Risk of seizures in a population of women with BRCA-positive metastatic breast cancer from an electronic health record database in the United States.

BACKGROUND: Incidence and risk factors for seizures among women with advanced breast cancer (BC) and brain metastases are not well characterized across treatment-related or clinical subtypes. This study leveraged a large real-world dataset to describe incidence and risk factors for seizures in BRCA-associated metastatic breast cancer. METHODS: The Optum® de-identified electronic health records database was used. Females with a BC diagnoses between 2008 and 2018, with clinic visits 12 months before BC index date, evidence of BRCA mutation (BRCA+), evidence of metastasis, and no previous cancers were included. Analyses were stratified by the overall BRCA+ cohort and 4 molecular phenotypes: HER2+/HR- (human epidermal growth factor 2/hormone receptor), HER2-/HR+, HER2+/HR+, and triple negative BC (TNBC; HER2-/HR-). Seizures were identified using diagnosis codes and natural language processing. Incidence, occurrence rates, and cumulative incidence of seizures from the diagnosis of metastasis to the end of follow up were calculated. Comparisons were made between phenotypes and stratified on PARP inhibitor use, diagnosed brain metastases, history of seizures, and anticonvulsants use before BC. All comparisons included age at metastasis, number of prior lines of treatment, and metastasis location as covariates. RESULTS: 27.8% of 7941 BRCA+ patients had ≥1 seizure over a mean follow-up time of 2.35 years. Incidence and occurrence rates were 11.83 (95% CI: 11.35-12.33) and 201.3 (95% CI: 198.05-204.50), respectively, per 100 person-years. HER2-/HR+ and TNBC patients had the lowest and highest seizure incidence rates, respectively (10.94 [95% CI: 10.23-11.71] and 16.83 [95% CI: 15.34-18.46]). With HER2-/HR+ as the reference group in a competing risk analysis, TNBC (hazard ratio, HR = 1.35; 95%CI: 1.21, 1.52; p < 0.001) and HER2+/HR- (HR = 1.29; 95%CI: 1.07, 1.56; p < 0.01) patients had a greater risk of seizures. Patients with diagnosed brain metastases or a history of seizures had higher seizure rates. Incidence trended higher with PARP inhibitor use, but patient numbers were low. CONCLUSIONS: This study provides novel real-world evidence on seizure incidence rates in BRCA+ BC patients, even those without diagnosed brain metastases, and underscores the need to understand patients' tumor phenotypes when assessing seizure risk. These findings may have implications for clinical practice and assessment of benefit-risk ratios of new therapeutic agents.

Urinary Tract Infection Epidemiology in NICUs in the United States.

OBJECTIVE: Our objective was to characterize the incidence, associated clinical factors, timing of infection, microbiology, and incidence of concordant blood culture of urinary tract infections (UTIs) in very low birth weight (VLBW <1,500g) infants. STUDY DESIGN: Multicenter observational cohort study of VLBW infants with gestational age (GA) ≤32 weeks, still hospitalized on postnatal day 7, and discharged 2010 to 2018 from Pediatrix Medical Group neonatal intensive care units. Demographic and clinical characteristics of infants with and without UTI were compared. Multivariable logistic regression evaluated adjusted odds of UTI diagnosis. RESULTS: Of 86,492 included infants, 5,988 (7%) had a UTI. The most common pathogen was Enterococcus spp. (20%), followed by Escherichia coli (19%) and Klebsiella spp. (18%). Candida spp. (6%) was the most common nonbacterial pathogen. Concordant-positive blood culture was present in 8% of infants with UTI diagnoses. UTI was associated with lower GA, male sex, vaginal delivery, prenatal steroid exposure, and longer duration of hospitalization. CONCLUSION: UTI is a common cause of infection in VLBW infants, especially among the smallest, most premature, male infants, and those with a longer duration of hospitalization. Neonatal clinicians should consider obtaining urine culture in the setting of late-onset sepsis evaluations in VLBW infants. KEY POINTS: · UTI is a common cause of LOS in VLBW infants.. · The most common pathogens are Enterococcus spp. and E. coli.. · UTI risk varies among different VLBW infant populations.. · Next steps should include evaluation of preventative measures..

Chronic opioid use and complication risks in women with endometriosis: A cohort study in US administrative claims.

