Pediatric Appendicitis Pathway Study
Condition: Appendicitis
MeSH terms: Appendicitis
Study type: Observational

Summary: 
      The purpose of this study is to test a standardized approach for children being evaluated for
      appendicitis in the emergency department. This means that all doctors would use the same
      approach to diagnose appendicitis in children in the emergency department. This pathway uses
      two scoring systems to identify patients who are at high and low risks of appendicitis. These
      scoring systems are based on the patient's symptoms, signs the doctor finds when examining
      the patient, and their blood tests. The goal of this part of the study is to determine if the
      investigators' pathway accurately identifies patients who have appendicitis.
    

Detailed description: 
      Methods:

      Overview:

      This study will consent and enroll a prospective cohort as well as incorporate a
      retrospective before and after chart review based on a HIPAA waiver of informed consent.

      The prospective portion will study pediatric patients ages 3-18 being evaluated for acute
      appendicitis in the OHSU/Doernbecher ED. Patients will be prospectively consented and
      enrolled by the CRISP program. The treating physician will document specific clinical
      predictors of acute appendicitis using a paper form. These criteria will be combined with
      routine laboratory measurements to identify patients at high and low risk for acute
      appendicitis based on two published and validated scoring systems.

      High risk patients will be directly admitted to the pediatric surgery service. Low risk
      patients will be observed further in the ED or discharged home with close outpatient
      follow-up based on the ED attending physician's judgment. Low risk patients will not be
      routinely consulted by pediatric surgery unless by the discretion of the ED attending.
      Patients at intermediate risk based on the scoring systems will continue evaluation in the ED
      at the discretion of the attending physician. Patients who are not definitively diagnosed
      with acute appendicitis by operative findings will be contacted by telephone at two weeks by
      a trained research assistant to assess for missed outcomes, the same follow up method used by
      Schneider et al. in another validation study of prediction rules for pediatric appendicitis.

      As this clinical protocol is being introduced in the OHSU/Doernbecher ED independently of the
      research study, patients not participating will likely also be treated according to a similar
      algorithm. The only difference will be that non-participating patients will have no data
      recorded except for that which is part of their regular clinical record, and will not be
      contacted for follow-up.

      Outcomes of interest for the prospective portion of the study include the sensitivity and
      specificity of the scoring systems for identifying acute appendicitis, as well as the
      accuracy of various diagnostic elements including history, exam, laboratory studies, and
      imaging.

      In order to assess the effect of the protocol on hospital-level outcomes, a retrospective
      before and after chart review study will also be conducted comparing the year before
      implementation to the year after. These patients will be retrospectively enrolled based on a
      HIPAA waiver of informed consent. Patients who consent to be included in the prospective
      portion of the study will also be included in this retrospective analysis. Outcomes of
      interest will include emergency department length of stay, time from arrival to inpatient bed
      or surgery, time to specialty pediatric surgery consultation, use of diagnostic imaging, and
      admission rate.

      Study Subjects:

      We will prospectively enroll a consecutive sample of all patients aged 3 through 18
      presenting to the OHSU ED for suspicion of appendicitis during the hours in which study staff
      are available. The high risk (Alvarado) criteria have been validated in this age group.
      Clinical Research Investigative Study Program (CRISP) volunteers who are on duty in the
      emergency department between the hours of 7 am and 11 pm will identify possible patients
      based on suggestive chief complaints (e.g abdominal pain, vomiting, etc) and approach the
      attending physician about whether the patient is being evaluated for possible appendicitis.
      If so, they will approach the family, consent them for participation, and prospectively
      collect data on a paper form (see data collection section below).

      Patients transferred from another facility to the ED will be included, including those with
      prior diagnostic imaging. Patients with symptoms greater than seven days will be excluded.

      For the before and after portion of the study, patients will be enrolled retrospectively
      based on screening of eligible charts in EPIC. Screening will be based on the chief
      complaints and diagnoses in EPIC including abdominal pain, vomiting, appendicitis etc. Charts
      identified by initial screening will be reviewed by a trained physician and included if they
      judge that there was concern on the part of the attending physician for appendicitis. Their
      information will be entered in an electronic database (see below). Patients will be entered
      in the retrospective portion of the study regardless of whether they were enrolled in the
      prospective section.

