OBJECTIVE:To evaluate the efficacy and safety of linaclotide in children with functional constipation (FC) by synthesizing evidence from randomized controlled trials (RCTs). DATA SOURCES:A systematic search of PubMed, Scopus, Cochrane Central Register of Controlled Trials, and Google Scholar was conducted from inception through December 2024. The protocol was registered in PROSPERO (CRD420251018285), and the review was performed according to PRISMA guidelines. STUDY SELECTION AND DATA EXTRACTION:RCTs comparing linaclotide with placebo in children (<18 years) with FC were included. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool. Certainty of evidence was evaluated using the GRADE framework. DATA SYNTHESIS:Three RCTs involving 309 pediatric patients were included. Random-effects models demonstrated significant improvements with linaclotide in stool consistency (MD = 0.56, 95% CI, 0.27-0.86; P = .0001) and reduction in straining (MD = -0.26, 95% CI, -0.42 to -0.10; P = .001). No significant effects were observed for spontaneous bowel movement frequency, complete spontaneous bowel movement frequency, or abdominal pain. Treatment-related adverse events were more frequent with linaclotide (relative risk [RR] = 2.93, 95% CI, 1.27-6.77), mainly due to increased diarrhea (RR = 3.81, 95% CI, 1.48-9.82). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE:Linaclotide may provide symptom relief for selected children with FC, particularly those with hard stools and straining despite conventional therapy. Clinicians should counsel families regarding diarrhea risk and monitor tolerability, while recognizing the limited long-term pediatric evidence. CONCLUSIONS:Linaclotide improves stool consistency and reduces straining in pediatric FC but does not consistently improve bowel frequency or global symptom resolution. Its safety profile is generally acceptable, although diarrhea is a notable adverse effect. Further long-term, independently funded trials are needed to define its optimal role in clinical practice.
OBJECTIVE:To compare pharmacokinetic, clinical outcomes, and regulatory evidence for apixaban 5 mg versus 2.5 mg twice daily in kidney failure on hemodialysis with atrial fibrillation (AF), and propose a framework for individualized dose selection. DATA SOURCES:PubMed, EMBASE, and the Cochrane Library were searched from inception through June 2026 using terms including apixaban, kidney failure, hemodialysis, AF, pharmacokinetics (PK), and dosing. STUDY SELECTION AND DATA EXTRACTION:PK studies, observational cohorts, randomized controlled trials (RCTs), network meta-analyses, regulatory documents, and guidelines evaluating apixaban dosing in kidney failure and AF were included. DATA SYNTHESIS:Five PK studies (n ≈ 112) showed 2.5 mg twice daily produced steady-state levels comparable to 5 mg in normal renal function, while 5 mg produced approximately 3-fold supratherapeutic exposure. Of the 3 observational studies, 2 linked 5 mg to lower mortality; 1 found 63% higher bleeding with 5 mg and no difference in stroke/systemic embolism (subdistribution hazard ratio (SHR) 1.01; 95% CI, 0.59-1.73) or death (hazard ratio [HR] 1.03; 95% CI, 0.77-1.38). Two RCTs (RENAL-AF and AXADIA-AFNET 8) were terminated early and remain underpowered. Confounding by indication, competing risk of death, and misapplication of dose-reduction criteria likely explain this paradox. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE:This review provides the first systematic reconciliation of this paradox, identifying confounding by indication, competing risk of death, and structural flaws in the US Food and Drug Administration (FDA) dose-reduction criteria as likely explanations for the discordance. It gives clinical pharmacists a framework for appraising the evidence rather than defaulting to the FDA label or PK data alone, and proposes a decision algorithm for individualized dosing, derived from expert opinion, PK, and observational data and requiring prospective validation. CONCLUSIONS:The optimal apixaban dose in kidney failure remains unresolved. Neither dose has been shown to reduce stroke versus no anticoagulation in this population. Dose selection should be individualized to patient-specific factors.
