J Clin Pharm Ther [JOURNAL]
Sun
200 papers
Evaluation of the Tocilizumab therapy in human cancers: Latest evidence and clinical potential.
Ghasemi K, Ghasemi K
J Clin Pharm Ther · 2022 Dec · PMID 36271617 · Publisher ↗
Tocilizumab (Actemra®), as the first human interleukin-6 receptor (IL-6R) antagonist, has been used in treating moderate to severe active rheumatoid arthritis (RA) patients who were undertreatment with one or more diseas...
Tocilizumab (Actemra®), as the first human interleukin-6 receptor (IL-6R) antagonist, has been used in treating moderate to severe active rheumatoid arthritis (RA) patients who were undertreatment with one or more disease-modifying anti-rheumatic drugs (DMARDs) and did not improve significantly. Tocilizumab also has been administrated and confirmed in several inflammatory-based diseases. Recently, tocilizumab has been prescribed to treat patients with advanced coronavirus disease (COVID-19) and is used as one of the effective drugs in reducing the increased inflammation in these patients. On the other hand, cancer treatment has been considered by researchers one of the most important challenges to human health. Regarding inflammatory-associated malignancies, it has been shown that inflammatory mediators such as interleukin-1 beta (IL-1β), IL-6, and tumour necrosis factor-alpha (TNF-α) may play a role in tumorigenesis, thus targeting these cytokines as evidence suggested can be useful in the treatment of these types of cancers. This review summarized the role of the IL-6/IL-6R axis in inflammation-based cancers and discussed the effectiveness and challenges of treating cancer with tocilizumab.
Risk factors for high-dose methotrexate associated toxicities in patients with primary central nervous system lymphoma.
Sun K, Tao H, Ding T … +4 more , Li Z, Qiu X, Zhong M, Wu Z
J Clin Pharm Ther · 2022 Dec · PMID 36259502 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Methotrexate (MTX) is an antimetabolic antitumor drug with high individual differences and may lead to severe toxicities in a considerable number of patients. This study aimed to explore the...
WHAT IS KNOWN AND OBJECTIVE: Methotrexate (MTX) is an antimetabolic antitumor drug with high individual differences and may lead to severe toxicities in a considerable number of patients. This study aimed to explore the factors influencing major adverse events in patients with primary central nervous system lymphoma treated with high-dose MTX (HD-MTX), which could be useful in clinical practice. METHODS: Fifty-four patients who received 175 courses of MTX at 3-8 g/m between January 2015 and December 2016 were enrolled in this study. We assessed the association between clinical characteristics, MTX pharmacokinetics, MTX delayed elimination, and adverse events, including hepatotoxicity, acute kidney injury (AKI), and myelosuppression. RESULTS AND DISCUSSION: A total of 124 adverse events occurred after MTX infusion. Using independent sample t-tests, we found that patients with myelosuppression had higher MTX area under the concentration-time curve up to 48 h after infusion (AUC ) (p = 0.001) and MTX peak concentration (C ) (p = 0.002). MTX concentrations at 48 and 72 h were higher in patients with AKI than in those without (p = 0.034 and p = 0.041, respectively). Using chi-square tests, we found that AKI was correlated with MTX elimination at either 48 h or 72 h (22.1% vs. 8.2%, p = 0.010). By multivariate logistic regression model, our results showed that baseline level of ALT and WBC had a significant effect on hepatotoxicity (OR = 1.079, 95% CI 1.044-1.116, p = 6.9 × 10 ; OR = 0.808, 95% CI 0.711-0.917, p = 0.001, respectively). Patient's age, eGFR before MTX infusion, and co-administration of vindesine had a significant effect on AKI (OR = 0.960, 95% CI 0.935-0.986, p = 0.003; OR = 1.009, 95% CI 1.001-1.017, p = 0.034; OR = 5.463, 95% CI 1.793-16.646, p = 0.003, respectively). LDH and Co-administration of vindesine had a significant effect on myelosuppression (OR = 0.985, 95% CI 0.972-0.998, p = 0.025; OR = 3.070, 95% CI 1.032-9.133, p = 0.044). WHAT IS NEW AND CONCLUSION: Our study demonstrated that co-administration of VDS, eGFR before MTX infusion, and the baseline index of laboratory examinations including ALT, WBC, LDH may be useful biomarkers for predicting MTX-induced toxicities.
Prevalence and risk factors associated with readmission with acute kidney injury in patients receiving vancomycin outpatient parenteral antimicrobial therapy.
Hamad Y, Nickel KB, Burnett YJ … +3 more , Hamad T, George IA, Olsen MA
J Clin Pharm Ther · 2022 Dec · PMID 36257600 · Full text
INTRODUCTION: Vancomycin is commonly used during outpatient parenteral antimicrobial therapy (OPAT). Therapeutic drug monitoring (TDM) of vancomycin is recommended to ensure effective and safe therapy, as use has been as...
