Science.gov

Sample records for inappropriate empiric antifungal

  1. Empiric antifungal therapy in patients with febrile neutropenia.

    PubMed

    Ferrara, Jenna J; MacDougall, Conan; Gallagher, Jason C

    2011-04-01

    Invasive fungal infections, most commonly candidiasis or aspergillosis, are a major cause of morbidity and mortality among patients with neutropenia. Difficulty in diagnosing invasive fungal infections in these patients complicates decisions regarding pharmacotherapy. Because of the difficult diagnosis and the significant morbidity and mortality of fungal infections in patients with neutropenia, systemic antifungal agents are used as empiric antifungal therapy in patients with febrile neutropenia who are not responding to antibacterial therapy. The pharmacotherapy of invasive fungal infections has evolved rapidly within the past several years as numerous antifungal agents--different formulations of amphotericin B, azoles, and echinocandins--have become available for use as empiric antifungal therapy in patients with febrile neutropenia. Various levels of evidence support the use of these agents for this indication. Their use is limited, however, by drug intolerance, drug interactions, adverse-event profiles, and limited activity with some mold species. Thus, considerations for selecting an antifungal drug for empiric use in patients with febrile neutropenia should include the epidemiology of fungal infections in the individual patient's institution and the specific clinical circumstances of the patient.

  2. Inappropriate continued empirical vancomycin use in a hospital with a high prevalence of methicillin-resistant Staphylococcus aureus.

    PubMed

    Kim, Nak-Hyun; Koo, Hei Lim; Choe, Pyoeng Gyun; Choe, Pyeong Gyun; Cheon, Shinhye; Kim, Moonsuk; Kim, Moon Suk; Lee, Myung Jin; Jung, Younghee; Jung, Young Hee; Park, Wan Beom; Song, Kyoung-Ho; Kim, Eu Suk; Bang, Ji Hwan; Kim, Hong Bin; Park, Sang Won; Kim, Nam Joong; Oh, Myoung-don; Kim, Eui Chong

    2015-02-01

    Vancomycin is frequently inappropriately prescribed, especially as empirical treatment. The aim of this study was to evaluate (i) the amount of inappropriate continued empirical vancomycin use as a proportion of total vancomycin use and (ii) the risk factors associated with inappropriate continued empirical vancomycin use. We reviewed the medical records of adult patients who had been prescribed at least one dose of parenterally administered vancomycin between January and June 2012, in a single tertiary care hospital. When empirically prescribed vancomycin treatment was continued after 96 h without documentation of beta-lactam-resistant Gram-positive microorganisms in clinical specimens with significance, the continuation was considered inappropriate, and the amount used thereafter was considered inappropriately used. We identified risk factors associated with inappropriate continued empirical vancomycin use by multiple logistic regression. During the study period, the amount of parenterally administered vancomycin prescribed was 34.2 defined daily doses (DDDs)/1,000 patient-days (1,084 prescriptions for 971 patients). The amount of inappropriate continued empirical vancomycin use was 8.5 DDDs/1,000 patient-days, which represented 24.9% of the total parenterally administered vancomycin used (8.5/34.2 DDDs/1,000 patient-days). By multivariate analyses, inappropriate continued empirical vancomycin use was independently associated with the absence of any documented etiological organism (adjusted odds ratio [aOR], 1.60 [95% confidence interval {CI}, 1.06 to 2.41]) and suspected central nervous system (CNS) infections (aHR, 2.33 [95% CI, 1.20 to 4.50]). Higher Charlson's comorbidity index scores were inversely associated with inappropriate continued empirical vancomycin use (aHR, 0.90 [95% CI, 0.85 to 0.97]). Inappropriate continued empirical vancomycin use represented 24.9% of the total amount of vancomycin prescribed, which indicates room for improvement.

  3. Outcome of inappropriate empirical antibiotic therapy in patients with Staphylococcus aureus bacteraemia: analytical strategy using propensity scores.

    PubMed

    Kim, S-H; Park, W-B; Lee, C-S; Kang, C-I; Bang, J-W; Kim, H-B; Kim, N-J; Kim, E-C; Oh, M D; Choe, K-W

    2006-01-01

    Patients with Staphylococcus aureus bacteraemia (SAB) who received either inappropriate or appropriate empirical therapy were compared by using two risk stratification models: (1) a cohort study using a propensity score to adjust for confounding by empirical treatment assignment; and (2) a propensity-matched case-control study. Inappropriate empirical therapy was modelled on the basis of patient characteristics, and included in the multivariate model to adjust for confounding. For case-matching analysis, patients with inappropriate empirical therapy (cases) were matched to those with appropriate empirical therapy (controls) on the basis of the propensity score (within 0.03 on a scale of 0-1). In total, 238 patients with SAB were enrolled in the cohort study. Characteristics associated with inappropriate empirical therapy were methicillin resistance, underlying haematological malignancy, no history of colonisation with methicillin-resistant S. aureus, and a long hospital stay before SAB. These variables were included in the propensity score, which had an area under the receiver operating characteristics curve of 85%. In the cohort study, SAB-related mortality was 39% (45/117) for inappropriate empirical therapy vs. 28% (34/121) for appropriate empirical therapy (odds ratio (OR) 1.60; 95% CI 0.93-2.76). After adjustment for independent predictors for mortality and the propensity score, inappropriate empirical therapy was not associated with mortality (adjusted OR 1.39; 95% CI 0.62-3.15). In the matched case-control study (50 pairs), SAB-related mortality was 32% (16/50) for inappropriate empirical therapy and 28% (14/50) for appropriate empirical therapy (McNemar's test; p 0.85; OR 1.15; 95% CI 0.51-2.64). In conclusion, inappropriate empirical therapy resulted in only a slight tendency towards increased mortality in patients with SAB.

  4. Empiric antifungal therapy and outcomes in extremely low birth weight infants with invasive candidiasis.

    PubMed

    Greenberg, Rachel G; Benjamin, Daniel K; Gantz, Marie G; Cotten, C Michael; Stoll, Barbara J; Walsh, Michele C; Sánchez, Pablo J; Shankaran, Seetha; Das, Abhik; Higgins, Rosemary D; Miller, Nancy A; Auten, Kathy J; Walsh, Thomas J; Laptook, Abbot R; Carlo, Waldemar A; Kennedy, Kathleen A; Finer, Neil N; Duara, Shahnaz; Schibler, Kurt; Ehrenkranz, Richard A; Van Meurs, Krisa P; Frantz, Ivan D; Phelps, Dale L; Poindexter, Brenda B; Bell, Edward F; O'Shea, T Michael; Watterberg, Kristi L; Goldberg, Ronald N; Smith, P Brian

    2012-08-01

    To assess the impact of empiric antifungal therapy for invasive candidiasis on subsequent outcomes in premature infants. This was a cohort study of infants with a birth weight ≤ 1000 g receiving care at Neonatal Research Network sites. All infants had at least one positive culture for Candida. Empiric antifungal therapy was defined as receipt of a systemic antifungal on the day of or the day before the first positive culture for Candida was drawn. We created Cox proportional hazards and logistic regression models stratified on propensity score quartiles to determine the effect of empiric antifungal therapy on survival, time to clearance of infection, retinopathy of prematurity, bronchopulmonary dysplasia, end-organ damage, and neurodevelopmental impairment (NDI). A total of 136 infants developed invasive candidiasis. The incidence of death or NDI was lower in infants who received empiric antifungal therapy (19 of 38; 50%) compared with those who had not (55 of 86; 64%; OR, 0.27; 95% CI, 0.08-0.86). There was no significant difference between the groups for any single outcome or other combined outcomes. Empiric antifungal therapy was associated with increased survival without NDI. A prospective randomized trial of this strategy is warranted. Copyright © 2012 Mosby, Inc. All rights reserved.

  5. Forum report: issues in clinical trials of empirical antifungal therapy in treating febrile neutropenic patients.

    PubMed

    Bennett, John E; Powers, John; Walsh, Thomas; Viscoli, Claudio; de Pauw, Ben; Dismukes, William; Galgiani, John; Glauser, Michel; Herbrecht, Raoul; Kauffman, Carol; Lee, Jeannette; Pappas, Peter; Rex, John; Verweij, Paul

    2003-04-15

    There is inferential evidence that some patients with prolonged neutropenia and fever not responding to antibacterial agents are at sufficient risk of deep mycoses to warrant empirical therapy, although superiority of an antifungal agent over placebo has not been conclusively demonstrated. Amphotericin B deoxycholate, liposomal amphotericin B, and intravenous itraconazole followed by oral itraconazole solution are licensed in the United States for this indication. Fluconazole and voriconazole have given favorable results in clinical trials of patients with low and high risk of deep mold infections, respectively. Design features that can profoundly influence outcome of empirical trials are (1) inclusion of low-risk patients, (2) failure to blind the study, (3) obscuration of antifungal effects by changing antibacterial antibiotics, (4) failure to balance both arms of the study in terms of patients with prior antifungal prophylaxis or with severe comorbidities, (5) the merging of end points evaluating safety with those of efficacy, and (6) choice of different criteria for resolution of fever.

  6. Is preemptive antifungal therapy a good alternative to empirical treatment in prolonged febrile neutropenia?

    PubMed

    Koch, Erica; Rada, Gabriel

    2016-06-09

    Patients with prolonged febrile neutropenia are at high risk of invasive fungal infection, so it has been standard practice to initiate empirical antifungal therapy in these cases. However, this strategy is associated with important toxicity, so diagnostic test-guided preemptive antifungal therapy has been proposed as an alternative. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified three systematic reviews including twelve studies overall. Four randomized controlled trials addressed the question of this article. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded it is not clear whether preemptive strategy affects mortality because the certainty of the evidence is very low, but it might slightly decrease the use of antifungal agents in patients with prolonged febrile neutropenia.

  7. Biomarker-based strategy for early discontinuation of empirical antifungal treatment in critically ill patients: a randomized controlled trial.

    PubMed

    Rouzé, Anahita; Loridant, Séverine; Poissy, Julien; Dervaux, Benoit; Sendid, Boualem; Cornu, Marjorie; Nseir, Saad

    2017-09-22

    The aim of this study was to determine the impact of a biomarker-based strategy on early discontinuation of empirical antifungal treatment. Prospective randomized controlled single-center unblinded study, performed in a mixed ICU. A total of 110 patients were randomly assigned to a strategy in which empirical antifungal treatment duration was determined by (1,3)-β-D-glucan, mannan, and anti-mannan serum assays, performed on day 0 and day 4; or to a routine care strategy, based on international guidelines, which recommend 14 days of treatment. In the biomarker group, early stop recommendation was determined using an algorithm based on the results of biomarkers. The primary outcome was the percentage of survivors discontinuing empirical antifungal treatment early, defined as a discontinuation strictly before day 7. A total of 109 patients were analyzed (one patient withdraw consent). Empirical antifungal treatment was discontinued early in 29 out of 54 patients in the biomarker strategy group, compared with one patient out of 55 in the routine strategy group [54% vs 2%, p < 0.001, OR (95% CI) 62.6 (8.1-486)]. Total duration of antifungal treatment was significantly shorter in the biomarker strategy compared with routine strategy [median (IQR) 6 (4-13) vs 13 (12-14) days, p < 0.0001). No significant difference was found in the percentage of patients with subsequent proven invasive Candida infection, mechanical ventilation-free days, length of ICU stay, cost, and ICU mortality between the two study groups. The use of a biomarker-based strategy increased the percentage of early discontinuation of empirical antifungal treatment among critically ill patients with suspected invasive Candida infection. These results confirm previous findings suggesting that early discontinuation of empirical antifungal treatment had no negative impact on outcome. However, further studies are needed to confirm the safety of this strategy. This trial was registered at Clinical

  8. A prospective, randomized study of empirical antifungal therapy for the treatment of chemotherapy-induced febrile neutropenia in children.

    PubMed

    Caselli, Désirée; Cesaro, Simone; Ziino, Ottavio; Ragusa, Pietro; Pontillo, Alfredo; Pegoraro, Anna; Santoro, Nicola; Zanazzo, Giulio; Poggi, Vincenzo; Giacchino, Mareva; Livadiotti, Susanna; Melchionda, Fraia; Chiodi, Marcello; Aricò, Maurizio

    2012-07-01

    Given that the rationale for empirical antifungal therapy in neutropenic children is limited and based on adult patient data, we performed a prospective, randomized, controlled trial that evaluated 110 neutropenic children with persistent fever. Those at high risk for invasive fungal infections (IFI) received caspofungin (Arm C) or liposomal amphotericinB (Arm B); those with a lower risk were randomized to receive Arm B, C, or no antifungal treatment (Arm A). Complete response to empirical antifungal therapy was achieved in 90/104 patients (86·5%): 48/56 at high risk (85·7%) [88·0% in Arm B; 83·9% in Arm C (P = 0·72)], and 42/48 at low risk (87·5%) [87·5% in control Arm A, 80·0% Arm B, 94·1% Arm C; (P = 0·41)]. None of the variables tested by multiple logistic regression analysis showed a significant effect on the probability to achieve complete response. IFI was diagnosed in nine patients (8·2%, 95% confidence interval, 3·8-15·0). This randomized controlled study showed that empirical antifungal therapy was of no advantage in terms of survival without fever and IFI in patients aged <18 years and defined with low risk of IFI. Higher risk patients, including those with relapsed cancer, appear to be the target for empirical antifungal therapy during protracted febrile neutropenia.

  9. Pharmacoeconomic analysis of voriconazole vs. caspofungin in the empirical antifungal therapy of febrile neutropenia in Australia.

    PubMed

    Al-Badriyeh, Daoud; Liew, Danny; Stewart, Kay; Kong, David C M

    2012-05-01

    In two major clinical trials, voriconazole and caspofungin were recommended as alternatives to liposomal amphotericin B for empirical use in febrile neutropenia. This study investigated the health economic impact of using voriconazole vs. caspofungin in patients with febrile neutropenia. A decision analytic model was developed to measure downstream consequences of empirical antifungal therapy. Clinical outcomes measured were success, breakthrough infection, persistent base-line infection, persistent fever, premature discontinuation and death. Treatment transition probabilities and patterns were directly derived from data in two relevant randomised controlled trials. Resource use was estimated using an expert clinical panel. Cost inputs were obtained from latest Australian sources. The analysis adopted the perspective of the Australian hospital system. The use of caspofungin led to a lower expected mean cost per patient than voriconazole (AU$40,558 vs. AU$41,356), with a net cost saving of AU$798 (1.9%) per patient. Results were most sensitive to the duration of therapy and the alternative therapy used post-discontinuation. In uncertainty analysis, the cost associated with caspofungin is less than that with voriconazole in 65.5% of cases. This is the first economic evaluation of voriconazole vs. caspofungin for empirical therapy. Caspofungin appears to have a higher probability of having cost-savings than voriconazole for empirical therapy. The difference between the two medications does not seem to be statistically significant however.

  10. Success rate and risk factors for failure of empirical antifungal therapy with itraconazole in patients with hematological malignancies: a multicenter, prospective, open-label, observational study in Korea.

    PubMed

    Kim, Soo-Jeong; Cheong, June-Won; Min, Yoo Hong; Choi, Young Jin; Lee, Dong-Gun; Lee, Je-Hwan; Yang, Deok-Hwan; Lee, Sang Min; Kim, Sung-Hyun; Kim, Yang Soo; Kwak, Jae-Yong; Park, Jinny; Kim, Jin Young; Kim, Hoon-Gu; Kim, Byung Soo; Ryoo, Hun-Mo; Jang, Jun Ho; Kim, Min Kyoung; Kang, Hye Jin; Cho, In Sung; Mun, Yeung Chul; Jo, Deog-Yeon; Kim, Ho Young; Park, Byeong-Bae; Kim, Jin Seok

    2014-01-01

    We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462).

  11. EPICO 3.0. Empirical antifungal therapy in critically-ill hematology patients.

    PubMed

    Llinares, Pedro; Ruiz, Isabel; Zaragoza, Rafael; Ferrer, Ricard; Rodríguez, Alejandro H; Maseda, Emilio; Grau, Santiago

    Although in the past decade the management of invasive fungal infections has improved, a number of controversies persist regarding empirical antifungal treatment in critically-ill hematology patients. To identify key clinical knowledge to elaborate a set of recommendations, with a high level of consensus, necessary for the approach to fungal infections in critically-ill hematology patients. A Spanish prospective questionnaire, which measures consensus through the Delphi technique, was anonymously answered and e-mailed by 30 multidisciplinary national experts, all specialists in fungal invasive infections from six scientific national societies; intensivists, anesthesiologists, microbiologists, pharmacologists and specialists in infectious diseases. They responded to 10 questions prepared by the coordination group after a thorough review of the literature published in the last few years. For a category to be selected, the level of agreement among the experts in each category must be equal to or greater than 70%. In a second round, 73 specialists attended a face-to-face meeting held after extracting the recommendations from the chosen topics, and validated the pre-selected recommendations and derived algorithm. Assess administering antifungal treatment to patients with high/medium risk factors and fever for over 4 days after onset of antibiotic therapy, and in the event of negative galactomannan or if no detection analysis has been performed and no relevant findings in the sinus and chest computed tomography (CT) have been detected, (1) in the case the patient did not receive prophylaxis, or was administered fluconazole, caspofungin treatment is recommended; (2) in the event the patient received prophylaxis with an azole with activity against filamentous fungi, the administration of liposomal amphotericin B is recommended and caspofungin as second choice therapy; (3) in the event that the prophylaxis received was an echinocandin, liposomal amphotericin B therapy is

  12. Effects of inappropriate empirical antibiotic therapy on mortality in patients with healthcare-associated methicillin-resistant Staphylococcus aureus bacteremia: a propensity-matched analysis.

    PubMed

    Yoon, Young Kyung; Park, Dae Won; Sohn, Jang Wook; Kim, Hyo Youl; Kim, Yeon-Sook; Lee, Chang-Seop; Lee, Mi Suk; Ryu, Seong-Yeol; Jang, Hee-Chang; Choi, Young Ju; Kang, Cheol-In; Choi, Hee Jung; Lee, Seung Soon; Kim, Shin Woo; Kim, Sang Il; Kim, Eu Suk; Kim, Jeong Yeon; Yang, Kyung Sook; Peck, Kyong Ran; Kim, Min Ja

    2016-07-15

    The purported value of empirical therapy to cover methicillin-resistant Staphylococcus aureus (MRSA) has been debated for decades. The purpose of this study was to evaluate the effects of inappropriate empirical antibiotic therapy on clinical outcomes in patients with healthcare-associated MRSA bacteremia (HA-MRSAB). A prospective, multicenter, observational study was conducted in 15 teaching hospitals in the Republic of Korea from February 2010 to July 2011. The study subjects included adult patients with HA-MRSAB. Covariate adjustment using the propensity score was performed to control for bias in treatment assignment. The predictors of in-hospital mortality were determined by multivariate logistic regression analyses. In total, 345 patients with HA-MRSAB were analyzed. The overall in-hospital mortality rate was 33.0 %. Appropriate empirical antibiotic therapy was given to 154 (44.6 %) patients. The vancomycin minimum inhibitory concentrations of the MRSA isolates ranged from 0.5 to 2 mg/L by E-test. There was no significant difference in mortality between propensity-matched patient pairs receiving inappropriate or appropriate empirical antibiotics (odds ratio [OR] = 1.20; 95 % confidence interval [CI] = 0.71-2.03). Among patients with severe sepsis or septic shock, there was no significant difference in mortality between the treatment groups. In multivariate analyses, severe sepsis or septic shock (OR = 5.45; 95 % CI = 2.14-13.87), Charlson's comorbidity index (per 1-point increment; OR = 1.52; 95 % CI = 1.27-1.83), and prior receipt of glycopeptides (OR = 3.24; 95 % CI = 1.08-9.67) were independent risk factors for mortality. Inappropriate empirical antibiotic therapy was not associated with clinical outcome in patients with HA-MRSAB. Prudent use of empirical glycopeptide therapy should be justified even in hospitals with high MRSA prevalence.

  13. Empirical antifungal therapy in patients with neutropenia and persistent or recurrent fever of unknown origin.

    PubMed

    Martino, Rodrigo; Viscoli, Claudio

    2006-01-01

    Persistent or recurrent fever of unexplained origin (PFUO) in neutropenic patients receiving antibiotic therapy is commonly treated with empirical antifungal therapy (EAFT). EAFT was established as an adequate management of PFUO around 20 years ago with conventional amphotericin B deoxycholate (c-AmB), despite its high rate of infusional and systemic toxicities. In recent years, EAFT trials for PFUO have used less toxic agents, such as the lipid formulations of AmB, the new azoles, and the echinocandin, caspofungin. In clinical trials, the lipid formulations of AmB [especially liposomal AmB (L-AmB)] provided similar efficacy with lower toxicity but at a much higher cost. Although rarely used in clinical practice, fluconazole is equivalent to c-AmB, provided patients at high risk of Aspergillus infections are excluded. Intravenous itraconazole was shown to be equivalent to c-AmB, with a lower toxicity. Voriconazole did not meet non-inferiority criteria when compared with L-AmB. Caspofungin was shown to be non-inferior to L-AmB and more effective in treating baseline invasive fungal infections. To date, alternatives to AmB have shown less toxicity, but improved efficacy is less clear. This is probably because of the weakness of the indication and to the consequent difficulty in establishing objective and reproducible endpoints for comparisons. The new challenge for physicians in this field is probably presumptive antifungal therapy, an approach based on patient risk-group stratification for developing invasive candidiasis or aspergillosis and/or the use of new diagnostic techniques to identify patients at a very early stage of infection.

  14. Consensus guidelines for the use of empiric and diagnostic-driven antifungal treatment strategies in haematological malignancy, 2014.

    PubMed

    Morrissey, C O; Gilroy, N M; Macesic, N; Walker, P; Ananda-Rajah, M; May, M; Heath, C H; Grigg, A; Bardy, P G; Kwan, J; Kirsa, S W; Slavin, M; Gottlieb, T; Chen, S

    2014-12-01

    Invasive fungal disease (IFD) causes significant morbidity and mortality in patients undergoing allogeneic haemopoietic stem cell transplantation or chemotherapy for haematological malignancy. Much of these adverse outcomes are due to the limited ability of traditional diagnostic tests (i.e. culture and histology) to make an early and accurate diagnosis. As persistent or recurrent fevers of unknown origin (PFUO) in neutropenic patients despite broad-spectrum antibiotics have been associated with the development of IFD, most centres have traditionally administered empiric antifungal therapy (EAFT) to patients with PFUO. However, use of an EAFT strategy has not been shown to have an overall survival benefit and is associated with excessive antifungal therapy use. As a result, the focus has shifted to developing more sensitive and specific diagnostic tests for early and more targeted antifungal treatment. These tests, including the galactomannan enzyme-linked immunosorbent assay and Aspergillus polymerase chain reaction (PCR), have enabled the development of diagnostic-driven antifungal treatment (DDAT) strategies, which have been shown to be safe and feasible, reducing antifungal usage. In addition, the development of effective antifungal prophylactic strategies has changed the landscape in terms of the incidence and types of IFD that clinicians have encountered. In this review, we examine the current role of EAFT and provide up-to-date data on the newer diagnostic tests and algorithms available for use in EAFT and DDAT strategies, within the context of patient risk and type of antifungal prophylaxis used. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

  15. Carbapenem resistance, inappropriate empiric treatment and outcomes among patients hospitalized with Enterobacteriaceae urinary tract infection, pneumonia and sepsis.

    PubMed

    Zilberberg, Marya D; Nathanson, Brian H; Sulham, Kate; Fan, Weihong; Shorr, Andrew F

    2017-04-17

    Drug resistance among gram-negative pathogens is a risk factor for inappropriate empiric treatment (IET), which in turn increases the risk for mortality. We explored the impact of carbapenem-resistant Enterobacteriaceae (CRE) on the risk of IET and of IET on outcomes in patients with Enterobacteriaceae infections. We conducted a retrospective cohort study in Premier Perspective database (2009-2013) of 175 US hospitals. We included all adult patients with community-onset culture-positive urinary tract infection (UTI), pneumonia, or sepsis as a principal diagnosis, or as a secondary diagnosis in the setting of respiratory failure, treated with antibiotics within 2 days of admission. We employed regression modeling to compute adjusted association of presence of CRE with risk of receiving IET, and of IET on hospital mortality, length of stay (LOS) and costs. Among 40,137 patients presenting to the hospital with an Enterobacteriaceae UTI, pneumonia or sepsis, 1227 (3.1%) were CRE. In both groups, the majority of the cases were UTI (51.4% CRE and 54.3% non-CRE). Those with CRE were younger (66.6+/-15.3 vs. 69.1+/-15.9 years, p < 0.001), and more likely to be African-American (19.7% vs. 14.0%, p < 0.001) than those with non-CRE. Both chronic (Charlson score 2.0+/-2.0 vs. 1.9+/-2.1, p = 0.009) and acute (by day 2: ICU 56.3% vs. 30.4%, p < 0.001, and mechanical ventilation 35.8% vs. 11.7%, p < 0.001) illness burdens were higher among CRE than non-CRE subjects, respectively. CRE patients were 3× more likely to receive IET than non-CRE (46.5% vs. 11.8%, p < 0.001). In a regression model CRE was a strong predictor of receiving IET (adjusted relative risk ratio 3.95, 95% confidence interval 3.5 to 4.5, p < 0.001). In turn, IET was associated with an adjusted rise in mortality of 12% (95% confidence interval 3% to 23%), and an excess of 5.2 days (95% confidence interval 4.8, 5.6, p < 0.001) LOS and $10,312 (95% confidence interval $9497, $11,126, p < 0

  16. Cost-Effectiveness Analysis Comparing Two Approaches for Empirical Antifungal Therapy in Hematological Patients with Persistent Febrile Neutropenia

    PubMed Central

    Gil-Navarro, M. Victoria; Aguilar-Guisado, Manuela; Espigado, Ildefonso; de Pipaón, Maite Ruiz Pérez; Falantes, José; Pachón, Jerónimo

    2013-01-01

    New approaches of empirical antifungal therapy (EAT) in selected hematological patients with persistent febrile neutropenia (PFN) have been proposed in recent years, but their cost-effectiveness has not been studied. The aim of this study was to compare the cost-effectiveness of two different approaches of EAT in hematological patients with PFN: the diagnosis-driven antifungal therapy (DDAT) approach versus the standard approach of EAT. A decision tree to assess the cost-effectiveness of both approaches was developed. Outcome probabilities and treatment pathways were extrapolated from two studies: a prospective cohort study following the DDAT approach and a randomized clinical trial following the standard approach. Uncertainty was undertaken through sensitivity analyses and Monte Carlo simulation. The average effectiveness and economic advantages in the DDAT approach compared to the standard approach were 2.6% and €5,879 (33%) per PFN episode, respectively. The DDAT was the dominant approach in the 99.5% of the simulations performed with average cost-effectiveness per PFN episode of €32,671 versus €52,479 in the EAT approach. The results were robust over a wide range of variables. The DDAT approach is more cost-effective than the EAT approach in the management of PFN in hematological patients. PMID:23856767

  17. The relationship between the success rate of empirical antifungal therapy with intravenous itraconazole and clinical parameters, including plasma levels of itraconazole, in immunocompromised patients receiving itraconazole oral solution as prophylaxis: a multicenter, prospective, open-label, observational study in Korea.

    PubMed

    Kim, Jin Seok; Cheong, June-Won; Kim, Yeo-Kyeoung; Park, Jinny; Mun, Yeung-Chul; Kang, Hye Jin; Yi, Hyeon Gyu; Lee, Je-Hwan; Kim, Yang Soo; Ryoo, Hun-Mo; Kim, Sung-Hyun; Kim, Ho Young; Kim, Jin Young; Lee, Dong-Gun; Kim, Hoon-Gu; Kim, Hawk; Joo, Young-Don; Min, Yoo Hong

    2014-01-01

    To identify the role of therapeutic drug monitoring of itraconazole (ITZ) in the setting of empirical antifungal therapy with intravenous (IV) ITZ, we performed a multicenter, prospective study in patients with hematological malignancies who had received antifungal prophylaxis with ITZ oral solution (OS). We evaluated the plasma levels of ITZ and hydroxy (OH) ITZ both before initiation of IV ITZ and on days 5-7 of IV ITZ. A total of 181 patients showed an overall success rate of 68.0 %. Prolonged baseline neutropenia and accompanying cardiovascular comorbidity were significantly associated with poor outcomes of the empirical antifungal therapy (P = 0.005 and P = 0.001, respectively). A significantly higher trough plasma level of OH ITZ per body weight was found in the patients who achieved success with empirical antifungal therapy (P = 0.036). There were no significant correlations between plasma concentrations of ITZ/OH ITZ (baseline or trough levels) and toxicities. Seven patients had a discontinuation of ITZ therapy due to toxicity. This study demonstrated that IV ITZ as empirical antifungal therapy was effective and therapeutic drug monitoring was helpful to estimate the outcome of empirical antifungal therapy in patients receiving antifungal prophylaxis with ITZ OS. To predict the outcome of empirical antifungal therapy with IV ITZ, we should evaluate baseline clinical characteristics and also perform the therapeutic drug monitoring of both ITZ and OH ITZ.

  18. Type of Antifungals: Does it Matter in Empirical Treatment of Otomycosis?

    PubMed

    Navaneethan, Nagendran; YaadhavaKrishnan, Raj Prakash Dharmapuri

    2015-03-01

    To evaluate the efficacy of clotrimazole, miconazole and fluconazole in empirical treatment of otomycosis in our tertiary care hospital and to appraise possible better outcome in otomycosis. Two hundred and ninety five patients who presented with clinical otomycosis at our Melmaruvathur Adiparasakthi Institute of medical sciences were incorporated in this study. Two hundred and fourteen patients who satisfied our criteria were recognized and they were randomly alienated into three groups A, B, C. Group A patients were advised to instill clotrimazole ear drops by themselves. Miconazole cream instillation were done by our trained personal in group B patients. Group C patients were advised to use fluconazole ear drops. Patients were educated to keep ear dry and instructed to come for evaluation in first and second week after initial visit. A randomized double blinded prospective study. In the first week, clotrimazole had a good response than miconazole and fluconazole in our patients and in the second week, our patients showed a drastic response in patients instilling flucanozole ear drops compared to those using micanozole and clotrimazole. This better outcome doesn't show statistical significance since p value is 0.882. Clotrimazole drops, miconazole cream and Fluconazole drops showed almost same therapeutic efficacy in Otomycosis.

  19. A randomized, double-blind, multicenter study of caspofungin versus liposomal amphotericin B for empiric antifungal therapy in pediatric patients with persistent fever and neutropenia.

    PubMed

    Maertens, Johan A; Madero, Luis; Reilly, Anne F; Lehrnbecher, Thomas; Groll, Andreas H; Jafri, Hasan S; Green, Michael; Nania, Joseph J; Bourque, Michael R; Wise, Beth Ann; Strohmaier, Kim M; Taylor, Arlene F; Kartsonis, Nicholas A; Chow, Joseph W; Arndt, Carola A S; DePauw, Ben E; Walsh, Thomas J

    2010-05-01

    Persistently febrile neutropenic children at risk for invasive fungal infections receive empiric antifungal therapy as a standard of care. However, little is known about the role of echinocandins and liposomal amphotericin B (L-AmB) for empiric antifungal therapy in pediatric patients. Patients between the ages of 2 to 17 years with persistent fever and neutropenia were randomly assigned to receive caspofungin (70 mg/m loading dose on day 1, then 50 mg/m daily [maximum 70 mg/d]) or L-AmB (3 mg/kg daily) in a 2:1 ratio. Evaluation of safety was the primary objective of the study. Efficacy was also evaluated, with a successful outcome defined as fulfilling all components of a prespecified 5-part composite endpoint. Suspected invasive fungal infections were evaluated by an independent, treatment-blinded adjudication committee. Eighty-two patients received study therapy (caspofungin 56, L-AmB 26), and 81 were evaluated for efficacy (caspofungin 56; L-AmB 25). Outcomes for safety and efficacy endpoints were similar for both study arms. Adverse drug-related event rates [95% confidence interval] were similar between the caspofungin and L-AmB groups (clinical 48.2% [34.7-62.0] versus 46.2% [26.6-66.6]; laboratory 10.7% [4.0-21.9] versus 19.2% [6.6-39.4]). Serious drug-related adverse events occurred in 1 (1.8%) of caspofungin-treated patients and 3 (11.5%) of L-AmB-treated patients. Overall success rates [95% CI] were 46.4% [33.4-59.5] for caspofungin and 32.0% [13.7-50.3] for L-AmB. Caspofungin and L-AmB were comparable in tolerability, safety, and efficacy as empiric antifungal therapy for persistently febrile neutropenic pediatric patients.

  20. Antifungal polypeptides

    DOEpatents

    Altier, Daniel J [Waukee, IA; Ellanskaya, Irina [Kyiv, UA; Ellanskaya, legal representative, Natalia; Gilliam, Jacob T [Norwalk, IA; Hunter-Cevera, Jennie [Elliott City, MD; Presnail, James K [Avondale, PA; Schepers, Eric [Port Deposit, MD; Simmons, Carl R [Des Moines, IA; Torok, Tamas [Richmond, CA; Yalpani, Nasser [Johnston, IA

    2009-09-15

    The invention relates to antifungal compositions and methods for protecting a plant from a fungal pathogen. Compositions including antifungal polypeptides isolated from a fungal fermentation broth are provided.

  1. Immediate versus deferred empirical antifungal (IDEA) therapy in high-risk patients with febrile neutropenia: a randomized, double-blind, placebo-controlled, multicenter study.

    PubMed

    Maschmeyer, G; Heinz, W J; Hertenstein, B; Horst, H-A; Requadt, C; Wagner, T; Cornely, O A; Löffler, J; Ruhnke, M

    2013-05-01

    Empirical antifungal therapy is widely used in high-risk neutropenic hematology patients with fever persisting for more than 4 days. This clinical trial assessed whether immediate empirical therapy with voriconazole could lower the rates of invasive fungal infections (IFIs) compared with this approach. In a double-blind, placebo-controlled, multicenter study, patients with acute leukemia undergoing chemotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) recipients were randomized to broad-spectrum antibacterial therapy plus voriconazole (immediate) or placebo (deferred) after the onset of neutropenic fever. If fever persisted for 96 h, patients were switched to open-label intravenous voriconazole; oral treatment was permitted after 96 h. The primary endpoint was the rate of proven/probable IFIs between Days 2 and 28 after fever onset in the modified intent-to-treat (mITT) complete-case population. One hundred and forty-seven patients were randomized to immediate (n = 81) or deferred (n = 66) voriconazole. In the mITT population, six patients in the immediate group and nine in the deferred group developed proven/probable IFI between Days 2 and 28 (p = 0.258). The safety profiles were similar in both groups. While immediate empirical therapy with voriconazole appears to be safe in febrile neutropenic high-risk patients, it was not associated with a significant reduction in IFIs compared with therapy deferred for 96 h after fever onset.

  2. Drug utilization study of systemic antifungal agents in a Brazilian tertiary care hospital.

    PubMed

    de Souza, Maria Clara Padovani; Dos Santos, Andrezza Gouvêa; Reis, Adriano Max Moreira

    2016-12-01

    Background The inappropriate use of systemic antifungal agents can result in unnecessary exposure, adverse events, increased microbial resistance and increased costs. Aim This study analysed the use of systemic antifungal agents and adherence to treatment guidelines for fungal infections. Setting A Brazilian tertiary hospital. Methods This cross-sectional study investigated 183 patients who were treated with systemic antifungals. Antifungal drugs were classified according to the fourth level of the Anatomical Therapeutic Chemical classification system. The appropriateness of treatments was analysed with respect to the indication, dose and potential drug-drug interactions. Descriptive and univariate statistical analyses were performed. The main outcome measure was the frequency of adherence to treatment guidelines for fungal infections. Results The number of established treatments was 320, with 163 (50.9 %) pre-emptive, 63 (19.7 %) targeted, 56 (17.5 %) empirical and 38 (11.9 %) prophylactic treatments. The overall adherence to the treatment guidelines was 29.4 %. The proportion of appropriate treatment considering indication, dosage and drug-drug interactions was 84.1, 67.8 and 47.2 %, respectively. The most commonly prescribed systemic antifungal agents were fluconazole in 170 (53.1 %), voriconazole in 43 (13.4 %) and amphotericin B deoxycholate in 36 (11.3 %) cases. Conclusion The study showed a low proportion of appropriate antifungal drug use; the dosage and drug-drug interactions criteria were the determining factors for the high percentage of non-adherence to treatment guidelines in the hospital. The profile of antifungal agents used showed the predominance of fluconazole as well as the use of new antifungal drugs.

  3. When inappropriate becomes beneficial.

    PubMed

    Arroja, José David; Zimmermann, Marc

    2015-03-01

    We report the case of a young man who accidentally received a prolonged electric discharge from electrical wires and released the electric source with the help of an inappropriate shock from his implantable cardioverter-defibrillator (ICD), after misinterpretation of the electrical signal by the device as a ventricular tachycardia. This case illustrates the "electrical noise" phenomenon, and underscores the need for precautions for patients with an ICD and their physicians.

  4. Antifungal combinations.

    PubMed

    Vitale, Roxana G; Afeltra, Javier; Dannaoui, Eric

    2005-01-01

    The increase in fungal infections and the change in fungal epidemiology is caused by the extensive use of antifungal agents to treat fungal infections that are being diagnosed in severly immunocompromised hosts. In addition, opportunistic fungal infections resistant to antifungal drugs have become increasingly common, and the armamentarium for treatment remains limited. A possible approach to overcoming these problems is to combine antifungal drugs, especially if the mechanisms of action are different. The in vitro test is the first step to evaluate possible antifungal combinations. In this chapter, the three most frequently used metholodologies are described: checkerboard, E-test, and time-kill curves. The description of each technique and intrepretaion of the results are addressed in detail.

  5. Antifungal drug resistance to azoles and polyenes.

    PubMed

    Masiá Canuto, Mar; Gutiérrez Rodero, Félix

    2002-09-01

    There is an increased awareness of the morbidity and mortality associated with fungal infections caused by resistant fungi in various groups of patients. Epidemiological studies have identified risk factors associated with antifungal drug resistance. Selection pressure due to the continuous exposure to azoles seems to have an essential role in developing resistance to fluconazole in Candida species. Haematological malignancies, especially acute leukaemia with severe and prolonged neutropenia, seem to be the main risk factors for acquiring deep-seated mycosis caused by resistant filamentous fungi, such us Fusarium species, Scedosporium prolificans, and Aspergillus terreus. The still unacceptably high mortality rate associated with some resistant mycosis indicates that alternatives to existing therapeutic options are needed. Potential measures to overcome antifungal resistance ranges from the development of new drugs with better antifungal activity to improving current therapeutic strategies with the present antifungal agents. Among the new antifungal drugs, inhibitors of beta glucan synthesis and second-generation azole and triazole derivatives have characteristics that render them potentially suitable agents against some resistant fungi. Other strategies including the use of high doses of lipid formulations of amphotericin B, combination therapy, and adjunctive immune therapy with cytokines are under investigation. In addition, antifungal control programmes to prevent extensive and inappropriate use of antifungals may be needed.

  6. Antifungal susceptibility testing: a primer for clinicians.

    PubMed

    Kuper, Kristi M; Coyle, Elizabeth A; Wanger, Audrey

    2012-12-01

    Antifungal susceptibility testing is not as commonly performed as antibacterial susceptibility testing. The methodology for detecting antifungal resistance is newer and requires different testing supplies that may not be readily available in a clinical laboratory setting. Breakpoints for molds are lacking. Yeast breakpoints are available for most antifungals but are continually updated based on epidemiologic surveillance. Reliable and reproducible antifungal susceptibility testing methods, as well as more research on the role of susceptibility testing in patient care, are necessary in order to provide the clinician with information that can be translated into positive clinical outcomes at the bedside. There are nuances with current testing methods that, if unrecognized, could lead to misinterpretation of results and inappropriate antifungal selection. Clinicians who have an understanding of qualitative and quantitative methods, automated susceptibility testing systems, and other commercial tests can successfully engage this knowledge to improve antifungal use and patient outcomes. This primer describes the common antifungal susceptibility tests used in the clinical microbiology laboratory and reviews literature related to the impact of appropriate drug selection, timing, fungal resistance mechanisms, pharmacokinetics, and pharmacodynamics on clinical outcomes. Both conventional and modern testing methods are discussed. © 2012 Pharmacotherapy Publications, Inc.

  7. Modern antifungal therapy for neutropenic fever.

    PubMed

    Corey, Melissa

    2006-06-01

    Empirical antifungal therapy has been shown to decrease the number of documented fungal infections in the setting of persistent fever during neutropenia. For decades, amphotericin B deoxycholate has been considered the agent of choice for first-line therapy in this setting. New antifungal agents associated with less toxicity, including the lipid formulations of amphotericin, voriconazole, and caspofungin, are now available and are considered to be suitable alternative first-line agents. In order to ensure appropriate therapy, however, the clinician must consider not only the differences between these antifungals but also patient-specific factors before initiating treatment.

  8. Nephrogenic Syndrome of Inappropriate Antidiuresis

    PubMed Central

    Feldman, Brian J.; Rosenthal, Stephen M.; Vargas, Gabriel A.; Fenwick, Raymond G.; Huang, Eric A.; Matsuda-Abedini, Mina; Lustig, Robert H.; Mathias, Robert S.; Portale, Anthony A.; Miller, Walter L.; Gitelman, Stephen E.

    2017-01-01

    SUMMARY The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia. We describe two infants whose clinical and laboratory evaluations were consistent with the presence of SIADH, yet who had undetectable arginine vasopressin (AVP) levels. We hypothesized that they had gain-of-function mutations in the V2 vasopressin receptor (V2R). DNA sequencing of each patient’s V2R gene (AVPR2) identified missense mutations in both, with resultant changes in codon 137 from arginine to cysteine or leucine. These novel mutations cause constitutive activation of the receptor and are the likely cause of the patients’ SIADH-like clinical picture, which we have termed “nephrogenic syndrome of inappropriate antidiuresis.” PMID:15872203

  9. Nephrogenic Syndrome of Inappropriate Antidiuresis

    PubMed Central

    Morin, D.; Tenenbaum, J.; Ranchin, B.; Durroux, T.

    2012-01-01

    Mutations in the vasopressin V2 receptor gene are responsible for two human tubular disorders: X-linked congenital nephrogenic diabetes insipidus, due to a loss of function of the mutant V2 receptor, and the nephrogenic syndrome of inappropriate antidiuresis, due to a constitutive activation of the mutant V2 receptor. This latter recently described disease may be diagnosed from infancy to adulthood, as some carriers remain asymptomatic for many years. Symptomatic children, however, typically present with clinical and biological features suggesting inappropriate antidiuretic hormone secretion with severe hyponatremia and high urine osmolality, but a low plasma arginine vasopressin level. To date, only two missense mutations in the vasopressin V2 receptor gene have been found in the reported patients. The pathophysiology of the disease requires fuller elucidation as the phenotypic variability observed in patients bearing the same mutations remains unexplained. The treatment is mainly preventive with fluid restriction, but urea may also be proposed. PMID:22518188

  10. Treatment for Inappropriate Sinus Tachycardia.

    PubMed

    Salazar Adum, Juan Pablo; Arora, Rohit

    Inappropriate Sinus Tachycardia (IST) is a chronic medical condition with a wide variety of clinical presentations making it, sometimes, very insidious at the time of the diagnosis. Several therapeutic options, including, pharmacotherapy, cardiac rehabilitation, and modification or ablation of the sinus node, have been proposed for the management of IST, but because of the complexity and lack of understanding of pathophysiology, it can be difficult to manage, despite the numerous treatment options currently available. The purpose of this review is to analyze the treatment for IST, focusing on the role of newer therapy and the potential benefits in the management of this cardiac rhythm disturbance.

  11. In vitro assessment of antifungal drug resistance.

    PubMed

    Holmberg, K

    1986-01-01

    Several studies have documented the variability in the susceptibility pattern of fungi to antifungal drugs, and fungi possess resistance determinants to negate the effects of antifungal agents. In vitro assessment of both resistance and susceptibility are measured by suitable concentration endpoints of the antifungal drug, the minimal inhibitory concentration (MIC). MICs serve as the main parameter to define the fungistatic action on fungi growing in culture. For the antifungals used for treatment of local mycoses, the limit between a MIC value indicating susceptibility and one indicating resistance is usually determined empirically on the basis of the correlation between MIC values, and either positive or negative response to chemotherapy. The principles of susceptibility testing of fungi are essentially the same as those for bacteria. However, testing with fungi must deal with the fact that interpretation of the results is complicated by inherent differences in fungal morphology, growth rate, and optimal culture conditions. Several factors could adversely affect the test results and must be considered in the design of susceptibility testing of fungi. It is obvious when the present data on fungal susceptibility testing are reviewed that much more work on standardization of techniques and interpretation of results is necessary. This presentation will focus on the in vitro susceptibility testing for determining primary and secondary drug resistance of griseofulvin and azole antifungal agents, and the correlation between the activities of these antifungals in vitro and in vivo.

  12. Resistance to antifungal therapies.

    PubMed

    Prasad, Rajendra; Banerjee, Atanu; Shah, Abdul Haseeb

    2017-02-28

    The evolution of antifungal resistance among fungal pathogens has rendered the limited arsenal of antifungal drugs futile. Considering the recent rise in the number of nosocomial fungal infections in immunocompromised patients, the emerging clinical multidrug resistance (MDR) has become a matter of grave concern for medical professionals. Despite advances in therapeutic interventions, it has not yet been possible to devise convincing strategies to combat antifungal resistance. Comprehensive understanding of the molecular mechanisms of antifungal resistance is essential for identification of novel targets that do not promote or delay emergence of drug resistance. The present study discusses features and limitations of the currently available antifungals, mechanisms of antifungal resistance and highlights the emerging therapeutic strategies that could be deployed to combat MDR.

  13. Social inappropriateness, executive control, and aging.

    PubMed

    Henry, Julie D; von Hippel, William; Baynes, Kate

    2009-03-01

    Age-related deficits in executive control might lead to socially inappropriate behavior if they compromise the ability to withhold inappropriate responses. Consistent with this possibility, older adults in the current study showed greater social inappropriateness than younger adults--as rated by their peers--and this effect was mediated by deficits in executive control as well as deficits in general cognitive ability. Older adults also responded with greater social inappropriateness to a provocative event in the laboratory, but this effect was unrelated to executive functioning or general cognitive ability. These findings suggest that changes in both social and cognitive factors are important in understanding age-related changes in social behavior.

  14. Antifungal nanoparticles and surfaces.

    PubMed

    Paulo, Cristiana S O; Vidal, Maria; Ferreira, Lino S

    2010-10-11

    Nosocomial fungal infections, an increasing healthcare concern worldwide, are often associated with medical devices. We have developed antifungal nanoparticle conjugates that can act in suspension or attach to a surface, efficiently killing fungi. For that purpose, we immobilized covalently amphotericin B (AmB), a potent antifungal agent approved by the FDA, widely used in clinical practice and effective against a large spectrum of fungi, into silica nanoparticles. These antifungal nanoparticle conjugates are fungicidal against several strains of Candida sp., mainly by contact. In addition, they can be reused up to 5 cycles without losing their activity. Our results show that the antifungal nanoparticle conjugates are more fungistatic and fungicidal than 10 nm colloidal silver. The antifungal activity of the antifungal nanoparticle conjugates is maintained when they are immobilized on a surface using a chemical adhesive formed by polydopamine. The antifungal nanocoatings have no hemolytic or cytotoxic effect against red blood cells and blood mononuclear cells, respectively. Surfaces coated with these antifungal nanoparticle conjugates can be very useful to render medical devices with antifungal properties.

  15. [Inappropriate prescription in elderly inpatients].

    PubMed

    Fajreldines, Ana V; Insua, Jorge T; Schnitzler, Eduardo

    2016-01-01

    One of the causes of preventable adverse drug events (EAM) in the older adult population is the inappropriate prescription (PIM), i.e. that prescription where risks outweigh clinical benefits. The aim of this study is to determine the incidence of PIM with Beers criteria and Screening Tool of older person's prescriptions (STOPP), Potentially Prescribing Omissions (PPO) with Screening Tool to alert doctors to Right Treatments (START), and the average costs of hospitalization. This is an incidence study on a sample of patients over 64 years hospitalized, from January to July 2014 at a university hospital. According to Beers criteria, PIM incidence was 61.4%, 65.4% with STOPP and 27.6% PPO with START. The EAM rate calculated was 15.2/100 admissions and 18.6 EAM / 1000 patient days. The OR of EAM with PIM according to Beers and STOPP was 1.49 (IC95% 1.68-4.66) and 1.17 (IC95% 0.62-2.24) respectively. The average cost of hospitalization in patients with EAM were higher than without EAM (p = 0.020). PIM results are in line with most of the studies cited, but slightly higher for Beers and STOPP and lower for START, and the rate of EAM is lower than the data found by Kanaan (18.7% vs. 15.2%). PIM contributes to the appearance of EAM. The costs of hospitalizations with EAM are higher than those without EAM, achieving level of significance.

  16. Triazole antifungals: a review.

    PubMed

    Peyton, L R; Gallagher, S; Hashemzadeh, M

    2015-12-01

    Invasive fungal infections and systemic mycosis, whether from nosocomial infection or immunodeficiency, have been on an upward trend for numerous years. Despite advancements in antifungal medication, treatment in certain patients can still be difficult for reasons such as impaired organ function, limited administration routes or poor safety profiles of the available antifungal medications. The growing number of invasive fungal species becoming resistant to current antifungal medications is of appreciable concern. Triazole compounds containing one or more 1,2,4-triazole rings have been shown to contain some of the most potent antifungal properties. Itracon-azole and fluconazole were some of the first triazoles synthesized, but had limitations associated with their use. Second-generation triazoles such as voriconazole, posa-conazole, albaconazole, efinaconazole, ravuconazole and isavuconazole are all derivatives of either itraconazole or fluconazole, and designed to overcome the deficiencies of their parent drugs. The goal of this manuscript is to review antifungal agents derived from triazole.

  17. Antifungal Treatment in Stem Cell Transplantation Centers in Turkey.

    PubMed

    Akan, Hamdi; Atilla, Erden

    2016-03-05

    Despite the development of various guidelines, the approach to antifungal treatment in stem cell transplantation centers differs according to country or even between centers. This led to the development of another survey that aims to understand the antifungal treatment policies of Turkish stem cell transplantation centers. Although there has been an increasing trend towards the use of diagnostic-based treatments in Turkey in the last few years, empirical treatment is still the main approach. The practices of the stem cell transplantation centers reflect the general trends and controversies in this area, while there is a considerable use of antifungal combination therapy.

  18. The frequency of inappropriate nonformulary medication alert overrides in the inpatient setting.

    PubMed

    Her, Qoua L; Amato, Mary G; Seger, Diane L; Beeler, Patrick E; Slight, Sarah P; Dalleur, Olivia; Dykes, Patricia C; Gilmore, James F; Fanikos, John; Fiskio, Julie M; Bates, David W

    2016-09-01

    Experts suggest that formulary alerts at the time of medication order entry are the most effective form of clinical decision support to automate formulary management. Our objectives were to quantify the frequency of inappropriate nonformulary medication (NFM) alert overrides in the inpatient setting and provide insight on how the design of formulary alerts could be improved. Alert overrides of the top 11 (n = 206) most-utilized and highest-costing NFMs, from January 1 to December 31, 2012, were randomly selected for appropriateness evaluation. Using an empirically developed appropriateness algorithm, appropriateness of NFM alert overrides was assessed by 2 pharmacists via chart review. Appropriateness agreement of overrides was assessed with a Cohen's kappa. We also assessed which types of NFMs were most likely to be inappropriately overridden, the override reasons that were disproportionately provided in the inappropriate overrides, and the specific reasons the overrides were considered inappropriate. Approximately 17.2% (n = 35.4/206) of NFM alerts were inappropriately overridden. Non-oral NFM alerts were more likely to be inappropriately overridden compared to orals. Alerts overridden with "blank" reasons were more likely to be inappropriate. The failure to first try a formulary alternative was the most common reason for alerts being overridden inappropriately. Approximately 1 in 5 NFM alert overrides are overridden inappropriately. Future research should evaluate the impact of mandating a valid override reason and adding a list of formulary alternatives to each NFM alert; we speculate these NFM alert features may decrease the frequency of inappropriate overrides. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. The inappropriate smile and zygomatic muscle activity.

    PubMed

    Azuma, Tukasa; Shimizu, Akira; Yamashita, Koh; Iwase, Masao; Kajimoto, Osami; Tatsumoto, Yoshihiro; Sumitsuji, Noboru

    2003-04-01

    Long-term recording of activity of the zygomatic muscle, the most important mimic muscle involved in smiling, was performed in 22 disorganized type schizophrenic patients with inappropriate smiles and 15 normal subjects in two separate experiments. During inappropriate smiles, the zygomatic muscle exhibited waxing and waning bursts of activity with an amplitude of 75 to 120 microV, which could not be distinguished from the activity observed during usual smiling in normal subjects. However, the duration of such activity tended to be longer when compared to that in usual smiling by normal subjects as well as by schizophrenic patients. In contrast to usual smiles, inappropriate smiles decreased with personal contact. When asked about their thoughts during smiling shortly after inappropriate smiles, more patients reported that they thought of nothing at all or something not necessarily pleasant rather than something pleasant that would be expected to induce smiling.

  20. Drug Utilization and Inappropriate Prescribing in Centenarians.

    PubMed

    Hazra, Nisha C; Dregan, Alex; Jackson, Stephen; Gulliford, Martin C

    2016-05-01

    To use primary care electronic health records (EHRs) to evaluate prescriptions and inappropriate prescribing in men and women at age 100. Population-based cohort study. Primary care database in the United Kingdom, 1990 to 2013. Individuals reaching the age of 100 between 1990 and 2013 (N = 11,084; n = 8,982 women, n = 2,102 men). Main drug classes prescribed and potentially inappropriate prescribing according to the 2012 American Geriatrics Society Beers Criteria. At the age of 100, 73% of individuals (79% of women, 54% of men) had received one or more prescription drugs, with a median of 7 (interquartile range 0-12) prescription items. The most frequently prescribed drug classes were cardiovascular (53%), central nervous system (CNS) (53%), and gastrointestinal (47%). Overall, 32% of participants (28% of men, 32% of women) who received drug prescriptions may have received one or more potentially inappropriate prescriptions, with temazepam and amitriptyline being the most frequent. CNS prescriptions were potentially inappropriate in 23% of individuals, and anticholinergic prescriptions were potentially inappropriate in 18% of individuals. The majority of centenarians are prescribed one or more drug therapies, and the prescription may be inappropriate for up to one-third of these individuals. Research using EHRs offers opportunities to understand prescribing trends and improve pharmacological care of the oldest adults. © 2016 The Authors. The Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society.

  1. Antifungal compounds from cyanobacteria.

    PubMed

    Shishido, Tânia K; Humisto, Anu; Jokela, Jouni; Liu, Liwei; Wahlsten, Matti; Tamrakar, Anisha; Fewer, David P; Permi, Perttu; Andreote, Ana P D; Fiore, Marli F; Sivonen, Kaarina

    2015-04-13

    Cyanobacteria are photosynthetic prokaryotes found in a range of environments. They are infamous for the production of toxins, as well as bioactive compounds, which exhibit anticancer, antimicrobial and protease inhibition activities. Cyanobacteria produce a broad range of antifungals belonging to structural classes, such as peptides, polyketides and alkaloids. Here, we tested cyanobacteria from a wide variety of environments for antifungal activity. The potent antifungal macrolide scytophycin was detected in Anabaena sp. HAN21/1, Anabaena cf. cylindrica PH133, Nostoc sp. HAN11/1 and Scytonema sp. HAN3/2. To our knowledge, this is the first description of Anabaena strains that produce scytophycins. We detected antifungal glycolipopeptide hassallidin production in Anabaena spp. BIR JV1 and HAN7/1 and in Nostoc spp. 6sf Calc and CENA 219. These strains were isolated from brackish and freshwater samples collected in Brazil, the Czech Republic and Finland. In addition, three cyanobacterial strains, Fischerella sp. CENA 298, Scytonema hofmanni PCC 7110 and Nostoc sp. N107.3, produced unidentified antifungal compounds that warrant further characterization. Interestingly, all of the strains shown to produce antifungal compounds in this study belong to Nostocales or Stigonematales cyanobacterial orders.

  2. Inappropriate hospital admissions: patient participation in research.

    PubMed

    Glasby, J; Littlechild, R

    Although political interest in reducing the number of inappropriate hospital admissions is mounting, methods for researching the rate of inappropriate admissions have several major limitations. Whereas traditional studies have tended to be predominantly subjective, more recent studies using clinical review instruments also have a number of limitations. Chief among these is the failure to consider the potential input of the individual patient. To illustrate some of the possible benefits of patient participation, this article cites findings from a study in Birmingham, which sought to involve individual older people in a research study into emergency hospital admissions.

  3. Antifungal pharmacokinetics and pharmacodynamics.

    PubMed

    Lepak, Alexander J; Andes, David R

    2014-11-10

    Successful treatment of infectious diseases requires choice of the most suitable antimicrobial agent, comprising consideration of drug pharmacokinetics (PK), including penetration into infection site, pathogen susceptibility, optimal route of drug administration, drug dose, frequency of administration, duration of therapy, and drug toxicity. Antimicrobial pharmacokinetic/pharmacodynamic (PK/PD) studies consider these variables and have been useful in drug development, optimizing dosing regimens, determining susceptibility breakpoints, and limiting toxicity of antifungal therapy. Here the concepts of antifungal PK/PD studies are reviewed, with emphasis on methodology and application. The initial sections of this review focus on principles and methodology. Then the pharmacodynamics of each major antifungal drug class (polyenes, flucytosine, azoles, and echinocandins) is discussed. Finally, the review discusses novel areas of pharmacodynamic investigation in the study and application of combination therapy.

  4. Antifungal Amphiphilic Aminoglycosides

    PubMed Central

    Chang, C.-W. T.; Takemoto, J.Y.

    2014-01-01

    The attachment of alkyl and other hydrophobic groups to traditional antibacterial kanamycins and neomycins creates amphiphilic aminoglycosides with altered antimicrobial properties. In this review, we summarize the discovery of amphiphilic kanamycins that are antifungal, but not antibacterial, and that inhibit the growth of fungi by perturbation of plasma membrane functions. With low toxicities against plant and mammalian cells, they appear to specifically target the fungal plasma membrane. These new antifungal agents offer new options for fighting fungal pathogens and are examples of reviving old drugs to confront new therapeutic challenges. PMID:25110571

  5. Children's Context Inappropriate Anger and Salivary Cortisol

    ERIC Educational Resources Information Center

    Locke, Robin L.; Davidson, Richard J.; Kalin, Ned H.; Goldsmith, H. Hill

    2009-01-01

    Some children show emotion that is not consistent with normative appraisal of the context and can therefore be defined as context inappropriate (CI). The authors used individual growth curve modeling and hierarchical multiple regression analyses to examine whether CI anger predicts differences in hypothalamic-pituitary-adrenal axis activity, as…

  6. Bullying and Inappropriate Behaviour among Faculty Personnel

    ERIC Educational Resources Information Center

    Meriläinen, Matti; Sinkkonen, Hanna-Maija; Puhakka, Helena; Käyhkö, Katinka

    2016-01-01

    This study focuses on the degree, nature and consequences of bullying or inappropriate behaviour among faculty personnel (n = 303) in a Finnish university. A total of 114 (38%) faculty members answered the email questionnaire. According to the results, 15% of the respondents had experienced bullying; in addition, 45% had experienced inappropriate…

  7. Bullying and Inappropriate Behaviour among Faculty Personnel

    ERIC Educational Resources Information Center

    Meriläinen, Matti; Sinkkonen, Hanna-Maija; Puhakka, Helena; Käyhkö, Katinka

    2016-01-01

    This study focuses on the degree, nature and consequences of bullying or inappropriate behaviour among faculty personnel (n = 303) in a Finnish university. A total of 114 (38%) faculty members answered the email questionnaire. According to the results, 15% of the respondents had experienced bullying; in addition, 45% had experienced inappropriate…

  8. Teachers' Beliefs about Inappropriate Behaviour: Challenging Attitudes?

    ERIC Educational Resources Information Center

    Grieve, Ann M.

    2009-01-01

    This paper focuses on taking a first step in the process of influencing teachers' attitudes by building a description of beliefs about inappropriate behaviour that can be used in staff development work to provoke dissonance-led change. It describes a study, undertaken in two parts, exploring teachers' attitudes to inclusion, and ascertaining their…

  9. Teachers' Beliefs about Inappropriate Behaviour: Challenging Attitudes?

    ERIC Educational Resources Information Center

    Grieve, Ann M.

    2009-01-01

    This paper focuses on taking a first step in the process of influencing teachers' attitudes by building a description of beliefs about inappropriate behaviour that can be used in staff development work to provoke dissonance-led change. It describes a study, undertaken in two parts, exploring teachers' attitudes to inclusion, and ascertaining their…

  10. Functional Analysis and Reduction of Inappropriate Spitting

    ERIC Educational Resources Information Center

    Carter, Stacy L.; Wheeler, John J.

    2007-01-01

    Functional analysis was used to determine the possible function of inappropriate spitting behavior of an adult woman who had been diagnosed with profound mental retardation. Results of an initial descriptive assessment indicated a possible attention function and led to an attention-based intervention, which was deemed ineffective at reducing the…

  11. Children's Context Inappropriate Anger and Salivary Cortisol

    ERIC Educational Resources Information Center

    Locke, Robin L.; Davidson, Richard J.; Kalin, Ned H.; Goldsmith, H. Hill

    2009-01-01

    Some children show emotion that is not consistent with normative appraisal of the context and can therefore be defined as context inappropriate (CI). The authors used individual growth curve modeling and hierarchical multiple regression analyses to examine whether CI anger predicts differences in hypothalamic-pituitary-adrenal axis activity, as…

  12. Functional Analysis and Reduction of Inappropriate Spitting

    ERIC Educational Resources Information Center

    Carter, Stacy L.; Wheeler, John J.

    2007-01-01

    Functional analysis was used to determine the possible function of inappropriate spitting behavior of an adult woman who had been diagnosed with profound mental retardation. Results of an initial descriptive assessment indicated a possible attention function and led to an attention-based intervention, which was deemed ineffective at reducing the…

  13. Newer antifungal agents.

    PubMed

    Türel, Ozden

    2011-03-01

    The frequency and spectrum of fungal infections have been increasing steadily over the last several decades. The reason for this increase may be explained by the increase in the number of immunocompromised patients due to malignancies, AIDS, invasive surgical procedures and transplantation. In parallel with this increase, several therapeutic options have become available but problems such as intrinsic or acquired antifungal resistance have led researchers to develop new antifungal drugs with expanded effectiveness. Reduced toxicity, enhancement of bioavailability and counteraction of resistance are features desired by clinicians. The aim of this article is to summarize the studies involving isavuconazole, ravuconazole, albaconazole, aminocandin and some other investigational antifungal agents. Most data on the clinical use of ravuconazole, isavuconazole and albaconazole are mainly available as meeting abstracts or limited to animal studies or Phase I/II studies in humans. These new antifungal agents in development offer extended half-lives, possibly reduced drug interaction profiles and good tolerance. In addition to activity against Candida and Aspergillus spp., they have a broad spectrum of activity including activity against resistant and emerging pathogens. The real possibilities of these agents will only be fully understood after adequate randomized clinical trials.

