Registro español de ablación con catéter. XXII informe oficial de la Asociación del Ritmo Cardiaco de la Sociedad Española de Cardiología (2022) / Spanish catheter ablation registry. 22nd official report of the Heart Rhythm Association of the Spanish Society of Cardiology (2022)

Introducción y objetivos: Se presentan los resultados del Registro español de ablación con catéter correspondientes a 2022. Métodos: Registro de actividad restrospectivo de los datos introducidos en la plataforma REDCap utilizando un formulario específico. Resultados: Participaron 103 centros (75 públicos, 28 privados) que comunicaron 23.360 procedimientos de ablación, con una media de 227±173 y una mediana de 202 [intervalo intercuartílico, 77-312] procedimientos por centro. Se ha producido un incremento muy significativo de la actividad (+5.419 casos,+30,2%) y de los centros participantes (10 centros más que en 2021). El procedimiento más frecuente sigue siendo la ablación de fibrilación auricular (FA) (el 35%, 8.185 casos) seguido de la ablación del istmo cavotricuspídeo (el 20%, 4.640 casos) y la taquicardia por reentrada intranodular (el 17%, 3.898 casos). Crecen todos los sustratos, especialmente la ablación de FA (+40%), y aumenta ligeramente el éxito agudo global, que alcanza el 96%, y disminuyen las tasas de complicaciones hasta el 1,8% (n=422) y de mortalidad (0,04%; n=10). Se realizaron 525 ablaciones en pacientes pediátricos (2,2%). Conclusiones: El Registro español de ablación con catéter recoge de manera sistemática e ininterrumpida la trayectoria nacional, que este año muestra un incremento muy significativo de la actividad en todos los sustratos, pero especialmente la referente a ablación de FA. Aumenta ligeramente la tasa de éxito y se reducen tanto la tasa de complicaciones como la mortalidad.(AU)

Introduction and objectives: This article presents results of the Spanish catheter ablation registry for the year 2022. MethodsData were retrospectively entered into a REDCap platform using a specific form. Results: A total of 103 centers participated (75 public, 28 private), which reported 23 360 ablation procedures, with a mean of 227±173 and a median of 202 [interquartile range, 77-312] procedures per center. Activity significantly increased (+5419 procedures,+30.2%) with more centers participating in the registry (10 more than in 2021). The most common procedure continued to be atrial fibrillation ablation (35%, 8185 procedures) followed by cavotricuspid isthmus ablation (20%, 4640 procedures), and intranodal re-entrant tachycardia (17%, 3898 procedures). There was an increase in all reported substrates, especially atrial fibrillation ablation (+40%), with slightly higher global acute success (96%) and lower complication rates (1.8%) and mortality (0.04%, n=10). In total, 525 procedures were performed in pediatric patients (2.2%). Conclusions: The Spanish catheter ablation registry systematically and continuously collects the national trajectory, which experienced a significant activity increase in 2022 in all of the reported substrates but especially in atrial fibrillation ablation. Acute success increased, while both complications and mortality decreased.(AU)

Hospital Characteristics and Early Enrollment Trends in the American College of Cardiology Voluntary Public Reporting Program.

