A journal of The Children’s Medical Center of Dayton SUMMER 2010 VOLUME 22 NUMBER 2 CME accredited articles FREE CME credits available Implementation of a nitrous oxide service Page 3 Undifferentiated high grade pleomorphic sarcoma Page 6 Evaluating for osteroporosis at Dayton Children’s Page 7 Frequency of childhood cancer types diagnosed and treated at Dayton Children’s Page 9 Genetic testing update Page 11 News and Updates Page 15 2 Pediatric Forum A journal of The Children’s Medical Center of Dayton SPONSORSHIP/ACCREDITATION INFORMATION Physician accreditation statement and credit designation Wright State University (WSU) Boonshoft School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. WSU Boonshoft School of Medicine designates this educational activity for a maximum of 2.0 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity. 1 Children’s Plaza Dayton, Ohio 45404-1815 Obtaining CME credit 937-641-3000 To obtain CME credit, read, reflect on childrensdayton.org articles, complete and return the answer sheet and program evaluation to: Pediatric Forum is produced for the professional staff and referring physicians of The Children’s Medical Center of Dayton by the marketing communications department. The purpose of Pediatric Forum is to provide information and news about pediatric health care issues and to provide information about clinical services and management issues of Dayton Children’s. Sue Strader, coordinator Department of Continuing Medical Education The Children’s Medical Center of Dayton One Children’s Plaza Dayton, OH 45404-1815 Fax 937-641-5931 The answer sheet and program evaluation must be received by August 31, 2011 for the credit to be awarded. Upon completion of all requirements, WSU will issue a memorandum of credit to you for your permanent records. As an organization accredited for CME, WSU Boonshoft School of Medicine fully complies with the legal requirements of the Americans with Disabilities Act rules and regulations. If any participant is in need of accommodations, written requests should be submitted at least one month in advance. Target audience This education activity is designed for pediatricians, family physicians and related child health care providers. Educational objectives • Articles will review commonly encountered clinical conditions and provide updates in pediatric medical and surgical care. • Each individual article will have activity-specific learning objectives. Affiliations/disclosures of authors Lucinda Brown, RN The Children’s Medical Center of Dayton Elizabeth Ey, MD The Children’s Medical Center of Dayton Dawn Light, MD, MPH The Children’s Medical Center of Dayton L. David Mirkin, MD The Children’s Medical Center of Dayton Ruthann Pfau, PhD The Children’s Medical Center of Dayton Jenna J. Wheeler, MD Wright State University Boonshoft School of Medicine L. David Mirkin, MD Dr. Mirkin has nothing to disclose with regard to commercial support. Dr. Mirkin does not plan on discussing unlabeled/investigational uses of a commercial product. Ruthann Pfau, PhD Dr. Pfau has nothing to disclose with regard to commercial support. Dr. Pfau does not plan on discussing unlabeled/investigational uses of a commercial product. Jenna J. Wheeler, MD Ms. Wheeler has nothing to disclose with regard to commercial support. Ms. Wheeler does not plan on discussing unlabeled/investigational uses of a commercial product. The content and views presented are those of the author and do not necessarily reflect those of the publisher, The Children’s Medical Center of Dayton. Unlabeled use of products may be mentioned. Before prescribing any medicine, primary references and full prescribing information should be consulted. Author conflict of interest information It is the policy of Wright State University to ensure balance, independence, objectivity and scientific rigor in all educational activities. All authors contributing to our programs are expected to disclose any relationships they may have with commercial companies whose products or services may be mentioned so that participants may evaluate the objectivity of the program. In addition, any discussion of off-label, experimental or investigational use of drugs or devices will be disclosed by the authors. Contributing authors reported the following: Lucinda Brown, RN Ms. Brown has nothing to disclose with regard to commercial support. Ms. Brown does not plan on discussing unlabeled/investigational uses of a commercial product. Elizabeth Ey, MD Dr. Ey has nothing to disclose with regard to commercial support. Dr. Ey does not plan on discussing unlabeled/investigational uses of a commercial product. Dawn Light, MD, MPH Dr. Light has nothing to disclose with regard to commercial support. Dr. Light does not plan on discussing unlabeled/investigational uses of a commercial product. EDITORIAL BOARD Arthur Pickoff, MD, chairperson Cindy Asher, RN Emmett Broxson, Jr, MD Lisa Coffey Elvira R. Jaballas, MD L. David Mirkin, MD Sherman Alter, MD Continuing medical education liaison David Kinsaul, FACHE President and Chief Executive Officer Thomas Murphy, MD, MPH Vice President for Medical Affairs Jeffrey Christian, MD Chairman of the Professional Staff NITROUS OXIDE — IMPLEMENTATION OF A NITROUS OXIDE SERVICE Objectives Following the completion of this article, the reader should be able to: 1. Discuss the history of the use of nitrous oxide. 2. Identify patients who can benefit from the use of nitrous oxide. 3. Explain the contraindications and side effects of nitrous oxide. Overview and History Since its discovery 150 years ago, nitrous oxide (N2O) has been used to provide pain and anxiety relief for patients undergoing surgical procedures. Nitrous oxide/oxygen (N2O/O2) is often used as an adjunct to supplement general anesthesia. Many disciplines use N2O/O2 as an effective means to provide pain and anxiety control during outpatient and ambulatory procedures. It has been used for dental procedures, medical imaging studies and procedures performed in the emergency department (ED). The use of N2O/O2 has gained popularity for many reasons. This inhaled gas can be titrated easily to meet the patient’s physiologic and psychological needs. The gas leaves the patient’s system quickly and can be reversed with minimal side effects.1 Nitrous oxide has been cited in the literature for years as a safe and effective drug. In the late 1800s, a professor documented its use in 193,000 cases with no adverse reactions. Ruben, a Danish researcher, cites three million cases using N2O/O2 in the dental office without any adverse reactions.1 More recently used as a mild analgesic and sedative, N2O is administered with oxygen from safe equipment that allows no more than 70% N2O and no less than 30% O2 to be delivered at any time. The pediatric patient is mildly sedated and can respond to commands. Protective reflexes such as cough and gag are left intact and the elimination of the drug is rapid. Recovery is complete in a short time and the child may go home. This is unlike the period of time the child must stay to recover after receiving opioids and/or benzodiazepines. The American Society of Anesthesiologists (ASA) and the American Dental Association (ADA) have published guidelines which speak to the use of N2O/O2. These guidelines were developed in 2002 and direct the trends and practice of N2O/O2.2,3 ASA guidelines were intended for use by non-anesthesiologists in practice settings where children undergo painful procedures and are required to be still for a period of time. Both sets of guidelines refer to the use of N2O/O2 in concentrations greater than 50% and the use of nitrous oxide with other medications such as midazolam. Moderate sedation is achieved in these cases. The use of nitrous oxide alone and in concentrations less than 50% produces anxiolysis in the pediatric patient and not moderate sedation. 