Discordant association of the <Emphasis Type="Italic">CREBRF</Emphasis> rs373863828 A allele with increased BMI and protection from type 2 diabetes in Māori and Pacific (Polynesian) people living in Aotearoa/New Zealand

Aims/hypothesis

The A (minor) allele of CREBRF rs373863828 has been associated with increased BMI and reduced risk of type 2 diabetes in the Samoan populations of Samoa and American Samoa. Our aim was to test rs373863828 for associations with BMI and the odds of type 2 diabetes, gout and chronic kidney disease (CKD) in Māori and Pacific (Polynesian) people living in Aotearoa/New Zealand.

Methods

Linear and logistic regression models were used to analyse the association of the A allele of CREBRF rs373863828 with BMI, log-transformed BMI, waist circumference, type 2 diabetes, gout and CKD in 2286 adults. The primary analyses were adjusted for age, sex, the first four genome-wide principal components and (where appropriate) BMI, waist circumference and type 2 diabetes. The primary analysis was conducted in ancestrally defined groups and association effects were combined using meta-analysis.

Results

For the A allele of rs373863828, the effect size was 0.038 (95% CI 0.022, 0.055, p?=?4.8?×?10^?6) for log-transformed BMI, with OR 0.59 (95% CI 0.47, 0.73, p?=?1.9?×?10^?6) for type 2 diabetes. There was no evidence for an association of genotype with variance in BMI (p?=?0.13), and nor was there evidence for associations with serum urate (β?=?0.012 mmol/l, p_corrected?=?0.10), gout (OR 1.00, p?=?0.98) or CKD (OR 0.91, p?=?0.59).

Conclusions/interpretation

Our results in New Zealand Polynesian adults replicate, with very similar effect sizes, the association of the A allele of rs373863828 with higher BMI but lower odds of type 2 diabetes among Samoan adults living in Samoa and American Samoa.

     

Hypertension and the development of New onset chronic kidney disease over a 10 year period: a retrospective cohort study in a primary care setting in Malaysia

Background

Little is known about the rate of progression to chronic kidney disease (CKD) among hypertensive patients, particularly at the primary care level. This study aims to examine risk factors associated with new onset CKD among hypertensive patients attending a primary care clinic.

Methods

This is a 10-year retrospective cohort study of 460 patients with hypertension who were on treatment. Patient information was collected from patient records. CKD was defined as a glomerular filtration rate <60?ml/min per 1.73?m² (Cockcroft-Gault equation). Multiple logistic regression statistics was used to test the association in newly diagnosed CKD.

Results

The incidence of new CKD was 30.9% (n?=?142) with an annual rate of 3%. In multivariate logistic regression analysis, factors associated with development of new onset of CKD among hypertensive patients were older age (odds ratio [OR] 1.123, 95% confidence interval [CI] 1.078-1.169), presence of diabetes (OR 2.621, 95% CI 1.490-4.608), lower baseline eGFR (OR 1.041, 95% CI 0.943-0.979) and baseline hyperuricaemia (OR 1.004, 95% CI 1.001-1.007).

Conclusions

The progression to new onset CKD is high among urban multiethnic hypertensive patients in a primary care population. Hence every effort is needed to detect the presence of new onset CKD earlier. Hypertensive patients who are older, with underlying diabetes, hyperuricaemia and lower baseline eGFR are associated with the development of CKD in this population.

     

Urinary mitochondrial DNA level as a biomarker of tissue injury in non-diabetic chronic kidney diseases

Background

Urinary mitochondrial DNA (mtDNA) fragment level has been proposed as a biomarker of chronic kidney disease (CKD). In this study, we determine the relation between urinary mtDNA level and rate of renal function deterioration in non-diabetic CKD.

Methods

We recruited 102 non-diabetic CKD patients (43 with kidney biopsy that showed non-specific nephrosclerosis). Urinary mtDNA level was measured and compared to baseline clinical and pathological parameters. The patients were followed 48.3?±?31.8?months for renal events (need of dialysis or over 30% reduction in estimated glomerular filtration rate [eGFR]).

