Subgroup Analyses by European Country-Specific Reimbursement Requirements Confirm Efficacy for Ixekizumab in Psoriasis.

BACKGROUND: Biologic drugs are generally recommended for treating moderate-to-severe psoriasis. While eligibility criteria are primarily defined by clinical treatment guidelines, access to these therapies varies between European countries and is regulated by country-specific reimbursement criteria. This post-hoc subgroup analysis of integrated data from two phase III trials (UNCOVER-2 and -3) reports the efficacy of ixekizumab relative to that of etanercept in patients with moderate-to-severe plaque psoriasis selected into groups defined by original reimbursement criteria from eight European countries. METHODS: This analysis included baseline and 12-week data from the ixekizumab- and etanercept-treated study populations from UNCOVER-2 and -3. Patients were classified as meeting/not meeting each country-specific biologic eligibility criterion. Efficacy was defined by Psoriasis Area and Severity Index (PASI) 75, 90, and 100 response rates and by Dermatology Life Quality Index (DLQI) (0,1) response rates. Treatment responses across subgroups were analysed using logistic regression models. RESULTS: PASI 75/90/100 response rates were significantly higher for ixekizumab-treated patients than for etanercept-treated patients at week 12 (P<0.05), irrespective of whether predefined reimbursement criteria were met, for all countries, with the exception of PASI 100 response in those meeting reimbursement criteria in Belgium, where sample size was very small. Clinical efficacy outcomes were corroborated by proportions of patients achieving DLQI (0,1) responses. CONCLUSIONS: The overall high efficacy of ixekizumab, and the consistency of the higher treatment effect compared with etanercept, in patients with moderate-to-severe psoriasis across a range of European biologic treatment reimbursement eligibility criteria provides new insights to inform treatment decisions in clinical practice. J Drugs Dermatol. 2022;21(6):659-667. doi:10.36849/JDD.6620.

Single-Pulse Transcranial Magnetic Stimulation for the preventive treatment of difficult-to-treat migraine: a 12-month prospective analysis.

BACKGROUND: Initial evidence have shown the short-term efficacy of sTMS in the acute and preventive treatment of migraine. It is unknown whether this treatment approach in the long-term is effective and well tolerated in difficult-to-treat migraine. METHODS: This is a prospective, single centre, open-label, real-world analysis conducted in difficult-to-treat patients with high-frequency episodic migraine (HFEM) and chronic migraine (CM) with and without medication overuse headache (MOH), who were exposed to sTMS therapy. Patients responding to a three-month sTMS treatment, continued the treatment and were assessed again at month 12. The cut-off outcome for treatment continuation was reduction in the monthly moderate to severe headache days (MHD) of at least 30% (headache frequency responders) and/or a ≥ 4-point reduction in headache disability using the Headache Impact test-6 (HIT-6) (headache disability responders). RESULTS: One hundred fifty-three patients were included in the analysis (F:M = 126:27, median age 43, IQR 32.3-56.8). At month 3, 93 out of 153 patients (60%) were responders to treatment. Compared to baseline, the median reduction in monthly headache days (MHD) for all patients at month 3 was 5.0 days, from 18.0 (IQR: 12.0-26.0) to 13.0 days (IQR: 5.75-24.0) (P = 0.002, r = - 0.29) and the median reduction in monthly migraine days (MMD) was 4.0 days, from 13.0 (IQR: 8.75-22.0) to 9.0 (IQR: 4.0-15.25) (P = 0.002, r = - 0.29). Sixty-nine out of 153 patients (45%) reported a sustained response to sTMS treatment at month 12. The percentage of patients with MOH was reduced from 52% (N = 79/153) at baseline to 19% (N = 29/153) at month 3, to 8% (N = 7/87) at month 12. There was an overall median 4-point reduction in HIT-6 score, from 66 (IQR: 64-69) at baseline to 62 at month 3 (IQR: 56-65) (P < 0.001, r = - 0.51). A total of 35 mild/moderate adverse events were reported by 23 patients (15%). One patient stopped sTMS treatment due to scalp sensitivity. CONCLUSIONS: This open label analysis suggests that sTMS may be an effective, well-tolerated treatment option for the long-term prevention of difficult-to-treat CM and HFEM.

Unusual Near-Horizon Cosmic-Ray-like Events Observed by ANITA-IV.

