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Robert Wieder,1,2 Jeffrey L Carson,2,3 Brian L Strom2 1Department of Medicine, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Rutgers University, Newark, NJ, USA; 2Rutgers Biomedical and Health Sciences, Rutgers University, Newark, NJ, USA; 3Department of Medicine, Robert Wood Johnson Medical School, Rutgers Biomedical and Health Sciences, Rutgers University, New Brunswick, NJ, USACorrespondence: Robert WiederRutgers New Jersey Medical School, 205 South Orange Avenue Cancer Center H1296, Newark, NJ 07103, USATel +1 973-972-4871Fax +1 973-972-2668Email wiederro@njms.rutgers.eduBackground: We report faculty affairs lessons from the formation and academic restructuring of Rutgers Biomedical and Health Sciences. Our approach may be a blueprint for development of a new track system that can be adapted by other institutions, after consideration of their own special circumstances.Methods: We created new Appointments and Promotions guidelines consisting of one Tenure Track and four Non-Tenure Tracks, each with different missions. We restructured faculty performance evaluations to include mission-based criteria, an expanded rating scale, and specific expectations. After negotiating these new processes with our faculty union, we enacted central oversight to ensure uniform application of these processes and their associated criteria. We communicated the guidelines and the evaluation system widely. We created programs for universal mentoring, publishing education, diversity, and faculty development.Results: All faculty in our seven schools went through track selection. Anxiety and incomplete understanding improved after implementation. Evaluations with expectations for the following year and an expanded scale for more nuanced assessment served as mentoring tools. Requirements for mentor assignments and diversity education created an atmosphere of nurturing and inclusion. Publications, extramural support, and faculty satisfaction increased after implementation of the guidelines.Conclusion: Lessons included the need to review and learn from guidelines at other institutions, to create tracks that align with different jobs, the necessity for central oversight for uniform application of criteria, the need for extensive and frequent communication with faculty, and that fear of change is only reduced after evidence of success of a new structure. The most important lesson was that faculty rise to expectations when clear, ambitious criteria are delineated and universally applied.Keywords: academic restructuring, faculty tracks, faculty development, faculty mentoring, faculty evaluations, faculty diversity

Background: The use of pioglitazone, a thiazolidinedione (TZD), may increase the risk of bladder cancer in patients with type 2 diabetes. In this study, we assessed the risk of bladder cancer associated with the use of TZDs and between pioglitazone and rosiglitazone, an alternative TZD.Methods: We conducted a retrospective cohort study of patients with type 2 diabetes mellitus who initiated treatment with a TZD (n = 18 459 patients) or a sulfonylurea (SU) (n = 41 396 patients) between July 1, 2000, and August 31, 2010, using The Health Improvement Network database in the United Kingdom. Incident cancers were identified for 196 708 person-years of follow-up. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of bladder cancer in the TZD cohort compared with the SU cohort (referent), adjusted for potential confounders. Risk associated with increasing duration of drug exposure was also examined. All statistical tests were two-sided.Results: We identified 60 incident bladder cancers in the TZD cohort and 137 cancers in the SU cohort. No difference in bladder cancer risk was found between the two cohorts (TZD vs SU, HR = 0.93, 95% CI = 0.68 to 1.29) in analyses that did not account for duration of exposure. However, the risk of bladder cancer was increased among patients with the longest duration of TZD vs SU therapy (≥ 5 years of use, HR = 3.25, 95% CI = 1.08 to 9.71) and among those with the longest time since initiation of therapy (≥ 5 years since first use, HR = 2.53, 95% CI = 1.12 to 5.77). Risk of bladder cancer also increased with increasing time since initiation of pioglitazone (P (trend) < .001) and rosiglitazone (P (trend) = .006). Comparison of pioglitazone to rosiglitazone use did not demonstrate difference in cancer risk (P = .49).Conclusion: Long-term TZD therapy (≥ 5 years) in patients with type 2 diabetes may be associated with an increased risk of bladder cancer, which may be common to all TZDs. [ABSTRACT FROM AUTHOR]

Objective: Some preclinical in vivo studies and limited human data suggest a possible increased risk of bladder cancer with pioglitazone therapy. This is an interim report of an ongoing cohort study examining the association between pioglitazone therapy and the risk of bladder cancer in patients with diabetes.Research Design and Methods: This study includes 193,099 patients in the Kaiser Permanente Northern California diabetes registry who were ≥40 years of age between 1997 and 2002. Those with prior bladder cancer were excluded. Ever use of each diabetes medication (defined as two or more prescriptions within 6 months) was treated as a time-dependent variable. Cox regression-generated hazard ratios (HRs) compared pioglitazone use with nonpioglitazone use adjusted for age, sex, race/ethnicity, diabetes medications, A1C, heart failure, household income, renal function, other bladder conditions, and smoking.Results: The group treated with pioglitazone comprised 30,173 patients. There were 90 cases of bladder cancer among pioglitazone users and 791 cases of bladder cancer among nonpioglitazone users. Overall, ever use of pioglitazone was not associated with risk of bladder cancer (HR 1.2 [95% CI 0.9-1.5]), with similar results in men and women (test for interaction P = 0.8). However, in the a priori category of >24 months of therapy, there was an increased risk (1.4 [1.03-2.0]). Ninety-five percent of cancers diagnosed among pioglitazone users were detected at early stage.Conclusions: In this cohort of patients with diabetes, short-term use of pioglitazone was not associated with an increased incidence of bladder cancer, but use for more than 2 years was weakly associated with increased risk. [ABSTRACT FROM AUTHOR]

