Corruption in the Middle East and the Limits of Conventional Approaches

Die Unzufriedenheit mit der verbreiteten Korruption war 2011/2012 eine wesentliche Ursache für die arabischen Unruhen und weitere Aufstände weltweit. Der Fall Jordanien zeigt allerdings, dass konventionelle Ansätze zur Bekämpfung von Korruption nicht ausreichen. Eine angemessene Strategie gegen Korruption muss diese als ein Problem der Verteilungsgerechtigkeit und nicht des Strafrechts verstehen. Wie in allen anderen arabischen Staaten ist die Unzufriedenheit in der Bevölkerung über die offensichtliche Korruption auch in Jordanien beträchtlich. Allerdings wird im Allgemeinen nicht über Fälle von Bestechung und Erpressung geklagt, die weniger häufig vorkommen, sondern über lokale Praktiken politischer Patronage und Begünstigung, die unter dem Begriff "Wasta" zusammengefasst werden. "Wasta" wurde bislang als Form der Korruption und strafrechtliches Problem angesehen, weshalb Versuche zur Eindämmung überwiegend ineffizient blieben: "Wasta"-Praktiken werden in der Regel nicht mit Rechtsverstößen verbunden, sondern bewegen sich innerhalb formal legaler Verfahren. Konventionelle Ansätze zur Bekämpfung von Korruption, die sich an rechtsstaatlichen Grundsätzen und Transparenz orientieren, sind deshalb nicht zielführend. Demokratisierung allein ist ebenfalls ungeeignet, das Problem „Wasta” zu lösen. In der parlamentarischen Praxis macht "Wasta" den Großteil der Aktivitäten aller Parlamentsmitglieder aus. Diese werden deshalb als persönliche Dienstleister für ihre Wahlbezirke und nicht als Mitglieder einer gesetzgebenden Körperschaft wahrgenommen. Gleichzeitig hält die Bevölkerung das Parlament für eine zutiefst korrupte Institution. "Wasta" wird problematisch, wenn diese Praxis zu einem ungleichen Zugang der Bürger zu öffentlichen Ressourcen führt. Statt sich nur auf politische und administrative Reformen zu konzentrieren, muss der Fokus der Bekämpfung auf den (Wieder-)Aufbau wohlfahrtsstaatlicher Strukturen gelegt werden, zu denen alle Bürger gleichermaßen Zugang haben

Design and rationale of DUTCH-AF:a prospective nationwide registry programme and observational study on long-term oral antithrombotic treatment in patients with atrial fibrillation

Introduction Anticoagulation therapy is pivotal in the management of stroke prevention in atrial fibrillation (AF). Prospective registries, containing longitudinal data are lacking with detailed information on anticoagulant therapy, treatment adherence and AF-related adverse events in practice-based patient cohorts, in particular for non-vitamin K oral anticoagulants (NOAC). With the creation of DUTCH-AF, a nationwide longitudinal AF registry, we aim to provide clinical data and answer questions on the (anticoagulant) management over time and of the clinical course of patients with newly diagnosed AF in routine clinical care. Within DUTCH-AF, our current aim is to assess the effect of non-adherence and non-persistence of anticoagulation therapy on clinical adverse events (eg, bleeding and stroke), to determine predictors for such inadequate anticoagulant treatment, and to validate and refine bleeding prediction models. With DUTCH-AF, we provide the basis for a continuing nationwide AF registry, which will facilitate subsequent research, including future registry-based clinical trials. Methods and analysis The DUTCH-AF registry is a nationwide, prospective registry of patients with newly diagnosed 'non-valvular' AF. Patients will be enrolled from primary, secondary and tertiary care practices across the Netherlands. A target of 6000 patients for this initial cohort will be followed for at least 2 years. Data on thromboembolic and bleeding events, changes in antithrombotic therapy and hospital admissions will be registered. Pharmacy-dispensing data will be obtained to calculate parameters of adherence and persistence to anticoagulant treatment, which will be linked to AF-related outcomes such as ischaemic stroke and major bleeding. In a subset of patients, anticoagulation adherence and beliefs about drugs will be assessed by questionnaire. Ethics and dissemination This study protocol was approved as exempt for formal review according to Dutch law by the Medical Ethics Committee of the Leiden University Medical Centre, Leiden, the Netherlands. Results will be disseminated by publications in peer-reviewed journals and presentations at scientific congresses