INTRODUCTION: Vancomycin is commonly used during outpatient parenteral antimicrobial therapy (OPAT). Therapeutic drug monitoring (TDM) of vancomycin is recommended to ensure effective and safe therapy, as use has been associated with acute kidney injury (AKI). METHODS: The MarketScan® Commercial Database was queried from 2010 to 2016 to identify patients aged 18-64 years discharged from an inpatient hospitalization on vancomycin OPAT. The primary endpoint was hospital readmission with AKI within 6 weeks of index hospital discharge. TDM was defined as at least one vancomycin level obtained during outpatient therapy. Bivariate analysis was used to examine associations with outcomes; significant factors were incorporated into a multivariable logistic regression model. RESULTS: A total of 14,196 patients were included in the study; median age was 54 years and 53.8% were male. Readmission with AKI occurred in 385 (2.7%) and was independently associated with chronic kidney disease (aOR 2.63 [95%CI 1.96-3.52]), congestive heart failure (1.81 [1.34-2.44]), chronic liver disease (1.74 [1.17-2.59]), hypertension (1.73 [1.39-2.17]), septicemia (1.61 [1.30-2.00]), and concomitant OPAT with IV penicillins (1.73 [1.21-2.49]) while skin and soft tissue infection (0.67 [0.54-0.83]) and surgical site infection (0.74 [0.59-0.93]) were associated with lower risk of readmission with AKI. TDM was not associated with lower risk of readmission with AKI. CONCLUSION: Chronic kidney disease, congestive heart failure, hypertension, chronic liver disease, septicemia, and concomitant OPAT with IV penicillins were significantly associated with higher risk of readmission with AKI during vancomycin OPAT.
Management of drug-induced neutropenia, thrombocytopenia, and anaemia after solid organ transplantation: A comprehensive review.
Baradaran H, Hashem Zadeh A, Dashti-Khavidaki S … +1 more , Laki B
J Clin Pharm Ther · 2022 Dec · PMID 36250775 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Advances in the development of more effective immunosuppressive drugs have increased graft survival and drug induced adverse effects. Haematological complications including neutropenia, throm...
WHAT IS KNOWN AND OBJECTIVE: Advances in the development of more effective immunosuppressive drugs have increased graft survival and drug induced adverse effects. Haematological complications including neutropenia, thrombocytopenia, and anaemia are common side effects that affect the grafts' and patients' outcomes. Several studies have stated the important role of various medications in haematological complications after transplantation. They have reported the incidence and different mechanisms of drug induced cytopenia, as well as an overview of possible treatment modalities. However, there is no comprehensive protocol for the management of these complications following transplantation. This narrative review was performed to develop a comprehensive practical approach for management of drug induced haematological complications following solid organ transplantation. METHOD: PubMed, Embase, Cochrane library, Web of Science, and Google scholar databases were searched without time limitations until March, 2021. In addition, some valid drug information data bases (Uptodate and Micromedex) were searched for detailed information until October, 2021. RESULTS AND DISCUSSION: Several immunosuppressive and antimicrobial medications may induce neutropenia, thrombocytopenia or anaemia following transplantation. Most of these agents cause dose-related cytopenia, which resolves with dose reduction or drug withdrawal. However, any change in medications may result in negative consequences such as severe infections, bleeding, cardiovascular complications, acute allograft rejection, and graft or patient loss. Thus, cautious evaluation of the patient's condition and the pharmacological properties of the culprit medication are required. WHAT IS NEW AND CONCLUSION: Three algorithms are presented to guide healthcare providers in the stepwise management of drug-induced neutropenia, thrombocytopenia, and anaemia after solid organ transplantation.
Heparin-induced persistent hyperthermia with recurrent hyponatremia in hip fracture: Case report and review of literature.
Huang Z, Wu X, Zhang S … +6 more , Liu Z, Guo Q, Ouyang Y, Wang H, Lin W, Song Y
J Clin Pharm Ther · 2022 Nov · PMID 36222222 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Heparin is a commonly used anticoagulant in clinic. Persistent hyperthermia with recurrent hyponatremia caused by heparin is an extremely rare drug fever, which is difficult to judge in the e...
WHAT IS KNOWN AND OBJECTIVE: Heparin is a commonly used anticoagulant in clinic. Persistent hyperthermia with recurrent hyponatremia caused by heparin is an extremely rare drug fever, which is difficult to judge in the early stage and is often misdiagnosed. CASE SUMMARY: A 74-year-old elderly woman was admitted to our hospital due to left hip pain with limited mobility for 9 h. She was diagnosed with a femoral neck fracture, and continuous heparin anticoagulation was initiated. On the night of surgery, the patient developed high fever with a drop in the serum sodium concentration. Based on the patient's symptoms, signs, and results of the laboratory tests, postoperative absorptive heat and infectious fever were ruled out. After heparin discontinuation, her temperature and serum sodium concentration returned to the baseline levels. WHAT IS NEW AND CONCLUSION: Heparin can cause persistent or recurrent hyponatremia and should be considered in the identification of the aetiology this condition.
