Sep 172014
 
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Angiotensin-neprilysin inhibition versus enalapril in heart failure.

N Engl J Med. 2014 Sep 11;371(11):993-1004

Authors: McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR, PARADIGM-HF Investigators and Committees

Abstract
BACKGROUND: We compared the angiotensin receptor-neprilysin inhibitor LCZ696 with enalapril in patients who had heart failure with a reduced ejection fraction. In previous studies, enalapril improved survival in such patients.
METHODS: In this double-blind trial, we randomly assigned 8442 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either LCZ696 (at a dose of 200 mg twice daily) or enalapril (at a dose of 10 mg twice daily), in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure, but the trial was designed to detect a difference in the rates of death from cardiovascular causes.
RESULTS: The trial was stopped early, according to prespecified rules, after a median follow-up of 27 months, because the boundary for an overwhelming benefit with LCZ696 had been crossed. At the time of study closure, the primary outcome had occurred in 914 patients (21.8%) in the LCZ696 group and 1117 patients (26.5%) in the enalapril group (hazard ratio in the LCZ696 group, 0.80; 95% confidence interval [CI], 0.73 to 0.87; P<0.001). A total of 711 patients (17.0%) receiving LCZ696 and 835 patients (19.8%) receiving enalapril died (hazard ratio for death from any cause, 0.84; 95% CI, 0.76 to 0.93; P<0.001); of these patients, 558 (13.3%) and 693 (16.5%), respectively, died from cardiovascular causes (hazard ratio, 0.80; 95% CI, 0.71 to 0.89; P<0.001). As compared with enalapril, LCZ696 also reduced the risk of hospitalization for heart failure by 21% (P<0.001) and decreased the symptoms and physical limitations of heart failure (P=0.001). The LCZ696 group had higher proportions of patients with hypotension and nonserious angioedema but lower proportions with renal impairment, hyperkalemia, and cough than the enalapril group.
CONCLUSIONS: LCZ696 was superior to enalapril in reducing the risks of death and of hospitalization for heart failure. (Funded by Novartis; PARADIGM-HF ClinicalTrials.gov number, NCT01035255.).

PMID: 25176015 [PubMed - indexed for MEDLINE]

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Sep 162014
 
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Role of body temperature in diagnosing bacterial infection in nursing home residents.

J Am Geriatr Soc. 2014 Jan;62(1):135-40

Authors: Sloane PD, Kistler C, Mitchell CM, Beeber AS, Bertrand RM, Edwards AS, Olsho LE, Hadden LS, Bateman JR, Zimmerman S

Abstract
OBJECTIVES: To provide empirically based recommendations for incorporating body temperature into clinical decision-making regarding diagnosing infection in nursing home (NH) residents.
DESIGN: Retrospective.
SETTING: Twelve North Carolina NHs.
PARTICIPANTS: NH residents (N = 1,007) with 1,858 randomly selected antibiotic prescribing episodes.
MEASUREMENTS: Maximum prescription-day temperature plus the three most recent nonillness temperatures were recorded for each prescribing episode. Two empirically based definitions of fever were developed: population-based (population mean nonillness temperature plus 2 population standard deviations (SDs)) and individualized (individual mean nonillness temperature plus 2 population SDs). These definitions were used along with previously published fever criteria and Infectious Diseases Society of America (IDSA) criteria to determine how often each prescribing episode was associated with a "fever" according to each definition.
RESULTS: Mean population nonillness temperature was 97.7 ± 0.5 ºF. If "normal" were defined as less than 2 SDs above the mean, fever would be defined as any temperature above 98.7 ºF, and the previously published fever cutpoints and the IDSA criteria are 4.8 SDs above this mean. Between 30% and 32% of the 1,858 prescribing episodes examined were associated with temperatures more than 2 SDs above the population mean nonillness temperature, whereas only 10% to 11% of episodes met the previously published and IDSA fever definitions.
CONCLUSION: Clinicians should apply empirically based definitions to assess fever in NH residents. Furthermore, low fever prevalence in residents treated with antibiotics according to all definitions suggests that some prescribing may not be associated with acute bacterial infection.

