Journal of Pharmacy Technology最新文献

Background: Dexmedetomidine is a centrally acting alpha-2-adrenoceptor agonist that is usually used in the intensive care unit (ICU) for its sedative, analgesic, and anxiolytic properties. Studies have shown that dexmedetomidine can be an effective adjunct analgesic, but they are limited and usually use a population of intubated patients. To better evaluate the role of dexmedetomidine use in the adult ICU, more information needs to be gathered on its analgesic effect and its utility in non-intubated patients.

Methods: This study was a retrospective cohort analysis between adult non-intubated ICU patients on dexmedetomidine and non-intubated ICU patients not on dexmedetomidine who were admitted to a 302-bed tertiary academic medical center between October 1, 2022, and August 31, 2023. Inclusion criteria necessitated an as-needed opioid order with a corresponding pain score and at least 1 other pain assessment and no history of symptomatic bradycardia, nor could it be present on admission. The primary study objective was to assess the amount of morphine milligram equivalents (MMEs) received during ICU admission with concomitant dexmedetomidine infusion. Secondary outcomes included the time to first dose of rescue opioid analgesia and ICU length of stay.

Results: A total of 38 patients were included. Baseline demographics did not differ significantly between groups. There was a significant statistical difference in the total amount of MMEs received, with the dexmedetomidine group having significantly less than the control group (P < 0.001). The dexmedetomidine group also had a significantly longer time to first rescue analgesia dose (P = 0.025) and a significantly increased incidence of delirium (P < 0.001). There was no difference in other adverse events between groups.

Conclusion: Dexmedetomidine significantly decreased MME requirements and increased time to first rescue analgesia dose in non-intubated ICU patients without increasing adverse effects but was associated with an increased incidence of delirium.

Background: Since the advent of the MIST2 trial, the combined instillation of dornase and alteplase has become an effective nonsurgical treatment option for empyema and pleural fluid collection. Percutaneous drainage of abdominal abscesses and fluid collections, rather than open surgical treatment, also has become commonplace. The are several case reports and studies on the use of fibrinolytics to drain abdominal fluid collections but no literature reporting use of both alteplase and dornase for abdominal administration.

Objective: We present a case series from an academic medical center where dornase therapy was added to fibrinolytic therapy to treat intra-abdominal fluid collections, hematoma, and abdominal drainage catheters with low output.

Methods: This is an institutional review board-approved retrospective case series of 13 patients who underwent combination use of alteplase and dornase via intra-abdominal route. The primary objective was to assess for increased drain output, reduction in size of the fluid collection, and adverse events.

Results: Many patients had improved drain output after dornase-alteplase therapy. One patient had significant bleeding complications.

Conclusions: All patients were discharged alive from the hospital. Clinical success was difficult to define due to variable goals of therapy. Further data are needed to establish the safety and efficacy of this practice, especially compared with intra-abdominal alteplase alone. Patients in our series generally received larger doses of alteplase than in prior studies due to use of dosing modeled on the MIST2 trial. Based on the limited experience of our study, we recommend holding therapeutic anticoagulation during the administration of intra-abdominal dornase-alteplase.

Background: No head-to-head comparisons of semaglutide formulations currently exist in the literature. In practice, many may think that oral and injectable semaglutide formulations are interchangeable, although there is currently limited real-world data to determine whether this is accurate.

Objective: The purpose of this study was to determine the effect of oral versus injectable semaglutide on hemoglobin A_1C (HbA_1C) and weight in patients with type 2 diabetes (T2D).

Methods: This was a retrospective single-center review of adult patients who had a diagnosis of T2D and were treated with oral or injectable semaglutide between November 1, 2019, and July 31, 2022. Primary outcome was a comparison of changes in HbA_1C (%) and weight (kg) from baseline to 6 months between patients receiving oral versus injectable semaglutide, stratified according to highest dose received. Secondary outcomes included frequency of dose reductions and discontinuations, achievement of clinical goals, and presence of an embedded clinical pharmacist at patients' primary care office.

Results: A total of 105 patients were included. Patients experienced mean decreases in HbA_1C and weight from baseline to 6 months of -1.75% (P < 0.001) and -3.64 kg (P = 0.015), respectively, in the oral semaglutide group and -1.35% (P < 0.001) and -5.26 kg (P < 0.001), respectively, in the injectable semaglutide group. When directly comparing semaglutide formulations, oral semaglutide demonstrated a 0.4% greater numerical reduction in HbA_1C (P = 0.523) and injectable semaglutide demonstrated a 1.62-kg greater numerical reduction in weight (P = 0.312). Adverse events (AEs) occurred more frequently with oral semaglutide than with injectable semaglutide (16.7% vs 4.9%). Discontinuation due to AEs was more common with oral semaglutide.

Conclusion: In this study, patients with T2D who received oral semaglutide demonstrated greater reductions in HbA_1C, whereas those treated with injectable semaglutide had greater reductions in weight, although there were no statistically significant reductions in HbA_1C or weight between the 2 formulations. Rates of AEs and discontinuation were more common in the oral semaglutide group.