Serial cardiac biomarkers, pulmonary artery pressures and traditional parameters of fluid status in relation to prognosis in patients with chronic heart failure:Design and rationale of the BioMEMS study

AimsHeart failure (HF), a global pandemic affecting millions of individuals, calls for adequate predictive guidance for improved therapy. Congestion, a key factor in HF-related hospitalizations, further underscores the need for timely interventions. Proactive monitoring of intracardiac pressures, guided by pulmonary artery (PA) pressure, offers opportunities for efficient early-stage intervention, since haemodynamic congestion precedes clinical symptoms.MethodsThe BioMEMS study, a substudy of the MONITOR-HF trial, proposes a multifaceted approach integrating blood biobank data with traditional and novel HF parameters. Two additional blood samples from 340 active participants in the MONITOR-HF trial were collected at baseline, 3-, 6-, and 12-month visits and stored for the BioMEMS biobank. The main aims are to identify the relationship between temporal biomarker patterns and PA pressures derived from the CardioMEMS-HF system, and to identify the biomarker profile(s) associated with the risk of HF events and cardiovascular death.ConclusionSince the prognostic value of single baseline measurements of biomarkers like N-terminal pro-B-type natriuretic peptide is limited, with the BioMEMS study we advocate a dynamic, serial approach to better capture HF progression. We will substantiate this by relating repeated biomarker measurements to PA pressures. This design rationale presents a comprehensive review on cardiac biomarkers in HF, and aims to contribute valuable insights into personalized HF therapy and patient risk assessment, advancing our ability to address the evolving nature of HF effectively.Design and rationale of the BioMEMS study. QoL, quality of life. Graphical abstract is created with BioRender.com imag

Reduction of atrial tachyarrhythmia episodes during the overdrive pacing period using the post-mode switch overdrive pacing (PMOP) algorithm

BACKGROUND Early recurrences within 10 minutes after termination of an atria[ tachyarrhythmia, such as atria[ tachycardia (AT), atrial flutter, or atrial fibrillation (AF) episodes, account for a large part of paroxysmal AT/AF episodes. It is unclear whether these arrhythmias can be suppressed by overdrive pacing. OBJECTIVE We set out to prove that overdrive pacing is effective in preventing early recurrences of AT/AF. METHODS This AT500 (DDDRP device, Bakken Research Center Medtronic, Maastricht, The Netherlands) post-mode switch overdrive pacing (PMOP) study is a randomized controlled trial designed to test the efficacy of overdrive pacing on the suppression of early recurring AT/AF episodes. With the PMOP feature, overdrive pacing is activated 12 ventricular beats after device-confirmed termination of an AT/AF episode with a programmed duration and rate. If at least four episodes of 1 minute in duration occurred within the run-in period of 1 month, patients were randomized to one of the three settings (PMOP off and PMOP 10 minutes at 90 bpm or 120 bpm) for 2 months. At 2 and 4 months, patients were crossed over to another arm. At 6 months, all patients were programmed with PMOP on at 90 bpm for 30 minutes. RESULTS We enrolled 122 and randomized 50 patients. Sixty percent of all stored AT/AF episodes occurred within 10 minutes after a previous episode; 31% occurred after device-determined termination and before the device reached the overdrive rate (17-27 ventricular beats after termination), and 29% of the episodes occurred white the device was pacing at the programmed overdrive rate. Thirty-seven percent of the average percentage of episodes during the overdrive period was prevented by the randomized settings of PMOP 90 bpm/10 min (P =.01, paired t-test, n = 39) and 120 bpm/10 min (P =.03, n = 35). In addition, for the nonrandomized setting of PMOP 90 bpm/30 min, the average number of episodes during the overdrive period was significantly smaller than the percentage of episodes occurring during the corresponding off period of 30 minutes (P =.05, n = 33). No significant differences in burden and episodes were found between the PMOP settings and the corresponding off periods. CONCLUSIONS This is the first randomized controlled clinical trial to prove that overdrive pacing is effective in preventing early recurrences of AT/AF. However, shortcomings of the PMOP algorithm, such as late activation, need further improvement

Does flecainide regain its antiarrhythmic activity after electrical cardioversion of persistent atrial fibrillation?

