[Diagnostics and treatment of suicidality; a matter of customization]. / Diagnostiek en behandeling van suïcidaliteit; een kwestie van maatwerk.

This article illustrates the importance of conducting a comprehensive analysis of suicidality through the case study of an adolescent patient dealing with both depressive disorder and obsessive-compulsive disorder. The aim of treating suicidality is to address the underlying psychiatric conditions and factors contributing to the disorder. This necessitates a thorough evaluation of the treatment environment, the establishment of continuous care, and ensuring safety. By utilizing a new model to distinguish various forms of suicidal behavior and examining suicidality as a distinct phenomenon, it becomes possible to create individualized diagnostic and treatment approaches, along with effective risk assessments. In the presented patient, intrusive thoughts significantly impacted her suicidality. The treatment approach for patient A involved employing eye movement dual task (EMDT), exposure therapy and strategies to enhance autonomy. This approach aims to reduce suicidality, facilitate recovery, and alleviate the fear of losing control.

Caesarean section rate reduced by a redesigned birthing room. Results of a quality improvement intervention at a hospital in Democratic Republic of Congo.

OBJECTIVE: To evaluate the influence of a new birthing room at a tertiary hospital in eastern Democratic Republic of Congo (DRC), on the caesarean section (CS) rate in women classified as Robson group 1, i.e., nulliparous women at term with spontaneous onset of labour of one foetus in cephalic presentation. METHOD: As part of quality improvement interventions, a new birthing room designed to promote person-centredness was constructed at the labour ward at Panzi General Referral Hospital in DRC. In a quasi-experimental study on women classified as Robson 1, a comparison was performed between the group being cared for in the new birthing room and the group being cared for in the general birthing room. The main outcome measure was CS rate. RESULTS: In the new person-centred birthing room, the CS rate was 17.1 % versus 28.4 % in women cared for in the general birthing room (p-value 0.001). There was also a higher presence of accompanying persons (p-value < 0.0001) and less use of synthetic oxytocin for the augmentation of labour (p-value 0.024). No difference in fear and childbirth experience was identified between women in the two rooms. CONCLUSION: The results demonstrate that it is possible, in a low-income country as the Democratic Republic of Congo, to reduce the CS rate in women classified as Robson 1 by adapting the birthing environment to be more person-centred, without compromising other obstetric and neonatal outcomes.

Cardiac [99mTc]Tc-hydroxydiphosphonate uptake on bone scintigraphy in patients with hereditary transthyretin amyloidosis: an early follow-up marker?

PURPOSE: There is a need for early quantitative markers of potential treatment response in patients with hereditary transthyretin (ATTRv) amyloidosis to guide therapy. This study aims to evaluate changes in cardiac tracer uptake on bone scintigraphy in ATTRv amyloidosis patients on different treatments. METHODS: In this retrospective cohort study, outcomes of 20 patients treated with the transthyretin (TTR) gene silencer patisiran were compared to 12 patients treated with a TTR-stabilizer. Changes in NYHA class, cardiac biomarkers in serum, wall thickness, and diastolic parameters on echocardiography and NYHA class during treatment were evaluated. RESULTS: Median heart/whole-body (H/WB) ratio on bone scintigraphy decreased from 4.84 [4.00 to 5.31] to 4.16 [3.66 to 4.81] (p < .001) in patients treated with patisiran for 29 [15-34] months. No changes in the other follow-up parameters were observed. In patients treated with a TTR-stabilizer for 24 [20 to 30] months, H/WB ratio increased from 4.46 [3.24 to 5.13] to 4.96 [ 3.39 to 5.80] (p = .010), and troponin T increased from 19.5 [9.3 to 34.0] ng/L to 20.0 [11.8 to 47.8] ng/L (p = .025). All other parameters did not change during treatment with a TTR-stabilizer. CONCLUSION: A change in cardiac tracer uptake on bone scintigraphy may be an early marker of treatment-specific response or disease progression in ATTRv amyloidosis patients.

Clinical and self-reported markers of reproductive function in female survivors of childhood Hodgkin lymphoma.