Background: Inpatient use of intravenous iron has been increasing. Ferric gluconate is traditionally given once daily. Twice-daily dosing provides faster iron repletion, but there are limited data to support the safety of twice-daily dosing.

Objective: The aim of this study was to investigate the safety of twice-daily dosing for ferric gluconate compared with daily dosing.

Methods: This was an institutional review board-approved retrospective observational study of hospitalized adult patients who received intravenous ferric gluconate 250 mg daily or twice daily between January 1 and April 3, 2022. The primary composite safety outcome included hypotension, infusion reaction, rapid response alert, or escalation in level of care. Secondary outcomes included total amount of iron received, hospital length of stay, and changes in laboratory values.

Results: A total of 126 patients were included in this study, with 63 patients in each group. The primary outcome occurred in 29 patients (46%) in the twice-daily group compared with 36 patients (57.1%) in the daily group (relative risk = 0.81; 95% CI, 0.57-1.13; P = 0.212). Changes in iron, hemoglobin, and transferrin saturation were similar between the 2 groups. Median length of stay was statistically shorter in the twice-daily group (7.79 days) compared with the daily group (12.9 days; p = 0.006).

Conclusions: In this retrospective single-center study of hospitalized adult patients, those who received intravenous ferric gluconate twice daily did not experience an increased rate of a composite safety outcome of hypotension, infusion reactions, or escalation in level of care compared with those with daily dosing.

Purpose: To evaluate judicious antibiotic prescribing of benzathine penicillin G (BPG) after implementation of an electronic health record-based medication shortage alert during a critical drug shortage.

Methods: This was an institutional review board-approved retrospective cohort study of patients aged ≥3 months who received BPG between May 9, 2023, and February 28, 2024. The study included inpatient and outpatient visits after implementing a BPG medication shortage alert; patients with severe penicillin allergy, neurosyphilis, or congenital syphilis were excluded. Judicious BPG use was defined as use in patients diagnosed with primary, secondary, or latent syphilis or if they were prescribed a BPG alternative in response to the medication shortage alert; nonjudicious use included BPG for alternative diagnoses. Social determinants of health were assessed as exposure variables of interest. A separate cohort of syphilis patients receiving BPG or alternative therapy (i.e., doxycycline) was described.

Results: A total of 453 patients were included. Most patients were non-Hispanic Black (n = 273, 60%) men (n = 272, 60%) with a median (interquartile range) age of 32 (22-44) years. Of these, 318 (70%) received judicious BPG, whereas 135 (30%) received nonjudicious BPG. The most nonjudicious diagnosis was streptococcal pharyngitis (n = 128, 95%). Variables associated with judicious use included age >32 years (adjusted odds ratio [adjOR], 2.273; 95% CI, 1.488-3.472), male sex (adjOR, 1.835; 95% CI, 1.206-2.792), and black race (adjOR, 1.847; 95% CI, 1.212-2.815). Among a cohort of 128 syphilis patients who received BPG (n = 64, 50%) or doxycycline (n = 64, 50%), those who received doxycycline were more likely be uninsured (35 [54.7%] vs 43 [67.2%]; P = .15) and receive outpatient treatment (3 [4.7%] vs 12 [18.7%]; P = .13).

Conclusion: Despite implementing an electronic health record drug shortage alert, 30% of BPG use was nonjudicious and mostly for pharyngitis.

Objective: To characterize randomized controlled trials (RCTs) of pharmacological interventions (prescription medications, nonprescription medications, and supplements) for the management of moderate to severe traumatic brain injury (MSTBI). Data sources: Systematic searches were conducted in MEDLINE, PubMed, Scopus, CINAHL, EMBASE, and PsycINFO for RCTs up to December 2022 inclusive in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Study selection and data extraction: Inclusion criteria were RCT study design; participants' mean age ≥ 18 years and ≥ 50% had MSTBI; examined ≥ 1 pharmacological intervention(s), either alone or in combination with other interventions. Two independent reviewers conducted Cochrane risk of bias assessment. Data synthesis: Three hundred thirteen RCTs (1978-2022) met inclusion criteria. A total of 146 unique pharmacotherapies and supplements were studied. The most frequently studied intervention was mannitol (n = 20 RCTs). Mean sample size was 230.4 (4-12 737) and 195 studies (62.3%) were conducted in the acute phase post-MSTBI. Four hundred thirty-five unique outcome measures (OMs) were studied; the most common OMs used were Glasgow Outcome Scale (GOS) (29.4%), mortality (25.2%), and intracranial pressure (25.2%), Glasgow Coma Scale (GCS) (19.5%), and mean arterial pressure (17.3%), and heart rate (10%). Of the included studies, only 7% (n = 22) had low risk of bias. Conclusion: The paucity of high-quality studies, variability in RCT methodology, sample sizes, and OMs utilization, as well as the low number of RCTs conducted in the subacute- and chronic-phase after injury pose a challenge for conducting meta-analyses to provide strong recommendations for informed decision-making in clinical practice.

