ABSTRACT
The transcription factor receptor-interacting protein 140 (RIP140) regulates intestinal homeostasis and tumorigenesis through Wnt signaling. In this study, we investigated its effect on the Notch/HES1 signaling pathway. In colorectal cancer (CRC) cell lines, RIP140 positively regulated HES1 gene expression at the transcriptional level via a recombining binding protein suppressor of hairless (RBPJ)/neurogenic locus notch homolog protein 1 (NICD)-mediated mechanism. In support of these in vitro data, RIP140 and HES1 expression significantly correlated in mouse intestine and in a cohort of CRC samples, thus supporting the positive regulation of HES1 gene expression by RIP140. Interestingly, when the Notch pathway is fully activated, RIP140 exerted a strong inhibition of HES1 gene transcription controlled by the level of HES1 itself. Moreover, RIP140 directly interacts with HES1 and reversed its mitogenic activity in human CRC cells. In line with this observation, HES1 levels were associated with a better patient survival only when tumors expressed high levels of RIP140. Our data identify RIP140 as a key regulator of the Notch/HES1 signaling pathway, with a dual effect on HES1 gene expression at the transcriptional level and a strong impact on colon cancer cell proliferation.
Subject(s)
Cell Proliferation , Colonic Neoplasms , Gene Expression Regulation, Neoplastic , Nuclear Receptor Interacting Protein 1 , Transcription Factor HES-1 , Animals , Humans , Mice , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Colonic Neoplasms/metabolism , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Nuclear Receptor Interacting Protein 1/metabolism , Receptors, Notch/metabolism , Receptors, Notch/genetics , Signal Transduction , Transcription Factor HES-1/metabolism , Transcription Factor HES-1/geneticsABSTRACT
Background: Despite current recommendation, vaccination coverage (VC) for patients with heart failure (HF) remains far too limited. Aims: To evaluate the VC of HF patients followed in our hospital center and investigate the barriers to vaccination and the ways to address them. Methods: This was a cross-sectional monocentric descriptive study conducted between December 2019 and January 2021 at the University Hospital of Montpellier, France. Patients with HF history hospitalized in cardiology unit (CU) and patients in a HF telemonitoring program (TP) were included. An interview was conducted by a pharmacist to find out the patient's vaccination status against influenza and pneumococcus. For non-vaccinated patients, opinion and willingness to be vaccinated were also obtained. Results: Data from 335 patients were collected (185 in CU, 150 in TP). The mean age was 69.3 years and the proportion of males was 72%. About 65% were vaccinated against influenza in the last year (60% in CU, 72% in TP, p = 0.022) and 22% were up to date with pneumococcal vaccination (11% in CU, 35% in TP, p < 0.001). Among patients not vaccinated, 17% refused vaccination. Among unvaccinated patients who consider vaccination, 69% wanted to be vaccinated by their general practitioner (GP). Conclusions: The VC of HF patients remains insufficient. Patients in TP are more vaccinated than patients in CU, which could involve better management. The low rate of vaccinated patients is mainly explained by a lack of awareness. The medical team, including the clinical pharmacist by his dedicated time during medication reconciliation may play a major role in the management of hospitalized patients as well as GP's as local actors.
ABSTRACT
Aim: The transcription factor RIP140 (receptor interacting protein of 140 kDa) is involved in intestinal tumorigenesis. It plays a role in the control of microsatellite instability (MSI), through the regulation of MSH2 and MSH6 gene expression. The aim of this study was to explore its effect on the expression of POLK, the gene encoding the specialized translesion synthesis (TLS) DNA polymerase κ known to perform accurate DNA synthesis at microsatellites. Methods: Different mouse models and engineered human colorectal cancer (CRC) cell lines were used to analyze by RT-qPCR, while Western blotting and luciferase assays were used to elucidate the role of RIP140 on POLK gene expression. Published DNA microarray datasets were reanalyzed. The in vitro sensitivity of CRC cells to methyl methane sulfonate and cisplatin was determined. Results: RIP140 positively regulates, at the transcriptional level, the expression of the POLK gene, and this effect involves, at least partly, the p53 tumor suppressor. In different cohorts of CRC biopsies (with or without MSI), a strong positive correlation was observed between RIP140 and POLK gene expression. In connection with its effect on POLK levels and the TLS function of this polymerase, the cellular response to methyl methane sulfonate was increased in cells lacking the Rip140 gene. Finally, the association of RIP140 expression with better overall survival of CRC patients was observed only when the corresponding tumors exhibited low levels of POLK, thus strengthening the functional link between the two genes in human CRC. Conclusion: The regulation of POLK gene expression by RIP140 could thus contribute to the maintenance of microsatellite stability, and more generally to the control of genome integrity.