The Inflation Reduction Act: A boon for the generic and biosimilar industry.
Niazi SK
J Clin Pharm Ther · 2022 Nov · PMID 36207987 · Full text
WHAT IS KNOWN AND OBJECTIVE: After more than a year of negotiation, a $740 billion climate and health care bill known as The Inflation Reduction Act (IRA) became law on 16 August 2022. In addition to its impact on the en...
WHAT IS KNOWN AND OBJECTIVE: After more than a year of negotiation, a $740 billion climate and health care bill known as The Inflation Reduction Act (IRA) became law on 16 August 2022. In addition to its impact on the environment, job creation and reducing inflation, a key focus is to reduce the burden of Medicare by over $100B per year and other benefits to 65 million Medicare patients. A fixed number of top expenditures drugs that have stayed as single-source chemical products for 8 years and the biologicals for 12 years; 2 years more are allowed if the approval of a generic or biosimilar is imminent. Once a second source appears, as a generic or biosimilar, the price reduction is removed. The number of products negotiated for price reduction goes from 10 to 20 over the years and stays fixed at this number. Reaching any significant number out of the 14,000 reimbursed will take forever if biosimilars and generics keep entering. The IRA does not apply to private markets. METHODS: The IRA legislation and related statutes were analysed in consultation with legal teams; the spending data were derived from the CMS portals and the FDA databases to rank the most likely products selected when the selection process is initiated. RESULTS AND DISCUSSION: The savings to Medicare will come from reducing the price of only a few products, primarily with $1B and upward spending; when Plan B product scheduling enters, these will be at the bottom of the selection because of their lower expenditure. The total number of products subject to price reduction may be negligible if generics and biosimilars are introduced after the exclusivity period of the listed drug or reference product. The private market with an 80% share may benefit due to price spillover but mainly by the expedited entry of generics and biosimilars. WHAT IS NEW AND THE CONCLUSION: The entry of generics and biosimilars will now be encouraged by brand-name product companies, reducing the intellectual property hurdles like the "patent dance" for biosimilars. The IRA includes restrictions to prevent the brand name companies from exploiting the entry of generics and biosimilars to assure their independence.
Double filtration plasmapheresis for hypertriglyceridemic acute pancreatitis caused by fat overload syndrome.
Wu C, Xu T, Yi Z … +4 more , Song N, Zhou Y, Liang F, Zhang B
J Clin Pharm Ther · 2022 Nov · PMID 36205441 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Severe hypertriglyceridemia (HTG) can cause acute pancreatitis (AP). CASE SUMMARY: We report a patient with acute lymphoblastic leukaemia who received long-term intravenous parenteral nutriti...
WHAT IS KNOWN AND OBJECTIVE: Severe hypertriglyceridemia (HTG) can cause acute pancreatitis (AP). CASE SUMMARY: We report a patient with acute lymphoblastic leukaemia who received long-term intravenous parenteral nutrition solution without monitoring of the serum triglyceride (TG) level, which resulted in fat overload syndrome and HTG-AP. WHAT IS NEW AND CONCLUSION: Double filtration plasmapheresis was performed to eliminate the TGs and treat the AP.
Acinetobacter baumannii: Pathogenesis, virulence factors, novel therapeutic options and mechanisms of resistance to antimicrobial agents with emphasis on tigecycline.
Dehbanipour R, Ghalavand Z
J Clin Pharm Ther · 2022 Nov · PMID 36200470 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Acinetobacter baumannii is one of the most important nosocomial pathogens with the ability to cause infections such as meningitis, pneumonia, urinary tract, septicaemia and wound infections....
WHAT IS KNOWN AND OBJECTIVE: Acinetobacter baumannii is one of the most important nosocomial pathogens with the ability to cause infections such as meningitis, pneumonia, urinary tract, septicaemia and wound infections. A wide range of virulence factors are responsible for pathogenesis and high mortality of A. baumannii including outer membrane proteins, lipopolysaccharide, capsule, phospholipase, nutrient- acquisition systems, efflux pumps, protein secretion systems, quarom sensing and biofilm production. These virulence factors contribute in pathogen survival in stressful conditions and antimicrobial resistance. COMMENT: According to the World Health Organization (WHO), A. baumannii is one of the most resistant pathogens of ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, A. baumannii, Pseudomonas aeruginosa and Enterobacter spp.). In recent years, resistance to a wide range of antibiotics in A. baumannii has significantly increased and the high emergence of extensively drug resistant (XDR) isolates is challenging. Among therapeutic antibiotics, resistance to tigecycline as a last resort antibiotic has become a global concern. Several mechanisms are involved in tigecycline resistance, the most important of which is RND (Resistance-Nodulation-Division) family efflux pumps overexpression. The development of new therapeutic strategies to confront A. baumannii infections has been very promising in recent years. WHAT IS NEW AND CONCLUSION: In the present review we highlight microbiological and virulence traits in A. baumannii and peruse the tigecycline resistance mechanisms and novel therapeutic options. Among the novel therapeutic strategies we focus on combination therapy, drug repurposing, novel antibiotics, bacteriophage therapy, antimicrobial peptides (AMPs), human monoclonal antibodies (Hu-mAbs), nanoparticles and gene editing.
