Echocardiography-Defined Pulmonary Hypertension in Multiple Myeloma: Risk Factors and Impact on Outcomes.

OBJECTIVES: Survival of patients with multiple myeloma (MM) has improved as a result of therapeutic advances. There is evidence that some patients with MM develop pulmonary hypertension (PH). The objective of this study was to identify risk factors of echocardiographic PH and its impact on outcomes of patients with MM. METHODS: We conducted a retrospective study of patients with MM (N = 359) diagnosed between 2000 and 2011 within the Geisinger Medical Center. Chart review was conducted on the subgroup of patients who underwent a transthoracic echocardiogram within 2 years of being diagnosed as having MM. RESULTS: A total of 34% of patients (N = 123/359) underwent transthoracic echocardiogram and 32% (N = 39/123) had echocardiography-defined PH. PH was significantly associated with older age (70.5 vs 65.3 years; P = 0.019), greater left atrial diameter (4.0 vs 3.7 cm; P = 0.025), and a trend toward decreased renal function. PH was not associated with myeloma-specific features. Fewer patients with PH underwent hematopoietic stem cell transplantation compared with those without PH (10% vs 30%; P = 0.018). There was no significant difference in survival between the PH and non-PH groups (P = 0.2775). CONCLUSIONS: Echocardiography-defined PH was found in a sizeable minority of our MM cohort. Although the specific etiology of PH can be determined only through a prospective clinical evaluation, including right heart catheterization, our results suggest that PH in patients with MM is secondary to left heart disease and perhaps impaired renal function. Patients with PH were significantly less likely to undergo hematopoietic stem cell transplantation. Future studies should assess the etiology of PH, its impact on treatment decisions, and prognosis of patients with MM.

Risk stratification in acute pulmonary embolism: frequency and impact on treatment decisions and outcomes.

OBJECTIVES: Guidelines have recommended that risk stratification be performed in patients diagnosed with an acute pulmonary embolism (PE). No study has described the use of risk stratification in routine clinical practice. The purpose of this study was to measure the frequency and impact of risk stratification on treatment decisions and outcomes in patients admitted with acute PE. METHODS: A retrospective cohort study was conducted of all of the patients admitted with acute PE at two Geisinger community-based teaching hospitals between 2006 and 2011. Baseline demographics, vital signs, and relevant clinical variables were recorded. The Pulmonary Embolism Severity Index was calculated for each patient. Risk stratification was defined as the measurement of either a biomarker or an echocardiogram within 24 hours of admission. The outcomes measured were short-term adverse events (in-hospital mortality or need for intensive care) and 30-day mortality. RESULTS: The mean age for the study cohort (n = 889) was 61 ± 17 years and 52% were men. Overall, 59% of study subjects were risk stratified. The frequency of risk stratification did not change over time. Risk stratification was associated with assignment to a higher acuity of care and increased use of thrombolysis and inferior vena cava filter placement. When controlling for severity of illness, risk stratification was a significant predictor of worsened short-term adverse outcome (odds ratio 3.43, 95% confidence interval 1.75-6.74, P < 0.001) but was not associated with improved 30-day mortality (odds ratio 1.14, 95% confidence interval 0.66-1.95, P = 0.64). CONCLUSIONS: Risk stratification is frequently performed in patients admitted with acute PE and has had a stable prevalence during a 5-year period. The use of risk stratification in acute PE is associated with assignment to higher levels of care and with more advanced treatments. Despite more intense treatment, risk stratification does not improve either short-term outcomes or 30-day mortality.

Outcomes of noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease in the United States, 1998-2008.

RATIONALE: The patterns and outcomes of noninvasive, positive-pressure ventilation (NIPPV) use in patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease (COPD) nationwide are unknown. OBJECTIVES: To determine the prevalence and trends of noninvasive ventilation for acute COPD. METHODS: We used data from the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample to assess the pattern and outcomes of NIPPV use for acute exacerbations of COPD from 1998 to 2008. MEASUREMENTS AND MAIN RESULTS: An estimated 7,511,267 admissions for acute exacerbations occurred from 1998 to 2008. There was a 462% increase in NIPPV use (from 1.0 to 4.5% of all admissions) and a 42% decline in invasive mechanical ventilation (IMV) use (from 6.0 to 3.5% of all admissions) during these years. This was accompanied by an increase in the size of a small cohort of patients requiring transition from NIPPV to IMV. In-hospital mortality in this group appeared to be worsening over time. By 2008, these patients had a high mortality rate (29.3%), which represented 61% higher odds of death compared with patients directly placed on IMV (95% confidence interval, 24-109%) and 677% greater odds of death compared with patients treated with NIPPV alone (95% confidence interval, 475-948%). With the exception of patients transitioned from NIPPV to IMV, in-hospital outcomes were favorable and improved steadily year by year. CONCLUSIONS: The use of NIPPV has increased significantly over time among patients hospitalized for acute exacerbations of COPD, whereas the need for intubation and in-hospital mortality has declined. However, the rising mortality rate in a small but expanding group of patients requiring invasive mechanical ventilation after treatment with noninvasive ventilation needs further investigation.

