Identifying acute coronary syndrome patients approaching end-of-life

Background

Acute coronary syndrome (ACS) is common in patients approaching the end-of-life (EoL), but these patients rarely receive palliative care. We compared the utility of a palliative care prognostic tool (Gold Standards Framework (GSF)) and the Global Registry of Acute Coronary Events (GRACE) score, to help identify patients approaching EoL.

Methods and Findings

172 unselected consecutive patients with confirmed ACS admitted over an eight-week period were assessed using prognostic tools and followed up for 12 months. GSF criteria identified 40 (23%) patients suitable for EoL care while GRACE identified 32 (19%) patients with ≥10% risk of death within 6 months. Patients meeting GSF criteria were older (p = 0.006), had more comorbidities (1.6±0.7 vs. 1.2±0.9, p = 0.007), more frequent hospitalisations before (p = 0.001) and after (0.0001) their index admission, and were more likely to die during follow-up (GSF+ 20% vs GSF- 7%, p = 0.03). GRACE score was predictive of 12-month mortality (C-statistic 0.75) and this was improved by the addition of previous hospital admissions and previous history of stroke (C-statistic 0.88).

Conclusions

This study has highlighted a potentially large number of ACS patients eligible for EoL care. GSF or GRACE could be used in the hospital setting to help identify these patients. GSF identifies ACS patients with more comorbidity and at increased risk of hospital readmission.     

Diabetes mellitus and mortality after acute coronary syndrome as a first or recurrent cardiovascular event

Background

Diabetes Mellitus (DM) is associated with adverse cardiovascular prognosis. However, the risk associated with DM may vary between individuals according to their overall cardiovascular risk burden. Therefore, we aimed to determine whether DM is associated with poor outcome in patients presenting with Acute Coronary Syndrome (ACS) according to the index episode being a first or recurrent cardiovascular event.

Methods and Findings

We conducted a retrospective analysis of a prospective cohort study involving 2499 consecutively admitted patients with confirmed ACS in 11 UK hospitals during 2003. Usual care was provided for all participants. Demographic factors, co-morbidity and treatment (during admission and at discharge) factors were recorded. The primary outcome was all cause mortality (median 2 year follow up), compared for cohorts with and without DM according to their prior cardiovascular disease (CVD) disease status. Adjusted analyses were performed with Cox proportional hazards regression analysis. Within the entire cohort, DM was associated with an unadjusted 45% increase in mortality. However, in patients free of a history of CVD, mortality of those with and without DM was similar (18.8% and 19.7% respectively; p = 0.74). In the group with CVD, mortality of patients with DM was significantly higher than those without DM (46.7% and 33.2% respectively; p<0.001). The age and sex adjusted interaction between DM and CVD in predicting mortality was highly significant (p = 0.002) and persisted after accounting for comorbidities and treatment factors (p = 0.006). Of patients free of CVD, DM was associated with smaller elevation of Troponin I (p<0.001). However in patients with pre-existing CVD Troponin I was similar (p = 0.992).

Conclusions

DM is only associated with worse outcome after ACS in patients with a pre-existing history of CVD. Differences in the severity of myocyte necrosis may account for this. Further investigation is required, though our findings suggest that aggressive primary prevention of CVD in patients with DM may have beneficially modified their first presentation with (and mortality after) ACS.     

Genome-wide assessment for genetic variants associated with ventricular dysfunction after primary coronary artery bypass graft surgery

Background

Postoperative ventricular dysfunction (VnD) occurs in 9–20% of coronary artery bypass graft (CABG) surgical patients and is associated with increased postoperative morbidity and mortality. Understanding genetic causes of postoperative VnD should enhance patient risk stratification and improve treatment and prevention strategies. We aimed to determine if genetic variants associate with occurrence of in-hospital VnD after CABG surgery.

Methods

A genome-wide association study identified single nucleotide polymorphisms (SNPs) associated with postoperative VnD in male subjects of European ancestry undergoing isolated primary CABG surgery with cardiopulmonary bypass. VnD was defined as the need for ≥2 inotropes or mechanical ventricular support after CABG surgery. Validated SNPs were assessed further in two replication CABG cohorts and meta-analysis was performed.