OBJECTIVE:To compare the efficacy and safety of 14-day vonoprazan-tetracycline (VT) dual therapy versus bismuth-containing quadruple therapy (BQT) for Helicobacter pylori eradication. DATA SOURCES:PubMed/MEDLINE, Scopus, Cochrane Library, and Google Scholar were systematically searched from database inception through July 1, 2026, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Search terms included combinations of "Helicobacter pylori," "vonoprazan," "tetracycline," "dual therapy," "bismuth quadruple therapy," "eradication," and "randomized controlled trial (RCT)." STUDY SELECTION AND DATA EXTRACTION:Eligible studies were RCTs comparing 14-day VT dual therapy with BQT in adults with confirmed H pylori infection. Two reviewers independently screened studies, extracted data, and assessed risk of bias. Random-effects meta-analyses were performed using pooled risk ratios (RRs) with 95% confidence intervals (CIs), and certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. DATA SYNTHESIS:Three RCTs involving 1050 participants were included. Vonoprazan-tetracycline dual therapy achieved eradication rates comparable to BQT in intention-to-treat (RR = 1.00, 95% CI, 0.93-1.07), per-protocol (RR = 0.97, 95% CI, 0.93-1.01), and modified intention-to-treat analyses (RR = 1.01, 95% CI, 0.97-1.06). Vonoprazan-tetracycline significantly reduced total adverse events (TAEs) (RR = 0.31, 95% CI, 0.21-0.45), treatment discontinuation due to adverse events (RR = 0.12, 95% CI, 0.02-0.87), nausea (RR = 0.17, 95% CI, 0.08-0.35), and diarrhea (RR = 0.22, 95% CI, 0.08-0.67). The GRADE assessment demonstrated moderate-certainty evidence for efficacy outcomes and high-certainty evidence for most safety outcomes. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE:Vonoprazan-tetracycline dual therapy offers a simplified, penicillin-sparing regimen with eradication efficacy comparable to BQT and substantially improved tolerability. These findings support VT as a clinically relevant alternative for patients in whom treatment adherence, adverse effects, or penicillin avoidance are important considerations. CONCLUSIONS:Vonoprazan-tetracycline dual therapy provides eradication efficacy comparable to BQT while offering a significantly improved safety profile. Larger multinational RCTs are needed to confirm these findings and further define its role in first-line H pylori eradication.
OBJECTIVE:To compare the efficacy and safety of levetiracetam versus sodium valproate as antiseizure therapy in children with new-onset epilepsy or established status epilepticus. DATA SOURCES:PubMed, Cochrane Library, Embase, and Scopus were searched from inception to March 2026, without language restriction, using combinations of "epilepsy," "status epilepticus," "pediatric," "levetiracetam," and "sodium valproate," with hand-searching of reference lists. STUDY SELECTION AND DATA EXTRACTION:Randomized controlled trials and cohort studies of levetiracetam versus sodium valproate in children (≤18 years) were eligible. Two reviewers independently screened records, extracted data, and appraised quality (Cochrane RoB 2; Newcastle-Ottawa Scale for the cohort study). Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects Mantel-Haenszel model, with certainty graded by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. DATA SYNTHESIS:Eight studies (7 randomized trials and 1 prospective cohort) were included. Levetiracetam and sodium valproate were comparably effective for seizure freedom (RR = 1.01; 95% CI = 0.93-1.10) and for failure to achieve seizure freedom (RR = 1.00; 95% CI = 0.73-1.36). Levetiracetam significantly reduced overall AEs (RR = 0.78; 95% CI = 0.68-0.89) and weight gain (RR = 0.22; 95% CI = 0.10-0.46), both high certainty. Behavioral changes (RR = 2.15; 95% CI = 0.81-5.70) and skin rash (RR = 1.01; 95% CI = 0.50-2.04) did not differ significantly. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE:This is among the first meta-analyses to pool pediatric data for these agents across both new-onset epilepsy and status epilepticus and to grade outcome certainty. The findings support levetiracetam as a preferred initial monotherapy when weight, tolerability, reproductive safety, or interaction risk is a priority, with behavioral monitoring during use. CONCLUSIONS:Levetiracetam and sodium valproate offer similar seizure control in pediatric epilepsy and status epilepticus, but levetiracetam has a more favorable safety profile, particularly for adverse effects and weight gain. High-quality pediatric trials with longer follow-up are needed to confirm the long-term efficacy.
