Impact of elexacaftor/tezacaftor/ivacaftor on respiratory colonization in an adult cystic fibrosis clinic.

BACKGROUND: Little research has been completed on the correlation between cystic fibrosis (CF) modulator therapy and its effect on respiratory cultures in CF patients. This study evaluated the effect of elexacaftor/tezacaftor/ivacaftor (ETI) on respiratory colonization with Pseudomonas aeruginosa. METHODS: This single center, IRB approved, retrospective chart review compared patient data two years immediately prior to ETI initiation with patient data two years post-initiation from January 2017-December 2022. Patients were included in the study if they were at least 18 years old with a diagnosis of CF and had at least one month of ETI dispensed, at least one sputum culture obtained, and were currently on ETI. Those who had not been seen since ETI initiation or received a bilateral lung transplant were excluded. The primary outcome was rate of patients with respiratory colonization post-ETI. Colonization was defined as two or more positive P. aeruginosa cultures in a 12-month period. Decolonization was defined as three consecutive negative P. aeruginosa cultures after previous colonization. Key secondary outcomes included average time to discontinuation of mucolytic therapy and relative risk of pulmonary exacerbation. RESULTS: A significant reduction (p<0.001) in colonization with P. aeruginosa was observed with 49 patients in the pre-ETI group compared to 25 in the post-ETI group meeting the definition of colonization (n=79). Average time to discontinuation of mucolytic therapy was 14 months (p=0.002). Relative risk of pulmonary exacerbation was 4.80 (p<0.001). CONCLUSIONS: ETI use resulted in reduced colonization with P. aeruginosa, discontinuation of mucolytic therapy, and decreased frequency of pulmonary exacerbation.

Initiation of Buprenorphine/Naloxone on Rates of Discharge Against Medical Advice.

Objective: Evidence shows that patients with opioid use disorder (OUD) have an increased rate of discharge against medical advice (DAMA) as well as higher rates of hospital readmission. Therefore, the objective of this study was to determine if inpatient initiation of buprenorphine/naloxone in patients with OUD is associated with decreased rates of DAMA. Methods: This was a single center retrospective cohort study conducted at a level 1, academic medical center. The study included patients with OUD admitted to the Internal Medicine service from January through May of both 2018 and 2019 for an admitting diagnosis other than opioid withdrawal. The primary endpoint was rate of DAMA among OUD patients not initiated on opioid agonist therapy compared to those initiated on buprenorphine/naloxone. The secondary endpoint was the association between factors of the initiation process on rates of DAMA. Patients were excluded if they were discharged in less than 24 hours or received intermittent administration of buprenorphine/naloxone. Results: The rate of DAMA in OUD patients not initiated on buprenorphine/naloxone was 13.85% compared to 2.56% in those initiated on buprenorphine/naloxone (P = .048). Conclusion: In OUD patients initiated on buprenorphine/naloxone, the rate of DAMA was significantly lower than those who were not. This data supports the importance of optimizing the opportunity to initiate buprenorphine/naloxone in the acute care setting to minimize withdrawal symptoms therefore reducing the rate of DAMA. Ultimately increasing the ability to adequately treat the primary reason for admission and potentially decreasing readmission rates. Further studies are needed to evaluate this impact as this study is limited to a small sample size therefore lacking adequate power.

Calcineurin Inhibitor-Based Maintenance Immunosuppression in Lung Transplant Recipients: Optimal Serum Levels for Managing Acute Rejection and Renal Function.

BACKGROUND: Although effective for curtailing alloimmune responses, calcineurin inhibitors (CNIs) have an adverse-effect profile that includes nephrotoxicity. In lung transplant (LTx) recipients, the optimal serum levels of the CNI tacrolimus necessary to control alloimmune responses and minimize nephrotoxicity are unknown. METHODS: This retrospective, single-center study reviewed tacrolimus whole blood trough levels (BTLs), grades of acute cellular rejection (ACR), acute rejection scores, and creatinine clearance (CrCl) obtained in LTx recipients within the first year after their transplant procedure. Comparisons were made between the first 90 days post LTx (when tacrolimus BTLs were maintained >10 µg/L) and the remainder of the post-LTX year (when BTLs were <10 µg/L). RESULTS: Despite tacrolimus mean BTLs being higher during the first 90 days post LTx compared with the remainder of the first post-LTx year (10.4 ± 0.3 µg/L vs 9.5 ± 0.3 µg/L, P < .0001) there was no association with lower grades of ACR (P = .24). The intensity of ACR (as determined by acute rejection scores) did not correlate with tacrolimus mean BTLs at any time during the first posttransplant year (P = .79). During the first 90 days post LTx there was a significant decline in CrCl and a correlation between increasing tacrolimus mean BTLs and declining CrCl (r = -0.26, P = .03); a correlation that was not observed during the remainder of the year (r = -0.09, P = .52). CONCLUSIONS: In LTx recipients, maintaining BTLs of the CNI tacrolimus >10µg/L did not result in superior control of acute rejection responses but was associated with declining renal function.