Case Report of Nursing Care for a Pregnant Woman With Cystic Fibrosis.

Life expectancy for individuals with cystic fibrosis (CF) has significantly increased during the last few decades, and subsequently, more women with CF are considering pregnancy. A detailed understanding of the management of pregnancy, specific pulmonary treatments, and necessary medications is essential to provide specialized care for women with CF. In this article, we present the physical and psychosocial aspects of care for pregnant women with CF and describe a case involving the planned pregnancy of a nulliparous woman with CF. We suggest vigilant monitoring for adequate nutrition, weight gain, and pulmonary function throughout pregnancy as implications for nursing care.

Contributions of COPD, asthma, and ten comorbid conditions to health care utilization and patient-centered outcomes among US adults with obstructive airway disease.

BACKGROUND: Among persons with obstructive airway disease, the relative contributions of chronic obstructive pulmonary disease (COPD), asthma, and common comorbid conditions to health care utilization and patient-centered outcomes (PCOs) have not been previously reported. METHODS: We followed a total of 3,486 persons aged ≥40 years with COPD, asthma, or both at baseline, from the Medical Expenditure Panel Survey (MEPS) cohorts enrolled annually from 2008 through 2012 for 1 year. MEPS is a prospective observational study of US households recording self-reported COPD, asthma, and ten medical conditions: angina, arthritis, cancer, coronary heart disease, cognitive impairment, diabetes, hypertension, lung cancer, myocardial infarction, and stroke/transient ischemic attack. We studied the separate contributions of these conditions to health care utilization (all-cause and respiratory disease hospitalization, any emergency department [ED] visit, and six or more outpatient visits) and PCOs (seven or more days spent in bed due to illness, incident loss of mobility, and incident decline in self-perceived health). RESULTS: COPD made the largest contributions to all-cause and respiratory disease hospitalization and ED visits, while arthritis made the largest contribution to outpatient health care. Arthritis and COPD, respectively, made the greatest contributions to the PCOs. CONCLUSION: COPD made the largest and second largest contributions to health care utilization and PCOs among US adults with obstructive airway disease. The twelve medical conditions collectively accounted for between 52% and 61% of the health care utilization outcomes and between 53% and 68% of the PCOs. Cognitive impairment, diabetes, hypertension, and stroke also made significant contributions.

Medical Malpractice: Reform for Today's Patients and Clinicians.

The current system of medical malpractice does a poor job of serving the best interests of physicians or patients. Economic and societal forces are shifting the nature of health care from the individual physician to a system of health care professionals, characterized by accountable care organizations. In particular, more physicians are employed, quality and outcomes are routinely measured, and reimbursement is moving to value-based purchasing. Medical malpractice likewise needs to transition to a new model that is consistent with the modern era of patient-centered care. Collective accountability, the concept that patient care is the responsibility of all the members of the health care organization, requires malpractice reform that reflects a systems-based practice of medicine. Enterprise liability, coupled with medical error communication and resolution programs, provides the legal framework necessary for the patient-centered practice of medicine in today's environment.

The role of statins in cancer prevention and treatment.

Statins inhibit the activity of the rate-limiting enzyme in the cholesterol biosynthetic pathway, HMG-CoA reductase, and are widely prescribed for lowering plasma lipid levels. Several statins have antitumor effects in experimental models, and observational studies suggest that this anticancer activity in the laboratory may translate into effective treatments and/or preventive strategies for certain human cancers. This paper reviews the laboratory and clinical evidence that statins have anticancer activity, discusses the possible mechanisms by which tumor growth may be inhibited by this class of drugs, and outlines strategies for the evaluation of these agents in the prevention and treatment of human cancers.

