Increased Risk of Colorectal Cancer in Individuals With a History of Serrated Polyps.

BACKGROUND AND AIMS: Serrated polyp (SPs) are precursors to 20% to 30% of cases of colorectal tumors, but patients' long-term risk after removal of SPs is poorly understood. We investigated the risk of colorectal cancer (CRC) in individuals with a history of SPs. METHODS: We performed a retrospective cohort study of Kaiser Permanente Northern California members who underwent colonoscopy from 2006 through 2016. Study participants were categorized based on the size and location of SPs. We used Cox proportional hazards modeling to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association of CRC diagnosed more than 1 year after colonoscopy, with polyp type vs no polyp after adjustment for year of colonoscopy, age, sex, race/ethnicity, and smoking history. RESULTS: The study included 233,393 individuals, of whom 445 developed incident CRC. At 10 years, the cumulative incidence rates of CRC for individuals with no polyp, proximal small SPs, proximal large SPs, and distal SPs were 4.7 (95% CI, 4.0-5.6), 14.8 (95% CI, 9.0-24.3), 30.2 (95% CI, 13.2-68.4), and 5.9 (95% CI, 3.6-9.5) per 1000 persons, respectively. In patients with SPs, risk of CRC was not increased until 3 years or more after the first colonoscopy (HR for small proximal SPs 2.6; 95% CI, 1.7-3.9 and HR for large proximal SPs 8.0; 95% CI, 3.6-16.1). The presence of synchronous adenomas increased the risk for CRC (HR for proximal SPs with synchronous adenomas 4.0; 95% CI, 3.0-5.5 and HR for distal SPs with synchronous adenomas 2.4; 95% CI, 1.7-3.4). CONCLUSIONS: In a retrospective analysis of a large cohort of individuals examined by colonoscopy, we found that risk of incident CRC increased in individuals with proximal SPs (large SPs in particular) 3 years or more after the colonoscopy. These findings support guidelines that recommend surveillance colonoscopy for individuals with SPs.

A Transparent and Adaptable Method to Extract Colonoscopy and Pathology Data Using Natural Language Processing.

Key variables recorded as text in colonoscopy and pathology reports have been extracted using natural language processing (NLP) tools that were not easily adaptable to new settings. We aimed to develop a reliable NLP tool with broad adaptability. During 1996-2016, Kaiser Permanente Northern California performed 401,566 colonoscopies with linked pathology. We randomly sampled 1000 linked reports into a Training Set and developed an NLP tool using SAS® PERL regular expressions. The NLP tool captured five colonoscopy and pathology variables: type, size, and location of polyps; extent of procedure; and quality of bowel preparation. We used a Validation Set (N = 3000) to confirm the variables' classifications using manual chart review as the reference. Performance of the NLP tool was assessed using the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen's κ. Cohen's κ ranged from 93 to 99%. The sensitivity and specificity ranged from 95 to 100% across all categories. For categories with prevalence exceeding 10%, the PPV ranged from 97% to 100% except for adequate quality of preparation (prevalence 92%), for which the PPV was 65%. For categories with prevalence below 10%, the PPVs ranged from 62% to 100%. NPVs ranged from 94% to 100% except for the "complete" extent of procedure, for which the NPV was 73%. Using information from a large community-based population, we developed a transparent and adaptable NLP tool for extracting five colonoscopy and pathology variables. The tool can be readily tested in other healthcare settings.

Comparative effectiveness study of face-to-face and teledermatology workflows for diagnosing skin cancer.

BACKGROUND: The effectiveness and value of teledermatology and face-to-face workflows for diagnosing lesions are not adequately understood. OBJECTIVE: We compared the risks of biopsy and cancer diagnosis among 2 face-to-face workflows (direct referral and roving dermatologist) and 4 teledermatology workflows. METHODS: Retrospective study of 59,279 primary care patients presenting with a lesion from January through June 2017. RESULTS: One teledermatology workflow achieved high-resolution images with use of a dermatoscope-fitted digital camera, a picture archiving and communication system, and image retrieval to a large computer monitor (in contrast to a smartphone screen). Compared with direct referral, this workflow was associated with a 9% greater probability of cancer detection (95% confidence interval [CI], 2%-16%), a 4% lower probability of biopsy (relative risk, 0.96; 95% CI, 0.93-0.99), and 39% fewer face-to-face visits (relative risk, 0.61; 95% CI, 0.57-0.65). Other workflows were less effective. LIMITATIONS: Differing proficiencies across teledermatology workflows and selection of patients for direct referral could have caused bias. CONCLUSION: Implementation is critical to the effectiveness of teledermatology.

