Order controls disordered droplets: structure-function relationships in C9ORF72-derived poly(PR).

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have been thought as two distinct neurodegenerative diseases. However, recent genetic screening and careful investigations found the genetic and pathological overlap among these disorders. Hexanucleotide expansions in intron 1 of C9ORF72 are a leading cause of familial ALS and familial FTD. These expansions facilitate the repeat-associated non-ATG-initiated translation (RAN translation), producing five dipeptide repeat proteins (DRPs), including Arg-rich poly(PR: Pro-Arg) and poly(GR: Gly-Arg) peptides. Arg is a positively charged, highly polar amino acid that facilitates interactions with anionic molecules such as nucleic acids and acidic amino acids via electrostatic forces and aromatic amino acids via cation-π interaction, suggesting that Arg-rich DRPs underlie the pathophysiology of ALS via Arg-mediated molecular interactions. Arg-rich DRPs have also been reported to induce neurodegeneration in cellular and animal models via multiple mechanisms; however, it remains unclear why the Arg-rich DRPs exhibit such diverse toxic properties, because not all Arg-rich peptides are toxic. In this mini-review, we discuss the current understanding of the pathophysiology of Arg-rich C9ORF72 DRPs and introduce recent findings on the role of Arg distribution as a determinant of the toxicity and its contribution to the pathogenesis of ALS.

The Arabidopsis HY2 Gene Acts as a Positive Regulator of NaCl Signaling during Seed Germination.

Phytochromobilin (PΦB) participates in the regulation of plant growth and development as an important synthetase of photoreceptor phytochromes (phy). In addition, Arabidopsis long hypocotyl 2 (HY2) appropriately works as a key PΦB synthetase. However, whether HY2 takes part in the plant stress response signal network remains unknown. Here, we described the function of HY2 in NaCl signaling. The hy2 mutant was NaCl-insensitive, whereas HY2-overexpressing lines showed NaCl-hypersensitive phenotypes during seed germination. The exogenous NaCl induced the transcription and the protein level of HY2, which positively mediated the expression of downstream stress-related genes of RD29A, RD29B, and DREB2A. Further quantitative proteomics showed the patterns of 7391 proteins under salt stress. HY2 was then found to specifically mediate 215 differentially regulated proteins (DRPs), which, according to GO enrichment analysis, were mainly involved in ion homeostasis, flavonoid biosynthetic and metabolic pathways, hormone response (SA, JA, ABA, ethylene), the reactive oxygen species (ROS) metabolic pathway, photosynthesis, and detoxification pathways to respond to salt stress. More importantly, ANNAT1-ANNAT2-ANNAT3-ANNAT4 and GSTU19-GSTF10-RPL5A-RPL5B-AT2G32060, two protein interaction networks specifically regulated by HY2, jointly participated in the salt stress response. These results direct the pathway of HY2 participating in salt stress, and provide new insights for the plant to resist salt stress.

Wire mesh capped DRPS based bronchial dosimeter for personal inhalation dosimetry due to radon progeny.

A study has been carried out to experimentally determine the calibration factor (CF) of the passive bronchial dosimeter, which consists of a direct radon progeny sensor capped with a 100-wire mesh. First, the CF was determined in controlled environmental conditions simulated in a calibration chamber. With aerosol concentrations varying from 104p cm-3to 105p cm-3and relative humidity varying from 60% to 80% in the chamber, CF was observed to be nearly constant with an average value of (3.8 ± 0.5) × 10-3mSv tracks-1cm2. Then, the CF was determined in real indoor environments in which it was again observed to be almost constant and the mean value was found to be (5.6 ± 0.1) × 10-3mSv tracks-1cm2. Pooling all the data on CFs obtained under controlled conditions and in real indoor environments, a lognormal distribution of the CF was observed with a geometric mean and geometric standard deviation of 0.0052 mSv tracks-1cm2and 1.28 respectively. The experimentally determined value of CF was found to be in close agreement with the theoretically estimated value, taking into consideration the unattached fraction of radon progeny. This dosimeter is passive, cheap, lightweight and, moreover, the CF being stable against environmental variations, will be useful in monitoring inhalation doses due to radon progeny for occupational workers.

