Clinical Updates

Accelerating Advances in Epilepsy Surgery
Accelerating Advances in Epilepsy Surgery 1024 683 Abbie Miller

One program is bringing together clinical care, surgery and research to create a brighter future for children with intractable epilepsy. Childhood-onset epilepsy affects 1% of children worldwide. Up to a third of patients with epilepsy will have medically refractory epilepsy, continuing to have seizures despite using two or more antiseizure medications. Options for this group…

Unraveling the Genetic Mystery Behind a Rare Pediatric Disease
Unraveling the Genetic Mystery Behind a Rare Pediatric Disease 980 429 Wendy Margolin

Prune belly syndrome (PBS) is a rare, congenital urologic disease, affecting an estimated 1 out of 50,000 births. While most urologists will see fewer than three cases of PBS in their careers, Nationwide Children’s Hospital’s Linda Baker, MD, has treated more than 50 patients and met and counseled nearly 200 in the last 15 years.…

Supporting Optimal Developmental Outcomes After Neonatal Opioid Withdrawal Syndrome
Supporting Optimal Developmental Outcomes After Neonatal Opioid Withdrawal Syndrome 1024 575 Abbie Miller
Toddler playing with toys

Children with prenatal opioid exposure have a higher risk for developmental and behavioral concerns. Prenatal opioid exposure is still far too common. Experts estimate that one infant who has been exposed to opioids is born every 15 minutes in the United States.  While standard diagnostic criteria for neonatal opioid withdrawal syndrome (NOWS) were recently proposed,…

Scalable Delivery of Universal Suicide Prevention in Schools
Scalable Delivery of Universal Suicide Prevention in Schools 1024 657 Pam Georgiana

Implementing the Signs of Suicide (SOS) Prevention and Screening Program   Suicide is the second-leading cause of death among youth ages 10 to 19 years, and data indicate no sign of it decreasing as a major public health issue. While acute care and crisis intervention are critical efforts to reduce adolescent suicide rates, there is…

Infliximab Biosimilars Improve Growth Outcomes in Children With Inflammatory Bowel Disease
Infliximab Biosimilars Improve Growth Outcomes in Children With Inflammatory Bowel Disease 1024 683 Mary Bates, PhD

Treatment with either the infliximab originator or a biosimilar improves clinical and growth outcomes. In a new study, researchers at Nationwide Children’s Hospital report that children with inflammatory bowel disease showed similar growth and clinical outcomes whether they were treated with the infliximab originator or a biosimilar agent. The results add to the growing literature…

Integrating PCOS Research and Clinical Care for Adolescents
Integrating PCOS Research and Clinical Care for Adolescents 1024 575 Pam Georgiana
Black and white image of teen girl posing outside

Researchers at Nationwide Children’s are participating in building the first-ever national registry of adolescent Polycystic Ovary Syndrome (PCOS) patient data through a National Institutes of Health (NIH)-funded research grant. The grant will collect patient data from more than 12 multidisciplinary PCOS clinics, including Nationwide Children’s. PCOS is a hormonal imbalance that can cause irregular menstrual…

How Are Insulin Pumps Being Utilized for Patients with Type 1 Diabetes?
How Are Insulin Pumps Being Utilized for Patients with Type 1 Diabetes? 1024 683 Pam Georgiana

A multicenter observational study of 22,000 children and adults shows improving quality of life for patients with type 1 diabetes.    Type 1 diabetes diagnoses are increasing among children, particularly those in racial/ethnic minority groups. New technology, specifically insulin pumps and continuous glucose monitoring (CGM) systems, may improve quality of life and long-term outcomes. However,…

Quality Improvement Approach Reduces Pediatric Asthma Emergency Department Visits by 33%
Quality Improvement Approach Reduces Pediatric Asthma Emergency Department Visits by 33% 770 513 JoAnna Pendergrass, DVM

With institutional support, a primary care-based quality improvement initiative markedly reduced asthma-related emergency department visits for children with asthma. Researchers at Nationwide Children’s Hospital implemented a quality improvement (QI) project that reduced pediatric asthma emergency department (ED) visits by 33% from 2010 to 2019. Stephen Hersey, MD, a pediatrician in Nationwide Children’s section of primary…