OBJECTIVE:The objective of this study is to review the efficacy and safety of doravirine/islatravir for the treatment of HIV-1 infection. DATA SOURCES:A literature search was conducted in PubMed and Google Scholar (January 2016-June 2026) using the search terms doravirine or MK-1439 and islatravir or MK-8591. Other resources included abstracts presented at recent conferences and the prescribing information. STUDY SELECTION AND DATA EXTRACTION:All English-language studies assessing the efficacy and safety of doravirine/islatravir for the treatment of HIV-1 infection were included. DATA SYNTHESIS:Doravirine is an established second-generation nonnucleoside reverse transcriptase inhibitor. Islatravir is a new nucleoside reverse transcriptase inhibitor that uniquely interferes with translocation and is highly active against HIV-1. Doravirine/islatravir once daily was shown to be safe and effective in three phase 3 clinical trials, using a lower dose of islatravir (0.25 mg), after a higher dose (0.75 mg) was shown in earlier trials to reduce total lymphocyte and CD4+ T-cell counts. The FDA approved this combination for the treatment of HIV-1 infection in adults who are virologically suppressed on stable antiretroviral therapy with no history of virologic treatment failure and no known resistance to doravirine.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:Doravirine/islatravir is the first integrase strand transfer inhibitor-free 2-drug regimen indicated for the treatment of HIV-1 infection. The combination could be useful for patients who want to simplify their regimen and those who cannot receive an integrase inhibitor. CONCLUSIONS:Doravirine/islatravir is safe and effective as a 2-drug regimen for the treatment of HIV-1 infection.
OBJECTIVE:This article reviews the published data encompassing the development, pharmacology, efficacy, and safety of obecabtagene autoleucel, summarizing data from pivotal clinical studies and clinical relevance in the treatment of relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia (B-ALL). DATA SOURCES:A literature review was conducted in PubMed and Clinicaltrials.gov from inception through May 2026, using terms "AUCATZYL®," "obecabtagene autoleucel," "obe-cel," "AUTO1," and "CAR-T cell therapy." STUDY SELECTION AND DATA EXTRACTION:Clinical data and studies were limited to those published in the English language which discussed the safety and efficacy of obecabtagene autoleucel. DATA SYNTHESIS:Obecabtagene autoleucel (obe-cel) is an autologous CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy using a novel CAT19 single-chain variable fragment designed with an intermediate affinity and fast binding off-rate mechanism. In the pivotal FELIX study, an overall remission rate of 77% was achieved in the primary adult cohort (IIa), with a median event-free survival rate of 11.9 months across all cohorts. Safety data indicate a manageable toxicity profile, and economic models suggest significant cost savings regarding adverse event management.Relevance to Patient Care and Clinical Practice in Comparison to Existing Agents:Obe-cel provides a new treatment option for adults with R/R B-ALL, a population that historically faces poor prognosis and high recurrence rates. CONCLUSION:While logistical complexities and high acquisition costs remain an access barrier to CAR-T cell therapies, obe-cel's molecular design and safety profile represent a significant advancement in the care of patients with R/R B-ALL.
BACKGROUND:Phenytoin is a highly protein-bound medication and monitored due to its narrow therapeutic range. Free phenytoin serum concentratinos (fPHTm) are not readily available in many institutions. OBJECTIVE:To evaluate whether population-specific correction factors (CFs) improve estimated free phenytoin serum concentrations (fPHTe) compared with traditional Winter-Tozer CF. METHODS:This retrospective review included adults with same-day measured total phenytoin serum concentrations (mPHT), fPHTm, albumin, and blood urea nitrogen (BUN) values. Patients were stratified by active/breakthrough seizures, intermittent hemodialysis (IHD), or adults younger than 65. Patient-specific fPHTm percentages were used in the estimation of fPHTe. RESULTS:Of 126 phenytoin levels reviewed, 66 met inclusion criteria. Population-specific CFs demonstrated lower bias and greater precision. In patients with active/breakthrough seizures and BUN <50 mg/dL, CF 0.29 improved accuracy compared with CF 0.2 (reduced mean percentage error [MPE] -59.59 vs -111.99 - indicating overprediction, root mean square error [RMSE] 1.79 vs 2.91), with similar trends when BUN exceeded 50 g/dL. A preliminary finding among adult patients younger than 65 showed better performance with a CF 0.275 than CF 0.2, with lower MPE (-40.43 vs -78.98) and RMSE (1.32 vs 2.16). In the IHD cohort, CF 0.201 outperformed CF 0.1 (MPE -74.40 vs -197.53 and RMSE 2.07 vs 5.32). CONCLUSION AND RELEVANCE:Population-specific CF estimated fPHTe more accurately and precisely than traditional CF. Findings remain preliminary due to limited representation, and further research is needed to improve CF selection across various subgroups.