Implications of Statin Use on Vasopressor Therapy in the Setting of Septic Shock.

Background: Pleiotropic anti-inflammatory and immunomodulatory effects of statins have been associated with improved outcomes in the critically ill population. Objective: To evaluate the implications of prior statin use on the duration of vasopressor therapy in the setting of septic shock. Methods: This was a retrospective, multicenter study of adult patients who were diagnosed with septic shock. Patients were included if they were treated with any vasopressor for greater than 6 hours from the time of admission. The primary outcome was to compare the duration of vasopressor therapy in patients with septic shock with and without previous statin exposure. Results: A total of 88 statin-exposed cases and 205 unexposed controls were included in the analysis. Despite 92% of statin-exposed patients being reinitiated on therapy within 24 hours, the duration of vasopressors did not differ between groups (44 hours, statin group vs 53 hours, control group, P = .51). There were also no mortality differences between the statin group and the controls (40% vs 47%, P = .27). Conclusions: Long-term statin exposure does not impact the duration of vasopressor therapy in septic shock. The lack of differences in clinical outcomes supports the concept that sepsis involves pro- and anti-inflammatory pathways as well as other nonimmunologic pathways. Results lend further credence to the recent conceptualization of sepsis, with complications leading to organ dysfunction caused not primarily due to inflammatory responses but by a dysregulated response to infection.

N-Acetylcysteine Use in Non-Acetaminophen-Induced Acute Liver Failure.

This article will review the available evidence related to the management of non-acetaminophen induced acute liver failure with N-acetylcysteine. Randomized controlled trials and a meta-analysis were included in this review. The efficacy of N-acetylcysteine in the treatment of acute liver failure from causes other than acetaminophen toxicity was evaluated. The efficacy of N-acetylcysteine in non-acetaminophen-induced acute liver failure is limited to specific patient populations. Patients classified as Coma Grade I or II are more likely to benefit from the use of this agent. The use of N-acetylcysteine is associated with improved transplant-free survival, not overall survival, in adults. N-Acetylcysteine does not improve the overall survival of patients with non-acetaminophen-induced acute liver failure but may be beneficial in those patients with Coma Grades I-II. Liver transplantation remains the only definitive therapy in advanced disease.

Comparison of Patients Receiving Long-Term Metformin Therapy and Vitamin B12 Monitoring.

Background: Metformin may cause vitamin B12 deficiency that can present with symptoms of peripheral neuropathy. Lack of vitamin B12 serum concentration monitoring could result in vitamin B12 deficiency progression, worsening of symptoms, and unnecessary medication. Objectives: The purpose of this study was to (a) compare the influence of the rate of symptoms consistent with vitamin B12 deficiency on obtaining vitamin B12 serum concentrations in patients using metformin; (b) assess if vitamin B12 serum concentrations were ordered as a routine monitoring parameter. Methods: This retrospective case-control study evaluated patients receiving metformin. Patients in the case group had documented symptoms or diagnosis of peripheral neuropathy or macrocytic anemia, while those in the control group did not. The primary outcome was frequency of vitamin B12 serum concentration assessment. The secondary outcomes included frequency of vitamin B12 serum concentration assessment for patients presenting with symptoms or diagnosis of peripheral neuropathy or macrocytic anemia. Results: Analysis included 355 patients (116 cases, 239 controls). The cases were 5 times more likely to have a serum vitamin B12 serum concentrations drawn versus controls (odds ratio [OR] = 5.83, 95% confidence interval [CI] = 3.47-9.77, P < .001). Patients with a diagnosis of peripheral neuropathy or macrocytic anemia were 4 times more likely to have a serum vitamin B12 concentration drawn than those who did not (peripheral neuropathy: OR = 4.92, 95% CI = 2.95-8.21, P < .001; macrocytic anemia: OR = 5.41, 95% CI = 1.30-20.97, P = .007). Conclusions: Cases were more likely to have vitamin B12 serum concentrations assessed than patients without symptoms. The majority of patients taking metformin did not have routine vitamin B12 serum concentration assessments for medication adverse event monitoring.