Outcomes Associated with Serum Calcium Level in Men with Non-Dialysis-Dependent Chronic Kidney Disease

Background and objectives: Elevated serum calcium has been associated with increased mortality in dialysis patients, but it is unclear whether the same is true in non-dialysis-dependent (NDD) chronic kidney disease (CKD). Outcomes associated with low serum calcium are also not well-characterized.Design, setting, participants, & measurements: We examined associations of baseline, time-varying, and time-averaged serum calcium with all-cause mortality in a historic prospective cohort of 1243 men with moderate and advanced NDD CKD by using Cox models.Results: The association of serum calcium with mortality varied according to the applied statistical models. Higher baseline calcium and time-averaged calcium were associated with higher mortality (multivariable adjusted hazard ratio (95% confidence interval): 1.31 (1.13, 1.53); P < 0.001 for a baseline calcium 1 mg/dl higher). However, in time-varying analyses, lower calcium levels were associated with increased mortality.Conclusions: Higher serum calcium is associated with increased long-term mortality (as reflected by the baseline and time-averaged models), and lower serum calcium is associated with increased short-term mortality (as reflected by the time-varying models) in patients with NDD CKD. Clinical trials are warranted to determine whether maintaining normal serum calcium can improve outcomes in these patients.Mineral and bone disorders in chronic kidney disease (CKD) (1) have emerged as novel mortality risk factors in dialysis patients (2–8). Some of these abnormalities (such as serum phosphorus and parathyroid hormone (PTH) levels) have also been implicated in similar ways in patients with non-dialysis-dependent (NDD) CKD (9–12). Serum calcium''s effect on outcomes has been the focus of attention mainly in dialysis patients, where calcium metabolism is significantly distorted (13–19). The use of calcium-containing phosphate binders further complicates the picture because these medications could be involved in the etiology of vascular calcification (20,21), and their roles as therapeutic agents have been intensely debated (22). Supporting the potential role for calcium in cardiovascular disease were epidemiologic studies showing an association between higher calcium and increased mortality (2–8). Some of the same studies have also suggested that extremely low calcium levels may themselves be deleterious (2,3), which has ultimately resulted in recommendations to attain a low-normal serum calcium level in dialysis patients (23). Studies examining the role of calcium in NDD CKD patients are fewer and failed to unequivocally show an association between abnormal calcium levels and vascular calcification (24–27). No study has yet examined the association of calcium levels with mortality in NDD CKD.We examined the association of serum calcium levels with all-cause mortality in a large number of male US veterans with moderate and advanced NDD CKD at a single medical institution.     

Short-Term Comparative Outcomes Associated with the Use of GP IIb/IIIa Antagonists in Patients Undergoing Coronary Intervention

Background:Platelet glycoprotein (GP) IIb/IIIa antagonists reduce the occurrence of death, myocardial infarction (MI) and urgent revascularization among patients undergoing percutaneous coronary intervention (PCI). Despite a similar mechanism of platelet inhibition, the three currently approved agents vary widely in cost. Purpose: The purpose of this prospectively designed, retrospective analysis was to determine clinical outcomes for patients receiving abciximab, tirofiban or eptifibatide as adjunctive therapy during PCI at a single center. We hypothesized that there would be no difference in outcomes during hospitalization following PCI in patients receiving tirofiban or eptifibatide compared with those patients who received abciximab. Outcomes examined included in-hospital mortality, hemorrhagic procedural complications, need for recatheterization, peak creatine kinase following intervention and length of hospital stay (LOS). Results: Two hundred and sixty seven consecutive patients in whom GP IIb/IIIa antagonist therapy was initiated in the catheterization laboratory for PCI were analyzed. Abciximab-treated patients were more likely to be undergoing primary (p<0.001) and rescue (p=0.022) PCI and to have received fibrinolytic therapy (p=0.013) when compared to patients receiving tirofiban or eptifibatide. There were no significant differences between abciximab- and non abciximab-treated patients in either the primary PCI or non primary PCI groups in any of the studied endpoints. In patients undergoing primary PCI, abciximab-treated patients when compared with non abciximab-treated patients exhibited a trend toward an increase in hospital LOS (7.8±7.0 d vs 6.2±3.9, p=0.19) and in the frequency of hemmorhagic complications (22.1% vs 5.3%, p=0.11). In patients not receiving fibrinolytic therapy, abciximab-treated patients experienced a trend toward increased hemmorhagic complications following PCI when compared to non abciximab-treated patients (10.2% vs 6.0%, p=0.28). Complications distant from the vascular access site comprised 62.5% of hemmorhagic complications in the abciximab-treated group, but only 20% of the complications in the non-abciximab treated population (p<0.001). These data suggest no differences in acute outcomes between groups of patients receiving abciximab or other approved GP IIb/IIIa antagonists highlighting a potential significant cost saving. These data will require interpretation following the publication of comparative trials.     

