Maturitas - Articles in Press

Update of the evolution of breast cancer incidence in relation to hormone replacement therapy use in Belgium and review of other countries - Uncorrected Proof

Caroline Antoine, Lieveke Ameye, Marianne Paesmans, Serge Rozenberg — 2012-05-16

Abstract: Background: Several studies reported a decrease in breast cancer (BC) incidence, subsequent to the decrease in hormone replacement therapy (HRT) use.Aim: Although Belgium has one of the highest incidences of BC in Europe and one of the highest rates of HRT use, we were unable, in a previous study, to observe a significant association between BC incidence and HRT changes. In this updated report we added the BC data from incidence years 2007 and 2008.Material and method: We used European standardized incidence rates for invasive BC in the age class 50–69 years for Flanders (1999–2008), Brussels and Wallonia (2004–2008), obtained from IMS Health HRT sales data (1997–2008) for Brussels, Flanders and Wallonia. The association between BC incidence and HRT use was analyzed using generalized estimating equations (GEE) in order to take into consideration the dependency between the subsequent data points.Results: There was a significant association between the invasive BC incidence rate and estimated rate of HRT users in the previous year: p-value<0.001.Conclusion: Although this study is hampered by a number of limitations, these data support the idea that the drop in BC incidence can be partly attributed to the decrease in HRT use. Since HRT remains the most used medication for climacteric symptoms, we encourage the creation of a prospective registry in Europe, collecting detailed data in various European countries, in order to assess the adjusted increase in BC risk associated with HRT, which may be population and regimen dependent.

Lycopene for the prevention and treatment of benign prostatic hyperplasia and prostate cancer: A systematic review - Uncorrected Proof

Dragan Ilic, Marie Misso — 2012-05-16

Abstract: Background: Prostate cancer is a leading cancer affecting men worldwide. Benign prostatic hyperplasia (BPH) is a common disease of the prostate affecting men as they age, and a risk factor for developing prostate cancer. Lycopene is a member of the carotenoid family, whose strong anti-oxidant properties have been hypothesised to assist in the prevention and treatment of BPH and prostate cancer. The aim of this systematic review was to examine the effectiveness of lycopene for the prevention and treatment of BPH and prostate cancer.Methods: A search of the MEDLINE, EMBASE, AMED (Allied and Complementary Medicine) and the Cochrane Library databases was performed for published randomised controlled trials (RCTs) comparing lycopene to placebo (or other interventions) for the treatment of BPH and prostate cancer. All included studies were assessed for methodological quality using the Cochrane Collaboration's risk of bias tool.Results: Eight RCTs met the inclusion criteria for this systematic review. All included studies were heterogeneous with respect to their design and implementation of lycopene. Methodological quality of three studies was assessed as posing a ‘high’ risk of bias, two a ‘low’ risk of bias and the remaining three an ‘unclear’ risk of bias. Meta-analysis of four studies identified no significant decrease in the incidence of BPH (RR (relative risk)=0.95, 95%CI 0.63, 1.44) or prostate cancer diagnosis (RR=0.92, 95%CI 0.66, 1.29) between men randomised to receive lycopene and the comparison group. Meta-analysis of two studies indicated a decrease in PSA levels in men diagnosed with prostate cancer, who received lycopene (MD (mean difference)=−1.58, 95%CI −2.61, −0.55).Conclusions: Given the limited number of RCTs published, and the varying quality of existing studies, it is not possible to support, or refute, the use of lycopene for the prevention or treatment of BPH or prostate cancer.

The obesity paradox: Methodological considerations based on epidemiological and clinical evidence—New insights - Uncorrected Proof

Christina-Maria Kastorini, Demosthenes B. Panagiotakos — 2012-05-14

Abstract: Despite the well-known association of obesity with increased mortality and the development of chronic diseases, an “obesity paradox” has been reported in several patient categories; i.e., overweight and obese patients have a better prognosis than normal or low-weight individuals. The present review aims to identify potential factors lying beneath the beneficial effect of overweight and obesity. In particular, the role of nutritional status, malnutrition and catabolic state, as well as intentional vs. unintentional weight loss and the possibility of a U-shape relationship between body mass index and survival will be examined. Furthermore, methodological considerations framing the obesity paradox will be presented and discussed.

