Methods and approaches for developing plain language versions of guidelines recommendations: Scoping review protocol.

AIMS AND OBJECTIVES: This is a protocol of a scoping review that will aim to synthesise methodological evidence on formulating plain language versions of recommendations from guidelines both for clinical practice and for public health. METHOD: We will conduct a search in MEDLINE (Ovid), Embase (Ovid) databases, and webpages of guidelines developers with no language and date limitations. The title/abstract and full-text screening will be performed by two reviewers independently. The team of reviewers will extract data on methods used for developing plain language versions of recommendations in a standardised manner. The data analysis and synthesis will be presented narratively in tabular form. RESULTS AND CONCLUSION: We will conduct a scoping review based on this protocol.

Challenges in prospective observational studies evaluating pressure ulcer costs: how to price the items correctly.

OBJECTIVE: Pressure ulcers (PUs) are a significant healthcare problem with a negative impact on patients' quality of life and incurring substantial healthcare expenses. Our study aimed to analyse the costs of treating PUs in hospitalised patients in the Czech Republic, in the context of current treatment procedures and price levels, and to pilot-test the detailed methodology developed. METHOD: A prospective, observational, non-interventional study was conducted at the Clinic of Anesthesiology, Resuscitation and Intensive Medicine, the Internal Medicine Department and the Surgical Department of the University Hospital Ostrava. The study included all hospitalised patients with a PU from March-May 2021. Data were collected using the hospital information system. A bottom-up, person-based approach to cost analysis was used, based on a comprehensive cost structure using accurate patient-specific consumption records. RESULTS: The length of hospitalisations ranged from 1-31 (mean: 12.7) days. The average cost of PU treatment per hospitalisation was calculated at €1579. The average daily cost of PU treatment was €179, including antibiotic therapy (ATB) and €112 without ATB. Most of the costs were associated with ATB (38.6%) and caregivers' time (35.9%). Based on the results, a predictive model was developed to estimate the cost of treating a hospitalised patient with a PU, which could be used in future research to assess the costs of treating these patients. CONCLUSION: We have faced many challenges in the methodology of preparation of cost analysis (e.g., how to count amorphous topical agents and sprays, how to properly identify PUs, how to price the positioning aids and mattresses, and how to relate the ATB treatment to the PU). This analysis provides important input for developing a comprehensive and more accurate methodology for monitoring PU costs in hospitalised patients, applicable in clinical practice for inpatient healthcare providers.

Mortality related to pressure ulcers in Czech Republic - Analyses of national health registries.

BACKGROUND: Pressure ulcers/pressure injuries (PUs/PIs) relate to decreasing quality of life, prolonged hospitalisation, the increased economic cost of care, and increased mortality. That's why this study focused on one of the mentioned factors - mortality. OBJECTIVES: The study analyses national data in the Czech Republic to map the mortality phenomenon comprehensively based on data from national health registries. METHOD: The retrospective, nationwide cross-sectional data analysis of data collected by the National Health Information System (NHIS) has been provided in the period 2010-2019 with a special focus on 2019. Hospitalisations with PUs/PIs were identified by reporting L89.0-L89.9 diagnosis as a primary or secondary hospitalisation diagnosis. We also included all the patients who died in the given year with an L89 diagnosis reported in 365 days prior the death. RESULTS: In 2019, 52.1% of patients with reported PUs/PIs were hospitalised, and 40.8% were treated on an outpatient basis. The most common underlying cause of death mortality diagnosis (43.7%) in these patients was the diseases of the circulatory system. Patients who die in a healthcare facility while hospitalised with an L89 diagnosis generally have a higher category of PUs/PIs than persons who die outside a healthcare facility. CONCLUSION: The proportion of patients dying in a health facility is directly proportional to the increasing PUs/PIs category. In 2019, 57% of patients with PUs/PIs died in a healthcare facility, and 19% died in the community. In 24% of patients who died in the healthcare facility, PUs/PIs were reported 365 days before the death.

Identification of telehealth nursing approaches in the light of the COVID-19 pandemic-A literature review.