3 What is nitrous oxide and how is it administered? Nitrous oxide is a colorless, odorless gas which has anxiolytic, amnesic and mild-to-moderate analgesic properties. It has a rapid onset of effect and rapid recovery, typically taking less than five minutes. The child is able to remain awake, follow minimal commands and have minimal side effects. Procedures using nitrous oxide include lumbar puncture, bone marrow aspiration, venous cannulation, dressing changes and urethral catherization.4 Standard delivery devices that provide a continuous flow of nitrous oxide, titratable from 0-70%, have a fail-safe mechanism which terminates nitrous oxide flow in event of cessation of oxygen flow. These systems also have a non-rebreathing valve to prevent exhaled gas from contaminating the system and an emergency air inlet. A scavenging apparatus designed to eliminate exhaled nitrous oxide is an integral part of the equipment and minimizes exposure of health care providers to nitrous oxide. Dental nasal hoods are used to administer nitrous oxide. These hoods are scented but also can be scented by the choice of the child based on his or her favorite flavor. Nitrous oxide does have an abuse potential so when not in use, the gas needs to be secured in a locked storage cabinet.1 Elizabeth Ey, MD Elizabeth Ey, MD, is medical director of medical imaging at Dayton Children’s. Dr. Ey is board certified in diagnostic radiology and has a certificate of added qualification in pediatric radiology. She performs angiography and interventional studies such as drainages, biopsies and intraoperative image guidance. Lucinda Brown, RN Lucinda Brown, RN, is a clinical nurse specialist at Dayton Children’s. She is on the board of directors for the Society of Pediatric Nurses and the American Pediatric Surgical Nurses Association. She is also a certified Pediatric Advanced Life Support faculty. Program development An interdisciplinary team was formed at The Children’s Medical Center of Dayton to implement a nitrous oxide program in medical imaging and the ED. This team was a component of a larger team which had spent two years reviewing the literature and developing a procedural pain pathway including the use of patient preparation/ coaching/distraction, topical A literature search was performed and programs reviewed across the United States including a program in place at Minnesota Children’s.4 Hospital approval was obtained for the service and the process. A policy, procedure, order set, documentation forms and patient education materials were developed (Figure 1). Practitioners received extensive education and were credentialed to order or educated to administer nitrous oxide. Child life specialists were involved in this project as the use of guided imagery or helping patients think of a “happy place” is an important part of the successful use of Figure 1 Would you like Nitrous Oxide to be used during your child’s procedure again? 83% NO Did you feel that the use of nitrous oxide helped your child tolerate the procedure better by relaxing? YES Nitrous Oxide Family Survey NA Children who are candidates for nitrous oxide use must be three years of age and have a pre-procedure assessment. When used by itself (without other medications) at concentrations lower than 50%, nitrous oxide is not considered to provide moderate sedation; however, the process for moderate sedation is followed. This process includes a pre-procedure assessment, consent for use and discharge by use of moderate sedation criteria. Contraindications include any condition where air is trapped in the body (pneumothorax, intestinal obstruction and middle ear occlusion), increased intracranial pressure, pregnancy, vitamin B12 deficiency, impaired level of consciousness, history of bleomycin administration, intoxication with drugs or alcohol and current or recovering drug addiction. In addition, nitrous oxide can only be delivered via a staff member who has received education and training. Side effects may include lethargy, headache, confusion, dizziness and nausea. The potential for side effects are decreased when the patient has a slow induction and emergence from the gas. anesthetics and sedation. Dentists and dental techs routinely administer nitrous oxide across the United States; however the use of nitrous oxide by other health care providers is limited by state law. Ohio does allow nurses to administer nitrous oxide by order of physicians but not advanced practice nurses. 13% 4% YES Patient selection and contraindications NO 4 91% 9% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Previous methods used were distraction, positioning and versed. Figure 2 Nitrous Oxide Family Survey How would you rate the overall effectiveness of Nitrous Oxide? 90 78% 80 70 60 50 40 30 20 10 0 13% 4% 4% 0% Not Effective Somewhat Effective Effective There was a total of 23 family surveys conducted. Very Effective NA nitrous oxide. The dental service was instrumental in providing the expertise to initiate this program. An audit tool also was initiated so that data could be obtained regarding patient, family and staff satisfaction. Process Nitrous oxide sedation has been successfully implemented in medical imaging at Dayton Children’s. This form of sedation is used primarily for bladder catheterization prior to voiding cystourethrography (VCUG). One advantage of nitrous oxide sedation is the sedation effect wears off quickly which permits the child to sense how full the bladder is and to void during the procedure when requested. Nitrous oxide is offered when the procedure is scheduled and requested by the referring physician. The patient must meet the appropriate guidelines for nitrous oxide and must follow the pre-sedation guidelines for moderate conscious sedation. Staff in medical imaging have been pleased with the rapid recovery for patients after nitrous oxide; however, the implementation time for entire nitrous oxide sedation is lengthy, still approximately two hours. Discussions are ongoing to determine if this can be shortened and made more efficient. When patients and families are surveyed regarding their experience with nitrous oxide sedation, the comments have been very positive. Data review To evaluate the effectiveness of nitrous oxide use, a survey is given to the family and the administering nurse providing the nitrous oxide to the patient. The return of these surveys has been significant and the data is collated by quality resource management. Several questions are asked on the family survey but the three most important questions/responses are regarding effectiveness, ease of use and probability of using again (Figure 2). Notably, families felt nitrous oxide helped their children tolerate the procedure by relaxing and they welcome the use of the nitrous oxide again. The staff felt nitrous oxide was effective (81 percent), easy to use (100 percent) and that they would use the gas again (88 percent). The staff also noted that patients exhibited very few side effects (94 percent felt no side effects at all). Plans to expand the service include increasing utilization in the ED and laboratory for patients who are challenged with blood draws. References 1. Clark, M and Brunick, A. Handbook of Nitrous Oxide and Oxygenation. Second Edition. Philadelphia: Mosby, 2003. 