Pulmonary embolism and 3-month outcomes in 4036 patients with venous thromboembolism and chronic obstructive pulmonary disease: data from the RIETE registry

Background

Patients with chronic obstructive pulmonary disease (COPD) have a modified clinical presentation of venous thromboembolism (VTE) but also a worse prognosis than non-COPD patients with VTE. As it may induce therapeutic modifications, we evaluated the influence of the initial VTE presentation on the 3-month outcomes in COPD patients.

Methods

COPD patients included in the on-going world-wide RIETE Registry were studied. The rate of pulmonary embolism (PE), major bleeding and death during the first 3 months in COPD patients were compared according to their initial clinical presentation (acute PE or deep vein thrombosis (DVT)).

Results

Of the 4036 COPD patients included, 2452 (61%; 95% CI: 59.2-62.3) initially presented with PE. PE as the first VTE recurrence occurred in 116 patients, major bleeding in 101 patients and mortality in 443 patients (Fatal PE: first cause of death). Multivariate analysis confirmed that presenting with PE was associated with higher risk of VTE recurrence as PE (OR, 2.04; 95% CI: 1.11-3.72) and higher risk of fatal PE (OR, 7.77; 95% CI: 2.92-15.7).

Conclusions

COPD patients presenting with PE have an increased risk for PE recurrences and fatal PE compared with those presenting with DVT alone. More efficient therapy is needed in this subtype of patients.     

Correlates of in-hospital deaths among hospitalizations with pulmonary embolism: findings from the 2001-2008 National Hospital Discharge Survey

Background

Deep vein thrombosis and pulmonary embolism (PE) are responsible for substantial mortality, morbidity, and impaired health-related quality of life. The aim of this study was to evaluate the correlates of in-hospital deaths among hospitalizations with a diagnosis of PE in the United States.

Methods

By using data from the 2001−2008 National Hospital Discharge Survey, we assessed the correlates of in-hospital deaths among 14,721 hospitalizations with a diagnosis of PE and among subgroups stratified by age, sex, race, days of hospital stay, type of admission, cancer, pneumonia, and fractures. We produced adjusted rate ratios (aRR) and 95% confidence intervals using log-linear multivariate regression models.

Results

Regardless of the listing position of diagnostic codes, we observed an increased likelihood of in-hospital death in subgroups of hospitalizations with ages 50 years and older (aRR = 1.82−8.48), less than 7 days of hospital stay (aRR = 1.43−1.57), cancer (aRR = 2.10−2.28), pneumonia (aRR = 1.79−2.20), or fractures (aRR = 2.18) (except for first-listed PE), when compared to the reference groups with ages 1−49 years, 7 days or more of hospital stay, without cancer, pneumonia, or fractures while adjusting for covariates. In addition, we observed an increased likelihood of in-hospital death for first-listed PE in hospitalizations of women, when compared to those of men (aRR = 1.45).

Conclusions

The results of this study provide support for identifying, developing, and implementing effective, evidence-based clinical assessment and management strategies to reduce PE-related morbidity and mortality among hospitalized PE patients who may have concurrent health conditions including cancer, pneumonia, and fractures.     

Determinants of Venous Thromboembolism among Hospitalizations of US Adults: A Multilevel Analysis

Background

Venous thromboembolism (VTE) is a significant clinical and public health concern. We evaluated a variety of multilevel factors—demographics, clinical and insurance status, preexisting comorbid conditions, and hospital characteristics—for VTE diagnosis among hospitalizations of US adults.

Methods

We generated adjusted odds ratios with 95% confidence intervals (CIs) and determined sources of outcome variation by conducting multilevel logistic regression analysis of data from the 2011 Nationwide Inpatient Sample that included 6,710,066 hospitalizations of US adults nested within 1,039 hospitals.

Results

Among hospitalizations of adults, age, sex, race or ethnicity, total days of hospital stay, status of health insurance, and operating room procedure were important determinants of VTE diagnosis; each of the following preexisting comorbid conditions—acquired immune deficiency syndrome, anemia, arthritis, congestive heart failure, coagulopathy, hypertension, lymphoma, metastatic cancer, other neurological disorders, obesity, paralysis, pulmonary circulation disorders, renal failure, solid tumor without metastasis, and weight loss—was associated independently with 1.04 (95% CI: 1.02−1.06) to 2.91 (95% CI: 2.81−3.00) times increased likelihood of VTE diagnosis than among hospitalizations of adults without any of these corresponding conditions. The presence of 2 or more of such conditions was associated a 180%−450% increased likelihood of a VTE diagnosis. Hospitalizations of adults who were treated in urban hospitals were associated with a 14%−15% increased likelihood of having a VTE diagnosis than those treated in rural hospitals. Approximately 7.4% of the total variation in VTE diagnosis occurred between hospitals.

