Medication Order Errors at Hospital Admission Among Children With Medical Complexity.

OBJECTIVES: We sought to characterize the nature and prevalence of medication order errors (MOEs) occurring at hospital admission for children with medical complexity (CMC), as well as identify the demographic and clinical risk factors for CMC experiencing MOEs. METHODS: Prospective cohort study of 1233 hospitalizations for CMC from November 1, 2015, to October 31, 2016, at 2 children's hospitals. Medication order errors at admission were identified prospectively by nurse practitioners and a pharmacist through direct patient care. The primary outcome was presence of at least one MOE at hospital admission. Statistical methods used included χ2 test, Fisher exact tests, and generalized linear mixed models. RESULTS: Overall, 6.1% (n = 75) of hospitalizations had ≥1 MOE occurring at admission, representing 112 total identified MOEs. The most common MOEs were incorrect dose (41.1%) and omitted medication (34.8%). Baclofen and clobazam were the medications most commonly associated with MOEs. In bivariable analyses, MOEs at admission varied significantly by age, assistance with medical technology, and numbers of complex chronic conditions and medications (P < 0.05). In multivariable analysis, patients receiving baclofen had the highest adjusted odds of MOEs at admission (odds ratio, 2.2 [95% confidence interval, 1.2-3.8]). CONCLUSIONS: Results from this study suggest that MOEs are common for CMC at hospital admission. Children receiving baclofen are at significant risk of experiencing MOEs, even when orders for baclofen are correct. Several limitations of this study suggest possible undercounting of MOEs during the study period. Further investigation of medication reconciliation processes for CMC receiving multiple chronic, home medications is needed to develop effective strategies for reducing MOEs in this vulnerable population.

Preoperative hematocrit and platelet count are associated with blood loss during spinal fusion for children with neuromuscular scoliosis.

AIM: To assess the relationship of preoperative hematology laboratory results with intraoperative estimated blood loss and transfusion volumes during posterior spinal fusion for pediatric neuromuscular scoliosis. METHODS: Retrospective chart review of 179 children with neuromuscular scoliosis undergoing spinal fusion at a tertiary children's hospital between 2012 and 2017. The main outcome measure was estimated blood loss. Secondary outcomes were volumes of packed red blood cells, fresh frozen plasma, and platelets transfused intraoperatively. Independent variables were preoperative blood counts, coagulation studies, and demographic and surgical characteristics. Relationships between estimated blood loss, transfusion volumes, and independent variables were assessed using bivariable analyses. Classification and Regression Trees were used to identify variables most strongly correlated with outcomes. RESULTS: In bivariable analyses, increased estimated blood loss was significantly associated with higher preoperative hematocrit and lower preoperative platelet count but not with abnormal coagulation studies. Preoperative laboratory results were not associated with intraoperative transfusion volumes. In Classification and Regression Trees analysis, binary splits associated with the largest increase in estimated blood loss were hematocrit ≥44% vs. <44% and platelets ≥308 vs. <308 × 109/L. CONCLUSIONS: Preoperative blood counts may identify patients at risk of increased bleeding, though do not predict intraoperative transfusion requirements. Abnormal coagulation studies often prompted preoperative intervention but were not associated with increased intraoperative bleeding or transfusion needs.

Hospital Volumes of Inpatient Pediatric Surgery in the United States.

BACKGROUND: Perioperative outcomes of children depend on the skill and expertise in managing pediatric patients, as well as integration of surgical, anesthesiology, and medical teams. We compared the types of pediatric patients and inpatient surgical procedures performed in low- versus higher-volume hospitals throughout the United States. METHODS: Retrospective analysis of 323,258 hospitalizations with an operation for children age 0 to 17 years in 2857 hospitals included in the Agency for Healthcare Research and Quality (AHRQ) Kids' Inpatient Database (KID) 2016. Hospitals were categorized by their volume of annual inpatient surgical procedures. Specific surgeries were distinguished with the AHRQ Clinical Classification System. We assessed complex chronic conditions (CCCs) using Feudtner and Colleagues' system. RESULTS: The median annual volume of pediatric inpatient surgeries across US hospitals was 8 (interquartile range [IQR], 3-29). The median volume of inpatient surgeries for children with a CCC was 4 (IQR, 1-13). Low-volume hospitals performed significantly fewer types of surgeries (median 2 vs 131 types of surgeries in hospitals with 1-24 vs ≥2000 volumes). Appendectomy and fixation of bone fracture were among the most common surgeries in low-volume hospitals. As the volume of surgical procedures increased from 1 to 24 to ≥2000, the percentage of older children ages 11 to 17 years decreased (70.9%-32.0% [P < .001]) and the percentage of children with a CCC increased (11.2%-60.0% [P < .001]). CONCLUSIONS: Thousands of US hospitals performed inpatient surgeries on few pediatric patients, including those with CCCs who have the highest risk of perioperative morbidity and mortality. Evaluation of perioperative decision making, workflows, and pediatric clinicians in low- and higher-volume hospitals is warranted.