AIMS: This study aimed to identify recommendations for quality nursing care provision, focusing on the possibilities of delivering telehealth nursing at the national level in the Czech Republic. BACKGROUND: The significant growth in the use of technology in health care has changed the environment for patient care and how health care is provided. The COVID-19 pandemic has shown the requirement for telemedicine use in everyday clinical practice. EVALUATION: A literature review aims to find guidelines, recommendations, manuals, standards or consensus papers published in 2017-2022. KEY ISSUES: In total, 12 guidelines were identified. Based on a critical evaluation carried out by two experts, the World Health Organization guideline focused on digital interventions to strengthen the health system has been identified. This guideline was evaluated to be of the highest quality and in line with the Grading of Recommendations, Assessment, Development and Evaluations methodology. CONCLUSION: The provision of telemedicine nursing interventions is currently limited at the national level and is not entirely accepted in reimbursement yet. The interprofessional collaboration will be initiated to make recommendations for specific patient groups. IMPLICATIONS FOR NURSING MANAGEMENT: Selected guidelines can be recommended for national adoption to set up and support nursing interventions in telemedicine, including nursing management settings.

How the COVID-19 pandemic influences the prevalence of pressure injuries in the Czech Republic: A nationwide analysis of a health registry in 2020.

BACKGROUND: COVID-19 significantly influences the overall patient status and, in severe symptomatology, the ability to move and the low oxygenation of the tissue for the ventilated patient in Intensive Care Units (ICU). There is a higher risk for Pressure injuries (PIs) development. OBJECTIVES: The nationwide analyses of the National health register aimed to compare the prevalence of PIs reported before the pandemic COVID-19 started and during the pandemic in 2020. METHOD: A retrospective, nationwide cross-sectional analysis of data regarding the STROBE checklist collected by the National Health Information System (NHIS), focusing on the PIs reporting based on the International Classification of Diseases (ICD-10) diagnoses L89.0-L89.9 for PIs in 2020. The data from the pandemic period of COVID-19 in 2020 were compared to the prevalence of PI cases in the period 2010-2019 in the Czech Republic in all hospitalized patients. RESULTS: The total number of admissions for L89 in 2020 was 14,441, of which 1509 (10.4%) also had COVID-19. In the ICU were 4386 admissions, 12.1% of which also had COVID-19. A higher proportion of PIs is observed in patients hospitalized with COVID-19 than in patients without COVID-19 (2.62% vs 0.81%, respectively 1.05% vs 0.46% when standardized to the 2013 ESP = European Standard Population). In patients hospitalized in ICU, 3.68% with COVID-19 had PIs vs 1.42% without COVID-19 had PIs (1.97% vs 0.81% using the 2013 ESP). CONCLUSION: The national health registers analyses have proven that the prevalence of PIs was higher among patients hospitalized with the SARS-CoV-2 infection.

A ten-year follow-up of the prevalence of pressure injuries in the Czech Republic: Analysis of the National Registry.

The study aims to follow up on the analysis of Pressure injuries (PIs) prevalence conducted between 2007 and 2014 and after the new methodological requirements for PIs surveillance establishment at the national level. A retrospective, nationwide cross-sectional analysis of data regarding the STROBE checklist was collected by the National Health Information System (NHIS). The International Classification of Diseases (ICD-10) diagnoses L89.0-L89.9 for PIs were used in the period 2010-2019. A total of 264 442 records of patients with diagnoses of L89.0-L89.9 were identified from 2010 to 2019 (26 444 patients per year on average). The numbers are increasing every year, and there is a 40% increase between 2010 and 2019. When comparing recorded PIs, the percentage of PIs occurrence in category I decreased, and the number of PIs in category IV increased in the second analysed period. Still, in absolute numbers, there is an increase across all categories. The age of patients with recorded PIs also rose slightly in the second analysed period. We have proven the PIs prevalence increase in an ageing population.

Addressing Challenges When Applying GRADE to Public Health Guidelines: A Scoping Review Protocol and Pilot Analysis.

This is a protocol for a scoping review that aims to determine how guideline authors using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach have addressed previously identified challenges related to public health. The Joanna Briggs Institute (JBI) methodology for scoping reviews will be followed. We will search and screen titles of guidelines for all languages published in 2013-2021 in: the GIN library, BIGG database, Epistemonikos GRADE guidelines repository, GRADEpro Database, MAGICapp, NICE and WHO websites. Two reviewers will independently screen full texts of the documents identified. The following information will be extracted: methods used for identifying different stakeholders and incorporating their perspectives; methods for identification and prioritization of non-health outcomes; methods for determining thresholds for decision-making; methods for incorporating and grading evidence from non-randomized studies; methods for addressing concerns with conditional recommendations in public health; methods for reaching consensus; additional methodological concerns; and any modifications made to GRADE. A combination of directed content analysis and descriptive statistics will be used for data analysis, and the findings presented narratively in a tabular and graphical form. In this protocol, we present the pilot results from 13 identified eligible guidelines issued between January and August 2021. We will publish the full review results when they become available.