Conclusion

The presence of certain comorbidities and hospital contextual factors is associated with significantly elevated likelihood of VTE diagnosis among hospitalizations of adults. The findings of this study underscore the importance of clinical risk assessment and adherence to evidence-based clinical practice guidelines in preventing VTE, as well as the need to evaluate potential contextual factors that might modify the risk of VTE among hospitalized patients.     

An Economic Evaluation of Venous Thromboembolism Prophylaxis Strategies in Critically Ill Trauma Patients at Risk of Bleeding

Background

Critically ill trauma patients with severe injuries are at high risk for venous thromboembolism (VTE) and bleeding simultaneously. Currently, the optimal VTE prophylaxis strategy is unknown for trauma patients with a contraindication to pharmacological prophylaxis because of a risk of bleeding.

Methods and Findings

Using decision analysis, we estimated the cost effectiveness of three VTE prophylaxis strategies—pneumatic compression devices (PCDs) and expectant management alone, serial Doppler ultrasound (SDU) screening, and prophylactic insertion of a vena cava filter (VCF)—in trauma patients admitted to an intensive care unit (ICU) with severe injuries who were believed to have a contraindication to pharmacological prophylaxis for up to two weeks because of a risk of major bleeding. Data on the probability of deep vein thrombosis (DVT) and pulmonary embolism (PE), and on the effectiveness of the prophylactic strategies, were taken from observational and randomized controlled studies. The probabilities of in-hospital death, ICU and hospital discharge rates, and resource use were taken from a population-based cohort of trauma patients with severe injuries (injury severity scores >12) admitted to the ICU of a regional trauma centre. The incidence of DVT at 12 weeks was similar for the PCD (14.9%) and SDU (15.0%) strategies, but higher for the VCF (25.7%) strategy. Conversely, the incidence of PE at 12 weeks was highest in the PCD strategy (2.9%), followed by the SDU (1.5%) and VCF (0.3%) strategies. Expected mortality and quality-adjusted life years were nearly identical for all three management strategies. Expected health care costs at 12 weeks were Can$55,831 for the PCD strategy, Can$55,334 for the SDU screening strategy, and Can$57,377 for the VCF strategy, with similar trends noted over a lifetime analysis.

Conclusions

The attributable mortality due to PE in trauma patients with severe injuries is low relative to other causes of mortality. Prophylactic placement of VCF in patients at high risk of VTE who cannot receive pharmacological prophylaxis is expensive and associated with an increased risk of DVT. Compared to the other strategies, SDU screening was associated with better clinical outcomes and lower costs. Please see later in the article for Editors'' Summary     

DVT Surveillance Program in the ICU: Analysis of Cost-Effectiveness

Background

Venous Thrombo-embolism (VTE – Deep venous thrombosis (DVT) and/or pulmonary embolism (PE) – in traumatized patients causes significant morbidity and mortality. The current study evaluates the effectiveness of DVT surveillance in reducing PE, and performs a cost-effectiveness analysis.

Methods

All traumatized patients admitted to the adult ICU underwent twice weekly DVT surveillance by bilateral lower extremity venous Duplex examination (48-month surveillance period – SP). The rates of DVT and PE were recorded and compared to the rates observed in the 36-month pre-surveillance period (PSP). All patients in both periods received mechanical and pharmacologic prophylaxis unless contraindicated. Total costs – diagnostic, therapeutic and surveillance – for both periods were recorded and the incremental cost for each Quality Adjusted Life Year (QALY) gained was calculated.

Results

4234 patients were eligible (PSP – 1422 and SP – 2812). Rate of DVT in SP (2.8%) was significantly higher than in PSP (1.3%) – p<0.05, and rate of PE in SP (0.7%) was significantly lower than that in PSP (1.5%) – p<0.05. Logistic regression demonstrated that surveillance was an independent predictor of increased DVT detection (OR: 2.53 – CI: 1.462–4.378) and decreased PE incidence (OR: 0.487 – CI: 0.262–0.904). The incremental cost was $509,091/life saved in the base case, translating to $29,102/QALY gained. A sensitivity analysis over four of the parameters used in the model indicated that the incremental cost ranged from $18,661 to $48,821/QALY gained.

