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Holocene evolution of the western Louisiana-Texas Coast, USA : response to sea-level rise and climate change
\"The Western Louisiana and Texas coast is vulnerable to sea-level rise due to low gradients, high subsidence, and depleted sediment supply. This Memoir describes the response of coastal environments to variable rates of sea-level rise and sediment supply during Holocene to modern time. This volume is a wake-up call about the potential magnitude of coastal change over decadal to centennial time scales\"-- Provided by publisher.
Book
Oral Bisphosphonate use Reduces Cardiovascular Events in a Cohort of Danish Patients Referred for Bone Mineral Density
Abstract
Context
The cardiovascular (CV) safety of oral bisphosphonates (oBPs) is uncertain.
Objective
Determine the risk of CV events in oBP users referred for bone mineral density (BMD) testing compared with matched controls.
Design
Cohort study.
Setting
Danish national prescription registry enriched with local hospital data from Odense.
Participants
Individuals aged ≥45 years referred for BMD testing.
Exposure
oBP.
Outcomes
Hospitalization for any CV event. Secondary study outcomes were specific CV events. Negative (inguinal hernia surgery and ingrown toenail) and positive (fragility fracture) control outcomes assessed systemic bias. Cox proportional hazards models were fitted to estimate hazard ratio (HR) and 95% confidence intervals.
Results
There were 2565 oBP users (82.6% women) and 4568 (82.3% women) propensity score–matched controls. Alendronate accounted for 96% of oBP prescription. A total of 406 (15.8%) CV events occurred in oBP users (rate = 73.48 [66.67-80.98]); rate = events divided by person-time; and 837 (18.3%) events in controls (rate = 104.73 [97.87-112.07]) with an adjusted HR of 0.68 (95% CI 0.60-0.77). Additional adjustment for BMD did not attenuate estimates (HR 0.67; 95% CI 0.58-0.78]. Similar results were seen for secondary outcomes where risk reductions were seen regarding atrial fibrillation, stroke, heart failure, and aneurysms. Positive and negative control outcome analyses identified minimal residual confounding.
Conclusion
Oral BP users experienced a 33% reduced risk of CV events. This observational real-world study adds to a growing body of evidence for cardioprotection by oBP that warrants testing in a randomized setting.
Journal Article
Effect of osteoporosis medications on vascular and valvular calcification: a systematic review and meta-analysis
Objective
Vascular calcification shares many features with skeletal mineralisation and shares an inverse relationship with osteoporosis (skeletal de-mineralisation). However, medications that reduce bone loss (anti-resorptives) have had inconsistent effects on extra-skeletal mineralisation (i.e. vascular and valvular calcification). As such, this paper aims to synthesise existing literature examining the effect of anti-resorptive treatments on extra-skeletal (vascular and valvular) calcification across populations.
Methods
Medline and Embase were searched (inception to October 2024) for studies that assessed the association between anti-resorptive medication use and vascular/valvular calcification. Pooled standardised mean differences (SMDs) with 95% confidence intervals (CI) were calculated for all outcomes, using random-effects model. Leave-one-out sensitivity analyses were performed for internal validity.
Results
Of 4071 articles screened, 33 were included in the review, and 15 (2344 participants) had data available for meta-analysis. Anti-resorptive use was associated with non-significant, small magnitude improvements in abdominal aortic calcification (decreased value), coronary artery calcification (decreased value) and ejection fraction (increased value) but significant small reduction in aortic valve area (representing less calcification on the valve) with standardised mean difference of − 0.45 (95% confidence interval (CI) − 0.99; 0.08,
I
2
= 84%), − 1.19 (95% CI − 2.92; 0.55,
I
2
= 91%), − 0.67 (95% CI − 1.72; 0.38,
I
2
= 94%), 0.26 (95% CI − 0.14; 0.66,
I
2
= 62%) and 0.56 (95% CI 0.07; 1.06,
I
2
= 76%), respectively.
Conclusion
The significance of small positive effect of anti-resorptives on aortic stenosis is clinically uncertain. Despite strong biological links between vascular calcification and skeletal mineralisation, anti-resorptives do not appear to have a strong favourable influence on extra-skeletal mineralisation. This suggests that mechanisms that link vascular calcification with osteoporosis may be acting in pathways not influenced by anti-resorptives.
