Toward an Interdisciplinary Approach to Constructing Care Delivery Pathways From Electronic Health Care Databases to Support Integrated Care in Chronic Conditions: Systematic Review of Quantification and Visualization Methods.

BACKGROUND: Electronic health care databases are increasingly used for informing clinical decision-making. In long-term care, linking and accessing information on health care delivered by different providers could improve coordination and health outcomes. Several methods for quantifying and visualizing this information into data-driven care delivery pathways (CDPs) have been proposed. To be integrated effectively and sustainably into routine care, these methods need to meet a range of prerequisites covering 3 broad domains: clinical, technological, and behavioral. Although advances have been made, development to date lacks a comprehensive interdisciplinary approach. As the field expands, it would benefit from developing common standards of development and reporting that integrate clinical, technological, and behavioral aspects. OBJECTIVE: We aimed to describe the content and development of long-term CDP quantification and visualization methods and to propose recommendations for future work. METHODS: We conducted a systematic review following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations. We searched peer-reviewed publications in English and reported the CDP methods by using the following data in the included studies: long-term care data and extracted data on clinical information and aims, technological development and characteristics, and user behaviors. The data are summarized in tables and presented narratively. RESULTS: Of the 2921 records identified, 14 studies were included, of which 13 (93%) were descriptive reports and 1 (7%) was a validation study. Clinical aims focused primarily on treatment decision-making (n=6, 43%) and care coordination (n=7, 50%). Technological development followed a similar process from scope definition to tool validation, with various levels of detail in reporting. User behaviors (n=3, 21%) referred to accessing CDPs, planning care, adjusting treatment, or supporting adherence. CONCLUSIONS: The use of electronic health care databases for quantifying and visualizing CDPs in long-term care is an emerging field. Detailed and standardized reporting of clinical and technological aspects is needed. Early consideration of how CDPs would be used, validated, and implemented in clinical practice would likely facilitate further development and adoption. TRIAL REGISTRATION: PROSPERO CRD42019140494; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=140494. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-033573.

Investigating potential disparities in clinical trial eligibility and enrollment at an NCI-designated comprehensive cancer center.

BACKGROUND: Although barriers to trial accrual are well-reported, few studies have explored trial eligibility and trial offers as potential drivers of disparities in cancer clinical trial enrollment. METHODS: We identified patients with gastrointestinal (GI) or head/neck (HN) malignancies who were seen as new patients at the University of Michigan Health Rogel Cancer Center in 2016. By exhaustive review of the electronic medical record, we assessed the primary outcomes: (1) eligibility for, (2) documented offer of, and (3) enrollment in a clinical trial. All 41 of the clinical trials available to these patients were considered. Independent variables included clinical and non-clinical patient-related factors. We assessed associations between these variables and the primary outcomes using multivariable regression. RESULTS: Of 1446 patients, 43% were female, 15% were over age 75, 6% were Black. 305 (21%) patients were eligible for a clinical trial. Among eligible patients, 154 (50%) had documentation of a trial offer and 90 (30%) enrolled. Among the GI cohort, bivariate analyses demonstrated that older age was associated with decreased trial eligibility. Bivariate analyses also demonstrated that Black race was associated with increased trial offer. After adjustment, patients 75 or older were less likely to be eligible for a clinical trial in the GI cohort; however, we found no significant associations between race and any of the outcomes after adjustment. Among eligible GI patients, we found no significant associations between non-clinical factors and enrollment. Among the HN cohort, bivariate analyses demonstrated that female sex, older age, Black race, and unpartnered marital status were associated with decreased likelihood of trial offer; however, we found no significant associations between race, age, and marital status and any of the outcomes after adjustment. We found no significant associations between non-clinical factors and eligibility after adjustment; however, women were less likely to be offered and to enroll in a clinical trial in the HN cohort. CONCLUSION: Factors associated with eligibility, documented offer, and enrollment differed between disease site cohorts at our institution. Future work is needed to ensure the equitable inclusion of women and elderly patients in clinical trials.