BACKGROUND: Women with endometriosis are prescribed opioids for pain relief but may be vulnerable to chronic opioid use given their comorbidity profile. METHODS: A cohort study was conducted in the Clinformatics™ DataMart database between 2006 and 2017 comparing women aged 18-50 years with endometriosis (N = 36 373) to those without (N = 2 172 936) in terms of risk of chronic opioid use, opioid dependence diagnosis, and opioid overdose. Chronic opioid use was defined as ≥120 days' supply dispensed or ≥10 fills of an opioid during any 365-day interval. Among women with endometriosis, we evaluated factors associated with higher risk of chronic opioid use and quantified the risk of complications associated with the use of opioids. RESULTS: Women with endometriosis were at greater risk for chronic opioid use (OR: 3.76; 95%CI: 3.57-3.96), dependence (OR: 2.73, 95%CI: 2.38-3.13) and overdose (OR: 4.34, 95%CI: 3.06-6.15) compared to women without. Chronic users displayed dose escalation and increase in days supplied over time, as well as co-prescribing with benzodiazepines and sedatives. Approximately 34% of chronic users developed constipation, 20% experienced falls, and 8% reported dizziness. Among endometriosis patients, women in younger age groups, those with other comorbidities associated with pain symptoms, as well as those with depression or anxiety were at a higher risk of developing chronic opioid use. CONCLUSIONS: Women with endometriosis had a four times greater risk of chronic opioid use compared to women without. Multimorbidity among these patients was associated with the elevated risk of chronic opioid use and should be taken into account during treatment selection.

Validation of claims-based algorithms to identify patients with psoriasis.

PURPOSE: Accurately identifying patients with psoriasis (PsO) is crucial for generating real-world evidence on PsO disease course and treatment utilization. METHODS: We developed nine claims-based algorithms for PsO using a combination of the International Classification of Diseases (ICD)-9 codes, specialist visit, and medication dispensing using Medicare linked to electronic health records data (2013-2014) in two healthcare provider networks in Boston, Massachusetts. We calculated positive predictive value (PPV) and 95% confidence interval (CI) for each algorithm using the treating physician's diagnosis of PsO via chart review as the gold standard. Among the confirmed PsO cases, we assessed their PsO disease activity. RESULTS: The nine claims-based algorithms identified 990 unique patient records. Of those, 918 (92.7%) with adequate information were reviewed. The PPV of the algorithms ranged from 65.1 to 82.9%. An algorithm defined as ≥1 ICD-9 diagnosis code for PsO and ≥1 prescription claim for topical vitamin D agents showed the highest PPV (82.9%). The PPV of the algorithm requiring ≥2 ICD-9 diagnosis codes and ≥1 prescription claim for PsO treatment excluding topical steroids was 81.1% but higher (82.5%) when ≥1 diagnosis was from a dermatologist. Among 411 PsO patients with adequate information on PsO disease activity in EHRs, 1.5-5.8% had no disease activity, 31.3-36.8% mild, and 26.9-35.1% moderate-to-severe across the algorithms. CONCLUSIONS: Claims-based algorithms based on a combination of PsO diagnosis codes and dispensing for PsO-specific treatments had a moderate-to-high PPV. These algorithms can serve as a useful tool to identify patients with PsO in future real-world data pharmacoepidemiologic studies.

Burden of Coronary Heart Disease Rehospitalizations Following Acute Myocardial Infarction in Older Adults.

