Annals of Pharmacotherapy最新文献

Background: Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator utilized for the treatment of right ventricular dysfunction in the cardiac surgery patient population, which carries a risk of developing methemoglobinemia. The actual frequency of methemoglobinemia is not well defined.

Objective: The purpose of this study was to evaluate the incidence of methemoglobinemia in a cardiothoracic surgery intensive care unit (ICU) patient population.

Methods: This was a single-center, retrospective cohort study of 208 cardiothoracic surgery ICU patients who received at least 24 hours of iNO between July 1, 2020 and July 1, 2022. Patients were excluded if they did not have methemoglobin levels collected, received less than 24 hours of iNO therapy, or had documented use of other inhaled vasodilatory therapy during the same admission.

Results: A total of 208 patients were included. Zero patients in this study developed methemoglobinemia. The median duration of iNO therapy was 4 (interquartile range [IQR] = 2.4 to 6.5) days, and the median dose of iNO was 20 (IQR = 20-40) ppm. The median number of methemoglobin levels collected was 3 (IQR = 2-5), with a median methemoglobin level of 1.3% (IQR = 0.9%-1.7 %).

Conclusion and relevance: Our findings suggest that treatment with iNO in adult cardiothoracic surgery ICU patients has a low risk of developing methemoglobinemia. In addition, the outcomes collected provide information regarding iNO use, adverse events, and health care resource use in clinical practice. Routine monitoring of methemoglobin levels may not be necessary for this patient population. Further research is needed to assess the true risk of methemoglobinemia and to establish the appropriate frequency of monitoring in this group.

Background: In patients with septic shock, intravenous (IV) hydrocortisone is recommended when there is an ongoing vasopressor requirement. Guidelines recommend IV hydrocortisone 200 mg/day administered as a continuous infusion or 50 mg every 6 hours. To prevent waste during a hydrocortisone shortage and reduce cost, our institution implemented a dosing regimen of 100 mg every 12 hours.

Objectives: The primary objective of this study was to compare the impact of hydrocortisone 100 mg IV every 12 hours vs 50 mg IV every 6 hours on clinical outcomes in patients with septic shock.

Methods: This was a retrospective, multicenter study that evaluated patients admitted from April 2022 to September 2023 to a Greater Charlotte Atrium Health facility. Adult patients diagnosed via the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) codes with sepsis, severe sepsis, or septic shock receiving ≥15 mcg/min of norepinephrine equivalents requiring ≥ 24 hours of hydrocortisone were included. The primary outcome was time to shock reversal. Secondary outcomes included in-hospital mortality, hospital and intensive care unit (ICU) length of stay, and hyperglycemia.

Results: Of 446 screened patients, 111 were included. Median Sequential Organ Failure Assessment scores and Charlson Comorbidity Index were similar among groups. The median time to shock reversal was 56 [34-81] hours in the every 12 hours group compared to 65 [39-101] hours in the every 6 hours group (P = 0.21). In-hospital mortality was comparable between the every 6 hours group and the every 12 hours group (51.9% vs 45.6%, P = 0.51). There was no difference in hospital or ICU length of stay nor in incidence of hyperglycemic episodes between groups.

Conclusion and relevance: There was no difference in the primary outcome of time to shock reversal or any secondary outcome between hydrocortisone groups. This alternative hydrocortisone dosing strategy may warrant further evaluation in large, prospective studies.

Background: Current data suggest that short-course therapy for Pseudomonas aeruginosa ventilator-associated pneumonia (PA-VAP) may increase the risk of recurrent pneumonia. To decrease antibiotic exposure without adversely impacting clinical outcomes, risk stratification based on clinical response may identify optimal candidates for short-course therapy.

Objective: The purpose of this study was to determine whether early response to therapy correlated with the risk of recurrence in patients with PA-VAP.

Methods: This was a retrospective cohort study of patients with PA-VAP admitted to the Detroit Medical Center from January 2020 to July 2022. Those with improvements in at least 2 out of 3 objective measures of clinical response (PaO₂/FiO₂, fever, and leukocyte count) at 72 hours after therapy initiation were classified as early responders. The primary outcome was PA-VAP recurrence within 28 days of initial VAP onset.

Results: A total of 73 patients were included in the analysis: early response (n = 43) and delayed response (n = 30). Patients with an early response had a significantly decreased risk of 28-day PA-VAP recurrence compared to those with a delayed response (21% vs 43%, P = 0.04). Multivariable logistic regression found that PaO₂/FiO₂ > 240 mm Hg at 72 hours was associated with a decreased risk of 28-day PA-VAP recurrence (odds ratio [OR] = 0.25, 95% confidence interval [CI] = 0.07 to 0.90), whereas duration of antibiotics ≤8 days was associated with an increased risk of 28-day PA-VAP recurrence (OR = 4.74, 95% CI = 1.31 to 17.18).