Conclusions

Surveillance of traumatized ICU patients increases DVT detection and reduces PE incidence. Costs in terms of QALY gained compares favorably with other interventions accepted by society.     

Atherosclerotic cardiovascular disease and dermatomyositis: an analysis of the Nationwide Inpatient Sample survey

Introduction

Increased rates of cardiovascular disease are implicated in several rheumatologic diseases. Our aim was to characterize dermatomyositis hospitalizations and evaluate cardiovascular-associated mortality in this patient population.

Methods

We examined the frequency and mortality rates of several atherosclerotic cardiovascular diagnoses and procedures among hospitalized adult patients with dermatomyositis using data from the US Nationwide Inpatient Sample (NIS) from 1993 to 2007. We compared the odds of death among hospitalized dermatomyositis patients with each cardiovascular diagnosis or procedure to those without, as well as to controls with cardiovascular diagnoses, using logistic regression.

Results

A total of 50,322 hospitalizations of dermatomyositis patients occurred between 1993 and 2007 (mean age 58 years, and 73% female). Of all dermatomyositis hospitalizations, 20% were associated with a concurrent atherosclerotic cardiovascular diagnosis or procedure. The overall in-hospital mortality was 5.7%. Dermatomyositis patients with any associated atherosclerotic cardiovascular diagnosis or procedure were twice as likely to die during the inpatient stay compared to dermatomyositis patients who did not have atherosclerotic cardiovascular disease (OR = 2.0 95% CI 1.7-2.5, p < 0.0001). The odds ratio for death in patients with both dermatomyositis and cardiovascular disease compared to controls with cardiovascular disease alone was 1.98 (95% CI 1.57-2.48) in multivariate adjusted models.

Conclusions

Approximately one fifth of dermatomyositis hospitalizations in the US were associated with an atherosclerotic cardiovascular diagnosis or procedure. These patients have double the risk of in-hospital death in comparison with controls and dermatomyositis patients without a cardiovascular diagnosis, making identification of these groups important for both prognostic purposes and clinical care.     

Reduction of Thromboembolic Events in Meningioma Surgery: A Cohort Study of 724 Consecutive Patients

Background

Meningiomas are associated with the highest postoperative rate of venous thromboembolic events (VTE) among all intracranial tumors. The aim of this study is to compare two entirely different VTE prophylaxis regimens in 724 consecutive patients undergoing meningioma surgery.

Methods

Two cohorts at a single institution treated with different regimens to prevent VTE were reviewed retrospectively. Cohort A (n = 482; 314 females, mean age 57 years, range: 11–87 years) received our institutional regimen during the years 1999–2006, consisting of low-molecular-weight heparin (LMWH) and compression stockings. For cohort B (n = 242; 163 females, mean age 56.8 years, range: 16–90 years), during the years 2008–2010, the management included intraoperative 10°–20° leg elevation with intermittent pneumatic compression (IPC), heparin and LMWH administration. We compared the incidence of the endpoints pulmonary embolism (PE), deep venous thrombosis (DVT), hemorrhage and death, taking into account several known associated risk factors.

Results

For all endpoints, we observed a more favorable outcome with the new regimen. The difference in incidence of PEs (cohort A: 38/482, 8%; cohort B: 6/242, 2.5%) reached statistical significance (p = 0.002). In general, patients with skull base meningiomas had a higher risk for PE (OR 2.77). Regarding VTE prophylaxis, an adjusted subgroup analysis suggests that the new regimen is particularly beneficial for patients with skull base meningiomas.

Conclusions

We recommend perioperative prophylaxis using a management composed of intraoperative leg-elevation, IPC, early heparin administration and LMWH to reduce the risk for PE.     

A clinical in-hospital prognostic score for acute exacerbations of COPD

Background

The use of a severity score to help orientation decisions could improve the efficiency of care for acute exacerbations of COPD (AECOPD). We previously developed a score (‘2008 score’, based on age, dyspnea grade at steady state and number of clinical signs of severity) predicting in-hospital mortality in patients with AECOPD visiting emergency departments (EDs). External validity of this score remained to be assessed.