  14. The role of the multidisciplinary team in antifungal stewardship.

    PubMed

    Agrawal, Samir; Barnes, Rosemary; Brüggemann, Roger J; Rautemaa-Richardson, Riina; Warris, Adilia

    2016-11-01

    There are a variety of challenges faced in the management of invasive fungal diseases (IFD), including high case-fatality rates, high cost of antifungal drugs and development of antifungal resistance. The diagnostic challenges and poor outcomes associated with IFD have resulted in excessive empirical use of antifungals in various hospital settings, exposing many patients without IFD to potential drug toxicities as well as causing spiralling antifungal drug costs. Further complexity arises as different patient groups show marked variation in their risk for IFD, fungal epidemiology, sensitivity and specificity of diagnostic tests and the pharmacokinetics and pharmacodynamics of antifungal drugs. To address these issues and to ensure optimal management of IFD, specialist knowledge and experience from a range of backgrounds is required, which extends beyond the remit of most antibiotic stewardship programmes. The first step in the development of any antifungal stewardship (AFS) programme is to build a multidisciplinary team encompassing the necessary expertise in the management of IFD to develop and implement the AFS programme. The specific roles of the key individuals within the AFS team and the importance of collaboration are discussed in this article.

  15. Drug reimbursement: Indicators of inappropriate resource allocation

    PubMed Central

    Bégaud, Bernard; Bergman, Ulf; Eichler, Hans-Georg; Leufkens, Hubert G M; Meier, Peter J

    2002-01-01

    Aims In many countries, governments and third parties find themselves paying for (reimbursing) unproven, inadequate products limiting their ability to invest in therapies with evidence of relevant patient benefit. We examined how three characteristics, level of therapeutic evidence, susceptibility of inappropriate prescribing, and intercountry variation can be used to identify inefficiencies in pharmaceutical reimbursement among four European Union countries, Austria, Belgium, the Netherlands and Sweden. Methods Specific classes of medicines were chosen to provide useful examples of how healthcare resources could be reallocated. A high level of therapeutic evidence was defined as a substantial body of evidence in at least one indication with clear-cut support of relevant patient benefit. The susceptibility of inappropriate prescribing was defined as the likelihood of prescribing a drug outside the scenario for which clear-cut evidence (if any) has been documented to produce relevant benefit for the patient. The intercountry variation represents the variation in utilization of reimbursed drugs across the four countries. Results The combination of these characteristics provides a useful tool for assessing appropriate reimbursement decisions. It would be beneficial to healthcare payers as well as patients to move resources from products that have a low level of therapeutic evidence and a high susceptibility of inappropriate prescribing to products with a high level of therapeutic evidence and low susceptibility of inappropriate prescribing, and to use intercountry variation as a signal of drug classes that should be subject to further scrutiny. Conclusions A method is presented to help policy-makers identify inefficiencies in the spending of limited health care resources, and to reallocate resources to products that have been shown to improve patient care through evidence-based medicine. PMID:12445033

  16. Prescribing Pattern of Antifungal Medications at a Tertiary Care Hospital in Oman

    PubMed Central

    Alzaabi, Mohammed A.; Alghafri, Fatma

    2016-01-01

    Introduction Inappropriate use of antifungal agents is implicated in the global burden of antifungal resistance, adverse outcomes like persistent infections, unnecessary exposure and increased cost. Data collection from time to time is to be done in order to have a check on the resistance/sensitivity pattern of the commonly prescribed antifungal drugs. Aim To describe the pattern of antifungal drug prescription and administration to patients attending a university hospital in Oman. Materials and Methods This was a descriptive, retrospective cross-sectional study conducted at Sultan Qaboos University Hospital (SQUH), a university hospital in Oman that covered the electronic patient’s data for a period of one year (January 2013 to December 2013). The study included inpatients and outpatients of all ages and both genders attending SQUH and receiving antifungal medications at the study period. Frequencies and percentages were reported for categorical variables, while the mean and standard deviation were used to summarize the data for continuous variables. Results A total of 1353 antifungal drug prescriptions were prescribed for 244 patients. More than half of all antifungal drug prescriptions were prescribed by haematology, infectious disease and family medicine departments. The majority of patients to whom these drugs were prescribed were diagnosed to have infectious diseases followed by prophylactic use in leukaemias and immunocompromised conditions. Fluconazole was the most commonly prescribed antifungal drug (n=715, 52.8%) followed by nystatin and voriconazole (n=233; 17.2% and n=152; 11.2%, respectively). Conclusion This study will help in understanding antifungal prescription practices and help in directing future studies and also in developing local policies for appropriate use of antifungal drugs. PMID:28208876

  17. Antifungal drug resistance mechanisms.

    PubMed

    Pemán, Javier; Cantón, Emilia; Espinel-Ingroff, Ana

    2009-05-01

    Antifungal resistance is a prominent feature in the management of invasive mycoses, with important implications for morbidity and mortality. Microbiological resistance, the most common cause of refractory infection, is associated with a fungal pathogen for which an antifungal MIC is higher than average or within the range designated as the resistant breakpoint. Four major mechanisms of resistance to azoles have been described in Candida spp.: decreased intracellular drug concentration by activation of efflux systems or reduction of drug penetration, modification of the target site, upregulation of the target enzyme and development of bypass pathways. Conversely, echinocandins are a poor substrate for multidrug efflux transporters, and their mechanisms of resistance are associated with point mutations and/or overexpression of FKS1 and FKS2 genes. Acquired resistance to flucytosine results from defects in its metabolism through enzymatic mutations, whereas resistance to amphotericin B may be mediated by increased catalase activity or defects in ergosterol biosynthesis.

  18. Antifungal susceptibility testing.

    PubMed Central

    Rex, J H; Pfaller, M A; Rinaldi, M G; Polak, A; Galgiani, J N

    1993-01-01

    Unlike antibacterial susceptibility testing, reliable antifungal susceptibility testing is still largely in its infancy. Many methods have been described, but they produce widely discrepant results unless such factors as pH, inoculum size, medium formulation, incubation time, and incubation temperature are carefully controlled. Even when laboratories agree upon a common method, interlaboratory agreement may be poor. As a result of numerous collaborative projects carried out both independently and under the aegis of the Subcommittee on Antifungal Susceptibility Testing of the National Committee for Clinical Laboratory Standards, the effects of varying these factors have been extensively studied and a standard method which minimizes interlaboratory variability during the testing of Candida spp. and Cryptococcus neoformans has been proposed. This review summarizes this work, reviews the strengths and weaknesses of the proposed susceptibility testing standard, and identifies directions for future work. PMID:8269392

  19. Antifungal susceptibility testing.

    PubMed

    Rex, J H; Pfaller, M A; Rinaldi, M G; Polak, A; Galgiani, J N

    1993-10-01

    Unlike antibacterial susceptibility testing, reliable antifungal susceptibility testing is still largely in its infancy. Many methods have been described, but they produce widely discrepant results unless such factors as pH, inoculum size, medium formulation, incubation time, and incubation temperature are carefully controlled. Even when laboratories agree upon a common method, interlaboratory agreement may be poor. As a result of numerous collaborative projects carried out both independently and under the aegis of the Subcommittee on Antifungal Susceptibility Testing of the National Committee for Clinical Laboratory Standards, the effects of varying these factors have been extensively studied and a standard method which minimizes interlaboratory variability during the testing of Candida spp. and Cryptococcus neoformans has been proposed. This review summarizes this work, reviews the strengths and weaknesses of the proposed susceptibility testing standard, and identifies directions for future work.

  20. EUCAST breakpoints for antifungals.

    PubMed

    Rodríguez-Tudela, Juan L; Arendrup, Maiken C; Cuenca-Estrella, Manuel; Donnelly, J Peter; Lass-Flörl, Cornelia

    2010-03-01

    Susceptibility testing of fungi and development of interpretative breakpoints has become increasingly important due to the growing incidence of invasive fungal infections, the number and classes of antifungals, and the emerging reports of acquired resistance. The subcommittee on antifungal susceptibility testing of the European Committee on Antibiotic Susceptibility Testing (EUCAST) has developed standards for susceptibility testing of fermentative yeasts and molds as well as proposing breakpoints for fluconazole and voriconazole against Candida. The aim of this work is to describe the EUCAST process of setting breakpoints for antifungals. Five aspects are evaluated during the process of developing breakpoints: 1) the most common dosage used in each European country, 2) the definition of the wild-type population for each target microorganism at the species level and the determination of epidemiological cutoffs, 3) the drug's pharmacokinetics and 4) pharmacodynamics, including Monte Carlo simulations, and 5) the correlation of MICs with clinical outcome of patients treated with the compound. When insufficient data are available (e.g., due to lack of information on the clinical outcome of infections caused by isolates with an elevated MIC), epidemiological cutoff values, rather than breakpoints, are recommended until the necessary information becomes available.

  1. Antifungal Lock Therapy

    PubMed Central

    Walraven, Carla J.

    2013-01-01

    The widespread use of intravascular devices, such as central venous and hemodialysis catheters, in the past 2 decades has paralleled the increasing incidence of catheter-related bloodstream infections (CR-BSIs). Candida albicans is the fourth leading cause of hospital-associated BSIs. The propensity of C. albicans to form biofilms on these catheters has made these infections difficult to treat due to multiple factors, including increased resistance to antifungal agents. Thus, curing CR-BSIs caused by Candida species usually requires catheter removal in addition to systemic antifungal therapy. Alternatively, antimicrobial lock therapy has received significant interest and shown promise as a strategy to treat CR-BSIs due to Candida species. The existing in vitro, animal, and patient data for treatment of Candida-related CR-BSIs are reviewed. The most promising antifungal lock therapy (AfLT) strategies include use of amphotericin, ethanol, or echinocandins. Clinical trials are needed to further define the safety and efficacy of AfLT. PMID:23070153

  2. Functional analysis and treatment of inappropriate verbal behavior.

    PubMed Central

    Dixon, M R; Benedict, H; Larson, T

    2001-01-01

    The present study examined the possible function of inappropriate verbal behavior of an adult man who had been diagnosed with both mental retardation and psychosis. Results of a functional analysis indicated that inappropriate verbal utterances were maintained by attention. An intervention consisting of the differential reinforcement of appropriate verbal behavior effectively reduced the inappropriate behavior. PMID:11678535

  3. Catheter ablation of inappropriate sinus tachycardia.

    PubMed

    Gianni, Carola; Di Biase, Luigi; Mohanty, Sanghamitra; Gökoğlan, Yalçın; Güneş, Mahmut F; Horton, Rodney; Hranitzky, Patrick M; Burkhardt, J David; Natale, Andrea

    2016-06-01

    Catheter ablation for inappropriate sinus tachycardia (IST) is recommended for patients symptomatic for palpitations and refractory to other treatments. The current approach consists in sinus node modification (SNM), achieved by ablation of the cranial part of the sinus node to eliminate faster sinus rates while trying to preserve chronotropic competence. This approach has a limited efficacy, with a very modest long-term clinical success. To overcome this, proper patient selection is crucial and an epicardial approach should always be considered. This brief review will discuss the current role and limitations of catheter ablation in the management of patients with IST.

  4. POPI (Pediatrics: Omission of Prescriptions and Inappropriate prescriptions): development of a tool to identify inappropriate prescribing.

    PubMed

    Prot-Labarthe, Sonia; Weil, Thomas; Angoulvant, François; Boulkedid, Rym; Alberti, Corinne; Bourdon, Olivier

    2014-01-01

    Rational prescribing for children is an issue for all countries and has been inadequately studied. Inappropriate prescriptions, including drug omissions, are one of the main causes of medication errors in this population. Our aim is to develop a screening tool to identify omissions and inappropriate prescriptions in pediatrics based on French and international guidelines. A selection of diseases was included in the tool using data from social security and hospital statistics. A literature review was done to obtain criteria which could be included in the tool called POPI. A 2-round-Delphi consensus technique was used to establish the content validity of POPI; panelists were asked to rate their level of agreement with each proposition on a 9-point Likert scale and add suggestions if necessary. 108 explicit criteria (80 inappropriate prescriptions and 28 omissions) were obtained and submitted to a 16-member expert panel (8 pharmacists, 8 pediatricians hospital-based -50%- or working in community -50%-). Criteria were categorized according to the main physiological systems (gastroenterology, respiratory infections, pain, neurology, dermatology and miscellaneous). Each criterion was accompanied by a concise explanation as to why the practice is potentially inappropriate in pediatrics (including references). Two round of Delphi process were completed via an online questionnaire. 104 out of the 108 criteria submitted to experts were selected after 2 Delphi rounds (79 inappropriate prescriptions and 25 omissions). POPI is the first screening-tool develop to detect inappropriate prescriptions and omissions in pediatrics based on explicit criteria. Inter-user reliability study is necessary before using the tool, and prospective study to assess the effectiveness of POPI is also necessary.

  5. POPI (Pediatrics: Omission of Prescriptions and Inappropriate Prescriptions): Development of a Tool to Identify Inappropriate Prescribing

    PubMed Central

    Prot-Labarthe, Sonia; Weil, Thomas; Angoulvant, François; Boulkedid, Rym; Alberti, Corinne; Bourdon, Olivier

    2014-01-01

    Introduction Rational prescribing for children is an issue for all countries and has been inadequately studied. Inappropriate prescriptions, including drug omissions, are one of the main causes of medication errors in this population. Our aim is to develop a screening tool to identify omissions and inappropriate prescriptions in pediatrics based on French and international guidelines. Methods A selection of diseases was included in the tool using data from social security and hospital statistics. A literature review was done to obtain criteria which could be included in the tool called POPI. A 2-round-Delphi consensus technique was used to establish the content validity of POPI; panelists were asked to rate their level of agreement with each proposition on a 9-point Likert scale and add suggestions if necessary. Results 108 explicit criteria (80 inappropriate prescriptions and 28 omissions) were obtained and submitted to a 16-member expert panel (8 pharmacists, 8 pediatricians hospital-based −50%- or working in community −50%-). Criteria were categorized according to the main physiological systems (gastroenterology, respiratory infections, pain, neurology, dermatology and miscellaneous). Each criterion was accompanied by a concise explanation as to why the practice is potentially inappropriate in pediatrics (including references). Two round of Delphi process were completed via an online questionnaire. 104 out of the 108 criteria submitted to experts were selected after 2 Delphi rounds (79 inappropriate prescriptions and 25 omissions). Discussion Conclusion POPI is the first screening-tool develop to detect inappropriate prescriptions and omissions in pediatrics based on explicit criteria. Inter-user reliability study is necessary before using the tool, and prospective study to assess the effectiveness of POPI is also necessary. PMID:24978045

  6. A prospective, multicentre survey on antifungal therapy in neutropenic paediatric haematology patients.

    PubMed

    Cesaro, Simone; Pagano, Livio; Caira, Morena; Carraro, Francesca; Luciani, Matteo; Russo, Delia; Colombini, Antonella; Morello, William; Viale, Pierluigi; Rossi, Giuseppe; Tridello, Gloria; Pegoraro, Anna; Nosari, Annamaria; Aversa, Franco

    2013-01-01

    Invasive fungal infections are a frequent complication after intensive chemotherapy. The aims of this prospective study were to describe the use of antifungal therapy and to report which strategy was routinely adopted to guide the introduction of antifungal therapy. A total of 321 febrile episodes in 160 paediatric patients affected by acute leukaemia or non-Hodgkin-lymphoma were investigated. Antifungal therapy was used in 100 of 321 febrile episodes (31%), and classified as empiric in 73 episodes, diagnostic-driven in 25 episodes and targeted in 2 episodes. Switching to a second-line antifungal therapy was needed in 28 of 100 episodes (28%) and was classified as empiric in 10 episodes (36%), diagnostic-driven in 17 episodes (61%) and targeted in 1 episode (4%). In 9 of 28 episodes (32%), switching to a third-line antifungal therapy was performed and was classified as empiric in 2 episodes (22%), diagnostic-driven in 6 episodes (67%) and targeted in 1 episode (11%). Invasive fungal infections was reported in 23 of 100 episodes: confirmed in 4 episodes, probable in 8 episodes, and possible in 11 episodes. Attributable mortality was 2.8%. Antifungal therapy was still used mostly empirically, whereas as fever persisted, its modification was guided by a diagnostic-driven approach.

  7. Inappropriateness of breast imaging: cost analysis.

    PubMed

    Pistolese, Chiara Adriana; Ciarrapico, Anna Micaela; della Gatta, Francesca; Simonetti, Giovanni

    2013-09-01

    The aim of this study was to assess how an incorrect indication for an examination may affect the diagnostic workup and diagnosis as well as healthcare expenditure. We considered all the requests for breast imaging (mammography, ultrasound and magnetic resonance imaging) received by our radiology department between October 2010 and December 2010, and assessed their appropriateness based on the patient's age and the clinical question, if present. We then analysed the unnecessary costs resulting from inappropriate requests. Out of a total of 1500 requests for ultrasound examination, the request was appropriate in 855 (57%) cases; out of a total of 2350 requests for mammography, the request was appropriate in 493 (21%) cases; out of a total of 100 requests for magnetic resonance imaging, the request was appropriate in 83 (83%) cases. The cost deriving from inappropriate requests was 51,235.04 Euros. Improving the timeliness of diagnosis is an important goal to be pursued by enhancing the available health services, improving communication and coordination of the different professionals involved and optimising diagnostic pathways in order to reduce healthcare spending.

  8. Treatment of inappropriate sinus tachycardia with ivabradine.

    PubMed

    Annamaria, Martino; Lupo, Pier Paolo; Foresti, Sara; De Ambroggi, Guido; de Ruvo, Ermenegildo; Sciarra, Luigi; Cappato, Riccardo; Calo, Leonardo

    2016-06-01

    Inappropriate sinus tachycardia (IST) often causes palpitations, dyspnea, and exercise intolerance, that are generally treated with beta blockers and non-dihydropyridine calcium-channel antagonists. Ivabradine, a selective inhibitor of cardiac pacemaker If current, has recently emerged as an effective and safe alternative to conventional drugs for IST. We performed a systematic overview of clinical studies on the therapeutic yield of ivabradine in patients with inappropriate sinus tachycardia, published in MEDLINE database from January 2000 to March 2015. Overall, five case reports were found, all showing efficacy of ivabradine in subjects affected by IST. Eight non-randomized clinical studies demonstrated short- and medium-term safety and efficacy of ivabradine administration in IST, also in adjunction to or in comparison with metoprolol. One double-blind randomized crossover study also showed that ivabradine is superior to placebo for heart rate (HR) reduction and symptoms control in patients affected by IST. Ivabradine is effective and safe in short- and medium-term treatment of IST. However, long-term follow-up studies and randomized studies comparing ivabradine with beta blockers are still lacking.

  9. Functional analysis and treatment of multiply controlled inappropriate mealtime behavior.

    PubMed

    Bachmeyer, Melanie H; Piazza, Cathleen C; Fredrick, Laura D; Reed, Gregory K; Rivas, Kristi D; Kadey, Heather J

    2009-01-01

    Functional analyses identified children whose inappropriate mealtime behavior was maintained by escape and adult attention. Function-based extinction procedures were tested individually and in combination. Attention extinction alone did not result in decreases in inappropriate mealtime behavior or a significant increase in acceptance. By contrast, escape extinction alone resulted in a decrease in inappropriate mealtime behavior and an increase in acceptance. However, inappropriate mealtime behavior did not decrease to clinically acceptable levels. A combined extinction technique (i.e., escape and attention extinction) resulted in a decrease in inappropriate mealtime behavior to clinically acceptable levels and high and stable acceptance.

  10. Antifungal adjuvants: Preserving and extending the antifungal arsenal.

    PubMed

    Butts, Arielle; Palmer, Glen E; Rogers, P David

    2017-02-17

    As the rates of systemic fungal infections continue to rise and antifungal drug resistance becomes more prevalent, there is an urgent need for new therapeutic options. This issue is exacerbated by the limited number of systemic antifungal drug classes. However, the discovery, development, and approval of novel antifungals is an extensive process that often takes decades. For this reason, there is growing interest and research into the possibility of combining existing therapies with various adjuvants that either enhance activity or overcome existing mechanisms of resistance. Reports of antifungal adjuvants range from plant extracts to repurposed compounds, to synthetic peptides. This approach would potentially prolong the utility of currently approved antifungals and mitigate the ongoing development of resistance.

  11. Inappropriately ordered echocardiograms are related to socioeconomic status.

    PubMed

    Silverman, Gabriel P; Vyse, Stuart; Silverman, David I

    2012-01-01

    Although the appropriateness of ordering tests is increasingly measured, the demographic characteristics of patients receiving inappropriate cardiac tests, such as echocardiograms, have seldom been studied. The authors hypothesized that particular patient characteristics might influence the frequency of inappropriate echocardiogram ordering. Demographics and appropriateness were examined in a consecutive series of 535 inpatients receiving echocardiograms at a metropolitan hospital; inappropriate tests were ordered in 9% of cases. Disabled patients received a significantly higher proportion of inappropriate echocardiograms compared to both retired and employed patients. Among patients receiving repeat echocardiograms, Medicaid patients were significantly more likely to receive inappropriately ordered echocardiograms than patients with either Medicare or private insurance. In conclusion, certain socioeconomic and demographic characteristics are associated with a higher incidence of inappropriate test ordering. Further research into the causal factors behind this association may be useful to reduce inappropriate test ordering.

  12. Tissue Penetration of Antifungal Agents

    PubMed Central

    Felton, Timothy; Troke, Peter F.

    2014-01-01

    SUMMARY Understanding the tissue penetration of systemically administered antifungal agents is critical for a proper appreciation of their antifungal efficacy in animals and humans. Both the time course of an antifungal drug and its absolute concentrations within tissues may differ significantly from those observed in the bloodstream. In addition, tissue concentrations must also be interpreted within the context of the pathogenesis of the various invasive fungal infections, which differ significantly. There are major technical obstacles to the estimation of concentrations of antifungal agents in various tissue subcompartments, yet these agents, even those within the same class, may exhibit markedly different tissue distributions. This review explores these issues and provides a summary of tissue concentrations of 11 currently licensed systemic antifungal agents. It also explores the therapeutic implications of their distribution at various sites of infection. PMID:24396137

  13. New facets of antifungal therapy.

    PubMed

    Chang, Ya-Lin; Yu, Shang-Jie; Heitman, Joseph; Wellington, Melanie; Chen, Ying-Lien

    2017-02-17

    Invasive fungal infections remain a major cause of morbidity and mortality in immunocompromised patients, and such infections are a substantial burden to healthcare systems around the world. However, the clinically available armamentarium for invasive fungal diseases is limited to 3 main classes (i.e., polyenes, triazoles, and echinocandins), and each has defined limitations related to spectrum of activity, development of resistance, and toxicity. Further, current antifungal therapies are hampered by limited clinical efficacy, high rates of toxicity, and significant variability in pharmacokinetic properties. New antifungal agents, new formulations, and novel combination regimens may improve the care of patients in the future by providing improved strategies to combat challenges associated with currently available antifungal agents. Likewise, therapeutic drug monitoring may be helpful, but its present use remains controversial due to the lack of available data. This article discusses new facets of antifungal therapy with a focus on new antifungal formulations and the synergistic effects between drugs used in combination therapy.

  14. Syndrome of inappropriate antidiuresis in doxylamine overdose

    PubMed Central

    Carrascosa, Miguel F; Caviedes, José-Ramón Salcines; Lucena, M Isabel; Cuadrado-Lavín, Antonio

    2012-01-01

    Doxylamine succinate, an H1-antihistamine drug, is commonly used as sleep-inducing agent as well as therapy for nausea and vomiting in pregnancy. At usual doses, it may cause impairment of cognitive and psychomotor performance, anticholinergic effects, agitation and postural hypotension. Besides, since this drug is frequently involved in either accidental or intentional overdoses, it seems relevant to bear in mind other possible toxic effects. We report a case of acute severe hyponatremia in the setting of a syndrome of inappropriate antidiuresis (SIAD), an apparent new adverse effect linked to doxylamine overdose. The Naranjo adverse drug reaction probability scale indicated a probable relationship between doxylamine intake and SIAD development. SIAD may be considered as a potential, serious adverse reaction of doxylamine overdose. Clinicians should consider this aetiological possibility when attending patients suffering from hyponatremia. PMID:23166178

  15. Syndrome of inappropriate antidiuresis in doxylamine overdose.

    PubMed

    Carrascosa, Miguel F; Caviedes, José-Ramón Salcines; Lucena, M Isabel; Cuadrado-Lavín, Antonio

    2012-11-19

    Doxylamine succinate, an H(1)-antihistamine drug, is commonly used as sleep-inducing agent as well as therapy for nausea and vomiting in pregnancy. At usual doses, it may cause impairment of cognitive and psychomotor performance, anticholinergic effects, agitation and postural hypotension. Besides, since this drug is frequently involved in either accidental or intentional overdoses, it seems relevant to bear in mind other possible toxic effects. We report a case of acute severe hyponatremia in the setting of a syndrome of inappropriate antidiuresis (SIAD), an apparent new adverse effect linked to doxylamine overdose. The Naranjo adverse drug reaction probability scale indicated a probable relationship between doxylamine intake and SIAD development. SIAD may be considered as a potential, serious adverse reaction of doxylamine overdose. Clinicians should consider this aetiological possibility when attending patients suffering from hyponatremia.

  16. Inappropriate medication use in the elderly.

    PubMed

    Petrarca, Alicia M; Lengel, Aaron J; Mangan, Michelle N

    2012-08-01

    STOPP (Screening Tool of Older Persons' Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment) are relatively new, validated tools that increasingly are used together to identify prescribing errors in elderly patients. This article reviews two studies that have directly compared STOPP with the Beers criteria, which is the current standard tool used to identify potentially inappropriate medications (PIMs) in older patients. Both studies reveal greater correlations to adverse drug events (ADEs) with PIMs defined by STOPP than with those defined by the Beers criteria, suggesting STOPP may be more useful in practice. Additional studies are needed to confirm STOPP's greater sensitivity and to determine whether its use translates to improved patient outcomes such as decreased morbidity, mortality, and health care costs. If so, pharmacists should consider implementation of STOPP (with or without START) in practice to improve care for the elderly population.

  17. Current evidence of antifungal prophylaxis and therapy in pediatric patients.

    PubMed

    Giacchino, Mareva; Milano, Giuseppe Maria; Carraro, Francesca; Bezzio, Stefania; Pegoraro, Anna; Aversa, Franco; Cesaro, Simone

    2011-02-24

    Invasive fungal infections (IFI) are an important complication in pediatric haematological and oncological patients who undergo intensive chemotherapy for leukemia, solid tumour at advanced stage or relapsed, and hematopoietic stem cell transplantation. The incidence of IFI is lower than bacterial infection but mortality rate remains high. This review is designed to help paediatric oncologists in choosing the appropriate anti-fungal strategy and agents for prophylaxis, empirical, pre-emptive and specific therapy on the basis of published evidence.

  18. Current evidence of antifungal prophylaxis and therapy in pediatric patients

    PubMed Central

    Giacchino, Mareva; Milano, Giuseppe Maria; Carraro, Francesca; Bezzio, Stefania; Pegoraro, Anna; Aversa, Franco; Cesaro, Simone

    2011-01-01

    Invasive fungal infections (IFI) are an important complication in pediatric haematological and oncological patients who undergo intensive chemotherapy for leukemia, solid tumour at advanced stage or relapsed, and hematopoietic stem cell transplantation. The incidence of IFI is lower than bacterial infection but mortality rate remains high. This review is designed to help paediatric oncologists in choosing the appropriate anti-fungal strategy and agents for prophylaxis, empirical, pre-emptive and specific therapy on the basis of published evidence. PMID:21647279

  19. The impact of hospital discharge on inappropriate hospital stay.

    PubMed

    Panis, Lambert J G G; Verheggen, Frank W S M; Pop, Peter; Prins, Martin H

    2004-01-01

    Appropriate hospital stay should be effective, efficient and tailored to patient needs. Previous studies have found that on average 20 per cent of hospital stay is inappropriate. Within obstetrics, inappropriate hospital stay consists mostly of delays in hospital discharge. The specific goals of this study were to reduce inappropriate hospital stay by fine-tuning patient logistics, increasing efficiency and providing more comfortable surroundings. New policies using strict discharge criteria were implemented. Total inappropriate hospital stay decreased from 13.3 to 7.2 per cent. The delay in discharge procedures halved. P-charts showed a decrease in inappropriate hospital stay, indicating the current process to be stable. Concludes that a significant reduction in inappropriate hospital stay was found following the implementation of innovative hospital discharge policies, indicating greater efficiency and accessibility of hospital services.

  20. Codeine-induced syndrome of inappropriate antidiuretic hormone: case report.

    PubMed

    Karahan, Samet; Karagöz, Hatice; Erden, Abdulsamet; Avcı, Deniz; Esmeray, Kübra

    2014-03-01

    The syndrome of inappropriate antidiuretic hormone was first described in 1957 by Schwartz, and is characterised by hyponatraemia, inappropriately increased urine osmolality and urine sodium, and decreased serum osmolality in a euvolemic patient without edema. A patient with the syndrome of inappropriate antidiuretic hormone should have normal cardiac, renal, adrenal, hepatic, and thyroid functions and should not take any diuretics. We present a case of the syndrome of inappropriate antidiuretic hormone caused by codeine and associated with reduced urine volume, increased urine sodium, and decreased serum sodium concentration. The syndrome of inappropriate antidiuretic hormone is a disease that can lead to morbidity and even mortality. Clinicians should measure serum electrolytes intermittently in order to avoid missing the diagnosis of the syndrome of inappropriate antidiuretic hormone in patients using opioid.

  1. Antifungal activity of substituted aurones.

    PubMed

    Sutton, Caleb L; Taylor, Zachary E; Farone, Mary B; Handy, Scott T

    2017-02-15

    Novel antifungals are in high demand as there is a growing resistance to antifungals currently in use. In particular, opportunistic fungal infections caused by Candida spp. are on the rise with infections by this genus accounting for the most severe fungal infections following chemotherapy, implantation procedures, and in patients with HIV/AIDS. A series of simple aurone analogs were synthesized and screened for antifungal activity versus Candida spp. Several compounds displayed activity at 100μM, with two having IC50 values below 20μM for three species of Candida. One of the compounds tested here also exhibits anti-biofilm activity for mid-maturation growth.

  2. Syndrome of inappropriate antidiuretic hormone secretion from concomitant use of itraconazole and vindesine.

    PubMed

    Zhou, H; Li, L; Zhou, Y; Han, Y

    2017-08-06

    Several studies have reported that itraconazole-induced inhibition of vincristine (VCR) metabolism might result in neurological impairment and syndrome of inappropriate antidiuretic hormone (SIADH). However, there are few reports concerning adverse drug reactions (ADRs) resulting from concomitant use of vindesine (VDS) and itraconazole. Here, we report the first case of adverse drug interactions (ADIs) between itraconazole and VDS in a Chinese child with acute lymphocytic leukaemia (ALL). A 4-year-old boy was diagnosed with standard-risk ALL and was receiving VDS (3 mg/m(2) ) for maintenance therapy and itraconazole for IFI recurrence. Severe neurotoxicity, consisting mainly of trismus and SIADH, was noticed after 7 days of VDS administration. After discontinuation of itraconazole and its replacement with caspofungin, the patient recovered from neurological signs and symptoms. The ADIs can be explained by VDS accumulation owing to inherent loss of CYP3A5 (*3/*3) function, and inhibition of CYP3A4 activity by itraconazole. Syndrome of inappropriate antidiuretic hormone from co-administration of itraconazole and VDS has not previously been reported to our knowledge. We suggest that the concomitant use of these drugs should be avoided if possible. The use of alternative antifungal drugs (AFDs) should be considered, and ADRs should be closely monitored when the combination of itraconazole and VDS is unavoidable. © 2017 John Wiley & Sons Ltd.

  3. Mechanisms of echinocandin antifungal drug resistance

    PubMed Central

    Perlin, David S.

    2015-01-01

    Fungal infections due to Candida and Aspergillus species cause extensive morbidity and mortality, especially among immunosuppressed patients, and antifungal therapy is critical to patient management. Yet only a few drug classes are available to treat invasive fungal diseases, and this problem is compounded by the emergence of antifungal resistance. Echinocandin drugs are the preferred choice to treat candidiasis. They are the first cell wall–active agents and target the fungal-specific enzyme glucan synthase, which catalyzes the biosynthesis of β-1,3-glucan, a key cell wall polymer. Therapeutic failures occur rarely among common Candida species, with the exception of Candida glabrata, which are frequently multidrug resistant. Echinocandin resistance in susceptible species is always acquired during therapy. The mechanism of resistance involves amino acid changes in hot-spot regions of Fks subunits of glucan synthase, which decrease the sensitivity of the enzyme to drug. Cellular stress response pathways lead to drug adaptation, which promote the formation of resistant fks strains. Clinical factors promoting echinocandin resistance include empiric therapy, prophylaxis, gastrointestinal reservoirs, and intra-abdominal infections. A better understanding of the echinocandin resistance mechanism, along with cellular and clinical factors promoting resistance, will promote more effective strategies to overcome and prevent echinocandin resistance. PMID:26190298

  4. Inappropriate treatment of traumatic dental injuries.

    PubMed

    Dorney, B

    1999-08-01

    Traumatic dental injuries are emergencies that must be treated expediently and efficiently to reduce pain and to restore function and appearance. With an increase in the incidence of traumatic dental injuries in our community (I) it is essential that the dental practitioner has "up-to-date" knowledge of dental trauma. The peak incidences of injury are 2-4 years and 8-10 years of age, with statistics revealing 30% of children suffer trauma to the primary dentition, and 22% of children suffer trauma to the permanent dentition by the age of 14 (I). The male to female ratio is 2:1. Aside from the emergency treatment and clinical decisions that must be made at the time of injury there is a need for long-term follow-up because of the high incidences of complications (2, 3). The factors that will influence the extent of injury will be energy impact, the direction of the impacting object, its shape and its resilience (4). Recent articles have raised concerns about inappropriate treatment for traumatic dental injuries (5, 6). This report will look at one such case.

  5. What to do about Inappropriate Behavior

    NASA Astrophysics Data System (ADS)

    Durand, Bernice

    2011-01-01

    If you believe you are a victim of harassment, bias, or prejudice, your first need is to know what person you should confide in who would be qualified to help you understand and go through the process of resolving your difficult situation. You will be best off if you have an accessible, trustworthy institutional infrastructure in place for dealing with inappropriate behavior. The exact nature of the infrastructure varies among institutions; but it starts with leadership from the top person in every unit, for example the university president, the dean, the department chair, and the research group leader. A good "safety net” structure also includes a reliable system for reporting and addressing problems before they escalate; an institutional "enforcer” who is widely known to mean business; and trainings and frequent publicity about the consequences of such behavior. The components of a good structure, as well as some alternative routes to take if you don't have such a system, will be described in the contexts of different types of institutions; and you will learn the criteria for prohibited behaviors. There will be time for analysis and discussion of scenarios taken from real incidents, altered to protect privacy.

  6. The Risks of Inappropriateness in Cardiac Imaging

    PubMed Central

    Picano, Eugenio

    2009-01-01

    The immense clinical and scientific benefits of cardiovascular imaging are well-established, but are also true that 30 to 50% of all examinations are partially or totally inappropriate. Marketing messages, high patient demand and defensive medicine, lead to the vicious circle of the so-called Ulysses syndrome. Mr. Ulysses, a typical middle-aged “worried-well” asymptomatic subject with an A-type coronary personality, a heavy (opium) smoker, leading a stressful life, would be advised to have a cardiological check-up after 10 years of war. After a long journey across imaging laboratories, he will have stress echo, myocardial perfusion scintigraphy, PET-CT, 64-slice CT, and adenosine-MRI performed, with a cumulative cost of >100 times a simple exercise-electrocardiography test and a cumulative radiation dose of >4,000 chest x-rays, with a cancer risk of 1 in 100. Ulysses is tired of useless examinations, exorbitant costs. unaffordable even by the richest society, and unacceptable risks. PMID:19543412

  7. The risks of inappropriateness in cardiac imaging.

    PubMed

    Picano, Eugenio

    2009-05-01

    The immense clinical and scientific benefits of cardiovascular imaging are well-established, but are also true that 30 to 50% of all examinations are partially or totally inappropriate. Marketing messages, high patient demand and defensive medicine, lead to the vicious circle of the so-called Ulysses syndrome. Mr. Ulysses, a typical middle-aged "worried-well" asymptomatic subject with an A-type coronary personality, a heavy (opium) smoker, leading a stressful life, would be advised to have a cardiological check-up after 10 years of war. After a long journey across imaging laboratories, he will have stress echo, myocardial perfusion scintigraphy, PET-CT, 64-slice CT, and adenosine-MRI performed, with a cumulative cost of >100 times a simple exercise-electrocardiography test and a cumulative radiation dose of >4,000 chest x-rays, with a cancer risk of 1 in 100. Ulysses is tired of useless examinations, exorbitant costs. unaffordable even by the richest society, and unacceptable risks.

  8. [CyberKnife can cause inappropriate shock].

    PubMed

    Cakmak, Nazmiye; Yılmaz, Hale; Sayar, Nurten; Erer, Betül

    2012-12-01

    Implantable cardioverter-defibrillators (ICD) have been increasingly used to treat life-threatening ventricular tachyarrhythmias. Although they have life-saving capabilities, they are very sensitive to electromagnetic energy sources. It has been reported that many problems associated with the detection of tachyarrhythmias and termination of the mechanism of the ICDs occur due to electromagnetic interference (EMI). In spite of the fact that EMI has been decreasingly observed with the latest generation ICDs, problems may still occur during radiotherapy. The CyberKnife is the latest stereotactic radio-surgery technology in the field of radiotherapy, and is currently being used for the treatment of malign neoplasm in the body. It is especially preferred for the treatment of advanced stage and metastatic tumors. Five ICD shocks were detected in a patient during a routine follow-up visit. When the patient was evaluated, it was determined that he underwent radiotherapy with CyberKnife technology because of lung metastasis and rectal adenocarcinoma. He received the ICD shocks while he was on radiotherapy. When the stored intracardiac electrograms in the memory of the ICD were investigated, it was established that the shocks were inappropriate shocks due to oversensing because of the exposure to EMI.

  9. [Syndrome of inappropriate secretion of antidiuretic hormone].

    PubMed

    Krysiak, Robert; Okopień, Bogusław

    2014-01-01

    Hyponatremia is a commonly encountered electrolyte abnormality in clinical practice and in some groups of patients is associated with significant morbidity and mortality. Although the pathophysiology of this disturbance is complex, its understanding is vital to the disorder's evaluation and treatment. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the commonest form of euvolemic hyponatremia and is the clinical and biochemical manifestation of a wide range of disease processes, mostly associated with malignancy, pulmonary, or neurologic disorders, and of pharmacotherapy. Symptoms vary depending on the severity of hyponatremia and, if occur, can range from weakness, mild headache, muscle cramps, nausea, and vomiting to convulsions, coma, and death. Identifying the underlying disorder remains an integral part of the diagnostic evaluation of patients. The most frequently used treatment options include water restriction, oral intake of salt, hypertonic saline and vaptans, being nonpeptide vasopressin antagonists interfering with the antidiuretic effect of the hormone. The aim of our paper is to present a practical diagnostic approach and management of SIADH, with a particular emphasis on the results of recent studies.

  10. Antifungal pharmacodynamics: Latin America's perspective.

    PubMed

    Gonzalez, Javier M; Rodriguez, Carlos A; Agudelo, Maria; Zuluaga, Andres F; Vesga, Omar

    The current increment of invasive fungal infections and the availability of new broad-spectrum antifungal agents has increased the use of these agents by non-expert practitioners, without an impact on mortality. To improve efficacy while minimizing prescription errors and to reduce the high monetary cost to the health systems, the principles of pharmacokinetics (PK) and pharmacodynamics (PD) are necessary. A systematic review of the PD of antifungals agents was performed aiming at the practicing physician without expertise in this field. The initial section of this review focuses on the general concepts of antimicrobial PD. In vitro studies, fungal susceptibility and antifungal serum concentrations are related with different doses and dosing schedules, determining the PD indices and the magnitude required to obtain a specific outcome. Herein the PD of the most used antifungal drug classes in Latin America (polyenes, azoles, and echinocandins) is discussed. Copyright © 2016 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

  11. Mechanisms of Antifungal Drug Resistance

    PubMed Central

    Cowen, Leah E.; Sanglard, Dominique; Howard, Susan J.; Rogers, P. David; Perlin, David S.

    2015-01-01

    Antifungal therapy is a central component of patient management for acute and chronic mycoses. Yet, treatment choices are restricted because of the sparse number of antifungal drug classes. Clinical management of fungal diseases is further compromised by the emergence of antifungal drug resistance, which eliminates available drug classes as treatment options. Once considered a rare occurrence, antifungal drug resistance is on the rise in many high-risk medical centers. Most concerning is the evolution of multidrug- resistant organisms refractory to several different classes of antifungal agents, especially among common Candida species. The mechanisms responsible are mostly shared by both resistant strains displaying inherently reduced susceptibility and those acquiring resistance during therapy. The molecular mechanisms include altered drug affinity and target abundance, reduced intracellular drug levels caused by efflux pumps, and formation of biofilms. New insights into genetic factors regulating these mechanisms, as well as cellular factors important for stress adaptation, provide a foundation to better understand the emergence of antifungal drug resistance. PMID:25384768

  12. The Deceleration of Inappropriate Comments by a Natural Consequence

    ERIC Educational Resources Information Center

    Lovitt, Thomas C.; And Others

    1973-01-01

    The characters of this study were two boys in a class for pupils with learning disabilities. After an initial assessment, which revealed that the inappropriate verbalizations occurred about twice each day, the peer-manager, contingent on each inappropriate remark, moved away from the subject to another desk explaining to the subject why he was…

  13. 20 CFR 369.4 - Inappropriate use of the seal.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Inappropriate use of the seal. 369.4 Section... OF THE SEAL OF THE RAILROAD RETIREMENT BOARD § 369.4 Inappropriate use of the seal. The Railroad Retirement Board shall not grant permission for use of the seal in those instances where use of the seal will...

  14. 20 CFR 369.4 - Inappropriate use of the seal.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Inappropriate use of the seal. 369.4 Section... OF THE SEAL OF THE RAILROAD RETIREMENT BOARD § 369.4 Inappropriate use of the seal. The Railroad Retirement Board shall not grant permission for use of the seal in those instances where use of the seal will...

  15. 20 CFR 369.4 - Inappropriate use of the seal.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Inappropriate use of the seal. 369.4 Section... OF THE SEAL OF THE RAILROAD RETIREMENT BOARD § 369.4 Inappropriate use of the seal. The Railroad Retirement Board shall not grant permission for use of the seal in those instances where use of the seal will...

  16. Functional Analysis and Treatment of Multiply Controlled Inappropriate Mealtime Behavior

    ERIC Educational Resources Information Center

    Bachmeyer, Melanie H.; Piazza, Cathleen C.; Fredrick, Laura D.; Reed, Gregory K.; Rivas, Kristi D.; Kadey, Heather J.

    2009-01-01

    Functional analyses identified children whose inappropriate mealtime behavior was maintained by escape and adult attention. Function-based extinction procedures were tested individually and in combination. Attention extinction alone did not result in decreases in inappropriate mealtime behavior or a significant increase in acceptance. By contrast,…

  17. Response Consequences to Televised Modeled Sex-Inappropriate Play Behavior

    ERIC Educational Resources Information Center

    Wolf, Thomas M.

    1975-01-01

    Boys and girls were exposed to a same- or opposite-sex televised peer model who played with a sex-inappropriate toy for the children. The model was then administered positive or negative reinforcement or no consequences by a female adult figure. Girls played with the sex-inappropriate toy more than boys following exposure, particularly when the…

  18. Assessing Students' Perceptions of Inappropriate and Appropriate Teacher Humor

    ERIC Educational Resources Information Center

    Frymier, Ann Bainbridge; Wanzer, Melissa Bekelja; Wojtaszczyk, Ann M.

    2008-01-01

    This study replicated and extended a preliminary typology of appropriate and inappropriate teacher humor and advanced three explanations for differences in interpretations of teacher humor. Students were more likely to view teacher humor as inappropriate when it was perceived as offensive and when it demeaned students as a group or individually.…

  19. Assessing Student Perceptions of Inappropriate and Appropriate Teacher Humor

    ERIC Educational Resources Information Center

    Frymier, Ann Bainbridge; Wanzer, Melissa Bekelja; Wojtaszczyk, Ann M.

    2007-01-01

    This study replicated and extended Wanzer, Frymier, Wojtaszczyk, and Smith's (2006) preliminary typology of appropriate and inappropriate teacher humor and advanced three explanations for differences in interpretations of teacher humor. Students were more likely to view teacher humor as inappropriate when it was perceived as offensive and when it…

  20. [Law 6/84: "an inappropriate law"].

    PubMed

    Barroco, L E

    1994-01-01

    The intervention of Dr. Luis Elmano Barroco was evaluated at a meeting on March 19, 1994, on the topic of the state of abortion after 10 years of the new abortion law. Some aspects of the law of 1984 are characterized as inappropriate and inadequate because of the experience of the maternity ward of Dr. Alfredo da Costa. It was expected that in the wake of the publication of the law, official health care institutions would provide services for termination of pregnancy in accordance with legal indications. However, a survey carried out by the Association for Family Planning in July 1993 revealed that more than 50% of hospitals did not perform abortions because of the inexistence of specialized services or lack of resources or on grounds of conscientious objection. Even a revision of the abortion law does not take into consideration the fact that before 12 weeks of gestation it is difficult to precisely confirm grave lesions or the physical and psychological state of health of the pregnant woman which could be potentially life threatening. It was not taken into account either that it is impossible to diagnose definitively chromosomal aberrations, severe diseases, and fetal malformation before the 16th week. The law did not contemplate the prevailing socioeconomical conditions either that lead to clandestine abortion with high morbidity and mortality from cervical lesions, uterine perforation, infections, sepsis, and salpingitis. Prenatal diagnosis for eugenic abortion can be carried out by cytogenetic analysis of the amniotic fluid and ecography, but such diagnosis probably amounts to only 30-40% of risk cases in the whole country. A recent study by the Johns Hopkins University indicated that the chance of survival of a child born before 24 weeks is nil, therefore the limit of induced abortion should be extended to the 24th week to facilitate diagnosis of possible genetic abnormalities.

  1. Inappropriate treatments for patients with cognitive decline.

    PubMed

    Robles Bayón, A; Gude Sampedro, F

    2014-01-01

    Some treatments are inappropriate for patients with cognitive decline. We analyse their use in 500 patients and present a literature review. Benzodiazepines produce dependence, and reduce attention, memory, and motor ability. They can cause disinhibition or aggressive behaviour, facilitate the appearance of delirium, and increase accident and mortality rates in people older than 60. In subjects over 65, low systolic blood pressure is associated with cognitive decline. Maintaining this figure between 130 and 140 mm Hg (145 in patients older than 80) is recommended. Hypocholesterolaemia < 160 mg/dl is associated with increased morbidity and mortality, aggressiveness, and suicide; HDL-cholesterol<40 mg/dl is associated with memory loss and increased vascular and mortality risks. Old age is a predisposing factor for developing cognitive disorders or delirium when taking opioids. The risks of prescribing anticholinesterases and memantine to patients with non-Alzheimer dementia that is not associated with Parkinson disease, mild cognitive impairment, or psychiatric disorders probably outweigh the benefits. Anticholinergic drugs acting preferentially on the peripheral system can also induce cognitive side effects. Practitioners should be aware of steroid-induced dementia and steroid-induced psychosis, and know that risk of delirium increases with polypharmacy. Of 500 patients with cognitive impairment, 70.4% were on multiple medications and 42% were taking benzodiazepines. Both conditions were present in 74.3% of all suspected iatrogenic cases. Polypharmacy should be avoided, if it is not essential, especially in elderly patients and those with cognitive impairment. Benzodiazepines, opioids and anticholinergics often elicit cognitive and behavioural disorders. Moreover, systolic blood pressure must be kept above 130 mm Hg, total cholesterol levels over 160 mg/dl, and HDL-cholesterol over 40 mg/dl in this population. Copyright © 2012 Sociedad Española de Neurolog

  2. Reconsidering "The inappropriateness of conventional cephalometrics".

    PubMed

    Bookstein, Fred L

    2016-06-01

    Of all the articles on cephalometrics this journal has published over the last half-century, the one most cited across the scientific literature is the 1979 lecture "The inappropriateness of conventional cephalometrics" by Robert Moyers and me. But the durable salience of this article is perplexing, as its critique was misdirected (it should have been aimed at the craniometrics of the early twentieth century, not merely the roentgenographic extension used in the orthodontic clinic) and its proposed remedies have all failed to establish themselves as methods of any broad utility. When problems highlighted by Moyers and me have been resolved at all, the innovations that resolved them owe to tools very different from those suggested in our article and imported from fields quite a bit farther from biometrics than we expected back in 1979. One of these tools was the creation de novo of a new abstract mathematical construction, statistical shape space, in the 1980s and 1990s; another was a flexible and intuitive new graphic, the thin-plate spline, for meaningfully and suggestively visualizing a wide variety of biological findings in these spaces. On the other hand, many of the complaints Moyers and I enunciated back in 1979, especially those stemming from the disarticulation of morphometrics from the explanatory styles and purposes of clinical medicine, remain unanswered even today. The present essay, a retrospective historical meditation, reviews the context of the 1979 publication, its major themes, and its relevance today. This essay is dedicated to the memory of Robert E. Moyers on the 100th anniversary of the American Journal of Orthodontics and Dentofacial Orthopedics.

  3. [Current considerations in syndrome of inappropriate secretion of antidiuretic hormone/syndrome of inappropriate antidiuresis].

    PubMed

    Velasco Cano, M V; Runkle de la Vega, Isabelle

    2010-05-01

    The syndrome of inappropriate secretion of antidiuretic hormone (SIADH)/syndrome of inappropriate antidiuresis is characterized by a hypotonic hyponatremia, with an insufficiently diluted urine given the plasmatic hypoosmolality, in the absence of hypovolemia (with or without a third space), hypotension, renal or heart failure, cirrhosis of the liver, hypothyroidism, adrenal insufficiency, vomiting, or other non-osmotic stimuli of ADH secretion. The response of ADH to the infusion of hypertonic saline divides SIADH into 4 different types. In type D, there is no alteration in ADH secretion. Rather, the defect is the maintained permeability of kidney aquaporin-2 channels to water. Activating mutations of the V2 receptor have been identified. The most frequent cause of SIADH is the use of drugs that induce secretion of the hormone. Old age is per se a risk factor for its development. SIADH is underdiagnosed, and hospitalization often worsens the clinical situation, due to an iatrogenic excess in the use of oral and i.v. liquids, often hypotonic, together with a reduction in salt intake. Treatment is directed towards normalization of natremia when possible, together with the avoidance of both hyponatremic encephalopathy as well as the osmotic demyelinization syndrome. Cases of "appropriate" secretion of ADH with normovolemic hyponatremia and high mortality rates should be treated with the same urgency as SIADH--such is the case of post-surgical hyponatremia.

  4. Update on Antifungal Drug Resistance

    PubMed Central

    Shor, Erika; Zhao, Yanan

    2015-01-01

    Invasive fungal infections remain a major source of global morbidity and mortality, especially among patients with underlying immune suppression. Successful patient management requires antifungal therapy. Yet, treatment choices are restricted due to limited classes of antifungal agents and the emergence of antifungal drug resistance. In some settings, the evolution of multidrug-resistant strains insensitive to several classes of antifungal agents is a major concern. The resistance mechanisms responsible for acquired resistance are well characterized and include changes in drug target affinity and abundance, and reduction in the intracellular level of drug by biofilms and efflux pumps. The development of high-level and multidrug resistance occurs through a stepwise evolution of diverse mechanisms. The genetic factors that influence these mechanisms are emerging and they form a complex symphony of cellular interactions that enable the cell to adapt and/or overcome drug-induced stress. Drivers of resistance involve a complex blend of host and microbial factors. Understanding these mechanisms will facilitate development of better diagnostics and therapeutic strategies to overcome and prevent antifungal resistance. PMID:26120512

  5. Prevalence of inappropriate tuberculosis treatment regimens: a systematic review

    PubMed Central

    Langendam, M.W.; van der Werf, M.J.; Huitric, E.; Manissero, D.

    2012-01-01

    A potential threat to the success of new tuberculosis (TB) drugs is the development of resistance. Using drugs in appropriate regimens, such as those recommended in the World Health Organization (WHO) treatment guidelines, prevents the development of resistance. We performed a systematic review to assess the prevalence of inappropriate prescription of TB drugs for the treatment of TB. MEDLINE, EMBASE and other databases were searched for relevant articles in January 2011. Observational studies published from 2000 that included TB patients receiving treatment were selected. A treatment regimen was considered inappropriate if the regimen was not a WHO recommended regimen. 37 studies were included. Inappropriate treatment regimens were prescribed in 67% of studies. The percentage of patients receiving inappropriate regimens varied between 0.4% and 100%. In 19 studies the quality of treatment regimen reporting was low. Despite the fact that assessment of inappropriate treatment was hampered by low quality of reporting, our data indicate a reasonable amount of inappropriate prescription of TB treatment regimens. Thus, there is a risk that new drugs will be used in inappropriate treatment regimens, even with WHO guidelines in place, introducing the risk of resistance development. This article highlights the need to improve implementation of the WHO treatment of TB guidelines. PMID:22005923

  6. Comparison of echinocandin antifungals

    PubMed Central

    Eschenauer, Gregory; DePestel, Daryl D; Carver, Peggy L

    2007-01-01

    The incidence of invasive fungal infections, especially those due to Aspergillus spp. and Candida spp., continues to increase. Despite advances in medical practice, the associated mortality from these infections continues to be substantial. The echinocandin antifungals provide clinicians with another treatment option for serious fungal infections. These agents possess a completely novel mechanism of action, are relatively well-tolerated, and have a low potential for serious drug–drug interactions. At the present time, the echinocandins are an option for the treatment of infections due Candida spp (such as esophageal candidiasis, invasive candidiasis, and candidemia). In addition, caspofungin is a viable option for the treatment of refractory aspergillosis. Although micafungin is not Food and Drug Administration-approved for this indication, recent data suggests that it may also be effective. Finally, caspofungin- or micafungin-containing combination therapy should be a consideration for the treatment of severe infections due to Aspergillus spp. Although the echinocandins share many common properties, data regarding their differences are emerging at a rapid pace. Anidulafungin exhibits a unique pharmacokinetic profile, and limited cases have shown a potential far activity in isolates with increased minimum inhibitory concentrations to caspofungin and micafungin. Caspofungin appears to have a slightly higher incidence of side effects and potential for drug–drug interactions. This, combined with some evidence of decreasing susceptibility among some strains of Candida, may lessen its future utility. However, one must take these findings in the context of substantially more data and use with caspofungin compared with the other agents. Micafungin appears to be very similar to caspofungin, with very few obvious differences between the two agents. PMID:18360617

  7. Special Issue: Novel Antifungal Drug Discovery

    PubMed Central

    Poeta, Maurizio Del

    2016-01-01

    This Special Issue is designed to highlight the latest research and development on new antifungal compounds with mechanisms of action different from the ones of polyenes, azoles, and echinocandins. The papers presented here highlight new pathways and targets that could be exploited for the future development of new antifungal agents to be used alone or in combination with existing antifungals. A computational model for better predicting antifungal drug resistance is also presented. PMID:28058254

  8. Treating chromoblastomycosis with systemic antifungals.

    PubMed

    Bonifaz, Alexandro; Paredes-Solís, Vanessa; Saúl, Amado

    2004-02-01

    Chromoblastomycosis is a subcutaneous mycosis for which there is no treatment of choice but rather, several treatment options, with low cure rates and many relapses. The choice of treatment should consider several conditions, such as the causal agent (the most common one being Fonsecaea pedrosoi ), extension of the lesions, clinical topography and health status of the patient. Most oral and systemic antifungals have been used; the best results have been obtained with itraconazole and terbinafine at high doses, for a mean of 6 - 12 months. In extensive and refractory cases, chemotherapy with oral antifungals may be associated with thermotherapy (local heat and/or cryosurgery). Limited or early cases may be managed with surgical methods, always associated with oral antifungal agents. It is important to determine the in vitro sensitivity of the major causal agents to the various drugs, by estimating the minimum inhibitory concentration, as well as drug tolerability and drug interactions.

  9. Antifungal Prophylaxis in Immunocompromised Patients

    PubMed Central

    Vazquez, Lourdes

    2016-01-01

    Invasive fungal infections (IFIs) represent significant complications in patients with hematological malignancies. Chemoprevention of IFIs may be important in this setting, but most antifungal drugs have demonstrated poor efficacy, particularly in the prevention of invasive aspergillosis. Antifungal prophylaxis in hematological patients is currently regarded as the gold standard in situations with a high risk of infection, such as acute leukemia, myelodysplastic syndromes, and autologous or allogeneic hematopoietic stem cell transplantation. Over the years, various scientific societies have established a series of recommendations for antifungal prophylaxis based on prospective studies performed with different drugs. However, the prescription of each agent must be personalized, adapting its administration to the characteristics of individual patients and taking into account possible interactions with concomitant medication. PMID:27648203

  10. Management of inappropriate sexual behaviors in dementia: a literature review.

    PubMed

    Tucker, Inese

    2010-08-01

    This paper reviews published literature on the pharmacological and non-pharmacological treatment of inappropriate sexual behavior in dementia. A literature search of Psychinfo and Cochrane databases was performed and data from case reports and case series were analyzed. No randomized controlled trials exist for any treatment of sexual disinhibition in dementia and there are no trials comparing different pharmacological agents. Case reports and case series report a wide range of pharmacotherapies as efficacious in the treatment of inappropriate sexual behaviors in dementia. There is only one case report of non-pharmacological strategies to manage inappropriate sexual behavior. Inappropriate sexual behaviors in dementia can be difficult to treat. Frequently, multiple psychoactive medications are used and many pharmacotherapies are trialed prior to finding an effective agent. More research is needed to clarify the usefulness of these medications and to identify non-pharmacological strategies to prevent unnecessary use of medications.

  11. Biochemical approaches to selective antifungal activity. Focus on azole antifungals.

    PubMed

    Vanden Bossche, H; Marichal, P; Gorrens, J; Coene, M C; Willemsens, G; Bellens, D; Roels, I; Moereels, H; Janssen, P A

    1989-01-01

    Azole antifungals (e.g. the imidazoles: miconazole, clotrimazole, bifonazole, imazalil, ketoconazole, and the triazoles: diniconazole, triadimenol, propiconazole, fluconazole and itraconazole) inhibit in fungal cells the 14 alpha-demethylation of lanosterol or 24-methylenedihydrolanosterol. The consequent inhibition of ergosterol synthesis originates from binding of the unsubstituted nitrogen (N-3 or N-4) of their imidazole or triazole moiety to the heme iron and from binding of their N-1 substituent to the apoprotein of a cytochrome P-450 (P-450(14)DM) of the endoplasmic reticulum. Great differences in both potency and selectivity are found between the different azole antifungals. For example, after 16h of growth of Candida albicans in medium supplemented with [14C]-acetate and increasing concentrations of itraconazole, 100% inhibition of ergosterol synthesis is achieved at 3 x 10(-8) M. Complete inhibition of this synthesis by fluconazole is obtained at 10(-5) M only. The agrochemical imidazole derivative, imazalil, shows high selectivity, it has almost 80 and 98 times more affinity for the Candida P-450(s) than for those of the piglet testes microsomes and bovine adrenal mitochondria, respectively. However, the topically active imidazole antifungal, bifonazole, has the highest affinity for P-450(s) of the testicular microsomes. The triazole antifungal itraconazole inhibits at 10(-5) M the P-450-dependent aromatase by 17.9, whereas 50% inhibition of this enzyme is obtained at about 7.5 x 10(-6)M of the bistriazole derivative fluconazole. The overall results show that both the affinity for the fungal P-450(14)DM and the selectivity are determined by the nitrogen heterocycle and the hydrophobic N-1 substituent of the azole antifungals. The latter has certainly a greater impact. The presence of a triazole and a long hypdrophobic nonligating portion form the basis for itraconazole's potency and selectivity.

  12. Antifungal Compounds from Piper Species

    PubMed Central

    Xu, Wen-Hui; Li, Xing-Cong

    2013-01-01

    This review documents chemical structures and antifungal activities of 68 compounds isolated from 22 Piper species of the plant family Piperaceae. These compounds include amides, flavonoids, prenylated benzoic acid derivatives, lignans, phenylpropanoids, butenolides, and cyclopentendiones. Some of them may serve as leads for potential pharmaceutical or agricultural fungicide development. PMID:24307889

  13. Antifungal resistance in yeast vaginitis.

    PubMed Central

    Dun, E.

    1999-01-01

    The increased number of vaginal yeast infections in the past few years has been a disturbing trend, and the scientific community has been searching for its etiology. Several theories have been put forth to explain the apparent increase. First, the recent widespread availability of low-dosage, azole-based over-the-counter antifungal medications for vaginal yeast infections encourages women to self-diagnose and treat, and women may be misdiagnosing themselves. Their vaginitis may be caused by bacteria, parasites or may be a symptom of another underlying health condition. As a result, they may be unnecessarily and chronically expose themselves to antifungal medications and encourage fungal resistance. Second, medical technology has increased the life span of seriously immune compromised individuals, yet these individuals are frequently plagued by opportunistic fungal infections. Long-term and intense azole-based antifungal treatment has been linked to an increase in resistant Candida and non-Candida species. Thus, the future of limiting antifungal resistance lies in identifying the factors promoting resistance and implementing policies to prevent it. PMID:10907778

  14. Antifungal Application of Nonantifungal Drugs

    PubMed Central

    Stylianou, Marios; Kulesskiy, Evgeny; Lopes, José Pedro; Granlund, Margareta; Wennerberg, Krister

    2014-01-01

    Candida species are the cause of 60% of all mycoses in immunosuppressed individuals, leading to ∼150,000 deaths annually due to systemic infections, whereas the current antifungal therapies either have toxic side effects or are insufficiently efficient. We performed a screening of two compound libraries, the Enzo and the Institute for Molecular Medicine Finland (FIMM) oncology collection library, for anti-Candida activity based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. From a total of 844 drugs, 26 agents showed activity against Candida albicans. Of those, 12 were standard antifungal drugs (SADs) and 7 were off-target drugs previously reported to be active against Candida spp. The remaining 7 off-target drugs, amonafide, tosedostat, megestrol acetate, melengestrol acetate, stanozolol, trifluperidol, and haloperidol, were identified with this screen. The anti-Candida activities of the new agents were investigated by three individual assays using optical density, ATP levels, and microscopy. The antifungal activities of these drugs were comparable to those of the SADs found in the screen. The aminopeptidase inhibitor tosedostat, which is currently in a clinical trial phase for anticancer therapy, displayed a broad antifungal activity against different Candida spp., including Candida glabrata. Thus, this screen reveals agents that were previously unknown to be anti-Candida agents, which allows for the design of novel therapies against invasive candidiasis. PMID:24277040

  15. Antifungal activity against Candida biofilms.

    PubMed

    Iñigo, Melania; Pemán, Javier; Del Pozo, Jose L

    2012-10-01

    Candida species have two distinct lifestyles: planktonic, and surface-attached communities called biofilms. Mature C. albicans biofilms show a complex three-dimensional architecture with extensive spatial heterogeneity, and consist of a dense network of yeast, hyphae, and pseudohyphae encased within a matrix of exopolymeric material. Several key processes are likely to play vital roles at the different stages of biofilm development, such as cell-substrate and cell-cell adherence, hyphal development, and quorum sensing. Biofilm formation is a survival strategy, since biofilm yeasts are more resistant to antifungals and environmental stress. Antifungal resistance is a multifactorial process that includes multidrug efflux pumps, target proteins of the ergosterol biosynthetic pathway. Most studies agree in presenting azoles as agents with poor activity against Candida spp. biofilms. However, recent studies have demonstrated that echinocandins and amphotericin B exhibit remarkable activity against C. albicans and Candida non-albicans biofilms. The association of Candida species with biofilm formation increases the therapeutic complexity of foreign body-related yeast infections. The traditional approach to the management of these infections has been to explant the affected device. There is a strong medical but also economical motivation for the development of novel anti-fungal biofilm strategies due to the constantly increasing resistance of Candida biofilms to conventional antifungals, and the high mortality caused by related infections. A better description of the extent and role of yeast in biofilms may be critical for developing novel therapeutic strategies in the clinical setting.