Safety of trastuzumab deruxtecan: A meta-analysis and pharmacovigilance study.
Guo Z, Ding Y, Wang M … +3 more , Liu J, Zhai Q, Du Q
J Clin Pharm Ther · 2022 Nov · PMID 36200429 · Full text
WHAT IS KNOWN AND OBJECTIVE: This study aimed to explore the safety profile of trastuzumab deruxtecan (T-DXd, formerly DS-8201a) using multi-source medical data. METHODS: We explored trastuzumab deruxtecan related advers...
WHAT IS KNOWN AND OBJECTIVE: This study aimed to explore the safety profile of trastuzumab deruxtecan (T-DXd, formerly DS-8201a) using multi-source medical data. METHODS: We explored trastuzumab deruxtecan related adverse events (AEs) in clinical trials available in ClinicalTrials.gov and electronic databases (MEDLINE, EMBASE and PubMed) up to July 16, 2022. Meta-analysis was performed by using incidence rate with 95%CIs. In the pharmacovigilance study of FDA Adverse Event Reporting System (FAERS), the reporting odds ratio (ROR) and the medicines and healthcare products regulatory agency (MHRA) methods were used to analyse the real-world AEs (up to June 28, 2022). RESULTS AND DISCUSSION: A 8 clinical trials enrolled 1457 patients were included. The most common AEs of any grade were gastrointestinal disorders and blood and lymphatic system disorders. The most common AE of grade 3 or higher was neutropenia (21.4%, 95%CI: 14.7%-28.1%, I = 91%). The incidence of interstitial lung disease (ILD) and decreased left ventricular ejection fraction were 10.9% (95%CI: 7.2%-14.5%, I = 82%) and 1.2% (95%CI: 0.7%-2.2%, I = 98%), respectively. A total of 1244 AE reports were identified in the pharmacovigilance study. Gastrointestinal toxicity (ROR = 21.65), myelosuppression (ROR = 36.88), interstitial lung disease (ROR = 50.30), pneumonitis (ROR = 36.59), decreased ejection fraction (ROR = 16.08), and taste disorder (ROR = 14.06) mentioned in the instructions showed strong signals. Also, ascites (ROR = 14.90), lung opacity (ROR = 78.80), pulmonary fibrosis (ROR = 5.59), and increased KL-6 (ROR = 1761.97), which were not mentioned in the instructions, showed strong signals. WHAT IS NEW AND CONCLUSION: Trastuzumab deruxtecan was well tolerated, and more attention should be paid on ILD as well as decreased ejection fraction.
The effect of the clinical pharmacist in minimizing drug-related problems and related costs in the intensive care unit in Turkey: A non-randomized controlled study.
Ayhan YE, Karakurt S, Sancar M
J Clin Pharm Ther · 2022 Nov · PMID 36196779 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Drug-related problems (DRPs) are common in hospitalized patients in intensive care unit (ICU). The aim of the study is to reduce DRPs and associated costs with clinical pharmacist's (CP) reco...
WHAT IS KNOWN AND OBJECTIVE: Drug-related problems (DRPs) are common in hospitalized patients in intensive care unit (ICU). The aim of the study is to reduce DRPs and associated costs with clinical pharmacist's (CP) recommendations. METHODS: The study is a prospective, non-randomized controlled study conducted in the ICU for a total of 6 months (1 January 2021-30 June 2021) in 2-month control, 2-month study, and 2-month control periods. Patients who were hospitalized for more than 24 h and used more than one medication were included in the study. The PCNE V9.1 Classification system was used in the classification of DRPs. During the intervention period, CP recommendations for DRPs were proposed to the healthcare team. RESULTS AND DISCUSSION: A total of 146 patients were included in the study. A total of 1061 DRPs from all periods were detected. The most common causes of DRPs were potential drug-drug interactions (31.76%), high dose (12.44%), and dose timing instruction errors (9.24%). For 347 DRPs identified during the study period, 259 interventions (74.63%) were recommended, and 238 (91.89%) were accepted by physicians. Interventions were mostly made as interrupting/discontinuing the drug (28.02%), changing the dose (25.27%), changing the instructions for use (20.32%), and starting a new drug (15.93%). Cost savings were achieved with CP recommendations applied. WHAT IS NEW AND CONCLUSION: The CP's recommendations were highly accepted by the healthcare team. With the CP's participation in routine patient rounds in the healthcare team of the ICU, drug-related costs would also decrease.
Influence of genetic variants on remifentanil sensitivity in Chinese women.
Niu H, Zhao S, Wang Y … +5 more , Huang S, Zhou R, Wu Z, Song W, Chen X
J Clin Pharm Ther · 2022 Nov · PMID 36196520 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Significant individual differences have been observed in pain sensitivity and analgesic effect of opioids. Previous studies have shown that genetic factors contributed to analgesics requireme...