Results

Over 100 SNPs were associated with VnD (P<10⁻⁴), with one SNP (rs17691914) encoded at 3p22.3 reaching genome-wide significance (P_{additive model} = 2.14×10⁻⁸). Meta-analysis of validation and replication study data for 17 SNPs identified three SNPs associated with increased risk for developing postoperative VnD after adjusting for clinical risk factors. These SNPs are located at 3p22.3 (rs17691914, OR_{additive model} = 2.01, P = 0.0002), 3p14.2 (rs17061085, OR_{additive model} = 1.70, P = 0.0001) and 11q23.2 (rs12279572, OR_{recessive model} = 2.19, P = 0.001).

Conclusions

No SNPs were consistently associated with strong risk (OR_{additive model}>2.1) of developing in-hospital VnD after CABG surgery. However, three genetic loci identified by meta-analysis were more modestly associated with development of postoperative VnD. Studies of larger cohorts to assess these loci as well as to define other genetic mechanisms and related biology that link genetic variants to postoperative ventricular dysfunction are warranted.     

Presentation and outcome of tuberculous meningitis in a high HIV prevalence setting

Background

Mycobacterium tuberculosis is a common, devastating cause of meningitis in HIV-infected persons. Due to international rollout programs, access to antiretroviral therapy (ART) is increasing globally. Starting patients with HIV-associated tuberculous meningitis (TBM) on ART during tuberculosis (TB) treatment may increase survival in these patients. We undertook this study to describe causes of meningitis at a secondary-level hospital in a high HIV/TB co-infection setting and to determine predictors of mortality in patients with TBM.

Methods

A retrospective review of cerebrospinal fluid findings and clinical records over a six-month period (March 2009–August 2009). Definite, probable and possible TBM were diagnosed according to published case definitions.

Results

TBM was diagnosed in 120/211 patients (57%) with meningitis. In 106 HIV-infected patients with TBM, six-month all-cause mortality was lower in those who received antiretroviral therapy (ART) during TB treatment; hazard ratio = 0.30 (95% CI = 0.08–0.82). Factors associated with inpatient mortality in HIV-infected patients were 1) low CD4⁺ count at presentation; adjusted odds ratio (AOR) = 1.4 (95% confidence interval [CI] = 1.03–1.96) per 50 cells/µL drop in CD4⁺ count and, 2) higher British Medical Research Council TBM disease grade (2 or 3 versus 1); AOR = 4.8 (95% CI = 1.45–15.87).

Interpretation

Starting ART prior to or during TB treatment may be associated with lower mortality in patients with HIV-associated TBM. Advanced HIV and worse stage of TBM disease predict in-hospital mortality in patients presenting with TBM.     

Readmission rates of patients discharged against medical advice: a matched cohort study

Objective

We compared the readmission rates and the pattern of readmission among patients discharged against medical advice (AMA) to control patients discharged with approval over a one-year follow-up period.

Methods

A retrospective matched-cohort study of 656 patients(328 were discharged AMA) who were followed for one year after their initial hospitalization at an urban university-affiliated teaching hospital in Vancouver, Canada that serves a population with high prevalence of addiction and psychiatric disorders. Multivariate conditional logistic regression was used to examine the independent association of discharge AMA on 14-day related diagnosis hospital readmission. We fit a multivariate conditional negative binomial regression model to examine the readmission frequency ratio between the AMA and non-AMA group.

Principal Findings

AMA patients were more likely to be homeless (32.3% vs. 11%) and have co-morbid conditions such as psychiatric illnesses, injection drug use, HIV, hepatitis C and previous gastrointestinal bleeding. Patients discharged AMA were more likely to be readmitted: 25.6% vs. 3.4%, p<0.001 by day 14. The AMA group were more likely to be readmitted within 14 days with a related diagnosis than the non-AMA group (Adjusted Odds Ratio 12.0; 95% Confidence Interval [CI]: 3.7–38.9). Patients who left AMA were more likely to be readmitted multiple times at one year compared to the non-AMA group (adjusted frequency ratio 1.6; 95% CI: 1.3–2.0). There was also higher all-cause in-hospital mortality during the 12-month follow-up in the AMA group compared to non-AMA group (6.7% vs. 2.4%, p = 0.01).