PMID: 25180381 [PubMed - in process]

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Sep 052014
 
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Impact of COPD on the Mortality and Treatment of Patients Hospitalized with Acute Decompensated Heart Failure (The Worcester Heart Failure Study).

Chest. 2014 Sep 4;

Authors: Fisher K, Stefan M, Darling C, Lessard D, Goldberg RJ

Abstract
ABSTRACT: Background:Chronic obstructive pulmonary disease(COPD) is a common co-morbidity in patients with heart failure, yet little is known about the impact of this condition in patients with acute decompensated heart failure (ADHF), especially from a more generalizable, community-based perspective. The primary objective of this study was to describe the in-hospital and post discharge mortality and treatment of patients hospitalized with ADHF according to COPD status. Methods:The study population consisted of patients hospitalized with ADHF at all 11 medical centers in central Massachusetts during 4 study years: 1995, 2000, 2002, and 2004. Patients were followed through 2010 for determination of their vital status. Results:Of the 9,748 patients hospitalized with ADHF during the years under study, 35.9% had a history of COPD. The average age of this population was 76.1 years, 43.9% were men, and 93.3% were white. At the time of hospital discharge, patients with COPD were less likely to have received evidence-based heart failure medications, including beta-blockers and ACE inhibitors/angiotensin receptor blockers, than patients without COPD. Multivariable adjusted in-hospital death rates were similar for patients with and without COPD. However, among patients who survived to hospital discharge, patients with COPD had a significantly higher risk of dying at 1 (adjusted RR 1.10; 95% CI 1.06, 1.14) and 5-years (adjusted RR 1.40; 95% CI 1.28, 1.42) after hospital discharge than patients who were not previously diagnosed with COPD. Conclusions:COPD is a common co-morbidity in patients hospitalized with ADHF and is associated with a worse long-term prognosis. Further research is required to understand the complex interactions of these diseases and ensure that patients with ADHF and COPD receive optimal treatment modalities.
Background: Chronic obstructive pulmonary disease(COPD) is a common co-morbidity in patients with heart failure, yet little is known about the impact of this condition in patients with acute decompensated heart failure (ADHF), especially from a more generalizable, community-based perspective. The primary objective of this study was to describe the in-hospital and post discharge mortality and treatment of patients hospitalized with ADHF according to COPD status.
Methods: The study population consisted of patients hospitalized with ADHF at all 11 medical centers in central Massachusetts during 4 study years: 1995, 2000, 2002, and 2004. Patients were followed through 2010 for determination of their vital status.
Results: Of the 9,748 patients hospitalized with ADHF during the years under study, 35.9% had a history of COPD. The average age of this population was 76.1 years, 43.9% were men, and 93.3% were white. At the time of hospital discharge, patients with COPD were less likely to have received evidence-based heart failure medications, including beta-blockers and ACE inhibitors/angiotensin receptor blockers, than patients without COPD. Multivariable adjusted in-hospital death rates were similar for patients with and without COPD. However, among patients who survived to hospital discharge, patients with COPD had a significantly higher risk of dying at 1 (adjusted RR 1.10; 95% CI 1.06, 1.14) and 5-years (adjusted RR 1.40; 95% CI 1.28, 1.42) after hospital discharge than patients who were not previously diagnosed with COPD.
Conclusions: COPD is a common co-morbidity in patients hospitalized with ADHF and is associated with a worse long-term prognosis. Further research is required to understand the complex interactions of these diseases and ensure that patients with ADHF and COPD receive optimal treatment modalities.

PMID: 25188234 [PubMed - as supplied by publisher]

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Sep 052014
 
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Outcomes after Hospitalization in Idiopathic Pulmonary Fibrosis: a cohort study.

