed how different combinations of trehalose, orange essential oils and carrageenan can affect edible film properties. These changes represent important information for further research and the possible practical application of these edible matrices.

Background: Mammalian target of rapamycin (mTOR) inhibitor-associated stomatitis (mIAS) is a frequent adverse event (AE) associated with mTOR inhibitor therapy and can impact treatment adherence. The objectives are to evaluate two steroid-based mouthrinses for preventing/ameliorating mIAS in patients with metastatic breast cancer (MBC) treated with everolimus., Materials and Methods: This prospective, randomized phase II study enrolled 100 postmenopausal patients with hormone receptor-positive MBC within the US Oncology Network who were initiating therapy with an aromatase inhibitor + everolimus (AIE; 10 mg/day). Patients were randomized to prophylactic therapy with one of two oral rinses (Arm 1: Miracle Mouthwash [MMW] 480 mL recipe: 320 mL oral Benadryl [diphenhydramine; Johnson & Johnson, New Brunswick, NJ, USA], 2 g tetracycline, 80 mg hydrocortisone, 40 mL nystatin suspension, water; or Arm 2: prednisolone [P] 15 mg/5 mL oral solution, 1.8% alcohol). Patients were instructed to swish/expectorate 10 mL of the assigned rinse for 1-2 minutes four times daily starting with day 1 of AIE treatment, for the first 12 weeks., Results: A total of 100 patients received treatment (49 MMW; 51 P). The incidence of stomatitis/oral AEs during the first 12 weeks was 35% ( n  = 17/49) and 37% (19/51) in the MMW and P arms, respectively. The incidence of grade 2 oral AEs was 14% (7/49) and 12% (6/51) with MMW or P, respectively. There were two grade 3 oral AEs (MMW arm) and no grade 4 events. There was one everolimus dose reduction (MMW) and six dose delays (four MMW, two P) and one dose reduction + delay (MMW) during the first 12 weeks of treatment. No patients stopped steroid mouthwash therapy because of rinse-related toxicity., Conclusion: Prophylactic use of steroid-containing oral rinses can prevent/ameliorate mIAS in patients with MBC treated with AIE. MMW + hydrocortisone is an affordable option, as is dexamethasone oral rinse., Implications for Practice: This prospective phase-II study showed that two steroid-containing mouthrinses substantially reduced incidences of all-grade and grade ≥2 stomatitis and related oral adverse events (AEs), and the number of everolimus dose-delays and/or dose-reduction in metastatic breast cancer (MBC) patients receiving everolimus treatment plus an aromatase inhibitor. Both oral rinses were well tolerated and demonstrated similar efficacy. Prophylactic use of steroid mouth rinse provides a cost-effective option that substantially decreases the incidence and severity of mammalian target of rapamycin (mTOR) inhibitor-associated stomatitis and related oral AEs as well as the need for dose modification in MBC patients undergoing treatment with an mTOR inhibitor., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2019.)

Background: Hormonal therapies and single-agent sequential chemotherapeutic regimens are the standards of care for HER2 - metastatic breast cancer (MBC). However, treating patients with hormone-refractory and triple negative (TN) MBC remains challenging. We report the results of combined ixabepilone and carboplatin in a single-arm phase II trial., Patients and Methods: In the present prospective analysis of hormone receptor-positive (HR + )/HER2 - and TN MBC cohorts, patients could have received 0 to 2 chemotherapy regimens for MBC before enrollment. All patients received ixabepilone 20 mg/m 2 and carboplatin (area under the curve, 2.5) on days 1 and 8 every 21 days. The primary endpoint was the objective response rate (ORR). The secondary objectives included progression-free survival (PFS), clinical benefit rate (CBR), overall survival (OS), and toxicity., Results: We enrolled 54 HR + and 49 TN patients (median, 1 previous chemotherapy regimen for metastatic disease; most in addition to adjuvant chemotherapy). The ORR was 34% and 30.4% for the HR + and TN patients, respectively, with a corresponding CBR of 56.6% and 41.3%. The ORRs were similar in taxane-pretreated patients (ORR, 31.4% and 28.6% for HR + and TN patients, respectively). The median OS was 17.9 months for HR + patients and 12.5 months for TN patients. The median PFS was similar for both groups at 7.6 months. Grade 3/4 nonhematologic toxicities included neuropathy (9%) and fatigue (8%). Nine patients developed grade 3/4 neuropathy, 7 of whom had received previous taxane treatment., Conclusion: Ixabepilone plus carboplatin is active even in later-line HR + and TN disease. Toxicities were manageable without cumulative myelosuppression. This combination is a reasonable option for those patients with MBC who require combination chemotherapy., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: We conducted a randomized phase III study to determine whether patients with early breast cancer would benefit from the addition of capecitabine (X) to a standard regimen of doxorubicin (A) plus cyclophosphamide (C) followed by docetaxel (T)., Experimental Design: Treatment comprised eight cycles of AC→T (T dose: 100 mg/m(2) on day 1) or AC→XT (X dose: 825 mg/m(2) twice daily, days 1-14; T dose: 75 mg/m(2) on day 1). The primary endpoint was 5-year disease-free survival (DFS)., Results: Of 2,611 women, 1,304 were randomly assigned to receive AC→T and 1,307 to receive AC→XT. After a median follow-up of 5 years, the study failed to meet its primary endpoint [HR, 0.84; 95% confidence interval (CI), 0.67-1.05; P = 0.125]. A significant improvement in overall survival, a secondary endpoint, was seen with AC→XT versus AC→T (HR, 0.68; 95% CI, 0.51-0.92; P = 0.011). There were no unexpected adverse events. Of patients with estrogen receptor (ER)-positive/HER2-negative disease, 70% of whom were node-positive, 26% and 59% had tumors with a centrally assessed Ki-67 score of <10% or <20%, respectively, and only 17 (2%) and 53 (6%) DFS events, respectively, occurred in these groups at 7 years., Conclusions: The very low event rate in patients with ER-positive, low Ki-67 cancers, regardless of nodal status, strongly suggests that these patients should not be enrolled in adjuvant trials that assess 5-year DFS rates and that central Ki-67 analyses can identify these patients., (©2015 American Association for Cancer Research.)