ANITA's fourth long-duration balloon flight in 2016 detected 29 cosmic-ray (CR)-like events on a background of 0.37_{-0.17}^{+0.27} anthropogenic events. CRs are mainly seen in reflection off the Antarctic ice sheets, creating a phase-inverted waveform polarity. However, four of the below-horizon CR-like events show anomalous noninverted polarity, a p=5.3×10^{-4} chance if due to background. All anomalous events are from locations near the horizon; ANITA-IV observed no steeply upcoming anomalous events similar to the two such events seen in prior flights.

Abortion Access in Ohio's Changing Legislative Context, 2010-2018.

Objectives. To examine abortion utilization in Ohio from 2010 to 2018, a period when more than 15 abortion-related laws became effective.Methods. We evaluated changes in abortion rates and ratios examining gestation, geographic distribution, and abortion method in Ohio from 2010 to 2018. We used data from Ohio's Office of Vital Statistics, the Centers for Disease Control and Prevention's Abortion Surveillance Reports, the American Community Survey, and Ohio's Public Health Data Warehouse.Results. During 2010 through 2018, abortion rates declined similarly in Ohio, the Midwest, and the United States. In Ohio, the proportion of early first trimester abortions decreased; the proportion of abortions increased in nearly every later gestation category. Abortion ratios decreased sharply in most rural counties. When clinics closed, abortion ratios dropped in nearby counties.Conclusions. More Ohioans had abortions later in the first trimester, compared with national patterns, suggesting delays to care. Steeper decreases in abortion ratios in rural versus urban counties suggest geographic inequity in abortion access.Public Health Implications. Policies restricting abortion access in Ohio co-occur with delays to care and increasing geographic inequities. Restrictive policies do not improve reproductive health.

A prospective case series of sphenopalatine ganglion pulsed radiofrequency therapy for refractory chronic cluster headache.

BACKGROUND AND PURPOSE: The management options for chronic cluster headache (CCH) are limited and a significant proportion of patients become refractory to pharmacological treatments. Pulsed radiofrequency (PRF) of the sphenopalatine ganglion (SPG) may present an efficacious, minimally invasive treatment modality for patients with refractory CCH. We describe the clinical outcomes of 14 patients with refractory CCH treated with PRF of the SPG. METHODS: Patients with medically refractory CCH who underwent percutaneous SPG-PRF treatment between January 2016 and April 2019 were included in this report. Patients obtaining at least 30% reduction in weekly cluster attacks for at least 3 months were defined as responders. Treatment-related side effects were collected. RESULTS: A total of 14 patients were included in this report (nine males). At a median follow-up of 6.5 (range 6-13) months post-procedure, eight patients (57.1%) were defined as responders to the treatment. Six patients were non-responders and reported either a reduction in frequency and severity of attacks for <3 months (2/6), no improvement (2/6) or temporary worsening of symptoms (1/6). The majority of patients (63.6%, n = 7/11) treated with >45 V were responders compared with responders treated with 45 V (33.3%, n = 1/3). Five patients (35.7%) experienced post-procedural side effects. CONCLUSION: This case series suggests that PRF targeting the SPG might offer a safe, minimally invasive and effective treatment for medically refractory CCH. Given the small number of cases and the short follow-up, larger and more robust studies will be needed to confirm our findings.

Neonatal Organ and Tissue Donation for Research: Options Following Death by Natural Causes.

The donation of organs and tissues from neonates (birth to 28 days) for transplantation has been a relatively infrequent occurrence. Less common has been the use of neonatal organs and tissues for research. Specific ethical and legal questions beg for rational and transparent guidelines with which to evaluate referrals of potential donors. Donation of organs and tissues from a neonate can play a key role in the care and support provided to families by health care professionals around the time of a neonate's death. We report on the recovery of neonatal organs and tissues for research. A working group made up of bioethicists, neonatologists, lawyers, obstetric practioners as well as organ procurement and tissue banking professionals evaluated legal, ethical and medical issues. Neonatal donor family members were also consulted. Our primary goals were (a) to ensure that referrals were made in compliance with all applicable federal and state laws, regulations and institutional protocols, and (b) to follow acceptable ethical standards. Algorithms and policies designed to assist in the evaluation of potential neonatal donors were developed. Neonatal donation is proving increasingly valuable for research into areas including diabetes, pulmonary, gastrointestinal, genitourinary and neurological development, rheumatoid arthritis, autism, childhood psychiatric and neurologic disorders, treatment of MRSA infection and pediatric emergency resuscitation. The development of policies and procedures will assist medical professionals who wish to offer the option of donation to family members anticipating the death of a neonate.