PURPOSE: To evaluate the impact of treatment for Hodgkin lymphoma (HL) on clinical reproductive markers and pregnancy outcomes. METHODS: This study was embedded within the DCOG LATER-VEVO study; a Dutch, multicenter, retrospective cohort study between 2004 and 2014. Serum anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH), inhibin B, antral follicle count (AFC), and self-reported (first) pregnancy outcomes were evaluated in female childhood HL survivors and controls. RESULTS: 84 HL survivors and 798 controls were included, aged 29.6 and 32.7 years old at time of assessment. Median age at HL diagnosis was 13.4 years. Cyclophosphamide equivalent dose (CED-score) exceeded 6000 mg/m2 in 56 women and 14 survivors received pelvic irradiation. All clinical markers were significantly deteriorated in survivors (odds-ratio for low AMH (< p10) 10.1 [95% CI 4.9; 20.6]; low AFC (< p10) 4.6 [95% CI 2.1; 9.9]; elevated FSH (> 10 IU/l) 15.3 [95% CI 5.7; 41.1], low Inhibin B (< 20 ng/l) 3.6 [ 95% CI 1.7; 7.7], p < 0.001). Pregnancy outcomes were comparable between survivors and controls (± 80% live birth, ± 20% miscarriage). However, survivors were significantly younger at first pregnancy (27.0 years vs 29.0 years, P = 0.04). Adjusted odds-ratio for time to pregnancy > 12 months was 2.5 [95% CI 1.1; 5.6] in survivors, p = 0.031. Adverse outcomes were specifically present after treatment with procarbazine and higher CED-score. CONCLUSION: HL survivors appear to have an impaired ovarian reserve. However, chance to achieve pregnancy seems reassuring at a young age. Additional follow-up studies are needed to assess fertile life span and reproductive potential of HL survivors, in particular for current HL treatments that are hypothesized to be less gonadotoxic.

[Fatal epidermal necrosis due to methotrexate use]. / Fatale epidermale necrose door methotrexaatgebruik.

A 53-year-old patient with known psoriasis presented with painful erosive plaques in existing psoriasis lesions, ulcerations in the mouth, and leukopenia. She used 10 mg of methotrexate daily without folic acid prophylaxis. During admission she developed pancytopenia, liver failure and acute kidney injury. She died after developing toxic shock syndrome. We aim to describe the use and toxic effects of methotrexate, how to recognise toxicity clinically and histologically, and treatment options.

Determining biota succession in a domestic wastewater pond system after treatment with a specific consortium microalgae.

Wastewater stabilization ponds (WSPs) rely on the metabolic activities of the inhabiting microbiota to treat wastewater. A selected consortium of Chlorella vulgaris and Chlorella protothecoides were used to manipulate the natural resident microalgae assemblage to improve the treatment performance of a domestic wastewater pond treatment system in a coastal region. Since information is lacking about the resulting influence on the composition or succession of the phytoplankton or associated microbiota assemblage, the current study aimed to determine how dosing with the microalgae C. vulgaris and C. protothecoides change the efficiency of wastewater effluent treatment, as well as the composition and succession of the natural occurring phytoplankton and microbial assemblage throughout WSP system. After a year of specific microalgae inoculations, the effluent in part complied with the standards set by the Department of Water Affairs and Forestry (DWAF) and the USA, Environmental Protection Agency (EPA). The cyanobacteria Microcystis aeruginosa dominated the sixth (75%) and seventh pond (97%) before the inoculation with C. vulgaris and C. protothecoide commenced. After 12 inoculation events C. vulgaris and C. protothecoides were dominant in ponds three to seven while the dominant microbial groups were Bacteroidetes, Cyanobacteria, Firmicutes, Planctomycetes, Proteobacteria, Spirochaetes, Synergistetes and Verrucomicrobia. After the microalgae treatment, the WSP effluent were more compliant regarding to the set guidelines for effluent than prior to microalgae treatment. Based on the ability of the C. vulgaris and C. protothecoides to improve the effluent water quality, it was evident that the consortium of microalgae can be use improve domestic wastewater effluent in rural nutrient sensitive catchments. Supplementary Information: The online version contains supplementary material available at 10.1007/s40201-022-00840-z.

Evaluation of CBCT based dose calculation in the thorax and pelvis using two generic algorithms.