Month-of-Birth Effect on Muscle Mass and Strength in Community-Dwelling Older Women: The French EPIDOS Cohort.

Background. Vitamin D is involved in muscle health and function. This relationship may start from the earliest stages of life during pregnancy when fetal vitamin D relies on maternal vitamin D stores and sun exposure. Our objective was to determine whether there was an effect of the month of birth (MoB) on muscle mass and strength in older adults. Methods. Data from 7598 community-dwelling women aged ≥ 70 years from the French multicentric EPIDOS cohort were used in this analysis. The quadricipital strength was defined as the mean value of 3 consecutive tests of the maximal isometric voluntary contraction strength of the dominant lower limb. The muscle mass was defined as the total appendicular skeletal muscle mass measured using dual energy X-ray absorptiometry scanner. The MoB was used as a periodic function in regressions models adjusted for potential confounders including age, year of birth, latitude of recruitment center, season of testing, body mass index, number of comorbidities, IADL score, regular physical activity, sun exposure at midday, dietary protein intake, dietary vitamin D intake, use vitamin D supplements, history and current use of corticosteroids. Results. A total of 7133 older women had a measure of muscle strength (mean age, 80.5 ± 3.8 years; mean strength, 162.3 ± 52.1 N). Data on total ASM were available from 1321 women recruited in Toulouse, France (mean, 14.86 ± 2.04 kg). Both the sine and cosine functions of MoB were associated with the mean quadricipital strength (respectively ß = -2.1, p = 0.045 and ß = -0.5, p = 0.025). The sine function of MoB was associated with total ASM (ß = -0.2, p = 0.013), but not the cosine function (ß = 0.1, p = 0.092). Both the highest value of average quadricipital strength (mean, 163.4 ± 20.2 N) and the highest value of total ASM (15.24 ± 1.27 kg) were found among participants born in August. Conclusions. Summer-early fall months of birth were associated with higher muscle mass and strength in community-dwelling older women.

Higher dietary vitamin D intake is associated with better survival among older women: Results from the French EPIDOS cohort.

Background: Hypovitaminosis D, a condition highly common among older adults, is associated with 35-percent increased all-cause mortality. In contrast, vitamin D supplementation prevents all-cause mortality. The possible role of the dietary intake of vitamin D on mortality remains yet unknown. Objectives: The objective of this prospective study was to determine all-cause mortality risk according to baseline dietary vitamin D intake among older adults while accounting for potential confounders including dietary calcium intake. Methods: Vitamin D and calcium dietary intakes were estimated at baseline from a self-administered food frequency questionnaire among 3,066 community-dwelling older women aged ≥75 years, recruited in the French EPIDOS cohort between 1992 and 1994, and for whom information about vital status was available in 2010. Dietary vitamin D and calcium intakes were defined as low if <400 IU/day or <1,200 mg/day, respectively. Results: The mean ± SD age of the whole cohort was 80.1 ± 3.6 years at baseline. The median survival time from baseline for participants with low dietary vitamin D intake was 11.5 years [95% confidence interval (CI): 11.0-11.9] vs. 12.2 years (95% CI: 11.7-12.9) for those consuming more than 400 IU/day (p = 0.003). Among those with calcium dietary intake <1,200 mg/day, a vitamin D consumption of 400 IU/day and over had a significant positive effect on all-cause mortality (RR: 0.86, p < 0.05). However, no association was retrieved between dietary vitamin D intake and all-cause mortality among participants with dietary calcium intake ≥1,200 mg/day. Conclusion: Higher dietary vitamin D intake was associated with better survival in the study cohort, specifically among those consuming <1,200 mg/day of dietary calcium.

Trends in postmenopausal osteoporosis treatment in France during the period 2007-2016: A nationwide claims database analysis.