Predicting Pharmacist Dispensing Practices and Comfort Related to Pre-exposure Prophylaxis for HIV Prevention (PrEP).

To identify factors associated with pharmacist dispensing practice and comfort counseling patients about pre-exposure prophylaxis for HIV prevention (PrEP). Cross-sectional 2016 census of Indiana managing pharmacists measured PrEP awareness, comfort dispensing and counseling patients. Modified Poisson models with robust error variance estimated relative risks and confidence intervals. 15.8% of 284 pharmacists had dispensed PrEP and 11.6% had consulted about it. Dispensing and comfort counseling were associated with confidence in knowledge about PrEP medication adherence and adverse effects of PrEP medication; awareness about PrEP before the survey, number of full time pharmacists in their pharmacy, and increases in new HIV cases from 2015 to 2016 in communities served. Comfort counseling about PrEP was associated with the belief that pharmacists can be an important resource for HIV and HCV treatment.

Approach to cardiopulmonary resuscitation induced consciousness, an emergency medicine perspective.

BACKGROUND: Cardiopulmonary resuscitation (CPR) remains the key intervention following cardiac arrest because of its ability to continue circulation. Recent focus on high quality compressions during CPR has coincided with more frequent encounters of CPR Induced Consciousness (CPRIC). CPRIC represents a poorly understood patient experience during CPR and defined as signs of consciousness and pain perception during CPR. METHODS: Articles were selected using PubMed, MEDLINE, CINAHL and Scopus search for the keywords "cardiopulmonary resuscitation", "consciousness", "awareness", "resuscitation", "cardio-cerebral resuscitation", "agitation" and "patient experience" yielding 336 articles. Results and their references were assessed for relevance. Articles were filtered by English language and the keyword. Case reports and case series were included. All remaining articles were reviewed and findings were discussed. RESULTS: A total of ten articles were selected, which included data on 123 cases. Sample size varied per study from 1 to 112. Studies included cases of out-of-hospital cardiac arrest and in hospital cardiac arrest. Compressions were manually provided in most cases. Patient total recall was reported in 40% of cases. Use of sedation was reported in 40% of cases. CONCLUSIONS: There is need for continued research to better describe, explain and manage the phenomena of CPRIC. From the articles reviewed here, it is clear that further investigation has the potential to properly elucidate the patient experience including lasting psychological effects of CPRIC. Importantly, there is need for more than recognition of CPRIC from national authorities. Future research efforts should focus on establishing guidelines for the use of sedation and physical restraints, as well as the potential impact of treating CPRIC on survival.

Observation of an Unusual Upward-Going Cosmic-Ray-like Event in the Third Flight of ANITA.

We report on an upward traveling, radio-detected cosmic-ray-like impulsive event with characteristics closely matching an extensive air shower. This event, observed in the third flight of the Antarctic Impulsive Transient Antenna (ANITA), a NASA-sponsored long-duration balloon payload, is consistent with a similar event reported in a previous flight. These events could be produced by the atmospheric decay of an upward-propagating τ lepton produced by a ν_{τ} interaction, although their relatively steep arrival angles create tension with the standard model neutrino cross section. Each of the two events have a posteriori background estimates of ≲10^{-2} events. If these are generated by τ-lepton decay, then either the charged-current ν_{τ} cross section is suppressed at EeV energies, or the events arise at moments when the peak flux of a transient neutrino source was much larger than the typical expected cosmogenic background neutrinos.

Optimal sequencing of ibrutinib, idelalisib, and venetoclax in chronic lymphocytic leukemia: results from a multicenter study of 683 patients.