The effect of whole body vibration on balance, mobility and falls in older adults: A systematic review and meta-analysis - Uncorrected Proof

Freddy M.H. Lam, Ricky W.K. Lau, Raymond C.K. Chung, Marco Y.C. Pang — 2012-05-10

Abstract: This systematic review aimed to examine the effect of WBV on balance, mobility and falls among older adults. The databases used included MEDLINE, the Excerpta Medica database, the Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library Databases of Systematic Reviews, Physiotherapy Evidence Database (PEDro), PubMed, and Science Citation Index (last search in October 2011). Randomized controlled trials that investigated the effect of WBV on balance, mobility or falls in older adults were included in this review. The PEDro score was used to examine the methodological quality of the selected studies. The effect of WBV on balance, mobility and fall-related outcomes were extracted. The data extraction and rating were performed by a researcher and the results were confirmed by the principal investigator. Meta-analysis was done if 3 or more studies measured the same outcome of interest. Among 920 articles screened, fifteen articles (thirteen trials) satisfied the criteria and were included in this review. Methodological quality was good for six of the studies (PEDro score=6–7). Meta-analysis revealed that WBV has a significant treatment effect in Tinetti Total Score (p<0.001), Tinetti Body Balance Score (p=0.010) and Timed-Up-and-Go test (p=0.004). No significant improvement was noted in Tinetti Gait Score after WBV training (p=0.120). The effect of WBV on other balance/mobility outcomes and fall rate remains inconclusive. To conclude, WBV may be effective in improving relatively basic balance ability and mobility among older adults, particularly frailer ones. More good-quality WBV trials are required.

Potential mechanisms of postmenopausal endometriosis - Uncorrected Proof

Charlotte L. Bendon, Christian M. Becker — 2012-05-10

Abstract: Endometriosis is a chronic gynaecological disorder, the cause of which remains a subject of controversy. Oestrogen dependence is considered central to development and progression, and endometriosis is widely viewed as a disease of the premenopausal years, which normally regresses during the menopause. Increasingly however, reports of cases of postmenopausal endometriosis challenge our current understanding of the pathophysiology and raise further questions concerning the processes involved. Exploring the limited evidence available on postmenopausal disease we attempt to draw comparisons with pre-menopausal endometriosis, and in doing so to propose mechanisms for postmenopausal disease that are compatible with our current general understanding of the condition.

Efficacy and safety of high dose intramuscular or oral cholecalciferol in vitamin D deficient/insufficient elderly - Uncorrected Proof

Ayse Tellioglu, Sibel Basaran, Rengin Guzel, Gulsah Seydaoglu — 2012-05-10

Abstract: Objectives: To evaluate and compare the effects and safety of high dose intramuscular (IM) or oral cholecalciferol on 25-hydroxyvitamin D [25(OH)D] levels, muscle strength and physical performance in vitamin D deficient/insufficient elderly.Study design: Randomized prospective study.Main outcome measures: 116 ambulatory individuals aged 65years or older living in a nursing home were evaluated. Eligible patients with 25(OH)D levels <30ng/ml (n=66) were randomized to IM or Oral groups according to the administration route of 600,000IU cholecalciferol. Demographic and descriptive data were collected. Biochemical response was measured at baseline, 6th and 12th weeks. Muscle strength was measured from quadriceps by using a hand-held dynamometer and physical performance was evaluated by short physical performance battery (SPPB) at the beginning and 12th week.Results: Among the screened ambulatory elderly only 5.2% (n=6) had adequate vitamin D levels. 37.1% (n=43) were vitamin D deficient and 57.7% (n=67) were insufficient. After administration of one megadose of vitamin D, mean serum 25(OH)D levels increased significantly at 6th week (32.72±9.0ng/ml) and at 12th week (52.34±14.2ng/ml) compared with baseline (11.76±7.6ng/ml) in IM group (p<0.0001). In Oral group levels were 47.57±12.7ng/ml, 42.94±13.4ng/ml and 14.87±6.9ng/ml, respectively (p<0.0001). At 12th week the increase in IM group was significantly higher than Oral group (p=0.003).At the end of the study period, serum 25(OH)D levels were ≥30ng/ml in all patients in IM group and in 83.3% of the patients in the Oral group. Quadriceps muscle strength and SPPB total score increased significantly in both groups and SPPB balance subscale score increased only in IM group. Six patients (9.6%) developed hypercalciuria, no significant adverse events were observed.Conclusion: In vitamin D deficient/insufficient elderly, a single megadose of cholecalciferol increased vitamin D levels significantly and the majority of the patients reached optimal levels. Although both administration routes are effective and appear to be safe, IM application is more effective in increasing 25(OH)D levels and balance performance.