Comparison of Methods of Clinical Trial Emulation Utilizing Data From the Comparison of AMD Treatment Trial (CATT) and the IRIS® Registry.

Purpose: We used exact matching and inverse propensity score weighting (IPSW) using real-world data (RWD) from the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) to emulate the 2 pro re nata (prn) treatment arms from the Comparison of AMD Treatment Trial (CATT) and to compare the outcomes of the RWD arms to the 2 monthly treatment arms from the clinical trial. Design: Retrospective cohort study utilizing deidentified electronic health record registry data and patient-level deidentified clinical trial data. Subjects: All treatment-naive patient eyes with neovascular age-related macular degeneration treated with ranibizumab or bevacizumab only for 1 year from either the CATT or the IRIS Registry. Methods: Patients were identified in the IRIS Registry between October 1, 2015 and December 31, 2019. After all nonimaging-based inclusion and exclusion criteria from the CATT were applied, patient eyes receiving bevacizumab or ranibizumab only on a prn basis were identified as the eligible cohort. Exact matching and ISPW was applied based on age, gender, and baseline visual acuity. Main Outcome Measures: Mean change in visual acuity, in approximated ETDRS letters, between baseline and 1 year for the IRIS Registry prn treatment arms generated by exact matching and IPSW. Results: We identified 427 eyes treated with ranibizumab prn and 771 eyes treated with bevacizumab prn. Using exact matching, 98% (n = 281) of CATT patient eyes in the bevacizumab monthly treatment arm and 87% (n = 261) of CATT patient eyes in the ranibizumab monthly treatment arm were matched to a patient eye in the IRIS Registry. For the ranibizumab prn treatment arm, patient eyes generated using exact matching gained 1.9 letters and those generated using IPSW gained 2.8 letters (exact matching: 1.9 letters ± 14.0 vs. IPSW: 2.8 letters ± 15.0 letters, P = 0.43). For the bevacizumab prn treatment arm, patient eyes generated using exact matching gained 2.4 letters and those generated using IPSW gained 2.1 letters (exact matching: 2.4 letters ± 15.4 vs. IPSW: 2.1 letters ± 16.0 letters, P = 0.79). Conclusions: Both exact matching and IPSW produced similar results in emulating the prn treatment arms of the CATT using IRIS Registry data and patient-level clinical trial data. Similar to prior real-world studies, the clinical outcomes were significantly worse in the IRIS Registry treatment arms compared with the clinical trial. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Impact of Anti-VEGF Treatment and Patient Characteristics on Vision Outcomes in Neovascular Age-related Macular Degeneration: Up to 6-Year Analysis of the AAO IRIS® Registry.

Purpose: To evaluate anti-VEGF treatment patterns and the influence of patient demographic and clinical characteristics on up to 6-year vision outcomes in neovascular age-related macular degeneration. Design: Retrospective, multicenter, noninterventional registry study with up to 6 years of follow-up. Participants: A cohort of 254 655 eyes (226 767 patients) with first anti-VEGF injection and at least 2 years of follow-up; 160 423 eyes had visual acuity (VA) data. Methods: Anonymized patient data were collected in the United States through the IRIS® Registry (Intelligent Research in Sight). Main Outcome Measures: Changes in VA from baseline; frequency of and gaps between intravitreal anti-VEGF injections; treatment discontinuations; switching anti-VEGF agents; and influence of baseline clinical and demographic characteristics on VA. Results: After a mean VA increase of 3.0 ETDRS letters at year 1, annual decreases led to a net loss from baseline of 4.6 letters after 6 years. Patients with longer follow-ups had better baseline and follow-up VA. From a mean of 7.2 in year 1 and 5.6 in year 2, mean injections plateaued between 4.2 to 4.6 in years 3 through 6. Treatment was discontinued in 38.8% of eyes and switched in 32.3%. When adjusting for differences at baseline, every additional injection resulted in a 0.68 letter improvement from baseline to year 1; thus, multiple injections in a year have the potential to be clinically meaningful. Older age, male gender, Medicaid insurance, and not being treated by a retina specialist were associated with a higher likelihood of vision loss at year 1. Of the patients, 58.5% lost ≥ 10 letters VA at least once during follow-up, with 14.5% of patients experiencing sustained poor vision after a median of 3.4 years. Conclusions: After modest mean VA improvement with intravitreal anti-VEGF injections at year 1, patients netted a loss of VA by year 6. Injection frequency decreased over time, and this was paired with a relatively high rate of discontinuation. Modeling suggested that more frequent injections were associated with better VA. Difficulty with continuous adherence to frequent intravitreal injections may have contributed to undertreatment resulting in less-than-optimal vision outcomes. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