Objective: The authors compared 1-year mortality rates associated with ziprasidone and olanzapine in real-world use.Method: The Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC) was an open-label, randomized, postmarketing large simple trial that enrolled patients with schizophrenia (N=18,154) in naturalistic practice in 18 countries. The primary outcome measure was nonsuicide mortality in the year after initiation of assigned treatment. Patients were randomly assigned to receive treatment with either ziprasidone or olanzapine and followed for 1 year by unblinded investigators providing usual care. A physician-administered questionnaire was used to collect baseline demographic information, medical and psychiatric history, and concomitant medication use. Follow-up information on hospitalizations and emergency department visits, patients' vital status, and current antipsychotic drug status was collected and reported by treating psychiatrists. Post hoc analyses of sudden death, a secondary endpoint, were also conducted.Results: The incidence of nonsuicide mortality within 1 year of initiating pharmacotherapy was 0.91 for ziprasidone (N=9,077) and 0.90 for olanzapine (N=9,077). The relative risk was 1.02 (95% CI=0.76-1.39). This finding was confirmed in numerous secondary and sensitivity analyses.Conclusions: Despite the known risk of QTc prolongation with ziprasidone treatment, the findings of this study failed to show that ziprasidone is associated with an elevated risk of nonsuicidal mortality relative to olanzapine in real-world use; the study excludes a relative risk larger than 1.39 with a high probability. However, the study was neither powered nor designed to examine the risk of rare events like torsade de pointes. [ABSTRACT FROM AUTHOR]

Background: Studies that have looked at the effectiveness of computerized decision support systems to prevent drug-drug interactions have reported modest results because of low response by the providers to the automated alerts.Objective: To evaluate, within an inpatient computerized physician order entry (CPOE) system, the incremental effectiveness of an alert that required a response from the provider, intended as a stronger intervention to prevent concurrent orders of warfarin and non-steroidal anti-inflammatory drugs (NSAIDs).Design: Randomized clinical trial of 1963 clinicians assigned to either an intervention group receiving a customized electronic alert requiring affirmative response or a control group receiving a commercially available passive alert as part of the CPOE. The study duration was 2 August 2006 to 15 December 2007.Measurements: Alert adherence was compared between study groups.Results: The proportion of desired ordering responses (ie, not reordering the alert-triggering drug after firing) was lower in the intervention group (114/464 (25%) customized alerts issued) than in the control group (154/560 (28%) passive alerts firing). The adjusted OR of inappropriate ordering was 1.22 (95% CI 0.69 to 2.16).Conclusion: A customized CPOE alert that required a provider response had no effect in reducing concomitant prescribing of NSAIDs and warfarin beyond that of the commercially available passive alert received by the control group. New CPOE alerts cannot be assumed to be effective in improving prescribing, and need evaluation. [ABSTRACT FROM AUTHOR]

Background: Warfarin is the primary therapy to prevent stroke and venous thromboembolism. Significant periods of nonadherence frequently go unreported by patients and undetected by providers. Currently, no comprehensive screening tool exists to help providers assess the risk of nonadherence at the time of initiation of warfarin therapy.Methods: This article reports on a prospective cohort study of adults initiating warfarin therapy at two anticoagulation clinics (university- and Veterans Affairs-affiliated). Nonadherence, defined by failure to record a correct daily pill bottle opening, was measured daily by electronic pill cap monitoring. A multivariable logistic regression model was used to develop a point system to predict daily nonadherence to warfarin.Results: We followed 114 subjects for a median of 141 days. Median nonadherence of the participants was 14.4% (interquartile range [IQR], 5.8-33.8). A point system, based on nine demographic, clinical, and psychosocial factors, distinguished those demonstrating low vs high levels of nonadherence: four points or fewer, median nonadherence 5.8% (IQR, 2.3-14.1); five points, 9.1% (IQR, 5.9-28.6); six points, 14.5% (IQR, 7.1-24.1); seven points, 14.7% (IQR, 7.0-34.7); and eight points or more, 29.3% (IQR, 15.5-41.9). The model produces a c-statistic of 0.66 (95% CI, 0.61-0.71), suggesting modest discriminating ability to predict day-level warfarin nonadherence.Conclusions: Poor adherence to warfarin is common. A screening tool based on nine demographic, clinical, and psychosocial factors, if further validated in other patient populations, may help to identify groups of patients at lower risk for nonadherence so that intensified efforts at increased monitoring and intervention can be focused on higher-risk patients. [ABSTRACT FROM AUTHOR]