Healthy ageing in women: Is moderate drinking the secret ingredient? - Corrected Proof

Qi Sun, Francine Grodstein — 2012-05-07

Owing to much-improved food security, public health interventions, and clinical treatments, life expectancy in developed countries has reached the mid-70s and is projected to approach or even exceed age 90 years in the next century. Meanwhile, as the oldest segment of the population grows continuously in developed countries, the prevalence of age-related chronic diseases or conditions, such as cancer, type 2 diabetes, cognitive impairment, and functional limitations, is also increasing rapidly, and health expenditures have skyrocketed, leading to tremendous burdens to the economy, society, and individuals .

Reminiscence therapy in dementia: A review - Uncorrected Proof

Maria Cotelli, Rosa Manenti, Orazio Zanetti — 2012-05-07

Abstract: Dementia is a progressive disorder that impacts several cognitive functions. However, some aspects of cognitive function are preserved until late in the disease and can therefore be the targets of specific interventions. The rehabilitation of cognitive function disorders represents an expanding area of neurological rehabilitation, and it has recently attracted growing political, social and ethical attention. Here, we review the efficacy of reminiscence therapy to improve cognitive functions and/or mood. Available studies suggest that reminiscence therapy can improve mood and some cognitive abilities. Further studies, based on larger patient samples including placebo and control conditions, should be conducted to identify the optimal conditions for such treatment protocols.

Menopausal symptoms: Do life events predict severity of symptoms in peri- and post-menopause? - Uncorrected Proof

Filipa Pimenta, Isabel Leal, João Maroco, Catarina Ramos — 2012-05-03

Abstract: Objective: Hormonal changes during menopausal transition are linked to physical and psychological symptoms’ emergence. This study aims to explore if life events predict menopausal symptoms.Methods: This cross-sectional research encompasses a community sample of 992 women who answered to socio-demographic, health, menopause-related and lifestyle questionnaires; menopausal symptoms and life events were assessed with validated instruments. Structural equation modeling was used to build a causal model.Results: Menopausal status predicted only three symptoms: skin/facial hair changes (β=.136; p=.020), sexual (β=.157; p=.004) and, marginally, vasomotor symptoms (β=.094; p=.054). Life events predicted depressive mood (β=−.391; p=.002), anxiety (β=−.271; p=.003), perceived cognitive impairment (β=−.295; p=.003), body shape changes (β=−.136; p=.031), aches/pain (β=−.212; p=.007), skin/facial hair changes (β=−.171; p=.021), numbness (β=−.169; p=.015), perceived loss of control (β=−.234; p=.008), mouth, nails and hair changes (β=−.290; p=.004), vasomotor (β=−.113; p=.044) and sexual symptoms (β=−.208; p=.009).Conclusions: Although women in peri- and post-menopausal manifested higher symptoms’ severity than their pre-menopausal counterparts, only three of the menopausal symptoms assessed were predicted by menopausal status. Since the vast majority of menopausal symptoms’ severity was significantly influenced by the way women perceived their recent life events, it is concluded that the symptomatology exacerbation, in peri- and post-menopausal women, might be due to life conditions and events, rather than hormonal changes (nonetheless, the inverse influence should be investigated in future studies). Therefore, these should be accounted for in menopause-related clinical and research settings.

Factor structure and normative data of the Greene Climacteric Scale among postmenopausal Portuguese women - Corrected Proof

2012-04-30

Abstract: Objectives: The purposes of the present study were to assess the factorial structure and reliability of the Greene Climacteric Scale (GCS), and provide normative data for a sample of postmenopausal Portuguese women.Methods: A sample of 401 Caucasian women, with ages between 47 and 91 years, divided into four age groups (47–57: 31.4%, 58–68: 40.4%, 69–79: 21.4% and ≥80: 6.7%), voluntarily participated in the study. The Greene Climacteric Scale aims to measure psychological symptoms divided into anxiety and depression, somatic and vasomotor symptoms with a total of 21 items. Data were analyzed by reliability, correlation and confirmatory factor analyses. Age group differences in the raw and the standardized scores of symptoms clusters were investigated by means of ANOVA procedures.Results: The CFA performed supported the 4-factor structure specified by Greene (*CFI=0.937; SRMR=0.046; *RMSEA (90%IC)=0.050 (0.042–0.058). The computed internal consistency estimates ranged from 0.73 to 0.90. Vasomotor symptoms (hot flushes and sweating at night) were experienced most frequently by the younger age group (47–57 years) while nonspecific symptoms (e.g. difficulty in concentrating, feeling tired or lacking in energy, breathing difficulties) were reported more frequently by the older age groups.Conclusions: Our results suggest that the Portuguese version of the GCS is a reliable and a valid instrument for the measurement of climacteric-related factors in postmenopausal women.

