Donation frequency of blood donors participating in a prospective cohort study of iron status.

BACKGROUND: Blood centers are interested in understanding determinants of frequent blood donation. We hypothesized that participation in uncompensated research could result in higher donation rates. STUDY DESIGN AND METHODS: Donation rates for 2425 subjects from six US blood centers enrolled in the Retrovirus Epidemiology Donor Study-II Donor Iron Status Evaluation Study were compared to those of nonenrolled donors (n = 202,383). Over 15 months, we compared mean donation rates and adjusted rate ratios (RRs) between enrolled and nonenrolled for three subgroups, first-time, reactivated, and frequent donors, and donation rates before and after the study enrollment period for frequent donors only. RESULTS: Enrolled donors had higher 15-month mean donation rates than nonenrolled donors (first-time, 1.21 [RR = 1.91]; reactivated, 1.68 [RR = 1.83]; frequent, 3.40 [RR = 1.12]). However, frequent donors donated at approximately the same rate after enrollment as they did before enrollment in the study (3.62 per 15 months [RR = 1.12]). CONCLUSION: Donors enrolled in the study donated at a higher rate than nonenrolled donors, but frequent donors remained consistent in their donation frequency both before and after enrollment. Although increased donation rates could have been causally related to study enrollment, we cannot rule out an enrollment bias whereby more committed donors were more likely to enroll in the study.

Reversal of skeletal effects of endocrine treatments in the Intergroup Exemestane Study.

The adjuvant use of aromatase inhibitors in breast cancer is associated with adverse effects on bone health. We previously reported a decline in bone mineral density (BMD) following the switch from tamoxifen to exemestane in the Intergroup Exemestane Study (IES). Here we report effects of endocrine treatment withdrawal on BMD, bone turnover markers (BTM) and fracture rates. 4,724 patients took part in IES, and 206 patients were included in a bone sub-study. BMD and BTM were assessed pre-randomization, during and after the end of treatment (EOT). To evaluate treatment withdrawal effects, 12- and 24-month post EOT BMD results are available for 122 and 126 patients, respectively. Similar patient numbers had BTM measured post EOT. Following treatment withdrawal, the differences in BMD observed between the two endocrine strategies were partially reversed. At 24 months from EOT, spine BMD increased by 1.53% (95%CI 0.63-2.43; p = 0.001) after stopping exemestane and fell by 1.93% (95%CI -2.91 to 0.95; p = 0.0002) following tamoxifen withdrawal. A similar pattern of changes was observed at the hip. At 2 years post EOT, BMD changes from baseline were similar with both treatment strategies. Corresponding inverse changes in BTM were seen, with an increase following tamoxifen withdrawal and a reduction after exemestane. A higher number of fractures occurred during exemestane treatment, but fracture rates were similar after treatment withdrawal. With the switch strategy used in IES, the on treatment adverse bone effects of exemestane are reversed. Ongoing monitoring of BMD is therefore not routinely required.

Effect of pamidronate on bone loss after kidney transplantation: a randomized trial.

BACKGROUND: Kidney transplantation is associated with an increased risk of bone fracture and rapid loss of bone mineral density after kidney transplantation. STUDY DESIGN: Randomized controlled trial. SETTING & PARTICIPANTS: Patients were randomly assigned to treatment (n = 46) or control (no treatment; n = 47) groups. Patients were stratified according to parathyroid hormone level and sex. Those with parathyroid hormone level less than 150 pg/mL were excluded. INTERVENTION: The treatment and control groups received pamidronate, 1 mg/kg, perioperatively and then at 1, 4, 8, and 12 months or no treatment, respectively. All received calcium (500 mg) and vitamin D (400 units) daily. Immunosuppression was cyclosporine and prednisolone, with no difference in dosing between the 2 groups. OUTCOMES & MEASUREMENTS: Bone mineral density was evaluated by means of dual-energy x-ray absorptiometry of the lumbar spine and hip at baseline and 3, 6, 12, and 24 months, with the primary end point at 1 year of percentage of change in bone mineral density from baseline. Clinical fractures were recorded and also evaluated by means of spinal radiographs at baseline and 1 and 2 years. RESULTS: Pamidronate protected bone mineral density at the lumbar spine; bone mineral density increased by 2.1% in the treatment group and decreased by 5.7% in the control group at 12 months (P = 0.001). Protection was also seen in Ward's area of the hip (P = 0.002) and the total hip (P = 0.004). There was no difference in femoral neck bone mineral density loss between the 2 groups. Fracture rates in the treatment and control groups were 3.3% and 6.4% per annum, respectively. LIMITATIONS: This study was not powered to detect differences in fracture rates. CONCLUSION: Pamidronate protects against posttransplantation bone loss at the lumbar spine and Ward's area of the hip.

The effects of Vitamin D metabolites on expression of genes for calcium transporters in human duodenum.

