Managing menopausal symptoms and associated clinical issues in breast cancer survivors

Objective: Review evidence to guide management of menopausal signs and symptoms in women after breast cancer and make recommendations accordingly. Evidence: Randomized controlled clinical trials, observational studies, evidence-based guidelines, and expert opinion from professional societies. Background: Symptoms and clinical problems associated with estrogen depletion—sleep disorders, vulvovaginal atrophy (VVA), vasomotor symptoms (VMS), mood changes, depressive symptoms, cardiovascular disease, osteopenia, and osteoporosis—confront the estimated 9.3 million breast cancer survivors globally. Recommendations: Following breast cancer, women should not generally be treated with menopausal hormone therapy or tibolone but should optimize lifestyle. Women with moderate to severe symptoms may benefit from mind–brain behavior or nonhormone, pharmacologic therapy. The selective serotonin/noradrenaline reuptake inhibitors and gabapentenoid agents improve VMS and quality of life. For osteoporosis, nonhormonal agents are available. Treatment of VVA remains an area of unmet need. Low-dose vaginal estrogen is absorbed in small amounts with blood levels remaining within the normal postmenopausal range but could potentially stimulate occult breast cancer cells, and although poorly studied, is not generally advised, particularly for those on aromatase inhibitors. Intravaginal dehydroepiandrosterone and oral ospemiphene have been approved to treat dyspareunia, but safety after breast cancer has not been established. Vaginal laser therapy is being used for VVA but efficacy from sham-controlled studies is lacking. Therapies undergoing development include lasofoxifene, neurokinin B inhibitors, stellate ganglion blockade, vaginal testosterone, and estetrol. Conclusions: Nonhormone options and therapies are available for treatment of estrogen depletion symptoms and clinical problems after a diagnosis of breast cancer. Individualization of treatment is essential

Treatment of symptoms of the menopause: an endocrine society clinical practice guideline

Objective: The objective of this document is to generate a practice guideline for the management and treatment of symptoms of the menopause. Participants: The Treatment of Symptoms of the Menopause Task Force included six experts, a methodologist, and a medical writer, all appointed by The Endocrine Society. Evidence: The Task Force developed this evidenced-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned three systematic reviews of published data and considered several other existing meta-analyses and trials. Consensus Process: Multiple e-mail communications, conference calls, and one face-to-face meeting determined consensus. Committees of The Endocrine Society, representatives from endorsing societies, and members of The Endocrine Society reviewed and commented on the drafts of the guidelines. The Australasian Menopause Society, the British Menopause Society, European Menopause and Andropause Society, the European Society of Endocrinology, and the International Menopause Society (co-sponsors of the guideline) reviewed and commented on the draft. Conclusions: Menopausal hormone therapy (MHT) is the most effective treatment for vasomotor symptoms and other symptoms of the climacteric. Benefits may exceed risks for the majority of symptomatic postmenopausal women who are under age 60 or under 10 years since the onset of menopause. Health care professionals should individualize therapy based on clinical factors and patient preference. They should screen women before initiating MHT for cardiovascular and breast cancer risk and recommend the most appropriate therapy depending on risk/benefit considerations. Current evidence does not justify the use of MHT to prevent coronary heart disease, breast cancer, or dementia. Other options are available for those with vasomotor symptoms who prefer not to use MHT or who have contraindications because these patients should not use MHT. Low-dose vaginal estrogen and ospemifene provide effective therapy for the genitourinary syndrome of menopause, and vaginal moisturizers and lubricants are available for those not choosing hormonal therapy. All postmenopausal women should embrace appropriate lifestyle measures

Biomass burning and pollution aerosol over North America: Organic components and their influence on spectral optical properties and humidification response

