Melanocortin-4 receptor complexity in energy homeostasis,obesity and drug development strategies.

The melanocortin-4 receptor (MC4R) has been critically investigated for the past two decades, and novel findings regarding MC4R signalling and its potential exploitation in weight loss therapy have lately been emphasized. An association between MC4R and obesity is well established, with disease-causing mutations affecting 1% to 6% of obese patients. More than 200 MC4R variants have been reported, although conflicting results as to their effects have been found in different cohorts. Most notably, some MC4R gain-of-function variants seem to rescue obesity and related complications via specific pathways such as beta-arrestin (ß-arrestin) recruitment. Broadly speaking, however, dysfunctional MC4R dysregulates satiety and induces hyperphagia. The picture at the mechanistic level is complicated as, in addition to the canonical G stimulatory pathway, the ß-arrestin signalling pathway and ions (particularly calcium) seem to interact with MC4R signalling to contribute to or alleviate obesity pathogenesis. Thus, the overall complexity of the MC4R signalling spectra has broadened considerably, indicating there is great potential for the development of new drugs to manage obesity and its related complications. Alpha-melanocyte-stimulating hormone is the major endogenous MC4R agonist, but structure-based ligand discovery studies have identified possible superior and selective agonists that can improve MC4R function. However, some of these agonists characterized in vitro and in vivo confer adverse effects in patients, as demonstrated in clinical trials. In this review, we provide a comprehensive insight into the genetics, function and regulation of MC4R and its contribution to obesity. We also outline new approaches in drug development and emerging drug candidates to treat obesity.

Blockchain-Based Authentication and Trust Management Mechanism for Smart Cities.

Security has always been the main concern for the internet of things (IoT)-based systems. Blockchain, with its decentralized and distributed design, prevents the risks of the existing centralized methodologies. Conventional security and privacy architectures are inapplicable in the spectrum of IoT due to its resource constraints. To overcome this problem, this paper presents a Blockchain-based security mechanism that enables secure authorized access to smart city resources. The presented mechanism comprises the ACE (Authentication and Authorization for Constrained Environments) framework-based authorization Blockchain and the OSCAR (Object Security Architecture for the Internet of Things) object security model. The Blockchain lays out a flexible and trustless authorization mechanism, while OSCAR makes use of a public ledger to structure multicast groups for authorized clients. Moreover, a meteor-based application is developed to provide a user-friendly interface for heterogeneous technologies belonging to the smart city. The users would be able to interact with and control their smart city resources such as traffic lights, smart electric meters, surveillance cameras, etc., through this application. To evaluate the performance and feasibility of the proposed mechanism, the authorization Blockchain is implemented on top of the Ethereum network. The authentication mechanism is developed in the node.js server and a smart city is simulated with the help of Raspberry Pi B+. Furthermore, mocha and chai frameworks are used to assess the performance of the system. Experimental results reveal that the authentication response time is less than 100 ms even if the average hand-shaking time increases with the number of clients.

Knowledge and practice of adolescent females about menstruation and menstruation hygiene visiting a public healthcare institute of Quetta, Pakistan.

BACKGROUND: The current study is aimed to assess menstruation-related knowledge and practices of adolescent females visiting a public health care institute of Quetta city, Pakistan. METHODS: A questionnaire-based cross-sectional survey was conducted. Nine hundred and twenty three female adolescents attending general out-patient departments of Mohtarma Shaheed Benazir Bhutto Hospital Quetta, Balochistan, was approached for data collection. Based on the objectives of the study, descriptive analysis was conducted and SPSS v. 21.0 was used for the data analysis. RESULTS: Demographic characteristics revealed that the mean age of the respondents was 15 years. Mothers' (67%) were the main source of menstruation-related information. Majority (77.7%) of our respondents never had a class or session regarding menstruation-related education in their schools. About (44%) knew that menstruation is a physiological phenomenon while 60.2% knew that menstrual blood comes from the vagina. Nearly 40% of our study respondents missed their schools because of menarche. The use of absorbent material was frequent (90%) among the adolescent females and (68.7%) used commercially available sanitary napkins/pads. Although majority of the respondents (58.2%) were not taking baths during menstruation, 80.5% do cleaned their genitalia with water during menstruation. CONCLUSION: Female adolescents of our study had certain misconception regarding menstruation because of poor access to health-related education. Education can be provided at healthcare facilities, residential area as well as religious centers. Adolescent reproductive health should be included in the school curriculum; this will influence general reproductive health of females.