  16. Antifungal activity of juniper extracts

    USDA-ARS?s Scientific Manuscript database

    Sawdust from three species of Juniperus (i.e., J. virginianna, J. occidentalis, and J. ashei) were extracted with hexane or ethanol and the extracts tested for antifungal activity against four species of wood-rot fungi. These species studied represent the junipers with the greatest potential for co...

  17. Preemptive Antifungal Therapy for Febrile Neutropenic Hematological Malignancy Patients in China

    PubMed Central

    Yuan, Wei; Ren, Jinhai; Guo, Xiaonan; Guo, Xiaoling; Cai, Shengxin

    2016-01-01

    Background The aim of this study was to evaluate the efficiency, adverse effects, and pharmacoeconomic impact of empirical and preemptive antifungal therapy for febrile neutropenic hematological malignancy patients in China. Material/Methods Patients with febrile neutropenia during hematological malignancy were randomly divided into an empirical group and a preemptive group. The preemptive antifungal treatment was initiated if patient status was confirmed by clinical manifestation, imaging diagnosis, 1-3-β-D glucan(G) testing, and galactomannan (GM) test. The treatment was ended 2 weeks later if the patient was recovered from neutropenia. Voriconazole was used as the first-line medicine. All patients received intravenous administration of voriconazole every 12 h, with an initiating dose of 400 mg, then the dose was reduced to 200 mg. Results The overall survival rate was 97.1% and 94.6% in the empirical group and preemptive group, respectively, with no significant difference observed (χ2=1.051, P=0.305). However, the occurrence rate of invasive fungal disease (IFD) in the preemptive group was 9.2% vs. 2.2% in the empirical group. Moreover, the mortality rate due to IFD was 0.7% and 2.3% for the empirical group and preemptive group, respectively. The average duration and cost of preemptive antifungal therapy were 13.8±4.7 days and 8379.00±2253.00 RMB, respectively, which were lower than for empirical therapy. However, no significant differences were observed for incidence of adverse effects and hospital stay between the 2 groups. Conclusions Preemptive antifungal therapy for patients with febrile neutropenic hematological malignancy demonstrated a similar survival rate as with empirical therapy but is economically favorable in a Chinese population. PMID:27819257

  18. Demand for emergency health service: factors associated with inappropriate use

    PubMed Central

    Carret, Maria LV; Fassa, Anaclaudia G; Kawachi, Ichiro

    2007-01-01

    Background The inappropriate use of emergency room (ER) service by patients with non-urgent health problems is a worldwide problem. Inappropriate ER use makes it difficult to guarantee access for real emergency cases, decreases readiness for care, produces negative spillover effects on the quality of emergency services, and raises overall costs. Methods We conducted a cross-sectional study in a medium-sized city in southern Brazil. The urgency of the presenting complaint was defined according to the Hospital Urgencies Appropriateness Protocol (HUAP). Multivariable Poisson regression was carried out to examine factors associated with inappropriate ER use. Results The study interviewed 1,647 patients over a consecutive 13-day sampling period. The prevalence of inappropriate ER use was 24.2% (95% CI 22.1–26.3). Inappropriate ER use was inversely associated with age (P = 0.001), longer stay in the waiting room, longer duration of symptoms and morning shift. However, the determinants of inappropriate ER use differed according age groups (P value for interaction = 0.04). Within the younger age-group (15–49 years), inappropriate ER use was higher among females, patients who reported visiting the ER because there was no other place to go, patients reporting that the doctor at the regular place of care refused to attend to them without a prior appointment, and individuals who reported that the PHC clinic which they use is open for shorter periods during the day. Among older patients (50+ years), those with highest level of education, absence of self-reported chronic diseases and lack of social support were more likely to engage in higher inappropriate ER use. Conclusion Efforts should be made to redirect inappropriate ER demand. Besides expanding access to, and improving the quality of primary and secondary care, it is important to mobilize social support for older patients, to enhance the relationship between different levels of care, as well as to develop campaigns to

  19. Prevalence and correlates of inappropriate use of benzodiazepines in Kosovo.

    PubMed

    Tahiri, Zejdush; Kellici, Suela; Mone, Iris; Shabani, Driton; Qazimi, Musa; Burazeri, Genc

    2017-08-01

    In post-war Kosovo, the magnitude of inappropriate use of benzodiazepines is unknown to date. The aim of this study was to assess the prevalence and correlates of continuation of intake of benzodiazepines beyond prescription (referred to as "inappropriate use") in the adult population of Gjilan region in Kosovo. A cross-sectional study was conducted in Gjilan region in 2015 including a representative sample of 780 individuals attending different pharmacies and reporting use of benzodiazepines (385 men and 395 women; age range 18-87 years; response rate: 90%). A structured questionnaire was administered to all participants inquiring about the use of benzodiazepines and socio-demographic characteristics. Overall, the prevalence of inappropriate use of benzodiazepines was 58%. In multivariable-adjusted models, inappropriate use of benzodiazepines was significantly associated with older age (OR 1.7, 95% CI 1.1-2.7), middle education (OR 1.8, 95% CI 1.2-2.7), daily use (OR 1.4, 95% CI 1.1-2.0) and addiction awareness (OR 2.7, 95% CI 2.0-3.8). Furthermore, there was evidence of a borderline relationship with rural residence (OR 1.2, 95% CI 0.9-1.7). Our study provides novel evidence about the prevalence and selected correlates of inappropriate use of benzodiazepines in Gjilan region of Kosovo. Health professionals and policymakers in Kosovo should be aware of the magnitude and determinants of drug misuse in this transitional society.

  20. Universal antifungal therapy is not needed in persistent febrile neutropenia: a tailored diagnostic and therapeutic approach

    PubMed Central

    Aguilar-Guisado, Manuela; Martín-Peña, Almudena; Espigado, Ildefonso; Ruiz Pérez de Pipaon, Maite; Falantes, José; de la Cruz, Fátima; Cisneros, José M.

    2012-01-01

    Background Giving antifungal therapy exclusively to selected patients with persistent febrile neutropenia may avoid over-treatment without increasing mortality. The aim of this study was to validate an innovative diagnostic and therapeutic approach based on assessing patients’ risk profile and clinical criteria in order to select those patients requiring antifungal therapy. The efficacy of this approach was compared to that of universal empirical antifungal therapy. Design and Methods This was a prospective study which included all consecutive adult hematology patients with neutropenia and fever refractory to 5 days of empirical antibacterial therapy admitted to a teaching hospital in Spain over a 2-year period. A diagnostic and therapeutic approach based on clinical criteria and risk profile was applied in order to select patients for antifungal therapy. The sensitivity, specificity and negative predictive value of this approach and also the overall success rate, according to the same criteria of efficacy described in classical clinical trials, were analyzed. Results Eighty-five episodes were included, 35 of them (41.2%) in patients at high risk of invasive fungal infections. Antifungal therapy was not indicated in 33 episodes (38.8%). The overall incidence of proven and probable invasive fungal infections was 14.1%, all of which occurred in patients who had received empirical antifungal therapy. The 30-day crude mortality rate was 15.3% and the invasive fungal infection-related mortality rate was 2.8% (2/72). The overall success rate following the diagnostic and therapeutic approach was 36.5% compared with 33.9% and 33.7% obtained in the trial by Walsh et al. The sensitivity, specificity and negative predictive value of the study approach were 100%, 52.4% and 100%, respectively. Conclusions Based on the high negative predictive value of this diagnostic and therapeutic approach in persistent febrile neutropenia patients with hematologic malignancies or patients

  1. Universal antifungal therapy is not needed in persistent febrile neutropenia: a tailored diagnostic and therapeutic approach.

    PubMed

    Aguilar-Guisado, Manuela; Martín-Peña, Almudena; Espigado, Ildefonso; Ruiz Pérez de Pipaon, Maite; Falantes, José; de la Cruz, Fátima; Cisneros, José M

    2012-03-01

    Giving antifungal therapy exclusively to selected patients with persistent febrile neutropenia may avoid over-treatment without increasing mortality. The aim of this study was to validate an innovative diagnostic and therapeutic approach based on assessing patients' risk profile and clinical criteria in order to select those patients requiring antifungal therapy. The efficacy of this approach was compared to that of universal empirical antifungal therapy. This was a prospective study which included all consecutive adult hematology patients with neutropenia and fever refractory to 5 days of empirical antibacterial therapy admitted to a teaching hospital in Spain over a 2-year period. A diagnostic and therapeutic approach based on clinical criteria and risk profile was applied in order to select patients for antifungal therapy. The sensitivity, specificity and negative predictive value of this approach and also the overall success rate, according to the same criteria of efficacy described in classical clinical trials, were analyzed. Eighty-five episodes were included, 35 of them (41.2%) in patients at high risk of invasive fungal infections. Antifungal therapy was not indicated in 33 episodes (38.8%). The overall incidence of proven and probable invasive fungal infections was 14.1%, all of which occurred in patients who had received empirical antifungal therapy. The 30-day crude mortality rate was 15.3% and the invasive fungal infection-related mortality rate was 2.8% (2/72). The overall success rate following the diagnostic and therapeutic approach was 36.5% compared with 33.9% and 33.7% obtained in the trial by Walsh et al. The sensitivity, specificity and negative predictive value of the study approach were 100%, 52.4% and 100%, respectively. Based on the high negative predictive value of this diagnostic and therapeutic approach in persistent febrile neutropenia patients with hematologic malignancies or patients who have received a hematopoietic stem cell

  2. Rates of inappropriate laboratory test utilization in Ontario.

    PubMed

    Chami, Nadine; Simons, Janet E; Sweetman, Arthur; Don-Wauchope, Andrew C

    2017-10-01

    Medical laboratory tests ordered redundantly represent one of the targets for reducing diagnostic testing without negatively, and possibly positively, affecting patient care. We study a clearly defined category of excessive laboratory utilization for nine analytes where inappropriate diagnostic testing is defined in terms of the time interval between tests; that is, ordering a test too soon following the previous order of the same test. Population data from the near universal public Ontario Health Insurance Plan for the years 2006-2010 are employed where the tests are fulfilled by community medical laboratories. The analytes selected for consideration are thyroid stimulating hormone, hemoglobin A1c, lipid profile, serum protein electrophoresis, immunofixation, quantitative immunoglobulins, Vitamin D, Vitamin B12, and folate. For the nine analytes studied, the percentage of inappropriate tests ranged from 6% to 20%. Large proportions of these inappropriate tests were completed >2weeks prior to the minimum threshold to reorder defined by practice guidelines and/or were repeated excessively within a year. Between 60% and 85% of the time, the ordering physician of an inappropriate test was the same physician who ordered the previous test. Specialists were more likely than primary care physicians to order repeat tests too soon. A sizeable proportion of testing for these analytes was inappropriate according to practice guidelines. It is recommended that systems for preventing unnecessary repeat testing are investigated by the funding agencies and that reducing inappropriate testing be considered as a design element for electronic medical records and related information technology systems. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  3. Inappropriate home albuterol use during an acute asthma exacerbation.

    PubMed

    Clayton, Kelly; Monroe, Kathy; Magruder, Teresa; King, William; Harrington, Kathy

    2012-12-01

    Increased asthma morbidity and mortality is associated with inappropriate home self-management skills. To examine the proportion of children presenting to the emergency department (ED) with an acute asthma exacerbation with incorrect home use of their albuterol inhaler and to identify factors associated with improper treatment. Caregivers of children with asthma aged 4 to 14 years, presenting to the ED with an asthma exacerbation, participated in the study. Interviewers collected caregiver's perceived severity of the asthma exacerbation and home albuterol use before the ED visit. National Asthma Education and Prevention Program guidelines were used to classify home albuterol use as appropriate or inappropriate. Home albuterol use for the current asthma exacerbation was categorized as inappropriate (56 [68%]) and appropriate (26 [32%]) for 84 participants. Thirty-nine of the inappropriate group undertreated, with 24 not giving albuterol frequently enough and 15 without albuterol at home. Other reasons for incorrect home albuterol use included: no spacer, overtreating, overreacting, and using a controller medicine for quick relief. Those with appropriate albuterol use were more likely to have their child hospitalized for asthma in the past 48 months (P=.004). Caregivers with inappropriate use perceived their child's asthma exacerbation as more severe (P<.001) compared with physician rating. Physicians rated asthma severity higher in the appropriate group than the inappropriate group (P<.001). A significant proportion of caregivers incorrectly treat children's asthma exacerbation with albuterol. Despite perceiving their children's asthma exacerbations as more severe, most undertreat with albuterol. Correctly assessing asthma symptom severity and appropriate home albuterol use may be linked to disease experience. Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  4. Antifungal activity of some tetranortriterpenoids.

    PubMed

    Govindachari, T R; Suresh, G; Gopalakrishnan, G; Masilamani, S; Banumathi, B

    2000-06-01

    Natural tetranortriterpenoids such as cedrelone from Toona ciliata, azadiradione from Azadirachta indica, limonin, limonol and nomilinic acid from Citrus medica, along with some cedrelone derivatives were tested for their antifungal activity against Puccinia arachidis, a groundnut rust pathogen. Results show that cedrelone was the most effective in reducing rust pustule emergence. Replacement of functional groups or modification of the A or the B ring in cedrelone reduced the effectiveness indicating the importance of specific structural features for activity.

  5. T-wave oversensing and inappropriate shocks: a case report.

    PubMed

    Srivathsan, Komandoor; Scott, Luis R; Altemose, Gregory T

    2008-05-01

    A 27-year-old male with congenital long QT syndrome, SCN5A mutation experienced recurrent inappropriate exercise-related implantable cardioverter defibrillator (ICD) shocks. This device showed T-wave oversensing with double, which lead to these device discharges. Dynamic T-wave oversensing was reproducibly provoked at exercise treadmill testing and was confirmed as the mechanism leading to double counting. The insertion of a new pacing and sensing lead with increased R-wave amplitude did not solve the problem. Exchanging the existing ICD generator with one capable of automatic sensitivity control (Biotronik, Lexos DR, Biotronik, Berlin, Germany) completely eliminated T-wave oversensing and inappropriate shocks.

  6. Defensins: antifungal lessons from eukaryotes

    PubMed Central

    Silva, Patrícia M.; Gonçalves, Sónia; Santos, Nuno C.

    2014-01-01

    Over the last years, antimicrobial peptides (AMPs) have been the focus of intense research toward the finding of a viable alternative to current antifungal drugs. Defensins are one of the major families of AMPs and the most represented among all eukaryotic groups, providing an important first line of host defense against pathogenic microorganisms. Several of these cysteine-stabilized peptides present a relevant effect against fungi. Defensins are the AMPs with the broader distribution across all eukaryotic kingdoms, namely, Fungi, Plantae, and Animalia, and were recently shown to have an ancestor in a bacterial organism. As a part of the host defense, defensins act as an important vehicle of information between innate and adaptive immune system and have a role in immunomodulation. This multidimensionality represents a powerful host shield, hard for microorganisms to overcome using single approach resistance strategies. Pathogenic fungi resistance to conventional antimycotic drugs is becoming a major problem. Defensins, as other AMPs, have shown to be an effective alternative to the current antimycotic therapies, demonstrating potential as novel therapeutic agents or drug leads. In this review, we summarize the current knowledge on some eukaryotic defensins with antifungal action. An overview of the main targets in the fungal cell and the mechanism of action of these AMPs (namely, the selectivity for some fungal membrane components) are presented. Additionally, recent works on antifungal defensins structure, activity, and cytotoxicity are also reviewed. PMID:24688483

  7. Defensins: antifungal lessons from eukaryotes.

    PubMed

    Silva, Patrícia M; Gonçalves, Sónia; Santos, Nuno C

    2014-01-01

    Over the last years, antimicrobial peptides (AMPs) have been the focus of intense research toward the finding of a viable alternative to current antifungal drugs. Defensins are one of the major families of AMPs and the most represented among all eukaryotic groups, providing an important first line of host defense against pathogenic microorganisms. Several of these cysteine-stabilized peptides present a relevant effect against fungi. Defensins are the AMPs with the broader distribution across all eukaryotic kingdoms, namely, Fungi, Plantae, and Animalia, and were recently shown to have an ancestor in a bacterial organism. As a part of the host defense, defensins act as an important vehicle of information between innate and adaptive immune system and have a role in immunomodulation. This multidimensionality represents a powerful host shield, hard for microorganisms to overcome using single approach resistance strategies. Pathogenic fungi resistance to conventional antimycotic drugs is becoming a major problem. Defensins, as other AMPs, have shown to be an effective alternative to the current antimycotic therapies, demonstrating potential as novel therapeutic agents or drug leads. In this review, we summarize the current knowledge on some eukaryotic defensins with antifungal action. An overview of the main targets in the fungal cell and the mechanism of action of these AMPs (namely, the selectivity for some fungal membrane components) are presented. Additionally, recent works on antifungal defensins structure, activity, and cytotoxicity are also reviewed.

  8. Antibacterial and Antifungal Compounds from Marine Fungi

    PubMed Central

    Xu, Lijian; Meng, Wei; Cao, Cong; Wang, Jian; Shan, Wenjun; Wang, Qinggui

    2015-01-01

    This paper reviews 116 new compounds with antifungal or antibacterial activities as well as 169 other known antimicrobial compounds, with a specific focus on January 2010 through March 2015. Furthermore, the phylogeny of the fungi producing these antibacterial or antifungal compounds was analyzed. The new methods used to isolate marine fungi that possess antibacterial or antifungal activities as well as the relationship between structure and activity are shown in this review. PMID:26042616

  9. Antibacterial and antifungal compounds from marine fungi.

    PubMed

    Xu, Lijian; Meng, Wei; Cao, Cong; Wang, Jian; Shan, Wenjun; Wang, Qinggui

    2015-06-02

    This paper reviews 116 new compounds with antifungal or antibacterial activities as well as 169 other known antimicrobial compounds, with a specific focus on January 2010 through March 2015. Furthermore, the phylogeny of the fungi producing these antibacterial or antifungal compounds was analyzed. The new methods used to isolate marine fungi that possess antibacterial or antifungal activities as well as the relationship between structure and activity are shown in this review.

  10. Topical antifungals for seborrhoeic dermatitis

    PubMed Central

    Okokon, Enembe O; Verbeek, Jos H; Ruotsalainen, Jani H; Ojo, Olumuyiwa A; Bakhoya, Victor Nyange

    2015-01-01

    Background Seborrhoeic dermatitis is a chronic inflammatory skin condition that is distributed worldwide. It commonly affects the scalp, face and flexures of the body. Treatment options include antifungal drugs, steroids, calcineurin inhibitors, keratolytic agents and phototherapy. Objectives To assess the effects of antifungal agents for seborrhoeic dermatitis of the face and scalp in adolescents and adults. A secondary objective is to assess whether the same interventions are effective in the management of seborrhoeic dermatitis in patients with HIV/AIDS. Search methods We searched the following databases up to December 2014: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 11), MEDLINE (from 1946), EMBASE (from 1974) and Latin American Caribbean Health Sciences Literature (LILACS) (from 1982). We also searched trials registries and checked the bibliographies of published studies for further trials. Selection criteria Randomised controlled trials of topical antifungals used for treatment of seborrhoeic dermatitis in adolescents and adults, with primary outcome measures of complete clearance of symptoms and improved quality of life. Data collection and analysis Review author pairs independently assessed eligibility for inclusion, extracted study data and assessed risk of bias of included studies. We performed fixed-effect meta-analysis for studies with low statistical heterogeneity and used a random-effects model when heterogeneity was high. Main results We included 51 studies with 9052 participants. Of these, 45 trials assessed treatment outcomes at five weeks or less after commencement of treatment, and six trials assessed outcomes over a longer time frame. We believe that 24 trials had some form of conflict of interest, such as funding by pharmaceutical companies. Among the included studies were 12 ketoconazole trials (N = 3253), 11 ciclopirox trials (N = 3029), two lithium trials (N = 141

  11. Appropriate and Inappropriate Practices for Coaching Female Athletes

    ERIC Educational Resources Information Center

    Bryan, Charity; Sims, Sandra

    2014-01-01

    This article is intended to provide coaches, parents/guardians and school administrators with specific guidelines that identify coaching practices that are in the best interests of the adolescent female athlete (appropriate) and those that are counterproductive or even harmful (inappropriate). These guidelines can be used as a self-assessment for…

  12. Sexually Inappropriate or Abusive Behaviour among Pupils in Special Schools

    ERIC Educational Resources Information Center

    Fyson, Rachel

    2009-01-01

    In this article, Rachel Fyson of the Centre for Social Work in the School of Sociology and Social Policy at the University of Nottingham reports the findings of a study into sexually inappropriate or abusive behaviour occurring between pupils in special schools in four local authorities in England. The behaviours identified ranged from relatively…

  13. 28 CFR 51.35 - Disposition of inappropriate submissions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Disposition of inappropriate submissions. 51.35 Section 51.35 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR THE ADMINISTRATION OF SECTION 5 OF THE VOTING RIGHTS ACT OF 1965, AS AMENDED Processing of Submissions §...

  14. Hypercalcemia, inappropriate calcitriol levels, and tuberculosis on hemodialysis.

    PubMed

    Peces, R; Pobes, A; Díaz-Corte, C; Gago, E

    2000-08-01

    We describe a female patient undergoing hemodialysis who developed tuberculosis, hypercalcemia, and inappropriately elevated calcitriol levels. These findings suggest ectopic production of calcitriol by tuberculous granulomas. Successful treatment of tuberculosis led to a substantial decrease in the levels of calcium and calcitriol.

  15. Appropriate and Inappropriate Uses of Humor By Teachers

    ERIC Educational Resources Information Center

    Bekelja Wanzer, Melissa; Bainbridge Frymier, Ann; Wojtaszczyk, Ann M; Smith, Tony

    2006-01-01

    The use of humor in teaching has been linked to learning in several studies, although the research has been equivocal. The various types of humor used by teachers have also been investigated but not in terms of what students view as appropriate and inappropriate uses of humor. Participants in this study were asked to generate examples of…

  16. Functional Analysis and Treatment of Inappropriate Sexual Behavior.

    ERIC Educational Resources Information Center

    Fyffe, Christie E.; Kahng, SungWoo; Fittro, Ellen; Russell, David

    2004-01-01

    The results of a functional analysis showed that inappropriate sexual behaviors exhibited by a 9-year-old boy who had been diagnosed with traumatic brain injury were maintained by positive reinforcement in the form of social attention. An intervention consisting of functional communication training and extinction resulted in reduced levels of…

  17. Syndrome of inappropriate antidiuretic hormone secretion concurrent with liver disease in a dog.

    PubMed

    Kang, Min-Hee; Park, Hee-Myung

    2012-05-01

    A 5-year-old female Chihuahua was presented for acute collapse. Laboratory examinations showed markedly elevated levels of hepatobiliary enzymes. Empiric antibiotic therapy for bacterial infection of the liver was ineffective. The clinical signs worsened with the development of hyponatremia with hypoosmolality and elevated urine sodium levels. The dog was suspected of having acute cholangiohepatitis associated with an immune-mediated disease. Subsequently, it was diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH) on the basis of the specific disease criteria. Further tests showed normal function of the adrenal and thyroid glands, and MRI and cerebrospinal fluid (CSF) analysis did not show any intracranial diseases. Immunosuppressive therapy and water restriction resolved the clinical signs and improved the SIADH in this dog. This case indicates that SIADH can occur concurrently with suspected immune-mediated liver disease in dogs.

  18. Epidemiology and antifungal susceptibilities of yeasts causing vulvovaginitis in a teaching hospital.

    PubMed

    Gamarra, Soledad; Morano, Susana; Dudiuk, Catiana; Mancilla, Estefanía; Nardin, María Elena; de Los Angeles Méndez, Emilce; Garcia-Effron, Guillermo

    2014-10-01

    Vulvovaginal candidiasis is one of the most common mycosis. However, the information about antifungal susceptibilities of the yeasts causing this infection is scant. We studied 121 yeasts isolated from 118 patients with vulvovaginal candidiasis. The isolates were identified by phenotypic and molecular methods, including four phenotypic methods described to differentiate Candida albicans from C. dubliniensis. Antifungal susceptibility testing was performed according to CLSI documents M27A3 and M27S4 using the drugs available as treatment option in the hospital. Diabetes, any antibacterial and amoxicillin treatment were statistically linked with vulvovaginal candidiasis, while oral contraceptives were not considered a risk factor. Previous azole-based over-the-counter antifungal treatment was statistically associated with non-C.albicans yeasts infections. The most common isolated yeast species was C. albicans (85.2 %) followed by C. glabrata (5 %), Saccharomyces cerevisiae (3.3 %), and C. dubliniensis (2.5 %). Fluconazole- and itraconazole-reduced susceptibility was observed in ten and in only one C. albicans strains, respectively. All the C. glabrata isolates showed low fluconazole MICs. Clotrimazole showed excellent potency against all but seven isolates (three C. glabrata, two S. cerevisiae, one C. albicans and one Picchia anomala). Any of the strains showed nystatin reduced susceptibility. On the other hand, terbinafine was the less potent drug. Antifungal resistance is still a rare phenomenon supporting the use of azole antifungals as empirical treatment of vulvovaginal candidiasis.

  19. Antifungal activity of Juniperus essential oils against dermatophyte, Aspergillus and Candida strains.

    PubMed

    Cavaleiro, C; Pinto, E; Gonçalves, M J; Salgueiro, L

    2006-06-01

    The increasing resistance to antifungal compounds and the reduced number of available drugs led us to search therapeutic alternatives among aromatic plants and their essential oils, empirically used by antifungal proprieties. In this work the authors report on the antifungal activity of Juniperus essential oils (Juniperus communis ssp. alpina, J. oxycedrus ssp. oxycedrus and J. turbinata). Antifungal activity was evaluated by determination of MIC and MLC values, using a macrodilution method (NCCLS protocols), on clinical and type strains of Candida, Aspergillus and dermatophytes. The composition of the oils was ascertained by GC and GC/MS analysis. All essential oils inhibited test dermatophyte strains. The oil from leaves of J. oxycedrus ssp. oxycedrus is the most active, with MIC and MLC values ranging from 0.08-0.16 microl ml(-1) to 0.08-0.32 microl ml(-1), respectively. This oil is mainly composed of alpha-pinene (65.5%) and delta-3-carene (5.7%). J. oxycedrus ssp. oxycedrus leaf oil proved to be an emergent alternative as antifungal agent against dermatophyte strains. delta-3-Carene, was shown to be a fundamental compound for this activity. Results support that essential oils or some of their constituents may be useful in the clinical management of fungal infections, justifying future clinical trials to validate their use as therapeutic alternatives for dermatophytosis.

  20. Trehalose pathway as an antifungal target

    PubMed Central

    Perfect, John R.; Tenor, Jennifer L.; Miao, Yi; Brennan, Richard G.

    2017-01-01

    ABSTRACT With an increasing immunocompromised population which is linked to invasive fungal infections, it is clear that our present 3 classes of antifungal agents may not be sufficient to provide optimal management to these fragile patients. Furthermore, with widespread use of antifungal agents, drug-resistant fungal infections are on the rise. Therefore, there is some urgency to develop the antifungal pipeline with the goal of new antifungal agent discovery. In this review, a simple metabolic pathway, which forms the disaccharide, trehalose, will be characterized and its potential as a focus for antifungal target(s) explained. It possesses several important features for development of antifungal agents. First, it appears to have fungicidal characteristics and second, it is broad spectrum with importance across both ascomycete and basidiomycete species. Finally, this pathway is not found in mammals so theoretically specific inhibitors of the trehalose pathway and its enzymes in fungi should be relatively non-toxic for mammals. The trehalose pathway and its critical enzymes are now in a position to have directed antifungal discovery initiated in order to find a new class of antifungal drugs. PMID:27248439

  1. [Potentially inappropriate medications in geriatrics: Which tools to detect them?

    PubMed

    Desnoyer, Aude; Guignard, Bertrand; Lang, Pierre-Olivier; Desmeules, Jules; Vogt-Ferrier, Nicole; Bonnabry, Pascal

    2016-11-01

    Potentially inappropriate prescriptions include over-prescription, which refers to prescription of more drugs than clinically needed, mis-prescription which refers to incorrect prescription of a drug that is needed (as per drug, dose, drug interactions, duration of therapy, duplication, follow-up, etc.) and under-prescription which stands for failure to prescribe drugs that are needed. They are associated with adverse drug events, increased use of health-care services, morbimortality and health-care costs, and poorer quality of life. Due to polymorbidity and polypharmacy, potentially inappropriate prescription is common among the elderly. In the last 2 decades, explicit indicators to detect inappropriate prescriptions were developed in geriatrics. The aim of this review is to summarize, compare and critically review existing explicit criteria. We conducted a systematic literature search in PubMed, Embase, Cochrane Library and Google Scholar, from January 1991 to November 2015. The following keywords were used: "("inappropriate prescribing" [MeSH Terms] OR "medication errors" [MeSH Terms] AND "potentially inappropriate medications" [MeSH Terms] AND "elderly" [MeSH All field] AND "explicit criteria" [MeSH Terms])". Articles describing the development of new list of explicit indicators dedicated to geriatrics, in English and in French, were included in this review. Their characteristics, organization, content, and assessments of their validity and of the optimal tool for geriatrics are presented. Fourteen lists of explicit indicators were included in the review. An organization based on physiological systems and pathologies, as observed in ACOVE, 5th version of Beers criteria and STOPP/START enables quick application in general practice. A low overlap among criteria was observed between tools. This may be due to a lack of completeness for some tools. Mimica, ACOVE, PIEA, and STOPP/START are the most exhaustive ones, only the last three addressing the under

  2. Antifungal Activity of Citrus Essential Oils.

    PubMed

    Jing, Li; Lei, Zhentian; Li, Ligai; Xie, Rangjin; Xi, Wanpeng; Guan, Yu; Sumner, Lloyd W; Zhou, Zhiqin

    2014-03-27

    Citrus essential oils (CEOs) are a mixture of volatile compounds consisting mainly of monoterpene hydrocarbons and are widely used in the food and pharmaceutical industries because of their antifungal activities. To face the challenge of growing public awareness and concern about food and health safety, studies concerning natural biopreservatives have become the focus of multidisciplinary research efforts. In the past decades, a large amount of literature has been published on the antifungal activity of CEOs. This paper reviews the advances of research on CEOs and focuses on their in vitro and food antifungal activities, chemical compositions of CEOs, and the methods used in antifungal assessment. Furthermore, the antifungal bioactive components in CEOs and their potential mechanism of action are summarized. Finally, the applications of CEOs in the food industry are discussed in an attempt to provide new information for future utilization of CEOs in modern industries.

  3. Antifungal Activity of C-27 Steroidal Saponins

    PubMed Central

    Yang, Chong-Ren; Zhang, Ying; Jacob, Melissa R.; Khan, Shabana I.; Zhang, Ying-Jun; Li, Xing-Cong

    2006-01-01

    As part of our search for new antifungal agents from natural resources, 22 C-27 steroidal saponins and 6 steroidal sapogenins isolated from several monocotyledonous plants were tested for their antifungal activity against the opportunistic pathogens Candida albicans, Candida glabrata, Candida krusei, Cryptococcus neoformans, and Aspergillus fumigatus. The results showed that the antifungal activity of the steroidal saponins was associated with their aglycone moieties and the number and structure of monosaccharide units in their sugar chains. Within the 10 active saponins, four tigogenin saponins (compounds 1 to 4) with a sugar moiety of four or five monosaccharide units exhibited significant activity against C. neoformans and A. fumigatus, comparable to the positive control amphotericin B. The antifungal potency of these compounds was not associated with cytotoxicity to mammalian cells. This suggests that the C-27 steroidal saponins may be considered potential antifungal leads for further preclinical study. PMID:16641439

  4. Ultraviolet induction of antifungal activity in plants.

    PubMed

    Schumpp, O; Bruderhofer, N; Monod, M; Wolfender, J-L; Gindro, K

    2012-11-01

    Ultraviolet-C irradiation as a method to induce the production of plant compounds with antifungal properties was investigated in the leaves of 18 plant species. A susceptibility assay to determine the antifungal susceptibility of filamentous fungi was developed based on an agar dilution series in microtiter plates. UV irradiation strongly induced antifungal properties in five species against a clinical Fusarium solani strain that was responsible for an onychomycosis case that was resistant to classic pharmacological treatment. The antifungal properties of three additional plant species were either unaffected or reduced by UV-C irradiation. This study demonstrates that UV-C irradiation is an effective means of modulating the antifungal activity of very diverse plants from a screening perspective.

  5. Antifungal Susceptibilities of Paecilomyces Species

    PubMed Central

    Aguilar, C.; Pujol, I.; Sala, J.; Guarro, J.

    1998-01-01

    The MICs and minimum fungicidal concentrations (MFCs) of amphotericin B, miconazole, itraconazole, ketoconazole, fluconazole, and flucytosine for 52 isolates of Paecilomyces species were evaluated by the broth microdilution method, largely based on the recommendations of the National Committee for Clinical Laboratory Standards (document M27-A). The fungal isolates tested included 16 P. variotii, 11 P. lilacinus, 9 P. marquandii, 6 P. fumosoroseus, 4 P. javanicus, and 2 P. viridis isolates and 1 isolate of each of the following species: P. carneus, P. farinosus, P. fulvus, and P. niveus. The MFCs and the MICs at which 90% of isolates were inhibited (MIC90s) for the six antifungal agents were remarkably high; the MIC50s indicated that amphotericin B, miconazole, itraconazole, and ketoconazole had good activities, while fluconazole and flucytosine demonstrated poor efficacy. The ranges of the MICs were generally wider and lower than those of the MFCs. There were significant susceptibility differences among the species. All species with the exception of P. variotii were highly resistant to fluconazole and flucytosine; P. variotii was susceptible to flucytosine. Amphotericin B and the rest of the azoles showed good activity against P. variotii, while all the antifungal agents assayed showed low efficacy against P. lilacinus. PMID:9660991

  6. Active packaging with antifungal activities.

    PubMed

    Nguyen Van Long, N; Joly, Catherine; Dantigny, Philippe

    2016-03-02

    There have been many reviews concerned with antimicrobial food packaging, and with the use of antifungal compounds, but none provided an exhaustive picture of the applications of active packaging to control fungal spoilage. Very recently, many studies have been done in these fields, therefore it is timely to review this topic. This article examines the effects of essential oils, preservatives, natural products, chemical fungicides, nanoparticles coated to different films, and chitosan in vitro on the growth of moulds, but also in vivo on the mould free shelf-life of bread, cheese, and fresh fruits and vegetables. A short section is also dedicated to yeasts. All the applications are described from a microbiological point of view, and these were sorted depending on the name of the species. Methods and results obtained are discussed. Essential oils and preservatives were ranked by increased efficacy on mould growth. For all the tested molecules, Penicillium species were shown more sensitive than Aspergillus species. However, comparison between the results was difficult because it appeared that the efficiency of active packaging depended greatly on the environmental factors of food such as water activity, pH, temperature, NaCl concentration, the nature, the size, and the mode of application of the films, in addition to the fact that the amount of released antifungal compounds was not constant with time. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Systemic antifungal activity of pyrrolnitrin.

    PubMed

    Gordee, R S; Matthews, T R

    1969-05-01

    The antifungal activity of pyrrolnitrin, previously shown to be effective against superficial infections, was evaluated against experimental systemic mycoses. Pyrrolnitrin was inhibitory in vitro at <0.78 to 100 mug/ml to Candida albicans, Cryptococcus neoformans, Blastomyces dermatitidis, Sporotrichum schenckii, and Histoplasma capsulatum. Pyrrolnitrin activity was reduced about 90% in sera. After multiple subcutaneous doses of pyrrolnitrin at 20 mg/kg, activity was recovered in mouse blood and urine as well as kidney, liver, and brain homogenates. Multiple daily doses (50 mg/kg) of this antibiotic were effective in reducing by 74% the number of viable cells of C. albicans recovered from kidney homogenates. Multiple doses (15 mg/kg) resulted in a 74% reduction in the number of C. neoformans from brain homogenates. Pyrrolnitrin was ineffective in reducing the recovery of B. dermatitidis or H. capsulatum from liver or spleen homogenates of infected mice. When compared with amphotericin B, hamycin, 5-fluorocytosine, and saramycetin, this antibiotic was less effective. This study indicates that pyrrolnitrin would have limited usefulness as a systemic antifungal agent.

  8. [Appropriate and inappropriate use of indwelling urinary catheters].

    PubMed

    Janzen, Jolien; Geerlings, Suzanne E

    2012-01-01

    Many hospitalized patients receive a urinary catheter during their stay. In 21-54% of patients, however, there is no appropriate indication for this. The most significant complication caused by the use of urinary catheters is the development of a urinary tract infection (UTI), one of the most common nosocomial infections. In 71-80% of hospital acquired UTIs a urinary catheter is present. The duration of the presence of a catheter is the major risk factor for catheter-associated UTI. Reducing the number of inappropriate catheterisations is an effective way of preventing catheter-related UTIs. Inappropriate use of indwelling urinary catheters can be reduced by maintaining strict guidelines on justifiable indications for inserting a urinary catheter, verifying daily whether the indication still applies, and by timely removal of the catheter when it is not or no longer needed.

  9. [Inappropriate use of health resources and the trivialisation of medicine].

    PubMed

    Segura Benedicto, Andreu; Giner Ruiz, Vicente

    2013-05-01

    One of the main problems of our health care system is its excessive use. The most evident results of this misuse are the waste of resources and the iatrogenic consequences that are not justified by any expectations in health improvement. Among the possible causes of this inappropriate use, the trivialization of medical practice should be emphasized. This entails not only a loss of respect and consideration, but facilitates and even stimulates reckless use. Although patients and health care workers are both responsible for this recklessness, politicians and health care managers should be held responsible more so. Without a real emancipation allowing health care users and the population to control the factors that determine their health, it is unlikely that the inappropriate use of health resources and its associated iatrogenic consequences will be reduced. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  10. Inappropriate secretion of antidiuretic hormone treated with frusemide.

    PubMed

    Decaux, G; Waterlot, Y; Genette, F; Hallemans, R; Demanet, J C

    1982-07-10

    Seven out of nine patients with chronic inappropriate secretion of antidiuretic hormone were successfully treated with 40 mg frusemide daily. One patient needed 80 mg, and the remaining patient achieved only a small increase in diuresis after 40 mg frusemide; this was probably related to his low creatinine clearance. In order to maintain a salt intake high enough to compensate for the loss of urine electrolytes 3 to 6 g sodium chloride was added as tablets to the sodium-free diet in six patients. Hypokalaemia occurred in five patients but was easily corrected with either supplements of potassium chloride or a potassium-sparing diuretic. These findings add further weight to evidence that Frusemide is a good alternative for the treatment of patients with inappropriate secretion of antidiuretic hormone who cannot tolerate water restriction.

  11. Inappropriate secretion of antidiuretic hormone treated with frusemide.

    PubMed Central

    Decaux, G; Waterlot, Y; Genette, F; Hallemans, R; Demanet, J C

    1982-01-01

    Seven out of nine patients with chronic inappropriate secretion of antidiuretic hormone were successfully treated with 40 mg frusemide daily. One patient needed 80 mg, and the remaining patient achieved only a small increase in diuresis after 40 mg frusemide; this was probably related to his low creatinine clearance. In order to maintain a salt intake high enough to compensate for the loss of urine electrolytes 3 to 6 g sodium chloride was added as tablets to the sodium-free diet in six patients. Hypokalaemia occurred in five patients but was easily corrected with either supplements of potassium chloride or a potassium-sparing diuretic. These findings add further weight to evidence that Frusemide is a good alternative for the treatment of patients with inappropriate secretion of antidiuretic hormone who cannot tolerate water restriction. PMID:6805839

  12. Advances in understanding and treatment of feline inappropriate elimination.

    PubMed

    Herron, Meghan E

    2010-11-01

    Feline inappropriate elimination is the number one behavioral reason for relinquishment of cats to shelters and has historically been the most commonly reported feline problem addressed by behavior professionals. Veterinarians are hence challenged to uncover the underlying motivation for this behavior so that an accurate diagnosis can be made and an effective treatment plan implemented. Before a behavioral diagnosis can be made, underlying medical disease must be addressed, making a comprehensive physical evaluation imperative. After all medical issues have been addressed, a behavior diagnoses list is made based on detailed historical information obtained from the cat owner. A distinction is first established between marking and inappropriate toileting, according to elimination postures described by the owner and the social relevance of the sites of inappropriate eliminations. Next, inadequacies of the litter box management are identified and subsequent aversions and preferences, including litter box aversion, substrate aversion, location aversion, substrate preference, and location preference, can be diagnosed. The practitioner should be cognizant of the fact that anxiety from the environment and social conflict may play a major role in both marking and inappropriate toileting behaviors. Once both the medical and behavioral diagnoses are established, a treatment plan catered to the individual cat, owner, and household environment can be formulated. This should include acceptable forms of marking when indicated, appropriate litter box management and hygiene, reduction of environmental stressors, including resolution of social conflict in multicat households, proper treatment and restricted access to soiled areas, pheromone application, and, when indicated, anxiolytic drug therapy. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. Potentially inappropriate prescribing in a population of frail elderly people.

    PubMed

    Récoché, Isabelle; Lebaudy, Cécile; Cool, Charlène; Sourdet, Sandrine; Piau, Antoine; Lapeyre-Mestre, Maryse; Vellas, Bruno; Cestac, Philippe

    2017-02-01

    Background Frailty is a clinical syndrome highly predictive of functional decline after a stress or a medical event, such as adverse drug events. Objective To describe the prevalence of potentially inappropriate prescribing in a population of frail elderly patients. Setting Geriatric day hospital for assessment of frailty and prevention of disability, Toulouse, France. Method A cross-sectional study performed from January to April 2014. Two pharmacists retrospectively analyzed the prescriptions of elderly patients who were sent to the day hospital to assess their frailty and to be given a personalized plan of care and prevention. Potentially inappropriate prescribing was defined by combining explicit criteria: Laroche list, screening tool of older people's prescriptions, and screening tool to alert to right treatment with an implicit method (drug utilization review for each medication). Prescriptions' optimizations were then suggested to the geriatricians of the day hospital and classified according to criteria defined by the French Society of Clinical Pharmacy. Main outcome measure Prevalence of potentially inappropriate prescribing. Results Among the 229 patients included, 71.2% had potentially inappropriate prescribing. 76 patients (33.2%) had at least one drug without any valid indication. 51 (22.3%) had at least one drug with an unfavorable benefit-to-risk ratio according to their clinical and biological data, 42 (18.3%) according to the Laroche list and 38 (16.6%) had at least one drug with questionable efficacy. Conclusion Our work shows that the incidence of PIP is high in the frail elderly and that, in most cases, it could be avoided with an adequate and regular reassessment of the prescriptions. In future, prescription optimization will be integrated into the personalized medical care plan to further prevent drug-related disability.

  14. Pregnancy with known syndrome of inappropriate antidiuretic hormone.

    PubMed

    Nawathe, A; Govind, A

    2013-01-01

    Syndrome of inappropriate antidiuretic hormone (SIADH) is rarely encountered in pregnancy. We report a case of severe hyponatraemia with idiopathic SIADH. A total of 18 cases of hyponatraemia in pregnancy have been reported; seven fit the criteria of SIADH. Unlike our case, none were diagnosed before pregnancy. Of the cases, 13 were associated with pre-eclampsia. Our patient developed intrauterine growth restriction (IUGR) but did not develop pre-eclampsia.

  15. Inappropriate use of potent topical glucocorticoids in infants.

    PubMed

    Ozon, Alev; Cetinkaya, Semra; Alikasifoglu, Ayfer; Gonc, E Nazli; Sen, Yaşar; Kandemir, Nurgün

    2007-02-01

    Topical therapy with glucocorticoids (GCs) is used commonly in chronic dermatoses. Side effects are less common compared to systemic use; however, newer potent preparations may have serious side effects. A potential danger is their inappropriate use. Three infants who developed iatrogenic Cushing's syndrome and prolonged adrenal suppression in the course of GC therapy for simple diaper dermatitis are described. One patient also developed steatohepatitis which is uncommon with local GCs.

  16. Requests for "inappropriate" treatment based on religious beliefs.

    PubMed Central

    Orr, R D; Genesen, L B

    1997-01-01

    Requests by patients or their families for treatment which the patient's physician considers to be "inappropriate" are becoming more frequent than refusals of treatment which the physician considers appropriate. Such requests are often based on the patient's religious beliefs about the attributes of God (sovereignty, omnipotence), the attributes of persons (sanctity of life), or the individual's personal relationship with God (communication, commands, etc). We present four such cases and discuss some of the basic religious tenets of the three Abrahamic faith traditions as they relate to such requests. We suggest that religious reasons for requesting "inappropriate" treatment are "special" and deserve serious consideration. We offer guidance to assist clinicians and clinical ethicists as they attempt to resolve these conflicts, emphasising the importance of understanding the religious beliefs of the patient/surrogate and suggesting the assistance of a religious interpreter. We suggest open discussion with patients and families of both the clinical situation and the theological basis for these requests. We also suggest that clinicians use additional religious doctrines or principles from patients' own traditions to balance the reasons behind the requests. We conclude that most persistent requests for "inappropriate" treatment should be honoured. PMID:9220325

  17. Detecting Inappropriate Access to Electronic Health Records Using Collaborative Filtering.

    PubMed

    Menon, Aditya Krishna; Jiang, Xiaoqian; Kim, Jihoon; Vaidya, Jaideep; Ohno-Machado, Lucila

    2014-04-01

    Many healthcare facilities enforce security on their electronic health records (EHRs) through a corrective mechanism: some staff nominally have almost unrestricted access to the records, but there is a strict ex post facto audit process for inappropriate accesses, i.e., accesses that violate the facility's security and privacy policies. This process is inefficient, as each suspicious access has to be reviewed by a security expert, and is purely retrospective, as it occurs after damage may have been incurred. This motivates automated approaches based on machine learning using historical data. Previous attempts at such a system have successfully applied supervised learning models to this end, such as SVMs and logistic regression. While providing benefits over manual auditing, these approaches ignore the identity of the users and patients involved in a record access. Therefore, they cannot exploit the fact that a patient whose record was previously involved in a violation has an increased risk of being involved in a future violation. Motivated by this, in this paper, we propose a collaborative filtering inspired approach to predicting inappropriate accesses. Our solution integrates both explicit and latent features for staff and patients, the latter acting as a personalized "finger-print" based on historical access patterns. The proposed method, when applied to real EHR access data from two tertiary hospitals and a file-access dataset from Amazon, shows not only significantly improved performance compared to existing methods, but also provides insights as to what indicates an inappropriate access.

  18. Requests for "inappropriate" treatment based on religious beliefs.

    PubMed

    Orr, R D; Genesen, L B

    1997-06-01

    Requests by patients or their families for treatment which the patient's physician considers to be "inappropriate" are becoming more frequent than refusals of treatment which the physician considers appropriate. Such requests are often based on the patient's religious beliefs about the attributes of God (sovereignty, omnipotence), the attributes of persons (sanctity of life), or the individual's personal relationship with God (communication, commands, etc). We present four such cases and discuss some of the basic religious tenets of the three Abrahamic faith traditions as they relate to such requests. We suggest that religious reasons for requesting "inappropriate" treatment are "special" and deserve serious consideration. We offer guidance to assist clinicians and clinical ethicists as they attempt to resolve these conflicts, emphasising the importance of understanding the religious beliefs of the patient/surrogate and suggesting the assistance of a religious interpreter. We suggest open discussion with patients and families of both the clinical situation and the theological basis for these requests. We also suggest that clinicians use additional religious doctrines or principles from patients' own traditions to balance the reasons behind the requests. We conclude that most persistent requests for "inappropriate" treatment should be honoured.

  19. Inappropriate requests for magnetic resonance scans of the shoulder.

    PubMed

    Freeman, Richard; Khanna, Sanjay; Ricketts, David

    2013-11-01

    Magnetic resonance imaging (MRI) scans are a useful investigation for some shoulder pathology. They are costly however and a significant burden on radiology departments. In most cases clinical examination, plain radiography or ultrasound scan (USS) are sufficient for a diagnosis. There are no current UK guidelines regarding MRI shoulder scan requests. We reviewed 100 consecutive MRI shoulder scan requests and the associated formal reports; other investigations were also assessed. Overall, 56% of MRI scans were ordered inappropriately. Shoulder consultant's requests were more appropriate than other groups (70% vs. 38%. p = 0.04). Excluding shoulder consultants 63 % of scans were inappropriately ordered. Shoulder consultants were more likely to order a preceding X-ray (80% vs. 53% respectively, p = 0.03). Of those with a clinical diagnosis of cuff pathology only 29% had an USS. A high percentage of MRI shoulder scans are performed inappropriately. Shoulder consultants are more appropriate in their ordering than other groups. If all groups performed as well 50 % less MRI scans would need to be performed.

  20. Detecting Inappropriate Access to Electronic Health Records Using Collaborative Filtering

    PubMed Central

    Menon, Aditya Krishna; Jiang, Xiaoqian; Kim, Jihoon; Vaidya, Jaideep; Ohno-Machado, Lucila

    2013-01-01

    Many healthcare facilities enforce security on their electronic health records (EHRs) through a corrective mechanism: some staff nominally have almost unrestricted access to the records, but there is a strict ex post facto audit process for inappropriate accesses, i.e., accesses that violate the facility’s security and privacy policies. This process is inefficient, as each suspicious access has to be reviewed by a security expert, and is purely retrospective, as it occurs after damage may have been incurred. This motivates automated approaches based on machine learning using historical data. Previous attempts at such a system have successfully applied supervised learning models to this end, such as SVMs and logistic regression. While providing benefits over manual auditing, these approaches ignore the identity of the users and patients involved in a record access. Therefore, they cannot exploit the fact that a patient whose record was previously involved in a violation has an increased risk of being involved in a future violation. Motivated by this, in this paper, we propose a collaborative filtering inspired approach to predicting inappropriate accesses. Our solution integrates both explicit and latent features for staff and patients, the latter acting as a personalized “finger-print” based on historical access patterns. The proposed method, when applied to real EHR access data from two tertiary hospitals and a file-access dataset from Amazon, shows not only significantly improved performance compared to existing methods, but also provides insights as to what indicates an inappropriate access. PMID:24683293

  1. Inappropriateness in laboratory medicine: an elephant in the room?

    PubMed Central

    Bovo, Chiara; Ciaccio, Marcello

    2017-01-01

    Appropriateness of diagnostic testing can be conventionally described as prescription of the right test, using the right method, at the right time, to the right patient, with the right costs and for producing the right outcome. There is ongoing debate about the real burden of inappropriateness in laboratory diagnostics. The media coverage of this issue has also recently led to either over- or under-emphasizing the clinical, organizational and economic consequences. This is quite problematic, inasmuch as some reliable data are available in the current scientific literature, showing that inappropriateness of laboratory testing can be as high as 70%. This is especially evident for, though not limited to, cancer biomarkers testing, in which the practice of avoidable tests ordering is dramatically magnified. The reasons beyond inappropriateness are many and multifaceted, entailing wrong habits, resistance to changes, poor culture, insufficient education and healthcare inefficiencies. There are many unfavorable consequences attributable to avoidable testing, including unjustified incremental costs, derangement of laboratory efficiency and potential patient safety issues. The tentative solutions to this important problem necessitate that policymakers, local hospital administrators, laboratory professionals, clinicians, patients' associations and diagnostic companies join the efforts and embark in the same landmark effort for disseminating a better culture of appropriateness. PMID:28275627

  2. Primary antifungal prophylaxis in acute myeloblastic leukemia and myelodysplastic syndrome--still an open question?

    PubMed

    Rüping, Maria J G T; Vehreschild, Jörg J; Cornely, Oliver A

    2010-01-01

    In this review, we aim to compare different early treatment strategies of invasive fungal diseases in patients undergoing induction chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome. Three treatment approaches--prophylactic, empiric, and preemptive treatment--are subject to continuous discussion among physicians treating patients at risk. Considering the available clinical basis of evidence, we opt for antifungal prophylaxis with posaconazole 200 mg tid po as our primary prophylactic strategy, while the employment of preemptive treatment should be delayed until more accurate diagnostic tools become available. In addition to antifungal prophylaxis, empiric treatment with caspofungin or L-AmB may be administered to patients with fever resistant to broad-spectrum antibiotic treatment and without radiographic findings typical of invasive fungal disease.

  3. In Vitro Antifungal Susceptibility of Environmental Isolates of Cryptococcus spp. from the West Region of Cameroon.

    PubMed

    Dongmo, William; Kechia, Frederick; Tchuenguem, Roland; Nangwat, Claude; Yves, Iwewe; Kuiate, Jules-Roger; Dzoyem, Jean Paul

    2016-11-01

    Cryptococcus neoformans is responsible of cryptococcosis, a life-threatening infection that affects healthy and immunocompromised individuals. It is the first cause of adult acute meningitis in some sub-Saharan African countries with a mortality rate of about 100% in cases of inappropriate therapy. This study aimed at examining the occurrence and the antifungal patterns of Cryptococcus isolates from pigeon droppings and bat guanos in the west region of Cameroon. A total of 350 samples were randomly collected from three selected localities of west region of Cameroon. The identification was performed based on capsule production assessed by Indian ink preparation. Additional tests performed were urea broth, glycine and tryptophan assimilation tests. The antifungal susceptibility test was performed by the broth microdilution method. Mycological analysis led to the identification of 98 isolates, of which 57 isolates of C. neoformans var. gattii and 41 isolates of C. neoformans var. neoformans. All the isolates showed resistance to antifungals tested except nystatin which showed MIC mean values ranging between 0.5 µg/mL and 0.65 µg/mL. The prevalence of C. neoformans in pigeons and bats excreta in the west region of Cameroon is 28.57 %. C. neoformans var. gattii and C. neoformans var. neoformans are the main serotypes. Isolates found to be resistant to fluconazole and ketoconazole. Our results emphasize the need for further study on the molecular epidemiology in comparison with clinical isolates.

  4. Bias in the study of prediction of change: a Monte Carlo simulation study of the effects of selective attrition and inappropriate modeling of regression toward the mean.

    PubMed

    Gustavson, Kristin; Borren, Ingrid

    2014-12-17

    Medical researchers often use longitudinal observational studies to examine how risk factors predict change in health over time. Selective attrition and inappropriate modeling of regression toward the mean (RTM) are two potential sources of bias in such studies. The current study used Monte Carlo simulations to examine bias related to selective attrition and inappropriate modeling of RTM in the study of prediction of change. This was done for multiple regression (MR) and change score analysis. MR provided biased results when attrition was dependent on follow-up and baseline variables to quite substantial degrees, while results from change score analysis were biased when attrition was more strongly dependent on variables at one time point than the other. A positive association between the predictor and change in the health variable was underestimated in MR and overestimated in change score analysis due to selective attrition. Inappropriate modeling of RTM, on the other hand, lead to overestimation of this association in MR and underestimation in change score analysis. Hence, selective attrition and inappropriate modeling of RTM biased the results in opposite directions. MR and change score analysis are both quite robust against selective attrition. The interplay between selective attrition and inappropriate modeling of RTM emphasizes that it is not an easy task to assess the degree to which obtained results from empirical studies are over- versus underestimated due to attrition or RTM. Researchers should therefore use modern techniques for handling missing data and be careful to model RTM appropriately.

  5. Potentially inappropriate medications among older adults in Pelotas, Southern Brazil.

    PubMed

    Lutz, Bárbara Heather; Miranda, Vanessa Irribarem Avena; Bertoldi, Andréa Dâmaso

    2017-06-22

    To assess the use of potentially inappropriate medications among older adults. This is a population-based cross-sectional study with 1,451 older individuals aged 60 years or more in the city of Pelotas, State of Rio Grande do Sul, Brazil, in 2014. We have investigated the use of medications in the last 15 days. Using the Beers criteria (2012), we have verified the use of potentially inappropriate medications and their relationship with socioeconomic and demographic variables, polypharmacy, self-medication, and burden of disease. Among the 5,700 medications used, 5,651 could be assessed as to being inappropriate. Of these, 937 were potentially inappropriate for the older adults according to the 2012 Beers criteria (16.6%). Approximately 42.4% of the older adults studied used at least one medication considered as potentially inappropriate. The group of medications for the nervous system accounted for 48.9% of the total of the potentially inappropriate medications. In the adjusted analysis, the variables female, advanced age, white race, low educational level, polypharmacy, self-medication, and burden of disease were associated with the use of potentially inappropriate medications. It is important to known the possible consequences of the use of medication among older adults. Special attention should be given to the older adults who use polypharmacy. Specific lists should be created with more appropriate medications for the older population in the National Essential Medicine List. Avaliar o uso de medicamentos potencialmente inadequados entre idosos. Estudo transversal de base populacional com 1.451 idosos com 60 anos ou mais em Pelotas, RS, em 2014. Investigou-se o uso de medicamentos nos últimos 15 dias. Utilizando os critérios de Beers (2012), verificou-se a potencial inadequação dos medicamentos e sua relação com variáveis socioeconômicas e demográficas, polifarmácia, automedicação e carga de doença. Dentre os 5.700 medicamentos utilizados, 5

  6. An antifungal protein from ginger rhizomes.

    PubMed

    Wang, Hexiang; Ng, Tzi Bun

    2005-10-14

    There are very few reports on antifungal proteins from rhizomes and there is none from the family of Zingiberaceae. An antifungal protein with a novel N-terminal sequence was isolated from ginger rhizomes utilizing a protocol that involved ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, and fast protein liquid chromatography on Superdex 75. The protein was unadsorbed on DEAE-cellulose and adsorbed on Affi-gel blue gel. It exhibited an apparent molecular mass of 32kDa and exerted antifungal activity toward various fungi including Botrytis cinerea, Fusarium oxysporum, Mycosphaerella arachidicola, and Physalospora piricola.

  7. Laboratory tests of antifungal drugs.

    PubMed Central

    Holt, R J

    1975-01-01

    The procedures evolved in the author's laboratory over the past 20 years for the microbiological assessment of antifungal drugs are described; methods are detailed for the estimation of the sensitivity of pathogenic fungi to therapeutic agents and for the assay of those agents in body fluids. The preparation and maintenance of stock reference solutions of the drugs, the culture media used, and the incubation temperature and time are discussed. Sensitivity tests by paper disc and by liquid titration for minimal inhibitory and cidal concentrations estimated are described, and the importance of standardized initial inocula is emphasized. Two groups of assay procedures are given, the liquid dilution and the agar diffusion methods, and suitable indicator organisms for both methods are named. The paper concludes with a discussion on the problem of differential assays when two antimycotic agents are in simultaneous clinical use. Images PMID:765359

  8. Chemogenomic profiling predicts antifungal synergies

    PubMed Central

    Jansen, Gregor; Lee, Anna Y; Epp, Elias; Fredette, Amélie; Surprenant, Jamie; Harcus, Doreen; Scott, Michelle; Tan, Elaine; Nishimura, Tamiko; Whiteway, Malcolm; Hallett, Michael; Thomas, David Y

    2009-01-01

    Chemotherapies, HIV infections, and treatments to block organ transplant rejection are creating a population of immunocompromised individuals at serious risk of systemic fungal infections. Since single-agent therapies are susceptible to failure due to either inherent or acquired resistance, alternative therapeutic approaches such as multi-agent therapies are needed. We have developed a bioinformatics-driven approach that efficiently predicts compound synergy for such combinatorial therapies. The approach uses chemogenomic profiles in order to identify compound profiles that have a statistically significant degree of similarity to a fluconazole profile. The compounds identified were then experimentally verified to be synergistic with fluconazole and with each other, in both Saccharomyces cerevisiae and the fungal pathogen Candida albicans. Our method is therefore capable of accurately predicting compound synergy to aid the development of combinatorial antifungal therapies. PMID:20029371

  9. Antifungal proteins: More than antimicrobials?

    PubMed Central

    Hegedüs, Nikoletta; Marx, Florentine

    2013-01-01

    Antimicrobial proteins (AMPs) are widely distributed in nature. In higher eukaryotes, AMPs provide the host with an important defence mechanism against invading pathogens. AMPs of lower eukaryotes and prokaryotes may support successful competition for nutrients with other microorganisms of the same ecological niche. AMPs show a vast variety in structure, function, antimicrobial spectrum and mechanism of action. Most interestingly, there is growing evidence that AMPs also fulfil important biological functions other than antimicrobial activity. The present review focuses on the mechanistic function of small, cationic, cysteine-rich AMPs of mammals, insects, plants and fungi with antifungal activity and specifically aims at summarizing current knowledge concerning additional biological properties which opens novel aspects for their future use in medicine, agriculture and biotechnology. PMID:23412850

  10. Posaconazole prophylaxis--impact on incidence of invasive fungal disease and antifungal treatment in haematological patients.

    PubMed

    Peterson, Lisa; Ostermann, Julia; Rieger, Heidi; Ostermann, Helmut; Rieger, Christina Theresa

    2013-11-01

    Since two large-scale, randomised studies on posaconazole prophylaxis have demonstrated a clear benefit for patients at high risk for contracting invasive fungal disease (IFD), posaconazole prophylaxis has been adopted as standard of care for this patient collective. Several years on from implementation at our institution, we wanted to evaluate its impact on the incidence and use of empirical antifungal therapy in a real-life setting. We analysed retrospectively incidence and severity of IFD in high-risk patients with prophylaxis, using a historical cohort as comparator. A total of 200 patients had either received the extended spectrum triazole posaconazole in prophylactic dosage of 200 mg tid or empirical antifungal therapy. Disease events were analysed by application of the revised EORTC/MSG definitions for IFD. Before posaconazole prophylaxis, we recorded 57/100 cases of IFD which was reduced to 28/100 with prophylaxis. The empirical use of antifungal drugs was reduced to 41% from 91% in the non-prophylaxis cohort. Furthermore, we observed a shift in the categorisation of IFD according to EORTC/MSG criteria. Our data suggest that posaconazole was effective in reducing the rate and probability of invasive fungal disease in high-risk patients.

  11. Synthesis, antifungal activities and qualitative structure activity relationship of carabrone hydrazone derivatives as potential antifungal agents.

    PubMed

    Wang, Hao; Ren, Shuang-Xi; He, Ze-Yu; Wang, De-Long; Yan, Xiao-Nan; Feng, Jun-Tao; Zhang, Xing

    2014-03-11

    Aimed at developing novel fungicides for relieving the ever-increasing pressure of agricultural production caused by phytopathogenic fungi, 28 new hydrazone derivatives of carabrone, a natural bioactive sesquisterpene, in three types were designed, synthesized and their antifungal activities against Botrytis cinerea and Colletotrichum lagenarium were evaluated. The result revealed that all the derivatives synthesized exhibited considerable antifungal activities in vitro and in vivo, which led to the improved activities for carabrone and its analogues and further confirmed their potential as antifungal agents.

