Pharmacotherapy最新文献

{"title":"The power and pitfalls of underpowered studies.","authors":"Ryan M Carnahan, Grant D Brown","doi":"10.1002/phar.4605","DOIUrl":"10.1002/phar.4605","url":null,"abstract":"<p><p>This article reflects on the potential value and many pitfalls of underpowered studies to help authors and readers consider whether and how they contribute meaningfully to the published literature. A basic introduction to power and sample size calculations is provided. Several problems that can arise in analysis and publication of underpowered studies are described. In addition, features of underpowered studies that may provide value are proposed, including when the hypothesis test of interest is a limited part of the story, the data is rich enough to showcase interesting features of the population of interest, when the rarity or ubiquity of events is an important finding, and when the study is preregistered to reduce the impact of publication bias. Several reporting guidelines for underpowered studies are also suggested.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"698-700"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of intravenous iron on bacterial infection risk immediately following kidney transplantation.","authors":"Spenser E January, Casey A Dubrawka, Kristin Progar, Karli Kurwicki, Rowena Delos Santos","doi":"10.1002/phar.4608","DOIUrl":"10.1002/phar.4608","url":null,"abstract":"<p><strong>Background: </strong>Kidney transplant recipients are at higher risk of infections due to immunosuppression, especially in the perioperative period after receiving induction therapy. Administration of iron has been linked to bacterial infections. This study investigated if receipt of intravenous iron at the time of kidney transplant increased bacterial infections post-transplant.</p><p><strong>Methods: </strong>This single-center, retrospective study compared patients who received intravenous iron at the time of kidney transplant to those who did not. Patients were followed for 12 weeks after transplant. The primary outcome was incidence of bacterial infections following transplant; hemoglobin and transfusion needs were also examined.</p><p><strong>Results: </strong>A total of 416 patients who received intravenous iron were compared to 416 patients who did not. Bacterial infections were similar between groups (14.4% iron group vs. 15.9% non-iron group). Intravenous iron did not influence bacterial infections on univariable or multivariable analyses when other infection confounders were accounted for. Patients who did not receive intravenous iron required more packed red blood cell transfusions in the 3 months following transplantation, but this was driven by factors other than intravenous iron as demonstrated by a post-hoc analysis.</p><p><strong>Conclusions: </strong>Intravenous iron did not increase the risk of bacterial infections in the immediate post-kidney transplant setting. Bacterial infections after transplant were associated with female sex, increasing age at transplant, receipt of transfusions, and increased duration of urinary catheters.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"722-729"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ERRATUM.","authors":"","doi":"10.1002/phar.2876","DOIUrl":"10.1002/phar.2876","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"754"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10363185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"Comparative adherence trajectories of oral disease-modifying agents in multiple sclerosis\".","authors":"","doi":"10.1002/phar.2846","DOIUrl":"10.1002/phar.2846","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"753"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10032491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world effectiveness of monoclonal antibody inhibitors of PCSK9 in patients with heterozygous familial hypercholesterolemia: A retrospective cohort study.","authors":"Rebecca Siemens, Mark Pryjma, Susan Buchkowsky, Arden R Barry","doi":"10.1002/phar.4609","DOIUrl":"10.1002/phar.4609","url":null,"abstract":"<p><strong>Background: </strong>Heterozygous familial hypercholesterolemia (HeFH) is a genetic condition that is associated with a high risk of atherosclerotic cardiovascular disease (ASCVD) due to elevated lipid levels. Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody inhibitors have been shown to reduce low-density lipoprotein cholesterol (LDL-C) substantially. This study aimed to assess the real-world effectiveness of PCSK9 inhibitor therapy among patients with HeFH.</p><p><strong>Methods: </strong>Retrospective cohort study of patients with probable or definite HeFH on a PCSK9 inhibitor at a specialized lipid clinic between 2015 and 2022. The primary objective was the proportion of patients who attained a ≥50% reduction in LDL-C after 12 months of treatment.</p><p><strong>Results: </strong>In total, 141 patients were screened and 95 were included. Mean age was 63 years, 51% were female, and mean baseline LDL-C level was 4.0 mmol/L (155 mg/dL). A majority of patients (60%) had statin intolerance, and 73% were on ezetimibe. The most common PCSK9 inhibitor was evolocumab (94%). Overall, 74% of patients achieved a ≥50% reduction in LDL-C after 12 months of therapy. Mean LDL-C concentration decreased to 1.7 mmol/L (66 mg/dL) (approximately 59% reduction from baseline) after 12 months of follow-up but increased to 1.9 mmol/L (73 mg/dL) after ≥24 months of follow-up. Similar trends were observed in non-high-density lipoprotein cholesterol and apolipoprotein B. Lipoprotein(a) was significantly reduced by 45% over 12 months. Twelve percent of patients permanently discontinued therapy. Barriers to PCSK9i use were mostly related to cost.</p><p><strong>Conclusions: </strong>In a real-world cohort of HeFH patients, most of which were intolerant to statins, a high majority were able to achieve a ≥50% reduction in LDL-C after 12 months of PCSK9 inhibitor therapy (mean reduction of approximately 59%), which is similar to clinical trial data of patients with ASCVD. A significant reduction in non-high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a) were also observed.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"730-737"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends in the appropriateness of oral antibiotic prescriptions dispensed in the United States from 2010 to 2018.","authors":"Mahek Garg, Veena Venugopalan, Scott M Vouri, Vakaramoko Diaby, Nicole M Iovine, Debbie L Wilson, Haesuk Park","doi":"10.1002/phar.4604","DOIUrl":"10.1002/phar.4604","url":null,"abstract":"<p><strong>Background: </strong>One of the goals established by the United States National Action Plan to Combat Antibiotic-Resistant Bacteria is to reduce inappropriate outpatient antibiotic prescriptions by 50% by 2020. Recent data on the achievement of this goal is lacking. The objective of our study was to examine recent trends in the appropriateness of oral antibiotic prescriptions dispensed to a commercially insured population in outpatient settings in the United States to quantify the relative trend in inappropriate antibiotic prescribing from 2010 to 2018.</p><p><strong>Methods: </strong>Our cross-sectional analysis examined oral antibiotic prescriptions dispensed in outpatient settings using the IBM MarketScan Commercial Data from January 2010 to December 2018. Trends in the annual proportion of antibiotic prescriptions classified as appropriate, potentially appropriate, inappropriate, or without any medical visit during a 7 days look-back period were estimated using multivariable generalized linear models with Poisson distribution adjusting for beneficiaries' demographic and infectious conditions.</p><p><strong>Results: </strong>Approximately 170 million oral antibiotic prescriptions were dispensed to 86 million beneficiaries during 2010 to 2018. The mean age of the study population was 34.5 (±19.1) years, with 58.4% females and 24.6% children. We observed a 12.9% (95% Confidence Interval [CI] = 12.6%-13.2%; p < 0.01) decline in rates of antibiotic use, from 832 to 727 prescriptions per 1000 beneficiaries, from 2010 to 2018. The proportion of prescriptions classified as appropriate increased by 36.7% (95% CI = 36.4%-36.9%; p < 0.01); potentially appropriate prescriptions increased by 9.3% (95% CI = 9.1%-9.4%; p < 0.01); whereas inappropriate prescriptions and those without a medical visit declined by 11.3% (95% CI = 11.2%-11.4%; p < 0.01) and 14.0% (95% CI = 13.9%-14.2%; p < 0.01), respectively. Similar declining trends were observed in use and proportion of inappropriate prescriptions for broad-spectrum antibiotics. In 2018, amoxicillin and azithromycin were the most common appropriate and inappropriate prescription fills, respectively.