ABSTRACT
Background and objectives: Renal failure is a contraindication for some glucose-lowering drugs and requires dosage adjustment for others, particularly biguanides, sulfonylureas, and inhibitors of dipeptidyl peptidase 4. In this study, we assessed adherence to prescription recommendations for glucose-lowering drugs according to renal function in hospitalized diabetic subjects. Materials and Methods: This prospective cohort study was carried out over a 2-year period in a university hospital. Glomerular filtration rate (GFR) was determined by averaging all measurements performed during hospitalization. Glucose-lowering drug dosages were analyzed according to the recommendations of the relevant medical societies. Results: In total, 2071 diabetic patients (53% hospitalized in cardiology units) were examined. GFR was <30 mL/min/1.73 m2 in 13.4% of these patients, 30-44 in 15.1%, 45-60 in 18.3%, and >60 in 53.3%. Inappropriate oral glucose-lowering treatments were administered to 273 (13.2%) patients, including 53 (2.6%) with a contraindication. In cardiology units, 53.1% and 14.3% of patients had GFRs of <60 and <30 mL/min/1.73 m2, respectively, and 179 (15.4%) patients had a contraindication or were prescribed an excessive dose of glucose-lowering drugs. Conclusions: We showed that the burden of inappropriate prescriptions is high in diabetic patients. Given the high number of patients receiving these medications, particularly in cardiology units, a search for potential adverse effects related to these drugs should be performed.
Subject(s)
Diabetes Mellitus, Type 2 , Hypoglycemic Agents , Inappropriate Prescribing , Cardiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Endocrinology , Glucose , Guideline Adherence , Humans , Hypoglycemic Agents/adverse effects , Inpatients , Internal Medicine , Kidney/physiology , Kidney/physiopathology , Prospective StudiesABSTRACT
Microsatellite instability (MSI) is related to the alteration of mismatch repair (MMR) genes and plays a key role in colorectal cancer (CRC) pathogenesis. We previously reported that the transcription factor Nuclear Receptor Interacting Protein 1 (NRIP1) is involved in sporadic intestinal tumorigenesis. The aim of this study was to decipher its role in MSI CRC. By using different mouse models and engineered cell lines, we demonstrated that NRIP1 increased MSH2 and MSH6 MMR gene transcription and mRNA/protein levels. In human CRC cells, NRIP1 expression was associated with decreased MSI and the hypermutator phenotype, and with resistance to chemotherapy drugs. Using a cohort of 194 CRC patients, we detected in 22% of the cases a MSI-induced frameshift mutation in the NRIP1 coding sequence. This genetic alteration generates a truncated protein with a dominant negative activity that increased human CRC cell proliferation and impaired the regulation of MSH2 and MSH6 gene expression. Moreover, the NRIP1 mutant correlated with a decreased overall survival of patients with advanced CRC, especially when MLH1-deficient. By decreasing the expression of MSH2 and MSH6 gene expression, the NRIP1 variant may amplify MLH1-dependent CRC progression and behave as a new prognostic marker of advanced MSI CRC.
ABSTRACT
OBJECTIVES: Emergency department (ED) overcrowding is a problem for the delivery of adequate and timely emergency care. To improve patient flow and the admission process, the quick prediction of a patient's need for admission is crucial. We aimed to investigate the variables associated with hospitalisation after an ED visit, with a particular focus on the variables related to medication. METHODS: This prospective study was conducted from 2011 to 2018 in subacute medical ED of a French University Hospital. Specialised EDs (paediatric, gynaecologic, head and neck and psychiatric) and the outpatient unit of the ED were not included. Participation in this study was proposed to all adult patients who underwent a medication history interview with a pharmacist. Pharmacists conducted structured interviews for the completion of the medication history and the detection of adverse drug events (ADE). Relations between patient characteristics and hospitalisation were analysed using logistic regression. RESULTS: Among the 14 511 included patients, 5972 (41.2%) were hospitalised including 69 deaths. In total, 7458 patients (51.4%) took more than 5 medications and 2846 patients (19.6%) had an ADE detected during the ED visit. In hospitalised patients, bleeding (32.2%) and metabolic disorders (16.8%) were the most observed ADE symptoms. Variables associated with increased hospital admission included 2 demographic variables (age, male gender), 4 clinical variables (renal and hepatic failures, alcohol addiction, ED visit for respiratory reason) and 6 medication-related variables (medications >5, use of blood, systemic anti-infective, metabolism and antineoplastic/immunomodulating medications and ADE). CONCLUSION: We identified variables associated with hospitalisation including drug-related variables. These results point out the importance and the relevance of collecting medication data in a subacute medical ED (study registered on ClinicalTrials.gov, NCT03442010).