  12. Anaerobic Bacteremia: Impact of Inappropriate Therapy on Mortality

    PubMed Central

    Lee, Yangsoon; Park, Yongjung; Kim, Myungsook; Choi, Jun Yong; Yong, Dongeun; Jeong, Seok Hoon

    2016-01-01

    Background Investigation on incidence and mortality of anaerobic bacteremia (AB) is clinically relevant in spite of its infrequent occurrence and not often explored, which report varies according to period and institutions. Therefore, it is necessary to analyze the incidence and risk factors related to mortality and assess clinical outcomes of AB in current aspect. Materials and Methods Characteristics of AB patients and anaerobic bacteria from blood culture at a university hospital in 2012 were reviewed retrospectively. The correlation between risk factors and 28-day patient mortality was analyzed. Results A total of 70 non-duplicated anaerobic bacteria were isolated from blood of 70 bacteremia patients in 2012. The history of cardiovascular disease as host's risk factor was statistically significant (P = 0.0344) in univariate and multivariate analysis. Although the inappropriate therapy was not statistically significant in univariate and multivariate analysis, the survival rate of bacteremia was significantly worse in patients who had inappropriate therapy compared with those underwent appropriate therapy (hazard ratio, 5.4; 95% confidence interval, 1.7–6.9; P = 0.004). The most frequently isolated organism was Bacteroides fragilis (32 isolates, 46%), followed by Bacteroides thetaiotaomicron (10, 14%), and non-perfringens Clostridium (7, 10%). Conclusion The incidence of AB in 2012 was 2.3% (number of AB patients per 100 positive blood culture patients) and the mortality rate in patients with clinically significant AB was 21.4%. In addition, AB was frequently noted in patients having malignancy and the survival rate of AB was significantly worse in patients who received inappropriate therapy compared with those underwent appropriate therapy. PMID:27433379

  13. Early state research on antifungal natural products.

    PubMed

    Negri, Melyssa; Salci, Tânia P; Shinobu-Mesquita, Cristiane S; Capoci, Isis R G; Svidzinski, Terezinha I E; Kioshima, Erika Seki

    2014-03-07

    Nosocomial infections caused by fungi have increased greatly in recent years, mainly due to the rising number of immunocompromised patients. However, the available antifungal therapeutic arsenal is limited, and the development of new drugs has been slow. Therefore, the search for alternative drugs with low resistance rates and fewer side effects remains a major challenge. Plants produce a variety of medicinal components that can inhibit pathogen growth. Studies of plant species have been conducted to evaluate the characteristics of natural drug products, including their sustainability, affordability, and antimicrobial activity. A considerable number of studies of medicinal plants and alternative compounds, such as secondary metabolites, phenolic compounds, essential oils and extracts, have been performed. Thus, this review discusses the history of the antifungal arsenal, surveys natural products with potential antifungal activity, discusses strategies to develop derivatives of natural products, and presents perspectives on the development of novel antifungal drug candidates.

  14. Chitin synthase inhibitors as antifungal agents.

    PubMed

    Chaudhary, Preeti M; Tupe, Santosh G; Deshpande, Mukund V

    2013-02-01

    Increased risk of fungal diseases in immunocompromised patients, emerging fungal pathogens, limited repertoire of antifungal drugs and resistance development against the drugs demands for development of new and effective antifungal agents. With greater knowledge of fungal metabolism efforts are being made to inhibit specific enzymes involved in different biochemical pathways for the development of antifungal drugs. Chitin synthase is one such promising target as it is absent in plants and mammals. Nikkomycin Z, a chitin synthase inhibitor is under clinical development. Chitin synthesis in fungi, chitin synthase as a target for antifungal agent development, different chitin synthase inhibitors isolated from natural sources, randomly synthesized and modified from nikkomycin and polyoxin are discussed in this review.

  15. Antifungal susceptibility of Malassezia pachydermatis biofilm.

    PubMed

    Figueredo, Luciana A; Cafarchia, Claudia; Otranto, Domenico

    2013-11-01

    Antifungal resistance has been associated with biofilm formation in many microorganisms, but not yet in Malassezia pachydermatis. This saprophytic yeast can cause otitis and dermatitis in dogs and has emerged as an important human pathogen, responsible for systemic infections in neonates in intensive care units. This study aims to evaluate the in vitro antifungal susceptibility of M. pachydermatis strains, in both their planktonic and sessile forms, to fluconazole, miconazole, ketoconazole, itraconazole, posaconazole, terbinafine and voriconazole using the XTT assay and Clinical and Laboratory Standards Institute (CLSI) microdilution method. The minimum inhibitory concentration (MIC) values recorded for each drug were significantly higher for sessile cells relative to planktonic cells to the extent that ≥ 90% of M. pachydermatis strains in their sessile form were classified as resistant to all antifungal agents tested. Data suggest that M. pachydermatis biofilm formation is associated with antifungal resistance, paving the way towards investigating drug resistance mechanisms in Malassezia spp.

  16. Aripiprazole-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH).

    PubMed

    Bachu, Kalyan; Godkar, Darshan; Gasparyan, Anna; Sircar, Padmini; Yakoby, Mila; Niranjan, Selvanayagam

    2006-01-01

    Aripiprazole is a newer atypical antipsychotic agent used for effective treatment of schizophrenia. It significantly reduces unwanted side effects of older typical antipsychotics by targeting, with high affinity, dopamine D2/D3 and serotonin 5-HT1A/5-HT-2A receptors. Its documented mechanism of action makes it an unlikely agent to cause syndrome of inappropriate antidiuretic hormone secretion (SIADH). We present the first reported case of SIADH caused by aripiprazole in a patient with history of schizophrenia without other precipitating factors to explain hyponatremia or SIADH.

  17. Syndrome of inappropriate secretion of antidiuretic hormone due to desvenlafaxine.

    PubMed

    Lee, Gary tin-ho; Leung, Jess lam-ming

    2013-01-01

    Hyponatremia secondary to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is not uncommon in patients receiving treatment of selective serotonin reuptake inhibitors or venlafaxine. This is a case report of a 47-year-old man with depression, who developed hyponatremia after commencing treatment with desvenlafaxine. To our knowledge, this is the first case in which desvenlafaxine-associated SIADH was reported since the introduction of the drug. Physicians should be aware of the possibility of desvenlafaxine-associated hyponatremia in patients under age of 65. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Reduction in inappropriate therapy and mortality through ICD programming.

    PubMed

    Moss, Arthur J; Schuger, Claudio; Beck, Christopher A; Brown, Mary W; Cannom, David S; Daubert, James P; Estes, N A Mark; Greenberg, Henry; Hall, W Jackson; Huang, David T; Kautzner, Josef; Klein, Helmut; McNitt, Scott; Olshansky, Brian; Shoda, Morio; Wilber, David; Zareba, Wojciech

    2012-12-13

    The implantable cardioverter-defibrillator (ICD) is highly effective in reducing mortality among patients at risk for fatal arrhythmias, but inappropriate ICD activations are frequent, with potential adverse effects. We randomly assigned 1500 patients with a primary-prevention indication to receive an ICD with one of three programming configurations. The primary objective was to determine whether programmed high-rate therapy (with a 2.5-second delay before the initiation of therapy at a heart rate of ≥200 beats per minute) or delayed therapy (with a 60-second delay at 170 to 199 beats per minute, a 12-second delay at 200 to 249 beats per minute, and a 2.5-second delay at ≥250 beats per minute) was associated with a decrease in the number of patients with a first occurrence of inappropriate antitachycardia pacing or shocks, as compared with conventional programming (with a 2.5-second delay at 170 to 199 beats per minute and a 1.0-second delay at ≥200 beats per minute). During an average follow-up of 1.4 years, high-rate therapy and delayed ICD therapy, as compared with conventional device programming, were associated with reductions in a first occurrence of inappropriate therapy (hazard ratio with high-rate therapy vs. conventional therapy, 0.21; 95% confidence interval [CI], 0.13 to 0.34; P<0.001; hazard ratio with delayed therapy vs. conventional therapy, 0.24; 95% CI, 0.15 to 0.40; P<0.001) and reductions in all-cause mortality (hazard ratio with high-rate therapy vs. conventional therapy, 0.45; 95% CI, 0.24 to 0.85; P=0.01; hazard ratio with delayed therapy vs. conventional therapy, 0.56; 95% CI, 0.30 to 1.02; P=0.06). There were no significant differences in procedure-related adverse events among the three treatment groups. Programming of ICD therapies for tachyarrhythmias of 200 beats per minute or higher or with a prolonged delay in therapy at 170 beats per minute or higher, as compared with conventional programming, was associated with reductions in

  19. Medically Inappropriate or Futile Treatment: Deliberation and Justification 1

    PubMed Central

    Misak, Cheryl J.; White, Douglas B.; Truog, Robert D.

    2016-01-01

    This paper reframes the futility debate, moving away from the question “Who decides when to end what is considered to be a medically inappropriate or futile treatment?” and toward the question “How can society make policy that will best account for the multitude of values and conflicts involved in such decision-making?” It offers a pragmatist moral epistemology that provides us with (1) a clear justification of why it is important to take best standards, norms, and physician judgment seriously and (2) a clear justification of why ample opportunity must be made for patients, families, and society to challenge those standards and norms. PMID:26681796

  20. Quetiapine-Induced Syndrome of Inappropriate Secretion of Antidiuretic Hormone.

    PubMed

    Koufakis, Theocharis

    2016-01-01

    The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) can be induced by various conditions, including malignant neoplasms, infections, central nervous system disorders, and numerous drugs. We here report a case of a 65-year-old female patient, treated with quetiapine for schizophrenia, who presented with generalized tonic-clonic seizures and was finally diagnosed with quetiapine-induced SIADH. Quetiapine-associated hyponatremia is extremely uncommon and only a few, relevant reports can be found in the literature. This case underlines the fact that patients on antipsychotic medication and more specifically on quetiapine should be closely monitored and routinely tested for electrolyte disorders.

  1. Oncological emergencies: syndrome of inappropriate antidiuretic hormone secretion (SIADH).

    PubMed

    Matwiejczuk, Sylwester; Püsküllüoğlu, Miroslawa; Zygulska, Aneta L

    2014-01-01

    Excessive secretion of vasopressin in the course of Syndrome of Inappropriate Antidiuretic Hormone Secretion is a common cause of hyponatremia in cancer patients. Clinical symptoms depend on the cause, rate of change of sodium level and their absolute values. Treatment options include fluid restrictions, intravenous administration of hypertonic sodium chloride solutions, loop diuretics and vaptans. The sodium level should not be adjusted too fast, because it may lead to irreversible brain damage. The article presents pathophysiology, diagnostics and recommendations of management of this oncological emergency.

  2. Syndrome of inappropriate antidiuretic hormone secretion associated with olfactory neuroblastoma.

    PubMed

    Yumusakhuylu, Ali Cemal; Binnetoglu, Adem; Topuz, Muhammet Fatih; Bozkurtlar, Emine Baş; Baglam, Tekin; Sari, Murat

    2013-11-01

    This study reports a patient having olfactory neuroblastoma complicated by syndrome of inappropriate antidiuretic hormone secretion. Olfactory neuroblastoma is a rare tumor that begins in the olfactory membrane. Only 10 cases have been reported previously. Because of having nonspecific symptoms, most patients manifest at an advanced stage at the time of diagnosis. Olfactory neuroblastoma may show local invasion and/or distant metastasis. We demonstrated preoperatively clinical and biochemical parameters consistent with antidiuretic hormone syndrome turned to normal ranges after the treatment. Surgery, chemotherapy, and radiotherapy are the choices of treatment; among these, surgery is an indispensible treatment.

  3. Inappropriate antidiuretic hormone secretion due to squamous cell lung cancer.

    PubMed

    Kotoulas, Christophoros; Panagiotou, Ioannis; Tsipas, Panteleimon; Koutoulakis, Emmanouil

    2015-06-01

    The syndrome of inappropriate secretion of antidiuretic hormone is a disorder of impaired water excretion caused by the inability to suppress secretion of antidiuretic hormone. It has been commonly associated with small cell carcinoma. The association of this syndrome with squamous cell lung carcinoma has rarely been reported, with only 4 cases over the past two decades in the English literature. We describe the case of a 75-year-old Caucasian male who developed the syndrome after a right pneumonectomy for down-staged squamous cell lung cancer previously treated with neoadjuvant platinum-based chemotherapy and radiotherapy.

  4. Syndrome of Inappropriate Antidiuretic Hormone Secretion Following Liver Transplantation.

    PubMed

    Takagi, Kosei; Yagi, Takahito; Shinoura, Susumu; Umeda, Yuzo; Yoshida, Ryuichi; Nobuoka, Daisuke; Watanabe, Nobuyuki; Kuise, Takashi; Fuji, Tomokazu; Araki, Hiroyuki; Fujiwara, Toshiyoshi

    2017-02-01

    Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is an extremely rare cause of hyponatremia post-liver transplantation. A 15-year-old Japanese girl with recurrent cholangitis after Kasai surgery for biliary atresia underwent successful living donor liver transplantation. Peritonitis due to gastrointestinal perforation occurred. Hyponatremia gradually developed but improved after hypertonic sodium treatment. One month later, severe hyponatremia rapidly recurred. We considered the hyponatremia's cause as SIADH. We suspected that tacrolimus was the disease's cause, so we used cyclosporine instead, plus hypertonic sodium plus water intake restriction, which improved the hyponatremia. Symptomatic hyponatremia manifested by SIADH is a rare, serious complication post-liver transplantation.

  5. Inappropriate Halsted mastectomy and patient volume in Italian hospitals.

    PubMed Central

    Grilli, R; Mainini, F; Penna, A; Bertolini, G; Scorpiglione, N; Torri, V; Liberati, A

    1993-01-01

    To study whether Halsted mastectomy was used only when properly indicated, a prospective survey was undertaken on the process of care of 985 breast cancer patients seen consecutively at 62 general hospitals in Northern and Central Italy. Overall, 79% of Halsted mastectomies were performed inappropriately. The procedure was less likely to be performed on more educated patients and, other factors considered, on those seen at hospitals with larger volume. We conclude that the measurement of utilization of a surgical procedure for which only a few appropriate indications exist may help identify important relationships between hospital characteristics and quality of surgical care. PMID:8259814

  6. Development of Prophylactic Anti-Fungal Preparations.

    DTIC Science & Technology

    1980-10-01

    telly OW blocke Topical Anti-fungal Prophylaxis Sodium Pyrithione Chemical Assay Drug Persistence, Stratum Corneum Experimental Human Ringworm ...against common ringworm infection.a chemical assay for sodium pyrithione (a known anti-fungal drug) was developed in stratum corneum and its...prophylactic use when and if needed to combat superficial ringworm infections./ Work carried out under this contract and the citations of commercial

  7. Ototopical antifungals and otomycosis: a review.

    PubMed

    Munguia, Raymundo; Daniel, Sam J

    2008-04-01

    There has been an increase in the prevalence of otomycosis in recent years. This has been linked to the extensive use of antibiotic eardrops. Treatment of otomycosis is challenging, and requires a close follow-up. We present a review of the literature on otomycosis, the topical antifungals most commonly used, and discuss their ototoxic potential. Candida albicans and Aspergillus are the most commonly identified organisms. Antifungals from the Azole class seem to be the most effective, followed by Nystatin and Tolnaftate.

  8. Relationship between age and inappropriate implantable cardioverter-defibrillator therapy in MADIT-RIT (Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy).

    PubMed

    Biton, Yitschak; Huang, David T; Goldenberg, Ilan; Rosero, Spencer; Moss, Arthur J; Kutyifa, Valentina; McNitt, Scott; Strasberg, Boris; Zareba, Wojciech; Barsheshet, Alon

    2016-04-01

    There is limited data regarding the relationship between age and inappropriate therapy among patients with an implantable cardioverter-defibrillator (ICD) and resynchronization therapy. We aimed to investigate this relationship and the effect of ICD programming on inappropriate therapy by age. In the Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) 1500 patients were randomized to 3 ICD programming arms: (A) conventional with ventricular tachycardia (VT) therapy ≥170; (B) high-rate cutoff with VT therapy ≥200, and (C) prolonged 60-second delay for VT therapy ≥170. We investigated the relationship between age, the risk of inappropriate ICD therapy (including antitachycardia pacing [ATP] or shock), and ICD programming. Cumulative incidence function Kaplan-Meier graphs showed an inverse relationship between increasing quartiles of age (Q1: ≤55, Q2: 56-64, Q3: 65-71, and Q4: ≥72 years) and the risk for inappropriate therapy. Multivariate analyses showed that each increasing decade of life was associated with 34% (P < .001), 27% (P < .001), and 26% (P < .001) reduction in the risk of inappropriate shock, inappropriate ATP, and any inappropriate therapy, respectively. Treatment arms B and C as compared with arm A were associated with a significant reduction in the risk of inappropriate therapies across all age quartiles (P < .001 for all). Among patients with a primary prevention indication for an ICD, there is an inverse relationship between age and inappropriate ICD therapy. Innovative ICD programming of high-rate cutoff or prolonged delay for VT therapy is associated with significant reductions in inappropriate therapy among all age groups. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  9. Real-Time Clinical Decision Support Decreases Inappropriate Plasma Transfusion.

    PubMed

    Shah, Neil; Baker, Steven A; Spain, David; Shieh, Lisa; Shepard, John; Hadhazy, Eric; Maggio, Paul; Goodnough, Lawrence T

    2017-08-01

    To curtail inappropriate plasma transfusions, we instituted clinical decision support as an alert upon order entry if the patient's recent international normalized ratio (INR) was 1.7 or less. The alert was suppressed for massive transfusion and within operative or apheresis settings. The plasma order was automatically removed upon alert acceptance while clinical exception reasons allowed for continued transfusion. Alert impact was studied comparing a 7-month control period with a 4-month intervention period. Monthly plasma utilization decreased 17.4%, from a mean ± SD of 3.40 ± 0.48 to 2.82 ± 0.6 plasma units per hundred patient days (95% confidence interval [CI] of difference, -0.1 to 1.3). Plasma transfused below an INR of 1.7 or less decreased from 47.6% to 41.6% (P = .0002; odds ratio, 0.78; 95% CI, 0.69-0.89). The alert recommendation was accepted 33% of the time while clinical exceptions were chosen in the remaining cases (active bleeding, 31%; other clinical indication, 33%; and apheresis, 2%). Alert acceptance rate varied significantly among different provider specialties. Clinical decision support can help curtail inappropriate plasma use but needs to be part of a comprehensive strategy including audit and feedback for comprehensive, long-term changes.

  10. The problem of automation: Inappropriate feedback and interaction, not overautomation

    NASA Technical Reports Server (NTRS)

    Norman, Donald A.

    1989-01-01

    As automation increasingly takes its place in industry, especially high-risk industry, it is often blamed for causing harm and increasing the chance of human error when failures occur. It is proposed that the problem is not the presence of automation, but rather its inappropriate design. The problem is that the operations are performed appropriately under normal conditions, but there is inadequate feedback and interaction with the humans who must control the overall conduct of the task. When the situations exceed the capabilities of the automatic equipment, then the inadequate feedback leads to difficulties for the human controllers. The problem is that the automation is at an intermediate level of intelligence, powerful enough to take over control that which used to be done by people, but not powerful enough to handle all abnormalities. Moreover, its level of intelligence is insufficient to provide the continual, appropriate feedback that occurs naturally among human operators. To solve this problem, the automation should either be made less intelligent or more so, but the current level is quite inappropriate. The overall message is that it is possible to reduce error through appropriate design considerations.

  11. [Prevalence of potentially inappropriate drug prescription in the elderly].

    PubMed

    Fajreldines, A; Insua, J; Schnitzler, E

    2016-01-01

    One of the causes of preventable adverse drug events (ADES) in older patients constitutes inappropriate prescription of drugs (PIM). The PIM is where risks exceed the clinical benefit. Several instruments can be use to measure this problem, the most used are: a) Beers criteria; b) Screening tool to Older People Potentially inappropriate Prescription (STOPP); c) Screening tool to Alert Doctors to Right Appropriate indicated Treatments (START); d) The Medication Appropriateness Index (MAI). This study aims to assess the prevalence of PIM, in a population of older adults in three clinical scopes of university hospital. cross sectional study of 300 cases from a random sample of fields: hospitalization (n=100), ambulatory (n=100) and emergency (n=100), all patients over 65 years old or more who where treated at our hospital. 1355 prescription drugs were analized, finding patients hospitalized (PIM) of 57.7%, 55%, 26%, and 80% according to Beers, in ambulatory 36%, 36.5%, 5% and 52% with the same tools and in emergency 35%, 35%, 6% y 52% with the same tools. Was found significant association the PIM with polipharmacy with Beers, STOPP and MAI. results can be compare to world literature (26-80% vs 11-73.1%). The STOPP-START used in an integrated manner would be best estimating the problem of PIM. Copyright © 2016 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Multidrug resistance after inappropriate tuberculosis treatment: a meta-analysis

    PubMed Central

    van der Werf, Marieke J.; Langendam, Miranda W.; Huitric, Emma; Manissero, Davide

    2012-01-01

    We conducted a systematic review and meta-analysis to assess the evidence for the postulation that inappropriate tuberculosis (TB) regimens are a risk for development of multidrug-resistant (MDR)-TB. MEDLINE, EMBASE and other databases were searched for relevant articles in January 2011. Cohort studies including TB patients who received treatment were selected and data on treatment regimen, drug susceptibility testing results and genotyping results before treatment and at failure or relapse were abstracted from the articles. Four studies were included in the systematic review and two were included in the meta-analysis. In these two studies the risk of developing MDR-TB in patients who failed treatment and used an inappropriate treatment regimen was increased 27-fold (RR 26.7, 95% CI 5.0–141.7) when compared with individuals who received an appropriate treatment regimen. This review provides evidence that supports the general opinion that the development of MDR-TB can be caused by inadequate treatment, given the drug susceptibility pattern of the Mycobacterium tuberculosis bacilli. It should be noted that only two studies provided data for the meta-analysis. The information can be used to advocate for adequate treatment for patients based on drug resistance profiles. PMID:22005918

  13. Non-random species loss in bacterial communities reduces antifungal volatile production.

    PubMed

    Hol, W H Gera; Garbeva, Paolina; Hordijk, Cornelis; Hundscheid, P J; Gunnewiek, Paulien J A Klein; Van Agtmaal, Maaike; Kuramae, Eiko E; De Boer, Wietse

    2015-08-01

    The contribution of low-abundance microbial species to soil ecosystems is easily overlooked because there is considerable overlap between metabolic abilities (functional redundancy) of dominant and subordinate microbial species. Here we studied how loss of less abundant soil bacteria affected the production of antifungal volatiles, an important factor in the natural control of soil-borne pathogenic fungi. We provide novel empirical evidence that the loss of soil bacterial species leads to a decline in the production of volatiles that suppress root pathogens. By using dilution-to-extinction for seven different soils we created bacterial communities with a decreasing number of species and grew them under carbon-limited conditions. Communities with high bacterial species richness produced volatiles that strongly reduced the hyphal growth of the pathogen Fusarium oxysporum. For most soil origins loss of bacterial species resulted in loss of antifungal volatile production. Analysis of the volatiles revealed that several known antifungal compounds were only produced in the more diverse bacterial communities. Our results suggest that less abundant bacterial species play an important role in antifungal volatile production by soil bacterial communities and, consequently, in the natural suppression of soil-borne pathogens.

  14. Women's use of over-the-counter antifungal medications for gynecologic symptoms.

    PubMed

    Ferris, D G; Dekle, C; Litaker, M S

    1996-06-01

    Over-the-counter (OTC) antifungal products for vulvovaginal candidiasis (VVC) have gained tremendous popularity, as evidenced by staggering increases in sales since the products were switched from prescription-only to OTC status. The rapid escalation in the sale of these products may imply that women are using them inappropriately. The purposes of this study were to determine (1) whether women could correctly diagnose VVC and common genitourinary tract problems after reading classic case scenarios, (2) whether women could correctly select the appropriate treatment for these cases, and (3) whether a previous diagnosis of VVC by a clinician had any effect on a woman's ability to self-diagnose and self-treat VVC. Women 16 years of age and older were recruited from medical and community sites to complete a 63-question survey instrument designed to assess their knowledge of the symptoms and signs of pelvic inflammatory disease, bacterial vaginosis, acute cystitis, vaginal trichomoniasis, and vulvovaginal candidiasis after reading classic case scenarios. A total of 601 women completed the questionnaire, 552 subjects and 49 medically trained women who served as a criterion standard for comparison. Of the 552 subjects, 365 reported a prior diagnosis of VCC and 154 reported no such prior diagnosis. The medically trained cohort was more accurate in diagnosing VVC (83.7% correct) than were subjects who had received a prior diagnosis of VVC (34.5% correct), and more accurate than subjects without a previous diagnosis of VVC (11.0% correct, P < .001). A greater percentage of subjects in whom VVC had been previously diagnosed, as compared with the medically trained cohort, would use OTC agents inappropriately for pelvic inflammatory disease (6.7% vs 4.3%, respectively; P = NS), bacterial vaginosis (14.6% vs 6.4%, respectively; P = .028), urinary tract infection (2.0% vs 0%, respectively; P < .001), and vaginal trichomoniasis (11.8% vs 6.6%, respectively; P = .048). A minority of

  15. Syndrome of inappropriate antidiuretic hormone secretion associated with desvenlafaxine.

    PubMed

    Liew, Ellise D; Alderman, Christopher P

    2014-04-01

    To report a case of syndrome of inappropriate anti-diuretic hormone (SIADH) secretion associated with desvenlafaxine. A 57-year old female with hyponatraemia. Her medications included desvenlafaxine, and symptoms included nausea, anxiety and confusion. The serum sodium at this time was 120 mmol/L, serum osmolality was 263 mosmol/kg, urine osmolality 410 mosmol/kg and urine sodium 63 mmol/L, consistent with a diagnosis of SIADH. Desvenlafaxine was ceased and fluid restriction implemented. After 4 days the sodium increased to 128 mmol/L and fluid restriction was relaxed. During her further 3 weeks inpatient admission the serum sodium ranged from 134 to 137 mmol/L during treatment with mirtazapine. SIADH has been widely reported with a range of antidepressants. This case report suggests that desvenlafaxine might cause clinically significant hyponatremia. Clinicians should be aware of the potential for antidepressants to cause hyponatremia,and take appropriate corrective action where necessary.

  16. Bioethics for clinicians: 16. Dealing with demands for inappropriate treatment

    PubMed Central

    Weijer, C; Singer, P A; Dickens, B M; Workman, S

    1998-01-01

    Demands by Patients or their Families for treatment thought to be inappropriate by health care providers constitute an important set of moral problems in clinical practice. A variety of approaches to such cases have been described in the literature, including medical futility, standard of care and negotiation. Medical futility fails because it confounds morally distinct cases: demand for an ineffective treatment and demand for an effective treatment that supports a controversial end (e.g., permanent unconsciousness). Medical futility is not necessary in the first case and is harmful in the second. Ineffective treatment falls outside the standard of care, and thus health care workers have no obligation to provide it. Demands for treatment that supports controversial ends are difficult cases best addressed through open communication, negotiation and the use of conflict-resolution techniques. Institutions should ensure that fair and unambiguous procedures for dealing with such cases are laid out in policy statements. PMID:9805031

  17. The Prevalence of Inappropriate Image Duplication in Biomedical Research Publications.

    PubMed

    Bik, Elisabeth M; Casadevall, Arturo; Fang, Ferric C

    2016-06-07

    Inaccurate data in scientific papers can result from honest error or intentional falsification. This study attempted to determine the percentage of published papers that contain inappropriate image duplication, a specific type of inaccurate data. The images from a total of 20,621 papers published in 40 scientific journals from 1995 to 2014 were visually screened. Overall, 3.8% of published papers contained problematic figures, with at least half exhibiting features suggestive of deliberate manipulation. The prevalence of papers with problematic images has risen markedly during the past decade. Additional papers written by authors of papers with problematic images had an increased likelihood of containing problematic images as well. As this analysis focused only on one type of data, it is likely that the actual prevalence of inaccurate data in the published literature is higher. The marked variation in the frequency of problematic images among journals suggests that journal practices, such as prepublication image screening, influence the quality of the scientific literature.

  18. Herpes zoster ophthalmicus and syndrome of inappropriate antidiuretic hormone secretion.

    PubMed

    Kucukardali, Yasar; Solmazgul, Emrullah; Terekeci, Hakan; Oncul, Oral; Turhan, Vedat

    2008-01-01

    The syndrome of inappropriate antidiuretic hormone (SIADH) secretion is a common consequence of neurologic and pulmonary infections as well as drug intake and many other clinical situations. This report describes SIADH that developed in an elderly woman with single dermatomal herpes varicella zoster ophthalmicus without evidence of varicella zoster encephalitis or dissemination. A 76-year-old woman was admitted to our department for evaluation of left facial pain, confusion and disorientation. Further investigation revealed hyponatremia 112 mEq/L, low serum osmolality, high urine osmolality, normal renal function, normal adrenal and thyroid hormones, and high plasma vasopressin 40 pg/mL. These results indicate that the hyponatremia in this case was due to SIADH and that SIADH was caused by an increased release of vasopressin probably because of the antiviral drug (acyclovir) or infection of varicella zoster virus (VZV) in a single dermatome.

  19. Inappropriate use of proton pump inhibitors in a local setting

    PubMed Central

    Chia, Christopher Tze Wei; Lim, Wan Peng; Vu, Charles Kien Fong

    2014-01-01

    INTRODUCTION There are growing concerns that the use of proton pump inhibitors (PPIs) may be inappropriate in instances that do not conform to evidence-based indications. This point-prevalence study aimed to investigate the frequency, indications and appropriateness of use of PPIs in hospitalised patients on a randomly chosen day. METHODS On a randomly chosen day, all inpatients were documented, and those on any form of PPIs on that day were determined. Indications for maintaining these patients on PPIs were obtained from the electronic medical records, which were then recorded and cross-referenced against a list of accepted indications adapted from the US Food and Drug Administration (FDA)-approved list. RESULTS In all, 1,025 inpatients were documented. Of the 477 (46.5%) inpatients using PPIs, only 219 (45.9%) fulfilled the FDA-approved indications, while the majority (n = 258, 54.1%) did not. Overall, PPIs were not strictly indicated for use in 206 (43.2%) inpatients, according to FDA criteria. Of the 477 inpatients on PPIs, 52 (10.9%) had borderline indications based on expert consensus/guidelines other than FDA criteria. CONCLUSION Although the use of PPIs is prevalent in hospitals, less than half of the hospitalised patients using PPIs in our study had evidence-based indications that supported such use. The overuse of PPIs has a negative impact on healthcare costs and may lead to adverse effects. Steps to curb the inappropriate use of PPIs should address factors such as indications for the initiation of PPIs, and reassessment of the need for ongoing PPI use in inpatients upon discharge and during outpatient reviews. PMID:25091884

  20. Hypercalcitoninemia and inappropriate calciuria in the acute trauma patient.

    PubMed

    Koch, S M; Mehlhorn, U; Baggstrom, E; Donovan, D; Allen, S J

    1996-09-01

    This study was undertaken to determine the role of calcium-regulatory hormones (calcitonin [CT], parathyroid hormone [PTH], and vitamin D analogs) during the first 48 hours after acute trauma. Eleven acutely traumatized patients admitted to the shock-trauma intensive care unit (STICU) in a tertiary care teaching hospital were enrolled. Eleven same-day elective surgery patients served as the control group. Levels of ionized calcium (Ca2+), total calcium, magnesium, phosphate, CT, PTH, vitamin D analogs, electrolyte supplementation, and renal electrolyte loss were recorded during the first 48 hours after admission to the STICU. Control-group measurements consisted of Ca2+ and CT. At admission, 91% of the patients had ionized hypocalcemia (1.04 +/- 0.10 mmol/L). Ca2+ levels increased significantly over time (1.13 +/- 0.08 at 24 hours; 1.16 +/- 0.07 at 48 hours) but remained below the control-group value (1.28 +/- 0.05; P < .05) despite supplementation. Ninety-one percent of the patients had increased CT values at admission, 91% at 24 hours, and 78% at 48 hours. Median CT values in the trauma patients were higher throughout the study than in the control group (P < .05). Urinary calcium loss in the trauma patients was within the normal range. PTH and vitamin D analog values were within the normal range throughout the study. Multiple regression analysis did not show any significant correlation between electrolytes and hormone or protein concentrations. Acute trauma patients have ionized hypocalcemia associated with inappropriate urinary calcium loss, increased CT levels, and normal PTH and vitamin D analog values. We believe the degree of calciuria we observed was inappropriate in the context of ionized hypocalcemia. The cause of these increased CT levels is unclear. Our results suggest that Ca(2+)-regulatory mechanisms may be disrupted in the acute trauma patient.

  1. ASDCD: Antifungal Synergistic Drug Combination Database

    PubMed Central

    Chen, Ming; Liu, Ming-Xi; Ren, Wei; Wang, Quan-Xin; Zhang, Li-Xin; Yan, Gui-Ying

    2014-01-01

    Finding effective drugs to treat fungal infections has important clinical significance based on high mortality rates, especially in an immunodeficient population. Traditional antifungal drugs with single targets have been reported to cause serious side effects and drug resistance. Nowadays, however, drug combinations, particularly with respect to synergistic interaction, have attracted the attention of researchers. In fact, synergistic drug combinations could simultaneously affect multiple subpopulations, targets, and diseases. Therefore, a strategy that employs synergistic antifungal drug combinations could eliminate the limitations noted above and offer the opportunity to explore this emerging bioactive chemical space. However, it is first necessary to build a powerful database in order to facilitate the analysis of drug combinations. To address this gap in our knowledge, we have built the first Antifungal Synergistic Drug Combination Database (ASDCD), including previously published synergistic antifungal drug combinations, chemical structures, targets, target-related signaling pathways, indications, and other pertinent data. Its current version includes 210 antifungal synergistic drug combinations and 1225 drug-target interactions, involving 105 individual drugs from more than 12,000 references. ASDCD is freely available at http://ASDCD.amss.ac.cn. PMID:24475134

  2. [Recent advances in the study of new antifungal lead compounds].

    PubMed

    Wang, Sheng-zheng; Sheng, Chun-quan; Zhang, Wan-nian

    2010-08-01

    In recent years, the incidence and mortality rate of invasive fungal infection have increased dramatically, and it is of great significance to develop novel antifungal agents with new chemical structure and new mode of action. In this review, novel antifungal lead compounds reported from 2007 to 2009 are reviewed. Moreover, their chemical structures, antifungal activities and structure-activity relationships have been summarized, which can provide useful information for future study of antifungal agents.

  3. Antifungal drug discovery: the process and outcomes

    PubMed Central

    Calderone, Richard; Sun, Nuo; Gay-Andrieu, Francoise; Groutas, William; Weerawarna, Pathum; Prasad, Sridhar; Alex, Deepu; Li, Dongmei

    2014-01-01

    New data suggest that the global incidence of several types of fungal diseases have traditionally been under-documented. Of these, mortality caused by invasive fungal infections remains disturbingly high, equal to or exceeding deaths caused by drug-resistant tuberculosis and malaria. It is clear that basic research on new antifungal drugs, vaccines and diagnostic tools is needed. In this review, we focus upon antifungal drug discovery including in vitro assays, compound libraries and approaches to target identification. Genome mining has made it possible to identify fungal-specific targets; however, new compounds to these targets are apparently not in the antimicrobial pipeline. We suggest that ‘repurposing’ compounds (off patent) might be a more immediate starting point. Furthermore, we examine the dogma on antifungal discovery and suggest that a major thrust in technologies such as structural biology, homology modeling and virtual imaging is needed to drive discovery. PMID:25046525

  4. New Antifungal Pyranoisoflavone from Ficus tikoua Bur.

    PubMed Central

    Wei, Shaopeng; Wu, Wenjun; Ji, Zhiqin

    2012-01-01

    Considering the undesirable attributes of synthetic fungicides and the availability of Ficus species in China, the stem of Ficus tikoua Bur. was investigated. One new antifungal pyranoisoflavone, 5,3′,4′-trihydroxy-2″,2″-dimethylpyrano (5″,6″:7,8) isoflavone (1), together with two known isoflavones, wighteone (2) and lupiwighteone (3) (with previously reported antifungal activities), were isolated from ethyl acetate extract by bioassay-guided fractionation. Their structures were determined by spectroscopic analysis, such as NMR (1H-1H COSY, HMQC, HMBC and NOESY), IR, UV and HRMS, as well as ESI-MSn analyses. The antifungal activities of 1–3 against Phytophthora infestans were evaluated by direct spore germination assay, and the IC50 values were 262.442, 198.153 and 90.365 μg·mL−1, respectively. PMID:22837700

  5. Adaptive evolution in subterranean termite antifungal peptides.

    PubMed

    Bulmer, M S; Lay, F; Hamilton, C

    2010-10-01

    We identified and analysed mRNA sequences of two immune proteins from the subterranean termites Reticulitermes flavipes and Reticulitermes virginicus. These proteins correspond to two immune proteins described in the distantly related termite genus Nasutitermes; termicin, which is a small antifungal peptide, and GNBP2, which functions both as a broad pattern recognition receptor and a direct antifungal effector. A population genetic analysis of nucleotide intraspecific polymorphism and interspecific divergence indicates that a selective sweep has reduced polymorphism in the termicins. Moreover, this selective sweep appears to have been driven by the positive selection of beneficial amino acid changes in the antifungal peptide. In contrast, the pattern of polymorphism and divergence in GNBP2 corresponds to the standard neutral model of evolution. © 2010 The Authors. Insect Molecular Biology © 2010 The Royal Entomological Society.

  6. Identification and antifungal susceptibility of Candida species isolated from bloodstream infections in Konya, Turkey.

    PubMed

    Dagi, Hatice Turk; Findik, Duygu; Senkeles, Cigdem; Arslan, Ugur

    2016-05-31

    In this study, our aim was to identify Candida species isolated from bloodstream infections and to determine their susceptibilities to various antifungal agents to demonstrate the local resistance profiles and to guide empirical treatment for clinicians. Two hundred Candida isolates (95 Candida albicans, 105 non-albicans Candida strains) were included in the study. Candida species were identified by conventional, biochemical and molecular methods. Antifungal susceptibility tests for amphotericin B, fluconazole, voriconazole, posaconazole, caspofungin and anidulafungin were performed with broth microdilution method according to the Clinical and Laboratory Standards Institute M27-A3 document. Of the 200 Candida strains, the most prevalent species were C. albicans (47.5 %), Candida glabrata (18.0 %) and Candida parapsilosis complex (14.0 %). All Candida species except for three (1.5 %) Candida kefyr strains were susceptible to amphotericin B. Only one (2.8 %) C. glabrata was resistant to fluconazole (MIC ≥ 64 μg/ml), and the others (97.2 %) exhibited dose-dependent susceptibility. All species, but C. glabrata strains, were susceptible to fluconazole. Resistance to voriconazole, posaconazole, caspofungin and anidulafungin was not detected in any strain. Candida albicans were susceptible to all antifungal drugs. Three C. kefyr strains were resistant to amphotericin B. Only one C. glabrata was resistant to fluconazole. All the strains were susceptible to voriconazole, posaconazole, caspofungin and anidulafungin. In vitro antifungal susceptibility tests should be performed to select of appropriate and effective antifungal therapy, and monitor the development of resistance.

  7. Antifungal agents in neonates: issues and recommendations.

    PubMed

    Almirante, Benito; Rodríguez, Dolors

    2007-01-01

    Fungal infections are responsible for considerable morbidity and mortality in the neonatal period, particularly among premature neonates. Four classes of antifungal agents are commonly used in the treatment of fungal infections in pediatric patients: polyene macrolides, fluorinated pyrimidines, triazoles, and echinocandins. Due to the paucity of pediatric data, many recommendations for the use of antifungal agents in this population are derived from the experience in adults. The purpose of this article was to review the published data on fungal infections and antifungal agents, with a focus on neonatal patients, and to provide an overview of the differences in antifungal pharmacology in neonates compared with adults. Pharmacokinetic data suggest dosing differences in children versus adult patients with some antifungals, but not all agents have been fully evaluated. The available pharmacokinetic data on the amphotericin B deoxycholate formulation in neonates exhibit considerable variability; nevertheless, the dosage regimen suggested in the neonatal population is similar to that used in adults. More pharmacokinetic information is available on the liposomal and lipid complex preparations of amphotericin B and fluconazole, and it supports their use in neonates; however, the optimal dosage and duration of therapy is difficult to establish. All amphotericin-B formulations, frequently used in combination with flucytosine, are useful for treating disseminated fungal infections and Candida meningitis in neonates. Fluconazole, with potent in vitro activity against Cryptococcus neoformans and almost all Candida spp., has been used in neonates with invasive candidiasis at dosages of 6 mg/kg/day, and for antifungal prophylaxis in high-risk neonates. There are limited data on itraconazole, voriconazole, and posaconazole use in neonates. Caspofungin, which is active against Candida spp. and Aspergillus spp., requires higher doses in children relative to adults, and dosing is

  8. Human mycoses and advances in antifungal therapy.

    PubMed

    Fromtling, R A

    2001-04-01

    The 11th Focus on Fungal Infections meeting was held in Washington, D.C., U.S.A., March 1416, 2001. At the conference, there were well-attended sessions that focused on the pathogenesis and therapy of fungal disease. This report focuses on new information on fungal incidence and pathogenesis as well as on the in vitro and clinical experience of established antifungal drugs (fluconazole, itraconazole, amphotericin B, liposomal formulations of amphotericin B, terbinafine) and the newer antifungal compounds approved for use (e.g., caspofungin) and in development (the new-generation azoles: voriconazole, posaconazole, ravuconazole, and the candins, micafungin and anidulafungin).

  9. Antifungal activity of Agapanthus africanus extractives.

    PubMed

    Singh, D N; Verma, N; Raghuwanshi, S; Shukla, P K; Kulshreshtha, D K

    2008-06-01

    The ethanolic extract of the rhizomes of Agapanthus africanus showed antifungal activity. In bioassay guided fractionation, n-butanol fraction exhibited significant activity against human pathogens. A saponin, (25R)-spirost-7-en-2alpha,3beta,5alpha-triol-3-O-[alpha-L-rhamnopyranosyl(1-->2)-[beta-D-galactopyranosyl (1-->3)] beta-D-glucopyranoside (1), responsible for the antifungal activity and having MIC value of 15.6 microg/ml against Trychophyton mentagrophytes and Sporothrix schenekii, was isolated and identified as active constituent of the plant.

  10. Using Precorrection to Manage Inappropriate Academic and Social Behaviors

    ERIC Educational Resources Information Center

    Crosby, Shane; Jolivette, Kristine; Patterson, DaShaunda

    2006-01-01

    This article illustrates a proactive strategy, precorrection, for addressing problem academic and social behaviors with students. Practical classroom scenarios are provided to give teachers a step-by-step guide of how to implement this seven-step preventative strategy. Empirical support for and the benefits of precorrection also are discussed.…

  11. Association between Physician Specialty and Risk of Prescribing Inappropriate Pill Splitting

    PubMed Central

    Chou, Chia-Yu; Hsu, Chia-Chen; Chiang, Shu-Chiung; Ho, Chin-Chin; Chou, Chia-Lin; Wu, Min-Shan; Chang, Yuh-Lih; Tsai, Han-Yi; Chen, Tzeng-Ji; Chou, Yueh-Ching

    2013-01-01

    Background Prescription errors that occur due to the process of pill splitting are a common medication problem; however, available prescription information involving inappropriate pill splitting and its associated factors is lacking. Methods We retrospectively evaluated a cohort of ambulatory prescriptions involving extended-release or enteric-coated formulations in a Taiwan medical center during a 5-month period in 2010. For this study, those pill splitting prescriptions involving special oral formulations were defined as inappropriate prescriptions. Information obtained included patient demographics, prescriber specialty and prescription details, which were assessed to identify factors associated with inappropriate pill splitting. Results There were 1,252 inappropriate prescriptions identified in this cohort study, representing a prescription frequency for inappropriate pill splitting of 1.0% among 124,300 prescriptions with special oral formulations. Among 35 drugs with special oral formulations in our study, 20 different drugs (57.1%, 20/35) had ever been prescribed to split. Anti-diabetic agents, cardiovascular agents and central nervous system agents were the most common drug classes involved in inappropriate splitting. The rate of inappropriate pill splitting was higher in older (over 65 years of age) patients (1.1%, 832/75,387). Eighty-seven percent (1089/1252) of inappropriate prescriptions were prescribed by internists. The rate of inappropriate pill splitting was highest from endocrinologists (3.4%, 429/12,477), nephrologists (1.3%, 81/6,028) and cardiologists (1.3%, 297/23,531). Multivariate logistic regression analysis revealed that the strongest factor associated with individual specific drug of inappropriate splitting was particular physician specialties. Conclusion This study provides important insights into the inappropriate prescription of special oral formulation related to pill splitting, and helps to aggregate information that can assist

  12. FUNCTIONAL ANALYSIS OF INAPPROPRIATE SOCIAL INTERACTIONS IN STUDENTS WITH ASPERGER'S SYNDROME

    PubMed Central

    Roantree, Christina F; Kennedy, Craig H

    2012-01-01

    We analyzed the inappropriate social interactions of 3 students with Asperger's syndrome whose behavior was maintained by social positive reinforcement. We tested whether inappropriate social behavior was sensitive to social positive reinforcement contingencies and whether such contingencies could be reversed to increase the probability of socially appropriate responding. Our results show that social positive reinforcers can be identified for inappropriate social interactions and that appropriate social behaviors can be sensitive to reinforcement contingency reversals. PMID:23060671

  13. Functional analysis of inappropriate social interactions in students with Asperger's syndrome.

    PubMed

    Roantree, Christina F; Kennedy, Craig H

    2012-01-01

    We analyzed the inappropriate social interactions of 3 students with Asperger's syndrome whose behavior was maintained by social positive reinforcement. We tested whether inappropriate social behavior was sensitive to social positive reinforcement contingencies and whether such contingencies could be reversed to increase the probability of socially appropriate responding. Our results show that social positive reinforcers can be identified for inappropriate social interactions and that appropriate social behaviors can be sensitive to reinforcement contingency reversals.

  14. Tumor lysis associated with sudden onset of syndrome of inappropriate antidiuretic hormone secretion.

    PubMed

    Saintigny, Pierre; Chouahnia, Kader; Cohen, Régis; Pailler, Marie-Christine; Brechot, Jeanne-Marie; Morere, Jean-François; Breau, Jean-Luc

    2007-01-01

    Syndrome of inappropriate antidiuretic hormone secretion is frequent in small-cell lung carcinomas. We report on a case of syndrome of inappropriate antidiuretic hormone secretion after each of the first 2 cycles of chemotherapy for small-cell lung cancer. The association with chemotherapy-induced tumor lysis is proposed, particularly based on the course of antidiuretic hormone levels, and a review of the literature is presented. Syndrome of inappropriate antidiuretic hormone secretion can occur during tumor lysis syndrome.

  15. Statistical Significance Is Not a "Kosher Certificate" for Observed Effects: A Critical Analysis of the Two-Step Approach to the Evaluation of Empirical Results.

    ERIC Educational Resources Information Center

    Cahan, Sorel

    2000-01-01

    Shows why the two-step approach proposed by D. Robinson and J. Levine (1997) is inappropriate for the evaluation of empirical results and reiterates the preferred approach of increased sample size and the computation of confidence intervals. (SLD)

  16. Unexplained abdominal pain as a driver for inappropriate therapeutics: an audit on the use of intravenous proton pump inhibitors.

    PubMed

    Lai, Pauline Siew Mei; Wong, Yin Yen; Low, Yong Chia; Lau, Hui Ling; Chin, Kin-Fah; Mahadeva, Sanjiv

    2014-01-01

    Background. Proton pump inhibitors (PPIs) are currently the most effective agents for acid-related disorders. However, studies show that 25-75% of patients receiving intravenous PPIs had no appropriate justification, indicating high rates of inappropriate prescribing. Objective. To examine the appropriate use of intravenous PPIs in accordance with guidelines and the efficacy of a prescribing awareness intervention at an Asian teaching institution. Setting. Prospective audit in a tertiary hospital in Malaysia. Method. Every 4th intravenous PPI prescription received in the pharmacy was screened against hospital guidelines. Interventions for incorrect indication/dose/duration were performed. Patients' demographic data, medical history and the use of intravenous PPI were collected. Included were all adult inpatients prescribed intravenous PPI. Main Outcome Measure. Proportion of appropriate IV PPI prescriptions. Results. Data for 106 patients were collected. Most patients were male [65(61.3%)], Chinese [50(47.2%)], with mean age ± SD = 60.3 ± 18.0 years. Most intravenous PPI prescriptions were initiated by junior doctors from the surgical [47(44.3%)] and medical [42(39.6%)] departments. Only 50/106(47.2%) patients had upper gastrointestinal endoscopy/surgery performed to verify the source of bleeding. Unexplained abdominal pain [81(76.4%)] was the main driver for prescribing intravenous PPIs empirically, out of which 73(68.9%) were for suspected upper gastrointestinal bleed. Overall, intravenous PPI was found to be inappropriately prescribed in 56(52.8%) patients for indication, dose or duration. Interventions on the use of intravenous PPI were most effective when performed by senior doctors (100%), followed by clinical pharmacists (50%), and inpatient pharmacists (37.5%, p = 0.027). Conclusion. Inappropriate intravenous PPI usage is still prevalent despite the enforcement of hospital guidelines. The promotion of prescribing awareness and evidence-based prescribing

  17. Inappropriate left ventricular mass and poor outcomes in patients with angina pectoris and normal ejection fraction.

    PubMed

    Huang, Bao-Tao; Peng, Yong; Liu, Wei; Zhang, Chen; Huang, Fang-Yang; Wang, Peng-Ju; Zuo, Zhi-Liang; Liao, Yan-Biao; Chai, Hua; Li, Qiao; Zhao, Zhen-Gang; Luo, Xiao-Lin; Ren, Xin; Huang, Kai-Sen; Meng, Qing-Tao; Chen, Chi; Huang, De-Jia; Chen, Mao

    2015-03-01

    Although inappropriate left ventricular mass has been associated with clustered cardiac geometric and functional abnormalities, its predictive value in patients with coronary artery disease is still unknown. This study examined the association of inappropriate left ventricular mass with clinical outcomes in patients with angina pectoris and normal ejection fraction. Consecutive patients diagnosed with angina pectoris whose ejection fraction was normal were recruited from 2008 to 2012. Inappropriate left ventricular mass was determined when the ratio of actual left ventricular mass to the predicted one exceeded 150%. The primary endpoint was a composite of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. Clinical outcomes between the inappropriate and appropriate left ventricular mass group were compared before and after propensity matching. Of the total of 1515 participants, 18.3% had inappropriate left ventricular mass. Patients with inappropriate left ventricular mass had a higher composite event rate compared with those with appropriate left ventricular mass (11.2 vs. 6.6%, P=0.010). Multivariate Cox regression analyses showed that inappropriate left ventricular mass was an independent risk factor for adverse events (adjusted hazard ratio, 1.59; 95% confidence interval, 1.03-2.45; P=0.035). The worse outcome in patients with inappropriate left ventricular mass was further validated in a propensity matching cohort and patients with the traditional definition of left ventricular hypertrophy. Inappropriate left ventricular mass was associated with an increased risk of adverse events in patients with angina pectoris and normal ejection fraction.

  18. Physician Factors Associated with Polypharmacy and Potentially Inappropriate Medication Use.

    PubMed

    Ie, Kenya; Felton, Maria; Springer, Sydney; Wilson, Stephen A; Albert, Steven M

    2017-01-01

    Despite accumulating evidence about the harm of polypharmacy in family medicine, few studies have investigated factors related to polypharmacy. The objective of this study was to explore factors related to physicians' prescribing behavior. We conducted a survey of physicians at 5 family medicine residency practices and a linked health record review of their patients ≥65 years old. The determinants of physicians' mean number of prescriptions and potentially inappropriate medications (PIMs) were examined using a generalized linear model. A total of 61 physicians (38 residents, 23 fellows/faculty) completed the survey, and 2103 visits by 932 patients seen by these physicians were analyzed. The mean numbers of prescriptions and PIMs per visit per physician were 9.50 and 0.46, respectively. After controlling for patient race and age, low prescribers were more likely to consider the number of medications (P = .007) and benefit/risk information for deprescribing (P = .017) when making prescribing decisions. Use of the Beers List was marginally significant in lower PIM prescribing (P = .05). Physicians' sex, duration of experience, and perceived confidence were not associated with prescribing patterns. Conscious consideration concerning the number of medications and benefit/risk information, as well as using the Beers List, were associated with less polypharmacy and fewer PIMs. © Copyright 2017 by the American Board of Family Medicine.

  19. The spectrum of inappropriate pituitary thyrotropin secretion associated with hyperthyroidism

    SciTech Connect

    Gharib, H.; Carpenter, P.C.; Scheithauer, B.W.; Service, F.J.

    1982-09-01

    Two patients with overproduction of thyroid-stimulating hormone (TSH) are described. The first patient, a 25-year-old man with recurrent hyperthyroidism, had a pituitary adenoma and highly elevated levels of TSH. While the patient was receiving 0.3 mg of thyroid daily, and basal TSH level was 161 microM/ml. Despite an increase in the thyroid hormone therapy, serum TSH levels remained elevated. The administration of thyrotropin-releasing hormone (TRH) or dexamethasone resulted in no changes in TSH level. The second patient was an 18-year-old man who had inappropriately elevated levels of TSH 3 months after radioiodine therapy for hyperthyroidism. A gradual increase in thyroid hormone replacement therapy decreased the serum TSH levels from 250 to 14.8 microM/ml. The administration of TRH led to huge increases of TSH. Dexamethasone inhibited basal TSH but not TRH-stimulated TSH levels. The overproduction of TSH was attributed to autonomous, neoplastic secretion in the first case and to partial, selective pituitary thyrotroph resistance to thyroid hormone in the second.

  20. Turkish high school students' definitions for parallelograms: appropriate or inappropriate?

    NASA Astrophysics Data System (ADS)

    Cansiz Aktaş, Meral

    2016-05-01

    The aim of this study was to investigate the appropriateness of high school students' definitions. The participants in this study were 269 high school students from a public school in Ordu city, which is on the Black Sea coast of Turkey. The participants were asked to write their definitions with no time constraints. In the analysis of the definitions, students' ability to distinguish necessary and sufficient conditions and their ability to use appropriate mathematical terminology were taken into account. The task used in this study enabled us to mirror students' difficulties and inadequacies about their definitions of a parallelogram. The findings indicated that most of the students defined parallelogram inappropriately because they had used incomplete or incorrect statements. On the other hand, for the appropriate definitions, it was found that the number of uneconomical definitions was almost the same as the number of economical ones. At the end of the study, it was suggested that defining activities should be integrated into curriculums explicitly and should be given importance in our mathematic lessons.

  1. Experimental analysis of response covariation among compliant and inappropriate behaviors.

    PubMed Central

    Parrish, J M; Cataldo, M F; Kolko, D J; Neef, N A; Egel, A L

    1986-01-01

    Reliable changes in a variety of behaviors, or classes of behaviors, when only one is manipulated experimentally, have demonstrated that even topographically dissimilar responses can be functionally related. We investigated such a relationship between topographically different child behaviors (compliance and inappropriate activities) by using a methodology that tests for response covariation. Five conditions were provided to sequentially increase and decrease first one and then the other of these behaviors, with the degree of covariation between the two behaviors (i.e., the relationship between changes in the targeted and nontargeted behaviors) being the finding of interest. Results showed that, regardless of the intervention used, the behavior targeted, or the direction manipulated, the nontargeted behavior reliably covaried inversely with the targeted one. The findings have immediate relevance to the clinical treatment of multiple behavior problems exhibited by children. Furthermore, the study of relationships between responses and the processes underlying these relationships can have important implications for understanding the complexity characteristic of human behavior not yet analyzed by behavioral research. PMID:3771417

  2. Potential therapeutic misadministration due to inappropriate electron beam field shaping.

    PubMed

    Olch, A J; Fallen, R; Conrad, J; Lavey, R S

    2000-01-01

    Lead or cerrobend blocking strips are used to shape electron treatment fields when an appropriate custom insert is not available. For the Varian 2100C accelerator, the structural supports of the electron applicators impede the free placement of these field-shaping strips on the open custom insert frame while placement at the top of the applicator is unimpeded. We have investigated the dosimetric ramifications of placing field shaping strips at the top level of the 15x15 applicator for 6, 9, and 16 MeV electrons. Our results demonstrate as much as a 30% dose decrease and 2 cm penumbral increase when this is done compared to field shaping at the insert level. The magnitude of this dosimetric error qualifies as a therapeutic misadministration in many states depending on how many treatments are delivered in this manner. Based on this finding, we recommend that routine use of lead strip blocking be discouraged in favor of custom inserts due to the potential for inappropriate placement on some linear accelerators.

  3. When is diagnostic testing inappropriate or irrational? Acceptable regret approach.

    PubMed

    Hozo, Iztok; Djulbegovic, Benjamin

    2008-01-01

    The authors provide a new model within the framework of theories of bounded rationality for the observed physicians' behavior that their ordering of diagnostic tests may not be rational. Contrary to the prevailing thinking, the authors find that physicians do not act irrationally or inappropriately when they order diagnostic tests in usual clinical practice. When acceptable regret (i.e., regret that a decision maker finds tolerable upon making a wrong decision) is taken into account, the authors show that physicians tend to order diagnostic tests at a higher level of pretest probability of disease than predicted by expected utility theory. They also show why physicians tend to overtest when regret about erroneous decisions is extremely small. Finally, they explain variations in the practice of medicine. They demonstrate that in the same clinical situation, different decision makers might have different acceptable regret thresholds for withholding treatment, for ordering a diagnostic test, or for administering treatment. This in turn means that for some decision makers, the most rational strategy is to do nothing, whereas for others, it may be to order a diagnostic test, and still for others, choosing treatment may be the most rational course of action.

  4. Between two beds: inappropriately delayed discharges from hospitals.

    PubMed

    Holmås, Tor Helge; Islam, Mohammad Kamrul; Kjerstad, Egil

    2013-12-01

    Acknowledging the necessity of a division of labour between hospitals and social care services regarding treatment and care of patients with chronic and complex conditions, is to acknowledge the potential conflict of interests between health care providers. A potentially important conflict is that hospitals prefer comparatively short length of stay (LOS) at hospital, while social care services prefer longer LOS all else equal. Furthermore, inappropriately delayed discharges from hospital, i.e. bed blocking, is costly for society. Our aim is to discuss which factors that may influence bed blocking and to quantify bed blocking costs using individual Norwegian patient data, merged with social care and hospital data. The data allow us to divide hospital LOS into length of appropriate stay (LAS) and length of delay (LOD), the bed blocking period. We find that additional resources allocated to social care services contribute to shorten LOD indicating that social care services may exploit hospital resources as a buffer for insufficient capacity. LAS increases as medical complexity increases indicating hospitals incentives to reduce LOS are softened by considerations related to patients’ medical needs. Bed blocking costs constitute a relatively large share of the total costs of inpatient care.

  5. The Prevalence of Inappropriate Image Duplication in Biomedical Research Publications

    PubMed Central

    Casadevall, Arturo; Fang, Ferric C.

    2016-01-01

    ABSTRACT Inaccurate data in scientific papers can result from honest error or intentional falsification. This study attempted to determine the percentage of published papers that contain inappropriate image duplication, a specific type of inaccurate data. The images from a total of 20,621 papers published in 40 scientific journals from 1995 to 2014 were visually screened. Overall, 3.8% of published papers contained problematic figures, with at least half exhibiting features suggestive of deliberate manipulation. The prevalence of papers with problematic images has risen markedly during the past decade. Additional papers written by authors of papers with problematic images had an increased likelihood of containing problematic images as well. As this analysis focused only on one type of data, it is likely that the actual prevalence of inaccurate data in the published literature is higher. The marked variation in the frequency of problematic images among journals suggests that journal practices, such as prepublication image screening, influence the quality of the scientific literature. PMID:27273827

  6. Inappropriate eating behavior: a longitudinal study with female adolescents

    PubMed Central

    Fortes, Leonardo de Sousa; Almeida, Sebastião de Sousa; Cipriani, Flávia Marcele; Ferreira, Maria Elisa C.

    2014-01-01

    Objective: To evaluate the inappropriate eating behaviors (IEB) of female adolescents over a one-year period. Methods: 290 adolescents aged between 11 and 14 years old participated in the three research stages (T1: first four months, T2: second four months and T3: third four months). The Eating Attitudes Test (EAT-26) was applied to assess the IEB. Weight and height were measured to calculate body mass index (BMI) in the three study periods. Analysis of variance for repeated measures was used to analyze the data, adjusted for the scores of the Body Shape Questionnaire and the Brazil Economic Classification Criteria. Results: Girls at T1 showed a higher frequency of IEB compared to T2 (p=0.001) and T3 (p=0.001). The findings also indicated higher values for BMI in T3 in relation to T1 (p=0.04). The other comparisons did not show statistically significant differences. Conclusions: IEB scores of female adolescents declined over one year. PMID:24676195

  7. Effects of appropriate and inappropriate odors on product evaluations.

    PubMed

    Schifferstein, Hendrik N J; Miciiaut, Anne M K

    2002-12-01

    In accounting for an odorant's effect on the evaluation of a product, both the odor's intrinsic pleasantness and its appropriateness for that particular product are relevant. When comparing the effects of pleasant smells, consumers are likely to prefer products with appropriate smells to those with an inappropriate smell. We investigated the effect of adding congruent and incongruent odorants on product evaluations for each of three product categories: food (tea, instant whip, cake mix), personal care (shampoo, deodorant, lip balm), and household products (cream cleaner, air freshener, furniture wax). In a between-subjects design, 96 respondents judged scented and unscented products presented in commercial packages of major national brands. The respondents assessed the overall evaluation, 14 to 19 beliefs about the product, buying intention, and the frequency of use for each product. Respondents were instructed to evaluate each product as they would in a store. Although congruency ratings between odor and product show that the manipulation of congruency was successful, no main effect was found for the congruency on overall evaluations of the products. To account for this unexpected finding, we speculate that congruency between odor and product may be more important during product consumption or product use than during its selection. In addition, the odor's effects may have been attenuated in our experiment because we asked our respondents to rate each product on the attribute 'has a nice smell'.

  8. Resveratrol lacks antifungal activity against Candida albicans.

    PubMed

    Collado-González, Mar; Guirao-Abad, José P; Sánchez-Fresneda, Ruth; Belchí-Navarro, Sarai; Argüelles, Juan-Carlos

    2012-06-01

    The putative candicidal activity of resveratrol is currently a matter of controversy. Here, the antifungal activity as well as the antioxidant response of resveratrol against Candida albicans, have been tested in a set of strains with a well-established genetic background At the doses usually employed in antifungal tests (10-40 μg/ml), resveratrol has no effect on the exponential growth of the C. albicans CAI.4 strain, a tenfold increase (400 μg/ml) was required in order to record a certain degree of cell killing, which was negligible in comparison with the strong antifungal effect caused by the addition of amphotericin B (5 μg/ml). An identical pattern was recorded in the prototrophic strains of C. albicans SC5314 and RM-100, whereas the oxidative sensitive trehalose-deficient mutant (tps1/tps1 strain) was totally refractory to the presence of resveratrol. In turn, the serum-induced yeast-to-hypha transition remained unaffected upon addition of different concentrations of resveratrol. Determination of endogenous trehalose and catalase activity, two antioxidant markers in C. albicans; revealed no significant changes in their basal contents induced by resveratrol. Collectively, our results seem to dismiss a main antifungal role as well as the therapeutic application of resveratrol against the infections caused by C. albicans.

  9. [In vitro antifungal activity of anidulafungin].

    PubMed

    Quindós, Guillermo; Eraso, Elena

    2008-06-01

    Anidulafungin is a new and very useful pharmacological tool for the treatment of invasive mycoses. The antifungal spectrum of anidulafungin reaches the most common pathogenic fungi. Anidulafungin is especially active against the genera Candida and Aspergillus. Its antifungal mechanism is based on the inhibition of the beta-1,3-D-glucan synthesis, an essential molecule for the cell wall architecture, with different consequences for Candida and Aspergillus, being anidulafungin fungicide for the former and fungistatic for the latter. This review describes the in vitro antifungal spectrum of anidulafungin based in the scientific and medical literature of recent years. We can underline that most than 99% of Candida isolates are susceptible to < or = 2 microg/ml of anidulafungin. MIC are very low (< or =0.125 microg/ml) for most clinical isolates of the species Candida albicans, Candida glabrata, Candida tropicalis and Candida krusei while Candida parapsilosis and Candida guilliermondii isolates are susceptible to anidulafungin concentrations < or = 2 microg/ml. An excellent activity of anidulafungin has been also described against Aspergillus, Pneumocystis and other fungi. However, its activity is very low against Cryptococcus and the Zygomycetes. The excellent activity of anidulafungin has made this antifungal a first line therapeutic indication for candidemia and invasive candidiasis in non-neutropenic patients.