Results

The median urinary mtDNA level was 1519.42 (inter-quartile range 511.81–3073.03) million copy/mmol creatinine. There were significant correlations between urinary mtDNA level and baseline eGFR (r?=?0.429, p?<?0.001), proteinuria (r?=?0.368, p?<?0.001), severity of glomerulosclerosis (r?=???0.537, p?<?0.001), and tubulointerstitial fibrosis (r?=???0.374, p?=?0.014). The overall rate of eGFR decline was ??2.18?±?5.94?ml/min/1.73m² per year. There was no significant correlation between the rate of eGFR decline and urinary mtDNA level. By univariate analysis, urinary mtDNA level predicts dialysis-free survival, but the result became insignificant after adjusting for clinical and histological confounding factors.

Conclusion

Urinary mtDNA levels have no significant association with the rate of renal function decline in non-diabetic CKD, although the levels correlate with baseline renal function, proteinuria, and the severity of histological damage. Urinary mtDNA level may be a surrogate marker of permanent renal damage in non-diabetic CKD.

     

Perturbations of the anti-ageing hormone Klotho in patients with type 1 diabetes and microalbuminuria

Aims/hypothesis

Patients with type 1 diabetes and microalbuminuria are at high risk of cardiovascular disease (CVD) and end-stage renal disease. Soluble Klotho is an anti-ageing circulating hormone involved in phosphate metabolism and vascular homeostasis through protective effects on the endothelium and antioxidant actions. The role of soluble Klotho in patients with type 1 diabetes and microalbuminuria is unknown.

Methods

In a cross-sectional single-centre study we evaluated the levels of circulating serum soluble Klotho in 33 participants with type 1 diabetes and a history of microalbuminuria (receiving renin–angiotensin system [RAS] inhibitors) and 45 participants with type 1 diabetes without a history of microalbuminuria (not receiving RAS or other antihypertensive drugs). All participants had an eGFR >45 ml/min, duration of diabetes >20 years and no history of CVD. Serum soluble Klotho levels were measured by a validated immunoassay.

Results

Participants with microalbuminuria had significantly lower levels of serum Klotho compared with those without microalbuminuria (median [interquartile range], 659.3 [525.3, 827.6] vs 787.7 [629.5, 1007]; p?=?0.023). This difference persisted after adjustment for variables including age and eGFR. In a subgroup of 30 individuals with and without microalbuminuria, other markers of phosphate balance were not significantly different.

Conclusions/interpretation

In individuals with type 1 diabetes, microalbuminuria is associated with soluble Klotho deficiency. Further studies are required to determine whether soluble Klotho is causally related to the development of cardio-renal disease in type 1 diabetes.

     

Klotho Regulates Cigarette Smoke-Induced Autophagy: Implication in Pathogenesis of COPD

Introduction

Chronic obstructive pulmonary disease is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation. Autophagy is a fundamental cellular process that eliminates long-lived proteins and damaged organelles through lysosomal degradation pathway, though its role in human diseases remains unclear. We hypothesized that an anti-aging protein, Klotho plays an important role in regulating autophagy in response to cigarette smoke (CS).

Methods

Autophagy was measured by detecting LC3-I and LC3-II expressions. The regulation of autophagy expression by cigarette smoke extract (CSE) was studied in vitro, and small-interfering RNA (siRNA) and recombinant Klotho were employed to investigate the role of Klotho on CSE-induced autophagy. Protein levels and phosphorylation were measured by Western blot assay.

Results

CS exposure resulted in induction of autophagy in alveolar macrophages. Pretreatment of cells with Klotho attenuated CS-induced autophagy whereas knockdown of Klotho augmented CS-induced autophagy. Klotho inhibited phosphorylation of ERK, Akt, and IGF-1 in CSE-stimulated cells.

Conclusions

These data suggest that Klotho plays a critical role in the regulation of CS-induced autophagy and have important implications in understanding the mechanisms of CS-induced cell death and senescence.

     

Klotho: a novel biomarker for cancer

Background

The Klotho gene was originally identified as an anti-aging gene in 1997. Recent studies have demonstrated aberrant expression of Klotho in a number of cancers, including breast cancer, lung cancer, hepatocellular carcinoma (HCC), and so on.

Methods

A literature search focusing on dysregulation of Klotho and its possible mechanisms in cancer was performed.

