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The team of Deputy and Associate Editors Heribert Schunkert, Sharlene Day and Peter SchwartzThe European Heart Journal (EHJ) wants to attract high-class submissions dealing with genetic findings that help how much does generic cipro cost to improve the mechanistic understanding and the therapy of cardiovascular diseases. In charge of identifying such articles is a mini-team of experts on genetics, Heribert Schunkert, Sharlene Day, and Peter Schwartz.Genetic findings have contributed enormously to the molecular understanding of cardiovascular diseases. A number of diseases including various channelopathies, cardiomyopathies, and metabolic disorders have been elucidated based on a monogenic inheritance and the detection of disease-causing mutations in large families how much does generic cipro cost. More recently, the complex genetic architecture of common cardiovascular diseases such as atrial fibrillation or coronary artery disease has become increasingly clear.

Moreover, genetics became a how much does generic cipro cost sensitive tool to characterize the role of traditional cardiovascular risk factors in the form of Mendelian randomized studies. However, the real challenge is still ahead, i.e., to bridge genetic findings into novel therapies for the prevention and treatment of cardiac diseases. The full cycle from identification of a family with hypercholesterolaemia due how much does generic cipro cost to a proprotein convertase subtilisin/kexin type 9 (PCSK-9) mutation to successful risk lowering by PCSK-9 antibodies illustrates the power of genetics in this regard.With its broad expertise, the new EHJ editorial team on genetics aims to cover manuscripts from all areas in which genetics may contribute to the understanding of cardiovascular diseases. Prof.

Peter Schwartz is a world-class expert how much does generic cipro cost on channelopathies and pioneered the field of long QT syndrome. He is an experienced clinical specialist on cardiac arrhythmias of genetic origins and a pioneer in the electrophysiology of the myocardium. He studied in Milan, worked at the University of Texas for 3 years and, as Associate Professor, at the University of Oklahoma 4 months/year for 12 years. He has been Chairman of Cardiology at the University of Pavia for 20 years and since 1999 acts as an extraordinary professor at the Universities of Stellenbosch how much does generic cipro cost and Cape Town for 3 months/year.Prof.

Sharlene M. Day is how much does generic cipro cost Director of Translational Research in the Division of Cardiovascular Medicine and Cardiovascular Institute at the University of Pennsylvania. She trained at the University of Michigan and stayed on as faculty as the founding Director of the Inherited Cardiomyopathy and Arrhythmia Program before moving to the University of Pennsylvania in 2019. Like Prof how much does generic cipro cost.

Schwartz, her research programme covers the full spectrum from clinical medicine to basic research with a focus on hypertrophic cardiomyopathy. Both she and Prof how much does generic cipro cost. Schwartz have developed inducible pluripotent stem cell models of human monogenic cardiac disorders as a platform to study the underlying biological mechanisms of disease.Heribert Schunkert is Director of the Cardiology Department in the German Heart Center Munich. He trained in the Universities of Aachen and Regensburg, Germany and how much does generic cipro cost for 4 years in various teaching hospitals in Boston.

Before moving to Munich, he was Director of the Department for Internal Medicine at the University Hospital in Lübeck. His research interest shifted from the molecular biology of the renin–angiotensin system to complex genetics of atherosclerosis. He was amongst the first to conduct genome-wide association meta-analyses, which allowed the identification of numerous genetic variants that contribute to coronary artery disease, peripheral arterial disease, or aortic stenosis.The how much does generic cipro cost editorial team on cardiovascular genetics aims to facilitate the publication of strong translational research that illustrates to clinicians and cardiovascular scientists how genetic and epigenetic variation influences the development of heart diseases. The future perspective is to communicate genetically driven therapeutic targets as has become evident already with the utilization of interfering antibodies, RNAs, or even genome-editing instruments.In this respect, the team encourages submission of world-class genetic research on the cardiovascular system to the EHJ.

The team is also pleased to cooperate with the novel Council how much does generic cipro cost on Cardiovascular Genomics which was inaugurated by the ESC in 2020.Conflict of interest. None declared.Andros TofieldMerlischachen, Switzerland Published on behalf of the European Society of Cardiology. All rights reserved how much does generic cipro cost. © The Author(s) 2020.

For permissions, please how much does generic cipro cost email. Journals.permissions@oup.com.With thanks to Amelia Meier-Batschelet, Johanna Huggler, and Martin Meyer for help with compilation of this article. For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts.This is a Focus Issue on genetics. Described as the ‘single largest unmet need in cardiovascular medicine’, heart failure with preserved ejection fraction (HFpEF) remains an how much does generic cipro cost untreatable disease currently representing 65% of new HF diagnoses. HFpEF is more frequent among women and is associated with a poor prognosis and unsustainable healthcare costs.1,2 Moreover, the variability in HFpEF phenotypes amplifies the complexity and difficulties of the approach.3–5 In this perspective, unveiling novel molecular targets is imperative.

In a State of the Art Review article entitled ‘Leveraging clinical epigenetics in heart failure with preserved ejection fraction. A call for individualized therapies’, authored by Francesco Paneni from the University of Zurich in Switzerland, and colleagues,6 the authors note that epigenetic modifications—defined as changes of how much does generic cipro cost DNA, histones, and non-coding RNAs (ncRNAs)—represent a molecular framework through which the environment modulates gene expression.6 Epigenetic signals acquired over a lifetime lead to chromatin remodelling and affect transcriptional programmes underlying oxidative stress, inflammation, dysmetabolism, and maladaptive left ventricular (LV) remodelling, all conditions predisposing to HFpEF. The strong involvement of epigenetic signalling in this setting makes the epigenetic information relevant for diagnostic and therapeutic purposes in patients with HFpEF. The recent advances in high-throughput sequencing, computational epigenetics, and machine learning have enabled the how much does generic cipro cost identification of reliable epigenetic biomarkers in cardiovascular patients.

In contrast to genetic tools, epigenetic biomarkers mirror the contribution of environmental cues and lifestyle changes, and their reversible nature offers a promising opportunity to monitor disease states. The growing understanding of chromatin and ncRNA biology has led to the development of several Food and Drug Administration (FDA)-approved ‘epi-drugs’ (chromatin modifiers, mimics, and anti-miRs) able to prevent transcriptional alterations how much does generic cipro cost underpinning LV remodelling and HFpEF. In the present review, Paneni and colleagues discuss the importance of clinical epigenetics as a new tool to be employed for a personalized management of HFpEF.Sick sinus syndrome (SSS) is a complex cardiac arrhythmia and the leading indication for permanent pacemaker implantation worldwide. It is characterized by pathological sinus bradycardia, sinoatrial how much does generic cipro cost block, or alternating atrial brady- and tachyarrhythmias.

Symptoms include fatigue, reduced exercise capacity, and syncope. Few studies have been conducted on the basic mechanisms of SSS, and therapeutic limitations reflect how much does generic cipro cost an incomplete understanding of the pathophysiology.7 In a clinical research entitled ‘Genetic insight into sick sinus syndrome’, Rosa Thorolfsdottir from deCODE genetics in Reykjavik, Iceland, and colleagues aimed to use human genetics to investigate the pathogenesis of SSS and the role of risk factors in its development.8 The authors performed a genome-wide association study (GWAS) of >6000 SSS cases and >1 000 000 controls. Variants at six loci associated with SSS. A full genotypic model best described the p.Gly62Cys association, with an odds ratio (OR) of 1.44 for heterozygotes and a disproportionally large OR of 13.99 for homozygotes.

All the how much does generic cipro cost SSS variants increased the risk of pacemaker implantation. Their association with atrial fibrillation (AF) varied, and p.Gly62Cys was the only variant not associating with any other arrhythmia or cardiovascular disease. They also tested 17 exposure phenotypes in polygenic score (PGS) and Mendelian how much does generic cipro cost randomization analyses. Only two associated with risk of SSS in Mendelian randomization—AF and lower heart rate—suggesting causality.

Powerful PGS analyses provided convincing evidence against causal associations for body mass index, cholesterol, triglycerides, and type 2 diabetes (P how much does generic cipro cost >. 0.05) (Figure 1). Figure 1Summary of genetic insight into the pathogenesis of sick sinus how much does generic cipro cost syndrome (SSS) and the role of risk factors in its development. Variants at six loci (named by corresponding gene names) were identified through genome-wide association study (GWAS), and their unique phenotypic associations provide insight into distinct pathways underlying SSS.

Investigation of the role of risk factors in SSS development supported a causal role for atrial fibrillation (AF) and heart rate, and provided convincing evidence against causality for body how much does generic cipro cost mass index (BMI), cholesterol (HDL and non-HDL), triglycerides, and type 2 diabetes (T2D). Mendelian randomization did not support causality for coronary artery disease, ischaemic stroke, heart failure, PR interval, or QRS duration (not shown in the figure). Red and blue arrows represent positive and negative associations, respectively (from Thorolfsdottir RB, Sveinbjornsson G, Aegisdottir HM, Benonisdottir S, Stefansdottir L, Ivarsdottir EV, Halldorsson GH, Sigurdsson JK, Torp-Pedersen C, Weeke PE, Brunak S, Westergaard D, Pedersen OB, Sorensen E, Nielsen KR, Burgdorf KS, Banasik K, Brumpton B, Zhou W, Oddsson A, Tragante V, Hjorleifsson KE, Davidsson OB, Rajamani S, Jonsson S, Torfason B, Valgardsson AS, Thorgeirsson G, Frigge ML, Thorleifsson G, Norddahl GL, Helgadottir A, Gretarsdottir S, Sulem P, Jonsdottir I, Willer CJ, Hveem K, Bundgaard H, Ullum H, Arnar DO, Thorsteinsdottir U, Gudbjartsson DF, Holm H, Stefansson K. Genetic insight how much does generic cipro cost into sick sinus syndrome.

See pages 1959–1971.).Figure 1Summary of genetic insight into the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development. Variants at six loci (named by corresponding gene names) were identified through how much does generic cipro cost genome-wide association study (GWAS), and their unique phenotypic associations provide insight into distinct pathways underlying SSS. Investigation of the role of risk factors in SSS development supported a causal role for atrial fibrillation (AF) and heart rate, and provided convincing evidence against causality for body mass index (BMI), cholesterol (HDL and non-HDL), triglycerides, and type 2 diabetes (T2D). Mendelian randomization did not support causality for coronary artery disease, ischaemic stroke, heart failure, PR interval, or QRS duration how much does generic cipro cost (not shown in the figure).

Red and blue arrows represent positive and negative associations, respectively (from Thorolfsdottir RB, Sveinbjornsson G, Aegisdottir HM, Benonisdottir S, Stefansdottir L, Ivarsdottir EV, Halldorsson GH, Sigurdsson JK, Torp-Pedersen C, Weeke PE, Brunak S, Westergaard D, Pedersen OB, Sorensen E, Nielsen KR, Burgdorf KS, Banasik K, Brumpton B, Zhou W, Oddsson A, Tragante V, Hjorleifsson KE, Davidsson OB, Rajamani S, Jonsson S, Torfason B, Valgardsson AS, Thorgeirsson G, Frigge ML, Thorleifsson G, Norddahl GL, Helgadottir A, Gretarsdottir S, Sulem P, Jonsdottir I, Willer CJ, Hveem K, Bundgaard H, Ullum H, Arnar DO, Thorsteinsdottir U, Gudbjartsson DF, Holm H, Stefansson K. Genetic insight how much does generic cipro cost into sick sinus syndrome. See pages 1959–1971.).Thorolfsdottir et al. Conclude that they report the associations of variants at six loci with SSS, including a missense variant in KRT8 that confers high risk in homozygotes and points to a mechanism specific to SSS how much does generic cipro cost development.

Mendelian randomization supports a causal role for AF in the development of SSS. The article is accompanied by an Editorial by Stefan Kääb from LMU Klinikum in Munich, Germany, and colleagues.9 The authors conclude that the limitations of the work challenge clinical translation, but do not diminish the multiple interesting findings of Thorolfsdottir et al., bringing us closer to the finishing line of unlocking SSS genetics to develop new therapeutic strategies. They also highlight that this study represents a considerable accomplishment for the field, but also clearly highlights upcoming challenges and indicates areas where further research is warranted on our way on the translational road to personalized medicine.Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder that affects ∼1 in every 3500 live-born male infants, making how much does generic cipro cost it the most common neuromuscular disease of childhood. The disease is caused by mutations in the dystrophin gene, which lead to dystrophin deficiency in muscle cells, resulting in decreased fibre stability and continued degeneration.

The patients present how much does generic cipro cost with progressive muscle wasting and loss of muscle function, develop restrictive respiratory failure and dilated cardiomyopathy, and usually die in their late teens or twenties from cardiac or respiratory failure.10 In a clinical research article ‘Association between prophylactic angiotensin-converting enzyme inhibitors and overall survival in Duchenne muscular dystrophy. Analysis of registry data’ Raphaël Porcher from the Université de Paris in France, and colleagues estimate the effect of prophylactic angiotensin-converting enzyme (ACE) inhibitors on survival in DMD.11 The authors analysed the data from the French multicentre DMD-Heart-Registry. They estimated the association between the prophylactic prescription of ACE inhibitors and event-free survival in 668 patients between the ages of 8 and 13 years, with normal left how much does generic cipro cost ventricular function, using (i) a Cox model with intervention as a time-dependent covariate. (ii) a propensity-based analysis comparing ACE inhibitor treatment vs.

