The Frog Sign Revisited

The frog sign is a classic physical examination finding of typical atrioventricular nodal re-entrant tachycardia. We present the case of a 78-year-old man with recurrent, symptomatic supraventricular tachycardia referred for ablation in whom the frog sign was observed during physical examination

Lead-associated endocarditis: the important role of methicillin-resistant Staphylococcus aureus.

BACKGROUND: Infection is a potentially life-threatening complication of cardiac device implantation. Lead-associated endocarditis (LAE) may be the most serious complication since it is associated with a high mortality. METHODS: The medical records of patients referred to our institution for the treatment of LAE between 1999 and 2007 were reviewed. RESULTS: A total of 51 of 107 patients referred for device-related infections met the criteria for LAE. Of these, 19 occurred within 6 months of their most recent procedure (early), while the remaining 32 occurred more than 6 months later (mean = 31.9 months post procedure). Devices included pacemakers in 33 patients and ICDs in 18 patients. The most common organism responsible for infection was Staphylococcus aureus (S. aureus) followed by coagulase-negative staphylocci (22%) and streptococci (12%). Methicillin-resistant S. aureus (MRSA) accounted for 67% of the S. aureus infections. Coagulase-negative staphylococci were responsible for only 26% of early and 19% of late cases. A distant site of infection was common (26/51 = 51%), particularly in patients with MRSA LAE. The device and leads were removed percutaneously in all patients. Only one patient failed to respond to intravenous antibiotics. CONCLUSIONS: Our data suggest that methicillin-resistant S. aureus is an important pathogen in LAE. Since many infections occur months after the last device procedure, hematogenous spread of organisms from a distant site may be an important contributing factor. These data suggest that strategies to prevent hematogenous infection, particularly with S. aureus, are critical in patients with implantable cardiac devices

Validation of a Novel, Non-Invasive System for Autonomic Profiling in Healthy Volunteers

Noninvasive profiling of the autonomic nervous system has been shown to have prognostic value in patients with myocardial infarction, CHF and diabetes. The ANSAR system (ANX 3.0, Philadelphia, PA) is a new commercially available system that utilizes respiratory rate, HR and BP to assess on-going sympathovagal modulation during various maneuvers known to evoke autonomic perturbations. Instead of using conventional Fast Fourier Transform for frequency domain analysis, a Continuous Wavelet Transform (CWT) is used to generate numerical and graphical data. The system calculates Low Frequency Area (LFA, analogous to LF Power) and Respiratory Frequency Area (RFA, analogous to High Frequency Power.) A time domain index (pNN50 is also calculated

Trends in permanent pacemaker implantation in the United States from 1993 to 2009: increasing complexity of patients and procedures.

OBJECTIVES: This study sought to define contemporary trends in permanent pacemaker use by analyzing a large national database. BACKGROUND: The Medicare National Coverage Determination for permanent pacemaker, which emphasized single-chamber pacing, has not changed significantly since 1985. We sought to define contemporary trends in permanent pacemaker use by analyzing a large national database. METHODS: We queried the Nationwide Inpatient Sample to identify permanent pacemaker implants between 1993 and 2009 using the International Classification of Diseases-Ninth Revision-Clinical Modification procedure codes for dual-chamber (DDD), single-ventricular (VVI), single-atrial (AAI), or biventricular (BiV) devices. Annual permanent pacemaker implantation rates and patient demographics were analyzed. RESULTS: Between 1993 and 2009, 2.9 million patients received permanent pacemakers in the United States. Overall use increased by 55.6%. By 2009, DDD use increased from 62% to 82% (p \u3c 0.001), whereas single-chamber ventricular pacemaker use fell from 36% to 14% (p = 0.01). Use of DDD devices was higher in urban, nonteaching hospitals (79%) compared with urban teaching hospitals (76%) and rural hospitals (72%). Patients with private insurance (83%) more commonly received DDD devices than Medicaid (79%) or Medicare (75%) recipients (p \u3c 0.001). Patient age and Charlson comorbidity index increased over time. Hospital charges ($2011) increased 45.3%, driven by the increased cost of DDD devices. CONCLUSIONS: There is a steady growth in the use of permanent pacemakers in the United States. Although DDD device use is increasing, whereas single-chamber ventricular pacemaker use is decreasing. Patients are becoming older and have more medical comorbidities. These trends have important health care policy implications

16-year trends in the infection burden for pacemakers and implantable cardioverter-defibrillators in the United States 1993 to 2008.