Summary
This systematic review and meta-analysis summarises the effect of anti-resorptives on vascular and valvular calcification. There is a small, positive effect of anti-resorptives on aortic stenosis, though this is of uncertain clinical importance.
Journal Article
Association between circulating adipocytokine concentrations and microvascular complications in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of controlled cross-sectional studies
The adipocytokines leptin and adiponectin have been variously associated with diabetic microvascular complications. No comprehensive clinical data exist examining the association between adipocytokines and the presence of these complications.
This is a systematic review of cross-sectional studies comparing circulating adipocytokines in patients with type 2 diabetes mellitus (T2DM), with and without microvascular complications. Studies were retrieved from MEDLINE, EMBASE, Scopus and Cochrane databases. Study quality was evaluated using a modified Newcastle–Ottawa Scale. Meta-analysis was performed using an inverse-variance model, providing standardised mean differences (SMD) and 95% confidence intervals (CI). Heterogeneity was determined by I2 statistic.
Amongst 554 identified studies, 28 were included in the review. Study quality range was 3.5–9 (maximum 11). Higher leptin levels were associated with microalbuminuria (SMD=0.41; 95% CI=0.14–0.67; n=901; p=0.0003), macroalbuminuria (SMD=0.68; 95% CI=0.30–1.06; n=406; p=0.0004), and neuropathy (SMD=0.26; 95% CI=0.07–0.44; n=609; p=0.008). Higher adiponectin levels were associated with microalbuminuria (SMD=0.55; 95% CI=0.29–0.81, n=274; p<0.001), macroalbuminuria (SMD=1.37; 95% CI=0.78–1.97, n=246; p<0.00001), neuropathy (SMD=0.25; 95% CI=0.14–0.36; n=1516; p<0.00001), and retinopathy (SMD=0.38; 95% CI=0.25–0.51; n=1306; p<0.00001). Meta-regression suggested no influence of body mass index and duration of diabetes on effect size, and a weak trend in terms of age on effect size.
Our meta-analysis suggests leptin and adiponectin levels are higher in T2DM patients with microvascular complications. Studies were limited by cross-sectional design. Large prospective analyses are required to validate these findings.
Journal Article
Low Relative Lean Mass is Associated with Increased Likelihood of Abdominal Aortic Calcification in Community-Dwelling Older Australians
Age-related loss of skeletal muscle is associated with increased risk of functional limitation and cardiovascular (CV) mortality. In the elderly abdominal aortic calcification (AAC) can increase CV risk by altering aortic properties which may raise blood pressure and increase cardiac workload. This study investigated the association between low muscle mass and AAC in community-dwelling older Australians. Data for this cross-sectional analysis were drawn from a 2010 sub-study of the Melbourne Collaborative Cohort Study in the setting of community-dwelling older adults. Three hundred and twenty-seven participants [mean age = 71 ± 6 years; mean BMI = 28 ± 5 kg/m
2
; females
n
= 199 (62 %)] had body composition determined by dual-energy x-ray absorptiometry (DXA) and AAC determined by radiography. Participants were stratified into tertiles of sex-specific BMI-normalised appendicular lean mass (ALM). Those in the lowest tertile were considered to have low relative muscle mass. Aortic calcification score (ACS) was determined visually as the extent of calcification on the aortic walls between L1 and L4 vertebrae (range: 0–24). Severe AAC was defined as ACS ≥ 6. Prevalence of any AAC was highest in participants with low relative muscle mass (74 %) compared to the middle (65 %) and upper (53 %) tertiles (
p
trend = 0.006). The lower ALM/BMI tertile had increased odds (Odds ratio = 2.3; 95 % confidence interval: 1.1–4.6;
p
= 0.021) of having any AAC; and having more severe AAC (2.2; 1.2–4.0;
p
= 0.009) independent of CV risk factors, serum calcium and physical activity. AAC is more prevalent and severe in community-dwelling older adults with low relative muscle mass. Maintaining muscle mass could form part of a broader primary prevention strategy in reducing AAC.