2. ASA Task Force: Practice guidelines for sedation and analgesia by non-anesthesiologists, Anesthesiology 96(4):1004, 2002. 3. American Dental Association: Guidelines for the use of conscious sedation, deep sedation, and general anesthesia for dentists, ADA House of Delegates, October, 2002, American Dental Association. 4. Farrell, M, Drake, G, Rucker, D, Finkelstein, M, and Zier, J. Creation of a Registered NurseAdministered Nitrous Oxide Sedation Program for Radiology and Beyond. Pediatric Nursing. 2008; 34:29-35. 5 CME Questions 1. Contraindications to the use of nitrous oxide include a.Pneumothorax b.Concurrent use of vancomycin c.Anemia d.Increased blood pressure 2. Side effects of rapid induction of or emergence from nitrous oxide include a.Respiratory arrest b.Decreased blood pressure c.Hallucinations d.Nausea 3. The maximum concentration of nitrous oxide that can be administered is a.80% b.50% c.70% d.30% 6 L. David Mirkin, MD David Mirkin, MD, serves as medical director of pathology and the clinical laboratory at Dayton Children’s. He is professor of pathology and pediatrics at Wright State Boonshoft School of Medicine. UNDIFFERENTIATED HIGH GRADE PLEOMORPHIC SARCOMA Case Study Case Discussion A 16-year-old male presented with a large lumbar mass extending from T10 to L4 without involvement of the muscles or spinal structures. A birthmark had developed in a cluster of moles that was removed with neotil at 9 years of age. Ten months before the current visit, the mass began to enlarge and after being treated with coconut oil, by suggestion of a naturalist, eroded and bled. The mass was removed surgically. Undifferentiated high grade pleomorphic sarcoma is rare in children. The most commonly affected site is the deep soft tissue of the extremities. A few patients present with malaise, fever and weight loss, and in the case of retroperitoneal lesions, abdominal pain. It may appear after a long interval (average 10 to 12 years) following radiation and may also arise in chronic ulcers and scars. Local recurrence in most series has been in the range of 50 to 60 percent and metastases occurred in 20 to 30 percent of cases. The surgical specimen consisted of a dark red ovoid, one half covered by extensively ulcerated skin, 18.l5 cm x 17.0 cm x 14.0 cm, weighing 1,612 g. The deep surface of resection showed a circumscribed fascia-like appearance. Sectioning demonstrated a massive hemorrhage and a Objective yellow central Following the completion of area of necrothis article, the reader should sis 6.0 cm in be able to: diameter. 1. Recognize the main clinical and morphological features of this neoplasm and to evaluate some of the therapeutic strategies. Microscopic examination revealed a highly cellular, markedly pleomorphic and extensively necrotic malignant neoplasm infiltrating margins of resection composed of spindle or round, occasionally multinucleated cells with generous cytoplasm. Marked anaplasia and atypical mitotic figures were observed (Figure 1). Differential diagnosis included pleomorphic rhabdomyosarcoma, fibrosarcoma, melanoma and pleomorphic sarcomatoid carcinoma. Immunoperoxidase stains for myogenin, desmin, myo-D1, actin and S100 were negative. Ultrastructure shows relatively undifferentiated, non-specific fibroblast-like or histiocytic-like features. Surgery, adjuvant radiotherapy and chemotherapy are part of the treatment. Doxorubicin and ifosfamide have been used for over 15 years for sarcomas of the extremities. Gemcitabine and docetaxel have been tried as a useful combination in metastatic sarcoma. References 1. Weiss SW and Goldblum JR. Malignant fibrous histiocytoma (pleomorphic undifferentiated sarcoma). Soft Tissue Tumors. 5th ed. Philadelphia, PA: Mosby; 2008:406-414. 2. Montgomery E. Malignant fibrous histiocytoma. In: Silverberg SG et al eds. Surgical Pathology and Cytopathology. 4th ed. Philadelphia, PA: Churchill Livingstone; 2006: 333-335. 3. Fletcher CDM, van den Berg E, Molenaar WM. Pleomorphic malignant fibrous histiocytoma/ undifferentiated high grade pleomorphic sarcoma. In: Fletcher CDM, Unni KK, Mertens F. eds. Tumours of Soft Tissue and Bone. Lyon, France: IARCPress; 2002:120-122. CME Questions 4. Undifferentiated high grade pleomorphic sarcomas are rare in children. a.True b.False 5. The most commonly affected site is the deep soft tissue of the extremities. a.True b.False 6. The neoplasm may arise in chronic ulcers and scars. a.True b.False EVALUATING FOR OSTEROPOROSIS AT DAYTON CHILDREN’S Objectives Following the completion of this article, the reader should be able to: 1. Describe indications for bone densitometry in children. 2. Apply normative T and Z scores in planning clinical interventions. 3. Appreciate the costs of CT densitometry for children. QCT uses the in-house CT and provides a technically more accurate estimate of bone density. No measurable gonadal exposure for the low-dose methods normally used for QCT exists. The QCT radiation exposure to the bone marrow is five millirem to the whole body, compared to a chest x-ray which would be about 3 millirem to the whole body. Why Screen for Bone Mineral Density? Medical Imagers at Dayton Children’s can finally confidently evaluate pediatric patients for evidence of osteopenia and osteoporosis. Our newest CT scanner is capable of QCT (Quanitative Computed Tomography) and we have concluded that UCSF pediatric normative data is an appropriate comparison standard for our population. Osteopenia results when bone synthesis is not enough to offset normal bone loss. This can be suggested on plain films and is a strong risk factor for osteoporosis. Osteoporosis is a condition characterized by a decrease in the density of bone, decreasing its strength and resulting in fragile bones. The amount of calcification in the bones can be calculated and completed using DXA (dual energy absorptiometry) or QCT. DXA vs. QCT bone densitometry DXA uses a smaller radiation dose, but requires a standalone machine and is less useful in patients with arthritis, severe spinal deformity and prior surgery. 