PURPOSE: To describe the trends in the pharmacological management of postmenopausal osteoporosis in France during the period 2007-2016. METHOD: This cross-sectional, yearly repeated study of patients in France used the nationwide claims database 'Échantillon Généraliste de Bénéficiaires' (EGB), covering a 1 in 97 representative sample of approximately 600,000 individuals insured by the main French public insurance scheme. For women aged 50-89 years, prescriptions for all anti-osteoporosis medications (AOMs) marketed in France during the study period (bisphosphonates alone or used in combination with calcium, selective estrogen receptor modulators, strontium ranelate, teriparatide or denosumab) were identified in each calendar year. Initiation of any AOM in a calendar year was defined by the absence of a prescription for any AOM within the 2 previous calendar years. Incidence was calculated for all AOM prescriptions and initial prescriptions for AOM. RESULTS: Marked changes were observed in the rates of women receiving any AOM, with a slight increase from 2007 to 2009 (from 10.22 to 10.42 per 100 patient-years [PY]), then a plateau in 2009-2010, followed by a rapid and more than twofold decrease until 2016 (from 10.39 to 5.02 per 100 PY). The decrease in the overall rate of women initiating an AOM showed a rapid halving from 2007 to 2012 (from 2.56 to 1.15 per 100 PY), followed by a plateau in the range of 0.90-1.0 per 100 PY during the period 2013-2016. In contrast, the use of calcium/vitamin D has been rapidly increasing as the only prevention and exclusive intervention for postmenopausal osteoporosis, from 10.6% of women in 2007 to 47.7% in 2016. The profile of patients initiating AOM changed substantially over the 10-year period. Despite a stable mean age of approximately 69 years, an increasing proportion of women with severe chronic comorbidities (from 34.9% to 43.3%), history of fractures (from 7.8% to 13.3%) or high-dose steroid use (from 2.9% to 8.4%) was observed. The decline of AOM initiation was associated with a marked reduction of prescriptions during the study period: by 64.2% for primary care physicians; by 36.7% for specialty doctors; and by 18.4% for rheumatologists. CONCLUSION: These findings suggest a general trend toward an AOM uptake that is increasingly limited to a fraction of patients who are at high risk of fractures. In the context of an aging population and declining prescription rates for AOM, these data highlight an increasing treatment gap among women in France with osteoporosis, which is similar to that seen in other European countries and in the USA.

Development and Validation of a Predictive Model of Hypovitaminosis D in General Adult Population: SCOPYD Study.

The worldwide global increase in serum 25-hydroxyvitamin D (25(OH)D) measurements has led some countries to restrict reimbursement for certain clinical situations only. Another approach could consist in providing physicians with screening tools in order to better target blood test prescription. The objective of the SCOPYD study was to identify the best combination of predictors of serum VitD concentration among adults aged 18-70 years. Potential risk factors for VitD deficiency were collected using a comprehensive self-administered questionnaire. A multivariable linear regression was used to build a predictive model of serum 25(OH)D concentration. Among 2488 participants, 1080 (43.4%) had VitD deficiency (<50 nmol/L) and 195 (7.8%) had severe deficiency (<25 nmol/L). The final model included sunlight exposure in the preceding week and during the last holidays, month of blood sampling, age, sex, body mass index, skin phototype, employment, smoking, sport practice, latitude, and VitD supplementation in preceding year. The area under the curve was 0.82 (95% CI (0.78; 0.85)) for severe deficiency. The model predicted severe deficiency with a sensitivity of 77.9% (95% CI (69.1; 85.7)) and a specificity of 68.3% (95% CI (64.8; 71.9)). We identified a set of predictors of severe VitD deficiency that are easy to collect in routine that may help to better target patients for serum 25(OH)D concentration determination.

The Effects of Foot Reflexology on Chemotherapy-Induced Nausea and Vomiting in Patients with Digestive System or Lung Cancer: Protocol for a Randomized Controlled Trial.