Conclusions

Patients discharged AMA were more likely to be homeless and have multiple co-morbid conditions. At one year follow-up, the AMA group had higher readmission rates, were predisposed to multiple readmissions and had a higher in-hospital mortality. Interventions to reduce discharges AMA in high-risk groups need to be developed and tested.     

Incidence and severity of coronary artery disease in patients with atrial fibrillation undergoing first-time coronary angiography

Background

In standard reference sources, the incidence of coronary artery disease (CAD) in patients with atrial fibrillation (AF) ranged between 24 and 46.5%. Since then, the incidence of cardiovascular risk factors (CRF) has increased and modern treatment strategies (“pill in the pocket”) are only applicable to patients without structural heart disease. The aim of this study was to investigate the incidence and severity of CAD in patients with AF.

Methods

From January 2005 until December 2009, we included 261 consecutive patients admitted to hospital with paroxysmal, persistent or permanent AF in this prospective study. All patients underwent coronary angiography and the Framingham risk score (FRS) was calculated. Patients with previously diagnosed or previously excluded CAD were excluded.

Results

The overall incidence of CAD in patients presenting with AF was 34%; in patients >70 years, the incidence of CAD was 41%. The incidence of patients undergoing a percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) was 21%. Patients with CAD were older (73±8 years vs 68±10 years, p = 0.001), had significantly more frequent hypercholesterolemia (60% vs 30%, p<0.001), were more frequent smokers (26% vs 13%, p = 0.017) and suffered from angina more often (37% vs 2%, p<0.001). There was a significant linear trend among the FRS categories in percentage and the prevalence of CAD and PCI/CABG (p<0.0001).

Conclusions

The overall incidence of CAD in patients presenting with AF was relatively high at 34%; the incidence of PCI/CABG was 21%. Based upon increasing CRF in the western world, we recommend a careful investigation respecting the FRS to either definitely exclude or establish an early diagnosis of CAD – which could contribute to an early and safe therapeutic strategy considering type Ic antiarrhythmics and oral anticoagulation.     

Craniectomy for malignant cerebral infarction: prevalence and outcomes in US hospitals

Object

Randomized trials have demonstrated the efficacy of craniectomy for the treatment of malignant cerebral edema following ischemic stroke. We sought to determine the prevalence and outcomes related to this by using a national database.

Methods

Patient discharges with ischemic stroke as the primary diagnosis undergoing craniectomy were queried from the US Nationwide Inpatient Sample from 1999 to 2008. A subpopulation of patients was identified that underwent thrombolysis. Two primary end points were examined: in-hospital mortality and discharge to home/routine care. To facilitate interpretations, adjusted prevalence was calculated from the overall prevalence and two age-specific logistic regression models. The predictive margin was then generated using a multivariate logistic regression model to estimate the probability of in-hospital mortality after adjustment for admission type, admission source, length of stay, total hospital charges, chronic comorbidities, and medical complications.

Results

After excluding 71,996 patients with the diagnosis of intracranial hemorrhage and posterior intracranial circulation occlusion, we identified 4,248,955 adult hospitalizations with ischemic stroke as a primary diagnosis. The estimated rates of hospitalizations in craniectomy per 10,000 hospitalizations with ischemic stroke increased from 3.9 in 1999–2000 to 14.46 in 2007–2008 (p for linear trend<0.001). Patients 60+ years of age had in-hospital mortality of 44% while the 18–59 year old group was found to be 24%(p = 0.14). Outcomes were comparable if recombinant tissue plasminogen activator had been administered.

Conclusions

Craniectomy is being increasingly performed for malignant cerebral edema following large territory cerebral ischemia. We suspect that the increase in the annual incidence of DC for malignant cerebral edema is directly related to the expanding collection of evidence in randomized trials that the operation is efficacious when performed in the correct patient population. In hospital mortality is high for all patients undergoing this procedure.     