Clinically relevant drug-drug interactions among elderly people with dementia.

PURPOSE: Increased numbers of drugs and changes in pharmacokinetic and pharmacodynamic parameters among elderly people contribute to increased prevalence of adverse drug reactions. Drug-drug interactions (DDIs) are an important reason for admission to hospital and elderly people with dementia are particularly vulnerable. The aims of the present study were to assess the occurrence and characteristics of clinically relevant DDIs and to investigate potential risk factors associated with DDIs among elderly people with dementia. METHODS: People ≥ 65 years with dementia, admitted to two hospitals in Northern Sweden, were included. The medical records of 458 patients were reviewed. Clinically relevant DDIs were identified using the Janusmed interactions database. Pharmacological classification was conducted using Stockley's classification system. RESULTS: A total of 401 DDIs were identified among 43.2% of the study population, of which 98.5% had interactions that may require dose adjustment and 7.6% had drug combinations that should be avoided. Pharmacodynamic interactions were most common, of which furosemide-citalopram (n = 35) were most frequently observed. Omeprazol-citalopram (n = 25) was the most common drug combination among pharmacokinetic interactions. Citalopram and warfarin were the most commonly involved drug substances. An association was found between a higher number of medications being prescribed and having at least one DDI. CONCLUSION: Clinically relevant drug-drug interactions are prevalent among elderly people with dementia living in Northern Sweden. Drug-drug interactions should be identified in order to manage and prevent adverse outcomes. This is particularly important among this group of people especially when multiple medications are being prescribed.

Variations in drug-related problems detected by multidisciplinary teams in Norwegian nursing homes and home nursing care.

OBJECTIVE: Traditionally, nursing homes have been associated with suboptimal drug therapy and drug-related problems (DRPs). In contrast, less is known about drug safety in homecare. The aim of this study was to describe and compare DRPs in older persons across two care settings: nursing homes and home nursing care. DESIGN: Cross-sectional study using descriptive and inferential statistics. SETTING: Nursing homes (n = 5) and home nursing care units (n = 8) across nine municipalities in the middle of Norway. PARTICIPANTS: Multidisciplinary medication reviews for 61 nursing home residents and 93 patients receiving home nursing care performed over the 2013-2014 period, were mapped and examined (N = 154). MAIN OUTCOME MEASURES: DRPs classified by a Norwegian Classification Tool. RESULTS: In all, 740 DRPs were detected in the total sample, 227 in nursing homes and 513 in home nursing care. DRPs were significantly higher among patients receiving home-based care (Mean =5.5) compared to patients in nursing homes (Mean =3.7, p = 0.002). Among the problem categories, the need for additional drug was most frequent in nursing homes (p = 0.001), while documentation discrepancies reached the highest numbers in patients receiving home nursing care (p = 0.000). Additionally, patients in home nursing care had more problems concerning adverse reactions (p = 0.060); however, this was not statistically significant. Differences in DRP categories leading to changes in the patients' medication lists were also discovered. CONCLUSIONS: The frequency of unclear documentation and adverse reactions found in the homecare setting is alarming. This is an important issue given the trend in aged care towards caring people in their own homes. Further research is warranted to explore how different care settings may influence the safety of pharmacotherapy for older persons. Key Points Drug related problems are a significant cause of concern among patients receiving home nursing care as well as for patients living in nursing homes. The findings of this study showed that: •Significantly more DRPs were detected among patients receiving home nursing care than patients living in nursing homes. •While patients living in nursing homes were often undermedicated, documentation discrepancies were more frequent in home nursing care. •DRP categories leading to changes on the medication lists differed between the settings.

Community Pharmacist Training-and-Communication Network and Drug-Related Problems in Patients With CKD: A Multicenter, Cluster-Randomized, Controlled Trial.