IRIS® Registry (Intelligent Research In Sight) Analysis of the Incidence of Monovision in Cataract Patients with Bilateral Monofocal Intraocular Lens Implantation.

Purpose: To determine the incidence of pseudophakic monovision among patients bilaterally implanted with monofocal intraocular lenses (IOLs) and to characterize the distribution of myopic offsets achieved. Patients and Methods: This retrospective database study included data on patients receiving care from ophthalmologists who contributed to the Academy IRIS® (Intelligent Research In Sight) Registry. Anonymized data were collected, including patient age, ethnicity, procedure data (CPT code, date, laterality), and postoperative manifest refractive spherical equivalent (MRSE) in both eyes implanted with monofocal or monofocal toric IOLs. No data regarding IOL manufacturer, model, or power were collected. One primary outcome measure was the percentage of patients achieving monovision (defined as emmetropia within ±0.25 diopters [D] in one eye and a myopic offset of ≥0.50 D in the fellow eye) among all patients receiving bilateral monofocal IOLs at the time of cataract surgery between January 1, 2016, and September 1, 2019, with at least 90 days of follow-up. Other primary outcomes included the distribution and frequency of myopic offsets (anisometropia) between eyes. Results: Of the 16,765 people receiving bilateral monofocal IOLs within the study period, 4796 (28.6%) achieved emmetropia in at least one eye, as defined by an MRSE within ± 0.25 D. The incidence of monovision among these patients was 34.2% (1638/4796). One-quarter (24.7%; 405/1638) of patients who achieved monovision had a myopic offset between 0.50 and 0.74 D, with more than one-third (35.2%; 576/1638) falling within 0.75-1.24 D and 18.0% within 1.25-1.74 D. A myopic offset ≥1.75 D was observed in 22.1% (362/1638) of patients who achieved monovision. Conclusion: Pseudophakic monovision for presbyopia correction was achieved in ~34% of patients in the IRIS Registry bilaterally implanted with monofocal IOLs, with myopic offsets typically ranging from 0.5 to 1.24 D.

Dry Age-Related Macular Degeneration: Distribution of Visual Acuity and Progression Risk in a Large Registry.

INTRODUCTION: Understanding the progression to geographic atrophy (GA) in late dry age-related macular degeneration (dAMD) can support development opportunities for dAMD treatments. We characterized dAMD by distribution of visual acuity (VA) categories and evaluated VA progression risk by disease stage. METHODS: This retrospective observational study used data from the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) to identify patients diagnosed with dAMD in ≥ 1 eye from January 2016 through December 2019 (index date) with ≥ 1 visit and ≥ 1 VA measurement recorded post-index date. Patients were followed until the date of last visit, last contribution for diagnosing provider, or diagnosis of neovascular AMD post-index. Models were utilized to describe the distribution of VA categories and progression to worsening VA. RESULTS: Data from 593,277 patients were analyzed. At baseline, 64.4% had mild disease, 29.4% intermediate, and 2.9%/3.3% had GA with/without subfoveal involvement. Most patients with mild (88.4%) and intermediate (79.7%) disease and GA without subfoveal involvement (57.1%) had baseline VA ≥ 20/63 in the study eye; 72.0% of patients with GA with subfoveal involvement had VA < 20/63. Modeled results showed lower VA with more progressive stage at baseline. Annual probability of stable dAMD based on baseline stage ranged from 82.1% (GA without) to 92.3% (GA with subfoveal involvement). Annual progression probability to GA without/with subfoveal involvement was 0.4% for mild and 5.5% for intermediate disease and from dry to neovascular AMD, 0.5% for mild and 8.0% for intermediate disease. CONCLUSIONS: Results from this analysis of a large database of electronic health records complement those from randomized trials and show that patients with more advanced dAMD have lower VA at baseline and that VA progression is generally faster with each progressive stage. Together these findings highlight the disease burden and trajectory of dAMD as well as opportunities for addressing unmet needs.