Economic evaluations of interventions for the prevention and treatment of pressure ulcers: an umbrella review protocol.

OBJECTIVE: The objective of this review is to synthesize the findings of economic evaluations of preventing or treating pressure ulcers. INTRODUCTION: Pressure ulcers are one of the most common preventable complications characterized by local tissue injury. Pressure ulcers increase mortality rates, impair quality of life, increase the length of hospital stay, and alter overall health outcomes. Published studies have found higher costs associated with treating pressure ulcers than preventing them, with treatment cost varying based on the pressure ulcer category (the greater the category, the higher the cost). We will systematically review the evidence on preventing or treating pressure ulcers from an economic perspective. INCLUSION CRITERIA: We will include systematic reviews that investigate both the cost and outcomes associated with the prevention or treatment of pressure ulcers. Systematic reviews dealing with economic evaluation of wound care or management will be excluded if they have not provided separate information for pressure ulcers. METHODS: Epistemonikos, MEDLINE, NHS Economic Evaluation Database, and the Canadian Agency for Drugs and Technologies in Health (CADTH) website will be searched for relevant systematic reviews from inception and without any language restrictions. Titles and abstracts will be screened at the initial stage, followed by full-text screening. Quality assessment will be done using the standard JBI critical appraisal instrument for systematic reviews and research syntheses. Article screening, data extraction, and quality assessment will be performed by two reviewers independently. All economic health outcomes will be considered under the primary outcomes of the study. SYSTEMATIC REVIEW REGISTRATION NUMBER: Open Science Framework (https://osf.io/9y2a7/).

Quality assessment of clinical practice guidelines for perioperative care and use of GRADE: a systematic review protocol.

INTRODUCTION: Perioperative care is a broad field covering an array of elective and emergency procedures. Clinical practice guidelines (CPGs) for perioperative care exist with various degrees of methodological quality. We intend to critically appraise them using AGREE II instrument and investigate the use of Grading of Recommendations, Assessment, Development and Evaluations (GRADE). METHODS AND ANALYSIS: We searched MEDLINE (Ovid), Epistemonikos, Cochrane Database of Systematic Reviews and PROSPERO and did not identify any similar systematic review in this area. We will search databases, repositories and websites of guideline developers and medical societies, including MEDLINE (Ovid), Embase (Ovid), DynaMed, the GIN international guideline library and registry of guidelines in development, BIGG international database of GRADE guidelines, ECRI Guideline Trust or National Institute for Clinical Evidence to identify all CPGs for perioperative care in an adult population in a general clinical setting. We will include CPGs, expert guidance, position papers, guidance documents and consensus statements published in the last 5 years by experts or international organisations that provide guidance or recommendations in the available full text with no geographical or language limitation. Excluded will be those containing only good practice statements. Two independent reviewers will perform critical appraisal using the AGREE II tool. The data presented in a narrative and tabular form will include the results of the critical appraisal for all identified CPGs for all AGREE II domains and an assessment of the use of the GRADE approach. ETHICS AND DISSEMINATION: Ethics approval is not required. We will disseminate the findings through professional networks and conference presentations and will publish the results.

Representation of Parkinson's disease and atypical Parkinson's syndromes in the Czech Republic-A nationwide retrospective study.