Background: Ibrutinib, idelalisib, and venetoclax are approved for treating CLL patients in the United States. However, there is no guidance as to their optimal sequence. Patients and methods: We conducted a multicenter, retrospective analysis of CLL patients treated with kinase inhibitors (KIs) or venetoclax. We examined demographics, discontinuation reasons, overall response rates (ORR), survival, and post-KI salvage strategies. Primary endpoint was progression-free survival (PFS). Results: A total of 683 patients were identified. Baseline characteristics were similar in the ibrutinib and idelalisib groups. ORR to ibrutinib and idelalisib as first KI was 69% and 81%, respectively. With a median follow-up of 17 months (range 1-60), median PFS and OS for the entire cohort were 35 months and not reached. Patients treated with ibrutinib (versus idelalisib) as first KI had a significantly better PFS in all settings; front-line [hazard ratios (HR) 2.8, CI 1.3-6.3, P = 0.01], relapsed-refractory (HR 2.8, CI 1.9-4.1, P < 0.001), del17p (HR 2.0, CI 1.2-3.4, P = 0.008), and complex karyotype (HR 2.5, CI 1.2-5.2, P = 0.02). At the time of initial KI failure, use of an alternate KI or venetoclax had a superior PFS when compared with chemoimmunotherapy. Furthermore, patients who discontinued ibrutinib due to progression or toxicity had marginally improved outcomes if they received venetoclax (ORR 79%) versus idelalisib (ORR 46%) (PFS HR .6, CI.3-1.0, P = 0.06). Conclusions: In the largest real-world experience of novel agents in CLL, ibrutinib appears superior to idelalisib as first KI. Furthermore, in the setting of KI failure, alternate KI or venetoclax therapy appear superior to chemoimmunotherapy combinations. The use of venetoclax upon ibrutinib failure might be superior to idelalisib. These data support the need for trials testing sequencing strategies to optimize treatment algorithms.

Systematic review and meta-analysis of the impact of preconception lifestyle interventions on fertility, obstetric, fetal, anthropometric and metabolic outcomes in men and women.

STUDY QUESTION: What is the impact of preconception lifestyle interventions on live birth, birth weight and pregnancy rate? SUMMARY ANSWER: Lifestyle interventions showed benefits for weight loss and increased natural pregnancy rate, but not for live birth or birth weight. WHAT IS KNOWN ALREADY: Evidence on the practice and content of preconception counseling and interventions is variable and limited. STUDY DESIGN, SIZE, DURATION: Systematic review and meta-analysis (MA). Main search terms were those related to preconception lifestyle. Database searched were Ovid MEDLINE(R), EBM Reviews, PsycINFO, EMBASE and CINAHL Plus. No language restriction was placed on the published articles. The final search was performed on 10 January 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were non-pregnant women of childbearing age intent on conceiving or their male partners. Exclusion criteria include participants with BMI < 18 kg/m2, animal trials, hereditary disorder in one or both partners and trials focusing solely on alcohol or smoking cessation/reduction, micronutrient supplementation, or diabetes control. Anthropometric, fertility, obstetric and fetal outcomes were assessed. Bias and quality assessments were performed. MAIN RESULTS AND THE ROLE OF CHANCE: The search returned 1802 articles and eight studies were included for analysis. Populations targeted were primarily overweight or obese subfertile women seeking reproductive assistance, with few community-based studies and none including men. MA showed greater reduction in weight (n = 3, P < 0.00001, mean difference: -3.48 kg, 95% CI: -4.29, -2.67, I2 = 0%) and BMI (n = 2, P < 0.00001, mean difference: -1.40 kg/m2, 95% CI: -1.95, -0.84, I2 = 24%) with intervention. The only significant fertility outcome was an increased natural pregnancy rate (n = 2, P = 0.003, odds ratio: 1.87, CI: 1.24, 2.81, I2 = 0%). No differences were observed for ART adverse events, clinical pregnancy, pregnancy complications, delivery complications, live birth, premature birth, birth weight, neonatal mortality or anxiety. Risk of bias were high for three studies, moderate for three studies and low for two studies, Attrition bias was moderate or high in majority of studies. LIMITATIONS, REASONS FOR CAUTION: Results were limited to subfertile or infertile women who were overweight or obese undergoing ART with no studies in men. The heterogeneous nature of the interventions in terms of duration and regimen means no conclusions could be made regarding the method or components of optimal lifestyle intervention. Attrition bias itself is an important factor that could affect efficacy of interventions. WIDER IMPLICATIONS OF THE FINDINGS: Existing preconception lifestyle interventions primarily targeted overweight and obese subfertile women undergoing ART with a focus on weight loss. It is important to note that natural conception increased with lifestyle intervention. This emphasizes the need for further research exploring optimal components of preconception lifestyle interventions in the broader population and on the optimal nature, intensity and timing of interventions. STUDY FUNDING/COMPETING INTEREST(S): No conflict of interest declared. C.L.H. is a National Heart Foundation Postdoctoral Research Fellow. B.H. is funded by an Alfred Deakin Postdoctoral Research Fellowship. H.J.T. and B.W.M. hold NHMRC Practitioner fellowships. L.J.M. is supported by a SACVRDP Fellowship; a program collaboratively funded by the NHF, the South Australian Department of Health and the South Australian Health and Medical Research Institute. PROSPERO REGISTRATION NUMBER: CRD42015023952.