Oral contraceptive (OC) use has been linked to increased risk of breast cancer, largely on the basis of studies conducted before 1990. In the Case-Control Surveillance Study, a US hospital-based case-control study of medication use and cancer, the authors assessed the relation of OC use to breast cancer risk among 907 case women with incident invasive breast cancer (731 white, 176 black) and 1,711 controls (1,152 white, 559 black) interviewed from 1993 to 2007. They evaluated whether the association differed by ethnicity or tumor hormone receptor status. After control for breast cancer risk factors, the multivariable odds ratio for 1 year or more of OC use, relative to less than 1 year of use, was 1.5 (95% confidence interval: 1.2, 1.8). The estimates were similar within age strata (<50 years and >or= 50 years). The odds ratios were larger for use within the previous 10 years, long-duration use, and black ethnicity, but these differences were not statistically significant. The association of OC use with breast cancer risk did not differ according to the estrogen or progestogen receptor status of the tumor. These results suggest that OC use is associated with an increased risk of breast cancer diagnosed in recent years. [ABSTRACT FROM AUTHOR]

Ages at menarche and first birth are established risk factors for breast cancer. The interval between these ages may also affect risk, since the breast is more susceptible to carcinogenic insults during this period than during the parous period. However, few investigators have studied this relation. Using logistic regression, the authors evaluated associations between the timing of reproductive events and breast cancer risk among 4,013 cases and 4,069 controls enrolled in a multicenter, population-based US case-control study of White and African-American women (1994-1998). For White, parous premenopausal and postmenopausal women, those who had an interval of > or =16 years between the ages of menarche and first birth had 1.5-fold (95% confidence interval (CI): 1.0, 2.2) and 1.4-fold (95% CI: 1.1, 1.8) increased risks of breast cancer, respectively, in comparison with those who had < or =5 years between these ages. Adjusting for age at first birth altered these risk estimates somewhat, to odds ratios of 1.5 (95% CI: 0.8, 2.9) and 1.0 (95% CI: 0.6, 1.5), respectively. These associations were stronger for lobular and hormone-receptor-positive tumors but were absent among premenopausal African-American women. The authors conclude that the interval between age at menarche and age at first birth is associated with the risk of hormonally sensitive types of breast cancer, particularly among White women. [ABSTRACT FROM AUTHOR]

Combined hormone replacement therapy (CHRT) containing estrogens and progestins is associated with breast cancer risk. The authors evaluated interactions between CHRT use and progestin metabolism genotypes at CYP3A4 and the progesterone receptor (PGR) and their effects on breast cancer risk using the population-based Women's Insights and Shared Experiences (WISE) Study (1999-2002) of postmenopausal Caucasian women (522 breast cancer cases, 708 controls). The authors observed an elevated risk of ductal tumors in women with 3 or more years of CHRT use and PGR 331A alleles compared with those who had neither factor (odds ratio = 3.35, 95% confidence interval (CI): 1.13, 9.99; two-sided p(interaction) = 0.035). They also observed an elevated risk of progesterone receptor-positive tumors in women who had had 3 or more years of CHRT use and PGR 331A alleles compared with those who had neither factor (odds ratio = 3.82, 95% CI: 1.26, 11.55; p = 0.028). Finally, they observed an increased risk of estrogen receptor-negative tumors in women without CHRT exposure and CYP3A4*1B alleles compared with those who had neither factor (odds ratio = 6.46, 95% CI: 2.02, 20.66; p = 0.024), although the biologic interpretation of this result requires further study. When stratified by recency of use, PGR effects were observed only in current CHRT users, while CYP3A4 effects were observed only in former CHRT users. Breast cancer risk in women who have used CHRT may be influenced by genetic factors involved in progestin metabolism. [ABSTRACT FROM AUTHOR]

The purpose of this study was to estimate the incidence of hospital-acquired pressure ulcers among elderly patients hospitalized for hip fracture surgery and to identify extrinsic factors that are associated with increased risk. We conducted a secondary analysis of data abstracted from medical records at 20 hospitals in Pennsylvania, Texas, New Jersey, and Virginia. Participants were patients aged 60 years and older admitted with hip fracture to the study hospitals between 1983 and 1993. The incidence of hospital-acquired pressure ulcers was 8.8% (95% confidence interval 8.2%-9.4%). After adjusting for confounding variables, longer wait before surgery, intensive care unit stay, longer surgical procedure, and general anesthesia were significantly associated with higher pressure ulcer risk. Extrinsic factors may be important markers for high pressure ulcer risk in hospitalized hip fracture patients. Although it is not possible to eliminate factors such as requiring an intensive care unit stay or having a long surgical procedure, it may be possible to develop interventions that minimize pressure ulcer risk in patients who experience these factors. [ABSTRACT FROM AUTHOR]