Objective: To review the safety, efficacy, and tolerability of zuranolone for the treatment of postpartum depression.

Data sources: A literature search was conducted through PubMed using the following terms: zuranolone, postpartum depression, perinatal depression, SAGE-217, and allopregnanolone analogue.

Study selection and data extraction: Articles describing the pharmacology, pharmacokinetics, efficacy, safety, and/or tolerability of zuranolone were included in this review.

Data synthesis: Zuranolone is an allopregnanolone analogue that works through modulation of the GABA_A receptor. Clinical trials have demonstrated that compared with placebo, zuranolone is effective in treating patients with postpartum depression. Common adverse events associated with zuranolone include fatigue, somnolence, headache, dizziness, diarrhea, sedation, upper respiratory tract infection, and nausea.

Conclusions: Pharmacotherapeutic options to treat postpartum depression include selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors, with the medication brexanolone (the first allopregnanolone analogue) reserved for severe postpartum depression. Zuranolone, the newest medication in its class, is without the same limitations as brexanolone, thus affording providers an additional easy-to-use option for treating postpartum depression.

Purpose: Prompt treatment of sepsis and septic shock is critical as delays increase mortality risk. Various tools, such as electronic alerts, standardized order sets, and rapid response teams, are used to expedite sepsis bundled care, yet their individual effects on outcomes and antimicrobial timing are unclear. This study evaluated the impact of an Inpatient Code Sepsis protocol, featuring an overhead page and order set, on mortality in hospitalized patients with sepsis and septic shock. Methods: A retrospective cohort study was conducted at a 371-bed hospital from July 1, 2020, to July 31, 2023. Hospitalized adults (≥18 years) diagnosed with sepsis and septic shock before and after the Inpatient Code Sepsis protocol implementation were included. The primary outcome was 30-day all-cause mortality; secondary outcomes were hospital length of stay, 30-day readmission, and time to antibiotic administration. Patients were excluded if they were identified for sepsis without infection, had sepsis due to non-bacterial causes, lost to follow-up within 30 days of admission, received empiric antibiotics in an emergency department or outside hospital, or were missing antibiotic administration time. Results: A total of 138 patients were included in the analysis. Mortality within 30 days did not significantly differ preprotocol and postprotocol (p = 0.381). However, a significant reduction in time to antibiotic administration was noted postimplementation (p < 0.05). Hospital length of stay and 30-day readmission showed no significant changes. Conclusion: The Inpatient Code Sepsis protocol did not impact 30-day mortality but did improve the time to antibiotic administration.

Retatrutide, a hormone receptor agonist targeting glucagon, glucagon-like peptide 1, and glucose-dependent insulinotropic polypeptide, is being developed to treat obesity. A literature review from April 2019 to April 2024 included such terms as "retatrutide," "LY3437943," "overweight," and "obesity." Phase I proof-of-concept studies led to phase II trials showing up to 24% body weight reduction and nearly 20 cm waist circumference reduction. The most common adverse effects were gastrointestinal. Ongoing phase II and III studies aim to further evaluate the safety and efficacy of retatrutide as a novel triagonist for obesity treatment.

Background: Closed system transfer devices (CSTD) help to reduce the exposure of healthcare professionals to hazardous drugs. They may be used in stability studies conducted on anticancer drugs. During a stability study about polyolefin bags of gemcitabine, Tevadaptor® device was suspected of causing a bias in the evaluation of the concentrations of the first aliquots extracted from the bags.

Objective: The objectives are to determine whether the use of a CSTD to prepare a drug solution and to withdraw it from a bag can interfere on the measured concentration compared to the expected one and to suggest hypothesis to explain the phenomenon.

Method: In the first experiment, three polyolefin bags of gemcitabine (5.4 mg/mL) were prepared under aseptic conditions using the Tevadaptor Luer Lock Adaptor®. The day of preparation, five aliquots of 3.8 ml each were sequentially withdrawn from each polyolefin bag using the same device. After one day, a new aliquot was withdrawn from each bag. In the second experiment, three polyolefin bags of gemcitabine (5.4 mg/ml) were prepared under aseptic conditions using a needle. One aliquot was extracted using a needle after the preparation from each bag, and another aliquot was extracted after one day. The concentrations of all aliquots were measured by liquid chromatography coupled to a photodiode array detector during the same run.

Results and discussion: The concentrations of the first aliquots extracted on day zero from the polyolefin bags using the Tevadaptor Luer Lock Adaptor® exhibit an overestimation of 26% ([95%CI: 23%-29%] P<0.001) compared to the others. Overestimation is not found for subsequent aliquots, or while using a needle to bypass the Tevadaptor® device.

Conclusion: This case highlights the bias that may arise when using CSTDs in stability studies. They should be used with comprehensive understanding of their technical specifications.