Modulator Therapy Improves Chronic Sinus Disease in Individuals with Cystic Fibrosis
Modulator Therapy Improves Chronic Sinus Disease in Individuals with Cystic Fibrosis 1024 683 Mary Bates, PhD

Following 1 year of therapy, patients showed improved sinus CT metrics and clinical outcomes. Over the last decade, the development of cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs has revolutionized the treatment of cystic fibrosis (CF). The most widely used modulator is the triple combination elexacaftor-tezacaftor-ivacaftor (ETI), which is approved for people with CF…

What Pulmonologists Need to Know About Respiratory Insufficiency in Neuromuscular Disease
What Pulmonologists Need to Know About Respiratory Insufficiency in Neuromuscular Disease 600 400 Katie Brind'Amour, PhD, MS, CHES

The RIND Study Group has released new consensus criteria to proactively identify hypoventilation in children with neuromuscular diseases. Recently released consensus criteria from an expert panel of pediatric pulmonologists and sleep specialists define and provide diagnosis guidance surrounding respiratory insufficiency in neuromuscular disease (RIND). The results from the 15-member RIND Study Group’s Delphi study, published…

Magnetically Controlled Limb Lengthening Devices Safe for Patients With Programmable Implantable Devices, Study Shows
Magnetically Controlled Limb Lengthening Devices Safe for Patients With Programmable Implantable Devices, Study Shows 1024 683 Erin Gregory
Dr. Iobst with patient

Recent study evaluated the safety and efficacy of using magnetically controlled intramedullary nails in patients with programmable implantable devices, shedding light on a previously unexplored area of orthopedic surgery. In a pivotal study published in the Strategies in Trauma and Limb Reconstruction, led by Christopher A. Iobst, MD, a pediatric orthopedic surgeon at Nationwide Children’s…

Adolescents With Concussion May Benefit from More Cognitive Activity as Early as the First Week After Injury
Adolescents With Concussion May Benefit from More Cognitive Activity as Early as the First Week After Injury 1024 575 Laura Dattner

A new study shows limiting screen time and returning to school early following a concussion may hasten recovery timelines. In a study published in British Journal of Sports Medicine, researchers with the Center for Injury Research and Policy, Division of Sports Medicine, Center for Biobehavioral Health, and Division of Emergency Medicine at Nationwide Children’s Hospital evaluated…

Introducing Nationwide Children’s Hospital’s Behavioral Health Learning Library
Introducing Nationwide Children’s Hospital’s Behavioral Health Learning Library 1024 683 Pam Georgiana

Access the free educational resource for health care providers interested in evidence-based courses. Jennifer B. Reese, PsyD, is a clinical child psychologist at Nationwide Children’s and manages behavioral health and training at Big Lots Behavioral Health Services. She is concerned about the national shortage of experienced behavioral health support for children. “Because there is a…

Neurorehabilitation for Children With Batten Disease
Neurorehabilitation for Children With Batten Disease 1024 683 Lauren Dembeck

Therapy should be tailored to each child’s needs. Batten disease comprises a rare group of related genetic disorders characterized by progressive neurodegeneration. The disease primarily presents in childhood as seizures, vision loss, and developmental regression. Neurorehabilitation services, including physical therapy (PT), occupational therapy (OT), and speech-language pathology therapy (SLP), can delay loss of function and…

RSV in Infants and High-Risk Children: A Commentary on the Roll-out of a New Preventive Medication
RSV in Infants and High-Risk Children: A Commentary on the Roll-out of a New Preventive Medication 1024 575 Pam Georgiana

According to the Centers for Disease Control and Prevention (CDC), respiratory syncytial virus (RSV) causes more than 2 million outpatient visits, as many as 80,000 hospitalizations, and 100 to 300 deaths in children under 5 years old annually. Infants under 6 months of age are at the most significant risk of hospitalization. Although the highest…

National Health Crisis: Treating Tobacco Dependence in Adolescents
National Health Crisis: Treating Tobacco Dependence in Adolescents 1024 575 Pam Georgiana
Teen girl with backpack

Partners For Kids® offers a free tool to support primary care providers use nicotine replacement therapy to increase smoking cessation success. In 2023, the Centers for Disease Control and Prevention (CDC) reported that more than 6.6% of middle school students and about 12.6% of high school students regularly use a tobacco product. Almost 2% of…