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Pharmaceutical Preparations , Adult , Child , Drug-Related Side Effects and Adverse Reactions/epidemiology , Emergency Service, Hospital , Hospitalization , Hospitals, University , Humans , Male , Prospective StudiesABSTRACT
AIM: The aim of this study was to evaluate the clinical, economic, and organizational impact of clinical pharmacist services added to an adult orthopedic and trauma surgery unit in a university hospital. METHODS: This was a prospective, observational study performed from January to February 2017. All pharmacists' interventions were documented, and their clinical, economic, and organizational impact and the probability of adverse drug events (ADEs) were assessed using the clinical, economic and organizational scale three-dimensional scale. An expert panel composed of three clinical pharmacists, one surgeon and one anesthetist classified the pharmacist intervention. The potential clinical impact was determined through a consensus by the expert panel. Cost avoidance was calculated for serious ADEs with a major impact by avoiding an additional cost of 4912 per event and taking into account the probability of ADE occurrence. RESULTS: The pharmacists performed 1014 interventions for 28 days with a 95.3% acceptance rate by prescribers. Thirty-nine interventions were rated to have a major clinical impact (3.8%). The organizational impact was estimated favorable for 856 (84.4%) pharmacist interventions. Cost avoidance was estimated at 24,364, and the indirect costs benefit was estimated at 11,864 during the study. The cost-benefit ratio of the clinical pharmacist intervention was 1.94 in savings for every 1 invested. CONCLUSIONS: Clinical pharmacist services in an orthopedic and trauma surgery department have the potential to improve patient outcomes and avoid healthcare costs. Furthermore, the presence of a pharmacist in surgical units allows for communication between the unit and the pharmacy, which produces better fluidity and improves the quality of care.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Pharmacy Service, Hospital , Adult , Cost-Benefit Analysis , Humans , Pharmacists , Prospective StudiesABSTRACT
OBJECTIVES: Adverse drug events (ADEs) are a major public health issue in hospitals. They are difficult to detect because of incomplete or unavailable medication history. In this study, we aimed to assess the rate and characteristics of ADEs identified by pharmacists in an emergency department (ED) to identify factors associated with ADEs. METHODS: In this prospective observational study, we included consecutive adult patients presenting to the ED of a French 2600-bed tertiary care university hospital from November 2011 to April 2015. Clinical pharmacists conducted structured interviews and collected the medication history to detect ADEs (i.e., injuries resulting directly or indirectly from adverse drug reactions and noncompliance to medication prescriptions). Unsure ADE cases were reviewed by an expert committee. Relations between patient characteristics, type of ED visit, and ADE risk were analyzed using logistic regression. RESULTS: Among the 8275 included patients, 1299 (15.7%) presented to the ED with an ADE. The major ADE symptoms were bleeding, endocrine problems, and neurologic disorders. Moreover, ADEs led to the ED visit, hospitalization, and death in 87%, 49.3%, and 2.2% of cases, respectively. Adverse drug event risk was independently associated with male sex, ED visit for neurological symptoms, visit to the ED critical care unit, or ED short stay hospitalization unit, use of blood, anti-infective, antineoplastic, and immunomodulating drugs. CONCLUSIONS: This study improves the knowledge about ADE characteristics and on the patients at risk of ADE. This could help ED teams to better identify and manage ADEs and to improve treatment quality and safety.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Pharmacists , Adult , Drug-Related Side Effects and Adverse Reactions/epidemiology , Emergency Service, Hospital , Hospitalization , Humans , Male , Prospective StudiesABSTRACT