Frequency and predictors of anxiety and depression among pregnant women attending tertiary healthcare institutes of Quetta City, Pakistan.

BACKGROUND: Anxiety and depression (A&D) are commonly reported among pregnant women from all over the world; however, there is a paucity of workable data from the developing countries including Pakistan. The current study, therefore, aims to find out the frequency and predictors of A&D among pregnant women attending a tertiary healthcare institutes in the city of Quetta, in the Balochistan province, Pakistan. METHODS: A questionnaire based, cross-sectional survey was conducted. The pre-validated Hospital Anxiety and Depression Scale (HADS) were used to assess the frequency of A&D among study respondents. Anxiety and depression scores were calculated via standard scoring procedures while logistic regression was used to identify the predictors of A&D. SPSS v. 20 was used for data analysis and p < 0.05 was taken as significant. RESULTS: Seven hundred and fifty pregnant women responded to the survey. The majority of the respondents belonged to age group of 26-35 year (424, 56.4%) and had no formal education (283, 37.6%). Furthermore, 612 (81.4%) of the respondents were unemployed and had urban residencies (651, 86.6%). The mean anxiety score was 10.08 ± 2.52; the mean depression score was 9.51 ± 2.55 and the total HADS score was 19.23 ± 3.91 indicating moderate A&D among the current cohort. Logistic regression analysis reported significant goodness of fit (Chi square = 17.63, p = 0.030, DF = 3), indicating that the model was advisable. Among all variables, age had a significant association when compared with HADS scores [adjusted OR (odds ratios) = 1.23, 95% CI = 1.13-1.62, p < 0.001]. CONCLUSION: Moderate A&D was reported among the study respondents. Furthermore, age was highlighted as a predictor of A&D. The evidence from this study provides a motion of support programs for anxious and depressed pregnant women. The benefits of implementing good mental health in antenatal care have long-lasting benefits for both mother and infant. Therefore, there is a need to incorporate A&D screening in the existing antenatal programs.

A qualitative study exploring perceptions and attitudes of community pharmacists about extended pharmacy services in Lahore, Pakistan.

BACKGROUND: In recent decades, community pharmacies reported a change of business model, whereby a shift from traditional services to the provision of extended roles was observed. However, such delivery of extended pharmacy services (EPS) is reported from the developed world, and there is scarcity of information from the developing nations. Within this context, the present study was aimed to explore knowledge, perception and attitude of community pharmacists (CPs) about EPS and their readiness and acceptance for practice change in the city of Lahore, Pakistan. METHODS: A qualitative approach was used to gain an in-depth knowledge of the issues. By using a semi-structured interview guide, 12 CPs practicing in the city of Lahore, Pakistan were conveniently selected. All interviews were audio-taped, transcribed verbatim, and were then analyzed for thematic contents by the standard content analysis framework. RESULTS: Thematic content analysis yielded five major themes. (1) Familiarity with EPS, (2) current practice of EPS, (3) training needed to provide EPS, (4) acceptance of EPS and (5) barriers toward EPS. Majority of the CPs were unaware of EPS and only a handful had the concept of extended services. Although majority of our study respondents were unaware of pharmaceutical care, they were ready to accept practice change if provided with the required skills and training. Lack of personal knowledge, poor public awareness, inadequate physician-pharmacist collaboration and deprived salary structures were reported as barriers towards the provision of EPS at the practice settings. CONCLUSION: Although the study reported poor awareness towards EPS, the findings indicated a number of key themes that can be used in establishing the concept of EPS in Pakistan. Over all, CPs reported a positive attitude toward practice change provided to the support and facilitation of health and community based agencies in Pakistan.