1. To establish a diagnosis of osteoporosis or assess its severity in the context of general clinical care. 2. To monitor bone density in patients receiving glucocorticoid therapy. 3. To diagnose patients at risk for bone loss due to chemotherapy, neuromuscular weakness, endocrine disease and non-weight bearing. Which are Common Indications for Screening in Children? 4 Cystic Fibrosis 4 Family History of Osteoporosis 4 Numerous fractures 4 Chronic Renal Disease 4 Long-term use of steroids 4 Muscular Dystrophy 4 Disorders/FTT 4 Cachexic /Malabsorption 4 Cerebral Palsy 4 Endocrine Disorders The CPT code for QCT bone densitometry is 76070, CT Bone Density study. How is QCT obtained? A lateral scout view allows the technologist to localize the vertebral levels. A 1 cm thick scan is obtained at L1 and L2. For each level, the average bone mineral density in (mg/cc K2HPO4) is calculated for a 5 cc voxel of vertebral marrow. These values are matched to age/gender similar standard values. Patients are assessed based on where their scores fall on a bell curve. The T and Z scores are standard deviation values for the patients compared to the mean. T-score shows the amount of bone the patient has compared to a young adult of the same gender with peak bone mass.2 4 >-1 = normal 4 -1 to -2.5 = osteopenia 4 <-2.5 osteoporosis Z score is a T-score corrected for age. Most experts recommend using Z-scores rather than T-scores for younger men, premenopausal women and children. Hematology, pulmonary and nephrology clinicians order majority of scans, however a relatively large population of other children probably can benefit from screening. Though most children tested are normal, 25 percent are osteopenic and 13 percent are osteoporotic. 7 Dawn Light, MD, MPH Dawn Light, MP, MPH, completed a family practice fellowship in faculty development at the University of North Carolina in Chapel Hill in addition to a faculty development fellowship and a diagnostic radiology residency at Madigan Army Medical Center in Washington. Dr. Light is a member of the American College of Radiology and the Order of Military Medical Merit among others. 8 References 1. Gilsanz V, Varterasian M, Senac MO, Cann CE. 1986. Quantitative spinal mineral analysis in children. Ann Radiol 29:380-382. 2. Gilsanz V. Bone density in children: a review of the available techniques and indications European Journal of Radiology, Volume 26, Issue 2, Pages 177-182. 3. Gilsanz V, Gibbens DT, Roe TF, Carlson M, Senac MO, Boechat MI, Huang HK,Schulz EE, Libanati CR, Cann CE. 1988. Vertebral bone density in children: Effect of Puberty. Radiology 166:847-850 4. Clark EM, Tobias JH, Ness AR. Association Between Bone Density an Fractures in Children: A Systematic Review and Metaanalysis. Pediatrics Vol. 117 No. 2 February 2006, pp. e291-e297. 5. http://www.nof.org/osteoporosis/bmdtest.htm example: Curesearch. Available at http://nccf. org/our_research/index. Accessed March 11, 2008. Table 1 Normal Osteopenia Osteoporosis The Initial Experience at Dayton Children’s BURK ALL BMT ALL LCH ALL HL AED REN ALL AML/BMT CP ALL OSARC ALL FX GI ALL ALL ST NHL AED CF ALL ALL FX ALL HL CGD ST ALL REN TH/GH ALL REN CP DEF ALL BURK REN ALL/NHL ALL ALL BMT FX HODG ST ALL CF ALL ALL ST RENAL RENAL ALL FX ST CF FX RENAL ST TEF ALL REN FX/CP ALL ALL ALL SLE ALL/BMT FX/CP FX OP +1 Z-score -2.6 BR CA -5 CME Questions 7. How can you explain the radiation dose of QCT to a parent? a.The QCT radiation exposure to the bone marrow is 5 millirem to the whole body compared to a chest x-ray which would be about 3 millirem to the whole body b.There is no radiation with QCT c.There is no radiation with DEXA scan d.None of the above 6. http://www.niams.nih.gov/ Health_Info/Bone/Bone_Health/ Juvenile/default.asp 8. T-score compares your patient to a young adult of the same gender with peak bone mass. a.True b.False 7. http://www.bestbonesforever. gov/ (patient site) 9. Z score is a T-score corrected for age. a.True b.False 8. http://www.qct.com/Pages/ What_is_QCT.html 10. Which of the following is not a common indication for bone densitometry? a. Long term steroid use for pulmonary and heme-onc patients b. Patients with renal disease c. Osteogenesis Imperfecta d. Patients with CP e. Patients with history of multiple fractures FREQUENCY OF CHILDHOOD CANCER TYPES DIAGNOSED AND TREATED AT DAYTON CHILDREN’S: A COMPARISON TO NATIONAL DATA. Objectives Following the completion of this article, the reader should be able to: 1. Understand the types of childhood cancer diagnosed at Dayton Children’s (DC) from 1994-2007. 2. Compare the types of pediatric cancer diagnosed at this institution from 1994- 2007 to a national database of childhood cancer pertaining to the same interval. This study examines the occurrence of various cancers diagnosed and treated at Dayton Children’s (DC) as compared to national occurrence trends from 19942007 and to determine, of the 10 cancers selected, if DC has an incidence rate for a particular cancer that varies significantly from national data. This study included patients </= 20 years old (yo) at time of diagnosis with a primary pathologic diagnosis for one of the following: leukemia, brain and nervous system tumor, Wilms tumor, neuroblastoma, Hodgkin lymphoma, non-Hodgkin lymphoma (NHL), rhabdomyosarcoma, retinoblastoma, osteosarcoma or Ewing sarcoma. Background While the five-year survival rate for childhood cancer has been rising over past decades, approximately one out of every 315 children less than 20 years of age will be diagnosed with some form of cancer. Approximately 12,500 new childhood cancer diagnoses in the United States are made annually. Of the total annual cancer diagnoses, leukemias account for 30 percent, brain and nervous sys- tem tumors 22 percent, neuroblastomas 7 percent, Wilms tumors 6 percent, non-Hodgkin lymphomas (NHL) including Burkitt 4.2 percent, Hodgkin lymphomas 4 percent, both rhabdomyosarcomas and retinoblastomas 3 percent each, osteosarcomas 2 percent, Ewing sarcomas 1.8 percent and the remaining 20 percent are attributed to various other cancer types. Methods Data were compiled from the Oncolog reporting system used by DC to document all cancer cases diagnosed and treated at this facility from 1994-2007 totaling 728 patients. Data including patient’s medical record number, age at diagnosis and year of diagnosis were recorded. Diagnoses were confirmed using the Powerpath pathology reporting system to obtain each medical record number and corresponding histology/pathology reports. Medical records were viewed via the HBOC network for all patients who did not have a definitive pathology report in the Powerpath system. Exclusion criteria included any patient with an unclear diagnosis (three patients), those patients age >/= 21 yo at time of diagnosis (three patients) and patients with a secondary cancer or nonmalignant diagnosis (five patients) for a population of 717 patients after exclusion. The data obtained were then compared with national data, regarding the percent of overall childhood cancers for which each specific diagnosis is responsible. Ten specific cancer diagnoses