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.

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.

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.

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.

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.

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.

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.