No treatment how much does generic cipro cost. And (iii) a set of sensitivity analyses. The study outcomes were (i) overall survival and (ii) hospitalizations for HF or acute respiratory failure. Among the patients included in the DMD-Heart-Registry, 576 were eligible for this study, how much does generic cipro cost of whom 390 were treated with an ACE inhibitor prophylactically.

Death occurred in 53 patients (13.5%) who were and 60 patients (32.3%) who were not treated prophylactically with an ACE inhibitor. In a Cox model, with intervention as a time-dependent variable, the how much does generic cipro cost hazard ratio (HR) associated with ACE inhibitor treatment was 0.49 for overall mortality after adjustment for baseline variables. In the propensity-based analysis, with 278 patients included in the treatment group and 302 in the control group, ACE inhibitors were associated with a lower risk of death (HR 0.32) and hospitalization for HF (HR 0.16) (Figure 2). All sensitivity analyses yielded similar how much does generic cipro cost results.

Figure 2Graphical Abstract (from Porcher R, Desguerre I, Amthor H, Chabrol B, Audic F, Rivier F, Isapof A, Tiffreau V, Campana-Salort E, Leturcq F, Tuffery-Giraud S, Ben Yaou R, Annane D, Amédro P, Barnerias C, Bécane HM, Béhin A, Bonnet D, Bassez G, Cossée M, de La Villéon G, Delcourte C, Fayssoil A, Fontaine B, Godart F, Guillaumont S, Jaillette E, Laforêt P, Leonard-Louis S, Lofaso F, Mayer M, Morales RJ, Meune C, Orlikowski D, Ovaert C, Prigent H, Saadi M, Sochala M, Tard C, Vaksmann G, Walther-Louvier U, Eymard B, Stojkovic T, Ravaud P, Duboc D, Wahbi K. Association between how much does generic cipro cost prophylactic angiotensin-converting enzyme inhibitors and overall survival in Duchenne muscular dystrophy. Analysis of registry data. See pages 1976–1984.).Figure 2Graphical Abstract (from Porcher R, Desguerre I, Amthor H, Chabrol B, Audic F, Rivier F, Isapof A, Tiffreau V, Campana-Salort E, Leturcq F, Tuffery-Giraud S, Ben Yaou R, Annane D, Amédro P, Barnerias C, Bécane HM, Béhin A, Bonnet D, Bassez G, Cossée M, de La Villéon G, Delcourte C, Fayssoil A, Fontaine B, Godart F, Guillaumont S, Jaillette E, Laforêt P, Leonard-Louis S, Lofaso F, Mayer M, Morales RJ, Meune C, Orlikowski D, Ovaert C, Prigent H, Saadi M, Sochala M, Tard C, how much does generic cipro cost Vaksmann G, Walther-Louvier U, Eymard B, Stojkovic T, Ravaud P, Duboc D, Wahbi K.

Association between prophylactic angiotensin-converting enzyme inhibitors and overall survival in Duchenne muscular dystrophy. Analysis of registry data. See pages how much does generic cipro cost 1976–1984.).Porcher et al. Conclude that prophylactic treatment with ACE inhibitors in DMD is associated with a significantly higher overall survival and lower rate of hospitalization for management of HF.

The manuscript is accompanied by an Editorial by Mariell Jessup and colleagues from the American Heart Association in Dallas, Texas, USA.12 The authors describe how cardioprotective strategies have been investigated in a number of cardiovascular disorders and successfully how much does generic cipro cost incorporated into treatment regimens for selected patients, including ACE inhibitors in patients with and without diabetes and coronary artery disease, angiotensin receptor blockers and beta-blockers in Marfan syndrome, and ACE inhibitors and beta-blockers in patients at risk for chemotherapy-related toxicity. They conclude that Porcher et al. Have now convincingly demonstrated that even very young patients with DMD can benefit from the life-saving intervention of ACE inhibition.Hypertrophic cardiomyopathy (HCM) is characterized by unexplained LV hypertrophy and often caused how much does generic cipro cost by pathogenic variants in genes that encode the sarcomere apparatus. Patients with HCM may experience atrial and ventricular arrhythmias and HF.

However, disease expression and severity are highly how much does generic cipro cost variable. Furthermore, there is marked diversity in the age of diagnosis. Although childhood-onset disease is how much does generic cipro cost well documented, it is far less common. Owing to its rarity, the natural history of childhood-onset HCM is not well characterized.12–14 In a clinical research article entitled ‘Clinical characteristics and outcomes in childhood-onset hypertrophic cardiomyopathy’, Nicholas Marston from the Harvard Medical School in Boston, MA, USA, and colleagues aimed to describe the characteristics and outcomes of childhood-onset HCM.15 They performed an observational cohort study of >7500 HCM patients.

HCM patients were stratified by age at diagnosis [<1 year (infancy), 1–18 years (childhood), >18 years (adulthood)] and assessed for composite endpoints including HF, life-threatening ventricular arrhythmias, AF, and an overall composite that also included stroke and death. Stratifying by age of diagnosis, 2.4% of how much does generic cipro cost patients were diagnosed in infancy, 14.7% in childhood, and 2.9% in adulthood. Childhood-onset HCM patients had an ∼2%/year event rate for the overall composite endpoint, with ventricular arrhythmias representing the most common event in the first decade following the baseline visit, and HF and AF more common by the end of the second decade. Sarcomeric HCM was more common in childhood-onset HCM (63%) and carried a worse prognosis than non-sarcomeric how much does generic cipro cost disease, including a >2-fold increased risk of HF and 67% increased risk of the overall composite outcome.

When compared with adult-onset HCM, those with childhood-onset disease were 36% more likely to develop life-threatening ventricular arrhythmias and twice as likely to require transplant or a ventricular assist device.The authors conclude that patients with childhood-onset HCM are more likely to have sarcomeric disease, carry a higher risk of life-threatening ventricular arrythmias, and have greater need for advanced HF therapies. The manuscript is accompanied by an Editorial by Juan Pablo Kaski from the University College London (UCL) Institute of Cardiovascular Science in London, UK.16 Kaski concludes that the field of HCM is now entering the era of personalized medicine, with how much does generic cipro cost the advent of gene therapy programmes and a focus on treatments targeting the underlying pathophysiology. Pre-clinical data suggesting that small molecule myosin inhibitors may attenuate or even prevent disease expression provide cause for optimism, and nowhere more so than for childhood-onset HCM. An international collaborative approach involving basic, translational, and clinical science is now needed to characterize disease expression and progression and develop novel therapies for childhood HCM.Dilated cardiomyopathy (DCM) is a heart muscle disease characterized by LV dilatation and systolic dysfunction in the absence of abnormal loading conditions or how much does generic cipro cost coronary artery disease.

It is a major cause of systolic HF, the leading indication for heart transplantation, and therefore a major public health problem due to the important cardiovascular morbidity and mortality.17,18 Understanding of the genetic basis of DCM has improved in recent years, with a role for both rare and common variants resulting in a complex genetic architecture of the disease. In a translational research article entitled ‘Genome-wide association analysis in dilated cardiomyopathy reveals two new players in systolic heart failure on chromosomes 3p25.1 and 22q11.23’, Sophie how much does generic cipro cost Garnier from the Sorbonne Université in Paris, France, and colleagues conducted the largest genome-wide association study performed so far in DCM, with >2500 cases and >4000 controls in the discovery population.19 They identified and replicated two new DCM-associated loci, on chromosome 3p25.1 and chromosome 22q11.23, while confirming two previously identified DCM loci on chromosomes 10 and 1, BAG3 and HSPB7. A PGS constructed from the number of risk alleles at these four DCM loci revealed a 27% increased risk of DCM for individuals with eight risk alleles compared with individuals with five risk alleles (median of the referral population). In silico annotation and functional 4C-sequencing analysis on induced pluripotent stem cell (iPSC)-derived cardiomyocytes identified SLC6A6 as the most likely DCM gene at the 3p25.1 locus.

This gene encodes a taurine how much does generic cipro cost transporter whose involvement in myocardial dysfunction and DCM is supported by numerous observations in humans and animals. At the 22q11.23 locus, in silico and data mining annotations, and to a lesser extent functional analysis, strongly suggested SMARCB1 as the candidate culprit gene.Garnier et al. Conclude that their how much does generic cipro cost study provides a better understanding of the genetic architecture of DCM and sheds light on novel biological pathways underlying HF. The manuscript is accompanied by an Editorial by Elizabeth McNally from the Northwestern University Feinberg School of Medicine in Chicago, USA, and colleagues.20 The authors conclude that methods to integrate common and rare genetic information will continue to evolve and provide insight on disease progression, potentially providing biomarkers and clues for useful therapeutic pathways to guide drug development.

At present, rare cardiomyopathy variants how much does generic cipro cost have clinical utility in predicting risk, especially arrhythmic risk. PGS analyses for HF or DCM progression are expected to come to clinical use, especially with the addition of broader GWAS-derived data. Combining genetic how much does generic cipro cost risk data with clinical and social determinants should help identify those at greatest risk, offering the opportunity for risk reduction.In a Special Article entitled ‘Influenza vaccination. A ‘shot’ at INVESTing in cardiovascular health’, Scott Solomon from the Brigham and Women’s Hospital, Harvard Medical School in Boston, MA, USA, and colleagues note that the link between viral respiratory and non-pulmonary organ-specific injury has become increasingly appreciated during the current antibiotics disease 2019 (buy antibiotics) cipro.21 Even prior to the cipro, however, the association between acute with influenza and elevated cardiovascular risk was evident.

The recently how much does generic cipro cost published results of the NHLBI-funded INVESTED trial, a 5200-patient comparative effectiveness study of high-dose vs. Standard-dose influenza treatment to reduce cardiopulmonary events and mortality in a high-risk cardiovascular population, found no difference between strategies. However, the broader implications of influenza treatment as a strategy to reduce morbidity in high-risk patients remains extremely important, with randomized control trial and observational data supporting vaccination in high-risk patients with cardiovascular disease. Given a favourable risk–benefit profile and widespread availability at generally low cost, the authors contend that influenza vaccination should remain a centrepiece of cardiovascular risk mitigation and describe the how much does generic cipro cost broader context of underutilization of this strategy.

Few therapeutics in medicine offer seasonal efficacy from a single administration with generally mild, transient side effects and exceedingly low rates of serious adverse effects. control measures such as physical distancing, hand washing, and the use of masks during the buy antibiotics cipro have already been associated with substantially how much does generic cipro cost curtailed incidence of influenza outbreaks across the globe. Appending annual influenza vaccination to these measures represents an important public health and moral imperative.The issue is complemented by two Discussion Forum articles. In a contribution entitled ‘Management of acute coronary how much does generic cipro cost syndromes in patients presenting without persistent ST-segment elevation and coexistent atrial fibrillation’, Paolo Verdecchia from the Hospital S.

Maria della Misericordia in Perugia, Italy, and colleagues comment on the recently published contribution ‘2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. The Task Force for the management of acute coronary syndromes in patients how much does generic cipro cost presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC)’.22,23 A response to Verdecchia’s comment has been supplied by Collet et al.24The editors hope that readers of this issue of the European Heart Journal will find it of interest. References1Sorimachi H, Obokata M, Takahashi N, Reddy YNV, Jain CC, Verbrugge FH, Koepp KE, Khosla S, Jensen MD, Borlaug BA. Pathophysiologic importance of visceral adipose tissue in women with heart failure and preserved ejection fraction.

Eur Heart J how much does generic cipro cost 2021;42:1595–1605.2Omland T. Targeting the endothelin system. A step towards a precision medicine approach how much does generic cipro cost in heart failure with preserved ejection fraction?. Eur Heart J 2019;40:3718–3720.3Reddy YNV, Obokata M, Wiley B, Koepp KE, Jorgenson CC, Egbe A, Melenovsky V, Carter RE, Borlaug BA.

The haemodynamic basis how much does generic cipro cost of lung congestion during exercise in heart failure with preserved ejection fraction. Eur Heart J 2019;40:3721–3730.4Obokata M, Kane GC, Reddy YNV, Melenovsky V, Olson TP, Jarolim P, Borlaug BA. The neurohormonal basis of pulmonary hypertension how much does generic cipro cost in heart failure with preserved ejection fraction. Eur Heart J 2019;40:3707–3717.5Pieske B, Tschöpe C, de Boer RA, Fraser AG, Anker SD, Donal E, Edelmann F, Fu M, Guazzi M, Lam CSP, Lancellotti P, Melenovsky V, Morris DA, Nagel E, Pieske-Kraigher E, Ponikowski P, Solomon SD, Vasan RS, Rutten FH, Voors AA, Ruschitzka F, Paulus WJ, Seferovic P, Filippatos G.

How to diagnose heart failure how much does generic cipro cost with preserved ejection fraction. The HFA-PEFF diagnostic algorithm. A consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). Eur Heart J 2019;40:3297–3317.6Hamdani N, Costantino S, Mügge A, Lebeche D, Tschöpe C, Thum T, how much does generic cipro cost Paneni F.