Results and conclusions

Downregulation of Klotho was found in several cancers, such as pancreatic cancer, HCC, and other tumors. Epigenetic modulation, such as promoter methylation and histone deacetylation, also contributed to the dysregulation of Klotho in cancers. Downregulation of Klotho resulted in promoted proliferation and reduced apoptosis of cancer cells. The relevant mechanisms include the fibroblast growth factor signaling, the insulin-like growth factor 1 receptor pathway, and the Wnt/β-catenin signaling pathway. Furthermore, the Klotho protein hopefully provides new insights into cancer target treatment.

     

Time of injury affects urinary biomarker predictive values for acute kidney injury in critically ill,non-septic patients

Background

The predictive value of acute kidney injury (AKI) urinary biomarkers may depend on the time interval following tubular injury, thereby explaining in part the heterogeneous performance of these markers that has been reported in the literature. We studied the influence of timing on the predictive values of tubular proteins, measured before the rise of serum creatinine (SCr) in critically ill, non-septic patients.

Methods

Seven hundred adult critically ill patients were prospectively included for urine measurements at four time-points prior to the rise in serum creatinine (T?=?0, -16, -20 and -24 h). Patients with sepsis and or AKI at ICU entry were excluded. The urinary excretion of the proteins, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), which are up-regulated in the distal and proximal tubules, respectively, were measured as well as the constitutive cytoplasmatic enzymes, π- and α-glutathione-S-transferase (GST), which are released by the distal and proximal tubules, respectively.

Results

Five hundred and forty-three subjects were eligible for further analyses; however, 49 developed AKI in the first 48 h. Both NGAL (P?=?0.001 at T?=?-24 vs. non-AKI patients) and KIM-1 (P?<?0.0001 at T?=?0 vs. non-AKI patients) concentrations gradually increased until AKI diagnosis, whereas π- and α-GST peaked at T?=?-24 before AKI (P?=?0.006 and P?=?0.002, respectively vs. non-AKI patients) and showed a rapid decline afterwards. The predictive values at T?=?-24 prior to AKI were modest for π- and α-GST, whereas NGAL sufficiently predicted AKI at T?=?-24 and its predictive power improved as the time interval to AKI presentation decreased (area under the receiver operating characteristic curve; AUC?=?0.79, P?<?0.0001). KIM-1 was a good discriminator at T?=?0 only (AUC?=?0.73, P?<?0.0001).

Conclusions

NGAL, KIM-1, pi- and alpha-GST displayed unique and mutually incomparable time dependent characteristics during the development of non-sepsis related AKI. Therefore, the time-relationship between the biomarker measurements and the injurious event influences the individual test results.

     

Treatment with Dalteparin is Associated with a Lower Risk of Bleeding Compared to Treatment with Unfractionated Heparin in Patients with Renal Insufficiency

BACKGROUND

Low molecular weight heparins (LMWHs) have been cautiously used in patients with chronic kidney disease (CKD) due to fear of accumulation. Dalteparin, however, has shown minimal tendency to accumulate in patients with CKD and may be safe to use in this patient population.

OBJECTIVE

We compared the incidence of clinically significant bleeding in patients with CKD receiving therapeutic doses of dalteparin to that of patients with CKD receiving therapeutic doses of UFH.

DESIGN

This was a retrospective cohort study.

SUBJECTS

Inpatients with CKD (GFR?<?60 ml/min) who were treated with therapeutic dalteparin or UFH were included in the study

MAIN MEASURES

Primary outcome was major bleeding within 10 days of anticoagulation, identified by ICD-9 code and confirmed by chart review. Demographic characteristics, laboratory values, comorbidities, prior bleeding history and inpatient medications were extracted for each admission from the electronic medical record. Logistic regression models were created to examine the association between choice of anticoagulant and bleeding rates, after adjustment for demographic and clinical characteristics.

KEY RESULTS

Dalteparin-treated patients were significantly less likely to experience a major bleed than patients treated with UFH (1.14 % vs. 3.49 %, p?<?0.001). The reduced likelihood of bleeding associated with dalteparin treatment remained significant after adjustment for patient characteristics (HR 0.39, 95 % CI: 0.21–0.70, p?<?0.0001). A stratified analysis for subgroups with GFR< 30 mL/min and with GFR between 30 and 60 mL/min showed that dalteparin was still associated with lower odds of bleeding compared to treatment with unfractionated heparin, but the difference was nonsignificant for GFR< 30 (HR 0.35, 95 % CI: 0.11–1.15), even after adjustment (OR 0.37, 95 % CI: 0.11–1.22).