Journal Article
Aortic Calcification is Associated with Five-Year Decline in Handgrip Strength in Older Women
The objective of the study was to determine the association between AAC and neuromuscular function over 5 years. Participants in this study were ambulant women over 70 years old residing in Perth, Western Australia who participated in the Calcium Intake Fracture Outcomes Study, a randomised controlled trial of calcium supplementation. 1046 women (mean age = 74.9 ± 2.6 years; BMI = 27.1 ± 4.4 kg/m2) were included. Lateral spine images captured during bone density testing were scored for AAC (AAC24; 0–24) at baseline. Severe AAC (AACsev) was defined using established cut points (AAC24 ≥ 6). At baseline and follow-up, isometric grip strength was assessed using a dynamometer. Mobility was assessed by the Timed-Up-and-Go (TUG) test. Using pre-defined criteria, muscle weakness was considered as grip strength < 22 kg and poor mobility defined as TUG > 10.2 s. A subset of women had appendicular lean mass (ALM) determined by dual-energy X-ray absorptiometry at baseline and follow-up (n = 261). AACsev was evident in 193 (18.5%) women. Average decline in grip strength after 5 years was greater in those with AACsev than those without (3.6 ± 3.7 vs. 2.9 ± 4.2 kg; p = 0.034). This remained significant after adjustment for age, treatment allocation, diabetes, smoking history, renal function, medical record-derived prevalent vascular disease, BMI and physical activity (β = − 0.184; 95% confidence interval: − 0.361, − 0.008; p = 0.040). AACsev was not associated with 5-year changes in TUG or ALM in univariable or multivariable analyses (all p > 0.05). In older women, severe aortic calcification was associated with greater 5-year decline in muscle strength, but not TUG or ALM. These findings support the concept that vascular disease may have an effect on the loss of muscular strength.
Journal Article
Effects of vitamin D supplementation on inflammatory markers in heart failure: a systematic review and meta-analysis of randomized controlled trials
Vitamin D is reported to have anti-inflammatory properties; however the effects of vitamin D supplementation on inflammation in patients with heart failure (HF) have not been established. We performed a systematic review and meta-analysis examining effects of vitamin D supplementation on inflammatory markers in patients with HF. MEDLINE, CINAHL, EMBASE, All EBM, and Clinical Trials registries were systematically searched for RCTs from inception to 25 January 2017. Two independent reviewers screened all full text articles (no date or language limits) for RCTs reporting effects of vitamin D supplementation (any form, route, duration, and co-supplementation) compared with placebo or usual care on inflammatory markers in patients with heart failure. Two reviewers assessed risk of bias and quality using the grading of recommendations, assessment, development, and evaluation approach. Seven studies met inclusion criteria and six had data available for pooling (n = 1012). In meta-analyses, vitamin D-supplemented groups had lower concentrations of tumor necrosis factor-alpha (TNF-α) at follow-up compared with controls (n = 380; p = 0.04). There were no differences in C-reactive protein (n = 231), interleukin (IL)-10 (n = 247) or IL-6 (n = 154) between vitamin D and control groups (all p > 0.05). Our findings suggest that vitamin D supplementation may have specific, but modest effects on inflammatory markers in HF.
Journal Article
New advances in the treatment of generalized lipodystrophy: role of metreleptin
Recombinant methionyl human leptin or metreleptin is a synthetic leptin analog that has been trialed in patients with leptin-deficient conditions, such as leptin deficiency due to mutations in the leptin gene, hypothalamic amenorrhea, and lipodystrophy syndromes. These syndromes are characterized by partial or complete absence of adipose tissue and hormones derived from adipose tissue, most importantly leptin. Patients deficient in leptin exhibit a number of severe metabolic abnormalities such as hyperglycemia, hypertriglyceridemia, and hepatic steatosis, which can progress to diabetes mellitus, acute pancreatitis, and hepatic cirrhosis, respectively. For the management of these abnormalities, multiple therapies are usually required, and advanced stages may be progressively difficult to treat. Following many successful trials, the US Food and Drug Administration approved metreleptin for the treatment of non-HIV-related forms of generalized lipodystrophy. Leptin replacement therapy with metreleptin has, in many cases, reversed these metabolic complications, with improvements in glucose-insulin-lipid homeostasis, and regression of fatty liver disease. Besides being effective, a daily subcutaneous administration of metreleptin is generally safe, but the causal association between metreleptin and immune complications (such as lymphoma) is still unclear. Moreover, further investigation is needed to elucidate mechanisms by which metreleptin leads to the development of anti-leptin antibodies. Herein, we review clinical aspects of generalized lipodystrophy and the pharmacological profile of metreleptin. Further, we examine studies that assessed the safety and efficacy of metreleptin, and outline some clinical perspectives on the drug.