Leveraging clinical epigenetics in heart failure with preserved ejection fraction. A call for individualized how much does generic cipro cost therapies. Eur Heart J 2021;42:1940–1958.7Corrigendum to. 2018 ESC how much does generic cipro cost Guidelines for the diagnosis and management of syncope.

Eur Heart J 2018;39:2002.8Thorolfsdottir RB, Sveinbjornsson G, Aegisdottir HM, Benonisdottir S, Stefansdottir L, Ivarsdottir EV, Halldorsson GH, Sigurdsson JK, Torp-Pedersen C, Weeke PE, Brunak S, Westergaard D, Pedersen OB, Sorensen E, Nielsen KR, Burgdorf KS, Banasik K, Brumpton B, Zhou W, Oddsson A, Tragante V, Hjorleifsson KE, Davidsson OB, Rajamani S, Jonsson S, Torfason B, Valgardsson AS, Thorgeirsson G, Frigge ML, Thorleifsson G, Norddahl GL, Helgadottir A, Gretarsdottir S, Sulem P, Jonsdottir I, Willer CJ, Hveem K, Bundgaard H, Ullum H, Arnar DO, Thorsteinsdottir U, Gudbjartsson DF, Holm H, Stefansson K. Genetic insight how much does generic cipro cost into sick sinus syndrome. Eur Heart J 2021;42:1959–1971.9Tomsits P, Claus S, Kääb S. Genetic insight how much does generic cipro cost into sick sinus syndrome.

Is there a pill for it or how far are we on the translational road to personalized medicine?. Eur Heart J 2021;42:1972–1975.10Hoffman EP, Fischbeck KH, Brown RH, Johnson M, Medori R, Loike JD, Harris JB, Waterston R, Brooke M, Specht L, Kupsky W, Chamberlain J, Caskey T, Shapiro F, Kunkel LM. Characterization of how much does generic cipro cost dystrophin in muscle-biopsy specimens from patients with Duchenne’s or Becker’s muscular dystrophy. N Engl J Med 1988;318:1363–1368.11Porcher R, Desguerre I, Amthor H, Chabrol B, Audic F, Rivier F, Isapof A, Tiffreau V, Campana-Salort E, Leturcq F, Tuffery-Giraud S, Ben Yaou R, Annane D, Amédro P, Barnerias C, Bécane HM, Béhin A, Bonnet D, Bassez G, Cossée M, de La Villéon G, Delcourte C, Fayssoil A, Fontaine B, Godart F, Guillaumont S, Jaillette E, Laforêt P, Leonard-Louis S, Lofaso F, Mayer M, Morales RJ, Meune C, Orlikowski D, Ovaert C, Prigent H, Saadi M, Sochala M, Tard C, Vaksmann G, Walther-Louvier U, Eymard B, Stojkovic T, Ravaud P, Duboc D, Wahbi K.

Association between how much does generic cipro cost prophylactic angiotensin-converting enzyme inhibitors and overall survival in Duchenne muscular dystrophy. Analysis of registry data. Eur Heart J 2021;42:1976–1984.12Owens how much does generic cipro cost AT, Jessup M. Cardioprotection in Duchenne muscular dystrophy.

Eur Heart J 2021;42:1985–1987.13Semsarian how much does generic cipro cost C, Ho CY. Screening children at risk for hypertrophic cardiomyopathy. Balancing benefits and harms how much does generic cipro cost. Eur Heart J 2019;40:3682–3684.14Lafreniere-Roula M, Bolkier Y, Zahavich L, Mathew J, George K, Wilson J, Stephenson EA, Benson LN, Manlhiot C, Mital S.

Family screening for hypertrophic cardiomyopathy. Is it time how much does generic cipro cost to change practice guidelines?. Eur Heart J 2019;40:3672–3681.15Marston NA, Han L, Olivotto I, Day SM, Ashley EA, Michels M, Pereira AC, Ingles J, Semsarian C, Jacoby D, Colan SD, Rossano JW, Wittekind SG, Ware JS, Saberi S, Helms AS, Ho CY. Clinical characteristics and outcomes in childhood-onset hypertrophic cardiomyopathy how much does generic cipro cost.

Eur Heart J 2021;42:1988–1996.16Kaski JP. Childhood-onset hypertrophic how much does generic cipro cost cardiomyopathy research coming of age. Eur Heart J 2021;42:1997–1999.17Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi F, Charron P, Dubourg O, Kühl U, Maisch B, McKenna WJ, Monserrat L, Pankuweit S, Rapezzi C, Seferovic P, Tavazzi L, Keren A. Classification of the cardiomyopathies how much does generic cipro cost.

A position statement from the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2008;29:270–276.18Crea how much does generic cipro cost F. Machine learning-guided phenotyping of dilated cardiomyopathy and treatment of heart failure by antisense oligonucleotides. The future has begun.

Eur Heart J 2021;42:139–142.19Garnier S, Harakalova M, Weiss S, Mokry M, Regitz-Zagrosek how much does generic cipro cost V, Hengstenberg C, Cappola TP, Isnard R, Arbustini E, Cook SA, van Setten J, Calis JJA, Hakonarson H, Morley MP, Stark K, Prasad SK, Li J, O’Regan DP, Grasso M, Müller-Nurasyid M, Meitinger T, Empana JP, Strauch K, Waldenberger M, Marguiles KB, Seidman CE, Kararigas G, Meder B, Haas J, Boutouyrie P, Lacolley P, Jouven X, Erdmann J, Blankenberg S, Wichter T, Ruppert V, Tavazzi L, Dubourg O, Roizes G, Dorent R, de Groote P, Fauchier L, Trochu JN, Aupetit JF, Bilinska ZT, Germain M, Völker U, Hemerich D, Raji I, Bacq-Daian D, Proust C, Remior P, Gomez-Bueno M, Lehnert K, Maas R, Olaso R, Saripella GV, Felix SB, McGinn S, Duboscq-Bidot L, van Mil A, Besse C, Fontaine V, Blanché H, Ader F, Keating B, Curjol A, Boland A, Komajda M, Cambien F, Deleuze JF, Dörr M, Asselbergs FW, Villard E, Trégouët DA, Charron P. Genome-wide association analysis in dilated cardiomyopathy reveals two new players in systolic heart failure on chromosomes 3p25.1 and 22q11.23. Eur Heart how much does generic cipro cost J 2021;42:2000–2011.20Fullenkamp DE, Puckelwartz MJ, McNally EM. Genome-wide association for heart failure.

From discovery to clinical use how much does generic cipro cost. Eur Heart J 2021;42:2012–2014.21Bhatt AS, Vardeny O, Udell JA, Joseph J, Kim K, Solomon SD. Influenza vaccination how much does generic cipro cost. A ‘shot’ at INVESTing in cardiovascular health.

Eur Heart J 2021;42:2015–2018.22Verdecchia how much does generic cipro cost P, Angeli F, Cavallini C. Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation and coexistent atrial fibrillation. Eur Heart J 2021;42:2019.23Collet JP, Thiele H, Barbato E, Barthélémy O, Bauersachs J, Bhatt DL, Dendale P, Dorobantu M, Edvardsen T, Folliguet T, Gale CP, Gilard M, Jobs A, Jüni P, Lambrinou E, Lewis BS, Mehilli J, Meliga E, Merkely B, Mueller C, Roffi M, Rutten FH, Sibbing D, Siontis GCM. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment how much does generic cipro cost elevation.

Eur Heart J 2021;42:1289–1367.24Collet JP, Thiele H. Management of acute coronary syndromes in how much does generic cipro cost patients presenting without persistent ST-segment elevation and coexistent atrial fibrillation – Dual versus triple antithrombotic therapy. Eur Heart J 2021;42:2020–2021. Published on how much does generic cipro cost behalf of the European Society of Cardiology.

All rights reserved. © The Author(s) how much does generic cipro cost 2021. For permissions, please email. Journals.permissions@oup.com..

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New survey insights released to mark Digital Health Week 2020November 16, 2020 (Toronto) — Canadians and health care providers have http://es.keimfarben.de/cheap-cialis-canada met the unprecedented challenge of the buy antibiotics cipro head-on by embracing change in the what does a cipro pill look like way health care is delivered — from in-person to virtual. This week is Digital Health Week and to mark the occasion Canada Health Infoway (Infoway) is sharing research conducted in partnership with what does a cipro pill look like Environics that digs into this substantial shift and what Canadians want for their digital health future. This latest research project, A Healthy Dialogue, is one of the largest public consultations about digital health ever conducted in Canada. The consultation reached more than 58,000 Canadians — including those underserved by the health system — who shared how they thought technology would impact their care experience.The research reveals[i]:An overwhelming majority (92%) of Canadians want technology that makes health care as convenient as other aspects of their lives.More than half (53%) of Canadians who have used health technology in the past year say it helped them avoid an in-person visit to a provider or an emergency room.Of those Canadians who received virtual care during the cipro, 91% were satisfied with the experience, 86% agreed that virtual care tools can be important alternatives to seeing doctors in-person, and more than three-quarters (76%) are willing to what does a cipro pill look like use virtual care after the cipro.“We’ve gone from talking about ways to further integrate digital health into everyday health care to living it. The events of the past year have accelerated our digital health progress significantly and have proven to Canadians just how important and helpful digital health can be,” says Michael Green, President and CEO of Infoway.

€œDigital Health Week is an important time to celebrate our progress and acknowledge the hard work of all those who have made it possible.”While technology can help reduce barriers and improve access to health care, the research also found that nearly six in 10 Canadians feel they don’t know what does a cipro pill look like enough about digital health apps and services. As Canada’s digital health agency, Infoway is committed to working with its partners to address these gaps through activities like Digital Health Week.About Infoway’s Commitment to ResearchA Healthy Dialogue is part of Infoway’s commitment to contributing to digital health research in Canada what does a cipro pill look like. To support health care organizations, clinicians, policy maker and patients, families and caregivers, Infoway conducts research into the value of digital health solutions as well as clinicians’ and Canadians’ attitudes and perceptions. To learn more about the results from A Healthy Dialogue, what does a cipro pill look like please visit https://www.infoway-inforoute.ca/en/component/edocman/resources/reports/3850-a-healthy-dialogue-executive-summary. To learn about Infoway’s other research initiatives, please visit www.infoway-inforoute.ca/en/what-we-do/research-and-insights.About Digital Health Week — #ThinkDigitalHealthDigital Health Week was created to celebrate how digital health is transforming care across the country and to increase awareness about the value and benefits of digital health for all Canadians.

Digital Health Week is what does a cipro pill look like supported by 60+ organizations. Join the conversation and share your what does a cipro pill look like story. #ThinkDigitalHealth.About Canada Health InfowayInfoway helps to improve the health of Canadians by working with partners to accelerate the development, adoption and effective use of digital health across Canada. Through our investments, we help deliver better quality and what does a cipro pill look like access to care and more efficient delivery of health services for patients and clinicians. Infoway is an independent, not-for-profit organization funded by the federal government.

Visit www.infoway-inforoute.ca.[i] A national survey of about 6,900 Canadians what does a cipro pill look like was conducted from December 2019-February 2020, pre-buy antibiotics. A follow-up survey was conducted in June 2020 with about 2,200 of the original 6,900, to see if their views had shifted since the cipro began.-30-Media Inquiries.

New survey insights released to mark Digital Health Week 2020November 16, 2020 (Toronto) — Canadians and health care More hints providers have met the how much does generic cipro cost unprecedented challenge of the buy antibiotics cipro head-on by embracing change in the way health care is delivered — from in-person to virtual. This week is Digital Health Week and to mark the occasion Canada Health Infoway (Infoway) is sharing research conducted in partnership with Environics that digs into this substantial shift and what how much does generic cipro cost Canadians want for their digital health future. This latest research project, A Healthy Dialogue, is one of the largest public consultations about digital health ever conducted in Canada.

The consultation reached more than 58,000 Canadians — including those underserved by the health system — who shared how they thought technology would impact their care experience.The research reveals[i]:An overwhelming majority (92%) of Canadians want technology that makes health how much does generic cipro cost care as convenient as other aspects of their lives.More than half (53%) of Canadians who have used health technology in the past year say it helped them avoid an in-person visit to a provider or an emergency room.Of those Canadians who received virtual care during the cipro, 91% were satisfied with the experience, 86% agreed that virtual care tools can be important alternatives to seeing doctors in-person, and more than three-quarters (76%) are willing to use virtual care after the cipro.“We’ve gone from talking about ways to further integrate digital health into everyday health care to living it. The events of the past year have accelerated our digital health progress significantly and have proven to Canadians just how important and helpful digital health can be,” says Michael Green, President and CEO of Infoway. €œDigital Health Week is an important time to celebrate our progress and acknowledge the hard work of all those who have made it possible.”While how much does generic cipro cost technology can help reduce barriers and improve access to health care, the research also found that nearly six in 10 Canadians feel they don’t know enough about digital health apps and services.

As Canada’s digital health agency, Infoway is committed to working with its partners to address these gaps through activities like Digital Health Week.About Infoway’s Commitment to ResearchA Healthy Dialogue is part of Infoway’s commitment how much does generic cipro cost to contributing to digital health research in Canada. To support health care organizations, clinicians, policy maker and patients, families and caregivers, Infoway conducts research into the value of digital health solutions as well as clinicians’ and Canadians’ attitudes and perceptions. To learn more about the results from A how much does generic cipro cost Healthy Dialogue, please visit https://www.infoway-inforoute.ca/en/component/edocman/resources/reports/3850-a-healthy-dialogue-executive-summary.