CONCLUSION

In patients with CKD, treatment with therapeutic dose dalteparin was associated with lower rates of bleeding than treatment with unfractionated heparin. For patients with severe CKD (GFR< 30), dalteparin was shown to be at least as safe as unfractionated heparin.

     

Keystrokes,Mouse Clicks,and Gazing at the Computer: How Physician Interaction with the EHR Affects Patient Participation

Background

Evidence is mixed regarding how physicians' use of the electronic health record (EHR) affects communication in medical encounters.

Objective

To investigate whether the different ways physicians interact with the computer (mouse clicks, key strokes, and gaze) vary in their effects on patient participation in the consultation, physicians’ efforts to facilitate patient involvement, and silence.

Design

Cross-sectional, observational study of video and event recordings of primary care and specialty consultations.

Participants

Thirty-two physicians and 217 patients.

Main Measures

Predictor variables included measures of physician interaction with the EHR (mouse clicks, key strokes, gaze). Outcome measures included active patient participation (asking questions, stating preferences, expressing concerns), physician facilitation of patient involvement (partnership-building and supportive talk), and silence.

Key Results

Patients were less active participants in consultations in which physicians engaged in more keyboard activity (b?=??0.002, SE?=?0.001, p?=?0.02). More physician gaze at the computer was associated with more silence in the encounter (b?=?0.21, SE?=?0.09, p?=?0.02). Physicians’ facilitative communication, which predicted more active patient participation (b?=?0.65, SE?=?0.14, p?<?0.001), was not related to EHR activity measures.

Conclusions

Patients may be more reluctant to actively participate in medical encounters when physicians are more physically engaged with the computer (e.g., keyboard activity) than when their behavior is less demonstrative (e.g., gazing at EHR). Using easy to deploy communication tactics (e.g., asking about a patient’s thoughts and concerns, social conversation) while working on the computer can help physicians engage patients as well as maintain conversational flow.

     

Spanish modified version of the palliative care outcome scale–symptoms renal: cross-cultural adaptation and validation

Background

Patients with chronic kidney disease (CKD) have a high symptoms burden that is related to a poor health-related quality of life (HRQoL) and high costs of care. Validated instruments may be useful for assessing the symptoms and monitoring outcomes in these patients. The Palliative care Outcome Scale-Symptoms Renal (POS-S Renal) is a patient-reported outcome measure for assessing symptoms in CKD stage 4–5. This study is the first cross-cultural adaptation and psychometric analysis of this clinical tool. The purpose of this study is to carry out a cross-cultural adaptation of the POS-S Renal for Spanish-speaking patients, and to perform an analysis of the psychometric properties of this questionnaire.

Methods

The English version of the POS-S Renal was culturally adapted and translated into Spanish using a double forward and backward method. An expert panel evaluated the content validity. The questionnaire was pilot-tested in 30 patients. A total of 200 patients with CKD stage 4–5 filled in a modified Spanish version of the POS-S Renal and the MSAS-SF. Statistical analysis to evaluate the psychometric properties of the questionnaire was carried out.

Results

The content validity index (CVI) was 0.97, which indicated that the content of the instrument is an adequate reflection of the symptoms in advanced CKD (ACKD). The factor analysis indicated a two-factor solution explaining 35.05% of total variance. The confirmatory factor analysis (CFA) demonstrated that the two factor model was well supported (comparative fit index?=?0.98, root mean square error of approximation?=?0.068). This assessment tool demonstrated a satisfactory test–retest reliability (r?=?0.909 to factor 1, r?=?0.695 to factor 2, r?=?0.887 to total score), good internal consistency to factor 1 (α?=?0.78) and moderate internal consistency to factor 2 (α?=?0.56). Concurrent criterion-related validity with MSAS-SF was also demonstrated, with r?=?0.860, which indicated a high degree of correlation with a validated instrument that has been used in patients with ACKD.

Conclusions

The Spanish modified version of the POS-S Renal is a reliable and valid instrument that can be used to assess symptoms in Spanish patients with CKD stage 4–5.