were compared to national data using the exact binomial method (Table 1). The goal was to find any variation from national data at DC 9 L. David Mirkin, MD David Mirkin, MD, serves as medical director of pathology and the clinical laboratory at Dayton Children’s. He is professor of pathology and pediatrics at Wright State University Boonshoft School of Medicine. and Table 1 1994-2007 Dayton Children’s cancer occurrence trends compared with national occurrence trends N=717 # Patients with diagnosis Percent N *Wilms tumor 25 3.49 National percent 6.00 *Ewing sarcoma 24 3.35 1.80 Total leukemia 208 29.01 30.00 ALL 167 23.29 AML 37 5.16 JMML 3 0.42 APML 1 0.14 Total brain/nervous system tumors 160 22.32 Glioma, all types 31 4.32 Astrocytoma, other types 30 4.18 Other 30 4.18 Medulloblastoma/PNET 28 3.91 Pilocytic astrocytoma 20 2.79 Ependymoma 17 2.37 GBM 3 0.42 Schwannoma 1 0.14 Neuroblastoma 36 5.2 Total lymphoma 63 8.79 Hodgkin lymphoma 36 5.02 Non-Hodgkin lymphoma 27 3.77 4.20 Osteosarcoma 22 3.07 2.00 Rhabdomyosarcoma 15 2.09 3.00 Retinoblastoma 13 1.81 <3.00 Jenna J. Wheeler, MD 22.00 7.00 4.00 * Signifies statistically significant different percentages of specific cancers diagnosed at Dayton Children’s compared to nationally. Jenna Wheeler, MD, is a PGY3 pediatric resident at Rainbow Babies and Children’s Hospital in Cleveland, Ohio. She received her medical school degree from Wright State University Boonshoft School of Medicine and will begin a pediatric critical care medicine fellowship July 2011. 10 Acknowledgments: I would like to thank the following for their contributions to this study and to this article: Elizabeth Koelker, tumor registrar; Adrienne Stolfi, MSPH; Nancy Bangert, RN; John Pascoe, MD, MPH; and, Emmett Broxson, MD. using a one proportion report for each diagnosis, hypothesis testing, calculation of confidence intervals (CI) and a Bonferroni correction of our p value for statistical significance (p=0.05/10=0.005). All hypothesis tests and 95 percent CI were performed using the NCSS statistical software. Table 2 Comparison of childhood cancer data obtained at Dayton Children’s to that of the national database % N at DC 95 % Confidence interval p value *Wilms tumor 3.49 2.27-5.10 0.0045 *Ewing sarcoma 3.35 2.16-4.94 0.0034 Total leukemia 29.01 25.71-32.48 0.57 Total brain and nervous system tumors 22.32 19.32-25.54 0.86 Results Neuroblastoma 5.02 3.54-6.88 0.04 Hodgkin lymphoma 5.02 3.54-6.88 0.18 The occurrence rates for eight of the 10 cancers studied were found to be very similar to the national data, specifically the following: total leukemia 29.01 percent (95 percent CI: 25.71-32.48, p=0.57); total brain and nervous system tumors 22.32 percent (95 percent CI: 19.32-25.54, p=0.86); neuroblastoma 5.02 percent (95 percent CI: 3.54-6.88, p=0.04); Hodgkin lymphoma 5.02 percent (95 percent CI: 3.54-6.88, p=0.18); NHL 3.77 percent (95 percent CI: 2.505.43, p=0.58); rhabdomyosarcoma 2.09 percent (95 percent CI: 1.18-3.43, p=0.16); retinoblastoma 1.81 percent (95 percent CI: 0.97-3.08, p=0.06); and, osteosarcoma 3.07 percent (95 percent CI: 1.93-4.61, p=0.05) (Table 2). Non-Hodgkin lymphoma 3.77 2.50-5.43 0.58 Osteosarcoma 3.07 1.93-4.61 0.05 Rhabdomyosarcoma 2.09 1.18-3.43 0.16 Retinoblastoma 1.81 0.97-3.08 0.06 Wilms tumor and Ewing sarcoma both showed a statistically significant difference from the national occurrence trend. Wilms tumor occurrence was statistically lower at DC at 3.49 percent (95 percent CI: 2.27-5.10, p=0.0045) with the national percentage being 6.00 percent. It also was found that the prevalence of Ewing sarcoma was significantly higher at DC at 3.35 percent (95 percent CI: 2.16-4.94, p=0.0034) compared with national data of 1.8 percent (Table 2). Discussion This study has shown that a statistically significant increased occurrence of Ewing sarcoma exists at DC. The reason for this increase is currently unknown and warrants further study to determine a Type of cancer * p values <0.005 were considered statistically significant cause or a commonality between patients. Such cause may provide important information to clinicians regarding their patients. This study also has shown a statistically significant decreased rate of Wilms tumor diagnoses, which corresponds to the mild decrease found via the Surveillance, Epidemiology and End Results (SEER) program report including data from 1992-2004. Again, the reason for this decrease at DC is unknown and searching for a cause can provide a subject for further studies. If a definitive reason is later elicited, it may become important to clinicians located at other institutions as a way to potentially lower their occurrence rates as well. References 1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA: A Cancer Journal for Clinicians. 2006; 56; 106-130. 2. Steele JR, Wellemeyer AS, Hansen MJ, et al. Childhood cancer research network: a North American pediatric cancer registry. Cancer Epidemiology Biomarkers & Prevention. 2006: 15: 1241-1242. 3. Curesearch. Available at http:// nccf.org/our_research/index. Accessed March 11, 2008. 4. American Cancer Society. Available at www.cancer.org. Accessed March 18, 2008. 5. Massey Cancer Center. Available at www.massey.vcu.edu/ typesofcancer/?pid=1581. Accessed March 18, 2008. 6. Linabery AM and Ross JA. Trends in childhood cancer incidence in the U.S. Cancer. 2008; 112 (2); 416-432. CME Questions 11. The overall five-year survival rate for childhood cancers is increasing. a.True b.False 12. The childhood cancer type accounting for the highest percentage of annual new cancer diagnoses is leukemia. a.True b.False 13. The 1992-2004 SEER program report demonstrated a decrease in the number of annual diagnoses of Wilms tumor. a.True b.False GENETIC TESTING UPDATE: MICROARRAY-BASED COMPARATIVE GENOMIC HYBRIDIZATION Objectives Following the completion of this article, the reader should be able to: 1. Describe the essential difference between standard FISH and aCGH testing. 2. List two situations where aCGH testing may be useful. 