BACKGROUND: The side effects of chemotherapy, specifically chemotherapy-induced nausea and vomiting, are a concern for patients. To relieve these side effects, antiemetic drugs are recommended. However, some patients report that these drugs are not sufficiently effective. Moreover, patients with chronic disease, including cancer, are increasingly interested in complementary and alternative medicines, and express the desire for nonpharmacological treatments to be used in hospitals. Foot reflexology is a holistic approach that is reported to significantly reduce the severity of chemotherapy-induced nausea and vomiting in patients with breast cancer. Some of the chemotherapy treatments for patients with lung and digestive system cancer are moderately or highly emetic. OBJECTIVE: The primary objective of this study is to assess the benefits of foot reflexology, together with conventional treatments, on the severity and frequency of chemotherapy-induced nausea and vomiting in patients with lung or digestive system cancer. The secondary objectives to be assessed are quality of life, anxiety, and self-esteem. METHODS: This study is an open-label randomized controlled trial conducted over 22 months (18 months intervention and 4 months follow-up). Eligible participants are patients with a lung or digestive system cancer with an indication for platinum-based chemotherapy. Participants are randomized into two groups: conventional care with foot reflexology and conventional care without foot reflexology. Foot reflexology sessions (30 minutes) are performed on an outpatient or inpatient basis. It was estimated that 40 participants per group will be required. The benefits of foot reflexology will be assessed by comparing the relative change in the severity of nausea and vomiting, as assessed by a visual analogue scale, and the frequency of these side effects between the two groups. The secondary objectives will be assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire; Hospital and Anxiety Depression Scale; and Body Image Questionnaire. RESULTS: This study was approved by the regional ethics committee (Île de France X CPP) on April 3, 2018 (No. ID RCB 2018-A00571-54). Enrollment started in June 2018. Data analysis will be performed during the second quarter of 2020 and results will be published in the last quarter of 2020. CONCLUSIONS: The lack of knowledge regarding the efficacy and safety of foot reflexology limits oncologists to recommend it for this use. This study will provide evidence of the benefits of foot reflexology. If efficacy is confirmed, foot reflexology may be a promising complement to conventional antiemetic drugs. TRIAL REGISTRATION: Clinicaltrials.gov NCT03508180; https://www.clinicaltrials.gov/ct2/show/NCT03508180. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/17232.

Inequalities in Financial Distress, Symptoms, and Quality of Life Among Patients with Advanced Cancer in France and the U.S.

BACKGROUND: Financial distress (FD) is common among patients with advanced cancer. Our purpose was to compare the frequency and intensity of FD and its associations with symptom distress and quality of life (QOL) in these patients in France and the U.S. MATERIALS AND METHODS: In this secondary analysis of two cross-sectional studies, we assessed data on 292 patients who received cancer care at a public hospital or a comprehensive cancer center in France (143 patients) or the U.S. (149 patients). Outpatients and hospitalized patients over 18 years of age with advanced lung or breast or colorectal or prostate cancer were included. Diagnosed cognitive disorder was considered a noninclusion criterion. Advanced cancer included relapse or metastasis or locally advanced cancer or at least a second-line chemotherapy regimen. Patients self-rated FD and assessed symptoms, psychosocial distress, and QOL on validated questionnaires. RESULTS: The average patient age was 59 years, and 144 (49%) were female. FD and high intensity were reported more frequently in U.S. patients than in French (respectively 129 [88%] vs. 74 [52%], p < .001; 100 [98%] vs. 48 [34%], p < .001,). QOL was rated higher by the U.S. patients than by the French (69 [SD, 18] vs. 63 [SD, 18], p = .003). French patients had more psychological symptoms such as anxiety (8 [SD, 4] vs. 6 [SD, 5], p = .008). Associations were found between FD and U.S. residence, FD and single status (0.907, p = .023), and FD and metastasis (1.538, p = .036). In contrast, negative associations were found between FD and older age (-0.052, p = .003) and FD and France residence (-3.376, p = .001). CONCLUSION: Regardless of health care system, FD is frequent in patients with advanced cancer. U.S. patients were more likely to have FD than French patients but reported better QOL. Further research should focus on factors contributing to FD and opportunities for remediation. IMPLICATIONS FOR PRACTICE: Suffering is experienced in any component of the lives of patients with a life-threatening illness. Financial distress (FD) is one of the least explored cancer-related symptoms, and there are limited studies describing its impact on this frail population. This study highlights the high frequency and severity of FD in patients with advanced cancer in the U.S. and France as well as its impact on their physical and emotional symptoms and their quality of life in these different health care systems. It is necessary for all health care providers to explore and evaluate the presence of FD in patients living with life-threatening illnesses.