Conclusion and relevance: This study found that early clinical response and improvement in PaO₂/FiO₂ were associated with a decreased risk of PA-VAP recurrence. Individualized treatment durations based on clinical response may allow clinicians to safely utilize shorter antibiotic courses for PA-VAP.

The Multistate Pharmacy Jurisprudence Examination (MPJE), despite its name, does not facilitate multistate pharmacy practice, instead requiring pharmacists to pass separate, state-specific law examinations-a process that is increasingly seen as outdated and inefficient. The proposed Uniform MPJE, targeted to launch in 2026, aims to standardize pharmacy law testing nationwide. This article examines the rationale behind the MPJE, questioning the necessity of any pharmacy law examination in an era of technological advancement, evolving regulatory models, and interprofessional parity. With some states already eliminating the MPJE without evidence of public harm, eliminating any law examination may be more aligned with the future of pharmacy practice rather than adopting a new examination.

Background: Low body weight is a recognized risk factor for bleeding with standard enoxaparin thromboprophylaxis (40 mg daily). Although reduced enoxaparin doses are used for venous thromboembolism (VTE) prevention in low-weight patients, data on bleeding and VTE outcomes remain limited.

Objective: To evaluate rates of bleeding and VTE with the use of fixed dose of enoxaparin 30 mg daily in low-weight surgical patients.‎Methods:A retrospective, single-center cohort study included low-weight surgical patients who received enoxaparin 30 mg daily from January 2018 to March 2024. The primary outcome was major ‎bleeding within 30 days postoperatively. Secondary outcomes included rates of overall bleeding ‎‎(major plus clinically relevant nonmajor bleeding) within 30 days and VTE events within 90 days. Risk factors were examined using logistic regression analysis or χ² tests.

Results: Data from 129 patients were analyzed. Six (4.7%) patients experienced major bleeding without fatality or bleeding at a critical anatomic site. The overall bleeding rate was 17.1% (n = 22). Five (3.8%) patients developed a VTE, including 2 pulmonary embolism events. Decreasing body weight (odds ratio [OR] = 0.89, 95% confidence interval [CI] = 0.81-0.97, P = 0.01), lower preoperative hemoglobin (OR = 0.97, 95% CI = 0.97-0.99, P = 0.04), and longer surgery durations (OR = 1.2, 95% CI = 1.05-1.40, P = 0.007) were independently associated with an increased risk of developing a bleeding event.

Conclusion and relevance: In low-weight surgical patients, thromboprophylaxis with a reduced fixed dose of enoxaparin (30 mg daily) appears safe, with a major bleeding rate below 5%, comparable with rates observed with standard dosing thromboprophylaxis in landmark trials of surgical patients. Among low-weight patients, the lower body weight, preoperative anemia, and prolonged surgical duration were independently associated with increased bleeding risk. These findings highlight the importance of individualized risk assessment when considering a reduced fixed dose of enoxaparin for VTE prevention in low-weight patients undergoing surgery.

Objective: To review the efficacy and safety of lenacapavir for the prevention of HIV-1 infection.

Data sources: Clinical trials and review articles were obtained through August 2025 using search terms lenacapavir, GS-CA1, GS-6207, capsid inhibitor, preexposure prophylaxis, and PrEP.

Study selection and data extraction: All relevant articles, trials, and abstracts in the English language were included.

Data synthesis: Lenacapavir uses a novel mechanism for HIV prevention administered through subcutaneous injection. In a counterfactual design, lenacapavir arms demonstrated superior efficacy for prevention against a background HIV incidence rate across a variety of populations and gender identities. Adverse events commonly reported include injection-site reactions, which may include nodules, pain, or swelling at the injection site.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:The extended dosing frequency of lenacapavir may uniquely serve patients at risk of HIV acquisition who are unable or unwilling to take oral prevention medications. The mechanism of action for lenacapavir is not duplicative of other medications used in first-line antiretroviral regimens and thus may not risk resistance to regularly used classes if resistance occurs. Lenacapavir is a moderate cytochrome P450 inhibitor and thus may have interactions with other medications; however, neither renal nor hepatic dose adjustments are required.

Conclusions: Lenacapavir provides a long-acting injectable option for people seeking a pharmacologic prevention agent against HIV-1. Despite injection-site reactions being relatively common, these did not present a barrier to treatment continuation among trial participants.

Objective: The objective of the study was to review acoramidis, a new transthyretin stabilizer, for treatment of transthyretin amyloid cardiomyopathy by means of pharmacology, efficacy, and safety.

Data sources: An Embase, PubMed, and ClinicalTrials.gov search was conducted using the keywords acoramidis, Attruby, and AG10.