BACKGROUND: Appropriate training for community pharmacists may improve the quality of medication use. Few studies have reported the impact of such programs on medication management for patients with chronic kidney disease (CKD). STUDY DESIGN: Multicenter, cluster-randomized, controlled trial. SETTING & PARTICIPANTS: Patients with CKD stage 3a, 3b, or 4 from 6 CKD clinics (Quebec, Canada) and their community pharmacies. INTERVENTION: Each cluster (a pharmacy and its patients) was randomly assigned to either ProFiL, a training-and-communication network program, or the control group. ProFiL pharmacists completed a 90-minute interactive web-based training program on use of medications in CKD and received a clinical guide, patients' clinical summaries, and facilitated access to the CKD clinic. OUTCOMES: Drug-related problems (primary outcome), pharmacists' knowledge and clinical skills, and patients' clinical attributes (eg, blood pressure and glycated hemoglobin concentration). MEASUREMENTS: Drug-related problems were evaluated the year before and after the recruitment of patients using a validated set of significant drug-related problems, the Pharmacotherapy Assessment in Chronic Renal Disease (PAIR) criteria. Pharmacists' questionnaires were completed at baseline and after 1 year. Clinical attributes were documented at baseline and after 1 year using available information in medical charts. RESULTS: 207 community pharmacies, 494 pharmacists, and 442 patients with CKD participated. After 1 year, the mean number of drug-related problems per patient decreased from 2.16 to 1.60 and from 1.70 to 1.62 in the ProFiL and control groups, respectively. The difference in reduction of drug-related problems per patient between the ProFiL and control groups was -0.32 (95% CI, -0.63 to -0.01). Improvements in knowledge (difference, 4.5%; 95% CI, 1.6%-7.4%) and clinical competencies (difference, 7.4%; 95% CI, 3.5%-11.3%) were observed among ProFiL pharmacists. No significant differences in clinical attributes were observed across the groups. LIMITATIONS: High proportion of missing data on knowledge and clinical skills questionnaire (34.6%) and clinical attributes (11.1%). CONCLUSIONS: Providing community pharmacists with essential clinical data, appropriate training, and support from hospital pharmacists with expertise in nephrology increases pharmacists' knowledge and reduces drug-related problems in patients with CKD who are followed up in clinics incorporating a multidisciplinary health care team.

Development of an aggregated system for classifying causes of drug-related problems.

BACKGROUND: More than 20 different types of classification systems for drug-related problems (DRPs) and their causes have been developed. Classification is necessary to describe and assess clinical, organizational, and economic impacts of DRPs through documentation of collected data. However, many researchers have judged classification systems incomplete when describing their data, and have modified them or developed their own. This variability between systems has made study comparisons difficult. OBJECTIVES: To perform a category-by-category comparison of the content of selected DRP classification systems to construct an aggregated cause-of-DRP classification system containing the content of all systems. METHOD: DRP classification systems were identified after a literature review, with 7 chosen based on their use in varied health care settings, geographical diversity, frequency of use, and method of development. These systems were critically analyzed, and the content of each category was compared and aggregated where appropriate. A hierarchy of categories was constructed to include all content from all systems. Any modifications that previous studies may have made to the 7 systems were also cross-referenced to ensure that no concepts were missing from the newly aggregated system. Clinical examples to optimize application, and instructions for when or when not to use categories, were developed. Interrater agreement for classification of the causes of DRPs from 10 medication reviews was performed between 3 clinical pharmacists and the authors' gold standard. RESULTS: We found variation in developmental methods, category descriptions, number and types of categories, and validation methods between the 7 selected systems, together with intermingling of categories identified as causes of DRPs with DRPs themselves. A hierarchical classification system was constructed consisting of 9 cause-of-DRP categories, 33 subcategories, and 58 sub-subcategories, for which interrater agreements were 82.5%, 74.6%, and 58.8%, respectively. CONCLUSION: An aggregated classification system was constructed through a unique and transparent developmental process that may provide the most comprehensive description of causes of DRPs to date. This may facilitate teaching of pharmaceutical care, comparisons of clinical practice, and measurement of the effectiveness of pharmaceutical care interventions.