OBJECTIVES: We analyzed the infection burden associated with the implantation of cardiac implantable electrophysiological devices (CIEDs) in the United States for the years 1993 to 2008. BACKGROUND: Recent data suggest that the rate of infection following CIED implantation may be increasing. METHODS: The Nationwide Inpatient Sample (NIS) discharge records were queried between 1993 and 2008 using the 9th Revision of the International Classification of Diseases (ICD-9-CM). CIED infection was defined as either: 1) ICD-9 code for device-related infection (996.61) and any CIED procedure or removal code; or 2) CIED procedure code along with systemic infection. Patient health profile was evaluated by coding for renal failure, heart failure, respiratory failure, and diabetes mellitus. The infection burden and patient health profile were calculated for each year, and linear regression was used to test for changes over time. RESULTS: During the study period (1993 to 2008), the incidence of CIED infection was 1.61%. The annual rate of infections remained constant until 2004, when a marked increase was observed, which coincided with an increase in the incidence of major comorbidities. This was associated with a marked increase in mortality and in-hospital financial charges. CONCLUSIONS: The infection burden associated with CIED implantation is increasing over time and is associated with prolonged hospital stays and high financial costs

Quantifying risks and interventions that have affected the burden of diarrhoea among children younger than 5 years : an analysis of the Global Burden of Disease Study 2017

Background Many countries have shown marked declines in diarrhoea! disease mortality among children younger than 5 years. With this analysis, we provide updated results on diarrhoeal disease mortality among children younger than 5 years from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) and use the study's comparative risk assessment to quantify trends and effects of risk factors, interventions, and broader sociodemographic development on mortality changes in 195 countries and territories from 1990 to 2017. Methods This analysis for GBD 2017 had three main components. Diarrhoea mortality was modelled using vital registration data, demographic surveillance data, and verbal autopsy data in a predictive, Bayesian, ensemble modelling tool; and the attribution of risk factors and interventions for diarrhoea were modelled in a counterfactual framework that combines modelled population-level prevalence of the exposure to each risk or intervention with the relative risk of diarrhoea given exposure to that factor. We assessed the relative and absolute change in diarrhoea mortality rate between 1990 and 2017, and used the change in risk factor exposure and sociodemographic status to explain differences in the trends of diarrhoea mortality among children younger than 5 years. Findings Diarrhoea was responsible for an estimated 533 768 deaths (95% uncertainty interval 477 162-593 145) among children younger than 5 years globally in 2017, a rate of 78.4 deaths (70.1-87.1) per 100 000 children. The diarrhoea mortality rate ranged between countries by over 685 deaths per 100 000 children. Diarrhoea mortality per 100 000 globally decreased by 69.6% (63.1-74.6) between 1990 and 2017. Among the risk factors considered in this study, those responsible for the largest declines in the diarrhoea mortality rate were reduction in exposure to unsafe sanitation (13.3% decrease, 11.2-15.5), childhood wasting (9.9% decrease, 9.6-10.2), and low use of oral rehydration solution (6.9% decrease, 4-8-8-4). Interpretation Diarrhoea mortality has declined substantially since 1990, although there are variations by country. Improvements in sociodemographic indicators might explain some of these trends, but changes in exposure to risk factors-particularly unsafe sanitation, childhood growth failure, and low use of oral rehydration solution-appear to be related to the relative and absolute rates of decline in diarrhoea mortality. Although the most effective interventions might vary by country or region, identifying and scaling up the interventions aimed at preventing and protecting against diarrhoea that have already reduced diarrhoea mortality could further avert many thousands of deaths due to this illness. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.Peer reviewe

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress

Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017

Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2\ub75th percentile and 100 as the 97\ub75th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59\ub74 (IQR 35\ub74–67\ub73), ranging from a low of 11\ub76 (95% uncertainty interval 9\ub76–14\ub70) to a high of 84\ub79 (83\ub71–86\ub77). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030