Objectives

To test the predictive properties of the ‘2008 score’ in a population of patients hospitalized in medical respiratory wards for AECOPD, and determine whether a new score specifically derived from this population would differ from the previous score in terms of components or predictive performance.

Methods

Data from a cohort study in 1824 patients hospitalized in a medical ward for an AECOPD were analyzed. Patients were categorized using the 2008 score and its predictive characteristics for in-hospital mortality rates were assessed. A new score was developed using multivariate logistic regression modeling in a randomly selected derivation population sample followed by testing in the remaining population (validation sample). Robustness of results was assessed by case-by-case validation.

Results

The 2008 score was characterized by a c-statistic at 0.77, a sensitivity of 69% and a specificity of 76% for prediction of in-hospital mortality. The new score comprised the same variables plus major cardiac comorbidities and was characterized by a c-statistic of 0.78, a sensitivity of 77% and specificity of 66%.

Conclusions

A score using simple clinical variables has robust properties for predicting the risk of in-hospital death in patients hospitalized for AECOPD. Adding cardiac comorbidities to the original score increased its sensitivity while decreasing its specificity.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-014-0099-9) contains supplementary material, which is available to authorized users.     

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.     

Prevalence of Comorbidities and Their Impact on Hospital Management and Short-Term Outcomes in Vietnamese Patients Hospitalized with a First Acute Myocardial Infarction

Background

Cardiovascular disease is one of the leading causes of morbidity and mortality in Vietnam. We conducted a pilot study of Hanoi residents hospitalized with a first acute myocardial infarction (AMI) at the Vietnam National Heart Institute in Hanoi for purposes of describing the prevalence of cardiovascular (CVD) and non-CVD comorbidities and their impact on hospital management, in-hospital clinical complications, and short-term mortality in these patients.

Methods

The study population consisted of 302 Hanoi residents hospitalized with a first AMI at the largest tertiary care medical center in Hanoi in 2010.

Results

The average age of study patients was 66 years and one third were women. The proportions of patients with none, any 1, and ≥ 2 CVD comorbidities were 34%, 42%, and 24%, respectively. Among the CVD comorbidities, hypertension was the most commonly reported (59%). There were decreasing trends in the proportion of patients who were treated with effective cardiac medications and coronary interventions as the number of CVD comorbidities increased. Patients with multiple CVD comorbidities tended to develop acute clinical complications and die at higher rates during hospitalization compared with patients with no CVD comorbidities (Odds Ratio: 1.40; 95% Confidence Interval: 0.40–4.84).

Conclusions

Our data suggest that patients with multiple cardiac comorbidities tended to experience high in-hospital death rates in the setting of AMI. Full-scale surveillance of Hanoi residents hospitalized with AMI at all Hanoi hospitals is needed to confirm these findings. Effective strategies to manage Vietnamese patients hospitalized with AMI who have multiple comorbidities are warranted to improve their short-term prognosis.     

Symptomatic and Incidental Venous Thromboembolic Disease Are Both Associated with Mortality in Patients with Prostate Cancer

Introduction

The association between malignancy and venous thromboembolic disease (VTE) is well established. The independent impact of VTE, both symptomatic and incidental, on survival in patients with prostate cancer is not known. We conducted a retrospective cohort study to evaluate the effect of VTE of survival in prostate cancer.

Methods

Data regarding clinical characteristics, treatment and outcomes of 453 consecutive prostate cancer patients were collected. Fisher exact (categorical variables) and t-test (continuous variables) were utilized to test associations with VTE and mortality. Survival was estimated using the Kaplan Meier method. A Cox regression model was used to model the mortality hazard ratio (HR).

Results

At diagnosis, 358 (83%) patients had early stage disease, 43 (10%) had locally advanced disease and 32 (7%) had metastatic disease. During the follow up period, 122 (27%) patients died and 41 (9%) developed VTE (33 deep vein thrombosis, 5 pulmonary embolism, and 3 patients with both DVT and PE). Twenty-five VTE events were symptomatic and 16 were incidentally diagnosed on CT scans obtained for other reasons. VTE was associated with increased mortality [HR 6.89 (4.29–11.08), p<0.001] in a multivariable analysis adjusted for cancer stage, performance status, treatments and co-morbidities. There was no difference in survival between patients who had symptomatic and incidental VTE.