Safety and clinical outcome of thrombolysis in ischaemic stroke using a perfusion CT mismatch between 3 and 6 hours

Objective

It may be possible to thrombolyse ischaemic stroke (IS) patients up to 6 h by using penumbral imaging. We investigated whether a perfusion CT (CTP) mismatch can help to select patients for thrombolysis up to 6 h.

Methods

A cohort of 254 thrombolysed IS patients was studied. 174 (69%) were thrombolysed at 0–3 h by using non-contrast CT (NCCT), and 80 (31%) at 3–6 h (35 at 3–4.5 h and 45 at 4.5–6 h) by using CTP mismatch criteria. Symptomatic intracerebral haemorrhage (SICH), the mortality and the modified Rankin Score (mRS) were assessed at 3 months. Independent determinants of outcome in patients thrombolysed between 3 and 6 h were identified.

Results

The baseline characteristics were comparable in the two groups. There were no differences in SICH (3% v 4%, p = 0.71), any ICH (7% v 9%, p = 0.61), or mortality (16% v 9%, p = 0.15) or mRS 0–2 at 3 months (55% v 54%, p = 0.96) between patients thrombolysed at 0–3 h (NCCT only) or at 3–6 h (CTP mismatch). There were no significant differences in outcome between patients thrombolysed at 3–4.5 h or 4.5–6 h. The NIHSS score was the only independent determinant of a mRS of 0–2 at 3 months (OR 0.89, 95% CI 0.82–0.97, p = 0.007) in patients treated using CTP mismatch criteria beyond 3 h.

Conclusions

The use of a CTP mismatch model may help to guide thrombolysis decisions up to 6 h after IS onset.     

Decreased glomerular filtration rate is associated with mortality and cardiovascular events in patients with hypertension: a prospective study

Background

Few studies reported the associations between decreased glomerular filtration rate (GFR) and mortality, coronary heart disease (CHD), and stroke in hypertensive patients. We aim to assess the associations between GFR and mortality, CHD, and stroke in hypertensive patients and to evaluate whether low GFR can improve the prediction of these outcomes in addition to conventional cardiovascular risk factors.

Methods and Findings

This is an observational prospective study and 3,711 eligible hypertensive patients aged ≥5 years from rural areas of China were used for the present analysis. The associations between eGFR and outcomes, followed by a median of 4.9 years, were evaluated using Cox proportional hazards models adjusting for other potential confounders. Low eGFR was independently associated with risk of all-cause mortality, cardiovascular mortality, and incident stroke [multivariable adjusted hazard ratios (95% confidence intervals) for eGFR <60 ml/min/1.73 m² relative to eGFR ≥90 ml/min/1.73 m² were 1.824 (1.047–3.365), 2.371 (1.109–5.068), and 2.493 (1.193–5.212), respectively]. We found no independent association between eGFR and the risk of CHD. For 4-year all-cause and cardiovascular mortality, integrated discrimination improvement (IDI) was positive when eGFR were added to traditional risk factors (1.51%, P = 0.016, and 1.99%, P = 0.017, respectively). For stroke and CHD events, net reclassification improvements (NRI) were 5.9% (P = 0.012) and 1.8% (P = 0.083) for eGFR, respectively.

Conclusions

We have established an inversely independent association between eGFR and all-cause mortality, cardiovascular mortality, and stroke in hypertensive patients in rural areas of China. Further, addition of eGFR significantly improved the prediction of 4-year mortality and stroke over and above that of conventional risk factors. We recommend that eGFR be incorporated into prognostic assessment for patients with hypertension in rural areas of China.

Limitations

We did not have sufficient information on atrial fibrillation to control for the potential covariate. These associations should be further confirmed in future.     

Five-year prognosis in an incident cohort of people presenting with acute myocardial infarction

Background

Following an AMI, it is important for patients and their physicians to appreciate the subsequent risk of death, and the potential benefits of invasive cardiac procedures and secondary preventive therapy. Studies, to-date, have focused largely on high-risk populations. We wished to determine the risk of death in a population-derived cohort of 2,887 patients after a first acute myocardial infarction (AMI).

Methods

Logistic regression and survival analysis were conducted to investigate the effect of different baseline characteristics, pharmacological therapies and revascularization procedures on coronary heart disease (CHD) and all-cause mortality outcomes.

