Accounting for informative observation process in transition models of binary longitudinal outcome: Application to medical record data.

When extracting medical record data to form a retrospective cohort, investigators typically focus on a pre-specified study window, and select subjects who had hospital visits during that study window. However, such data extraction may suffer from an informative observation process, since sicker patients may have hospital visits more frequently. For example, Consecutive Pregnancy Study is a retrospective cohort study of women with multiple pregnancies in 23 Utah hospitals from 2003 to 2010, where the interest is to understand the risk factors of recurrent pregnancy outcomes, such as preterm birth. The observation process is informative in the sense that, women with adverse pregnancy outcomes may be less likely/willing/able to endure subsequent pregnancies. We proposed a three-part joint model with shared random effects structure to address this analytic complication. Particularly, a first-order transition model is used to model the longitudinal binary outcome; a gamma regression model is assumed for the inter-pregnancy intervals; a continuation ratio model specifies the probability of continuing with more births in the future. We note that the latter two parts give rise to a parametric cure-rate survival model. The performance of the proposed method was examined in extensive simulation studies, with both correctly and mis-specified models. The analyses of Consecutive Pregnancy Study data further demonstrate the inadequacies of fitting the transition model alone ignoring the informative observation process.

Time to Positive Blood and Cerebrospinal Fluid Cultures in Hypothermic Young Infants.

BACKGROUND AND OBJECTIVE: Hypothermia in young infants may be secondary to an invasive bacterial infection. No studies have explored culture time-to-positivity (TTP) in hypothermic infants. Our objective was to compare TTP of blood and cerebrospinal fluid (CSF) cultures between pathogenic and contaminant bacteria in hypothermic infants ≤90 days of age. METHODS: Secondary analysis of a retrospective cohort of 9 children's hospitals. Infants ≤90 days of age presenting to the emergency department or inpatient setting with hypothermia from September 1, 2017, to May 5, 2021, with positive blood or CSF cultures were included. Differences in continuous variables between pathogenic and contaminant organism groups were tested using a 2-sample t test and 95% confidence intervals for the mean differences reported. RESULTS: Seventy-seven infants met inclusion criteria. Seventy-one blood cultures were positive, with 20 (28.2%) treated as pathogenic organisms. Five (50%) of 10 positive CSF cultures were treated as pathogenic. The median (interquartile range [IQR]) TTP for pathogenic blood cultures was 16.8 (IQR 12.7-19.2) hours compared with 26.11 (IQR 20.5-48.1) hours for contaminant organisms (P < .001). The median TTP for pathogenic organisms on CSF cultures was 34.3 (IQR 2.0-53.7) hours, compared with 58.1 (IQR 52-72) hours for contaminant CSF organisms (P < .186). CONCLUSIONS: Our study is the first to compare the TTP of blood and CSF cultures between pathogenic and contaminant bacteria in hypothermic infants. All pathogenic bacteria in the blood grew within 36 hours. No difference in TTP of CSF cultures between pathogenic and contaminant bacteria was detected.

Insurance-mandated weight management program completion before bariatric surgery provides no long-term clinical benefit.

BACKGROUND: There is no evidence that insurance-mandated weight loss before bariatric surgery affects outcomes. OBJECTIVE: This retrospective study evaluated the relationship between insurance-mandated weight management program (WMP) completion before primary bariatric surgery and postoperative outcomes. SETTING: Suburban academic medical center. METHODS: Patients who underwent laparoscopic Roux-en-Y gastric bypass (LRYGB, n = 572) or sleeve gastrectomy (SG, n = 484) from 2014 to 2019 were dichotomized to presence (LRYGB n = 431, SG n = 348) or absence (LRYGB n = 141, SG n = 136) of insurance-mandated WMP completion. Primary endpoints included follow-up rate, percent total weight loss (%TWL), and percent excess weight loss (%EWL) through 60 months after surgery. The Mann-Whitney U test compared between-group means with significance at P < .05. RESULTS: Follow-up rate, %TWL, and %EWL were not different (P = NS) up to 60 months postoperation between groups for either surgery. Both LRYGB and SG patients without WMP completion maintained greater %TWL (LRYGB: 34.4 ± 11.1% versus 29.8 ± 11.0%, P = .159; SG: 21.4 ± 10.0% versus 18.2 ± 10.5%, P = .456) and %EWL (LRYGB: 71.3 ± 26.3% versus 67.6 ± 26.5%, P = .618; SG: 49.2 ± 18.8% versus 47.5 ± 28.8%, P = .753) at 36 months after surgery. Secondarily, duration of time to get to surgery was significantly greater among yes-WMP patients (LRYGB: 178 days versus 121 days, P < .001; SG: 169 days versus 95 days, P < .001). CONCLUSION: Insurance-mandated WMP completion before bariatric surgery delays patient access to surgery without improving postoperative weight loss potential and must be abandoned.

Assessing Opioid Use Disorder Treatments in Trials Subject to Non-Adherence via a Functional Generalized Linear Mixed-Effects Model.

The opioid crisis in the United States poses a major threat to public health due to psychiatric and infectious disease comorbidities and death due to opioid use disorder (OUD). OUD is characterized by patterns of opioid misuse leading to persistent heavy use and overdose. The standard of care for treatment of OUD is medication-assisted treatment, in combination with behavioral therapy. Medications for opioid use disorder have been shown to improve OUD outcomes, including reduction and prevention of overdose. However, understanding the effectiveness of such medications has been limited due to non-adherence to assigned dose levels by study patients. To overcome this challenge, herein we develop a model that views dose history as a time-varying covariate. Proceeding in this fashion allows the model to estimate dose effect while accounting for lapses in adherence. The proposed model is used to conduct a secondary analysis of data collected from six efficacy and safety trials of buprenorphine maintenance treatment. This analysis provides further insight into the time-dependent treatment effects of buprenorphine and how different dose adherence patterns relate to risk of opioid use.