A systematic review of body fat distribution and mortality in older people - Uncorrected Proof

Su-Hsin Chang, Tracey S. Beason, Jean M. Hunleth, Graham A. Colditz — 2012-04-30

Abstract: We conducted a systematic review investigating body fat distribution in older adults and its association with morbidity and mortality. Our search yielded 2702 citations. Following three levels of screening, 25 studies were selected to evaluate the association between body fat distribution and comorbidity, and 17 studies were used in the mortality analysis. Most of the selected studies in our analyses used anthropometric measures, e.g., body mass index (BMI), waist circumference, and waist–hip ratio; relatively few studies used direct measures, such as body fat/lean mass, and percentage body fat. Studies reported inconsistent findings regarding the strongest predictor(s) of morbidity and mortality. However, the majority of studies suggested that BMI per se was not the most appropriate predictor of morbidity and mortality in the elderly because of its inability to discern or detect age-related body fat redistribution. In addition, studies using BMI found that the optimal BMI range for the lowest mortality in the elderly was overweight (25kg/m2≤BMI<30kg/m2) or mildly obese (30kg/m2≤BMI<35kg/m2). Our findings suggest that the current clinical guidelines, recommending that overweight and obesity are major risk factors for increased morbidity and mortality are not applicable to this population. Therefore, the central message of this review is to admonish the government to establish new guidelines specifically for this population, using a combination of body fat distribution measurements, and to certify that these guidelines will not be applied to inappropriate populations.

Factors associated with premature ovarian failure, early menopause and earlier onset of menopause in Japanese women - Corrected Proof

2012-04-27

Abstract: Objective: The purpose of this study is to clarify the median age at natural menopause and the proportions of women with premature ovarian failure (POF) and early menopause (EM) by using Kaplan–Meier cumulative estimates and differences in reproductive and lifestyle factors associated with POF, EM and median age at menopause in a large population of Japanese women.Subjects and methods: This study is a cross-sectional analysis of the Japan Nurses’ Health Study (JNHS). We analyzed data for 24,152 pre- and postmenopausal women who were 40 years or older at the JNHS baseline survey.Results: The overall estimated median age at natural menopause was 52.1years, and the proportions of women with POF and EM were 0.28% and 1.67%, respectively. Older generation, cigarette smoking, low body mass index, regular menstruation cycles at 18–22years of age, nulliparity and unilateral oophorectomy were associated with earlier onset of natural menopause.Only unilateral oophorectomy was associated with increased risk of POF, and nulliparity and unilateral oophorectomy were associated with increased risk of EM.Conclusion: Unilateral oophorectomy is a common factor associated with earlier onset of menopause, EM and POF, although other reproductive and lifestyle factors are not associated with POF or EM.

The dynamics of the relationship between diabetes incidence and low income: Longitudinal results from Canada's National Population Health Survey - Corrected Proof

2012-04-20

Abstract: This paper sheds light on the dynamic relationship between people's experiences of low income and the development of type 2 diabetes (T2DM) by moving beyond the static perspective provided by cross-sectional studies to a long-term approach informed by longitudinal analyses. Methods: We analyzed data from the Canadian National Population Health Survey (NPHS) conducted by Statistics Canada from 1994 to 2007. The longitudinal sample is composed of 17,276 respondents (8046 males, 9230 females) 12 years of age or older. We further developed an algorithm to distinguish T2DM from other types of diabetes. Proportional hazard models with time-varying predictors were used to explore the dynamics of the relationship between low income and T2DM. Results: The results suggest that living in low income and experiencing persistent low income are significant precursors of developing T2DM. Being in low income in the previous cycle of T2DM onset was associated with 77% higher risk of T2DM (hazard ratio 1.77; 95% CI: 1.48–2.12). The association between low income and diabetes incidence remains significant after adjusting for age, sex, health behaviors, and psychological distress (hazard ratio 1.24; 95% CI: 1.02–1.52). Conclusion: This study contributes to the under-developed research examining longitudinally the relationship between socioeconomic status and diabetes incidence. Employing this long-term approach, this study calls attention to the primary effect of socioeconomic position on diabetes incidence that cannot be explained entirely by behavioral factors. Findings draw attention to the need to address the role played in T2DM by the inequitable distribution of the social determinants of health.