Study selection and data extraction: We included full-text, English-language studies that evaluated the pharmacology, efficacy, and safety of acoramidis in transthyretin amyloid cardiomyopathy.

Data synthesis: Acoramidis slows or halts the accumulation of amyloid deposits in the heart by binding to the thyroxine-binding sites on the tetrameric transthyretin (TTR) protein preventing the TTR tetramer from dissociating into monomers. Acoramidis did not achieve statistical significance in terms of mortality reduction, but it outperformed placebo with respect to death from any cause, cardiovascular-related hospitalization, change in N-terminal pro-B-type natriuretic peptide, and change in 6-minute walk distance. In addition, by the end of the phase II clinical trial all acoramidis-treated patients achieved normal serum TTR concentrations. The overall incidence of subjects who experienced any treatment-emergent adverse events was similar between the acoramidis and placebo groups.Relevance to patient care and clinical practice in comparison to existing drugs:Acoramidis is the second TTR stabilizer approved for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM). Each medication to manage ATTR-CM similarly decreases the combined endpoints of all-cause mortality and progression of heart failure symptoms, when adjusted for risk factors. However, its place in therapy remains unclear among the treatment options for the management of ATTR-CM due to the lack of head-to-head trials.

Conclusions: Acoramidis is an effective and safe medication for the treatment of transthyretin amyloidosis cardiomyopathy.

Background: Patients with traumatic brain injury (TBI) may develop paroxysmal sympathetic hyperactivity (PSH), a syndrome manifesting as cyclic increases in vital signs and motor activity. Previous studies show propranolol mitigating sympathetic symptoms and negative outcomes, but few reports assess its effect on body temperature.

Objective: The purpose of this study was to determine if propranolol attenuates hyperthermia secondary to PSH in patients with TBI.

Methods: This study evaluated febrile patients with TBI treated with propranolol. The primary outcome was the difference in maximum (Tmax), minimum (Tmin), and average (Tavg) daily temperatures and temperature variability (Tvar). Secondary outcomes included similar evaluation of heart rate (HR) and mean arterial pressure (MAP), differences in a modified clinical features scale (mCFS), and number of infectious work-ups before and after propranolol initiation. Data were collected one day before, the day of, and 3 days after propranolol initiation. Repeated measures analysis of variance (ANOVA) was used to evaluate vital sign differences among days of therapy. Post-hoc Tukey's tests were performed to identify between-day differences if they existed.

Results: Fifty-nine patients were included. The majority were male (76.3%) and had a severe TBI (78.0%). Tmax, Tmin, Tavg, and Tvar were all not different between Day -1 and Day 3. Tmax decreased from 38.6 ± 0.11°C on Day 0 (the day of propranolol initiation) to 38.3 ± 0.14°C on Day 3 (P = 0.22). Maximum and average HRs were significantly decreased after propranolol initiation on Day 3 (P < 0.001) and on Days 2 (P = 0.04) and 3 (P = 0.01), respectively. Changes in MAP were not statistically significant. The mCFS and number of infectious work-ups were significantly lower after propranolol initiation.

Conclusion and relevance: Temperature was not significantly decreased after propranolol initiation in patients with TBI and hyperthermia; however, HR and mCFS were significantly lower. Larger studies are needed to characterize the effect of propranolol on temperature in patients with PSH.

Background: Intravenous (IV) ganciclovir is used in the management of herpesvirus infections, including cytomegalovirus (CMV). Ganciclovir is usually administered inpatient given the need for close monitoring of laboratory parameters.

Objective: This study describes our experience with administering IV ganciclovir via an outpatient parenteral antimicrobial therapy (OPAT) program.

Methods: This is a retrospective review of patients discharged on IV ganciclovir via OPAT at a tertiary medical center from August 2019 to August 2024. Demographics and treatment outcomes were collected.

Results: Ganciclovir was the preferred agent in all patients either due to concern for gastrointestinal absorption or provider preference. Eighteen patients with a median age of 59.5 (interquartile range [IQR]: 53-65) years met criteria. The most common underlying immunocompromising condition was receipt of a transplanted organ in 16 (88.9%) patients, most commonly heart (8 patients) and kidney transplants (7 patients). Median duration of therapy after hospital discharge was 22 (IQR: 20-27) days. Fifteen (83.3%) patients transitioned to valganciclovir on completion of parenteral therapy either as secondary prophylaxis or continuation of therapy. The most common adverse event was leukopenia in 6 (33.3%) patients. One patient developed acute kidney injury (AKI) requiring dose modification and eventual discontinuation.

Conclusion and relevance: Ganciclovir via OPAT is a viable option in patients requiring an extended duration of IV therapy. In our cohort of 18 patients, only one had early discontinuation of therapy due to ganciclovir-related AKI. Close monitoring of labs and an established OPAT protocol can allow for successful completion of therapy.