The role of Vitamin D in the regulation of calcium absorption in the intestine is well recognized but the mechanisms of the effects on human genes are surprisingly poorly understood. We have determined the expression of transcripts of the apical membrane calcium transporter TRPV6, the cytoplasmic calcium binding protein calbindin-D9k, the basolateral plasma membrane Ca(2+)-ATPase (PMCA1) and the Vitamin D receptor (VDR) in normal endoscopic duodenal mucosal biopsies using quantitative real-time RT-PCR and related baseline expression to Vitamin D metabolites. TRPV6 transcript levels have been shown to be significantly correlated with serum 1,25(OH)(2)D levels in men, but not overall in women, where negative effects of age predominate. TRPV6 and VDR expression were significantly related in both men and women, but were significantly lower in older women. Associations with bone mineral density and fractional calcium absorption were also studied. In a second series of subjects, duodenal biopsies were incubated in organ culture for 6h with Vitamin D metabolites. TRPV6 expression was significantly increased by 1,25(OH)(2)D(3) (10(-9)mol/l) as was PMCA1 to a much smaller extent. TRPV6 expression also increased with 25(OH)D(3). CYP27B1 expression was found in all samples, and CYP24 transcripts were detected after incubation with 1,25(OH)(2)D(3) or 25(OH)D(3).

Disaster Impact on Impoverished Area of US: An Inter-Professional Mixed Method Study.

Introduction In the foothills of the Cumberland Mountains, in central Appalachia (a region that spans 13 states in the US), sits an economically distressed and rural community of the United States. Once a thriving coal-mining area, this region now is reported as one of the hardest places to live in the US. Southeastern Kentucky, located in a remote, rocky, mountainous area surrounded by rivers and valleys and prone to flooding, experienced a major flood in Spring 2013 causing significant damage to homes and critical infrastructure. Purpose Aims of the study were to: (1) identify and better understand the contextual variables compounding the impact of a disaster event that occurred in Spring 2013; (2) identify ways participants managed antecedent circumstances, risk, and protective factors to cope with disaster up to 12 months post-event; and (3) further determine implications for community-focused interventions that may enhance recovery for vulnerable populations to promote greater outcomes of adaptation, wellness, and readiness. METHODS: Using an ethnographic mixed-methods approach, an inter-collaborative team conducted face-to-face interviews with (N=12) Appalachian residents about their disaster experience, documented observations and visual assessment of need on an observation tool, and used photography depicting structural and environmental conditions. A Health and Emergency Preparedness Assessment Survey Tool was used to collect demographic, health, housing, environment, and disaster readiness assessment data. Community stakeholders facilitated purposeful sampling through coordination of scheduled home visits. RESULTS: Triangulation of all data sources provided evidence that the community had unique coping strategies related to faith and spirituality, cultural values and heritage, and social support to manage antecedent circumstances, risk, and protective factors during times of adversity that, in turn, enhanced resilience up to 12 months post-disaster. The community was found to have an innate capacity to persevere and utilize resources to manage and transcend adversity and restore equilibrium, which reflected components of resilience that deserve greater recognition and appreciation. CONCLUSION: Resilience is a foundational concept for disaster science. A model of resilience for the rural Appalachia community was developed to visually depict the encompassing element of community-based interventions that may enhance coping strategies, mitigate risk factors, integrate protective factors, and strengthen access. Community-based interventions are recommended to strengthen resilience, yielding improved outcomes of adaptation, health and wellness, and disaster readiness. Banks LH , Davenport LA , Hayes MH , McArthur MA , Toro SN , King CE , Vazirani HM . Disaster impact on impoverished area of US: an inter-professional mixed method study. Prehosp Disaster Med. 2016;31(6):583-592.

Skeletal effects of exemestane on bone-mineral density, bone biomarkers, and fracture incidence in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES): a randomised controlled study.

BACKGROUND: Tamoxifen preserves bone in postmenopausal women, but non-steroidal aromatase inhibitors accelerate bone loss and increase fracture risk. We aimed to study the effect on bone health in a subgroup of women included in the Intergroup Exemestane Study (IES), a large randomised trial that compared the switch to the steroidal aromatase inhibitor exemestane with continuation of tamoxifen in the adjuvant treatment of postmenopausal breast cancer. METHODS: Results were analysed from 206 evaluable patients from the IES, in which postmenopausal women with histologically confirmed and completely resected unilateral breast cancer (that was oestrogen-receptor positive or of unknown status), who were disease-free after 2-3 years of treatment with tamoxifen were randomised to continue oral tamoxifen 20 mg/day or switch to oral exemestane 25 mg/day to complete a total of 5 years of adjuvant endocrine therapy. The primary endpoint was change in bone-mineral density (BMD) assessed by dual energy X-ray absorptiometry. Changes in biochemical markers of bone turnover were also analysed in this substudy, and the incidence of fractures in the entire study reported. The IES is registered on the Current Controlled Trials website . FINDINGS: Within 6 months of switching to exemestane, BMD was lowered by 0.051 g/cm(3) (2.7%; 95% CI 2.0-3.4; p<0.0001) at the lumbar spine and 0.025 g/cm(3) (1.4%; 0.8-1.9; p<0.0001) at the hip compared with baseline. BMD decreases were only 1.0% (0.4-1.7; p=0.002) and 0.8% (0.3-1.4; p=0.003) in year 2 at the lumbar spine and hip, respectively. No patient with BMD in the normal range at trial entry developed osteoporosis. Bone resorption and formation markers increased at all time points in women receiving exemestane (p<0.001). With a median follow-up in all IES participants (n=4274) of 58 months, 162 (7%) and 115 (5%) patients in the exemestane and tamoxifen groups, respectively, had fractures (odds ratio 1.45 [1.13-1.87]; p=0.003). INTERPRETATION: These results indicate that the increase in survival shown previously with the IES switch strategy is achieved at the expense of some detriment to skeletal health, so the risk-benefit ratio to women needs to be individually assessed.