Preventive service utilization among adults with cystic fibrosis covered by private insurance is comparable to the general population.

BACKGROUND: As the life expectancy of the cystic fibrosis (CF) population is lengthening with modulator therapies, diligent age-appropriate screening and preventive care are increasingly vital for long-term health and wellbeing. METHODS: We performed a retrospective analysis comparing rates of receiving age- and sex-appropriate preventive services by commercially insured adult people with CF (PwCF) and adults without CF from the general population (GP) via the Truven Health MarketScan database (2012-2018). RESULTS: We captured 25,369 adults with CF and 488,534 adults from the GP in the United States. Comparing these groups, we found that 43% versus 39% received an annual preventive visit, 28% versus 28% were screened for chlamydia, 38% versus 37% received pap smears every 3 years (21-29-year-old females), 33% versus 31% received pap smears every 5 years (30-64-year-old females), 55% versus 44% received mammograms, 23% versus 21% received colonoscopies, and 21% versus 20% received dyslipidemia screening (all screening rates expressed per 100 person-years). In age-stratified analysis, 18-27-year-old PwCF had a lower rate of annual preventive visits compared to adults in the same age group of the GP (27% versus 42%). CONCLUSIONS: We discovered a comparable-to-superior rate of preventive service utilization in adults with CF relative to the GP, except in young adulthood from 18-27 years. Our findings establish the importance of meeting the primary care needs of adults with CF and call for development of strategies to improve preventive service delivery to young adults.

Cystic fibrosis transmembrane conductance regulator modulators and the exocrine pancreas: A scoping review.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve pulmonary outcomes in subjects with cystic fibrosis (CF); however, the effects on pancreatic manifestations are not well characterized. We hypothesized that CFTR modulators would improve measures of exocrine pancreatic function and outcomes. METHODS: We performed a systematic search to identify studies reporting measures of the exocrine pancreas in humans treated with CFTR modulators. Only studies reporting baseline and on-treatment assessments were included. RESULTS: Of 630 identified studies, 41 met inclusion criteria. CFTR modulators reduced acute pancreatitis events by 85% overall (rate ratio 0.15, 95% confidence interval (CI) 0.04, 0.52), with a greater effect seen in the subgroup with pancreas sufficient CF (PS-CF) (rate ratio 0.13 (95% CI 0.03, 0.53). Among 293 subjects with baseline and on-treatment evaluation of pancreas sufficiency, 253 were pancreas insufficient at baseline and 54 (21.3%) converted to pancreas sufficiency. Of 32 subjects with baseline FE-1 values <200 mcg/g, 16 (50%) increased to ≥200 mcg/g. Serum trypsin decreased by a mean of 565.9 ng/mL (standard deviation (SD) 311.8), amylase decreased by 38.2 U/L (SD 57.6), and lipase decreased by 232.3 U/L (SD 247.7). CONCLUSIONS: CFTR modulator use reduces acute pancreatitis frequency and improves indirect measures of exocrine pancreas function. Future interventional studies that evaluate the mechanism and impact of CFTR modulators on acute pancreatitis and pancreas sufficiency in patients with CFTR dysfunction are warranted.