Interventions to improve physical activity during pregnancy: a systematic review on issues of internal and external validity using the RE-AIM framework.

BACKGROUND: Physical activity (PA) during pregnancy has significant health benefits for the mother and her child; however, many women reduce their activity levels during pregnancy and most are not sufficiently active. Given the important health benefits of PA during pregnancy, evidence that supports research translation is vital. OBJECTIVES: To determine the extent to which physical activity interventions for pregnant women report on internal and external validity factors using the RE-AIM framework (reach, efficacy/effectiveness, adoption, implementation, and maintenance). SEARCH STRATEGY: Ten databases were searched up to 1 June 2015. Eligible published papers and unpublished/grey literature were identified using relevant search terms. SELECTION CRITERIA: Studies had to report on physical activity interventions during pregnancy, including measures of physical activity during pregnancy at baseline and at least one point post-intervention. Randomised controlled trials and quasi-experimental studies that had a comparator group were included. DATA COLLECTION AND ANALYSIS: Reporting of RE-AIM dimensions were summarised and synthesised across studies. MAIN RESULTS: The reach (72.1%) and efficacy/effectiveness (71.8%) dimensions were commonly reported; however, the implementation (28.9%) and adoption (23.2%) dimensions were less commonly reported and no studies reported on maintenance. CONCLUSIONS: This review highlights the under-reporting of issues of contextual factors in studies of physical activity during pregnancy. The translation of physical activity interventions during pregnancy could be improved through reporting of representativeness of participants, clearer reporting of outcomes, more detail on the setting and staff who deliver interventions, costing of interventions and the inclusion of process evaluations and qualitative data. TWEETABLE ABSTRACT: The systematic review highlights the under-reporting of contextual factors in studies of physical activity during pregnancy.

Comparison of three targeted approaches to screening for abdominal aortic aneurysm based on cardiovascular risk.

BACKGROUND: Abdominal aortic aneurysm (AAA) continues to be a significant health burden yet few countries have implemented a comprehensive screening programme. Screening typically places emphasis on men aged over 65 years; however, there is concern that other at-risk groups may be underidentified. The present study examined three potential screening strategies based on cardiovascular risk. METHODS: The prevalence of AAA was determined by abdominal ultrasound imaging in over 50-year-olds of either sex undergoing coronary angiography, vascular laboratory assessment of peripheral arterial disease, or community-based cardiovascular disease (CVD) event risk assessment. A fourth group, consisting of volunteers aged over 60 years who had no symptoms or signs of cardiovascular disease, was used as a comparator group. RESULTS: A total AAA prevalence of 4·4 per cent was detected across all three strategies (137 of 3142 individuals), compared with 1·0 per cent in the CVD-free group. Male sex, age and smoking were all associated with greater AAA prevalence. Although AAA prevalence was lowest using the community-based strategy, those with an AAA detected were on average 7 years younger than those with AAAs detected with the other two strategies (P < 0·001). CONCLUSION: Different strategies, based on CVD risk, resulted in AAA prevalence rates that were significantly greater than that in CVD-free individuals. This may provide opportunities for a targeted approach to community AAA screening in parts of the world where more sophisticated national screening programmes do not exist.

Characteristics of Four Upward-Pointing Cosmic-Ray-like Events Observed with ANITA.

We report on four radio-detected cosmic-ray (CR) or CR-like events observed with the Antarctic Impulsive Transient Antenna (ANITA), a NASA-sponsored long-duration balloon payload. Two of the four were previously identified as stratospheric CR air showers during the ANITA-I flight. A third stratospheric CR was detected during the ANITA-II flight. Here, we report on characteristics of these three unusual CR events, which develop nearly horizontally, 20-30 km above the surface of Earth. In addition, we report on a fourth steeply upward-pointing ANITA-I CR-like radio event which has characteristics consistent with a primary that emerged from the surface of the ice. This suggests a possible τ-lepton decay as the origin of this event, but such an interpretation would require significant suppression of the standard model τ-neutrino cross section.