Conclusion

Venous thromboembolic disease, both symptomatic and incidental, is a predictor of poor survival in patients with prostate cancer, especially those with advanced disease. Further studies are needed to evaluate the benefit of prophylactic and therapeutic anticoagulation in this population.     

Influenza Pneumonia Surveillance among Hospitalized Adults May Underestimate the Burden of Severe Influenza Disease

Background

Studies seeking to estimate the burden of influenza among hospitalized adults often use case definitions that require presence of pneumonia. The goal of this study was to assess the extent to which restricting influenza testing to adults hospitalized with pneumonia could underestimate the total burden of hospitalized influenza disease.

Methods

We conducted a modelling study using the complete State Inpatient Databases from Arizona, California, and Washington and regional influenza surveillance data acquired from CDC from January 2003 through March 2009. The exposures of interest were positive laboratory tests for influenza A (H1N1), influenza A (H3N2), and influenza B from two contiguous US Federal Regions encompassing the study area. We identified the two outcomes of interest by ICD-9-CM code: respiratory and circulatory hospitalizations, as well as critical illness hospitalizations (acute respiratory failure, severe sepsis, and in-hospital death). We linked the hospitalization datasets with the virus surveillance datasets by geographic region and month of hospitalization. We used negative binomial regression models to estimate the number of influenza-associated events for the outcomes of interest. We sub-categorized these events to include all outcomes with or without pneumonia diagnosis codes.

Results

We estimated that there were 80,834 (95% CI 29,214–174,033) influenza-associated respiratory and circulatory hospitalizations and 26,760 (95% CI 14,541–47,464) influenza-associated critical illness hospitalizations. When a pneumonia diagnosis was excluded, the estimated number of influenza-associated respiratory and circulatory hospitalizations was 24,816 (95% CI 6,342–92,624). The estimated number of influenza-associated critical illness hospitalizations was 8,213 (95% CI 3,764–20,799). Around 30% of both influenza-associated respiratory and circulatory hospitalizations, as well as influenza-associated critical illness hospitalizations did not have pneumonia diagnosis codes.

Conclusions

Surveillance studies which only consider hospitalizations that include a diagnosis of pneumonia may underestimate the total burden of influenza hospitalizations.     

Bronchiectasis-Associated Hospitalizations in Germany, 2005–2011: A Population-Based Study of Disease Burden and Trends

Background

Representative population-based data on the epidemiology of bronchiectasis in Europe are limited. The aim of the present study was to investigate the current burden and the trends of bronchiectasis-associated hospitalizations and associated conditions in Germany in order to inform focused patient care and to facilitate the allocation of healthcare resources.

Methods

The nationwide diagnosis-related groups hospital statistics for the years 2005–2011 were used in order to identify hospitalizations with bronchiectasis as any hospital discharge diagnosis according to the International Classification of Diseases, 10th revision, code J47, (acquired) bronchiectasis. Poisson log-linear regression analysis was used to assess the significance of trends. In addition, the overall length of hospital stay (LOS) and the in-hospital mortality in comparison to the nationwide overall mortality due to bronchiectasis as the primary diagnosis was assessed.

Results

Overall, 61,838 records with bronchiectasis were extracted from more than 125 million hospitalizations. The average annual age-adjusted rate for bronchiectasis as any diagnosis was 9.4 hospitalizations per 100,000 population. Hospitalization rates increased significantly during the study period, with the highest rate of 39.4 hospitalizations per 100,000 population among men aged 75–84 years and the most pronounced average annual increases among females. Besides numerous bronchiectasis-associated conditions, chronic obstructive pulmonary disease (COPD) was most frequently found in up to 39.2% of hospitalizations with bronchiectasis as the primary diagnosis. The mean LOS was comparable to that for COPD. Overall, only 40% of bronchiectasis-associated deaths occurred inside the hospital.

Conclusions

The present study provides evidence of a changing epidemiology and a steadily increasing prevalence of bronchiectasis-associated hospitalizations. Moreover, it confirms the diversity of bronchiectasis-associated conditions and the possible association between bronchiectasis and COPD. As the major burden of disease may be managed out-of-hospital, prospective patient registries are needed to establish the exact prevalence of bronchiectasis according to the specific underlying condition.     