Effect of hot flushes on cardiovascular autonomic responsiveness: A randomized controlled trial on hormone therapy - Corrected Proof

2012-04-19

Abstract: Objectives: To compare the responses of heart rate and blood pressure to various autonomic tests in women with and without pre-treatment hot flushes during estradiol and estradiol+medroxyprogesterone acetate (MPA) use.Study design and main outcome measures: Hundred and fifty recently postmenopausal women (72 with and 78 without hot flushes) were randomized to receive transdermal estradiol (1mg/day), oral estradiol (2mg/day) alone or in combination with MPA (5mg/day), or placebo for six months. Cardiovascular responsiveness was comprehensively assessed with controlled and deep breathing, active orthostatic test, Valsalva maneuver and handgrip test.Results: Hot flushes were accompanied with a significant reduction (−2.2±0.7 vs. 1.3±1.1beats/min, p=0.03) in resting heart rate during estradiol-only treatment; the route of estradiol administration was no factor in this regard. This effect was attenuated by the addition of MPA to oral estradiol. Hot flushes were also associated with reduced maximal heart rate in response to handgrip during the use of estradiol-only therapy (−2.2±1.3 vs. 2.8±1.5beats/min, p=0.038); again, the MPA addition eliminated this effect. Hot flushes were accompanied with lowered resting but augmented blood pressure responses to handgrip test during all hormone regimens, whereas in women without hot flushes estradiol-only regimen tended to elevate diastolic resting blood pressure.Conclusions: Hot flushes appear as determinants for cardiovascular responses to hormone therapy. Estradiol-only therapy causes beneficial changes in cardiovascular regulation in flushing women, and these are blunted, in part, by the addition of MPA.

Women's experiences of Group Cognitive Behaviour Therapy for hot flushes and night sweats following breast cancer treatment: An interpretative phenomenological analysis - Corrected Proof

Janet Balabanovic, Beverley Ayers, Myra S. Hunter — 2012-04-16

Abstract: Objectives: Many women with breast cancer experience problematic treatment-related menopausal symptoms (HF/NS). This study explores how these women experienced a Group Cognitive Behaviour Therapy (CBT) intervention to help them manage their treatment-related HF/NS. The study was conducted as part of a randomised control trial/RCT (MENOS 1) evaluating the intervention among this target group.Methods: In-depth semi-structured interviews were conducted with twenty trial participants to explore how they experienced the intervention and its effects. The interviews were analysed using interpretative phenomenological analysis.Results: The analysis revealed four superordinate themes: Making sense of symptom change; new ways of coping and regaining control; tailoring the treatment to meet individual needs and resources; and valuing the group context, social support and social comparisons. All the women found Group CBT improved their ability to cope with their HF/NS, while also developing an appreciation of the role of psychological factors in their symptom experience. Through the knowledge and understanding acquired women developed a more accepting stance to their symptoms, as well as gaining a ‘sense of control’.Conclusions: The results are consistent with the main RCT outcomes which showed that Group CBT led to a clinically significant reduction in ‘HF/NS problem rating’ relative to ‘treatment as usual’, as well as improvements in mood and physical and social functioning. The results complement the trial outcomes by illuminating women's experience of different components of the intervention and highlighting possible mechanisms of change.

The quantification of vitamin D receptors in coronary arteries and their association with atherosclerosis - Corrected Proof

2012-04-16

Abstract: Objective: The activated vitamin D receptor (VDR) may have an important role in vascular health. The objective of this study was to determine whether there is an association between the expression of VDRs in coronary arteries and the extent of diet-induced atherosclerosis.Methods: Utilizing a cohort of 39 postmenopausal female cynomolgus monkeys with varying stages of atherosclerosis, histologic sections of the left anterior descending artery (LAD) were analyzed for plaque cross-sectional area, plaque thickness, and VDR quantity using immunohistochemical H-score analysis. The quantities of VDRs were analyzed as a continuous variable and were divided at the median intimal H-score into high vs. low groupings.Results: In the LAD, a significant negative correlation was observed between the quantity of VDR and plaque size (both cross-sectional area [p<0.001] and plaque thickness [p<0.001]). Monkeys in the low VDR group had a significantly greater cross-sectional plaque area (1.2mm2) and greater plaque thickness (0.3mm) than those in the high VDR group (0.4mm2, p=0.005; 0.1mm, p=0.003, respectively).Conclusions: Lower concentrations of VDRs in a main coronary artery were associated with greater atherosclerotic plaque size in postmenopausal female monkeys. Given that coronary artery atherosclerosis is a major cause of coronary heart disease in postmenopausal women, further research to ascertain the relationship between VDRs and atherosclerosis is warranted.