In this paper we address two topical questions: How do the quality of governance and agricultural intensification impact on spatial expansion of agriculture? Which aspects of governance are more likely to ensure that agricultural intensification allows sparing land for nature? Using data from the Food and Agriculture Organization, the World Bank, the World Database on Protected Areas, and the Yale Center for Environmental Law and Policy, we estimate a panel data model for six South American countries and quantify the effects of major determinants of agricultural land expansion, including various dimensions of governance, over the period 1970-2006. The results indicate that the effect of agricultural intensification on agricultural expansion is conditional on the quality and type of governance. When considering conventional aspects of governance, agricultural intensification leads to an expansion of agricultural area when governance scores are high. When looking specifically at environmental aspects of governance, intensification leads to a spatial contraction of agriculture when governance scores are high, signaling a sustainable intensification process.

Background: Previous results suggest that docetaxel plus cyclophosphamide improves disease-free survival (DFS) and overall survival compared with doxorubicin plus cyclophosphamide in early stage breast cancer. We assessed the addition of 1 year of trastuzumab to a non-anthracycline regimen, docetaxel plus cyclophosphamide, in patients with HER2-amplified early stage breast cancer and examined whether this regimen was equally effective in patients with TOP2A-amplified and TOP2A-non-amplified disease., Methods: This was an open-label, single-group, phase 2 study. Eligible patients were aged 18-75 years; had Eastern Cooperative Oncology Group performance status of 1 or less; HER2-amplified early stage breast cancer; operable, histologically confirmed, invasive carcinoma of the breast; adequate tumour specimen available for FISH analysis of TOP2A status; and adequate haematological, renal, hepatic, and cardiac function. Patients received four 21-day cycles of intravenous docetaxel 75 mg/m(2), plus intravenous cyclophosphamide 600 mg/m(2), plus intravenous trastuzumab 4 mg/kg (loading dose) on day 1 and 2 mg/kg on days 1, 8, and 15 during chemotherapy, followed by trastuzumab 6 mg/kg every three weeks for the remainder of 1 year. The primary endpoint was 2-year DFS in TOP2A-amplified and TOP2A-non-amplified patients; the primary analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00493649., Findings: 493 patients were enrolled between June 15, 2007, and Aug 5, 2009. After a median follow-up of 36·1 months (IQR 35·5-36·7), 2-year DFS was 97·8% (95% CI 94·2-99·2) and 2-year overall survival was 99·5% (95% CI 96·2-99·9) for the 190 patients with TOP2A-amplified disease; 2-year DFS was 97·9% (95% CI 94·9-99·1) and 2-year overall survival was 98·8% (95% CI 96·2-99·6) for the 248 patients with TOP2A-non-amplified disease; 55 patients were not assessable for TOP2A status. In the 486 patients who received at least one dose of study drug, the most common adverse events of any grade were fatigue (284 patients, 58·4%), neutropenia (250, 51·4%), and nausea (217, 44·7%). The most common grade 3-4 toxic effects were neutropenia (229, 47·1%), febrile neutropenia (30, 6·2%), fatigue (21, 4·3%), and diarrhoea (16, 3·3%). Cardiac dysfunction occurred in 29 (6·0%) patients (12 [2·5%] grade 1, 15 [3·1%] grade 2, and two [0·4%] grade 3). 23 patients had at least one study-related serious adverse event. 16 patients stopped trastuzumab because of cardiac dysfunction., Interpretation: A short, four-cycle regimen of docetaxel and cyclophosphamide combined with trastuzumab could be an option for adjuvant treatment of women with lower risk HER2-amplified early breast cancer, irrespective of TOP2A status., Funding: Sanofi., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Introduction and Aims: To provide an overview of the principle of current breast MRI, the available evidence concerning its indications and optimum use and future potentials., Methods and Results: To date sensitivities of 90-91% have been achieved with a specificity of 72-75%. MRI is the most sensitive method for detecting invasive carcinoma and comparable to mammography concerning detection of DCIS. The achievable specificity, false positive and biopsy rates, however, are much lower than for screening mammography thus do not allow its use for screening of the general population. Indications with proven advantages concern screening of women at high risk and special diagnostic problems that cannot be solved by conventional imaging and percutaneous biopsy: search for primary tumour in CUP syndrome, differentiation of nipple retraction, differentiation of scarring versus recurrence and selected difficult cases. There is no proven benefit for its general use for preoperative staging. One major problem may concern the imperfect interface between imaging and surgery. Further research is also needed for the use of MRI in women at intermediate risk. In women at low risk MRI screening is not recommended. Novel possibilities of MRI concern diffusion weighted imaging as well as MR spectroscopy. Their value for improved lesion differentiation is not yet fully established. Their main potential appears to concern an improved and earlier prediction of response to neoadjuvant therapy. Future developments might address development of more specific contrast agents, replacement of vascular enhancing agents by special MR techniques, testing of sodium MRI or image fusion with other imaging modalities., Discussion/conclusion: MRI allows new patho-physiological information and thus can complement the information available by conventional methods. Present research should concentrate on improving specificity, improving the interface of imaging and surgery and has to include outcome analyses. Due to issues of specificity the responsible use of MRI should be limited to appropriate indications., (Copyright © 2013. Published by Elsevier Ltd.)