Intervention for Diagnosis of Deep Vein Thrombosis in Acute Stroke Patients: A Hospital-Based Study

Background

Immobile stroke patients are at high risk of deep vein thrombosis (DVT). Demographic studies suggest a low incidence of DVT in Asian patients, but that might be underestimated.

Objective

Intervention by in-hospital case management for diagnosis of DVT in patients with acute stroke.

Patients and Methods

Intervention was defined as: recommendation of D-dimer test for patients who are immobile by day 4 after stroke onset and compression ultrasonography if the level of D-dimer is ≥500 ng/ml. Treating physicians were notified by case managers before they failed to do so for qualified patients. Data of patients hospitalized 12 months before and 8 months after the intervention, including basic demographics, Glasgow Coma Scale score, National Institute of Health Stroke Scale (NIHSS) score, laboratory results, and examination reports, was retrieved from electronic medical records for analysis by code searches for acute stroke.

Results

A total of 2523 patients were identified. 1528 were before and 995 after intervention. More patients after intervention had D-dimer test and ultrasound examination than that before intervention (22.1% vs 8.6%, P<0.001 and 15.1% vs 1.2%, P<0.001, respectively). Ultrasound diagnosis of DVT was significantly more after than before intervention (2.0% vs 0.3%, P<0.001). DVT was 55.7 per 1000 in patients with a NIHSS score≧18. Male sex (Odds ratio 0.33, 95% confidence intervals: 0.11–0.98), NIHSS score (Odds ratio 1.05, 95% confidence intervals: 1.00–1.09), and intervention (Odds ratio 5.39, 95% confidence intervals: 1.88–15.44) were independent predictors of ultrasound diagnosis of DVT.

Conclusions

Intervention by in-hospital case management may be an effective strategy for improvement of under-diagnosis of DVT in acute stroke patients.     

Fluctuation of Serum Sodium and Its Impact on Short and Long-Term Mortality following Acute Pulmonary Embolism

Background

Baseline hyponatremia predicts acute mortality following pulmonary embolism (PE). The natural history of serum sodium levels after PE and the relevance to acute and long-term mortality after the PE is unknown.

Methods

Clinical details of all patients (n = 1023) admitted to a tertiary institution from 2000–2007 with acute PE were retrieved retrospectively. Serum sodium results from days 1, 3–4, 5–6, and 7 of admission were pre-specified and recorded. We excluded 250 patients without day-1 sodium or had <1 subsequent sodium assessment, leaving 773 patients as the studied cohort. There were 605 patients with normonatremia (sodium≥135 mmol/L throughout admission), 57 with corrected hyponatremia (day-1 sodium<135 mmol/L, then normalized), 54 with acquired hyponatremia and 57 with persistent hyponatremia. Patients’ outcomes were tracked from a state-wide death registry and analyses performed using multivariate-regression modelling.

Results

Mean (±standard deviation) day-1 sodium was 138.2±4.3 mmol/L. Total mortality (mean follow-up 3.6±2.5 years) was 38.8% (in-hospital mortality 3.2%). There was no survival difference between studied (n = 773) and excluded (n = 250) patients. Day-1 sodium (adjusted hazard ratio [aHR] 0.89, 95% confidence interval [CI] 0.83–0.95, p = 0.001) predicted in-hospital death. Relative to normonatremia, corrected hyponatremia increased the risk of in-hospital death 3.6-fold (95% CI 1.20–10.9, p = 0.02) and persistent hyponatremia increased the risk 5.6-fold (95% CI 2.08–15.0, p = 0.001). Patients with either persisting or acquired hyponatremia had worse long-term survival than those who had corrected hyponatremia or had been normonatremic throughout (aHR 1.47, 95% CI 1.06–2.03, p = 0.02).

Conclusion

Sodium fluctuations after acute PE predict acute and long-term outcome. Factors mediating the correction of hyponatremia following acute PE warrant further investigation.     

Blood Coagulation Parameters and Platelet Indices: Changes in Normal and Preeclamptic Pregnancies and Predictive Values for Preeclampsia

Background

Preeclampsia (PE) is an obstetric disorder with high morbidity and mortality rates but without clear pathogeny. The dysfunction of the blood coagulation-fibrinolysis system is a salient characteristic of PE that varies in severity, and necessitates different treatments. Therefore, it is necessary to find suitable predictors for the onset and severity of PE.