Pharmaceutical interventions for drug-related problems in the neonatal intensive care unit: incidence, types, and acceptability.

Background: Drug-related problems (DRPs) are widespread in hospitalized neonates, but studies on the prevalence of DRPs in this population are limited. The presence of clinical pharmacists on multidisciplinary teams helps prevent and reduce DRPs. Aim: This investigation aimed to identify and classify the incidence of DRPs in the neonatal intensive care unit (NICU), to determine the determining factors associated with DRPs and to document clinical pharmacists' interventions, outcomes, acceptance rates and clinical significance. Method: A prospective descriptive hospital study was conducted from August to November 2023 at the NICU of Children's University Hospital, Assiut University, Egypt. DRPs were classified using the Pharmaceutical Care Network of Europe (PCNE) classification V9.1. Results: Three hundred sixteen neonates were included in the study, with a mean gestational age of 34 ± 4 weeks and a mean birth weight of 2.03 ± 0.85 kg. A total of 1723 DRPs occurred among 283 neonates (89.6%), an average of 5.5 ± 5.1 DRPs per patient. The main types were treatment effectiveness (P1) (799, 46.4%), followed by others (P3) (469, 27.2%), and treatment safety (P2) (455, 26.4%). The leading causes were dose selection (C3) (1264, 61.9%) and "other domain" (C9) (543, 26.6%). Of the 2149 interventions introduced by pharmacists, 98.8% were accepted and 93% were accepted, and fully implemented. As a result, 92% of the DRPs were resolved. Both length of hospital stay and number of medications were significantly associated with DRPs. Conclusion: DRPs are common in the NICU; this study demonstrated the crucial role of clinical pharmacists in identifying and resolving DRPs.

Pharmacist-Led Interventions to Reduce Drug-Related Problems in Prescribing for Pediatric Outpatients in a Developing Country: A Randomized Controlled Trial.

OBJECTIVE: To evaluate a pharmacist-led intervention's effectiveness in reducing drug-related problems (DRPs ( related to prescriptions for pediatric outpatients. METHODS: We conducted a randomized controlled trial. We recruited and randomly assigned 31 physicians to control or intervention groups. We collected 775 prescriptions (375 from the control group and 400 from the intervention group) at the start. For 3 weeks, intervention physicians received additional information and meetings with pharmacists in addition to the usual practices of the hospital. We then collected prescriptions at the end of the study. We classified DRPs, based on reliable references (Supplemental Table S1) at baseline and endpoint (a week after the intervention). The primary outcome was the proportion of prescriptions with DRPs, and secondary outcomes were the proportions of prescriptions with specific DRP types. RESULTS: The influence of the intervention on general DRPs and specific DRPs was the study's main finding. The pharmacist-led intervention helped reduce the prescriptions with DRPs proportion in the intervention group to 41.0%, compared with 49.3% in the control group (p < 0.05). The DRPs proportion related to the timing of administration relative to meals, unlike the other DRP types, increased in the control group (from 31.7% to 34.9%) and decreased in the intervention group (from 31.3% to 25.3%), with a significant difference between the 2 groups at endpoint (p < 0.01). Patients aged >2 to ≤6 years (OR, 1.871; 95% CI, 1.340-2.613) and receiving ≥5 drugs (OR, 5.037; 95% CI, 2.472-10.261) were at greater risk of experiencing DRPs related to prescribing. CONCLUSIONS: A pharmacist-led intervention improved DRP occurrence related to physicians' prescribing. Pharmacists could be involved in in-depth research with physicians in the prescribing process to provide tailored interventions.

Transcriptome sequencing of wolf spider Lycosa sp. (Araneae: Lycosidae) venom glands provides insights into the evolution and diversity of disulfide-rich toxins.