WHAT IS KNOWN AND OBJECTIVE: Significant individual differences have been observed in pain sensitivity and analgesic effect of opioids. Previous studies have shown that genetic factors contributed to analgesics requirement obviously. Therefore, we investigated the role of genetic polymorphisms in the sensitivity to the analgesic effect of remifentanil in this study. METHODS: One hundred thirty-seven patients undergoing gynaecological surgery were observed. Before procedures, we measured the basal pain threshold of each patient, including the pressure pain threshold and pressure pain tolerance threshold. Subsequently, patients received a continuous remifentanil infusion for 15 min at a constant rate of 0.2 μg/(kg min). The pain thresholds were measured again after the remifentanil infusion. Moreover, respiratory depression was estimated using oxygen saturation during infusion. DNA was extracted from peripheral venous blood and genotyped using SNaPshot technology. RESULTS AND DISCUSSION: Polymorphisms were found in genes associated with the individual variation in analgesia. Participants carrying OPRM1 rs9397685 AA, ADRB1 rs1801253 CC, and GCH1 rs8007267 CC polymorphisms showed higher sensitivity to analgesic effect induced by remifentanil, and the participants carrying the OPRD1 rs2234918 TT showed lower sensitivity to remifentanil-related respiratory depression. Moreover, individual susceptibility to remifentanil increases with age. WHAT IS NEW AND CONCLUSION: Gene variation in OPRM1 rs9397685 AA, ADRB1 rs1801253 CC, GCH1 rs8007267 CC, and OPRD1 rs2234918 TT were related to the conspicuous interindividual differences in the analgesia and respiratory depression of remifentanil, mainly by affecting the target protein receptors and relative metabolic enzymes.
Clinical and laboratory responses to tigecycline in children.
Aslan K, Kiliç Ö, Kiral E … +3 more , Bozan G, Bör Ö, Dinleyici EÇ
J Clin Pharm Ther · 2022 Oct · PMID 36196509 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: The frequency of multidrug-resistant bacterial infections is increasing worldwide. Tigecycline may be an important option for children with life-threatening nosocomial infections due to multi...
WHAT IS KNOWN AND OBJECTIVE: The frequency of multidrug-resistant bacterial infections is increasing worldwide. Tigecycline may be an important option for children with life-threatening nosocomial infections due to multidrug-resistant bacteria. However, there are few published data on the use of tigecycline in paediatric patients. By examining the results of tigecycline use in children, we aimed to draw attention to the fact that tigecycline may be an alternative in the treatment of resistant infections in children. METHODS: Paediatric patients treated with tigecycline from 1 January 2010 to 31 October 2018 at Eskişehir Osmangazi University Medical Faculty, which is a tertiary hospital, were analysed retrospectively to assess the efficacy and safety of tigecycline treatment in children. Patients using tigecycline were identified using the pharmacy database. Clinical and laboratory data were obtained from the files. RESULTS AND DISCUSSION: This study included 91 children aged 7 months to 17.5 years; 52 were female (57.1%). At least one predisposing factor was present in 98.9% of the patients. Fifty-one bacteria were isolated from 44 patients. The tigecycline resistance rate was 3.9%. Only 2 of 91 patients experienced one or more side effects of tigecycline. Tigecycline can be used as salvage therapy in resistant infections where options are limited, although definitive conclusions about the efficacy and safety of tigecycline in children cannot be reached. WHAT IS NEW AND CONCLUSION: Tigecycline may be a safe and important option in paediatric nosocomial infections due to resistant bacteria. Resistant bacterial infections have become more common in recent years, its treatment becomes a difficult problem. Tigecycline has a broad-spectrum antibacterial activity including resistant pathogens.
Comparing analgesic efficacy of the regional block with different-volume ropivacaine after a modified radical mastectomy.
Yuan YJ, Xue FS, Tian T
J Clin Pharm Ther · 2022 Nov · PMID 36194014 · Publisher ↗
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The effect of chemotherapy on survival in oldest old patients with nonmetastatic triple negative breast cancer: A populationbased observational study.
Wu B, Sun C, Sun X … +1 more , Li X
J Clin Pharm Ther · 2022 Nov · PMID 36175133 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Chemotherapy is the primary pharmacotherapy of triple-negative breast cancer (TNBC). But the benefit of adjuvant chemotherapy in the oldest old TNBC patients remains controversial. Hence, we...