The role of dietary antioxidants in type 2 diabetes and neurodegenerative disorders: An assessment of the benefit profile.

Healthy diet is vital to cellular health. The human body succumbs to numerous diseases which afflict severe economic and psychological burdens on the patient and family. Oxidative stress is a possible crucial regulator of various pathologies, including type 2 diabetes and neurodegenerative diseases. It generates reactive oxygen species (ROS) that trigger the dysregulation of essential cellular functions, ultimately affecting cellular health and homeostasis. However, lower levels of ROS can be advantageous and are implicated in a variety of signaling pathways. Due to this dichotomy, the terms oxidative "eustress," which refers to a good oxidative event, and "distress," which can be hazardous, have developed. ROS affects multiple signaling pathways, leading to compromised insulin secretion, insulin resistance, and ß-cell dysfunction in diabetes. ROS is also associated with increased mitochondrial dysfunction and neuroinflammation, aggravating neurodegenerative conditions in the body, particularly with age. Treatment includes drugs/therapies often associated with dependence, side effects including non-selectivity, and possible toxicity, particularly in the long run. It is imperative to explore alternative medicines as an adjunct therapy, utilizing natural remedies/resources to avoid all the possible harms. Antioxidants are vital components of our body that fight disease by reducing oxidative stress or nullifying the excess toxic free radicals produced under various pathological conditions. In this review, we focus on the antioxidant effects of components of dietary foods such as tea, coffee, wine, oils, and honey and the role and mechanism of action of these antioxidants in alleviating type 2 diabetes and neurodegenerative disorders. We aim to provide information about possible alternatives to drug treatments used alone or combined to reduce drug intake and encourage the consumption of natural ingredients at doses adequate to promote health and combat pathologies while reducing unwanted risks and side effects.

The Impact of COVID-19 on the Prevalence and Perception of Telehealth Use in the Middle East and North Africa Region: Survey Study.

BACKGROUND: Due to the COVID-19 pandemic, telehealth has become a safer way to access health care. The telehealth industry has rapidly expanded over the last decade as a modality to provide patient-centered care. However, the prevalence of its use and patient acceptability remains unclear in the Middle East and North Africa (MENA) region. OBJECTIVE: The primary aim was to assess the prevalence of telehealth use before and during the pandemic by using social media (Instagram) as an online platform for survey administration across different countries simultaneously. Our secondary aim was to assess the perceptions regarding telehealth among those using it. METHODS: An Instagram account that reaches 130,000 subjects daily was used to administer a questionnaire that assessed the current prevalence of telehealth use and public attitudes and acceptability toward this modality of health care delivery during the COVID-19 pandemic. RESULTS: A total of 1524 respondents participated in the survey (n=1356, 89% female; median age 31 years), of whom 97.6% (n=1487) lived in the Gulf Cooperation Council (GCC) region. Prior to COVID-19, 1350 (88.6%) had no exposure to telehealth. Following the COVID-19 pandemic, telehealth use increased by 251% to a total of 611 users (40% of all users). About 89% (571/640) of telehealth users used virtual visits for specialist visits. Of the 642 participants who reported using telehealth, 236 (36.8%) reported their willingness to continue using telehealth, 241 (37.5%) were unsure, and 164 (25.5%) did not wish to continue to use telehealth after the COVID-19 pandemic. An inverse trend, although not statistically significant, was seen between willingness to continue telehealth use and the number of medical comorbidities (odds ratio [OR] 0.81, 95% CI 0.64-1.03; P=.09). Compared to the respondents who chose only messaging as the modality they used for telehealth, respondents who chose both messaging and phone calls were significantly less likely to recommend telehealth (OR 0.42, 95% CI 0.22-0.80; P=.009). Overall, there was general satisfaction with telehealth, and respondents reported that telehealth consultations made them feel safer and saved both time and money. CONCLUSIONS: Telehealth use increased dramatically after the COVID-19 pandemic, and telehealth was found to be acceptable among some young adult groups on Instagram. However, further innovation is warranted to increase acceptability and willingness to continue telehealth use for the delivery of health care.