Dry age-related macular degeneration (dAMD) is a disease that progressively worsens over time. As the disease progresses, patients start to lose their vision, leading to a substantial burden on their quality of life and finances due to the need for increased healthcare services. As of 2022, there are no medications available to reverse or stop worsening of dAMD. This study used real-world data from a large registry of electronic health records to increase the understanding of how patients progress through the stages of dAMD. By reviewing patient records, we were able to identify approximately 600,000 patients with confirmed dAMD. These patients were then followed over time, and we were able to confirm that patients with a lower ability to see at the beginning of our review period had more advanced dAMD. We also found that as patients' disease worsened, their vision also decreased. These findings highlight the need for new medication options to reverse or delay the worsening of dAMD and improve the quality of life for patients.

Academy IRIS® Registry Analysis of Incidence of Laser Capsulotomy Due to Posterior Capsule Opacification After Intraocular Lens Implantation.

Purpose: Academy IRIS® (Intelligent Research in Sight) Registry was used to determine the incidence of postoperative neodymium-doped yttrium aluminum garnet laser capsulotomy (Nd:YAG) and time to posterior capsular opacification (PCO) diagnosis based on intraocular lens (IOL) type and brand. Methods: This retrospective analysis included eyes implanted with 1 of 2 IOL brands, with ≥365 days of follow-up available in the IRIS Registry, and ≥2 visits within 180 days of surgery. Analyses included Nd:YAG incidence due to PCO within 1 year after surgery by IOL type and brand, mean time to PCO diagnosis, and mean time to Nd:YAG. Results: Of 89,947 eyes after cataract surgery, 24,834 (28%) had PCO diagnosis within 365 days, and 9262 (10%) underwent Nd:YAG; 4.1% of 57,523 eyes with monofocal and 21.2% of 32,424 eyes with diffractive multifocal (MF) or diffractive extended depth of focus (EDOF) IOLs had Nd:YAG. Nd:YAG was 3.2 times more likely in eyes with diffractive MF or diffractive EDOF IOLs versus monofocal. For monofocal IOLs, 3.2% of eyes with AcrySof® and 8.1% of eyes with Tecnis® had Nd:YAG (P<0.0001). For diffractive MF or diffractive EDOF IOLs, 13.0% of eyes with AcrySof and 21.7% of eyes with Tecnis had Nd:YAG (P<0.0001). Nd:YAG risk was 2.4 times higher in eyes with Tecnis versus AcrySof IOLs. Overall, mean time to PCO diagnosis and Nd:YAG was 150.7 and 180.7 days. Mean time to PCO for monofocal versus diffractive MF or diffractive EDOF IOLs was 165.3 versus 139.7 days (P<0.0001). Mean time to Nd:YAG for monofocal versus diffractive MF or diffractive EDOF IOLs was 196.4 versus 175.3 days (P<0.05). Conclusion: Real-world data for AcrySof and Tecnis IOLs revealed lower Nd:YAG rates and longer time to PCO diagnosis and Nd:YAG after monofocal versus diffractive multifocal or diffractive EDOF implantation. Nd:YAG rates were significantly lower with AcrySof versus Tecnis IOLs.

Hospital-level factors associated with nonoperative management in common pediatric surgical procedures.

PURPOSE: Our purpose was to examine patient- and hospital-level factors associated with nonoperative management in common pediatric surgical diagnoses. METHODS: Using the 2012 Kid's Inpatient Database (KID), we identified patients <20 years old diagnosed with cholecystitis (CHOL), bowel obstruction (BO), perforated appendicitis (PA), or spontaneous pneumothorax (SPTX). Logistic regression models were used to identify factors associated with nonoperative management. RESULTS: Of 36,026 admissions for the diagnoses of interest, 7472 (20.7%) were managed nonoperatively. SPTX had the highest incidence of NONOP (55.9%; n = 394), while PA had the lowest incidence (9.2%; n = 1641). Utilization of operative management varied significantly between hospitals. Patients diagnosed with BO (OR 0.41; 95% CI 0.30-0.56) and SPTX (OR 0.28; 95% CI 0.14-0.56) had decreased odds of operative management when treated at an urban, teaching hospital compared to a rural hospital. Patients with PA had increased odds of operative management when treated at an urban, teaching hospital (OR 2.42; 95% CI 1.78-3.30). Hospital-level factors associated with decreased odds of nonoperative management included urban, nonteaching status (OR 0.54; 95% CI 0.31-0.91) and location in the South (OR 0.53; 95% CI 0.34-83) and West (OR 0.47; 95% CI 0.30-0.74). CONCLUSIONS: Despite representing more than 20% of pediatric surgical care for several conditions, nonoperative management is an understudied aspect of care with significant variation that warrants further research. LEVEL OF EVIDENCE: III.

