J Postgrad Med. 2021 Sep 13. doi: 10.4103/jpgm.JPGM_1335_20. Online ahead of print.

ABSTRACT

Drug-induced hemolytic anemia (DIHA) is a rare complication of drug therapy and usually underdiagnosed. Cefoperazone/sulbactam is a compound prepared from the third generation of cephalosporin and β-lactamase inhibitor. There are limited data of DIHA induced from cefoperazone/sulbactam. A 93-year-old female patient, who had an operation on the biliary tract 3 months ago, was admitted to our hospital with an abdominal infection. After cefoperazone/sulbactam was given as anti-infection treatment, the patient developed hemolytic anemia on the third day. Cefoperazone/sulbactam was discontinued and replaced with meropenem. Subsequently the level of red blood cells, hemoglobin, and hematocrit returned to normal. Clinicians should pay attention to monitoring the possible adverse reactions during the use of cefoperazone/sulbactam and should be aware of the occurrence of DIHA, so as to give timely treatment.

PMID:34528516 | DOI:10.4103/jpgm.JPGM_1335_20

Int J Clin Pract. 2021 Sep 14:e14864. doi: 10.1111/ijcp.14864. Online ahead of print.

ABSTRACT

BACKGROUND: In an era of rapid evolution in health care delivery, major changes have occurred within the profession of pharmacist. Because the impact of pharmacist-led interventions in the hospital setting has been well-studied and showed mixed findings on drug-related readmissions, all-cause emergency department visits, and mortality, this systematic review focused on services provided by pharmacists in the community or ambulatory care setting without being limited to a specific intervention or outcome.

OBJECTIVE: To investigate the impact of pharmacist-led interventions, categorized into clinical medication review (CMR), adherence review (AR), and prescription review (PR) on various aspects of patient care (clinical, behavioral, economic, and humanistic outcomes in ambulatory care setting) and understand which particular intervention makes the greatest contribution.

METHODS: A literature search was conducted using MEDLINE, Embase, and the Cochrane Library for publications from 2000 onwards.

FINDINGS AND INTERPRETATION: A total of 31 relevant publications corresponding to 27 controlled trials (CTs) and 4 observational studies were selected. CMR was the most studied pharmacist-led intervention (n=19, 61.29 %), followed by AR (n=6, 19.3%). CMR demonstrated a favorable effect on different clinical outcomes mainly the management of drug-related problems and adverse events, and it also contributed the most to the reduction of healthcare costs. AR was the most effective intervention to improve patient's adherence. CMR alone or combined with AR both raised equally the patient's satisfaction.

CONCLUSION: Our results showed that CMR can play a major role in the management of drug-related problems and economic issues. AR can significantly improve patient compliance. Larger, standardized, and rigorously designed intervention studies are needed to help decision-makers to select appropriate interventions leading to meaningful improvements in patient care.

PMID:34523204 | DOI:10.1111/ijcp.14864

Reg Anesth Pain Med. 2021 Sep 14:rapm-2021-102498. doi: 10.1136/rapm-2021-102498. Online ahead of print.

ABSTRACT

BACKGROUND: Tranexamic acid (TXA) decreases hemorrhage-related mortality in trauma patients and is increasingly being used during obstetric and orthopedic surgeries. Inadvertent intrathecal injection of TXA is a rare, potentially lethal event leading to dose-dependent cardiotoxicity and neurotoxicity. TXA enhances neuronal excitation by antagonizing inhibitory γ-aminobutyric acid type A and glycine receptors. Until now, mechanistic-based pharmacological treatments targeting multiple central nervous system receptors have been advocated for use in such cases, with no data on intrathecal TXA elimination techniques.

CASE PRESENTATION: A patient scheduled for hip surgery accidentally received 350 mg of intrathecal TXA instead of levobupivacaine. The clinical picture progressed from spinal segmental myoclonus to generalized convulsions and malignant arrhythmias. The treatment consisted of ventriculolumbar perfusion with normal saline at a rate of 50 mL/hour starting 5 hours after TXA administration and inhalational sedation with sevoflurane, in addition to drugs acting on multiple receptors at different central nervous system levels. Over 2 months the neurological status improved, although it was not complete.