Cystic fibrosis patients on cystic fibrosis transmembrane conductance regulator modulators have a reduced incidence of cirrhosis.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators significantly improve pulmonary function in patients with cystic fibrosis (CF) but the effect on hepatobiliary outcomes remains unknown. We hypothesized that CF patients on CFTR modulators would have a decreased incidence of cirrhosis compared to patients not on CFTR modulators or on ursodiol. AIM: To investigate the effect of CFTR modulators on the development of cirrhosis in patients with CF. METHODS: A retrospective analysis was performed using Truven MarketScan from January 2012 through December 2017 including all patients with a diagnosis of CF. Patients were excluded if they underwent a liver transplantation or if they had other etiologies of liver disease including viral hepatitis or alcohol use. Subjects were grouped by use of CFTR modulators, ursodiol, dual therapy, or no therapy. The primary outcome was development of cirrhosis. Kaplan-Meier curves estimated the incidence of cirrhosis and log-rank tests compared incidence curves between treatment groups. RESULTS: A total of 7201 patients were included, of which 955 (12.6%) used a CFTR modulator, 529 (7.0%) used ursodiol, 105 (1.4%) used combination therapy, and 5612 (74.3%) used neither therapy. The incidence of cirrhosis was 0.1% at 1 year and 0.7% at 4 years in untreated patients, 5.9% and 10.1% in the Ursodiol group, and 1.0% and 1.0% in patients who received both therapies. No patient treated with CFTR modulators alone developed cirrhosis. Patients on CFTR modulators alone had lower cirrhosis incidence than untreated patients (P = 0.05), patients on Ursodiol (P < 0.001), and patients on dual therapy (P = 0.003). The highest incidence of cirrhosis was found among patients treated with Ursodiol alone, compared to untreated patients (P < 0.001) or patients on Ursodiol and CFTR modulators (P = 0.01). CONCLUSION: CFTR modulators are associated with a reduction in the incidence of cirrhosis compared to other therapies in patients with CF.

Outcomes of inpatient cholecystectomy among adults with cystic fibrosis in the United States.

BACKGROUND: Symptomatic biliary and gallbladder disorders are common in adults with cystic fibrosis (CF) and the prevalence may rise with increasing CF transmembrane conductance regulator modulator use. Cholecystectomy may be considered, but the outcomes of cholecystectomy are not well described among modern patients with CF. AIM: To determine the risk profile of inpatient cholecystectomy in patients with CF. METHODS: The Nationwide Inpatient Sample was queried from 2002 until 2014 to investigate outcomes of cholecystectomy among hospitalized adults with CF compared to controls without CF. A propensity weighted sample was selected that closely matched patient demographics, patient's individual comorbidities, and hospital characteristics. The propensity weighted sample was used to compare outcomes among patients who underwent laparoscopic cholecystectomy. Hospital outcomes of open and laparoscopic cholecystectomy were compared among adults with CF. RESULTS: A total of 1239 inpatient cholecystectomies were performed in patients with CF, of which 78.6% were performed laparoscopically. Mortality was < 0.81%, similar to those without CF (P = 0.719). In the propensity weighted analysis of laparoscopic cholecystectomy, there was no difference in mortality, or pulmonary or surgical complications between patients with CF and controls. After adjusting for significant covariates among patients with CF, open cholecystectomy was independently associated with a 4.8 d longer length of stay (P = 0.018) and an $18449 increase in hospital costs (P = 0.005) compared to laparoscopic cholecystectomy. CONCLUSION: Patients with CF have a very low mortality after cholecystectomy that is similar to the general population. Among patients with CF, laparoscopic approach reduces resource utilization and minimizes post-operative complications.

Cystic Fibrosis Transmembrane Conductance Regulator Modulator Use Is Associated With Reduced Pancreatitis Hospitalizations in Patients With Cystic Fibrosis.

INTRODUCTION: Acute pancreatitis (AP) occurs among patients with pancreas-sufficient cystic fibrosis (PS-CF) but is reportedly less common among patients with pancreas-insufficient cystic fibrosis (PI-CF). The incidence of AP may be influenced by cystic fibrosis transmembrane conductance regulator (CFTR) modulator use. We hypothesized that CFTR modulators would reduce AP hospitalizations, with the greatest benefit in PS-CF. METHODS: MarketScan (2012-2018) was queried for AP hospitalizations and CFTR modulator use among patients with CF. Multivariable Poisson models that enabled crossover between CFTR modulator treatment groups were used to analyze the rate of AP hospitalizations on and off therapy. Pancreas insufficiency was defined by the use of pancreas enzyme replacement therapy. RESULTS: A total of 10,417 patients with CF were identified, including 1,795 who received a CFTR modulator. AP was more common in PS-CF than PI-CF (2.9% vs 0.9%, P = 0.007). Overall, the observed rate ratio of AP during CFTR modulator use was 0.33 (95% confidence interval [CI] 0.10, 1.11, P = 0.07) for PS-CF and 0.38 (95% CI 0.16, 0.89, P = 0.03) for PI-CF, indicating a 67% and 62% relative reduction in AP hospitalizations, respectively. In a subset analysis of 1,795 patients who all had some CFTR modulator use, the rate ratio of AP during CFTR modulator use was 0.36 (95% CI 0.13, 1.01, P = 0.05) for PS-CF and 0.53 (95% CI 0.18, 1.58, P = 0.26) for PI-CF. DISCUSSION: CFTR modulator use is associated with a reduction in AP hospitalizations among patients with CF. These observational data support the prospective study of CFTR modulators to reduce AP hospitalizations among patients with CF.