  10. Antifungal activity of ajoene derived from garlic.

    PubMed Central

    Yoshida, S; Kasuga, S; Hayashi, N; Ushiroguchi, T; Matsuura, H; Nakagawa, S

    1987-01-01

    The antifungal activity of six fractions derived from garlic was investigated in an in vitro system. Ajoene had the strongest activity in these fractions. The growth of both Aspergillus niger and Candida albicans was inhibited by ajoene at less than 20 micrograms/ml. Images PMID:3555334

  11. Synthetic Multivalent Antifungal Peptides Effective against Fungi

    PubMed Central

    Li, Jianguo; Nandhakumar, Muruganantham; Aung, Thet Tun; Goh, Eunice; Chang, Jamie Ya Ting; Saraswathi, Padhmanaban; Tang, Charles; Safie, Siti Radiah Binte; Lin, Lim Yih; Riezman, Howard; Lei, Zhou; Verma, Chandra S.; Beuerman, Roger W.

    2014-01-01

    Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. B4010 displayed better antifungal properties than natamycin and amphotericin B. The peptide retained significant activity in the presence of monovalent/divalent cations, trypsin and serum and tear fluid. Moreover, B4010 is non-haemolytic and non-toxic to mice by intraperitoneal (200 mg/kg) or intravenous (100 mg/kg) routes. S. cerevisiae mutant strains with altered membrane sterol structures and composition showed hyper senstivity to B4010. The peptide had no affinity for cell wall polysaccharides and caused rapid dissipation of membrane potential and release of vital ions and ATP when treated with C. albicans. We demonstrate that additives which alter the membrane potential or membrane rigidity protect C. albicans from B4010-induced lethality. Calcein release assay and molecular dynamics simulations showed that the peptide preferentially binds to mixed bilayer containing ergosterol over phophotidylcholine-cholesterol bilayers. The studies further suggested that the first arginine is important for mediating peptide-bilayer interactions. Replacing the first arginine led to a 2–4 fold decrease in antifungal activities and reduced membrane disruption properties. The combined in silico and in vitro approach should facilitate rational design of new tetravalent antifungal peptides. PMID:24498363

  12. Lipid-based antifungal agents: current status.

    PubMed

    Arikan, S; Rex, J H

    2001-03-01

    Immunocompromised patients are well known to be predisposed to developing invasive fungal infections. These infections are usually difficult to diagnose and more importantly, the resulting mortality rate is high. The limited number of antifungal agents available and their high rate of toxicity are the major factors complicating the issue. However, the development of lipid-based formulations of existing antifungal agents has opened a new era in antifungal therapy. The best examples are the lipid-based amphotericin B preparations, amphotericin B lipid complex (ABLC; Abelcet), amphotericin B colloidal dispersion (ABCD; Amphotec or Amphocil), and liposomal amphotericin B (AmBisome). These formulations have shown that antifungal activity is maintained while toxicity is reduced. This progress is followed by the incorporation of nystatin into liposomes. Liposomal nystatin formulation is under development and studies of it have provided encouraging data. Finally, lipid-based formulations of hamycin, miconazole, and ketoconazole have been developed but remain experimental. Advances in technology of liposomes and other lipid formulations have provided promising new tools for management of fungal infections.

  13. Evaluation of antifungal combination against Cryptococcus spp.

    PubMed

    Reichert-Lima, Franqueline; Busso-Lopes, Ariane F; Lyra, Luzia; Peron, Isabela Haddad; Taguchi, Hideaki; Mikami, Yuzuru; Kamei, Katsuiko; Moretti, Maria Luiza; Schreiber, Angelica Z

    2016-09-01

    The second cause of death among systemic mycoses, cryptococcosis treatment represents a challenge since that 5-flucytosine is not currently available in Brazil. Looking for alternatives, this study evaluated antifungal agents, alone and combined, correlating susceptibility to genotypes. Eighty Cryptococcus clinical isolates were genotyped by URA5 gene restriction fragment length polymorphism. Antifungal susceptibility was assessed following CLSI-M27A3 for amphotericin (AMB), 5-flucytosine (5FC), fluconazole (FCZ), voriconazole (VRZ), itraconazole (ITZ) and terbinafine (TRB). Drug interaction chequerboard assay evaluated: AMB + 5FC, AMB + FCZ, AMB + TRB and FCZ + TRB. Molecular typing divided isolates into 14 C. deuterogattii (VGII) and C. neoformans isolates were found to belong to genotype VNI (n = 62) and VNII (n = 4). C. neoformans VNII was significantly less susceptible than VNI (P = 0.0407) to AMB; C. deuterogattii was significantly less susceptible than VNI and VNII to VRZ (P < 0.0001). C. deuterogattii was less susceptible than C. neoformans VNI for FCZ (P = 0.0170), ITZ (P < 0.0001) and TRB (P = 0.0090). The combination FCZ + TRB showed 95.16% of synergistic effect against C. neoformans genotype VNI isolates and all combinations showed 100% of synergism against genotype VNII isolates, suggesting the relevance of cryptococcal genotyping as it is widely known that the various genotypes (now species) have significant impact in antifungal susceptibilities and clinical outcome. In difficult-to-treat cryptococcosis, terbinafine and different antifungal combinations might be alternatives to 5FC.

  14. Effectiveness of an OTC topical antifungal powder.

    PubMed

    Conwill, J

    1993-04-01

    Independent clinical testing of products provide unbiased data for practicing clinicians to make an informed decision when confronted with the evaluation of new products. This study examines the effectiveness of an OTC antifungal powder on a small patient population (N = 33) with cutaneous monilial infections. Results and recommendations are discussed.

  15. Antifungal diterpenes from Hypoestes serpens (Acanthaceae).

    PubMed

    Rasoamiaranjanahary, Lalao; Marston, Andrew; Guilet, David; Schenk, Kurt; Randimbivololona, Fanantenanirainy; Hostettmann, Kurt

    2003-02-01

    Two new diterpenes, fusicoserpenol A and dolabeserpenoic acid A, with antifungal activity, were isolated from leaves of Hypoestes serpens (Acanthaceae). Their structures were elucidated by means of spectrometric methods including 1D and 2D NMR experiments and MS analysis. X-ray crystallographic analysis confirmed the structure of fusicoserpenol A and established the relative configuration.

  16. Antifungal activity of Cynara scolymus L. extracts.

    PubMed

    Zhu, X F; Zhang, H X; Lo, R

    2005-01-01

    Chloroform, ethanol and ethyl acetate extracts of Cynara scolymus L. leaves, heads and stems were tested for their antifungal activity using the agar-well diffusion assay technique. The leaves extracts and the ethanol fractions were found to be the most effective extract against all the tested organisms.

  17. Synthesis and antifungal activities of miltefosine analogs

    USDA-ARS?s Scientific Manuscript database

    Nine alkylphosphocholine derivatives (3a-3i) were prepared by modifying the choline structural moiety and the alkyl chain length of miltefosine (hexadecylphosphocholine), a broad-spectrum antifungal compound that has shown modest therapeutic efficacy in a mouse model of cryptococcosis. The synthetic...

  18. Inappropriate medication use in elderly lebanese outpatients: prevalence and risk factors.

    PubMed

    Saab, Yolande B; Hachem, Alya; Sinno, Soha; El-Moalem, Habib

    2006-01-01

    Inappropriate use of medications has become an international cause for concern in geriatric patients, who are at high risk of drug-related morbidity. This study is the first attempt to determine the prevalence of inappropriate drug use in elderly Lebanese outpatients, using community pharmacy data, and to identify factors that predict potentially inappropriate drug intake in this population. Records of elderly patients aged > or =65 years were selected from different community pharmacies. Each patient profile was reviewed and to confirm patient record information, in-person interviews were conducted with elderly patients between November 2004 and May 2005 by qualified pharmacists. Based on a literature review describing guidelines for the inappropriate use of medications in the elderly, courses of therapy were assessed and classified as either appropriate or inappropriate. Courses of therapy that were judged inappropriate were further classified according to the specific area of inappropriate use (i.e. Beers' criteria, duplicate therapy, indication, dose, dose frequency including missing doses, duration and discontinuation of therapy, adverse effects, drug-drug and/or drug-disease interactions, and poor memory). Statistical analyses were performed to estimate the prevalence of inappropriate medication use and to identify potentially predictive factors of such use arising from patients' sociodemographic characteristics, health factors and drug regimen intake. A total of 350 elderly patient profiles were reviewed, from which 277 evaluable records were obtained. More than half (59.6%) of the patients taking drugs at the time of the study were taking at least one inappropriate medication. Inappropriate medication use was most frequently identified in terms of Beers' criteria (22.4%), missing doses (18.8%) or incorrect frequency of administration of drugs (13.0%). Factors predicting potentially inappropriate drug intake included female sex (65.7% vs 53.3% for males, p

  19. Cinnamaldehyde and its derivatives, a novel class of antifungal agents.

    PubMed

    Shreaz, Sheikh; Wani, Waseem A; Behbehani, Jawad M; Raja, Vaseem; Irshad, Md; Karched, Maribasappa; Ali, Intzar; Siddiqi, Weqar A; Hun, Lee Ting

    2016-07-01

    The last few decades have seen an alarming rise in fungal infections, which currently represent a global health threat. Despite extensive research towards the development of new antifungal agents, only a limited number of antifungal drugs are available in the market. The routinely used polyene agents and many azole antifungals are associated with some common side effects such as severe hepatotoxicity and nephrotoxicity. Also, antifungal resistance continues to grow and evolve and complicate patient management, despite the introduction of new antifungal agents. This suitation requires continuous attention. Cinnamaldehyde has been reported to inhibit bacteria, yeasts, and filamentous molds via the inhibition of ATPases, cell wall biosynthesis, and alteration of membrane structure and integrity. In this regard, several novel cinnamaldehyde derivatives were synthesized with the claim of potential antifungal activities. The present article describes antifungal properties of cinnamaldehyde and its derivatives against diverse classes of pathogenic fungi. This review will provide an overview of what is currently known about the primary mode of action of cinnamaldehyde. Synergistic approaches for boosting the effectiveness of cinnamaldehyde and its derivatives have been highlighted. Also, a keen analysis of the pharmacologically active systems derived from cinnamaldehyde has been discussed. Finally, efforts were made to outline the future perspectives of cinnamaldehyde-based antifungal agents. The purpose of this review is to provide an overview of current knowledge about the antifungal properties and antifungal mode of action of cinnamaldehyde and its derivatives and to identify research avenues that can facilitate implementation of cinnamaldehyde as a natural antifungal.

  20. Antifungal prophylaxis during neutropenia and immunodeficiency.

    PubMed Central

    Lortholary, O; Dupont, B

    1997-01-01

    Fungal infections represent a major source of morbidity and mortality in patients with almost all types of immunodeficiencies. These infections may be nosocomial (aspergillosis) or community acquired (cryptococcosis), or both (candidiasis). Endemic mycoses such as histoplasmosis, coccidioidomycosis, and penicilliosis may infect many immunocompromised hosts in some geographic areas and thereby create major public health problems. With the wide availability of oral azoles, antifungal prophylactic strategies have been extensively developed. However, only a few well-designed studies involving strict criteria have been performed, mostly in patients with hematological malignancies or AIDS. In these situations, the best dose and duration of administration of the antifungal drug often remain to be determined. In high-risk neutropenic or bone marrow transplant patients, fluconazole is effective for the prevention of superficial and/or systemic candidal infections but is not always able to prolong overall survival and potentially selects less susceptible or resistant Candida spp. Primary prophylaxis against aspergillosis remains investigative. At present, no standard general recommendation for primary antifungal prophylaxis can be proposed for AIDS patients or transplant recipients. However, for persistently immunocompromised patients who previously experienced a noncandidal systemic fungal infection, prolonged suppressive antifungal therapy is often indicated to prevent a relapse. Better strategies for controlling immune deficiencies should also help to avoid some potentially life-threatening deep mycoses. When prescribing antifungal prophylaxis, physicians should be aware of the potential emergence of resistant strains, drug-drug interactions, and the cost. Well-designed, randomized, multicenter clinical trials in high-risk immunocompromised hosts are urgently needed to better define how to prevent severe invasive mycoses. PMID:9227863

  1. Impact of a Cybernetic System of Feedback to Physicians on Inappropriate Hospital Use.

    ERIC Educational Resources Information Center

    Studnicki, James; And Others

    1985-01-01

    A cybernetic control program was designed to reduce inappropriate days of hospitalization for Medicare patients in four Western Maryland counties. Hospital stays for patients of 282 physicians were reviewed by physician advisers, with attention to the physician's volume of hospitalized patients and the number of inappropriate days of care.…

  2. Inappropriate shock delivery due to interference between a washing machine and an implantable cardioverter defibrillator.

    PubMed

    Kolb, Christof; Schmieder, Sebastian; Schmitt, Claus

    2002-12-01

    Electromagnetic interference with implantable cardioverter defibrillators (ICD) can cause inappropriate delivery of therapies or temporary inhibition of ICD functions. The presented case describes electromagnetic interference between a washing machine and an ICD resulting in an inappropriate discharge of the device due to false detection of ventricular fibrillation.

  3. Effects of Video Self-Modeling on Inappropriate Behavior in Elementary School Students.

    ERIC Educational Resources Information Center

    Schwan, Gerald R.; Holzworth, William A.

    This investigation attempts to determine whether or not elementary school student's inappropriate classroom behavior can be altered through the use of a video self-modeling procedure (VSM). The frequency of inappropriate behavior was observed from videotapes and recorded for twenty six subjects, thirteen of whom were placed in a VSM group and…

  4. Inappropriate Word Extensions in the Speech of Young Language-Disordered Children.

    ERIC Educational Resources Information Center

    Chapman, Kathy; And Others

    1983-01-01

    The frequency and type of inappropriate word extensions (i.e., use of ball for moon) in the spontaneous speech of nine young language disordered children (2.8 to 3.4 years old) were studied. The percentage of inappropriate word extensions of these children was comparable to that of normal children at the same level of linguistic development.…

  5. Functional Analysis of Inappropriate Social Interactions in Students with Asperger's Syndrome

    ERIC Educational Resources Information Center

    Roantree, Christina F.; Kennedy, Craig H.

    2012-01-01

    We analyzed the inappropriate social interactions of 3 students with Asperger's syndrome whose behavior was maintained by social positive reinforcement. We tested whether inappropriate social behavior was sensitive to social positive reinforcement contingencies and whether such contingencies could be reversed to increase the probability of…

  6. Functional Analysis of Inappropriate Social Interactions in Students with Asperger's Syndrome

    ERIC Educational Resources Information Center

    Roantree, Christina F.; Kennedy, Craig H.

    2012-01-01

    We analyzed the inappropriate social interactions of 3 students with Asperger's syndrome whose behavior was maintained by social positive reinforcement. We tested whether inappropriate social behavior was sensitive to social positive reinforcement contingencies and whether such contingencies could be reversed to increase the probability of…

  7. Inappropriate utilization of SPECT myocardial perfusion imaging on the USA-Mexico border.

    PubMed

    Lalude, Omosalewa O; Gutarra, Mell F; Pollono, Eduardo N; Lee, Soyoung; Tarwater, Patrick M

    2014-06-01

    The American College of Cardiology/American Society of Nuclear Cardiology published revised appropriate use criteria (AUC) for SPECT MPI in 2009. We assessed adherence to these guidelines and factors associated with inappropriate utilization at the University Medical Center. The AUC was applied retrospectively to 420 SPECT MPI studies. Two-sample t test, Fisher's exact test, and multivariable logistic regression models were used for analysis. There were 322 appropriate (86%) and 54 (14%) inappropriate studies. The odds of having an inappropriate test increased with younger age (P < .001) and female gender (P < .001). Subjects with diabetes (P = .007) and chest pain (P < .001) were less likely to have an inappropriate test. Academic outpatients were three times more likely to have an inappropriate study (P = .123), while community PCPs were 5.6 times (P = .011) and community cardiologists eight times more likely to order inappropriate tests (P = .031). Inappropriate SPECT MPI in low risk younger women is an important issue on the USA-Mexico border. Initiatives to reduce inappropriate SPECT MPI should focus on a few indications and evaluation of cardiovascular symptoms in younger age women in outpatient/community practices.

  8. Relationships between Inappropriate Behaviors and Other Factors in Young Children with Visual Impairments.

    ERIC Educational Resources Information Center

    Bak, Sunhi

    1999-01-01

    A study used the ABILITIES Index to assess the relationship of inappropriate behaviors to social skills and behavior, vision, intellectual function, and intentional communication in 202 children (ages 6-59 months) with visual impairments. Results indicate inappropriate and unusual behavior continued to increase between birth and age 5. (CR)

  9. The use of medroxyprogesterone acetate for the treatment of sexually inappropriate behaviour in patients with dementia

    PubMed Central

    Light, Stacy Anderson; Holroyd, Suzanne

    2006-01-01

    Sexually inappropriate behaviour in a patient with dementia can be a problem for caregivers. Little research has been done concerning treatment for this behavioural disorder. The hormone medroxyprogesterone acetate (MPA) is a known, but infrequently used, treatment option. We describe a series of 5 cases in which MPA was used successfully to control inappropriate sexual behaviours in men with dementia. PMID:16575429

  10. Impact of potential inappropriate NSAIDs use in chronic pain.

    PubMed

    Ussai, S; Miceli, L; Pisa, F E; Bednarova, R; Giordano, A; Della Rocca, G; Petelin, R

    2015-01-01

    Pain remains one of the main reasons for medical consultation worldwide: moderate- to severe-intensity pain occurs in 19% of adult Europeans, seriously affecting the quality of their social and working lives. Nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended for long-term use and a careful surveillance to monitor for toxicity and efficacy is critical. This study aims to assess: 1) the pattern of use of NSAIDs and opioids in a population covered by a cloud-based pharmacovigilance surveillance system; and 2) potential inappropriate use. A retrospective 18-months systematic analysis on patients' pain treatment was performed. The primary endpoint was evaluating the prevalence of NSAIDs and opioids use and the duration of therapy regimen. The secondary endpoint was to investigate the prevalence of NSAIDs taken for >21 consecutive days concomitant with drugs for peptic ulcer and gastroesophageal reflux disease (GORD) or antiplatelet drugs. The yearly cost for individual users of concomitant NSAIDs for more than 21 consecutive days and of GORD medications has been estimated. A total of 3,050 subjects with chronic pain were enrolled; 97% of them took NSAIDs for >21 consecutive days; about one-fourth of these users also received drugs for peptic ulcer and GORD (Anatomical Therapeutic Chemical code A02B). The yearly cost foran individual who uses NSAIDs for >21 consecutive days as well as concomitant GORD medications is 61.23 euros. In total, 238 subjects (8%) using NSAIDs for >21 days also received one antiplatelet agent. About 11% of subjects received opioids at least once and only 2% of them carried on the therapy for more than 90 consecutive days. In evaluating the escalation in dosage as a proxy of dependence risk, this study shows no dosage escalation in our cohort of chronic pain population - that is to say we show no risk of dependence.

  11. Drivers for inappropriate fever management in children: a systematic review.

    PubMed

    Kelly, M; McCarthy, S; O'Sullivan, R; Shiely, F; Larkin, P; Brenner, M; Sahm, L J

    2016-08-01

    Background Fever is one of the most common childhood symptoms and accounts for numerous consultations with healthcare practitioners. It causes much anxiety amongst parents as many struggle with managing a feverish child and find it difficult to assess fever severity. Over- and under-dosing of antipyretics has been reported. Aim of the review The aim of this review was to synthesise qualitative and quantitative evidence on the knowledge, attitudes and beliefs of parents regarding fever and febrile illness in children. Method A systematic search was conducted in ten bibliographic databases from database inception to June 2014. Citation lists of studies and consultation with experts were used as secondary sources to identify further relevant studies. Titles and abstracts were screened for inclusion according to pre-defined inclusion and exclusion criteria. Quantitative studies using a questionnaire were analysed using narrative synthesis. Qualitative studies with a semi-structured interview or focus group methodology were analysed thematically. Results Of the 1565 studies which were screened for inclusion in the review, the final review comprised of 14 studies (three qualitative and 11 quantitative). Three categories emerged from the narrative synthesis of quantitative studies: (i) parental practices; (ii) knowledge; (iii) expectations and information seeking. A further three analytical themes emerged from the qualitative studies: (i) control; (ii) impact on family; (iii) experiences. Conclusion Our review identifies the multifaceted nature of the factors which impact on how parents manage fever and febrile illness in children. A coherent approach to the management of fever and febrile illness needs to be implemented so a consistent message is communicated to parents. Healthcare professionals including pharmacists regularly advise parents on fever management. Information given to parents needs to be timely, consistent and accurate so that inappropriate fever

  12. Potential misuse and inappropriate prescription practices involving opioid analgesics.

    PubMed

    Liu, Ying; Logan, Joseph E; Paulozzi, Leonard J; Zhang, Kun; Jones, Christopher M

    2013-08-01

    Opioid misuse and abuse are growing concerns among the medical and public health communities. To examine the prevalence of indicators for potential opioid misuse in a large, commercially insured adult population. We adapted existing indicators developed by expert panels to include having overlapping opioid prescriptions, overlapping opioid and benzodiazepine prescriptions, long-acting/ extended release (LA/ER) opioids for acute pain,and high daily doses of opioids (>100 morphine milligram equivalents). These indicators were assessed among continuously enrolled individuals aged 18-64 years from the 2009 Truven Health MarketScan databases. Analyses were stratified by sex. We identified 3,391,599 eligible enrollees who received at least 1 opioid prescription. On average, enrollees obtained 3.3 opioid prescriptions, and the average annual days of supply was 47 days. Twice as many enrollees received opioid prescriptions for acute pain as for chronic pain. About a quarter of the enrollees had at least 1 indicator of either potential misuse by patients or inappropriate prescription practices by providers. About 15% of enrollees had high daily doses;7.8% had opioid overlap; and 7.9% had opioid and benzodiazepine overlap. Among those prescribed LA/ER opioids, 24.3% were treated for acute pain. Overlap indicators were more common among women. Our findings underscore the critical need to develop programs aimed at promoting appropriate use of opioids. Retrospective opioid utilization reviews similar to our analyses can potentially help managed care organizations and healthcare providers improve patient care and reduce the risk of adverse outcomes related to these medications.

  13. Impact of potential inappropriate NSAIDs use in chronic pain

    PubMed Central

    Ussai, S; Miceli, L; Pisa, F E; Bednarova, R; Giordano, A; Rocca, G Della; Petelin, R

    2015-01-01

    Pain remains one of the main reasons for medical consultation worldwide: moderate- to severe-intensity pain occurs in 19% of adult Europeans, seriously affecting the quality of their social and working lives. Nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended for long-term use and a careful surveillance to monitor for toxicity and efficacy is critical. This study aims to assess: 1) the pattern of use of NSAIDs and opioids in a population covered by a cloud-based pharmacovigilance surveillance system; and 2) potential inappropriate use. A retrospective 18-months systematic analysis on patients’ pain treatment was performed. The primary endpoint was evaluating the prevalence of NSAIDs and opioids use and the duration of therapy regimen. The secondary endpoint was to investigate the prevalence of NSAIDs taken for >21 consecutive days concomitant with drugs for peptic ulcer and gastroesophageal reflux disease (GORD) or antiplatelet drugs. The yearly cost for individual users of concomitant NSAIDs for more than 21 consecutive days and of GORD medications has been estimated. A total of 3,050 subjects with chronic pain were enrolled; 97% of them took NSAIDs for >21 consecutive days; about one-fourth of these users also received drugs for peptic ulcer and GORD (Anatomical Therapeutic Chemical code A02B). The yearly cost foran individual who uses NSAIDs for >21 consecutive days as well as concomitant GORD medications is 61.23 euros. In total, 238 subjects (8%) using NSAIDs for >21 days also received one antiplatelet agent. About 11% of subjects received opioids at least once and only 2% of them carried on the therapy for more than 90 consecutive days. In evaluating the escalation in dosage as a proxy of dependence risk, this study shows no dosage escalation in our cohort of chronic pain population - that is to say we show no risk of dependence. PMID:25926717

  14. [Prevalence of inappropriate prescription to polymedicated patients over 65 years old in a rural health area].

    PubMed

    Terol-Fernández, J; Faus-Felipe, V; Díez-Rodríguez, M; del Rio-Urenda, S; Labajos-Manzanares, M T; González-Correa, J A

    2016-01-01

    Describe the inappropriate prescription to polymedicated patients over 65 years old in rural areas. An observational, descriptive, cross-sectional study conducted in health care units in the Guadalhorce Valley, a rural area of Malaga, Spain. The district has a catchment population of about 144,993 inhabitants. This study is focused on the population that is older than 65 years, and who use 10 or more medications (4.344 patients). The study has as a primary variable: the rates of inappropriate prescription. These are classified using the Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) criteria, as well as the criteria of the strategy of the approach to polymedicated of the Andalusian Health System. An application was used to create individualised forms that identified inappropriate prescribing criteria. For each patient, we used variables, such as the unit, drug group, medications, dose, and use of the STOPP and Andalusian Health System criteria were recorded for each patient. More than one-third (35.5%) of all patients have inappropriate prescription, according to STOPP criteria, related to some health problem (direct problems). The large majority (94%) have potentially inappropriate prescription according to the criteria of the Andalusian Health System. If the criteria directly related to prescribing medication for people over 65 (general) is taken into account, 100% of patients have some form of inappropriate or potentially inappropriate prescribing. The prevalence of polypharmacy and inappropriate prescription is a real problem in the population over 65 years old. An informatics tool provides us with the facilities to identify and approach inappropriate prescribing. Copyright © 2015 SECA. Published by Elsevier Espana. All rights reserved.

  15. Frequency and cost of potentially inappropriate prescribing for older adults: a cross-sectional study

    PubMed Central

    Morgan, Steven G.; Hunt, Jordan; Rioux, Jocelyn; Proulx, Jeffery; Weymann, Deirdre; Tannenbaum, Cara

    2016-01-01

    Background: Many medications pose greater health risks when prescribed for older adults, compared with available pharmacologic and nonpharmacologic alternatives. We sought to quantify the frequency and cost of potentially inappropriate prescribing for older women and men in Canada. Methods: Using data for 2013 from the National Prescription Drug Utilization Information System database, which contains prescription claims from publicly financed drug plans in all provinces except for Quebec, we identified the frequency of prescribing and cost of potentially inappropriate medications dispensed to provincial drug plan enrollees aged 65 years or more. Potentially inappropriate prescriptions were defined with the use of the American Geriatrics Society's 2012 version of the Beers Criteria for potentially inappropriate medication use in older adults. Results: For the 6 provinces with relatively complete data coverage (British Columbia, Alberta, Saskatchewan, Manitoba, Ontario and Prince Edward Island), 37% of older people filled 1 or more prescription meeting the Beers Criteria. A higher proportion of women (42%) than men (31%) filled potentially inappropriate prescriptions. The highest rates of prescribing of potentially inappropriate medications were among women aged 85 or more (47%). Benzodiazepines and other hypnotics were the leading contributors to the overall frequency of and sex differences in prescribing of potentially inappropriate drugs among older adults. We estimated that $75 per older Canadian, or $419 million in total, was spent on potentially inappropriate medications outside of hospital settings in 2013. Interpretation: Prescribing of potentially inappropriate medications for older adults is common and costly in Canada, especially for women. Multipronged and well-coordinated strategies to reduce the use and cost of potentially inappropriate drugs would likely generate significant health system savings while simultaneously generating major benefits to

  16. A multicentre study of antifungal strategies and outcome of Candida spp. peritonitis in intensive-care units.

    PubMed

    Montravers, P; Mira, J-P; Gangneux, J-P; Leroy, O; Lortholary, O

    2011-07-01

    Information on the species causing Candida peritonitis, their in vitro susceptibility, antifungal strategies in this setting and patient outcome is still scarce. AmarCand was a prospective, non-interventional study in 271 adult intensive-care unit (ICU) patients with proven invasive Candida infection who received systemic antifungal therapy (France, 2005-2006). Of these ICU patients, 93 (median age 65 years, simplified acute physiology score II 52) had Candida peritonitis, including 73 nosocomial peritonitis, 53 concomitant bacterial peritoneal infections and 26 candidaemias. Candida species were C. albicans (n = 63/108 isolates, 58%), C. glabrata (n = 22, 20%), C. krusei (n = 9), C. kefyr (n = 5), C. parapsilosis (n = 3), C. tropicalis (n = 3), C. ciferii (n = 2) and C. lusitaniae (n = 1). Of tested isolates, 28% were fluconazole-resistant or susceptible dose-dependent (C. albicans 3/32, C. glabrata 9/14, C. krusei 4/4). Empiric antifungal treatment was started 1 day (median) after peritonitis diagnosis, with fluconazole (n = 2 patients), caspofungin (n = 12), voriconazole (n = 3), amphotericin B (n = 2), or a combination (n = 4). Following susceptibility testing, empiric antifungal treatment was judged inadequate in 9/45 (20%) patients and modified in 30 patients (fluconazole was replaced by caspofungin (n = 14) or voriconazole (n = 4)). Mortality in ICU was 38% (35/93) and was not influenced by type of Candida species, fluconazole susceptibility, time to treatment, candidaemia, nosocomial acquisition, or concomitant bacterial infection. No specific factors for death were identified. In summary, a high proportion of fluconazole-resistant or susceptible dose-dependent strains was cultured. These results confirm the high mortality rates of Candida peritonitis and plead for additional investigation in this population. Antifungal treatment for severe cases of Candida peritonitis in ICU patients remains the standard care.

  17. Factors associated with suitability of empiric antibiotic therapy in hospitalized patients with bloodstream infections.

    PubMed

    Grossman, Chagai; Keller, Nathan; Bornstein, Gil; Ben-Zvi, Ilan; Koren-Morag, Nira; Rahav, Galia

    2017-06-01

    Bacteremia is associated with high morbidity and mortality rates. Initiation of inadequate empiric antibiotic therapy is associated with a worse outcome. The aim of this study was to establish the prevalence and the factors associated with inappropriate empiric antibiotic therapy in patients hospitalized with bacteremia. A cross-sectional study was conducted during January 2010-December 2011 at the medical wards of the Chaim Sheba Medical Center, Israel. The records of all patients with bacteremia were reviewed. Clinical and laboratory characteristics, bacteremic pathogens and antimicrobial agents were retrieved from the medical records. Factors associated with appropriateness of empiric antibiotic therapy were assessed. A total of 681 eligible adults were included in the study. Antibiotic therapy was found to be inappropriate in 138 (20.2%) patients (95% C.I. 17.2-23.2). The rate of appropriateness was not related to the type of antibiotic regimen and the type of bacteria. Patients with healthcare-associated infections were more likely to be administrated inappropriate antibiotic therapy. Patients with primary bloodstream infections were also more likely to be administrated inappropriate antibiotic therapy. Empiric combination therapy was more likely to be appropriate than monotherapy, except for an aminoglycosides-based combination. Combination empiric antibiotic therapy should be considered in patients with healthcare-associated infections and in those with primary bloodstream infections.

  18. Epidemiology and antifungal susceptibility of candidemia isolates of non-albicans Candida species from cancer patients.

    PubMed

    Wu, Ping-Feng; Liu, Wei-Lun; Hsieh, Min-Han; Hii, Ing-Moi; Lee, Yu-Lin; Lin, Yi-Tsung; Ho, Mao-Wang; Liu, Chun-Eng; Chen, Yen-Hsu; Wang, Fu-Der

    2017-10-11

    Candidemia is a growing concern worldwide, and its species distribution has shifted toward non-albicans Candida in recent decades, especially in patients with malignancy. This study aimed to update the epidemiology and antifungal susceptibility of non-albicans candidemia isolates from the cancer patients. Adult cancer patients with non-albicans candidemia were recruited, and clinical data were retrospectively collected from five medical centers in Taiwan from 1 July 2011 to 30 June 2014. In vitro susceptibility was determined by the broth dilution method using a Sensititre YeastOne system and interpreted according to the guidelines of the Clinical and Laboratory Standards Institute. A total of 346 episodes of non-albicans candidemia were identified in cancer patients. Candida tropicalis was the most common species (n=145, 41.9%) and had the highest resistance rate to fluconazole (n=17, 13.9%) among all the preserved isolates, including C. tropicalis, Candida glabrata and Candida parapsilosis. A higher Charlson comorbidity index, non-albicans candidemia due to C. tropicalis, neutropenia and septic shock were independent predictors of 28-day mortality. In conclusion, the species distribution and antifungal susceptibility of non-albicans candidemia isolates in our study differed from those in Western countries, providing useful information about local epidemiology for the selection of empirical antifungal agents for cancer patients.

  19. In vitro antifungal susceptibility of coelomycete agents of black grain eumycetoma to eight antifungals.

    PubMed

    Ahmed, Sarah Abdalla; de Hoog, G Sybren; Stevens, David A; Fahal, Ahmed H; van de Sande, Wendy W J

    2015-04-01

    Fungal mycetoma (eumycetoma) represents one of the most difficult infections to appropriately manage. The current recommended treatment is based on extensive surgical debridement combined with prolonged antifungal therapy with ketoconazole or itraconazole. Despite the different phylogenetic positions of black-grain eumycetoma species, they are all treated with the same antifungal agents. The in vitro antifungal susceptibility of coelomycetous eumycetoma agents in the order of Pleosporales presently is largely unknown. Here we determined the in vitro activity of eight antifungal agents against seven species causing human eumycetoma using the Sensititre YeastOne method. High minimum inhibitory concentrations (MICs) were found with fluconazole, caspofungin, flucytosine, and amphotericin B. Voriconazole and posaconazole were found to be active against all species tested. Of the species included in the investigation, MICs of Medicopsis romeroi differed from the rest of the mycetoma causative agents belonging to the order of the Pleosporales. We found significantly lower MICs for amphotericin B and significantly higher MICs for fluconazole, ketoconazole, and itraconazole against this species. Our results emphasised that identification of black grain mycetoma agent is important as well as performing susceptibility testing before starting of antifungal treatment. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. In vitro antifungal activity of topical and systemic antifungal drugs against Malassezia species.

    PubMed

    Carrillo-Muñoz, Alfonso Javier; Rojas, Florencia; Tur-Tur, Cristina; de Los Ángeles Sosa, María; Diez, Gustavo Ortiz; Espada, Carmen Martín; Payá, María Jesús; Giusiano, Gustavo

    2013-09-01

    The strict nutritional requirements of Malassezia species make it difficult to test the antifungal susceptibility. Treatments of the chronic and recurrent infections associated with Malassezia spp. are usually ineffective. The objective of this study was to obtain in vitro susceptibility profile of 76 clinical isolates of Malassezia species against 16 antifungal drugs used for topical or systemic treatment. Isolates were identified by restriction fragment length polymorphism. Minimal inhibitory concentrations (MIC) were obtained by a modified microdilution method based on the Clinical Laboratory Standards Institute reference document M27-A3. The modifications allowed a good growth of all tested species. High in vitro antifungal activity of most tested drugs was observed, especially triazole derivatives, except for fluconazole which presented the highest MICs and widest range of concentrations. Ketoconazole and itraconazole demonstrated a great activity. Higher MICs values were obtained with Malassezia furfur indicating a low susceptibility to most of the antifungal agents tested. Malassezia sympodialis and Malassezia pachydermatis were found to be more-susceptible species than M. furfur, Malassezia globosa, Malassezia slooffiae and Malassezia restricta. Topical substances were also active but provide higher MICs than the compounds for systemic use. The differences observed in the antifungals activity and interspecies variability demonstrated the importance to studying the susceptibility profile of each species to obtain reliable information for defining an effective treatment regimen.

  1. An antifungal peptide from the coconut.

    PubMed

    Wang, H X; Ng, T B

    2005-12-01

    A chromatographic procedure consisting of ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on CM-cellulose, and gel filtration by fast performance liquid chromatography on Supedex 75 was utilized to isolate a 10 kDa antifungal peptide from coconut flesh. The peptide was unadsorbed on DEAE-cellulose, but adsorbed on Affi-gel blue gel and CM-cellulose. It displayed antifungal activity against Fusarium oxysporum, Mycosphaerella arachidicola and Physalospora piricola. The IC50 values of its inhibitory activities on mycelial growth in M. arachidicola and HIV-1 reverse transcriptase activity were respectively 1.2 and 52.5 microM.

  2. Antibacterial and Antifungal Activities of Spices

    PubMed Central

    Liu, Qing; Meng, Xiao; Li, Ya; Zhao, Cai-Ning; Tang, Guo-Yi; Li, Hua-Bin

    2017-01-01

    Infectious diseases caused by pathogens and food poisoning caused by spoilage microorganisms are threatening human health all over the world. The efficacies of some antimicrobial agents, which are currently used to extend shelf-life and increase the safety of food products in food industry and to inhibit disease-causing microorganisms in medicine, have been weakened by microbial resistance. Therefore, new antimicrobial agents that could overcome this resistance need to be discovered. Many spices—such as clove, oregano, thyme, cinnamon, and cumin—possessed significant antibacterial and antifungal activities against food spoilage bacteria like Bacillus subtilis and Pseudomonas fluorescens, pathogens like Staphylococcus aureus and Vibrio parahaemolyticus, harmful fungi like Aspergillus flavus, even antibiotic resistant microorganisms such as methicillin resistant Staphylococcus aureus. Therefore, spices have a great potential to be developed as new and safe antimicrobial agents. This review summarizes scientific studies on the antibacterial and antifungal activities of several spices and their derivatives. PMID:28621716

  3. Photodynamic therapy as an antifungal treatment

    PubMed Central

    LIANG, YI; LU, LI-MING; CHEN, YONG; LIN, YOU-KUN

    2016-01-01

    Photodynamic therapy (PDT) involves the systemic or topical application of a photosensitizer (PS), alongside the selective illumination of the target lesion with light of an appropriate wavelength, in order to promote localized oxidative photodamage and subsequent cell death. Numerous studies have demonstrated that PDT is highly effective in the destruction of fungi in vitro. The mechanism underlying the effects of PDT results from the photons of visible light of an appropriate wavelength interacting with the intracellular molecules of the PS. Reactive species are produced as a result of the oxidative stress caused by the interaction between the visible light and the biological tissue. At present, no antifungal treatment based on PDT has been licensed. However, antifungal PDT is emerging as an area of interest for research. PMID:27347012

  4. Antibacterial and Antifungal Activities of Spices.

    PubMed

    Liu, Qing; Meng, Xiao; Li, Ya; Zhao, Cai-Ning; Tang, Guo-Yi; Li, Hua-Bin

    2017-06-16

    Infectious diseases caused by pathogens and food poisoning caused by spoilage microorganisms are threatening human health all over the world. The efficacies of some antimicrobial agents, which are currently used to extend shelf-life and increase the safety of food products in food industry and to inhibit disease-causing microorganisms in medicine, have been weakened by microbial resistance. Therefore, new antimicrobial agents that could overcome this resistance need to be discovered. Many spices-such as clove, oregano, thyme, cinnamon, and cumin-possessed significant antibacterial and antifungal activities against food spoilage bacteria like Bacillus subtilis and Pseudomonas fluorescens, pathogens like Staphylococcus aureus and Vibrio parahaemolyticus, harmful fungi like Aspergillus flavus, even antibiotic resistant microorganisms such as methicillin resistant Staphylococcus aureus. Therefore, spices have a great potential to be developed as new and safe antimicrobial agents. This review summarizes scientific studies on the antibacterial and antifungal activities of several spices and their derivatives.

  5. Azole antifungal agents: emphasis on new triazoles.

    PubMed Central

    Saag, M S; Dismukes, W E

    1988-01-01

    Many advances have been made in antifungal therapy over the last three decades. Itraconazole and fluconazole, two investigational triazole agents, are the most recent additions to the list of antifungal drugs. This review has focused primarily on their mechanisms of action, favorable pharmacologic properties, and spectra of activity against a broad range of systemic pathogens. Itraconazole and fluconazole show much promise as orally active agents, with less potential for toxicity than the currently available azoles. Fluconazole and, to a lesser degree, itraconazole are especially promising therapies for cryptococcal meningitis. In addition, fluconazole may prove to be highly effective in urinary tract infections caused by Candida species and other fungi. Ongoing and future clinical trials will more clearly define the specific roles of itraconazole and fluconazole in the treatment of systemic mycoses. PMID:2831809

  6. Antifungal activity of thiophenes from Echinops ritro.

    PubMed

    Fokialakis, Nikolas; Cantrell, Charles L; Duke, Stephen O; Skaltsounis, Alexios L; Wedge, David E

    2006-03-08

    Extracts from 30 plants of the Greek flora were evaluated for their antifungal activity using direct bioautography assays with three Colletotrichum species. Among the bioactive extracts, the dichloromethane extract of the radix of Echinops ritro (Asteraceae) was the most potent. Bioassay-guided fractionation of this extract led to the isolation of eight thiophenes. Antifungal activities of isolated compounds together with a previously isolated thiophene from Echinops transiliensis were first evaluated by bioautography and subsequently evaluated in greater detail using a broth microdilution assay against plant pathogens Colletotrichum acutatum, Colletotrichum fragariae, Colletotrichum gloeosporioides, Botrytis cinerea, Fusarium oxysporum, Phomopsis viticola, and Phomopsis obscurans. 5'-(3-Buten-1-ynyl)-2,2'-bithiophen (1), alpha-terthienyl (2), and 2-[pent-1,3-diynyl]-5-[4-hydroxybut-1-ynyl]thiophene (5) at 3 and 30 microM were active against all three Colletotrichum species, F. oxysporum, P. viticola, and P. obscurans.

  7. Antifungal activity of 10 Guadeloupean plants.

    PubMed

    Biabiany, Murielle; Roumy, Vincent; Hennebelle, Thierry; François, Nadine; Sendid, Boualem; Pottier, Muriel; Aliouat, El Moukhtar; Rouaud, Isabelle; Lohézic-Le Dévéhat, Françoise; Joseph, Henry; Bourgeois, Paul; Sahpaz, Sevser; Bailleul, François

    2013-11-01

    Screening of the antifungal activities of ten Guadeloupean plants was undertaken to find new extracts and formulations against superficial mycoses such as onychomycosis, athlete's foot, Pityriasis versicolor, as well as the deep fungal infection Pneumocystis pneumonia. For the first time, the CMI of these plant extracts [cyclohexane, ethanol and ethanol/water (1:1, v/v)] was determined against five dermatophytes, five Candida species, Scytalidium dimidiatum, a Malassezia sp. strain and Pneumocystis carinii. Cytotoxicity tests of the most active extracts were also performed on an HaCat keratinocyte cell line. Results suggest that the extracts of Bursera simaruba, Cedrela odorata, Enterolobium cyclocarpum and Pluchea carolinensis have interesting activities and could be good candidates for developing antifungal formulations.

  8. Effectiveness of a physician‐oriented feedback intervention on inappropriate hospital stays

    PubMed Central

    Antón, Pedro; Peiró, Salvador; Aranaz, Jesús M; Calpena, Rafael; Compañ, Antonio; Leutscher, Edith; Ruíz, Vicenta

    2007-01-01

    Objective To evaluate the effectiveness of a combined intervention to reduce inappropriate hospital stays. Design Quasi‐experimental pre‐test/post‐test with a non‐equivalent control group. Setting Three teaching hospitals in the National Health System in Alicante, Spain. Study participants Intervention group (2 Surgical Units with 1451 hospital stays) and control group (1 Surgical Unit with 1268 hospital stays). Intervention Structured oral presentation followed by direct feedback to surgeons about their own percentages of inappropriate stays and daily evaluation of appropriateness by the surgeons during their rounds. Main outcome measures Reduction in the percentage of inappropriate stays identified by the Appropriateness Evaluation Protocol during the intervention period compared to the basal period. Results The intervention group reduced its percentage of inappropriate stays from 14.3% to 7.9% (absolute reduction: –6.40; 95% CI –10.7 to –2.14; relative reduction: 44.8%), while no changes occurred in the control group. The reduction was in the number of inappropriate stays attributable to the patients' medical management that went from 12.7% to 5.8% (absolute reduction: –6.92; 95% CI –10.90 to –2.92), while no significant changes occurred in inappropriate stays due to other causes. Conclusions A combined intervention of feedback and physician participation in appropriateness evaluations is effective in reducing the percentage of inappropriate hospital stays, particularly those attributable to conservative medical patterns at discharge. PMID:17234871

  9. Identifying Risk Factors Associated with Inappropriate Use of Acid Suppressive Therapy at a Community Hospital

    PubMed Central

    Bodukam, Vijay; Saigal, Kirit; Bahl, Jaya; Wang, Yvette; Hanlon, Alexandra; Lu, Yinghui; Davis, Michael

    2016-01-01

    Purpose. By examining the prescribing patterns and inappropriate use of acid suppressive therapy (AST) during hospitalization and at discharge we sought to identify the risk factors associated with such practices. Methods. In this retrospective observational study, inpatient records were reviewed from January 2011 to December 2013. Treatment with AST was considered appropriate if the patient had a known specific indication or met criteria for stress ulcer prophylaxis. Results. In 2011, out of 58 patients who were on AST on admission, 32 were newly started on it and 23 (72%) were inappropriate cases. In 2012, out of 97 patients on AST, 61 were newly started on it and 51 (84%) were inappropriate cases. In 2013, 99 patients were on AST, of which 48 were newly started on it and 36 (75%) were inappropriate cases. 19% of the patients inappropriately started on AST were discharged on it in three years. Younger age, female sex, and 1 or more handoffs between services were significantly associated with increased risk of inappropriate AST. Conclusion. Our findings reflect inappropriate prescription of AST which leads to increase in costs of care and unnecessarily puts the patient at risk for potential adverse events. The results of this study emphasize the importance of examining the patient's need for AST at each level of care especially when the identified risk factors are present. PMID:27818680

  10. Yeasts isolated from nosocomial urinary infections: antifungal susceptibility and biofilm production.

    PubMed

    de Freitas, Alessandra Ribeiro; Baeza, Lilian Cristiane; Faria, Maria Graciela Iecher; Dota, Kelen Fátima Dalben; Godoy Martínez, Patrício; Svidzinski, Terezinha Inez Estivalet

    2014-01-01

    Urinary Candida infections in the hospital environment are frequent and need to be better understood. To compare the results of antifungal susceptibility profiles of yeasts isolated from patients with urinary infections obtained by broth microdilution method (BM) and by disk diffusion (DD), and also evaluate the capacity of these yeasts to form biofilms. Only yeasts obtained from pure urine cultures with counts higher than 10(5) colony-forming units per milliliter, without bacteria development, of symptomatic patients were included. The isolates were identified by classical methods and the antifungal susceptibility tests were performed with the following drugs: amphotericin B, ketoconazole, fluconazole, itraconazole, voriconazole and caspofungin. The biofilm studies were carried out in polystyrene microtitration plates. Ninety-five yeasts isolates were analyzed, including 40 Candida albicans, 31 Candida glabrata, 24 Candida tropicalis. In general, the majority of the isolates were susceptible to the tested drugs but some resistance was observed, especially against fluconazole. Great variability in the antifungal susceptibility results was observed with the different tested drugs and a few discrepancies were observed between both methods. We suggest that in case of DD resistance this result should be confirmed by BM, the standard method. C. tropicalis isolates showed high biofilm production (91.7%) compared to C. albicans (82.5%) and C. glabrata (61.3%), with statistical significance (p=0.0129). Candiduria in critical patients requires major attention and a better control. The different susceptibility results obtained in this study showed the need to identify yeasts up to the species level, especially in patients with urinary tract infection. The development of techniques of antifungal susceptibility tests can help the clinicians in the empiric treatment of candiduria. Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights

  11. Econazole imprinted textiles with antifungal activity.

    PubMed

    Hossain, Mirza Akram; Lalloz, Augustine; Benhaddou, Aicha; Pagniez, Fabrice; Raymond, Martine; Le Pape, Patrice; Simard, Pierre; Théberge, Karine; Leblond, Jeanne

    2016-04-01

    In this work, we propose pharmaceutical textiles imprinted with lipid microparticles of Econazole nitrate (ECN) as a mean to improve patient compliance while maintaining drug activity. Lipid microparticles were prepared and characterized by laser diffraction (3.5±0.1 μm). Using an optimized screen-printing method, microparticles were deposited on textiles, as observed by scanning electron microscopy. The drug content of textiles (97±3 μg/cm(2)) was reproducible and stable up to 4 months storage at 25 °C/65% Relative Humidity. Imprinted textiles exhibited a thermosensitive behavior, as witnessed by a fusion temperature of 34.8 °C, which enabled a larger drug release at 32 °C (temperature of the skin) than at room temperature. In vitro antifungal activity of ECN textiles was compared to commercial 1% (wt/wt) ECN cream Pevaryl®. ECN textiles maintained their antifungal activity against a broad range of Candida species as well as major dermatophyte species. In vivo, ECN textiles also preserved the antifungal efficacy of ECN on cutaneous candidiasis infection in mice. Ex vivo percutaneous absorption studies demonstrated that ECN released from pharmaceutical textiles concentrated more in the upper skin layers, where the fungal infections develop, as compared to dermal absorption of Pevaryl®. Overall, these results showed that this technology is promising to develop pharmaceutical garments textiles for the treatment of superficial fungal infections. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Antifungal activity of Eugenia umbelliflora against dermatophytes.

    PubMed

    Machado, Karina E; Cechinel Filho, Valdir; Cruz, Rosana C B; Meyre-Silva, Christiane; Cruz, Alexandre Bella

    2009-09-01

    Antifungal activities of Eugenia umbelliflora Berg. (Myrtaceae) were tested in vitro against a panel of standard and clinical isolates of human fungal pathogens (dermatophytes and opportunistic saprobes). Methanol extracts of leaves and fruits of E. umbelliflora were separately prepared and partitioned, to yield dichloromethane (DCM), ethyl acetate (EtOAc) and aqueous fractions (Aq). Three compounds (1-3) were obtained from the DCM extract using chromatographic procedures. Antifungal assays were performed using agar dilution techniques. Both extracts (fruits and leaves), their DCM and EtOAc fractions, and compound 2 (betulin and betulinic acid) presented selective antifungal activity against dermatophytes (Epidermophyton floccosum, Microsporum canis, Microsporum gypseum, Trichophyton rubrum, Trichophyton mentagrophytes), with MIC values between 200 and 1000 microg/mL, and interestingly, inhibited 4/5 species with MIC values of < or = 500 microg/mL. The aqueous fractions of fruits and leaves, and compounds 1 (alpha, beta amyrin) and 3 (taraxerol) were inactive up to the maximum concentrations tested (1000 microg/mL).

  13. Strategies to manage antifungal drug resistance.

    PubMed

    Tseng, Hsiang-Kuang; Perfect, John R

    2011-02-01

    Invasive fungal infections continue to cause significant morbidity and mortality in immunocompromised hosts. From more than half a million deaths from cryptococcosis in sub-Saharan Africa to an unchanging death rate from invasive candidiasis, despite three antifungal classes of drugs, insights into better strategies to reduce therapeutic failures or resistance are needed. This review examines the issues around antifungal drug resistance from both a basic description of the failures and how they are detected to the variety of issues that need to be addressed to help prevent failures for successful management. The reader will gain an understanding of the clinical complexities in this patient population for management of invasive fungal infections. Throughout the review, principles of management are given along with some specific clinical examples to illustrate the issues and frame the knowledge base. From this discussion it is hoped that the clinician can use the insights provided to manage individual patients and find links to the evidence-based material that support its conclusions. Also, this review specifically identifies the limitations of present management and directs clinicians to gather additional information and provide even better treatment strategies. Invasive fungal infections are life-threatening complications of serious underlying diseases. Their management can be complicated by both direct and clinical drug resistance and by understanding these possibilities and correcting them; most patients can be successfully managed with present antifungal drugs if the underlying diseases can be controlled.

  14. Current and Emerging Azole Antifungal Agents

    PubMed Central

    Sheehan, Daniel J.; Hitchcock, Christopher A.; Sibley, Carol M.

    1999-01-01

    Major developments in research into the azole class of antifungal agents during the 1990s have provided expanded options for the treatment of many opportunistic and endemic fungal infections. Fluconazole and itraconazole have proved to be safer than both amphotericin B and ketoconazole. Despite these advances, serious fungal infections remain difficult to treat, and resistance to the available drugs is emerging. This review describes present and future uses of the currently available azole antifungal agents in the treatment of systemic and superficial fungal infections and provides a brief overview of the current status of in vitro susceptibility testing and the growing problem of clinical resistance to the azoles. Use of the currently available azoles in combination with other antifungal agents with different mechanisms of action is likely to provide enhanced efficacy. Detailed information on some of the second-generation triazoles being developed to provide extended coverage of opportunistic, endemic, and emerging fungal pathogens, as well as those in which resistance to older agents is becoming problematic, is provided. PMID:9880474

  15. Hydroxytyrosol expresses antifungal activity in vitro.

    PubMed

    Zoric, Natasa; Horvat, Igor; Kopjar, Nevenka; Vucemilovic, Ante; Kremer, Dario; Tomic, Sinisa; Kosalec, Ivan

    2013-08-01

    Hydroxytyrosol (HT) is a potent antioxidant found in olive oil and leaves. Using several in vitro approaches, we tested antifungal activity of HT. HT showed broad spectrum of antifungal activity against medically important yeasts and dermatophyte strains with MIC values ranging between 97.6 µgml⁻¹ and 6.25 mgml⁻¹. The antimicrobial activity of HT was also tested using the time-kill methodology. Below the MIC value, HT showed potent damage of cell wall of Candida albicans ATCC 10231 using fluorescent dye-exclusion method. At the subinhibitory concentration, HT also influenced dimorphic transition of Candida indicating that HT is inhibitor of germ-tube formation as one of the most important virulence factor of C. albicans. Furthermore, HT showed disturbances in cell surface hydrophobicity (CSH) of C. albicans. The in vitro results indicate that HT caused a significant cell wall damage and changes in CSH as well as inhibition of germ-tube formation as virulence factor of C. albicans. The study indicates that HT has a considerable in vitro antifungal activity against medically important yeasts.

  16. Antifungal ellagitannin isolated from Euphorbia antisyphilitica Zucc

    PubMed Central

    Ascacio-Valdés, Juan; Burboa, Edgardo; Aguilera-Carbo, Antonio F; Aparicio, Mario; Pérez-Schmidt, Ramón; Rodríguez, Raúl; Aguilar, Cristóbal N

    2013-01-01

    Objective To study antifungal activity of a new ellagitannin isolated from the plant residues of Euphorbia antisyphilitica (E. antisyphilitica) Zucc in the wax extraction process. Methods An extract was prepared from dehydrated and pulverized residues and fractionated by liquid chromatography on Amberilte XAD-16, until obtained an ellagitannin-rich ethanolic fraction which was treated by rotaevaporation to recover the ellagitannin as fine powder. An aqueous solution was prepared and treated through ionic exchange liquid chromatography (Q XL) and gel permeation chromatography (G 25). The ellagitannin-rich fraction was thermogravimetrically evaluated (TGA and DTA) to test the thermo-stability of ellagic acid (monomeric unit). Then ellagitannin powder was analyzed by infrared spectrospcopy to determinate the functional groups and, also mass spectroscopy was used to determine the molecular ion. Results The principal functional groups of ellagitannin were determined, the molecular weight was 860.7 g/mol; and an effective antifungal activity against phytopathogenic fungi was demonstrated. Conclusions It can be concluded that the new ellagitannin (860.7 g/mol) isolated from E. antisyphilitica Zucc is an effective antifungal agent against Alternaria alternata, Fusarium oxyzporum, Colletotrichum gloeosporoides and Rhizoctnia solani. PMID:23570015

  17. The utility of antifungal agents for asthma.

    PubMed

    Gore, Robin B

    2010-01-01

    Recent work demonstrates that patients with refractory asthma are likely to be sensitized to environmental fungi and that specific antifungal treatments may be of benefit to this group. The relationships among fungal sensitization, exposure and asthma severity are imperfectly understood. Exposure to environmental fungi occurs ubiquitously and there is emerging evidence that internal airways colonization could be a source of ongoing exposure. Antifungal treatments appear to improve asthma-related quality of life. Such treatments are generally well tolerated but there are potential side-effects. The mechanisms behind the clinical improvements are not yet fully established. Antifungal treatments are used in some centres for patients with refractory asthma. Further research needs to explore the questions of patient selection, optimum duration of therapy and the prediction and management of azole-corticosteroid drug interactions. Advances in our understanding of the fungal molecular allergome and in our understanding of the allergic importance of small hyphal fragments may help to more precisely define the relationships among fungal sensitization, exposure and asthma severity.

  18. Inappropriate ordering of lumbar spine magnetic resonance imaging: are providers Choosing Wisely?

    PubMed

    Gidwani, Risha; Sinnott, Patricia; Avoundjian, Tigran; Lo, Jeanie; Asch, Stevem M; Barnett, Paul G

    2016-02-01

    To analyze inappropriate use of magnetic resonance imaging (MRI) for patients with low back pain in a healthcare system with no financial incentives for overuse. We used administrative data to assess the appropriateness of lumbar spine (LS) MRI in the Veterans Health Administration. All veterans who received LS MRI in the outpatient setting in fiscal year 2012 were included. We based our assessments of appropriateness on CMS criteria, which have been endorsed by the National Quality Forum. Generalized estimating equations were used to evaluate characteristics of inappropriate scans. Of the 110,661 LS MRIs performed, 31% were classified as inappropriate. Most scans that were considered appropriate were characterized as such because they were preceded by conservative therapy (53%). "Red flag" conditions were responsible for a much smaller percentage of scans being considered appropriate; 13% of scans were preceded by conservative therapy and were performed in patients with a red flag condition, while only 4% of scans were considered appropriate because of red flag conditions only. Scans ordered in the emergency department and in urgent care, primary care, and internal medicine clinics were most likely to be classified as inappropriate. Resident physicians were significantly less likely than other provider types to order inappropriate LS MRIs (odds ratio, 0.80; P < .0001). Approximately 24% of providers ordered 74% of inappropriate scans. We found that 31% of LS MRIs were inappropriate in a healthcare system largely absent of financial and other incentives for ordering. The problem of inappropriate ordering of LS MRI is concentrated in a small number of providers; any provider-facing interventions to reduce inappropriate order should therefore be targeted, rather than aimed at all providers who order LS MRI.

  19. Frequency of Inappropriate Medication Prescription in Hospitalized Elderly Patients in Italy

    PubMed Central

    Napolitano, Francesco; Izzo, Maria Teresa; Di Giuseppe, Gabriella; Angelillo, Italo F.; Castaldo, Vincenzo; De Stefano, Andreo A; Dell'Aversano, Raffaele; di Mauro, Maurizio; Iodice, Vincenzo; Iovine, Carmine; Matarazzo, Giuseppe; Rota, Giacomo; Sciambra, Antonio

    2013-01-01

    Background Older people often need comprehensive treatment, including many medications, and polypharmacy is common. The aims of this cross-sectional investigation were to examine the potentially inappropriate medication during the hospitalization and to identify the factors that may influence such inappropriateness among elderly in Italy. Methods A sample of 605 individuals aged 65 years and older admitted in non-academic public acute care hospitals was randomly selected. Prescription of inappropriate medications were evaluated during the period from the day of admission to a randomly preselected day (index day). Beers Criteria were used to evaluate appropriateness. Results At least one potentially inappropriate medication prescription from the day of hospital admission to the index day has been observed in 188 patients (31.1%), and respectively 84.1% and 15.9% of them had received one or two inappropriate medications. A total of 15 medications was prescribed inappropriately to these 188 patients, for 215 times with a total of 1143 doses. The multivariate logistic regression analysis revealed that the significant predictors for having at least one potentially inappropriate medication prescription during the hospitalization were: patients having an elementary education level, a lower pre-admission performance-based measure of basic activities of daily living, having received an inappropriate drug before the hospitalization, a hospital stay in the general and in the specialties surgical wards, a longer length of hospital stay from the admission to the index day, and having received a higher number of drugs from the day of the hospital admission to the index day. The most prevalent inappropriate medications administered were ketorolac (27.4%), amiodarone (19.1%), and clonidine (11.2%). Conclusions This study supports the need for clinical guidelines implementation to assist physicians in choosing the most appropriate drugs for the elderly and for effective education

  20. [NEW ANTIFUNGAL DRUGS FOR PREVENTION AND TREATMENT OF VISCERAL MYCOSES].

    PubMed

    Pilmis, Benoît; Lortholary, Olivier; Lanternier, Fanny L

    2015-12-01

    Invasive fungal infections are increasing due to the increase in the number of at risk patients. The antifungal armamentarium has been improved the last few years with new galenic for ampoetericin B, the widening of the azole spectrum with voriconazole, poscaonazole and isavuconazole and the launch of a new antifungal class, the eschinocandins, currently represented by casoefungin and micftungin. The aim of this work is to provide an update in new antifungal drugs available.

  1. Antifungal Susceptibility Testing of Ascomycetous Yeasts Isolated from Animals

    PubMed Central

    Álvarez-Pérez, Sergio; García, Marta E.; Peláez, Teresa; Martínez-Nevado, Eva

    2016-01-01

    Recent studies suggest that antifungal resistance in yeast isolates of veterinary origin may be an underdiagnosed threat. We tested a collection of 92 ascomycetous yeast isolates that were obtained in Spain from birds, mammals and insects for antifungal susceptibility. MICs to amphotericin B and azoles were low, and no resistant isolates were detected. Despite these results, and given the potential role of animals as reservoirs of resistant strains, continuous monitoring of antifungal susceptibility in the veterinary setting is recommended. PMID:27216048

  2. ANTIFUNGAL ACTIVITY OF SOME COLEUS SPECIES GROWING IN NILGIRIS

    PubMed Central

    Nilani, P.; Duraisamy, B.; Dhanabal, P.S.; khan, Saleemullah; Suresh, B.; Shankar, V.; Kavitha, K.Y.; Syamala, G.

    2006-01-01

    The in vitro antifungal activity of solvent extracts of Coleus forskohlii, Coleus blumei and Coleus barbatus were compared by testing against some pathogenic fungi like Aspergillus niger, Aspergillus fumigatus, Aspergillus ruantii, Proteus vulgaris and Candida albicans. The petroleum ether extract of Coleus forskohlii and Coleus barbatus exhibited significant antifungal activity against all the selected organisms. The extracts of Coleus blumei did not show any significant antifungal activity against the selected organisms. PMID:22557230

  3. Distribution of the antifungal agents sordarins across filamentous fungi.

    PubMed

    Vicente, Francisca; Basilio, Angela; Platas, Gonzalo; Collado, Javier; Bills, Gerald F; González del Val, Antonio; Martín, Jesús; Tormo, José R; Harris, Guy H; Zink, Deborah L; Justice, Michael; Kahn, Jennifer Nielsen; Peláez, Fernando

    2009-01-01

    Sordarins are a class of natural antifungal agents which act by specifically inhibiting fungal protein synthesis through their interaction with the elongation factor 2, EF2. A number of natural sordarins produced by diverse fungi of different classes have been reported in the literature. We have run an exhaustive search of sordarin-producing fungi using two different approaches consecutively, the first one being a differential sensitivity screen using a sordarin-resistant mutant yeast strain run in parallel with a wild type strain, and the second one an empiric screen against Candida albicans followed by early detection of sordarins by LC-MS analysis. Using these two strategies we have detected as many as 22 new strains producing a number of different sordarin analogues, either known (sordarin, xylarin, zofimarin) or novel (isozofimarin and 4'-O-demethyl sordarin). Sordarin and xylarin were the most frequently found compounds in the class. The producing strains were subjected to sequencing of the ITS region to determine their phylogenetic affinities. All the strains were shown to belong to the Xylariales, being distributed across three families in this order, the Xylariaceae, the Amphisphaeriaceae, and the Diatrypaceae. Despite being screened in large numbers, we did not find sordarin production in any other fungal group, including those orders where sordarin producing fungi are known to exist (i.e., Sordariales, Eurotiales, and Microascales), suggesting that the production of sordarin is a trait more frequently associated to members of the Xylariales than to any other fungal order.