Long-term follow-up of pediatric open and laparoscopic inguinal hernia repair.

BACKGROUND: Pediatric laparoscopic inguinal hernia repair is not widely accepted. STUDY DESIGN: Children 0-14 years who underwent inguinal hernia repair during 2010-2016 at Kaiser Permanente Northern California were classified into five groups: (1) open unilateral repair without contralateral exploration; (2) open unilateral repair with contralateral laparoscopic exploration ("open+explore"); (3) open bilateral repair; (4) laparoscopic unilateral repair; and (5) laparoscopic bilateral repair. Outcomes included ipsilateral reoperation, metachronous contralateral repair, incision time, and complications. RESULTS: The study included 1697 children. Follow-up averaged 3.6 years after open (N = 1156) and 2.6 years after laparoscopic (N = 541) surgery. Metachronous contralateral repair was performed in 3.8% (26/683) of patients with open unilateral surgery without contralateral exploration, 0.7% (2/275) of open+explore patients, and 0.9% (3/336) of laparoscopic unilateral patients (p < 0.01). Ipsilateral repair was performed in 0.8% (10/1156) of open repairs and 0.3% (2/541) of laparoscopic repairs. Chart review confirmed 5 postoperative infections in 1156 patients with open surgery (0.43%) and 6 infections in 541 patients with laparoscopic surgery (1.11%) (p = 0.11). CONCLUSION: Our study's laparoscopic and open approaches have similar low ipsilateral reoperation rates, incision times, and complications. The use of laparoscopy to visualize the contralateral side resulted in a significantly lower rate of metachronous contralateral repair. LEVEL OF EVIDENCE: Level III.

Understanding Nonadherence with Hydroxychloroquine Therapy in Systemic Lupus Erythematosus.

OBJECTIVE: Hydroxychloroquine (HCQ) is a cornerstone to managing systemic lupus erythematosus (SLE), yet adherence to medication is poor. We sought to measure the association of adherence with 5 "dimensions of adherence" as articulated by the World Health Organization for chronic conditions: the patient's socioeconomic status, and patient-, condition-, therapy-, and healthcare system-related factors. Our longterm goal is to generate evidence to design effective interventions to increase adherence. METHODS: The retrospective cohort study included Kaiser Permanente Northern California patients ≥ 18 years old during 2006-2014, with SLE and ≥ 2 consecutive prescriptions for HCQ. Adherence was calculated from the medication possession ratio and dichotomized as < 80% versus ≥ 80%. Predictor variables were obtained from the electronic medical record and census data. We used multivariable logistic regression to estimate adjusted OR and 95% CI. RESULTS: The study included 1956 patients. Only 58% of patients had adherence ≥ 80%. In adjusted analyses, socioeconomic variables did not predict adherence. Increasing age (65-89 yrs compared with ≤ 39 yrs: OR 1.44, 95% CI 1.07-1.93), white race (p < 0.05), and the number of rheumatology visits in the year before baseline (≥ 3 compared with 0 or 1: OR 1.47, 95% CI 1.18-1.83) were positively associated with adherence. The rheumatologist and medical center providing care were not associated with adherence. CONCLUSION: At our setting, as in other settings, about half of patients with SLE were not adherent to HCQ therapy. Differences in adherence by race/ethnicity suggest the possibility of using tailored interventions to increase adherence. Qualitative research is needed to elucidate patient preferences for adherence support.

Proton Pump Inhibitors, H2 Blocker Use, and Risk of Inflammatory Bowel Disease in Children.

