To determine whether childhood antianaerobic antibiotic exposure is associated with the development of inflammatory bowel disease (IBD).
This retrospective cohort study employed data from 464 UK ...ambulatory practices participating in The Health Improvement Network. All children with ≥ 2 years of follow-up from 1994 to 2009 were followed between practice enrollment and IBD development, practice deregistration, 19 years of age, or death; those with previous IBD were excluded. All antibiotic prescriptions were captured. Antianaerobic antibiotic agents were defined as penicillin, amoxicillin, ampicillin, penicillin/β-lactamase inhibitor combinations, tetracyclines, clindamycin, metronidazole, cefoxitin, carbapenems, and oral vancomycin.
A total of 1072426 subjects contributed 6.6 million person-years of follow-up; 748 developed IBD. IBD incidence rates among antianaerobic antibiotic unexposed and exposed subjects were 0.83 and 1.52/10000 person-years, respectively, for an 84% relative risk increase. Exposure throughout childhood was associated with developing IBD, but this relationship decreased with increasing age at exposure. Exposure before 1 year of age had an adjusted hazard ratio of 5.51 (95% confidence interval CI: 1.66-18.28) but decreased to 2.62 (95% CI: 1.61-4.25) and 1.57 (95% CI: 1.35-1.84) by 5 and 15 years, respectively. Each antibiotic course increased the IBD hazard by 6% (4%-8%). A dose-response effect existed, with receipt of >2 antibiotic courses more highly associated with IBD development than receipt of 1 to 2 courses, with adjusted hazard ratios of 4.77 (95% CI: 2.13-10.68) versus 3.33 (95% CI: 1.69-6.58).
Childhood antianaerobic antibiotic exposure is associated with IBD development.
ObjectiveGut microbiota influence metabolic pathways related to the pathogenesis of obesity, insulin-resistance and diabetes. Antibiotic therapy can alter the microbiota, and is commonly used in ...western countries. We sought to evaluate whether past antibiotic exposure increases diabetes risk.Research design and methodsWe conducted a nested case–control study using a large population-based database from the UK. The cases were defined as those with incident diagnosis of diabetes. For every case, four eligible controls matched on age, sex, practice-site, and duration of follow-up before index-date were selected using incidence-density sampling. Exposure of interest was antibiotic therapy >1 year before index-date. Odds ratios (ORs) and 95% CIs were estimated using conditional logistic regression. The risk was adjusted for BMI, smoking, last glucose level, and number of infections before index-date, as well as past medical history of coronary artery disease and hyperlipidaemia.ResultsThe study included 208 002 diabetic cases and 815 576 matched controls. Exposure to a single antibiotic prescription was not associated with higher adjusted diabetes risk. Treatment with two to five antibiotic courses was associated with increase in diabetic risk for penicillin, cephalosporins, macrolides and quinolones with adjusted OR ranging from 1.08 (95% CI 1.05–1.11) for penicillin to 1.15 (95% CI 1.08–1.23) for quinolones. The risk increased with the number of antibiotic courses and reached 1.37 (95% CI 1.19–1.58) for more than 5 courses of quinolones. There was no association between exposure to anti-virals and anti-fungals and diabetes risk.ConclusionsExposure to certain antibiotic groups increases diabetes risk.
Abstract Background & Aims Childhood obesity is increasing and is associated with adult obesity. Antibiotics have been used to promote weight gain in livestock for several decades. Antibiotics are ...commonly prescribed for children, but it is not clear how exposure to antibiotics early in life affects risk for obesity. We performed a population-based cohort study to assess the association between antibiotic exposure before age 2 years and obesity at age 4 years. Methods We performed a retrospective cohort study of 21,714 children in The Health Improvement Network —a population-representative dataset of more than 10 million individuals derived from electronic medical records from 1995 through 2013 in the United Kingdom. Eligible subjects were registered within 3 months of birth with complete follow-up and height and weight were recorded within 12 months of their 4th birthday. Antibiotic exposure was assessed before age 2 years, and classified based on anti-anaerobic activity. The primary outcome was obesity at age 4 years. We performed logistic regression analyses, adjusting for maternal and sibling obesity, maternal diabetes, mode of delivery, socioeconomic status, year and country of birth, and urban dwelling. Results In the cohort, 1306 of the children (6.4%) were obese at 4 years of age. Antibiotic exposure was associated with an increased risk of obesity at 4 years (odds ratio OR=1.21; 95% confidence interval CI, 1.07–1.38). Odds ratios increased with repeated exposures: for 1–2 prescriptions, OR=1.07 (95% CI, 0.91-1.23); for 3–5 prescriptions, OR=1.41 (95% CI, 1.20–1.65); for 6 or more prescriptions, OR=1.47 (95% CI, 1.19–1.82). Antifungal agents were not associated with obesity (OR=0.81; 95% CI, 0.59–1.11). Conclusions Administration of 3 or more courses of antibiotics before children reach an age of 2 years is associated with an increased risk of early childhood obesity.