Toxoplasmosis in a post-transplant bronchoalveolar lavage: a case report.

Toxoplasma gondii usually causes an asymptomatic and then latent infection in human adults; however, a potentially fatal disseminated form can occur in immunocompromised patients. Given that the diagnosis of acute Toxoplasma infection, as opposed to latent disease, relies on finding direct evidence of T. gondii infection in tissue, pathologic examination is critical. There have only been a few reports describing the cytomorphology of Toxoplasma in exfoliative cytology, and no reports of the findings in Thin Prep. In this report, we describe a fatal case of toxoplasmosis in a cardiac transplant patient that was diagnosed by respiratory cytopathology. Although the extracellular organisms were well visualized on the Wright-Giemsa stained cytospin, they were only faintly seen on the Pap-stained cytospin trapped within mucin and were not easily appreciated on the ThinPrep slides nor the H&E stained cell block sections. An immunohistochemical stain for Toxoplasma performed on the cell block was strongly positive, and an autopsy performed on the patient confirmed disseminated infection. Our case illustrates that the diagnosis of Toxoplasma in exfoliative cytology specimens can be challenging since organisms are not well visualized on ThinPrep or Pap-stained material; therefore, Wright-Giemsa stained material can be particularly helpful.

The relationship between pulmonary emphysema and kidney function in smokers.

BACKGROUND: It has been reported that the prevalence of kidney dysfunction may be increased in patients exposed to tobacco with airflow obstruction. We hypothesized that kidney dysfunction would associate with emphysema rather than with airflow obstruction measured by the FEV1. METHODS: Five hundred eight current and former smokers completed a chest CT scan, pulmonary function tests, medical questionnaires, and measurement of serum creatinine. Glomerular filtration rates (eGFRs) were estimated using the method of the Chronic Kidney Disease Epidemiology Collaboration. Quantitative determinants of emphysema and airway dimension were measured from multidetector chest CT scans. RESULTS: The mean age was 66 ± 7 years, and mean eGFR was 101 ± 22 mL/min/1.73 m². Univariate and multivariate analysis showed a significant association between radiographically measured emphysema and eGFR: Participants with 10% more emphysema had an eGFR that was lower by 4.4 mL/min/1.73 m² (P = .01), independent of airflow obstruction (FEV1), age, sex, race, height, BMI, diabetes mellitus, hypertension, coronary artery disease, patient-reported dyspnea, pack-years of smoking, and current smoking. There was no association between eGFR and either FEV1 or quantitative CT scan measures of airway dimension. CONCLUSIONS: More severe emphysema, rather than airflow obstruction, is associated with kidney dysfunction in tobacco smokers, independent of common risk factors for kidney disease. This finding adds to recent observations of associations between emphysema and comorbidities of COPD, including osteoporosis and lung cancer, which are independent of the traditional measure of reduced FEV1. The mechanisms and clinical implications of kidney dysfunction in patients with emphysema need further investigation.

Overview of current therapeutic approaches for pulmonary hypertension.

There have been tremendous strides in the management of pulmonary hypertension over the past 20 years with the introduction of targeted medical therapies and overall improvements in surgical treatment options and general supportive care. Furthermore, recent data shows that the survival of those with pulmonary arterial hypertension is improving. While there has been tremendous progress, much work remains to be done in improving the care of those with secondary forms of pulmonary hypertension, who constitute the majority of patients with this disorder, and in the optimal treatment approach in those with pulmonary arterial hypertension. This article will review general and targeted medical treatment, along with surgical interventions, of those with pulmonary hypertension.

Elevated N-terminal pro-brain natriuretic peptide is associated with mortality in tobacco smokers independent of airflow obstruction.