3. List two situations where aCGH will not detect an existing chromosome abnormality. Twentieth Century Cytogenetics Remember how simple cytogenetic testing used to be? A normal chromosome test meant a patient had 46 chromosomes, with either two Xs or one X and one Y, and no obvious extra, missing pieces or rearrangements of those 23 pairs of chromosomes. Then came high resolution chromosome analysis—still the gold standard—and small deletions, duplications and rearrangements of 4-10 million base pairs of DNA were more easily identified. Later on, fluorescence in situ hybridization (FISH) detected changes in number of copies of a specific chromosomal region using small fluorescently labeled pieces of DNA from known locations (probes) that attached to matching DNA in cells or chromosomes on a slide. The probe stuck to its matching DNA sequence, the target, and fluoresce, leaving a glowing spot on the cell or chromosome where the probe had found its match. Cells with two fluorescing spots, or signals, had two copies of the target DNA, while a deletion of target DNA sequence meant only one glowing signal would be evident. Similarly, a genetic duplication of the DNA target produced three probe signals. With FISH, submicroscopic deletions invisible with standard cytogenetic banding were suddenly easily detectable. Changes of 100,000 DNA base pairs were routinely detected, as long as one had a probe for the exact target. Panels of FISH probes designed to detect the chromosomal subtelomeric regions provided simultaneous detection of the tips of all the chromosomes to look for otherwise invisible rearrangements at the telomeres. Clinical reports listing dozens of children with non-syndromic developmental delays who had submicroscopic and subtelomeric chromosome rearrangements excited laboratorians and caregivers alike. Finally, geneticists began to diagnose some of those patients with tiny imbalances that had been suspected to exist but weren’t able to be found! Fast forward to 2010 Amazing advances in technology have resulted in the rapid evolution of genetic testing approaches. New technology allows detection of ever-smaller changes in the number of copies of DNA. One of the new tools to emerge has been microarray technology. A microarray is essentially a container that allows one specimen—one patient—to undergo numerous tests all at once. Just as many kinds of software exist for different functions of a computer, different forms of microarray exist to evaluate different aspects of a person’s genes such as integrity of sequence, function, or absence of a copy as well as to determine the origin of a tumor, or the genetic similarities between species. In the chromosome lab, microarraybased comparative genome hybridization, more commonly referred to as aCGH, simultaneously measures the number of DNA copies at thousands of points along each chromosome. It’s rather like performing hundreds of thousands of FISH tests at the same time. The microarray for aCGH is collection of thousands of tiny DNA fragments from individual chromosomes, like FISH probes, usually arranged into a grid of tiny spots on a microscope slide. Very small changes in the DNA copy number, down to a few thousand base pairs of DNA, are detected by comparing the DNA content of the patient with a normal control DNA known to have two copies of all DNA sequences. The patient DNA is tagged with a fluorescent green label, and mixed with an equal amount of normal control DNA, which is tagged with a fluorescent red label. The mixture is added to the array container, where the labeled DNA sequences find and stick to the probe spots on the array grid. A computerized scanner measures and records the amount of red and green fluorescent signal from each spot, matches that data with its chromosomal origin, and reports a result. Thus, for each DNA sample, thousands of FISH-like tests are combined into one big test. The aCGH technique is a departure from traditional cytogenetic and FISH approaches, as no observation of whole cells or chromosomes occurs. Only pure copy number gains and losses will be reliably identified. Clinically important rearrangement of genetic material, even if it disrupts gene structure or function, cannot be identified with this technique, so standard chromosome analysis still has an important role to play. Chromosomal mosaicism, where some cells change while others do 11 Ruthann Pfau, PhD Ruthann Pfau, PhD, is an ABMG board-certified clinical cytogeneticist and genetic counselor at Dayton Children’s. She is an associate professor of clinical pediatrics at Wright State University Boonshoft School of Medicine and has been with the department of medical genetics for seven years. 12 not, cannot always be identified with array analysis. Despite these limitations, aCGH has dramatically increased identification of genomic copy number variation among the population of infants with multiple congenital anomalies. Additionally, children with developmental delays and autism with normal high resolution chromosomes have an increased frequency of aCGH abnormalities. In some cases, the genomic copy number changes are unequivocally linked to specific developmental profiles, while in others; children may inherit these changes from apparently typical parents. Results are often framed as normal, likely pathogenic, likely benign or undetermined significance. Important to note is a normal aCGH result ONLY reflects the number of copies present, not the proper function, or even proper structure of those genes. In general, pathogenic copy number changes are larger than 500 kb in size. An estimated one percent of pathogenic cytogenetic abnormalities such as low level markers chromosomes, low-level mosaicism under ~30 percent, or de novo inversions, translocations or other rearrangements will not be detected with this new technology. Interpretations such as normal or likely pathogenic are fairly straight forward to explain to families. However, copy number variation of uncertain significance is more challenging to elucidate. Sometimes abbreviated VOUS or VUS, no reports may exist of these gains or losses in the medical literature, either in normal or syndromic individuals. Parental evaluation may be helpful, as finding that a typical parent has the same copy number variant as the child can be indicative of a benign change which can be quite reassuring. Table 1 Detection Rates of Cytogenomic Abnormalities aCGH – Chromosome Fragile Subtelomere Clinically analysis X FISH significant Multiple Anomalies/IUGR1 10% - - 19% Non-syndromic MR2 4% 4% 6% 17% 2-4% 2% low 7% 7% 1% 2% 10% 1.81 0.97-3.08 0.06 Autism Spectrum Disorders3, 4, 5 Developmental Delays, postnatal6, 7 Retinoblastoma When considering which test to order, the clinician is faced with another level of choice: Cytogenomic arrays may be based on oligonucleotides (Oligo arrays), single nucleotide polymorphisms (SNP or snip arrays) or bacterial artificial chromosomes (BAC arrays, currently less commonly used). Each of these array platforms has individual strengths and weaknesses. BAC arrays are less commonly used because of the higher resolution oligo and SNP arrays. SNP arrays have more individual targets, but also may have a higher frequency of detecting variations of uncertain significance. SNP arrays can detect some cases of uniparental disomy, a rare cause of genomic disease. Consanguinity also may be identified with a SNP array. Both the 1 M SNP array with a 5 kb backbone, close spacing of probes, and the 180 K oligo array with a 25 kb backbone, more spread out spacing of probes, offer overall resolution fairly equivalent: 50-100 kb resolution for the SNP array versus 75 kb for the oligo array. A SNP array analysis often costs more than an oligo array with similar sensitivity. Genetic evaluation for MR/ DD and autism is a complicated process, and while aCGH provides an excellent tool for diagnosing a genetic cause in a subpopulation of these patients, clinicians are cautioned to consider single gene testing as well. Single gene traits such as Fragile X syndrome, Rett syndrome, and PTEN-associated macrocephaly/autism syndrome are caused by