      Number of Study Subjects:

      Based on a projected admission rate of 500 patients per year for suspected appendicitis, and
      an admission rate of 50%, we expect 1000 eligible patients to be seen in the OHSU emergency
      department annually. As the CRISP volunteers are present only 16 hours per day, with the
      expectation that 75% of the patient volume presents during those hours, and based on a 50%
      enrollment of eligible patients, we expect to prospectively enroll 375 patients in one year.
      Based on a prevalence of appendicitis of 30% and specificity of the high risk criteria of
      78.8% in a previous study evaluating the high risk criteria, our projected sample size will
      yield of confidence interval for specificity of +/- 4.5%. For the low-risk criteria's
      previously demonstrated sensitivity of 98%, our sample size should yield a confidence
      interval for sensitivity of less than +/- 4%.

      The before and after portion of the study will enroll patients for a full year before and
      after implementation to avoid the seasonal variation which is especially inherent in a
      teaching hospital. Expected enrollment will therefore be 2000 patients.

      Prevalence rates in previous studies have ranged from 10 to 92% depending on inclusion
      criteria. Those studies with the highest prevalence rate included only patients who received
      who underwent surgery for suspected appendicitis. In studies with broad inclusion criteria
      similar to ours, (e.g. ED evaluation for acute abdominal pain, surgical evaluation for
      possible appendicitis), prevalence ranged from 10 to 61%.

      Special Patient Populations:

      Patients will be selected by the entry criteria described above. No special groups or
      vulnerable populations are specifically chosen for inclusion, but may be included within the
      general study population. There will be no specific exclusions on the basis of gender or
      ethnic groups. Consent forms will be translated into Spanish by ViaLanguage. Spanish speaking
      parents of limited English proficiency will be consented by professional in-person or
      telephone translator. Other limited English proficiency parents will be excluded.

      Consent:

      For the prospective portion of the study, eligible parents will be consented for enrollment
      by the CRISP volunteers using the attached consent forms. Children ages 7-18 will be asked to
      assent using the attached form.

      For the retrospective portion, patients will be enrolled based on a HIPAA waiver of informed
      consent, with all data coming from the clinical record.

      Study Procedure:

      Patients enrolled in the prospective cohort portion of the study will be treated according to
      the clinical pathway (see attached). This protocol was developed in collaboration between the
      departments of emergency medicine and pediatric surgery. The pathway standardizes the routine
      treatment of pediatric patients being evaluated for appendicitis (e.g. lab ordering, pain
      medications, nursing assessments) as well as triages patients to further evaluation based on
      validated low and high risk scoring systems including historical, physical exam, and
      laboratory elements. Deviation from the pathway will be allowed at the discretion of the
      treating physician.

      As this pathway is being implemented as a departmental protocol (similar to many other
      clinical pathways already in use in the emergency department) independent of the study,
      non-enrolled patients will also be treated according to it at the discretion of the treating
      physician. The only difference in treatment between enrolled and non-enrolled patients will
      be that data will be recorded independently from the patient's clinical record for those
      enrolled in the study, and enrolled patients will receive telephone follow-up two weeks after
      discharge if needed to determine outcomes.

      The pathway and form for tabulating low and high risk clinical and laboratory criteria will
      be available for clinician reference for both enrolled and non-enrolled patients, but will
      not be retained after the visit for those not participating in the study.

      The retrospective portion of the study will be based on EPIC chart review of patients being
      evaluated for appendicitis in the twelve month periods before and after implementation of the
      study.

      Data Collection and Analysis:

      Both the retrospective and prospective portions of the study will collect the following data:
      Patient demographics including age and gender. Duration of symptoms. Visit characteristics
      including referral from clinic, inter-hospital transfer, or presentation directly to the OHSU
      ED. Studies performed within the 72 hours before and after emergency department arrival: CT
      scan and abdominal/pelvic ultrasound, complete blood count, differential, urinalysis, urine
      pregnancy tests, metabolic panel, liver function tests, lipase. Time variables: time of
      emergency department room assignment, time of emergency department disposition, time of
      incision for patients undergoing surgery. Disposition will be classified as home, ED
      observation (defined by an ED stay >8 hours), surgery (including admission to inpatient with
      operation within 4 hours), inpatient observation (no operation within 4 hours of admission).