BACKGROUND: Parkinson's disease is a progressive neurodegenerative disease which causes health problem that affects more patients in the past few years. To be able to offer appropriate care, epidemiological analyses are crucial at the national level and its comparison with the international situation. AIM: The demographic description of reported patients with parkinsonism (including Parkinson's disease and atypical parkinsonian syndromes) according to the International Classification of Diseases (ICD-10) from the national health registries. METHODS: Retrospective analysis of data available from the National Health Information System-NHIS and the National Registry of Reimbursed Health Services (NRRHS). Analyzed epidemiological data are intending to determine the regional and specific prevalence of Parkinsonism in the Czech Republic. The International Classification of Diseases diagnoses (ICD-10) of G20 (Parkinson's disease-PD) and G23.1, G23.2, G23.3 (other degenerative disorders of basal ganglia), and G31.8 (another degenerative disease of basal ganglia) from the period of 2012 to 2018 were included into the analysis. RESULTS: We identified 78 453 unique patients from national registries in the period 2012 to 2018. Diagnoses of G20, G23.1, G23.2, and G31.8 were registered as the principal diagnoses in 76.6% of all individual patients. CONCLUSION: We have found a growing number of patients coded with ICD-10 of dg. G20, G23.1, G23.2, G23.3, or G31.8 (N = 27 891 in 2012, and N = 30 612 in 2018). We have proven regional differences in the prevalence of Parkinson´s diagnoses. Therefore we assume most likely also differences in the care of patients with PD based on the availability of specialty care centers.

Compliance with standard precautions in inpatient healthcare settings in the Czech Republic: a cross-sectional survey.

OBJECTIVE: The study evaluates compliance with declared hygienic standards carried out by healthcare professionals in clinical practice within their scope of direct patient care and the maintenance of medical tools and devices in healthcare facilities in the Czech Republic. METHODS: Cross-sectional questionnaire study focused on the standards of safe health care. All 80 addressed healthcare providers were also involved in the 2018 Adverse Event Reporting System (AERS) pilot project. Responses were scored on a 6-level scale, from "always" (100 points) to "never" (0 points). The evaluation was performed according to the frequency of responses and the average index (max. 100 points). Data analysis was performed using IBM SPSS Statistics version 22 (level of significance 1% and 5%). RESULTS: There were statistically processed 2,016 questionnaires (100%). Most respondents stated their job classification as non-medical healthcare professionals (NHP) working at a patient's bedside (73%), physicians (16%), or other NHP (11%). As per their medical specialty, 43% of the respondents practice internal medicine, 28% surgery, 14% psychiatry, 9% long-term inpatient care, and 6% stated other fields of medicine. The lowest declared compliance was registered in the statement "I use a face mask when exposure to air-transmitted pathogens is anticipated" (rating index 80 points). The highest compliance (99.4 points) was registered in the statement: "I discard used sharp materials into sharps containers." CONCLUSION: In the surveyed healthcare facilities within the Czech Republic, overall compliance with hygiene standards is at a good level. Declared differences in compliance with hygiene standards in the selected items of the questionnaire are influenced by multiple factors. Generally, a higher level of compliance is linked to increasing age, years of practice, and a higher level of education. When comparing professional groups, a higher level of compliance with hygiene standards was registered in the NHP group.

Use of high-density EEG in patients with Parkinson's disease treated with deep brain stimulation.

The number of reports on cognitive changes related to deep brain stimulation (DBS) surgery in Parkinson's disease (PD) is growing. The aim of the review was to assess whether high-density electroencephalography (HD EEG) in patients with DBS treatment for PD is used and mentioned as a research method for the assessment of cognitive function changes after DBS of the subthalamic nucleus. The HD EEG examination method demonstrates the effects of DBS on changes of connectivity among various areas of the brain using changes in bioelectric potentials recorded on the scalp during examination. The search results yielded seven studies on the possibility of using HD EEG to investigate changes in bioelectric potentials with various protocols (motor tasks, auditory stimuli). Based on the results, HD EEG appears to be a feasible research method in patients with PD and established DBS therapy. Therefore, we plan to use HD EEG to demonstrate the effects of DBS on changes of connectivity among various areas of the brain utilizing changes in bioelectric potentials recorded on the scalp during HD EEG examination.

Czech national project 'Clinical Practice Guidelines' methodology and current results.