Implanted Hemodynamic Monitoring in Patients With Fontan Circulation
Implanted Hemodynamic Monitoring in Patients With Fontan Circulation 150 150 Mary Bates, PhD

Pulmonary artery pressures obtained with the CardioMEMSTM system may be clinically useful. In a new study, researchers from The Ohio State University and Nationwide Children’s Hospital report on the use of invasive implanted hemodynamic monitoring (IHM) in patients with Fontan circulation. The findings suggest that IHM pressures in these patients are more closely associated with…

Changing the Landscape of Blood Disorder Treatments: A Long Time Coming
Changing the Landscape of Blood Disorder Treatments: A Long Time Coming 1024 574 Alaina Doklovic

New therapies, from virus-mediated gene therapy to CRISPR-based treatments, are poised to change the clinical landscape of blood disorder treatments and outcomes.   For more than two decades experts have been searching for curative therapies for blood disorders. They have invested time, money and expertise to bring these therapies to fruition, something that the Division…

Kids With Concussions Need Specialized Assessment and Care
Kids With Concussions Need Specialized Assessment and Care 1024 683 Sean Rose, MD

Learn why cutting-edge care and research specifically for children matters. The 2020 National Health Interview Survey reported that 6.8% of children experience symptoms of a concussion or brain injury in their lifetime. However, only 3.9% had received a diagnosis or treatment of a concussion or brain injury from a health care provider. The Concussion Center…

Transforming Treatment for Paratesticular Rhabdomyosarcoma in Adolescents through Robotics
Transforming Treatment for Paratesticular Rhabdomyosarcoma in Adolescents through Robotics 1024 683 Erin Gregory

Retroperitoneal lymph node dissection (RPLND) has been a crucial component of treating testicular and paratesticular cancers for over a century. Recent advancements in minimally invasive techniques, such as robotic-assisted methods, have expanded the applicability of RPLND, offering reduced morbidity and faster recovery. However, concerns persist regarding the equivalence of oncological outcomes compared to traditional open…

Ensuring All Children Have Access to Behavioral Health Care
Ensuring All Children Have Access to Behavioral Health Care 531 213 Pam Georgiana

New study reports the results of integrating psychologists into primary care clinics. Cody A. Hostutler, PhD, a psychologist in the Department of Pediatric Psychology and Neuropsychology at Nationwide Children’s, is concerned about the mental health of the children and adolescents visiting primary care centers. “There is a mental health crisis for kids happening right now.…

What Other Screening Tests Should be Administered to Celiac Disease Patients?
What Other Screening Tests Should be Administered to Celiac Disease Patients? 1024 575 Mary Bates, PhD

Eliminating some labs may reduce costs without impacting quality of patient care. Researchers from Nationwide Children’s Hospital found that several screening laboratory tests currently recommended for pediatric patients newly diagnosed with celiac disease are infrequently abnormal. In a new study published in the Journal of Pediatrics, they suggest a more streamlined approach to decrease the…

Surgical Hip Dislocation as a Treatment Modality in Children and Adolescents
Surgical Hip Dislocation as a Treatment Modality in Children and Adolescents 150 150 Pam Georgiana

What was once a complicated surgery has now become a safe and effective way to treat many hip conditions.   Treatment of hip conditions and disorders in children and adolescents can be tricky. Doctors must have a thorough understanding of the patient’s anatomy, growth plates, and blood supply, as well as the existence of any…

Expanding Access to Genomic Testing in Level IV Neonatal Intensive Care Units
Expanding Access to Genomic Testing in Level IV Neonatal Intensive Care Units 1024 575 Pam Georgiana
conceptual art of DNA

Recent study identifies variations in availability and highlights opportunities to improve access to genomic testing in the United States and Canada. In the Nationwide Children’s Hospital neonatal intensive care unit, patients needing rapid genome sequencing can get it on demand without administrative approval. However, that is not the case in all level IV neonatal intensive…

Congenital Heart Disease and Extracardiac Phenotypes Associated With Novel Pathogenic Variant in GATA6
Congenital Heart Disease and Extracardiac Phenotypes Associated With Novel Pathogenic Variant in GATA6 1024 575 Jessica Nye, PhD