Risk factors for gastrointestinal complications after spinal fusion in children with cerebral palsy.

DESIGN: Prospective cerebral palsy (CP) registry review. OBJECTIVES: (1) Evaluate the incidence/risk factors of gastrointestinal (GI) complications in CP patients after spinal fusion (SF); and (2) investigate the validity of the modified Clavien-Dindo-Sink classification. BACKGROUND: Perioperative GI complications result in increased length of stay (LOS) and patient morbidity/mortality. However, none have analyzed the outcomes of GI complications using an objective classification system. METHODS: A prospective/multicenter CP database identified 425 children (mean, 14.4 ± 2.9 years; range, 7.9-21 years) who underwent SF. GI complications were categorized using the modified Clavien-Dindo-Sink classification. Grades I-II were minor complications and grades III-V major. Patients with and without GI complications were compared. RESULTS: 87 GI complications developed in 69 patients (16.2%): 39 minor (57%) and 30 major (43%). Most common were pancreatitis (n = 45) and ileus (n = 22). Patients with preoperative G-tubes had 2.2 × odds of developing a GI complication compared to oral-only feeders (OR 2.2; 95% CI 0.98-4.78; p = 0.006). Similarly, combined G-tube/oral feeders had 6.7 × odds compared to oral-only (OR 6.7; 95% CI 3.10-14.66; p < 0.001). The likelihood of developing a GI complication was 3.4 × with normalized estimated blood loss (nEBL) ≥ 3 ml/kg/level fused (OR 3.41; 95% CI 1.95-5.95; p < 0.001). Patients with GI complications had more fundoplications (29% vs. 17%; p = 0.03) and longer G-tube fasting periods (3 days vs. 2 days; p < 0.001), oral fasting periods (5 days vs. 2 days; p < 0.001), ICU admissions (6 days vs. 3 days; p = 0.002), and LOS (15 days vs. 8 days; p < 0.001). LOS correlated with the Clavien-Dino-Sink classification. CONCLUSION: Gastrointestinal complications such as pancreatitis and ileus are not uncommon after SF in children with CP. This is the first study to investigate the validity of the modified Clavien-Dindo-Sink classification in GI complications after SF. Our results suggest a correlation between complication severity grade and LOS. The complexity of perioperative enteral nutritional supplementation requires prospective studies dedicated to enteral feeding protocols. LEVEL OF EVIDENCE: Therapeutic-level III.

Pediatric complex care and surgery comanagement: Preparation for spinal fusion.

The aim of this study is to assess the impact of preoperative comanagement with complex care pediatricians (CCP) on children with neuromuscular scoliosis undergoing spinal fusion. We performed chart review of 79 children aged 5-21 years undergoing spinal fusion 1/2014-6/2016 at a children's hospital, with abstraction of clinical documentation from preoperative health evaluations performed regularly by anesthesiologists and irregularly by a CCP. Preoperative referrals to specialists, labs, tests, and care plans needed last minute for surgical clearance were measured. The mean age at surgery was 14 (SD 3) years; cerebral palsy (64%) was the most common neuromuscular condition. Thirty-nine children (49%) had a preoperative CCP evaluation a median 63 days (interquartile range (IQR) 33-156) before the preanesthesia visit. Children with CCP evaluation had more organ systems affected by coexisting conditions than children without an evaluation (median 11 (IQR 9-12) vs. 8 (IQR 5-11); p < .001). The rate of last-minute care coordination activities required for surgical clearance was lower for children with versus without CCP evaluation (1.8 vs. 3.6). A lower percentage of children with CCP evaluation required last-minute development of new preoperative plans (26% vs. 50%, p = .002). Children with CCP involvement were better prepared for surgery, requiring fewer last-minute care coordination activities for surgical clearance.

One Size Does Not Fit All: A Perspective on the American Society of Anesthesiologists Physical Status Classification for Pediatric Patients.