CONCLUSIONS: For the first time, the feasibility and possible clinical efficacy of combined treatment with ventriculolumbar perfusion and inhalational sedation with sevoflurane were demonstrated. A referral to a neurosurgical facility is recommended in patients with acute TXA-induced neurotoxicity and cardiotoxicity.

PMID:34521684 | DOI:10.1136/rapm-2021-102498

Rev Esp Enferm Dig. 2021 Sep 15. doi: 10.17235/reed.2021.8295/2021. Online ahead of print.

ABSTRACT

We present a 47 year-old man with a personal history of malignant melanoma (pT3bN2M0) radically removed, who was receiving adjuvant Nivolumab for prevention of recurrence. He was admitted to our service complaining of epigastric pain and hyporexia after receiving the 9º dose of Nivolumab. He underwent a preferential esophagogastroduodenoscopy which showed an intense inflammation limited to the stomach. Macroscopically all the mucosa was erythematosus, edematous, with friability and large ulcerations covered with fibrin. Multiple biopsies revealed inflammatory neutrophilic infiltration in the epithelium, cellular apoptosis and crypt microabscesses, all of which was related to Nivolumab drug-induced pangastritis. No form of Helicobacter Pylori was identified. A medical treatment with double dose of proton-pump inhibitor and definitive cessation of Nivolumab was established, becoming the patient rapidly asymptomatic. The immune checkpoint inhibitors are becoming a widespread treatment in the Oncology field. Nivolumab is a PD-L1 inhibitor, leading to the activation of the cytotoxic immune response carried out by LT-CD8 (1). Despite the immune-mediated adverse events related to the lower gastrointestinal tract are well known; the gastritis or the esophagitis remain sporadic effects (2). They can appear several months after the beginning of the treatment but also after its discontinuation. The differential diagnosis must be reached by excluding pathologies such as infectious gastritis, vasculitis, Crohn´s disease or Behçet syndrome, so as to the pathologist should always know the involvement of this treatment in order to achieve a reliable diagnosis (3). The role of Helicobater Pylori must be highlighted in this case. Since it is capable of simulating or even worsening the immune-mediated gastritis, not only its identification but also its eradication becomes essential (4). The treatment is based on the immediate cessation of the immunotherapy, the gastric acid suppression and high doses of corticosteroids in the most severe cases. The benefits of immunosuppressive treatment using infliximab have been well shown in refractory cases (5).

PMID:34521205 | DOI:10.17235/reed.2021.8295/2021

Blood. 2021 Sep 14:blood.2020009039. doi: 10.1182/blood.2020009039. Online ahead of print.

ABSTRACT

Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by pathologic deposition of immunoglobulin light chains as amyloid fibrils in vital organs, leading to organ impairment and eventual death. That the process is reversible was evidenced in an in vivo experimental model in which fibril-reactive chimeric monoclonal antibody (mAb) 11-1F4 directly targeted human light-chain amyloid deposits and effected their removal via a phagocyte-mediated response. To determine tolerability and potential amyloidolytic effect of this agent (now designated mAb CAEL-101), we conducted a phase 1a/b study involving 27 patients, most of whom had manifestations of organ involvement. This was an open label study in which phase 1a patients received mAb CAEL-101 as a single intravenous infusion, with escalating dose levels from 0.5 mg/m2 to 500 mg/m2 to establish the maximum tolerated dose (MTD). In phase 1b, the antibody was administered as a graded series of four weekly infusions. For both phases, there were no drug-related serious adverse events or dose-limiting toxicities among recipients and the MTD was not reached. Majority of patients had deep hematologic responses but persistent organ disease prior to treatment. Fifteen of 24 patients (63%) who manifested cardiac, renal, hepatic, gastrointestinal, or soft tissue involvement had a therapeutic response to mAb CAEL-101 as evidenced by serum biomarkers or objective imaging modalities with median time to response of 3 weeks. Infusions of mAb CAEL-101 were well-tolerated and, for the majority, resulted in improved organ function, notably for those with cardiac impairment. This trial was registered at www.clinicaltrials.gov as NCT02245867.

