Delays to care in infantile epileptic spasms syndrome: Racial and ethnic inequities.

OBJECTIVE: Non-Hispanic (NH) Black children are less likely to receive a standard treatment course for infantile epileptic spasms syndrome (IESS) than White/NH children at pediatric tertiary care epilepsy centers in the United States. However, if inequities exist in time to diagnosis is unknown. Diagnostic delays as little as 1 week can be associated with worse developmental outcomes. METHODS: Diagnostic delays were evaluated in a retrospective cohort of 100 children with new onset IESS between January 2019 and May 2022. RESULTS: Children with Black, Indigenous, and People of Color (BIPOC) caregivers were more likely to experience clinically significant delays in referral from first provider to neurologist, when compared to White/NH children, even after controlling for other demographic and clinical variables (odds ratio = 4.98, confidence interval = 1.24-19.94, p = .023). SIGNIFICANCE: Disproportionate diagnostic delays place BIPOC children at risk of adverse developmental and epilepsy outcomes. Further interventional prospective and qualitative studies are needed to address inequities in care.

Discharge Practices for Infants with Bronchopulmonary Dysplasia: A Survey of National Experts.

OBJECTIVE: To establish consensus practices among a panel of national experts for the discharge of premature infants with bronchopulmonary dysplasia (BPD) from the hospital to home. STUDY DESIGN: We conducted a Delphi study that included US neonatologists and pediatric pulmonologists from the Bronchopulmonary Dysplasia Collaborative to establish consensus practices-defined as recommendations with at least 80% agreement-for infants with BPD being discharged from the hospital. Specifically, we evaluated recommendations for diagnostic tests to be completed around discharge, follow-up respiratory care, and family education. RESULTS: Thirty-one expert participants completed 3 rounds of surveys, with a 99% response rate (92 of 93). Consensus was established that infants with moderate-severe BPD (ie, those who remain on respiratory support at 36 weeks) and those discharged on oxygen should be targeted for in-person pulmonary follow-up within 1 month of hospital discharge. Specialized neonatal follow-up is an alternative for infants with mild BPD. Infants with moderate or severe BPD should have an echocardiogram performed after 36 weeks to screen for pulmonary hypertension. Infants with BPD warrant additional evaluations if they have growth restriction or poor growth, pulmonary hypertension, or tachypnea and if they are discharged to home on oxygen, diuretics, or nonoral feeds. CONCLUSIONS: This Delphi survey establishes expert consensus around best practices for follow-up respiratory management and routine evaluation for infants with BPD surrounding neonatal discharge. Areas of disagreement for which consensus was not established are discussed.

Higher In Vivo Fecal Concentrations of Clostridioides difficile Toxins A and B in Patients With North American Pulsed-Field Gel Electrophoresis Type 1/Ribotype 027 Strain Infection.

Ultrasensitive, quantitative Clostridioides difficile stool toxin measurement demonstrated significantly higher concentrations of toxins A and B in patients infected with the North American pulsed-field gel electrophoresis type 1/ribotype 027 (NAP-1/027) strain compared with other strains, providing in vivo confirmation of the in vitro association between NAP-1/027 and elevated toxin production.

Global optimization of the Michaelis-Menten parameters using physiologically-based pharmacokinetic (PBPK) modeling and chloroform vapor uptake data in F344 rats.

Objective: To quantify metabolism, a physiologically based pharmacokinetic (PBPK) model for a volatile compound can be calibrated with the closed chamber (i.e. vapor uptake) inhalation data. Here, we introduce global optimization as a novel component of the predictive process and use it to illustrate a procedure for metabolic parameter estimation.Materials and methods: Male F344 rats were exposed in vapor uptake chambers to initial concentrations of 100, 500, 1000, and 3000 ppm chloroform. Chamber time-course data from these experiments, in combination with optimization using a chemical-specific PBPK model, were used to estimate Michaelis-Menten metabolic constants. Matlab® simulation software was used to integrate the mass balance equations and to perform the global optimizations using MEIGO (MEtaheuristics for systems biology and bIoinformatics Global Optimization - Version 64 bit, R2016A), a toolbox written for Matlab®. The cost function used the chamber time-course data and least squares to minimize the difference between data and simulation values.Results and discussion: The final values estimated for Vmax (maximum metabolic rate) and Km (affinity constant) were 1.2 mg/h and a range between 0.0005 and 0.6 mg/L, respectively. Also, cost function plots were used to analyze the dose-dependent capacity to estimate Vmax and Km within the experimental range used. Sensitivity analysis was used to assess identifiability for both parameters and show these kinetic data may not be sufficient to identify Km.Conclusion: In summary, this work should help toxicologists interested in optimization techniques understand the overall process employed when calibrating metabolic parameters in a PBPK model with inhalation data.