</p><p><strong>Conclusion: </strong>Although antibiotic use and inappropriate prescribing declined steadily from 2010 to 2018 in the United States, this study demonstrates that we have not achieved the national goal of reducing inappropriate antibiotic prescribing by 50%.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"701-710"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolving resistance landscape in gram-negative pathogens: An update on β-lactam and β-lactam-inhibitor treatment combinations for carbapenem-resistant organisms.","authors":"Christina Koenig, Joseph L Kuti","doi":"10.1002/phar.2950","DOIUrl":"10.1002/phar.2950","url":null,"abstract":"<p><p>Antibiotic resistance has become a global threat as it is continuously growing due to the evolution of β-lactamases diminishing the activity of classic β-lactam (BL) antibiotics. Recent antibiotic discovery and development efforts have led to the availability of β-lactamase inhibitors (BLIs) with activity against extended-spectrum β-lactamases as well as Klebsiella pneumoniae carbapenemase (KPC)-producing carbapenem-resistant organisms (CRO). Nevertheless, there is still a lack of drugs that target metallo-β-lactamases (MBL), which hydrolyze carbapenems efficiently, and oxacillinases (OXA) often present in carbapenem-resistant Acinetobacter baumannii. This review aims to provide a snapshot of microbiology, pharmacology, and clinical data for currently available BL/BLI treatment options as well as agents in late stage development for CRO harboring various β-lactamases including MBL and OXA-enzymes.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"658-674"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Update on the clinical applications of SGLTis: Insight to benefits beyond hypoglycemic and cardiorenal protection.","authors":"Shibing Tao, Shanlan Guo, Nanwei Tong","doi":"10.1002/phar.2952","DOIUrl":"10.1002/phar.2952","url":null,"abstract":"<p><p>Sodium glucose cotransporter inhibitor (SGLTi) drugs have been widely used in clinical practice. In addition to their benefits in hyperglycemia, heart failure (HF), and kidney disease, their effects on obesity, metabolic dysfunction-associated steatotic liver disease (MASLD, formerly named nonalcoholic fatty liver disease [NAFLD]), polycystic ovarian syndrome (PCOS), abnormal lipid metabolism, hyperuricemia, obstructive sleep apnea syndrome (OSAS), anemia, and syndrome of inappropriate antidiuresis (SIAD, formerly named syndrome of inappropriate antidiuretic hormone [SIADH]) have been explored. In this review, we searched the data of clinical randomized controlled trials (RCTs) and meta-analyses of SGLTis in patients with diabetes from the PubMed library between January 1, 2020, and February 1, 2024. According to our review, certain SGLTis exhibit relatively superior clinical safety and effectiveness for treating the abovementioned diseases. Proper utilization of SGLTis in these patients can provide additional medication options for patients with different disease scenarios. However, studies of SGLTis in these diseases are relatively rare, with shortcomings such as small sample sizes and short intervention periods. Therefore, further large-scale, long-term, well-designed studies are needed to clarify the findings.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"642-657"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fixed dose daptomycin: An opportunity for pharmacokinetic/pharmacodynamic optimization in Staphylococcus aureus infections.","authors":"Katie B Olney, Manjunath P Pai, Jenni K Thomas, Donna R Burgess, William J Olney, Rebecca A Bruning, Kamron A Griffith, Danielle V Casaus, Elizabeth Crance, James Z Porterfield, David S Burgess","doi":"10.1002/phar.4602","DOIUrl":"10.1002/phar.4602","url":null,"abstract":"<p><strong>Background: </strong>Daptomycin is a high-use intravenous antimicrobial agent affording the convenience of once-daily dosing. Prior studies suggest an opportunity to use a more operationally convenient fixed rather than weight-based dosing but this approach has not been studied prospectively.</p><p><strong>Methods: </strong>This study quantified the probability of toxicity and efficacy end points by prospectively testing a fixed dose regimen of daptomycin (750 mg) in obese and non-obese adults. At least, three daptomycin concentrations were measured at steady-state for each patient. A population pharmacokinetic model was constructed to evaluate concentration-time profiles and investigate covariates of daptomycin clearance. Simulations were performed to evaluate the probability of achieving efficacy (24-h area under the curve (AUC_0-24) ≥ 666 mg∙h/L) and toxicity (minimum concentration (C _min) ≥24.3 mg/L) targets for fixed (500-1000 mg) and weight-based (6-12 mg/kg) daptomycin doses.