Do acute elevations of serum creatinine in primary care engender an increased mortality risk?

Background: The significant impact Acute Kidney Injury (AKI) has on patient morbidity and mortality emphasizes the need for early recognition and effective treatment. AKI presenting to or occurring during hospitalisation has been widely studied but little is known about the incidence and outcomes of patients experiencing acute elevations in serum creatinine in the primary care setting where people are not subsequently admitted to hospital. The aim of this study was to define this incidence and explore its impact on mortality. Methods: The study cohort was identified by using hospital data bases over a six month period. Inclusion criteria: People with a serum creatinine request during the study period, 18 or over and not on renal replacement therapy. The patients were stratified by a rise in serum creatinine corresponding to the Acute Kidney Injury Network (AKIN) criteria for comparison purposes. Descriptive and survival data were then analysed. Ethical approval was granted from National Research Ethics Service (NRES) Committee South East Coast and from the National Information Governance Board. Results: The total study population was 61,432. 57,300 subjects with ‘no AKI’, mean age 64.The number (mean age) of acute serum creatinine rises overall were, ‘AKI 1’ 3,798 (72), ‘AKI 2’ 232 (73), and ‘AKI 3’ 102 (68) which equates to an overall incidence of 14,192 pmp/year (adult). Unadjusted 30 day survival was 99.9% in subjects with ‘no AKI’, compared to 98.6%, 90.1% and 82.3% in those with ‘AKI 1’, ‘AKI 2’ and ‘AKI 3’ respectively. After multivariable analysis adjusting for age, gender, baseline kidney function and co-morbidity the odds ratio of 30 day mortality was 5.3 (95% CI 3.6, 7.7), 36.8 (95% CI 21.6, 62.7) and 123 (95% CI 64.8, 235) respectively, compared to those without acute serum creatinine rises as defined. Conclusions: People who develop acute elevations of serum creatinine in primary care without being admitted to hospital have significantly worse outcomes than those with stable kidney function

Health Measurement Scales: Methodological Issues

Health scales or indices are composite tools aiming to measure a variety of clinical conditions, behaviors, attitudes and beliefs that are difficult to be measured quantitatively. During the past years, these tools have been extensively used in cardiovascular disease prevention. The already proposed scales have shown good ability in assessing individual characteristics, but had moderate predictive ability in relation to the development of chronic diseases and various other health outcomes. In this review, methodological issues for the development of health scales are discussed. Specifically, the selection of the appropriate number of components, the selection of classes for each component, the use of weights of scale components and the role of intra- or inter-correlation between components are discussed. Based on the current literature the use of components with large number of classes, as well as the use of specific weights for each scale component and the low-to-moderate inter-correlation rate between the components, is suggested in order to increase the diagnostic accuracy of the tool

Vitamin D and breast cancer: interpreting current evidence

Preclinical investigations and selected clinical observational studies support an association between higher vitamin D intake and 25-hydroxyvitamin D levels with lower breast cancer risk. However, the recently updated report from the Institute of Medicine concluded that, for cancer and vitamin D, the evidence was 'inconsistent and insufficient to inform nutritional requirements'. Against this background, reports examining vitamin D intake, 25-hydroxyvitamin D levels and breast cancer incidence and outcome were reviewed. Current evidence supports the pursuit of several research questions but not routine 25-hydroxyvitamin D monitoring and vitamin D supplementation to reduce breast cancer incidence or improve breast cancer outcome

Pretreatment Serum Concentrations of 25-Hydroxyvitamin D and Breast Cancer Prognostic Characteristics: A Case-Control and a Case-Series Study