      Patients who were seen at another facility for this same condition within 72 hours of coming
      to OHSU should have had the relevant part of that medical record sent with the patient, by
      fax, or by electronic medical record (Kaiser HealthConnect or PACS imaging system). If those
      records were not sent, the CRISP volunteer will obtain written permission on the HIPAA
      release of information (see attached). This will be immediately faxed to the referring
      facility so that this vital information is available to the treating physician for the
      patient's care in the emergency department as well as for the study purposes.

      For the prospective portion of the study, consented patients will also have the specific
      signs and symptoms required for the calculation of the two scores documented on a form by the
      ED attending physician (see attached). This form will also ask the physician to rate their
      level of clinical suspicion for appendicitis prior to completing the scoring system. In the
      prospective study, sensitivities and specificities of the high and low risk criteria will be
      calculated for diagnosing appendicitis. Imaging study outcomes will be based on the
      interpretation of the attending radiologist in the clinical chart. These interpretations will
      then be classified as positive, negative, or indeterminate by a physician blinded to the
      final diagnosis. Data will be analyzed both including and excluding patients with imaging
      performed before transfer, as this may alter the use of the pathway.

      Subjects in the prospective portion of the trial who do not have a surgically confirmed
      diagnosis of appendicitis made during their hospitalization will be contacted by phone by a
      research assistant (medical student or physician). The primary outcomes of interest will be
      whether the patient was subsequently diagnosed with appendicitis. Other data will include all
      subsequent medical visits and diagnostic studies, time until cessation of symptoms, and
      alternative diagnoses made.

      Time outcomes and rates of imaging and laboratory utilization will be compared in the periods
      before and after implementation of the protocol in appropriate regression models
      incorporating variables considered to be of importance a-priori including age, gender, and
      pediatric ED census at the time of arrival by six hour block. Rates and location of pediatric
      surgery consultation (ED versus inpatient) will also be recorded. Key outcomes will also be
      analyzed in an interrupted-time-series fashion, looking at outcomes month by month in order
      to track the immediate versus sustained effect of the protocol implementation.

      Paper data collection forms will be transcribed to a Microsoft Access database kept on a
      secured server at OHSU. Analysis will be conducted using STATA 11. Data analysis will be
      performed at the Oregon Health Sciences University Department of Emergency Medicine. No data
      will be shared outside of OHSU.

      Ethical Considerations:

      Once the records have been entered in a Microsoft Access database kept on a secure server
      with limited access at OHSU, records will be de-identified prior to analysis. The date of
      visit will be changed to include only the month and date of birth will be converted to age in
      order that they will not be identifiable. With these safeguards, we are confident that we can
      adequately protect patient confidentiality.

      Risks:

      The risk of participation in this study is that the clinical decision rules could result in
      treatment that was inferior to that which would have occurred without this treatment pathway.
      However, as the pathway is being implemented in the emergency department as a care standard,
      patients would likely be treated according to it whether or not they participated in the
      study. The other risk of participation is loss of privacy if confidential data were to be
      compromised.

      As these risks are minimal, interim analysis or a data safety monitoring plan is unnecessary.

      Data Safety Monitoring Plan:

      Safety will be monitored by the investigators and the department of emergency medicine
      continuous quality assurance (CQI) process. The CQI process automatically flags all returns
      to the emergency department within 48 hours of discharge and forwards them for review monthly
      by the CQI committee. Cases of missed appendicitis, and other diagnoses require specific
      treatment or hospitalization identified by two-week telephone follow up will be reviewed by
      the CQI committee as well as the investigators and the division chief of pediatric emergency
      medicine (Dr. Spiro). Cases of patient admitted to emergency department observation who were
      subsequently admitted to the hospital will be identified by the research assistant and
      reviewed by the investigators.
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        A consecutive sample of all patients ages 3 through 18 presenting to the Oregon Health and
        Science University (OHSU) emergency department (ED) for suspicion of appendicitis during
        the hours in which study staff are available will be prospectively enrolled.
      
Keywords: Pediatric Appendicitis; Pathway