PMID:34521113 | DOI:10.1182/blood.2020009039

Schmerz. 2021 Sep 13. doi: 10.1007/s00482-021-00589-8. Online ahead of print.

ABSTRACT

INTRODUCTION: Intellectual and developmental disabilities (IDD) include conditions associated with physical, learning, language, behavioural, and/or intellectual impairment. Pain is a common and debilitating secondary condition compromising functional abilities and quality of life.

OBJECTIVES: This article addresses scientific and clinical challenges in pain assessment and management in individuals with severe IDD.

METHODS: This Clinical Update aligns with the 2019 IASP Global Year Against Pain in the Vulnerable and selectively reviews recurring issues as well as the best available evidence and practice.

RESULTS: The past decade of pain research has involved the development of standardized assessment tools appropriate for individuals with severe IDD; however, there is little empirical evidence that pain is being better assessed or managed clinically. There is limited evidence available to inform effective pain management practices; therefore, treatment approaches are largely empiric and highly variable. This is problematic because individuals with IDD are at risk of developing drug-related side effects, and treatment approaches effective for other populations may exacerbate pain in IDD populations. Scientifically, we are especially challenged by biases in self-reported and proxy-reported pain scores, identifying valid outcome measures for treatment trials, being able to adequately power studies due to small sample sizes, and our inability to easily explore the underlying pain mechanisms due to compromised ability to self-report.

CONCLUSION: Despite the critical challenges, new developments in research and knowledge translation activities in pain and IDD continue to emerge, and there are ongoing international collaborations.

PMID:34515871 | DOI:10.1007/s00482-021-00589-8

ERJ Open Res. 2021 Sep 6;7(3):00004-2021. doi: 10.1183/23120541.00004-2021. eCollection 2021 Jul.

ABSTRACT

Patients with COPD often have reduced physical activity, which can impair health status. Real-world data can provide valuable information on the health and functional status of patients with COPD treated with tiotropium/olodaterol. AERIAL® (ClinicalTrials.gov NCT03165045) was a German, non-interventional study of patients with COPD receiving treatment with tiotropium/olodaterol under real-world conditions for ∼6 weeks. The primary end-point was the proportion of patients achieving a decrease of ≥0.4 points in Clinical COPD Questionnaire (CCQ) score. The CCQ-4 subdomain was used to assess functional status, and the Physician's Global Evaluation (PGE) scale was used to assess the patients' general condition. Safety was assessed, as well as patient satisfaction and willingness to continue treatment. Out of 1351 screened patients, 1322 were treated and 1140 comprised the full analysis set. The primary end-point was met: 66.3% of patients achieved a ≥0.4-point decrease in overall CCQ score (mean±sd decrease 0.78±0.95). Mean±sd decreases in CCQ symptoms and functional state subdomains were 0.84±1.06 and 0.75±1.05 points, respectively. PGE scores improved. One fatality (not treatment-related) and 23 drug-related adverse events were recorded, most commonly nausea and vertigo. >85% of patients were satisfied/very satisfied with tiotropium/olodaterol overall and with the Respimat® device, both in terms of inhalation and handling. Most patients (95.2%) expressed willingness to continue treatment. Patients with COPD treated with tiotropium/olodaterol via Respimat® in routine clinical practice had clinically relevant improvements in health and functional status compared with baseline.

PMID:34513983 | PMC:PMC8419313 | DOI:10.1183/23120541.00004-2021

Front Oncol. 2021 Aug 26;11:743055. doi: 10.3389/fonc.2021.743055. eCollection 2021.