Recent evidence has linked childhood antibiotic use and microbiome disturbance to autoimmune conditions. This study tested the hypothesis that antibiotic exposure was associated with newly diagnosed ...juvenile idiopathic arthritis (JIA).
We performed a nested case-control study in a population-representative medical records database from the United Kingdom. Children with newly diagnosed JIA were compared with age- and gender-matched control subjects randomly selected from general practices containing at least 1 case, excluding those with inflammatory bowel disease, immunodeficiency, or other systemic rheumatic diseases. Conditional logistic regression was used to examine the association between antibacterial antibiotics (including number of antibiotic courses and timing) and JIA after adjusting for significant confounders.
Any antibiotic exposure was associated with an increased rate of developing JIA (adjusted odds ratio: 2.1 95% confidence interval: 1.2-3.5). This relationship was dose dependent (adjusted odds ratio over 5 antibiotic courses: 3.0 95% confidence interval: 1.6-5.6), strongest for exposures within 1 year of diagnosis, and did not substantively change when adjusting for number or type of infections. In contrast, nonbacterial antimicrobial agents (eg, antifungal, antiviral) were not associated with JIA. In addition, antibiotic-treated upper respiratory tract infections were more strongly associated with JIA than untreated upper respiratory tract infections.
Antibiotics were associated with newly diagnosed JIA in a dose- and time-dependent fashion in a large pediatric population. Antibiotic exposure may play a role in JIA pathogenesis, perhaps mediated through alterations in the microbiome.
Current screening guidelines for colorectal cancer (CRC) do not consider thyroid dysfunction as a risk factor for disease development. We sought to determine the risk of developing CRC in patients ...with thyroid dysfunction, with and without thyroid hormone replacement (THR).
We conducted a nested case-control study using a large population-based medical records database from the United Kingdom. Study case patients were defined as those with any medical code of CRC. Subjects with familial colorectal cancer syndromes or inflammatory bowel disease (IBD) were excluded. For every case patient, four eligible control patients matched on age, sex, practice site, and duration of follow-up before index date were selected using incidence density sampling. Exposure was THR therapy before index date. We further divided the THR unexposed group into patients with hypothyroidism (TSH > 4 mg/dl), patients with hyperthyroidism (TSH < 0.4 mg/dl), and subjects without documented thyroid abnormality. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for CRC were estimated using conditional logistic regression. All statistical tests were two-sided.
We identified 20990 CRC patients and 82054 control patients. The adjusted odds ratio for CRC associated with THR was 0.88 (95% CI = 0.79 to 0.99, P = .03) and 0.68 (95% CI = 0.55 to 0.83, P < .001) for treatment initiated five to 10 years and more than 10 years before index date, respectively. This protective association increased with cumulative duration of therapy. In contrast, hyperthyroidism (adjusted OR = 1.21, 95% CI = 1.08 to 1.36, P = .001) or untreated hypothyroidism (adjusted OR = 1.16, 95% CI = 1.08 to 1.24, P < .001) were associated with increased risk of CRC.
Long-term THR is associated with a decreased risk of CRC. Hyperthyroidism and untreated hypothyroidism are associated with modestly elevated risk of CRC.
The supplementation of electronic health records data with administrative claims data may be used to capture outcome events more comprehensively in longitudinal observational studies. This study ...investigated the utility of administrative claims data to identify outcomes across health systems using a comparative effectiveness study of different types of bariatric surgery as a model.
This observational cohort study identified patients who had bariatric surgery between 2007 and 2015 within the HealthCore Anthem Research Network (HCARN) database in the National Patient-Centered Clinical Research Network (PCORnet) common data model. Patients whose procedures were performed in a member facility affiliated with PCORnet Clinical Research Networks (CRNs) were selected. The outcomes included a 30-day composite adverse event (including venous thromboembolism, percutaneous/operative intervention, failure to discharge and death), and all-cause hospitalization, abdominal operation or intervention, and in-hospital death up to 5 years after the procedure. Outcomes were classified as occurring within or outside PCORnet CRN health systems using facility identifiers.
We identified 4899 patients who had bariatric surgery in one of the PCORnet CRN health systems. For 30-day composite adverse event, the inclusion of HCARN multi-site claims data marginally increased the incidence rate based only on HCARN single-site claims data for PCORnet CRNs from 3.9 to 4.2%. During the 5-year follow-up period, 56.8% of all-cause hospitalizations, 31.2% abdominal operations or interventions, and 32.3% of in-hospital deaths occurred outside PCORnet CRNs. Incidence rates (events per 100 patient-years) were significantly lower when based on claims from a single PCORnet CRN only compared to using claims from all health systems in the HCARN: all-cause hospitalization, 11.0 (95% Confidence Internal CI: 10.4, 11.6) to 25.3 (95% CI: 24.4, 26.3); abdominal operations or interventions, 4.2 (95% CI: 3.9, 4.6) to 6.1 (95% CI: 5.7, 6.6); in-hospital death, 0.2 (95% CI: 0.11, 0.27) to 0.3 (95% CI: 0.19, 0.38).