Objectives

We aimed to evaluate blood coagulation parameters and platelet indices as potential predictors for the onset and severity of PE.

Methods

Blood samples from 3 groups of subjects, normal pregnant women (n = 79), mild preeclampsia (mPE) (n = 53) and severe preeclampsia (sPE) (n = 42), were collected during early and late pregnancy. The levels of coagulative parameters and platelet indices were measured and compared among the groups. The receiver-operating characteristic (ROC) curves of these indices were generated, and the area under the curve (AUC) was calculated. The predictive values of the selected potential parameters were examined in binary regression analysis.

Results

During late pregnancy in the normal pregnancy group, the activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and platelet count decreased, while the fibrinogen level and mean platelet volume (MPV) increased compared to early pregnancy (p<0.05). However, the PE patients presented with increased APTT, TT, MPV and D-dimer (DD) during the third trimester. In the analysis of subjects with and without PE, TT showed the largest AUC (0.743) and high predictive value. In PE patients with different severities, MPV showed the largest AUC (0.671) and ideal predictive efficiency.

Conclusion

Normal pregnancy causes a maternal physiological hypercoagulable state in late pregnancy. PE may trigger complex disorders in the endogenous coagulative pathways and consume platelets and FIB, subsequently activating thrombopoiesis and fibrinolysis. Thrombin time and MPV may serve as early monitoring markers for the onset and severity of PE, respectively.     

Extended Anticoagulant and Aspirin Treatment for the Secondary Prevention of Thromboembolic Disease: A Systematic Review and Meta-Analysis

Background

Patients who have had an unprovoked deep venous thrombosis (DVT) or pulmonary embolus (PE) are at a high risk for recurrent venous thromboembolism (VTE). Extended “life-long” anticoagulation has been recommended in these patients. However, the risk benefit ratio of this approach is controversial and the role of the direct oral anticoagulants (DOACs) and aspirin is unclear. Furthermore, in some patients with a “weak provoking factor” there is clinical equipoise regarding continuation or cessation of anticoagulant therapy after treatment of the acute VTE event.

Objective

A systematic review and meta-analysis to determine the risks (major bleeding) and benefits (recurrent VTE and mortality) of extended anticoagulation with vitamin k antagonists (VKA), DOACs and aspirin in patients with an unprovoked VTE and in those patients with clinical equipoise regarding continuation or cessation of anticoagulant therapy. In addition, we sought to determine the risk of recurrent VTE events once extended anti-thrombotic therapy was discontinued.

Data Sources

MEDLINE, Cochrane Register of Controlled Trials, citation review of relevant primary and review articles.

Study Selection

Randomized placebo-controlled trials (RCTs) that compared the risk of recurrent VTE in patients with an unprovoked DVT or PE who had been treated for at least 3 months with a VKA or a DOAC and were then randomized to receive an oral anti-thrombotic agent or placebo for at least 6 additional months. We included studies that included patients in whom clinical equipoise existed regarding the continuation or cessation of anticoagulant therapy.

Data Extraction

Independent extraction of articles by both authors using predefined data fields, including study quality indicators. Data were abstracted on study size, study setting, initial event (DVT or PE), percentage of patients where the initial VTE event was unprovoked, the number of recurrent VTE events, major bleeds and mortality during the period of extended anticoagulation in the active treatment and placebo arms. In addition, we recorded the event rate once extended treatment was stopped. Meta-analytic techniques were used to summarize the data. Studies were grouped according to the type of anti-thrombotic agent.

Data Synthesis

Seven studies which enrolled 6778 patients met our inclusion criteria; two studies evaluated the extended use of Coumadin, three studies evaluated a DOAC and two studies evaluated the use of aspirin. The duration of followup varied from 6 to 37 months. In the Coumadin and aspirin studies 100% of the randomized patients had an unprovoked VTE, while in the DOAC studies between 73.5% and 93.2% of the VTE events were unprovoked. In the control group recurrent VTE occurred in 9.7% of patients compared to 2.8% in the active treatment group (OR 0.21; 95% CI 0.11–0.42, p<0.0001). VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with VKA and DOACs being significantly more effective than aspirin. Major bleeding events occurred in 12 patients in the control group (0.4%) and 25 of 3815 (0.6%) patients in the active treatment group (OR 1.64; 95% CI 0.69–3.90, NS). There were 39 (1.3%) deaths in control patients and 33 (0.9%) deaths in the anti-thrombotic group during the treatment period (OR 0.73; 95% CI 0.40–1.33, NS). Patients whose initial VTE event was a PE were more likely to have a recurrent PE than a DVT. The annualized event rate after discontinuation of extended antithrombotic therapy was 4.4% in the control group and 6.5% in the active treatment arm.