OBJECTIVE: First, the aim of the study was to assess the prevalence, characteristics, and severity of unintended medication discrepancies (UMDs) and medication errors (MEs) at admission and discharge of hospitalization. Second, the aim of the study was to identify clinical and hospitalization factors associated with risk of UMDs as well as characteristics of the medication reconciliation process associated with UMDs detection. METHODS: This prospective observational study included all adult patients admitted from 2013 to 2015 in the Endocrinology-Diabetology-Nutrition Department of Montpellier Hospital, France. Clinical pharmacists conducted medication reconciliation by collecting the best possible medication history from different sources and comparing it with admission and discharge prescriptions to identify discrepancies. Unintended medication discrepancies corrected by the physician were considered as MEs. Risk factors of UMDs were identified with logistic regression. RESULTS: Of 904 patients included, 266 (29.4%) had at least one UMD, at admission or at discharge. In total, 378 (98.2%) of 385 UMDs were considered to be MEs. Most MEs were omissions (59.3%). Medication errors were serious or very serious in 36% of patients and had potentially moderate severity in almost 40% of patients. The risk of UMDs increased constantly with the number of treatments (P < 0.001). Thyroid (adjusted odds ratio [OR] = 1.79, 95% CI = 1.12-2.86) and infectious diseases (adjusted OR = 1.80, 95% CI = 1.17-2.78) were associated with UMDs risk at admission. The best type of source for the detection of UMDs was the general practitioner or nurse (OR = 2.64, 95% CI = 1.51-4.63). CONCLUSIONS: Unintended medication discrepancies are frequent at hospital and depend on intrinsic clinical parameters but also on practice of medication reconciliation process, such as number and type of sources used.
Subject(s)
Medication Reconciliation , Patient Discharge , Adult , Delivery of Health Care , Hospitalization , Hospitals , Humans , Medication Errors/prevention & control , Patient Admission , Pharmacists , Risk FactorsABSTRACT
OBJECTIVES: This study aimed to investigate a potential daily-life concern for patients with diabetes hypoglycemia while driving by (1) estimating their incidence in insulin-treated drivers, (2) determining factors associated with their occurrence, and (3) analyzing patients' behavior regarding prevention of hypoglycemia. METHODS: We conducted an observational study from November 2013 to May 2018 in the endocrinology-diabetology-nutrition department of our university hospital. All patients treated for diabetes older than 18 years admitted in the department were eligible. A specific questionnaire assessing attitudes, knowledge, and consequences of hypoglycemia was provided. In this study, only insulin-treated patients who regularly drive were analyzed. RESULTS: On the 233 insulin-treated drivers included, 45 (19%) self-reported at least 1 hypoglycemia while driving in the preceding year. Two factors were significantly associated with their occurrence: type 1 diabetes (odds ratio [OR] = 3.19; 95% confidence interval [CI] = 1.55-6.57) and experiences of asymptomatic hypoglycemia (OR = 2.20; 95% CI = 1.05-4.63). Awareness of the treatment hypoglycemia risk because of information provided by a medical specialist was also but nonsignificantly associated with hypoglycemia while driving (OR = 2.61; 95% CI = 0.86-7.92). Forty-one patients (18%) combined those 3 variables, 20 (49%) of them self-reported hypoglycemia while driving. Thirty-four percent of the patients never carried carbohydrates for hypoglycemia correction. Seventy-six percent do not monitor blood glucose level before driving. CONCLUSIONS: Our questionnaire allowed us to highlight that 19% our cohort of insulin-treated drivers declared experiencing hypoglycemia while driving. Risk factors identified and prevention data collected should help us better target patient education.
