Annals of Pharmacotherapy最新文献

Background: Poor adherence to lipid-lowering drugs in diabetic patients with dyslipidemia increases has been linked with an increased cardiovascular risk. A better understanding of the determinants of adherence to lipid-lowering drugs and treatment satisfaction among people with diabetes and dyslipidemia is crucial.

Objective: We aimed to assess the prevalence of adherence to lipid-lowering drugs, identify its determinant factors, and evaluate treatment satisfaction among users of lipid-lowering drugs who have diabetes and dyslipidemia.

Methods: We surveyed 398 adult patients with diabetes and dyslipidemia, using a validated medication adherence survey (Adherence to Refills and Medications Scale) and a validated treatment satisfaction survey (Treatment Satisfaction Questionnaire for Medication, TSQM). Sociodemographic and medical history data were collected through questionnaires.

Results: The prevalence of poor medication adherence was 36%. Factors associated with poor adherence included adverse reactions to medications, lack of medication availability, and lack of family support. Adherent patients reported lower low-density lipoprotein-cholesterol (LDL-C) and total cholesterol levels, higher treatment satisfaction, and a higher prevalence of cardiovascular disease and comorbidities. Having a family history of dyslipidemia was negatively associated with adherence, while the number of comorbidities positively influenced it. The scores of TSQM components such as effectiveness, global satisfaction, and convenience were significantly higher in people who were adherent or achieved the LDL-C target.

Conclusion and relevance: Our findings highlight the need for interventions targeting several factors impacting adherence to lipid-lowering drugs in patients with diabetes and dyslipidemia. Managing adverse effects, leveraging family support, and ensuring medication access represent crucial aspects of improving adherence and potentially mitigating cardiovascular risks in this high-risk population.

Parkinsonism induced by dopamine receptor antagonists, traditionally considered completely reversible following offending drug withdrawal, may unmask a degenerative parkinsonism in the patients with an underlying subclinical disease. In elderly patients, parkinsonism induced by the calcium channel blockers such as piperazine derivates cinnarizine and flunarizine may persist following drug discontinuation resulting in a permanent nonprogressive syndrome fulfilling the criteria for tardive parkinsonism. Whether this outcome occurs also following exposure to dopamine receptor antagonists such as neuroleptics and benzamide derivates or represents a class effect of the voltage-gated L-type calcium channel blockers, such as cinnarizine and flunarizine, due to their complex pharmacodynamic properties remains to be established.

Background: Owing to increasing local Escherichia coli resistance and current guidelines for the treatment of acute pyelonephritis (APN) over 14 years old, an evaluation of local prescribing patterns is warranted.

Objective: The purpose of this study was to evaluate local prescribing patterns and appropriateness of antibiotics in acute uncomplicated APN.

Methods: This is a retrospective cohort study of female patients aged 18 to 89 years diagnosed with APN and positive urine culture growing E. coli. Exclusion criteria included pregnancy, immunocompromised status, and complicated urinary tract infections. Outcomes included antibiotic appropriateness and its effects on hospital admission, hospital length of stay, and 30-day readmission.

Results: Between 2017 and 2022, 308 female patients were diagnosed with APN and had positive urine cultures, with 104 seen only in the emergency department (ED) and 109 admitted to the hospital. Patients seen in the ED had a significant increase in E. coli resistance to discharge antibiotics (12.5% vs 2.8%, P = 0.0070). In those patients discharged on antibiotics resistant to E. coli, significantly more patients returned to the ED in 30 days (31.3% vs 10.7%, P = 0.0155).

Conclusion and relevance: Patients seen only in the ED were more likely to have resistant organisms to discharge antibiotics compared with those admitted to the hospital. Patients discharged on antibiotics resistant to E. coli had a 3-fold increase in returning to the ED within 30 days regardless of admitted location. Follow-up of all cultures should be performed, and patients resistant to discharge antibiotics should be contacted and antibiotic regimens changed.