OBJECTIVE:To review the pharmacology, efficacy, and safety of subcutaneous depemokimab-ulaa as add-on therapy in the treatment of severe eosinophilic asthma. DATA SOURCES:PubMed database, Embase, and ClinicalTrials.gov were searched using the following terms: depemokimab, depemokimab-ulaa, Exdensur, and GSK3511294. STUDY SELECTION AND DATA EXTRACTION:Articles published in English between January 2020 and March 2026, related to pharmacology, safety, efficacy, and clinical trials, were reviewed. Four studies met inclusion criteria. DATA SYNTHESIS:In phase 3 trials, SWIFT-1 and SWIFT-2, depemokimab-ulaa demonstrated comparable reductions in elevated blood eosinophil (EOS) counts when compared to other interleukin-5 (IL-5) targeting therapies in patients with severe eosinophilic asthma. The annualized exacerbation rates were 0.46 and 0.56 with depemokimab-ulaa vs 1.11 and 1.08 with placebo (P < .001), respectively. There were no differences in other outcomes that were studied. In the phase 3 NIMBLE trial, depemokimab-ulaa did not meet the noninferiority margin when patients were switched from other anti-IL-5 therapies. Depemokimab-ulaa maintained a favorable safety profile, with no serious adverse events or deaths considered to be related to the drug.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:When compared with other anti-IL-5 agents, depemokimab-ulaa might serve as an effective alternative option with its twice-yearly dosing offering a significant advantage potentially improving patient adherence and clinical outcomes. CONCLUSION:Depemokimab-ulaa's twice-yearly dosing offers a convenient alternative to other anti-IL-5 therapies as add-on treatment for severe eosinophilic asthma.
Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) provide significant renoprotection in chronic kidney disease, but their efficacy in autosomal dominant polycystic kidney disease (ADPKD) remains unclear. Objective: To systematically assess preclinical and clinical data regarding the effectiveness, safety, and mechanisms of SGLT2i in ADPKD. Data Sources: PubMed, Embase, and Scopus were searched from database inception to May 2026. Eligibility Criteria: Preclinical polycystic kidney models and clinical trials/observational studies of ADPKD evaluating any SGLT2i. Methods: Two reviewers independently screened studies and extracted data following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 standards. Bias was evaluated using SYRCLE and relevant clinical tools. Results: Eleven studies satisfied the inclusion criteria: 4 preclinical rodent models, 1 current randomized controlled trial, and 6 observational/case-based clinical investigations. Preclinical results consistently showed decreased cyst load, inflammation, and fibrosis while also enhancing renal hemodynamics. Emerging clinical evidence demonstrated advantages in managing blood pressure, decreasing proteinuria, and improving metabolic measures, with slight or inconsistent effects on overall kidney volume. Diverse clinical data prevented quantitative meta-analysis. Relevance to Patient Care and Clinical Practice: This review addresses a significant gap by comparing the functional and structural renal outcomes of SGLT2i in ADPKD. It indicates that although SGLT2i provides multi-pathway functional nephroprotection (natriuretic, anti-inflammatory, antifibrotic), structural reduction of cyst growth needs additional clinical validation. These results provide reassurance to clinicians concerning short-term safety and advocate for the use of SGLT2i as effective supplements to control blood pressure, metabolic markers, and proteinuria in ADPKD, regardless of structural kidney alterations. Conclusion: Preclinical findings suggest that SGLT2i provides renal protection in ADPKD through metabolic, anti-inflammatory, and antifibrotic mechanisms. Nevertheless, well-structured randomized controlled trials are necessary to validate long-term clinical effectiveness and safety.
