The effect of anastrozole on bone mineral density during the first 5 years of adjuvant treatment in postmenopausal women with early breast cancer

PURPOSE: The administration of aromatase inhibitors is associated with bone loss in postmenopausal women. We assessed changes in bone mineral density (BMD) from baseline to 60 months of treatment in patients receiving anastrozole as initial adjuvant therapy. METHODS: Postmenopausal women with hormone receptor-positive breast cancer receiving anastrozole as adjuvant therapy at our center since 2004 were enrolled in this study. BMD was assessed by dual-energy X-ray absorptiometry at baseline and after 6, 12, 24, 36, 48 and 60 months. Oral bisphosphonate (Bis) treatment was initiated when patients were diagnosed with osteoporosis having a T-score of −2.5 or lower. RESULTS: Fifty-five patients were enrolled in the study between 2004 and 2011, and the mean follow-up period was 53.6 months. Thirty-five patients were administered Bis (risedronate in 27 patients, alendronate in 8 patients). After 6 months of hormone therapy, BMD decreased by 0.5% from baseline at the lumbar spine (LS) and BMD decreased by 1.5% at the femoral neck (FN). However, BMD increased by 1.9% at the LS and BMD decreased by 1.5% at the FN for 60 months of treatment. In patients treated with upfront Bis (n = 19), 5.4% BMD increase from baseline was noted at the LS whereas in those without Bis (n = 21) BMD decreased by 4.3% from baseline within 24 months (P < 0.0001). Fractures were observed in 4 patients (7.3%), and 1 patient (1.8%) had a fragility fracture. CONCLUSIONS: Upfront treatment of Bis with anastrozole significantly increased BMD at the LS and an optimal use of Bis would not increase bone fractures. TRIAL REGISTRATION: UMIN000001757

Nutritional Management in a 101-Year-Old Woman with Physical Inactivity and General Weakness: A Case Report

Japan has the world’s highest life longevity, and centenarian patients are no longer rare. However, sufficient information related to centenarians is not available. Herein, we report the case of a 101-year-old centenarian woman who recovered from extreme inactivity and general weakness, mainly through nutritional management at home, to understand instances of nutritional management in centenarians. The patient developed lethargy, with a rapid decline in activity levels and food intake. She was diagnosed with senility by a primary doctor. We concluded that she had no problems with feeding and swallowing and predicted that her motivation to eat had decreased. We planned an intervention that lasted three months. To reduce the risk of aspiration, we paid attention to her posture while eating. To stimulate her appetite, we increased the variety and color of food items. To consider both the texture of food and safety, we changed the form of foods from paste (IDDSI Level 4)-like to solid food of regular size as much as possible. We recommended that the patient consume her favorite sweet between meals to enjoy eating. Two and half months after the initial intervention, the patient’s inactivity and general weakness improved dramatically, which was recognized by her willingness to eat, laugh loudly, and hum, although she could not speak clearly. The patient finally was able to have dinner with her family

Nutritional Management in a 101-Year-Old Woman with Physical Inactivity and General Weakness: A Case Report

Japan has the world&rsquo;s highest life longevity, and centenarian patients are no longer rare. However, sufficient information related to centenarians is not available. Herein, we report the case of a 101-year-old centenarian woman who recovered from extreme inactivity and general weakness, mainly through nutritional management at home, to understand instances of nutritional management in centenarians. The patient developed lethargy, with a rapid decline in activity levels and food intake. She was diagnosed with senility by a primary doctor. We concluded that she had no problems with feeding and swallowing and predicted that her motivation to eat had decreased. We planned an intervention that lasted three months. To reduce the risk of aspiration, we paid attention to her posture while eating. To stimulate her appetite, we increased the variety and color of food items. To consider both the texture of food and safety, we changed the form of foods from paste (IDDSI Level 4)-like to solid food of regular size as much as possible. We recommended that the patient consume her favorite sweet between meals to enjoy eating. Two and half months after the initial intervention, the patient&rsquo;s inactivity and general weakness improved dramatically, which was recognized by her willingness to eat, laugh loudly, and hum, although she could not speak clearly. The patient finally was able to have dinner with her family

Synthesis of N-substituted 2-arylpyrroles by the reaction of (η2-imine)titanium complexes with 3,3-diethoxypropyne

(η2-Imine)Ti(O-i-Pr)2 complexes generated from arylaldehyde imines and a divalent titanium reagent, Ti(O-i-Pr)4/2i-PrMgCl, reacted with 3,3-diethoxypropyne to afford 2-arylpyrroles

Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study

Background Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial. Methods We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II\ue2\u80\u93IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators, staff, and outcome assessors were masked to treatment assignment. The primary efficacy endpoint was the change from baseline to week 26 in MG-ADL total score measured by worst-rank ANCOVA. The efficacy population set was defined as all patients randomly assigned to treatment groups who received at least one dose of study drug, had a valid baseline MG-ADL assessment, and at least one post-baseline MG-ADL assessment. The safety analyses included all randomly assigned patients who received eculizumab or placebo. This trial is registered with ClinicalTrials.gov, number NCT01997229. Findings Between April 30, 2014, and Feb 19, 2016, we randomly assigned and treated 125 patients, 62 with eculizumab and 63 with placebo. The primary analysis showed no significant difference between eculizumab and placebo (least-squares mean rank 56\uc2\ub76 [SEM 4\uc2\ub75] vs 68\uc2\ub73 [4\uc2\ub75]; rank-based treatment difference \ue2\u88\u9211\uc2\ub77, 95% CI \ue2\u88\u9224\uc2\ub73 to 0\uc2\ub796; p=0\uc2\ub70698). No deaths or cases of meningococcal infection occurred during the study. The most common adverse events in both groups were headache and upper respiratory tract infection (ten [16%] for both events in the eculizumab group and 12 [19%] for both in the placebo group). Myasthenia gravis exacerbations were reported by six (10%) patients in the eculizumab group and 15 (24%) in the placebo group. Six (10%) patients in the eculizumab group and 12 (19%) in the placebo group required rescue therapy. Interpretation The change in the MG-ADL score was not statistically significant between eculizumab and placebo, as measured by the worst-rank analysis. Eculizumab was well tolerated. The use of a worst-rank analytical approach proved to be an important limitation of this study since the secondary and sensitivity analyses results were inconsistent with the primary endpoint result; further research into the role of complement is needed. Funding Alexion Pharmaceuticals