Epidemiology and burden of nasal congestion

Nasal congestion, which may be described as fullness, obstruction, reduced airflow, or being "stuffed up," is a commonly encountered symptom in clinical practice. Systematic study of congestion has largely considered it as a component of a disease state. Conditions associated with congestion include nasal polyposis, obstructive sleep apnea, and anatomic variation; however, most information on the burden of congestion comes from studies of allergic rhinitis and rhinosinusitis, diseases of which congestion is the major symptom. Congestion can be caused by other rhinologic conditions, such as non-allergic rhinitis, viral or bacterial rhinitis, and vasomotor rhinitis. Allergic rhinitis affects as much as one quarter of the population worldwide and imposes a significant economic burden. Additionally, allergic rhinitis significantly impairs quality of life; congestion causes allergic rhinitis sufferers decreased daytime productivity at work or school and reduces night-time sleep time and quality. Annually, rhinosinusitis affects tens of millions of Americans and leads to approximately $6 billion in overall health care expenditures; it has been found to be one of the most costly physical conditions for US employers. Given the high prevalence and significant social and economic burden of nasal congestion, this symptom should be a key consideration in treating patients with rhinologic disease, and there continues to be a significant unmet medical need for effective treatment options for this condition. © 2010 Stewart et al

Impact of the implantable cardioverter-defibrillator on rehospitalizations

Patients who survive out-of-hospital ventricular tachycardia or ventricular fibrillation are at risk of sudden cardiac death and often return to hospital after initial discharge. The frequency and duration of readmittance to hospital are not well known. Thus, the purpose of this study was to evaluate the impact of the implantable cardioverter defibrillator on frequency and duration of hospitalizations. Methods Between 1989 and 1993, 38 consecutive patients who had drug-refractory ventricular tachyarrhythmias were selected for the study. A total of 38 patients were implanted with the implantable cardioverter-defibrillator in accordance with the guidelines of the European Society of Cardiology. This analysis includes 35 of the 38 patients (92%). All hospitalizations which occurred one year before and one year after were studied. Clinical information for all patients was obtained by consulting medical records and by interviewing personal general practitioners. Results The annual number of hospitalizations before and after implantation of the implantable cardioverter defibrillator was, respectively, 3·28 ± 2 hospitalizations/patient/year and 0·88 ± 1·23 hospitalizations/patient/year (P<0·05). Before implantation of the implantable cardioverter-defibrillator, patients were hospitalized a mean of 32·94 plusmn; 24·18 days/patient/year and after, 9·31 ± 32·14 days/patient/year (P<0·05). The number of hospitalizations for cardiac reasons decreased by 90%. Before implantation, the most frequent cause was ventricular tachyarrhythmia (47 hospitalizations for ventricular tachycardia and eight for ventricular fibrillation), while after implantation, it was as a result of the shock from the implantable cardioverter defibrillator (II hospitalizations). The number of hospitalizations for non-cardiac reasons were similar in the two time periods. Of the 35 patients, 26 (74%) had at least one appropriate successful ventricular tachycardia interrupted by the implantable cardioverter-defibrillator, while 17 patients (49%) had their ventricular fibrillation terminated. There is a significant difference in the rate of hospitalizations to intensive care units (ICU) between the two periods. Before implantation, 30% of hospital days were spent in the ICU, with 3% after. Conclusions This study documents that the implantable cardioverter-defibrillator not only reduces the frequency and duration of hospital stays, but reduces admissions to the more expensive units in hospital. Taking into account the reduction in hospitalizations, the payback period for the implantation of an implantable cardioverter-defibrillator is 19 months. (Eur Heart J 1996; 17: 1565-1571

Is there an isolated arrhythmogenic right atrial myocarditis?

Two cases with drug refractory ectopic atrial tachycardia are described. A map-guided partial resection of the right atrium (RA) was done after preoperative endocardial catheter mapping hadshown well-defined areas of fractionated RA potentials. Intraoperatively, there were no aneurysmal formations present as described by other authors. Histopathologic examination of the resected tissue showed atrial myocarditis in both patients. Postoperative right ventricular myocardial biopsies revealed no inflammatory tissue. A minor elevation of antibodies against echoviruses was found in one case. Postoperative electrophysiologic studies were negative. We conclude: focal RA myocarditis without concomitant ventricular myocarditis may represent one cause of drug-resistant ectopic atrial tachycardia. Map-guided surgical intervention may cure the diseas

Predictive models of syncope causes in an outpatient clinic

The investigation of unexplained syncope remains a challenging clinical problem. In the present study we sought to evaluate the diagnostic value of a standardized work-up focusing on non invasive tests in patients with unexplained syncope referred to a syncope clinic, and whether certain combinations of clinical parameters are characteristic of rhythmic and reflex causes of syncope. METHODS AND RESULTS: 317 consecutive patients underwent a standardized work-up including a 12-lead ECG, physical examination, detailed history with screening for syncope-related symptoms using a structured questionnaire followed by carotid sinus massage (CSM), and head-up tilt test. Invasive testings including an electrophysiological study and implantation of a loop recorder were only performed in those with structural heart disease or traumatic syncope. Our work-up identified an etiology in 81% of the patients. Importantly, three quarters of the causes were established non invasively combining head-up tilt test, CSM and hyperventilation testing. Invasive tests yielded an additional 7% of diagnoses. Logistic analysis identified age and number of significant prodromes as the only predictive factors of rhythmic syncope. The same two factors, in addition to the duration of the ECG P-wave, were also predictive of vasovagal and psychogenic syncope. These factors, optimally combined in predictive models, showed a high negative and a modest positive predictive value. CONCLUSION: A standardized work-up focusing on non invasive tests allows to establish more than three quarters of syncope causes. Predictive models based on simple clinical parameters may help to distinguish between rhythmic and other causes of syncop