genetic changes involving individual genes. Many of these changes involve only one or a few DNA base pairs. These types of single gene disorders are not detectable with aCGH. So, where does this leave the clinician? Considering the increased sensitivity of the microarray, some are calling for this test to be performed before high resolution chromosomes. Others disagree, since a higher risk with arrays of discovering a genomic variant (copy number change) of uncertain significance exists, necessitating parental array evaluation to determine whether the change is hereditary or de novo. Some complexity also exists with so called susceptibility loci, in which copy number changes may cause problems in the child, but not in a parent or sibling. Family counseling with such uncertain information can be frustrating for clinicians and families. A major consideration for families is third-party payor coverage: some payors will not cover microarray aCGH testing, deeming it investigational. As the test is currently several times more expensive than standard chromosomes, families with high deductibles or out-of-pocket expenses may be reluctant to pursue aCGH; preauthorization is recommended. In contrast, cytogenetics and FISH are less expensive, and covered by most payors. At Dayton Children’s, a new aCGH tool is now available: a 105K oligo array using an internationally standardized design (International Standardization of Cytogenomic Arrays, or ISCA). Current recommendations for utilization of this service in conjunction with chromosome and FISH testing are as follows: Standard Chromosome studies: High index of clinical suspicion for identifiable syndromes, such as trisomy 21, 13, 18, monosomy X; results in 48 hours for STAT newborns FISH tests: When specific microdeletion syndromes are suspected (NOTE: if considering multiple microdeletion studies and/or subtelomere FISH, aCGH will be more sensitive and more economical – order aCGH instead). High-resolution chromosomes with reflex to aCGH (when chromosomes are normal): multiple anomalies, developmental delay/dysmorphism, pervasive developmental disorder (also consider fragile X testing), idiopathic mental retardation aCGH: Previous normal chromosome study, or for further characterization of previously detected chromosome abnormality Autism study: Fragile X and high resolution chromosome analysis; reflex to aCGH if both are normal Summary Clinicians have long suspected that ever-smaller changes in DNA copy number can and do exist, and that even tiny changes may impact human growth and development. If a single base pair change (point mutation) can lead to something as drastic as achondroplasia or Duchenne muscular dystrophy, larger blocks of DNA with extra or missing copies can certainly impact development. Microarray-based CGH has provided clinicians with a 21st century tool with which they can begin to discern these formerly elusive genomic imbalances. aCGH is a valuable technology to aid in the diagnosis of genomic imbalance or genomic copy number variation, particularly in cases where symptoms are non-syndromic or non-specific. Varying platforms for aCGH have particular strengths and weaknesses, with oligo arrays offering a similar sensitivity as SNP arrays, often at a lower cost. delays or unexplained/nonsyndromic developmental and or physical abnormalities. Ordering aCGH analysis on patients. This test can be ordered: 4 As a reflex test, to be performed after high resolution chromosomes are normal, by using test order code CHROBX. 4 As a stand-alone test, with previous normal chromosome and fragile X analysis, by using test code MACGHB. References 1. Lu et al. Pediatrics 122 (6): 1310. (2008) aCGH WILL detect changes of copy number of specific sequences of DNA, including gain or loss of copies of entire genes and parts of genes. 2. Rauch A, Am J Med Genet A 140A:2063–2074 (2006) aCGH WILL detect changes of copy number which MAY be harmless. 4. Reddy KS, BMC Medical Genetics 2005, 6:3 aCGH WILL NOT detect sequence changes or point mutations within individual genes. aCGH WILL NOT detect copy number changes of genomic regions for which no probes exist on the microarray. aCGH WILL NOT detect point mutations or small sequence changes or copy number changes below the threshold of resolution, which can depend on the specific platform. A lower threshold of detection MAY result in an increase in detection of copy number changes of uncertain significance. When to order aCGH for patients: Dayton Children’s medical genetics specialists recommend aCGH testing in accordance with published guidelines for evaluation of children with developmental 13 3. Yping S, Pediatrics Volume 125: 4, April 2010 e727-e735. 5. Battaglia A Am J Med Genet C Semin Med Genet. 2006 Feb 15; Vol. 142C (1), pp. 8-12. 6. Yu S Clin Genet 2005: 68: 436–441 7. Stankewiecz P, Current Opinion in Genetics & Development 2007, 17: 182–192 CME Questions 14. aCGH will detect Single Gene Disorders. a.True b.False 15. aCGH can detect subtelomeric deletions. a.True b.False 16. aCGH cannot detect low-level cytogenetic mosaicism. a.True b.False 17. aCGH can detect balanced translocations or inversions. a.True b.False 14 PROGRAM EVALUATION 1. Did the material presented in this publication meet the mission to enhance health care delivery in our region through education based on the essentials and policies of the Accreditation Council for Continuing Medical Education? c Strongly agree c Agree c Neutral c Disagree c Strongly disagree Pediatric Forum Volume 22 Number 2 2. Did the material presented in this publication meet the educational objectives stated? c Met the stated objectives c Did not meet the stated objectives 3. Did the material presented in this publication have a commercial bias? 4. Physician accreditation statement and credit designation Wright State University (WSU) Boonshoft School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. WSU Boonshoft School of Medicine designates this educational activity for a maximum of 2.0 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity. c Yes c No Please rate the contents of this issue using the following scale: 1 = Poor, 2 = Fair, 3 = Good, 4 = Very good, 5 = Excellent (Circle one response for each.) Poor Excellent Timely, up-to-date? 1 2 3 4 5 Practical? 1 2 3 4 5 Relevant to your practice? 1 2 3 4 5 5. Please describe any changes you plan to make in your clinical practice based on the information presented in this program. _____________________________________________________________________________________________ 6. Are there any other topics you would like to have addressed in this publication or future educational programs for health care providers? c Yes c No If yes, please describe:_____________________________________________________________ _____________________________________________________________________________________________ 7. Please describe how you will incorporate information obtained from this publication into your practice_ ____________ _____________________________________________________________________________________________ 8. Letter to the editor (may be published in next issue)_____________________________________________________ _____________________________________________________________________________________________ _____________________________________________________________________________________________ PROGRAM TEST Your Answers to CME Questions (Please circle the BEST answer.) Please type or print clearly 1. a b c d Name 2. a b c d 3. a b c d 4 Complete the program evaluation. 