Chest. 2014 Sep 4;

Authors: Brown AW, Fischer CP, Shlobin OA, Buhr RG, Ahmad S, Weir NA, Nathan SD

Abstract
Abstract: Background:The outcomes of IPF patients who undergo hospitalization have not been well characterized. We sought to evaluate the frequency and impact of all-cause as well as respiratory-related hospitalizations on the subsequent course and survival of patients with IPF. Methods:The records of IPF patients evaluated at a tertiary center were examined for cause and duration of hospitalization. Data on subsequent patient outcomes was collated. Results:The IPF cohort consisted of 592 patients, 25.3% of whom were hospitalized subsequent to their IPF diagnosis. A respiratory-related etiology accounted for 77.3% of these hospitalizations. The median transplant-free survival for all patients was 23.3 [IQR:7.6-63.6] months from time of consultation. Transplant-free survival after hospital admission was much worse for patients with a respiratory hospitalization compared to a non-respiratory hospitalization (median survival: 2.8 [IQR: 0.63-16.2] vs. 27.7 [IQR: 7.4-59.6] months, p=0.0004). Multivariate analyses demonstrated that both all-cause and respiratory-related hospitalizations were strongly associated with mortality after adjusting for baseline demographics. Among patients with a respiratory hospitalization, 22.4% died while in the hospital while 16.4% eventually went onto lung transplantation. Conclusions:Hospitalizations are common events in IPF patients. Most hospitalizations are respiratory-related and are associated with high in-hospital mortality and limited survival beyond discharge. Both all-cause hospitalization and respiratory hospitalization are associated with mortality, and therefore either could be utilized as an endpoint in IPF clinical trials.
Background: The outcomes of IPF patients who undergo hospitalization have not been well characterized. We sought to evaluate the frequency and impact of all-cause as well as respiratory-related hospitalizations on the subsequent course and survival of patients with IPF.
Methods: The records of IPF patients evaluated at a tertiary center were examined for cause and duration of hospitalization. Data on subsequent patient outcomes was collated.
Results: The IPF cohort consisted of 592 patients, 25.3% of whom were hospitalized subsequent to their IPF diagnosis. A respiratory-related etiology accounted for 77.3% of these hospitalizations. The median transplant-free survival for all patients was 23.3 [IQR:7.6-63.6] months from time of consultation. Transplant-free survival after hospital admission was much worse for patients with a respiratory hospitalization compared to a non-respiratory hospitalization (median survival: 2.8 [IQR: 0.63-16.2] vs. 27.7 [IQR: 7.4-59.6] months, p=0.0004). Multivariate analyses demonstrated that both all-cause and respiratory-related hospitalizations were strongly associated with mortality after adjusting for baseline demographics. Among patients with a respiratory hospitalization, 22.4% died while in the hospital while 16.4% eventually went onto lung transplantation.
Conclusions: Hospitalizations are common events in IPF patients. Most hospitalizations are respiratory-related and are associated with high in-hospital mortality and limited survival beyond discharge. Both all-cause hospitalization and respiratory hospitalization are associated with mortality, and therefore either could be utilized as an endpoint in IPF clinical trials.

PMID: 25188694 [PubMed - as supplied by publisher]

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Sep 052014
 
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Ultrasound guided medical thoracoscopy in the absence of pleural effusion.