BACKGROUND: Tobacco use is associated with an increased prevalence of cardiovascular disease. N-terminal pro-brain natiuretic peptide (NT-proBNP), a widely available biomarker that is associated with cardiovascular outcomes in other conditions, has not been investigated as a predictor of mortality in tobacco smokers. We hypothesized that NT-proBNP would be an independent prognostic marker in a cohort of well-characterized tobacco smokers without known cardiovascular disease. METHODS: Clinical data from 796 subjects enrolled in two prospective tobacco exposed cohorts was assessed to determine factors associated with elevated NT-proBNP and the relationship of these factors and NT-proBNP with mortality. RESULTS: Subjects were followed for a median of 562 (IQR 252-826) days. Characteristics associated with a NT-proBNP above the median (≥49 pg/mL) were increased age, female gender, and decreased body mass index. By time-to-event analysis, an NT-proBNP above the median (≥49 pg/mL) was a significant predictor of mortality (log rank p = 0.02). By proportional hazard analysis controlling for age, gender, cohort, and severity of airflow obstruction, an elevated NT-proBNP level (≥49 pg/mL) remained an independent predictor of mortality (HR = 2.19, 95% CI 1.07-4.46, p = 0.031). CONCLUSIONS: Elevated NT-proBNP is an independent predictor of mortality in tobacco smokers without known cardiovascular disease, conferring a 2.2 fold increased risk of death. Future studies should assess the ability of this biomarker to guide further diagnostic testing and to direct specific cardiovascular risk reduction inventions that may positively impact quality of life and survival.

Doppler-defined pulmonary hypertension in medical intensive care unit patients: Retrospective investigation of risk factors and impact on mortality.

Pulmonary hypertension (PH) is poorly characterized in the critically ill. No prior studies describe the burden of or outcomes associated with PH in a general medical intensive care unit population. We hypothesize that PH is an important comorbidity prevalent in the modern medical intensive care unit. We undertook a preliminary investigation to define the consequences of Doppler-defined PH in the critically ill. A single-center retrospective case-control study of medical intensive care patients admitted over a 1-year period was conducted. Eligible patients had an echocardiogram within 4 days of admission. PH was defined to include both pulmonary arterial and venous hypertension and required a tricuspid regurgitant jet velocity ≥3 m/sec. Cases and controls were compared for comorbidities, illness severity, diagnoses, and mortality. Multivariable regression was performed to identify clinical features associated with PH and mortality. 299 (21% of admissions) patients had an eligible echocardiogram. Patients with PH (N=126) had a higher unadjusted mortality than did controls (N=173) (37% vs. 25%, P=0.04) and PH remained significantly associated with mortality after controlling for other clinical factors (HR=1.59, 95% CI=1.03-2.44, P=0.036). Low ejection fraction (OR=2.21, 95% CI=1.19-4.11, P=0.012) and pulmonary embolism (OR=4.28, 95% CI=1.59-11.5, P=0.004) were independently associated with PH. Doppler-defined PH is associated with mortality in the critically ill. Prospective studies are needed to define the prevalence of pulmonary venous hypertension versus pulmonary arterial hypertension, and the clinical consequences of each, in a general medical intensive care unit population.

Peripherally inserted central venous catheter-associated thrombosis: retrospective analysis of clinical risk factors in adult patients.

BACKGROUND: Peripherally inserted central catheters (PICC) are common venous access devices. Clinical conditions and therapies that increase the risk of PICC-associated thrombosis have not been studied. METHODS: We performed a retrospective case-control analysis of all adult patients who underwent placement of a PICC at our hospital over a three-year period (n = 1296). Clinical variables examined were indication for PICC placement, active cancer treatment, history of DVT, diabetes mellitus, and use of prophylactic anticoagulation. RESULTS: The overall incidence of PICC-associated DVT was 2% (n = 27). Active cancer therapy was significantly associated with PICC-associated DVT (OR 3.5, 95% CI 1.3-9.8). The use of prophylactic anticoagulation did not reduce this risk. CONCLUSIONS: Patients who suffered a PICC-associated DVT were more likely to be undergoing treatment for cancer. This risk was not lowered by the use of prophylactic anticoagulation. These results suggest a need for prospective studies on effective anticoagulation for patients at high risk for PICC-associated DVT.

The statins: multifunctional antithrombotic and antineoplastic drugs.

Statins are approved by the Food and Drug Administration (FDA) for the treatment of hypercholesterolemia and have shown remarkable activity in preventing cardiovascular morbidity and mortality. The versatility of statins is increasingly being appreciated, however, and lowering cholesterol is only one attribute among many shared by this class of drugs. Most statins appear to have antithrombotic activity that is unrelated to the ability to reduce cholesterol levels, and several have significant antitumor effects. This article reviews the laboratory and clinical evidence that statins have antithrombotic and anticancer activity, discusses the ways in which these two activities intersect, and proposes novel uses for statins for the treatment of conditions other than hypercholesterolemia.