Enhancing drug therapy in ostomy patients: Best practice recommendations for medication management.

BACKGROUND: Ostomy surgery is a common procedure that poses various challenges for patients and healthcare professionals. There are numerous guidelines addressing different ostomy-related problems (ORPs) and supporting an interdisciplinary approach for ostomy care, but evidence-based literature for optimizing drug therapy after ostomy surgery is lacking. AIM: To investigate and characterize typical ORPs in relation to drug therapy and provide best practice recommendations from a pharmaceutical point of view. METHODS: Patients with an ileo- or colostomy were consecutively enrolled in a prospective, interventional monocentric cohort study during hospitalization, with particular attention to medication. A clinical pharmacist assessed DRPs by performing level 3 medication reviews and patient interviews. Pharmacists' interventions (PIs) were evaluated by two senior clinical pharmacists and documented in DokuPIK (Documentation of Pharmacists' Interventions in the Hospital). Following interdisciplinary discussions, physicians either accepted or rejected the proposed changes in drug therapy. Comparisons were made between ileostomy and colostomy patients regarding type and extent of PIs. RESULTS: Out of the 80 patients included in the cohort, 54 (67.5%) had an ileostomy and 26 (32.5%) a colostomy. In this study, 288 PIs were documented (234 ileostomy vs. 54 colostomy), of wich 94.0% were accepted and implemented by the physicians. The most common reason for PIs in both subgroups (29.6% ileostomy vs. 26.1% colostomy) was a missing drug although indicated (e.g. no loperamide, but high stoma output). The proportion of PIs associated with the ostomy was higher in ileostomy patients (48.3% ileostomy vs. 31.5% colostomy; p = 0.025). Typical ORPs were extracted and analyzed as case studies including recommendations for their respective management and prevention. CONCLUSION: This study highlights the importance of clinical pharmacists being a part of interdisciplinary teams to collaboratively improve ostomy care and patient safety. Especially ileostomy patients are more vulnerable for ORPs in the context of drug therapy and need to be monitored carefully.

Efficacy of Tigecycline as Salvage Therapy in Multidrug-Resistant Febrile Neutropenia in Patients with Acute Leukemia-A Single Center Analysis.

Severe infectious complications remain the main cause of mortality in leukemia patients due to a long period of profound neutropenia. Standardized regimens for antimicrobial, antifungal, and antiviral prophylaxis and therapy in neutropenic patients have improved infection-associated mortality. Nevertheless, many patients are refractory to these multidrug approaches. Tigecycline is a last-resort antibiotic with a broad-spectrum activity; unfortunately, clinical experience in multidrug-resistant febrile neutropenia is limited. The aim was to evaluate the efficacy of tigecycline treatment in comparison to standard treatment in this patient cohort. In this single center analysis, we analyzed the clinical courses of 73 patients with acute leukemia and diagnosis of febrile neutropenia resistant to hospital-based multidrug escalation levels who continued on a standard approach without antibiotics as the last resort (n = 30) or were switched to tigecycline in addition to carbapenem treatment (n = 43). We observed comparable overall response rates (decrease in C-reactive protein or resolution of fever) in both patient cohorts. Switching the antibiotic approach to tigecycline showed lower absolute sepsis (33% vs. 47%, p = 0.235) and infection-associated mortality rates (5% vs. 13%, p = 0.221). Prospective larger randomized studies are necessary to underline these results and to be able to generate reliable statistics.

Potentially Inappropriate Medication Use in Multimorbid Elderly Inpatients: Differences Between the FORTA, PRISCUS and STOPP Ratings.