Results from epidemiologic studies on the relationship between vitamin D and breast cancer risk are inconclusive. It is possible that vitamin D may be effective in reducing risk only of specific subtypes due to disease heterogeneity.In case-control and case-series analyses, we examined serum concentrations of 25-hydroxyvitamin D (25OHD) in relation to breast cancer prognostic characteristics, including histologic grade, estrogen receptor (ER), and molecular subtypes defined by ER, progesterone receptor (PR) and HER2, among 579 women with incident breast cancer and 574 controls matched on age and time of blood draw enrolled in the Roswell Park Cancer Institute from 2003 to 2008. We found that breast cancer cases had significantly lower 25OHD concentrations than controls (adjusted mean, 22.8 versus 26.2 ng/mL, p<0.001). Among premenopausal women, 25OHD concentrations were lower in those with high- versus low-grade tumors, and ER negative versus ER positive tumors (p≤0.03). Levels were lowest among women with triple-negative cancer (17.5 ng/mL), significantly different from those with luminal A cancer (24.5 ng/mL, p = 0.002). In case-control analyses, premenopausal women with 25OHD concentrations above the median had significantly lower odds of having triple-negative cancer (OR = 0.21, 95% CI = 0.08-0.53) than those with levels below the median; and every 10 ng/mL increase in serum 25OHD concentrations was associated with a 64% lower odds of having triple-negative cancer (OR = 0.36, 95% CI = 0.22-0.56). The differential associations by tumor subtypes among premenopausal women were confirmed in case-series analyses.In our analyses, higher serum levels of 25OHD were associated with reduced risk of breast cancer, with associations strongest for high grade, ER negative or triple negative cancers in premenopausal women. With further confirmation in large prospective studies, these findings could warrant vitamin D supplementation for reducing breast cancer risk, particularly those with poor prognostic characteristics among premenopausal women

Female heterozygotes for the hypomorphic R40H mutation can have ornithine transcarbamylase deficiency and present in early adolescence: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Ornithine transcarbamylase deficiency is the most common hereditary urea cycle defect. It is inherited in an X-linked manner and classically presents in neonates with encephalopathy and hyperammonemia in males. Females and males with hypomorphic mutations present later, sometimes in adulthood, with episodes that are frequently fatal.</p> <p>Case presentation</p> <p>A 13-year-old Caucasian girl presented with progressive encephalopathy, hyperammonemic coma and lactic acidosis. She had a history of intermittent regular episodes of nausea and vomiting from seven years of age, previously diagnosed as abdominal migraines. At presentation she was hyperammonemic (ammonia 477 μmol/L) with no other biochemical indicators of hepatic dysfunction or damage and had grossly elevated urinary orotate (orotate/creatinine ratio 1.866 μmol/mmol creatinine, reference range <500 μmol/mmol creatinine) highly suggestive of ornithine transcarbamylase deficiency. She was treated with intravenous sodium benzoate and arginine and made a rapid full recovery. She was discharged on a protein-restricted diet. She has not required ongoing treatment with arginine, and baseline ammonia and serum amino acid concentrations are within normal ranges. She has had one further episode of hyperammonemia associated with intercurrent infection after one year of follow up. An R40H (c.119G>A) mutation was identified in the ornithine transcarbamylase gene (<it>OTC</it>) in our patient confirming the first symptomatic female shown heterozygous for the R40H mutation. A review of the literature and correspondence with authors of patients with the R40H mutation identified one other symptomatic female patient who died of hyperammonemic coma in her late teens.</p> <p>Conclusions</p> <p>This report expands the clinical spectrum of presentation of ornithine transcarbamylase deficiency to female heterozygotes for the hypomorphic R40H <it>OTC </it>mutation. Although this mutation is usually associated with a mild phenotype, females with this mutation can present with acute decompensation, which can be fatal. Ornithine transcarbamylase deficiency should be considered in the differential diagnosis of unexplained acute confusion, even without a suggestive family history.</p

Vitamin D receptor ChIP-seq in primary CD4+ cells: relationship to serum 25-hydroxyvitamin D levels and autoimmune disease

PMCID: PMC3710212This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Sediment-laden sea ice in southern Hudson Bay: Entrainment, transport, and biogeochemical implications