Importance: Limited data exist regarding the characteristics of hospitals that do and do not participate in voluntary public reporting programs. Objective: To describe hospital characteristics and trends associated with early participation in the American College of Cardiology (ACC) voluntary reporting program for cardiac catheterization-percutaneous coronary intervention (CathPCI) and implantable cardioverter-defibrillator (ICD) registries. Design, Setting, and Participants: This cross-sectional study analyzed enrollment trends and characteristics of hospitals that did and did not participate in the ACC voluntary public reporting program. All hospitals reporting procedure data to the National Cardiovascular Data Registry (NCDR) CathPCI or ICD registries that were eligible for the public reporting program from July 2014 (ie, program launch date) to May 2017 were included. Stepwise logistic regression was used to identify hospital characteristics associated with voluntary participation. Enrollment trends were evaluated considering the date US News & World Report (USNWR) announced that it would credit participating hospitals. Data analysis was performed from March 2017 to January 2018. Main Outcomes and Measures: Hospital characteristics and participation in the public reporting program. Results: By May 2017, 561 of 1747 eligible hospitals (32.1%) had opted to participate in the program. Enrollment increased from 240 to 376 hospitals (56.7%) 1 month after the USNWR announcement that program participation would be considered as a component of national hospital rankings. Compared with hospitals that did not enroll, program participants had increased median (IQR) procedural volumes for PCI (481 [280-764] procedures vs 332 [186-569] procedures; P < .001) and ICD (114 [56-220] procedures vs 62 [25-124] procedures; P < .001). Compared with nonparticipating hospitals, an increased mean (SD) proportion of participating hospitals adhered to composite discharge medications after PCI (0.96 [0.03] vs 0.92 [0.07]; P < .001) and ICD (0.88 [0.10] vs 0.81 [0.12]; P < .001). Hospital factors associated with enrollment included participation in 5 or more NCDR registries (odds ratio [OR],1.98; 95% CI, 1.24-3.19; P = .005), membership in a larger hospital system (ie, 3-20 hospitals vs ≤2 hospitals in the system: OR, 2.29; 95% CI, 1.65-3.17; P = .001), participation in an NCDR pilot public reporting program of PCI 30-day readmissions (OR, 2.93; 95% CI, 2.19-3.91; P < .001), university affiliation (vs government affiliation: OR, 3.85, 95% CI, 1.03-14.29; P = .045; vs private affiliation: OR, 2.22; 95% CI, 1.35-3.57; P < .001), Midwest location (vs South: OR, 1.47; 95% CI, 1.06-2.08; P = .02), and increased comprehensive quality ranking (4 vs 1-2 performance stars in CathPCI: OR, 8.08; 95% CI, 5.07-12.87; P < .001; 4 vs 1 performance star in ICD: OR, 2.26; 95% CI, 1.48-3.44; P < .001) (C statistic = 0.829). Conclusions and Relevance: This study found that one-third of eligible hospitals participated in the ACC voluntary public reporting program and that enrollment increased after the announcement that program participation would be considered by USNWR for hospital rankings. Several hospital characteristics, experience with public reporting, and quality of care were associated with increased odds of participation.

Repercusión de la pandemia COVID-19 en la práctica de la cardiología intervencional en Chile: datos aportados por la encuesta del grupo Stent-Save a Life! LATAM working group / Decrease in the activity of interventional cardiology in Chile: a report from the "Stent-Save a Life! LATAM working group"

RESUMEN: Introducción: El Stent-Save a Life! (SSL) LATAM working group diseñó una encuesta para objetivar la reducción de la actividad de los laboratorios de hemodinamia en Latinoamérica durante la pandemia COVID-19. Ante la amenaza de nuevos confinamientos en Chile, nos propusimos objetivar las consecuencias de la primera ola de contagios en nuestra actividad. Objetivos: Discutir la repercusión de la pandemia en la cardiología intervencional en Chile. Métodos: El grupo SSL realizó una encuesta telemática a todos los países de Latinoamérica incluido Chile. Se registraron las coronariografías (CAG), intervenciones coronarias percutáneas (ACTP) e intervenciones estructurales, comparando dos períodos determinados por el confinamiento por la pandemia, cada uno de dos semanas. Pre-COVID-19: período previo al confinamiento, y COVID-19: período durante el confinamiento. Se analizan, a partir de esta encuesta, los resultados aplicados a nuestro país. Resultados: Se obtuvo respuesta de trece centros. Hubo una reducción en el número global de procedimientos entre período Pre-COVID-19 y COVID-19 de un 65,1%. Se reportó una disminución de 67% en las CAG, de un 59,4% en las ACTP y de un 92% en los procedimientos terapéuticos estructurales. Entre ambos períodos se redujo la consulta por Síndrome Coronario Agudo por elevación del segmento ST (SCACEST) en 40,8%. Conclusiones: En nuestro país se objetivó una reducción marcada de la actividad asistencial de la cardiología intervencional durante la pandemia COVID-19 y una disminución significativa en el número de pacientes tratados por SCACEST. Los resultados de nuestro país son similares a los reportados por países de Latinoamérica, Europa y Norteamérica.