BACKGROUND: The American Society of Anesthesiologists physical status (ASA-PS) classification system is used worldwide to classify patients based on comorbid conditions before general anesthesia. Despite its popularity, the ASA-PS classification system has been shown to have poor interrater reliability due to its subjective definitions, especially when applied to the pediatric population. We hypothesized that the clarification of ASA-PS definitions to better reflect pediatric conditions would improve the accuracy of ASA-PS applied to this population. METHODS: A stratified, randomized sample of 120 pediatric surgical cases was collected from a tertiary-care pediatric hospital. A team of senior anesthesiologists reclassified ASA-PS within this patient sample using the suggested pediatric-specific ASA-PS definitions. Interrater reliability was measured using intraclass correlation (ICC) and Fleiss κ statistic. In addition, a qualitative study component using small focus groups of senior anesthesiologists identified areas of ambiguity within the ASA-PS system. RESULTS: Among the 90 reclassifications within each ASA-PS group, 42.2% (n = 38) of ASA-PS I were upgraded to ASA-PS II, and 36.7% (n = 33) of ASA-PS II were upgraded to ASA-PS III. In addition, 28.9% (n = 26) of ASA-PS III were upgraded to ASA-PS IV, and 24.4% (n = 22) of ASA-PS IV were downgraded to III. ICC across the reclassified ASA-PS categories was 0.77 (95% confidence interval [CI], 0.71-0.83; P < .001) demonstrating strong overall agreement. Fleiss κ statistic was lowest in ASA-PS II and III patients (κ = 0.41 and κ = 0.30, respectively) indicating lower agreement beyond chance within these subgroups. Focus groups revealed common themes such as active sequelae of disease, active versus well-controlled presence of comorbidities, and the possible inclusion of functional limitations as important considerations. CONCLUSIONS: The ASA-PS classification system has several benefits including ease-of-use, simplicity, and flexibility. However, revising the ASA-PS system to provide better guidance for pediatric patients could be valuable. While this study demonstrates good interrater reliability with the included ASA-PS pediatric definitions, further work is needed to clarify accurate assignment of ASA-PS within the midrange of the scale (ASA-PS II and III) and explore its implementation in other institutions.

Parent Perspectives on Short-Term Recovery After Spinal Fusion Surgery in Children With Neuromuscular Scoliosis.

Family perspectives on short-term recovery after spinal fusion for neuromuscular scoliosis are essential for improving patient outcomes. Semistructured interviews were conducted with 18 families of children within 3 months after spinal fusion performed August 2017 to January 2019 at a children's hospital. Interviews were recorded, transcribed, and coded line-by-line by 2 independent reviewers using grounded theory to identify themes. Five themes emerged among families when reflecting back on the postoperative recovery: (1) communicating and making shared decisions regarding postoperative care in a patient- and family-centered manner, (2) setting hospital discharge goals and being ready for discharge, (3) planning for transportation from hospital to home, (4) acquiring supports for caregiving at home after discharge, and (5) anticipating a long recovery at home. Important family perceptions were elicited about the recovery of children from spinal fusion for neuromuscular scoliosis that will inform better perioperative planning for clinicians, future patients, and their families.

Parent-to-Parent Advice on Considering Spinal Fusion in Children with Neuromuscular Scoliosis.

OBJECTIVES: To convey advice from families whose children recently underwent spinal fusion to families whose children are under consideration for initial spinal fusion for neuromuscular scoliosis and to providers who counsel families on this decision. STUDY DESIGN: We interviewed 18 families of children who underwent spinal fusion between August 2017 and January 2019 at a freestanding children's hospital. We conducted phone interviews a median of 65 (IQR 51-77) days after surgery. We audio recorded, transcribed, and coded (line-by-line) interviews using grounded theory by 2 independent reviewers, and discussed among investigators to induce themes associated with surgical decision making and preparation. RESULTS: Six themes emerged about decision making and preparation for spinal fusion: (1) simplify risks and benefits; it is easy to get lost in the details; (2) families prolonging the decision whether or not to pursue spinal fusion surgery may not benefit the child; (3) anticipate anxiety and fear when making a decision about spinal fusion; (4) realize that your child might experience a large amount of pain; (5) anticipate a long recovery and healing process after spinal fusion; and (6) be engaged and advocate for your child throughout the perioperative spinal fusion process. CONCLUSIONS: Parents of children who had recently undergone spinal fusion had strong perceptions about what information to convey to families considering surgery, which may improve communication between future parents and physicians. Further investigation is needed to assess how best to incorporate the wisdom and experiences of parent peers into shared decision making and preparation for spinal fusion in children with neuromuscular scoliosis.