OBJECTIVES: Evidence suggests use of proton pump inhibitors (PPIs) and H2 blockers may provoke disease flares in individuals with established inflammatory bowel disease (IBD); however, there are no studies investigating the relationship of these medications with risk of developing pediatric IBD. The hypothesis was that use of acid suppression therapy in children might be associated with development of pediatric IBD. METHODS: This was a nested case-control study of 285 Kaiser Permanente Northern California members, age ≤21 years diagnosed with IBD from 1996 to 2016. Four controls without IBD were matched to each case on age, race, and membership status at the case's index date. Disease risk scores (DRS) were computed for each subject. Odds ratios and 95% confidence intervals were calculated by using conditional logistic regression models adjusted for DRS. RESULTS: The children's mean age was 15.1 ± 2.6 years and 49.5% were female. Six cases (n = 3 Crohn's disease [CD], n = 3 ulcerative colitis [UC]) and 6 controls were prescribed PPIs and 10 cases (n = 7 CD, n = 3 UC) and 28 controls were prescribed H2 blockers. The OR for the association of at least 1 PPI or H2 blocker prescription with subsequent IBD was 3.6 (95% CI, 1.1-11.7) for PPIs and 1.6 (95% CI, 0.7-3.7) for H2 blockers. CONCLUSIONS: Early-life PPI use appears to be associated with subsequent IBD risk. These findings have implications for clinical treatment of children with gastrointestinal symptoms and warrant further investigation in a larger cohort.

Immediate sequential bilateral cataract surgery: surgeon preferences and concerns.

OBJECTIVE: We surveyed cataract surgeons to gain insight into their perceptions of and attitudes about immediate sequential bilateral cataract surgery (ISBCS). DESIGN: Cross-sectional. PARTICIPANTS: All active cataract surgeons in Kaiser Permanente Northern California in 2016. METHODS: Online survey that asked cataract surgeons why they did or did not perform ISBCS, their interest in offering ISBCS, concerns about the procedure, and desired supports. RESULTS: Of the 165 active cataract surgeons, 107 (65%) participated in the survey, of whom 92 (86%) responded that they currently practiced ISBCS and 15 (14%) reported that they did not. For ISBCS surgeons, patient convenience (95%) and patient request (91%) were the top reasons for performing the procedure. For surgeons who do not perform ISBCS, the most commonly cited concerns were not having the postoperative refractive outcome from the first eye to guide intraocular lens selection in the second eye (80%) and risk of bilateral vision loss (73%). Among those who do not perform ISBCS, 9 (60%) identified the need for evidence-based patient selection criteria to support a decision to adopt the procedure. In addition, many surgeons in both groups wanted streamlined patient education materials and established protocols. CONCLUSION: Patient centeredness is a key construct of contemporary health care delivery, and in an era of low complication risk, many patients request ISBCS; the number of these surgeries has increased. In our capitated health care system, the great majority of surgeons perform ISBCS for the convenience of their patients. Providing surgeons with guidelines and tools to support ISBCS likely would increase adoption.

Reducing risk of Clostridium difficile infection and overall use of antibiotic in the outpatient treatment of urinary tract infection.

BACKGROUND: Risk of community-acquired Clostridium difficile infection (CA-CDI) following antibiotic treatment specifically for urinary tract infection (UTI) has not been evaluated. METHODS: We conducted a nested case-control study at Kaiser Permanente Northern California, 2007-2010, to assess antibiotic prescribing and other factors in relation to risk of CA-CDI in outpatients with uncomplicated UTI. Cases were diagnosed with CA-CDI within 90 days of antibiotic use. We used matched controls and confirmed case-control eligibility through chart review. Antibiotics were classified as ciprofloxacin (most common), or low risk (nitrofurantoin, sulfamethoxazole/trimethoprim), moderate risk, or high risk (e.g. cefpodoxime, ceftriaxone, clindamycin) for CDI. We computed the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the relationship of antibiotic treatment for uncomplicated UTI and history of relevant gastrointestinal comorbidity (including gastrointestinal diagnoses, procedures, and gastric acid suppression treatment) with risk of CA-CDI using logistic regression analysis. RESULTS: Despite the large population, only 68 cases were confirmed with CA-CDI for comparison with 112 controls. Female sex [81% of controls, adjusted odds ratio (OR) 6.3, CI 1.7-24), past gastrointestinal comorbidity (prevalence 39%, OR 2.3, CI 1.1-4.8), and nongastrointestinal comorbidity (prevalence 6%, OR 2.8, CI 1.4-5.6) were associated with increased CA-CDI risk. Compared with low-risk antibiotic, the adjusted ORs for antibiotic groups were as follows: ciprofloxacin, 2.7 (CI 1.0-7.2); moderate-risk antibiotics, 3.6 (CI 1.2-11); and high-risk antibiotics, 11.2 (CI 2.4-52). CONCLUSIONS: Lower-risk antibiotics should be used for UTI whenever possible, particularly in patients with a gastrointestinal comorbidity. However, UTI can be managed through alternative approaches. Research into the primary prevention of UTI is urgently needed.