Heterogeneous estrogen receptor expression in circulating tumor cells suggests diverse mechanisms of fulvestrant resistance.

Fulvestrant is a dose dependent selective estrogen receptor (ER) down-regulator (SERD) used in ER-positive metastatic breast cancer (MBC). Nearly all patients develop resistance. We performed molecular analysis of circulating tumor cells (CTC) to gain insight into fulvestrant resistance. Preclinical studies were performed with cultured breast cancer cells spiked into human blood and analyzed on the CellSearch(®) system. Clinical data are limited to a subset of patients with ER-positive MBC from a previously reported pilot trial whose disease was progressing on fulvestrant (N = 7) or aromatase inhibitors (AIs) (N = 10). CTCs were enumerated and phenotyped for ER and B-cell lymphoma (BCL2) using the CellSearch(®) CXC kit. In preclinical modeling, tamoxifen and AIs resulted in stabilized ER expression, whereas fulvestrant eliminated it. Five of seven patients progressing on fulvestrant had ≥5CTC/7.5 ml WB. Two of these five, treated with 500 mg/month fulvestrant, had no detectable CTC-expression of ER and BCL2 (an ER regulated gene). Three patients had heterogeneous CTC-ER and BCL2 expression indicating incomplete degradation of the ER target by fulvestrant. Two of these patients received 250 mg/month whereas the third patient received 500 mg/month fulvestrant. Her cancer harbored a mutation (Y537S) in the estrogen receptor alpha gene (ESR1). All seven ER positive patients progressing on AIs had heterogeneous CTC-ER expression. These results suggest heterogeneous mechanisms of resistance to fulvestrant, including insufficient dosage, ESR1 mutation, or conversion to dependence on non-ER pathways. CTC enumeration, phenotyping, and genotyping might identify patients who would benefit from fulvestrant dose escalation versus switching to alternative therapies.

Low Osteoporosis Treatment Initiation Rate in Women after Distal Forearm or Proximal Humerus Fracture: A Healthcare Database Nested Cohort Study.

Treatment initiation rates following fragility fractures have often been reported to be low and in recent years numerous programs have been implemented worldwide to increase them. This study aimed at describing osteoporosis (OP) treatment initiation in a representative sample of women who were hospitalized for a distal forearm fracture (DFF) or proximal humerus fracture (PHF) in 2009-2011 in France. The data source was a nationwide sample of 600,000 individuals, extracted from the French National Insurance Healthcare System database. All women aged 50 years and older who were hospitalized for a DFF or PHF between 2009 and 2011 and who had not received any OP treatment in the preceding 12 months were included in a retrospective cohort study. OP treatments initiated during the year following the fracture were analyzed. From 2009 to 2011, 729 women were hospitalized for a DFF or a PHF and 284 were on OP treatment at the time of the fracture occurrence. Among the 445 women who had no prevalent OP treatment, 131 (29.4%) received supplementation treatment only (vitamin D and/or calcium) and 42 (9.4%) received a pharmacologic OP treatment in the year following their fracture. Pharmacological OP treatments included bisphosphonates (n = 21), strontium ranelate (n = 14), hormone replacement therapy (n = 4), or raloxifene (n = 3). General practitioners prescribed 75% of initial OP treatments. Despite the guidelines published in 2006 and the numerous initiatives to promote post-fracture OP treatment, OP treatment initiation rate in women who were hospitalized for a fragility fracture remained low in 2009-2011 in France.

Impact of vitamin D supplementation on health-care use in a 25-hydroxyvitamin D-tested population in France: a population-based descriptive cohort study.