Comparing Diagnostic Evaluations for Rectal Bleeding and Breast Lumps in Primary Care: a Retrospective Cohort Study.

BACKGROUND: Inadequate diagnostic evaluations of breast lumps and rectal bleeding in primary care are an important source of medical errors. Delays appear particularly common in evaluation of rectal bleeding. Comparing pursuit and completion of diagnostic testing for these two conditions within the same practice settings could help highlight barriers and inform interventions. OBJECTIVES: To examine processes undertaken for diagnostic evaluations of breast lumps and rectal bleeding within the same practices and to compare them with regard to (a) the likelihood that diagnostic tests are ordered according to guidelines and (b) the timeliness of order placement and completion. DESIGN: A retrospective cohort study using explicit chart abstraction methods. PARTICIPANTS: Three hundred women aged 30-80 presenting with breast lumps and 300 men and women aged 40-80 years presenting with rectal bleeding to 15 academically affiliated primary care practices, 2012-2016. MAIN MEASURES: Rates and timing of test ordering and completion and patterns of visits and communications. KEY RESULTS: At initial presentation, physicians ordered recommended imaging or procedures at higher rates for patients with breast lumps compared to those with rectal bleeding (97% vs. 86% of patients recommended to receive imaging or endoscopy; p < 0.01). Most (90%) patients with breast lumps completed recommended diagnostic testing within 1 month, versus 31% of patients with rectal bleeding (p < 0.01). By 1 year, 7% of patients with breast lumps had not completed indicated imaging, versus 27% of those with rectal bleeding. Patients with breast lumps had fewer subsequent primary care visits related or unrelated to their symptom and had fewer related communications with specialists. LIMITATIONS: The study relied on documented care, and findings may be most generalizable to academically affiliated institutions. CONCLUSIONS: Diagnostic processes for rectal bleeding were less frequently guideline-concordant and timely than those for breast lumps. The largest discrepancies occurred in initial ordering of indicated tests and the timeliness of test completion.

Predicting Postoperative Physiologic Decline After Surgery.

BACKGROUND: Projecting postoperative recovery in pediatric surgical patients is challenging. We assessed how the patients' number of complex chronic conditions (CCCs) and chronic medications interacted with active health issues to influence the likelihood of postoperative physiologic decline (PoPD). METHODS: A prospective study of 3295 patients undergoing elective surgery at a freestanding children's hospital. During preoperative clinical evaluation, active health problems, CCCs, and medications were documented. PoPD (compromise of cardiovascular, respiratory, and/or neurologic systems) was measured prospectively every 4 hours by inpatient nurses. PoPD odds were estimated with multivariable logistic regression. Classification and regression tree analysis distinguished children with the highest and lowest likelihood of PoPD. RESULTS: Median age at surgery was 8 years (interquartile range: 2-15); 2336 (70.9%) patients had a CCC; and 241 (7.3%) used ≥11 home medications. During preoperative evaluation, 1556 (47.2%) patients had ≥1 active health problem. After surgery, 882 (26.8%) experienced PoPD. The adjusted odds of PoPD were 1.2 (95% confidence interval [CI]: 1.0-1.4) for presence versus absence of an active health problem; 1.4 (95% CI: 1.0-1.9) for ≥11 vs 0 home medications; and 2.2 (95% CI: 1.7-2.9) for ≥3 vs 0 CCCs. In classification and regression tree analysis, the lowest rate of PoPD (8.6%) occurred in children without an active health problem at the preoperative evaluation; the highest rate (57.2%) occurred in children with a CCC who used ≥11 home medications. CONCLUSIONS: Greater than 1 in 4 pediatric patients undergoing elective surgery experienced PoPD. Combinations of active health problems at preoperative evaluation, polypharmacy, and multimorbidity distinguished patients with a low versus high risk of PoPD.

Association of Home Respiratory Equipment and Supply Use with Health Care Resource Utilization in Children.