Defining the association between operative time and outcomes in children's surgery.

INTRODUCTION: Prolonged operative time (OT) is considered a reflection of procedural complexity and may be associated with poor outcomes. Our purpose was to explore the association between prolonged OT and complications in children's surgery. METHODS: 182,857 cases from the 2012-2014 NSQIP-Pediatric were organized into 33 groups. OT for each group was analyzed by quartile, and regression models were used to determine the relationship between prolonged OT and complications. RESULTS: Variations in OT existed for both short and long procedures. Cases in the longest quartile had twice the odds of postoperative complications after adjusting for age, sex and BMI (OR 1.85; 95% CI 1.78-1.91). Procedure-specific prolonged OT was associated with postoperative complications for the majority (85%) of procedural groupings. Prolonged OT was associated with minor complications in gynecologic (OR 4.17; 95% CI 2.19-7.96), urologic (OR 2.88; 95% CI 2.40-3.44), and appendix procedures (OR 2.88; 95% CI 2.49-3.34). There were increased odds of major complications in foregut (OR 6.56; 95% CI 4.99-8.64), gynecologic (OR 3.07; 95% CI 1.84-5.13), and spine procedures (OR 2.99; 95% CI 2.57-3.28). CONCLUSIONS: Prolonged OT is associated with increased odds of postoperative complications across a spectrum of children's surgical procedures. Factors contributing to prolonged OT merit further investigation and may serve as a target for future quality improvement. LEVEL OF EVIDENCE: Level III.

Comparison of Outcomes between Individuals with Pure and Mixed Lupus Nephritis: A Retrospective Study.

INTRODUCTION: Lupus nephritis (LN) is a serious organ manifestation of systemic lupus erythematosus. Histologic overlap is relatively common in the six pathologic classes (I to VI) of LN. For example, mixed proliferative LN (MPLN) often includes features of classes III & V or classes IV & V combined. We performed a comparative evaluation of renal outcomes in patients with MPLN to patients with pure proliferative LN (PPLN) against pre-specified renal outcomes, and we also identified predictor of clinical outcomes among those with PPLN and MPLN. HYPOTHESIS: Individuals with MPLN will have worse short-term renal outcomes compared to those with PPLN. METHODS: We retrospectively reviewed 278 adult LN patients (≥18 years old) identified from an Emory University Hospital registry of native renal biopsies performed between January 2000 and December 2011. The final analytic sample consisted of individuals with a diagnosis of PPLN (n = 60) and MPLN (n = 96). We analyzed differences in clinical and laboratory characteristics at baseline. We also assessed associations between LN category and renal outcomes (complete remission and time to ESRD) with logistic and Cox proportional hazards models within two years of baseline. RESULTS: The study population was predominantly female (83.97%) and African American (71.8%) with a mean age of 33.4 years at baseline. Over a median follow up of 1.02 years, we did not find any statistically significant associations between MPLN and the development of ESRD or remission when compared to patients with PPLN (adjusted HR = 0.30, 95% CI = 0.07, 1.26). CONCLUSION: There was no association between mixed or pure histopathologic features of LN at presentation and rate of complete or partial remission but higher baseline eGFR was associated with a lower probability of complete remission among patients with lupus nephritis.

Non-viable Borrelia burgdorferi induce inflammatory mediators and apoptosis in human oligodendrocytes.

In previous studies, exposure to live Borrelia burgdorferi was shown to induce inflammation and apoptosis of human oligodendrocytes. In this study we assessed the ability of non-viable bacteria (heat killed or sonicated) to induce inflammatory mediators and cell death. Both heat-killed and sonicated bacteria induced release of CCL2, IL-6, and CXCL8 from oligodendrocytes in a dose dependent manner. In addition, non-viable B. burgdorferi also induced cell death as evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and another cell viability assay. These results suggest that spirochetal residues left after bacterial demise, due to treatment or otherwise, may continue to be pathogenic to the central nervous system.