Background: Medical treatment of women with established osteoporosis may decrease the incidence of future fractures. Postmenopausal women who have sustained a distal radial fracture have decreased bone-mineral density and nearly twice the risk of a future hip fracture. The purpose of this study was to evaluate the adequacy of diagnosis and treatment of osteoporosis in postmenopausal women following an acute fracture of the distal part of the radius.Methods: A retrospective cohort study was performed with use of a claims database that includes more than three million patients, from thirty states, enrolled in multiple health plans. All women, fifty-five years of age or older, who sustained a distal radial fracture between July 1, 1994, and June 30, 1997, were identified in the database. Only patients with at least six months of continuous and complete medical and pharmaceutical health-care coverage from the date of the fracture were enrolled, to ensure that all health-care claims would be captured in the database. This cohort of patients was then evaluated to determine the proportion who had undergone either a diagnostic bone-density scan or treatment with any recommended medication for established osteoporosis (estrogen, a bisphosphonate, or calcitonin) within six months following the fracture.Results: A search of the database identified 1,162 women, fifty-five years of age or older, who had a distal radial fracture. Of these 1,162 patients, thirty-three (2.8 percent) underwent a bone-density scan and 266 (22.9 percent) were treated with at least one of the medications approved for treatment of established osteoporosis. Twenty women had both a bone-density scan and drug treatment. Therefore, only 279 (24.0 percent) of the 1,162 women who sustained a distal radial fracture underwent either diagnostic evaluation or treatment of osteoporosis. There was a significant decrease in the rate of treatment of osteoporosis with increasing patient age at the time of the fracture (p < 0.0001).Conclusions: Current physician practice may be inadequate for the diagnosis and treatment of osteoporosis in postmenopausal women who have sustained a distal radial fracture. [ABSTRACT FROM AUTHOR]

In laboratory studies, some antidepressants caused increased growth of mammary tumors. The relation of use of these drugs to the development of breast cancer was examined in a hospital-based case-control study. Information, including lifetime medication history, was collected by interview from 5,814 women with primary breast cancer diagnosed within the previous year, 5,095 women with primary malignancies of other sites, and 5,814 women with other conditions. Relative risks were estimated by using unconditional multiple logistic regression for regular use (> or =4 days per week for > or =4 weeks beginning > or =1 year before admission) of antidepressants and structurally similar drugs. With reference to never use of each drug, relative risks were statistically compatible with 1.0 for selective serotonin reuptake inhibitors (SSRI), tricyclics, other antidepressants, phenothiazines, and antihistamines; results were very similar using both control groups. There were no significant increases in risk for any category of regular use, stratified according to cumulative duration of use or time interval since the most recent use or for any individual drug within the broader classes. However, the estimate for regular SSRI use in the previous year, 1.8, was of borderline statistical significance (95% confidence interval: 1.0, 3.3). The findings do not support an overall association between the use of antidepressants, phenothiazines, or antihistamines and breast cancer. However, the results for SSRIs are not entirely reassuring. [ABSTRACT FROM AUTHOR]

Background: Although antibiotic prophylaxis against infective endocarditis is recommended, the true risk factors for infective endocarditis are unclear.Objective: To quantitate the risk for endocarditis from dental treatment and cardiac abnormalities.Design: Population-based, case-control study.Setting: 54 hospitals in the Philadelphia area.Patients: Persons with community-acquired infective endocarditis not associated with intravenous drug use were compared with community residents, matched by age, sex, and neighborhood of residence.Measurements: Information on demographic characteristics, host risk factors, and dental treatment was obtained from structured telephone interviews, dental records, and medical records.Results: During the preceding 3 months, dental treatment was no more frequent among case-patients than controls (adjusted odds ratio, 0.8 [95% CI, 0.4 to 1.5]). Of 273 case-patients, 104 (38%) knew of previous cardiac lesions compared with 17 controls (6%) (adjusted odds ratio, 16.7 [CI, 7.4 to 37.4]). Case-patients more often had a history of mitral valve prolapse (adjusted odds ratio, 19.4 [CI, 6.4 to 58.4]), congenital heart disease (adjusted odds ratio, 6.7 [CI, 2.3 to 19.4]), cardiac valvular surgery (adjusted odds ratio, 74.6 [CI, 12.5 to 447]), rheumatic fever (adjusted odds ratio, 13.4 [CI, 4.5 to 39.5]), and heart murmur without other known cardiac abnormalities (adjusted odds ratio, 4.2 [CI, 2.0 to 8.9]). Among case-patients with known cardiac lesions--the target of prophylaxis--dental therapy was significantly (P = 0.03) less common than among controls (adjusted odds ratio, 0.2 [CI, 0.04 to 0.7] over 3 months). Few participants received prophylactic antibiotics.Conclusions: Dental treatment does not seem to be a risk factor for infective endocarditis, even in patients with valvular abnormalities, but cardiac valvular abnormalities are strong risk factors. Few cases of infective endocarditis would be preventable with antibiotic prophylaxis, even with 100% effectiveness assumed. Current policies for prophylaxis should be reconsidered. [ABSTRACT FROM AUTHOR]