Regional practice norms for the care of childhood cancer survivors at risk for cardiomyopathy: A Delphi study.

BACKGROUND: Treatment-associated cardiomyopathy is a leading cause of morbidity and mortality for childhood cancer survivors (CCS). As evidence is not available to guide the management of CCS at risk for cardiomyopathy, we aim to describe the collective opinion of regional experts for the care of these patients using a consensus-based Delphi methodology. PROCEDURE: Nineteen physicians from the New England region who care for CCS treated with cardiotoxic therapy (anthracyclines, thoracic radiation) participated in a Delphi panel querying their management approach, using three rounds of anonymous questionnaires formatted as five clinical scenarios. Consensus ≥ 89% agreement. RESULTS: The response rate was 100% for the first round and 95% for subsequent rounds. Panelists reached consensus on screening asymptomatic CCS with serial echocardiograms (94%) and electrocardiograms (89%), with some disagreement on frequency during pregnancy (83%). All panelists agreed with exercise promotion, with no restrictions on weight training. Consensus was reached on indications for referrals; cardiology for asymptomatic left ventricular dysfunction (ALVD) (100%) and maternal-fetal medicine for pregnancy (94%). In the scenario of ALVD, there was disagreement on the benefit of additional cardiac testing (50% cardiologists recommended cardiac MRI), and although all panelists endorsed treating with angiotension-converting enzyme (ACE) inhibitors, most adult cardiologists (75%) also recommended therapy with beta blockers, compared with none of the pediatric cardiologists or primary-care physicians. CONCLUSIONS: Despite a lack of evidence to guide the management of CCS at risk for cardiomyopathy, a panel of regional physicians reached consensus on managing most clinical scenarios. A controversial area requiring further study is the medical management of ALVD.

The management of childhood cancer survivors at risk for stroke: A Delphi survey of regional experts.

BACKGROUND: Evidence is not available to guide management of childhood cancer survivors (CCS) at risk for radiation-associated cerebral vascular disease (CVD) and stroke. We propose to use a consensus-based methodology to describe the collective opinion of regional experts for the care of these patients and identify areas of controversy. PROCEDURE: Thirty physicians from the New England region who care for CCS participated in a Delphi panel querying their management approach (imaging, laboratory tests, medications, counseling, referrals) to a CCS treated with cranial radiation formatted as five clinical scenarios (asymptomatic, small- and large-vessel CVD, transient ischemia, stroke) in three rounds of anonymous questionnaires. Consensus defined as ≥90% agreement. RESULTS: Response rate was 100% for all three rounds. Panelists reached consensus on laboratory tests to assess stroke risk factors, stroke risk and prevention counseling, brain imaging to monitor survivors with known CVD, and acute care for stroke symptoms. Only 67% panelists agreed with MRI screening asymptomatic survivors with no history of CVD, 87% endorsed aspirin as stroke prevention for large-vessel CVD and 57% for small-vessel CVD. There was no consensus on specialty referrals. Overall, panelists practicing at large institutions and neurology subspecialists were more likely to advocate for screening, interventions, and referrals. CONCLUSIONS: Despite lack of evidence to guide stroke prevention in CCS treated with cranial radiation, a panel of regional physicians reached consensus on managing most clinical scenarios. Controversial areas requiring further study are surveillance imaging for asymptomatic survivors, aspirin for stroke prevention, and indications for specialty referral.

Ten Rules for Antibiotic Prescribing.

Antibiotic use has come under increased scrutiny because of the emergence of multidrug-resistant organisms.Many have called for restricting use of antibiotics in humans and animals, finding strategies to reduce the spreadof resistant organisms and development of new anti-infectives. The challenge for many clinicians is identifyingwhen antibiotics are needed, which ones to use and how long to use them. This article offers practical advice foridentifying when antibiotics are beneficial and curbing inappropriate use.

The role of antiviral therapy in immunocompromised patients with herpes simplex virus meningitis.