OBJECTIVE: Chronic vitamin D deficiency has been associated in some patients with diffuse musculoskeletal pain. These unspecific symptoms may partly explain why vitamin D deficiency is often diagnosed late. Our aim was to analyse health-care claims after vitamin D supplementation in patients likely to have vitamin D deficiency. DESIGN: Ambulatory health-care claims were compared before and after a vitamin D supplementation prescribed following a 25-hydroxyvitamin D assay. SETTING: Health Insurance Fund (FHIF) database of the Rhône-Alpes area, France. SUBJECTS: Among patients reimbursed for a 25-hydroxyvitamin D assay between 1 December 2008 and 31 January 2009, those supplemented with vitamin D after the assay were matched on the date of assay to patients who did not receive vitamin D. RESULTS: Among the 3023 patients who had a 25-hydroxyvitamin D assay, 935 were consequently supplemented and matched to 935 patients not supplemented. Their median age was 50·0 and 49·5 years, respectively. Patients supplemented decreased their muscle relaxant consumption whereas no change was observed in the reference group, the difference between the two groups was significant (P=0·03). Second and third Pain Relief Ladder prescriptions decreased in both groups but not significantly differently between groups (P=0·58). There was a decrease in prescriptions of biological examination in both groups with no significant difference. CONCLUSIONS: Besides a decrease in muscle relaxant prescriptions in the supplemented group, it was difficult to assess the impact of vitamin D supplementation in patients likely to have vitamin D deficiency. Prospective cohort studies and randomized trials are needed to assess the efficiency of screening and supplementing vitamin D deficiency.

Perineal retraining improves conservative treatment for faecal incontinence: a multicentre randomized study.

BACKGROUND: Anal incontinence is a frequent complaint that profoundly affects quality of life. Our aim was to determine whether perineal retraining gives additional benefits to standard medical treatment. METHODS: Patients with anal incontinence and a Wexner score >4 were randomly assigned to standard conservative treatment (control) or perineal retraining, including biofeedback, in addition to standard treatments (biofeedback). Diaries, self-administered questionnaires and satisfaction scores quantified the benefits. Self-evaluated improvement was the primary outcome measure. A score ≥3 (in an improvement scale from -5 to +5) defined success. RESULTS: Overall, 157 patients were included; 80 in the control group (75% females, mean age 60.1 ± 13.2 years) and 77 in the biofeedback group (79% females, mean age 61.9 ± 10.2 years). After a 4-month follow-up, the success rate was significantly higher in the biofeedback group (57% versus 37%; p<0.021). In the biofeedback group, daily stool frequency, leakage, and faecal urgency significantly decreased, and daily non-urgent perception of stool increased. Conversely, symptomatic scores and quality of life scales did not significantly differ between groups. In a multivariate model, the adjusted odds ratio showed that perineal retraining was significantly associated with a higher chance of self-rated improvement (adjusted Odd Ratio [95%CI]: 2.34 [1.14-4.80]; p=0.021). CONCLUSIONS: Perineal retraining offers a moderate but significant benefit for patients suffering from anal incontinence.

Identification of first proadrenomedullin N-terminal 20 peptide (PAMP) modulator by means of virtual screening and NMR interaction experiments.

PAMP (proadrenomedullin N-terminal 20 peptide) is a regulatory peptide that is detected in a large variety of cell types and exerts important biological activities. PAMP acts as a potent angiogenic factor and decorates microtubules in cells from different origins, controlling tubulin polymerization. A high-throughput docking-based virtual screening was performed, followed by a competitive monoclonal antibody assay on selected compounds, and a detailed (1)H, (15)N NMR spectroscopy study. This procedure has allowed us to describe the first small molecule capable of interacting with PAMP and potentially modulate its biological activity. Molecular modeling methods such as docking and molecular dynamics were carried out to obtain a theoretical model of binding mode. Finally a directed in vivo angiogenesis assay (DIVAA) showed that the small molecule by itself has pro-angiogenic properties.

Higher vitamin D dietary intake is associated with lower risk of alzheimer's disease: a 7-year follow-up.