ABSTRACT

The tyrosine kinase inhibitors (TKIs), including sorafenib, remain one first-line antitumor treatment strategy for advanced hepatocellular carcinoma (HCC). However, many problems exist with the current orally administered TKIs, creating a heavy medical burden and causing severe side effects. In this work, we prepared a novel microcrystalline formulation of sorafenib that not only achieved sustainable release and long action in HCC tumors but also relieved side effects, as demonstrated by fundus microcirculation imaging. The larger the size of the microcrystalline formulation of sorafenib particle, the slower the release rates of sorafenib from the tumor tissues. The microcrystalline formulation of sorafenib with the largest particle size was named as Sor-MS. One intratumor injection (once administration) of Sor-MS, but not Sor-Sol (the solution formulation of sorafenib as a control), could slow the release of sorafenib in HCC tumor tissues and in turn inhibited the in vivo proliferation of HCC or the expression of EMT/pro-survival-related factors in a long-acting manner. Moreover, compared with oral administration, one intratumor injection of Sor-MS not only facilitated a long-acting antitumor effect but also relieved side effects of sorafenib, avoiding damage to the capillary network of the eye fundus, as evidenced by fundus microcirculation imaging. Therefore, preparing sorafenib as a novel microcrystal formulation could facilitate a long-acting antitumor effect and relieve drug-related side effects.

PMID:34513717 | PMC:PMC8426437 | DOI:10.3389/fonc.2021.743055

CNS Neurosci Ther. 2021 Sep 12. doi: 10.1111/cns.13724. Online ahead of print.

ABSTRACT

AIMS: Human urinary kallidinogenase (HUK) has shown favorable efficacies in acute ischemic stroke (AIS) treatment. We sought confirmation of the safety and efficacy of HUK for AIS in a large population.

METHODS: RESK study enrolled patients with AIS of anterior circulation to receive HUK infusion. The primary endpoint was the incidence of treatment-emergent adverse events (AEs). Secondary endpoints assessed neurological and functional improvements and stroke recurrent rate.

RESULTS: Of 1206 eligible patients, 1202 patients received at least one dose of HUK infusion and 983 (81.5%) completed the study. The incidence of treatment-emergent AEs and serious AEs were 55.99% and 2.41%, respectively. Pre-specified AEs of special interest occurred in 21.71% of patients, but the majority were mild and unrelated to therapy. Hypertension, age, treatment time, and drug combination were identified to be associated with drug-related blood pressure reduction. Neurological and functional evaluations revealed favorable outcomes from baseline to post-treatment assessment. The cumulative recurrence rate of stroke was 2.50% during the 90-day assessment.

CONCLUSION: HUK had an acceptable safety and tolerability profile in AIS patients. Besides, HUK demonstrated the neurological and functional improvements in AIS, further confirming its clinical efficacy in a real-world large population.

PMID:34510762 | DOI:10.1111/cns.13724

Drug Ther Bull. 2021 Sep 11:dtb-2021-000052. doi: 10.1136/dtb.2021.000052. Online ahead of print.

ABSTRACT

Overview of: Chalitsios CV, Shaw DE, McKeever TM. Risk of osteoporosis and fragility fractures in asthma due to oral and inhaled corticosteroids: two population-based nested case-control studies. Thorax 2021;76:2-28.

PMID:34509977 | DOI:10.1136/dtb.2021.000052

ESMO Open. 2021 Sep 9;6(5):100231. doi: 10.1016/j.esmoop.2021.100231. Online ahead of print.

ABSTRACT

BACKGROUND: Proton-pump-inhibitors (PPIs) are frequently prescribed for the management of anticancer drug-related gastrointestinal symptoms. Palbociclib is a weak base with pH-dependent solubility and potential drug-drug interaction at the absorption level may affect clinical pharmacokinetics. The current study was aimed at investigating the effect of co-administration of PPIs and palbociclib on progression-free survival (PFS) in metastatic breast cancer (mBC) patients.