Constituting children's bodily integrity.

Children have a constitutional right to bodily integrity. Courts do not hesitate to vindicate that right when children are abused by state actors. Moreover, in at least some cases, a child's right to bodily integrity applies within the family, giving the child the right to avoid unwanted physical intrusions regardless of the parents' wishes. Nonetheless, the scope of this right vis-à-vis the parents is unclear; the extent to which it applies beyond the narrow context of abortion and contraception has been almost entirely unexplored and untheorized. This Article is the first in the legal literature to analyze the constitutional right of minors to bodily integrity within the family by spanning traditionally disparate doctrinal categories such as abortion rights; corporal punishment; medical decisionmaking; and nontherapeutic physical interventions such as tattooing, piercing, and circumcision. However, the constitutional right of minors to bodily integrity raises complex philosophical questions concerning the proper relationship between family and state, as well as difficult doctrinal and theoretical issues concerning the ever-murky idea of state action. This Article canvasses those issues with the ultimate goal of delineating a constitutional right of bodily security and autonomy for children.

Underexpression of tumour suppressor LKB1 in clear cell renal cell carcinoma is common and confers growth advantage in vitro and in vivo.

BACKGROUND: Evidence suggests that dysregulation of energy-sensing pathways closely associates with renal cell carcinoma (RCC) development. The metabolic regulation is largely controlled by 5'-AMP activated protein kinase (AMPK) which is activated through phosphorylation by LKB1. METHODS: The expression of LKB1 was determined by reverse transcription-PCR using 10 clinical clear cell RCC (ccRCC) samples and their adjacent normal renal parenchyma, and by immunohistochemical staining of two tissue microarrays containing 201 ccRCC and 26 normal kidney samples. Expression of LKB1 was knocked down in human ccRCC 786-O cells (shLKB1) and compared with cells expressing scrambled control shRNA (shControl). AMPK signalling, proliferation, invasion, and VEGF secretion was measured. The cells were subcutaneously injected into mice to determine tumour growth in vivo. RESULTS: At the protein and transcript levels, a significant reduction in LKB1 expression in tumour compared with normal tissue was found. In vitro, knockdown of LKB1 resulted in reduced AMPK signalling and increased cellular proliferation, invasion, and VEGF secretion compared with shControl cells. In vivo, growth of shLKB1 ccRCC xenografts in nude mice was significantly increased compared with shControl xenografts. CONCLUSION: Collectively, our results suggest that LKB1 acts as a tumour suppressor in most sporadic cases of ccRCC and that underexpression of LKB1 is a common event in the disease.

Ivabradine: pre-clinical and clinical evidence in the setting of ventricular arrhythmias.

BACKGROUND: Ivabradine, an agent lowering the heart rate, acting as a funny current (If) specific inhibitor, is responsible for the sinoatrial node's spontaneous depolarization. According to current guidelines, it is indicated in specific heart failure populations and as a second-line treatment option to improve angina in chronic coronary syndromes. REVIEW OF LITERATURE: The role of ivabradine in the setting of ventricular arrhythmias has been studied in both experimental and clinical studies. Specifically, experimental studies have examined the role of ivabradine in acute myocardial ischemia, reperfusion, digitalis-induced ventricular arrhythmias, and catecholaminergic polymorphic ventricular tachycardia showing promising results. In addition, clinical studies have shown a beneficial role of ivabradine in reducing ventricular arrhythmias. Ivabradine reduced premature ventricular contractions in combination with beta-blockers in dilated cardiomyopathy patients. Similarly, in catecholaminergic polymorphic ventricular tachycardia, ivabradine reduced dobutamine-induced premature ventricular complexes and improved ventricular arrhythmias burden. On the other hand, current data show no beneficial role of ivabradine in reducing ventricular arrhythmias in myocardial ischemia. CONCLUSIONS: Randomized clinical trials are needed to elucidate the role of ivabradine in reducing the burden of ventricular arrhythmias in various clinical settings. HIPPOKRATIA 2022, 26 (2):49-54.