  4. Nonanoic Acid, an Antifungal Compound from Hibiscus syriacus Ggoma

    PubMed Central

    Jang, Yun-Woo; Jung, Jin-Young; Lee, In-Kyoung

    2012-01-01

    The root of Hibiscus syriacus (Malvaceae) has been used for treatment of fungal diseases such as tinea pedis (athlete's foot). In this study, we investigated the antifungal constituent of the root of Hibiscus syriacus Ggoma, which was produced by a mutation breeding using gamma ray irradiation, and compared the antifungal activity of H. syriacus Ggoma and its parent type. According to the results, the methanolic extract of H. syriacus Ggoma exhibited four times higher antifungal activity than its parent type against Trichophyton mentagrophytes. Following purification through various column chromatographies, the antifungal substance was identified as nonanoic acid on the basis of spectroscopic analysis. PMID:22870060

  5. Antifungal Resistance and New Strategies to Control Fungal Infections

    PubMed Central

    Vandeputte, Patrick; Ferrari, Selene; Coste, Alix T.

    2012-01-01

    Despite improvement of antifungal therapies over the last 30 years, the phenomenon of antifungal resistance is still of major concern in clinical practice. In the last 10 years the molecular mechanisms underlying this phenomenon were extensively unraveled. In this paper, after a brief overview of currently available antifungals, molecular mechanisms of antifungal resistance will be detailed. It appears that major mechanisms of resistance are essential due to the deregulation of antifungal resistance effector genes. This deregulation is a consequence of point mutations occurring in transcriptional regulators of these effector genes. Resistance can also follow the emergence of point mutations directly in the genes coding antifungal targets. In addition we further describe new strategies currently undertaken to discover alternative therapy targets and antifungals. Identification of new antifungals is essentially achieved by the screening of natural or synthetic chemical compound collections. Discovery of new putative antifungal targets is performed through genome-wide approaches for a better understanding of the human pathogenic fungi biology. PMID:22187560

  6. Nonanoic Acid, an Antifungal Compound from Hibiscus syriacus Ggoma.

    PubMed

    Jang, Yun-Woo; Jung, Jin-Young; Lee, In-Kyoung; Kang, Si-Yong; Yun, Bong-Sik

    2012-06-01

    The root of Hibiscus syriacus (Malvaceae) has been used for treatment of fungal diseases such as tinea pedis (athlete's foot). In this study, we investigated the antifungal constituent of the root of Hibiscus syriacus Ggoma, which was produced by a mutation breeding using gamma ray irradiation, and compared the antifungal activity of H. syriacus Ggoma and its parent type. According to the results, the methanolic extract of H. syriacus Ggoma exhibited four times higher antifungal activity than its parent type against Trichophyton mentagrophytes. Following purification through various column chromatographies, the antifungal substance was identified as nonanoic acid on the basis of spectroscopic analysis.

  7. Ergosterol biosynthesis in Aspergillus fumigatus: its relevance as an antifungal target and role in antifungal drug resistance.

    PubMed

    Alcazar-Fuoli, Laura; Mellado, Emilia

    2012-01-01

    Ergosterol, the major sterol of fungal membranes, is essential for developmental growth and the main target of antifungals that are currently used to treat fatal fungal infections. Emergence of resistance to existing antifungals is a current problem and several secondary resistance mechanisms have been described in Aspergillus fumigatus clinical isolates. A full understanding of ergosterol biosynthetic control therefore appears to be essential for improvement of antifungal efficacy and to prevent antifungal resistance. An ergosterol biosynthesis pathway in A. fumigatus has been proposed with 14 sterol intermediates resulting in ergosterol and another secondary final compound C-24 ethyl sterol. Transcriptomic analysis of the A. fumigatus response to host-imposed stresses or antifungal agents is expanding our understanding of both sterol biosynthesis and the modes of action of antifungal drugs. Ultimately, the identification of new targets for novel drug design, or the study of combinatorial effects of targeting sterol biosynthesis together with other metabolic pathways, is warranted.

  8. Ergosterol biosynthesis in Aspergillus fumigatus: its relevance as an antifungal target and role in antifungal drug resistance

    PubMed Central

    Alcazar-Fuoli, Laura; Mellado, Emilia

    2013-01-01

    Ergosterol, the major sterol of fungal membranes, is essential for developmental growth and the main target of antifungals that are currently used to treat fatal fungal infections. Emergence of resistance to existing antifungals is a current problem and several secondary resistance mechanisms have been described in Aspergillus fumigatus clinical isolates. A full understanding of ergosterol biosynthetic control therefore appears to be essential for improvement of antifungal efficacy and to prevent antifungal resistance. An ergosterol biosynthesis pathway in A. fumigatus has been proposed with 14 sterol intermediates resulting in ergosterol and another secondary final compound C-24 ethyl sterol. Transcriptomic analysis of the A. fumigatus response to host-imposed stresses or antifungal agents is expanding our understanding of both sterol biosynthesis and the modes of action of antifungal drugs. Ultimately, the identification of new targets for novel drug design, or the study of combinatorial effects of targeting sterol biosynthesis together with other metabolic pathways, is warranted. PMID:23335918

  9. Invasive candidiasis in Pakistan: clinical characteristics, species distribution and antifungal susceptibility

    PubMed Central

    Farooqi, J. Q.; Jabeen, K.; Saeed, N.; Iqbal, N.; Malik, B.; Lockhart, S. R.; Zafar, A.; Brandt, M. E.; Hasan, R.

    2015-01-01

    This study reports for the first time, to our knowledge, descriptive epidemiological data for 18 invasive Candida isolates from Pakistan, including species identification and antifungal susceptibility against fluconazole, itraconazole, voriconazole, caspofungin, micafungin, anidulafungin and amphotericin. Risk factors for invasive candidiasis (IC) were determined for 96 patients from Karachi, Pakistan. In adults and neonates, Candida tropicalis (38 and 36 %, respectively) was the most common species, followed in adults by Candida parapsilosis (17.8 %), Candida glabrata (15.9 %) and Candida albicans (12.3 %). C. albicans (21 %) was the second most common in neonates. In children, C. albicans (31.9 %), C. tropicalis (26.4 %) and C. parapsilosis (19.4 %) were the most common. C. albicans IC was significantly associated with paediatric age [crude odds ratio (COR) 3.46, 95% confidence interval (CI) 1.63–7.32]. Rare species made up 17.5% of the total isolates studied. Resistance to fluconazole was seen in C. glabrata (15.0%) and Candida krusei (100.0%). Only one isolate (C. glabrata) was resistant to all three echinocandins. Low MICs of fluconazole for 98% (184/188) of isolates tested support its continued use as an empiric therapy for IC. Non-C. albicans IC was associated with the use of β lactam inhibitor combinations (COR 3.16, 95% CI 1.05–9.57). Use of healthcare devices was documented in 85.4% of IC patients, whilst 75.0% had been admitted to special care units. Surprisingly, 66.7% of patients with IC were not obviously immunosuppressed. The high frequency of modifiable risk factors in this population indicates that candidaemia can be reduced with stringent antibiotic and infection control measures. These data will be useful for empiric selection of antifungals in Karachi, and contribute to global assessments of antifungal resistance. PMID:23105021

  10. Inappropriate use of urinary catheters in patients admitted to medical wards in a university hospital.

    PubMed

    Fernández-Ruiz, Mario; Calvo, Beatriz; Vara, Rebeca; Villar, Rocío N; Aguado, José María

    2013-10-01

    The prevalence and predisposing factors were determined for inappropriate urinary catheterization (UC) among inpatients in medical wards. A cross-sectional study was conducted including all patients aged ≥ 18 years admitted to medical wards in a 1300-bed tertiary-care centre, and who had a urinary catheter in place on the day of the survey. Of 380 patients observed, 46 (12.1%) had a urinary catheter in place. Twelve of them (26.1%) were inappropriately catheterized. The most common indication for inappropriate UC was urine output monitoring in a cooperative, non-critically ill patient. Inappropriateness was associated with increased age, poor functional status, urinary incontinence, dementia, and admission from a long-term care facility. Further educational efforts should be focused on improving catheterization prescribing practices by physicians. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  11. The Effects of a Token Economy on First Grade Students Inappropriate Social Behavior.

    ERIC Educational Resources Information Center

    Shook, Suzan C.; And Others

    1990-01-01

    Studies the effectiveness of a token economy on specific inappropriate social behaviors of three first grade students. Suggests that token economy systems can be very effective in decreasing disruptive behaviors of primary aged students. (MG)

  12. Pharmacotherapy for inappropriate sexual behaviors in dementia: a systematic review of literature.

    PubMed

    Ozkan, Banu; Wilkins, Kirsten; Muralee, Sunanda; Tampi, Rajesh R

    2008-01-01

    The aim of this study is to systematically review the published literature on pharmacotherapy for inappropriate sexual behaviors in dementia. Literature search of the 5 databases (PubMed, MEDLINE, EMBASE, PsychINFO, and COCHRANE collaboration) and the analysis of the data available for the pharmacotherapeutic treatments of inappropriate sexual behaviors in dementia were carried out. There are no published randomized controlled trials of pharmacotherapy for inappropriate sexual behaviors in dementia, but available data form uncontrolled trials, case series, and individual case reports suggest efficacy for antidepressants, antipsychotics, mood stabilizers, hormonal agents, cimetidine, and pindolol for the treatment of these behaviors. Although there are no controlled data for the treatment of inappropriate sexual behaviors in dementia, available data suggest efficacy for some commonly used pharmacotherapeutic agents.

  13. Identification of Antifungal Substances of Lactobacillus sakei subsp. ALI033 and Antifungal Activity against Penicillium brevicompactum Strain FI02

    PubMed Central

    Huh, Chang Ki; Hwang, Tae Yean

    2016-01-01

    This study was performed to investigate the antifungal substances and the antifungal activity against fungi of lactic acid bacteria (LAB) isolated from kimchi. LAB from kimchi in Imsil showed antifungal activity against Penicillium brevicompactum strain FI02. LAB LI031 was identified as Lactobacillus sakei subsp. Antifungal substances contained in L. sakei subsp. ALI033 culture media were unstable at high pH levels. Both, the control and proteinase K and protease treated samples showed clear zones, suggesting that the antifungal substances produced by ALI033 were non-protein substances unaffected by protesases. Both, the control and catalase showed clear zones, suggesting that the antifungal metabolite was not H2O2. The molecular weights of the antifungal substances were ≤3,000 Da. The organic acid content of crude antifungal substances produced by L. sakei subsp. ALI033 showed high concentrations of lactic acid (502.47 mg/100 g). Therefore, these results suggest that antifungal substance produced by L. sakei subsp. ALI033 is most likely due to its ability in producing organic acid. PMID:27069906

  14. Identification of Antifungal Substances of Lactobacillus sakei subsp. ALI033 and Antifungal Activity against Penicillium brevicompactum Strain FI02.

    PubMed

    Huh, Chang Ki; Hwang, Tae Yean

    2016-03-01

    This study was performed to investigate the antifungal substances and the antifungal activity against fungi of lactic acid bacteria (LAB) isolated from kimchi. LAB from kimchi in Imsil showed antifungal activity against Penicillium brevicompactum strain FI02. LAB LI031 was identified as Lactobacillus sakei subsp. Antifungal substances contained in L. sakei subsp. ALI033 culture media were unstable at high pH levels. Both, the control and proteinase K and protease treated samples showed clear zones, suggesting that the antifungal substances produced by ALI033 were non-protein substances unaffected by protesases. Both, the control and catalase showed clear zones, suggesting that the antifungal metabolite was not H2O2. The molecular weights of the antifungal substances were ≤3,000 Da. The organic acid content of crude antifungal substances produced by L. sakei subsp. ALI033 showed high concentrations of lactic acid (502.47 mg/100 g). Therefore, these results suggest that antifungal substance produced by L. sakei subsp. ALI033 is most likely due to its ability in producing organic acid.

  15. Reduction in inappropriate hospital use based on analysis of the causes

    PubMed Central

    2012-01-01

    Background To reduce inappropriate admissions and stays with the application of an improvement cycle in patients admitted to a University Hospital. The secondary objective is to analyze the hospital cost saved by reducing inadequacy after the implementation of measures proposed by the group for improvement. Methods Pre- and post-analysis of a sample of clinical histories studied retrospectively, in which the Appropriateness Evaluation Protocol (AEP) was applied to a representative hospital sample of 1350 clinical histories in two phases. In the first phase the AEP was applied retrospectively to 725 admissions and 1350 stays. The factors associated with inappropriateness were analysed together with the causes, and specific measures were implemented in a bid to reduce inappropriateness. In the second phase the AEP was reapplied to a similar group of clinical histories and the results of the two groups were compared. The cost of inappropriate stays was calculated by cost accounting. Setting: General University Hospital with 426 beds serving a population of 320,000 inhabitants in the centre of Murcia, a city in south-eastern Spain. Results Inappropriate admissions were reduced significantly: 7.4% in the control group and 3.2% in the intervention group. Likewise, inappropriate stays decreased significantly from 24.6% to 10.4%. The cost of inappropriateness in the study sample fell from 147,044 euros to 66,642 euros. The causes of inappropriateness for which corrective measures were adopted were those that showed the most significant decrease. Conclusions It is possible to reduce inadequacy by applying measures based on prior analysis of the situation in each hospital. PMID:23075150

  16. Inappropriate implantable cardioverter defibrillator shock from a transcutaneous muscle stimulation device therapy.

    PubMed

    Siu, Chung-Wah; Tse, Hung-Fat; Lau, Chu-Pak

    2005-06-01

    Inappropriate shock from implantable cardioverter defibrillator (ICD) may result from external electromagnetic interference (EMI), especially for unipolar ventricle sensing. Previous case reports and small in-vitro safety study suggested that endocardial bipolar lead system may be immune from EMI resulting from transcutaneous electrical neuromuscle stimulation (TENS) therapy. This report presents an unusual case of inappropriate discharge in a patient with ICD of endocardial bipolar lead system, receiving TENS from a commercially available device.

  17. Eliminating inappropriate classroom behavior using a DRO schedule: a preliminary study.

    PubMed

    Ramasamy, R; Taylor, R L; Ziegler, E W

    1996-06-01

    The purpose of this study was to eliminate out-of-seat behavior of a 14-yr.-old boy with learning disabilities using a single-subject design. Based on functional analysis, a Differential Reinforcement of Other Behavior interval schedule was used to eliminate an inappropriate behavior. During baseline, an average of 15 out-of-seat behavior problems were recorded. After 4 wk. of intervention, the inappropriate out-of-seat behavior was eliminated and on-task behavior improved.

  18. Inappropriateness of Cardiovascular Radiological Imaging Testing; A Tertiary Care Referral Center Study

    PubMed Central

    Carpeggiani, Clara; Marraccini, Paolo; Morales, Maria Aurora; Prediletto, Renato; Landi, Patrizia; Picano, Eugenio

    2013-01-01

    Aims Radiological inappropriateness in medical imaging leads to loss of resources and accumulation of avoidable population cancer risk. Aim of the study was to audit the appropriateness rate of different cardiac radiological examinations. Methods and Principal Findings With a retrospective, observational study we reviewed clinical records of 818 consecutive patients (67±12 years, 75% males) admitted from January 1-May 31, 2010 to the National Research Council – Tuscany Region Gabriele Monasterio Foundation cardiology division. A total of 940 procedures were audited: 250 chest x-rays (CXR); 240 coronary computed tomographies (CCT); 250 coronary angiographies (CA); 200 percutaneous coronary interventions (PCI). For each test, indications were rated on the basis of guidelines class of recommendation and level of evidence: definitely appropriate (A, including class I, appropriate, and class IIa, probably appropriate), uncertain (U, class IIb, probably inappropriate), or inappropriate (I, class III, definitely inappropriate). Appropriateness was suboptimal for all tests: CXR (A = 48%, U = 10%, I = 42%); CCT (A = 58%, U = 24%, I = 18%); CA (A = 45%, U = 25%, I = 30%); PCI (A = 63%, U = 15%, I = 22%). Top reasons for inappropriateness were: routine on hospital admission (70% of inappropriate CXR); first line application in asymptomatic low-risk patients (42% of CCT) or in patients with unchanged clinical status post-revascularization (20% of CA); PCI in patients either asymptomatic or with miscellaneous symptoms and without inducible ischemia on non-invasive testing (36% of inappropriate PCI). Conclusion and Significance Public healthcare system – with universal access paid for with public money – is haemorrhaging significant resources and accumulating avoidable long-term cancer risk with inappropriate cardiovascular imaging prevention. PMID:24312272

  19. Prompt correction of endotracheal tube positioning after intubation prevents further inappropriate positions.

    PubMed

    Rigini, Nugzar; Boaz, Mona; Ezri, Tiberiu; Evron, Shmuel; Trigub, Dimitry; Jackobashvilli, Simon; Izakson, Alexander

    2011-08-01

    To determine whether the timely correction of endotracheal tube (ETT) positioning prevents further inappropriate positions. Prospective crossover study. University-affiliated hospital. 44 adult, ASA physical status 1, 2, and 3 patients undergoing open or laparoscopic abdominal procedures. ETT positioning was verified by both auscultation and fiberoptic bronchoscopy (FOB), after intubation, and before extubation. In laparoscopic procedures, two additional measurements were performed: after maximal abdominal gas insufflation and with head-down position. An ETT in the bronchus or at the carina was considered an inappropriate placement. An ETT ≤ one cm from the carina was considered a critical placement. The frequency of inappropriate and critical ETT positioning with both auscultation and FOB and the number of ETTs that remained in an incorrect position despite repositioning. FOB detected 5 inappropriately positioned ETTs, 4 of which were also detected by chest auscultation (P = 0.99). Critical positioning was detected by FOB in 6 patients, three of which were also detected by auscultation (P = 0.24). There were 15 other "out-of-desired range" positions (out of the 3-5 cm range) - one placed too high and 14 placed too low, while 18 were placed within the range of positions. All patients with inappropriate ETT positioning were women (P = 0.005). Age, body mass index, Mallampati grade > 3, thyromental distance < 6 cm, or laryngoscopy grade ≥ 2 were not associated with either inappropriate or critical placement. No episodes of inappropriate or critical positioning were detected by FOB or auscultation at the end of surgery. Early detection and prompt correction of inappropriate ETT positioning after intubation prevented further ETT migration into undesired positions. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. [Inappropriate prescription and administration of medications in 10 nursing homes in Alsace, France].

    PubMed

    Rousseau, A; Rybarczyk-Vigouret, M C; Vogel, T; Lang, P-O; Michel, B

    2016-04-01

    Medication care is a complicated process in nursing homes. The aim of the study was to offer an overview of inappropriate medication prescription and administration practices in nursing homes in Alsace in order to propose improvement actions to remedy the weaknesses identified. This study was conducted prospectively in 10 nursing homes under contract with community pharmacies in Alsace. The practices of prescription were examined to determine the prevalence of potentially inappropriate medications, inappropriate and contraindicated medication associations. Crushing and opening practices were also assessed, daily treatment costs were calculated. Two hundred and eighty-four residents were included (age: 87.1 ± 5.6 years). The average number of drugs per resident was 8.1 ± 4.0 (daily treatment cost: 4.19 ± 5.21 €). On average, 1.5 drugs ± 1.4 per prescription were considered as potentially inappropriate (daily treatment cost: 0.49 ± 0.76 €). The contraindication associations concerned 8 % of prescriptions and involved potentially inappropriate drugs in 60 % of cases. Inappropriate associations mainly concerned nervous system drugs. Thirty-three residents were taking more than 2 psychotropic drugs; 23 had more than one benzodiazepine. Regarding drug administration, practices differed from one nursing home to another. Crushing was performed in 8 nursing homes. It concerned 20 residents (7 %) and 69 drugs. In 50 %, the crushing decision was made by nurses without physician or pharmacist supervision. Fifty-seven percent of crushed drugs had a formulation which did not allow crushing (n=39 drugs). The analysis of those items led to the proposal of improvement actions. This study pointed out inappropriate medication practices. Tracking tools for inappropriate clinical practices could be operated by physicians, pharmacists and nursing teams through coordinated multidisciplinary approaches. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. Impact of appropriate empirical antimicrobial therapy on outcome of dogs with septic peritonitis.

    PubMed

    Dickinson, Amy E; Summers, Jennifer F; Wignal, Jamie; Boag, Amanda K; Keir, Iain

    2015-01-01

    To determine whether appropriate empirical antimicrobial therapy influenced survival in dogs with septic peritonitis. Retrospective case series (2003-2011). University teaching hospital. Eighty-six dogs with cytological confirmation or positive bacterial culture of abdominal sepsis and subsequent surgical intervention. None. Forty-nine of 86 dogs (57%) survived to hospital discharge. Thirty-seven of 86 dogs were classified as having ''abdominal infection,'' 31/86 as ''severe sepsis,'' and the remaining 18/86 as in ''septic shock.'' Mortality was greatest in the ''septic shock'' category (94%). Empirical antimicrobial treatments were appropriate in 41/78 dogs (52.6%). Appropriateness was not associated with treatment outcome overall or when compared between sepsis severity groups. Antimicrobials had been given in the 30 days before admission in 63/86 (73.3%) dogs. Prior therapy with antimicrobials showed no association with outcome (P = 0.512) but was associated with subsequent inappropriate empirical antimicrobial selection (P = 0.031). Recent abdominal surgery was associated with subsequent inappropriate empirical antimicrobial selection (P = 0.021). In this population, appropriateness of empirical antimicrobial choice was not associated with survival to discharge. Previous antimicrobial administration or abdominal surgery was associated with subsequent inappropriate empirical antimicrobial selection. © Veterinary Emergency and Critical Care Society 2014.

  2. The influence of the Pharmaceutical Benefits Scheme (PBS) on inappropriate prescribing in Australian nursing homes.

    PubMed

    King, Michelle A; Roberts, Michael S

    2007-02-01

    To determine the prevalence of inappropriate prescribing, defined by applying modified Beers' criteria, and to examine the influence of the Pharmaceutical Benefits Scheme (PBS), Australia's national scheme for subsidising medicines, on inappropriate prescribing. Cross-sectional survey of nursing home records, including 7-days data from medication charts. Fiveteen randomly selected nursing homes (998 residents) in Southeast Queensland and Northern New South Wales, Australia. The prevalence of inappropriate prescribing as defined by modified Beers' criteria and its correlation with PBS restrictions. 18.5% of residents were ordered one or more inappropriate medications, and 1.5% of residents were ordered two or more. The level of PBS restriction and the percentage of residents ordered a medication were highly correlated (p = -0.87, P < 0.001). Medications in Beers' criteria that were not listed (subsidised) on the PBS were not ordered for any resident. PBS medicines with subsidies restricted to certain populations or indications were ordered for 0% to 0.1% of residents. Dextropropoxyphene, diazepam, amitriptyline and methyldopa were the only medications in Beers' criteria prescribed to more than 0.5% of residents. Dextropropoxyphene was only subsidised for war veterans, with a caution warning of its potential to cause drug dependence, while diazepam, amitriptyline and methyldopa were listed on the PBS without any subsidy restrictions. Increases in the level of PBS restriction were associated with decreases in the prevalence of inappropriate prescribing, The targeting of drug subsidies to reduce inappropriate prescribing warrants further investigation.

  3. Emergency readmissions to paediatric surgery and urology: The impact of inappropriate coding.

    PubMed

    Peeraully, R; Henderson, K; Davies, B

    2016-04-01

    Introduction In England, emergency readmissions within 30 days of hospital discharge after an elective admission are not reimbursed if they do not meet Payment by Results (PbR) exclusion criteria. However, coding errors could inappropriately penalise hospitals. We aimed to assess the accuracy of coding for emergency readmissions. Methods Emergency readmissions attributed to paediatric surgery and urology between September 2012 and August 2014 to our tertiary referral centre were retrospectively reviewed. Payment by Results (PbR) coding data were obtained from the hospital's Family Health Directorate. Clinical details were obtained from contemporaneous records. All readmissions were categorised as appropriately coded (postoperative or nonoperative) or inappropriately coded (planned surgical readmission, unrelated surgical admission, unrelated medical admission or coding error). Results Over the 24-month period, 241 patients were coded as 30-day readmissions, with 143 (59%) meeting the PbR exclusion criteria. Of the remaining 98 (41%) patients, 24 (25%) were inappropriately coded as emergency readmissions. These readmissions resulted in 352 extra bed days, of which 117 (33%) were attributable to inappropriately coded cases. Conclusions One-quarter of non-excluded emergency readmissions were inappropriately coded, accounting for one-third of additional bed days. As a stay on a paediatric ward costs up to £500 a day, the potential cost to our institution due to inappropriate readmission coding was over £50,000. Diagnoses and the reason for admission for each care episode should be accurately documented and coded, and readmission data should be reviewed at a senior clinician level.

  4. Emotion Knowledge and Attentional Differences in Preschoolers Showing Context-Inappropriate Anger.

    PubMed

    Locke, Robin L; Lang, Nichole J

    2016-08-01

    Some children show anger inappropriate for the situation based on the predominant incentives, which is called context-inappropriate anger. Children need to attend to and interpret situational incentives for appropriate emotional responses. We examined associations of context-inappropriate anger with emotion recognition and attention problems in 43 preschoolers (42% male; M age = 55.1 months, SD = 4.1). Parents rated context-inappropriate anger across situations. Teachers rated attention problems using the Child Behavior Checklist-Teacher Report Form. Emotion recognition was ability to recognize emotional faces using the Emotion Matching Test. Anger perception bias was indicated by anger to non-anger situations using an adapted Affect Knowledge Test. 28% of children showed context-inappropriate anger, which correlated with lower emotion recognition (β = -.28) and higher attention problems (β = .36). Higher attention problems correlated with more anger perception bias (β = .32). This cross-sectional, correlational study provides preliminary findings that children with context-inappropriate anger showed more attention problems, which suggests that both "problems" tend to covary and associate with deficits or biases in emotion knowledge.

  5. [Potentially inappropriate prescribing in hospitalized patients with comparative study between prescription by internist and geriatricians].

    PubMed

    Pardo-Cabello, A J; Bermudo-Conde, S; Manzano-Gamero, V

    2014-01-01

    To analyze potentially inappropriate prescribing in hospitalized patients and compare the prescription by internists and geriatricians. Cross-sectional study in hospitalized patients older than 65 years. We recorded prevalence of potentially inappropriate prescriptions according to the criteria of "Screening Tool of Older Person's Prescriptions". We included 95 hospitalized patients over 65 years with a median age of 79 years (interquartile range: 73-82 years) and 50.5% female. One hundred eighty-three potentially inappropriate prescriptions were detected in 81 patients (85.2% of patients). The most frequent potentially inappropriate prescription were the prolonged use of inhibitors of proton pump high dose (32.6% of patients), the use of benzodiazepines in patients prone to falling (23.2% of patients), the prolonged use of long-acting benzodiazepines (21.1% of patients) and prolonged use of neuroleptic as hypnotics (21.1% of patients). In comparative study between medical specialties, significant differences were found in mean number of drugs (P = 0.0001) and in prolonged use of neuroleptics as hypnotics (P = 0.015). A high percentage of hospitalized patients older than 65 years receive potentially inappropriate prescribing. Prolonged use of inhibitors of the proton pump at high doses was the most frequent potentially inappropriate prescribing criterion.

  6. Optimization of Antifungal Extracts from Ficus hirta Fruits Using Response Surface Methodology and Antifungal Activity Tests.

    PubMed

    Chen, Chuying; Wan, Chunpeng; Peng, Xuan; Chen, Yuhuan; Chen, Ming; Chen, Jinyin

    2015-10-29

    The fruits of Ficus hirta (FH) display strong antifungal activity against Penicillium italicum and Penicillium digitatum. In order to optimize the extraction conditions of antifungal extracts from FH fruit, various extraction parameters, such as ethanol concentration, extraction time, solvent to solid ratio and temperature, were chosen to identify their effects on the diameters of inhibition zones (DIZs) against these two Penicillium molds. Response surface methodology (RSM) was applied to obtain the optimal combination of these parameters. Results showed that the optimal extraction parameters for maximum antifungal activity were: 90% (v/v) ethanol concentration, 65 min extraction time, 31 mL/g solvent to solid ratio and 51 °C temperature. Under the abovementioned extraction conditions, the experimental DIZs values obtained experimentally were 57.17 ± 0.75 and 39.33 ± 0.82 mm, which were very close to the values of 57.26 and 39.29 mm predicted by the model. Further, nine kinds of phytopathogens were tested in vitro to explore the antifungal activity of the FH extracts. It was found for the first time that the FH extracts showed significant inhibition on the growth of P. italicum, A. citri, P. vexans, P. cytosporella and P. digitatum.

  7. Antifungal and antiviral products of marine organisms

    PubMed Central

    Cheung, Randy Chi Fai; Pan, Wen Liang; Chan, Yau Sang; Yin, Cui Ming; Dan, Xiu Li; Wang, He Xiang; Fang, Evandro Fei; Lam, Sze Kwan; Ngai, Patrick Hung Kui; Xia, Li Xin; Liu, Fang; Ye, Xiu Yun; Zhang, Guo Qing; Liu, Qing Hong; Sha, Ou; Lin, Peng; Ki, Chan; Bekhit, Adnan A; Bekhit, Alaa El-Din; Wan, David Chi Cheong

    2017-01-01

    Marine organisms including bacteria, fungi, algae, sponges, echinoderms, mollusks, and cephalochordates produce a variety of products with antifungal activity including bacterial chitinases, lipopeptides, and lactones; fungal (−)-sclerotiorin and peptaibols, purpurides B and C, berkedrimane B and purpuride; algal gambieric acids A and B, phlorotannins; 3,5-dibromo-2-(3,5-dibromo-2-methoxyphenoxy)phenol, spongistatin 1, eurysterols A and B, nortetillapyrone, bromotyrosine alkaloids, bis-indole alkaloid, ageloxime B and (−)-ageloxime D, haliscosamine, hamigeran G, hippolachnin A from sponges; echinoderm triterpene glycosides and alkene sulfates; molluscan kahalalide F and a 1485-Da peptide with a sequence SRSELIVHQR; and cepalochordate chitotriosidase and a 5026.9-Da antifungal peptide. The antiviral compounds from marine organisms include bacterial polysaccharide and furan-2-yl acetate; fungal macrolide, purpurester A, purpurquinone B, isoindolone derivatives, alterporriol Q, tetrahydroaltersolanol C and asperterrestide A, algal diterpenes, xylogalactofucan, alginic acid, glycolipid sulfoquinovosyldiacylglycerol, sulfated polysaccharide p-KG03, meroditerpenoids, methyl ester derivative of vatomaric acid, lectins, polysaccharides, tannins, cnidarian zoanthoxanthin alkaloids, norditerpenoid and capilloquinol; crustacean antilipopolysaccharide factors, molluscan hemocyanin; echinoderm triterpenoid glycosides; tunicate didemnin B, tamandarins A and B and; tilapia hepcidin 1–5 (TH 1–5), seabream SauMx1, SauMx2, and SauMx3, and orange-spotted grouper β-defensin. Although the mechanisms of antifungal and antiviral activities of only some of the afore-mentioned compounds have been elucidated, the possibility to use those known to have distinctly different mechanisms, good bioavailability, and minimal toxicity in combination therapy remains to be investigated. It is also worthwhile to test the marine antimicrobials for possible synergism with existing drugs. The

  8. Histone deacetylases: Targets for antifungal drug development

    PubMed Central

    Kmetzsch, Livia

    2015-01-01

    The interaction of pathogens and its hosts causes a drastic change in the transcriptional landscape in both cells. Among the several mechanisms of gene regulation, transcriptional initiation is probably the main point. In such scenario, the access of transcriptional machinery to promoter is highly regulated by post-translational modification of histones, such as acetylation, phosphorylation and others. Inhibition of histone deacetylases is able to reduce fungal pathogens fitness during infection and, therefore, is currently being considered for the development of new antifungal therapy strategies. PMID:26151486

  9. Nylon-3 Polymers with Selective Antifungal Activity

    PubMed Central

    Liu, Runhui; Chen, Xinyu; Hayouka, Zvika; Chakraborty, Saswata; Falk, Shaun P.; Weisblum, Bernard; Masters, Kristyn S.; Gellman, Samuel H.

    2013-01-01

    Host-defense peptides inhibit bacterial growth but show little toxicity toward mammalian cells. A variety of synthetic polymers have been reported to mimic this antibacterial selectivity; however, achieving comparable selectivity for fungi is more difficult because these pathogens are eukaryotes. Here, we report nylon-3 polymers based on a novel subunit that display potent antifungal activity (MIC = 3.1 μg/mL for C. albicans) and favorable selectivity (IC10 > 400 μg/mL for 3T3 fibroblast toxicity; HC10 > 400 μg/mL for hemolysis). PMID:23547967

  10. Nylon-3 polymers with selective antifungal activity.

    PubMed

    Liu, Runhui; Chen, Xinyu; Hayouka, Zvi; Chakraborty, Saswata; Falk, Shaun P; Weisblum, Bernard; Masters, Kristyn S; Gellman, Samuel H

    2013-04-10

    Host-defense peptides inhibit bacterial growth but show little toxicity toward mammalian cells. A variety of synthetic polymers have been reported to mimic this antibacterial selectivity; however, achieving comparable selectivity for fungi is more difficult because these pathogens are eukaryotes. Here we report nylon-3 polymers based on a novel subunit that display potent antifungal activity (MIC = 3.1 μg/mL for Candida albicans ) and favorable selectivity (IC10 > 400 μg/mL for 3T3 fibroblast toxicity; HC10 > 400 μg/mL for hemolysis).

  11. In Vitro Antifungal Susceptibility of Cryptococcus gattii

    PubMed Central

    Trilles, Luciana; Fernández-Torres, Belkys; dos Santos Lazéra, Márcia; Wanke, Bodo; Guarro, Josep

    2004-01-01

    We have determined the in vitro susceptibilities of 57 strains of Cryptococcus gattii to nine antifungal agents and have compared the MICs for these strains with those for C. neoformans. MICs were determined by a microdilution reference method. Albaconazole and ravuconazole (MICs of 0.04 and 0.05 μg/ml, respectively) showed the best activities. Micafungin showed no activity (MIC of >128 μg/ml). In general, C. gattii was less susceptible than C. neoformans to all drugs tested, with the exception of amphotericin B and flucytosine. PMID:15472349

  12. Chemical modification of antifungal polyene macrolide antibiotics

    NASA Astrophysics Data System (ADS)

    Solovieva, S. E.; Olsufyeva, E. N.; Preobrazhenskaya, M. N.

    2011-02-01

    The review summarizes advances in the methods for the synthesis of polyene antibiotics (amphotericin B, partricin A, etc.) and investigations of the structure-activity relationship made in the last 15 years. State-of-the-art approaches based on the combination of the chemical synthesis and genetic engineering are considered. Emphasis is given to the design of semisynthetic antifungal agents against chemotherapy-resistant pathogens having the highest therapeutic indices. Recent results of research on the mechanisms of action of polyenes are outlined.

  13. Progress in antibacterial and antifungal chemotherapy.

    PubMed

    Fromtling, R A

    2000-08-01

    The European Society of Clinical Microbiology and Infectious Diseases sponsored the 10th European Congress on Clinical Microbiology and Infectious Diseases in Stockholm, Sweden, May 28-31, 2000. At the ECMID, well-attended sessions were held which focused on the pathogenesis and therapy of viral, bacterial and fungal diseases. This report focuses on new information on resistance to antibacterial agents, including data from recent surveillance studies, and the in vitro and investigational clinical activity of new antibacterial (moxifloxacin, telithromycin) and antifungal (fluconazole, itraconazole, voriconazole, amphotericin B, liposomal formulations of amphotericin B, terbinafine and the candins) drugs.

  14. In vitro antifungal susceptibility of Cryptococcus gattii.

    PubMed

    Trilles, Luciana; Fernández-Torres, Belkys; Lazéra, Márcia dos Santos; Wanke, Bodo; Guarro, Josep

    2004-10-01

    We have determined the in vitro susceptibilities of 57 strains of Cryptococcus gattii to nine antifungal agents and have compared the MICs for these strains with those for C. neoformans. MICs were determined by a microdilution reference method. Albaconazole and ravuconazole (MICs of 0.04 and 0.05 microg/ml, respectively) showed the best activities. Micafungin showed no activity (MIC of >128 microg/ml). In general, C. gattii was less susceptible than C. neoformans to all drugs tested, with the exception of amphotericin B and flucytosine.

  15. Terconazole - a new broad-spectrum antifungal.

    PubMed

    Van Cutsem, J; Van Gerven, F; Zaman, R; Janssen, P A

    1983-01-01

    Terconazole, a new triazole ketal, is found to be highly active in vitro on a wide range of yeasts and mycelium-forming fungi. The in vitro activity depends largely on the medium used. In vitro it is a potent antifungal agent in preventing the morphogenetic transformation of the yeast into the (pseudo-)mycelium form of Candida albicans. In vivo terconazole is highly active in topical treatment of various experimental models of dermatophytosis and candidosis. It also possesses moderate oral broad-spectrum activity. No side effects were observed.

  16. [Methods for in vitro antifungal susceptibility testing].

    PubMed

    Dannaoui, Eric

    2006-01-01

    During the last years, a large amount of work has been completed to improve the methods used for in vitro antifungal susceptibility testing. Reference techniques are currently available both for yeasts and filamentous fungi, but in some instances, technical improvement are needed. Etest is another well standardized method that can be used as an alternative on a routine basis in the clinical microbiology laboratory. Studies of in vitro-in vivo correlations have led to the definition of susceptibility breakpoints for yeasts for fluconazole, itraconazole, and flucytosine.

  17. Antifungal activity of Piper diospyrifolium Kunth (Piperaceae) essential oil

    PubMed Central

    Vieira, Silvia Cristina Heredia; de Paulo, Luis Fernando; Svidzinski, Terezinha Inez Estivaleti; Dias Filho, Benedito Prado; Nakamura, Celso Vataru; de Souza, Amanda; Young, Maria Cláudia Marx; Cortez, Diógenes Aparício Garcia

    2011-01-01

    In vitro activity of the essential oil from Piper diospyrifolium leaves was tested using disk diffusion techniques. The antifungal assay showed significant potencial antifungal activity: the oil was effective against several clinical fungal strains. The majority compounds in the essential oil were identified as sesquiterpenoids by GC-MS and GC-FID techniques. PMID:24031717

  18. Nosocomial Candidiasis: Antifungal Stewardship and the Importance of Rapid Diagnosis.

    PubMed

    Pfaller, Michael A; Castanheira, Mariana

    2016-01-01

    Candidemia and other forms of candidiasis are associated with considerable excess mortality and costs. Despite the addition of several new antifungal agents with improved spectrum and potency, the frequency of Candida infection and associated mortality have not decreased in the past two decades. The lack of rapid and sensitive diagnostic tests has led to considerable overuse of antifungal agents resulting in increased costs, selection pressure for resistance, unnecessary drug toxicity, and adverse drug interactions. Both the lack of timely diagnostic tests and emergence of antifungal resistance pose considerable problems for antifungal stewardship. Whereas antifungal stewardship with a focus on nosocomial candidiasis should be able to improve the administration of antifungal therapy in terms of drug selection, proper dose and duration, source control and de-escalation therapy, an important parameter, timeliness of antifungal therapy, remains a victim of slow and insensitive diagnostic tests. Fortunately, new proteomic and molecular diagnostic tools are improving the time to species identification and detection. In this review we will describe the potential impact that rapid diagnostic testing and antifungal stewardship can have on the management of nosocomial candidiasis.

  19. Cuticular antifungals in spiders: density- and condition dependence.

    PubMed

    González-Tokman, Daniel; Ruch, Jasmin; Pulpitel, Tamara; Ponton, Fleur

    2014-01-01

    Animals living in groups face a high risk of disease contagion. In many arthropod species, cuticular antimicrobials constitute the first protective barrier that prevents infections. Here we report that group-living spiders produce cuticular chemicals which inhibit fungal growth. Given that cuticular antifungals may be costly to produce, we explored whether they can be modulated according to the risk of contagion (i.e. under high densities). For this purpose, we quantified cuticular antifungal activity in the subsocial crab spider Diaea ergandros in both natural nests and experimentally manipulated nests of varying density. We quantified the body-condition of spiders to test whether antifungal activity is condition dependent, as well as the effect of spider density on body-condition. We predicted cuticular antifungal activity to increase and body-condition to decrease with high spider densities, and that antifungal activity would be inversely related to body-condition. Contrary to our predictions, antifungal activity was neither density- nor condition-dependent. However, body-condition decreased with density in natural nests, but increased in experimental nests. We suggest that pathogen pressure is so important in nature that it maintains high levels of cuticular antifungal activity in spiders, impacting negatively on individual energetic condition. Future studies should identify the chemical structure of the isolated antifungal compounds in order to understand the physiological basis of a trade-off between disease prevention and energetic condition caused by group living, and its consequences in the evolution of sociality in spiders.

  20. Cuticular Antifungals in Spiders: Density- and Condition Dependence

    PubMed Central

    González-Tokman, Daniel; Ruch, Jasmin; Pulpitel, Tamara; Ponton, Fleur

    2014-01-01

    Animals living in groups face a high risk of disease contagion. In many arthropod species, cuticular antimicrobials constitute the first protective barrier that prevents infections. Here we report that group-living spiders produce cuticular chemicals which inhibit fungal growth. Given that cuticular antifungals may be costly to produce, we explored whether they can be modulated according to the risk of contagion (i.e. under high densities). For this purpose, we quantified cuticular antifungal activity in the subsocial crab spider Diaea ergandros in both natural nests and experimentally manipulated nests of varying density. We quantified the body-condition of spiders to test whether antifungal activity is condition dependent, as well as the effect of spider density on body-condition. We predicted cuticular antifungal activity to increase and body-condition to decrease with high spider densities, and that antifungal activity would be inversely related to body-condition. Contrary to our predictions, antifungal activity was neither density- nor condition-dependent. However, body-condition decreased with density in natural nests, but increased in experimental nests. We suggest that pathogen pressure is so important in nature that it maintains high levels of cuticular antifungal activity in spiders, impacting negatively on individual energetic condition. Future studies should identify the chemical structure of the isolated antifungal compounds in order to understand the physiological basis of a trade-off between disease prevention and energetic condition caused by group living, and its consequences in the evolution of sociality in spiders. PMID:24637563

  1. Antifungal cyclic peptides from the marine sponge Microscleroderma herdmani

    USDA-ARS?s Scientific Manuscript database

    Screening natural product extracts from National Cancer Institute Open Repository for antifungal discovery afforded hits for bioassay-guided fractionation. Upon LC-MS analysis of column fractions with antifungal activities to generate information on chemical structure, two new cyclic hexapeptides, m...

  2. Advances in synthetic approach to and antifungal activity of triazoles

    PubMed Central

    Kumar, Nitin; Drabu, Sushma; Sharma, Pramod Kumar

    2011-01-01

    Summary Several five membered ring systems, e.g., triazole, oxadiazole dithiazole and thiadiazole with three heteroatoms at symmetrical or asymmetrical positions have been studied because of their interesting pharmacological properties. In this article our emphasis is on synthetic development and pharmacological activity of the triazole moiety which exhibit a broad spectrum of pharmacological activity such as antifungal, antibacterial, anti-inflammatory and anticancer etc. Triazoles have increased our ability to treat many fungal infections, for example, candidiasis, cryptococcal meningitis, aspergillosis etc. However, mortality due to these infections even with antifungal therapy is still unacceptably high. Therefore, the development of new antifungal agents targeting specific fungal structures or functions is being actively pursued. Rapid developments in molecular mycology have led to a concentrated search for more target antifungals. Although we are entering a new era of antifungal therapy in which we will continue to be challenged by systemic fungal diseases, the options for treatment will have greatly expanded. PMID:21804864

  3. [S-Acyl derivatives of thiosalicylamides having antifungal activity. II].

    PubMed

    Mazza, M; Modena, T; Montanari, L; Pavanetto, F

    1978-07-01

    Some S-acyl derivatives of N-alkylthiosalicylamides [Table I: substances (I leads to XXXI)] were prepared and tested for antifungal activity. The substances, most of which had not been previously reported, were prepared by condensation of 2-mercapto-N-alkylbenzamides with suitable acylating agents. The antifungal activity of the compounds was tested in vitro against Candida albicans and Trichophyton mentagrophytes. For some compounds the was tested activity against the above strains fungicidal, Candida tropicalis and Saccharomyces cerevisiae. Many of the compounds proved to have high antifungal activity comparable with that of Clotrimazol. The results extended knowledge on the structure-antifungal activity relationships of this class of compounds. The compounds with the highest antifungal activity were: 2-acetylmercapto-N,n-heptylbenzamide (XXVIII); 2-acetylmercapto-5-Cl-N,n-propylbenzamide (XIV); 2-acetylmercapto-N,n-octylbenzamide (XXXI); 2-acetylmercapto-N,n-pentylbenzamide (XXV); 2-acetylmercapto-N,n-hexylbenzamide (XXVII).

  4. Emerging Threats in Antifungal-Resistant Fungal Pathogens

    PubMed Central

    Sanglard, Dominique

    2016-01-01

    The use of antifungal drugs in the therapy of fungal diseases can lead to the development of antifungal resistance. Resistance has been described for virtually all antifungal agents in diverse pathogens, including Candida and Aspergillus species. The majority of resistance mechanisms have also been elucidated at the molecular level in these pathogens. Drug resistance genes and genome mutations have been identified. Therapeutic choices are limited for the control of fungal diseases, and it is tempting to combine several drugs to achieve better therapeutic efficacy. In the recent years, several novel resistance patterns have been observed, including antifungal resistance originating from environmental sources in Aspergillus fumigatus and the emergence of simultaneous resistance to different antifungal classes (multidrug resistance) in different Candida species. This review will summarize these current trends. PMID:27014694

  5. Clinical effectiveness of itraconazole as antifungal prophylaxis in AML patients undergoing intensive chemotherapy in the modern era.

    PubMed

    Keighley, C L; Manii, P; Larsen, S R; van Hal, S

    2017-02-01

    Antifungal prophylaxis regimens vary between centres, informed by local epidemiology and antifungal stewardship practices. The advantages of itraconazole over posaconazole prophylaxis include maintaining the utility of azole therapy for suspected breakthrough invasive fungal infection (bIFI). We examined the effectiveness and tolerability of itraconazole as prophylaxis in acute myeloid leukaemia (AML) patients. We sought to determine the rate of probable and proven bIFI in the context of itraconazole prophylaxis in a real-life setting. Eighty-four patients corresponded to 175 episodes of primary antifungal prophylaxis with itraconazole solution (200 mg twice daily) as prophylaxis supported by a dedicated clinical pharmacist during induction, re-induction and consolidation chemotherapy for AML between January 2010 and January 2014. Assessment of clinical course included blinded review of all radiology scans. Episodes of bIFI were categorised according to consensus criteria. A low rate of bIFI (6/175, 3.4 %) occurred with the use of itraconazole. Tolerance was excellent with adverse events consisting predominantly of deranged liver function tests reported in 7/175 (4 %). Therapeutic drug monitoring performed at clinicians' discretion demonstrated appropriate levels in 12/14 (86 %). Persisting fever and suspicion of invasive fungal infection (IFI) led to empiric antifungal therapy with voriconazole or caspofungin in 33/175 episodes (19 %), ceased after a median of 5 days following investigation in 16/175 (9 %). In this setting, itraconazole is effective and well-tolerated as prophylaxis. An additional benefit was seen in empiric therapy of suspected bIFI with amphotericin formulations kept in reserve. Local epidemiology is vital in guiding prophylaxis strategy.

  6. Effect of Significant Weight Change on Inappropriate Implantable Cardioverter-Defibrillator Therapy.

    PubMed

    Daimee, Usama A; Biton, Yitschak; Aktas, Mehmet K; Zannad, Faiez; Klein, Helmut; Szepietowska, Barbara; McNitt, Scott; Polonsky, Bronislava; Wang, Paul J; Zareba, Wojciech; Moss, Arthur J; Kutyifa, Valentina

    2017-01-01

    Weight loss has been associated with adverse outcomes among heart failure (HF) patients, including those receiving cardiac resynchronization therapy with defibrillator (CRT-D). The effect of significant weight change on inappropriate implantable cardioverter-defibrillator (ICD) therapy among CRT-D patients is not well understood. We evaluated the impact of significant weight change at 1 year on subsequent inappropriate ICD therapy during follow-up among 993 CRT-D patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy. Patients were divided into three subgroups based on weight change at 1 year after enrollment: weight loss (weight loss ≥ 5%), weight gain (weight gain ≥ 5%), and stable weight (weight loss and weight gain < 5%). The primary end point was inappropriate ICD therapy. Secondary end point included inappropriate ICD therapy related to supraventricular arrhythmias (SVAs). There were 102 (10.3%) patients who experienced weight loss, 689 (69.4%) whose weight was stable, and 202 (20.3%) who gained weight at 1 year. Patients with weight loss had increased risk of subsequent inappropriate ICD therapy relative to patients with stable weight (hazard ratio [HR] = 2.35, 95% confidence interval [CI]: 1.39-3.98, P = 0.001) or weight gain (HR = 2.27, 95% CI: 1.18-4.38, P = 0.014). Furthermore, patients losing weight were at greater risk of subsequent inappropriate ICD therapy related to SVAs when compared to patients with stable weight (HR = 2.16, 95% CI: 1.18-3.95, P = 0.013) or weight gain (HR = 2.02, 95% CI: 0.95-4.29, P = 0.068). In mild HF patients receiving CRT-D, significant weight loss at 1 year is associated with increased risk of subsequent inappropriate ICD therapy, including risk related to SVAs. © 2016 Wiley Periodicals, Inc.

  7. Potentially inappropriate prescriptions for older patients in long-term care

    PubMed Central

    Rancourt, Carol; Moisan, Jocelyne; Baillargeon, Lucie; Verreault, René; Laurin, Danielle; Grégoire, Jean-Pierre

    2004-01-01

    Background Inappropriate medication use is a major healthcare issue for the elderly population. This study explored the prevalence of potentially inappropriate prescriptions (PIPs) in long-term care in metropolitan Quebec. Methods A cross sectional chart review of 2,633 long-term care older patients of the Quebec City area was performed. An explicit criteria list for PIPs was developed based on the literature and validated by a modified Delphi method. Medication orders were reviewed to describe prescribing patterns and to determine the prevalence of PIPs. A multivariate analysis was performed to identify predictors of PIPs. Results Almost all residents (94.0%) were receiving one or more prescribed medication; on average patients had 4.8 prescribed medications. A majority (54.7%) of treated patients had a potentially inappropriate prescription (PIP). Most common PIPs were drug interactions (33.9% of treated patients), followed by potentially inappropriate duration (23.6%), potentially inappropriate medication (14.7%) and potentially inappropriate dosage (9.6%). PIPs were most frequent for medications of the central nervous system (10.8% of prescribed medication). The likelihood of PIP increased significantly as the number of drugs prescribed increased (odds ratio [OR]: 1.38, 95% confidence interval [CI]: 1.33 – 1.43) and with the length of stay (OR: 1.78, CI: 1.43 – 2.20). On the other hand, the risk of receiving a PIP decreased with age. Conclusion Potentially inappropriate prescribing is a serious problem in the highly medicated long-term care population in metropolitan Quebec. Use of explicit criteria lists may help identify the most critical issues and prioritize interventions to improve quality of care and patient safety. PMID:15488143

  8. Frequency and factors associated with inappropriate for intervention cardiac catheterization laboratory activation.

    PubMed

    Patel, Apurva; Parikh, Roosha; Poddar, Kanhaiya L; Ellis, Stephen G; Tuzcu, E Murat; Kapadia, Samir R

    2016-06-01

    Current guidelines emphasize timely coronary intervention with a door to balloon time of ≤90min for favorable survival impact after STEMI. Efforts to achieve these targets may result in unnecessary emergent angiography for inappropriate activations. Evaluate the frequency, trend and factors which are significantly associated with inappropriate for intervention cardiac catheterization laboratory (CCL) activation. We analyzed 1764 consecutive emergent CCL activation for possible ST segment elevation myocardial infarction (STEMI) between 7/2005 and 8/2013. Inappropriate for intervention activation was defined as negative STEMI (incorrect diagnosis: insignificant coronary lesion, not requiring any intervention) and inappropriate patients (true STEMI but poor CCL candidacy). Inappropriate for intervention CCL activation occurred in 317 patients (17.9%): 292 incorrect diagnosis (negative STEMI diagnosis), 25 inappropriate patients, with no difference in the frequency based on time of the day (18.6% regular hours vs. 17.6% off-hours, p=0.6). On multivariable analysis, female gender (OR 1.9 [1.2-3.0]), African American race (OR 1.9[1.3-2.7]), and prior coronary artery bypass graft surgery (OR 3.6 [2.3-5.5]) were significantly associated with incorrect diagnosis (negative STEMI diagnosis) (all p<0.005) and hyperlipidemia (OR 0.2 [0.1-0.3]), tobacco use (OR 0.2 [0.1-0.3]), and stroke/TIA (OR 0.2 [0.1-0.4]) had a significant inverse association (all p<0.001). ST Elevation with no reciprocal depression and pericarditis/myocarditis were the most common ECG finding and etiology respectively. Inappropriate for intervention CCL activation is not uncommon and should be closely monitored to maximize resource utilization. Females, African American patients with few or no risk factors and patients presenting ST elevation but no reciprocal depression constitute a population that may require attention. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Systemic Antifungal Activity of Pyrrolnitrin1

    PubMed Central

    Gordee, Robert S.; Matthews, Thomas R.

    1969-01-01

    The antifungal activity of pyrrolnitrin, previously shown to be effective against superficial infections, was evaluated against experimental systemic mycoses. Pyrrolnitrin was inhibitory in vitro at <0.78 to 100 μg/ml to Candida albicans, Cryptococcus neoformans, Blastomyces dermatitidis, Sporotrichum schenckii, and Histoplasma capsulatum. Pyrrolnitrin activity was reduced about 90% in sera. After multiple subcutaneous doses of pyrrolnitrin at 20 mg/kg, activity was recovered in mouse blood and urine as well as kidney, liver, and brain homogenates. Multiple daily doses (50 mg/kg) of this antibiotic were effective in reducing by 74% the number of viable cells of C. albicans recovered from kidney homogenates. Multiple doses (15 mg/kg) resulted in a 74% reduction in the number of C. neoformans from brain homogenates. Pyrrolnitrin was ineffective in reducing the recovery of B. dermatitidis or H. capsulatum from liver or spleen homogenates of infected mice. When compared with amphotericin B, hamycin, 5-fluorocytosine, and saramycetin, this antibiotic was less effective. This study indicates that pyrrolnitrin would have limited usefulness as a systemic antifungal agent. PMID:5785951

  10. Antifungal Th Immunity: Growing up in Family

    PubMed Central

    Borghi, Monica; Renga, Giorgia; Puccetti, Matteo; Oikonomou, Vasileios; Palmieri, Melissa; Galosi, Claudia; Bartoli, Andrea; Romani, Luigina

    2014-01-01

    Fungal diseases represent an important paradigm in immunology since they can result from either the lack of recognition or over-activation of the inflammatory response. Current understanding of the pathophysiology underlying fungal infections and diseases highlights the multiple cell populations and cell-signaling pathways involved in these conditions. A systems biology approach that integrates investigations of immunity at the systems-level is required to generate novel insights into this complexity and to decipher the dynamics of the host–fungus interaction. It is becoming clear that a three-way interaction between the host, microbiota, and fungi dictates the types of host–fungus relationship. Tryptophan metabolism helps support this interaction, being exploited by the mammalian host and commensals to increase fitness in response to fungi via resistance and tolerance mechanisms of antifungal immunity. The cellular and molecular mechanisms that provide immune homeostasis with the fungal biota and its possible rupture in fungal infections and diseases will be discussed within the expanding role of antifungal Th cell responses. PMID:25360137

  11. Microbial Biotransformation to Obtain New Antifungals

    PubMed Central

    Bianchini, Luiz F.; Arruda, Maria F. C.; Vieira, Sergio R.; Campelo, Patrícia M. S.; Grégio, Ana M. T.; Rosa, Edvaldo A. R.

    2015-01-01

    Antifungal drugs belong to few chemical groups and such low diversity limits the therapeutic choices. The urgent need of innovative options has pushed researchers to search new bioactive molecules. Literature regarding the last 15 years reveals that different research groups have used different approaches to achieve such goal. However, the discovery of molecules with different mechanisms of action still demands considerable time and efforts. This review was conceived to present how Pharmaceutical Biotechnology might contribute to the discovery of molecules with antifungal properties by microbial biotransformation procedures. Authors present some aspects of (1) microbial biotransformation of herbal medicines and food; (2) possibility of major and minor molecular amendments in existing molecules by biocatalysis; (3) methodological improvements in processes involving whole cells and immobilized enzymes; (4) potential of endophytic fungi to produce antimicrobials by bioconversions; and (5) in silico research driving to the improvement of molecules. All these issues belong to a new conception of transformation procedures, so-called “green chemistry,” which aims the highest possible efficiency with reduced production of waste and the smallest environmental impact. PMID:26733974

  12. Antimicrobial peptides as potential new antifungals.

    PubMed

    Müller, F M; Lyman, C A; Walsh, T J

    1999-01-01

    Ribosomally synthesized natural antimicrobial peptides (AP) and their synthetic derivatives are small, cationic, amphipathic molecules of 12-50 amino acids with unusually broad activity spectra. These peptides kill microorganisms by a common mechanism, which involves binding to the lipid bilayer of biological membranes, forming pores, and ultimately followed by cell lysis. Several AP from mammals, amphibians, insects, plants and their synthetic derivatives demonstrate promising in vitro activity against various pathogenic fungi including azole-resistant Candida albicans strains. In addition to their antimicrobial activity, some AP such as lactoferrin, interact with a variety of host cells and can increase the activity of natural killer and lymphokine activated killer cells. Pretreatment of polymorphonuclear neutrophil leukocytes (PMN) or monocytes with these AP also may upregulate superoxide release. AP as potential new antifungal agents offer some advantages, such as rapid killing of pathogenic fungi and the difficulty to raise mutants resistant to these peptides. AP are limited by their nonselective toxicity, stability, immunogenicity and their costs of production. Potential clinical applications of AP in the future have to be further explored in preclinical and clinical studies to assess their impact as a new class of antifungals.

  13. Selective sweeps in Cryptocercus woodroach antifungal proteins.

    PubMed

    Velenovsky, Joseph F; Kalisch, Jessica; Bulmer, Mark S

    2016-10-01

    We identified the antifungal gene termicin in three species of Cryptocercus woodroaches. Cryptocercus represents the closest living cockroach lineage of termites, which suggests that the antifungal role of termicin evolved prior to the divergence of termites from other cockroaches. An analysis of Cryptocercus termicin and two β-1,3-glucanase genes (GNBP1 and GNBP2), which appear to work synergistically with termicin in termites, revealed evidence of selection in these proteins. We identified the signature of past selective sweeps within GNBP2 from Cryptocercus punctulatus and Cryptocercus wrighti. The signature of past selective sweeps was also found within termicin from Cryptocercus punctulatus and Cryptocercus darwini. Our analysis further suggests a phenotypically identical variant of GNBP2 was maintained within Cryptocercus punctulatus, Cryptocercus wrighti, and Cryptocercus darwini while synonymous sites diverged. Cryptocercus termicin and GNBP2 appear to have experienced similar selective pressure to that of their termite orthologues in Reticulitermes. This selective pressure may be a result of ubiquitous entomopathogenic fungal pathogens such as Metarhizium. This study further reveals the similarities between Cryptocercus woodroaches and termites.

  14. Law of Empires.

    ERIC Educational Resources Information Center

    Martz, Carlton

    2001-01-01

    This issue of "Bill of Rights in Action" explores issues raised by empires and imperial law. The first article, "Clash of Empires: The Fight for North America," looks at the clash of empires and the fight for North America during the 18th century. The second article, "When Roman Law Ruled the Western World," examines…

  15. Antifungal Resistance, Metabolic Routes as Drug Targets, and New Antifungal Agents: An Overview about Endemic Dimorphic Fungi.

    PubMed

    Parente-Rocha, Juliana Alves; Bailão, Alexandre Melo; Amaral, André Correa; Taborda, Carlos Pelleschi; Paccez, Juliano Domiraci; Borges, Clayton Luiz; Pereira, Maristela

    2017-01-01

    Diseases caused by fungi can occur in healthy people, but immunocompromised patients are the major risk group for invasive fungal infections. Cases of fungal resistance and the difficulty of treatment make fungal infections a public health problem. This review explores mechanisms used by fungi to promote fungal resistance, such as the mutation or overexpression of drug targets, efflux and degradation systems, and pleiotropic drug responses. Alternative novel drug targets have been investigated; these include metabolic routes used by fungi during infection, such as trehalose and amino acid metabolism and mitochondrial proteins. An overview of new antifungal agents, including nanostructured antifungals, as well as of repositioning approaches is discussed. Studies focusing on the development of vaccines against antifungal diseases have increased in recent years, as these strategies can be applied in combination with antifungal therapy to prevent posttreatment sequelae. Studies focused on the development of a pan-fungal vaccine and antifungal drugs can improve the treatment of immunocompromised patients and reduce treatment costs.

  16. A multicenter phase 2 study of empirical low-dose liposomal amphotericin B in patients with refractory febrile neutropenia.

    PubMed

    Miyao, Kotaro; Sawa, Masashi; Kurata, Mio; Suzuki, Ritsuro; Sakemura, Reona; Sakai, Toshiyasu; Kato, Tomonori; Sahashi, Satomi; Tsushita, Natsuko; Ozawa, Yukiyasu; Tsuzuki, Motohiro; Kohno, Akio; Adachi, Tatsuya; Watanabe, Keisuke; Ohbayashi, Kaneyuki; Inagaki, Yuichiro; Atsuta, Yoshiko; Emi, Nobuhiko

    2017-01-01

    Invasive fungal infection (IFI) is a major life-threatening problem encountered by patients with hematological malignancies receiving intensive chemotherapy. Empirical antifungal agents are therefore important. Despite the availability of antifungal agents for such situations, the optimal agents and administration methods remain unclear. We conducted a prospective phase 2 study of empirical 1 mg/kg/day liposomal amphotericin B (L-AMB) in 80 patients receiving intensive chemotherapy for hematological malignancies. All enrolled patients were high-risk and had recurrent prolonged febrile neutropenia despite having received broad-spectrum antibacterial therapy for at least 72 hours. Fifty-three patients (66.3 %) achieved the primary endpoint of successful treatment, thus exceeding the predefined threshold success rate. No patients developed IFI. The treatment completion rate was 73.8 %, and only two cases ceased treatment because of adverse events. The most frequent events were reversible electrolyte abnormalities. We consider low-dose L-AMB to provide comparable efficacy and improved safety and cost-effectiveness when compared with other empirical antifungal therapies. Additional large-scale randomized studies are needed to determine the clinical usefulness of L-AMB relative to other empirical antifungal therapies.

  17. Effect of a centralized prescription network on inappropriate prescriptions for opioid analgesics and benzodiazepines

    PubMed Central

    Dormuth, Colin R.; Miller, Tarita A.; Huang, Anjie; Mamdani, Muhammad M.; Juurlink, David N.

    2012-01-01

    Background: Opioid analgesics and benzodiazepines are often misused in clinical practice. We determined whether implementation of a centralized prescription network offering real-time access to patient-level data on filled prescriptions (PharmaNet) reduced the number of potentially inappropriate prescriptions for opioids and benzodiazepines. Methods: We conducted a time series analysis using prescription records between Jan. 1, 1993, and Dec. 31, 1997, for residents of the province of British Columbia who were receiving social assistance or were 65 years or older. We calculated monthly percentages of filled prescriptions for an opioid or a benzodiazepine that were deemed inappropriate (those issued by a different physician and dispensed at a different pharmacy within 7 days after a filled prescription of at least 30 tablets of the same drug). Results: Within 6 months after implementation of PharmaNet in July 1995, we observed a relative reduction in inappropriate filled prescriptions for opioids of 32.8% (95% confidence interval [CI] 31.0%–34.7%) among patients receiving social assistance; inappropriate filled prescriptions for benzodiazepines decreased by 48.6% (95% CI 43.2%–53.1%). Similar and statistically significant reductions were observed among residents 65 years or older. Interpretation: The implementation of a centralized prescription network was associated with a dramatic reduction in inappropriate filled prescriptions for opioids and benzodiazepines. PMID:22949563

  18. Effect of a centralized prescription network on inappropriate prescriptions for opioid analgesics and benzodiazepines.