PURPOSE: This work examines the dosimetric performance of two algorithms creating a corrected CBCT (corrCBCT) and a virtual CT (vCT) implemented in a commercial treatment planning system. METHODS: 60 patients distributed across all patient groups treated with curative intent at Vejle Hospital (breast, lung, prostate and anal/rectal cancer) were selected for the present study. Clinical treatment plans were recalculated on corrCBCT and vCT, as well as a reference CT (refCT) acquired as close in time to the CBCT image as possible. Recalculated doses were compared using gamma analysis, as well as by comparing D98%, D50%, and D2% for all delineated targets and organs at risk. RESULTS: High dosimetric accuracy is demonstrated on both the corrCBCT and vCT. Gamma 2%/2mm pass rates >98% were found for all patients except two outliers still having >93% pass rates. Equivalence of all evaluated dose metrics within ±1Gy was observed for all patient groups, while the pelvic patients additionally showed equivalence for all metrics within ±1% of the refCT dose. For the thoracic patients, equivalence within ±2.5% was established for all metrics except median dose to the ipsilateral lung, calculated on corrCBCT for the breast patient group. CONCLUSION: The corrCBCT and vCT images are shown in excellent dosimetric agreement with refCT images, and show high potential for future use for streamlined adaptive radiotherapy workflows.

A case report: Hypoxic ischemic encephalopathy & pneumonia in a neonate after SARS-CoV-2 intrauterine transmission.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) is primarily transmitted via respiratory droplet or aerosol route. However, there is mounting evidence for intrauterine transmission. We report on a late preterm infant with suspected intrauterine acquisition of SARS-CoV-2 who experienced birth depression, hypoxic ischemic encephalopathy, multisystem organ involvement, and late onset COVID-19 pneumonia [22].

Hospital-related costs of sepsis around the world: A systematic review exploring the economic burden of sepsis.

AIM: The aim of this study was to examine the quality of manuscripts reporting sepsis health care costs and to provide an overview of hospital-related expenditures for sepsis in adult patients around the world. METHODS: We systematically searched the PubMed, EMBASE, Cochrane and Google Scholar to identify relevant studies between January 2010 and January 2022. We selected articles that provided costs and cost-effectiveness analyses, defined sepsis and described their cost calculation method. All costs were adjusted to 2020 US dollars. Medians and interquartile ranges (IQRs) for various costs of sepsis were calculated. The quality of economic studies was assessed using the Drummond 10-item checklist. RESULTS: Overall, 26 studies met our eligibility criteria. The mean total hospital costs per patient varied largely, between €1101 and €91,951. The median (IQR) of the total sepsis costs per country were €36,191 (€17,158 - €53,349), which equals €50 (€34 - €84) per capita annually. The relative amount of healthcare budget spent on sepsis was 2.65%, which equals 0.33% of the gross national product (GNP). CONCLUSION: While general sepsis costs are high, there is considerable variability between countries regarding the costs of sepsis. Further studies examining the impact on sepsis costs, especially on the general ward, can help justify, design and monitor initiatives on prevention, diagnosis, and treatment of this time-critical and potentially preventable disease.

Adherence to guideline-based quality indicators in early pregnancy care in hospitals with and without an early pregnancy assessment unit.

RESEARCH QUESTION: How do hospitals with and without an early pregnancy assessment unit (EPAU) adhere to guideline-based quality indicators for an EPAU relating to logistics, access to services and quality of early pregnancy care? DESIGN: A qualitative interview study assessing the adherence to 19 quality indicators in four hospitals with an EPAU and four hospitals without an EPAU in the Netherlands. For each quality indicator, a ratio for guideline adherence was calculated. Overall non-adherence per hospital was defined as less than 100% adherence to the 19 quality indicators. RESULTS: Non-adherence was seen in three indicators (3/19 [16%]) for hospitals with an EPAU and in five indicators (5/19 [26%]) for hospitals without an EPAU. A standard digital system for the registration of ultrasound findings and clear explanation of all treatment options was present in all hospitals with an EPAU and in three hospitals without an EPAU. Certified ultrasound training for working staff members was absent in all hospitals. A discrete waiting area was present in one hospital with an EPAU compared with none of the hospitals without an EPAU. Self-referrals from women with a previous ectopic pregnancy was accepted in one hospital with and in one hospital without an EPAU. CONCLUSIONS: Non-adherence to guideline-based quality indicators for an EPAU was about the same for hospitals with and without an EPAU in the Netherlands.

Resting heart rate and incident atrial fibrillation: A stratified Mendelian randomization in the AFGen consortium.