BACKGROUND:Terlipressin is a synthetic vasopressin analogue that is indicated for the treatment of hepatorenal syndrome-acute kidney injury (HRS-AKI) to improve kidney function and haemodynamics. Despite its previous approval in Europe, terlipressin was Food and Drug Administration (FDA)-approved in 2022 in the United States. Historical standards of care, such as midodrine and octreotide (MO), are still used alternatively to terlipressin, and mortality benefit among treatments is unknown. OBJECTIVE:To examine the effects of terlipressin vs MO in hospitalized patients with HRS-AKI. METHODS:This single-centre, retrospective, cohort study was conducted at a large, tertiary academic medical centre. Data were collected from the electronic health record for patients admitted from July 2018 to July 2024. Patients ≥18 years of age admitted with International Classification of Diseases codes for cirrhosis, AKI, and clinical diagnosis of HRS were included. The primary outcome was the incidence of in-hospital mortality between patients receiving terlipressin vs MO. Descriptive statistics and parametric and non-parametric tests were utilized as appropriate. RESULTS:A total of 49 terlipressin patients and 30 MO patients were identified. The rate of in-hospital mortality was lower with terlipressin (n = 12, 24.5%) vs MO (n = 21, 70%) (P < .001). The mean hospital length of stay (days) was greater with terlipressin than MO (21.4 ± 14 vs 15.5 ± 8.4, P = .081) as was baseline serum creatinine (SCr) (2.94 ± 1.1 vs 1.89 ± 1.2 mg/dL, P < .05). Numerically more patients receiving terlipressin had a response to therapy (21/49 vs 12/30, P = .1033) with a similar decrease in SCr (-34.8 ± 21% vs -36.1 ± 21%, P = .86). The number of days from therapy initiation until the lowest SCr was less with terlipressin vs MO (4.97 ± 3.5 vs 7.92 ± 3.7, P = .02). CONCLUSION AND RELEVANCE:Terlipressin appears to effectively improve renal function and in-hospital mortality in patients with HRS-AKI compared with MO. Terlipressin may be used as a first-line treatment for HRS-AKI or after a trial of MO based on the study's results.
BACKGROUND:Awareness with paralysis is a growing concern in emergency department (ED) intubated patients who receive rocuronium for intubation. Following an internal audit that identified suboptimal adherence with postintubation sedation (PIS) practices, our institution launched an initiative to improve adherence to PIS standards. OBJECTIVE:Determine whether the multidisciplinary initiative decreased the time to initiation of PIS at institutionally recommended doses. METHODS:This pre-post intervention study was conducted at 2 institutions within a health care system, including an academic-affiliated hospital (site A) and a nonacademic-affiliated hospital (site B). The primary endpoint was the rate of PIS adherence before and after a multidisciplinary intervention that included education, order set modifications, and the establishment of clinical champions. Outcomes were compared across 3 groups: site AM (PIS managed by ED resident and supervising physicians), site AT (PIS managed by trauma resident and supervising physicians), and site B (PIS managed by ED supervising physicians). The order set changes were implemented at sites AM and B, but education and designation of clinical champions occurred only at site AM. RESULTS:PIS adherence rates at site AM increased from 1% in the preintervention period to 20% in the postintervention period (P < 0.001). There were no significant differences in PIS adherence rates between the preintervention and postintervention periods at sites AT and B. During the preintervention period, no significant differences in PIS adherence rates were observed across the groups, whereas during the postintervention period, site AM demonstrated significantly higher PIS adherence rates than sites AT and B. CONCLUSION AND RELEVANCE:This study demonstrated that a focused, multidisciplinary strategy can significantly improve adherence to PIS best practices in the ED. The marked improvements seen only at the site receiving the full intervention underscores the importance of combining education, workflow optimization, and clinical champions for successful practice change.
The juncture of an aging population and high prevalence of polypharmacy among older adults creates an urgency for better stewardship of medication use. Gaps in health care allow for medication-related problems to go unrecognized. As pharmacotherapy experts, pharmacists are positioned to address many of these limitations. However, pharmacists must be proactive to address high-risk medication use among community-dwelling older adults and overcome barriers that limit their capabilities to provide patient care in this setting.