OBJECTIVES The purpose of this study was to evaluate the hypothesis that presumed reversion of electrical remodeling after cardioversion of atrial fibrillation (AF) restores the efficacy of flecainide. BACKGROUND Flecainide loses its efficacy to cardiovert when AF has been present for more than 24 hours. Most probably, the loss is caused by atrial electrical remodeling. Studies suggest electrical remodeling is completely reversible within 4 days after restoration of sinus rhythm (SR). METHODS One hundred eighty-one patients with persistent AF (median duration 3 months) were included in this prospective study. After failure of pharmacologic cardioversion by flecainide 2 mg/kg IV (maximum 150 mg in 10 minutes) and subsequent successful electrical cardioversion, we performed intense transtelephonic rhythm monitoring three times daily for 1 month. In case of AF recurrence, a second cardioversion by flecainide was attempted as soon as possible. RESULTS AF recurred in 123 patients (68%). Successful cardioversion by flecainide occurred only when SR had been maintained for more than 4 days (7/51 patients [14%]). Failure to cardiovert was associated with a prolonged duration of the recurrent AF episode and concurrent digoxin use. Multivariate logistic regression confirmed that successful cardioversion was determined by digoxin use (odds ratio [OR] 0.093, P = .047) and by the interaction between the duration of SR and the (inverse) duration of recurrent AF (OR 6.499, P <.001). When flecainide was administered within 10 hours after AF onset and the duration of SR was greater than 4 days, the success rate was 58%. CONCLUSIONS Flecainide recovers its antiarrhythmic action after cardioversion of AF. However, successful pharmacologic cardioversion occurs only after SR has lasted at least 4 days and is expected only for recurrences having duration of a few hours. Immediate pharmacologic cardioversion of AF recurrence may be a worthwhile strategy for management of persistent A

Clinical Potential of Targeting Fibroblast Growth Factor-23 and αKlotho in the Treatment of Uremic Cardiomyopathy.

Chronic kidney disease is highly prevalent, affecting 10% to 15% of the adult population worldwide and is associated with increased cardiovascular morbidity and mortality. As chronic kidney disease worsens, a unique cardiovascular phenotype develops characterized by heart muscle disease, increased arterial stiffness, atherosclerosis, and hypertension. Cardiovascular risk is multifaceted, but most cardiovascular deaths in patients with advanced chronic kidney disease are caused by heart failure and sudden cardiac death. While the exact drivers of these deaths are unknown, they are believed to be caused by uremic cardiomyopathy: a specific pattern of myocardial hypertrophy, fibrosis, with both diastolic and systolic dysfunction. Although the pathogenesis of uremic cardiomyopathy is likely to be multifactorial, accumulating evidence suggests increased production of fibroblast growth factor-23 and αKlotho deficiency as potential major drivers of cardiac remodeling in patients with uremic cardiomyopathy. In this article we review the increasing understanding of the physiology and clinical aspects of uremic cardiomyopathy and the rapidly increasing knowledge of the biology of both fibroblast growth factor-23 and αKlotho. Finally, we discuss how dissection of these pathological processes is aiding the development of therapeutic options, including small molecules and antibodies, directly aimed at improving the cardiovascular outcomes of patients with chronic kidney disease and end-stage renal disease

Use of Systemic Therapies for Treatment of Psoriasis in Patients with a History of Treated Solid Tumours: Inference-Based Guidance from a Multidisciplinary Expert Panel