BACKGROUND: Both elevated and low resting heart rates are associated with atrial fibrillation (AF), suggesting a U-shaped relationship. However, evidence for a U-shaped causal association between genetically-determined resting heart rate and incident AF is limited. We investigated potential directional changes of the causal association between genetically-determined resting heart rate and incident AF. METHOD AND RESULTS: Seven cohorts of the AFGen consortium contributed data to this meta-analysis. All participants were of European ancestry with known AF status, genotype information, and a heart rate measurement from a baseline electrocardiogram (ECG). Three strata of instrumental variable-free resting heart rate were used to assess possible non-linear associations between genetically-determined resting heart rate and the logarithm of the incident AF hazard rate: <65; 65-75; and >75 beats per minute (bpm). Mendelian randomization analyses using a weighted resting heart rate polygenic risk score were performed for each stratum. We studied 38,981 individuals (mean age 59±10 years, 54% women) with a mean resting heart rate of 67±11 bpm. During a mean follow-up of 13±5 years, 4,779 (12%) individuals developed AF. A U-shaped association between the resting heart rate and the incident AF-hazard ratio was observed. Genetically-determined resting heart rate was inversely associated with incident AF for instrumental variable-free resting heart rates below 65 bpm (hazard ratio for genetically-determined resting heart rate, 0.96; 95% confidence interval, 0.94-0.99; p = 0.01). Genetically-determined resting heart rate was not associated with incident AF in the other two strata. CONCLUSIONS: For resting heart rates below 65 bpm, our results support an inverse causal association between genetically-determined resting heart rate and incident AF.

Impact of three co-occurring physical ecosystem engineers on soil Collembola communities.

The interplay between organisms with their abiotic environment may have profound effects within ecological networks, but are still poorly understood. Soil physical ecosystem engineers (EEs) modify the abiotic environment, thereby potentially affecting the distribution of other species, such as microarthropods. We focus on three co-occurring physical EEs (i.e. cattle, vegetation, macrodetritivore) known for their profound effect on soil properties (e.g. pore volume, microclimate, litter thickness). We determined their effects on Collembola community composition and life-form strategy (a proxy for vertical distribution in soil) in a European salt marsh. Soil cores were collected in grazed (compacted soil, under short and tall vegetation) and non-grazed areas (decompacted soil, under short and tall vegetation), their pore structure analysed using X-ray computed tomography, after which Collembola were extracted. Collembola species richness was lower in grazed sites, but abundances were not affected by soil compaction or vegetation height. Community composition differed between ungrazed sites with short vegetation and the other treatments, due to a greater dominance of epigeic Collembola and lower abundance of euedaphic species in this treatment. We found that the three co-occurring EEs and their interactions modify the physical environment of soil fauna, particularly through changes in soil porosity and availability of litter. This alters the relative abundance of Collembola life-forms, and thus the community composition within the soil. As Collembola are known to play a crucial role in decomposition processes, these compositional changes in litter and soil layers are expected to affect ecosystem processes and functioning.

The level and distribution of methyl-esters influence the impact of pectin on intestinal T cells, microbiota, and Ahr activation.

Pectins are dietary fibres that modulate T cell immunity, microbiota composition, and fermentation profiles, but how this is influenced by the degree of methyl-esterification (DM) and degree-of-blockiness (DB) of pectin is unknown. Here, we demonstrate that supplementation of DM19(high-DB), DM49(low-DB) and DM43(high-DB) pectins at a low dose increased the frequencies of intestinal T-helper (Th)1 and Th2 cells after 1 week of pectin supplementation in mice, whereas DM18(low-DB) did not. After 4 weeks of supplementation with those pectins, Th1 and Th2 frequencies returned to control levels, whereas Rorγt+ regulatory T-cell frequencies increased. These structure-dependent effects could derive from induced shifts in microbiota composition that differed between DM18(low-DB) pectin and the other pectins. T-cell-modulating effects were not short-chain-fatty acid-dependent, but rather through an increase in Aryl-hydrocarbon-receptor-activating components. Thus, pectins with a specific combination of DM and DB have an impact on intestinal T cell-immunity in mice, when supplemented at a low dose.

Emergence of Avian coronavirus Escape Mutants Under Suboptimal Antibody Titers.