Background: Antipsychotic polypharmacy, the coprescribing of 2 or more antipsychotics, carries risk but has a valid place in treating schizophrenia. Monotherapy is usually preferred according to best practice guidelines. Lack of documented prescribing reasons limits assessment of guideline adherence and therefore polypharmacy rationalisation. A pragmatic pharmacist-led intervention was implemented to address issues, including suboptimal documentation, contributing to non-guideline-adherent antipsychotic polypharmacy prescribing. Objective: To evaluate the impact of the intervention through a pre- versus post-intervention comparison of antipsychotic polypharmacy prevalence and prescribing burden, rate of documentation of prescribing reasons, and degree of guideline adherence. Methods: A retrospective, cross-sectional medical record audit was conducted to quantify polypharmacy prevalence, and the burden of its prescribing in terms of defined daily doses (DDDs) and maximum licensed daily doses (MLDDs). Documented prescribing reasons were noted and assessed against accepted practice guidelines. Findings were compared against those reported at baseline. Results: Post-intervention antipsychotic polypharmacy prevalence was 39.1% (vs 39.0% at baseline; P = 1.00). In the post-intervention polypharmacy cohort, mean combined DDD ± SD was 2.63 ± 1.16 (vs 2.84 ± 1.11 at baseline; P = 0.447) and mean combined MLDD ± SD was 136% ± 56% (vs 131% ± 39% at baseline; P = 0.675). Prescribing reasons were documented in 68.0% of audited polypharmacy cases (vs 36.7% at baseline; P = 0.012); 58.8% of documented reasons were guideline-adherent (vs 54.5% at baseline; P = 1.00). Conclusion and relevance: The intervention was not associated with changes in antipsychotic polypharmacy prevalence, magnitude nor degree of guideline adherence, but significantly improved rates of documentation. Compared with baseline, where prescribing reasons were largely unclear, the improved post-intervention documentation supported prescribers to make informed decisions about polypharmacy rationalisation. This research has reinforced the important role that pharmacists play in bridging communication gaps contributing to non-guideline-adherent polypharmacy.
Objective: To review recently Food and Drug Administration (FDA)-approved antibiotics (2017-2026) for complicated and resistant urinary tract infections (UTIs), focusing on their pharmacology, spectrum of activity, clinical evidence, and potential role in the management of UTIs specifically in women. Data sources and extraction: Information was obtained from FDA approval documents, prescribing information, pivotal clinical trials, and relevant peer-reviewed publications for antibiotics that were FDA-approved for UTIs between 2017 and 2026 using PubMed Central, MEDLINE, Scopus, and Web of Science databases. Data extracted included drug characteristics, approved indications, microbiological activity, efficacy and safety outcomes, and available evidence regarding use in women and special populations. Data synthesis: Urinary tract infections are among the most common infections in women, with approximately 50% of all women experiencing at least one UTI in their lifetime. The efficacy of traditional therapies (trimethoprim/sulfamethoxazole, nitrofurantoin, and fluoroquinolones) has been limited by the rising prevalence of resistant pathogens such as extended-spectrum beta-lactamase. Gender-specific factors, including safety in pregnancy and lactation, effects on vaginal flora, are discussed. This article offers practical guidance on how pharmacists and health care providers play a crucial role in integrating new UTI antibiotics into practice, optimizing dosing, monitoring for adverse effects, and educating patients. Relevance to patient care and clinical practice in comparison with existing drugs: Provides an updated evaluation of recently FDA-approved antibiotics for UTIs in women, highlighting their enhanced stability against broad-spectrum beta-lactamases, improved safety profiles, and activity against multidrug-resistant pathogens. These new agents may expand treatment options beyond traditional first-line therapies such as nitrofurantoin and trimethoprim/sulfamethoxazole and support more effective outpatient management of complicated and recurrent UTIs. Practical considerations for integrating these newer agents into clinical practice are reviewed, with emphasis on the role of pharmacists within interprofessional health care teams and antimicrobial stewardship programs in optimizing the care of women with UTIs. Conclusion: Emerging antibiotics offer promising new treatment options for multidrug-resistant UTIs in women and may improve outcomes while supporting antimicrobial stewardship. However, additional research is needed to address evidence gaps related to effectiveness, safety, and long-term clinical use.