During a research expedition in Hudson Bay in June 2018, vast areas of thick (>10 m), deformed sediment-laden sea ice were encountered unexpectedly in southern Hudson Bay and presented difficult navigation conditions for the Canadian Coast Guard Ship Amundsen. An aerial survey of one of these floes revealed a maximum ridge height of 4.6 m and an average freeboard of 2.2 m, which corresponds to an estimated total thickness of 18 m, far greater than expected within a seasonal ice cover. Samples of the upper portion of the ice floe revealed that it was isothermal and fresh in areas with sediment present on the surface. Fine-grained sediment and larger rocks were visible on the ice surface, while a pronounced sediment band was observed in an ice core. Initial speculation was that this ice had formed in the highly dynamic Nelson River estuary from freshwater, but δ^{18}O isotopic analysis revealed a marine origin. In southern Hudson Bay, significant tidal forcing promotes both sediment resuspension and new ice formation within a flaw lead, which we speculate promotes the formation of this sediment-laden sea ice. Historic satellite imagery shows that sediment-laden sea ice is typical of southern Hudson Bay, varying in areal extent from 47 to 118 km2 during June. Based on an average sediment particle concentration of 0.1 mg mL^{–1} in sea ice, an areal extent of 51,924 km2 in June 2018, and an estimated regional end-of-winter ice thickness of 1.5 m, we conservatively estimated that a total sediment load of 7.8 × 106 t, or 150 t km^{–2}, was entrained within sea ice in southern Hudson Bay during winter 2018. As sediments can alter carbon concentrations and light transmission within sea ice, these first observations of this ice type in Hudson Bay imply biogeochemical impacts for the marine system

Dietary intakes of flavan-3-ols and cardiovascular health: a field synopsis using evidence mapping of randomized trials and prospective cohort studies

Background: There is considerable interest in the impact of increased flavan-3-ol intake on cardiovascular disease (CVD) and diabetes outcomes. Through evidence mapping, we determined the extent of the evidence base to initiate a future systematic review investigating the impact of flavan-3-ol intake on CVD and diabetes outcomes. Methods: We developed a research protocol, convened a technical expert panel (TEP) to refine the specific research questions, conducted a systematic search in multiple databases, double-screened abstracts and full-text articles, performed data extractions, and synthesized the data. We focused on randomized controlled trials (RCTs) and prospective cohort studies which assessed intakes of flavan-3-ol from foods, beverages, and supplement/extract sources on biomarkers and clinical outcomes of CVD and diabetes. Results: Of 257 eligible articles, 223 and 34 publications contributed to 226 RCTs and 39 prospective cohort studies, respectively. In RCTs, the most frequently studied interventions were cocoa-based products (23.2%); berries (16.1%); tea in the form of green tea (13.9%), black tea (7.2%), or unspecified tea (3.6%); and red wine (11.2%). Mean total flavan-3-ol intake was highest in the cocoa-based trials (618.7 mg/day) and lowest in the interventions feeding red wine (123.7 mg/day). The most frequently reported outcomes were intermediate biomarkers including serum lipid levels (63.4%), blood glucose (50.9%), blood pressure (50.8%), flow-mediated dilation (21.9%), and high-sensitivity C-reactive protein (21.9%). The included 34 prospective cohort studies predominantly examined exposures to flavan-3-ols (26%), cocoa-based products (23.2%), berries (16.1%), and green tea (13.9%) and CVD incidence and mortality. Conclusion: Through a systematic, evidence-based approach, evidence mapping on flavan-3-ol intake and CVD outcomes demonstrated sufficient data relating to flavan-3ol intake and biomarkers and clinical outcomes of CVD and diabetes. The current evidence base highlights the distribution of available data which both support the development of a future systematic review and identified the research need for future long-term RCTs

A population-based cohort study on sun habits and endometrial cancer

Background:No large cohort study has examined the risk of endometrial cancer in relation to sun exposure.Methods:A population-based cohort study of 29 508 women who answered a questionnaire in 1990-92, of whom 24 098 responded to a follow-up enquiry in 2000-02. They were followed for an average of 15.5 years.Results:Among the 17 822 postmenopausal women included, 166 cases of endometrial cancer were diagnosed. We used a multivariate Cox regression analysis adjusting for age and other selected demographic variables to determine the risk of endometrial cancer. Women using sun beds >3 times per year reduced their hazard risk (HR) by 40% (0.6, 95% confidence interval (CI) 0.4-0.9) or by 50% when adjusting for body mass index or physical activity (HR 0.5, 95% CI 0.3-0.9), and those women who were sunbathing during summer reduced their risk by 20% (HR 0.8 95% CI 0.5-1.5) compared with women who did not expose themselves to the sun or to artificial sun (i.e., sun beds).Conclusion:Exposure to artificial sun by the use of sun beds >3 times per year was associated with a 40% reduction in the risk of endometrial cancer, probably by improving the vitamin D levels during winter.British Journal of Cancer advance online publication, 23 June 2009; doi:10.1038/sj.bjc.6605149 www.bjcancer.com