Chest. 2014 Sep 4;

Authors: Marchetti G, Valsecchi A, Indellicati D, Arondi S, Trigiani M, Pinelli V

Abstract
Abstract: BackgroundMedical Thoracoscopy (MT) is a diagnostic and therapeutic procedure, which permits to study the pleural space. The presence of pleural adhesions is the most important contraindication to performing MT. Lesions of the pleura in absence of pleural effusion are usually studied in video-assisted thoracoscopic surgery (VATS) with preoperative ultrasound evaluation. No data are available about ultrasound guided MT in the absence of pleural effusion. MethodsFrom January 2007 to June 2013, 622 consecutive MT were performed under US guide, without inducing a pneumothorax. A retrospective cohort of 29 patients affected by pleural diseases with no liquid was reviewed. The 5th-6th intercostals spaces along the midaxillary line with a good echographic 'sliding sign' and a normal appearance of the pleural line were chosen as the entry site. Pleural cavity was explored and biopsies were performed. ResultsThe mean age of the patient cohort was 62.8 years, 20 male and 9 female. Pleural adherence were avoided, an adequate number of pleural biopsies were performed. We never incurred in parenchymal lung injuries, bleeding or hematoma. 17 patients had a completely free pleural cavity, 4 cases a single pleural adhesion and 8 multiple pleural adhesions but in all cases endoscopic exploration was possible and biopsy adequate. The most frequent histhopathological diagnosis was malignant pleural mesothelioma. ConclusionWe have shown that thoracic ultrasound is accurate in identify intrathoracic adhesions and in experienced hands can guide medical thoracoscopy access, replacing VATS approach, even in the complete absence of pleural effusion.
Background: Medical Thoracoscopy (MT) is a diagnostic and therapeutic procedure, which permits to study the pleural space. The presence of pleural adhesions is the most important contraindication to performing MT. Lesions of the pleura in absence of pleural effusion are usually studied in video-assisted thoracoscopic surgery (VATS) with preoperative ultrasound evaluation. No data are available about ultrasound guided MT in the absence of pleural effusion.
Methods: From January 2007 to June 2013, 622 consecutive MT were performed under US guide, without inducing a pneumothorax. A retrospective cohort of 29 patients affected by pleural diseases with no liquid was reviewed. The 5th-6th intercostals spaces along the midaxillary line with a good echographic 'sliding sign' and a normal appearance of the pleural line were chosen as the entry site. Pleural cavity was explored and biopsies were performed.
Results: The mean age of the patient cohort was 62.8 years, 20 male and 9 female. Pleural adherence were avoided, an adequate number of pleural biopsies were performed. We never incurred in parenchymal lung injuries, bleeding or hematoma. 17 patients had a completely free pleural cavity, 4 cases a single pleural adhesion and 8 multiple pleural adhesions but in all cases endoscopic exploration was possible and biopsy adequate. The most frequent histhopathological diagnosis was malignant pleural mesothelioma.
Conclusion: We have shown that thoracic ultrasound is accurate in identify intrathoracic adhesions and in experienced hands can guide medical thoracoscopy access, replacing VATS approach, even in the complete absence of pleural effusion.

PMID: 25188712 [PubMed - as supplied by publisher]

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Sep 052014
 
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Differential diagnosis between bacterial infection and neoplastic fever in patients with advanced urological cancer: the role of procalcitonin.

Int J Urol. 2014 Jan;21(1):104-6

Authors: Yaegashi H, Izumi K, Kitagawa Y, Kadono Y, Konaka H, Mizokami A, Namiki M

Abstract
It is difficult to determine the cause of high fever in patients with advanced cancer, because they tend to have both neoplastic fever and concomitant bacterial infections with elevated white blood cells and C-reactive protein levels. Procalcitonin has been reported to be a valuable marker for bacterial infections in a wide range of clinical scenarios. However, there have been no studies regarding the usefulness of procalcitonin to differentiate between febrile episodes caused by bacterial infections and neoplastic fever in patients with advanced urological cancer. In the present study, 37 febrile episodes were retrospectively analyzed. Although there were no differences in white blood cell number, C-reactive protein level or body temperature between bacterial infections and non-bacterial infections, procalcitonin levels were significantly higher in the former than the latter. Our findings suggest that measurement of procalcitonin might be valuable to determine the cause of febrile episodes in patients with advanced urological cancer, and can help clinicians to make appropriate decisions for treatment.

PMID: 23600524 [PubMed - indexed for MEDLINE]

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