Association between CFTR modulators and changes in iron deficiency markers in cystic fibrosis.

BACKGROUND: Iron deficiency (ID) is a common extrapulmonary manifestation in cystic fibrosis (CF). CF transmembrane conductance regulator (CFTR) modulator therapies, particularly highly-effective modulator therapy (HEMT), have drastically improved health status in a majority of people with CF. We hypothesize that CFTR modulator use is associated with improved markers of ID. METHODS: In a multicenter retrospective cohort study across 4 United States CF centers 2012-2022, the association between modulator therapies and ID laboratory outcomes was estimated using multivariable linear mixed effects models overall and by key subgroups. Summary statistics describe the prevalence and trends of ID, defined a priori as transferrin saturation (TSAT) <20 % or serum iron <60 µg/dL (<10.7 µmol/L). RESULTS: A total of 568 patients with 2571 person-years of follow-up were included in analyses. Compared to off modulator therapy, HEMT was associated with +8.4 % TSAT (95 % confidence interval [CI], +6.3-10.6 %; p < 0.0001) and +34.4 µg/dL serum iron (95 % CI, +26.7-42.1 µg/dL; p < 0.0001) overall; +5.4 % TSAT (95 % CI, +2.8-8.0 %; p = 0.0001) and +22.1 µg/dL serum iron (95 % CI, +13.5-30.8 µg/dL; p < 0.0001) in females; and +11.4 % TSAT (95 % CI, +7.9-14.8 %; p < 0.0001) and +46.0 µg/dL serum iron (95 % CI, +33.3-58.8 µg/dL; p < 0.0001) in males. Ferritin was not different in those taking modulator therapy relative to off modulator therapy. Hemoglobin was overall higher with use of modulator therapy. The prevalence of ID was high throughout the study period (32.8 % in those treated with HEMT). CONCLUSIONS: ID remains a prevalent comorbidity in CF, despite availability of HEMT. Modulator use, particularly of HEMT, is associated with improved markers for ID (TSAT, serum iron) and anemia (hemoglobin).

Change in Code Status Orders of Hospitalized Adults With COVID-19 Throughout the Pandemic: A Retrospective Cohort Study.

Aim: Our aim was to examine how code status orders for patients hospitalized with COVID-19 changed over time as the pandemic progressed and outcomes improved. Methods: This retrospective cohort study was performed at a single academic center in the United States. Adults admitted between March 1, 2020, and December 31, 2021, who tested positive for COVID-19, were included. The study period included four institutional hospitalization surges. Demographic and outcome data were collected and code status orders during admission were trended. Data were analyzed with multivariable analysis to identify predictors of code status. Results: A total of 3615 patients were included with full code (62.7%) being the most common final code status order followed by do-not-attempt-resuscitation (DNAR) (18.1%). Time of admission (per every six months) was an independent predictor of final full compared to DNAR/partial code status (p = 0.04). Limited resuscitation preference (DNAR or partial) decreased from over 20% in the first two surges to 10.8% and 15.6% of patients in the last two surges. Other independent predictors of final code status included body mass index (p < 0.05), Black versus White race (0.64, p = 0.01), time spent in the intensive care unit (4.28, p = <0.001), age (2.11, p = <0.001), and Charlson comorbidity index (1.05, p = <0.001). Conclusions: Over time, adults admitted to the hospital with COVID-19 were less likely to have a DNAR or partial code status order with persistent decrease occurring after March 2021. A trend toward decreased code status documentation as the pandemic progressed was observed.

Acute kidney injury in cystic fibrosis patients treated with intravenous colistimethate sodium or tobramycin.

OBJECTIVES: Colistimethate sodium and tobramycin are important systemic antibiotics for treatment of cystic fibrosis (CF) pulmonary exacerbations but can induce acute kidney injury (AKI). We characterize the rate of AKI in CF patients treated with systemic colistimethate sodium compared with tobramycin. METHODS: This single-centre, retrospective cohort study included hospitalized CF patients treated with IV colistimethate sodium or tobramycin. The primary outcome was AKI defined using the RIFLE criteria. Multivariate logistic regression using a mixed model was performed to identify variables that were independently associated with AKI. RESULTS: Overall, 156 patients representing 507 care encounters were included. The OR of AKI was not increased with IV colistimethate sodium relative to IV tobramycin after adjusting for other potential predictor variables (aOR 1.00; 95% CI 0.16-6.03). The frequency of AKI was 9.5% across all encounters, 6.9% with IV colistimethate sodium and 9.9% with IV tobramycin, with RIFLE category R (risk) being the most common stage, accounting for 4.2% of encounters with IV colistimethate sodium and 9.2% with IV tobramycin. The concomitant use of another nephrotoxin (aOR 2.51; 95% CI 1.27-4.95) or the combination of vancomycin and piperacillin/tazobactam (aOR 5.95; 95% CI 2.05-17.3) were both associated with increased odds of AKI. CONCLUSIONS: Systemic treatment with colistimethate sodium or tobramycin in the CF patient population is associated with a similar rate of nephrotoxicity. However, clinicians should be mindful of the increased risk for AKI in patients treated with either IV colistimethate sodium or IV tobramycin when used concurrently with other nephrotoxic agents, particularly the combination of vancomycin and piperacillin/tazobactam.

If Your Heart Were to Stop: Characterization and Comparison of Code Status Orders in Adult Patients Admitted with COVID-19.

Aim: Our aim is to characterize code status documentation for patients hospitalized with novel coronavirus 2019 (COVID-19) during the first peak of the pandemic, when prognosis, resource availability, and provider safety were uncertain. Methods: This retrospective cohort study was performed at a single tertiary academic medical center. Adult patients admitted between March 1, 2020 and October 31, 2020 who tested positive for COVID-19 were included. Demographic and hospital outcome data were collected. Code status orders during this admission and prior admissions were trended. Data were analyzed with multivariable analysis to identify predictors of code status choice. Results: A total of 720 patients were included. The majority (70%) were full code and 12% were in do-not-attempt resuscitation (DNAR) status on admission; by discharge, 20% were DNAR. Age (p < 0.001), time in the intensive care unit (ICU) (p < 0.001), and having Medicaid (p = 0.04) compared to private insurance were predictors of DNAR. Fourteen percent had no code status order. Older age (p < 0.001), time in the ICU (p = 0.01), and admission to a teaching service (p < 0.001) were associated with having an order. Of patients with a prior admission (n = 227), 33.5% previously had no code status order and 44.5% had a different code status for their COVID-19 admission. Of those with a change, most transitioned to less aggressive resuscitation preferences. Conclusions: Most patients hospitalized with COVID-19 in our study elected to be full code. Almost half of patients with prepandemic admissions had a different code status during their COVID-19 admission, with a trend toward less aggressive resuscitation preference.