Currently in the Czech Republic, there does not exist such an institution as a 'National Centre for Clinical Practice Guidelines'. In 2017, there were about 123 professional medical organizations which developed about 1909 'guidelines' until 2017. However, the majority of these guidelines are 'expert opinion' or 'consensual' based 'guidance' or rather recommendations in the most cases missing a systematic approach that reflects evidence-based medicine principles and methods. The project is led by the Czech Health Research Council, the first partner is the Ministry of Health of the Czech Republic and the second partner is the Institute of Health Information and Statistics of the Czech Republic with support from policy makers, academics, clinicians and members of the Czech National Centre for Evidence-Based Healthcare and Knowledge Translations. This centre is an umbrella for three very important international collaborations which play a key role in Evidence-Based Healthcare, Evidence Synthesis, Evidence Implementation and trustworthy guidelines development. These are Cochrane Czech Republic, Masaryk University Grade Centre and the Czech Republic Centre for Evidence-Based Healthcare: The Joanna Briggs Institute Centre of Excellence.The main aim of this article is to present the Czech National Methodology of the Trustworthy Clinical Practice Guideline (CPG) development and the first results of the project 'Clinical Practice Guidelines'.A pilot phase of the project was realized during the first year of the project from January to December 2018. As the first step, there were established managing authorities including a Guarantee Committee and an Appraisal (Methodological) Committee. The Members of the Appraisal Committee developed a pilot version of the National Methodology of CPG development based on the best available approaches to Trustworthy CPGs development followed by testing on the first five pilot CPGs.

Development of Czech National Stroke Guidelines.

Despite a significant transformation of ischaemic stroke management, it remains one of the leading causes of death, disability, functional impairment and cognitive deficits. With the advent of intravenous thrombolysis and mechanical thrombectomy, stroke is not an untreatable disease, mostly occurring in older people, any more. The most common cause of cardioembolic strokes is atrial fibrillation or flutter and atrial fibrillation is the most prevalent arrhythmia.The aim of this short communication is to describe the methodology of the Czech stroke guidelines development.High-quality 2017 Australian Stroke Foundation stroke guideline was considered for adaptation and a new guideline was developed and disseminated.

Epidemiological analyses for preparation of Clinical Practice Guidelines related to acute coronary syndromes in the Czech Republic.

Coronary heart disease, sometimes also referred to as ischemic heart disease, remains the leading condition causing most deaths and disability-adjusted life years worldwide. Acute coronary syndrome (ACS) represents a subset that is defined by sudden reduction of blood supply in the coronary arteries. ACS consists of unstable angina, non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI).The current short communication aims to provide current ACS prevalence and incidence data analysis to inform development of clinical practice guidelines in the Czech Republic.The Institute of Health Information and Statistics of the Czech Republic has provided the data that are collected by the National Health Information System with the National Register of Reimbursed Health Services as a primary source providing data for the period from 2015 to 2017.There has been a slight decrease in the number of hospitalized patients for ACS in the Czech Republic from 2015 to 2017. Sex difference remains large, with majority (two thirds) of those hospitalized for unstable angina, NSTEMI, or STEMI being men. Hospitalization with STEMI is reported in younger age with no sex difference compared with NSTEMI and unstable angina.

Use of epidemiological analyses in Clinical Practice Guideline development focused on the diabetic patients treated with insulin.

The prevalence of diabetes is on the rise worldwide especially in developed countries. The aim of glucose management in all types of diabetes is to minimize chronic and acute complications associated with diabetes. All patients with type 1 diabetes mellitus (T1DM) require insulin. Main areas of technology advances in diabetes are continuous subcutaneous insulin infusion (CSII) and also continuous glucose monitoring systems for the management of patients with both types of diabetes. It is very important to analyse the epidemiological situation within each country before and during the clinical practice guidelines (CPGs) development and implementation. The analyses will allow us to monitor the effect of the CPG after its implementation.The aim of this short communication is to analyse the epidemiology of prevalence and incidence of diabetes mellitus and use of CSII to inform development of CPGs in the Czech Republic.The analysis is developed based on the data managed by Institute of Health Information and Statistics of the Czech Republic. We used the National Register of Reimbursed Health Services 2015-2017 as primary source, and the annual report type A (Ministry of Health) 1-01: for Diabetology (A MH 004) 2007-2017 was used as validation source. The presented data are related to the year 2016 because we were able to validate them based on the data from 2015 to 2017 for this cohort of patients.The number of patients with T1DM is increasing in the Czech Republic with no significant sex difference. Life expectancy is about 11 years lower in the T1DM population. The majority of the patients are in older age; however, these are not treated with CSII compared with the younger population. From 61 533 patients with T1DM, 81% were reported with acute and chronic complications in 2016. Only 5011 of these patients were reported as using CSII.