ABSTRACT: Background: The Stent-Save a Life! (SSL) LATAM working group designed a survey to demonstrate the reduction in the activity of cardiac catheterization laboratories in Latin America during the COVID-19 pandemic. Considering the risk of a new confinement in Chile, we decided to assess the impact of the first wave of contagions on our activity. Aims: To discuss the repercussion of the COVID-19 pandemic on the activity of interventional cardiology in Chile. Methods: The SSL group conducted a telematic survey in all Latin American countries. Coronary angiography, coronary interventions (PCI) and structural interventions were registered, comparing two periods of two weeks duration each: before and during COVID-19 confinement. Results obtained in Chile are analyzed. Results: Thirteen centers in Chile answered the survey. There was an overall decrease of 65.1% in the number of procedures between the pre and the post COVID-19 periods. Coronary angiographies decreased 67%, PCI 59.4% and therapeutical structural procedures 92%. The reduction in acute coronary syndrome with ST segment elevation (STEMI) was 40,8% between periods. Conclusions: In Chile, a significant reduction in healthcare activity related to interventional cardiology and a significant decrease in the number of patients treated with STEMI was observed during the COVID-19 pandemic. The results are similar to those reported by Latin American, European and North American countries.

Work-life balance: a comparison of women in cardiology and other specialties.

OBJECTIVE: Significant gender disparities exist in some medical specialties, particularly cardiology. We assessed work, personal life and work-life balance in women in cardiology in Australia and New Zealand (NZ), compared with other specialties, to determine factors that may contribute to the lack of women in the specialty. METHODS: This study is a prospective survey-based cohort study comparing cardiology and non-cardiology specialties. An online survey was completed by female doctors in Australia and NZ, recruited via email lists and relevant social media groups. The survey included demographics, specialty, stage of training, work hours/setting, children and relationships, career satisfaction, income and perceptions of specialty. RESULTS: 452 participants completed the survey (median age 36 years), of which 57 (13%) worked in cardiology. Of all respondents, 84% were partnered and 75% had children, with no difference between cardiology and non-cardiology specialties. Compared with non-cardiology specialties, women in cardiology worked more hours per week (median 50 hours vs 40 hours, p<0.001), were more likely to be on call more than once per week (33% vs 12%, p<0.001) and were more likely to earn an annual income >$3 00 000 (35% vs 10%, p<0.001). Women in cardiology were less likely to agree that they led a balanced life (33% vs 51%, p=0.03) or that their specialty was female friendly (19% vs 75%, p<0.001) or family friendly (20% vs 63%, p<0.001). CONCLUSIONS: Compared with other specialties, women in cardiology reported poorer work-life balance, greater hours worked and on-call commitments and were less likely to perceive their specialty as female friendly or family friendly. Addressing work-life balance may attract and retain more women in cardiology.

Inappropriate Use of Aspirin in Real-Life Cardiology Practice: Results from the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study (ASSOS) Study.

BACKGROUND: Indications and appropriateness of aspirin use have not been well investigated in Turkey. AIMS: To investigate the prescription patterns and appropriateness of aspirin in a real-world clinical setting. STUDY DESIGN: Cross-sectional study. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study (ASSOS) is a cross-sectional and multicenter study that included 5007 consecutive patients aged 18 or over who presented to 30 different cardiology outpatient clinics from 14 cities throughout Turkey. Only patients using aspirin (80-325 mg) were included. The study population was divided into 2 groups regarding the use of aspirin: primary prevention (PP) group and secondary prevention (SP) group. The indication of aspirin use was evaluated following the 2016 European Society of Cardiology (ESC) and the 2016 United States Preventative Services Task Force (USPTF) guidelines in the PP group. RESULTS: A total of 5007 patients (mean age 62.15 ± 11.05, 39% female) were enrolled. The PP group included 1132 (22.6%) patients, and the SP group included 3875 (77.4%) patients. Of the 1132 patients, inappropriate use of aspirin was determined in 100% of the patients according to the ESC guidelines, and 71% of the patients according to the USPTF guidelines. Multivariate logistic regression analysis showed age OR: 0.98 CI (0.97-0.99) P = .037, smoking OR: 0.60 CI (0.44-0.82) P = .001, heart failure OR: 2.11 CI (1.14-3.92) P = .017, hypertension OR: 0.51 CI (0.36-0.74) P < .001, diabetes mellitus OR: 0.34 CI (0.25-0.47) P < .001, oral anticoagulant use OR: 3.01 CI (1.10-8.25) P = .032, and female sex OR: 2.73 CI (1.96-3.80) P < .001 were independent predictors of inappropriate aspirin use in PP patients. CONCLUSION: Although there are considerable differences between the USPTF and the ESC guidelines with respect to recommendations for aspirin use in PP, inappropriate use of aspirin in Turkey is frequent in real-world practice for both guidelines. Besides, heart failure, oral anticoagulant use, and the female sex of the patients were independent predictors of inappropriate use of aspirin.