Wolf spiders in the genus Lycosa are important pest predators in agroforestry ecosystems, capable of feeding on a wide range of pests through the use of complex venom which can to quickly immobilize and kill prey. Because of these characteristics the toxins in wolf spiders venom may prove to be natural sources for novel drug development and biopesticides. To better understand the toxins in Lycosa venom we sequenced the transcriptome from venom glands from an undescribed species of Lycosa and comparatively analyzed the data using known protein motifs. A series of 19 disulfide-rich peptide (DRP) toxin sequences were identified and categorized into seven groups based on the number and arrangement of cysteine residues. Notably, we identified three peptide sequences with low identity to any known toxin, which may be toxin peptides specific to this species of Lycosa. In addition, to further understand the evolutionary relationships of disulfide-rich peptide toxins in spider venom, we constructed phylogenetic trees of DRP toxins from three spiders species and found that the Lycosa sp. DRPs are comparatively diverse with previous research results. This study reveals the toxin diversity of wolf spiders (Lycosa sp.) at the transcriptomic level and provides initial insights into the evolution of DRP toxins in spiders, enriching our knowledge of toxin diversity and providing new compounds for functional studies.

Evaluation of the Prevalence and Risk Factors of Drug-Related Problems in Hypertension and Type 2 Diabetes Mellitus Patients at a Tertiary Care Hospital: A Cross-Sectional Study.

Background Drug-related problems (DRPs) potentially interfere with the desired treatment goals which may lead to increased healthcare costs, morbidity, and mortality. Despite the negative consequences of DRPs, there is a lack of comprehensive research on their prevalence and risk factors, particularly in chronic diseases such as hypertension and type 2 diabetes mellitus (DM). This study aims to evaluate the prevalence and contributing factors of DRPs among hypertension, type 2 DM, and hypertension with type 2 DM in the outpatient general medicine department. Methodology A hospital-based, prospective, observational study was conducted over three months. DRPs were classified using the Helper-Strand classification. The potential risk factors contributing to DRPs were assessed using binary and multinomial logistic regression methods. A p-value <0.05 was considered statistically significant. Results Among the 236 study participants, DRPs were more prevalent in males, and the mean age of the participants was 51.73 ± 9.47 years. DRPs were found in 76% of the study participants, and the mean number of DRPs per patient was 1.16 ± 0.45. Among the identified DRPs, suboptimal therapeutic goals (33%) were the most frequently observed, followed by ineffective drugs (32%), medication non-adherence (23%), and drug-drug interaction (5%). Therapeutic duplication and overdose were less commonly encountered as DRPs. The presence of comorbidity (adjusted odds ratio (AOR) = 5.77), and smoking (AOR = 21.07) were found to be significant risk factors (p < 0.05) contributing to DRPs. Conclusions DRPs are more prevalent in hypertension, type 2 DM, and hypertension with type 2 DM. Age range (40-60 years), comorbidity, and smoking were found to be associated with a higher incidence of DRPs. The implementation of a multidisciplinary team approach involving clinical pharmacists and physicians can effectively identify the prevalence and determine the associated risk factors of DRPs and subsequently may help employ targeted interventions to mitigate the development of DRPs.

Impact of clinical pharmacist-led intervention for drug-related problems in neonatal intensive care unit a randomized controlled trial.