Background: Ketamine has been used in anesthesia, pain management, and major depressive disorder. It has recently been studied in patients with post-traumatic stress disorder (PTSD).

Objective: To determine the impact of ketamine on PTSD symptomatology and depression scores.

Methods: We conducted a literature search of Medline 1960 to May 20, 2023, and found 6 randomized controlled trials that met our inclusion criteria. We extracted data on the Clinician-Administered PTSD (CAPS), PTSD Checklist (PCL), or Montgomery-Asberg Depression Rating (MADRS) scales.

Results: The use of ketamine significantly reduced CAPS scores (n = 5, MD: -10.63 [95% CI -14.95 to -6.32]), PCL scores (n = 3, MD: -6.13 [95% CI -8.61 to -3.64]), and MADRS scores (n = 3, MD: -6.33 [95% CI -8.97 to -3.69]) at the maximal follow-up times versus control. Significant benefits were found at day 1 and weeks 1, 2, and 4 for CAPS and PCL scores as well as MADRS scores at day 1, week 1, and week 4 for ketamine versus control. The time to PTSD relapse was prolonged in the patients receiving ketamine versus control (n = 2, 15.74 days [95% CI 3.57 to 29.91 days]). More dry mouth (n = 2, OR 5.85 [95% CI 1.32 to 25.95]), dizziness (n = 2, OR 3.83 [95% CI 1.28 to 11.41]), and blurred vision (n = 2, OR 7.57 [1.00 to 57.10]) occurred with ketamine than control therapy.

Conclusions and relevance: Ketamine modestly reduced PTSD and depression scores as early as 1 day of therapy, but the longevity of effect needs to be determined. Given similar magnitude of benefit with SSRIs and venlafaxine, ketamine would not supplant these traditional options for chronic use.

Objective: To review the pharmacology, efficacy, and safety of intravenous sulbactam-durlobactam (SUL-DUR) in the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections.

Data sources: PubMed databases and ClinicalTrials.gov were searched using the following terms: Sulbactam Durlobactam, ETX2514, Xacduro, Sulbactam-ETX2514, ETX2514SUL.

Study selection and data extraction: Articles published in English between January 1985 and September 13, 2023, related to pharmacology, safety, efficacy, and clinical trials were reviewed.

Data synthesis: A phase II trial compared SUL-DUR with placebo with imipenem and cilastatin in both groups. Overall treatment success in the microbiological intention-to-treat analysis was reported in 76.6% of patients in the SUL-DUR group compared with 81% patients in the placebo group. A phase III trial compared SUL-DUR with colistin in adults with confirmed CRAB infections. Patients received either SUL-DUR or colistin and background therapy with imipenem-cilastatin. SUL-DUR was noninferior to colistin for 28-day all-cause mortality (19% vs 32.3%, treatment difference -13.2%; 95% CI [-30.0 to 3.5]).

Relevance to patient care and clinical practice in comparison to existing drugs: Clinicians have limited options to treat CRAB infections. SUL-DUR has demonstrated efficacy against CRAB in patients with pneumonia and may be considered a viable treatment option. Nonetheless, potential impact of concomitant imipenem-cilastatin as background therapy on clinical trial findings is unclear. Further studies are needed to elucidate the role of SUL-DUR alone or in combination with other active antimicrobials for the treatment of CRAB infections.

Conclusions: SUL-DUR has shown to be predominantly noninferior to alternative antibiotics in the treatment of pneumonias caused by CRAB, making it a viable treatment option. Further postmarketing data is needed to ascertain its role in other infections.

Objectives: We aimed to evaluate the high-quality literature on the frequency and nature of major adverse cardiac events (MACE) associated with either hydroxychloroquine (HCQ) or chloroquine (CQ).

Data sources: We searched Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Central from 1996 onward using search strategies created in collaboration with medical science librarians.