BACKGROUND: Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are important causes of acute neurologic illness. Although the role of acyclovir in treating HSV encephalitis is clear, the role of antiviral therapy in HSV meningitis remains controversial. METHODS: In this retrospective observational study, we reviewed the charts of all patients with cerebrospinal fluid specimens positive for HSV-1 or HSV-2 by polymerase chain reaction between July 2000 and November 2012. Patients' charts were reviewed for demographic data, clinical presentation, treatment, and clinical outcomes. RESULTS: Forty-two patient-episodes were clinically classified as meningitis. In 6 episodes (14.3%), patients with meningitis received no antivirals, whereas the remaining episodes were treated with an oral antiviral (n = 11 [26.2%]), combination intravenous and oral therapy (n = 22 [52.4%]), or intravenous acyclovir alone (n = 3 [7.1%]). Six patients had recurrent episodes of meningitis and all recovered without any neurologic sequelae. Neurologic outcomes were significantly improved with antiviral therapy in immunocompromised patients with herpes meningitis (P < .05), but not in the 27 patient-episodes among immunocompetent patients (P = 1.0), as no neurologic sequelae were noted in this group. CONCLUSIONS: Most patients with HSV meningitis rapidly improve, but immunocompromised hosts have more neurologic sequelae and may benefit from antiviral therapy. Our data suggest symptomatic treatment alone for immunocompetent patients with HSV meningitis, avoiding the cost and side effects of prolonged intravenous acyclovir therapy; in contrast, immunocompromised patients had improved outcomes and would therefore benefit from antiviral therapy.

Communication: Molecular-level insights into asymmetric triblock copolymers: network and phase development.

Molecularly asymmetric triblock copolymers progressively grown from a parent diblock copolymer can be used to elucidate the phase and property transformation from diblock to network-forming triblock copolymer. In this study, we use several theoretical formalisms and simulation methods to examine the molecular-level characteristics accompanying this transformation, and show that reported macroscopic-level transitions correspond to the onset of an equilibrium network. Midblock conformational fractions and copolymer morphologies are provided as functions of copolymer composition and temperature.

Advice to Clinicians From Expectant Parents at Extreme Prematurity: A Multimethod Study.

BACKGROUND AND OBJECTIVES: Despite recommendations for patient-centered counseling on extreme prematurity, clinicians often miss opportunities to communicate in a way that facilitates parental knowledge, decision-making, and emotional support. In this study, we aimed to determine empirical, parent-derived recommendations and advice for clinicians counseling on extreme prematurity. METHODS: Pregnant women (and their partners) admitted at 22 0/7 to 25 6/7 weeks' estimated gestation participated in postantenatal counseling semi-structured interviews or questionnaires to explore parental preferences in the counseling process, including advice to clinicians. Thematic analysis was performed. RESULTS: A total of 39 interviews and 47 questionnaires, representing 62 total prenatal consultations, were completed. Thematic analysis of participants' advice to clinicians from both interview and questionnaire data resulted in 14 parent-derived recommendations to clinicians who counsel expectant parents at extreme prematurity. Parental recommendations related to compassionately engaging, supporting, and communicating with families, as well as aligning teams and following up. CONCLUSIONS: We present an empirical parent-derived, family-centered, and practical approach for clinicians counseling on extreme prematurity. Future studies should include a more diverse patient population and assess the impact of these recommendations on the counseling process and outcomes.

Nonoperative Versus Operative Treatment of Z-Type Comminuted Clavicle Fractures in Adolescents: A Prospective Substratified Cohort Analysis.