The goal of clinical research is to differentiate among the different possible types of associations between the factors under study: no association, artifactual association, indirect association, and causal association. This article is intended as a brief overview of the research methods used in clinical research to differentiate these types of associations. It begins with an overview of the scientific method and the types of errors that can be made (i.e., random error, confounding, and bias). It then discusses the criteria supporting the causal nature of an association (i.e., how can one tell when an association is causal?). The criteria reviewed are (1) coherence with existing information; (2) time sequence; (3) specificity; (4) consistency; and (5) strength. Included within the last are quantitative strength, dose-response relation, and study design. Finally, the article provides a very brief outline of the available research designs, i.e. , experimental studies, cohort studies, case-control studies, analyses of secular trends, case series, and case reports, and the advantages and disadvantages associated with each. [ABSTRACT FROM AUTHOR]

The purpose of this study was to validate the changes in acute pain measurement scales that are most strongly associated with a patient-determined indicator of clinical importance. Measures of pain intensity and pain relief are commonly used outcomes in therapeutic clinical trials. Recent studies of the properties of acute pain measures have provided data defining the cut-off points that are best associated with clinically important differences. Validation of these findings in another clinical trial data set is important. Data were obtained from the titration phase of a recently conducted randomized controlled clinical trial of oral transmucosal fentanyl citrate (OTFC), which compared OTFC to immediate release morphine sulfate (MSIR) for the treatment of cancer-related acute breakthrough pain. Changes in pain intensity and pain relief were recorded every 15 minutes for 60 minutes and global medication performance recorded at the end of each study pain episode. At any titration step, if the patient felt that the first dose of the study medication did not provide adequate relief within 30 minutes, an additional rescue medication could be taken. To find the level of each pain scale best associated with this measure of the adequacy of pain relief, the calculated sensitivity, specificity, and accuracy for different cut-off points of the measured pain scales were compared to whether or not the patient needed rescue medication. The overall ability of the pain measures to discriminate episodes for which a rescue was not needed was calculated using area under the receiver operating characteristics (ROC) curves. Data were analyzed from 134 OTFC-naive patients who collected data on 1307 episodes of breakthrough pain. Using the criteria of a balanced sensitivity and specificity, the best cut-off points were determined to be: 33% for the percent pain intensity difference; > or =2 for the raw pain intensity difference on a 0-10 numeric rating scale; > or =2 (i.e., moderate or better) for pain relief; > or =33% for the percent maximum total pain relief; and > or =2 (good or better) for global medication performance. ROC area under the curve ranged from 0.839 to 0.862 for each of the pain measures listed above, calculated at 60 minutes. These data indicate that the pain scale cut-off points that are best associated with a patient-derived measure of a clinically important difference closely approximate those found in an earlier study. ROC analysis provided evidence that the overall pain measures were strongly associated with not requiring an "additional dose of rescue medication." Thus, the cut-off points determined for these pain scales provide a good surrogate measure of a patient-determined clinically important response. This provides support for the usefulness of these values in future clinical trials of pain therapy. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to estimate the period prevalence and incidence of pressure ulcer among those 65 years of age and older.Methods: We used a patient-record database called the General Practice Research Database (GPRD). Subjects were 65 years of age and older and cases were ascertained based on strict inclusion and exclusion criteria. The accuracy of the ascertainment strategy was estimated using mailed physician-answered questionnaires. Annual period prevalence and age-specific incidence were estimated per 100 person-years with exact 95% confidence intervals (CI).Results: The accuracy of our ascertainment strategy was excellent, with a positive predictive value of 100% (95% CI: 92%,100%) and negative predictive value of 95% (85%, 95%). Over 200,000 person-years of data were analyzed. The annual period prevalence of pressure ulcer among those 65 years of age and older varied from 0.31% to 0.70%. The incidence varied significantly with advancing patient age from 0.18 to 3.36 per 100-person years (p < 0.001) but was not associated with gender (p = 0.95).Conclusions: Pressure ulcers are seen in the general practice setting. They are most likely to occur in those over 85 years of age. Preventative strategies within the general practice setting should concentrate on the oldest of the elderly. [ABSTRACT FROM AUTHOR]