Subject(s)
Diabetes Mellitus, Type 2 , Hypoglycemia , Blood Glucose , Humans , Hypoglycemia/chemically induced , Hypoglycemia/epidemiology , Hypoglycemic Agents/adverse effects , Incidence , Insulin/adverse effects , Risk FactorsABSTRACT
BACKGROUND: Medication errors (ME) can be reduced through preventive strategies such as medication reconciliation. Such strategies are often limited by human resources and need targeting high risk patients. AIMS: To develop a score to identify patients at risk of ME detected during medication reconciliation in a specific population from internal medicine unit. METHODS: Prospective observational study conducted in an internal medicine unit of a French University Hospital from 2012 to 2016. Adult hospitalised patients were eligible for inclusion. Medication reconciliation was conducted by a pharmacist and consisted in comparing medication history with admission prescription to identify MEs. Risk factors of MEs were analysed using multivariate stepwise logistic regression model. A risk score was constructed using the split-sample approach. The split was done at random (using a fixed seed) to define a development data set (N = 1256) and a validation sample (N = 628). A regression coefficient-base scoring system was used adopting the beta-Sullivan approach (Sullivan's scoring). RESULTS: Pharmacists detected 740 MEs in 368/1884 (19.5%) patients related to medication reconciliation. Female gender, number of treatments >7, admission from emergency department and during night or weekend were significantly associated with a higher risk of MEs. Risk score was constructed by attributing 1 or 2 points to these variables. Patients with a score ≥3 (OR [95% CI] 3.10 [1.15-8.37]) out of 5 (OR [95% CI] 8.11 [2.89-22.78]) were considered at high risk of MEs. CONCLUSIONS: Risk factors identified in our study may help prioritising patients admitted in internal medicine units who may benefit the most from medication reconciliation (ClinicalTrials.gov number NCT03422484).
Subject(s)
Medication Errors , Medication Reconciliation , Adult , Female , Hospitalization , Humans , Internal Medicine , Medication Errors/prevention & control , Patient Admission , PharmacistsABSTRACT
OBJECTIVES: The aim of this study was to determine the effect of pharmacists' interventions (PI) on the potential clinical impact of medication errors, including the lack of therapeutic optimisation of patients with cardiologic diseases, such as heart failure and acute coronary syndrome). METHODS: This was an observational, prospective study conducted in the cardiology department of a French university hospital centre for a duration of 9 months. All prescriptions were analysed and PI were registered for clinical rating by pharmacists and cardiologist. RESULTS: A total of 532 PI cases were recorded in 339 patients, with a mean of 1.57 (±1.04) PI. The PI acceptance rate was 98.1%. "Dose adjustment" and "introduction therapy" were the most common interventions and represented 38.0% and 32.9%, respectively, of all PI. Statins were the most frequently involved drugs (18.1%), followed by ACE (Angiotensin Converting Enzyme) inhibitors (10.9%) and antiplatelet agents (9.3%). Moreover, 13.8% of PI potentially avoided a severe or very severe clinical impact (n = 71) and 38.6% had a significant impact altering the quality of life (n = 198). There was no significant difference between the average score performed by the clinical pharmacist included in the cardiology team and the one obtained by the cardiologist (P = .797). In contrast, a significant difference was observed for the average score established by the pharmacist localised in central pharmacy versus the rating of the cardiologist (P < .001). CONCLUSIONS: The collaboration between clinical pharmacists and cardiologists in the medical units seems to be beneficial to the quality of prescriptions, including the implementation of recommendations. The good rate of PI acceptance and the similar rating with the cardiologist show that there is a change in perspective of the pharmacist, being closer to the clinical reality.
Subject(s)
Acute Coronary Syndrome/drug therapy , Drug Prescriptions/statistics & numerical data , Medication Errors/prevention & control , Adult , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Cardiologists/statistics & numerical data , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Middle Aged , Pharmacists/statistics & numerical data , Pharmacy Service, Hospital , Prospective StudiesABSTRACT
AIMS: Biomarkers are not recommended until now to guide the management of patients with heart failure (HF). Soluble suppression of tumorigenicity 2 (sST2) appears as a promising biomarker. The current study considered pre-discharged sST2 values as a guide for medical management in patients admitted for acute HF decompensation, in an attempt to reduce hospital readmission. METHODS AND RESULTS: STADE-HF was a blinded prospective randomized controlled trial and included 123 patients admitted for acute HF. They were randomized into the usual treatment group (unknown sST2 level) or the interventional treatment group, for whom sST2 level was known and used on Day 4 of hospitalization to guide the treatment. The primary endpoint was the readmission rate for any cause at 1 month. It occurred in 10 patients (19%) in the usual group and 18 (32%) in the sST2 group without statistical difference (P = 0.11). Post hoc analysis in the whole group shows that the mean duration of hospitalization was lower in patients with low sST2 (<37 ng/mL) at admission vs. high sST2 (8.5 ± 9.5 vs. 14.8 ± 14.9 days, respectively, P = 0.003). In addition, a decrease in sST2 greater than 18% is significantly associated with a lower readmission rate. CONCLUSIONS: Soluble suppression of tumorigenicity 2-guided therapy over a short period of time does not reduce readmissions. However, sST2 was clearly associated with duration of hospitalization, and the decrease in sST2 was associated with decreased rehospitalizations. Long-term outcome using sST2-guided therapy deserves further investigations.