OBJECTIVES: To compare the clinical, radiographic, and patient-reported outcomes of nonoperative and operative treatment of adolescents with comminuted "Z-type" midshaft clavicle fractures. DESIGN: Prospective observational cohort. SETTING: Eight tertiary care pediatric centers. PATIENT SELECTION CRITERIA: Patients aged 10-18 years who were treated either operatively or nonoperatively for a diaphyseal clavicle fracture between 2013 and 2017 were screened/enrolled at the time of injury. The current subcohort analysis was derived from a larger adolescent clavicle study population of 907 patients. OUTCOME MEASUREMENTS AND COMPARISONS: Complications and validated patient-reported outcome measures (PROs):(ASES, QuickDASH, Marx Shoulder Activity Score, EQ-5D, EQ-VAS, and patient satisfaction score) were compared between operative and nonoperative cohorts. RESULTS: Eighty-one patients (69 male [85.2%], 12 female; average age 15 years [11.1-18.7]; 78 with sports participation [96.2%]) were followed through bony healing and return to sports, while 59 patients (73%) completed 2-year follow-up with PROs, 26 of whom were treated nonoperatively and 33 treated operatively. All demographic and fracture characteristics were similar (P > 0.05) between the 2-year follow-up cohorts except for fracture shortening, which was greater in the operative cohort (23 vs. 29 mm, P = 0.01). After controlling for this potential confounder through both regression and propensity matched subgroup analysis, nonoperative versus operative cohorts showed no difference in rates of nonunion (0%), delayed union (0% vs. 2.3%, P = 1.0), symptomatic malunion (2.7% vs. 0%, P = 0.4), refracture (2.7% vs. 2.2%, P = 1.0), unexpected subsequent surgery (5.4% vs. 11.4%, P = 0.45), or clinically significant complications (5.4% vs. 16%, P = 0.17). There were no differences in any PROs between cohorts, both before and after controlling for the difference in fracture shortening (all P-values >0.05). CONCLUSIONS: In this prospective comparison of complications and 2-year PROs in adolescents with comminuted Z-type clavicle fractures, nonoperative and operative treatment yielded similar outcomes. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Comparison of 2 blood culture media shows significant differences in bacterial recovery for patients on antimicrobial therapy.

BACKGROUND: Antimicrobial removal devices in blood culture media are designed to remove antibiotics from the blood culture solution, thereby facilitating bacterial growth. How well these devices function clinically has not been established. METHODS: All blood drawn for culture from adult inpatients and emergency department visitors in a level I trauma center was placed in paired BACTEC Plus and BacT/Alert FAN culture media and studied simultaneously, consecutively, and prospectively between 1 February and 30 September 2011. All cultures were processed per standard laboratory protocols. RESULTS: Of 9395 total cultures collected, 1219 (13%) were positive, 831 were included, and 524 (33%) contained pathogens. BACTEC had a 4.5-hour faster detection time (P < .0001), and isolated exclusively 182 of 524 (35%; P < .001) pathogens, 136 of 345 (39%) of the gram-positive cocci (P < .001), 48 of 175 (27%; P = .02) of the gram-negative rods, 101 of 195 (52%) of Staphylococcus aureus (P < .001), and 59 of 120 (49%; P = .004) septic events. If active antibiotics had been dosed 0-4 or 4-48 hours prior to culture collection, the odds of that culture growing in BACTEC were 4.8- and 5.2-fold greater, respectively, than of growing in BacT/Alert (P < .0001). Both were equivalent in the recovery of yeast and when no antimicrobials were dosed. CONCLUSIONS: BACTEC media has faster time to detection and increased bacterial recovery over the BacT/Alert media in the following categories: overall growth, pathogens, septic events, gram-positive cocci, gram-negative rods, Staphylococcus aureus, and cultures where antimicrobials were dosed up to 48 hours before culture collection.

Baseline stool toxin concentration is associated with risk of recurrence in children with Clostridioides difficile infection.

BACKGROUND: In adults with Clostridioides difficile infection (CDI), higher stool concentrations of toxins A and B are associated with severe baseline disease, CDI-attributable severe outcomes, and recurrence. We evaluated whether toxin concentration predicts these presentations in children with CDI. METHODS: We conducted a prospective cohort study of inpatients aged 2-17 years with CDI who received treatment. Patients were followed for 40 days after diagnosis for severe outcomes (intensive care unit admission, colectomy, or death, categorized as CDI primarily attributable, CDI contributed, or CDI not contributing) and recurrence. Baseline stool toxin A and B concentrations were measured using ultrasensitive single-molecule array assay, and 12 plasma cytokines were measured when blood was available. RESULTS: We enrolled 187 pediatric patients (median age, 9.6 years). Patients with severe baseline disease by IDSA-SHEA criteria (n = 34) had nonsignificantly higher median stool toxin A+B concentration than those without severe disease (n = 122; 3,217.2 vs 473.3 pg/mL; P = .08). Median toxin A+B concentration was nonsignificantly higher in children with a primarily attributed severe outcome (n = 4) versus no severe outcome (n = 148; 19,472.6 vs 429.1 pg/mL; P = .301). Recurrence occurred in 17 (9.4%) of 180 patients. Baseline toxin A+B concentration was significantly higher in patients with versus without recurrence: 4,398.8 versus 280.8 pg/mL (P = .024). Plasma granulocyte colony-stimulating factor concentration was significantly higher in CDI patients versus non-CDI diarrhea controls: 165.5 versus 28.5 pg/mL (P < .001). CONCLUSIONS: Higher baseline stool toxin concentrations are present in children with CDI recurrence. Toxin quantification should be included in CDI treatment trials to evaluate its use in severity assessment and outcome prediction.