Systematic review of progesterone use by midlife and menopausal women - Corrected Proof

M. Joy Spark, Jon Willis — 2012-04-16

Abstract: Progesterone treatment for menopausal symptoms is still controversial. Progesterone levels fall during menopause transition, therefore some menopausal women may benefit from progesterone therapy. A systematic review was conducted of studies published from 2001 reporting on progesterone use to treat symptoms associated with menopause or postmenopausal women. Fourteen data bases were searched using the search terms progesterone, menopause, aged, female and human; exclusions were breast cancer, animal and contraception.Thirteen studies were selected for inclusion (11 clinical trials, 1 cohort study and 1 qualitative study), evaluating progesterone effects on menopausal symptoms, bone, sleep, skin, cognition, plasma lipids and plaque progression. Most studies were of low methodological quality (GRADE low or very low). Progesterone improved vasomotor symptoms and sleep quality, with minimal risk. Large studies designed to identify confounders, such as hormone levels, menopausal status and metabolism are required to understand the place of progesterone in clinical practice.

Haemoglobin predicts length of hospital stay after hip fracture surgery in older patients - Corrected Proof

2012-04-16

Abstract: Objectives: Treating anaemia in older patients who have undergone hip fracture surgery is to enhance functional recovery. The relationship between peri-operative haemoglobin levels and outcome after hip fracture surgery are controversial. We assessed whether higher haemoglobin levels predict length of hospital stay after hip fracture surgery in elderly subjects.Study design: A follow-up study in a historical cohort was performed in 317 patients aged 65 years old undergoing hip fracture surgery over the period 2004–2006 at the Leiden University Medical Centre.Mean outcome measures: Linear regression analysis was used to assess the association between pre- and post-operative haemoglobin level and length of hospital stay after controlling for age and sex.Results: Anaemia after hip fracture surgery was present among 86% of the patients. Length of hospital stay after hip fracture surgery in elderly subjects with post-operative anaemia (10.7 days) was significantly longer than in elderly subjects without post-operative anaemia (7.5 days, p=0.007). Post-operative haemoglobin levels and length of hospital stay were inversely related (p=0.013). The length of hospital stay was not related with pre-operative haemoglobin level.Conclusion: Higher postoperative haemoglobin levels predict shorter length of hospital stay after hip fracture surgery in the elderly. A definitive randomized clinical trial has to demonstrate whether this association is causal.

Erectile dysfunction and coronary disease: Evaluating the link - Corrected Proof

Graham Jackson — 2012-04-06

Abstract: Erectile dysfunction (ED) is common, affecting 40% of men over 40years of age (so-called 40 over 40) and 1 in 3 men over 70years of age. It is predominantly a vascular condition, often preceding a cardiovascular event by 3–5years. ED is associated as a consequence with acute coronary syndromes and increased cardiovascular and all-cause mortality. Its early identification therefore offers a window of opportunity for cardiovascular risk reduction. ED has for many a devastating impact on a couple's relationship. Its treatment is often successful, maintaining quality of life in the middle aged and elderly. ED should always be queried as part of the ongoing health care worker and patient relationship – its early detection may prevent early death.

Magnetic nanovectors for drug delivery - Corrected Proof

Jim Klostergaard, Charles E. Seeney — 2012-02-20

Abstract: Nanotechnology holds the promise of novel and more effective treatments for vexing human health issues. Among these are the use of nanoparticle platforms for site-specific delivery of therapeutics to tumors, both by passive and active mechanisms; the latter includes magnetic vectoring of magnetically responsive nanoparticles (MNP) that are functionalized to carry a drug payload that is released at the tumor. The conceptual basis, which actually dates back a number of decades, resides in physical (magnetic) enhancement, with magnetic field gradients aligned non-parallel to the direction of flow in the tumor vasculature, of existing passive mechanisms for extravasation and accumulation of MNP in the tumor interstitial fluid, followed by MNP internalization. In this review, we will assess the most recent developments and current status of this approach, considering MNP that are composed of one or more of the three elements that are ferromagnetic at physiological temperature: nickel, cobalt and iron. The effects on cellular functions in vitro, the ability to successfully vector the platform in vivo, the anti-tumor effects of such localized nano-vectors, and any associated toxicities for these MNP will be presented. The merits and shortcomings of nanomaterials made of each of the three elements will be highlighted, and a roadmap for moving this long-established approach forward to clinical evaluation will be put forth.

Nanoparticle delivery for metastatic breast cancer - Corrected Proof

2012-02-20

Abstract: Breast cancer represents a major ongoing public health problem as the most common non-cutaneous malignancy among U.S. women. While significant progress has been made in improving loco-regional treatments for breast cancer, relatively little progress has been made in diagnosing and treating patients with metastatic breast cancer. At present there are limited curative options for patients with breast cancer metastatic beyond regional nodes. Emerging nanotechnologies promise new approaches to early detection and treatment of metastatic breast cancer. Fulfilling the promise of nanotechnologies for patients with metastatic breast cancer will require delivery of nanomaterials to sites of metastatic disease. Future translational approaches will rely on an ever increasing understanding of the biology of breast cancer subtypes and their metastases. These important concepts will be highlighted and elucidated in this manuscript.