WHAT IS KNOWN AND OBJECTIVE: Chemotherapy is the primary pharmacotherapy of triple-negative breast cancer (TNBC). But the benefit of adjuvant chemotherapy in the oldest old TNBC patients remains controversial. Hence, we designed this population based observational study in order to assess the survival benefit of adjuvant chemotherapy in oldest old TNBC patients with early-stage disease. METHODS: TNBC patients aged 80 years and older that with stage I to III invasive disease were identified in the surveillance, epidemiology, and end results cancer database from 2010 to 2016. RESULTS AND DISCUSSION: Of 1611 patients enrolled, 1356 (84.17%) did not receive chemotherapy. Age, race, histology, grade, T stage, N stage, and radiation were found to be strong predictors of chemotherapy recipient by multivariate logistic regression analysis. Chemotherapy significantly prolonged overall survival (OS) (HR, 0.62, 95% CI: 0.49-0.79, p < 0.001), but did not significantly reduce breast cancer specific death (BCSD) (HR, 0.92, 95% CI: 0.63-1.35, p = 0.675). These results were further confirmed by propensity score matching analysis. Chemotherapy was associated with better OS in the subgroup of patients aged 80-84 years old (HR, 0.54, 95% CI: 0.40-0.74, p < 0.001), T2-4 stage disease (HR, 0.58, 95% CI: 0.44-0.76, p < 0.001), or grade 3-4 disease (HR, 0.54, 95% CI: 0.41-0.71, p < 0.001). However, chemotherapy did not reduce the cumulative incidence of BCSD in any subgroup. WHAT IS NEW AND CONCLUSION: Chemotherapy should be considered for TNBC patients aged 80-84 years old, T2-4 disease, or grade 3-4 disease.
Rapid infusion of infliximab biosimilars and the incidence and severity of infusion-related reactions in patients with inflammatory bowel disease.
Rusch C, Wood M, Kennedy AG … +2 more , Tompkins BJ, Frasca JD
J Clin Pharm Ther · 2022 Nov · PMID 36134561 · Full text
WHAT IS KNOWN AND OBJECTIVE: Infliximab is an anti-tumour necrosis factor agent used in the treatment of inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis. While the use of inflixima...
WHAT IS KNOWN AND OBJECTIVE: Infliximab is an anti-tumour necrosis factor agent used in the treatment of inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis. While the use of infliximab is well established in the treatment of IBD, there are now four recently FDA-approved infliximab biosimilars that are increasingly used due to their cost-benefit for patients, institutions and payors. In addition, shortening the length of infliximab infusions from 120 min (standard infusion) to 60 min or less (rapid infusion) has been shown to safely provide further cost-benefit while also improving patient convenience. The safety of rapid infusions has been well-established for the infliximab reference product, however, there are limited data available regarding the safety of rapid infusions for infliximab biosimilars. The purpose of this study was to compare the incidence and severity of infusion reactions among patients with IBD receiving rapid infusion of infliximab reference product compared with infliximab biosimilar. METHODS: This was a retrospective analysis of electronic health record data of patients with a diagnosis of IBD receiving an infliximab reference product or infliximab biosimilar infusion between December 2020 and December 2021. Patient-level variables included demographics, immunomodulator use, IBD-related hospitalization and infliximab trough concentration and antibody levels. Infusion-related variables of interest included total number of infusions, drug, dose, dosing interval, infusion time and use of pre-medications. Infusion-related reactions were defined as safety concerns documented by the administering nurse (anaphylaxis, shortness of breath, hypotension, swelling, rash, pruritus, hives, flushing, chest pain, muscle pain, joint pain, fevers, chills, headache or hypertension) or administration of emergency medications. Fisher's exact test was used to compare reaction rates. RESULTS AND DISCUSSION: A total of 188 patients met inclusion criteria for analysis, and a total of 1124 infusions were administered during the study period. There were no statistically significant differences among any of the pre-specified outcomes. There were no differences in the incidence of infusion reactions among rapid infusion (60 min) infliximab and infliximab biosimilars (p = 0.863). Additionally, there were no differences in the incidence of infusion reactions among standard infusion (120 min) infliximab and infliximab biosimilars (p = 0.993). Finally, there were no differences among the rate of infusion reactions between rapid infusion of infliximab biosimilars and standard infusion of infliximab biosimilars (p = 0.536). Eight patients experienced safety issues, with three patients requiring emergency medications (1.6% of 188 patients). WHAT IS NEW AND CONCLUSIONS: Rapid infusions of infliximab biosimilars were not associated with an increase in the incidence of infusion reactions compared with: rapid infusion of infliximab reference product, standard infusion of infliximab biosimilars, or standard infusion of infliximab reference product. This should reassure clinicians that rapid infusions of infliximab biosimilars are safe in clinical practice.
Predicting the effect of sirolimus on disease activity in patients with systemic lupus erythematosus using machine learning.
Wang DD, Li YF, Zhang C … +2 more , He SM, Chen X
J Clin Pharm Ther · 2022 Nov · PMID 36131617 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVES: The present study aimed to predict the effect of sirolimus on disease activity in patients with systemic lupus erythematosus (SLE) using machine learning and to recommend appropriate sirolim...
