Evaluating the appropriateness of antimicrobial treatment in hospitalized patients: a comparison of three methods.

BACKGROUND: Approximately 20-50% of antimicrobial therapy in hospitalized patients is considered inappropriate, which may be associated with increased morbidity and mortality. The best method for evaluation of appropriateness is not well defined. AIM: To evaluate the rate of appropriate antimicrobial therapy in a secondary hospital using three different methods, and determine the rate of agreement between the different methods. METHODS: A point prevalence study included all adult hospitalized patients receiving systemic antimicrobial therapy during 2016, screened on a single day. Clinical, laboratory and therapeutic data were collected from patient files, and appropriateness was rated with a qualitative evaluation by expert opinion. In addition, a quantitative evaluation was performed according to 11 quality indicators (QIs) rated for each patient. A strict definition of appropriateness was fulfilled if six essential QIs were met, and a lenient definition was fulfilled if at least five QIs were met. Agreement between methods was analysed using kappa statistic. FINDINGS: Among 106 patients included, rates of appropriateness of antimicrobial therapy ranged from 20% to 75%, depending on the method of evaluation. Very low agreement was found between the strict definition and expert opinion (kappa=0.068), and medium agreement was found between the lenient definition and expert opinion (kappa=0.45). CONCLUSIONS: Rates of appropriateness of antimicrobial therapy varied between evaluation methods, with low to moderate agreement between the different methods.

Multiple pathologies are common in Alzheimer patients in clinical trials.

OBJECTIVE: To determine the frequency of multiple pathology [Alzheimer Disease (AD) plus Vascular Dementia and/or Dementia with Lewy Bodies] in patients enrolled in clinical trials of AD therapy, and to compare the cognitive and functional assessments between patients with pure AD and AD with multiple pathology. METHODS: We conducted a retrospective analysis of patients with a clinical diagnosis of AD who were enrolled in AD therapy clinical trials and subsequently received an autopsy for confirmation of their diagnosis from 2000 to 2009. Performance on cognitive screening tests, namely Modified Mini Mental state (3MS) exam, Mini Mental state Exam (MMSE) and Functional Rating Scale (FRS) were compared between patients with pure AD and multiple pathology. RESULTS: Autopsy reports were available for 16/47 (34%) of deceased patients. Of these 16 patients, 5 (31%) had pure AD pathology, 10 (63%) had AD with other pathology, and 1 (6%) had non-AD pathology. Compared to patients with pure AD, patients with AD mixed with other pathology had poorer baseline FRS in problem-solving (p<0.01) and community affairs (p<0.02). CONCLUSION: While the strict enrollment criteria for clinical trials identified the presence of AD pathology in the majority of cases (15/16), multiple pathology was more common than pure AD in our series of autopsied patients. Premortem biomarkers that can distinguish between pure AD and AD with multiple pathology will be beneficial in future clinical trials and dementia patient management.

Cytology of benign multicystic peritoneal mesothelioma in peritoneal washings.

OBJECTIVE: To describe the cytological aspect of peritoneal washings in benign multicystic peritoneal mesothelioma (BMPM). METHODS: Three peritoneal washing specimens stained by standard cytological and histological procedures and analysed by light microscopy. RESULTS: The specimens showed an abundance of monomorphous mesothelial cells devoid of atypia or mitoses. The mesothelial cells were calretinin positive. They also showed numerous squamous metaplastic cells arranged in flat sheets or isolated cells. The background contained some inflammatory cells. CONCLUSION: The combination of cytology of the peritoneal washing, histology (cell block and surgical specimen) and clinical history allow differentiation of BMPM from other cystic lesions (cystic lymphangioma and malignant mesothelioma).

In situ hybridization study of cytokeratin 4, 13, 16 and 19 mRNAs in human developing junctional epithelium.

Cytokeratins (CKs) are now considered to be reliable markers for following the development and differentiation of epithelial tissue. We have investigated the pathway of differentiation in human developing junctional epithelium using monoclonal antibodies and two-dimensional gel electrophoresis of microdissected tissue to identify CK 19, CK 16, CK 14, CK 13, CK 6, CK 5, CK 4 in the junctional epithelium (JE) over partially erupted human teeth. The CK profile was similar to that of developing oral epithelia, suggesting that the junctional epithelium in teeth during eruption is of odontogenic origin. The present study used in situ hybridization to determine the distribution of the mRNAs of CKs 19, 16, 13 and 4 in human developing junctional epithelium and to examine the correlation between mRNAs and their encoded proteins. CK 19 mRNA was abundant in the basal cell layers of the primary junctional epithelium (PJE) but less concentrated in the suprabasal layers. CK16, 13 and 4 mRNAs were abundant in the basal cell layers of the PJE. The parabasal cell layers reacted intensely to the cRNA probe complementary to CK16 mRNA, as were the reactions in the suprabasal cell layers of the PJE for the CK 13 and 4 probes. Our results demonstrate that the PJE express the genes encoding for CKs 16 and 4 that have been revealed previously only by electrophoresis. They therefore confirm that the PJE is a well-differentiated stratified epithelium with a complex unique phenotype that produces CKs specific for basal cells (CK 19), CKs associated with hyperproliferation (CK 16), and finally those associated with stratification (CKs 4 and 13). Only synthesis of CK 19 protein and mRNA are strictly parallel. CKs 4 and 13 mRNAs are present in basal and suprasal cells, while their encoded proteins were not, except for CK 13 in suprabasal cell layers of PJE, where the amount of its mRNAs was coincident with the expression of the protein.

Cytokeratin profile of the junctional epithelium in partially erupted teeth.

This study uses cytokeratins (CK) as markers to investigate the phenotype of the junctional epithelium (JE) in partially erupted human teeth. The gingival samples, which were clinically healthy, were carefully dissected from the teeth. Cryostat sections were cut for histological staining, immunofluorescence microscopy and gel electrophoresis. Cytokeratins were extracted after microdissection. The basal and suprabasal epithelial cell markers, cytokeratins 4, 5, 13, 14 and 19 were detected with specific monoclonal antibodies. They showed that the junctional epithelium in erupting teeth has a complex topography. The cytokeratin immunohistochemical profile distinguished between the primary junctional epithelium (CK 5, 14 and 19 in basal and suprabasal cells and CK 13 faintly stained throughout the suprabasal layers) and the adjacent epithelium that had the same cytokeratin profile as the sulcular epithelium (CK 5, 14 and 19 in basal cells and CK 4 and 13 intensively stained in the suprabasal cells). Extraction, two-dimensional electrophoresis and western blotting showed that this transitional JE during eruption also contained CK 6, 16 and perhaps CK 4. Thus, the JE in erupting teeth shows patterns of CK distribution that are very similar to that of developing oral epithelia.

Chemically separated connective tissue grafts: clinical application and histological evaluation.

Subepithelial palatal connective tissue grafts, separated from the epithelium either chemically (n = 5) or surgically (n = 2) were inserted in patients presenting with gingival recession. Biopsies at the grafted tissue and a portion of non-keratinized mucosa were taken 12 months later. Histology showed keratinization of the newly formed epithelium, and interestingly a deep projection of epithelium into the connective tissue in almost all biopsies, sometimes with an enlargement and a cyst-like space. We conclude that chemical separation of epithelium and connective tissue is clinically feasible for connective tissue grafts and that the subepithelial connective tissue grafting technique should be modified to avoid this projection of epithelium.