PURPOSE: Studies of prognosis following acute myocardial infarction (AMI) conventionally examine the first recurrent coronary heart disease (CHD) event which may not adequately characterize the full burden of CHD hospitalizations. We therefore examined the cumulative number of CHD rehospitalizations following AMI among older adults in the United States. METHODS: We conducted a retrospective cohort study of 78,085 Medicare beneficiaries aged ≥66 years without recent CHD history who were hospitalized for AMI in 2000-2010. Counts of CHD rehospitalizations over a maximum of 10 years of follow-up were calculated. Characteristics were assessed through claims and enrollment information and associations with CHD rehospitalizations were evaluated using Poisson models. RESULTS: Over 25 % of beneficiaries were aged ≥85 years, 55 % were women, and 89 % were white. Comorbidities were common, including diabetes (22.9 %), hypertension (46.7 %), heart failure (10.3 %), and chronic obstructive pulmonary disease (19.2 %). Following AMI, 16,078 beneficiaries (20.6 %) were hospitalized for CHD a total of 23,132 times. Among those who experienced at least one CHD rehospitalization, 35.9 % had ≥2 CHD rehospitalizations (n = 5773, 7.4 % of all beneficiaries with AMI) in the ensuing decade. Associations of demographics, comorbidities, and index hospitalization characteristics with rates of first and total CHD rehospitalizations were largely similar. Age ≥85 years versus 66-69 years was more strongly associated with first (rate ratio [RR] 1.43) than total (RR 1.35) CHD rehospitalization (p < 0.05), as was male versus female sex (RR 1.13 and 1.07). CONCLUSIONS: Emphasizing the first recurrent CHD rehospitalization underestimates the burden of disease experienced among older adults with AMI.

Optimal use of available claims to identify a Medicare population free of coronary heart disease.

We examined claims-based approaches for identifying a study population free of coronary heart disease (CHD) using data from 8,937 US blacks and whites enrolled during 2003-2007 in a prospective cohort study linked to Medicare claims. Our goal was to minimize the percentage of persons at study entry with self-reported CHD (previous myocardial infarction or coronary revascularization). We assembled 6 cohorts without CHD claims by requiring 6 months, 1 year, or 2 years of continuous Medicare fee-for-service insurance coverage prior to study entry and using either a fixed-window or all-available look-back period. We examined adding CHD-related claims to our "base algorithm," which included claims for myocardial infarction and coronary revascularization. Using a 6-month fixed-window look-back period, 17.8% of participants without claims in the base algorithm reported having CHD. This was reduced to 3.6% using an all-available look-back period and adding other CHD claims to the base algorithm. Among cohorts using all-available look-back periods, increasing the length of continuous coverage from 6 months to 1 or 2 years reduced the sample size available without lowering the percentage of persons with self-reported CHD. This analysis demonstrates approaches for developing a CHD-free cohort using Medicare claims.

High rates of death and hospitalization follow bone fracture among hemodialysis patients.

Altered bone structure and function contribute to the high rates of fractures in dialysis patients compared to the general population. Fracture events may increase the risk of subsequent adverse clinical outcomes. Here we assessed the incidence of post-fracture morbidity and mortality in an international cohort of 34,579 in-center hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS). We estimated country-specific rates of fractures requiring a hospital admission and associated length of stay in the hospital. Incidence rates of death and of a composite event of death/rehospitalization were estimated for 1 year after fracture. Overall, 3% of participants experienced a fracture. Fracture incidence varied across countries, from 12 events/1000 patient-years (PY) in Japan to 45/1000 PY in Belgium. In all countries, fracture rates were higher in the hemodialysis group compared to those reported for the general population. Median length of stay ranged from 7 to 37 days in the United States and Japan, respectively. In most countries, postfracture mortality rates exceeded 500/1000 PY and death/rehospitalization rates exceeded 1500/1000 PY. Fracture patients had higher unadjusted rates of death (3.7-fold) and death/rehospitalization (4.0-fold) compared to the overall DOPPS population. Mortality and hospitalization rates were highest in the first month after the fracture and declined thereafter. Thus, the high frequency of fractures and increased adverse outcomes following a fracture pose a significant health burden for dialysis patients. Fracture prevention strategies should be identified and applied broadly in nephrology practices.

Temporal trends in fracture rates and postdischarge outcomes among hemodialysis patients.

