Calciotropic hormones and the risk of hip and nonspine fractures in older adults: the Health ABC Study

The effects of vitamin D and parathyroid hormone (PTH) levels on incident fracture remain uncertain. To test the hypothesis that increasing serum 25‐hydroxyvitamin D [25(OH)D] and decreasing PTH levels are associated with decreased risk of hip and any nonspine fracture, we conducted a prospective cohort study among 2614 community‐dwelling white and black participants, aged ≥70 years, from the Health, Aging and Body Composition (Health ABC) Study. Serum and plasma samples were drawn at year 2, which formed the baseline for this analysis. Serum 25(OH)D and intact PTH (1‐84) were measured using radioimmunoassay with DiaSorin reagents and EDTA plasma with a two‐site immunoradiometric assay kit, respectively. Incident fractures (hip and any nonspine) were assessed after year 2, every 6 months, by self‐report and validated by radiology reports. The median (interquartile range) follow‐up times for hip and any nonspine fractures were 6.4 (6.1–6.5) and 6.4 (5.5–6.5) years, respectively. Cox proportional hazards regression was used to estimate the hazard ratios (HR) with 95% confidence intervals (CI) for fracture. There were 84 hip and 247 nonspine fractures that occurred over the follow‐up period. The multivariable adjusted HRs (95% CIs) of hip fracture for participants in the lowest (≤17.78 ng/mL), second (17.79 to 24.36 ng/mL), and third quartiles (24.37 to 31.94 ng/mL) of 25(OH)D were 1.92 (0.97 to 3.83), 0.75 (0.32 to 1.72) and 1.86 (1.00 to 3.45), respectively, compared with participants in the highest 25(OH)D quartile (>31.94 ng/mL) (p trend = 0.217). Additional adjustment for IL‐6 (p = 0.107), PTH (p = 0.124), and hip areal bone mineral density (p = 0.137) attenuated HRs of hip fracture in the lowest quartile by 16.3%, 17.4%, and 26.1%, respectively. There was no evidence of an association between 25(OH)D and any nonspine fractures, or between PTH and hip or any nonspine fractures. We found limited evidence to support an association between calciotropic hormones and hip and nonspine fractures in older men and women. © 2012 American Society for Bone and Mineral Research.     

To what extent does IQ 'explain' socio-economic variations in function?

Background  

The aims of this study were to examine the extent to which higher intellectual abilities protect higher socio-economic groups from functional decline and to examine whether the contribution of intellectual abilities is independent of childhood deprivation and low birth weight and other socio-economic and developmental factors in early life.     

Defining Cure for Esophageal Cancer: Analysis of Actual 5-Year Survivors Following Esophagectomy

Background

Esophagectomy is the mainstay of curative treatment for localized esophageal cancer. However, what constitutes cure is not well defined. This study was undertaken to characterize actual 5-year survivors following esophagectomy and to determine prognostic factors for disease-specific survival (DSS) from 60 months.

Materials and Methods

Between 1987 and 2004, 398 consecutive patients underwent esophagectomy and had potential for 5 years follow-up. Clinicopathological factors associated with DSS from 5 years onward were analyzed.

Results

Median DSS was 25 months. Neoadjuvant therapy was administered to 159 of 398 (40%). There were 114 of 398 (29%) actual 5-year survivors. On multivariate analysis, 5-year survivors were significantly more likely to have lower T classification, N classification, and R0 resections compared with patients who died less than 5 years after surgery. There were 66 of 398 patients (17%) with positive margins, and 6 of these were 5-year survivors. Of the 114 5-year survivors, 17 (15%) subsequently died of esophageal cancer. Prognostic factors for DSS after surviving 5 years were age and T classification for patients treated with neoadjuvant therapy and surgery alone, respectively. Powerful prognostic factors from time of treatment, including nodal status, were no longer prognostic factors after surviving to 5 years.

Conclusions

No single clinicopathological variable negated survival to 5 years. Prognostication once surviving 5 years is difficult. The majority of 5-year survivors can be considered cured of esophageal cancer.     