The Need for Telemedicine Integration Into Adult Cardiology Training Curricula in Canada.

COVID-19 brought telemedicine to the forefront of clinical cardiology. We aimed to examine the extent of trainees' involvement in and comfort with telemedicine practices in Canada with the use of a web-based self-administered survey. Eighty-six trainees from 12 training programs completed the survey (65% response rate). Results showed that before COVID-19, 39 trainees (45%) had telemedicine exposure, compared with 67 (78%) after COVID-19 (P < 0.001). However, only 44 trainees (51%) reported being comfortable or very comfortable with the use of telemedicine. Of the 67 trainees who were involved in telemedicine, 4 (6%) had full supervision during virtual visits, 13 (19%) had partial supervision, and 50 (75%) had minimal or no supervision. Importantly, 67 trainees (78%) expressed the need for telemedicine-specific training and 64 (74%) were willing to have their virtual visits recorded for the purpose of evaluation and feedback. Furthermore, 47 (55%) felt strongly or very strongly positive about incorporating telemedicine into their future practice. The main perceived barriers to telemedicine use were concerns about patients' engagement, fear of weakening the patient-physician relationship, and unfamiliarity with telemedicine technology. These barriers, together with training in virtual physical examination skills and medicolegal aspects of telemedicine, are addressed in several established internal medicine telemedicine curricula that could be adapted by cardiology programs. In conclusion, while the degree of telemedicine involvement since COVID-19 was high, the trainees' comfort level with telemedicine practice remains suboptimal likely due to lack of training and inadequate staff supervision. Therefore, a cardiology telemedicine curriculum is needed to ensure that trainees are equipped to embrace telemedicine in cardiovascular clinical care.

Recommendations for Statistical Reporting in Cardiovascular Medicine: A Special Report From the American Heart Association.

Statistical analyses are a crucial component of the biomedical research process and are necessary to draw inferences from biomedical research data. The application of sound statistical methodology is a prerequisite for publication in the American Heart Association (AHA) journal portfolio. The objective of this document is to summarize key aspects of statistical reporting that might be most relevant to the authors, reviewers, and readership of AHA journals. The AHA Scientific Publication Committee convened a task force to inventory existing statistical standards for publication in biomedical journals and to identify approaches suitable for the AHA journal portfolio. The experts on the task force were selected by the AHA Scientific Publication Committee, who identified 12 key topics that serve as the section headers for this document. For each topic, the members of the writing group identified relevant references and evaluated them as a resource to make the standards summarized herein. Each section was independently reviewed by an expert reviewer who was not part of the task force. Expert reviewers were also permitted to comment on other sections if they chose. Differences of opinion were adjudicated by consensus. The standards presented in this report are intended to serve as a guide for high-quality reporting of statistical analyses methods and results.

[Care path for non-deferred elective hospitalizations in cardiology in the Covid-19 period]. / Percorso assistenziale per i ricoveri elettivi non differibili in cardiologia in periodo di Covid-19.

. Care path for non-deferred elective hospitalizations in cardiology in the Covid-19 period. INTRODUCTION: The novel coronavirus-19 (Covid-19) has rapidly resulted in a global pandemic. Our hospital had to postpone all elective admissions to increase capacity for COVID-19 patients. Therefore, a rearrangement of the elective admissions was necessary to guarantee a restart of ordinary procedures. AIM: To describe the organizational model adopted for elective procedures during the Covid-19 pandemic, to guarantee maximum safety for patients and healthcare workers. METHODS: Patients on waiting list for cardiac procedures were rearranged based on risks prioritization. Procedure of coronary angiography and cardiac devices (PM and ICD) implants or replacement took priority upon other cardiac procedures. Each patient underwent a telephone nurse triage to assess for any covid-19 symptoms. The hospital admissions were organized in accordance with health and safety measures declared by the National Institute of Health, with different paths according to the swab results. RESULTS: A total of 66 patients were contacted and 40 accepted the hospital admission (26 refused it, for fear of infection or covid-19 related family problems). No patient resulted positive to the nasal swab. CONCLUSIONS: In view of the impact on the health care system of this new pandemic, the choice of an appropriate pathway which can preserve patients' safety is essential, while guaranteeing the treatment of problems, such as cardiovascular diseases, with a high mortality rate.