</p><p><strong>Results: </strong>Thirty-one patients (16 females, 15 males) with median (interquartile range (IQR)) age of 50 (30, 62) years and weight of 74 (54, 156) kg were included in the final analysis. Fixed dose daptomycin (750 mg) resulted in similar exposure across weights with a median (IQR) AUC_0-24 of 819 (499, 1501) mg∙h/L and 749 (606, 1265) mg∙h/L in patients weighing ≤74 kg and >74 kg, respectively. Overall, male sex and increased kidney function necessitate higher fixed and weight-based doses to achieve efficacy. Creatine phosphokinase elevation was observed in two patients (6.5%) and predicted to be lower with fixed versus weight-based regimens.</p><p><strong>Conclusions: </strong>Fixed daptomycin dosing adjusted for sex and kidney function is expected to improve the efficacy-to-toxicity ratio, transitions of care, and costs compared to weight-based doses. However, no empiric dosing approach is predicted to achieve ≥90% efficacy while minimizing the risk of toxicity, so therapeutic drug monitoring should be considered on a patient-specific basis.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"615-622"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amoxicillin and penicillin G dosing in pediatric community-acquired pneumococcal pneumonia in the era of conjugate pneumococcal vaccines.","authors":"Dustin Huynh, Norint Tung, Quang Dam, Tri Tran, Kristina G Hulten, Christopher J Harrison, Sheldon L Kaplan, Allison Nguyen, Tyler H Do, Amartya Setty, Jennifer Le","doi":"10.1002/phar.2756","DOIUrl":"10.1002/phar.2756","url":null,"abstract":"<p><strong>Background: </strong>Parenteral penicillin G (PENG) and oral amoxicillin (AMOX) are recommended as treatment for pediatric community-acquired pneumonia (CAP). With recent epidemiologic penicillin susceptibility data for Streptococcus pneumoniae, the most common etiology of CAP, the objective of this study was to evaluate optimal dosing regimens of PENG and AMOX based on population pharmacokinetics linked to current susceptibility data.</p><p><strong>Methods: </strong>Using NONMEM v7.3, Monte Carlo simulations (N = 10,000) were conducted for AMOX 15 mg/kg/dose PO every 8 h (standard-dose), AMOX 45 mg/kg/dose PO every 12 h (high-dose), and PENG 62,500 units/kg/day IV every 6 h using six virtual subjects with ages spanning 3 months to 15 years old. The probability of target attainment (PTA) was determined for both serum and epithelial lining fluid (ELF) to achieve free drug concentrations above the minimum inhibitory concentration (%fT>MIC) across the population of pneumococci for 30%-50% of the dosing interval.</p><p><strong>Results: </strong>In 2018, all 21 (100%) pneumococcal isolates were susceptible to both PENG and AMOX based on Clinical and Laboratory Standards Institute (CLSI; MIC at 2 mg/L) breakpoints, and 15 of 21 (71%) were susceptible based on EUCAST (MIC at 0.5 mg/L) breakpoints. As compared to CLSI, EUCAST breakpoints consistently achieved higher PTA for all antibiotic regimens. At 50% fT>MIC in the serum at the susceptible MICs, standard-dose AMOX achieved >4% PTA (CLSI) and >86% PTA (EUCAST); high-dose AMOX achieved >73% PTA (CLSI) and >99% PTA (EUCAST); and PENG achieved 0% PTA (using CLSI) and 100% PTA (using EUCAST). Standard-dose AMOX, high-dose AMOX, and PENG achieved >71%, >93%, and 100% PTA, respectively, in the serum at 30%-50% fT>MIC when each patient was stochastically linked to an MIC based on the frequency distribution of national susceptibility data. The PTA was consistently lower in ELF as compared with serum for all regimens.</p><p><strong>Conclusion: </strong>Based on the recent rates of resistance, antibiotic doses evaluated provide appropriate exposure for pediatric CAP based on the serum and ELF data associated with predicted clinical and microbiologic success for pneumococcus. High-dose AMOX may still be required to treat pediatric CAP, especially if using CLSI breakpoints. Ongoing surveillance for resistance is essential.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"606-614"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10635908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}