Patients with ESRD have a substantially increased risk of bone fractures, but the burden of fractures has not been sufficiently characterized in this population. Here, we analyzed fracture rates and postdischarge outcomes using Medicare data from hemodialysis patients in the United States between 2000 and 2009. We assessed adjusted quarterly fracture rates (inpatient and outpatient) and consequences of postfracture hospitalization for seven categories of fracture location. Pelvis/hip, vertebral, and lower leg fractures were the most prevalent fracture types. Pelvis/hip fractures declined slightly from 29.6 to 20.6 per 1000 patient-years between early 2000 and late 2009, but the incidence rates for all other fracture types remained relatively constant. Median lengths of stay for the primary fracture hospitalization ranged from 5 days (interquartile range [IQR], 3-9 days) for forearm/wrist fractures to 8 days (IQR, 5-12 days) for femur fractures. The proportion of patients discharged from the primary hospitalization to a skilled-nursing facility ranged from 28% (ribs/sternum) to 47% (pelvis/hip). A negative binomial regression model suggested that patients had an adjusted mean of 3.8-5.2 additional hospitalizations during the year after discharge from the index hospitalization, varying by fracture type, comprising a mean of 33-52 inpatient days. Case-mix-adjusted mortality rates after discharge ranged from 0.43 to 0.91 per patient-year and were highest for vertebral, pelvis/hip, and femur fractures. In conclusion, fractures in the dialysis population are common and are associated with a substantially increased risk for death and hospitalization.

Morbidity and mortality of twins and triplets compared to singleton infants delivered between 26-34 weeks gestation in the United States.

OBJECTIVE: To describe in-hospital morbidities and mortality among twins and triplets delivered at ≥26 to ≤34 weeks gestational age (GA) while controlling for prematurity and growth restriction. STUDY DESIGN: Retrospective analysis of inborn infants discharged from a neonatal intensive care unit (NICU) managed by the Pediatrix Medical Group between 2010 and 2018. RESULT: Among 247 437 infants included, 27.4% were multiples. Adjusted for GA and other factors typically known prior to delivery, in-hospital morbidities varied by plurality and generally were more common in singletons. The odds of death prior to discharge were less for twins at 0.74 (95% CI: 0.67-0.83) and triplets at 0.69 (95% CI: 0.51-0.92) compared to singletons. CONCLUSION: Singletons experience greater morbidity and mortality compared to twins and triplets born ≥26 weeks to ≤34 weeks GA, except PDA requiring procedural intervention, ROP requiring treatment, and longer length of stay.

Longitudinal Molecular and Serological Evidence of SARS-CoV-2 Infections and Vaccination Status: Community-Based Surveillance Study (CONTACT).

INTRODUCTION: This prospective, longitudinal, community-based study, EpidemiologiCal POpulatioN STudy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Lake CounTy, Illinois (CONTACT), investigated coronavirus disease 2019 (COVID-19) immunity, occupational risks related to SARS-CoV-2 exposure, and long-term immunoglobulin G (IgG) seroconversion kinetics. METHODS: At baseline and follow up (3, 6, and 9 months), non-hospitalized adult participants provided nasal and blood serum specimens for molecular [reverse transcription polymerase chain reaction (RT-PCR)] and serological (IgG) testing (4 November 2020-30 October 2021). RESULTS: At baseline, 6.4% (65/1008) had evidence of current/prior SARS-CoV-2 infection. At 3, 6, and 9 months, positive PCR tests were obtained from 0.4% (3/781), 0.4% (3/733), and 0% (0/673) of participants, respectively. Positive IgG occurred at baseline and 3, 6, and 9 months in 4.5% (45/1008), 6.0% (48/799), 5.4% (39/733), and 2.8% (19/673) of participants, respectively. Of participants positive for IgG at baseline, 28 had a negative IgG test at a follow-up visit; of those 28, 21 had their first negative IgG test within 6 months. Participants were more likely to retain positive IgG if they were 18-29 years of age, were male, or had medium-high/high-risk occupations. A high vaccination rate (70% received ≥ 1 dose by 9 months) was observed. Influence of occupational status or characteristics on transmission and IgG, and COVID-19 vaccination trends, are shown. CONCLUSIONS: This study expands on prior studies assessing COVID-19 immunity and IgG seroconversion by including both RT-PCR and serologic testing and longitudinal follow-up of study participants. We observed decreased infection rates over the 9 month follow-up period as well as a decline in IgG persistency after 6 months. The findings from this community-based study regarding vaccinate rates, infection rates by PCR, and IgG persistency over time can help improve our understanding of COVID-19 immunity, occupational risks related to SARS-CoV-2 exposure, and the kinetics of long-term IgG seroconversion, which is important to help guide local and national mitigation strategies. CLINICAL TRIAL REGISTRATION: NCT04611230.

Prescribing practices of inhaled corticosteroids for premature infants in the neonatal intensive care unit.