To perform a quasispecies assessment of the effect of vaccine combinations and antibody titers on the emergence of Avian coronavirus (AvCoV) escape mutants, 5-week-old males from a commercial chicken breeder lineage were vaccinated intramuscularly with one dose of a monovalent (genotype GI-1) or a bivalent (genotypes GI-1 and GI-11 (n = 40 birds/group) AvCoV vaccine. Seven birds were kept as controls. Six weeks later, pools of sera of each group were prepared and incubated at virus neutralization doses of 10 and 10-1 with the Beaudette strain (GI-1) of AvCoV in VERO cells. Rescued viruses were then submitted to genome-wide deep sequencing for subconsensus variant detection. After treatment with serum from birds vaccinated with the bivalent vaccine at a titer of 10-1, an F307I variant was detected in the spike glycoprotein that mapped to an important neutralizing region, which indicated an escape mutant derived from natural selection. Further variants were detected in nonstructural proteins and non-coding regions that are not targets of neutralizing antibodies and might be indicators of genetic drift. These results indicate that the evolution of AvCoV escape mutants after vaccination depends on the type of vaccine strain and the antibody titer and must be assessed based on quasispecies rather than consensus dominant sequences only because quasispecies may be otherwise undetected.

Prognostic value of strain by feature-tracking cardiac magnetic resonance in arrhythmogenic right ventricular cardiomyopathy.

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by ventricular dysfunction and ventricular arrhythmias (VA). Adequate arrhythmic risk assessment is important to prevent sudden cardiac death. We aimed to study the incremental value of strain by feature-tracking cardiac magnetic resonance imaging (FT-CMR) in predicting sustained VA in ARVC patients. METHODS AND RESULTS: CMR images of 132 ARVC patients (43% male, 40.6 ± 16.0 years) without prior VA were analysed for global and regional right and left ventricular (RV, LV) strain. Primary outcome was sustained VA during follow-up. We performed multivariable regression assessing strain, in combination with (i) RV ejection fraction (EF); (ii) LVEF; and (iii) the ARVC risk calculator. False discovery rate adjusted P-values were given to correct for multiple comparisons and c-statistics were calculated for each model. During 4.3 (2.0-7.9) years of follow-up, 19% of patients experienced sustained VA. Compared to patients without VA, those with VA had significantly reduced RV longitudinal (P ≤ 0.03) and LV circumferential (P ≤ 0.04) strain. In addition, patients with VA had significantly reduced biventricular EF (P ≤ 0.02). After correcting for RVEF, LVEF, and the ARVC risk calculator separately in multivariable analysis, both RV and LV strain lost their significance [hazard ratio 1.03-1.18, P > 0.05]. Likewise, while strain improved the c-statistic in combination with RVEF, LVEF, and the ARVC risk calculator separately, this did not reach statistical significance (P ≥ 0.18). CONCLUSION: Both RV longitudinal and LV circumferential strain are reduced in ARVC patients with sustained VA during follow-up. However, strain does not have incremental value over RVEF, LVEF, and the ARVC VA risk calculator.

Protocol for a randomized controlled multicenter trial assessing the efficacy of leuprorelin for severe polycystic liver disease: the AGAINST-PLD study.

BACKGROUND: In patients with severe polycystic liver disease (PLD), there is a need for new treatments. Estrogens and possibly other female sex hormones stimulate growth in PLD. In some patients, liver volume decreases after menopause. Female sex hormones could therefore be a target for therapy. The AGAINST-PLD study will examine the efficacy of the GnRH agonist leuprorelin, which blocks the production of estrogen and other sex hormones, to reduce liver growth in PLD. METHODS: The AGAINST-PLD study is an investigator-driven, multicenter, randomized controlled trial. Institutional review board (IRB) approval was received at the University Medical Center of Groningen and will be collected in other sites before opening these sites. Thirty-six female, pre-menopausal patients, with a very large liver volume for age (upper 10% of the PLD population) and ongoing liver growth despite current treatment options will be randomized to direct start of leuprorelin or to 18 months standard of care and delayed start of leuprorelin. Leuprorelin is given as 3.75 mg subcutaneously (s.c.) monthly for the first 3 months followed by 3-monthly depots of 11.25 mg s.c. The trial duration is 36 months. MRI scans to measure liver volume will be performed at screening, 6 months, 18 months, 24 months and 36 months. In addition, blood will be drawn, DEXA-scans will be performed and questionnaires will be collected. This design enables comparison between patients on study treatment and standard of care (first 18 months) and within patients before and during treatment (whole trial). Main outcome is annualized liver growth rate compared between standard of care and study treatment. Secondary outcomes are PLD disease severity, change in liver growth within individuals and (serious) adverse events. The study is designed as a prospective open-label study with blinded endpoint assessment (PROBE). DISCUSSION: In this trial, we combined the expertise of hepatologist, nephrologists and gynecologists to study the effect of leuprorelin on liver growth in PLD. In this way, we hope to stop liver growth, reduce symptoms and reduce the need for liver transplantation in severe PLD. Trial registration Eudra CT number 2020-005949-16, registered at 15 Dec 2020. https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-005949-16 .