Purpose: This paper presents methods and operational results of a population-based case-control study examining the effects of oral contraceptive use on breast cancer risk among white and black women aged 35-64 years in five U.S. locations.Methods: Cases were women newly diagnosed with breast cancer during July 1994 through April 1998. Controls were identified through random digit dialing (RDD) using unclustered sampling with automated elimination of nonworking numbers. Sampling was density-based, with oversampling of black women. In-person interviews were conducted from August 1994 through December 1998. Blood samples were obtained from subsets of cases and controls, and tissue samples were obtained from subsets of cases. A computerized system tracked subjects through study activities. Special attention was devoted to minimizing exposure misclassification, because any exposure-disease associations were expected to be small.Results: An estimated 82% of households were screened successfully through RDD. Interviews were completed for 4575 cases (2953 whites; 1622 blacks) and 4682 controls (3021 whites; 1661 blacks). Interview response rates for cases and controls were 76.5% and 78.6%, respectively, with lower rates for black women and older women.Conclusions: The methodologic details of this large collaboration may assist researchers conducting similar investigations. [ABSTRACT FROM AUTHOR]

Purpose: To facilitate claims-based research on populations with juvenile idiopathic arthritis (JIA), we sought to validate an algorithm of new medication use as a proxy for worsening JIA disease activity., Methods: Using electronic health record data from three pediatric centers, we defined new JIA medication use as (re)initiation of disease-modifying antirheumatic drugs or glucocorticoids (oral or intra-articular). Data were collected from 201 randomly selected subjects with (101) or without (100) new medication use. We assessed the positive predictive value (PPV) and negative predictive value (NPV) based on a reference standard of documented worsening of JIA disease activity. The algorithm was refined to optimize test characteristics., Results: Overall, the medication-based algorithm had suboptimal performance in representing worsening JIA disease activity (PPV 69.3%, NPV 77.1%). However, algorithm performance improved for definitions specifying longer times after JIA diagnosis (≥1-year post-diagnosis: PPV 82.9%, NPV 80.0%) or after initiation of prior JIA treatment (≥1-year post-treatment: PPV 89.7%, NPV 80.0%)., Conclusion: An algorithm for new JIA medication use appears to be a reasonable proxy for worsening JIA disease activity, particularly when specifying new use ≥1 year since initiating a prior JIA medication. This algorithm will be valuable for conducting research on JIA populations within administrative claims databases., (© 2024 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Purpose: To evaluate the validity of ICD-10-CM code-based algorithms as proxies for influenza in inpatient and outpatient settings in the USA., Methods: Administrative claims data (2015-2018) from the largest commercial insurer in New Jersey (NJ), USA, were probabilistically linked to outpatient and inpatient electronic health record (EHR) data containing influenza test results from a large NJ health system. The primary claims-based algorithms defined influenza as presence of an ICD-10-CM code for influenza, stratified by setting (inpatient/outpatient) and code position for inpatient encounters. Test characteristics and 95% confidence intervals (CIs) were calculated using test-positive influenza as a reference standard. Test characteristics of alternative outpatient algorithms incorporating CPT/HCPCS testing codes and anti-influenza medication pharmacy claims were also calculated., Results: There were 430 documented influenza test results within the study period (295 inpatient, 135 outpatient). The claims-based influenza definition had a sensitivity of 84.9% (95% CI 72.9%-92.1%), specificity of 96.3% (95% CI 93.1%-98.0%), and PPV of 83.3% (95% CI 71.3%-91.0%) in the inpatient setting, and a sensitivity of 76.7% (95% CI 59.1%-88.2%), specificity of 96.2% (95% CI 90.6%-98.5%), PPV of 85.2% (95% CI 67.5%-94.1%) in the outpatient setting. Primary inpatient discharge diagnoses had a sensitivity of 54.7% (95% CI 41.5%-67.3%), specificity of 99.6% (95% CI 97.7%-99.9%), and PPV of 96.7% (95% CI 83.3%-99.4%). CPT/HCPCS codes and anti-influenza medication claims were present for few outpatient encounters (sensitivity 3%-10%)., Conclusions: In a large US healthcare system, inpatient ICD-10-CM codes for influenza, particularly primary inpatient diagnoses, had high predictive value for test-positive influenza. Outpatient ICD-10-CM codes were moderately predictive of test-positive influenza., (© 2024 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Background/objective: Given limited information on health care and treatment utilization for juvenile idiopathic arthritis (JIA) during the pandemic, we studied JIA-related health care and treatment utilization in a commercially insured retrospective US cohort., Methods: We studied rates of outpatient visits, new disease-modifying antirheumatic drug (DMARD) initiations, intra-articular glucocorticoid injections (iaGC), dispensed oral glucocorticoids and opioids, DMARD adherence, and DMARD discontinuation by quarter in March 2018-February 2021 (Q1 started in March). Incident rate ratios (IRR, pandemic vs prepandemic) with 95% confidence intervals (CIs) were estimated using multivariable Poisson or Quasi-Poisson models stratified by diagnosis recency (incident JIA, <12 months ago; prevalent JIA, ≥12 months ago)., Results: Among 1294 children diagnosed with JIA, total and in-person outpatient visits for JIA declined during the pandemic (IRR, 0.88-0.90), most markedly in Q1 2020. Telemedicine visits, while higher during the pandemic, declined from 21% (Q1) to 13% (Q4) in 2020 to 2021. During the pandemic, children with prevalent JIA, but not incident JIA, had lower usage of iaGC (IRR, 0.60; 95% CI, 0.34-1.07), oral glucocorticoids (IRR, 0.47; 95% CI, 0.33-0.67), and opioids (IRR, 0.44; 95% CI, 0.26-0.75). Adherence to and discontinuation of DMARDs was similar before and during the pandemic., Conclusions: In the first year of the pandemic, visits for JIA dropped by 10% to 12% in commercially insured children in the United States, declines partly mitigated by use of telemedicine. Pandemic-related declines in intra-articular glucocorticoids, oral glucocorticoids, and opioids were observed for children with prevalent, but not incident, JIA. These changes may have important implications for disease control and quality of life., Competing Interests: Disclosures: D.B.H. has received salary support and grant funding related to JIA from the Childhood Arthritis and Rheumatology Research Alliance, and honorarium