    PubMed

    Dormuth, Colin R; Miller, Tarita A; Huang, Anjie; Mamdani, Muhammad M; Juurlink, David N

    2012-11-06

    Opioid analgesics and benzodiazepines are often misused in clinical practice. We determined whether implementation of a centralized prescription network offering real-time access to patient-level data on filled prescriptions (PharmaNet) reduced the number of potentially inappropriate prescriptions for opioids and benzodiazepines. We conducted a time series analysis using prescription records between Jan. 1, 1993, and Dec. 31, 1997, for residents of the province of British Columbia who were receiving social assistance or were 65 years or older. We calculated monthly percentages of filled prescriptions for an opioid or a benzodiazepine that were deemed inappropriate (those issued by a different physician and dispensed at a different pharmacy within 7 days after a filled prescription of at least 30 tablets of the same drug). Within 6 months after implementation of PharmaNet in July 1995, we observed a relative reduction in inappropriate filled prescriptions for opioids of 32.8% (95% confidence interval [CI] 31.0%-34.7%) among patients receiving social assistance; inappropriate filled prescriptions for benzodiazepines decreased by 48.6% (95% CI 43.2%-53.1%). Similar and statistically significant reductions were observed among residents 65 years or older. The implementation of a centralized prescription network was associated with a dramatic reduction in inappropriate filled prescriptions for opioids and benzodiazepines.

  19. Empiric Antibiotic Therapy for Severe Sepsis and Septic Shock.

    PubMed

    Oshima, Taku; Kodama, Yoshiyuki; Takahashi, Waka; Hayashi, Yosuke; Iwase, Shinya; Kurita, Takeo; Saito, Daiki; Yamaji, Yoshihiro; Oda, Shigeto

    2016-04-01

    A retrospective study was conducted to investigate the validity and the effectiveness of early empiric antibiotic and de-escalation therapy for the treatment of severe sepsis and septic shock patients in the intensive care unit (ICU). Patients admitted to the ICU at Chiba University Hospital from January 1, 2010, to December 31, 2012, for the treatment of severe sepsis or septic shock were selected for analysis. One-hundred and ten patients were enrolled for the analysis. Carbapenems were selected most frequently (57.3%), followed by cephalosporins (22.7%), and penicillins (21.8%). Empiric antibiotic therapy was appropriate for 85 (77.3%) patients. Mortality rates for patients with inappropriate empiric therapy was 36.8%, whereas mortality rates for patients with appropriate empiric therapy was 17.5%. Among the patients with appropriate empiric antibiotic administration, de-escalation was associated with lower mortality rates of 5.0% for severe sepsis and 9.7% for septic shock patients. The mortality rates for the no de-escalation group were 19.0% and 35.7%, respectively. Empiric antibiotic therapy was acceptable for severe sepsis and septic shock patients treated in the ICU. The appropriate selection of empiric antibiotics was related to a greater rate of de-escalation and better survival. The risk of multi-drug-resistant bacterial infections was not as high as expected, but will need further attention in the future.

  20. Antifungal activity of medicinal plant extracts; preliminary screening studies.

    PubMed

    Webster, Duncan; Taschereau, Pierre; Belland, René J; Sand, Crystal; Rennie, Robert P

    2008-01-04

    In the setting of HIV and organ transplantation, opportunistic fungal infections have become a common cause of morbidity and mortality. Thus antifungal therapy is playing a greater role in health care. Traditional plants are a valuable source of novel antifungals. To assess in vitro antifungal activity of aqueous plant extracts. The minimum inhibitory concentrations were determined for each extract in the setting of human pathogenic fungal isolates. Plants were harvested and identification verified. Aqueous extracts were obtained and antifungal susceptibilities determined using serial dilutional extracts with a standardized microdilution broth methodology. Twenty-three fungal isolates were cultured and exposed to the plant extracts. Five known antifungals were used as positive controls. Results were read at 48 and 72 h. Of the 14 plants analyzed, Fragaria virginiana Duchesne, Epilobium angustifolium L. and Potentilla simplex Michx. demonstrated strong antifungal potential overall. Fragaria virginiana had some degree of activity against all of the fungal pathogens. Alnus viridis DC., Betula alleghaniensis Britt. and Solidago gigantea Ait. also demonstrated a significant degree of activity against many of the yeast isolates. Fragaria virginiana, Epilobium angustifolium and Potentilla simplex demonstrate promising antifungal potential.

  1. [Impact of potentially inappropriate drug usage on health insurance business results].

    PubMed

    Kirschke, Malin; Böhme, Jacqueline

    2014-09-01

    In Germany a list was drawn up that included 83 potentially inappropriate drugs. The PRISCUS list published in 2010 was intended to highlight certain problems in the pharmakotherapy of elderly patients and serve as a support for improved medicine safety. Almost a third of the insurance portfolio of the HALLESCHE Krankenversicherung aged over 75 years takes drugs that are on the PRISCUS list. Benzodiazepine and Z-drugs are taken most frequently. The costs per insurant with potentially inappropriate medication are on average higher than for policyholders who do not take drugs on the PRISCUS list. The costs per insurant are rising, with an increase in the number of PRISCUS agents being taken as well. However, there is still no scientific proof that potentially inappropriate drugs lead to adverse drug events.

  2. The effect of appropriate and inappropriate stimulus color on odor discrimination.

    PubMed

    Stevenson, Richard J; Oaten, Megan

    2008-05-01

    Color can strongly affect participants' self-report of an odor's qualities. In Experiment 1, we examined whether color influences a more objective measure of odor quality, discrimination. Odor pairs, presented in their appropriate color (e.g., strawberry and cherry in red water), an inappropriate color (e.g., strawberry and cherry in green water), or uncolored water were presented for discrimination. Participants made significantly more errors when odors were discriminated in an inappropriate color. In Experiment 2, the same design was utilized, but with an articulatory suppression task (AST), to examine whether the effect of color was mediated by identification or by a more direct effect on the percept. Here, the AST significantly improved discrimination for the inappropriate color condition, relative to Experiment 1. Although color does affect a more objective measure of odor quality, this is mediated by conceptual, rather than perceptual, means.

  3. Benzodiazepines and Geriatrics: What Clinical Practice Strategies Can Be Used to Reduce the Inappropriate Prescribing?

    PubMed

    Gregg, Jason A; Tyson, Ronald L; Cook, Donna

    2016-09-01

    In the elderly, Potentially Inappropriate Prescriptions (PIPs) are quite common and connected with adverse drug events (ADEs), hospital stays, increased medical acuities, and inefficacious healthcare. Benzodiazepines as a class have been identified as an independent risk factor for ADE's and shown to be associated with sedation and impairments in cognition, memory, and balance, lending to an increased risk for falls. Clinically inappropriate medications continue to be prescribed and preferred by many clinicians over non-pharmacological strategies despite continued evidence demonstrating poor outcomes in older adults. Due to the increasing evidence in positive elderly outcomes through the reduction in use of inappropriate drugs, medication reduction strategies are now required policy components in the Centers for Medicare and Medicaid Services regulations along with Medicare Part D. Quality measures now focus on extensive drug reviews with reduction strategies that incorporate use of: the Beers Criteria; multidisciplinary approaches; involving patients and caregivers; and de-prescribing strategies. © 2016 Association of Rehabilitation Nurses.

  4. [Consumption of drugs in over 65 in Porto (Portugal) and risk of potentially inappropriate medication prescribing].

    PubMed

    Eiras, Andreia; Teixeira, M Antonieta; González-Montalvo, Juan I; Castell, Maria-Victoria; Queipo, Rocio; Otero, Ángel

    2016-02-01

    To determine medication consumption in the older people from a central area of Oporto; determine the prevalence of prescription of Potentially Inappropriate Medication and to analyse the polypharmacy and other important connected factors. Cross-sectional study with a sample of 747 patients older than 64 years, who were attended in a Primary care health centre: USF Rainha D. Amélia, Oporto, Portugal. identification of all medication prescribed from electronic registers. Polypharmacy was considered more than 5 medication prescribed and Potential Inappropriate Medication was identified by Beers criteria 2012. The socio-demographic factors, diagnosis and health care services use were registered too. Logistic regression analysis was used to determine the association between co-variables. There were 89.2% (95%CI: 87.6-92.0) of the studied population with at least one prescription. The polypharmacy was present at 59.2% (95%CI: 55.7-62.7) of people. The Potential Inappropriate Medication was present in 37.0% (95%CI: 33.5-40.5) of the cases. The Potential Inappropriate Medication was related with increasing age [OR=1.02 (95%CI: 1.00-1.05)], polypharmacy [OR=4.45 (95%CI: 3.12-6.36)], and be diagnosed with depression/anxiety [OR=2.18 (95%CI: 1.36-3.51)] and/or arthrosis [OR=1.64 (95%CI: 1.11-2.42)]. The rate of medication prescription, polypharmacy and the prescription of Potentially Inappropriate Medication are very high in Portuguese population studied. The polypharmacy is the most important factor related with this potential inappropriate medication. The physician need to have carefully with prescription of the anxiolytic and anti-inflammatory pain drugs. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  5. Potentially Inappropriate Antihypertensive Prescriptions to Elderly Patients: Results of a Prospective, Observational Study.

    PubMed

    Márquez, Paola H Ponte; Torres, Olga H; San-José, Anonio; Vidal, Xavier; Agustí, Antonia; Formiga, Francesc; López-Soto, Alfonso; Ramírez-Duque, Nieves; Fernández-Moyano, Antonio; Garcia-Moreno, Juana; Arroyo, Juan A; Ruiz, Domingo

    2017-06-01

    Previous studies of antihypertensive treatment of older patients have focused on blood pressure control, cardiovascular risk or adherence, whereas data on inappropriate antihypertensive prescriptions to older patients are scarce. The aim of the study was to assess inappropriate antihypertensive prescriptions to older patients. An observational, prospective multicentric study was conducted to assess potentially inappropriate prescription of antihypertensive drugs, in patients aged 75 years and older with arterial hypertension (HTN), in the month prior to hospital admission, using four instruments: Beers, Screening Tool of Older Person's Prescriptions (STOPP), Screening Tool to Alert Doctors to the Right Treatment (START) and Assessing Care of Vulnerable Elders 3 (ACOVE-3). Primary care and hospital electronic records were reviewed for HTN diagnoses, antihypertensive treatment and blood pressure readings. Of 672 patients, 532 (median age 85 years, 56% female) had HTN. 21.6% received antihypertensive monotherapy, 4.7% received no hypertensive treatment, and the remainder received a combination of antihypertensive therapies. The most frequently prescribed antihypertensive drugs were diuretics (53.5%), angiotensin-converting enzyme inhibitors (ACEIs) (41%), calcium antagonists (32.2%), angiotensin receptor blockers (29.7%) and beta-blockers (29.7%). Potentially inappropriate prescription was observed in 51.3% of patients (27.8% overprescription and 35% underprescription). The most frequent inappropriately prescribed drugs were calcium antagonists (overprescribed), ACEIs and beta-blockers (underprescribed). ACEI and beta-blocker underprescriptions were independently associated with heart failure admissions [beta-blockers odds ratio (OR) 0.53, 95% confidence interval (CI) 0.39-0.71, p < 0.001; ACEIs OR 0.50, 95% CI 0.36-0.70, p < 0.001]. Potentially inappropriate prescription was detected in more than half of patients receiving antihypertensive treatment

  6. Emergency readmissions to paediatric surgery and urology: The impact of inappropriate coding

    PubMed Central

    Peeraully, R; Henderson, K; Davies, B

    2016-01-01

    Introduction In England, emergency readmissions within 30 days of hospital discharge after an elective admission are not reimbursed if they do not meet Payment by Results (PbR) exclusion criteria. However, coding errors could inappropriately penalise hospitals. We aimed to assess the accuracy of coding for emergency readmissions. Methods Emergency readmissions attributed to paediatric surgery and urology between September 2012 and August 2014 to our tertiary referral centre were retrospectively reviewed. Payment by Results (PbR) coding data were obtained from the hospital’s Family Health Directorate. Clinical details were obtained from contemporaneous records. All readmissions were categorised as appropriately coded (postoperative or nonoperative) or inappropriately coded (planned surgical readmission, unrelated surgical admission, unrelated medical admission or coding error). Results Over the 24-month period, 241 patients were coded as 30-day readmissions, with 143 (59%) meeting the PbR exclusion criteria. Of the remaining 98 (41%) patients, 24 (25%) were inappropriately coded as emergency readmissions. These readmissions resulted in 352 extra bed days, of which 117 (33%) were attributable to inappropriately coded cases. Conclusions One-quarter of non-excluded emergency readmissions were inappropriately coded, accounting for one-third of additional bed days. As a stay on a paediatric ward costs up to £500 a day, the potential cost to our institution due to inappropriate readmission coding was over £50,000. Diagnoses and the reason for admission for each care episode should be accurately documented and coded, and readmission data should be reviewed at a senior clinician level. PMID:26924486

  7. Antifungal activity of Brevibacillus laterosporus JX-5 and characterization of its antifungal components.

    PubMed

    Jiang, Hongxia; Wang, Xiaohui; Xiao, Chengze; Wang, Weiyan; Zhao, Xu; Sui, Junkang; Sa, Rongbo; Guo, Tai L; Liu, Xunli

    2015-10-01

    The establishment of safe and effective methods for controlling fungal disease is an urgent issue in agriculture and forestry. Microbiological control of plant disease is expected to achieve better results than use of chemically derived fungicides. This study aimed to establish Brevibacillus laterosporus JX-5 as a potential microbiological control agent of poplar canker. The bacterium was isolated from the poplar rhizosphere and demonstrated significant growth inhibition of several pathogenic fungi in vitro. The antifungal components of Br. laterosporus JX-5 were isolated and identified. The fermentation broth of Br. laterosporus JX-5 and its main antifungal component, designated as component B, reduced Botryosphaeria dothidea associated canker of the excised poplar branch by 70 and 90%, respectively. Component B is considerably heat-stable, adaptable to a broad pH range, and UV-resistant. It could inhibit Bo. dothidea by permeating the fungal membrane, fracturing the nuclei, damaging the cell wall, and eventually killing the pathogenic fungus. The antifungal activity exhibited by Br. laterosporus JX-5 and its bioactive metabolic products indicate its feasibility as a potential biocontrol agent for plant diseases.

  8. Functionalised isocoumarins as antifungal compounds: Synthesis and biological studies.

    PubMed

    Simic, Milena; Paunovic, Nikola; Boric, Ivan; Randjelovic, Jelena; Vojnovic, Sandra; Nikodinovic-Runic, Jasmina; Pekmezovic, Marina; Savic, Vladimir

    2016-01-01

    A series of novel 3-substituted isocoumarins was prepared via Pd-catalysed coupling processes and screened in vitro for antifungal activity against Candida species. The study revealed antifungal potential of isocoumarins possessing the azole substituents, which, in some cases, showed biological properties equal to those of clinically used voriconazole. Selected compounds were also screened against voriconazole resistant Candida krusei 6258 and a clinical isolate Candida parapsilosis CA-27. Although the activity against these targets needs to be improved further, the results emphasise additional potential of this new class of antifungal compounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Can agricultural fungicides accelerate the discovery of human antifungal drugs?

    PubMed

    Myung, Kyung; Klittich, Carla J R

    2015-01-01

    Twelve drugs from four chemical classes are currently available for treatment of systemic fungal infections in humans. By contrast, more than 100 structurally distinct compounds from over 30 chemical classes have been developed as agricultural fungicides, and these fungicides target many modes of action not represented among human antifungal drugs. In this article we introduce the diverse aspects of agricultural fungicides and compare them with human antifungal drugs. We propose that the information gained from the development of agricultural fungicides can be applied to the discovery of new mechanisms of action and new antifungal agents for the management of human fungal infections.

  10. Antifungal Susceptibility Testing of Ascomycetous Yeasts Isolated from Animals.

    PubMed

    Álvarez-Pérez, Sergio; García, Marta E; Peláez, Teresa; Martínez-Nevado, Eva; Blanco, José L

    2016-08-01

    Recent studies suggest that antifungal resistance in yeast isolates of veterinary origin may be an underdiagnosed threat. We tested a collection of 92 ascomycetous yeast isolates that were obtained in Spain from birds, mammals and insects for antifungal susceptibility. MICs to amphotericin B and azoles were low, and no resistant isolates were detected. Despite these results, and given the potential role of animals as reservoirs of resistant strains, continuous monitoring of antifungal susceptibility in the veterinary setting is recommended. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  11. Management of Postural Tachycardia Syndrome, Inappropriate Sinus Tachycardia and Vasovagal Syncope

    PubMed Central

    Raj, Satish

    2016-01-01

    Postural tachycardia syndrome (POTS), inappropriate sinus tachycardia (IST) and vasovagal syncope (VVS) are relatively common clinical syndromes that are seen by physicians in several disciplines. They are often not well recognised and are poorly understood by physicians, are associated with significant morbidity and cause significant frustration for both patients and their physicians. The 2015 Heart Rhythm Society Expert Consensus Statement on the Diagnosis and Treatment of Postural Tachycardia Syndrome, Inappropriate Sinus Tachycardia and Vasovagal Syncope provides physicians with an introduction to these disorders and initial recommendations on their investigation and treatment. Here we summarise the consensus statement to help physicians in the management of patients with these frequently distressing problems. PMID:27617091

  12. Potentially inappropriate screening colonoscopy in Medicare patients: variation by physician and geographic region.

    PubMed

    Sheffield, Kristin M; Han, Yimei; Kuo, Yong-Fang; Riall, Taylor S; Goodwin, James S

    2013-04-08

    Inappropriate use of colonoscopy involves unnecessary risk for older patients and consumes resources that could be used more effectively. To determine the frequency of potentially inappropriate colonoscopy in Medicare beneficiaries in Texas and to examine variation among physicians and across geographic regions. This retrospective cohort study used 100% Medicare claims data for Texas and a 5% sample from the United States from 2000 through 2009. We identified Medicare beneficiaries aged 70 years or older who underwent a colonoscopy from October 1, 2008, through September 30, 2009. Colonoscopies were classified as screening in the absence of a diagnosis suggesting an indication for the procedure. Screening colonoscopy was considered potentially inappropriate on the basis of patient age or occurrence too soon after colonoscopy with negative findings. The percentage of patients undergoing potentially inappropriate screening colonoscopy was estimated for each colonoscopist and hospital service area. A large percentage of colonoscopies performed in older adults were potentially inappropriate: 23.4% for the overall Texas cohort and 9.9%, 38.8%, and 24.9%, respectively, in patients aged 70 to 75, 76 to 85, or 86 years or older. There was considerable variation across the 797 colonoscopists in the percentages of colonoscopies performed that were potentially inappropriate. In a multilevel model including patient sex, race or ethnicity, number of comorbid conditions, educational level, and urban or rural residence, 73 colonoscopists had percentages significantly above the mean (23.9%), ranging from 28.7% to 45.5%, and 119 had percentages significantly below the mean (23.9%), ranging from 6.7% to 18.6%. The colonoscopists with percentages significantly above the mean were more likely to be surgeons, graduates of US medical schools, medical school graduates before 1990, and higher-volume colonoscopists than those with percentages significantly below the mean. Colonoscopist

  13. Terbinafine: novel formulations that potentiate antifungal activities.

    PubMed

    Ma, Y; Chen, X; Guan, S

    2015-03-01

    Terbinafine, an orally and topically active antifungal agent, has been available for the treatment of dermatophytic infections and onychomycosis for more than a decade. In addition, oral administration has been shown to be associated with drug-drug interactions, hepatotoxicity, low concentration at the infected sites, gastrointestinal and systemic side effects and other adverse effects. Since topical drug delivery can provide higher patient compliance, allow immediate access to the infected site and reduce unwanted systemic drug exposure, an improved topical drug delivery approach with high permeability, sustained release and prolonged retainment could overcome the limitations and side effects caused by oral administration. Conventional topical formulations cannot keep the drug in the targeted sites for a long duration of time and hence a novel drug delivery that can avoid the side effects while still providing sustained efficacy in treatment should be developed. This brief review of novel formulations based on polymers and nanostructure carriers provides insight into the efficacy and topical delivery of terbinafine.

  14. Overview of medically important antifungal azole derivatives.

    PubMed Central

    Fromtling, R A

    1988-01-01

    Fungal infections are a major burden to the health and welfare of modern humans. They range from simply cosmetic, non-life-threatening skin infections to severe, systemic infections that may lead to significant debilitation or death. The selection of chemotherapeutic agents useful for the treatment of fungal infections is small. In this overview, a major chemical group with antifungal activity, the azole derivatives, is examined. Included are historical and state of the art information on the in vitro activity, experimental in vivo activity, mode of action, pharmacokinetics, clinical studies, and uses and adverse reactions of imidazoles currently marketed (clotrimazole, miconazole, econazole, ketoconazole, bifonazole, butoconazole, croconazole, fenticonazole, isoconazole, oxiconazole, sulconazole, and tioconazole) and under development (aliconazole and omoconazole), as well as triazoles currently marketed (terconazole) and under development (fluconazole, itraconazole, vibunazole, alteconazole, and ICI 195,739). PMID:3069196

  15. Pomegranin, an antifungal peptide from pomegranate peels.

    PubMed

    Guo, Guang; Wang, He Xiang; Ng, Tzi Bun

    2009-01-01

    A new antifungal peptide designated as pomegranin, with an N-terminal sequence resembling that of rice disease resistance NB-S-LRR-like protein, was isolated from fresh pomegranate peels by ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, and gel filtration by fast protein liquid chromatography on Superdex 75. Pomegranin was unadsorbed on DEAE-cellulose but adsorbed on Affi-gel blue gel. It exhibited a molecular mass of 11 kDa in both gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It inhibited mycelial growth in the fungi Botrytis cinerea and Fusarium oxysporum with an IC(50) of 2 microM and 6.1 microM, respectively. It was devoid of hemagglutinating, ribonuclease, deoxyribonuclease and protease inhibitory activities.

  16. An antifungal peptide from baby lima bean.

    PubMed

    Wang, H X; Ng, T B

    2006-12-01

    A 6-kDa antifungal peptide with inhibitory activity on mycelial growth in Fusarium oxysporum, Mycosphaerella arachidicola, and Physalospora piricola was isolated from baby lima beans. The peptide suppressed growth in M. arachidicola with an IC(50) of 0.87 muM and inhibited activity of HIV-1 reverse transcriptase with an IC(50) of 4 muM. The peptide exhibited an N-terminal amino acid sequence similar to those of leguminous defensins. The isolation procedure comprised ion exchange chromatography on diethylaminoethyl (DEAE)-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on carboxymethyl (CM)-cellulose, and gel filtration by fast protein liquid chromatography on Superdex 75. The peptide was unadsorbed on DEAE-cellulose and Affi-gel blue gel but was adsorbed on CM-cellulose.

  17. Probiotics as Antifungals in Mucosal Candidiasis.

    PubMed

    Matsubara, Victor H; Bandara, H M H N; Mayer, Marcia P A; Samaranayake, Lakshman P

    2016-05-01

    Candidais an opportunistic pathogen that causes mucosal and deep systemic candidiasis. The emergence of drug resistance and the side effects of currently available antifungals have restricted their use as long-term prophylactic agents for candidal infections. Given this scenario, probiotics have been suggested as a useful alternative for the management of candidiasis. We analyzed the available data on the efficacy of probiotics in candidal colonization of host surfaces. A number of well-controlled studies indicate that probiotics, particularly lactobacilli, suppressCandidagrowth and biofilm development in vitro.A few clinical trials have also shown the beneficial effects of probiotics in reducing oral, vaginal, and enteric colonization byCandida; alleviation of clinical signs and symptoms; and, in some cases, reducing the incidence of invasive fungal infection in critically ill patients. Probiotics may serve in the future as a worthy ally in the battle against chronic mucosal candidal infections.

  18. Antifungal susceptibilities of bloodstream isolates of Candida species from nine hospitals in Korea: application of new antifungal breakpoints and relationship to antifungal usage.

    PubMed

    Won, Eun Jeong; Shin, Jong Hee; Choi, Min Ji; Lee, Wee Gyo; Park, Yeon-Joon; Uh, Young; Kim, Shine-Young; Lee, Mi-Kyung; Kim, Soo Hyun; Shin, Myung Geun; Suh, Soon Pal; Ryang, Dong Wook

    2015-01-01

    We applied the new clinical breakpoints (CBPs) of the Clinical and Laboratory Standards Institute (CLSI) to a multicenter study to determine the antifungal susceptibility of bloodstream infection (BSI) isolates of Candida species in Korea, and determined the relationship between the frequency of antifungal-resistant Candida BSI isolates and antifungal use at hospitals. Four hundred and fifty BSI isolates of Candida species were collected over a 1-year period in 2011 from nine hospitals. The susceptibilities of the isolates to four antifungal agents were determined using the CLSI M27 broth microdilution method. By applying the species-specific CBPs, non-susceptibility to fluconazole was found in 16.4% (70/428) of isolates, comprising 2.6% resistant and 13.8% susceptible-dose dependent isolates. However, non-susceptibility to voriconazole, caspofungin, or micafungin was found in 0% (0/370), 0% (0/437), or 0.5% (2/437) of the Candida BSI isolates, respectively. Of the 450 isolates, 72 (16.0%) showed decreased susceptibility to fluconazole [minimum inhibitory concentration (MIC) ≥4 μg/ml]. The total usage of systemic antifungals varied considerably among the hospitals, ranging from 190.0 to 7.7 defined daily dose per 1,000 patient days, and fluconazole was the most commonly prescribed agent (46.3%). By Spearman's correlation analysis, fluconazole usage did not show a significant correlation with the percentage of fluconazole resistant isolates at hospitals. However, fluconazole usage was significantly correlated with the percentage of fluconazole non-susceptible isolates (r = 0.733; P = 0.025) or the percentage of isolates with decreased susceptibility to fluconazole (MIC ≥4 μg/ml) (r = 0.700; P = 0.036) at hospitals. Our work represents the first South Korean multicenter study demonstrating an association between antifungal use and antifungal resistance among BSI isolates of Candida at hospitals using the new CBPs of the CLSI.

  19. Research to Identify Effective Antifungal Agents, 1991 Annual Report.

    SciTech Connect

    Schreck, Carl

    1991-09-01

    This study is a continuation of ``Research to Identify Effective Antifungal Agents'' sponsored by Bonneville Power Administration (Schreck et al. 1990). The objectives of the present study was to evaluate up to 10 candidate fungicides.

  20. Antifungal therapy for chronic rhinosinusitis: the controversy persists

    PubMed Central

    Rank, Matthew A.; Adolphson, Cheryl R.; Kita, Hirohito

    2014-01-01

    Purpose of review Chronic rhinosinusitis is a debilitating disease seen frequently by allergist–immunologists. Recent research examining the pathophysiological mechanisms and treatment options for chronic rhinosinusitis have yielded contradicting results, particularly in regard to the role of fungi and antifungal therapies. Recent findings Recent studies using antifungal therapies for chronic rhinosinusitis will be critically evaluated with careful attention to sample selection, length of the intervention, drug delivery system, drug stability and handling, assessment of compliance to study medications, and choice of outcome measures with attention to study power (both primary and secondary). Using this framework to evaluate currently available studies reveals limitations in studies showing a benefit for antifungal therapy and in studies showing no benefit (or harm). Summary Limitations in studies that either support or refute the benefit of antifungal therapy for chronic rhinosinusitis prevent any firm conclusions about its efficacy. PMID:19532095

  1. Solubility, photostability and antifungal activity of phenylpropanoids encapsulated in cyclodextrins.

    PubMed

    Kfoury, Miriana; Lounès-Hadj Sahraoui, Anissa; Bourdon, Natacha; Laruelle, Frédéric; Fontaine, Joël; Auezova, Lizette; Greige-Gerges, Hélène; Fourmentin, Sophie

    2016-04-01

    Effects of the encapsulation in cyclodextrins (CDs) on the solubility, photostability and antifungal activities of some phenylpropanoids (PPs) were investigated. Solubility experiments were carried out to evaluate the effect of CDs on PPs aqueous solubility. Loading capacities and encapsulation efficiencies of freeze-dried inclusion complexes were determined. Moreover, photostability assays for both inclusion complexes in solution and solid state were performed. Finally, two of the most widespread phytopathogenic fungi, Fusarium oxysporum and Botrytis cinerea, were chosen to examine the antifungal activity of free and encapsulated PPs. Results showed that encapsulation in CDs significantly increased the solubility and photostability of studied PPs (by 2 to 17-fold and 2 to 44-fold, respectively). Free PPs revealed remarkable antifungal properties with isoeugenol showing the lowest half-maximal inhibitory concentration (IC50) values of mycelium growth and spore germination inhibition. Encapsulated PPs, despite their reduced antifungal activity, could be helpful to solve drawbacks such as solubility and stability.

  2. Cryptic antifungal compounds active by synergism with polyene antibiotics.

    PubMed

    Kinoshita, Hiroshi; Yoshioka, Mariko; Ihara, Fumio; Nihira, Takuya

    2016-04-01

    The majority of antifungal compounds reported so far target the cell wall or cell membrane of fungi, suggesting that other types of antibiotics cannot exert their activity because they cannot penetrate into the cells. Therefore, if the permeability of the cell membrane could be enhanced, many antibiotics might be found to have antifungal activity. We here used the polyene antibiotic nystatin, which binds to ergosterol and forms pores at the cell membrane, to enhance the cellular permeability. In the presence of nystatin, many culture extracts from entomopathogenic fungi displayed antifungal activity. Among all the active extracts, two active components were purified and identified as helvolic acid and terramide A. Because the minimum inhibitory concentration of either compound was reduced four-fold in the presence of nystatin, it can be concluded that this screening method is useful for detecting novel antifungal activity.

  3. Research to Identify Effective Antifungal Agents, 1993 Annual Report.

    SciTech Connect

    Schreck, Carl

    1993-10-01

    This study is a continuation of ``Research to Identify Effective Antifungal Agents'' sponsored by Bonneville Power Administration (Schreck et al. 1990, 1991, and 1992). The objectives of the present study were to select and evaluate candidate fungicides.

  4. Dendritic Cells in Anti-Fungal Immunity and Vaccine Design

    PubMed Central

    Roy, René M.; Klein, Bruce S.

    2012-01-01

    Life-threatening fungal infections have increased in recent years while treatment options remain limited. The development of vaccines against fungal pathogens represents a key advance sorely needed to combat the increasing fungal disease threat. Dendritic cells (DC) are uniquely able to shape anti-fungal immunity by initiating and modulating naive T cell responses. Targeting DC may allow for the generation of potent vaccines against fungal pathogens. In the context of anti-fungal vaccine design, we describe the characteristics of the varied DC subsets, how DC recognize fungi, their function in immunity against fungal pathogens, and how DC can be targeted in order to create new anti-fungal vaccines. Ongoing studies continue to highlight the critical role of DC in anti-fungal immunity and will help guide DC-based vaccine strategies. PMID:22607797

  5. Inhibition of Rat and Human Steroidogenesis by Triazole Antifungals

    EPA Science Inventory

    Environmental chemicals that alter steroid production could interfere with male reproductive development and function. Three agricultural antifungal triazoles (myclobutanil, propiconazole and triadimefon) that are known to modulate expression of cytochrome P450 (CYP) genes and e...

  6. Antifungal activity of fruit pulp extract from Bromelia pinguin.

    PubMed

    Camacho-Hernández, I L; Chávez-Velázquez, J A; Uribe-Beltrán, M J; Ríos-Morgan, A; Delgado-Vargas, F

    2002-08-01

    The methanol extract of the fruit pulp of Bromelia pinguin was evaluated for its antifungal activity. The extract showed a significant activity against some Trichophyton strains, although Candida strains were generally insensitive.

  7. Inhibition of Rat and Human Steroidogenesis by Triazole Antifungals

    EPA Science Inventory

    Environmental chemicals that alter steroid production could interfere with male reproductive development and function. Three agricultural antifungal triazoles (myclobutanil, propiconazole and triadimefon) that are known to modulate expression of cytochrome P450 (CYP) genes and e...

  8. Antifungal drug resistance pattern of Candida. spp isolated from vaginitis in Ilam-Iran during 2013-2014

    PubMed Central

    Mohamadi, Jasem; Havasian, Mohamad Reza; Panahi, Jafar; Pakzad, Iraj

    2015-01-01

    Vaginal Candidiasis is the most common and important opportunistic fungal infection in women. By increasing use of antifungal drugs in recent years, it has caused drug resistance. This study aims to evaluate antifungal drugs susceptibility of Candida. spp isolated of women with vaginitis from Ilam-Iran during 2013-2014. samples were collected and cultured from 385 women with vaginitis, then Candida.spp was diagnosed by standard method. Antifungal drug susceptibility test for nystatin 100 unit/disk, fluconazole 10µg/disk, itraconazole 10µg/disk, ketoconazole 10µg/disk, amphotericinB 20µg/disk, clotrimazole 10µg/disk, posaconazole 5µg/disk, and voriconazole 1µg/disk were carried out by M44-A method(CLSI). From all culture positive samples, 150 isolates were Candida albicans and 89 isolates were non-albicans. The resistance to fluconazole, itraconazole, ketoconazole, clotrimazole, voriconazole, posaconazole, nystatin and amphotericin B was 76%, 62%, 72%, 55%, 6%, 7%, 1% and 0%. The highest resistance was seen for fluconazole , itraconazole, and the highest susceptible was seen for nystatin and amphotericin B. These results indicate nystatin and amphotericin B can be used as the first line for empirical therapy of vaginal candidiasis in the district. PMID:26124561

  9. Reducing the Impact of Inappropriate Items on Reviewable Computerized Adaptive Testing

    ERIC Educational Resources Information Center

    Yen, Yung-Chin; Ho, Rong-Guey; Liao, Wen-Wei; Chen, Li-Ju

    2012-01-01

    In a test, the testing score would be closer to examinee's actual ability when careless mistakes were corrected. In CAT, however, changing the answer of one item in CAT might cause the following items no longer appropriate for estimating the examinee's ability. These inappropriate items in a reviewable CAT might in turn introduce bias in ability…

  10. Psychological Factors in Risk Assessment and Management of Inappropriate Sexual Behaviour by Men with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Smith, Mark; Willner, Paul

    2004-01-01

    Aim: This study examined the responses of care managers and direct care staff to vignettes of inappropriate sexual behaviour (ISB) by a man with an intellectual disability. The aim was to identify psychological factors that influenced their assessment of risk and the perceived need for risk management strategies. Method: The vignettes varied in…

  11. [Characteristics of potentially inappropriate prescribing of drugs in elderly polypathological patients].

    PubMed

    Rivas-Cobas, Paula Carlota; Ramírez-Duque, Nieves; Gómez Hernández, Mercedes; García, Juana; Agustí, Antonia; Vidal, Xavier; Formiga, Francesc; López-Soto, Alfonso; Torres, Olga H; San-José, Antonio

    To analyse potentially inappropriate prescribing (PIP) in elderly polypathological patients (PP). Multicentre observational, prospective study of 672 patients aged 75 years and older hospitalised in Internal Medicine between April 2011 and March 2012. The Beers, STOPP-START and ACOVE criteria were used to detect potentially inappropriate prescribing and the results of PP and non-PP patients were compared. Of the 672 patients included, 419 (62%) were polypathological, of which 89.3% met PIP criteria versus 79.4% of non-polypathological patients (p <0.01). 40.3% of polypathological patients met at least one Beers criteria, 62.8% at least one STOPP criteria, 62.3% at least one START criteria and 65.6% at least one ACOVE criteria. The rate of potentially inappropriate prescribing was higher in polypathological patients regardless of the tool used. Given the high rate of potentially inappropriate prescribing in polypathological patients, strategies to improve prescribing adequacy must be developed. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. A multifaceted approach to decrease inappropriate antibiotic use in a pediatric outpatient clinic

    PubMed Central

    Al-Tawfiq, Jaffar A.; Alawami, Amel H.

    2017-01-01

    BACKGROUND: Inappropriate use of antimicrobial agents is the major cause for the development of resistance. Thus, it is important to include outpatient clinics in the development of antibiotic stewardship program. METHODS: We report a multifaceted approach to decrease inappropriate antibiotic use in upper respiratory tract infections (URTIs) in an outpatient pediatric clinic. The interventions included educational grand round, academic detailing, and prospective audit and feedback and peer comparison. RESULTS: During the study period, a total of 3677 outpatient clinic visits for URTIs were evaluated. Of all the included patients, 12% were <1 year of age, 42% were 1–5 years, and 46% were >5 years of age. Of the total patients, 684 (17.6%) received appropriate antibiotics, 2812 (76.4%) appropriately did not receive antibiotics, and 217 (6%) inappropriately received antibiotics. The monthly rate of prescription of inappropriate antibiotics significantly decreased from 12.3% at the beginning of the study to 3.8% at the end of the study (P < 0.0001). Antibiotic prescription among those who had rapid streptococcal antigen test (RSAT) was 40% compared with 78% among those who did not have RSAT (P < 0.0001). CONCLUSIONS: The combination of education and academic detailing is important to improve antibiotic use. PMID:28197223

  13. An Action Research Study of Intellectual Disabilities, Inappropriate Behaviors and Learned Helplessness

    ERIC Educational Resources Information Center

    Luper, Elizabeth P. S.; Lockley, Jeannie

    2008-01-01

    This study focused on a population of 36 female patients, aged 25 to 65, who were diagnosed with intellectual disabilities, all of whom had long-standing patterns of inappropriate behaviors. In an attempt to increase more appropriate behaviors in these patients, a set of standardized contingency rules were established. These rules were implemented…

  14. Use of Inappropriate and Inaccurate Conceptual Knowledge to Solve an Osmosis Problem.

    ERIC Educational Resources Information Center

    Zuckerman, June Trop

    1995-01-01

    Presents correct solutions to an osmosis problem of two high school science students who relied on inaccurate and inappropriate conceptual knowledge. Identifies characteristics of the problem solvers, salient properties of the problem that could contribute to the problem misrepresentation, and spurious correct answers. (27 references) (Author/MKR)

  15. Tyrosine kinase inhibitor-associated syndrome of inappropriate secretion of anti-diuretic hormone.

    PubMed

    Hill, Jordan; Shields, Jenna; Passero, Vida

    2016-10-01

    Hyponatremia is a common complication among cancer patients. Certain antineoplastic agents have been associated with syndrome of inappropriate secretion of anti-diuretic hormone-induced hyponatremia. The most common agents associated with secretion of anti-diuretic hormone are vinca alkaloids, platinum compounds, and alkylating agents. We report a case of secretion of anti-diuretic hormone associated with tyrosine kinase inhibitors.

  16. Use of Inappropriate and Inaccurate Conceptual Knowledge to Solve an Osmosis Problem.

    ERIC Educational Resources Information Center

    Zuckerman, June Trop

    1995-01-01

    Presents correct solutions to an osmosis problem of two high school science students who relied on inaccurate and inappropriate conceptual knowledge. Identifies characteristics of the problem solvers, salient properties of the problem that could contribute to the problem misrepresentation, and spurious correct answers. (27 references) (Author/MKR)

  17. Decreasing Inappropriate Vocalizations Using Classwide Group Contingencies and Color Wheel Procedures: A Component Analysis

    ERIC Educational Resources Information Center

    Kirk, Emily R.; Becker, Jennifer A.; Skinner, Christopher H., Fearrington, Jamie Yarbr; McCane-Bowling, Sara J.; Amburn, Christie; Luna, Elisa; Greear, Corinne

    2010-01-01

    Teacher referrals for consultation resulted in two independent teams collecting evidence that allowed for a treatment component evaluation of color wheel (CW) procedures and/or interdependent group-oriented reward (IGOR) procedures on inappropriate vocalizations in one third- and one first-grade classroom. Both studies involved the application of…

  18. Decreasing Inappropriate Vocalizations Using Classwide Group Contingencies and Color Wheel Procedures: A Component Analysis

    ERIC Educational Resources Information Center

    Kirk, Emily R.; Becker, Jennifer A.; Skinner, Christopher H., Fearrington, Jamie Yarbr; McCane-Bowling, Sara J.; Amburn, Christie; Luna, Elisa; Greear, Corinne

    2010-01-01

    Teacher referrals for consultation resulted in two independent teams collecting evidence that allowed for a treatment component evaluation of color wheel (CW) procedures and/or interdependent group-oriented reward (IGOR) procedures on inappropriate vocalizations in one third- and one first-grade classroom. Both studies involved the application of…

  19. Inappropriate gestational weight gain among teenage pregnancies: prevalence and pregnancy outcomes.

    PubMed

    Vivatkusol, Yada; Thavaramara, Thaovalai; Phaloprakarn, Chadakarn

    2017-01-01

    To study the prevalence and pregnancy outcomes of inappropriate gestational weight gain (GWG) among teenage pregnant women. A retrospective descriptive study was conducted on 2,165 teenage pregnant women who attended our antenatal clinic between January 2007 and August 2015. Adverse pregnancy outcomes, including maternal and neonatal outcomes of women with inappropriate GWG, including underweight and overweight, were studied and compared with those of women with appropriate GWG. Complete data of 1,943 women were obtained. Among these women, the mean age was 17.4±1.4 years and mean body mass index at first visit was 19.1±3.0 kg/m(2). The prevalence of inappropriate GWG was 61.7%. Underweight women were more likely to experience anemia and preterm delivery, whereas overweight women required more cesarean sections because of cephalopelvic disproportion and preeclampsia, compared to women with appropriate weight gain (all P<0.001). The rates of gestational diabetes mellitus among women who were underweight, overweight, or appropriate weight were not significantly different. More than 60% of teenage pregnancies showed inappropriate GWG. GWG had a significant impact on pregnancy outcomes.

  20. Abdominal pain and syndrome of inappropriate antidiuretic hormone secretion as clinical presentation of acute intermittent porphyria.

    PubMed

    Valle Feijóo, M L; Bermúdez Sanjurjo, J R; González Vázquez, L; Rey Martínez, M; de la Fuente Aguado, J

    2015-01-01

    Acute intermittent porphyria (AIP) is a rare condition characterized by abdominal pain and a wide range of nonspecific symptoms. We report the case of a woman with abdominal pain and syndrome of inappropriate antidiuretic hormone secretion (SIADH) as clinical presentation of AIP. The diagnosis was achieved through the etiologic study of the SIADH.

  1. The Burden of Inappropriate Emergency Department Pediatric Visits: Why Italy Needs an Urgent Reform

    PubMed Central

    Vedovetto, Alessio; Soriani, Nicola; Merlo, Emanuela; Gregori, Dario

    2014-01-01

    Objective To better understand the issue of inappropriate pediatric Emergency Department (ED) visits in Italy, including the impact of the last National Health System reform. Study Design A retrospective cohort study was conducted with five health care providers in the Veneto region (Italy) in a 2-year period (2010–2011). ED visits were considered “inappropriate” by evaluating both nursing triage and resource utilization, as addressed by the Italian Ministry of Health in 2007. Factors associated with inappropriate ED visits were identified. The cost of each visit was calculated. Principal Findings In total, 134,358 ED visits with 455,650 performed procedures were recorded in the 2-year period; of these, 76,680 (57.1 percent) were considered inappropriate ED visits. Patients likely to make inappropriate ED visits were younger, female, visiting the ED during night or holiday, when the primary care provider (PCP) is not available. Conclusion The National Health System reform aims to improve efficiency, effectiveness, and costs by opening PCP offices 24 hours a day and 7 days a week. This study highlights the need for a deep reorganization of the Italian Primary Care System not only providing a larger time availability but also treating the parents' lack of education on children's health. PMID:24495258

  2. Inappropriate shock delivery by implantable cardioverter defibrillator due to electrical interference with washing machine.

    PubMed

    Chongtham, Dhanaraj Singh; Bahl, Ajay; Kumar, Rohit Manoj; Talwar, K K

    2007-05-31

    We report a patient with hypertrophic cardiomyopathy who received an inappropriate implantable cardioverter defibrillator shock due to electrical interference from a washing machine. This electrical interference was detected as an episode of ventricular fibrillation with delivery of shock without warning symptoms.

  3. Electrocardiograhic findings resulting in inappropriate cardiac catheterization laboratory activation for ST-segment elevation myocardial infarction

    PubMed Central

    Shamim, Shariq; McCrary, Justin; Wayne, Lori; Gratton, Matthew

    2014-01-01

    Background Prompt reperfusion has been shown to improve outcomes in patients with acute ST-segment elevation myocardial infarction (STEMI) with a goal of culprit vessel patency in <90 minutes. This requires a coordinated approach between the emergency medical services (EMS), emergency department (ED) and interventional cardiology. The urgency of this process can contribute to inappropriate cardiac catheterization laboratory (CCL) activations. Objectives One of the major determinants of inappropriate activations has been misinterpretation of the electrocardiogram (ECG) in the patient with acute chest pain. Methods We report the ECG findings for all CCL activations over an 18-month period after the inception of a STEMI program at our institution. Results There were a total of 139 activations with 77 having a STEMI diagnosis confirmed and 62 activations where there was no STEMI. The inappropriate activations resulted from a combination of atypical symptoms and misinterpretation of the ECG (45% due to anterior ST-segment elevation) on patient presentation. The electrocardiographic abnormalities were particularly problematic in African-Americans with left ventricular hypertrophy. Conclusions In this single-center, prospective observational study, nearly half of the inappropriate STEMI activations were due to the misinterpretation of anterior ST-segment elevation and this finding was commonly seen in African-Americans with left ventricular hypertrophy. PMID:25009790

  4. Assertiveness for Librarians Harried by Inappropriate Lecture Hall and Classroom Assignments.

    ERIC Educational Resources Information Center

    Parker, J. Carlyle

    1990-01-01

    Describes problems encountered by public librarians when assisting students with assignments that are difficult or impossible to complete. Examples of librarians' successes in assertive, tactful communication with instructors and a list of solutions to inappropriate assignments are provided. Special emphasis is given to assignments dealing with…

  5. Inappropriate prescribing in older persons: A systematic review of medications available in different criteria.

    PubMed

    Lucchetti, Giancarlo; Lucchetti, Alessandra L G

    The present study aims to systematically review all potentially inappropriate medications for older persons included in prescribing criteria published in the last decade. A systematic review of published studies was performed. Articles describing the development of criteria for PIM Use in Older Adults published in the last decade and which provided a list of medications that should be considered inappropriate were included. The searches were conducted on Pubmed/Medline for articles published from 1st of January 2006 to 31st of December 2015. We analyzed the medications/classes reported in all criteria, most common classes and how many indications each medication made. From 778 articles, 14 articles were included in our analysis (containing 14 different criteria). Europe was responsible for 8 criteria (57.2% of total) followed by Asia (3 criteria) and USA (2 criteria). More than 85% used a Delphi method. There were 729 different medications/classes reported in all criteria. Diazepam was included in all 14 criteria followed by amitriptyline (13 criteria) and doxepin (12 criteria). We found benzodiazepines, NSAIDs, antihistamines and antipsychotics were the most common drugs reported as potentially inappropriate for older persons. The present study systematically compiled all medications included in 14 different criteria published last decade. Benzodiazepines, NSAIDs, antihistamines and antipsychotics were the most common drugs reported as potentially inappropriate for older persons. These results could help health professionals and panel experts to plan future criteria. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Students' Behaviors and Views of Paraphrasing and Inappropriate Textual Borrowing in an EFL Academic Setting

    ERIC Educational Resources Information Center

    Liao, Ming-Tzu; Tseng, Chiung-Ying

    2010-01-01

    This study examines skillful EFL writers' and less skillful writers' EFL performance and perceptions of paraphrasing and inappropriate text borrowing, the extent to which their performance matches perceptions, and the factors behind their problematic text borrowing. Ninety-five postgraduates and undergraduates in Taiwan accomplished a paraphrasing…

  7. A Comparison of Punishment and Positive Reinforcement Group Contingencies in the Modification of Inappropriate Classroom Behaviors

    ERIC Educational Resources Information Center

    Schonewille, Jack; And Others

    1978-01-01

    Measures the relative effectiveness of a short-term punishment versus a snort-term positive reinforcement contingency system for reducing the frequency of specific inappropriate behaviors of a group of senior elementary students. Students were directly involved in identifying the different types of discipline so that they might help determine the…

  8. Development of a Scale for Measuring Teachers' Attitudes toward Students' Inappropriate Behaviour

    ERIC Educational Resources Information Center

    Malak, Md. Saiful; Sharma, Umesh; Deppeler, Joanne M.

    2017-01-01

    This study aimed at developing a valid and reliable instrument for measuring attitudes of primary schoolteachers toward inappropriate student behaviour. A systematic approach was used to develop the scale. Results provide preliminary evidence that the new instrument (consisting of 13 items on a six-point Likert type scale) meets the standards for…

  9. Neurobrucellosis associated with syndrome of inappropriate antidiuretic hormone with resultant diabetes insipidus and hypothyroidism.

    PubMed

    Sturniolo, Giuseppe; Mondello, Placido; Bruno, Salvatore; Bonfatto, Orsola Elena; Frattima, Sabrina; Albanese, Antonio; Restivo, Roberta; Liberti, Giuseppe; Pasquali, Paolo; Marianelli, Cinzia

    2010-10-01

    Neurological involvement of the central nervous system in brucellosis is uncommon. We describe a rare case of meningoencephalitis due to Brucella melitensis infection, associated with the syndrome of inappropriate antidiuretic hormone secretion and leading to diabetes insipidus and hypothyroidism. Neurobrucellosis, although rare, should be considered in cases of neurological disease of unknown etiology.

  10. Improving Inappropriate Social Behavior of Autistic Students Using the LISTEN Intervention Strategy

    ERIC Educational Resources Information Center

    Al-Shammari, Zaid; Daniel, Cathy; Faulkner, Paula; Yawkey, Thomas D.

    2010-01-01

    A case study was conducted on the development of the LISTEN intervention strategy for use with autistic students to improve inappropriate social behaviors. The study was conducted in a special education classroom in an autism school in Kuwait. Examination of LISTEN Intervention Strategy applications included: duration of targeted behavior; methods…

  11. An Evaluation of Response Cost in the Treatment of Inappropriate Vocalizations Maintained by Automatic Reinforcement

    ERIC Educational Resources Information Center

    Falcomata, Terry S.; Roane, Henry S.; Hovanetz, Alyson N.; Kettering, Tracy L.; Keeney, Kris M.

    2004-01-01

    In the current study, we examined the utility of a procedure consisting of noncontingent reinforcement with and without response cost in the treatment of inappropriate vocalizations maintained by automatic reinforcement. Results are discussed in terms of examining the variables that contribute to the effectiveness of response cost as treatment for…

  12. An evaluation of response cost in the treatment of inappropriate vocalizations maintained by automatic reinforcement.

    PubMed

    Falcomata, Terry S; Roane, Henry S; Hovanetz, Alyson N; Kettering, Tracy L; Keeney, Kris M

    2004-01-01

    In the current study, we examined the utility of a procedure consisting of noncontingent reinforcement with and without response cost in the treatment of inappropriate vocalizations maintained by automatic reinforcement. Results are discussed in terms of examining the variables that contribute to the effectiveness of response cost as treatment for problem behavior maintained by automatic reinforcement.

  13. Context-Inappropriate Anger, Emotion Knowledge Deficits, and Negative Social Experiences in Preschool

    ERIC Educational Resources Information Center

    Locke, Robin L.; Miller, Alison L.; Seifer, Ronald; Heinze, Justin E.

    2015-01-01

    This study examined contextually inappropriate (CI) anger in relation to emotion recognition and situation knowledge, negative social experiences, and externalizing behavior among low-income 4-year-olds attending Head Start (n = 134). Approximately 23% showed anger when presented with positive/neutral slides and videos (valence-incongruent CI…

  14. Age-Related Differences in Judgments of Inappropriate Behavior are Related to Humor Style Preferences

    PubMed Central

    Stanley, Jennifer Tehan; Lohani, Monika; Isaacowitz, Derek M.

    2014-01-01

    Identifying social gaffes is important for maintaining relationships. Older adults are less able than young to discriminate between socially appropriate and inappropriate behavior in video clips. One open question is how these social appropriateness ratings relate to potential age differences in the perception of what is actually funny or not. In the present study, young, middle-aged, and older adults were equally able to discriminate between appropriate and inappropriate social behavior in a diverse set of clips relevant to both age groups. However, young and middle-aged adults rated the gaffe clips as funnier than control clips and young adults smiled more during the inappropriate clips than the control clips. Older adults did not show this pattern, suggesting that they did not find the inappropriate clips funny. Additionally, young adults endorsed a more aggressive humor style than middle-aged and older adults and aggressive humor style endorsement mediated age differences in social appropriateness ratings. Results are discussed in terms of possible mechanisms such as cohort differences in humor and developmental prioritization of certain humor styles, as well as the importance of investigating age differences in both abilities and preferences. PMID:25244473

  15. Performance Costs when Emotion Tunes Inappropriate Cognitive Abilities: Implications for Mental Resources and Behavior

    ERIC Educational Resources Information Center

    Storbeck, Justin

    2012-01-01

    Emotion tunes cognition, such that approach-motivated positive states promote verbal cognition, whereas withdrawal-motivated negative states promote spatial cognition (Gray, 2001). The current research examined whether self-control resources become depleted and influence subsequent behavior when emotion tunes an inappropriate cognitive tendency.…

  16. Context-Inappropriate Anger, Emotion Knowledge Deficits, and Negative Social Experiences in Preschool

    ERIC Educational Resources Information Center

    Locke, Robin L.; Miller, Alison L.; Seifer, Ronald; Heinze, Justin E.

    2015-01-01

    This study examined contextually inappropriate (CI) anger in relation to emotion recognition and situation knowledge, negative social experiences, and externalizing behavior among low-income 4-year-olds attending Head Start (n = 134). Approximately 23% showed anger when presented with positive/neutral slides and videos (valence-incongruent CI…

  17. 76 FR 61999 - Policy Statement: Inappropriate Design Approval Holder (DAH) Restrictions on the Use and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-06

    ... Federal Aviation Administration 14 CFR Part 21 Policy Statement: Inappropriate Design Approval Holder (DAH... Aviation Administration, DOT. ACTION: Proposed policy statement; notice of availability and request for public comments. SUMMARY: This document announces the availability of and request for public comments on...

  18. Unveiling common responses of Medicago truncatula to appropriate and inappropriate rust species

    PubMed Central

    Vaz Patto, Maria Carlota; Rubiales, Diego

    2014-01-01

    Little is known about the nature of effective defense mechanisms in legumes to pathogens of remotely related plant species. Some rust species are among pathogens with broad host range causing dramatic losses in various crop plants. To understand and compare the different host and nonhost resistance (NHR) responses of legume species against rusts, we characterized the reaction of the model legume Medicago truncatula to one appropriate (Uromyces striatus) and two inappropriate (U. viciae-fabae and U. lupinicolus) rusts. We found that similar pre and post-haustorial mechanisms of resistance appear to be operative in M. truncatula against appropriate and inappropriate rust fungus. The appropriate U. striatus germinated better on M. truncatula accessions then the inappropriate U. viciae-fabae and U. lupinicolus, but once germinated, germ tubes of the three rusts had a similar level of success in finding stomata and forming an appressoria over a stoma. However, responses to different inappropriate rust species also showed some specificity, suggesting a combination of non-specific and specific responses underlying this legume NHR to rust fungi. Further genetic and expression analysis studies will contribute to the development of the necessary molecular tools to use the present information on host and NHR mechanisms to breed for broad-spectrum resistance to rust in legume species. PMID:25426128

  19. The Effects of a Token Economy System on the Inappropriate Verbalizations of Emotional Support Students.

    ERIC Educational Resources Information Center

    Stover, Karen

    This paper reports on the application of a token economy approach to increase on-task behavior and decrease inappropriate "call-outs" of nine seventh and eighth grade Caucasian male students in a self-containted emotional support classroom. The program included a behavioral contract, token economy "bucks" kept in a classroom bank, and a list of 12…

  20. Reducing the Impact of Inappropriate Items on Reviewable Computerized Adaptive Testing

    ERIC Educational Resources Information Center

    Yen, Yung-Chin; Ho, Rong-Guey; Liao, Wen-Wei; Chen, Li-Ju

    2012-01-01

    In a test, the testing score would be closer to examinee's actual ability when careless mistakes were corrected. In CAT, however, changing the answer of one item in CAT might cause the following items no longer appropriate for estimating the examinee's ability. These inappropriate items in a reviewable CAT might in turn introduce bias in ability…

  1. Using an Electronic Highlighter to Eliminate the Negative Effects of Pre-Existing, Inappropriate Highlighting

    ERIC Educational Resources Information Center

    Gier, Vicki; Kreiner, David; Hudnell, Jason; Montoya, Jodi; Herring, Daniel

    2011-01-01

    The purpose of the present experiment was to determine whether using an active learning technique, electronic highlighting, can eliminate the negative effects of pre-existing, poor highlighting on reading comprehension. Participants read passages containing no highlighting, appropriate highlighting, or inappropriate highlighting. We hypothesized…

  2. Effects of Individualized Video Feedback Combined with Group Parent Training on Inappropriate Maternal Behavior

    ERIC Educational Resources Information Center

    Phaneuf, Leah; McIntyre, Laura Lee

    2007-01-01

    The effects of adding individualized video feedback (IVF) to Webster-Stratton's (2000, 2001) group-based parent training program (GT) were evaluated using a multiple baseline design across four mother-child dyads. During all phases of the study, inappropriate maternal behavior was recorded from videotapes of playtime with their preschoolers with…

  3. Inappropriate behaviors and hypersexuality in individuals with dementia: An overview of a neglected issue.

    PubMed

    Torrisi, Michele; Cacciola, Alberto; Marra, Angela; De Luca, Rosaria; Bramanti, Placido; Calabrò, Rocco Salvatore

    2017-06-01

    Behavioral and psychological symptoms of dementia are very common in patients affected by dementia, and are associated with high rates of institutionalization. Behavioral and psychological symptoms of dementia consist of aggressive behavior, delusions, hallucinations, depression, apathy, wandering, stereotyped and inappropriate sexual behavior. Interestingly, the latter has been reported to be relatively uncommon, but causing immense distress to patients and their caregivers. The genesis of inappropriate behavior is considered a combination of neurological, psychological and social factors. Although assessment is mainly carried out by clinical observation and interviews with caregivers, the most appropriate management of behavioral and psychological symptoms of dementia, including hypersexuality, is a combination of pharmacological and non-pharmacological interventions, according to specific symptoms, degree of cognitive dysfunction and subtype of dementia. The present narrative review will mainly focus on aggressiveness, disinhibition, aberrant motor, and sexually inappropriate behavior diagnostic work-up and treatment, in an attempt to provide both the patients and their caregivers with useful information to better manage these symptoms and improve their quality of life. Space is particularly dedicated to inappropriate sexual behavior, which is still considered a neglected issue. Geriatr Gerontol Int 2017; 17: 865-874. © 2016 Japan Geriatrics Society.

  4. Factors Underlying Students' Appropriate or Inappropriate Use of Scholarly Sources in Academic Writing, and Instructors' Responses

    ERIC Educational Resources Information Center

    Sivell, John

    2013-01-01

    At first glance it is surprising that--in remarkable contrast to grammatical or lexical failings which, while certainly not viewed as insignificant, are rarely greeted with outright anger or hostility--inappropriate documentation of scholarly sources so frequently provokes very harsh penalties. Rather than the constructively pedagogical approach…

  5. Chemosensitization as a Means to Augment Commercial Antifungal Agents

    PubMed Central

    Campbell, Bruce C.; Chan, Kathleen L.; Kim, Jong H.

    2012-01-01

    Antimycotic chemosensitization and its mode of action are of growing interest. Currently, use of antifungal agents in agriculture and medicine has a number of obstacles. Foremost of these is development of resistance or cross-resistance to one or more antifungal agents. The generally high expense and negative impact, or side effects, associated with antifungal agents are two further issues of concern. Collectively, these problems are exacerbated by efforts to control resistant strains, which can evolve into a treadmill of higher dosages for longer periods. This cycle in turn, inflates cost of treatment, dramatically. A further problem is stagnation in development of new and effective antifungal agents, especially for treatment of human mycoses. Efforts to overcome some of these issues have involved using combinations of available antimycotics (e.g., combination therapy for invasive mycoses). However, this approach has had inconsistent success and is often associated with a marked increase in negative side effects. Chemosensitization by natural compounds to increase effectiveness of commercial antimycotics is a somewhat new approach to dealing with the aforementioned problems. The potential for safe natural products to improve antifungal activity has been observed for over three decades. Chemosensitizing agents possess antifungal activity, but at insufficient levels to serve as antimycotics, alone. Their main function is to disrupt fungal stress response, destabilize the structural integrity of cellular and vacuolar membranes or stimulate production of reactive oxygen species, augmenting oxidative stress and apoptosis. Use of safe chemosensitizing agents has potential benefit to both agriculture and medicine. When co-applied with a commercial antifungal agent, an additive or synergistic interaction may occur, augmenting antifungal efficacy. This augmentation, in turn, lowers effective dosages, costs, negative side effects and, in some cases, countermands resistance

  6. Antileishmanial, antimicrobial and antifungal activities of some new aryl azomethines.

    PubMed

    Al-Kahraman, Yasser M S A; Madkour, Hassan M F; Ali, Dildar; Yasinzai, Masoom

    2010-01-28

    A series of eighteen azomethines has been synthesized by the reaction of appropriate primary aromatic amines with aryl and/or heteroaryl carboxaldehydes. The synthesized azomethines have been evaluated for their in vitro antileishmanial, antibacterial and antifungal activities. The results revealed some antifungal activity of most of the synthesized compounds, whereas the antileishmaniasis activity results highlighted that all synthesized azomethines inhibited parasite growth and most of them showed highly potent action towards Leishmania major promastigotes. No remarkable bactericidal activities were observed.

  7. Amphiphilic Tobramycin Analogues as Antibacterial and Antifungal Agents

    PubMed Central

    Shrestha, Sanjib K.; Fosso, Marina Y.; Green, Keith D.

    2015-01-01

    In this study, we investigated the in vitro antifungal activities, cytotoxicities, and membrane-disruptive actions of amphiphilic tobramycin (TOB) analogues. The antifungal activities were established by determination of MIC values and in time-kill studies. Cytotoxicity was evaluated in mammalian cell lines. The fungal membrane-disruptive action of these analogues was studied by using the membrane-impermeable dye propidium iodide. TOB analogues bearing a linear alkyl chain at their 6″-position in a thioether linkage exhibited chain length-dependent antifungal activities. Analogues with C12 and C14 chains showed promising antifungal activities against tested fungal strains, with MIC values ranging from 1.95 to 62.5 mg/liter and 1.95 to 7.8 mg/liter, respectively. However, C4, C6, and C8 TOB analogues and TOB itself exhibited little to no antifungal activity. Fifty percent inhibitory concentrations (IC50s) for the most potent TOB analogues (C12 and C14) against A549 and Beas 2B cells were 4- to 64-fold and 32- to 64-fold higher, respectively, than their antifungal MIC values against various fungi. Unlike conventional aminoglycoside antibiotics, TOB analogues with alkyl chain lengths of C12 and C14 appear to inhibit fungi by inducing apoptosis and disrupting the fungal membrane as a novel mechanism of action. Amphiphilic TOB analogues showed broad-spectrum antifungal activities with minimal mammalian cell cytotoxicity. This study provides novel lead compounds for the development of antifungal drugs. PMID:26033722

  8. In Vitro Antifungal Susceptibilities of Five Species of Sporothrix▿

    PubMed Central

    Marimon, Rita; Serena, Carolina; Gené, Josepa; Cano, Josep; Guarro, Josep

    2008-01-01

    Ninety-two isolates belonging to five species of the Sporothrix schenckii complex were tested in vitro against 12 antifungal agents, using a reference microdilution method. There were significant differences among the species; Sporothrix brasiliensis was the species that showed the best response to antifungals, and S. mexicana had the worst response. In general, terbinafine was the most active drug, followed by ketoconazole and posaconazole. PMID:18039919

  9. Antibacterial and antifungal activity of Indonesian ethnomedical plants.

    PubMed

    Goun, E; Cunningham, G; Chu, D; Nguyen, C; Miles, D

    2003-09-01

    Methylene chloride and methanol extracts of 20 Indonesian plants with ethnomedical uses have been assessed for in vitro antibacterial and antifungal properties by disk diffusion method. Extracts of the six plants: Terminalia catappa, Swietenia mahagoni Jacq., Phyllanthus acuminatus, Ipomoea spp., Tylophora asthmatica and Hyptis brevipes demonstrated high activity in this bioassay system. These findings should stimulate the search for novel, natural product such as new antibacterial and antifungal agents.