OBJECTIVE: Despite limited safety and efficacy data, inhaled corticosteroids (ICS) are prescribed to premature infants in the neonatal intensive care unit (NICU). We examined contemporary use and risk factors for ICS use in the NICU. STUDY DESIGN: Infants <33 weeks gestational age and <1500 gm birth weight discharged from Pediatrix Medical Group NICUs between 2010 and 2020 were included. We evaluated the association between ICS prescription and clinical characteristics using univariable and multivariable logistic regression. RESULTS: Of 74,123 infants from 308 NICUs, 9253 (12.5%) were prescribed ICS: budesonide, fluticasone, or beclomethasone. Diagnosis of bronchopulmonary dysplasia (BPD), earlier gestational age, male sex, longer mechanical ventilation, oxygen support, and systemic steroids were independent risk factors for ICS prescription. CONCLUSIONS: Use of ICS is common in many NICUs and is associated with a diagnosis of BPD and healthcare utilization. Prospective trials are needed to establish the safety, efficacy, and optimal indication in this vulnerable population.

Risk factors and epidemiology of spontaneous intestinal perforation among infants born at 22-24 weeks' gestational age.

OBJECTIVE: To describe the epidemiology, risk factors, and timing of spontaneous intestinal perforation (SIP) among infants born at 22-24 weeks' gestational age (GA). STUDY DESIGN: Observational cohort study among infants born at 22-24 weeks' GA in 446 neonatal intensive care units. RESULTS: We identified 9712 infants, of whom 379 (3.9%) developed SIP. SIP incidence increased with decreasing GA (P < 0.001). Antenatal magnesium (odds ratio (OR) 1.42; 95% confidence interval (CI), 1.09-1.85), antenatal indomethacin (OR 1.40; 95% CI, 1.06-1.85), postnatal indomethacin (OR 1.61; 95% CI, 1.23-2.11), and postnatal hydrocortisone exposure (OR 2.02; 95% CI 1.50-2.73) were associated with SIP. Infants who lost 15-20% (OR 1.77; 95% CI, 1.28-2.44) or >20% (OR 2.04; 95% CI, 1.46-2.85) of birth weight had higher odds of SIP than infants with weight loss <10%. CONCLUSIONS: Antenatal magnesium exposure, antenatal indomethacin exposure, postnatal hydrocortisone exposure, postnatal indomethacin exposure, and weight loss ≥15% were associated with SIP.

Trends in hip fracture rates in US hemodialysis patients, 1993-2010.

BACKGROUND: Changes in mineral and bone disorder treatment patterns and demographic changes in the dialysis population may have influenced hip fracture rates in US dialysis patients in 1993-2010. STUDY DESIGN: Retrospective follow-up study analyzing trends over time in hospitalized hip fracture rates. SETTING & PARTICIPANTS: Using Medicare data, we created 2 point-prevalent study cohorts for each study year. Hemodialysis cohorts included patients with Medicare as primary payer receiving hemodialysis in the United States on January 1 of each year; non-end-stage renal disease (ESRD) cohorts included Medicare beneficiaries 66 years or older on January 1 of each year. FACTORS: Age, sex, race, primary cause of ESRD, dual Medicare/Medicaid enrollment status, comorbid conditions. OUTCOMES: Hip fracture rates. MEASUREMENTS: Unadjusted hip fracture rates measured using number of events per 1,000 person-years in each year, then adjusted for patient characteristics. Poisson models estimated strata-specific event rates. RESULTS: The observed number of first hospitalized hip fracture events and the adjusted hip fracture rate increased steadily from 1993 (831 events; 11.9/1,000 person-years), peaked in 2004 (3,256 events; 21.9/1,000 person-years), and decreased through 2010 (2,912 events; 16.6/1,000 person-years). The trend for the subset of hemodialysis patients 66 years or older was similar to the trend for the full hemodialysis cohort; however, it differed markedly in magnitude and pattern from the non-ESRD Medicare cohort, for which rates were substantially lower and slowly decreasing since 1996. LIMITATIONS: Unable to provide causal explanations for observed changes; hip fractures identified through inpatient episodes; results do not describe hemodialysis patients without Medicare Parts A and B; laboratory values unavailable in the Medicare data set. CONCLUSIONS: Temporal trends in hip fracture rates among Medicare hemodialysis patients differ markedly from the steadily decreasing trend in non-ESRD Medicare beneficiaries, showing a relatively rapid increase until 2004 and relatively rapid decrease thereafter. Further research is needed to define associated factors.