Abstract Background Patients with treated solid tumours (TSTs) are a highly heterogeneous population at an increased risk for malignancy compared with the general population. When treating psoriasis in patients with a history of TSTs, clinicians are concerned about the immunosuppressive nature of psoriasis therapies, the possibility of augmenting cancer recurrence/progression, and infectious complications. No direct, high-level evidence exists to address these concerns. Objectives We aim to provide a structured framework supporting healthcare professional and patient discussions on the risks and benefits of systemic psoriasis therapy in patients with previously TSTs. Our goal was to address the clinically important question, “In patients with TSTs, does therapy with systemic agents used for psoriasis increase the risk of malignancy or malignancy recurrence?” Methods We implemented an inference-based approach relying on indirect evidence when direct clinical trial and real-world data were absent. We reviewed indirect evidence supporting inferences on the status of immune function in patients with TSTs. Recommendations on systemic psoriasis therapies in patients with TSTs were derived using an inferential heuristic. Results We identified five indirect indicators of iatrogenic immunosuppression informed by largely independent bodies of evidence: (1) overall survival, (2) rate of malignancies with psoriasis and systemic psoriasis therapies, (3) rate of infections with psoriasis and systemic psoriasis therapies, (4) common disease biochemical pathways for solid tumours and systemic psoriasis therapies, and (5) solid organ transplant outcomes. On the basis of review of the totality of this data, we provided inference-based conclusions and ascribed level of support for each statement. Conclusions Prior to considering new therapies for psoriasis, an understanding of cancer prognosis should be addressed. Patients with TSTs and a good cancer prognosis will have similar outcomes to non-TST patients when treated with systemic psoriasis therapies. For patients with TSTs and a poor cancer prognosis, the quality-of-life benefits of treating psoriasis may outweigh the theoretical risks.Plain Language Summary Patients with previously treated cancer have a higher chance of cancer recurrence compared with the general population. With cancer incidence rising worldwide, doctors across medical specialities will need to treat other medical conditions, including inflammatory diseases such as psoriasis, in these patients. Effective systemic therapies for psoriasis reduce immune cell activity. Accordingly, there are concerns that treatments for psoriasis could worsen cancer recurrence/progression and infectious complications. There is not enough quality evidence to make broad recommendations for treating other inflammatory conditions in patients with a history of cancer. To guide patient and doctor discussions, we asked: what are effective and safe treatments when patients with treated solid tumours need systemic therapy (pills or injections) for their psoriasis? We focused on patients with solid tumours and excluded blood and skin cancers. Our panel of experts, including 12 dermatologists and 3 medical oncologists, reviewed direct and indirect evidence to answer this question. Considering the totality of evidence reviewed, the expert panel drafted and rated their level of support for opinion statements on important considerations in treating patients with psoriasis who have a history of solid tumours. By making inferences on systemic psoriasis therapies in this heterogeneous population, we take the onus off individual physicians to review the indirect data. This process may help answer questions in other disease populations where direct evidence is scarce or absent. To support treatment decisions, doctors should have a guided conversation with the patient and their family on a case-by-case basis about the risks and benefits of treatment

An initial exploration of subtraction electrocardiography to detect myocardial ischemia in the prehospital setting

Background: In the prehospital triage of patients presenting with symptoms suggestive of acute myocardial ischemia, reliable myocardial ischemia detection in the electrocardiogram (ECG) is pivotal. Due to large interindividual variability and overlap between ischemic and nonischemic ECG-patterns, incorporation of a previous elective (reference) ECG may improve accuracy. The aim of the current study was to explore the potential value of serial ECG analysis using subtraction electrocardiography. Methods: SUBTRACT is a multicenter retrospective observational study, including patients who were prehospitally evaluated for acute myocardial ischemia. For each patient, an elective previously recorded reference ECG was subtracted from the ambulance ECG. Patients were classified as myocardial ischemia cases or controls, based on the in-hospital diagnosis. The diagnostic performance of subtraction electrocardiography was tested using logistic regression of 28 variables describing the differences between the reference and ambulance ECGs. The Uni-G ECG Analysis Program was used for state-of-the-art single-ECG interpretation of the ambulance ECG. Results: In 1,229 patients, the mean area-under-the-curve of subtraction electrocardiography was 0.80 (95%CI: 0.77–0.82). The performance of our new method was comparable to single-ECG analysis using the Uni-G algorithm: sensitivities were 66% versus 67% (p-value >.05), respectively; specificities were 80% versus 81% (p-value >.05), respectively. Conclusions: In our initial exploration, the diagnostic performance of subtraction electrocardiography for the detection of acute myocardial ischemia proved equal to that of state-of-the-art automated single-ECG analysis by the Uni-G algorithm. Possibly, refinement of both algorithms, or even integration of the two, could surpass current electrocardiographic myocardial ischemia detection

Use of Systemic Therapies for Treatment of Psoriasis in People Living with Controlled HIV: Inference-Based Guidance from a Multidisciplinary Expert Panel