Network-based identification and prioritization of key transcriptional factors of diabetic kidney disease.

Diabetic nephropathy (DN) is one of the most established microvascular complications of diabetes and a key cause of end-stage renal disease. It is well established that gene susceptibility to DN plays a critical role in disease pathophysiology. Therefore, many genetic studies have been performed to categorize candidate genes in prominent diabetic cohorts, aiming to investigate DN pathogenesis and etiology. In this study, we performed a meta-analysis on the expression profiles of GSE1009, GSE30122, GSE96804, GSE99340, GSE104948, GSE104954, and GSE111154 to identify critical transcriptional factors associated with DN progression. The analysis was conducted for all individual datasets for each kidney tissue (glomerulus, tubules, and kidney cortex). We identified distinct clusters of susceptibility genes that were dysregulated in a renal compartment-specific pattern. Further, we recognized a small but a closely connected set of these susceptibility genes enriched for podocyte differentiation, several of which were characterized as genes encoding critical transcriptional factors (TFs) involved in DN development and podocyte function. To validate the role of identified TFs in DN progression, we functionally validated the three main TFs (DACH1, LMX1B, and WT1) identified through differential gene expression and network analysis using the hyperglycemic zebrafish model. We report that hyperglycemia-induced altered gene expression of the key TF genes leads to morphological abnormalities in zebrafish glomeruli, pronephric tubules, proximal and distal ducts. This study demonstrated that altered expression of these TF genes could be associated with hyperglycemia-induced nephropathy and, thus, aids in understanding the molecular drivers, essential genes, and pathways that trigger DN initiation and development.

Clinical factors associated with left ventricular ejection fraction disparity in patients with left ventricular dysfunction undergoing multimodality imaging.

Drug and device therapy for heart failure is increasingly determined based on left ventricular ejection fraction. Significant disparity frequently exists between echocardiographic and nuclear scintigraphic techniques, even when testing is performed nearly simultaneously in clinically stable patients. In 119 patients with left ventricular dysfunction who underwent both echocardiography and stress testing with nuclear imaging within seven days (but with significant disparity in reported left ventricular ejection fraction), we identified four clinical variables which were associated with left ventricular ejection fraction difference. These clinical variables included atrial fibrillation, left ventricular hypertrophy, severe mitral regurgitation and paced rhythm.

Feasibility of a Generative Adversarial Network for Artifact Removal in Experimental Photoacoustic Imaging.

Photoacoustic tomography (PAT) reconstruction is an expeditiously growing interest among biomedical researchers because of its possible transition from laboratory to clinical pre-eminence. Nonetheless, the PAT inverse problem is yet to achieve an optimal solution in rapid and precise reconstruction under practical constraints. Precisely, the sparse sampling problem and random noise are the main impediments to attaining accuracy but in support of rapid PAT reconstruction. The limitations are associated with acquiring undersampled artifacts that deteriorate the optimality of the reconstruction task. Therefore, the former achievements of fast image formation limit the modality for clinical settings. Delving into the problem, here we explore a deep learning-based generative adversarial network (GAN) to improve the image quality by denoising and removing these artifacts. The specially designed attributes and unique manner of optimizing the problem, such as incorporating the data set limitations and providing stable training performance, constitute the main motivation behind the employment of GAN. Moreover, exploitation of the U-net variant as a generator network offers robust performance in terms of quality and computational cost, which is further validated with the detailed quantitative and qualitative analysis. The quantitatively evaluated structured similarity indexing method = 0.980 ± 0.043 and peak signal-to-noise ratio = 31 ± 0.002 dB state that the proposed solution provides the high-resolution image at the output, even training with a low-quality data set.

A Deep Learning Approach for the Photoacoustic Tomography Recovery From Undersampled Measurements.