Results

Within five years 44.4% of patients died (27.1% short-term [<30 days] and 23.7% longer-term [≥30 days]). Percutaneous transluminal coronary angioplasty (Adjusted Hazards Ratio (AHR) = 0.49, 95% Confidence Interval (CI) 0.26–0.93), β-blockers (AHR = 0.58, 95%CI 0.46–0.74) and statins (AHR = 0.60, 95%CI 0.47–0.77) were all associated with significant reductions in longer-term CHD-related mortality. However, not all patients received secondary preventive therapy (8.7%). Diabetes (AHR = 1.83, 95%CI 1.43–2.34), stroke (AHR = 1.73, 95%CI 1.35–2.22), heart failure (AHR = 1.69, 95%CI 1.28–2.22), smoking (AHR = 1.72, 95%CI 1.18–2.51) and obesity (>30 kg/m2; AHR = 1.39, 95%CI 1.01–1.90) increased the risk of longer-term mortality independent of other risk factors.

Conclusions

It is encouraging that the coronary procedure PTCA and pharmacological secondary prevention therapies were found to be strongly associated with an important reduced risk of subsequent death, although not all patients received these interventions. Smoking, being obese and having cardiovascular related disease at baseline were also associated with an increased likelihood of longer-term mortality, independent of other baseline characteristics. Thus, the provision of smoking cessation, advice on diet (for obese patients) and optimal treatment is likely to be crucial for reducing mortality in all patients after AMI.     

Effects of preoperative aspirin on cardiocerebral and renal complications in non-emergent cardiac surgery patients: a sub-group and cohort study

Background and Objective

Postoperative cardiocerebral and renal complications are a major threat for patients undergoing cardiac surgery. This study was aimed to examine the effect of preoperative aspirin use on patients undergoing cardiac surgery.

Methods

An observational cohort study was performed on consecutive patients (n = 1879) receiving cardiac surgery at this institution. The patients excluded from the study were those with preoperative anticoagulants, unknown aspirin use, or underwent emergent cardiac surgery. Outcome events included were 30-day mortality, renal failure, readmission and a composite outcome - major adverse cardiocerebral events (MACE) that include permanent or transient stroke, coma, perioperative myocardial infarction (MI), heart block and cardiac arrest.

Results

Of all patients, 1145 patients met the inclusion criteria and were divided into two groups: those taking (n = 858) or not taking (n = 287) aspirin within 5 days preceding surgery. Patients with aspirin presented significantly more with history of hypertension, diabetes, peripheral arterial disease, previous MI, angina and older age. With propensity scores adjusted and multivariate logistic regression, however, this study showed that preoperative aspirin therapy (vs. no aspirin) significantly reduced the risk of MACE (8.4% vs. 12.5%, odds ratio [OR] 0.585, 95% CI 0.355–0.964, P = 0.035), postoperative renal failure (2.6% vs. 5.2%, OR 0.438, CI 0.203–0.945, P = 0.035) and dialysis required (0.8% vs. 3.1%, OR 0.230, CI 0.071–0.742, P = 0.014), but did not significantly reduce 30-day mortality (4.1% vs. 5.8%, OR 0.744, CI 0.376–1.472, P = 0.396) nor it increased readmissions in the patients undergoing cardiac surgery.

Conclusions

Preoperative aspirin therapy is associated with a significant decrease in the risk of MACE and renal failure and did not increase readmissions in patients undergoing non-emergent cardiac surgery.     

Cardiovascular events in patients received combined fibrate/statin treatment versus statin monotherapy: Acute Coronary Syndrome Israeli Surveys data

Background

The effect of combination of fibrate with statin on major adverse cardiovascular events (MACE) following acute coronary syndrome (ACS) hospitalization is unclear. The main aim of this study was to investigate the 30-day rate of MACE in patients who participated in the nationwide ACS Israeli Surveys (ACSIS) and were treated on discharge with a fibrate (mainly bezafibrate) and statin combination vs. statin alone.