A qualitative study of the impact of a periacetabular osteotomy on patients' lives.

AIMS: The aim of this study was to understand the experience of mature patients who undergo a periacetabular osteotomy (PAO), a major hip-preserving surgical procedure that treats symptomatic hip dysplasia by realigning the acetabulum. Our aim was to improve our understanding of how the operation affected the lives of patients and their families, with a long-term goal of improving their experience. METHODS: We used a phenomenological approach with in-depth, semi-structured interviews to investigate the experience of seven female patients, aged between 25 and 40 years, who underwent a PAO. A modified homogeneity sampling approach coupled with criterion sampling was used. Inclusion criteria involved having at least one child at home and being in a committed relationship with a spouse or partner. RESULTS: Analysis of interview transcripts revealed five major themes: feelings of frustration before having a treatment plan; fear of the operation; the importance of understanding the procedure in order to feel in control of their care; feelings of helplessness, dependence, and depression during recovery; and the need for support during recovery. CONCLUSION: Our findings suggest that both the physical and psychosocial burdens of undergoing a PAO are great, with a major impact on the patient and their family. Many important issues lie outside the scope of what healthcare teams currently address. Cite this article: Bone Joint J 2022;104-B(7):781-785.

Fellows' Perspective of Educational Changes in Medical Sports Medicine During the COVID-19 Pandemic.

Background As a result of the coronavirus disease 2019 (COVID-19) pandemic, graduate medical education, along with most of daily life, was disrupted. The goal of this study was to explore the experiences of fellows in primary care/medical sports medicine (MSM) and view the changes made to training programs through their eyes. Methodology A questionnaire was developed to collect qualitative and quantitative data regarding the fellow's experiences in training from March to June 2020. Fellows on the American Medical Society for Sports Medicine list of current Sports Medicine Fellows in the United States and Canada were invited to participate. Of the 329 invited, 90 (27.4%) fellows returned questionnaires. Results MSM fellows highlighted positive adaptations as well as losses to their educational programs related to the pandemic. The biggest gain reported was additional learning time, and the greatest loss was to sports and event coverage. Most fellows reported attending collaborative sessions, and they noted an increase in didactics compared to pre-pandemic levels. The largest losses were noted in event coverage and training room exposures, with smaller declines in ultrasounds, procedures, and research experiences. They also described challenges, including changing clinical roles, managing social isolation and boredom, and balancing work and family responsibilities. Conclusions Fellows identified gains, losses, and challenges due to pandemic-related changes to their fellowship programs. Fellowship directors and educators in different fields can use this understanding of the fellows' experiences to build on current resources, further develop collaborative efforts, create new educational opportunities, and provide additional support for fellow learning.

Stool Toxin Concentration Does Not Distinguish Clostridioides difficile Infection from Colonization in Children Less Than 3 Years of Age.

In a prospective cohort study, stools from children <3 years with and without diarrhea who were Clostridioides difficile nucleic acid amplification test-positive underwent ultrasensitive and quantitative toxin measurement. Among 37 cases and 46 controls, toxin concentration distributions overlapped substantially. Toxin concentration alone does not distinguish C. difficile infection from colonization in young children.

Emergency department staff perceptions about the care of children with mental health conditions.

OBJECTIVE: The number of children with mental health (MH) conditions who present to the emergency department (ED) is increasing. This study aimed to gain insight into the lived experiences of ED staff caring for children with MH conditions and to understand perceptions of current ED resources and what is needed to optimize care. METHODS: This was a qualitative study informed by complexity science theory utilizing a phenomenological approach. We used purposeful sampling from urban and nonurban EDs with varying pediatric volume. Participants were pediatric emergency care coordinators and other ED staff. Semi-structured interviews were completed. The initial codebook was created using a concept driven approach. Constant comparative analysis and deductive reasoning was employed for thematic analysis. RESULTS: Thematic saturation by consensus was achieved with 24 interviews. Analysis found an overarching theme of moral distress of ED staff, compounded by frustration with barriers to care and perceptions of negative impact on care of other ED patients. Participants suggested the need for creation of patient, caregiver, ED staff, and ED leadership resources to enhance care. CONCLUSIONS: ED staff perceive children with MH conditions experience significant barriers to optimal care in the ED, which causes ED provider moral distress. Additionally, other ED patients are perceived to be subsequently negatively impacted. Our findings highlight urgency for funding for more resources that are dedicated to children in the ED setting to ensure both safe, patient-centered care, and to reduce the distress described by ED staff who care for them.