Evaluating real-world use of cinacalcet and biochemical response to therapy in US hemodialysis patients.

BACKGROUND/AIMS: Data describing real-world use and effectiveness of cinacalcet are limited. We aimed to characterize predictors of treatment and changes in secondary hyperparathyroidism (SHPT) biochemistry after cinacalcet initiation. METHODS: We studied 25,250 in-center hemodialysis patients from a large dialysis provider, alive through November 2004, with no prior cinacalcet prescription. Patients were followed until initiation of cinacalcet, censoring, death, or July 31, 2007. Initiators were further followed for dose titration and discontinuation. Predictors of these events were evaluated using Cox proportional hazards modeling. Biochemical parameters and other SHPT medication use were compared between baseline, pre-initiation, and post-initiation time points. RESULTS: Over an average of 1.25 years of follow-up, 30% of patients initiated cinacalcet therapy. Between baseline and initiation (mean of 386 days), parathyroid hormone (PTH) and phosphorus levels increased 78 and 7%, respectively, in these patients. After adjustment, cinacalcet initiation was associated with higher SHPT severity, younger age, African-American race, higher phosphorus levels, and more comorbidity. Within 1 month of initiation, median PTH was reduced by 15-30% and phosphorus by 3-5%. Reductions were sustained or increased over 12 months, depending on initiating PTH level and whether dose up-titration occurred. Discontinuation was common, although many patients reinitiated. CONCLUSIONS: A substantial proportion of patients experienced SHPT progression and initiated cinacalcet treatment. Reductions in biochemistry varied by disease severity and whether doses were titrated.

Racial differences in clinical use of cinacalcet in a large population of hemodialysis patients.

BACKGROUND/AIMS: African-Americans with end-stage renal disease receiving dialysis have more severe secondary hyperparathyroidism than Whites. We aimed to assess racial differences in clinical use of cinacalcet. METHODS: This retrospective cohort study used data from DaVita, Inc., for 45,589 prevalent hemodialysis patients, August 2004, linked to Centers for Medicare & Medicaid Services data, with follow-up through July 2007. Patients with Medicare as primary payer, intravenous vitamin D use, or weighted mean parathyroid hormone (PTH) level >150 pg/ml at baseline (August 1-October 31, 2004) were included. Cox proportional hazard modeling was used to evaluate race and other demographic and clinical characteristics as predictors of cinacalcet initiation, titration, and discontinuation. RESULTS: Of 16,897 included patients, 7,674 (45.4%) were African-American and 9,223 (54.6%) were white; 53.2% of cinacalcet users were African-American. Cinacalcet was prescribed for 47.7% of African-Americans and 34.5% of Whites, and for a greater percentage of African-Americans at higher doses at each PTH strata. After covariate adjustment, African-Americans were more likely than Whites to receive cinacalcet prescriptions (hazard ratio 1.17, p < 0.001). The direction and magnitude of this effect appeared to vary by age, baseline PTH, and calcium, and by elemental calcium use. African-Americans were less likely than Whites to have prescriptions discontinued and slightly more likely to undergo uptitration (hazard ratio 1.09, 95% confidence interval 0.995-1.188), but this relationship lacked statistical significance. CONCLUSION: Cinacalcet is prescribed more commonly and at higher initial doses for African-Americans than for Whites to manage secondary hyperparathyroidism.

Exploring large weight deletion and the ability to balance confounders when using inverse probability of treatment weighting in the presence of rare treatment decisions.