To learn about Infoway’s other research initiatives, please visit www.infoway-inforoute.ca/en/what-we-do/research-and-insights.About Digital Health Week — #ThinkDigitalHealthDigital Health Week was created to celebrate how digital health is transforming care across the country and to increase awareness about the value and benefits of digital health for all Canadians. Digital Health Week how much does generic cipro cost is supported by 60+ organizations. Join the conversation and share your story how much does generic cipro cost.

#ThinkDigitalHealth.About Canada Health InfowayInfoway helps to improve the health of Canadians by working with partners to accelerate the development, adoption and effective use of digital health across Canada. Through our investments, we help deliver how much does generic cipro cost better quality and access to care and more efficient delivery of health services for patients and clinicians. Infoway is an independent, not-for-profit organization funded by the federal government.

Visit www.infoway-inforoute.ca.[i] A national survey of about 6,900 Canadians was conducted from December how much does generic cipro cost 2019-February 2020, pre-buy antibiotics. A follow-up survey was conducted in June 2020 with about 2,200 of the original 6,900, to see if their views had shifted since the cipro began.-30-Media Inquiries.

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How to take cipro for uti

A broadly neutralising antibody to prevent HIV transmissionTwo HIV prevention trials how to take cipro for uti (HVTN 704/HPTN 085. HVTN 703/HPTN 081) enrolled 2699 at-risk cisgender men and transgender persons in the Americas and Europe and 1924 at-risk women in sub-Saharan Africa who were randomly assigned to receive the broadly neutralising antibody (bnAb) VRC01 or placebo (10 infusions at an interval of 8 weeks). Moderate-to-severe adverse events related to how to take cipro for uti VRC01 were uncommon.

In a prespecified pooled analysis, over 20 months, VRC01 offered an estimated prevention efficacy of ~75% against VRC01-sensitive isolates (30% of ciproes circulating in the trial regions). However, VRC01 did not prevent with other HIV isolates and how to take cipro for uti overall HIV acquisition compared with placebo. The data provide proof of concept that bnAb can prevent HIV acquisition, although the approach is limited by viral diversity and potential selection of resistant isolates.Corey L, Gilbert PB, Juraska M, et al.

Two randomized trials of neutralizing antibodies to how to take cipro for uti prevent HIV-1 acquisition. N Engl J Med. 2021;384:1003–1014.Seminal cytokine profiles are associated with the risk of HIV transmissionInvestigators analysed a panel of how to take cipro for uti 34 cytokines/chemokines in blood and semen of men (predominantly men who have sex with men) with HIV, comparing 21 who transmitted HIV to their partners and 22 who did not.

Overall, 47% of men had a recent HIV , 19% were on antiretroviral therapy and 84% were viraemic. The cytokine profile in seminal fluid, but not in blood, differed significantly between how to take cipro for uti transmitters and non-transmitters, with transmitters showing higher seminal concentrations of interleukin 13 (IL-13), IL-15 and IL-33, and lower concentrations of interferon‐gamma, IL-15, macrophage colony-stimulating factor (M-CSF), IL-17, granulocyte-macrophage CSF (GM-CSF), IL-4, IL-16 and eotaxin. Although limited, the findings suggest that the seminal milieu modulates the risk of HIV transmission, providing a potential development opportunity for HIV prevention strategies.Vanpouille C, Frick A, Rawlings SA, et al.

Cytokine network and sexual HIV transmission in men who have sex with men how to take cipro for uti. Clin Infect Dis. 2020;71:2655–2662.The challenge of estimating global treatment eligibility for chronic hepatitis B from incomplete datasetsWorldwide, over 250 million people are estimated to live how to take cipro for uti with chronic hepatitis B (CHB), although only ~11% is diagnosed and a minority receives antiviral therapy.

An estimate of the global proportion eligible for treatment was not previously available. A systematic how to take cipro for uti review analysed studies of CHB populations done between 2007 and 2018 to estimate the prevalence of cirrhosis, abnormal alanine aminotransferase, hepatitis B cipro DNA >2000 or >20 000 IU/mL, hepatitis B e-antigen, and overall eligibility for treatment as per WHO and other guidelines. The pooled treatment eligibility estimate was 19% (95% CI 18% to 20%), with about 10% requiring urgent treatment due to cirrhosis.

However, the estimate should be interpreted with caution due to incomplete data acquisition and reporting how to take cipro for uti in available studies. Standardised reporting is needed to improve global and regional estimates of CHB treatment eligibility and guide effective policy formulation.Tan M, Bhadoria AS, Cui F, et al. Estimating the proportion how to take cipro for uti of people with chronic hepatitis B cipro eligible for hepatitis B antiviral treatment worldwide.

A systematic review and meta-analysis. Lancet Gastroenterol Hepatol, 2021 how to take cipro for uti. 6:106–119.Broad geographical disparity in the contribution of HIV to the burden of cervical cancerThis systematic review and meta-analysis estimated the contribution of HIV to the global and regional burden of cervical cancer using data from 24 studies which included 236 127 women with HIV.

HIV markedly increased the risk how to take cipro for uti of cervical cancer (pooled relative risk 6.07. 95% CI 4.40 to 8.37). In 2018, how to take cipro for uti 4.9% (95% CI 3.6% to 6.4%) of cervical cancers were attributable to HIV globally, although the population-attributable fraction for HIV varied geographically, reaching 21% (95% CI 15.6% to 26.8%) in the African region.

Cervical cancer is preventable and treatable. Efforts are needed to expand access to HPV vaccination in sub-Saharan how to take cipro for uti Africa. More immediately, there is an urgent need to integrate cervical cancer screening within HIV services.Stelzle D, Tanaka LF, Lee KK, et al.

Estimates of the global burden of cervical how to take cipro for uti cancer associated with HIV. Lancet Glob Health. 2020.

9:e161–69.The complex relationship between serum vitamin D and persistence of high-risk human papilloma cipro Most cervical high-risk human papilloma cipro (hrHPV) s are transient and those that persist are more likely to progress to cancer. Based on the proposed immunomodulatory properties of vitamin D, a longitudinal study examined the association between serum concentrations of five vitamin D biomarkers and short-term persistent (vs transient or sporadic) detection of hrHPV in 72 women who collected monthly cervicovaginal swabs over 6 months. No significant associations were detected in the primary analysis.

In sensitivity analyses, after multiple adjustments, serum concentrations of multiple vitamin D biomarkers were positively associated with the short-term persistence of 14 selected hrHPV types. The relationship between vitamin D and hrHPV warrants closer examination. Studies should have longer follow-up, include populations with more diverse vitamin D concentrations and account for vitamin D supplementation.Troja C, Hoofnagle AN, Szpiro A, et al.

Understanding the role of emerging vitamin D biomarkers on short-term persistence of high-risk HPV among mid-adult women. J Infect Dis 2020. Online ahead of printPublished in STI—the editor’s choice.

One in five cases of with Neisseria gonorrhoeae clear spontaneouslyStudies have indicated that Neisseria gonorrhoeae (NG) s can resolve spontaneously without antibiotic therapy. A substudy of a randomised trial investigated 405 untreated subjects (71% men) who underwent both pretrial and enrolment NG testing at the same anatomical site (genital, pharyngeal and rectal). Based on nuclear acid amplification tests, 83 subjects (20.5%) showed clearance of the anatomical site within a median of 10 days (IQR 7–15) between tests.

Those with spontaneous clearance were less likely to have concurrent chlamydia (p=0.029) and dysuria (p=0.035), but there were no differences in age, gender, sexual orientation, HIV status, number of previous NG episodes, and symptoms other than dysuria between those with and without clearance. Given the high rate of spontaneous resolution, point-of-care NG testing should be considered to reduce unnecessary antibiotic treatment.Mensforth S, Ayinde OC, Ross J. Spontaneous clearance of genital and extragenital Neisseria gonorrhoeae.

Data from GToG. STI 2020. 96:556–561.BackgroundReproductive aged women are at risk of both pregnancy and sexually transmitted s (STI).

The modern contraceptive prevalence among married and unmarried women in South Africa is 54% and 64%, respectively, with injectable progestins being most widely used.1 Moreover, current global efforts aim towards all women having access to a range of reliable contraceptives options.2 The prevalences of chlamydia and gonorrhoea are high among women in Africa, particularly among younger women. A recent meta-analysis of over 37 000 women estimated prevalences for chlamydia and gonorrhoea by region and population type (South Africa clinic/community-based, Eastern Africa higher-risk and Southern/Eastern Africa clinic community-based). High chlamydia and gonorrhoea prevalences were found among 15–24 year-old South African women and high risk populations in East Africa.3 Both chlamydia and gonorrhoea are associated with numerous comorbidities including pelvic inflammatory disease (PID), ectopic pregnancy, infertility, increased risk of HIV and other STIs, as well as significant social harm.4While STIs are a significant global health burden, data on STI prevalence by gender and drivers of are limited, hindering an effective public health response.5 Moreover, data on the association between contraceptive use and risk of non-HIV STIs are limited.

The WHO recently reported stagnation in efforts to decrease global STI incidence.5 Understanding drivers of STI acquisition, including any possible associations with widely used contraceptive methods, is necessary to effectively target public health responses that reduce STI incidence and associated comorbidities.The ECHO Trial (ClinicalTrials.gov Identifier. NCT02550067) was a multicentre, open-label randomised trial of 7829 HIV-seronegative women seeking effective contraception in Eswatini, Kenya, South Africa and Zambia. Detailed trial methods and results have been published.6 7 We conducted a secondary analysis of ECHO trial data to evaluate absolute and relative chlamydia and gonorrhoea final visit prevalences among women randomised to intramuscular depot medroxyprogesterone acetate (DMPA-IM), a copper intrauterine device (IUD) and a levonorgestrel (LNG) implant.MethodsStudy design, participants and ethicsWomen were enrolled in the ECHO trial from December 2015 through September 2017.

Institutional review boards at each site approved the study protocol and women provided written informed consent before any study procedures. In brief, women who were not pregnant, HIV-seronegative, aged 16–35 years, seeking effective contraception, without medical contraindications, willing to use the assigned method for 18 months, reported not using injectable, intrauterine or implantable contraception for the previous 6 months and reported being sexually active, were enrolled. At every visit, participants received HIV risk reduction counselling, HIV testing and STI management, condoms and, as it became a part of national standard of care, HIV pre-exposure prophylaxis.

Counselling messages related to HIV risk were implemented consistently across the three groups throughout the trial.6The trial was implemented in accordance with the Declaration of Helsinki and Good Clinical Practice. Informed consent was obtained from participants or their parents/guardians and human experimentation guidelines of the United States Department of Health and Human Services and those of the authors' institution(s) were followed.Contraceptive exposureAt enrolment, women were randomly assigned (1:1:1) to DMPA-IM, copper IUD or LNG implant.6 Participants received an injection of 150 mg/mL DMPA-IM (Depo Provera. Pfizer, Puurs, Belgium) at enrolment and every 3 months until the final visit at 18 months after enrolment, a copper IUD (Optima TCu380A.

Injeflex, Sao Paolo, Brazil) or a LNG implant (Jadelle. Bayer, Turku, Finland) at enrolment. Women returned for follow-up visits at 1 month after enrolment to address initial contraceptive side-effects and every 3 months thereafter, for up to 18 months with later enrolling participants contributing 12 to 18 months of follow-up.

Visits included HIV serological testing, contraceptive counselling, syndromic STI management and safety monitoring.STI outcomesThe primary outcomes of this secondary analysis were prevalent chlamydia and gonorrhoea at the final visit. Syndromic STI management was provided at screening and all follow-up visits. Nucleic acid amplification testing (NAAT) for Chlamydia trachomatis and Neisseria gonorrhoeae was conducted at screening and final visits, at the visit of HIV detection for participants who became HIV infected and at clinical discretion.

Any untreated participants with positive NAAT results were contacted to return to the study clinic for treatment.CovariatesAt baseline (inclusive of screening and enrolment visits), we collected demographic, sexual and reproductive risk behaviour and reproductive and contraceptive history data. Baseline risk factors evaluated as covariates included age, whether the participant earned her own income, chlamydia and gonorrhoea status, herpes simplex cipro type 2 (HSV-2) sero-status and suspected PID. Final visit factors evaluated as covariates included number of sex partners in the past 3 months, number of new sex partners in the past 3 months, HIV serostatus, HSV-2 serostatus, condom use in the past 3 months, sex exchanged for money/gifts, sex during vaginal bleeding, follow-up time and number of pelvic examinations during follow-up.

Age and HSV-2 serostatus were evaluated for effect measure modification.Statistical analysisWe conducted analyses using R V.3.5.3 (Vienna, Austria), and log-binomial regression to estimate chlamydia and gonorrhoea prevalences within each contraceptive group and pairwise prevalence ratios (PR) between each arm in as-randomised and consistent use analyses.In the as-randomised analysis, we analysed participants by the contraceptive method assigned at randomisation independent of method adherence. We estimated crude point prevalences by arm and study site and pairwise adjusted PRs.In the consistent use analysis, we only included women who initiated use of their randomised contraceptive method and maintained randomised method adherence throughout follow-up. We estimated crude point prevalences by arm and pairwise adjusted PRs, with evaluation of age and HSV-2 status first as potential effect measure modifiers, and all covariates above as potential confounders.