Development of a Blueprint for Integrated Care for Vulnerable Pregnant Women.

PURPOSE: There has been increasing awareness of perinatal health and organisation of maternal and child health care in the Netherlands as a result of poor perinatal outcomes. Vulnerable women have a higher risk of these poor perinatal outcomes and also have a higher chance of receiving less adequate care. Therefore, within a consortium, embracing 100 organisations among professionals, educators, researchers, and policymakers, a joint aim was defined to support maternal and child health care professionals and social care professionals in providing adequate, integrated care for vulnerable pregnant women. DESCRIPTION: Within the consortium, vulnerability is defined as the presence of psychopathology, psychosocial problems, and/or substance use, combined with a lack of individual and/or social resources. Three studies focussing on population characteristics, organisation of care and knowledge, skills, and attitudes of professionals regarding vulnerable pregnant women, were carried out. Outcomes were discussed in three field consultations. ASSESSMENT: The outcomes of the studies, followed by the field consultations, resulted in a blueprint that was subsequently adapted to local operational care pathways in seven obstetric collaborations (organisational structures that consist of obstetricians of a single hospital and collaborating midwifery practices) and their collaborative partners. We conducted 12 interviews to evaluate the adaptation of the blueprint to local operational care pathways and its' embedding into the obstetric collaborations. CONCLUSION: Practice-based research resulted in a blueprint tailored to the needs of maternal and child health care professionals and social care professionals and providing structure and uniformity to integrated care provision for vulnerable pregnant women.

Rationale and design of the PHOspholamban RElated CArdiomyopathy intervention STudy (i-PHORECAST).

BACKGROUND: The p.Arg14del (c.40_42delAGA) phospholamban (PLN) pathogenic variant is a founder mutation that causes dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM). Carriers are at increased risk of malignant ventricular arrhythmias and heart failure, which has been ascribed to cardiac fibrosis. Importantly, cardiac fibrosis appears to be an early feature of the disease, occurring in many presymptomatic carriers before the onset of overt disease. As with most monogenic cardiomyopathies, no evidence-based treatment is available for presymptomatic carriers. AIMS: The PHOspholamban RElated CArdiomyopathy intervention STudy (iPHORECAST) is designed to demonstrate that pre-emptive treatment of presymptomatic PLN p.Arg14del carriers using eplerenone, a mineralocorticoid receptor antagonist with established antifibrotic effects, can reduce disease progression and postpone the onset of overt disease. METHODS: iPHORECAST has a multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) design. Presymptomatic PLN p.Arg14del carriers are randomised to receive either 50 mg eplerenone once daily or no treatment. The primary endpoint of the study is a multiparametric assessment of disease progression including cardiac magnetic resonance parameters (left and right ventricular volumes, systolic function and fibrosis), electrocardiographic parameters (QRS voltage, ventricular ectopy), signs and/or symptoms related to DCM and ACM, and cardiovascular death. The follow-up duration is set at 3 years. BASELINE RESULTS: A total of 84 presymptomatic PLN p.Arg14del carriers (n = 42 per group) were included. By design, at baseline, all participants were in New York Heart Association (NHYA) class I and had a left ventricular ejection fraction > 45% and < 2500 ventricular premature contractions during 24-hour Holter monitoring. There were no statistically significant differences between the two groups in any of the baseline characteristics. The study is currently well underway, with the last participants expected to finish in 2021. CONCLUSION: iPHORECAST is a multicentre, prospective randomised controlled trial designed to address whether pre-emptive treatment of PLN p.Arg14del carriers with eplerenone can prevent or delay the onset of cardiomyopathy. iPHORECAST has been registered in the clinicaltrials.gov-register (number: NCT01857856).