Nanoparticle therapeutics for prostate cancer treatment - Corrected Proof

Vanna Sanna, Mario Sechi — 2012-02-10

Abstract: The application of nanotechnology in medicine is offering many exciting possibilities in healthcare. Engineered nanoparticles have the potential to revolutionize the diagnosis and the therapy of several diseases, particularly by targeted delivery of anticancer drugs and imaging contrast agents. Prostate cancer, the second most common cancer in men, represents one of the major epidemiological problems, especially for patients in the advanced age. There is a substantial interest in developing therapeutic options for treatment of prostate cancer based on use of nanodevices, to overcome the lack of specificity of conventional chemotherapeutic agents as well as for the early detection of precancerous and malignant lesions. Herein, we highlight on the recent development of nanotechnology strategies adopted for the management of prostate cancer. In particular, the combination of targeted and controlled-release polymer nanotechnologies has recently resulted in the clinical development of BIND-014, a promising targeted Docetaxel-loaded nanoprototype, which can be validated for use in the prostate cancer therapy. However, several limitations facing nanoparticle delivery to solid tumours, such as heterogeneity of intratumoural barriers and vasculature, cytotoxicity and/or hypersensitivity reactions to currently available cancer nanomedicines, and the difficult in developing targeted nanoparticles with optimal biophysicochemical properties, should be still addressed for a successful tumour eradication.

Nanoparticle delivery for transdermal HRT - Corrected Proof

Pilar Valenzuela, James A. Simon — 2012-01-16

Abstract: Nanomedicine is an emerging technology and the first nano-engineered medical products have come to light in the last decade. Transdermal drug delivery has significant advantages compared to other routes of drug administration. Nanoparticles unique physical and chemical properties enable transport of substances directly into the skin. The objective of this paper is to review different aspects of nanoparticle delivery, generally, and discuss its current use for transdermal hormone therapy. Transdermal estrogen therapy remains the most effective treatment for bothersome menopausal symptoms, particularly in those women for whom the potential adverse effects associated with “first pass” hepatic metabolism are to be avoided. Available alternatives for transdermal estrogen delivery include patches, gels, sprays and lotions. Other non-oral therapies which likewise avoid “first pass” hepatic metabolism include: subcutaneous implants and vaginal rings. Some of the transdermal products are associated with mild adverse skin effects such as redness and irritation, but more severe and bothersome consequences include blistering and tattooing. Even the mild adverse skin effects are frequently cited as reasons for discontinuation. Micellar nanoparticle estradiol emulsion (MNPEE) is a lotion-like therapy which constitutes an alternative transdermal delivery system not requiring the permeation enhancers or temporary skin digestion, both of which increase the possibility of irritation. MNPEE's advantages include low fluctuation of plasma estradiol concentrations, infrequent skin related adverse effects, and pleasant cosmetic-like moisturizing properties. The efficacy of MNPEE for management of menopausal vasomotor symptoms has been demonstrated in a randomized placebo controlled trial , and the product is FDA approved for management of moderate to severe vasomotor symptoms. None of the observed adverse effects in the MNPEE group were statistically different from the placebo group . Studies addressing inadvertent transference of estradiol to the male partners of menopausal women using this delivery technology have demonstrated small, but real amounts of transference, which do not exceed the normal physiological male estradiol range. MNPEE is safe and effective for treatment of vasomotor symptoms and represents the commercial validation of nanoparticle technology for transdermal delivery of estrogen therapy (ET) for postmenopausal women with vasomotor symptoms.

Nanomedicine for the prevention, treatment and imaging of atherosclerosis - Corrected Proof

Costas Psarros, Regent Lee, Marios Margaritis, Charalambos Antoniades — 2012-01-09

Abstract: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in developed countries, with an increasing prevalence due to an aging population. The pathology underpinning CVD is atherosclerosis, a chronic inflammatory state involving the arterial wall. Accumulation of low density lipoprotein (LDL) laden macrophages in the arterial wall and their subsequent transformation into foam cells lead to atherosclerotic plaque formation. Progression of atherosclerotic lesions may gradually lead to plaque related complications and clinically manifest as acute vascular syndromes including acute myocardial or cerebral ischemia. Nanotechnology offers emerging therapeutic strategies, which may have advantage overclassical treatments for atherosclerosis. In this review, we present the potential applications of nanotechnology toward prevention, identification and treatment of atherosclerosis.