Study site and age were retained in the final model. Other covariates were retained if their inclusion in the base model led to a 10% change in the effect estimate through backwards selection.Supplementary analysesAdditional supporting analyses to assess postrandomisation potential sources of bias were conducted to inform interpretation of results. These include evaluation of recent sexual behaviour at enrolment, month 9 and the final visit.

Cohort participation (ie, follow-up time, early discontinuation and timing of randomised method discontinuation) and health outcomes (ie, final visit HIV and HSV-2 status) and frequency and results of pelvic examinations by STI status, site and visit month by randomised arm.ResultsA total of 7829 women were randomly assigned as follows. 2609 to the DMPA-IM group, 2607 to the copper IUD group and 2613 to the LNG implant group (figure 1). Participants were excluded if they were HIV positive at enrolment, did not have at least one HIV test or did not have chlamydia and gonorrhoea test results at the final visit.

Overall, 90%, 94% and 93% from the DMPA-IM, copper IUD and LNG implant groups, respectively, were included in analyses.Study profile. DMPA-IM, depot medroxy progesterone acetate. IUD, intrauterine device.

LNG, levonorgestrel." data-icon-position data-hide-link-title="0">Figure 1 Study profile. DMPA-IM, depot medroxy progesterone acetate. IUD, intrauterine device.

LNG, levonorgestrel.Participant characteristicsBaseline characteristics were similar across groups (table 1). Nearly two-third of enrolled women (63%) were aged 24 and younger and 5768 (74%) of the study population resided in South Africa.View this table:Table 1 Participant baseline and final visit characteristicsThe duration of participation averaged 16 months with no differences between randomised groups (table 1). A total of 1468 (19%) women either did not receive their randomised method or discontinued use during follow-up.

Overall method continuation rates were high with minimal differences between randomised groups when measured by person-years.6 The proportion, however, of method non-adherence as defined in this analysis (ie, did not receive randomised method at baseline or discontinued randomised method at any point during follow-up), was greater in the DMPA-IM group (26%), followed by the copper IUD (18%) and LNG implant (12%) groups. Timing of discontinuation also differed across methods. During the first 6 months, method discontinuation was highest in the copper IUD group (7%) followed closely by DMPA-IM (6%) and LNG implant (4%) groups.

Between 7 and 12 months of follow-up, it was highest in DMPA-IM group (15%), with equivalent proportions in the LNG implant (5%) and copper IUD (5%) groups.Point prevalences of chlamydia and gonorrhoea at baseline and final visitsIn total, 18% of women had chlamydia at baseline (figure 2A) and 15% at the final visit. Among women 24 years and younger, 22% and 20% had chlamydia at baseline and final visits, respectively. Women aged 25–35 at baseline were less likely to have chlamydia at both baseline (12%) and final visits (8%) compared with younger women.

Baseline chlamydia prevalence ranged from 5% in Zambia to 28% in the Western Cape, South Africa (figure 2B).Point prevalence (per 100 persons) of chlamydia and gonorrhoea at baseline and final visit by age category and study site region. Y-axis scale differs for chlamydia and gonorrhoea figures." data-icon-position data-hide-link-title="0">Figure 2 Point prevalence (per 100 persons) of chlamydia and gonorrhoea at baseline and final visit by age category and study site region. Y-axis scale differs for chlamydia and gonorrhoea figures.Among all women, 5% had gonorrhoea at baseline and the final visit (figure 2C).

Women aged 24 and younger were more likely to have gonorrhoea compared with women aged 25 and older at both baseline (5% vs 4%, respectively) and the final visit (6% vs 3%, respectively). Baseline gonorrhoea prevalence ranged from 3% in Zambia and Kenya to 9% in the Western Cape, South Africa (figure 2D). Similar prevalences were observed at the final visit.Point prevalences of chlamydia and gonorrhoea at final visit by randomised contraceptive methodFourteen per cent of women randomised to DMPA-IM, 15% to copper IUD and 17% to LNG implant had chlamydia at the final visit (table 2).View this table:Table 2 Chlamydia trachomatis and Neisseria gonorrhoeae prevalence at final visitThe prevalence of chlamydia did not significantly differ between DMPA-IM and copper IUD groups (PR 0.90, 95% CI (0.79 to 1.04)) or between copper IUD and LNG implant groups (PR 0.92, 95% CI (0.81 to 1.04)).

Women in the DMPA-IM group, however, had a significantly lower risk of chlamydia compared with the LNG implant group (PR. 0.83, 95% CI (0.72 to 0.95)). Findings from the consistent use analysis were similar, and neither age nor HSV-2 status modified the observed associations.Four per cent of women randomised to DMPA-IM, 6% to copper IUD and 5% to LNG implant had gonorrhoea at the final visit (table 2).

Gonorrhoea prevalence did not significantly differ between DMPA-IM and LNG implant groups (PR. 0.79, 95% CI (0.61 to 1.03)) or between copper IUD and LNG implant groups (PR. 1.18, 95% CI (0.93 to 1.49)).

Women in the DMPA-IM group had a significantly lower risk of gonorrhoea compared with women in the copper IUD group (PR. 0.67, 95% CI (0.52 to 0.87)). Results from as randomised and continuous use analyses did not differ.

And again, neither age nor HSV-2 status modified the observed associations.Clinical assessment by randomised contraceptive methodTo assess the potential for outcome ascertainment bias, we evaluated the frequency of pelvic examinations and abdominal/pelvic pain and discharge by study arm. Women in the copper IUD group were generally more likely to receive a pelvic examination during follow-up as compared with women in the DMPA-IM and LNG implant groups (online supplemental appendix 1). Similarly, abdominal/pelvic pain on examination or abnormal discharge was observed most frequently in the copper IUD group.

The number of pelvic examinations met the prespecified criteria for retention in the adjusted gonorrhoea model but not in the chlamydia model.Supplemental materialFrequency of syndromic symptoms and potential reAmong women who had chlamydia at baseline, 23% were also positive at the final visit (online supplemental appendix 2, figure 3A). Nine per cent of gonorrhoea-positive women at baseline were also positive at the final visit (online supplemental appendix 2, figure 3B). Across both baseline and final visits, a minority of women with chlamydia or gonorrhoea presented with signs and/or symptoms.

Among chlamydia-positive women, only 12% presented with either abnormal vaginal discharge and/or abdominal/pelvic pain at their test-positive visit (online supplemental appendix 2, figure 3C). Similarly, only 15% of gonorrhoea-positive women presented with abnormal vaginal discharge and/or abdominal/pelvic pain at their test-positive visit (online supplemental appendix 2, figure 3D).Potential re and symptoms among women with chlamydia or gonorrhoea. Data are pooled across the screening and final visits in figures (C) and (D).

Symptomatic is defined as presenting with abnormal vaginal discharge and/or abdominal/pelvic pain. Final visit is described as potential re because test of cure was not conducted following baseline diagnosis and treatment." data-icon-position data-hide-link-title="0">Figure 3 Potential re and symptoms among women with chlamydia or gonorrhoea. Data are pooled across the screening and final visits in figures (C) and (D).

Symptomatic is defined as presenting with abnormal vaginal discharge and/or abdominal/pelvic pain. Final visit is described as potential re because test of cure was not conducted following baseline diagnosis and treatment.DiscussionWe observed differences in final prevalences of chlamydia and gonorrhoea by contraceptive group in both as-randomised and consistent-use analyses. The DMPA-IM group had lower final visit chlamydia and gonorrhoea prevalences as compared with copper IUD and LNG implant groups, though only the DMPA-IM versus the copper IUD comparison of gonorrhoea and DMPA-IM versus LNG implant comparison of chlamydia reached statistical significance.

These are novel findings that have not previously been reported to our knowledge and were determined in a randomised trial setting with high participant retention, robust biomarker testing and high randomised method adherence. Interestingly, the copper IUD group had higher gonorrhoea and lower chlamydia prevalence compared with the LNG implant group, though neither finding was statistically significant.Two recent systematic reviews of the association between contraceptives and STIs found inconsistent and insufficient evidence on the association between the contraceptive methods under study in ECHO and chlamydia and gonorrhoea.8 9 Neither systematic review identified any randomised studies or any direct comparative evidence for DMPA-IM, copper IUD and LNG implant, thus enabling a unique scientific contribution from this secondary trial analysis. Nonetheless, these findings should be interpreted in light of biological plausibility, as well as the design strengths and limitations of this analysis.The emerging science on the biological mechanisms underlying HIV susceptibility demonstrates the complex relationship between the infectious pathogen, the host innate and adaptive immune response and the interaction of both with the vaginal microbiome and other -omes.

Data on these factors in relationship to chlamydia and gonorrhoea acquisition are much more limited but can be assumed to be equally complex. Vaginal microbiome composition, including microbial metabolic by-products, have been shown to significantly modify risk of HIV acquisition and to vary with exogenous hormone exposure, menstrual cycle phase, ethnicity and geography.10–12 These same biological principles likely apply to chlamydia and gonorrhoea susceptibility. While DMPA-IM has been associated with decreased bacterial vaginosis (BV), initiation of the copper IUD has been associated with increased BV prevalence, and BV is associated with chlamydia and gonorrhoea acquisition.13 14 Moreover, Lactobacillus crispatus, which is less abundant in BV, has been shown to inhibit HeLa cell by Chlamydia trachomatis and inhibits growth of Neisseria gonorrhoeae in animal models.15 16 In addition, microbial community state types that are deficient in Lactobacillus crispatus and/or dominated by dysbiotic species are associated with inflammation, which is a driver of both STI and HIV susceptibility.

Thus, while the exact mechanisms of chlamydia and gonorrhoea in the presence of exogenous hormones and varying host microbiomes are unknown, it is biologically plausible that these complex factors may result in differential susceptibility to chlamydia and gonorrhoea among DMPA-IM, copper IUD and LNG implant users.An alternative explanation for these findings may be postrandomisation differences in clinical care and/or sexual behaviour. Participants in the copper IUD arm were more likely to have pelvic examinations and more likely to have discharge compared with women in the DMPA-IM and LNG implant groups. While interim STI testing and/or treatment were not documented, women in the copper IUD arm may have been more likely to receive syndromic STI treatment during follow-up due to more examination and observed discharge.

More frequent STI treatment in the copper IUD group would theoretically lower the final visit point prevalence relative to women in the DMPA-IM and LNG implant arms, suggesting that the observed lower risk of STI in the DMPA-IM arm is not due to differential examination, testing and treatment. Differential sexual risk behaviour may also have influenced the results. As reported previously, women in the DMPA-IM group less frequently reported condomless sex and multiple partners than women in the other groups, and both DMPA-IM and LNG implant users less frequently reported new partners and sex during menses than copper IUD users.6 Statistical control of self-reported sexual risk behaviour in the consistent-use analysis may have been inadequate if self-reported sexual behaviour was inaccurately or insufficiently reported.A second alternative explanation may be differences in randomised method non-adherence, which was greater in the DMPA-IM group, compared with copper IUD and LNG implant groups.

Yet, the consistency of findings in the as-randomised and continuous use analyses suggests that method non-adherence had minimal effect on study outcomes. Taken as a whole, these findings indicate that there may be real differences in chlamydia and gonorrhoea risk associated with use of DMPA-IM, the copper IUD and LNG implant. However, any true differential risk by method must be evaluated in light of the holistic benefits and risks of each method.The high observed chlamydia and gonorrhoea prevalences, despite intensive counselling and condom provision, warrants attention, particularly among women ages 24 years and younger and among women in South Africa and Eswatini.

While the ECHO study was conducted in settings of high HIV/STI incidence, enrolment criteria did not purposefully target women at highest risk of HIV/STI in the trial communities, suggesting that the observed prevalences may be broadly applicable to women seeking effective contraception in those settings. Improved approaches are needed to prevent STIs, including options for expedited partner treatment, to prevent re.As expected, few women testing positive for chlamydia or gonorrhoea presented with symptoms (12% and 15%, respectively), and a substantial proportion of women who were positive and treated at baseline were infected at the final visit despite syndromic management during the follow-up. Given that syndromic management is the standard of care within primary health facilities in most trial settings, these data suggest that a large proportion of among reproductive aged women is missed, exacerbating the burden of curable STIs and associated morbidities.

Routine access to more reliable diagnostics, like NAAT and novel point-of-care diagnostic tests, will be key to managing asymptomatic STIs and reducing STI prevalence and related morbidities in these settings.17This secondary analysis of the ECHO trial has strengths and limitations. Strengths include the randomised design with comparator groups of equal STI baseline risk. Participants had high adherence to their randomised contraceptive method.6 While all participants received standardised clinical care and counselling, the unblinded randomisation may have allowed postrandomisation differences in STI risk over time by method.