Abstract Background People living with human immunodeficiency virus (PLHIV) have a similar prevalence of psoriasis as the general population, though incidence and severity correlate with HIV viral load. Adequately treating HIV early renders the infection a chronic medical condition and allows PLHIV with a suppressed viral load (PLHIV-s) to live normal lives. Despite this, safety concerns and a lack of high-level data have hindered the use of systemic psoriasis therapies in PLHIV-s. Objectives We aim to provide a structured framework that supports healthcare professionals and patients discussing the risks and benefits of systemic psoriasis therapy in PLHIV-s. Our goal was to address the primary question, are responses to systemic therapies for the treatment of psoriasis in PLHIV-s similar to those in the non-HIV population? Methods We implemented an inference-based approach relying on indirect evidence when direct clinical trial data were absent. In this instance, we reviewed indirect evidence supporting inferences on the status of immune function in PLHIV. Recommendations on systemic treatment for psoriasis in PLHIV were derived using an inferential heuristic. Results We identified seven indirect indicators of immune function informed by largely independent bodies of evidence: (1) functional assays, (2) vaccine response, (3) life expectancy, (4) psoriasis manifestations, (5) rate of infections, (6) rate of malignancies, and (7) organ transplant outcomes. Conclusions Drug-related benefits and risks when treating a patient with systemic psoriasis therapies are similar for non-HIV patients and PLHIV with a suppressed viral load and normalized CD4 counts. Prior to initiating psoriasis treatment in PLHIV, HIV replication should be addressed by an HIV specialist. Exercise additional caution for patients with a suppressed viral load and discordant CD4 responses on antiretroviral therapy

Quantification of fibroblast growth factor 23 and N-terminal pro-B-type natriuretic peptide to identify patients with atrial fibrillation using a high-throughput platform: A validation study.

BACKGROUND Large-scale screening for atrial fibrillation (AF) requires reliable methods to identify at-risk populations. Using an experimental semi-quantitative biomarker assay, B-type natriuretic peptide (BNP) and fibroblast growth factor 23 (FGF23) were recently identified as the most suitable biomarkers for detecting AF in combination with simple morphometric parameters (age, sex, and body mass index [BMI]). In this study, we validated the AF model using standardised, high-throughput, high-sensitivity biomarker assays. METHODS AND FINDINGS For this study, 1,625 consecutive patients with either (1) diagnosed AF or (2) sinus rhythm with CHA2DS2-VASc score of 2 or more were recruited from a large teaching hospital in Birmingham, West Midlands, UK, between September 2014 and February 2018. Seven-day ambulatory ECG monitoring excluded silent AF. Patients with tachyarrhythmias apart from AF and incomplete cases were excluded. AF was diagnosed according to current clinical guidelines and confirmed by ECG. We developed a high-throughput, high-sensitivity assay for FGF23, quantified plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and FGF23, and compared results to the previously used multibiomarker research assay. Data were fitted to the previously derived model, adjusting for differences in measurement platforms and known confounders (heart failure and chronic kidney disease). In 1,084 patients (46% with AF; median [Q1, Q3] age 70 [60, 78] years, median [Q1, Q3] BMI 28.8 [25.1, 32.8] kg/m2, 59% males), patients with AF had higher concentrations of NT-proBNP (median [Q1, Q3] per 100 pg/ml: with AF 12.00 [4.19, 30.15], without AF 4.25 [1.17, 15.70]; p < 0.001) and FGF23 (median [Q1, Q3] per 100 pg/ml: with AF 1.93 [1.30, 4.16], without AF 1.55 [1.04, 2.62]; p < 0.001). Univariate associations remained after adjusting for heart failure and estimated glomerular filtration rate, known confounders of NT-proBNP and FGF23. The fitted model yielded a C-statistic of 0.688 (95% CI 0.656, 0.719), almost identical to that of the derived model (C-statistic 0.691; 95% CI 0.638, 0.744). The key limitation is that this validation was performed in a cohort that is very similar demographically to the one used in model development, calling for further external validation. CONCLUSIONS Age, sex, and BMI combined with elevated NT-proBNP and elevated FGF23, quantified on a high-throughput platform, reliably identify patients with AF. TRIAL REGISTRATION Registry IRAS ID 97753 Health Research Authority (HRA), United Kingdom