Methods

The study population comprised 8,982 patients from the ACSIS 2000, 2002, 2004, 2006, 2008 and 2010 enrollment waves who were alive on discharge and received statin. Of these, 8,545 (95%) received statin alone and 437 (5%) received fibrate/statin combination. MACE was defined as a composite measure of death, recurrent MI, recurrent ischemia, stent thrombosis, ischemic stroke and urgent revascularization.

Results

Patients from the combination group were younger (58.1±11.9 vs. 62.9±12.6 years). However, they had significantly more co-morbidities (hypertension, diabetes), current smokers and unfavorable cardio-metabolic profiles (with respect to glucose, total cholesterol, triglyceride and HDL-cholesterol). Development of MACE was recorded in 513 (6.0%) patients from the statin monotherapy group vs. 13 (3.2%) from the combination group, p = 0.01. 30-day re-hospitalization rate was significantly lower in the combination group: 68 (15.6%) vs. 1691 (19.8%) of patients, respectively; p = 0.03. Multivariable analysis identified the fibrate/statin combination as an independent predictor of reduced risk of MACE with odds ratio of 0.54, 95% confidence interval 0.32–0.94.

Conclusion

A significantly lower risk of 30-day MACE rate was observed in patients receiving combined fibrate/statin treatment following ACS compared with statin monotherapy. However, caution should be exercised in interpreting these findings taking into consideration baseline differences between our observational study groups.     

Carotid artery stenting: a single center "real world" experience

Background

Percutaneous carotid artery stenting (CAS) became a widely used procedure in patients with symptomatic and asymptomatic carotid artery stenosis. However its role compared to carotid endarterectomy (CAD) remains questioned. We analysed the safety of carotid artery stenting program of a prospective CAS register program of a tertiary teaching hospital.

Method

Between July 2003 and December 2010, 208 patients underwent CAS procedure. Baseline, procedural and follow-up data were prospectively collected. Primary peri-interventional outcome was defined as 30-day major adverse events (MAE), including death, stroke or myocardial infarction, and mid- to long-term follow-up outcome included ipsilateral stroke, myocardial infarction or death. Secondary outcome was restenosis rate ≥50% per lesion.

Results

Unilateral carotid artery interventions were performed in 186 patients. In 22 patients CAS was performed bilaterally as stages procedures. The 30-day MAE rate was 1.9% consisting of two contralateral strokes and two ipsilateral stroke. Mean clinically follow-up was 22 months. Mid- to long-term MAE was 8.1% with 6.3% (n = 13) deaths, 1.9% (n = 4) myocardial infarctions and 0.9% (n = 2) ipsilateral stroke. The restenosis rate ≥50% per lesion was 4.3% at a mean follow-up of 22 months. Target lesion revascularization was performed in one patient, because of restenosis at 9 months follow-up after first CAS.

Conclusion

Implementation of a carotid artery stenting program at a tertiary, teaching hospital is a safe method for treatment of carotid artery stenosis. The adverse event rate during mid-to-long-term follow-up suggests an appropriate patient selection.     

Aromatase gene polymorphisms are associated with survival among patients with cardiovascular disease in a sex-specific manner

Introduction

CYP19A1 encodes aromatase, the enzyme responsible for the conversion of androgens to estrogens, and may play a role in variation in outcomes among men and women with cardiovascular disease. We sought to examine genetic variation in CYP19A1 for its potential role in sex differences in cardiovascular disease outcomes.

Methods

Caucasian individuals from two independent populations were assessed: 1) a prospective cohort of patients with acute coronary syndromes with 3-year mortality follow-up (n = 568) and 2) a nested case-control study from a randomized, controlled trial of hypertension patients with stable coronary disease in which the primary outcome was death, nonfatal myocardial infarction (MI) or nonfatal stroke (n = 619). Six CYP19A1 SNPs were genotyped (-81371 C>T, -45965 G>C, M201T, R264C, 80 A>G, and +32226 G>A). The sex*genotype interaction term was assessed for the primary outcome and compared by genotype in men and women when a significant interaction term was identified.