PATIENTS AND METHODS: Patients affected by estrogen receptor-positive, human epidermal growth factor receptor 2-negative mBC, who were candidates for first-line treatment with palbociclib, were enrolled in this retrospective observational study. Patients were defined as 'no concomitant PPIs' if no PPIs were administered during palbociclib treatment, and as 'concomitant PPIs' if the administration of PPIs covered the entire or not less than two-thirds of treatment with palbociclib. All clinical interventions were made according to clinical practice.

RESULTS: A total of 112 patients were enrolled in the study; 56 belonged to the 'no concomitant PPIs' group and 56 to the 'concomitant PPIs' group. Seventy-one patients were endocrine-sensitive and received palbociclib and letrozole, and 43 were endocrine-resistant and were treated with palbociclib and fulvestrant. The most prescribed PPI was lansoprazole. Patients taking PPIs had a shorter PFS than those taking palbociclib and endocrine therapy alone (14.0 versus 37.9 months, P < 0.0001). Multivariate analysis confirmed concomitant PPIs as the only independent predictive factor for shorter PFS (P = 0.0002). PFS was significantly longer in estrogen-sensitive mBC with no concomitant PPIs compared with patients taking PPIs or estrogen-resistant patients, with and without PPIs (P < 0.0001). No correlation with adverse events was found when considering grade >2 hematological toxicities [Common Terminology Criteria for Adverse Events (CTCAE) scale].

CONCLUSIONS: The present study demonstrates that concomitant use of PPIs in mBC patients treated with palbociclib has a detrimental effect on PFS. Therefore, it is recommended to prescribe PPIs with caution in these patients, strictly adhering to the indications in the summary of product characteristics (RCP).

PMID:34509802 | DOI:10.1016/j.esmoop.2021.100231

Am J Ophthalmol. 2021 Sep 9:S0002-9394(21)00441-4. doi: 10.1016/j.ajo.2021.08.018. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the safety and tolerability of single and multiple intravitreal injections of NGM621 in patients with geographic atrophy (GA) and to characterize the pharmacokinetics and immunogenic potential.

DESIGN: Multicenter, open-label, single- and multiple-dose phase 1 study.

METHODS: Fifteen patients enrolled at 4 sites in the United States. Participants had GA secondary to age-related macular degeneration, lesion size ≥2.5 mm2 and best-corrected visual acuity of 4 to 54 letters (20/80 to 20/800 Snellen equivalent) in the study eye and no history of choroidal neovascularization in either eye. Patients who met eligibility criteria were treated in a single ascending-dose phase (2 mg, 7.5 mg, 15 mg) or received 2 doses NGM621 15 mg 4 weeks apart in the multidose phase and were followed for 12 weeks (85 days). Assessments included adverse events, best-corrected visual acuity, low luminance visual acuity, vital signs, clinical laboratory evaluations, GA lesion area as measured by fundus autofluorescence, spectral domain optical coherence tomography, and pharmacokinetic, immunogenicity, and pharmacodynamic assessments.

RESULTS: All 15 participants completed the 12-week study. There were no serious adverse events and no drug-related adverse events, and no choroidal neovascularization developed in either eye. Mean visual acuity and GA lesion area appeared stable through week 12 for all cohorts. Pharmacokinetic analyses indicated that NGM621 serum exposures appeared to be dose proportional, and no antidrug antibodies were identified at any of the evaluated time points.

CONCLUSIONS: In this small, open-labelled, 12-week phase 1 study, NGM621 was safe and tolerable when administered intravitreally up to 15 mg.

PMID:34509438 | DOI:10.1016/j.ajo.2021.08.018

JNMA J Nepal Med Assoc. 2021 Jan 31;59(233):22-25. doi: 10.31729/jnma.5386.

ABSTRACT

INTRODUCTION: Doctors and nurses have a significant role in the detection of serious and unusual drug reactions. Effective implementation of an adverse drug reaction reporting system is required to ensure patient safety and quality care. This study's objective was to find the prevalence of good knowledge of adverse drug reaction reporting among the Doctors and nurses working in a tertiary care hospital.