National Trends of Hospitalizations in Cystic Fibrosis Highlight a Need for Pediatric to Adult Transition Clinics.

OBJECTIVES: We hypothesized that hospitalizations in cystic fibrosis (CF) would reflect the development of age-related comorbidities. METHODS: A retrospective analysis was performed using the Nationwide Inpatient Sample (2002-2017). Hospitalizations for which the principal diagnosis was CF were analyzed regarding age at discharge and presence of comorbidities. Trends were assessed for significance using the Cochran-Armitage test. RESULTS: The mean age of patients hospitalized for CF increased from 19.7 years in 2002 to 23.0 years in 2017 (P = 0.017). Several comorbidities are more than 10 times more prevalent among adults as compared with children, including congestive heart failure, substance abuse, and chronic kidney disease (P < 0.001). In addition, diabetes with chronic complications was more prevalent in adults than children (10.0% vs 3.9%; P < 0.001), as was hypertension (7.2% vs 1.3%; P < 0.001) and osteoporosis (10.2% vs 1.9%; P < 0.001). More than 65% of CF hospitalizations in 2017 were in individuals older than 18 years. CONCLUSIONS: Hospitalizations for adults with CF are increasing, and individuals with CF are developing age-related comorbidities. Providers equipped to manage the health care needs of adults need to be ready and able to care for this unique and growing patient population.

Patterns of Health Insurance Coverage and Lung Disease Progression in Adolescents and Young Adults with Cystic Fibrosis.

Rationale: Health insurance coverage has been implicated as a socioeconomic factor affecting clinical outcomes in patients with cystic fibrosis (CF), but evidence for this is mixed and varies by age.Objectives: Focusing on adolescents and young adults with CF, we examined how multiyear patterns of health insurance coverage were associated with lung function decline and related outcomes.Methods: We used data from the 2000 to 2015 CF Foundation Patient Registry to classify patients in three cohorts (ages 12-17 yr, adolescents; 18-23 yr, transitioning to adulthood; and 24-29 yr, young adults) according to health insurance coverage, as follows: continuous private, continuous public, intermittent public, and coverage gaps. The primary outcome was the percentage predicted forced expiratory volume in 1 second (FEV1pp), which was modeled using mixed-effects regression. Additional outcomes included outpatient visits, hospital days for pulmonary exacerbation treatment, bacterial colonization, and body mass index. Outcomes were assessed over a 6-year period (e.g., ages 12-17 yr), whereas exposures were assessed over the prior 6 years (e.g., ages 6-11 yr).Results: The three cohorts included 3,365, 2,800, and 1,807 patients, respectively. The highest rate of FEV1pp decline was found in the middle cohort, with the annual decline being steeper among patients with continuous public (-3.1/yr; 95% confidence interval [CI], -3.3 to -2.8) or intermittent public (-2.4/yr; 95% CI, -2.6 to -2.2) coverage compared with patients with continuous private coverage (-2.1/yr; 95% CI, -2.2 to -2.0). These differences were not explained by differences in outpatient care utilization.Conclusions: During the transition to adulthood, use of public insurance was associated with accelerated lung function decline among patients with CF. The role of insurance as a causal factor in this decline or proxy for other socioeconomic characteristics should be explored in further studies.