A study published in Pediatric Research describes a novel pathogenic variant in the gene GATA binding protein 6 (GATA6) associated with congenital heart disease (CHD), diabetes mellitus and necrotizing enterocolitis.   GATA is a family of transcription factors that encode zinc finger DNA binding proteins which are critical regulators during organogenesis. Pathogenic variants in three…

Enhancing Intestinal Rehabilitation Workflow with Disease-Specific Documentation Tools
Enhancing Intestinal Rehabilitation Workflow with Disease-Specific Documentation Tools 150 150 Erin Gregory

Structured data entry not only reduces the amount of time physicians are spending in the electronic health record but also opens the door for new research. A recent study published in JAMA Pediatrics by Nationwide Children’s Hospital’s Ethan Mezoff, MD, Jennifer Lee, MD, and team has shed light on a promising solution to improve the…

Treating Pediatric Melanoma: Ultrasound Surveillance vs. Completion Lymph Node Dissection for Sentinel Node Positive Patients
Treating Pediatric Melanoma: Ultrasound Surveillance vs. Completion Lymph Node Dissection for Sentinel Node Positive Patients 1024 683 Pam Georgiana

Treatments for pediatric melanoma are usually based on adult studies, but increasing recognition of the differences between pediatric and adult melanoma could change that. Pediatric melanoma is rare in the United States. The Skin Cancer Foundation reports that about 400 children under 20 years old are diagnosed with melanoma each year in the United States.…

Novel Cause of Brain Mosaicism and Focal Epilepsy Identified
Novel Cause of Brain Mosaicism and Focal Epilepsy Identified 1024 575 Abbie Miller

In Nature Genetics, researchers report a novel mechanism for the origin of brain chromosomal mosaicism and link brain mosaic chromosome 1q gain to a distinct clinical phenotype.   In most people, every cell in their body contains the same genetic information. However, sometimes people can have two or more genetically different sets of cells. This…

Increasing Same-Day Amoxicillin Graded Dose Challenges
Increasing Same-Day Amoxicillin Graded Dose Challenges 1024 683 JoAnna Pendergrass, DVM

A quality improvement initiative overcomes several barriers to de-labeling penicillin allergies. In a study published in The Journal of Allergy and Clinical Immunology: In Practice, a research team led by Margaret Redmond, MD, a pediatric allergist at Nationwide Children’s Hospital, reported on a quality improvement (QI) initiative that sustainably increased rates of same-day amoxicillin graded…

Building Hope, Recovery, and Life Beyond Substance Use Disorder
Building Hope, Recovery, and Life Beyond Substance Use Disorder 1024 702 Abbie Miller

Five years ago, Pediatrics Nationwide dedicated its fall issue to a comprehensive look at the effects of the opioid crisis on children and families. At that time, Sarah Parker was working hard to stay sober, recovering from the very crisis holding the nation’s attention. Parker grew up in Chillicothe, Ohio, halfway between Portsmouth, Ohio, the…

Whole Child, Whole Family Care
Whole Child, Whole Family Care 150 150 Abbie Miller and Jeb Phillips

Meeting the needs of children and caregivers with evidence-based programming and intentional support for access. Parenting a young child can be tough in the best circumstances. But when you overlay poverty, inequity, and concerns about employment and education on top of it, parenting a young child can feel overwhelming. Whitney Raglin Bignall, PhD, has dedicated…

Tissue Engineered Trachea: State of the Research
Tissue Engineered Trachea: State of the Research 150 150 Lauren Dembeck

The promise of tissue-engineered trachea grafts is moving closer to the clinic, as recent preclinical studies have shown successful implantation and neovascularization. Breathing is an essential biological function that provides our bodies with the oxygen necessary for survival. However, most of us rarely think about the biological structures that make it possible. The trachea, commonly…

Preventing Accidental Ingestion of Marijuana
Preventing Accidental Ingestion of Marijuana 1024 683 Abbie Miller

If you are a child, and you find a bag of fruit snacks — you don’t eat just one piece. The THC/marijuana products on the market today have an average of 10-20 mg in one serving. That’s one square of a chocolate bar, one gummy (which looks like a fruit snack) or one chip. “THC…

User Experiences with Subcutaneous DMPA
User Experiences with Subcutaneous DMPA 1024 683 Mary Bates, PhD