Photoacoustic tomography (PAT) is a propitious imaging modality, which is helpful for biomedical study. However, fast PAT imaging and denoising is an exigent task in medical research. To address the problem, recently, methods based on compressed sensing (CS) have been proposed, which accede the low computational cost and high resolution for implementing PAT. Nevertheless, the imaging results of the sparsity-based methods strictly rely on sparsity and incoherence conditions. Furthermore, it is onerous to ensure that the experimentally acquired photoacoustic data meets CS's prerequisite conditions. In this work, a deep learning-based PAT (Deep-PAT)method is instigated to overcome these limitations. By using a neural network, Deep-PAT is not only able to reconstruct PAT from a fewer number of measurements without considering the prerequisite conditions of CS, but also can eliminate undersampled artifacts effectively. The experimental results demonstrate that Deep-PAT is proficient at recovering high-quality photoacoustic images using just 5% of the original measurement data. Besides this, compared with the sparsity-based method, it can be seen through statistical analysis that the quality is significantly improved by 30% (approximately), having average SSIM = 0.974 and PSNR = 29.88 dB with standard deviation ±0.007 and ±0.089, respectively, by the proposed Deep-PAT method. Also, a comparsion of multiple neural networks provides insights into choosing the best one for further study and practical implementation.

Prescribing Patterns for Upper Respiratory Tract Infections: A Prescription-Review of Primary Care Practice in Quetta, Pakistan and the Implications.

Background: To identify and address the potential overuse of antibiotics, it is important to ascertain the prescribing practices of physicians. We, therefore, conducted this prescription analysis to document URTI-specific antibiotic prescription frequency in a public primary healthcare setting of Quetta city, Pakistan. Methods: A retrospective record review was conducted of all prescriptions for URTIs in Combined Military Hospital, Quetta from 1 March to 31st May 2021. The Mann-Whitney U and Jonckheere-Terpstra test was used to evaluate the association between the tendencies of a different group of prescribers. p-value of <0.05 was of statistical significance. Results: Over the 3 months, 50,705 prescriptions were screened and analyzed according to the established inclusion and exclusion criteria. A total of 4,126 (8.13%) URTI prescriptions met the inclusion criteria, of which 2,880 (69.80%) prescriptions contained antibiotics. Among all antibiotics, penicillins (Amoxicillin + Clavulanate) were the most prescribed antibiotic, constituting 1,323 (45.9%) of total antibiotics prescribed for all cases, followed by the Macrolide group 527 (18.2%). The Jonckheere-Terpstra test revealed a statistically significant association between the status of the prescriber and the diagnosis (p = 0.002). Furthermore, a moderate positive trend was reported with specialists being more competent in antibiotic prescribing based on their diagnosis, followed by postgraduates and house officers (τ = 0.322). Conclusion: The prescribing patterns for the management of URTIs in the hospital were inconsistent with current guidelines. Strict adherence to guidelines must be ensured and antibiotic prescribing for URTIs should be discouraged.

Hospital-wide code rates and mortality before and after implementation of a rapid response team.

CONTEXT: Rapid response teams have been shown in adult inpatients to decrease cardiopulmonary arrest (code) rates outside of the intensive care unit (ICU). Because a primary action of rapid response teams is to transfer patients to the ICU, their ability to reduce hospital-wide code rates and mortality remains unknown. OBJECTIVE: To determine rates of hospital-wide codes and mortality before and after implementation of a long-term rapid response team intervention. DESIGN, SETTING, AND PATIENTS: A prospective cohort design of adult inpatients admitted between January 1, 2004, and August 31, 2007, at Saint Luke's Hospital, a 404-bed tertiary care academic hospital in Kansas City, Missouri. Rapid response team education and program rollout occurred from September 1 to December 31, 2005. A total of 24 193 patient admissions were evaluated prior to the intervention (January 1, 2004, to August 31, 2005), and 24 978 admissions were evaluated after the intervention (January 1, 2006, to August 31, 2007). INTERVENTION: Using standard activation criteria, a 3-member rapid response team composed of experienced ICU staff and a respiratory therapist performed the evaluation, treatment, and triage of inpatients with evidence of acute physiological decline. MAIN OUTCOME MEASURES: Hospital-wide code rates and mortality, adjusted for preintervention trends. RESULTS: There were a total of 376 rapid response team activations. After rapid response team implementation, mean hospital-wide code rates decreased from 11.2 to 7.5 per 1000 admissions. This was not associated with a reduction in the primary end point of hospital-wide code rates (adjusted odds ratio [AOR], 0.76 [95% confidence interval {CI}, 0.57-1.01]; P = .06), although lower rates of non-ICU codes were observed (non-ICU AOR, 0.59 [95% CI, 0.40-0.89] vs ICU AOR, 0.95 [95% CI, 0.64-1.43]; P = .03 for interaction). Similarly, hospital-wide mortality did not differ between the preintervention and postintervention periods (3.22 vs 3.09 per 100 admissions; AOR, 0.95 [95% CI, 0.81-1.11]; P = .52). Secondary analyses revealed few instances of rapid response team undertreatment or underuse that may have affected the mortality findings. CONCLUSION: In this large single-institution study, rapid response team implementation was not associated with reductions in hospital-wide code rates or mortality.