BACKGROUND: Several classifications to identify and avoid use of potentially inappropriate medications (PIMs) in the elderly have been published. To what extent these classifications match each other and whether there are differences in the prevalence of PIM use at admission, during the inpatient stay and at discharge are largely unreported. OBJECTIVES: To determine the PIM prevalence in elderly patients at a university hospital, with a special focus on different classification systems and the chronological sequence, and to examine a possible association between PIM use and the reason for admission, as well as severe side effects and consequences of PIM use during hospitalization. METHODS: On the basis of the criteria provided by FORTA (Fit for the Aged), PRISCUS (Latin for 'time-honoured') and STOPP (Screening Tool of Older Persons' Potentially Inappropriate Prescriptions), medication in patients over the age of 65 years was screened retrospectively within four point prevalence analyses at admission, during the inpatient stay and at discharge. Evaluation of a possible association between PIM use and the primary diagnosis or severe side effects during hospitalization was performed according to an analysis using the World Health Organization Uppsala Monitoring Centre system for standardized case causality assessment. RESULTS: Of 200 patients, 176 (88 %) received at least one PIM at admission, during the inpatient stay and/or at discharge (116 patients according to FORTA, 113 according to PRISCUS and 138 according to STOPP). When the PIM prevalence was compared between the three different sets of criteria, STOPP identified significantly more patients receiving PIMs than FORTA (P = 0.022) and PRISCUS (P = 0.010). At the patient level and at the drug level, the use of PIMs increased during the inpatient stay; however, the PIM prevalence was similar at admission and at discharge, both at the patient level and at the drug level. CONCLUSION: Medication is rated significantly differently by FORTA, PRISCUS and STOPP. In addition, a significant rise in prescribing of PIMs during the inpatient stay illustrates that a reduction in PIM use during the inpatient stay is essential, as it is known that avoiding PIM use in older adults is one strategy to decrease the risk of adverse events.

A highly efficient type I ß-turn mimetic simulating an Asx-Pro-turn-like structure.

Asx-Pro-turns have been identified with high frequency in protein structures nucleating type I ß-turns. By bridging the amino acid side chain in position i with a nitrogen substituent in position i+2 by ring-closing olefin metathesis (RCM), peptide mimetics of type 1 could be developed. NMR based conformational investigations indicated a stable intramolecular H-bond constraining a U-turn conformation that was predicted to simulate a type I ß-turn.

Dopamine D2, D3, and D4 selective phenylpiperazines as molecular probes to explore the origins of subtype specific receptor binding.

Assembling phenylpiperazines with 7a-azaindole via different spacer elements, we developed subtype selective dopamine receptor ligands of types 1a,c, 2a, and 3a preferentially interacting with D4, D2, and D3, respectively. To complete this set, the methylthio analogues 2b and 3b exceeding the affinity of 2a and 3a by one order of magnitude and the structural intermediate 1b were synthesized. These chemically similar but biologically divergent target compounds served as molecular probes for radioligand displacement experiments, mutagenesis, and docking studies on homology models based on the recent crystal structure of the beta2-adrenergic receptor. Specific interactions with the highly conserved amino acids Asp3.32 and His6.55 and less conserved residues at positions 2.61, 2.64, 3.28, and 3.29 were identified. Inclusion of a carefully modeled extracellular loop 2 displayed two nonconserved residues in EL2 that differently contribute to ligand binding. Obviously, subtype selectivity is caused by nonconserved but frequently mediated by conserved amino acids.

Novel insights into GPCR-peptide interactions: mutations in extracellular loop 1, ligand backbone methylations and molecular modeling of neurotensin receptor 1.

Investigating prototypical interactions between NT(8-13) and the human neurotensin receptor 1 (hNTR1), we created a receptor-ligand model that was validated by site-directed mutagenesis and structure-activity relationship studies. Stabilization of the extracellular loop 1 (EL1) by pi-stacking clusters proved to be important for agonist binding when substitution of six conserved amino acids by alanine resulted in an agonist specific loss of maximal binding capacity. In agreement with our modeling studies, EL1 seems to adopt a clamp-type border area controlling the shape of the binding site crevice. Employing chemically manipulated peptide analogs as molecular probes, the impact of backbone modifications on receptor-ligand interaction, especially the influence on ligand conformation, was examined in binding studies and explained by in silico analysis.

Peptide backbone modifications on the C-terminal hexapeptide of neurotensin.

To compare backbone-induced susceptibilities with affinity changes that are caused by side-chain modifications in the respective positions, structure activity relationship studies on a series of NT(8-13) analogues were performed providing valuable insights into the major requirement for neurotensin receptor recognition and activation. The data led us to highly potent NTR1 ligands and the generation of a pharmacophore model that will be helpful for the discovery of therapeutically relevant non-peptidic NTR1 agonists.