related to JIA from the American College of Rheumatology, and unrelated grant funding from Danisco USA, Inc. Y.Y., A.L.N., and L.E.P. are employees of Carelon Research, Inc. Kevin Haynes is an employee of Janssen Research & Development. C.D.R. provides consultation to AbbVie and Novartis about therapies for JIA and advises the Department of Health and Human Services on autoimmune vaccine injuries. B.L.S. has received consulting fees from AbbVie and the Consumer Healthcare Products Association. L.E.P. has received research support from Sanofi unrelated to this work. C.H., S.C., A.D., and T.G. report no potential conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Population data on longitudinal trends for cholecystectomies and their outcomes are scarce. We evaluated the incidence and case fatality rate of emergency and ambulatory cholecystectomies in New Jersey (NJ) and whether the Medicaid expansion changed trends., Materials and Methods: A retrospective population cohort design was used to study the incidence of cholecystectomies and their case fatality rate from 2009 to 2018. Using linear and logistic regression we explored the trends of incidence and the odds of case fatality after versus before the January 1, 2014 Medicaid expansion., Results: Overall, 93,423 emergency cholecystectomies were performed, with 644 fatalities; 87,239 ambulatory cholecystectomies were performed, with fewer than 10 fatalities. The 2009 to 2018 annual incidence of emergency cholecystectomies dropped markedly from 114.8 to 77.5 per 100,000 NJ population (P < 0.0001); ambulatory cholecystectomies increased from 93.5 to 95.6 per 100,000 (P = 0.053). The incidence of emergency cholecystectomies dropped more after than before Medicaid expansion (P < 0.0001). The odds ratio for case fatality among those undergoing emergency cholecystectomies after versus before expansion was 0.85 (95% CI, 0.72-0.99). This decrease in case fatality, apparent only in those over age 65, was not explained by the addition of Medicaid., Conclusions: A marked decrease in the incidence of emergency cholecystectomies occurred after Medicaid expansion, which was not accounted for by a minimal increase in the incidence of ambulatory cholecystectomies. Case fatality from emergency cholecystectomy decreased over time due to factors other than Medicaid. Further work is needed to reconcile these findings with the previously reported lack of decrease in overall gallstone disease mortality in NJ., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Radiation pneumonitis and immune-related pneumonitis have been studied independently, but little information has emerged on the interactions between radiation therapy (RT) and immune checkpoint inhibition (ICI). We examine whether RT and ICI are synergistic in causing pneumonitis., Methods: A retrospective cohort was assembled using the Surveillance, Epidemiology, and End Results-Medicare database, including Medicare beneficiaries diagnosed with American Joint Committee on Cancer 7th ed. (AJCC) stages IIIB-IV NSCLC between 2013-2017. Exposures to RT and ICI were determined by evaluating for treatment within 12 months of diagnosis (RT group and ICI group) and for a second exposure (e.g., ICI after RT) within 3 months after the first exposure (RT + ICI group). Untreated controls were matched to treated patients who were diagnosed in the same three-month window. A validated algorithm for identifying cases of pneumonitis in claims data was used to evaluate for the outcome within 6 months after treatment. The primary outcome was the relative excess risk due to interaction (RERI), a quantitative measure of additive interaction between two treatments., Results: There were 18,780 patients included in the analysis with 9,345 (49.8%), 7,533 (40.2%), 1,332 (7.1%), and 550 (2.9%) in the control, RT, ICI, and RT + ICI groups, respectively. Relative to controls, the hazards ratios of pneumonitis were 11.5 (95% CI: 7.9 to 17.0), 6.2 (95% CI: 3.8 to 10.3), and 10.7 (95% CI: 6.0 to 19.2) in the RT, ICI, and RT-ICI groups, respectively. The RERIs were -6.1 (95% CI: -13.1 to -0.6, P=0.97) and -4.0 (95% CI: -10.7 to 1.5, P=0.91) in the unadjusted and adjusted analyses, respectively, consistent with no evidence of additive interaction (RERI ≤0) between RT and ICI., Conclusions: In this study of Medicare beneficiaries with advanced NSCLC, RT and ICI were, at most, additive rather than synergistic in causing pneumonitis. Pneumonitis risk in patients treated with RT and ICI is not more than could be expected from each therapy alone., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1649/coif). SKJ reports grants and contracts from Merck & Co, and consulting fees from Merck & Co and IMX Medical. JM reports grants and contracts Bristol Myers-Squibb, Celldex, Daiichi Sankyo, and Beyond Spring. SSN reports RSNA R&E Foundation Medical Student Grant, Chancellor’s Global Health Scholarship, the National Center for Advancing Translational Sciences Fellowship UL1, Consulting fees from Hibiscus BioTechnology, and Novocure travel grant. The other authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Background and Aims: Recent trends in mortality with gallstone disease remain scarce in the United States. Yet multiple changes in clinical management, such as rates of endoscopy, cholecystectomy, and cholecystostomy, and insurance access at the state level, may have occurred. Thus, we evaluated recent secular trends of mortality with gallstone disease in New Jersey., Methods: We performed a retrospective, cohort study of mortality from 2009 to 2018 using the National Center for Health Statistics, Restricted Mortality Files. The primary outcome was any death with an International Classifications of Disease, 10th Revision, Clinical Modification diagnosis code of gallstone disease in New Jersey. Simple linear regression was used to model trends of incidence of death., Results: 1580 deaths with diagnosed gallstone disease (dGD) occurred from 2009 to 2018. The annual trend of incidence of death was flat over 10 years. The incidence of death with dGD relative to all death changed only from 0.21% to 0.20% over 10 years. These findings were consistent also in 18 of 20 subgroup combinations, although the trend of death with dGD in Latinos 65 years or older increased [slope estimate 0.93, 95% confidence limit 0.42-1.43, P = .003]., Conclusion: The rate of death with dGD showed little change over the recent 10 years in New Jersey. This needs to be reproduced in other states and nationally. A closer examination of the changes in clinical care and insurance access is needed to help understand why they did not result in a positive change in this avoidable cause of death., Competing Interests: Conflicts of Interest: He has no other disclosures or potential conflicts of interest. Email: peckgr@rwjms.rutgers.edu. The remaining authors disclose no conflicts.

