Isotretinoin Exposure and Risk of Inflammatory Bowel Disease: A Systematic Review with Meta-Analysis and Trial Sequential Analysis.

BACKGROUND: Cases of inflammatory bowel disease (IBD) following isotretinoin use have been reported previously, but whether isotretinoin exposure is associated with IBD has been unclear. OBJECTIVE: The aim was to evaluate whether isotretinoin use is associated with IBD. METHODS: We performed a systematic review and searched MEDLINE, Embase, and CENTRAL databases from inception to January 27, 2023 for relevant case-control and cohort studies. Our outcome was the pooled odds ratio (OR) for IBD and its two subtypes (Crohn disease and ulcerative colitis) in relation to isotretinoin exposure. We conducted a random-effects model meta-analysis and a sensitivity analysis by excluding low-quality studies. A subgroup analysis was undertaken by including studies considering antibiotic use. A trial sequential analysis (TSA) was performed to test the robustness of the conclusiveness of our results. RESULTS: We included eight studies (four case-control and four cohort studies) with a total of 2,522,422 participants. The meta-analysis found no increased odds for IBD among patients receiving isotretinoin (OR 1.01; 95% confidence interval [CI] 0.80-1.27). Nor did the meta-analysis find increased odds for either Crohn disease (OR 0.87; 95% CI 0.65-1.15) or ulcerative colitis (OR 1.27; 95% CI 0.94-1.73) associated with isotretinoin exposure. The sensitivity and subgroup analyses produced similar results. In TSA, the Z-curve reached the futility boundaries when using relative risk reduction thresholds ranging from 5% to 15%. CONCLUSION: This meta-analysis with TSA found no evidence of an association of isotretinoin use with IBD. Isotretinoin should not be withheld because of unnecessary concerns for the development of IBD. PROSPERO REGISTRATION NO: CRD42022298886.

Clinical pharmacy interventions in intensive care unit patients.

WHAT IS KNOWN AND OBJECTIVE: The drug therapy of critically ill patients requires intensive evaluation and management due to their severity of illness. These patients often require complex medication regimens. This study analysed the pharmaceutical care provided by clinical pharmacists (CPs) in a single medical centre in Taiwan. In addition, we explored the drug-related problems (DRPs) experienced by patients in intensive care units (ICUs) to determine how to improve the quality and safety of drug therapy. METHODS: This retrospective study was conducted from February 2019 to January 2020. The CPs implemented Taiwan's National Health Insurance (NHI) Scheme for Improving Hospital Drug Safety and Quality programme to improve the safety and quality of drug therapy. The CPs included in the study had at least 2 years' clinical experience and had participated in an ICU team for at least 6 consecutive months. They provided individualized drug treatment evaluation and intervention. Content of care was documented in the Clinical Pharmacy Service Record. RESULTS AND DISCUSSION: A total of 4374 pharmacy care records were evaluated by 12 CPs. The major category of ICU pharmaceutical care was medication reconciliation (n = 2938; 67.2%). Most of the medication interventions were for errors in dosing or dosing frequency (n = 218; 55.8%). Patients with renal dysfunction required more pharmaceutical interventions than did patients with normal renal function (odds ratio = 1.63; 95% confidence interval 1.31-2.01). The main interventions were related to antimicrobial agents (n = 386; 81.3%). During the study period, 99.2% of interventions were accepted and 90.8% were changed within 24 hours. WHAT IS NEW AND CONCLUSION: Increased pharmaceutical interventions for patients with renal dysfunction compared with patients with normal renal function were observed. Most cases of inappropriate frequency of dosing or dosing of antimicrobial agents required intervention.

Coadministration of Erythromycin to Increase Tacrolimus Concentrations in Liver Transplant Recipients.

BACKGROUND: We evaluated the effects of using erythromycin (ERY) in liver transplant recipients to improve the early postoperative control of tacrolimus (TAC) concentration. METHODS: This study adopts a retrospective medical record analysis method from January 2015 to December 2017. Assessment items include TAC daily dose (D), TAC whole blood trough level (Co), rejection episodes, and adverse effects. The magnitude of ERY inhibition on TAC metabolism was decided by analyzing dose-corrected trough concentration (Co/D). Oral 250 mg ERY every day to every other day was prescribed when patients needed to swallow more than 10 capsules of TAC per day, TAC trough levels rose too slowly, and/or acute rejection occurred. TAC trough levels were obtained daily. ERY was stopped when the TAC trough level was above 10 ng/mL or rejection episode relieved. RESULTS: A total of 8 liver transplant recipients was collected. Oral ERY was administered at 6 to 13 days after transplantation. The duration of ERY regimen was 2 to 7 days. The average initial and maximum Co/D was 0.6 ± 0.0 and 1.8 ± 1.0. After ERY was deleted, Co/D was back to the value without ERY at about 2 to 20 days. The magnitude of interaction between tacrolimus and erythromycin is 1.4- to 4.6-fold. The highest dose of TAC was 10 to 12 mg/d. There were no drug-related complications during this period. Acute rejection relapsed in 1 patient after we stopped ERY. CONCLUSION: Coadministration of ERY and TAC is a strategic choice for liver transplant recipients whose TAC blood concentration was difficult in approaching therapeutic levels.