Effects of Calcium Antagonists on Atherogenesis

Calcium antagonists are able to reduce the development of atherosclerotic lesions in many animal models of atherosclerosis. Although the precise mechanisms of their antiatherogenic effects are unknown studies have shown interference with several patho-genetic mechanisms of the atherosclerotic disease process, namely preservation of en-dothelial integrity, reduced smooth muscle cell migration and proliferation, increased low density lipoprotein uptake and degradation in smooth muscle cells and a reduced synthesis of matrix components. Many of these effects are unrelated to their blocking effects on voltage-dependent slow calcium channels, and most effects have been observed with very high concentrations only. Furthermore, differing calcium antagonists seem to influence these mechanisms differently but available data are difficult to interpret because of differences in study design and models used. With the exception of data on calcium antagonists for secondary prevention after myocardial infarction and their influence on the rate of restenosis after percutaneous transluminal angioplasty, no data are available in man with respect to a possible influence on atherosclerosis. Results from on-going studies designed to address specifically this issue must be awaited to answer the question whether the experimental findings can be extended to human atherosclerosis.     

Lower Health Literacy is Associated with Poorer Health Status and Outcomes in Chronic Obstructive Pulmonary Disease

BACKGROUND

Limited health literacy is associated with poor outcomes in many chronic diseases, but little is known about health literacy in chronic obstructive pulmonary disease (COPD).

OBJECTIVE

To examine the associations between health literacy and both outcomes and health status in COPD.

PARTICIPANTS, DESIGN AND MAIN MEASURES

Structured interviews were administered to 277 subjects with self-report of physician-diagnosed COPD, recruited through US random-digit telephone dialing. Health literacy was measured with a validated three-item battery. Multivariable linear regression, controlling for sociodemographics including income and education, determined the cross-sectional associations between health literacy and COPD-related health status: COPD Severity Score, COPD Helplessness Index, and Airways Questionnaire-20R [measuring respiratory-specific health-related quality of life (HRQoL)]. Multivariable logistic regression estimated associations between health literacy and COPD-related hospitalizations and emergency department (ED) visits.

KEY RESULTS

Taking socioeconomic status into account, poorer health literacy (lowest tertile compared to highest tertile) was associated with: worse COPD severity (+2.3 points; 95 % CI 0.3–4.4); greater COPD helplessness (+3.7 points; 95 % CI 1.6–5.8); and worse respiratory-specific HRQoL (+3.5 points; 95 % CI 1.8–4.9). Poorer health literacy, also controlling for the same covariates, was associated with higher likelihood of COPD-related hospitalizations (OR?=?6.6; 95 % CI 1.3–33) and COPD-related ED visits (OR?=?4.7; 95 % CI 1.5–15). Analyses for trend across health literacy tertiles were statistically significant (p?<?0.05) for all above outcomes.

CONCLUSIONS

Independent of socioeconomic status, poor health literacy is associated with greater COPD severity, greater COPD helplessness, worse respiratory-specific HRQoL, and higher odds of COPD-related emergency health-care utilization. These results underscore that COPD patients with poor health literacy may be at particular risk for poor health-related outcomes.     

Calcium Antagonists in Patients with Type 2 Diabetes and Hypertension

Hypertension is twice as common in patients with diabetes compared to those without diabetes. It accounts for up to 75% of cardiovascular disease risk leading to the substantial increase in morbidity and mortality. Control of blood pressure in people with diabetes has been shown in randomized controlled trials to decrease cardiovascular risk and improve outcome especially in preventing stroke. A target blood pressure goal of <130/80 mm Hg is currently recommended for patients with diabetes. However, less than 1/3 of these patients achieve such a goal. This is in part due to the inherent difficulty in controlling blood pressure in these patients where hypertension is usually associated with increased salt sensitivity, volume expansion and isolated systolic hypertension. Therefore, patients with diabetes usually require multiple medications for optimal blood pressure control. Calcium channel antagonists have been shown in large clinical trials to be both safe and effective in controlling blood pressure in diabetic patients and will continue to play a major role in the management of hypertension in this population, particularly in the combination therapy that these patients usually require.     