METHODS: A descriptive cross-sectional study was conducted among doctors and nurses from 15 February 2020 to 15 July 2020 at Birat Medical College and Teaching Hospital. The convenience sampling method was used to select 192 study participants. A semi-structured questionnaire was used to know the knowledge concept of adverse drug reaction reporting. Ethical clearance was taken from IRC (PA-047/2076-77) of Birat Medical College and Teaching Hospital. Written informed consent was taken from each study participant. Collected data were entered in Microsoft Excel 2010 and analyzed by Statistical Package for the Social Sciences v23.

RESULTS: In total, 192 doctors and nurses, the questionnaires were distributed to 52 (27.1%) doctors and 140 (72.9%) nurses. The mean age of study participants was 28.14 years (SD±4.5). To know the prevalence of knowledge, 15 knowledge related questions of adverse drug reaction had asked. The majority of doctors and nurses had good knowledge about adverse drug reaction reporting, 75% and 64%, respectively.

CONCLUSIONS: Overall, doctors and nurses have had good knowledge of adverse drug reaction reporting. Data shows there is still more gap in training and experience on adverse drug reaction reporting systems.

PMID:34508460 | PMC:PMC7893394 | DOI:10.31729/jnma.5386

Adv Ther. 2021 Sep 10. doi: 10.1007/s12325-021-01893-6. Online ahead of print.

ABSTRACT

INTRODUCTION: The current study aimed to provide data on the effectiveness of the 10 cm2 rivastigmine patch in patients with Alzheimer's disease (AD) in a real-world setting in Taiwan.

METHODS: This was a 48-week, single-arm, open-label, observational, and post-marketing study conducted across seven centers in Taiwan between May 5, 2016 and July 10, 2017. Eligible patients (aged 55-95 years) treated with the 10 cm2rivastigmine patch were enrolled based on physicians' judgment and according to the Taiwan reimbursement criteria of the drug. Data were prospectively collected at Week 0 (baseline), Week 24, and Week 48. The primary endpoint was the change in the cognitive assessment screening instrument (CASI) scores at Week 48 versus baseline. The changes from baseline in clinical dementia rating (CDR), mini-mental state examination (MMSE), and neuropsychiatric inventory (NPI) scores were evaluated, as were treatment persistence and the safety profile.

RESULTS: Of the 285 eligible patients [full analysis set (FAS)], 216 (75.8%) completed the study protocol while 180 (63.2%) persisted on the 10 cm2 rivastigmine patch for the full 48 weeks. At baseline, 89.8% of patients had a CDR score of 0.5 or 1, while the change in CDR score at Week 48 was not significant. In the FAS, both the CASI and MMSE scores had numerical improvement at Week 24 but declined by 2.1 and 0.4 points, respectively, at Week 48 (p = 0.005 and p = 0.022). The increment in NPI scores was not significant. The most common drug-related adverse events (AEs) were pruritus (11.2%), nausea (3.5%), rash (3.2%), and vomiting (2.8%).

CONCLUSIONS: The use of the 10 cm2 rivastigmine patch in the mild stage of AD maintained cognitive function at Week 24 and neuropsychiatric function at Week 48. The treatment persistency and safety profile support the clinical tolerability of the rivastigmine patch in the management of mild-to-moderate AD in Taiwan.

PMID:34506009 | DOI:10.1007/s12325-021-01893-6

Int J Mol Sci. 2021 Aug 28;22(17):9347. doi: 10.3390/ijms22179347.

ABSTRACT

Colorectal cancer (CRC) is the second most commonly diagnosed cancer in females (incidence 16.4/10,000) and the third in males (incidence 23.4/10,000) worldwide. Surgery, chemotherapy (CTx), radiation therapy (RTx), or a combined treatment of those are the current treatment modalities for primary CRC. Chemotherapeutic drug-induced gastrointestinal (GIT) toxicity mainly presents as mucositis and diarrhea. Preclinical studies revealed that probiotic supplementation helps prevent CTx-induced side effects by reducing oxidative stress and proinflammatory cytokine production and promoting crypt cell proliferation. Moreover, probiotics showed significant results in preventing the loss of body weight (BW) and reducing diarrhea. However, further clinical studies are needed to elucidate the exact doses and most promising combination of strains to reduce or prevent chemotherapy-induced side effects. The aim of this review is to overview currently available literature on the impact of probiotics on CTx-induced side effects in animal studies concerning CRC treatment and discuss the potential mechanisms based on experimental studies' outcomes.