Conclusions

VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with DOACs and VKA being more effective than aspirin. The decision regarding life-long anticoagulation following an unprovoked DVT or PE should depend on the patients’ risk for recurrent PE as well as the patients’ values and preferences.     

Relationship between Longitudinal Continuity of Primary Care and Likelihood of Death: Analysis of National Insurance Data

Background

Continuity of care (COC) is a widely accepted core principle of primary care and has been associated with patient satisfaction, healthcare utilization and mortality in many, albeit small, studies.

Objective

To assess the relationship between longitudinal continuity with a primary care physician (PCP) and likelihood of death in the French general population.

Design

Observational study based on reimbursement claims from the French national health insurance (NHI) database for salaried workers (2007–2010).

Setting

Primary care.

Patients

We extracted data on the number and pattern of visits made to a PCP and excluded all patients who did not visit a PCP at least twice within 6 months. We recorded age, gender, comorbidities, social status, and deaths.

Main outcome measures

The primary endpoint was death by all causes. We measured longitudinal continuity of care (COC) with a PCP twice a year between 2007 and 2010, using the COC index developed by Bice and Boxerman. We introduced the COC index as time-dependent variables in a survival analysis after adjustment for age, gender and stratifying on comorbidities and social status.

Results

A total of 325 742 patients were included in the analysis. The average COC index ranged from 0.74 (SD: 0.35) to 0.76 (0.35) (where 1.0 is perfect continuity). Likelihood of death was lower in patients with higher continuity (hazard ratio for an increase in 0.1 of continuity, adjusted for age, sex, and stratified on comorbidities and social status: 0.96 [0.95–0.96]).

Conclusion

Higher longitudinal continuity was associated with a reduced likelihood of death.     

A meta-analysis of the risk of venous thromboembolism in inflammatory rheumatic diseases

Introduction

We performed a meta-analysis to investigate the risk of deep vein thrombosis (DVT) and/or pulmonary embolisms (PEs) in patients with inflammatory arthritis, vasculitis and connective tissue diseases (CTDs) (systemic lupus erythematosus (SLE), Sjögren’s syndrome, inflammatory myositis and systemic sclerosis (SSc)).

Methods

PubMed, Embase, the Cochrane databases and MEDLINE were searched to identify full-text English-language publications about adult patients with rheumatologic inflammatory diseases and venous thromboembolisms (VTEs). Data regarding rates of DVTs and PEs were extracted. Using random-effects models, pooled estimates for VTEs in individual and pooled diseases were compared with matched populations where possible. Studies were excluded if VTEs were described in the setting of pregnancy, postoperative outcomes or solely antiphospholipid antibody syndrome.

Results

Most of the 5,206 studies were excluded because they did not state the rate or incidence of VTEs. In total, 25 studies remained for analysis. Ten studies that included rheumatoid arthritis comprised an aggregate of 5,273,942 patients and 891,530,181 controls with a cumulative VTE incidence of 2.18% (95% confidence interval (CI): 1.82% to 2.54%) and an odds ratio of 2.23 (95% CI: 2.02 to 2.47) compared to age- and sex-matched populations. Ten studies comprised an aggregate of 54,697 SLE patients with a cumulative VTE incidence of 7.29% (95% CI: 5.82% to 8.75%). Four Sjögren’s syndrome studies comprising an aggregate of 25,100 patients demonstrated a cumulative VTE incidence of 2.18% (95% CI: 0.79% to 3.57%). Four studies of inflammatory myositis comprising an aggregate of 8,245 patients yielded a cumulative VTE incidence of 4.03% (95% CI: 2.38% to 5.67%). The SSc- and antineutrophil cytoplasmic antibody vasculitis–related cumulative VTE rates (four studies each) were 3.13% and 7.97%, respectively.

Conclusions

The inflammatory rheumatologic diseases studied were all associated with high rates of VTEs—more than three times higher than in the general population.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-014-0435-y) contains supplementary material, which is available to authorized users.