“I’d Know That My Child Was Out There”: Egg Donation,the Institutionalized “Ideal” Family,and Health Care Decision Making

This study investigates how young women of egg-donating age perceive egg donation. Using institutional theory, this study demonstrates how participants frame a health care decision, such as egg donation, utilizing familial ideals. Results revealed that women expressed the importance of ownership over their genetic material and that familial ideals encourage an ideal way to create a family, which egg donation only fits as a last resort. Results show that familial ideals reach past the institution of family into broader decision making, such as that of health care. Further, results show that as more families are constructed through assisted reproductive technologies, attempts should be made to gradually alter the familial ideal to encompass novel medical technologies such as egg donation.     

The role of previously unmeasured organic acids in the pathogenesis of severe malaria

IntroductionSevere falciparum malaria is commonly complicated by metabolic acidosis. Together with lactic acid (LA), other previously unmeasured acids have been implicated in the pathogenesis of falciparum malaria.MethodsIn this prospective study, we characterised organic acids in adults with severe falciparum malaria in India and Bangladesh. Liquid chromatography-mass spectrometry was used to measure organic acids in plasma and urine. Patients were followed until recovery or death.ResultsPatients with severe malaria (n=138), uncomplicated malaria (n=102), sepsis (n=32) and febrile encephalopathy (n=35) were included. Strong ion gap (mean±SD) was elevated in severe malaria (8.2 mEq/L±4.5) and severe sepsis (8.6 mEq/L±7.7) compared with uncomplicated malaria (6.0 mEq/L±5.1) and encephalopathy (6.6 mEq/L±4.7). Compared with uncomplicated malaria, severe malaria was characterised by elevated plasma LA, hydroxyphenyllactic acid (HPLA), α-hydroxybutyric acid and β-hydroxybutyric acid (all P<0.05). In urine, concentrations of methylmalonic, ethylmalonic and α-ketoglutaric acids were also elevated. Multivariate logistic regression showed that plasma HPLA was a strong independent predictor of death (odds ratio [OR] 3.5, 95 % confidence interval [CI] 1.6–7.5, P=0.001), comparable to LA (OR 3.5, 95 % CI 1.5–7.8, P=0.003) (combined area under the receiver operating characteristic curve 0.81).ConclusionsNewly identified acids, in addition to LA, are elevated in patients with severe malaria and are highly predictive of fatal outcome. Further characterisation of their sources and metabolic pathways is now needed.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-015-1023-5) contains supplementary material, which is available to authorized users.     

Genetic factors affecting the consistency and magnitude of changes in plasma cholesterol in response to dietary challenge

We examined the role of common genetic variation in determining the consistency and magnitude of change in plasma total cholesterol (TC) levels in response to two separate changes from a high-saturated (SFA) to a low-saturated/high-polyunsaturated-fat (PUFA) diet, in a group of free-living healthy men and women. Consistent responders were defined as those whose mean difference in the change in TC was within one SD of the mean for all participants, and the remainder were defined as variable responders. DNA was obtained from 55 individuals and genotype determined at the apolipoprotein (apo) B locus (signal peptide, SP), apoCIII (C1100-T) and lipoprotein lipase (LPL) gene loci (HindIII). In the 38 consistent responders, the apoBSP24 allele was significantly more common than in the 17 individuals with a variable response (0.29 vs. 0.12; p < 0.05). No other polymorphism showed a significant frequency difference between groups. In the group as a whole, the correlation between the change in TC level in response to the first and second dietary change was 0.28 (p = 0.05), but those with one or more apoB SP24 alleles and those with the apoCIII genotype CC had a significantly higher correlation than those with other genotypes (0.46 (p = 0.05) vs. 0.12 (NS) and 0.31 (p = 0.05) vs. 0.02 (NS), respectively). In the group as a whole, mean response left TC 10% higher on the SFA than on the PUFA diet, and neither apoB nor apoCIII genotypes affected the magnitude of this response. However, individuals with the LPL HindIII genotype H+ H+ had a significantly smaller change in mean TC in response to diet than those with one or more H- allele (9.3% vs. 14.4%; p = 0.03). Thus variation at the apoB and apoCIII loci affects the consistency of response to change in dietary fat content, while variation at the LPL gene locus affects magnitude of response.