Subject(s)
Heart Failure , Natriuretic Peptide, Brain , Heart Failure/therapy , Humans , Peptide Fragments , Pilot Projects , Prognosis , Prospective StudiesSubject(s)
Heart Failure , Chronic Disease , Heart Failure/drug therapy , Humans , Interdisciplinary Studies , Pilot ProjectsABSTRACT
BACKGROUND: Cardiovascular diseases are the first cause of mortality in patients with diabetes, and LDL-cholesterol is a well-established cardiovascular risk factor. This study aimed to assess rate of LDL-cholesterol target attainment among patients with diabetes at very-high cardiovascular risk treated with statins, and to identify predictive factors of non-attainment of target in this population. METHODS: Patients were recruited in the Nutrition-Diabetes unit of Montpellier University Hospital, France, from 2014 to 2017. We included all consecutive patients with type 1 or type 2 diabetes receiving statin treatment and at very-high cardiovascular risk according to 2016 ESC guidelines, therefore having a LDL-cholesterol target of <1.8â¯mmol/L. LDL-cholesterol levels were measured upon admission. Variables independently associated with non-attainment of LDL-Cholesterol target were assessed using multivariable logistic regression. RESULTS: 654 patients were included. Mean age was 63.8â¯years (SD 11.0), 41.9% were women and 42.3% had a history of cardiovascular disease. 59% of patients did not achieve LDL-cholesterol target, with a median value (interquartile range) of 2.4â¯mmol/L (2.1-2.9) versus 1.4â¯mmol/L (1.1-1.6) in patients at target. Risk of non-attainment of LDL-cholesterol target value was increased in women (odds ratio [95% confidence interval]: 2.27 [1.62-3.17]) and decreased in patients with history of coronary artery disease (0.64 [0.45-0.89]) or history of stroke or transient ischemic attack (0.59 [0.33-1.07]). CONCLUSIONS: Management of dyslipidemia is suboptimal, even in very-high risk patients with diabetes under statins. Lipid-lowering treatment should be intensified, in particular in very high risk patients with diabetes who are women or in primary cardiovascular prevention. Clinical Trial number: NCT03449784.
Subject(s)
Cardiovascular Diseases/blood , Cardiovascular Diseases/epidemiology , Cholesterol, LDL/blood , Diabetes Mellitus/blood , Diabetes Mellitus/epidemiology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Aged , Biomarkers/blood , Cardiovascular Diseases/drug therapy , Diabetes Mellitus/drug therapy , Female , France/epidemiology , Humans , Incidence , Male , Middle Aged , Risk Factors , Treatment OutcomeSubject(s)
Heart Failure/drug therapy , Interleukin-1 Receptor-Like 1 Protein/blood , Patient Readmission , Adrenergic beta-Antagonists/therapeutic use , Aminobutyrates/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Biphenyl Compounds , Cardiovascular Agents/therapeutic use , Drug Combinations , Female , Heart Failure/blood , Humans , Ivabradine/therapeutic use , Male , Mineralocorticoid Receptor Antagonists/therapeutic use , Patient Care Planning , Sodium Potassium Chloride Symporter Inhibitors/therapeutic use , Tetrazoles/therapeutic use , ValsartanABSTRACT
BACKGROUND: Medication errors (ME) are major public health issues in hospitals because of their consequences on patients' morbi-mortality. This study aims to evaluate the prevalence of ME at admission and discharge of hospitalization in diabetic and non-diabetic patients, and determine their potential clinical impact. METHOD: This prospective observational study was conducted at the Endocrinology-Diabetology-Nutrition Department. All adult patients admitted were eligible. A total of 904 patients were included, of which 671 (74.2%) with diabetes mellitus. Clinical pharmacists conducted medication reconciliation: they collected the Best Possible Medication History and then compared it with admission and discharge prescriptions to identify medication discrepancies. ME were defined as unintended medication discrepancies if corrected by the physician. RESULTS: Clinical pharmacists allowed correcting ME in 176/904 (19.5%) patients at admission and in 86/865 (9.9%) patients at discharge. More than half of ME were omissions. Diabetic patients were more affected by ME than non-diabetic patients, both at admission (22.1% vs 12.0%, p<0.001) and at discharge (11.4% vs 5.7%, p=0.01). The diabetic group also had more potentially severe and very severe ME. Diabetic patients had on average twice more medications than non-diabetic patients (8.7±4.5 vs 4.4±3.4, p<0.001). The polypharmacy associated with diabetes, but not diabetes mellitus itself, was identified as a risk factor of ME. CONCLUSIONS: The intervention of clinical pharmacists allowed correcting 378 ME in 25.8% of the cohort before they caused harm. Clinicians, pharmacists and other health care providers should therefore work together to improve patients' safety, in particular in high-risk patients such as diabetic patients.