Results

We identified a significant interaction between -81371 C>T and sex (p = 0.025) in the ACS population. The variant allele was associated with a 78% increase in mortality in men (HR 1.78, 95% confidence interval [CI] 1.08-2.94) and a nonsignificant 42% decrease in mortality among women (HR 0.58, 95% CI 0.22-1.54). We identified a similar association in the hypertensive CAD group, the -81371 C>T*sex interaction term was p<0.0001, with an associated 65% increase in death, MI, or stroke (HR 1.65, 95% CI 1.00-2.73) in men and a 69% decrease (HR 0.31, 95% CI 0.16-0.6) in women.

Conclusions

Using two independent populations, this study is the first to document a significant interaction between CYP19A1 genotype and sex on cardiovascular outcomes. These findings could illuminate potential mechanisms of sex differences in cardiovascular disease outcomes.     

Chronic kidney disease itself is a causal risk factor for stroke beyond traditional cardiovascular risk factors: a nationwide cohort study in Taiwan

Background

Cardiovascular disease (CVD) is a leading cause of mortality and morbidity in patients with chronic kidney disease (CKD). In Taiwan, CVD is dominated by strokes but there is no robust evidence for a causal relationship between CKD and stroke. This study aimed to explore such causal association.

Methods

We conducted a nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database from 2004 to 2007. Each patient identified was individually tracked for a full three years from the index admission to identify those in whom any type of stroke developed. The study cohort consisted of patients hospitalized with a principal diagnosis of CKD and no traditional cardiovascular risk factors at baseline (n = 1393) and an age-matched control cohort of patients hospitalized for appendectomies (n = 1393, a surrogate for the general population). Cox proportional hazard regression and propensity score model were used to compare the three-year stroke-free survival rate of the two cohorts after adjustment for possible confounding factors.

Results

There were 256 stroke patients, 156 (11.2%) in the study cohort and 100 (7.2%) in the control cohort. After adjusting for covariates, patients with primary CKD had a 1.94-fold greater risk for stroke (95% CI, 1.45–2.60; p<0.001) based on Cox regression and a 1.68-fold greater risk for stroke (95% CI, 1.25–2.25; p = 0.001) based on propensity score. This was still the case for two cohorts younger than 75 years old and without traditional cardiovascular risk factors.

Conclusions

This study of Taiwanese patients indicates that CKD itself is a causal risk factor for stroke beyond the traditional cardiovascular risk factors. Primary CKD patients have higher risk for stroke than the general population and all CKD patients, irrespective of the presence or severity of traditional cardiovascular risk factors, should be made aware of the stroke risk and monitored for stroke prevention.     

Initial presentations predict mortality in pulmonary tuberculosis patients--a prospective observational study

Background

Despite effective anti-TB treatments, tuberculosis remains a serious threat to public health and is associated with high mortality. Old age and multiple co-morbidities are known risk factors for death. The association of clinical presentations with mortality in pulmonary tuberculosis patients remains an issue of controversy.

Methods

This prospective observational study enrolled newly diagnosed, culture-proven pulmonary tuberculosis patients from five medical centers and one regional hospital, which were referral hospitals of TB patients. Radiographic findings and clinical symptoms were determined at the time of diagnosis. Patients who died for any reason during the course of anti-TB treatment were defined as mortality cases and death that occurred within 30 days of initiating treatment was defined as early mortality. Clinical factors associated with overall mortality and early mortality were investigated.

Results

A total of 992 patients were enrolled and 195 (19.7%) died. Nearly one-third (62/195, 31.8%) of the deaths occurred before or within 30 days of treatment initiation. Older age (RR = 1.04, 95%CI: 1.03–1.05), malignancy (RR = 2.42, 95%CI: 1.77–3.31), renal insufficiency (RR = 1.77, 95%CI: 1.12–2.80), presence of chronic cough (RR = 0.63, 95%CI: 0.47–0.84), fever (RR = 1.45, 95%CI: 1.09–1.94), and anorexia (RR = 1.49, 95%CI: 1.07–2.06) were independently associated with overall mortality. Kaplan-Meier survival analysis demonstrated significantly higher mortality in patients present with fever (p<0.001), anorexia (p = 0.005), and without chronic cough (p<0.001). Among patients of mortality, those with respiratory symptoms of chronic cough (RR = 0.56, 95%CI: 0.33–0.98) and dyspnea (HR = 0.51, 95%CI: 0.27–0.98) were less likely to experience early mortality. The radiological features were comparable between survivors and non-survivors.