PURPOSE: When medications are modified in response to changing clinical conditions, confounding by indication arises that cannot be controlled using traditional adjustment. Inverse probability of treatment weights (IPTWs) can address this confounding given assumptions of no unmeasured confounders and that all patients have a positive probability of receiving all levels of treatment (positivity). We sought to explore these assumptions empirically in the context of epoetin-alfa (EPO) dosing and mortality. METHODS: We developed a single set of IPTWs for seven EPO dose categories and evaluated achieved covariate balance, mortality hazard ratios, and confidence intervals using two levels of treatment model parameterization and weight deletion. RESULTS: We found that IPTWs improved covariate balance for most confounders, but was not optimal for prior hemoglobin. Including more predictors in the treatment model or retaining highly weighted individuals resulted in estimates closer to the null, although precision decreased. CONCLUSION: We chose to evaluate weights and covariate balance at a single time-point to facilitate an empirical analysis of model assumptions. These same assumptions are applicable to a time-dependent analysis, although empirical examination is not straight forward in that case. We find that the inclusion of rare treatment decisions and the high weights that result is needed for covariate balance under the positivity assumption. Removal of these influential weights can result in bias in either direction relative to the original confounding. It is therefore important to determine the reason for these rare patterns and whether inference is possible for all treatment levels.

Impact of Season and Other Factors on Initiation, Discontinuation, and Switching of Systemic Drug Therapy in Patients with Psoriasis: A Retrospective Study.

This study investigated whether systemic drug prescribing for psoriasis varies by season and other exacerbating factors. Eligible patients with psoriasis were assessed for each season for initiation, discontinuation, and switching of systemic drugs. A total of 360,787 patients were at risk of initiating any systemic drugs in 2016‒2019; 39,572 patients and 35,388 patients were at risk of drug discontinuation or switching to a biologic and a nonbiologic systemic drug, respectively. The initiation of biologic therapy in 2016‒2019 peaked in spring (1.28%), followed by summer (1.11%), fall (1.08%), and winter (1.01%). Nonbiologic systemic drugs followed a similar pattern. Those aged 30‒39 years, male, those with psoriatic arthritis, those who live in the South region, those who live in areas with lower altitudes, and those who live in areas with lower humidity had higher initiation with the same seasonality pattern. Discontinuation of biologic drugs peaked in summer, and switching of biologics was highest in spring. Season is associated with initiation, discontinuation, and switching, although seasonality pattern is less clear for nonbiologic systemic drugs. Approximately 14,280 more patients with psoriasis in the United States are estimated to initiate a biologic in spring than in other seasons, and over 840 more biologic users switched in spring than in winter. The findings may provide evidence for healthcare resource planning in psoriasis management.

Use of Dexmedetomidine and Opioids in Hospitalized Preterm Infants.

Importance: Dexmedetomidine, an α2-adrenergic agonist, is not approved by the Food and Drug Administration for use in premature infants. However, the off-label use of dexmedetomidine in premature infants has increased 50-fold in the past decade. Currently, there are no large studies characterizing dexmedetomidine use in US neonatal intensive care units (NICUs) or comparing the use of dexmedetomidine vs opioids in infants. Objectives: To describe dexmedetomidine use patterns in the NICU and examine the association between dexmedetomidine and opioid use in premature infants. Design, Setting, and Participants: A multicenter, observational cohort study was conducted from November 11, 2022, to April 4, 2023. Participants were inborn infants born between 22 weeks, 0 days, and 36 weeks, 6 days, of gestation at 1 of 383 Pediatrix Medical Group NICUs across the US between calendar years 2010 and 2020. Main Outcome and Measure: Exposure to medications of interest defined as total days of exposure, timing of use, and changes over time. Results: A total of 395 122 infants were included in the analysis. Median gestational age was 34 (IQR, 32-35) weeks, and median birth weight was 2040 (IQR, 1606-2440) g. There were 384 infants (0.1% of total; 58.9% male) who received dexmedetomidine. Infants who received dexmedetomidine were born more immature, had lower birth weight, longer length of hospitalization, more opioid exposure, and more days of mechanical ventilation. Dexmedetomidine use increased from 0.003% in 2010 to 0.185% in 2020 (P < .001 for trend), while overall opioid exposure decreased from 8.5% in 2010 to 7.2% in 2020 (P < .001 for trend). The median postmenstrual age at first dexmedetomidine exposure was 31 (IQR, 27-36) weeks, and the median postnatal age at first dexmedetomidine exposure was 3 (IQR, 1-35) days. The median duration of dexmedetomidine receipt was 6 (IQR, 2-14) days. Conclusion and Relevance: The findings of this multicenter cohort study of premature infants suggest that dexmedetomidine use increased significantly between 2010 and 2020, while overall opioid exposure decreased. Future studies are required to further examine the short- and long-term effects of dexmedetomidine in premature and critically ill infants.