BACKGROUND:Existing literature presents inconsistent findings regarding the association between selective serotonin reuptake inhibitors (SSRIs) and delirium, necessitating refined research clarifying the effect of SSRIs on delirium in older septic patients. OBJECTIVE:To examine the association between pre‑intensive care unit (ICU) SSRI use and delirium in older septic patients. METHODS:This study utilized data from the Medical Information Mart for Intensive Care (MIMIC)‑IV database. Multivariable logistic regression models were employed to quantify target correlations, with stratified assessments covering 3 SSRI exposure patterns (no use, pre‑ICU only, and continuous use), graded SSRI dosage, and specific drug type in relation to delirium. Subgroup analyses were performed to assess the link across different patient characteristics. Sensitivity analyses based on drug half‑lives were also conducted. RESULTS:A total of 11 768 older septic patients were included, of whom 754 used SSRIs before ICU admission. In the fully adjusted model, pre‑ICU SSRI use was linked to lower odds of delirium (odds ratio [OR] = 0.759, 95% confidence interval [CI] 0.637-0.901, P = 0.002). Continuous SSRI use during ICU stay showed no significant association (P = 0.493). Among dosage groups, only medium‑dose SSRIs were negatively associated with delirium (OR = 0.789, 95% CI 0.639-0.972, P = 0.027). Pre‑ICU citalopram use was significantly associated with reduced odds of delirium (OR = 0.660, 95% CI 0.495-0.874, P = 0.004). No significant interaction was identified in subgroup analyses (P for interaction > 0.05). Sensitivity analyses yielded results consistent with the primary findings. CONCLUSION AND RELEVANCE:Among MIMIC-IV aged sepsis patients, pre-ICU SSRIs (notably citalopram or moderate doses) link to lower delirium risk, with no correlation for in-ICU sustained medication. Preadmission SSRI data facilitate delirium risk evaluation; causality is unproven, and routine initiation, maintenance, or discontinuation of SSRIs solely for delirium prevention is not recommended. Individualized care balancing treatment needs, withdrawal and side effects awaits prospective verification.
BACKGROUND:Acute kidney injury (AKI) is common in critically ill patients, but the optimal dosing of beta-lactam antibiotics in this setting remains controversial. It is not known whether the benefit of initiating beta-lactams at normal doses outweighs the risk of accumulation and toxicity. OBJECTIVE:We aimed to evaluate the association between early dose adjustment of piperacillin/tazobactam (PT) and 28-day intensive care unit (ICU) mortality in critically ill patients with AKI. METHODS:We conducted a retrospective multicenter cohort study using the eICU Collaborative Research Database v2.0 and included adult ICU patients with AKI who received PT and had a pretreatment serum creatinine level corresponding to an estimated glomerular filtration rate (eGFR) <40 mL/min/1.73 m2. The exposure was PT dose in the first 24 hours, which was categorized as normal (≥13.5 g/24 h) or adjusted (<13.5 g/24 h). The primary outcome was 28-day ICU mortality. RESULTS:Among 1639 eligible patients, 224 (13.7%) received normal-dose PT and 1415 (86.3%) received adjusted doses. The overall 28-day ICU mortality was 11%, with significantly lower mortality in the normal-dose group (6.7%) compared with the adjusted-dose group (11.7%) (unadjusted odds ratio [OR] 1.85, 95% confidence interval [CI] 1.07-3.20; P = .028). After multivariable adjustment, early dose adjustment was independently associated with higher 28-day ICU mortality (adjusted OR 2.11, 95% CI 1.13-3.96; P = .020). Results were consistent across multiple subgroup and sensitivity analyses, but statistical significance was attenuated when the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used for eGFR estimation. CONCLUSION AND RELEVANCE:Early dose adjustment of PT in critically ill patients with AKI is associated with increased 28-day ICU mortality. This finding suggests that renal dose adjustment of PT should be deferred beyond the first 24 hours of therapy in this population. Prospective studies are needed to confirm this finding, define the optimal timing of subsequent dose adjustments, and assess safety outcomes.