It is possible that participants modified their risk-taking behaviour based on study counselling messages regarding the potential association between DMPA-IM and HIV.In conclusion, our analyses suggest that DMPA-IM users may have lower risk of chlamydia and gonorrhoea compared with LNG implant and copper IUD users, respectively. Further investigation is warranted to better understand the mechanisms of chlamydia and gonorrhoea susceptibility in the context of contraceptive use. Moreover, the high chlamydia and gonorrhoea prevalences in this population, independent of contraceptive method, warrants urgent attention.Key messagesThe prevalence of chlamydia and gonorrhoea varied by contraceptive method in this randomised trial.High chlamydia and gonorrhoea prevalences, despite intensive counselling and condom provision, warrants attention, particularly among young women in South Africa and Eswatini.Most chlamydia and gonorrhoea s were asymptomatic.

Therefore, routine access to reliable diagnostics are needed to effectively manage and prevent STIs in African women..

A broadly neutralising antibody to prevent HIV transmissionTwo HIV prevention trials http://www.ec-muttersholtz.ac-strasbourg.fr/ce1-fichiers-utiles-pour-vendredi-9-avril-2021/ (HVTN 704/HPTN how much does generic cipro cost 085. HVTN 703/HPTN 081) enrolled 2699 at-risk cisgender men and transgender persons in the Americas and Europe and 1924 at-risk women in sub-Saharan Africa who were randomly assigned to receive the broadly neutralising antibody (bnAb) VRC01 or placebo (10 infusions at an interval of 8 weeks). Moderate-to-severe adverse events related how much does generic cipro cost to VRC01 were uncommon.

In a prespecified pooled analysis, over 20 months, VRC01 offered an estimated prevention efficacy of ~75% against VRC01-sensitive isolates (30% of ciproes circulating in the trial regions). However, VRC01 how much does generic cipro cost did not prevent with other HIV isolates and overall HIV acquisition compared with placebo. The data provide proof of concept that bnAb can prevent HIV acquisition, although the approach is limited by viral diversity and potential selection of resistant isolates.Corey L, Gilbert PB, Juraska M, et al.

Two randomized trials of neutralizing antibodies to prevent HIV-1 how much does generic cipro cost acquisition. N Engl J Med. 2021;384:1003–1014.Seminal cytokine profiles are how much does generic cipro cost associated with the risk of HIV transmissionInvestigators analysed a panel of 34 cytokines/chemokines in blood and semen of men (predominantly men who have sex with men) with HIV, comparing 21 who transmitted HIV to their partners and 22 who did not.

Overall, 47% of men had a recent HIV , 19% were on antiretroviral therapy and 84% were viraemic. The cytokine profile in seminal fluid, but not in blood, differed significantly between transmitters and non-transmitters, with transmitters showing how much does generic cipro cost higher seminal concentrations of interleukin 13 (IL-13), IL-15 and IL-33, and lower concentrations of interferon‐gamma, IL-15, macrophage colony-stimulating factor (M-CSF), IL-17, granulocyte-macrophage CSF (GM-CSF), IL-4, IL-16 and eotaxin. Although limited, the findings suggest that the seminal milieu modulates the risk of HIV transmission, providing a potential development opportunity for HIV prevention strategies.Vanpouille C, Frick A, Rawlings SA, et al.

Cytokine network and sexual HIV how much does generic cipro cost transmission in men who have sex with men. Clin Infect Dis. 2020;71:2655–2662.The challenge of estimating global treatment eligibility for chronic hepatitis B from incomplete datasetsWorldwide, over 250 million people are estimated how much does generic cipro cost to live with chronic hepatitis B (CHB), although only ~11% is diagnosed and a minority receives antiviral therapy.

An estimate of the global proportion eligible for treatment was not previously available. A systematic review analysed studies of CHB populations done between 2007 and 2018 to estimate the prevalence of cirrhosis, abnormal alanine aminotransferase, hepatitis B cipro DNA >2000 or >20 000 IU/mL, hepatitis B e-antigen, and overall eligibility for treatment as per WHO and other how much does generic cipro cost guidelines. The pooled treatment eligibility estimate was 19% (95% CI 18% to 20%), with about 10% requiring urgent treatment due to cirrhosis.

However, the estimate should be interpreted with caution due how much does generic cipro cost to incomplete data acquisition and reporting in available studies. Standardised reporting is needed to improve global and regional estimates of CHB treatment eligibility and guide effective policy formulation.Tan M, Bhadoria AS, Cui F, et al. Estimating the proportion of people with chronic hepatitis B cipro eligible for hepatitis how much does generic cipro cost B antiviral treatment worldwide.

A systematic review and meta-analysis. Lancet Gastroenterol how much does generic cipro cost Hepatol, 2021. 6:106–119.Broad geographical disparity in the contribution of HIV to the burden of cervical cancerThis systematic review and meta-analysis estimated the contribution of HIV to the global and regional burden of cervical cancer using data from 24 studies which included 236 127 women with HIV.

HIV markedly increased the risk of cervical how much does generic cipro cost cancer (pooled relative risk 6.07. 95% CI 4.40 to 8.37). In 2018, 4.9% (95% CI 3.6% to 6.4%) of cervical cancers were attributable to HIV globally, although the how much does generic cipro cost population-attributable fraction for HIV varied geographically, reaching 21% (95% CI 15.6% to 26.8%) in the African region.

Cervical cancer is preventable and treatable. Efforts are needed how much does generic cipro cost to expand access to HPV vaccination in sub-Saharan Africa. More immediately, there is an urgent need to integrate cervical cancer screening within HIV services.Stelzle D, Tanaka LF, Lee KK, et al.

Estimates of the global burden of cervical cancer associated with HIV how much does generic cipro cost. Lancet Glob Health. 2020.

9:e161–69.The complex relationship between serum vitamin D and persistence of high-risk human papilloma cipro Most cervical high-risk human papilloma cipro (hrHPV) s are transient and those that persist are more likely to progress to cancer. Based on the proposed immunomodulatory properties of vitamin D, a longitudinal study examined the association between serum concentrations of five vitamin D biomarkers and short-term persistent (vs transient or sporadic) detection of hrHPV in 72 women who collected monthly cervicovaginal swabs over 6 months. No significant associations were detected in the primary analysis.

In sensitivity analyses, after multiple adjustments, serum concentrations of multiple vitamin D biomarkers were positively associated with the short-term persistence of 14 selected hrHPV types. The relationship between vitamin D and hrHPV warrants closer examination. Studies should have longer follow-up, include populations with more diverse vitamin D concentrations and account for vitamin D supplementation.Troja C, Hoofnagle AN, Szpiro A, et al.

Understanding the role of emerging vitamin D biomarkers on short-term persistence of high-risk HPV among mid-adult women. J Infect Dis 2020. Online ahead of printPublished in STI—the editor’s choice.

One in five cases of with Neisseria gonorrhoeae clear spontaneouslyStudies have indicated that Neisseria gonorrhoeae (NG) s can resolve spontaneously without antibiotic therapy. A substudy of a randomised trial investigated 405 untreated subjects (71% men) who underwent both pretrial and enrolment NG testing at the same anatomical site (genital, pharyngeal and rectal). Based on nuclear acid amplification tests, 83 subjects (20.5%) showed clearance of the anatomical site within a median of 10 days (IQR 7–15) between tests.

Those with spontaneous clearance were less likely to have concurrent chlamydia (p=0.029) and dysuria (p=0.035), but there were no differences in age, gender, sexual orientation, HIV status, number of previous NG episodes, and symptoms other than dysuria between those with and without clearance. Given the high rate of spontaneous resolution, point-of-care NG testing should be considered to reduce unnecessary antibiotic treatment.Mensforth S, Ayinde OC, Ross J. Spontaneous clearance of genital and extragenital Neisseria gonorrhoeae.

Data from GToG. STI 2020. 96:556–561.BackgroundReproductive aged women are at risk of both pregnancy and sexually transmitted s (STI).

The modern contraceptive prevalence among married and unmarried women in South Africa is 54% and 64%, respectively, with injectable progestins being most widely used.1 Moreover, current global efforts aim towards all women having access to a range of reliable contraceptives options.2 The prevalences of chlamydia and gonorrhoea are high among women in Africa, particularly among younger women. A recent meta-analysis of over 37 000 women estimated prevalences for chlamydia and gonorrhoea by region and population type (South Africa clinic/community-based, Eastern Africa higher-risk and Southern/Eastern Africa clinic community-based). High chlamydia and gonorrhoea prevalences were found among 15–24 year-old South African women and high risk populations in East Africa.3 Both chlamydia and gonorrhoea are associated with numerous comorbidities including pelvic inflammatory disease (PID), ectopic pregnancy, infertility, increased risk of HIV and other STIs, as well as significant social harm.4While STIs are a significant global health burden, data on STI prevalence by gender and drivers of are limited, hindering an effective public health response.5 Moreover, data on the association between contraceptive use and risk of non-HIV STIs are limited.

The WHO recently reported stagnation in efforts to decrease global STI incidence.5 Understanding drivers of STI acquisition, including any possible associations with widely used contraceptive methods, is necessary to effectively target public health responses that reduce STI incidence and associated comorbidities.The ECHO Trial (ClinicalTrials.gov Identifier. NCT02550067) was a multicentre, open-label randomised trial of 7829 HIV-seronegative women seeking effective contraception in Eswatini, Kenya, South Africa and Zambia. Detailed trial methods and results have been published.6 7 We conducted a secondary analysis of ECHO trial data to evaluate absolute and relative chlamydia and gonorrhoea final visit prevalences among women randomised to intramuscular depot medroxyprogesterone acetate (DMPA-IM), a copper intrauterine device (IUD) and a levonorgestrel (LNG) implant.MethodsStudy design, participants and ethicsWomen were enrolled in the ECHO trial from December 2015 through September 2017.

Institutional review boards at each site approved the study protocol and women provided written informed consent before any study procedures. In brief, women who were not pregnant, HIV-seronegative, aged 16–35 years, seeking effective contraception, without medical contraindications, willing to use the assigned method for 18 months, reported not using injectable, intrauterine or implantable contraception for the previous 6 months and reported being sexually active, were enrolled. At every visit, participants received HIV risk reduction counselling, HIV testing and STI management, condoms and, as it became a part of national standard of care, HIV pre-exposure prophylaxis.

Counselling messages related to HIV risk were implemented consistently across the three groups throughout the trial.6The trial was implemented in accordance with the Declaration of Helsinki and Good Clinical Practice. Informed consent was obtained from participants or their parents/guardians and human experimentation guidelines of the United States Department of Health and Human Services and those of the authors' institution(s) were followed.Contraceptive exposureAt enrolment, women were randomly assigned (1:1:1) to DMPA-IM, copper IUD or LNG implant.6 Participants received an injection of 150 mg/mL DMPA-IM (Depo Provera. Pfizer, Puurs, Belgium) at enrolment and every 3 months until the final visit at 18 months after enrolment, a copper IUD (Optima TCu380A.

Injeflex, Sao Paolo, Brazil) or a LNG implant (Jadelle. Bayer, Turku, Finland) at enrolment. Women returned for follow-up visits at 1 month after enrolment to address initial contraceptive side-effects and every 3 months thereafter, for up to 18 months with later enrolling participants contributing 12 to 18 months of follow-up.

Visits included HIV serological testing, contraceptive counselling, syndromic STI management and safety monitoring.STI outcomesThe primary outcomes of this secondary analysis were prevalent chlamydia and gonorrhoea at the final visit. Syndromic STI management was provided at screening and all follow-up visits. Nucleic acid amplification testing (NAAT) for Chlamydia trachomatis and Neisseria gonorrhoeae was conducted at screening and final visits, at the visit of HIV detection for participants who became HIV infected and at clinical discretion.

Any untreated participants with positive NAAT results were contacted to return to the study clinic for treatment.CovariatesAt baseline (inclusive of screening and enrolment visits), we collected demographic, sexual and reproductive risk behaviour and reproductive and contraceptive history data. Baseline risk factors evaluated as covariates included age, whether the participant earned her own income, chlamydia and gonorrhoea status, herpes simplex cipro type 2 (HSV-2) sero-status and suspected PID. Final visit factors evaluated as covariates included number of sex partners in the past 3 months, number of new sex partners in the past 3 months, HIV serostatus, HSV-2 serostatus, condom use in the past 3 months, sex exchanged for money/gifts, sex during vaginal bleeding, follow-up time and number of pelvic examinations during follow-up.

Age and HSV-2 serostatus were evaluated for effect measure modification.Statistical analysisWe conducted analyses using R V.3.5.3 (Vienna, Austria), and log-binomial regression to estimate chlamydia and gonorrhoea prevalences within each contraceptive group and pairwise prevalence ratios (PR) between each arm in as-randomised and consistent use analyses.In the as-randomised analysis, we analysed participants by the contraceptive method assigned at randomisation independent of method adherence. We estimated crude point prevalences by arm and study site and pairwise adjusted PRs.In the consistent use analysis, we only included women who initiated use of their randomised contraceptive method and maintained randomised method adherence throughout follow-up. We estimated crude point prevalences by arm and pairwise adjusted PRs, with evaluation of age and HSV-2 status first as potential effect measure modifiers, and all covariates above as potential confounders.

Study site and important source age were retained in the final model. Other covariates were retained if their inclusion in the base model led to a 10% change in the effect estimate through backwards selection.Supplementary analysesAdditional supporting analyses to assess postrandomisation potential sources of bias were conducted to inform interpretation of results. These include evaluation of recent sexual behaviour at enrolment, month 9 and the final visit.