Change in Health Insurance Coverage After Liver Transplantation Can Be Associated with Worse Outcomes

Background

Health insurance coverage changes for many patients after liver transplantation, but the implications of this change on long-term outcomes are unclear.

Aims

To assess post-transplant patient and graft survival according to change in insurance coverage within 1 year of transplantation.

Methods

We queried the United Network for Organ Sharing for patients between ages 18–64 years undergoing liver transplantation in 2002–2016. Patients surviving?>?1 year were categorized by insurance coverage at transplantation and the 1-year transplant anniversary. Multivariable Cox regression characterized the association between coverage pattern and long-term patient or graft survival.

Results

Among 34,487 patients in the analysis, insurance coverage patterns included continuous private coverage (58%), continuous public coverage (29%), private to public transition (8%) and public to private transition (4%). In multivariable analysis of patient survival, continuous public insurance (HR 1.29, CI 1.22, 1.37, p?<?0.001), private to public transition (HR 1.17, CI 1.07, 1.28, p?<?0.001), and public to private transition (HR 1.14, CI 1.00, 1.29, p?=?0.044), were associated with greater mortality hazard, compared to continuous private coverage. After disaggregating public coverage by source, mortality hazard was highest for patients transitioning from private insurance to Medicaid (HR vs. continuous private coverage?=?1.32; 95% CI 1.14, 1.52; p?<?0.001). Similar differences by insurance category were found for death-censored graft failure.

Conclusion

Post-transplant transition to public insurance coverage is associated with higher risk of adverse outcomes when compared to retaining private coverage.

     

Engagement and Outcomes Associated with Contextual Annotation Features of a Digital Health Solution

Background:Digital health solutions targeting diabetes self-care are popular and promising, but important questions remain about how these tools can most effectively help patients. Consistent with evidence of the salutary effects of note-taking in education, features that enable annotation of structured data entry might enhance the meaningfulness of the interaction, thereby promoting persistent use and benefits of a digital health solution.Method:To examine the potential benefits of note-taking, we explored how patients with type 2 diabetes used annotation features of a digital health solution and assessed the relationship between annotation and persistence in engagement as well as improvements in glycated hemoglobin (A1C). Secondary data from 3142 users of the BlueStar digital health solution collected between December 2013 and June 2017 were analyzed, with a subgroup of 372 reporting A1C lab values.Results:About a third of patients recorded annotations while using the platform. Annotation themes largely reflected self-management behaviors (diet, physical activity, medication adherence) and well-being (mood, health status). Early use of contextual annotations was associated with greater engagement over time and with greater improvements in A1C.Conclusions:Our research provides preliminary evidence of the benefits of annotation features in a digital health solution. Future research is needed to assess the causal impact of note-taking and the moderating role of thematic content reflected in notes.     

钙通道阻滞剂对PTCA术后再狭窄的预防作用

经皮腔内冠脉成形术 (PTCA)广泛应用于缺血性心脏病的治疗 ,但术后再狭窄的发生限制了 PTCA的远期疗效。据统计 PTCA术后再狭窄率为 30 %～5 0 % ,且主要发生于术后 3～ 6个月内 [1,2 ]。再狭窄的机制目前尚未完全明确。深入研究再狭窄的发生机制并寻找有效预防再狭窄的手段已成为当前面临的重要课题。1　 PTCA术后再狭窄的机制PTCA术后再狭窄的发生主要包括以下病理生理机制 [3 ] :早期的血管弹性回缩 ;血小板聚集和附壁血栓形成 ;新生内膜增殖和细胞外基质形成 ;动脉慢性的几何形态变化 (即血管重塑 )等。再狭窄的病理生理过程开…     

The Role of Calcium Antagonists in Stroke Prevention

Lowering elevated blood pressure significantly reduces the risk of stroke, but whether any specific type of antihypertensive medication is better for this purpose, independent of blood pressure-lowering effects, is controversial. Compared with placebo or no treatment, the point estimate for stroke reduction is the largest with calcium antagonists; all such studies used dihydropyridine compounds. When all clinical trials published through December 2004 are combined in meta-analysis, stroke is not significantly reduced when an initial dihydropyridine or nondihydropyridine calcium antagonist is compared with an initial diuretic or P blocker, but when the two subclasses are combined, stroke reduction (9%) is significant. The risk of heart failure, however, is significantly increased (by 29%) with the initial calcium antagonist. These estimates may change as newer trials are reported.     