     

Reducing Patients’ Unmet Concerns in Primary Care: the Difference One Word Can Make

Context

In primary, acute-care visits, patients frequently present with more than 1 concern. Various visit factors prevent additional concerns from being articulated and addressed.

Objective

To test an intervention to reduce patients’ unmet concerns.

Design

Cross-sectional comparison of 2 experimental questions, with videotaping of office visits and pre and postvisit surveys.

Setting

Twenty outpatient offices of community-based physicians equally divided between Los Angeles County and a midsized town in Pennsylvania.

Participants

A volunteer sample of 20 family physicians (participation rate?=?80%) and 224 patients approached consecutively within physicians (participation rate?=?73%; approximately 11 participating for each enrolled physician) seeking care for an acute condition.

Intervention

After seeing 4 nonintervention patients, physicians were randomly assigned to solicit additional concerns by asking 1 of the following 2 questions after patients presented their chief concern: “Is there anything else you want to address in the visit today?” (ANY condition) and “Is there something else you want to address in the visit today?” (SOME condition).

Main Outcome Measures

Patients’ unmet concerns: concerns listed on previsit surveys but not addressed during visits, visit time, unanticipated concerns: concerns that were addressed during the visit but not listed on previsit surveys.

Results

Relative to nonintervention cases, the implemented SOME intervention eliminated 78% of unmet concerns (odds ratio (OR)?=?.154, p?=?.001). The ANY intervention could not be significantly distinguished from the control condition (p?=?.122). Neither intervention affected visit length, or patients’; expression of unanticipated concerns not listed in previsit surveys.

Conclusions

Patients’ unmet concerns can be dramatically reduced by a simple inquiry framed in the SOME form. Both the learning and implementation of the intervention require very little time.

     

Effect of Gaining Insurance Coverage on Smoking Cessation in Community Health Centers: A Cohort Study

BACKGROUND

Community health center (CHC) patients have high rates of smoking. Insurance coverage for smoking cessation assistance, such as that mandated by the Affordable Care Act, may aid in smoking cessation in this vulnerable population.

OBJECTIVE

We aimed to determine if uninsured CHC patients who gain Medicaid coverage experience greater primary care utilization, receive more cessation medication orders, and achieve higher quit rates, compared to continuously uninsured smokers.

DESIGN

Longitudinal observational cohort study using electronic health record data from a network of Oregon CHCs linked to Oregon Medicaid enrollment data.

PATIENTS

Cohort of patients who smoke and who gained Medicaid coverage in 2008–2011 after ≥ 6 months of being uninsured and with ≥ 1 smoking assessment in the 24-month follow-up period from the baseline smoking status date. This group was propensity score matched to a cohort of continuously uninsured CHC patients who smoke (n?=?4140 matched pairs; 8280 patients).

INTERVENTION

Gaining Medicaid after being uninsured for ≥ 6 months.

MAIN MEASURES

‘Quit’ smoking status (baseline smoking status was ‘current every day’ or ‘some day’ and status change to ‘former smoker’ at a subsequent visit), smoking cessation medication order, and ≥ 6 documented visits (yes/no variables) at ≥ 1 smoking status assessment within the 24-month follow-up period.

KEY RESULTS

The newly insured had 40 % increased odds of quitting smoking (aOR?=?1.40, 95 % CI:1.24, 1.58), nearly triple the odds of having a medication ordered (aOR?=?2.94, 95 % CI:2.61, 3.32), and over twice the odds of having ≥ 6 follow-up visits (aOR?=?2.12, 95 % CI:1.94, 2.32) compared to their uninsured counterparts.

CONCLUSIONS

Newly insured patients had increased odds of quit smoking status over 24 months of follow-up than those who remained uninsured. Providing insurance coverage to vulnerable populations may have a significant impact on smoking cessation.

     

Two-dimensional speckle tracking echocardiography demonstrates no effect of active acromegaly on left ventricular strain

Background

Speckle tracking echocardiography (STE) allows for the study of myocardial strain (ε), a marker of early and subclinical ventricular systolic dysfunction. Cardiac disease may be present in patients with acromegaly; however, STE has never been used to evaluate these patients.

Objective

To evaluate left ventricular (LV) global longitudinal strain in patients with active acromegaly with normal LV systolic function.