Impact of the implantable cardioverter-defibrillator on rehospitalizations

Patients who survive out-of-hospital ventricular tachycardia or ventricular fibrillation are at risk of sudden cardiac death and often return to hospital after initial discharge. The frequency and duration of readmittance to hospital are not well known. Thus, the purpose of this study was to evaluate the impact of the implantable cardioverter defibrillator on frequency and duration of hospitalizations. METHODS: Between 1989 and 1993, 38 consecutive patients who had drug-refractory ventricular tachyarrhythmias were selected for the study. A total of 38 patients were implanted with the implantable cardioverter-defibrillator in accordance with the guidelines of the European Society of Cardiology. This analysis includes 35 of the 38 patients (92%). All hospitalizations which occurred one year before and one year after were studied. Clinical information for all patients was obtained by consulting medical records and by interviewing personal general practitioners. RESULTS: The annual number of hospitalizations before and after implantation of the implantable cardioverter-defibrillator was, respectively, 3.28 +/- 2.38 hospitalizations/ patient/year and 0.88 +/- 1.23 hospitalizations/patient/year (P &lt; 0.05). Before implantation of the implantable cardioverter-defibrillator, patients were hospitalized a mean of 32.94 +/- 24.18 days/patient/year and after, 9.31 +/- 32.14 days/patient/year (P &lt; 0.05). The number of hospitalizations for cardiac reasons decreased by 90%. Before implantation, the most frequent cause was ventricular tachyarrhythmia (47 hospitalizations for ventricular tachycardia and eight for ventricular fibrillation), while after implantation, it was as a result of the shock from the implantable cardioverter-defibrillator (11 hospitalizations). The number of hospitalizations for non-cardiac reasons were similar in the two time periods. Of the 35 patients, 26 (74%) had at least one appropriate successful ventricular tachycardia interrupted by the implantable cardioverter-defibrillator, while 17 patients (49%) had their ventricular fibrillation terminated. There is a significant difference in the rate of hospitalizations to intensive care units (ICU) between the two periods. Before implantation, 30% of hospital days were spent in the ICU, with 3% after. CONCLUSIONS: This study documents that the implantable cardioverter-defibrillator not only reduces the frequency and duration of hospital stays, but reduces admissions to the more expensive units in hospital. Taking into account the reduction in hospitalizations, the payback period for the implantation of an implantable cardioverter-defibrillator is 19 months

Is there an isolated arrhythmogenic right atrial myocarditis?

Two cases with drug refractory ectopic atrial tachycardia are described. A map-guided partial resection of the right atrium (RA) was done after preoperative endocardial catheter mapping had shown well-defined areas of fractionated RA potentials. Intraoperatively, there were no aneurysmal formations present as described by other authors. Histopathologic examination of the resected tissue showed atrial myocarditis in both patients. Postoperative right ventricular myocardial biopsies revealed no inflammatory tissue. A minor elevation of antibodies against echoviruses was found in one case. Postoperative electrophysiologic studies were negative. We conclude: focal RA myocarditis without concomitant ventricular myocarditis may represent one cause of drug-resistant ectopic atrial tachycardia. Map-guided surgical intervention may cure the disease

Tradeoff Between Stability and Multispecificity in the Design of Promiscuous Proteins

Natural proteins often partake in several highly specific protein-protein interactions. They are thus subject to multiple opposing forces during evolutionary selection. To be functional, such multispecific proteins need to be stable in complex with each interaction partner, and, at the same time, to maintain affinity toward all partners. How is this multispecificity acquired through natural evolution? To answer this compelling question, we study a prototypical multispecific protein, calmodulin (CaM), which has evolved to interact with hundreds of target proteins. Starting from high-resolution structures of sixteen CaM-target complexes, we employ state-of-the-art computational methods to predict a hundred CaM sequences best suited for interaction with each individual CaM target. Then, we design CaM sequences most compatible with each possible combination of two, three, and all sixteen targets simultaneously, producing almost 70,000 low energy CaM sequences. By comparing these sequences and their energies, we gain insight into how nature has managed to find the compromise between the need for favorable interaction energies and the need for multispecificity. We observe that designing for more partners simultaneously yields CaM sequences that better match natural sequence profiles, thus emphasizing the importance of such strategies in nature. Furthermore, we show that the CaM binding interface can be nicely partitioned into positions that are critical for the affinity of all CaM-target complexes and those that are molded to provide interaction specificity. We reveal several basic categories of sequence-level tradeoffs that enable the compromise necessary for the promiscuity of this protein. We also thoroughly quantify the tradeoff between interaction energetics and multispecificity and find that facilitating seemingly competing interactions requires only a small deviation from optimal energies. We conclude that multispecific proteins have been subjected to a rigorous optimization process that has fine-tuned their sequences for interactions with a precise set of targets, thus conferring their multiple cellular functions