Massive Diffuse Calcification of the Ascending Aorta and Minimal Focal Calcification of the Abdominal Aorta in Heterozygous Familial Hypercholesterolemia.

A 41-year-old woman, the mother of 3 offspring, with likely heterozygous familial hypercholesterolemia, had been asymptomatic until age 38 when angina pectoris and exertional dyspnea appeared leading to the discovery of severe multivessel coronary artery disease and a massively calcified ascending aorta. Coronary bypass grafting using the right and left internal mammary arteries did not alleviate the symptoms. Evidence of overt heart failure subsequently appeared and that led to heart transplantation at age 41. She died 22 days later. The occurrence of massive diffuse calcification of the ascending aorta and minimal focal calcification of the abdominal aorta is rare and in the patient described it appears to be the consequence of heterozygous familial hypercholesterolemia.

The Patient Satisfaction with Pharmacist Services Questionnaire (PSPSQ 2. 0) translation and validation study of the Urdu version

The study aimed to examine the psychometric properties of the Urdu version of Patient Satisfaction with Pharmacist Services Questionnaire (PSPSQ 2.0). We applied the forward-backward procedure to translate the PSPSQ 2.0 in the Urdu language. The test-retest reliability was assessed through Cronbach's alpha reliability analysis. The validity of the translated PSPSQ 2.0 was constructed by using Confirmatory Factor Analysis (CFA) through principal axis factoring extraction and Oblique rotation with Kaiser Normalization onto 2 predetermined factors. The Quality of Care (QOC) construct exhibited Cronbach's alpha values of 0.900 (Test) and α = 0.871 (Retest) at two-time points. The Interpersonal Relationship (IPR) Construct had alpha values of 0.845 (Test) and α = 0.819 (Retest). The Kaiser-Meyer-Olkin measure of sampling adequacy for the factor analysis was 0.899. Barlett's Test of Sphericity was significant (Chi-square = 1192.72; p < 0.05) revealing relationships of the data and suitability of CFA. Two factors explaining the total variance of 40% were extracted whereby loading values were acceptable (> 0.50) for all items of the translated version of PSPSQ 2.0. Results of this study conclude that the translated version of PSPSQ 2.0 is a valid instrument in regions where Urdu is a prime language of communication

Heart transplantation in the Ehlers-Danlos syndrome.

We describe a woman with Ehlers-Danlos syndrome and aortic aneurysm who experienced a myocardial infarction due to spontaneous left circumflex coronary artery dissection 3 weeks postpartum. She developed end-stage heart failure and subsequently underwent a successful orthotopic heart transplantation. To our knowledge, this is the first report of a heart transplant performed in an individual with Ehlers-Danlos syndrome.

Persistent hyperinsulinemic hypoglycemia of infancy - nesidioblastosis.

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or nesidioblastosis is a rare condition presenting with severe hypoglycemia. Prompt diagnosis and early pancreatectomy can save many of them, in spite of the magnitude of surgery. We present two cases in which near total pancreatectomy was performed with favourable outcome. Both patients are normoglycemic, with one requiring pancreatic enzyme supplements.