Nanotechnology for neurodegenerative disorders - Corrected Proof

Francesca Re, Maria Gregori, Massimo Masserini — 2012-01-09

Abstract: The efficacy, cellular uptake and specific transport of drugs and/or imaging agents to target organs, tissues and cells are common issues in the diagnosis and treatment of different disorders. In the case of neurodegenerative diseases, they represent complex problems, since brain targeting remains a still unsolved challenge in pharmacology, due to the presence of the blood–brain barrier, a tightly packed layer of endothelial cells that prevents unwanted substances to enter the brain. Engineered nanomaterials, objects with dimensions of 1–100nm, are providing interesting biomedical tools potentially able to solve these problems, thanks to their physico-chemical features and to the possibility of multi-functionalization, allowing to confer them different features at the same time, including the ability to cross the blood–brain barrier. This review focuses on the state-of-the-art of nanomaterials suitable for therapy and diagnostic imaging of the most common neurodegenerative disorders, as well as for neuroprotection and neuronal tissue regeneration. Finally, their potential neurotoxicity is discussed, and future nanotechnological approaches are described.

Nanomedicine for treatment of diabetes in an aging population: State-of-the-art and future developments - Corrected Proof

Silke Krol, Rutledge Ellis-Behnke, Piero Marchetti — 2011-12-21

Abstract: Nowadays diabetes, especially type 2 diabetes (which is strongly related to the Western diet and life-style), has developed worldwide into an epidemic disease. Nanomedicine aims to provide novel tools for diagnosis, therapy and point-of-care management of patients.Several nanotechnological approaches were developed to improve life quality for patients with insulin-dependent diabetes. They facilitate blood glucose management by non-invasive glucose measurement as well as insulin administration mainly by delivering the fragile protein as protected and targeted formulation via nasal or oral route.In the present review the oral or nasal insulin delivery by polymeric nanoparticles is discussed with focus on physiological change either related to the disease, diabetes or age-related metabolic variations influencing insulin release and bioavailability. One critical point is that new generations of targeted nanoparticle based drugs are developed and optimized for certain metabolic conditions. These conditions may change with age or disease. The influence of age-related factors such as immaturity in very young age, metabolic and physiologic changes in old age or insufficient animal models are still under-investigated not only in nanomedicine but also generally in pharmacology.Summarizing it can be noted that the bioavailability of insulin administered via routes others than subcutaneously is comparably low (max. 60%). Moreover factors like changed gut permeability as described for diabetes type 1 or other metabolic peculiarities such as insulin resistance in case of type 2 diabetes also play a role in affecting the development of novel nanoparticulated drug preparations and can be responsible for unsuccessful translation of promising animal results into human therapy.In future insulin nanoparticle development for diabetes must consider not only requirements imposed by the drug but also metabolic changes inflicted by disease or by age. Moreover new approaches are required for prevention of the disease.

Nanomedicines for chronic non-infectious arthritis: The clinician's perspective - Corrected Proof

Israel Rubinstein, Guy L. Weinberg — 2011-12-16

Abstract: Rheumatoid arthritis (RA) and osteoarthritis (OA) are prevalent chronic health conditions. However, despite recent advances in medical therapeutics, their treatment still represents an unmet medical need because of safety and efficacy concerns with currently prescribed drugs. Accordingly, there is an urgent need to develop and test new drugs for RA and OA that selectively target inflamed joints thereby mitigating damage to healthy tissues.Conceivably, biocompatible, biodegradable, disease-modifying antirheumatic nanomedicines (DMARNs) could represent a promising therapeutic approach for RA and OA. To this end, the unique physicochemical properties of drug-loaded nanocarriers coupled with pathophysiological characteristics of inflamed joints amplify bioavailability and bioactivity of DMARNs and promote their selective targeting to inflamed joints. This, in turn, minimizes the amount of drug required to control articular inflammation and circumvents collateral damage to healthy tissues. Thus, nanomedicine could provide selective control both in space and time of the inflammatory process in affected joints.However, bringing safe and efficacious DMARNs for RA and OA to the marketplace is challenging because regulatory agencies have no official definition of nanotechnology, and rules and definitions for nanomedicines are still being developed. Although existing toxicology tests may be adequate for most DMARNs, as new toxicity risks and adverse health effects derived from novel nanomaterials with intended use in humans are identified, additional toxicology tests would be required. Hence, we propose that detailed pre-clinical in vivo safety assessment of promising DMARNs leads for RA and OA, including risks to the general population, must be conducted before clinical trials begin.