Lung Allocation Score Thresholds Prioritize Survival After Lung Transplantation.

BACKGROUND: The lung allocation score (LAS) prioritizes lung transplant (LTx) candidates with poor transplant-free survival and expected survival benefit from LTx. Although patients with the highest LAS have the shortest waiting time, mortality benefit is unclear in this group, raising criticism that the LAS inappropriately prioritizes critically ill candidates. We aim to identify a threshold above which increasing LAS values do not predict increasing survival benefit. METHODS: The United Network for Organ Sharing Registry was queried for first-time adult LTx candidates with LAS ≥ 30 between May 2005 and December 2016. Survival was tracked from the time of listing through the posttransplant period and compared with survival while remaining on the waitlist, using proportional hazards regression. The survival benefit of LTx was modeled as a piecewise-constant time-dependent covariate, moderated by candidate LAS. RESULTS: Of the overall cohort (N = 21,157), LTx was particularly protective for 365 patients with an initial LAS of 70 to 79 (hazard ratio of death after undergoing LTx relative to remaining on the waitlist, 0.2; 95% CI, 0.1-0.3). However, the survival benefit of LTx did not meaningfully increase for 1,042 patients listed with even higher LAS. Among patients with cystic fibrosis, the survival benefit of LTx was constant above an LAS of approximately 50. CONCLUSIONS: Consistent survival benefit of LTx was observed among patients with an initial LAS of 70 and greater. This result supports equalizing priority for donor lung allocation for patients with LAS ≥ 70. A lower LAS threshold for maximum priority is indicated in patients with cystic fibrosis.

Risks associated with lung transplantation in cystic fibrosis patients.

INTRODUCTION: Survival after lung transplantation lags behind outcomes of other solid organ transplants, and complications from lung transplant are the second most common cause of death in cystic fibrosis. Evolving surgical techniques, therapeutics, and perioperative management have improved short-term survival after lung transplantation, yet have not translated into significant improvement in long-term mortality. Areas covered: We review risk factors for poor long-term outcomes among patients with cystic fibrosis undergoing lung transplantation to highlight areas for improvement. This includes reasons for organ dysfunction, complications of immunosuppression, further exacerbation of extrapulmonary complications of cystic fibrosis, and quality of life. A literature search was performed using PubMed-indexed journals. Expert commentary: There are multiple medical and socioeconomic barriers that threaten long-term survival following lung transplant for patients with cystic fibrosis. An understanding of the causes of each could elucidate treatment options. There is a lack of prospective, multicenter, randomized control trials due to cost, complexity, and feasibility. Ongoing prospective studies should be reserved for the most promising interventions identified in retrospective studies in order to improve long-term outcomes.

Health insurance and use of recommended routine care in adults with cystic fibrosis.

BACKGROUND: Low socioeconomic status is correlated with worse outcomes in patients with cystic fibrosis (CF). Whether insurance status impacts adherence to care in this population is unknown. METHODS: Patients ≥18 years old in the CF Foundation Patient Registry (2005-2013) were grouped based on reported annual insurance as private, public (Medicaid, Medicare or state medical assistance program), others or no insurance. Random effects logistic regression evaluated association between change in insurance status and annual use of recommended routine care. RESULTS: A total of 18 358 patients contributed 94 690 years of data to the analysis. In descriptive analysis, adherence to recommended routine care (≥4 clinic visits, ≥4 respiratory cultures and ≥2 pulmonary function tests per year) and recommended chronic medications for those with moderate to severe lung disease (dornase alfa and inhaled tobramycin or aztreonam if Pseudomoas aeruginosa in respiratory cultures) was most common in public insurance compared to other insurance types. In multivariable logistic regression, public insurance was associated with greater use of recommended care relative to private insurance (OR = 1.16; 95% confidence interval: 1.10-1.22; P < .001), while being uninsured was associated with lower odds of using recommended care (OR = 0.37; 95% confidence interval: 0.31-0.46; P < .001). CONCLUSIONS: For adults with CF in the United States, public insurance was associated with greater use of routine care than private coverage. Being uninsured was strongly associated with not using routine care. Further efforts to improve access to CF care should address the feasibility of universal and continuous insurance coverage in the CF population.