Design

Cross-sectional clinical study.

Methods

Patients with active acromegaly with no detectable heart disease and a control group were matched for age, gender, arterial hypertension and diabetes mellitus underwent STE. Global LV longitudinal ε (GLS), left ventricular mass index (LVMi), left ventricular ejection fraction (LVEF) and relative wall thickness (RWT) were obtained via two-dimensional (2D) echocardiography using STE.

Results

Thirty-seven patients with active acromegaly (mean age 45.6?±?13.8; 48.6% were males) and 48 controls were included. The mean GLS was not significantly different between the acromegaly group and the control group (in %, ?20.1?±?3.1 vs. ?19.4?±?2.2, p?=?0.256). Mean LVMi was increased in the acromegaly group (in g/m², 101.6?±?27.1 vs. 73.2?±?18.6, p?<?0.01). There was a negative correlation between LVMi and GLS (r?=??0.39, p?=?0.01).

Conclusions

Acromegaly patients, despite presenting with a higher LVMi when analyzed by 2D echocardiography, did not present with impairment in the strain when compared to a control group; this finding indicates a low chance of evolution to systolic dysfunction and agrees with recent studies that show a lower frequency of cardiac disease in these patients.

     

Fecal microbiota transplantation in a kidney transplant recipient with recurrent urinary tract infection

Purpose

We report on a kidney transplant recipient treated with fecal microbiota transplantation (FMT) for recurrent urinary tract infections.

Methods

FMT was administered via frozen capsulized microbiota. Before and after FMT, urinary, fecal and vaginal microbiota compositions were analyzed.

Results

The patient remained without symptoms after FMT.

Conclusions

Underlying mechanisms of action need to be addressed in depth by future research.

     

Insurance Coverage Predicts Mortality in Patients Transferred Between Hospitals: a Cross-Sectional Study

Background

Patients transferred between hospitals are at high risk of adverse events and mortality. The relationship between insurance status, transfer practices, and outcomes has not been definitively characterized.

Objective

To identify the association between insurance coverage and mortality of patients transferred between hospitals.

Design

We conducted a single-institution observational study, and validated results using a national administrative database of inter-hospital transfers.

Setting

Three ICUs at an academic tertiary care center validated by a nationally representative sample of inter-hospital transfers.

Patients

The single-institution analysis included 652 consecutive patients transferred from 57 hospitals between 2011 and 2012. The administrative database included 353,018 patients transferred between 437 hospitals.

Measurements

Adjusted inpatient mortality and 24-h mortality, stratified by insurance status.

Results

Of 652 consecutive transfers to three ICUs, we observed that uninsured patients had higher adjusted inpatient mortality (OR 2.67, p?=?0.021) when controlling for age, race, gender, Apache-II, and whether the patient was transferred from an ED. Uninsured were more likely to be transferred from ED (OR 2.3, p?=?0.026), and earlier in their hospital course (3.9 vs 2.0 days, p?=?0.002). Using an administrative dataset, we validated these observations, finding that the uninsured had higher adjusted inpatient mortality (OR 1.24, 95% CI 1.13–1.36, p?<?0.001) and higher mortality within 24 h (OR 1.33 95% CI 1.11–1.60, p?<?0.002). The increase in mortality was independent of patient demographics, referral patterns, or diagnoses.

Limitations

This is an observational study where transfer appropriateness cannot be directly assessed.

Conclusions

Uninsured patients are more likely to be transferred from an ED and have higher mortality. These data suggest factors that drive inter-hospital transfer of uninsured patients have the potential to exacerbate outcome disparities.

     

Measurement of glomerular filtration rate in patients undergoing obesity surgery

Background

Most studies on obesity surgery have measured renal function using the estimated GFR. However, due to the reduction of muscle mass, and therefore creatinine that accompanies weight loss, such measures can falsely suggest an improvement in renal function. To balance the risks of surgery versus any potential benefits on renal function, we need to be able to determine renal function using valid and reliable methodologies. In this pilot study we aimed to measure renal function in patients with CKD undergoing obesity surgery using the gold standard ⁵¹Cr-EDTA GFR clearance methodology which is independent of measures of muscle mass.