Fragmented QRS and mortality risk in patients with left ventricular dysfunction.

BACKGROUND: Fragmented QRS (fQRS) has been shown to predict cardiac events in select patient populations. Whether fQRS improves patient selection for primary prevention patients eligible for implantable cardioverter-defibrillator (ICD) therapy remains unknown. METHODS AND RESULTS: In a prospective, multisite cohort of 842 patients with left ventricular dysfunction (ejection fraction < or =35%) representing both ischemic and nonischemic etiology, the presence of fQRS on ECG was assessed using standardized criteria. The association between fQRS and all-cause and arrhythmic mortality was evaluated overall and stratified by ICD status using multivariable Cox regression models, adjusted for demographic, clinical, and treatment variables. Fragmented QRS was present in 274 (32.5%) patients, and there were 191 (22.7%) deaths during a mean follow-up of 40+/-17 months. Rates of all-cause mortality did not differ between the fQRS+ (19.7%) and fQRS- (24.1%) groups; adjusted hazard ratio, 0.88; 95% confidence interval, 0.63-1.22; P=0.43. Additionally, rates of arrhythmic mortality were similar between the fQRS+ (9.9%) and fQRS- (12.7%) groups: adjusted hazard ratio, 0.77; 95% confidence interval, 0.49-1.31; P=0.38. Subgroup analyses found no association between fQRS and mortality when the cohort was further stratified by ICD status, etiology of left ventricular dysfunction, wide (>/=120 ms) versus narrow (<120 ms) QRS duration, or fQRS myocardial territory. CONCLUSIONS: In this prospective, multisite cohort of primary prevention patients with left ventricular dysfunction, the presence of fQRS on ECG was not associated with a higher risk of either all-cause or arrhythmic mortality. These findings do not provide evidence that fQRS would be effective in risk stratifying primary prevention patients eligible for ICD therapy.

Acute mortality in hospitalized patients undergoing echocardiography with and without an ultrasound contrast agent: results in 18,671 consecutive studies.

OBJECTIVES: We sought to define acute mortality in hospitalized patients undergoing clinically indicated echocardiography with and without use of an ultrasound contrast agent. BACKGROUND: The U.S. Food and Drug Administration recently issued a boxed warning and new contraindications for the perflutren-containing ultrasound contrast agents following post-marketing reports of 4 patient deaths that were temporally related to Definity (Bristol-Myers Squibb Medical Imaging, Billerica, Massachusetts) administration. To appreciate the incremental risk of any medical procedure, the ambient risk of untoward outcome in the population in question must first be defined. There are no published data on short-term major adverse cardiac events in hospitalized patients undergoing echocardiography, either with or without administration of an ultrasound contrast agent. METHODS: A retrospective analysis of hospitalized patients undergoing clinically indicated echocardiography between January 2005 and October 2007, within Saint Luke's Health System, Kansas City, Missouri, was performed. Studies were separated into 2 groups, those performed without contrast enhancement (n = 12,475) and those performed with Definity (n = 6,196). Vital status within 24 h of the echocardiographic study was available for all patients using a combination of the Social Security Death Master File and Saint Luke's Health System medical records. Incidence of death within 24 h was compared by chi-square test between Definity and unenhanced procedures. RESULTS: Of the 18,671 patient events, 72 patients died within 24 h. Of those that underwent unenhanced echocardiography, 46 died within 24 h (0.37%). Of patients receiving Definity during the echocardiogram, 26 died within 24 h (0.42%). There was no statistical difference between these 2 groups (p = 0.60). No patient died within 1 h of the echocardiographic study. In a random sampling from the unenhanced (n = 201) and Definity groups (n = 202), patients who underwent Definity-enhanced echocardiography exhibited higher clinical acuity, and more significant comorbidities. CONCLUSIONS: Approximately 0.4% of hospitalized patients die within 24 h of echocardiography. There is no increased mortality risk associated with Definity-enhanced examinations, despite evidence for higher clinical acuity and more comorbid conditions in patients undergoing contrast studies.