Thermal analysis of aerosol size distributions provided size resolved volatility up to temperatures of 400°C during extensive flights over North America (NA) for the INTEX/ICARTT experiment in summer 2004. Biomass burning and pollution plumes identified from trace gas measurements were evaluated for their aerosol physiochemical and optical signatures. Measurements of soluble ionic mass and refractory black carbon (BC) mass, inferred from light absorption, were combined with volatility to identify organic carbon at 400°C (VolatileOC) and the residual or refractory organic carbon, RefractoryOC. This approach characterized distinct constituent mass fractions present in biomass burning and pollution plumes every 5–10 min. Biomass burning, pollution and dust aerosol could be stratified by their combined spectral scattering and absorption properties. The “nonplume” regional aerosol exhibited properties dominated by pollution characteristics near the surface and biomass burning aloft. VolatileOC included most water-soluble organic carbon. RefractoryOC dominated enhanced shortwave absorption in plumes from Alaskan and Canadian forest fires. The mass absorption efficiency of this RefractoryOC was about 0.63 m2 g−1 at 470 nm and 0.09 m2 g−1 at 530 nm. Concurrent measurements of the humidity dependence of scattering, γ, revealed the OC component to be only weakly hygroscopic resulting in a general decrease in γ with increasing OC mass fractions. Under ambient humidity conditions, the systematic relations between physiochemical properties and γ lead to a well-constrained dependency on the absorption per unit dry mass for these plume types that may be used to challenge remotely sensed and modeled optical properties

Gaining synthetic appreciation for the gedunin ABC ring system

Gedunin, first isolated in 1960, displays a remarkable range of biological activity, but has yet to receive dedicated synthetic attention from a ground up construction perspective. Presented herein is a successfully executed approach to the fully functionalized ABC ring system of this challengingly complex natural product

30 Years on Selected Issues in the Prevention of HIV among Persons Who Inject Drugs

After 30 years of extensive research on human immunodeficiency virus (HIV) among persons who inject drugs (PWID), we now have a good understanding of the critical issues involved. Following the discovery of HIV in 1981, epidemics among PWID were noted in many countries, and consensus recommendations for interventions for reducing injection related HIV transmission have been developed. While high-income countries have continued to develop and implement new Harm Reduction programs, most low-/middle-income countries have implemented Harm Reduction at very low levels. Modeling of combined prevention programming including needle exchange (NSP) and antiretroviral therapy (ARV) suggests that NSP be given the highest priority. Future HIV prevention programming should continue to provide Harm Reduction programs for PWID coupled with interventions aimed at reducing sexual transmission. As HIV continues to spread in low-and middle-income countries, it is important to achieve and maintain high coverage of Harm Reduction programs in these locations. As PWID almost always experience multiple health problems, it will be important to address these multiple problems within a comprehensive approach grounded in a human rights perspective

A phase I study of nolatrexed dihydrochloride in children with advanced cancer. A United Kingdom Children's Cancer Study Group Investigation

A phase I study of nolatrexed, administered as a continuous 5 day intravenous infusion every 28 days, has been undertaken for children with advanced malignancy. 16 patients were treated at 3 dose levels; 420, 640 and 768 mg/m2 24 h−1. 8 patients were evaluable for toxicity. In the 6 patients treated at 768 mg/m2 24 h−1, dose-limiting oral mucositis and myelosuppression were observed. Plasma nolatrexed concentrations and systemic exposure, measured in 14 patients, were dose related, with mean AUC values of 36 mg−1 ml−1 min−1, 50 mg ml−1 min−1 and 80 mg ml−1 min−1at the 3 dose levels studied. Whereas no toxicity was encountered if the nolatrexed AUC was <45 mg ml−1 min−1, Grade 3 or 4 toxicity was observed with AUC values of >60 mg ml−1 min−1. Elevated plasma deoxyuridine levels, measured as a surrogate marker of thymidylate synthase inhibition, were seen at all of the dose levels studied. One patient with a spinal primitive neuroectodermal tumour had stable disease for 11 cycles of therapy, and in two patients with acute lymphoblastic leukaemia a short-lived 50% reduction in peripheral lymphoblast counts was observed. Nolatrexed can be safely administered to children with cancer, and there is evidence of therapeutic activity as well as antiproliferative toxicity. Phase II studies of nolatrexed in children at the maximum tolerated dose of 640 mg/m2 24 h−1are warranted. © 2001 Cancer Research Campaign http://www.bjcancer.co