Introduction: Drug-related problems (DRPs) incidence is higher in neonatal intensive care units (NICUs), compared to other pediatric wards due to aspects like off-label medications, pharmacokinetic/dynamic variability, or organ dysfunction/immaturity. This study aimed to determine whether and to what extent a clinical pharmacist intervention improves medication safety and prevents DRPs [medication errors (MEs), adverse drug reactions (ADRs), drug-drug interactions (DDIs)]. Methods: A prospective, randomized, double blind, controlled study in NICU-admitted neonates was conducted. NICU patients were randomly assigned to the intervention (clinical pharmacist-led) (IG) or control group (standard care such as clinical diagnosis, pharmacotherapy) (CG). The clinical pharmacist was involved in the IG to identify-prevent-intervene MEs, or identify and monitor ADRs and DDIs. The primary outcome was the number of neonates who developed at least one DRP compared with those seen across IG and CG. Secondary outcomes included length of hospital stay, total number of drugs or DRP type. Results: Neonates were randomly assigned to CG (n = 52) or IG (n = 48). In total, 45%, 42%, and 16% of patients had at least 1 MEs, ADRs, and clinically significant DDIs, respectively. The number of patients with at least 1 ME was 28 (53%) and 17 (35%) in the CG and IG (p>0.05). The median (range) number of ME was higher in CG [1 (0-7)] than in IG [0 (0-4)] (p = 0.003). Applying regression analysis, the CG had 2.849 times more MEs than the IG (p<0.001). Furthermore, the number of patients (CG to IG) with at least one detected ADR or clinical DDI was 19 (36%) to 23 (47%) (p>0.05) and 4 (7%) to 12 (25%), respectively (p = 0.028). Conclusion: Clinical pharmacist availability to systematically and standardized identify, prevent and resolve DRPs among NICU patients is effective. Daily detailed clinical pharmacist observations and interventions enables prevention and monitoring of DRPs. Clinical Trial Registration ClinicalTrials.gov, identifier NCT04899960.

From dynamin related proteins structures and oligomers to membrane fusion mediated by mitofusins.

Mitochondria assemble in a highly dynamic network where interconnected tubules evolve in length and size through regulated cycles of fission and fusion of mitochondrial membranes thereby adapting to cellular needs. Mitochondrial fusion and fission processes are mediated by specific sets of mechano-chemical large GTPases that belong to the Dynamin-Related Proteins (DRPs) super family. DRPs bind to cognate membranes and auto-oligomerize to drive lipid bilayers remodeling in a nucleotide dependent manner. Although structural characterization and mechanisms of DRPs that mediate membrane fission are well established, the capacity of DRPs to mediate membrane fusion is only emerging. In this review, we discuss the distinct structures and mechanisms of DRPs that trigger the anchoring and fusion of biological membranes with a specific focus on mitofusins that are dedicated to the fusion of mitochondrial outer membranes. In particular, we will highlight oligomeric assemblies of distinct DRPs and confront their mode of action against existing models of mitofusins assemblies with emphasis on recent biochemical, structural and computational reports. As we will see, the literature brings valuable insights into the presumed macro-assemblies mitofusins may form during anchoring and fusion of mitochondrial outer membranes.

Chemerin Effect on the Endometrial Proteome of the Domestic Pig during Implantation Obtained by LC-MS/MS Analysis.

Chemerin (CHEM) is a hormone mainly expressed in adipocytes involved in the regulation of energy homeostasis and inflammatory response. CHEM expression has been demonstrated in the structures of the porcine hypothalamic-pituitary-gonadal axis, as well as in the uterus, trophoblasts and conceptuses of pigs. In this study, we performed high-throughput proteomic analyses (liquid chromatography with tandem mass spectrometry, LC-MS/MS) to examine the influence of CHEM (400 ng/mL) on differentially regulated proteins (DRPs) in the porcine endometrial tissue explants during implantation (15 to 16 days of gestation). Among all 352 DRPs, 164 were up-regulated and 188 were down-regulated in CHEM-treated group. DRPs were assigned to 47 gene ontology (GO) terms (p-adjusted < 0.05). Validation of four DRPs (IFIT5, TGFß1, ACO1 and PGRMC1) by Western blot analysis confirmed the veracity and accuracy of the LC-MS/MS method used in the present study. We suggest that CHEM, by modulating various protein expressions, takes part in the endometrial cell proliferation, migration and invasion at the time of implantation. It also regulates the endometrial immune response, sensitivity to P4 and the formation of new blood vessels. Additionally, CHEM appears to be an important factor involved in endothelial cell dysfunction during the pathogenesis of preeclampsia. The identification of a large number of DRPs under the influence of CHEM provides a valuable resource for understanding the molecular mechanisms of this hormone action during implantation, which is a prerequisite for better control of pig reproduction.