WHAT IS KNOWN AND OBJECTIVES: The present study aimed to predict the effect of sirolimus on disease activity in patients with systemic lupus erythematosus (SLE) using machine learning and to recommend appropriate sirolimus dosage regimen for patients with SLE. METHODS: The E model was selected for machine learning, where the evaluation indicator was the change rate of systemic lupus erythematosus disease activity index from baseline value. RESULTS: A total 103 patients with SLE were included for modelling, where the E , ET were -53.9%, 1.53 months in the final model respectively, and the evaluation of the final model was good. Further simulation found that the follow-up time to achieve 25%, 50%, 75% and 80% (plateau) E of sirolimus effecting on disease activity in patients with SLE were 0.51, 1.53, 4.59 and 6.12 months, respectively. In addition, the sirolimus dosage was flexible and adjusted according to drug concentration, where the intersection of sirolimus concentration range included in this study was about 8-10 ng/ml. WHAT IS NEW AND CONCLUSIONS: This study was the first time to predict the effect of sirolimus on disease activity in patients with SLE and in order to achieve better therapeutic effect maintaining a concentration of 8-10 ng/ml sirolimus for at least 6.12 months was necessary.
Men who have sex with men is the high-risk drug resistance population: A meta-analysis of HIV-1 drug resistance profiles and trends in China.
Yuan D, Liu Y, Zhou Y … +5 more , Shi L, Chen J, Lu J, Fu G, Wang B
J Clin Pharm Ther · 2022 Nov · PMID 36117263 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Except for the transmitted drug resistance (TDR)'s standard sampling and monitoring protocol, China's HIV-1 pretreatment drug resistance (PDR) and acquired drug resistance (ADR) results vary...
WHAT IS KNOWN AND OBJECTIVE: Except for the transmitted drug resistance (TDR)'s standard sampling and monitoring protocol, China's HIV-1 pretreatment drug resistance (PDR) and acquired drug resistance (ADR) results vary widely due to the studies' diverse background. This meta-analysis was conducted to comprehensively understand the drug resistance profiles of Chinese HIV/AIDS patients and compare the drug resistance differences among groups to provide a reference for the further improvement of treatment protocols. METHODS: Data sources for this study were WANFANG, VIP, CNKI, SinoMed, PubMed and Web of Science databases from January 1, 2010 to January 13, 2022. Data extracted from the literature were analyzed by R and Stata to evaluate the profile and changing trend of drug resistance in Chinese HIV/AIDS patients. RESULTS AND DISCUSSION: One hundred twenty-one literature were included. The combined PDR and ADR in the Chinese HIV/AIDS patients was 5.56% (95% CI: 4.77%-6.41%) and 51.33% (95% CI: 47.57%-55.38%), respectively. The time trend analysis shows the upward trend of PDR. There were significate differences in ADR among different sample sources, the ADR in the central region were higher than those in all other regions. The PDR in men who have sex with men (MSM) was lower the whole population, while the MSM's ADR was much higher than whole population. WHAT IS NEW AND CONCLUSION: PDR in China showed an upward trend and exceeded the 5% warning line but is still at a low level worldwide. ADR is stable and below the middle level globally; the comprehensively promoted free ART in China still has lasting effects. MSM is the high-risk drug resistance population, targeted treatment strategies should be used.
14-day famciclovir treatment significantly reduces the incidence of postherpetic neuralgia in elderly patients with herpes zoster.
Kong J, Wang H, Liu Y … +3 more , Xiao M, Wang J, Liu Q
J Clin Pharm Ther · 2022 Nov · PMID 36116793 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Pain is the main symptom of herpes zoster (HZ), whilst postherpetic neuralgia (PHN) is a long-term unbearable pain, which seriously affects the quality of life of patients and is also the mos...
WHAT IS KNOWN AND OBJECTIVE: Pain is the main symptom of herpes zoster (HZ), whilst postherpetic neuralgia (PHN) is a long-term unbearable pain, which seriously affects the quality of life of patients and is also the most intractable problem for clinicians. Early antiviral treatment is considered as a key measure to reduce acute pain and PHN. Nevertheless, most patients still have long-term pain after 7 days of antiviral treatment, and some patients will develop PHN. This study aimed to investigate whether prolonged duration of antiviral therapy could reduce HZ acute pain and the occurrence of PHN. METHODS: The outpatient data of HZ patients over 50 years old who visited the Dermatology Department from January 2016 to May 2018 were retrospectively analysed. According to the different courses of treatment of famciclovir (FCV), the patients were divided into 7-day FCV group and 14-day FCV group. The numerical rating scale (NRS) score at the first visit and on the 7th, 14th and 21st days after the start of treatment, the adverse drug reactions and the incidence of PHN were compared between the two groups. RESULTS: A total of 219 patients were involved in the analysis. For acute pain control, the 14-day FCV group was better than the 7-day FCV group. For patients with mild initial pain, there was no significant difference in NRS between the two treatments. For patients with moderate-to-severe initial pain, the NRS in the 14-day FCV group was significantly lower than that of the 7-day FCV group on the 14th and 21st days after starting treatment. PHN occurred in patients with moderate-to-severe initial pain, and the incidence was significantly lower in the 14-day FCV group than in the 7-day FCV group. There was no significant difference in the number of adverse reactions between the two groups. WHAT IS NEW AND CONCLUSION: Compared with the traditional 7-day antiviral therapy, the 14-day course of FCV can reduce the acute pain and the incidence of PHN in elderly patients with HZ, especially in patients with moderate to severe initial pain. Prolonging the course of medication did not increase the side effects.