Methods

Nine consecutive obese patients with CKD underwent obesity surgery. Their renal function was assessed using ⁵¹Cr-EDTA GFR, cystatin C and serum creatinine as well as using eGFR equations including MDRD CKD Epi, Cockcroft Gault and CKD Epi cystatin before and 12?months after surgery.

Results

Renal function using the ⁵¹Cr-EDTA measured GFR did not change significantly after surgery. Similar results were obtained when Cystatin C, CKD Epi cystatin, CKD Epi cystatin creatinine and adjusted Cockcroft Gault Creatinine clearance methods were used. In contrast there were either trends or significant improvements in renal function measured using the MDRD and CKD Epi equations.

Conclusions

In this pilot study using the gold standard ⁵¹Cr-EDTA method we found stabilisation in renal function after obesity surgery. Until further definitive data emerge it is critical to balance the risk and benefits of surgery, especially if renal function may not improve as often as previously suggested.

Trial registration

ClinicalTrials.gov NCT01507350. Registered June 2011.

     

Interventions to Improve Veterans’ Access to Care: A Systematic Review of the Literature

Objectives

To conduct a systematic review to address the following key questions: (1) what interventions have been successful in improving access for veterans with reduced health care access? (2) Have interventions that have improved health care access led to improvements in process and clinical outcomes?

Data Sources

OVID MEDLINE, CINAHL, PsychINFO.

Study Eligibility Criteria, Participants, and Interventions

English language articles published in peer-reviewed journals from 1990 to June 2010. All interventions designed to improve access to health care for US veterans that reported the impact of the intervention on perceived (e.g., satisfaction with access) or objective (e.g., travel time, wait time) access were included.

Appraisal and Synthesis Methods

Investigators abstracted data on study design, study quality, intervention, and impact of the intervention on access, process outcomes, and clinical outcomes.

Results

Nineteen articles (16 unique studies) met the inclusion criteria. While there were a small number of studies in support of any one intervention, all showed a positive impact on either perceived or objective measures of access. Implementation of Community Based Outpatient Clinics (n?=?5 articles), use of Telemedicine (n?=?5 articles), and Primary Care Mental Health Integration (n?=?6 articles) improved access. All 16 unique studies reported process outcomes, most often satisfaction with care and utilization. Four studies reported clinical outcomes; three found no differences.

Limitations

Included studies were largely of poor to fair methodological quality.

Conclusions and Implications of Key Findings

Interventions can improve access to health care for veterans. Increased access was consistently linked to increased primary care utilization. There was a lack of data regarding the link between access and clinical outcomes; however, the limited data suggest that increased access may not improve clinical outcomes. Future research should focus on the quality and appropriateness of care and clinical outcomes.

     

Soluble Klotho is not independently associated with cardiovascular disease in a population of dialysis patients

Background

Dialysis patients suffer from a high burden of cardiovascular disease (CVD). Partly this is due to progressive deterioration of calcium-phosphate homeostasis. Previous studies suggested that besides FGF-23, low levels of Klotho, a protein linked to aging, might constitute a key factor in this detrimental relationship. The purpose of the present study was to determine the relationship between serum Klotho (sKlotho) and the presence of CVD in dialysis patients.

Methods

Plasma levels of sKlotho were measured in a cohort of dialysis patients and related to left ventricular (LV) dysfunction (defined as a LV ejection fraction <45%) and LV mass using echocardiography. Coronary artery disease (CAD) and calcification score were assessed using computed tomography angiography. Abdominal aortic calcification score (AACscore) was measured by abdominal X-ray.

Results

We included 127 dialysis patients, 67?±?7 years old, 76% male, 67% on hemodialysis, median sKlotho 460 pg/mL (25th-75th percentile 350-620 pg/mL). Patients with a low sKlotho (<460 pg/mL) showed significantly more CAD (81% versus 61%; p?=?0.02) and LV dysfunction (19% versus 3%; p?<?0.01). However, after adjusting for confounders, sKlotho was not independently associated with the presence of CVD or the AACscore.

Conclusions

In the present cohort of dialysis patients, sKlotho was not independently associated with CVD. However, patients with a low sKlotho level (<460 pg/mL) did show CAD and LV dysfunction more frequently. Therefore, while sKlotho might be a marker for CVD in dialysis patients, the current data does not support a direct cardioprotective effect of sKlotho.