Drug-related problems of antibiotic use in gastroenteritis related to patient therapy outcomes at Universitas Gadjah Mada Hospital.

OBJECTIVES: Gastroenteritis is a disease of digestive system commonly occur among the people. Some cases of gastroenteritis are caused by bacteria, so it is treated by using antibiotics. Inappropriate use of antibiotics can be associated to Drug-Related Problems (DRPs). This study aims to identify patterns of potential DRPs of antibiotic use and analyze the effect of potential DRPs of antibiotic use toward the patient's therapeutic outcomes and length of stay. METHODS: This is a retrospective cross-sectional study carried out by using patient's medical record. The study population was gastroenteritis patients at the inpatient ward of Universitas Gadjah Mada Hospital during January 2018-June 2019. Then, SPSS was employed to analyze the data and the effect of potential DRPs toward therapeutic outcomes was analyzed by utilizing the chi-square method. RESULTS: More than half of gastroenteritis patients in Universitas Gadjah Mada Hospital were identified to have potential DRPs of antibiotic use. The most identified of potential DRPs was problems related to drug selection. Based on the chi-square analysis, there was no relationship between potential DRPs of antibiotic use and the therapeutic outcome. In addition, there was also no relationship between potential DRPs of antibiotic use and patient's length of stay. CONCLUSIONS: The potential DRPs of antibiotics use do not have a significant effect on the therapeutic outcome and length of stay of the gastroenteritis patients in Universitas Gadjah Mada Hospital.

Drug-related problems identified by clinical pharmacists in nephrology department of a tertiary hospital in China-a single center study.

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.

Drug-related problems among hospitalized cancer pain patients: an investigative single-arm intervention trial.

BACKGROUND: To evaluate the characteristics of drug-related problems (DRPs) in cancer pain patients, and to identify the impact of pharmacists' intervention in cancer pain associated DRPs. METHODS: In this investigative, single-arm intervention study, clinical pharmacists identified DRPs in cancer pain patients and provided interventions based on medication information, direct patient-pharmacist interview, and ward rounds with multi-disciplinary team (MDT). Types and causes of DRPs, interventions, acceptance and outcome were sorted based on Pharmaceutical Care Network Europe (PCNE) DRP classification V9.0, which includes 3 primary domains for problems, 9 for causes, 5 for interventions, 3 for acceptance, and 4 for DRPs status. RESULTS: Totally, 42 cancer pain patients were enrolled, and 47 DRPs in 33 (78.6%) patients were identified by clinical pharmacists. The major type of DRPs was treatment effectiveness (30; 63.8%) and treatment safety (17; 36.2%). For the "treatment effectiveness" category, the "effect of drug treatment not optimal" was dominant category (27/30; 90%). A total of 66 DRP causes were identified, and most of DRPs were caused by "drug selection" (27; 40.9%) and "dose selection" (16; 24.2%). Within the "drug selection" category, "no or incomplete drug treatment in spite of existing indication" was dominant category (25/27; 92.6%). According to DRPs, 159 interventions were provided by clinical pharmacists and 99.4% of interventions were accepted by prescribers or patients. Finally, 44 (93.6%) DRPs were solved. CONCLUSIONS: In cancer pain patients, insufficient pain control mainly caused by inappropriate selection and dosage of analgesics. Clinical pharmacists' interventions dramatically ameliorate these problems and bring about positive effects in cancer pain pharmacotherapy.

The effectiveness of an independent anti-neoplastic medication therapy management system in ambulatory cancer patients.