4. True False 4 Return your completed test and program evaluation by mail or fax to: Sue Strader, coordinator Department of Continuing Medical Education The Children’s Medical Center of Dayton One Children’s Plaza Dayton, OH 45404-1815 Fax: 937-641-5931 5. True False 6. True False 7. a b 8. True False 9. True False 10. a b 11. True False This sheet must be received by July 31, 2011 for the credit to be awarded. 12. True False 13. True False Upon completion of all requirements, Wright State University will issue a memorandum of credit to you for your permanent records. 14. True False 15. True False 16. True False 17. True False To obtain CME credit you must: 4 Read and reflect on each article. 4 Answer the questions from each article and complete this test. Practice name Street address c City d State/Zip code c d e Office telephone Office fax E-mail Signature NEWS AND UPDATES FROM DAYTON CHILDREN’S New specialty services Behavioral sleep medicine The Pediatric Sleep Center is now offering services from Zach Woessner, PsyD, licensed clinical psychologist. Dr. Woessner cares for patients with behavioral sleep conditions every Tuesday afternoon in the sleep clinic. Behavioral sleep conditions include sleep association, delayed sleep, bedtime stalling, nightmares and night terrors, and more. This service is for sleep-related issues and is not a general psychology referral. Referrals are made through the sleep clinic. Call 937-641-5004 for more information. Airway management clinic We are pleased to announce that Dayton Children’s, in collaboration with Nationwide Children’s, is now offering an airway management clinic monthly for children with airway conditions. These conditions include bronchomalacia, laryngomalacia, stridor, trach and ventilator dependents and more. Clinic is held the second Friday of every month, with morning clinic and afternoon surgical time as needed. Referrals should be made through pulmonary medicine. Questions? Call the pulmonary division at 937-641-3376. Scoliosis screening in schools Starting this fall, Dayton Children’s orthopedic division will begin assisting area schools with scoliosis screening. Free screenings will be provided to junior high school students throughout the region. Students identified with possible spine curvature will be referred to follow up with you, their primary care physician. We encourage you to perform a follow-up screening and if necessary, refer your patient to a pediatric orthopedic surgeon. Call 937-641-3010 for more information on scoliosis. Surgery Update Beginning in September, pediatric surgery will increase the frequency of clinics at the Specialty Care Center - Warren County to weekly. In addition, David P. Meagher, Jr, MD, will perform surgeries at Bidwell Surgery Center, conveniently located just behind the Specialty Care Center. In some cases, surgeries may be performed the same day as clinic visits. Refer your patients through pediatric surgery, online or by phone at 937-461-5020. New Infusion Pumps We are pleased to announce starting in November, Dayton Children’s will implement new “smart pump” technologies from CareFusion. These will help reduce medication errors during the administration of intravenous (IV) medications. Smart IV pumps act as an “assistant” to nurses and clinicians that administer IV medications at the point of care. Visit our website, childrensdayton.org to see the many ways Dayton Children’s is committed to providing the highest standard of patient safety and quality care. Home to the only accredited echo lab Dayton Children’s is currently only pediatric echocardiography laboratory in the Miami region to achieve accreditation in all modes of pediatric echocardiography including transthoracic, fetal and transesophageal. We recently received accreditation from the Intersocietal Commission for the Accreditation of Echocardiography Laboratories (ICAEL) for transesophageal echocardiography. Refer your patients through cardiology. KidsHealth looking for medical reviewers KidsHealth (kidshealth.com) is one of the top websites parents seek out for information on their children. Each article on the site is reviewed by physicians prior to publishing. Participants may review as many or little articles as time allows, and their information is displayed on the site. If you are interested in becoming a medical reviewer for KidsHealth, contact Moira Alter at 937-641-3618 or [email protected]. 15 Dayton Children’s welcomes new physicians Yelena Nicholson, DO, joins us from the pediatric endocrinology division at Nationwide Children’s Hospital. Dr. Nicholson completed a fellowship in pediatric endocrinology at Winthrop University Hospital and is board certified in pediatrics and pediatric endocrinology. She has special interest in diabetes and diabetes technology including insulin pumps. MSO membership tiers add benefits Shared Practice Solutions, LLC, (SPS) is a medical services organization (MSO) supported by Dayton Children’s. The goal of SPS is to provide high quality, value added services for primary and specialty care physician practices in the community. There are two levels of participation, with several discounted services including insurance, consulting, copying and medical services. To learn more about MSO services, visit the health care professionals section of our website, childrensdayton.org. Iris Soliman, MD, joins us from the department of anesthesia and critical care medicine at the Alfred I. duPont Hospital for Children in Wilmington, Delaware. Dr. Soliman is fellowship trained in pediatric anesthesia and intensive care, regional anesthesia and acute interventional pain management. She is board certified in anesthesiology with a special qualification in pain management. Nonprofit Organization U.S. Postage Paid Permit Number 323 Dayton, Ohio 16 The Children’s Medical Center of Dayton One Children’s Plaza Dayton, Ohio 45404-1815 KidsCare Link KidsCare Link is a web-based program that links you and your patients’ information to Dayton Children’s. Lab and imaging results, consultations and other notes are available at your convenience from your home or office computer. To request KidsCare Link for your office or for more information, contact Ruthie Laux or Kim Grant, physician relations managers, at 937-641-3498. The Right Care for the Right Reasons Dayton Children’s website has a brand new look As your pediatric experts, we’ve redesigned our website with you in mind. Find a doctor, get directions, CME or learn more about your patients’ health. childrensdayton.org/cms/provider
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