Purpose: To examine the outcome of breast cancer patients who have prior breast augmentation treated with lumpectomy followed by accelerated partial breast external intensity-modulated radiotherapy (APBIMRT) with image-guided radiotherapy (IGRT)., Methods and Materials: Four patients with previous elective subpectoral breast augmentation were enrolled on this APBIMRT trial. These four patients were treated with 10 equal twice daily 3.85 Gy fractions over 5 consecutive days (total dose of 38.5 Gy) using APBIMRT and IGRT. Patients were assessed for pain and cosmetic outcome (physician and a patient self-assessment)., Results: At last follow-up, two patients reported an excellent cosmetic results (at 2 years and at 8 months, respectively), one reported good cosmetic results (at 2 years), and one reported poor cosmetic results (at 20 months). Physicians rated the cosmetic outcomes as excellent in two (CEL; at 2 years and 8 months, respectively), good in one (CEL; at 20 months) and excellent in one (KTH; at 2 years). Three patients reported no breast/chest wall pain (two at 2 years and one at 1 year) and the fourth reported mild pain (at 20 months). The mean percent volume of ipsilateral breast receiving 100%, 75%, 50%, and 25% of the prescribed dose was 7.28%, 17.55%, 24.33%, and 33.1%, respectively. The mean breast, planning target volume (PTV), and implant volumes were 399.88 cc, 43.55 cc, and 313.36 cc, respectively. The mean breast prosthesis/total volume (breast tissue plus prosthesis) ratio was 44.55%. The mean PTV/ipsilateral breast and PTV/total volume ratios were 11.1% and 6.1%, respectively., Conclusion: The results show that a regimen of APBIMRT with IGRT is possible in patients who have prior breast augmentation., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Mammography screening is the only method presently considered appropriate for mass screening of asymptomatic women. Its frequent use, however, warrants diligent analysis of potential side effects. Radiation risk is far below the natural yearly risk of breast cancer and should not be used as an argument against screening. False-positive calls lead to additional imaging or histopathological assessment, mainly percutaneous breast biopsy. These measures are tolerated and accepted fairly well. Their number is limited by strict quality assurance and constant training. Interval cancers represent a limitation of breast screening that should prompt further research for optimization. Evaluation of overdiagnosis is a highly debated topic in the literature. According to the probably most realistic available calculations, overdiagnosis is acceptable as it is compensated by the potential mortality reduction. Nonetheless, this potential side effect warrants optimal adjustment of therapy to the patient's individual risk. The mortality reduction seen in randomized studies was confirmed by results from national screening programs. A recent case referent study indicated that improvements in mortality reduction run parallel to improved mammographic techniques. Use of less aggressive therapies is another valuable effect of screening. Awareness of potential problems, strict quality assurance, and further research should help to further develop screening programs.

Objective: To determine whether a telephone counseling program can improve psychosocial outcomes among breast cancer patients post-treatment., Methods: A randomized trial was conducted involving 21 hospitals and medical centers, with assessments (self-administered questionnaires) at baseline, 12 and 18 months post-enrollment. Eligibility criteria included early stage diagnosis, enrollment during last treatment visit, and the ability to receive the intervention in English. Endpoints included distress (Impact of Event Scale), depression (Center for Epidemiologic Studies Depression Scale), and two study-specific measures: sexual dysfunction and personal growth. The control group (n=152) received a resource directory for breast cancer; the intervention group (n=152) also received a one-year, 16 session telephone counseling program augmented with additional print materials., Results: Significant intervention effects were found for sexual dysfunction at 12 (p=0.03) and 18 months (p=0.04) and personal growth (12 months: p=0.005; 18 months: p=0.03). No differences by group were found in mean scores for distress and depression, with both groups showing significant improvement at 12 and 18 months (all p values for within-group change from baseline were