Perceptions on Diversity in Cardiology: A Survey of Cardiology Fellowship Training Program Directors.

Background The lack of diversity in the cardiovascular physician workforce is thought to be an important driver of racial and sex disparities in cardiac care. Cardiology fellowship program directors play a critical role in shaping the cardiology workforce. Methods and Results To assess program directors' perceptions about diversity and barriers to enhancing diversity, the authors conducted a survey of 513 fellowship program directors or associate directors from 193 unique adult cardiology fellowship training programs. The response rate was 21% of all individuals (110/513) representing 57% of US general adult cardiology training programs (110/193). While 69% of respondents endorsed the belief that diversity is a driver of excellence in health care, only 26% could quote 1 to 2 references to support this statement. Sixty-three percent of respondents agreed that "our program is diverse already so diversity does not need to be increased." Only 6% of respondents listed diversity as a top 3 priority when creating the cardiovascular fellowship rank list. Conclusions These findings suggest that while program directors generally believe that diversity enhances quality, they are less familiar with the literature that supports that contention and they may not share a unified definition of "diversity." This may result in diversity enhancement having a low priority. The authors propose several strategies to engage fellowship training program directors in efforts to diversify cardiology fellowship training programs.

Bias and Loss to Follow-Up in Cardiovascular Randomized Trials: A Systematic Review.

Background Loss to follow-up (LTFU) is common in randomized controlled trials. However, its potential impact on primary outcomes from cardiovascular randomized controlled trials is not known. Methods and Results We conducted a prospective systematic review (PROSPERO: CRD42019121959) for randomized controlled trials published in 8 leading journals over 5 years from January 2014 to December 2018. Extent, reporting, and handling of LTFU data were recorded, and the proportion of a trial's primary outcome results that lose statistical significance was calculated after making plausible assumptions for the intervention and control arms. These assumptions could drive differential treatment effects between the groups considering relative event incidence between LTFU participants and those included in the primary outcome. We identified 117 randomized controlled trials of which 91 (78%) trials reported LTFU, 23 (20%) reported no LTFU, and 3 (3%) trials did not report on whether LTFU occurred. The median percentage of study participants lost to follow-up was 2% (interquartile range, 0.33%-5.3%). Only 10 trials (9%) had a low cluster of risk factors for impairment in trial quality. The percentage of trials losing statistical significance varied from 2% when the relative event incidence for LTFU between the randomized groups was 1 for the intervention arm and 1.5 for the control arm to 16% when the relative event incidence was 3 for the intervention arm and 1 for the control arm. Conclusions Almost 1 in 6 (16%) cardiovascular randomized trials published in leading journals may have a change in the primary outcome if plausible assumptions are made about differential event rates of participants lost to follow up. There is scope for improvement arising from LTFU in randomized trials in cardiovascular medicine. Registration URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42019121959.

Coronavirus Disease 2019 Catheterization Laboratory Survey.

Background The coronavirus disease 2019 pandemic is expected to affect operations and lifestyles of interventional cardiologists around the world in unprecedented ways. Timely gathering of information on this topic can provide valuable insight and improve the handling of the ongoing and future pandemic outbreaks. Methods and Results A survey instrument developed by the authors was disseminated via e-mail, text messaging, WhatsApp, and social media to interventional cardiologists between April 6, 2020, and April 11, 2020. A total of 509 responses were collected from 18 countries, mainly from the United States (51%) and Italy (36%). Operators reported significant decline in coronary, structural heart, and endovascular procedure volumes. Personal protective equipment was available to 95% of respondents; however FIT-tested N95 or equivalent masks were available to only 70%, and 74% indicated absence of coronavirus disease 2019 pretesting. Most (83%) operators expressed concern when asked to perform cardiac catheterization on a suspected or confirmed coronavirus disease 2019 patient, primarily because of fear of viral transmission (88%). Although the survey demonstrated significant compliance with social distancing, high use of telemedicine (69%), and online education platforms (80%), there was concern over impending financial loss. Conclusions Our survey indicates significant reduction in invasive procedure volumes and concern for viral transmission. There is near universal adoption of personal protective equipment; however, coronavirus disease 2019 pretesting and access to FIT-tested N95 masks is suboptimal. Although there is concern over impending financial loss, substantial engagement in telemedicine and online education is reported.

