Vitamin D Status and its Association with Morbidity including Wasting and Opportunistic Illnesses in HIV-Infected Women in Tanzania.

Vitamin D has a potential role in preventing HIV-related complications, based on its extensive involvement in immune and metabolic function, including preventing osteoporosis and premature cardiovascular disease. However, this association has not been examined in large studies or in resource-limited settings. Vitamin D levels were assessed in 884 HIV-infected pregnant women at enrollment in a trial of multivitamin supplementation (excluding vitamin D) in Tanzania. Information on HIV related complications was recorded during follow-up (median, 70 months). Proportional hazards models and generalized estimating equations were used to assess the relationship of vitamin D status with these outcomes. Women with low vitamin D status (serum 25-hydroxyvitamin D<32 ng/mL) had 43% higher risk of reaching a body mass index (BMI) less than 18 kg/m(2) during the first 2 years of follow-up, compared to women with adequate vitamin D levels (hazard ratio [HR]: 1.43; 95% confidence intervals: [1.03-1.99]). The relationship between continuous vitamin D levels and risk of BMI less than 18 kg/m(2) during follow-up was inverse and linear (p=0.03). Women with low vitamin D levels had significantly higher incidence of acute upper respiratory infections (HR: 1.27 [1.04-1.54]) and thrush (HR: 2.74 [1.29-5.83]) diagnosed during the first 2 years of follow-up. Low vitamin D status was a significant risk factor for wasting and HIV-related complications such as thrush during follow-up in this prospective cohort in Tanzania. If these protective associations are confirmed in randomized trials, vitamin D supplementation could represent a simple and inexpensive method to improve health and quality of life of HIV-infected patients, particularly in resource-limited settings

Endocrine therapy and related issues in hormone receptor-positive early breast cancer: a roundtable discussion by the breast cancer therapy expert group (BCTEG)

Purpose: Management of breast cancer is a rapidly evolving field, and, although evidence-based guidelines are available for clinicians to provide direction on critical issues in patient care, clinicians often left to address these issues in the context of community practice situations with their patients. These include the patient’s comorbid conditions, actual versus perceived benefit of treatments, patient’s compliance as well as financial/reimbursement issues, and long-term tolerability of therapy. Methods: A meeting of global oncology experts was convened in January 2017 with the belief that there is a gap in clinical practice guidance on several fundamental issues in breast cancer care, particularly in the community setting, where oncologists may encounter multiple tumor types. The goal was to discuss some of the most important questions in this area and provide some guidance for practicing oncologists. Results: Topics addressed included risk of contralateral breast cancer recurrence in patients with estrogen receptor-positive early breast cancer who have undergone 5 years of adjuvant endocrine therapy, adverse events associated with endocrine therapy and their management, emergent data on adjuvant bisphosphonate therapy and its apparent benefit in reducing breast cancer recurrence, recent findings of extended adjuvant endocrine therapy trials, and the use of currently available genomic biomarker tests as a means of further informing treatment decisions. Conclusions: A summary of the discussion on these topics and several ‘expert opinion statements’ are provided herein in an effort to convey the collective insights of the panel as it relates to current standard practice

Options for early breast cancer follow-up in primary and secondary care : a systematic review

Background Both incidence of breast cancer and survival have increased in recent years and there is a need to review follow up strategies. This study aims to assess the evidence for benefits of follow-up in different settings for women who have had treatment for early breast cancer. Method A systematic review to identify key criteria for follow up and then address research questions. Key criteria were: 1) Risk of second breast cancer over time - incidence compared to general population. 2) Incidence and method of detection of local recurrence and second ipsi and contra-lateral breast cancer. 3) Level 1–4 evidence of the benefits of hospital or alternative setting follow-up for survival and well-being. Data sources to identify criteria were MEDLINE, EMBASE, AMED, CINAHL, PSYCHINFO, ZETOC, Health Management Information Consortium, Science Direct. For the systematic review to address research questions searches were performed using MEDLINE (2011). Studies included were population studies using cancer registry data for incidence of new cancers, cohort studies with long term follow up for recurrence and detection of new primaries and RCTs not restricted to special populations for trials of alternative follow up and lifestyle interventions. Results Women who have had breast cancer have an increased risk of a second primary breast cancer for at least 20 years compared to the general population. Mammographically detected local recurrences or those detected by women themselves gave better survival than those detected by clinical examination. Follow up in alternative settings to the specialist clinic is acceptable to women but trials are underpowered for survival. Conclusions Long term support, surveillance mammography and fast access to medical treatment at point of need may be better than hospital based surveillance limited to five years but further large, randomised controlled trials are needed

Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment

Background Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Methods/design Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to ~25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. Discussion This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

Potentially inappropriate medication in older participants of the Berlin Aging Study II (BASE-II) - Sex differences and associations with morbidity and medication use

INTRODUCTION: Multimorbidity in advanced age and the need for drug treatment may lead to polypharmacy, while pharmacokinetic and pharmacodynamic changes may increase the risk of adverse drug events (ADEs). OBJECTIVE: The aim of this study was to determine the proportion of subjects using potentially inappropriate medication (PIM) in a cohort of older and predominantly healthy adults in relation to polypharmacy and morbidity. METHODS: Cross-sectional data were available from 1,382 study participants (median age 69 years, IQR 67-71, 51.3% females) of the Berlin Aging Study II (BASE-II). PIM was classified according to the EU(7)-PIM and German PRISCUS (representing a subset of the former) list. Polypharmacy was defined as the concomitant use of at least five drugs. A morbidity index (MI) largely based on the Charlson Index was applied to evaluate the morbidity burden. RESULTS: Overall, 24.1% of the participants were affected by polypharmacy. On average, men used 2 (IQR 1-4) and women 3 drugs (IQR 1-5). According to PRISCUS and EU(7)-PIM, 5.9% and 22.6% of participants received at least one PIM, while use was significantly more prevalent in females (25.5%) compared to males (19.6%) considering EU(7)-PIM (p = 0.01). In addition, morbidity in males receiving PIM according to EU(7)-PIM was higher (median MI 1, IQR 1-3) compared to males without PIM use (median MI 1, IQR 0-2, p<0.001). CONCLUSION: PIM use occurred more frequently in women than in men, while it was associated with higher morbidity in males. As expected, EU(7)-PIM identifies more subjects as PIM users than the PRISCUS list but further studies are needed to investigate the differential impact of both lists on ADEs and outcome. KEY POINTS: We found PIM use to be associated with a higher number of regular medications and with increased morbidity. Additionally, we detected a higher prevalence of PIM use in females compared to males, suggesting that women and people needing intensive drug treatment are patient groups, who are particularly affected by PIM use

Assessing risk of breast cancer in an ethnically South-East Asia population (results of a multiple ethnic groups study)

10.1186/1471-2407-12-529BMC Cancer12-BCMA

Weight Loss and Mortality in Overweight and Obese Cancer Survivors: A Systematic Review

Background Excess adiposity is a risk factor for poorer cancer survival, but there is uncertainty over whether losing weight reduces the risk. We conducted a critical review of the literature examining weight loss and mortality in overweight or obese cancer survivors. Methods We systematically searched PubMed and EMBASE for articles reporting associations between weight loss and mortality (cancer-specific or all-cause) in overweight/obese patients with obesity-related cancers. Where available, data from the same studies on non-overweight patients were compared. Results Five articles describing observational studies in breast cancer survivors were included. Four studies reported a positive association between weight loss and mortality in overweight/obese survivors, and the remaining study observed no significant association. Results were similar for non-overweight survivors. Quality assessment indicated high risk of bias across studies. Conclusions There is currently a lack of observational evidence that weight loss improves survival for overweight and obese cancer survivors. However, the potential for bias in these studies is considerable and the results likely reflect the consequences of disease-related rather than intentional weight loss. There is a need for stronger study designs, incorporating measures of intentionality of weight loss, and extended to other cancers

Vitamin D supplementation and breast cancer prevention : a systematic review and meta-analysis of randomized clinical trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L