Long-Acting Calcium Antagonists in Patients with Coronary Artery Disease: A Meta-Analysis

Background

The use of calcium channel blockers (CCBs) in patients with coronary artery disease remains controversial, with reports of increased risk of myocardial infarction and all-cause mortality. Short-acting CCBs have an unfavorable hemodynamic profile. The role of long-acting CCBs in patients with coronary artery disease is unknown.

Methods

MEDLINE/CENTRAL/EMBASE database were searched from 1966 to August 2008 for randomized controlled trials of long-acting CCBs in patients with coronary artery disease with follow-up for at least 1 year. We extracted from the studies the baseline characteristics and 6 outcomes: all-cause mortality, cardiovascular mortality, nonfatal myocardial infarction, stroke, angina pectoris, and heart failure.

Results

Of the 100 randomized controlled trials of CCBs in patients with coronary artery disease, 15 studies evaluating 47,694 patients fulfilled our inclusion criteria. When compared with the comparison group (including placebo), CCBs were not associated with an increased risk of all-cause mortality (relative risk [RR] 0.99; 95% confidence interval [CI], 0.94-1.05), cardiovascular mortality (RR 1.03; 95% CI, 0.95-1.11), nonfatal myocardial infarction (RR 0.96; 95% CI, 0.87-1.06), or heart failure (RR 0.86; 95% CI, 0.71-1.05), and with a 21% reduction in the risk of stroke (95% CI, 0.70-0.89) and 18% reduction in the risk of angina pectoris (95% CI, 0.72-0.94). When compared with placebo, CCBs resulted in a 28% reduction in the risk of heart failure (95% CI, 0.73-0.92). The results were similar for both dihydropyridines and nondihydropyridine CCBs.

Conclusions

In patients with coronary artery disease, long-acting CCBs (either dihydropyridines or nondihydropyridines), were associated with a reduction in the risk of stroke, angina pectoris, and heart failure, with similar outcomes for other cardiovascular events as the comparison group.     

Health Outcomes Associated with Lung Function Decline and Respiratory Symptoms and Disease in a Community Cohort

Background: In workplace respiratory disease prevention, a thorough understanding is needed of the relative contributions of lung function loss and respiratory symptoms in predicting adverse health outcomes. Methods: Copenhagen City Heart Study respiratory data collected at 4 examinations (1976–2003) and morbidity and mortality data were used to investigate these relationships. With 15 or more years of follow-up for a hospital diagnosis of chronic obstructive pulmonary disease (COPD) morbidity, COPD or coronary heart disease (CHD) mortality, and all-cause mortality, risks for these outcomes were estimated in relation to asthma, chronic bronchitis, shortness of breath, and lung function level at examination 2 (1981–1983) or lung function decline established from examinations 1 (1976–1978) to 2 using 4 measures (FEV₁ slope, FEV₁ relative slope, American College of Occupational and Environmental Medicine's Longitudinal Normal Limit [LNL], or a limit of 90 milliliters per year [ml/yr]). These risks were estimated by hazard ratios (HR) and 95% confidence intervals (CI) adjusted for age, height-adjusted baseline forced expiratory volume in 1 second (FEV₁/height²), and height. Results: For COPD morbidity, the increasing trend in the HR (95% CI) by quartiles of the FEV₁ slope reached a maximum of 3.77 (2.76–5.15) for males, 6.12 (4.63–8.10) for females, and 4.14 (1.57–10.90) for never-smokers. Significant increasing trends were also observed for mortality, with females at higher risk. Conclusion: Lung function decline was associated with increased risk of COPD morbidity and mortality emphasizing the need to monitor lung function change over time in at-risk occupational populations.