Examining a transdiagnostic measure of repetitive thinking in depressed, formerly depressed and never-depressed individuals.

BACKGROUND: Evidence that repetitive negative thinking (RNT) is a shared feature of a number of disorders has prompted the need for transdiagnostic self-report instruments; that is, measures of RNT that can be administered to individuals irrespective of their diagnosis. The Repetitive Thinking Questionnaire (RTQ; McEvoy et al., 2010) was developed to meet this need, and its psychometric properties and capacity to predict psychopathology have been tested in undergraduate and clinically anxious samples. METHODS: We administered the RTQ to currently depressed (n = 29), formerly depressed (n = 61) and never-depressed (n = 93) community participants. RESULTS: The RTQ demonstrated good psychometric properties, with excellent internal consistency for the RNT subscale (α=.93) and good convergent validity with measures of negative affect and psychopathology symptoms (rs= .47-.61). In addition, and in accord with our predictions, currently depressed and recovered depressed participants reported more RNT than never-depressed participants, but currently and recovered depressed participants did not differ. In addition, RNT scores explained additional variance in depression and anxiety symptoms, after controlling for gender, age, neuroticism, state negative affect, and intolerance of uncertainty. LIMITATIONS: Our sample was drawn from the community but participants were not treatment-seeking, and we employed a cross-sectional design. DISCUSSION: Taken together with previous experimental and longitudinal studies, our results support the utility of addressing RNT in the treatment and prevention of relapse in depression. Moreover, these data confirm the utility of the RTQ as a brief, transdiagnostic self-report measure of RNT.

Health Insurance Coverage among Young Adult Survivors of Pediatric Heart Transplantation.

OBJECTIVE: To describe the change in health insurance after heart transplantation among adolescents, and characterize the implications of this change for long-term transplant outcomes. STUDY DESIGN: Patients age 15-18 years receiving first-time heart transplantation between 1999 and 2011 were identified in the United Network for Organ Sharing registry and included in the analysis if they survived at least 5 years. The primary exposure was change or continuity of health insurance coverage between the time of transplant and the 5-year follow-up. Cox proportional hazards models were used to determine the association between insurance status change and long-term (>5 years) patient and graft survival. RESULTS: The analysis included 366 patients (age 16 ± 1 years at transplant), of whom 205 (56%) had continuous private insurance; 96 (26%) had continuous public insurance; and 65 (18%) had a change in insurance status. In stepwise multivariable Cox regression, change in insurance status was associated with greater mortality hazard, compared with continuous private insurance (hazard ratio = 1.9; 95% CI: 1.1, 3.2; P = .016), whereas long-term patient and graft survival did not differ between patients with continuous public and continuous private insurance. CONCLUSIONS: Continuity of insurance coverage is associated with improved long-term clinical outcomes among adolescent heart transplant recipients who survive into adulthood.

The effect of the affordable care act dependent coverage provision on patients with cystic fibrosis.

BACKGROUND: The Patient Protection and Affordable Care Act (ACA), enacted in 2010, expanded private insurance coverage of young adults through the dependent coverage provision. This policy's implications for patients with cystic fibrosis (CF) are unknown. METHODS: The CF Foundation Patient Registry was used to identify patients seen at CF centers, 3 years before and after ACA implementation. Patients were grouped according to eligibility for the dependent care provision (18-25 years old in 2010) or ineligibility (26-35 years old). Year-level difference-in-difference logistic regressions evaluated the association between ACA enactment and insurance status (private, public, or no insurance). Routine annual care consistent with CF Foundation guidelines (≥4 clinic visits, ≥4 respiratory cultures, and ≥2 pulmonary function tests/year) was a secondary outcome. RESULTS: The analysis included 4,024 and 3,132 patients in the eligible and ineligible groups, respectively (35,353 patient-years). In the eligible group, 62% had private insurance before and after ACA; 18% had public insurance before and after ACA; and 5% switched from public to private insurance. In the eligible group, lack of insurance coverage became more common in the post-ACA period (relative risk ratio vs. private insurance [RRR] = 1.95; 95%CI: 1.57, 2.43; P < 0.001). Public insurance coverage also became more common (RRR = 1.50; 95%CI: 1.39, 1.62; P < 0.001). Use of routine care increased post-ACA, but more strongly in the ineligible group than in the eligible group. CONCLUSIONS: The ACA dependent coverage provision did not increase private insurance coverage or use of routine care among CF patients who were potentially affected by this policy. Pediatr Pulmonol. 2017;52:458-466. © 2017 Wiley Periodicals, Inc.