OBJECTIVE: To compare health care use and spending in children using vs not using respiratory medical equipment and supplies (RMES). STUDY DESIGN: Cohort study of 20 352 children age 1-18 years continuously enrolled in Medicaid in 2013 from 12 states in the Truven Medicaid MarketScan Database; 7060 children using RMES were propensity score matched with 13 292 without RMES. Home RMES use was identified with Healthcare Common Procedure Coding System and International Classification of Diseases codes. RMES use was regressed on annual per-member-per-year Medicaid payments, adjusting for demographic and clinical characteristics, including underlying respiratory and other complex chronic conditions. RESULTS: Of children requiring RMES, 47% used oxygen, 28% suction, 22% noninvasive positive-pressure ventilation, 17% tracheostomy, 8% ventilator, 5% mechanical in-exsufflator, and 4% high-frequency chest wall oscillator. Most children (93%) using RMES had a chronic condition; 26% had ≥6. The median per-member-per-year payments in matched children with vs without RMES were $24 359 vs $13 949 (P < .001). In adjusted analyses, payment increased significantly (P < .001 for all) with mechanical in-exsufflator (+$2657), tracheostomy (+$6447), suction (+$7341), chest wall oscillator (+$8925), and ventilator (+$20 530). Those increased payments were greater than the increase associated with a coded respiratory chronic condition (+$2709). Hospital and home health care were responsible for the greatest differences in payment (+$3799 and +$3320, respectively) between children with and without RMES. CONCLUSION: The use of RMES is associated with high health care spending, especially with hospital and home health care. Population health initiatives in children may benefit from consideration of RMES in comprehensive risk assessment for health care spending.

Associations of Coexisting Conditions with Healthcare Spending for Children with Cerebral Palsy.

OBJECTIVE: To determine which coexisting conditions have the strongest associations with healthcare use and spending among children with cerebral palsy (CP). STUDY DESIGN: Retrospective analysis of 16 695 children ages 0-18 years with CP - identified with International Classification of Diseases, Ninth Revision, Clinical Modification codes - using Medicaid from January 1, 2013 to December 31, 2013 from 10 states in the Truven MarketScan Medicaid Database. Using generalized linear models, we assessed which coexisting conditions (including medical technology) identified with Agency for Healthcare Research and Quality's Chronic Condition Indicators had the strongest associations with total healthcare spending across the healthcare continuum. RESULTS: Median per-patient annual Medicaid spending for children with CP was $12 299 (IQR $4826-$35 582). Most spending went to specialty (33.1%) and hospital (26.7%) care. The children had a median 6 (IQR 4-10) coexisting conditions; epilepsy was the most common (38.1%). Children with epilepsy accounted for 59.6% ($364 million) of all CP spending. In multivariable analysis, the coexisting conditions most strongly associated with increased spending were tracheostomy (median additional cost per patient = $56 567 [95%CI $51 386-61 748]) and enterostomy (median additional cost per patient = $25 707 [95%CI $23 753-27 660]). CONCLUSIONS: Highly prevalent in children with CP using Medicaid, coexisting conditions correlate strongly with healthcare spending. Tracheostomy and enterostomy, which indicate significant functional impairments in breathing and digestion, are associated with the highest spending. Families, providers, payers, and legislators may leverage these findings when designing policies positioned to enable the best health and care for children with cerebral palsy.

Well-Child Visits of Medicaid-Insured Children with Medical Complexity.

OBJECTIVE: Well-child visits (WCVs) help optimize children's health. We measured annual WCVs for children with medical complexity (CMC) and correlated WCVs with hospitalizations. STUDY DESIGN: This was a retrospective analysis of 93 121 CMC aged 1-18 years continuously enrolled in 10 state Medicaid programs in the Truven MarketScan Database between 2010 and 2014. CMC had a complex chronic condition or 3 or more chronic conditions of any complexity identified from International Classification of Diseases, Ninth Revision codes, and the use of 1 or more chronic medications. We measured the number of years with 1 or more WCVs. The χ2 test and logistic regression were used to assess the relationships of WCV-years with the children's characteristics and hospitalization. RESULTS: Over 5 years, 13.4% of CMC had 0 WCVs; 17.3% had WCVs in 1 year, 40.8% had WCVs in 2-3 years, and 28.5% had WCVs in 4-5 years. Fewer children received WCVs in 4-5 years when enrolled in Medicaid fee-for-service compared with managed care (20.9% vs 31.5%; P < .001) and when enrolled due to a disability compared with another reason (18.2% vs 32.2%; P < .001). The percentage of CMC hospitalized decreased as the number of years receiving WCV increased (21.5% at 0 years vs 16.9% at 5 years; P < .001). The adjusted odds of hospitalization were higher in CMC with WCVs in 0-4 years compared with CMC with WCVs in all 5 years (OR range across years, 1.1 [95% CI, 1.0-1.2] to 1.3 [95% CI, 1.3-1.4]). CONCLUSIONS: Most Medicaid-insured CMC do not receive annual WCVs consistently over time. Children with fewer annual WCVs have a higher likelihood of hospitalization. Further investigation is needed to improve the use of WCVs in CMC.