PMID:34502251 | DOI:10.3390/ijms22179347

Turk J Pharm Sci. 2021 Sep 1;18(4):517-526. doi: 10.4274/tjps.galenos.2020.66735.

ABSTRACT

Detecting drug-related problems (DRPs) is important in pharmaceutical care in for better therapeutic outcomes. Clinical pharmacists-led comprehensive medication management plays a crucial role in the rational use of drugs by preventing, identifying, and resolving DRPs. In this review, we aimed to determine the effect of interventions on patient outcomes performed by clinical pharmacists in Turkey. A systematic literature search was performed on PubMed, Google Scholar, EMBASE, Cochrane Library, and Turkish databases (ULAKBIM, Dergipark). The main categories were "clinical pharmacist", "intervention", and "Turkey". Two reviewers reviewed each article independently. Two independent reviewers screened all records and extracted data; disagreements were resolved through a consensus. Randomized controlled studies, pre- to post-intervention comparison studies, and cross-sectional studies including pharmacist-led interventions were included in the review. This review included 15 articles evaluating clinical pharmacist interventions. Ten studies (66.7%) focused on DRPs and pharmacist interventions to these problems, while the remaining 5 (33.3%) studies focused on patient education and adherence issues. Studies were conducted in oncology (33.3%), geriatrics (20.0%), chest diseases (13.3%), psychiatry (6.7%), cardiology (6.7%), and infectious diseases (6.7%) clinics. When results of studies are reviewed, most of the interventions were made at the prescriber level followed by the drug level and patient level. Problems were solved in 54.2-93.2% of DRPs, and adherence, patient knowledge, or skills were improved in most of the studies. Most of the studies were carried out within the scope of a postgraduate or doctorate thesis and yet various positive outcomes such as the prevention of side effects, increased quality of life, and decreased duration of hospital stay were observed with high positive rates of interventions, which indicate that other healthcare workers are ready to collaborate with the clinical pharmacists in Turkey.

PMID:34496559 | DOI:10.4274/tjps.galenos.2020.66735

Food Funct. 2021 Sep 8. doi: 10.1039/d1fo00953b. Online ahead of print.

ABSTRACT

Currently, drug-induced liver injury caused by acetaminophen (APAP) is the second leading cause of human liver transplantation. The only clinical antidote treatment for APAP-induced liver injury is N-acetyl-L-cysteine (NAC), which has many side effects. Chitooligosaccharides (COS) are processed from naturally occurring chitin through chemical desalting and deproteinization, biological enzymatic hydrolysis and other processes. In this study, we constructed in vitro and in vivo models of APAP-induced liver injury to study COS of two molecular weights (MWs), which are COST (MW ≤ 1000 Da) and COSM (MW ≤ 3000 Da). The results showed that COST and COSM can significantly reduce the levels of serum ALT and AST and liver MDA, TNF-α, IL-1β and IL-6, and increase the levels and activity of GSH, SOD, GSH-Px and CAT. A mechanistic study found that COST and COSM can significantly reduce the expression of liver CYP2E1, Keap1, p-ASK1/ASK1, p-MKK4/MKK4, p-JNK/JNK, Caspase-3 and Bax and increase the expression of Nrf2, HO-1, eNOS, SOD and Bcl-XL. COST and COSM can inhibit toxic APAP metabolism, inhibit oxidative damage and the apoptosis pathway, increase activation of the liver antioxidant pathway, and ultimately ameliorate APAP-induced liver oxidative damage.

PMID:34494629 | DOI:10.1039/d1fo00953b

FP Essent. 2021 Sep;508:33-40.