Use of epidemiological analyses in development of colorectal cancer clinical practice guidelines in the Czech Republic.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the fourth most common cause of cancer death worldwide. Crucial in CRC as well as for other effective diagnostics and treatment is the knowledge translation and implementation of the current best available evidence into clinical practice and public health. Clinical practice guidelines are one of the useful tools to be able to improve diagnostics and increase survival rate.The epidemiological analysis was performed based on the data of the Czech National Cancer Registry from 1977 to 2017. We have analysed incidence, prevalence, mortality and primary treatment of CRC in the Czech Republic.The incidence of CRC increased significantly from 1982 to 2002 and is higher in men compared with women based on the data from the National Health Information System in the Czech Republic. The majority of the patients with CRC were diagnosed in early stages. Women were diagnosed at slightly higher age than men. An increase in surgical therapy performed in primary treatment of early CRC was reported from 2006 to 2016. Relative time of survival increased in reported patients with CRC.This analysis reported significant changes in incidence of CRC in the last 40 years as well as in diagnostics and primary therapy in early stages of CRC in the last 12 years. The first ever evidence-based clinical practice guideline on diagnostics and therapy of early CRC in the Czech Republic was developed and disseminated.

Epidemiological analyses to inform stroke clinical practice guidelines development.

Stroke is one of the leading causes of mortality and the leading cause of functional impairment and cognitive deficits worldwide. It is important that clinical practice guidelines development is based on robust statistical and epidemiological data and their analysis throughout the whole process of guidelines development and implementation. The aim of this short communication is to analyse epidemiology of prevalence and incidence of ischaemic stroke, its main causes, brain imaging using MRI, recanalization therapies, secondary prevention with antiplatelet and anticoagulants, mortality data and to inform development of stroke clinical practice guidelines in the Czech Republic. The main analysed diagnosis was I63 (cerebral infarction) and secondary diagnoses were: I48 (atrial fibrillation and flutter), I35.9 (nonspecified aortic valve disease), Q21.1 (atrial septal defect) or I33.0 (acute and subacute endocarditis). We have also analysed use of brain imaging with MRI, recanalization treatment using intravenous thrombolysis and mechanical thrombectomy, stroke secondary prevention with antiplatelet drugs and anticoagulation as well as hospital admissions and mortality. In total, 159 344 patients were diagnosed with an ischaemic stroke from 2015 to 2017. Average prevalence of ischaemic stroke in the Czech Republic is 54.9 patients per 100 000. 22.2% of patients with stroke received intravenous thrombolysis or mechanical thrombectomy in 2017.

The Telomerase Complex Directly Controls Hematopoietic Stem Cell Differentiation and Senescence in an Induced Pluripotent Stem Cell Model of Telomeropathy.

Telomeropathies are rare disorders associated with impaired telomere length control mechanisms that frequently result from genetic mutations in the telomerase complex. Dyskeratosis congenita is a congenital progressive telomeropathy in which mutation in the telomerase RNA component (TERC) impairs telomere maintenance leading to accelerated cellular senescence and clinical outcomes resembling premature aging. The most severe clinical feature is perturbed hematopoiesis and bone-marrow failure, but the underlying mechanisms are not fully understood. Here, we developed a model of telomerase function imbalance using shRNA to knockdown TERC expression in human induced pluripotent stem cells (iPSCs). We then promoted in vitro hematopoiesis in these cells to analyze the effects of TERC impairment. Reduced TERC expression impaired hematopoietic stem-cell (HSC) differentiation and increased the expression of cellular senescence markers and production of reactive oxygen species. Interestingly, telomere length was unaffected in shTERC knockdown iPSCs, leading to conclusion that the phenotype is controlled by non-telomeric functions of telomerase. We then assessed the effects of TERC-depletion in THP-1 myeloid cells and again observed reduced hematopoietic and myelopoietic differentiative potential. However, these cells exhibited impaired telomerase activity as verified by accelerated telomere shortening. shTERC-depleted iPSC-derived and THP-1-derived myeloid precursors had lower phagocytic capacity and increased ROS production, indicative of senescence. These findings were confirmed using a BIBR1532 TERT inhibitor, suggesting that these phenotypes are dependent on telomerase function but not directly linked to telomere length. These data provide a better understanding of the molecular processes driving the clinical signs of telomeropathies and identify novel roles of the telomerase complex other than regulating telomere length.