BACKGROUND: Hypovitaminosis D is associated with cognitive decline among older adults. The relationship between vitamin D intakes and cognitive decline is not well understood. Our objective was to determine whether the dietary intake of vitamin D was an independent predictor of the onset of dementia within 7 years among women aged 75 years and older. METHODS: Four hundred and ninety-eight community-dwelling women (mean, 79.8 ± 3.8 years) free of vitamin D supplements from the EPIDemiology of OSteoporosis Toulouse cohort study were divided into three groups according to the onset of dementia within 7 years (ie, no dementia, Alzheimer's disease [AD], or other dementias). Baseline vitamin D dietary intakes were estimated from self-administered food frequency questionnaire. Age, body mass index, initial cognitive performance, education level, physical activity, sun exposure, disability, number of chronic diseases, hypertension, depression, use of psychoactive drugs, and baseline season were considered as potential confounders. RESULTS: Women who developed AD (n = 70) had lower baseline vitamin D intakes (mean, 50.3 ± 19.3 µg/wk) than nondemented (n = 361; mean intake = 59.0 ± 29.9 µg/wk, p = .027) or those who developed other dementias (n = 67; mean intake = 63.6 ± 38.1 µg/wk, p = .010). There was no difference between other dementias and no dementia (p = .247). Baseline vitamin D dietary intakes were associated with the onset of AD (adjusted odds ratio = 0.99 [95% confidence interval = 0.98-0.99], p = .041) but not with other dementias (p = .071). Being in the highest quintile of vitamin D dietary intakes was associated with a lower risk of AD compared with the lower 4 quintiles combined (adjusted odds ratio = 0.23 [95% confidence interval = 0.08-0.67], p = .007). CONCLUSIONS: Higher vitamin D dietary intake was associated with a lower risk of developing AD among older women.

[Vitamin D in the elderly: 5 points to remember]. / Vitamine D chez la personne âgée : les 5 points à retenir.

Vitamin D is a secosteroid hormone. Vitamin D receptors are present in the majority of body tissues. The manifestations of hypovitaminosis D - linked to dysfunction of target tissues - are various, including osteoporosis, cancer, tuberculosis, hypertension, multiple sclerosis, depression, dementia, sarcopenia, propensity to fall… The serum 25-hydroxyvitamin D threshold value to avoid these adverse health events is around 30 ng/mL. Only 15% of the elderly reach this target concentration. For the remaining 85% with no supplements, the severity of hypovitaminosis D appears to be a biomarker of chronic diseases and of frailty. Conversely, the supplementation for correction of hypovitaminosis D positively impacts bone and non-bone morbidities - such as risks of falls and fractures - and reduces the mortality rate. A daily intake of at least 800-1,000 IU supplemental vitamin D(3) per day is the key.

Fall prevention and vitamin D in the elderly: an overview of the key role of the non-bone effects.

Preventing falls and fall-related fractures in the elderly is an objective yet to be reached. There is increasing evidence that a supplementation of vitamin D and/or of calcium may reduce the fall and fracture rates. A vitamin D-calcium supplement appears to have a high potential due to its simple application and its low cost. However, published studies have shown conflicting results as some studies failed to show any effect, while others reported a significant decrease of falls and fractures. Through a 15-year literature overview, and after a brief reminder on mechanism of falls in older adults, we reported evidences for a vitamin D action on postural adaptations - i.e., muscles and central nervous system - which may explain the decreased fall and bone fracture rates and we underlined the reasons for differences and controversies between published data. Vitamin D supplementation should thus be integrated into primary and secondary fall prevention strategies in older adults.

Vitamin D and ageing: neurological issues.