ABSTRACT

Polypharmacy, defined as concurrent use of five or more drugs, can occur in patients of all ages. Polypharmacy may be appropriate or inappropriate. Appropriate polypharmacy is defined as "use of the correct drugs under appropriate conditions [in order] to treat the right diseases." A prescribed drug becomes inappropriate when its benefits no longer outweigh its risks. Inappropriate polypharmacy has been shown to increase the risks of hospitalization, adverse drug events, clinically relevant drug interactions, and all-cause mortality. Many tools are available to aid physicians in identifying inappropriate polypharmacy. Implicit tools, such as the Medication Appropriateness Index (MAI), provide guidance to be used alongside clinical judgement. Explicit tools, such as the American Geriatrics Society (AGS) Beers Criteria, provide lists of potentially inappropriate drugs and recommend alternatives. Collaboration with pharmacists is important in assessing drug appropriateness. It has been shown to reduce drug-related problems, emergency department visits, and hospitalizations and to improve overall patient health. A patient-centered, team-based approach is recommended in the process of deprescribing inappropriate drugs. Deprescribing should be approached in the same stepwise manner as prescribing of new drugs, and should include patient agreement to changes, evidence-based rationales, and use of dosage tapering strategies.

PMID:34491710

FP Essent. 2021 Sep;508:25-32.

ABSTRACT

Drug-drug interactions (DDIs) occur when one drug adds to or diminishes the effect of another drug (ie, pharmacodynamic interaction) or affects the absorption, distribution, metabolism, or excretion of another drug (ie, pharmacokinetic interaction). Such interactions cause 26% of all adverse drug events (ADEs) and are associated with a significant burden on the health care system through increased hospitalizations. Some of the most common DDIs result from alterations in drug metabolism through interactions with cytochrome P450 enzymes and absorption through interactions with P-glycoproteins. Other common DDIs occur because of additive effects, including combinations of drugs that increase the risk of seizures, prolong the QT interval, increase central nervous system depression, and increase the risk of serotonin syndrome. Drug-related clinical decision support has been shown to improve the quality of patient care and decrease ADE rates. However, alerts generated by such systems should be interpreted using clinical judgment to determine the risks and benefits of certain drugs on a patient-specific basis. Family physicians can prevent clinically significant DDIs and optimize drug safety by using drug interaction software, along with a general understanding of common DDI mechanisms and collaboration with pharmacists.

PMID:34491709

Ann Palliat Med. 2021 Aug;10(8):8701-8708. doi: 10.21037/apm-21-817.

ABSTRACT

BACKGROUND: There is a lack of data on drug-related problems (DRPs) occurring in nephrology department in China. The objective of this study was to identify and categorize the types and causes of DRPs and to assess their severity. DRPs were examined by clinical pharmacists and the results of their interventions were rated.

METHODS: Clinical pharmacists reviewed all medication orders for patients and documented clinical pharmacy services within a nine-month study period. The Pharmaceutical Care Network Europe (PCNE) classification (Version 9.00) was used to identify DRPs. Our Primary outcomes measured the number, causes, types, potential hazards of DRPs and the types and success rate of intervention.

RESULTS: Admission medication reconciliation data of 113 patients with chronic kidney disease (CKD) were collected and all of the medications were reviewed retrospectively. Exclude 26 patients who did not occurred DRPs, 87 patients (77%) identified 101 DRPs. The average DRP number per patient was 1.16. The most common type of problem was "treatment effectiveness P1" (84.16%; 85/101). The most common causes were "drug selection C1" (36.00%; 45/125), "dose selection C3" (29.60%; 37/125), and "patient related C7" (26.40%; 33/125). Clinical pharmacists totally proposed 249 interventions, of which 190 (76.31%) were fully accepted and implemented.

CONCLUSIONS: DRPs are common among CKD patients in the nephrology department. Hence the necessity for pharmaceutical care to be improved to ensure the ongoing safety of patients.

PMID:34488359 | DOI:10.21037/apm-21-817