BACKGROUND: Cancer has always been a serious health threat for human. Patients with cancer are at high risk of drug-related problems (DRPs) due to multi-morbidity associated polypharmacy. However, data is lacking in identifying and addressing potential DRPs in cancer patients in China. This study aims to investigate the prevalence of DRPs and evaluate the effectiveness of an independent anti-neoplastic medication therapy management (MTM) system in ambulatory cancer patients. METHODS: This is a retrospective study. An independent anti-neoplastic MTM system in Shanghai Jiao Tong University affiliated sixth People's Hospital was established in 2018 with the collaboration of oncologists, clinical pharmacists and software engineers. The system contains an independent clinic of pharmacy and MTM software. The software consisted of six modules to help clinical pharmacists serve the tumor patients. The six modules include medication therapy review, intervention plan, personal medication record, medication-related action plan, intervention and/or referral, and documentation and follow-up. RESULTS: A total of 173 eligible tumor patients visited the anti-neoplastic pharmaceutical clinic and were recorded in the independent anti-neoplastic MTM system from Jun 2018 to May 2019. The average clinic visits were 2.4 times of the study participants. Two thirds patients (117/173) had one or more identified DRPs in medication therapy review. Adverse drug reaction, potential drug interaction and non-adherence were the leading DRPs. 85.8% of DRPs could be resolved (cured or improved) in four weeks. Tumor patients showed medication adherence reached 84-100% after three or four times of follow-up and intervention. CONCLUSIONS: The participation of clinical pharmacists in managing polypharmacy tumor patients, with the independent anti-neoplastic MTM system, facilitated the identifying and solving DRPs, especially improving medication adherence of patients, and thus enhancing the effectiveness, safety and rational use of medication.

The influence of the gut microbiota on the bioavailability of oral drugs.

Due to its safety, convenience, low cost and good compliance, oral administration attracts lots of attention. However, the efficacy of many oral drugs is limited to their unsatisfactory bioavailability in the gastrointestinal tract. One of the critical and most overlooked factors is the symbiotic gut microbiota that can modulate the bioavailability of oral drugs by participating in the biotransformation of oral drugs, influencing the drug transport process and altering some gastrointestinal properties. In this review, we summarized the existing research investigating the possible relationship between the gut microbiota and the bioavailability of oral drugs, which may provide great ideas and useful instructions for the design of novel drug delivery systems or the achievement of personalized medicine.

Preliminary exploration on the role of clinical pharmacists in cancer pain pharmacotherapy.

BACKGROUND: More than half of cancer patients affected by cancer experience pain of moderate-tosevere intensity. Therefore, facilitating appropriate and safe administration of analgesics is crucial to the comprehensive management of cancer patients. In this article, we assessed medication adherence, pain relief, drug related problems (DRPs) and analgesics adverse events (AEs) in cancer pain patients based on a model of clinical pharmacy services. METHODS: In this prospective, single-arm intervention study, cancer pain patients admitted to our institution were eligible. According to different adherence, heterogeneity of pain, and individual treatment strategy, clinical pharmacists (CPs) provided comprehensive pain assessment and medication education for patients, as well as provided consultation and recommendation for physicians. CPs' pharmacy services were assessed through medication adherence, numbers of DRPs, acceptance of recommendation, pain intensity (PI), daily interference and AEs. RESULTS: A total of 42 patients were enrolled between November, 2018 and November, 2019. Compared to baseline, patients' medication adherence evaluated with a medication adherence scale showed a significantly improvement at 14 and at 28 days after receiving CPs' interventions (8 score vs. 7 score at 14 days and at 28 days, P<0.01). During the 28-day follow-up, a total of 63 interventions were put forward according to 57 identified DRPs in 33 patients (78.6%), and approximately 95% (60/63) of the interventions were accepted by physicians. PI and daily interference significantly improved on the third day after the interventions of CPs, and the improvement continued until day 28 (P<0.01). AEs caused by opioids occurred in 19 patients (45.2%), and the most common one was constipation (14 patients, 33.3%). CONCLUSIONS: CPs' comprehensive interventions for cancer pain patients were efficacious in improving their medication adherence and pain relief, as well as reducing incidence of AEs. Therefore, this promising model should be replicated in other medical centers.