OBJECTIVE: Vitamin D has been shown to have multiple biological targets mediated by the vitamin D receptor present in many cells. Specific actions on the central nervous system (CNS) have been described. The objective of this review was to describe the relationship between vitamin D and the nervous system throughout the different stages of life. METHODS: A bibliographical search was performed in the MedLine and Cochrane library databases. The keywords used were: 'vitamin D' and 'nervous system' and/or 'central nervous system' and/or 'nervous system diseases' and/or 'psychological tests' and/or 'neuropsychological tests' and/or 'mental disorders'. The search period ranged from 01/01/1988 to 31/10/2009. Two hundred and ninety-five abstracts were first identified after screening. A final selection of 127 articles was used for the purpose of this review. RESULTS: The studies published over the past 20 years provide an increasing number of arguments in favor of a life-long role of vitamin D on the nervous system as a whole, and in particular on the CNS. During cerebral development, vitamin D may act like a neurosteroid hormone in the areas of neurotransmission, neuroprotection, and neuroimmunomodulation. Moreover, vitamin D deficiency has been associated with neurological and psychiatric disorders. In older adults, hypovitaminosis D has been associated with neuromuscular disorders, dementia, and Parkinson's disease. Thus, vitamin D supplementation might have a protective effect against these neurological disorders. CONCLUSIONS: Vitamin D has been associated with many neurological functions and its deficiency with dysfunction. Low serum 25-hydroxyvitamin D concentrations can potentially be reversed. This simple and low-cost correction might contribute to the primo-secondary prevention of various neuropsychiatric disorders.

The impact of breast reconstruction on the delivery of chemotherapy.

BACKGROUND: : The purpose of this study was to evaluate the impact of postmastectomy breast reconstruction on the timing of chemotherapy. METHODS: : The authors included stage I-III breast cancer patients from 8 National Comprehensive Cancer Network institutions for whom guidelines recommended chemotherapy. Surgery type was categorized as breast-conserving surgery (BCS), mastectomy alone, mastectomy with immediate reconstruction (M + IR), or mastectomy with delayed reconstruction (M + DR). A Cox regression analysis was used to assess the association between surgery type and timing of chemotherapy initiation. RESULTS: : Of the 3643 patients, only 5.1% received it > or =8 weeks from surgery. In the multivariate analysis, higher stage, Caucasian and Hispanic race/ethnicity, lower body mass index, and absence of comorbid conditions were all significantly associated with earlier time to chemotherapy. There was also significant interaction among age, surgery, and chemotherapy delivery. Among women <60, time to chemotherapy was shorter for all surgery types compared with M + IR (statistical significant for all surgery types in the youngest age group and for BCS in women 40 to <50 years old). In contrast, among women > or =60, time to chemotherapy was shorter among women receiving M + IR or M + DR compared with those undergoing BCS or mastectomy alone, a difference that was statistically significant for the M + IR versus BCS comparison. CONCLUSIONS: : Immediate postmastectomy breast reconstruction does not appear to lead to omission of chemotherapy, but it is associated with a modest, but statistically significant, delay in initiating treatment. For most, it is unlikely that this delay has any clinical significance. Cancer 2010. (c) 2010 American Cancer Society.

Predictors and temporal trends of adjuvant aromatase inhibitor use in breast cancer.

After the first report of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial, adjuvant aromatase inhibitor use increased rapidly among National Comprehensive Cancer Network member institutions. Increased aromatase inhibitor use was associated with older age, vascular disease, overexpression of human epidermal growth factor receptor 2 (HER2), or more advanced stage, and substantial variation was seen among institutions. This article examines adjuvant endocrine therapy in postmenopausal women after the first report of the trial, identifies temporal relationships in aromatase inhibitor use, and examines characteristics associated with choice of endocrine therapy among 4044 postmenopausal patients with hormone receptor-positive nonmetastatic breast cancer presenting from July 1997 to December 2004. Multivariable logistic regression analysis examined temporal associations and characteristics associated with aromatase inhibitor use. Time-trend analysis showed increased aromatase inhibitor and decreased tamoxifen use after release of ATAC results (P < .0001). In multivariable regression analysis, institution (P <. 0001), vascular disease (P <. 0001), age (P = .0002), stage (P = .0002), and HER2 status (P = .0009) independently predicted aromatase inhibitor use. Institutional rates of use ranged from 15% to 66%. Adjuvant aromatase inhibitor use increased after the first report of ATAC, with this increase associated with older age, vascular disease, overexpression of HER2, or more advanced stage. Substantial variation was seen among institutions.