Journal Article
High calcium intake in men not women is associated with all-cause mortality risk: Melbourne Collaborative Cohort Study
SummaryThe risk of mortality associated with high dietary calcium is uncertain. Unlike a highly publicised study in Swedish women, high dietary calcium intake in men—not women—was associated with increased all-cause mortality.PurposeThe association of dietary calcium with mortality is controversial. A study of women from the Swedish Mammography Cohort (SMC) suggested higher calcium was associated with higher mortality risk, whilst a study of Australian adults from the Melbourne Collaborative Cohort Study (MCCS) suggested higher intakes were associated with lower mortality risk. Thus, we aimed to perform a sex-specific re-analysis of the MCCS to evaluate the association of dietary calcium with mortality outcomes and directly compare hazard estimates (95% confidence intervals) in women with those from the SMC.MethodsA prospective cohort study of community-dwelling Australian adults was conducted, in which 34,627 individuals (women 20,834 (60.2%); mean ± SD, age = 54 ± 8 years) were included at baseline after excluding those with prevalent cardiovascular (CV) disease, cancer or incomplete data. Energy-adjusted dietary calcium was categorised into the following levels of consumption (mg/day): < 600, 600–999, 1000–1399 and ≥ 1400. Mortality from all-causes, any cardiovascular disease and myocardial infarction was determined. Mortality hazards relative to intakes were estimated to be of 600–999 mg/day.ResultsIn women, hazard estimates for calcium intake of ≥ 1400 mg/day did not reach significance for all-cause (HR = 0.85; 0.66, 1.10) or CV (HR = 1.10; 0.69, 1.81) mortality in adjusted models. In men, intakes of ≥ 1400 mg/day were associated with a 42% increased all-cause mortality risk (HR = 1.42; 1.02, 1.99). There was a trend toward increased CV mortality (HR = 1.83; 0.94, 3.55).ConclusionContrary to findings from a similar study conducted in Swedish women, Australian women, after adjustment for cofounders showed no increase in mortality risk with high calcium intakes possibly reflecting differences in calcium handling dynamics, diet or lifestyle factors between the two countries. We identified an increased risk for men.
Journal Article
A Systematic Review and Meta-Analysis of Circulating Biomarkers Associated with Failure of Arteriovenous Fistulae for Haemodialysis
Arteriovenous fistula (AVF) failure is a significant cause of morbidity and expense in patients on maintenance haemodialysis (HD). Circulating biomarkers could be valuable in detecting patients at risk of AVF failure and may identify targets to improve AVF outcome. Currently there is little consensus on the relationship between circulating biomarkers and AVF failure. The aim of this systematic review was to identify circulating biomarkers associated with AVF failure.
Studies evaluating the association between circulating biomarkers and the presence or risk of AVF failure were systematically identified from the MEDLINE, EMBASE and Cochrane Library databases. No restrictions on the type of study were imposed. Concentrations of circulating biomarkers of routine HD patients with and without AVF failure were recorded and meta-analyses were performed on biomarkers that were assessed in three or more studies with a composite population of at least 100 participants. Biomarker concentrations were synthesized into inverse-variance random-effects models to calculate standardized mean differences (SMD) and 95% confidence intervals (CI).
Thirteen studies comprising a combined population of 1512 participants were included after screening 2835 unique abstracts. These studies collectively investigated 48 biomarkers, predominantly circulating molecules which were assessed as part of routine clinical care. Meta-analysis was performed on twelve eligible biomarkers. No significant association between any of the assessed biomarkers and AVF failure was observed.
This paper is the first systematic review of biomarkers associated with AVF failure. Our results suggest that blood markers currently assessed do not identify an at-risk AVF. Further, rigorously designed studies assessing biological plausible biomarkers are needed to clarify whether assessment of circulating markers can be of any clinical value. PROSPERO registration number CRD42016033845.
Journal Article