Pediatric Cardiology Specialist's Opinions Toward the Acceptability of Comfort Care for Congenital Heart Disease.

In order to evaluate physicians' willingness to seek legal action to mandate surgery when parents refuse surgery for various congenital heart lesions, we surveyed pediatric cardiologists and cardiovascular surgeons at 4 children's hospitals. We asked whether physicians would support parental refusal of surgery for specific heart defects and, if not, whether they would seek legal action to mandate surgery. We then analyzed associations between physicians' willingness to mandate surgery and national operative mortality rates for each lesion. We surveyed 126 cardiologists and 9 cardiac surgeons at four tertiary referral centers. Overall response rate was 77%. Greater than 70% of physicians would seek legal action and mandate surgery for the following lesions: ventricular septal defect, coarctation of the aorta, complete atrioventricular canal, transposition of the great arteries, tetralogy of Fallot, and unobstructed total anomalous pulmonary venous return. Surgery for all of these lesions has reported mortality rates of < 5%. Physicians were less likely to seek legal action when parents refused surgery for Shone complex, any single ventricle lesion, or any congenital heart disease accompanied by Trisomy 13 or Trisomy 18. Among experts in pediatric cardiology, there is widespread agreement about the appropriate response to parental refusal of surgery for most congenital heart lesions, and these lesions tended to be heart defects with lower surgical mortality rates. Lesions for which there was greater consensus among experts were those with the best outcomes. There was less consensus for lesions with higher mortality rates. Such surveys, revealing disagreement among expert professionals, can provide an operational definition of the current professional "gray zone" in which parental preferences should determine treatment.

Nuclear Cardiology in Asia.

Nuclear cardiology for patients with ischemic heart disease and cardiac failure is expanding in Asia, although quite heterogeneously. In Asia, Israel showed the highest utilization with more than 1000 scans/100,000 inhabitants a year followed by Korea, Japan, UAE, Turkey, Australia (250-999 scans/100,000). Saudi Arabia, Kuwait, Jordan, Lebanon, Iran, and Pakistan practiced 60-99 scans/100,000. Most of South East Asian countries, China, India, and Bangladesh practiced 1-50 scans/100,000 per year. Countries in Central Asia, Mongolia, Vietnam, Cambodia, Lao, Myanmar, Nepal, and Bhutan showed limited use or no nuclear cardiology practice. Myocardial perfusion imaging (MPI) in Asia was characterized by more frequent use of 201Tl, less use of weight-based 99mTc dosing, and a trend toward a lower rate of stress-only imaging. Accordingly, the effective dose in nuclear cardiology practices was higher than those of the rest of the world. 99Mo-99mTc generators are available in most countries, relying mainly on the global supply chain because there is little supply chain beyond countries within the region. In practice, the threshold values of left ventricular ejection fraction, end-systolic volume, and end-diastolic volume between normal and pathologic states were set based on the regional normal database in China and Japan because these values were dependent on age, gender, and body weight. The purpose of the MPI SPECT study was to evaluate myocardial ischemia in symptomatic patients with chest pain, effects of percutaneous coronary intervention and coronary artery bypass-graft, and cardiac function in patients with chronic heart failure. The ability of 99mTc-based MPI for predicting hard cardiac events was confirmed in Asian inhabitants with low risk of ischemic heart disease. Human resource development of nuclear medicine professional and public awareness of nuclear medicine is key issues to promote nuclear cardiology in Asia. International organizations such as the International Atomic Energy Agency and academic organizations in the region such as Asia Oceania Federation of Nuclear Medicine and Biology, Asia Regional Cooperative Council for Nuclear Medicine, East Asia Nuclear Medicine Association, and Arab Society of Nuclear Medicine have an important role in addition to national Societies of Nuclear Medicine in each country and region.