Conclusions

In addition to demographic characteristics, clinical presentations including the presence of fever, anorexia, and the absence of chronic cough, were also independent predictors for on-treatment mortality in pulmonary tuberculosis patients.     

Preventive antibacterial therapy in acute ischemic stroke: a randomized controlled trial

Background

Pneumonia is a major risk factor of death after acute stroke. In a mouse model, preventive antibacterial therapy with moxifloxacin not only prevents the development of post-stroke infections, it also reduces mortality, and improves neurological outcome significantly. In this study we investigate whether this approach is effective in stroke patients.

Methods

Preventive ANtibacterial THERapy in acute Ischemic Stroke (PANTHERIS) is a randomized, double-blind, placebo-controlled trial in 80 patients with severe, non-lacunar, ischemic stroke (NIHSS>11) in the middle cerebral artery (MCA) territory. Patients received either intravenous moxifloxacin (400 mg daily) or placebo for 5 days starting within 36 hours after stroke onset. Primary endpoint was infection within 11 days. Secondary endpoints included neurological outcome, survival, development of stroke-induced immunodepression, and induction of bacterial resistance.

Findings

On intention-to treat analysis (79 patients), the infection rate at day 11 in the moxifloxacin treated group was 15.4% compared to 32.5% in the placebo treated group (p = 0.114). On per protocol analysis (n = 66), moxifloxacin significantly reduced infection rate from 41.9% to 17.1% (p = 0.032). Stroke associated infections were associated with a lower survival rate. In this study, neurological outcome and survival were not significantly influenced by treatment with moxifloxacin. Frequency of fluoroquinolone resistance in both treatment groups did not differ. On logistic regression analysis, treatment arm as well as the interaction between treatment arm and monocytic HLA-DR expression (a marker for immunodepression) at day 1 after stroke onset was independently and highly predictive for post-stroke infections.

Interpretation

PANTHERIS suggests that preventive administration of moxifloxacin is superior in reducing infections after severe non-lacunar ischemic stroke compared to placebo. In addition, the results emphasize the pivotal role of immunodepression in developing post-stroke infections.

Trial Registration

Controlled-Trials.com ISRCTN74386719     

Sickness Absence following Coronary Revascularisation. A National Study of Women and Men of Working Age in Sweden 1994-2006

Background

Evidence based and gender specific knowledge about sickness absence following coronary revascularisation is lacking. The objective was to investigate sickness absence after a first coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) among women and men in a national Swedish study.

Materials and Methods

All patients 30–63 years of age, who underwent a first CABG (n = 22,985, 16% women) or PCI (40,891, 22% women) in Sweden between 1994 and 2006 were included. Information on sickness absence, co-morbidity, and other patient characteristics was obtained from national registers. Long-term sickness absence (LTSA) was defined as >180 and >90 sick-leave days in the first sick-leave spell following CABG and PCI, respectively. Prevalence ratio (PR) and 95% confidence interval (CI) of LTSA were calculated.

Findings

LTSA followed the interventions in 41% and 36% for CABG and PCI patients, respectively. Women had more often LTSA compared with men, (CABG PR = 1.23: 95% CI 1.19–1.28 and PCI PR = 1.19; 95% CI 1.16–1.23). A history of sickness absence the year before the intervention increased the risk for LTSA after the intervention in both genders. Among women, older age, or being self employed or unemployed was associated with a lower risk for LTSA. Among men previous cardiovascular disease, diabetes and low socio-economic position increased the risk. During the observation period, there was no change in sickness absence rates among PCI patients but an increase among CABG patients adjusting for patient characteristics.

Conclusion

This national study covering a 13-year period shows that long-term sickness absence following coronary revascularisation is common in Sweden, especially among women, and is associated with socio-economic position, co-morbidity, and sickness absence during the year before the intervention. Gender specific scientific knowledge about use and effects of sickness absence following coronary revascularisation is warranted for the patients, the treating physicians, the healthcare sector, and the society.