Cohort participation (ie, follow-up time, early discontinuation and timing of randomised method discontinuation) and health outcomes (ie, final visit HIV and HSV-2 status) and frequency and results of pelvic examinations by STI status, site and visit month by randomised arm.ResultsA total of 7829 women were randomly assigned as follows. 2609 to the DMPA-IM group, 2607 to the copper IUD group and 2613 to the LNG implant group (figure 1). Participants were excluded if they were HIV positive at enrolment, did not have at least one HIV test or did not have chlamydia and gonorrhoea test results at the final visit.

Overall, 90%, 94% and 93% from the DMPA-IM, copper IUD and LNG implant groups, respectively, were included in analyses.Study profile. DMPA-IM, depot medroxy progesterone acetate. IUD, intrauterine device.

LNG, levonorgestrel." data-icon-position data-hide-link-title="0">Figure 1 Study profile. DMPA-IM, depot medroxy progesterone acetate. IUD, intrauterine device.

LNG, levonorgestrel.Participant characteristicsBaseline characteristics were similar across groups (table 1). Nearly two-third of enrolled women (63%) were aged 24 and younger and 5768 (74%) of the study population resided in South Africa.View this table:Table 1 Participant baseline and final visit characteristicsThe duration of participation averaged 16 months with no differences between randomised groups (table 1). A total of 1468 (19%) women either did not receive their randomised method or discontinued use during follow-up.

Overall method continuation rates were high with minimal differences between randomised groups when measured by person-years.6 The proportion, however, of method non-adherence as defined in this analysis (ie, did not receive randomised method at baseline or discontinued randomised method at any point during follow-up), was greater in the DMPA-IM group (26%), followed by the copper IUD (18%) and LNG implant (12%) groups. Timing of discontinuation also differed across methods. During the first 6 months, method discontinuation was highest in the copper IUD group (7%) followed closely by DMPA-IM (6%) and LNG implant (4%) groups.

Between 7 and 12 months of follow-up, it was highest in DMPA-IM group (15%), with equivalent proportions in the LNG implant (5%) and copper IUD (5%) groups.Point prevalences of chlamydia and gonorrhoea at baseline and final visitsIn total, 18% of women had chlamydia at baseline (figure 2A) and 15% at the final visit. Among women 24 years and younger, 22% and 20% had chlamydia at baseline and final visits, respectively. Women aged 25–35 at baseline were less likely to have chlamydia at both baseline (12%) and final visits (8%) compared with younger women.

Baseline chlamydia prevalence ranged from 5% in Zambia to 28% in the Western Cape, South Africa (figure 2B).Point prevalence (per 100 persons) of chlamydia and gonorrhoea at baseline and final visit by age category and study site region. Y-axis scale differs for chlamydia and gonorrhoea figures." data-icon-position data-hide-link-title="0">Figure 2 Point prevalence (per 100 persons) of chlamydia and gonorrhoea at baseline and final visit by age category and study site region. Y-axis scale differs for chlamydia and gonorrhoea figures.Among all women, 5% had gonorrhoea at baseline and the final visit (figure 2C).

Women aged 24 and younger were more likely to have gonorrhoea compared with women aged 25 and older at both baseline (5% vs 4%, respectively) and the final visit (6% vs 3%, respectively). Baseline gonorrhoea prevalence ranged from 3% in Zambia and Kenya to 9% in the Western Cape, South Africa (figure 2D). Similar prevalences were observed at the final visit.Point prevalences of chlamydia and gonorrhoea at final visit by randomised contraceptive methodFourteen per cent of women randomised to DMPA-IM, 15% to copper IUD and 17% to LNG implant had chlamydia at the final visit (table 2).View this table:Table 2 Chlamydia trachomatis and Neisseria gonorrhoeae prevalence at final visitThe prevalence of chlamydia did not significantly differ between DMPA-IM and copper IUD groups (PR 0.90, 95% CI (0.79 to 1.04)) or between copper IUD and LNG implant groups (PR 0.92, 95% CI (0.81 to 1.04)).

Women in the DMPA-IM group, however, had a significantly lower risk of chlamydia compared with the LNG implant group (PR. 0.83, 95% CI (0.72 to 0.95)). Findings from the consistent use analysis were similar, and neither age nor HSV-2 status modified the observed associations.Four per cent of women randomised to DMPA-IM, 6% to copper IUD and 5% to LNG implant had gonorrhoea at the final visit (table 2).

Gonorrhoea prevalence did not significantly differ between DMPA-IM and LNG implant groups (PR. 0.79, 95% CI (0.61 to 1.03)) or between copper IUD and LNG implant groups (PR. 1.18, 95% CI (0.93 to 1.49)).

Women in the DMPA-IM group had a significantly lower risk of gonorrhoea compared with women in the copper IUD group (PR. 0.67, 95% CI (0.52 to 0.87)). Results from as randomised and continuous use analyses did not differ.

And again, neither age nor HSV-2 status modified the observed associations.Clinical assessment by randomised contraceptive methodTo assess the potential for outcome ascertainment bias, we evaluated the frequency of pelvic examinations and abdominal/pelvic pain and discharge by study arm. Women in the copper IUD group were generally more likely to receive a pelvic examination during follow-up as compared with women in the DMPA-IM and LNG implant groups (online supplemental appendix 1). Similarly, abdominal/pelvic pain on examination or abnormal discharge was observed most frequently in the copper IUD group.

The number of pelvic examinations met the prespecified criteria for retention in the adjusted gonorrhoea model but not in the chlamydia model.Supplemental materialFrequency of syndromic symptoms and potential reAmong women who had chlamydia at baseline, 23% were also positive at the final visit (online supplemental appendix 2, figure 3A). Nine per cent of gonorrhoea-positive women at baseline were also positive at the final visit (online supplemental appendix 2, figure 3B). Across both baseline and final visits, a minority of women with chlamydia or gonorrhoea presented with signs and/or symptoms.

Among chlamydia-positive women, only 12% presented with either abnormal vaginal discharge and/or abdominal/pelvic pain at their test-positive visit (online supplemental appendix 2, figure 3C). Similarly, only 15% of gonorrhoea-positive women presented with abnormal vaginal discharge and/or abdominal/pelvic pain at their test-positive visit (online supplemental appendix 2, figure 3D).Potential re and symptoms among women with chlamydia or gonorrhoea. Data are pooled across the screening and final visits in figures (C) and (D).

Symptomatic is defined as presenting with abnormal vaginal discharge and/or abdominal/pelvic pain. Final visit is described as potential re because test of cure was not conducted following baseline diagnosis and treatment." data-icon-position data-hide-link-title="0">Figure 3 Potential re and symptoms among women with chlamydia or gonorrhoea. Data are pooled across the screening and final visits in figures (C) and (D).

Symptomatic is defined as presenting with abnormal vaginal discharge and/or abdominal/pelvic pain. Final visit is described as potential re because test of cure was not conducted following baseline diagnosis and treatment.DiscussionWe observed differences in final prevalences of chlamydia and gonorrhoea by contraceptive group in both as-randomised and consistent-use analyses. The DMPA-IM group had lower final visit chlamydia and gonorrhoea prevalences as compared with copper IUD and LNG implant groups, though only the DMPA-IM versus the copper IUD comparison of gonorrhoea and DMPA-IM versus LNG implant comparison of chlamydia reached statistical significance.

These are novel findings that have not previously been reported to our knowledge and were determined in a randomised trial setting with high participant retention, robust biomarker testing and high randomised method adherence. Interestingly, the copper IUD group had higher gonorrhoea and lower chlamydia prevalence compared with the LNG implant group, though neither finding was statistically significant.Two recent systematic reviews of the association between contraceptives and STIs found inconsistent and insufficient evidence on the association between the contraceptive methods under study in ECHO and chlamydia and gonorrhoea.8 9 Neither systematic review identified any randomised studies or any direct comparative evidence for DMPA-IM, copper IUD and LNG implant, thus enabling a unique scientific contribution from this secondary trial analysis. Nonetheless, these findings should be interpreted in light of biological plausibility, as well as the design strengths and limitations of this analysis.The emerging science on the biological mechanisms underlying HIV susceptibility demonstrates the complex relationship between the infectious pathogen, the host innate and adaptive immune response and the interaction of both with the vaginal microbiome and other -omes.

Data on these factors in relationship to chlamydia and gonorrhoea acquisition are much more limited but can be assumed to be equally complex. Vaginal microbiome composition, including microbial metabolic by-products, have been shown to significantly modify risk of HIV acquisition and to vary with exogenous hormone exposure, menstrual cycle phase, ethnicity and geography.10–12 These same biological principles likely apply to chlamydia and gonorrhoea susceptibility. While DMPA-IM has been associated with decreased bacterial vaginosis (BV), initiation of the copper IUD has been associated with increased BV prevalence, and BV is associated with chlamydia and gonorrhoea acquisition.13 14 Moreover, Lactobacillus crispatus, which is less abundant in BV, has been shown to inhibit HeLa cell by Chlamydia trachomatis and inhibits growth of Neisseria gonorrhoeae in animal models.15 16 In addition, microbial community state types that are deficient in Lactobacillus crispatus and/or dominated by dysbiotic species are associated with inflammation, which is a driver of both STI and HIV susceptibility.

Thus, while the exact mechanisms of chlamydia and gonorrhoea in the presence of exogenous hormones and varying host microbiomes are unknown, it is biologically plausible that these complex factors may result in differential susceptibility to chlamydia and gonorrhoea among DMPA-IM, copper IUD and LNG implant users.An alternative explanation for these findings may be postrandomisation differences in clinical care and/or sexual behaviour. Participants in the copper IUD arm were more likely to have pelvic examinations and more likely to have discharge compared with women in the DMPA-IM and LNG implant groups. While interim STI testing and/or treatment were not documented, women in the copper IUD arm may have been more likely to receive syndromic STI treatment during follow-up due to more examination and observed discharge.

More frequent STI treatment in the copper IUD group would theoretically lower the final visit point prevalence relative to women in the DMPA-IM and LNG implant arms, suggesting that the observed lower risk of STI in the DMPA-IM arm is not due to differential examination, testing and treatment. Differential sexual risk behaviour may also have influenced the results. As reported previously, women in the DMPA-IM group less frequently reported condomless sex and multiple partners than women in the other groups, and both DMPA-IM and LNG implant users less frequently reported new partners and sex during menses than copper IUD users.6 Statistical control of self-reported sexual risk behaviour in the consistent-use analysis may have been inadequate if self-reported sexual behaviour was inaccurately or insufficiently reported.A second alternative explanation may be differences in randomised method non-adherence, which was greater in the DMPA-IM group, compared with copper IUD and LNG implant groups.

Yet, the consistency of findings in the as-randomised and continuous use analyses suggests that method non-adherence had minimal effect on study outcomes. Taken as a whole, these findings indicate that there may be real differences in chlamydia and gonorrhoea risk associated with use of DMPA-IM, the copper IUD and LNG implant. However, any true differential risk by method must be evaluated in light of the holistic benefits and risks of each method.The high observed chlamydia and gonorrhoea prevalences, despite intensive counselling and condom provision, warrants attention, particularly among women ages 24 years and younger and among women in South Africa and Eswatini.

While the ECHO study was conducted in settings of high HIV/STI incidence, enrolment criteria did not purposefully target women at highest risk of HIV/STI in the trial communities, suggesting that the observed prevalences may be broadly applicable to women seeking effective contraception in those settings. Improved approaches are needed to prevent STIs, including options for expedited partner treatment, to prevent re.As expected, few women testing positive for chlamydia or gonorrhoea presented with symptoms (12% and 15%, respectively), and a substantial proportion of women who were positive and treated at baseline were infected at the final visit despite syndromic management during the follow-up. Given that syndromic management is the standard of care within primary health facilities in most trial settings, these data suggest that a large proportion of among reproductive aged women is missed, exacerbating the burden of curable STIs and associated morbidities.

Routine access to more reliable diagnostics, like NAAT and novel point-of-care diagnostic tests, will be key to managing asymptomatic STIs and reducing STI prevalence and related morbidities in these settings.17This secondary analysis of the ECHO trial has strengths and limitations. Strengths include the randomised design with comparator groups of equal STI baseline risk. Participants had high adherence to their randomised contraceptive method.6 While all participants received standardised clinical care and counselling, the unblinded randomisation may have allowed postrandomisation differences in STI risk over time by method.

It is possible that participants modified their risk-taking behaviour based on study counselling messages regarding the potential association between DMPA-IM and HIV.In conclusion, our analyses suggest that DMPA-IM users may have lower risk of chlamydia and gonorrhoea compared with LNG implant and copper IUD users, respectively. Further investigation is warranted to better understand the mechanisms of chlamydia and gonorrhoea susceptibility in the context of contraceptive use. Moreover, the high chlamydia and gonorrhoea prevalences in this population, independent of contraceptive method, warrants urgent attention.Key messagesThe prevalence of chlamydia and gonorrhoea varied by contraceptive method in this randomised trial.High chlamydia and gonorrhoea prevalences, despite intensive counselling and condom provision, warrants attention, particularly among young women in South Africa and Eswatini.Most chlamydia and gonorrhoea s were asymptomatic.