Short-term inclusion of multi-site claims data only marginally increased the incidence rate computed from single-site claims data alone. Longer-term follow up captured a notable number of events outside of PCORnet CRNs. The findings suggest that supplementing claims data improves the outcome ascertainment in longitudinal observational comparative effectiveness studies.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background & Aims Antibodies against tumor necrosis factor-α are widely used to treat patients with Crohn's disease (CD). This study compared the effectiveness of infliximab and adalimumab, the ...2 most commonly used anti–tumor necrosis factor agents, in patients with CD. Methods We conducted a retrospective cohort study by using U.S. Medicare data from 2006 through 2010. Patients with CD who were new users of infliximab (n = 1459) or adalimumab (n = 871) after January 31, 2007, were included. Patients older than age 85 and those with rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis were excluded. The primary outcome measures were disease persistence on therapy at week 26, surgery (including bowel resection, creation of an ostomy, or surgical treatment of a perforation or abscess), and hospitalization for CD. Propensity score-adjusted logistic and Cox regression were used to compute adjusted odds ratios or hazard ratios and 95% confidence intervals (CIs). Results After 26 weeks of treatment, 49% of patients receiving infliximab remained on drug, compared with 47% of those receiving adalimumab (odds ratio, 0.98; 95% CI, 0.81–1.19). Fewer patients treated with infliximab underwent surgery than those treated with adalimumab, but this difference was not statistically significant (5.5 vs 6.9 surgeries per 100 person-years; hazard ratio, 0.79; 95% CI, 0.60–1.05). Rates of hospitalization did not differ between groups (hazard ratio, 0.88; 95% CI, 0.72–1.07). Conclusions We observed similar effectiveness of infliximab and adalimumab for CD on the basis of 3 clinically important outcome measures.
Purpose
Health plan claims may provide complete longitudinal data for timely, real‐world population‐level COVID‐19 assessment. However, these data often lack laboratory results, the standard for ...COVID‐19 diagnosis.
Methods
We assessed the validity of ICD‐10‐CM diagnosis codes for identifying patients hospitalized with COVID‐19 in U.S. claims databases, compared to linked laboratory results, among six Food and Drug Administration Sentinel System data partners (two large national insurers, four integrated delivery systems) from February 20–October 17, 2020. We identified patients hospitalized with COVID‐19 according to five ICD‐10‐CM diagnosis code‐based algorithms, which included combinations of codes U07.1, B97.29, general coronavirus codes, and diagnosis codes for severe symptoms. We calculated the positive predictive value (PPV) and sensitivity of each algorithm relative to laboratory test results. We stratified results by data source type and across three time periods: February 20–March 31 (Time A), April 1–30 (Time B), May 1–October 17 (Time C).
Results
The five algorithms identified between 34 806 and 47 293 patients across the study periods; 23% with known laboratory results contributed to PPV calculations. PPVs were high and similar across algorithms. PPV of U07.1 alone was stable around 93% for integrated delivery systems, but declined over time from 93% to 70% among national insurers. Overall PPV of U07.1 across all data partners was 94.1% (95% CI, 92.3%–95.5%) in Time A and 81.2% (95% CI, 80.1%–82.2%) in Time C. Sensitivity was consistent across algorithms and over time, at 94.9% (95% CI, 94.2%–95.5%).
Conclusion
Our results support the use of code U07.1 to identify hospitalized COVID‐19 patients in U.S. claims data.
Objective
To evaluate the relationship between tibial plateau angle (TPA) and strain in the intact cranial cruciate ligament (CCL) during axial loading.
Study Design
Ex vivo mechanical testing study.
...Sample Population
Cadaveric canine stifles (n = 6).
Methods
A bicentric and uni‐radial Slocum saw blade was used to perform the osteotomy on each stifle and a custom designed plate was secured to the leg. Each stifle was loaded and CCL strain and axial displacement were recorded. TPA was adjusted to −20°, −10°, 0°, +10°, +20° of normal. Change in the strain was assessed during the axial loading period.
Results
For all specimens, linear displacement of the femur and CCL strain increased with increasing axial load. Mean change in strain was 4.41, 5.26, 6.02, 6.3, and 7.39 at −20°, −10°, 0°, 10°, and 20°, respectively. The R‐squared for the linear regression equation was 0.91, suggesting a strong relationship between change in TPA and CCL strain.
Conclusions
The mechanical testing model used found CCL strain increased with increasing axial load regardless of the TPA. Decreasing TPA decreased strain in the intact CCL.
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