Whether patients undergo the more morbid and costly emergent rather than an elective type of surgery, may depend on many factors. Since tertiary prevention (preventing poor outcomes from emergency surgery) carries a much higher mortality than secondary prevention (preventing emergency surgery) or primary prevention (preventing the disease requiring surgery), the overall United States mortality might be reduced significantly, if emergency surgery could be avoided via high-quality primary prevention and non-surgical therapy or increasing elective surgery at the expense of emergency procedures, e.g., secondary prevention. The practice and study of acute care surgery then has the potential to broaden from a focus on the patient in the hospital emergency and operating rooms to the patient who no longer requires either, whose disease is treated or prevented in his/her/their community., Competing Interests: 1.Gregory L. Peck, DO, MPH, FACS participated sufficiently in the intellectual content and writing of the manuscript to take public responsibility for it. He has reviewed the manuscript, believe it represents valid work, and approves it for submission. He is currently supported by the NIH National Center for Advancing Translational Sciences’ (NCATS) Rutgers Clinical Translational Science KL2 Career Development Award (5 KL2 TR 3018-3). He has no potential conflict of interest. 2.Shawna V. Hudson, PhD participated sufficiently in the intellectual content and writing of the manuscript to take public responsibility for it. She has reviewed the manuscript, believe it represents valid work, and approves it for submission. She does not have direct support for this work and has no potential conflict of interest. 3.Jason A. Roy, PhD participated sufficiently in the intellectual content and writing of the manuscript to take public responsibility for it. He has reviewed the manuscript, believe it represents valid work, and approves it for submission. He does not have direct support for this work and has no potential conflict of interest. 4.Vicente H. Gracias, MD, FACS participated sufficiently in the intellectual content and writing of the manuscript to take public responsibility for it. He has reviewed the manuscript, believe it represents valid work, and approves it for submission. He does not have direct support for this work and has no potential conflict of interest. 5.Brian L. Strom, MD, MPH participated sufficiently in the intellectual content and writing of the manuscript to take public responsibility for it. He has reviewed the manuscript, believe it represents valid work, and approves it for submission. He does not have direct support for this work and has no potential conflict of interest.