Diagnostic Evaluation of Patients Presenting to Primary Care with Rectal Bleeding.

BACKGROUND: Rectal bleeding is a common, frequently benign problem that can also be an early sign of colorectal cancer. Diagnostic evaluation for rectal bleeding is complex, and clinical practice may deviate from available guidelines. OBJECTIVE: To assess the degree to which primary care physicians document risk factors for colorectal cancer among patients with rectal bleeding and order colonoscopies when indicated, and the likelihood of physicians ordering and patients receiving recommended colonoscopies based on demographic characteristics, visit patterns, and clinical presentations. DESIGN: Cross-sectional study using explicit chart abstraction methods. PARTICIPANTS: Three hundred adults, 40-80 years of age, presenting with rectal bleeding to 15 academically affiliated primary care practices between 2012 and 2016. MAIN MEASURES: 1) The frequency at which colorectal cancer risk factors were documented in patients' charts, 2) the frequency at which physicians ordered colonoscopies and patients received them, and 3) the odds of ordering and patients receiving recommended colonoscopies based on patient demographic characteristics, visit patterns, and clinical presentations. KEY RESULTS: Risk factors for colorectal cancer were documented between 9% and 66% of the time. Most patients (89%) with rectal bleeding needed a colonoscopy according to a clinical guideline. Physicians placed colonoscopy orders for 74% of these patients, and 56% completed the colonoscopy within a year (36% within 60 days). The odds of physicians ordering recommended colonoscopies were significantly higher in patients aged 50-64 years of age than in those aged 40-50 years (OR = 2.23, 95% CI: 1.04, 4.80), and for patients whose most recent colonoscopy was 5 or more years ago (OR = 4.04, 95% CI: 1.50, 10.83). The odds of physicians ordering and patients receiving recommended colonoscopies were significantly lower for each primary care visit unrelated to rectal bleeding (OR = 0.85, 95% CI: 0.75, 0.96). CONCLUSIONS: Diagnostic evaluation of patients presenting to primary care with rectal bleeding may be suboptimal because of inadequate risk factor assessment and prioritization of patients' other concurrent medical problems.

Tumor suppressors miR-143 and miR-145 and predicted target proteins API5, ERK5, K-RAS, and IRS-1 are differentially expressed in proximal and distal colon.

The colon differs regionally in local luminal environment, excretory function, and gene expression. Polycistronic microRNA (miR)-143 and miR-145 are downregulated early in colon cancer. We asked if these microRNAs (miRNAs) might be differentially expressed in the proximal vs. the distal colon, contributing to regional differences in protein expression. Primary transcripts and mature miR-143 and miR-145 were quantified by real-time PCR, putative targets were measured by Western blotting, and DNA methylation was assessed by sequencing bisulfite-treated DNA in proximal and distal normal colonic mucosa as well as colon cancers. Putative targets of these miRNAs were assessed following transfection with miR-143 or miR-145. Mean expression of mature miR-143 and miR-145 was 2.0-fold (P < 0.001) and 1.8-fold (P = 0.03) higher, respectively, in proximal than distal colon. DNA methylation or primary transcript expression of these miRNAs did not differ by location. In agreement with increased expression of miR-143 and miR-145 in proximal colon, predicted targets of these miRNAs, apoptosis inhibitor 5 (API5), ERK5, K-RAS, and insulin receptor substrate 1 (IRS-1), which are cell cycle and survival regulators, were expressed at a lower level in proximal than distal colon. Transfection of HCA-7 colon cancer cells with miR-145 downregulated IRS-1, and transfection of HT-29 colon cancer cells with miR-143 decreased K-RAS and ERK5 expression. In conclusion, miR-143 and miR-145 and the predicted target proteins API5, ERK5, K-RAS, and IRS-1 display regional differences in expression in the colon. We speculate that differences in these tumor suppressors might contribute to regional differences in normal colonic gene expression and modulate site-specific differences in malignant predisposition.