Survey reveals high satisfaction among adolescents and young adults using subcutaneous DMPA. Depot medroxyprogesterone acetate (DMPA) is a progestin-only injectable contraceptive that is used as a birth control method and in the treatment of heavy or painful menstrual periods, endometriosis, and for menstrual suppression. DMPA can be injected intramuscularly or subcutaneously, with no difference in…

Should You Offer Fentanyl Test Strips in Your Office?
Should You Offer Fentanyl Test Strips in Your Office? 150 150 Abbie Miller

Harm reduction approaches support the use of fentanyl test strips for individuals who are taking illicit substances but want to avoid fentanyl. Nichole Michaels, PhD, a principal investigator in the Center for Injury Research and Policy at Nationwide Children’s, is conducting two studies about the efficacy of offering and educating about fentanyl testing among adults.…

Combined Pediatric-Adult Anticoagulation Program Exceeds Goals
Combined Pediatric-Adult Anticoagulation Program Exceeds Goals 1024 580 Mary Bates, PhD

The program achieved excellent quality of anticoagulation therapy in children and adults. The goal of most anticoagulation programs is to improve the care of adult patients on warfarin therapy, specifically by treating and preventing thromboembolic events while minimizing bleeding risk. In a new study, researchers from Nationwide Children’s Hospital report excellent outcomes for a combined…

Recognizing the Benefits of Music and Massage Co-therapy in Pediatric Palliative Care
Recognizing the Benefits of Music and Massage Co-therapy in Pediatric Palliative Care 1024 680 JoAnna Pendergrass, DVM

For adolescent patients in home-based pediatric palliative care, co-treatment with music therapy and massage therapy benefits both the patients and their families. A case study recently published in Music & Medicine reported the benefits of co-treatment with music therapy and massage therapy for a patient in home-based pediatric palliative care. Complementary therapies, such as music…

QI Initiative Reduces Emergency Room Visits for Functional Constipation
QI Initiative Reduces Emergency Room Visits for Functional Constipation 1024 683 Katie Brind'Amour, PhD, MS, CHES

Preliminary data from a large accountable care organization’s quality improvement efforts suggest advanced care visits dropped 27% in two years. Partners For Kids (PFK), the nation’s oldest and largest pediatric accountable care organization, launched a series of quality improvement (QI) projects targeting disease management strategies that could significantly impact healthcare utilization and outcomes for children…

Ensuring Vulnerable Babies Receive the Benefits of Human Milk
Ensuring Vulnerable Babies Receive the Benefits of Human Milk 1024 575 Mary Bates, PhD
small baby with nose canula

A QI project increases human milk consumption among newborns hospitalized with congenital heart disease. The American Academy of Pediatrics and the World Health Organization recommend human milk for infants because of its important health benefits. However, most newborns with congenital heart disease (CHD) are separated from their mothers shortly after birth and admitted to a…

Safe, Minimally Invasive Upper Urinary Tract Surgery for Infants
Safe, Minimally Invasive Upper Urinary Tract Surgery for Infants 1024 575 Patti Doud
small baby with nose canula

Evidence supports robotic surgery as a safe approach to upper urinary tract procedures in infants 6 months or younger. While robotic surgery has risen in popularity and feasibility for procedures in both older children and adults alike, there has been little data to determine whether it’s a safe possibility for young children and infants. But…

Ask A Specialist: What Are the Recommendations for Sexually Transmitted Infections (STI) Screening in Primary Care?
Ask A Specialist: What Are the Recommendations for Sexually Transmitted Infections (STI) Screening in Primary Care? 1024 575 Cynthia Holland-Hall, MD
Teen girl with backpack

STI screening is recommended for all sexually active adolescents. According to the American Academy of Pediatrics, nearly 1 in 4 teens have an STI. Safe sexual practices and routine screening can prevent these infections – that’s where health care providers come in. By offering routine testing for all sexually active teens in addition to safe…

Fertility Concerns in Boys and Men With Sickle Cell Disease
Fertility Concerns in Boys and Men With Sickle Cell Disease 1024 575 Mary Bates, PhD
Color photo of Black father holding infant on shoulder in front of nursery background with clouds on the wall

Sickle cell disease and its treatments may impact fertility, but more research is needed to help counsel this population. Sickle cell disease (SCD) affects approximately 100,000 Americans, most of whom belong to underserved, minority populations. Advances in disease-modifying therapies, such as hydroxyurea, have led to better clinical outcomes. However, as more individuals with SCD survive…