The Relationship Between Post-Migration Stress and Psychological Disorders in Refugees and Asylum Seekers.

Refugees demonstrate high rates of post-traumatic stress disorder (PTSD) and other psychological disorders. The recent increase in forcible displacement internationally necessitates the understanding of factors associated with refugee mental health. While pre-migration trauma is recognized as a key predictor of mental health outcomes in refugees and asylum seekers, research has increasingly focused on the psychological effects of post-migration stressors in the settlement environment. This article reviews the research evidence linking post-migration factors and mental health outcomes in refugees and asylum seekers. Findings indicate that socioeconomic, social, and interpersonal factors, as well as factors relating to the asylum process and immigration policy affect the psychological functioning of refugees. Limitations of the existing literature and future directions for research are discussed, along with implications for treatment and policy.

A role of nucleus accumbens dopamine receptors in the nucleus accumbens core, but not shell, in fear prediction error.

Two experiments used an associative blocking design to study the role of dopamine receptors in the nucleus accumbens shell (AcbSh) and core (AcbC) in fear prediction error. Rats in the experimental groups were trained to a visual fear-conditioned stimulus (conditional stimulus [CS]) A in Stage I, whereas rats in the control groups were not. In Stage II, all rats received compound fear conditioning of the visual CSA and an auditory CSB. Rats were later tested for their fear responses to CSB. All rats received microinjections of saline or the D1-D2 receptor antagonist cis-(z)-flupenthixol prior to Stage II. These microinjections targeted either the AcbSh (Experiment 1) or the AcbC (Experiment 2). In each experiment, Stage I fear conditioning of CSA blocked fear learning to CSB. Microinjection of cis-(z)-flupenthixol (10 or 20 µg) into the AcbSh (Experiment 1) had no effect on fear learning or associative blocking. In contrast, microinjection of cis-(z)-flupenthixol (10 or 20 µg) into the AcbC (Experiment 2) attenuated blocking and so enabled fear learning to CSB. These results identify the AcbC as the critical locus for dopamine receptor contributions to fear prediction error and the associative blocking of fear learning.

Selecting danger signals: dissociable roles of nucleus accumbens shell and core glutamate in predictive fear learning.

Conditioned stimuli (CSs) vary in their reliability as predictors of danger. Animals must therefore select among CSs those that are appropriate to enter into an association with the aversive unconditioned stimulus (US). The actions of prediction error instruct this stimulus selection so that when prediction error is large, attention to the CS is maintained and learning occurs but when prediction is small attention to the CS is withdrawn and learning is prevented. Here we studied the role of glutamate acting at rat nucleus accumbens shell (AcbSh) and core (AcbC) α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in this selection of danger signals. Using associative blocking and unblocking designs in rats, we show that antagonizing AcbSh AMPA receptors via infusions of 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo[f]quinoxaline-2,3-dione (NBQX; 0.5 µg) prevents the unblocking of fear learning, whereas antagonizing AcbC AMPA receptors via infusions of NBQX (0.5 µg) prevents both the blocking and unblocking of fear learning. These results identify dissociable but complementary roles for AcbSh and AcbC glutamate acting at AMPA receptors in selecting danger signals: AcbSh AMPA receptors upregulate attention and learning to CSs that signal surprising USs, whereas AcbC AMPA receptors encode the predicted outcome of each trial.