Standardizing the Diagnostic Evaluation of Nonarthritic Hip Pain Through the Delphi Method.

BACKGROUND: Femoroacetabular impingement and acetabular dysplasia have gained increased attention as nonarthritic sources of pain and dysfunction in young, active patients. To date, no standardized approach to the diagnostic evaluation of nonarthritic hip pain has been identified, as previous work has focused on the diagnostic evaluation and management of patients with femoroacetabular impingement undergoing hip arthroscopy. PURPOSE: To explore the standard diagnostic evaluation practice of experts in the field of hip preservation surgery and combine their expertise through the Delphi method to form a standardized approach to the diagnostic evaluation of patients with nonarthritic hip pain. STUDY DESIGN: Consensus statement. METHODS: An expert panel made up of 18 orthopaedic surgeons with extensive experience in the treatment of nonarthritic hip disorders participated in this Delphi study. The Delphi panelists were presented with 4 clinical vignettes representing a spectrum of patients with nonarthritic hip pain. Three iterative survey rounds were presented to the panelists based on these clinical vignettes, and a 3-step classic Delphi method was used to establish consensus techniques in the diagnostic evaluation of nonarthritic hip pain. RESULTS: Total (100%) participation was gained, with all 18 experts completing all 3 Delphi survey rounds. Consensus (≥75% support) was achieved for some, if not all, vignettes for each of the following diagnostic domains: historical features, physical examination, radiographic sequences, radiographic interpretation, cross-sectional imaging, and ancillary diagnostics. CONCLUSION: In this Delphi study, we identified standardized diagnostic treatment approaches as derived from expert opinion for patients with nonarthritic hip pathomorphologies.

Development of a rubric for assessing delayed diagnosis of appendicitis, diabetic ketoacidosis and sepsis.

OBJECTIVES: Using case review to determine whether a patient experienced a delayed diagnosis is challenging. Measurement would be more accurate if case reviewers had access to multi-expert consensus on grading the likelihood of delayed diagnosis. Our objective was to use expert consensus to create a guide for objectively grading the likelihood of delayed diagnosis of appendicitis, new-onset diabetic ketoacidosis (DKA), and sepsis. METHODS: Case vignettes were constructed for each condition. In each vignette, a patient has the condition and had a previous emergency department (ED) visit within 7 days. Condition-specific multi-specialty expert Delphi panels reviewed the case vignettes and graded the likelihood of a delayed diagnosis on a five-point scale. Delayed diagnosis was defined as the condition being present during the previous ED visit. Consensus was defined as ≥75% agreement. In each Delphi round, panelists were given the scores from the previous round and asked to rescore. A case scoring guide was created from the consensus scores. RESULTS: Eighteen expert panelists participated. Consensus was achieved within three Delphi rounds for all appendicitis and sepsis vignettes. We reached consensus on 23/30 (77%) DKA vignettes. A case review guide was created from the consensus scores. CONCLUSIONS: Multi-specialty expert reviewers can agree on the likelihood of a delayed diagnosis for cases of appendicitis and sepsis, and for most cases of DKA. We created a guide that can be used by researchers and quality improvement specialists to allow for objective case review to determine when delayed diagnoses have occurred for appendicitis, DKA, and sepsis.

Sample Size Considerations: Basics for Preparing Clinical or Basic Research.

Background: Sample size estimation is an important and integral part of a research protocol. While "how large a sample?" is a simple question, the answer is only meaningful within the context of the research question. Methods: Clear definitions of the variable of interest and target population parameters are key to estimating sample size. In turn the sample must be sized such that it can accurately detect the 'effect' of interest, adequately represent the target population and maintain maximum design efficiency. Four basic pieces of information are utilized in most sample estimation across all clinical research: significance level, power, magnitude of effect and variability of the variable of interest. Results/Discussion: Preliminary determination of these will greatly facilitate work with a biostatistician or a computer application to create a sample size estimation. While applications can support relatively simple sample size calculations consultation with a biostatistician is recommended.