Hyperkalaemia and potassium binders: Retrospective observational analysis looking at the efficacy and cost effectiveness of calcium polystyrene sulfonate and sodium zirconium cyclosilicate.
Huda AB, Langford C, Lake J … +1 more , Langford N
J Clin Pharm Ther · 2022 Dec · PMID 36114759 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Hyperkalaemia is a common medical emergency in patients admitted to hospital. There is a limited evidence base supporting some of the commonly applied treatment strategies. Although, NICE has...
WHAT IS KNOWN AND OBJECTIVE: Hyperkalaemia is a common medical emergency in patients admitted to hospital. There is a limited evidence base supporting some of the commonly applied treatment strategies. Although, NICE has recommended the use of sodium zirconium cyclosilicate (SZC) (TA599) and patiromer (TA623) in both acute and chronic hyperkalaemia, there is a limited evidence base for their use in acute hyperkalaemia in the hospital setting, particularly when compared to the present standard of care calcium polystyrene sulfonate (CPS). METHODS: A retrospective review of the electronic patient record system across our hospital over a 6-month period identified 138 patients who received either SZC (65 patients) or CPS (73 patients) to manage hyperkalaemia, investigating their efficacy and cost effectiveness. Results were analysed using simple descriptive statistics. Based on the results a naïve cost comparison between the two drugs was made. RESULTS AND DISCUSSION: CPS and SZC both effectively reduced plasm potassium concentrations in patients with hyperkalaemia (6.07 and 6.03 mmol/L respectively) by 1.17 mmol/L and 1.24 mmol/L taking a similar amount of time to work (2.97 days vs. 3 days). The principle causes of hyperkalaemia identified were acute kidney injury, medication, and chronic kidney disease. Cost comparison analysis which took into account raw product price and time needed to dispense medications revealed that CPS has slightly better cost effectiveness compared to SZC albeit at a cost of increased staff input. WHAT IS NEW AND CONCLUSION: Both CPS and SZC were equally effective at lowering acutely raised potassium concentrations. The cost difference between the two products appears to be small. Claims regarding the benefits of newer agents over older established medications need to be properly explored in randomized trials rather than being based on small scale non-comparative studies.
Population pharmacokinetics and dosing optimization of olanzapine in Chinese paediatric patients: Based on the impact of sex and concomitant valproate on clearance.
Xiao T, Hu JQ, Liu SJ … +11 more , Lu HQ, Li XL, Kong W, Huang SQ, Zhu XQ, Zhang M, Lu HY, Ni XJ, Yang HL, Shang DW, Wen YG
J Clin Pharm Ther · 2022 Nov · PMID 36101489 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Olanzapine is an atypical antipsychotic drug used for mental disorders. There are limited studies providing sufficient pharmacokinetic data, thus the variability of concentrations of olanzapi...
WHAT IS KNOWN AND OBJECTIVE: Olanzapine is an atypical antipsychotic drug used for mental disorders. There are limited studies providing sufficient pharmacokinetic data, thus the variability of concentrations of olanzapine used in Chinese paediatric patients aged 10 to 17 years remains to be evaluated. METHODS: Therapeutic drug monitoring data were collected from 151 paediatric patients aged 10 to 17 years who received olanzapine. The model was developed with a NONMEM software program. The final model validation and evaluation were assessed by bootstrap, diagnostic scatter plots, and normalized prediction distribution error (NPDE). Regimens of different dosages were simulated to reach the target concentration levels of 20 ng/ml, by using the final model with typical parameters. RESULTS: The one-compartment model was considered the best fit for the data. Typical estimates of the absorption rate constant (Ka), apparent clearance (CL/F), and apparent distribution volume (V/F) in the final model were 0.142 h , 15.4 L/h, and 322 L, respectively. Sex and concomitant valproate (VPA) were included as significant predictors of olanzapine clearance, which was described by the following equation: CL/F = 15.4 × (1 + 0.546 × SEX) × (1 + 0.264 × VPA). Results of Monte-Carlo simulation suggested that male paediatric patients with concomitant VPA were advised to take no less than 15 mg per day of olanzapine orally, and in female paediatric patients with concomitant VPA, a dosing regimen of 10 mg may be sufficient to achieve the therapeutic range of olanzapine. WHAT IS NEW AND CONCLUSION: Our results identified concomitant valproate and sex as significant covariates in olanzapine population pharmacokinetics. Our model may be a useful tool for recommending dosage adjustments for physicians. The pharmacokinetics of olanzapine in patients aged 10 to 17 years was generally similar to that of adults and the elderly.
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