Assessing Respiratory Stability in Infants Hospitalized with Bronchopulmonary Dysplasia
Assessing Respiratory Stability in Infants Hospitalized with Bronchopulmonary Dysplasia 1024 683 Mary Bates, PhD

The Behavioral Signs of Respiratory Instability Scale is a valid, reliable measure of respiratory status and developmental ability. In a new study, researchers at Nationwide Children’s evaluated the Behavioral Signs of Respiratory Instability (BSRI) Scale, which was developed as an objective measure of developmental capacity of infants with severe forms of bronchopulmonary dysplasia (BPD). The…

Home Infusions of Infliximab for Inflammatory Bowel Disease
Home Infusions of Infliximab for Inflammatory Bowel Disease 1024 683 Mary Bates, PhD

With a standardized care approach, home infusions may be an effective alternative to hospital-based infusions. Pediatric inflammatory bowel disease (IBD) is often treated with infusions of infliximab in a hospital setting. However, these can be costly and present time and travel barriers to patients and their families. Due to these considerations and recent insurance mandates,…

Expanding Use of Trikafta for Cystic Fibrosis to Patients as Young as 2 Years Old
Expanding Use of Trikafta for Cystic Fibrosis to Patients as Young as 2 Years Old 1024 683 Karen McCoy, MD
Smiling boy outside

When I first started my pulmonary training, the average life expectancy in the United States was about 70 years, and the average life expectancy for someone with cystic fibrosis (CF) was 14 years! Intense study and pursuit of consistent care across the country yielded improvements. By 2010, with standards of treatment very consistent and implementation…

Implementation Science to Expand Contraception Access for Adolescents Hospitalized with Mental Health Issues
Implementation Science to Expand Contraception Access for Adolescents Hospitalized with Mental Health Issues 1024 575 Pam Georgiana
Black and white image of teen girl posing outside

Research has documented that adolescents with mental health concerns have a higher need for contraceptive counseling and care because they are at a higher risk for unintended pregnancy.[i] [ii] Unintended pregnancies can make mental health symptoms worse, especially depressive symptoms. [iii] Counseling and use of contraceptives are simple evidence-based strategies to reduce unplanned pregnancies. However,…

FDA Approves Micro-dystrophin Gene Therapy for Duchenne Muscular Dystrophy
FDA Approves Micro-dystrophin Gene Therapy for Duchenne Muscular Dystrophy 1024 632 Abbie Miller

On June 22, 2023, the FDA announced accelerated approval for SRP-9001/ELEVIDYS for Duchenne muscular dystrophy (DMD) following decades of research in the Center for Gene Therapy at Nationwide Children’s Hospital. The FDA approved the treatment for pediatric patients 4-5 years old with DMD. Jerry Mendell, MD, principal investigator in the Center for Gene Therapy at…

Exploring Disordered Eating Beyond Binge Eating in Youth with Obesity
Exploring Disordered Eating Beyond Binge Eating in Youth with Obesity 150 150 JoAnna Pendergrass, DVM

Youth with obesity can suffer from various disordered eating behaviors beyond binge eating. A holistic approach to caring for these youth can help improve their long-term physical and psychological health outcomes. A literature review recently published in Nutrients shed light on eating disorders beyond binge eating in youth with obesity. In this review, Eileen Chaves,…

Ask A Specialist: What Running Distances Are Safe for Children?
Ask A Specialist: What Running Distances Are Safe for Children? 1024 895 Gabriella Gonzales, MD and James MacDonald, MD, MPH

Sports Medicine experts offer advice for pediatricians about what age it is appropriate for children to run and train for races such as the 5K, 10K, half marathon and marathon. Running is a great activity! It requires very little equipment and can be done individually or with a team. Running can be beneficial for children…

Is Growth Hormone Replacement Safe Following Central Nervous System Tumors?
Is Growth Hormone Replacement Safe Following Central Nervous System Tumors? 1024 683 Mary Bates, PhD

Research suggests the benefits of growth hormone therapy outweigh the risks for pediatric cancer survivors. In a new review paper, researchers from Nationwide Children’s Hospital evaluated the risks and benefits associated with administering growth hormone to pediatric patients after diagnosis of a central nervous system tumor. The authors conclude that the therapy has many important…