Subject(s)
Diabetes Mellitus/drug therapy , Medication Errors/statistics & numerical data , Medication Reconciliation , Pharmacy Service, Hospital/standards , Adult , Aged , Comorbidity , Female , France , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Patient Admission , Patient Discharge , Patient Safety , Pharmacists , Polypharmacy , Prospective Studies , Risk FactorsABSTRACT
RIP140 is a transcriptional coregulator (also known as NRIP1) which plays very important physiological roles by finely tuning the activity of a large number of transcription factors. Noticeably, the RIP140 gene has been shown to be involved in the regulation of energy expenditure, in mammary gland development and intestinal homeostasis as well as in behavior and cognition. RIP140 is also involved in the regulation of various oncogenic signaling pathways and participates in the development and progression of solid tumors. This short review aims to summarize the role of this transcription factor on nuclear estrogen receptors, E2F and Wnt signaling pathways based on recent observations focusing on breast, ovary, liver and colon tumors.
Subject(s)
Adaptor Proteins, Signal Transducing/physiology , Neoplasms/metabolism , Nuclear Proteins/physiology , Transcription, Genetic , Estrogens/metabolism , Female , Humans , Male , Neoplasms/classification , Nuclear Receptor Interacting Protein 1 , Signal Transduction , Wnt Proteins/metabolismABSTRACT
RIP140 is a transcriptional coregulator, (also known as NRIP1), which finely tunes the activity of various transcription factors and plays very important physiological roles. Noticeably, the RIP140 gene has been implicated in the control of energy expenditure, behavior, cognition, mammary gland development and intestinal homeostasis. RIP140 is also involved in the regulation of various oncogenic signaling pathways and participates in the development and progression of solid tumors. During the past years, several papers have reported evidences linking RIP140 to hematologic malignancies. Among them, two recent studies with correlative data suggested that gene expression signatures including RIP140 can predict survival in chronic lymphocytic leukemia (CLL). This review aims to summarize the literature dealing with the expression of RIP140 in CLL and to explore the potential impact of this factor on transcription pathways which play key roles in this pathology.
Subject(s)
Adaptor Proteins, Signal Transducing/biosynthesis , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Nuclear Proteins/biosynthesis , Adaptor Proteins, Signal Transducing/genetics , Animals , Humans , Nuclear Proteins/genetics , Nuclear Receptor Interacting Protein 1ABSTRACT
Vitamin B6 is well-known for its role as a cofactor in many enzymatic reactions and recently, several epidemiological studies have highlighted the importance of this vitamin as a protective agent against various cancers: elevated vitamin B6 plasma levels were associated with a lower risk of colorectal cancer development, for example. In vivo studies have shown that vitamin B6 decreased cell proliferation and enhanced the immune response. At the cellular level, antioxidant, pro-apoptotic and anti-angiogenic effects have been identified. At the molecular level, vitamin B6 is able to inhibit the transactivation potential of various nuclear receptors. Interestingly, a recent paper has described the conjugation of vitamin B6 to RIP140 (receptor interacting protein of 140âkDa), a protein that acts as a transcriptional corepressor of nuclear receptors. This post-translational modification increases the transcriptional repression of RIP140 and regulates its subcellular localization and its ability to interact with different protein partners. Finally, vitamin B6 is involved in the methyl donor cycle ant thus, some of the antitumor properties of vitamin B6 may involve an indirect effect on the level of DNA or histone methylation. All of these mechanistic and clinical data justify further studies to decipher the mechanism of action of vitamin B6 and its clinical interest in combination with molecules typically used in chemotherapy or hormonal therapy.