Therefore, routine access to reliable diagnostics are needed to effectively manage and prevent STIs in African women..

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A quickening of the pulseIt’s late October buy cipro canada as I’m completing this Atoms. The autumn golds are fading (or falling), dusk arrives early and the Easterlies are building over the Baltic. This change of season is all rather exhilarating and, at the risk clumsy metaphor, finalising this month's running order (full of fresh and challenging papers) evoked the same buy cipro canada feeling. Space permits only a few mentions here—I could have chosen many more.Paediatric emergency medicineWe are excited about the launch of a new section, paediatric emergency medicine, convened and coordinated by our editorial colleague Cynthia Mollen from the Children’s Hospital Philadelphia.

It will feature original research, hypothesis generating ideas and review articles. We kickstart the series with two novel point of care buy cipro canada triage studies.Ketones and dehydrationAs we all keenly aware, assessment of dehydration in the absence of an immediate pre-illness weight is near impossible with next to no correlation between standard biochemical measures and degree of intracellular fluid deficit. Dumin and colleagues in Dublin assess another attractive potential marker, serum point-of-care ketones at triage and moderate-to-severe dehydration secondary to acute gastroenteritis on clinical assessment using the Gorelick Scale. See page 1157LAMPRapid molecular diagnostic testing, now establishing a foothold and is likely to be a major component of assessment and triage in the future.

Ferris and colleagues report on the use of point-of-care loop-mediated isothermal amplification (LAMP) in the diagnosis of meningococcal buy cipro canada disease (MD). Data from three UK emergency departments (ED) between 2017 and 2019 in which consecutive children attending the ED with features of MD were eligible for inclusion. The meningococcal LAMP test (index test and available within an hour of sampling) was performed on an oropharyngeal swab validity being tested against the reference buy cipro canada standard test of confirmation of invasive MD defined as positive N. Meningitidis culture or PCR result from a sterile site.

See page 1151Global healthSnakebiteIn 2017 snakebite envenoming was reinstated on the WHO list of neglected tropical diseases. With 5 million bites per annum, around 2 million envenomations, 100 000 deaths and many times more left with permanent physical and psychological sequelae, the annual morbidity and mortality buy cipro canada is among the highest of the group. Like other NTDs, snakebite is primarily a disease of poverty, climate change (related to deforestation and mining) rendering vulnerable populations even more vulnerable. The vast majority of snakebites occur in Africa (30% in children) Asia and Latin America with India buy cipro canada having the highest reported death toll.

This is the first of a two part series in which Sophie Pach, Jay Halbert and colleagues describe global snakebite epidemiology, moving on to management in the next instalment. See page 1135Low birth weight and cardiac surgeryGiven the 1.3 million incident cases annually and resource limitations, congenital heart disease is now one of the five most common causes of early child death globally, joining the perennials pneumonia and acute gastroenteritis. Cardiac surgery centres have proliferated in low- and middle-income countries (LMICs) buy cipro canada. There are compelling biological reasons for an association between lower birth weight and poorer outcomes in children with congenital heart disease from greater susceptibility to cardiomyocyte proliferation and left ventricular remodelling and the additional difficulty in operating.

Krishna Kumar study and Namachivayam’s editorial describe mortality data from a large South Indian centre in two epochs, 2011–2014 and 2015–2018 by birth weight adjusting for severity of defect, findings of importance in surgical provision planning. See pages 1140 and 1133Drugs and therapeutics sectionOral amoxicillin in neonates with suspected sepsisSepsis buy cipro canada accounts for 23% of all-cause global neonatal mortality across the globe outcomes being adversely affected by delayed care seeking and poor adherence to parenteral antibiotic regimens in low- and middle-income country settings. In many such settings, inpatient admission is not even an option so the need for effective oral treatment (as an adjunct to intramuscular aminoglycosides which themselves can be given on an outpatient basis) is pressing. Amoxicillin is an attractive option, though pharmacokinetic (PK) data in this age group is sparse, despite WHO recommendations for use where inpatient treatment is not feasible.

Mir and colleagues enrolled infants with signs of sepsis enrolled in an oral amoxicillin/intramuscular gentamicin treatment arm of a sepsis trial, (Simplified Antibiotic Therapy Trial (SATT)) in Karachi, Pakistan buy cipro canada. Pharmacokinetic sampling was performed at 0, 2–3 and 6–8 hours following an index dose of oral amoxicillin. Plasma concentrations were determined by high-performance liquid chromatography/mass spectrometry and values of ≥2 mg/L were considered as the buy cipro canada effect threshold, given the regional minimal inhibitory concentration (MIC) of resistant Streptococcus pneumoniae. Of 44 infants, 6 had positive blood cultures with predominant Gram-positive organisms.

Mean amoxicillin levels at 2–3 hours and 6–8 hours were, respectively, 5 and 8 times the MIC following the index dose. Based on these findings, oral amoxicillin has potential as a safe replacement of buy cipro canada parenteral ampicillin in newborn sepsis regimens including aminoglycosides, where hospitalisation is not feasible. The practical importance of this finding cannot be overstated. See page 1208The number of births globally each year with a diagnosis of congenital heart disease (CHD) is estimated at around 1.3 million1.

The majority of these (almost 90%) occur in low to middle-income countries buy cipro canada (LMICs). Many of the complex operations for CHD are performed in the newborn period. While neonatal buy cipro canada cardiac surgery comprises around 25% of the total CHD surgical volume, it accounts for more than 50% of postoperative mortality.Evidence from preclinical studies suggests that premature birth and the associated cessation of cardiomyocyte proliferation result in substantial alterations to the normal maturational processes in the newborn myocardium. An abnormal cardiac maturation trajectory ensues, which is characterised by cardiomyocyte hypertrophy, and a severalfold increase in extracellular matrix deposition in the myocardial interstium, often resulting in myocardial fibrosis.2 These changes can adversely influence contractility and conductivity of the myocardial muscle, leading to cardiac dysfunction and arrhythmia in the early postnatal period and beyond.2 When the added constraints of being born with a CHD are superimposed on these alterations, the adverse effects are likely to be magnified severalfold.

An immature neonatal myocardium is more susceptible to the effects of cardiopulmonary bypass and reperfusion injury during cardiac surgery and recovers less well than an older infant’s myocardium. A recent meta-analysis3 has shown that neonates born prematurely have persistently smaller ventricular dimensions, left ventricular diastolic dysfunction that worsens with age, impaired right ventricular systolic function and an buy cipro canada accelerated rate of left ventricular hypertrophy from the neonatal period through to childhood and adulthood. This suggests that even if an infant were to survive and be discharged from hospital after surgery, the risks were present lifelong. €¦.

A quickening of the http://terrassen-gartenmoebel.de/2018/07/16/hallo-welt/ pulseIt’s late October as how much does generic cipro cost I’m completing this Atoms. The autumn golds are fading (or falling), dusk arrives early and the Easterlies are building over the Baltic. This change of season is all rather exhilarating and, at the risk clumsy metaphor, finalising this month's running order (full of fresh and challenging how much does generic cipro cost papers) evoked the same feeling.

Space permits only a few mentions here—I could have chosen many more.Paediatric emergency medicineWe are excited about the launch of a new section, paediatric emergency medicine, convened and coordinated by our editorial colleague Cynthia Mollen from the Children’s Hospital Philadelphia. It will feature original research, hypothesis generating ideas and review articles. We kickstart the series with two novel point of care triage studies.Ketones and dehydrationAs we all keenly aware, assessment of dehydration how much does generic cipro cost in the absence of an immediate pre-illness weight is near impossible with next to no correlation between standard biochemical measures and degree of intracellular fluid deficit.

Dumin and colleagues in Dublin assess another attractive potential marker, serum point-of-care ketones at triage and moderate-to-severe dehydration secondary to acute gastroenteritis on clinical assessment using the Gorelick Scale. See page 1157LAMPRapid molecular diagnostic testing, now establishing a foothold and is likely to be a major component of assessment and triage in the future. Ferris and colleagues report on the use of how much does generic cipro cost point-of-care loop-mediated isothermal amplification (LAMP) in the diagnosis of meningococcal disease (MD).

Data from three UK emergency departments (ED) between 2017 and 2019 in which consecutive children attending the ED with features of MD were eligible for inclusion. The meningococcal LAMP test (index test and available within an hour of sampling) was performed on an oropharyngeal swab validity being how much does generic cipro cost tested against the reference standard test of confirmation of invasive MD defined as positive N. Meningitidis culture or PCR result from a sterile site.

See page 1151Global healthSnakebiteIn 2017 snakebite envenoming was reinstated on the WHO list of neglected tropical diseases. With 5 million bites per annum, around 2 million envenomations, 100 000 deaths and many times how much does generic cipro cost more left with permanent physical and psychological sequelae, the annual morbidity and mortality is among the highest of the group. Like other NTDs, snakebite is primarily a disease of poverty, climate change (related to deforestation and mining) rendering vulnerable populations even more vulnerable.

The vast majority of snakebites occur in Africa (30% how much does generic cipro cost in children) Asia and Latin America with India having the highest reported death toll. This is the first of a two part series in which Sophie Pach, Jay Halbert and colleagues describe global snakebite epidemiology, moving on to management in the next instalment. See page 1135Low birth weight and cardiac surgeryGiven the 1.3 million incident cases annually and resource limitations, congenital heart disease is now one of the five most common causes of early child death globally, joining the perennials pneumonia and acute gastroenteritis.

Cardiac surgery centres how much does generic cipro cost have proliferated in low- and middle-income countries (LMICs). There are compelling biological reasons for an association between lower birth weight and poorer outcomes in children with congenital heart disease from greater susceptibility to cardiomyocyte proliferation and left ventricular remodelling and the additional difficulty in operating. Krishna Kumar study and Namachivayam’s editorial describe mortality data from a large South Indian centre in two epochs, 2011–2014 and 2015–2018 by birth weight adjusting for severity of defect, findings of importance in surgical provision planning.

See pages 1140 and 1133Drugs and therapeutics sectionOral amoxicillin in neonates with suspected sepsisSepsis accounts for 23% of all-cause global neonatal mortality across the globe outcomes being adversely affected by delayed care how much does generic cipro cost seeking and poor adherence to parenteral antibiotic regimens in low- and middle-income country settings. In many such settings, inpatient admission is not even an option so the need for effective oral treatment (as an adjunct to intramuscular aminoglycosides which themselves can be given on an outpatient basis) is pressing. Amoxicillin is an attractive option, though pharmacokinetic (PK) data in this age group is sparse, despite WHO recommendations for use where inpatient treatment is not feasible.

Mir and colleagues enrolled infants with signs of sepsis enrolled in an oral amoxicillin/intramuscular gentamicin treatment arm of a sepsis trial, (Simplified Antibiotic Therapy Trial (SATT)) how much does generic cipro cost in Karachi, Pakistan. Pharmacokinetic sampling was performed at 0, 2–3 and 6–8 hours following an index dose of oral amoxicillin. Plasma concentrations were determined by high-performance liquid chromatography/mass how much does generic cipro cost spectrometry and values of ≥2 mg/L were considered as the effect threshold, given the regional minimal inhibitory concentration (MIC) of resistant Streptococcus pneumoniae.

Of 44 infants, 6 had positive blood cultures with predominant Gram-positive organisms. Mean amoxicillin levels at 2–3 hours and 6–8 hours were, respectively, 5 and 8 times the MIC following the index dose. Based on these findings, oral amoxicillin has potential as a safe replacement of parenteral ampicillin in newborn how much does generic cipro cost sepsis regimens including aminoglycosides, where hospitalisation is not feasible.

The practical importance of this finding cannot be overstated. See page 1208The number of births globally each year with a diagnosis of congenital heart disease (CHD) is estimated at around 1.3 million1. The majority of how much does generic cipro cost these (almost 90%) occur in low to middle-income countries (LMICs).

Many of the complex operations for CHD are performed in the newborn period. While neonatal cardiac surgery comprises around 25% of the total CHD surgical how much does generic cipro cost volume, it accounts for more than 50% of postoperative mortality.Evidence from preclinical studies suggests that premature birth and the associated cessation of cardiomyocyte proliferation result in substantial alterations to the normal maturational processes in the newborn myocardium. An abnormal cardiac maturation trajectory ensues, which is characterised by cardiomyocyte hypertrophy, and a severalfold increase in extracellular matrix deposition in the myocardial interstium, often resulting in myocardial fibrosis.2 These changes can adversely influence contractility and conductivity of the myocardial muscle, leading to cardiac dysfunction and arrhythmia in the early postnatal period and beyond.2 When the added constraints of being born with a CHD are superimposed on these alterations, the adverse effects are likely to be magnified severalfold.

An immature neonatal myocardium is more susceptible to the effects of cardiopulmonary bypass and reperfusion injury during cardiac surgery and recovers less well than an older infant’s myocardium. A recent meta-analysis3 has shown that neonates born prematurely have persistently smaller ventricular dimensions, how much does generic cipro cost left ventricular diastolic dysfunction that worsens with age, impaired right ventricular systolic function and an accelerated rate of left ventricular hypertrophy from the neonatal period through to childhood and adulthood. This suggests that even if an infant were to survive and be discharged from hospital after surgery, the risks were present lifelong.