Study selection and data extraction: Randomized controlled trials (RCTs) published in English language from January 1996 to September 2022, involving adult patients at least 18 years of age, were selected. Outcomes of interest were death, arrhythmias, syncope, and seizures. Random-effects meta-analyses were performed with a Treatment Arm Continuity Correction for single and double zero event studies.

Data synthesis: By study drug, there were 31 HCQ RCTs (n = 6677), 9 CQ RCTs (n = 622), and 1 combined HCQ-CQ trial (n = 105). Mortality was the most commonly reported MACE at 220 of 255 events (86.3%), with no reports of torsades de pointes or sudden cardiac death. There was no increased risk of MACE with exposure to HCQ-CQ compared with control (risk ratio [RR] = 0.90, 95% CI = 0.69-1.17, I² = 0%).

Relevance to patient care and clinical practice: These findings have important implications with respect to patient reassurance and updated guidance for prescribing practices of these medications.

Conclusions: Despite listing as QT-prolonging meds, HCQ-CQ did not increase the risk of MACE.

Background: Incretin therapies, comprised of the dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have been increasingly utilized for the treatment of type 2 diabetes (T2DM). Previous studies have conflicting results regarding risk of pancreatitis associated with these agents-some suggest an increased risk and others find no correlation. Adverse event reporting systems indicate that incretin therapies are some of the most common drugs associated with reports of pancreatitis.

Objectives: This study aimed to compare the odds of developing pancreatitis in veterans with T2DM prescribed an incretin therapy versus thiazolidinediones (TZDs: pioglitazone and rosiglitazone) within the Veterans Health Administration (VHA).

Methods: This was a retrospective cohort study analyzing veterans with T2DM first prescribed an incretin therapy or a TZD between January 1, 2011, and December 31, 2021. A diagnosis of pancreatitis within 365 days of being prescribed either therapy was counted as a positive case. Data was collected and analyzed utilizing VA's Informatics and Computing Infrastructure (VINCI) and an adjusted odds ratio was calculated.

Results: The TZD cohort consisted of 42 912 patients compared with the incretin cohort of 304 811 patients. The TZD cohort had a pancreatitis incidence rate of 1.94 cases per 1000 patients. The incretin cohort had a incidence rate of 2.06 cases per 1000 patients. An adjusted odds ratio found no statistical difference of pancreatitis cases between the TZD and incretin cohorts (adjusted odds ratio [AOR] = 0.94, 95% CI [0.75, 1.18]).

Conclusion and relevance: This retrospective cohort study of national VHA data found a relatively low incidence of pancreatitis in both cohorts, and an adjusted odds ratio found no statistical difference of pancreatitis in patients prescribed an incretin therapy compared with a control group. This data adds to growing evidence that incretin therapies do not seem to be associated with an increased risk of developing pancreatitis.

Objective: The objective of this study was to review the characteristics, efficacy, and safety of zuranolone in the management of postpartum depression (PPD).

Data sources: Literature was identified using PubMed (1966-August 2023) and EMBASE (1973-August 2023) and clinicaltrials.gov. Search terms included zuranolone, SAGE-217, and PPD with further limitation of those published in English.

Study selection and data extraction: Articles selected for inclusion included trials evaluating zuranolone for the treatment of PPD.

Data synthesis: Zuranolone was evaluated for the treatment of moderate to severe PPD in 2 phase III trials. Both studies resulted in statistically significant improvement in depressive symptoms at day 15 (P = 0.003 and P < 0.001). Sustained differences in remission rates favoring zuranolone were found in both studies at day 45 compared with placebo (P = 0.01 and P < 0.05). Zuranolone was well tolerated, with somnolence, dizziness, headache, and sedation reported as the most common side effects.

Relevance to patient care and clinical practice in comparison to existing drugs: Zuranolone is only the second medication approved by the Food and Drug Administration (FDA) for PPD and offers an advantage over brexanolone in that it can administered orally in the outpatient setting. The rapid onset of effect of zuranolone is advantageous to traditional antidepressant therapy which can be weeks to months; however, limited information is available on safety during lactation.

Conclusions: The recent FDA approval of oral zuranolone for PPD offers a second rapid-acting treatment for PPD, extending the opportunity for treatment to patients in the outpatient setting.

Background: Constipation impacts 58% to 83% of critically ill patients and is associated with increased time on mechanical ventilation, delirium, and increased length of stay (LOS) in the intensive care unit (ICU).

Objective: The purpose of this study was to evaluate the efficacy of enteral naloxegol (NGL) versus subcutaneous methylnaltrexone (MNTX) for the management of opioid-induced constipation (OIC) in critically ill patients.

Methods: A retrospective analysis was conducted on adult patients admitted to the ICU who received a parenteral opioid infusion for at least 4 hours and experienced no bowel movement (BM) within the 48-hour period preceding the administration of NGL or MNTX. The primary outcome was time to first BM from the start of NGL or MNTX therapy. Secondary outcomes included number of BMs 72 hours following NGL or MNTX administration, ICU LOS, and cost-effectiveness.

Results: After exclusion criteria were applied, 110 and 51 patients were included in the NGL and MNTX groups, respectively. With a 10% noninferiority margin, NGL was noninferior to MNTX (Wald statistic = 1.67; P = 0.047). Median time to first BM was 23.7 hours for NGL and 18.3 hours for MNTX patients. Median LOS was 14 days (NGL) and 12 days (MNTX), and the average number of BMs in 72 hours was 3.9 for NGL and 3.8 for MNTX. Using wholesale acquisition cost (WAC), the cost per BM for NGL and MNTX was $21.74 and $170.00, respectively.

Conclusion and relevance: This study determined that NGL and MNTX had similar time to BM. NGL appears to be a safe and effective alternative with cost-saving potential in treating OIC in critically ill patients.

Background: Drug pharmacokinetics (PK) are altered in neurocritically ill patients, and optimal levetiracetam dosing for seizure prophylaxis is unknown.

Objective: This study evaluates levetiracetam PK in critically ill patients with severe traumatic brain injury (sTBI) receiving intravenous levetiracetam 1000 mg every 8 (LEV8) to 12 (LEV12) hours for seizure prophylaxis.

Methods: This prospective, open-label study was conducted at a level 1 trauma, academic, quaternary care center. Patients with sTBI receiving seizure prophylaxis with LEV8 or LEV12 were eligible for enrollment. Five sequential, steady-state, postdose serum levetiracetam concentrations were obtained. Non-compartmental analysis (NCA) and compartmental approaches were employed for estimating pharmacokinetic parameters and projecting steady-state trough concentrations. Pharmacokinetic parameters were compared between LEV8 and LEV12 patients. Monte Carlo simulations (MCS) were performed to determine probability of target trough attainment (PTA) of 6 to 20 mg/L. A secondary analysis evaluated PTA for weight-tiered levetiracetam dosing.

Results: Ten male patients (5 LEV8; 5 LEV12) were included. The NCA-based systemic clearance and elimination half-life were 5.3 ± 1.2 L/h and 4.8 ± 0.64 hours. A one-compartment model provided a higher steady-state trough concentration for the LEV8 group compared with the LEV12 group (13.7 ± 4.3 mg/L vs 6.3 ± 1.7 mg/L; P = 0.008). Monte Carlo simulations predicted regimens of 500 mg every 6 hours, 1000 mg every 8 hours, and 2000 mg every 12 hours achieved therapeutic target attainment. Weight-tiered dosing regimens achieved therapeutic target attainment using a 75 kg breakpoint.

Conclusion and relevance: Neurocritically ill patients exhibit rapid levetiracetam clearance resulting in a short elimination half-life. Findings of this study suggest regimens of levetiracetam 500 mg every 6 hours, 1000 mg every 8 hours, or 2000 mg every 12 hours may be required for optimal therapeutic target attainment. Patient weight of 75 kg may serve as a breakpoint for weight-guided dosing to optimize levetiracetam therapeutic target attainment for seizure prophylaxis.