  10. Regional-Level Correlations in Inappropriate Imaging Rates for Prostate and Breast Cancers

    PubMed Central

    Makarov, Danil V.; Soulos, Pamela R.; Gold, Heather T.; Yu, James B.; Sen, Sounok; Ross, Joseph S.; Gross, Cary P.

    2015-01-01

    IMPORTANCE The association between regional norms of clinical practice and appropriateness of care is incompletely understood. Understanding regional patterns of care across diseases might optimize implementation of programs like Choosing Wisely, an ongoing campaign to decrease wasteful medical expenditures. OBJECTIVE To determine whether regional rates of inappropriate prostate and breast cancer imaging were associated. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study using the the Surveillance, Epidemiology, and End Results–Medicare linked database. We identified patients diagnosed from 2004 to 2007 with low-risk prostate (clinical stage T1c/T2a; Gleason score, ≤6; and prostate-specific antigen level, <10 ng/mL) or breast cancer (in situ, stage I, or stage II disease), based on Choosing Wisely definitions. MAIN OUTCOMES AND MEASURES In a hospital referral region (HRR)-level analysis, our dependent variable was HRR-level imaging rate among patients with low-risk prostate cancer. Our independent variable was HRR-level imaging rate among patients with low-risk breast cancer. In a subsequent patient-level analysis we used multivariable logistic regression to model prostate cancer imaging as a function of regional breast cancer imaging and vice versa. RESULTS We identified 9219 men with prostate cancer and 30 398 women with breast cancer residing in 84 HRRs. We found high rates of inappropriate imaging for both prostate cancer (44.4%) and breast cancer (41.8%). In the first, second, third, and fourth quartiles of breast cancer imaging, inappropriate prostate cancer imaging was 34.2%, 44.6%, 41.1%, and 56.4%, respectively. In the first, second, third, and fourth quartiles of prostate cancer imaging, inappropriate breast cancer imaging was 38.1%, 38.4%, 43.8%, and 45.7%, respectively. At the HRR level, inappropriate prostate cancer imaging rates were associated with inappropriate breast cancer imaging rates (ρ = 0.35; P < .01). At the patient level, a

  11. Isolation of Bacillus amyloliquefaciens Strains with Antifungal Activities from Meju

    PubMed Central

    Lee, Hwang A; Kim, Jeong Hwan

    2012-01-01

    Bacilli with fibrinolytic activities were isolated from traditionally-prepared Meju and some of these strains showed strong antifungal activities. One isolate, MJ1-4, showed the strongest antifungal activity. MJ1-4 and other isolates were identified as B. amyloliquefaciens strains by recA gene sequencing and RAPD-PCR results. B. amyloliqufaciens MJ1-4 efficiently inhibited an Aspergillus spp.-producing aflatoxin B1 (AFB1) and a Penicillium spp.-producing ochratoxin (OTA) in addition to other fungi. Antifungal activity of B. amyloliquefaciens MJ1-4 culture reached its maximum (40 AU/mg protein) in LB or TSB medium around 48 hr at 37°C. Antifungal activity of the concentrated culture supernatant was not decreased significantly by protease treatments, implying that the antifungal substance might not be a simple peptide or protein. Considering its antifungal and fibrinolytic activities together, B. amyloliquefaciens MJ1-4 can serve as a starter for fermented soyfoods such as Cheonggukjang and Doenjang. PMID:24471064

  12. Isolation of Bacillus amyloliquefaciens Strains with Antifungal Activities from Meju.

    PubMed

    Lee, Hwang A; Kim, Jeong Hwan

    2012-03-01

    Bacilli with fibrinolytic activities were isolated from traditionally-prepared Meju and some of these strains showed strong antifungal activities. One isolate, MJ1-4, showed the strongest antifungal activity. MJ1-4 and other isolates were identified as B. amyloliquefaciens strains by recA gene sequencing and RAPD-PCR results. B. amyloliqufaciens MJ1-4 efficiently inhibited an Aspergillus spp.-producing aflatoxin B1 (AFB1) and a Penicillium spp.-producing ochratoxin (OTA) in addition to other fungi. Antifungal activity of B. amyloliquefaciens MJ1-4 culture reached its maximum (40 AU/mg protein) in LB or TSB medium around 48 hr at 37°C. Antifungal activity of the concentrated culture supernatant was not decreased significantly by protease treatments, implying that the antifungal substance might not be a simple peptide or protein. Considering its antifungal and fibrinolytic activities together, B. amyloliquefaciens MJ1-4 can serve as a starter for fermented soyfoods such as Cheonggukjang and Doenjang.

  13. An antifungal peptide from Phaseolus vulgaris cv. brown kidney bean.

    PubMed

    Chan, Yau Sang; Wong, Jack Ho; Fang, Evandro Fei; Pan, Wen Liang; Ng, Tzi Bun

    2012-04-01

    A 5.4-kDa antifungal peptide, with an N-terminal sequence highly homologous to defensins and inhibitory activity against Mycosphaerella arachidicola (IC(50)= 3 μM), Setospaeria turcica and Bipolaris maydis, was isolated from the seeds of Phaseolus vulgaris cv. brown kidney bean. The peptide was purified by employing a protocol that entailed adsorption on Affi-gel blue gel and Mono S and finally gel filtration on Superdex 75. The antifungal activity of the peptide against M. arachidicola was stable in the pH range 3-12 and in the temperature range 0°C to 80°C. There was a slight reduction of the antifungal activity at pH 2 and 13, and the activity was indiscernible at pH 0, 1, and 14. The activity at 90°C and 100°C was slightly diminished. Deposition of Congo red at the hyphal tips of M. arachidicola was induced by the peptide indicating inhibition of hyphal growth. The lack of antiproliferative activity of brown kidney bean antifungal peptide toward tumor cells, in contrast to the presence of such activity of other antifungal peptides, indicates that different domains are responsible for the antifungal and antiproliferative activities.

  14. Antifungal effect and mechanism of garlic oil on Penicillium funiculosum.

    PubMed

    Li, Wen-Ru; Shi, Qing-Shan; Liang, Qing; Huang, Xiao-Mo; Chen, Yi-Ben

    2014-10-01

    Garlic oil is a kind of fungicide, but little is known about its antifungal effects and mechanism. In this study, the chemical constituents, antifungal activity, and effects of garlic oil were studied with Penicillium funiculosum as a model strain. Results showed that the minimum fungicidal concentrations (MFCs, v/v) were 0.125 and 0.0313 % in agar medium and broth medium, respectively, suggesting that the garlic oil had a strong antifungal activity. The main ingredients of garlic oil were identified as sulfides, mainly including disulfides (36 %), trisulfides (32 %) and monosulfides (29 %) by gas chromatograph-mass spectrometer (GC/MS), which were estimated as the dominant antifungal factors. The observation results by transmission electron microscope (TEM) and scanning electron microscope (SEM) indicated that garlic oil could firstly penetrate into hyphae cells and even their organelles, and then destroy the cellular structure, finally leading to the leakage of both cytoplasm and macromolecules. Further proteomic analysis displayed garlic oil was able to induce a stimulated or weakened expression of some key proteins for physiological metabolism. Therefore, our study proved that garlic oil can work multiple sites of the hyphae of P. funiculosum to cause their death. The high antifungal effects of garlic oil makes it a broad application prospect in antifungal industries.

  15. Magnitude of potentially inappropriate prescribing in Germany among older patients with generalized anxiety disorder

    PubMed Central

    Berger, Ariel; Mychaskiw, Marko; Dukes, Ellen; Edelsberg, John; Oster, Gerry

    2009-01-01

    Background Several medications commonly used to treat generalized anxiety disorder (GAD) have been designated "potentially inappropriate" for use in patients aged ≥65 years because their risks may outweigh their potential benefits. The actual extent of use of these agents in clinical practice is unknown, however. Methods Using a database with information from encounters with general practitioners (GP) in Germany, we identified all patients, aged ≥65 years, with any GP office visits or dispensed prescriptions with a diagnosis of GAD (ICD-10 diagnosis code F41.1) between 10/1/2003 and 9/30/2004 ("GAD patients"). Among GAD-related medications (including benzodiazepines, tricyclic antidepressants [TCAs], selective serotonin reuptake inhibitors, venlafaxine, hydroxyzine, buspirone, pregabalin, and trifluoperazine), long-acting benzodiazepines, selected short-acting benzodiazepines at relatively high dosages, selected TCAs, and hydroxyzine were designated "potentially inappropriate" for use in patients aged ≥ 65 years, based on published criteria. Results A total of 975 elderly patients with GAD were identified. Mean age was 75 years, and 72% were women; 29% had diagnoses of comorbid depression. Forty percent of study subjects received potentially inappropriate agents – most commonly, bromazepam (10% of all subjects), diazepam (9%), doxepin (7%), amitriptyline (5%), and lorazepam (5%). Twenty-three percent of study subjects received long-acting benzodiazepines, 10% received short-acting benzodiazepines at relatively high doses, and 12% received TCAs designated as potentially inappropriate. Conclusion GPs in Germany often prescribe medications that have been designated as potentially inappropriate to their elderly patients with GAD – especially those with comorbid depressive disorders. Further research is needed to ascertain whether there are specific subgoups of elderly patients with GAD for whom the benefits of these medications outweigh their risks. PMID

  16. A new algorithm to reduce inappropriate therapy in the S-ICD system.

    PubMed

    Brisben, Amy J; Burke, Martin C; Knight, Bradley P; Hahn, Stephen J; Herrmann, Keith L; Allavatam, Venugopal; Mahajan, Deepa; Sanghera, Rick; Gold, Michael R

    2015-04-01

    The subcutaneous ICD system (S-ICD) has been shown to be a safe and effective treatment for patients at risk for sudden cardiac death. This device reliably detects ventricular tachyarrhythmias with a low incidence of inappropriate shocks for supraventricular arrhythmias. However, T-wave oversensing (TWOS) is more common with the S-ICD compared with transvenous systems. We developed a novel discrimination algorithm to reduce TWOS without compromising tachyarrhythmia discrimination. The algorithm was developed using a database of recorded episodes, including 244 appropriate therapies for ventricular arrhythmias and 133 episodes with an inappropriate detection due to TWOS, and using a computer model that simulates the S-ICD system. An independent set of data of 161 TWOS episodes, 137 ventricular and 328 supraventricular episodes, was used to validate the algorithm on actual device hardware. The S-ICD performance with the new algorithm was compared with the S-ICD without the new algorithm. Development results showed a decrease in inappropriate charge due to TWOS by 30.7 ± 18%. All ventricular arrhythmias were appropriately detected and the time to appropriate charge initiation was not increased. System validation showed that the new algorithm avoided an inappropriate charge due to TWOS by 39.8 ± 11.4%. No decrease in ventricular arrhythmia sensitivity and no significant change in supraventricular specificity were observed. A new algorithm that uses correlation of the existing complex to previous complexes reduced TWOS episodes by approximately 40%. The algorithm has potential for a clinically meaningful decrease in inappropriate shocks. © 2015 Wiley Periodicals, Inc.

  17. Utilization of frozen plasma in Ontario: a provincewide audit reveals a high rate of inappropriate transfusions.

    PubMed

    Tinmouth, Alan; Thompson, Troy; Arnold, Donald M; Callum, Jeannie L; Gagliardi, Kate; Lauzon, Deborah; Owens, Wendy; Pinkerton, Peter

    2013-10-01

    Frozen plasma (FP) is frequently transfused inappropriately, an intervention that results in risk without benefit for the patient. To better understand current utilization practices in our region, we undertook a provincewide prospective audit to evaluate the clinical indications and appropriateness of FP transfusion. All hospitals in the Canadian province of Ontario with transfusion medicine services were invited to participate in a 5-day audit of FP utilization. FP dose, indication, and clinical patient data were collected for each transfusion request. Indications for FP transfusions were independently adjudicated as appropriate, inappropriate, or indeterminate based on predefined criteria. Seventy-six (49%) of 155 invited hospitals participated in the audit, which included 573 requests for 2012 units of FP. A total of 559 transfusions (1909 units) were administered. Of 573 requests, 164 (28.6%) were deemed inappropriate most often because: 1) they were administered to patients with an international normalized ratio below 1.5 or 2) they were administered in absence of bleeding or emergency surgery. The most frequent indications for FP transfusions were before surgery and warfarin reversal. Overall, patients admitted to the clinical areas of surgery, internal medicine, and the emergency department represented the largest users of FP, but this varied by hospital type (community vs. academic). The most frequently requested doses of FP were 2 and 4 units. This point-prevalence hospital audit revealed that transfusion of FP is frequently inappropriate. Focusing on reducing the two most common reasons for inappropriate FP transfusions could lead to a significant improvement in FP utilization. © 2013 American Association of Blood Banks.

  18. [Reasons for inappropriate prescribing of antibiotics in a high-complexity pediatric hospital].

    PubMed

    Ruvinsky, Silvina; Mónaco, Andrea; Pérez, Guadalupe; Taicz, Moira; Inda, Laura; Kijko, Ivana; Constanzo, Patricia; Bologna, Rosa

    2011-12-01

    Determine the reasons for inappropriate prescription of antibiotics and identify opportunities to improve prescription of these drugs in pediatric patients hospitalized in intermediate and intensive care units. A prospective, descriptive longitudinal study was conducted of pediatric patients in intermediate and intensive care units who received parenteral administration of antibiotics, with the exception of newborns, burn unit patients, and surgical prophylaxis patients. A univariate analysis and multiple logistic regression were performed. A total of 376 patients with a median of age of 50 months were studied (interquartile range [IQR] 14.5-127 months). Out of the total patients studied, 75% had one or more underlying conditions. A total of 40.6% of these patients had an oncologic pathology and 33.5% had neurological conditions. The remaining 25.9% had other underlying conditions. Antibiotic treatment was inappropriate in 35.6% of the patients studied (N = 134). In 73 (54.4%) of the 134 cases, inappropriate use was due to the type of antibiotic prescribed, the dose administered, or the treatment period. The 61 (45.5%) remaining cases did not require antibiotic treatment. In the multivariate analysis, the risk factors for inappropriate use of antibiotics were: administration of ceftriaxone OR 2 (95% CI, 1.3-3.7; P = 0.02); acute lower respiratory tract infection OR 1.8 (95% CI, 1.1-3.3; P < 0.04); onset of fever of unknown origin in hospital inpatients OR 5.55 (95% CI, 2.5-12; P < 0.0001); and febrile neutropenia OR 0.3 (95% CI, 0.1-0.7; P = 0.009). Inappropriate use of antibiotics was less common in the clinical conditions that were well-characterized. Prescribing practices that could be improved were identified through the preparation and circulation of guidelines for antibiotic use in hospital inpatients.

  19. Inappropriate asthma therapy—a tale of two countries: a parallel population-based cohort study

    PubMed Central

    Belhassen, Manon; Nibber, Anjan; Van Ganse, Eric; Ryan, Dermot; Langlois, Carole; Appiagyei, Francis; Skinner, Derek; Laforest, Laurent; Soriano, Joan B; Price, David

    2016-01-01

    Against recurrent controversies around the safety of short- and long-acting β2-agonists (SABA and LABA), and the National Review of Asthma Deaths inquiry in the United Kingdom, we investigated the prevalence of inappropriate therapy in asthma. Our study aimed to determine the prevalence of inappropriate use of asthma therapy in the United Kingdom and in France. Two interval, parallel, population-based cohorts (2007 and 2013) were developed in each country by using the UK OPCRD and the French EGB databases. Patients aged 6–40 years were studied over the 12-month period following inclusion, regarding overuse (⩾12 units) of SABA, use of LABA without inhaled corticosteroids (ICS) and ⩾2-fold higher use of LABA compared with that of ICS. Overall, 39,743 UK and 4,910 French patients were included in 2007, and 14,036 and 5,657 patients, respectively, were included in 2013. UK adults were more frequently exposed to SABA overuse compared with those in France in both periods, with an upward trend in the United Kingdom (P<0.05). In 2013, LABA use without ICS occurred in 0.1% and 1.5% of United Kingdom and French adults, respectively. Unbalanced use of LABA relative to ICS became marginal in both countries in 2013. Inappropriate use of therapy was less marked, but present, in children. Inappropriate therapy remains a common issue in asthma. Based on our figures, it may be estimated that >210,000 British and >190,000 French asthmatics aged 6–40 years were inappropriately treated in 2013. PMID:27735927

  20. The Impact of WHO Essential Medicines Policies on Inappropriate Use of Antibiotics.

    PubMed

    Holloway, Kathleen Anne; Rosella, Laura; Henry, David

    2016-01-01

    Inappropriate overuse of antibiotics contributes to antimicrobial resistance (AMR), yet policy implementation to reduce inappropriate antibiotic use is poor in low and middle-income countries. To determine whether public sector inappropriate antibiotic use is lower in countries reporting implementation of selected essential medicines policies. Results from independently conducted antibiotic use surveys in countries that did, and did not report implementation of policies to reduce inappropriate antibiotic prescribing, were compared. Survey data on four validated indicators of inappropriate antibiotic use and 16 self-reported policy implementation variables from WHO databases were extracted. The average difference for indicators between countries reporting versus not reporting implementation of specific policies was calculated. For 16 selected policies we regressed the four antibiotic use variables on the numbers of policies the countries reported implementing. Data were available for 55 countries. Of 16 policies studied, four (having a national Ministry of Health unit on promoting rational use of medicines, a national drug information centre and provincial and hospital drugs and therapeutics committees) were associated with statistically significant reductions in antibiotic use of ≥20% in upper respiratory infection (URTI). A national strategy to contain antibiotic resistance was associated with a 30% reduction in use of antibiotics in acute diarrheal illness. Policies seemed to be associated with greater effects in antibiotic use for URTI and diarrhea compared with antibiotic use in all patients. There were negative correlations between the numbers of policies reported implemented and the percentage of acute diarrhoea cases treated with antibiotics (r = -0.484, p = 0.007) and the percentage of URTI cases treated with antibiotics (r = -0.472, p = 0.005). Major study limitations were the reliance on self-reported policy implementation data and antibiotic use data

  1. Inappropriate prescribing of preventative medication in patients with life-limiting illness: a systematic review.

    PubMed

    Todd, Adam; Husband, Andy; Andrew, Inga; Pearson, Sallie-Anne; Lindsey, Laura; Holmes, Holly

    2017-06-01

    To systematically review the literature to examine the methods used to identify inappropriate prescribing of preventative medication in patients with life-limiting illness and to detail the nature of medications prescribed. A systematic literature search of 4 databases was undertaken (MEDLINE, EMBASE, CINAHL, PsycINFO) from inception to April 2015 to identify peer-reviewed, observational studies assessing inappropriate prescribing of preventative medication in patients with life-limiting illness. Inclusion criteria were: participants had a life-limiting illness; prescribed/dispensed/using preventative medication; medication appropriateness assessed as a specific study aim or outcome. We found 19 studies meeting our eligibility criteria. The methods used to assess medication appropriateness included criteria developed for the elderly such as the Beers Criteria, and Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) criteria, Delphi consensus and expert clinical opinion. Lipid-regulating drugs (12 studies), antihypertensive (11 studies) and antidiabetic medications (9 studies) were the most common classes of inappropriate medication identified. Patients with life-limiting illnesses are prescribed preventative medications considered inappropriate in the context of diminished life expectancy. The way in which preventative medication appropriateness is assessed in patients with life-limiting illness varies considerably-with some methodologies utilising criteria previously developed for elderly populations. Given this lack of standardisation, improving the prescribing in this context requires an approach that is specifically designed and validated for populations with life-limiting illness. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  2. Efficacy and Limitations of Tachycardia Detection Interval Guided Reprogramming for Reduction of Inappropriate Shock in Implantable Cardioverter-Defibrillator Patients.

    PubMed

    Fujiishi, Tamami; Niwano, Shinichi; Murakami, Masami; Nakamura, Hironori; Igarashi, Tazuru; Ishizue, Naruya; Oikawa, Jun; Kishihara, Jun; Fukaya, Hidehira; Niwano, Hiroe; Ako, Junya

    2016-05-25

    The avoidance of inappropriate shock therapy is an important clinical issue in implantable cardioverter-defibrillator (ICD) patients. We retrospectively analyzed therapeutic events in ICD patients, and the effect of tachycardia detection interval (TDI) and tachycardia cycle length (TCL) guided reprograming on the reduction of inappropriate ICD therapy. The clinical determinants of after reprogramming were also evaluated.A total of 254 consecutive ICD patients were included in the study, and the incidence of antitachycardia therapy was evaluated during the follow-up period of 27.3 ± 18.7 months. When inappropriate antitachycardia therapy appeared, TDI was reprogrammed not to exceed the detected TCL and the patients continued to be followed-up. Various clinical parameters were compared between patients with and without inappropriate ICD therapy. During the initial follow-up period of 18.6 ± 15.6 months, ICD therapy occurred in 127/254 patients (50%) including inappropriate antitachycardia pacing (ATP) (12.9%) and shock (44.35%). Determinants of initial inappropriate therapy were dilated cardiomyopathy (DCM), history of therapeutic hypothermia, and QRS duration. Of the 61 patients with inappropriate therapy, 24 received TCL guided reprogramming. During the additional observation period of 17.0 ± 16.8 months, inappropriate therapy recurred in 5/24 patients (2 ATP, 3 shocks). The determinant of these inappropriate therapy events after reprogramming was the presence of supraventricular tachycardia.By applying simple TCL and TDI guided reprogramming, inappropriate therapy was reduced by 79%. The determinant of inappropriate therapy after reprogramming was the presence of supraventricular tachycardia.

  3. Nationwide Study of Candidemia, Antifungal Use, and Antifungal Drug Resistance in Iceland, 2000 to 2011

    PubMed Central

    Asmundsdottir, Lena Ros; Erlendsdottir, Helga

    2013-01-01

    Candidemia is often a life-threatening infection, with highly variable incidence among countries. We conducted a nationwide study of candidemia in Iceland from 2000 to 2011, in order to determine recent trends in incidence rates, fungal species distribution, antifungal susceptibility patterns, and concurrent antifungal consumption. A total of 208 infection episodes in 199 patients were identified. The average incidence during the 12 years was 5.7 cases/100,000 population/year, which was significantly higher than that from 1990 to 1999 (4.3/100,000/year; P = 0.02). A significant reduction in the use of blood cultures was noted in the last 3 years of the study, coinciding with the economic crisis in the country (P < 0.001). Age-specific incidence rates were highest among patients at the extremes of age, 20.7/100,000 for <1 year of age and 18.1/100,000 for >60 years, and varied by gender. Age-specific incidence among males >80 years old was 28.6/100,000/year, and it was 8.3/100,000/year for females in this age group (P = 0.028). The 30-day survival rate among adult patients remained unchanged compared to that from 1990 to 1999 (70.4% versus 69.5%, P = 0.97). Candida albicans was the predominant species (56%), followed by C. glabrata (16%) and C. tropicalis (13%). The species distribution remained stable compared to that from previous decades. Fluconazole use increased 2.4-fold from 2000 to 2011, with no increase in resistance. In summary, the incidence of candidemia in Iceland has continued to increase but may have reached a steady state, and no increase in antifungal drug resistance has been noted. Decreased use of blood cultures toward the end of the study may have influenced detection rates. PMID:23269738

  4. Brief Report: Reduction of Inappropriate Vocalizations for a Child with Autism Using a Self-Management Treatment Program.

    ERIC Educational Resources Information Center

    Mancina, Catherine; Tankersley, Melody; Kamps, Debra; Kravits, Tammy; Parrett, Jean

    2000-01-01

    A study examined the effects of a self-management program used to reduce high rates of inappropriate vocalizations (e.g., humming, tongue clucking, perseveration, and echolalic words/phases) in a 12-year-old girl with autism. When self-management was applied to inappropriate vocalizations during leisure, prevocational, and reading tasks, the…

  5. The Nature of All "Inappropriate Referrals" Made to a Countywide Physical Activity Referral Scheme: Implications for Practice

    ERIC Educational Resources Information Center

    Johnston, Lynne Halley; Warwick, Jane; De Ste Croix, Mark; Crone, Diane; Sldford, Adrienne

    2005-01-01

    Objective: The aim of this study was to evaluate the impact of a centralised referral mechanism (CRM) upon the number and type of "inappropriate referrals" made to a countywide physical activity referral scheme. Design: Case study. Method: Phase 1: Hierarchical Content Analysis of 458 "inappropriate referrals" made to a countywide scheme over a…

  6. Potentially inappropriate drug use in older people: a nationwide comparison of different explicit criteria for population-based estimates

    PubMed Central

    Morin, Lucas; Fastbom, Johan; Laroche, Marie-Laure; Johnell, Kristina

    2015-01-01

    Aims The aim was to investigate the prevalence of potentially inappropriate medication use among older people in Sweden according to five different published sets of explicit criteria from Europe and the US. Methods This was a nationwide cross-sectional, register-based study across the whole of Sweden in 2008. All individuals aged 65 years and older were included (n = 1 346 709, both community-dwelling and institutionalized persons). We applied all drug-specific criteria included in the 2012 Beers Criteria, the Laroche’s list, the PRISCUS list, the NORGEP criteria and the Swedish National Board of Health and Welfare criteria. The main outcome was the potentially inappropriate drug use according to each set of criteria, separately and combined. Multivariate logistic regression models were used to identify individual factors associated with the use of potentially inappropriate drugs. Results The prevalence of potentially inappropriate medication use varied between the explicit criteria from 16% (NORGEP criteria) to 24% (2012 Beers criteria). Overall, 38% of the older people were exposed to potentially inappropriate drug use by at least one of the five sets of criteria. While controlling for other possible covariates, female gender, institutionalization and polypharmacy were systematically associated with inappropriate drug use, regardless of the set of explicit criteria we considered. Conclusion Although explicit criteria for inappropriate drug use among older people have been reported to be quite different in their content, they provide similar measures of the prevalence of potentially inappropriate drug use at the population level. PMID:25702921

  7. Brief Report: Reduction of Inappropriate Vocalizations for a Child with Autism Using a Self-Management Treatment Program.

    ERIC Educational Resources Information Center

    Mancina, Catherine; Tankersley, Melody; Kamps, Debra; Kravits, Tammy; Parrett, Jean

    2000-01-01

    A study examined the effects of a self-management program used to reduce high rates of inappropriate vocalizations (e.g., humming, tongue clucking, perseveration, and echolalic words/phases) in a 12-year-old girl with autism. When self-management was applied to inappropriate vocalizations during leisure, prevocational, and reading tasks, the…

  8. The Nature of All "Inappropriate Referrals" Made to a Countywide Physical Activity Referral Scheme: Implications for Practice

    ERIC Educational Resources Information Center

    Johnston, Lynne Halley; Warwick, Jane; De Ste Croix, Mark; Crone, Diane; Sldford, Adrienne

    2005-01-01

    Objective: The aim of this study was to evaluate the impact of a centralised referral mechanism (CRM) upon the number and type of "inappropriate referrals" made to a countywide physical activity referral scheme. Design: Case study. Method: Phase 1: Hierarchical Content Analysis of 458 "inappropriate referrals" made to a countywide scheme over a…

  9. Update on antifungal therapy with terbinafine.

    PubMed

    Gianni, C

    2010-06-01

    Terbinafine, a synthetic antifungal of allylamine class, has fungicidal activity against dermatophytes, moulds and certain dimorphic fungi and fungistatic activity against Candida albicans. Following oral administration the terbinafine is absorbed rapidly (>70%) and reaches within 2 hours the peak plasma concentration. The drug is highly lipophilic and keratophilic and is highly bound to plasma protein (>90%) with a bioavailability of 70% to 80%. The drug is rapidly delivered and it is present in the stratum corneum, sebum, nails and hair for months after stopping the medication. The drug has been proven to be the choice treatment in the therapy of onychomycosis as it is very effective, well tolerated and has a relatively low potential for drug interactions. The pharmacologic and pharmacokinetic properties of terbinafine give strong support to the possibility that the pulse therapy may be equally effective in onychomycoses, possibly reducing medication costs and drug exposure. Several therapeutic patterns have been proposed: weekly intermittent terbinafine (500 mg/d for 1 week each month for 4 months), or single-dose terbinafine (1000 mg per month for 4 months). Use of topical terbinafine 1% may be practical where the tinea involvement is not extensive or chronic. Recently, the terbinafine is available in a novel topical solution (film-forming solution--FFS) effective in the treatment of tinea pedis (athlete's foot).

  10. Antifungal and antibacterial activity of marine microorganisms.

    PubMed

    El Amraoui, B; El Amraoui, M; Cohen, N; Fassouane, A

    2014-03-01

    In order to explore marine microorganisms with pharmaceutical potential, marine bacteria, collected from different coastal areas of the Moroccan Atlantic Ocean, were previously isolated from seawater, sediment, marine invertebrates and seaweeds. The antimicrobial activities of these microorganisms were investigated against the pathogens involved in human pathologies. Whole cultures of 34 marine microorganisms were screened for antimicrobial activities using the method of agar diffusion against three Gram-positive bacteria, two Gram-negative bacteria, and against yeast. The results showed that among the 34 isolates studied, 28 (82%) strains have antimicrobial activity against at least one pathogen studied, 11 (32%) strains have antifungal activity and 24 (76%) strains are active against Gram-positive bacteria, while 21 (62%) strains are active against Gram-negative bacteria. Among isolates having antimicrobial activity, 14 were identified and were assigned to the genera Acinetobacter, Aeromonas, Alcaligenes, Bacillus, Chromobacterium, Enterococcus, Pantoea and Pseudomonas. Due to a competitive role for space and nutrient, the marine microorganisms can produce antibiotic substance; therefore, these marine microorganisms were expected to be potential resources of natural antibiotic products.

  11. New generation azole antifungals in clinical investigation.

    PubMed

    Girmenia, Corrado

    2009-09-01

    Considerable progress in treating systemic mycoses has been achieved in the past years through development of new drugs in association with more advanced diagnostic procedures. Here, we review the pharmacological, microbiological and clinical development progress with the so-called 'second generation' triazoles: voriconazole, posaconazole, ravuconazole, isavuconazole and albaconazole. All these drugs exhibit a favourable pharmacokinetic and toxicity profile and possess high activity against resistant and emerging pathogens. However, only voriconazole and posaconazole have been adequately investigated in Phase III studies and have been approved by the regulatory agencies in the treatment and prophylaxis of invasive fungal infections, respectively. On the contrary, ravuconazole, isavuconazole and albaconazole have not been investigated in adequate clinical trials and, in the absence of proper data, the real possibilities of these agents as competitors for the treatment and prevention of invasive mycoses in the clinical setting are still unknown. The drug interactions and the variability in the absorption and/or metabolism of the triazoles, in particular voriconazole and posaconazole, may determine an unpredictable exposure of the pathogens to the antifungal treatments. Literature evidences strongly support the use of therapeutic drug monitoring for these triazoles which may be crucial for the proper management of severe invasive fungal infections.

  12. Antifungal Indole Alkaloids from Winchia calophylla.

    PubMed

    Yang, Mei-Li; Chen, Jia; Sun, Meng; Zhang, Dong-Bo; Gao, Kun

    2016-05-01

    Ten indole alkaloids (1-10) were obtained from an antifungal extract of Winchia calophylla, of which two (2 and 4) were new. N(4)-Methyl-10-hydroxyl-desacetylakuammilin (2) was an akuammiline-type indole alkaloid. N(1)-Methyl-echitaminic acid (4) was an unusual zwitterion with a basic vincorine-type skeleton. This is the first report of 10 in W. calophylla. The structures of all of the compounds were determined based on spectroscopic data, and their bioactivities were assessed. Compound 1 showed potent activity against the plant pathogenic fungi of Penicillium italicum and Fusarium oxysporum f.sp cubens with IC50 s of 10.4 and 11.5 µM, respectively, and 3 inhibited Rhizoctonia solani with an IC50 of 11.7 µM. Compounds 2 and 4 showed weak cytotoxicity against the human leukemic cell line HL-60 in vitro with IC50 s of 51.4 and 75.3 µM, respectively. Compounds 1 and 2 displayed weak activity against acetylcholinesterase with IC50 s around 61.3 and 52.6 µM, respectively.

  13. Potato dextrose agar antifungal susceptibility testing for yeasts and molds: evaluation of phosphate effect on antifungal activity of CMT-3.

    PubMed

    Liu, Yu; Tortora, George; Ryan, Maria E; Lee, Hsi-Ming; Golub, Lorne M

    2002-05-01

    The broth macrodilution method (BMM) for antifungal susceptibility testing, approved by the National Committee for Clinical Laboratory Standards (NCCLS), was found to have deficiencies in testing of the antifungal activity of a new type of antifungal agent, a nonantibacterial chemically modified tetracycline (CMT-3). The high content of phosphate in the medium was found to greatly increase the MICs of CMT-3. To avoid the interference of phosphate in the test, a new method using potato dextrose agar (PDA) as a culture medium was developed. Eight strains of fungi, including five American Type Culture Collection strains and three clinical isolates, were used to determine the MICs of amphotericin B and itraconazole with both the BMM and the PDA methods. The MICs of the two antifungal agents determined with the PDA method showed 99% agreement with those determined with the BMM method within 1 log(2) dilution. Similarly, the overall reproducibility of the MICs with the PDA method was above 97%. Three other antifungal agents, fluconazole, ketoconazole, and CMT-3, were also tested in parallel against yeasts and molds with both the BMM and the PDA methods. The MICs of fluconazole and ketoconazole determined with the PDA method showed 100% agreement within 1 log(2) dilution of those obtained with the BMM method. However, the MICs of CMT-3 determined with the BMM method were as high as 128 times those determined with the PDA method. The effect of phosphate on the antifungal activity of CMT-3 was evaluated by adding Na2HPO4 to PDA in the new method. It was found that the MIC of CMT-3 against a Penicillium sp. increased from 0.5 microg/ml (control) to 2.0 microg/ml when the added phosphate was used at a concentration of 0.8 mg/ml, indicating a strong interference of Na2HPO4 with the antifungal activity of CMT-3. Except for fluconazole, all the other antifungal agents demonstrated clear end points among the yeasts and molds tested. Nevertheless, with its high reproducibility

  14. Breast cancer presenting with the syndrome of inappropriate secretion of antidiuretic hormone after simple mastectomy.

    PubMed

    Hashida, H; Honda, T; Morimoto, H; Sasaki, T; Aibara, Y; Yamanaka, M

    2001-09-01

    A 71-year-old woman showed disorientation 7 days after simple mastectomy for right breast cancer. Computed tomography of the brain was normal. The level of serum sodium was very low (110 mEq/l), while the urine sodium level was normal. The osmolality of urine was higher (342 mosmol/kg) than that of serum (220 mosmol/kg). These data suggested a syndrome of inappropriate secretion of antidiuretic hormone. A fluid restriction, infusion of hypertonic saline and administration of diuretics gradually increased the level of serum sodium. Subsequently, disorientation disappeared. This is a rare case of the syndrome of inappropriate secretion of antidiuretic hormone caused by simple mastectomy, a relatively minor surgical procedure.

  15. Inappropriate attitudes, fitness to practise and the challenges facing medical educators

    PubMed Central

    Whiting, Demian

    2007-01-01

    The author outlines a number of reasons why morally inappropriate attitudes may give rise to concerns about fitness to practise. He argues that inappropriate attitudes may raise such concerns because they can lead to harmful behaviours (such as a failure to give proper care or treatment), and because they are often themselves harmful (both because of the offence that they can cause and because of the unhealthy pall that they may cast over relations between healthcare practitioners and patients). He also outlines some of the challenges that the cultivation and assessment of attitudes in students raise for medical educators and some of the ways in which those challenges may be approached and possibly overcome. PMID:17971472

  16. Inappropriate Utilization in Fee-for-Service Medicare and Medicare Advantage Plans.

    PubMed

    Parashuram, Shriram; Kim, Seung; Dowd, Bryan

    2017-04-01

    This study uses a national multi-payer claims database to test for differences in potentially inappropriate emergency department (ED) visits and ambulatory care sensitive (ACS) admissions in fee-for-service (FFS) Medicare and Medicare Advantage (MA) plans. Rates of ACS admissions for MA enrollees were approximately one third those of FFS beneficiaries, controlling for covariates, which included the beneficiary's health status as represented by their risk score. This study then compared FFS and MA beneficiaries when they moved from one type of health plan to another. Again, controlling for covariates, potentially inappropriate ED visits and ACS admissions remained at their low baseline values for FFS beneficiaries who switched from FFS Medicare to MA plans, but rose for MA enrollees switching to FFS Medicare.

  17. The 'problem' with automation - Inappropriate feedback and interaction, not 'over-automation'

    NASA Technical Reports Server (NTRS)

    Norman, D. A.

    1990-01-01

    Automation in high-risk industry is often blamed for causing harm and increasing the chance of human error when failures occur. It is proposed that the problem is not the presence of automation, but rather its inappropriate design. The problem is that the operations are performed appropriately under normal conditions, but there is inadequate feedback and interaction with the humans who must control the overall conduct of the task. The problem is that the automation is at an intermediate level of intelligence, powerful enough to take over control which used to be done by people, but not powerful enough to handle all abnormalities. Moreover, its level of intelligence is insufficient to provide the continual, appropriate feedback that occurs naturally among human operators. To solve this problem, the automation should either be made less intelligent or more so, but the current level is quite inappropriate. The overall message is that it is possible to reduce error through appropriate design considerations.

  18. Urinary retention and syndrome of inappropriate antidiuretic hormone secretion (SIADH) secondary to impacted gravid uterus.

    PubMed

    Irani, M; Fisher, N; Mor, A; Bensinger, G

    2016-06-01

    Urinary retention is an emergency that rarely occurs during pregnancy. Previous case reports have suggested multiple risk factors that can cause the gravid uterus to become impacted in the pelvis leading to lower bladder or urethral compression with subsequent urinary retention. However, no cases of urinary obstruction in a pregnancy that was complicated with severe electrolyte imbalance have been reported. To our knowledge, we report the first case of a 31-year-old woman presenting at 8 weeks' gestation with acute urinary retention caused by a retroflexed, retroverted uterus with a 6-cm posterior uterine fibroid leading to syndrome of inappropriate antidiuretic hormone secretion and severe hyponatremia requiring intensive care unit admission. The cornerstones of effective management of urinary retention should include: (i) urgent bladder catheterization; (ii) assessment of sodium levels to rule out syndrome of inappropriate antidiuretic hormone secretion, and prompt treatment before neurological damage occurs; (iii) reduction of the impacted uterus; and (iv) monitoring for post-obstructive diuresis.

  19. Inappropriate Shocks and Power Delivery Using Adult Automatic External Defibrillator Pads in a Pediatric Patient.

    PubMed

    Tejman-Yarden, Shai; Katz, Uriel; Rubinstein, Marina; Attias, Yehuda; Yahia, Reem; Mishali, David; Glikson, Michael

    2017-02-21

    The use of automatic external defibrillators (AEDs) during pulseless resuscitations is considered safe and reliable, and was established as part of the guidelines in out-of-hospital events. Based on extensive studies, the use of the standard AED is now indicated in every age group with a preference of pediatric pad application for small children and babies. If unavailable, adult pads are recommended. We report a case of 2 inappropriate AED shocks that were delivered to a neonate during a pulseless resuscitation after application of adult pads. The 3.6-kg patient received 2 shocks, over 200 J each, for sinus bradycardia that was not detected by the device. Although treated inappropriately with high voltage, no cardiac or skin sequelae were detected, and the patient had normal cardiac and neurological development later on.

  20. Urea for long-term treatment of syndrome of inappropriate secretion of antidiuretic hormone.

    PubMed Central

    Decaux, G; Genette, F

    1981-01-01

    The efficacy of oral urea in producing a sufficiently high osmotic diuresis was tested in seven patients with the syndrome of inappropriate secretion of antidiuretic hormone. In all patients urea corrected the hyponatraemia despite a normal fluid intake. Five patients were controlled (serum sodium concentration greater than 128 mmol(mEq)/1) with a dose of 30 g urea daily, and two with 60 g daily. The patients who needed 30 g drank 1-2 1 of fluid daily, while those who needed 60 g drank up to 3.1 per day. No major side effects were noted, even after treatment periods of up to 270 days. These findings suggest that urea is a safe and efficacious treatment of the syndrome of inappropriate secretion of antidiuretic hormone. PMID:6794768

  1. Urea for long-term treatment of syndrome of inappropriate secretion of antidiuretic hormone.

    PubMed

    Decaux, G; Genette, F

    1981-10-24

    The efficacy of oral urea in producing a sufficiently high osmotic diuresis was tested in seven patients with the syndrome of inappropriate secretion of antidiuretic hormone. In all patients urea corrected the hyponatraemia despite a normal fluid intake. Five patients were controlled (serum sodium concentration greater than 128 mmol(mEq)/1) with a dose of 30 g urea daily, and two with 60 g daily. The patients who needed 30 g drank 1-2 1 of fluid daily, while those who needed 60 g drank up to 3.1 per day. No major side effects were noted, even after treatment periods of up to 270 days. These findings suggest that urea is a safe and efficacious treatment of the syndrome of inappropriate secretion of antidiuretic hormone.

  2. Oral fluconazole for empiric treatment of prolonged Fever in neutropenic patients: prospective study in 250 consecutive patients after stem cell transplantation.

    PubMed

    Stemmer, Salomon M; Maor, Yasmin; Hardan, Izhar

    2004-08-01

    Neutropenic patients who continue to be febrile despite adequate broad-spectrum antibacterial treatment require empirical antifungal therapy. The aim of the present study was to evaluate the safety and efficacy of oral fluconazole for empirical antifungal therapy in neutropenic patients with persistent fever. A prospective cohort design was used. The study sample included 250 consecutive patients with high-risk stage II, III, or responding metastatic breast cancer who received high-dose chemotherapy (HDC) with autologous peripheral blood progenitor stem cell transplantation. Those with neutropenic fever lasting more than 72 hours despite broad-spectrum antibacterial coverage were treated with fluconazole. Treatment was continued until fever dropped and/or neutrophil count recovered with blood cultures remaining negative. Antifungal treatment was required in 173 patients (69%). There were no cases of documented deep systemic fungal infection. Two patients (<1%) had positive blood cultures for fungi. None of the patients experienced toxicity related to fluconazole. There was one transplant-related death. Thirty-one patients (18%) were unable to complete the oral fluconazole protocol because of severe mucositis, and they received intravenous fluconazole at the same dose, with similar efficacy. Oral fluconazole is a safe and effective alternative to amphotericin B for empirical early antifungal treatment in persistent neutropenic fever in breast cancer patients undergoing HDC with autologous stem cell support. Further study of oral fluconazole and amphotericin B as empirical agents in other groups of patients with persistent neutropenic fever is warranted.

  3. Antifungal Hydroxy Fatty Acids Produced during Sourdough Fermentation: Microbial and Enzymatic Pathways, and Antifungal Activity in Bread

    PubMed Central

    Black, Brenna A.; Zannini, Emanuele; Curtis, Jonathan M.

    2013-01-01

    Lactobacilli convert linoleic acid to hydroxy fatty acids; however, this conversion has not been demonstrated in food fermentations and it remains unknown whether hydroxy fatty acids produced by lactobacilli have antifungal activity. This study aimed to determine whether lactobacilli convert linoleic acid to metabolites with antifungal activity and to assess whether this conversion can be employed to delay fungal growth on bread. Aqueous and organic extracts from seven strains of lactobacilli grown in modified De Man Rogosa Sharpe medium or sourdough were assayed for antifungal activity. Lactobacillus hammesii exhibited increased antifungal activity upon the addition of linoleic acid as a substrate. Bioassay-guided fractionation attributed the antifungal activity of L. hammesii to a monohydroxy C18:1 fatty acid. Comparison of its antifungal activity to those of other hydroxy fatty acids revealed that the monohydroxy fraction from L. hammesii and coriolic (13-hydroxy-9,11-octadecadienoic) acid were the most active, with MICs of 0.1 to 0.7 g liter−1. Ricinoleic (12-hydroxy-9-octadecenoic) acid was active at a MIC of 2.4 g liter−1. L. hammesii accumulated the monohydroxy C18:1 fatty acid in sourdough to a concentration of 0.73 ± 0.03 g liter−1 (mean ± standard deviation). Generation of hydroxy fatty acids in sourdough also occurred through enzymatic oxidation of linoleic acid to coriolic acid. The use of 20% sourdough fermented with L. hammesii or the use of 0.15% coriolic acid in bread making increased the mold-free shelf life by 2 to 3 days or from 2 to more than 6 days, respectively. In conclusion, L. hammesii converts linoleic acid in sourdough and the resulting monohydroxy octadecenoic acid exerts antifungal activity in bread. PMID:23315734

  4. Antifungal hydroxy fatty acids produced during sourdough fermentation: microbial and enzymatic pathways, and antifungal activity in bread.

    PubMed

    Black, Brenna A; Zannini, Emanuele; Curtis, Jonathan M; Gänzle, Michael G

    2013-03-01

    Lactobacilli convert linoleic acid to hydroxy fatty acids; however, this conversion has not been demonstrated in food fermentations and it remains unknown whether hydroxy fatty acids produced by lactobacilli have antifungal activity. This study aimed to determine whether lactobacilli convert linoleic acid to metabolites with antifungal activity and to assess whether this conversion can be employed to delay fungal growth on bread. Aqueous and organic extracts from seven strains of lactobacilli grown in modified De Man Rogosa Sharpe medium or sourdough were assayed for antifungal activity. Lactobacillus hammesii exhibited increased antifungal activity upon the addition of linoleic acid as a substrate. Bioassay-guided fractionation attributed the antifungal activity of L. hammesii to a monohydroxy C(18:1) fatty acid. Comparison of its antifungal activity to those of other hydroxy fatty acids revealed that the monohydroxy fraction from L. hammesii and coriolic (13-hydroxy-9,11-octadecadienoic) acid were the most active, with MICs of 0.1 to 0.7 g liter(-1). Ricinoleic (12-hydroxy-9-octadecenoic) acid was active at a MIC of 2.4 g liter(-1). L. hammesii accumulated the monohydroxy C(18:1) fatty acid in sourdough to a concentration of 0.73 ± 0.03 g liter(-1) (mean ± standard deviation). Generation of hydroxy fatty acids in sourdough also occurred through enzymatic oxidation of linoleic acid to coriolic acid. The use of 20% sourdough fermented with L. hammesii or the use of 0.15% coriolic acid in bread making increased the mold-free shelf life by 2 to 3 days or from 2 to more than 6 days, respectively. In conclusion, L. hammesii converts linoleic acid in sourdough and the resulting monohydroxy octadecenoic acid exerts antifungal activity in bread.

  5. Characterization of Antifungal Activity and Nail Penetration of ME1111, a New Antifungal Agent for Topical Treatment of Onychomycosis.

    PubMed

    Tabata, Yuji; Takei-Masuda, Naomi; Kubota, Natsuki; Takahata, Sho; Ohyama, Makoto; Kaneda, Kaori; Iida, Maiko; Maebashi, Kazunori

    2016-02-01

    Fungal nail infection (onychomycosis) is a prevalent disease in many areas of the world, with a high incidence approaching 23%. Available antifungals to treat the disease suffer from a number of disadvantages, necessitating the discovery of new efficacious and safe antifungals. Here, we evaluate the in vitro antifungal activity and nail penetration ability of ME1111, a novel antifungal agent, along with comparator drugs, including ciclopirox, amorolfine, terbinafine, and itraconazole. ME1111 showed potent antifungal activity against Trichophyton rubrum and Trichophyton mentagrophytes (the major etiologic agents of onychomycosis) strains isolated in Japan and reference fungal strains with an MIC range of 0.12 to 0.5 mg/liter and an MIC50 and MIC90 of 0.5 mg/liter for both. Importantly, none of the tested isolates showed an elevated ME1111 MIC. Moreover, the antifungal activity of ME1111 was minimally affected by 5% wool keratin powder in comparison to the other antifungals tested. The ME1111 solution was able to penetrate human nails and inhibit fungal growth in a dose-dependent manner according to the TurChub assay. In contrast, 8% ciclopirox and 5% amorolfine nail lacquers showed no activity under the same conditions. ME1111 demonstrated approximately 60-fold-greater selectivity in inhibition of Trichophyton spp. than of human cell lines. Our findings demonstrate that ME1111 possesses potent antidermatophyte activity, maintains this activity in the presence of keratin, and possesses excellent human nail permeability. These results suggest that ME1111 is a promising topical medication for the treatment of onychomycosis and therefore warrants further clinical evaluation. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  6. Characterization of Antifungal Activity and Nail Penetration of ME1111, a New Antifungal Agent for Topical Treatment of Onychomycosis

    PubMed Central

    Takei-Masuda, Naomi; Kubota, Natsuki; Takahata, Sho; Ohyama, Makoto; Kaneda, Kaori; Iida, Maiko; Maebashi, Kazunori

    2015-01-01

    Fungal nail infection (onychomycosis) is a prevalent disease in many areas of the world, with a high incidence approaching 23%. Available antifungals to treat the disease suffer from a number of disadvantages, necessitating the discovery of new efficacious and safe antifungals. Here, we evaluate the in vitro antifungal activity and nail penetration ability of ME1111, a novel antifungal agent, along with comparator drugs, including ciclopirox, amorolfine, terbinafine, and itraconazole. ME1111 showed potent antifungal activity against Trichophyton rubrum and Trichophyton mentagrophytes (the major etiologic agents of onychomycosis) strains isolated in Japan and reference fungal strains with an MIC range of 0.12 to 0.5 mg/liter and an MIC50 and MIC90 of 0.5 mg/liter for both. Importantly, none of the tested isolates showed an elevated ME1111 MIC. Moreover, the antifungal activity of ME1111 was minimally affected by 5% wool keratin powder in comparison to the other antifungals tested. The ME1111 solution was able to penetrate human nails and inhibit fungal growth in a dose-dependent manner according to the TurChub assay. In contrast, 8% ciclopirox and 5% amorolfine nail lacquers showed no activity under the same conditions. ME1111 demonstrated approximately 60-fold-greater selectivity in inhibition of Trichophyton spp. than of human cell lines. Our findings demonstrate that ME1111 possesses potent antidermatophyte activity, maintains this activity in the presence of keratin, and possesses excellent human nail permeability. These results suggest that ME1111 is a promising topical medication for the treatment of onychomycosis and therefore warrants further clinical evaluation. PMID:26643333

  7. Syndrome of inappropriate antidiuretic hormone secretion related to Guillain-Barré syndrome after laparoscopic cholecystectomy.

    PubMed

    Çakırgöz, Mensure Yılmaz; Duran, Esra; Topuz, Cem; Kara, Deniz; Turgut, Namigar; Türkmen, Ülkü Aygen; Turanç, Bülent; Dolap, Mustafa Önder; Hancı, Volkan

    2014-01-01

    Guillain-Barré Syndrome is one of the most common causes of acute polyneuropathy in adults. Recently, the occurrence of Guillain-Barré Syndrome after major and minor surgical operations has been increasingly debated. In Guillain-Barré syndrome, syndrome of inappropriate antidiuretic hormone secretion and dysautonomy are generally observed after maximal motor deficit. A 44-year-old male patient underwent a laparoscopic cholecystectomy for acute cholecystitis. After the development of a severe headache, nausea, diplopia, and attacks of hypertension in the early postoperative period, a computer tomography of the brain was normal. Laboratory tests revealed hyponatremia linked to syndrome of inappropriate antidiuretic hormone secretion, the patient's fluids were restricted, and furosemide and 3% NaCl treatment was initiated. On the second day postoperative, the patient developed numbness moving upward from the hands and feet, loss of strength, difficulty swallowing and respiratory distress. Guillain-Barré syndrome was suspected, and the patient was moved to intensive care. Cerebrospinal fluid examination showed 320 mg/dL protein, and acute motor-sensorial axonal neuropathy was identified by electromyelography. Guillain-Barré syndrome was diagnosed, and intravenous immune globulin treatment (0.4 g/kg/day, 5 days) was initiated. After 10 days in the intensive care unit, at which the respiratory, hemodynamic, neurologic and laboratory results returned to normal, the patient was transferred to the neurology service. Our case report indicates that although syndrome of inappropriate antidiuretic hormone secretion and autonomic dysfunction are rarely the initial characteristics of Guillain-Barré syndrome, the possibility of postoperative syndrome of inappropriate antidiuretic hormone secretion should be kept in mind. The presence of secondary hyponatremia in this type of clinical presentation may delay diagnosis. Copyright © 2013 Sociedade Brasileira de Anestesiologia

  8. Impact of oncology-related direct-to-consumer advertising: association with appropriate and inappropriate prescriptions.

    PubMed

    Abel, Gregory A; Chen, Kun; Taback, Nathan; Hassett, Michael J; Schrag, Deborah; Weeks, Jane C

    2013-03-01

    Little is known about the impact of direct-to-consumer advertising (DTCA) on appropriate versus inappropriate prescribing. Aromatase inhibitor (AI) therapy for breast cancer provides an ideal paradigm for studying this issue, because AIs have been the focus of substantial DTCA, and because they should only be used in postmenopausal women, age can serve as a simple surrogate marker of appropriateness. Data regarding national DTCA spending for the AIs were obtained from TNS Multimedia; hormonal therapy prescription data were obtained from IMS Health. Time series analyses were performed to characterize the association between monthly changes in DTCA spending for the AIs and monthly changes in the proportion of all new hormonal therapy prescriptions represented by the AIs from October 2005 to September 2007. Analyses were stratified by age, considering prescriptions for women ≤ 40 (likely premenopausal) to be inappropriate and those for women > 60 (likely postmenopausal) to be appropriate. Monthly dollars spent on AI-associated DTCA varied considerably ($118,600 to $22,019,660). Time series analysis revealed that for every million dollars spent on DTCA for the AIs, there was an associated increase 3 months later in the new AI prescription proportion of 0.15% for all ages (P < .0001) and 0.18% for those > 60 years (P < .0001), but no significant change for those ≤ 40 at any time from 0 to 6 months. DTCA for the AIs was associated with increases in appropriate prescriptions with no significant effect on inappropriate prescriptions, suggesting that DTCA may not foster inappropriate medication use for certain drug classes. Copyright © 2012 American Cancer Society.

  9. An automated technique to identify potential inappropriate traditional Chinese medicine (TCM) prescriptions.

    PubMed

    Yang, Hsuan-Chia; Iqbal, Usman; Nguyen, Phung Anh; Lin, Shen-Hsien; Huang, Chih-Wei; Jian, Wen-Shan; Li, Yu-Chuan

    2016-04-01

    Medication errors such as potential inappropriate prescriptions would induce serious adverse drug events to patients. Information technology has the ability to prevent medication errors; however, the pharmacology of traditional Chinese medicine (TCM) is not as clear as in western medicine. The aim of this study was to apply the appropriateness of prescription (AOP) model to identify potential inappropriate TCM prescriptions. We used the association rule of mining techniques to analyze 14.5 million prescriptions from the Taiwan National Health Insurance Research Database. The disease and TCM (DTCM) and traditional Chinese medicine-traditional Chinese medicine (TCMM) associations are computed by their co-occurrence, and the associations' strength was measured as Q-values, which often referred to as interestingness or life values. By considering the number of Q-values, the AOP model was applied to identify the inappropriate prescriptions. Afterwards, three traditional Chinese physicians evaluated 1920 prescriptions and validated the detected outcomes from the AOP model. Out of 1920 prescriptions, 97.1% of positive predictive value and 19.5% of negative predictive value were shown by the system as compared with those by experts. The sensitivity analysis indicated that the negative predictive value could improve up to 27.5% when the model's threshold changed to 0.4. We successfully applied the AOP model to automatically identify potential inappropriate TCM prescriptions. This model could be a potential TCM clinical decision support system in order to improve drug safety and quality of care. Copyright © 2016 John Wiley & Sons, Ltd.

  10. Recurrent Acute Decompensated Heart Failure Owing to Severe Iron Deficiency Anemia Caused by Inappropriate Habitual Bloodletting

    PubMed Central

    Lim, Woo-Hyun; Kim, Hack-Lyoung; Kim, Ki-Hwan; Na, Sang Hoon; Lee, Hyun-Jung; Kang, Eun Gyu; Seo, Jae-Bin; Chung, Woo-Young; Zo, Joo-Hee; Hong, Jung Ae; Kim, Kwangyoun; Kim, Myung-A

    2015-01-01

    A 68-year-old woman visited the emergency department twice with symptoms of acute heart failure including shortness of breath, general weakness, and abdominal distension. Laboratory findings showed extremely low level of serum hemoglobin at 1.4 g/dL. Echocardiographic examination demonstrated dilated left ventricular cavity with systolic dysfunction and moderate amount of pericardial effusion. In this patient, acute heart failure due to severe iron deficiency anemia was caused by inappropriate habitual bloodletting. PMID:26755934

  11. Inappropriate habits of antibiotic use among medical specialists and students in Vilnius

    PubMed Central

    Artūras, Barkus; Ingrida, Lisauskienė

    2016-01-01

    Introduction. The resistance to antibacterial drugs is an emerging worldwide problem. Numbers of inappropriate ways to use antibiotics contribute to this issue. Self-medication is one of them. This study seeks to find out how prevalent the self-medication with antibiotics, their storage at home and the inappropriate acquisition of antibacterial drugs are among medical specialists in Vilnius, Lithuania. Methods. A cross-sectional survey was conducted. To better identify the potential target groups, the respondents were classified according to their relation to medical care: physicians, other medical personnel, medical students and people, directly not related to medical care. Results. The overall actual self-medication with antibiotics rate was 4.0%. And, although the actual self-medication rate might seem rather low, the intended self-medication rate was 51.4%. Also, a prevalent antibacterial drugs storage at home (45.8%) with a wide variety of preparations was reported. Only 61.9% respondents received prescriptions for antibiotics from their treating physician. 7.6% used the non-prescribed medicines and 22.0% received a prescription from a physician, who was either their colleague or a familiar person. Conclusions. Inappropriate habits of antibiotic use are prevalent. While there were some differences between the research groups, most of them were not statistically significant. It means that measures should be taken targeting health care givers as well as the general population. Educational programs about the rational use of antibiotics may help reducing the improper habits of antibacterial drugs usage, including self-medication. Encouraging the electronic drug prescription may be beneficial while reducing the prevalent inappropriate acquisition of antibiotics.

  12. Physicians' perceptions and attitudes regarding inappropriate admissions and resource allocation in the intensive care setting.

    PubMed

    Giannini, A; Consonni, D

    2006-01-01

    Physicians' perceptions regarding intensive care unit (ICU) resource allocation and the problem of inappropriate admissions are unknown. We carried out an anonymous, self-administered questionnaire survey to assess the perceptions and attitudes of ICU physicians at all 20 ICUs in Milan, Italy, regarding inappropriate admissions and resource allocation. Eighty-seven percent (225/259) of physicians responded. Inappropriate admissions were acknowledged by 86% of respondents. The reasons given were clinical doubt (33%); limited decision time (32%); assessment error (25%); pressure from superiors (13%), referring clinician (11%) or family (5%); threat of legal action (5%); and an economically advantageous 'Diagnosis Related Group' (1%). Respondents reported being pressurized to make more 'productive' use of ICU beds by Unit heads (frequently 16%), hospital management (frequently 10%) and colleagues (frequently 4%). Five percent reported refusing appropriate admissions following 'indications' not to admit financially disadvantageous cases. Admissions after elective surgery prioritized patients from profitable surgical departments: frequently for 6% of respondents and occasionally for 15%. Sixty-seven percent said they frequently received requests for appropriate admissions when no beds were available. This was considered sufficient reason to withdraw treatment from patients with lower survival probability (sometimes 21%) or for whom nothing more could be done (sometimes 51%, frequently 11%). Inappropriate ICU admissions were perceived as a common event but were mainly attributed to difficulties in assessing suitability. Physicians were aware that their decisions were often influenced by factors other than medical necessity. Economic influences were perceived as limited but not negligible. Decisions to forgo treatment could be influenced by the need to admit other patients.

  13. Disciplinary proceedings for inappropriate prescription of opioid medications by medical practitioners in Australia (2010-2014).

    PubMed

    Mendelson, Danuta

    2014-12-01

    An analysis of 32 cases reported between July 2010 and September 2014 by professional disciplinary tribunals in New South Wales and Victoria against medical practitioners found guilty of inappropriately prescribing Sch 8 medications (mainly opioids) and Sch 4 drugs (mainly benzodiazepines) demonstrated, among others, a lengthy delay between the occurrence of the miscreant conduct and the conclusion of disciplinary proceedings. The study also raised questions about the appropriateness of utilising common criminal law theories of punishment and deterrence by non-judicial tribunals.

  14. Inappropriate Clostridium difficile Testing and Consequent Overtreatment and Inaccurate Publicly Reported Metrics.

    PubMed

    Kelly, Sean G; Yarrington, Michael; Zembower, Teresa R; Sutton, Sarah H; Silkaitis, Christina; Postelnick, Michael; Mikolajczak, Anessa; Bolon, Maureen K

    2016-12-01

    BACKGROUND The nationally reported metric for Clostridium difficile infection (CDI) relies solely on laboratory testing, which can result in overreporting due to asymptomatic C. difficile colonization. OBJECTIVE To review the clinical scenarios of cases of healthcare facility-onset CDI (HO-CDI) and to determine the appropriateness of C. difficile testing on the basis of presence of symptomatic diarrhea in order to identify areas for improvement. DESIGN Retrospective cohort study. SETTING Northwestern Memorial Hospital, a large, tertiary academic hospital in Chicago, Illinois. PATIENTS The cohort included all patients with a positive C. difficile test result who were reported to the National Healthcare Safety Network as HO-CDI during a 1-year study period. METHODS We reviewed the clinical scenario of each HO-CDI case. On the basis of documentation and predefined criteria, appropriateness of C. difficile testing was determined; cases were deemed appropriate, inappropriate, or indeterminate. Statistical analysis was performed to compare demographic and clinical parameters among the categories of testing appropriateness. RESULTS Our facility reported 168 HO-CDI cases to NHSN during the study period. Of 168 cases, 33 (19.6%) were judged to be appropriate tests, 25 (14.8%) were considered inappropriate, and 110 (65.5%) were indeterminate. Elimination of inappropriate testing would have improved our facility's standardized infection ratio from 0.962 to 0.819. CONCLUSION Approximately 15% of HO-CDI cases were judged to be tested inappropriately. Testing only patients with clinically significant diarrhea would more accurately estimate CDI incidence, reduce unnecessary antibiotic use, and improve facilities' performance of reportable CDI metrics. Improved documentation could facilitate targeted interventions. Infect Control Hosp Epidemiol 2016;1395-1400.

  15. Lack of appropriate investigations in making a diagnosis of syndrome of inappropriate antidiuretic hormone.

    PubMed

    Barnes, Alex; Li, Jordan Y Z; Gleadle, Jonathan M

    2017-03-01

    The syndrome of inappropriate antidiuretic hormone (SIADH) is reported as the most common cause of hyponatraemia. This retrospective cross-sectional study evaluated the diagnosis of SIADH in 110 hospitalised patients in an Australian tertiary hospital with reference to recently published clinical guidelines. Investigation of SIADH was incomplete in all but 20% of cases. Adrenal insufficiency and hypothyroidism were not excluded in a significant number of cases.

  16. Inappropriate Obligations for the T700 Technical, Engineering, and Logistical Services and Supplies Contract

    DTIC Science & Technology

    2014-09-17

    at www.dodig.mil Objective We determined whether the Department of Defense effectively managed the T700 Technical, Engineering, and Logistical...U.S. Army Aviation and Missile Life Cycle Management  Command and U.S. Army Contracting Command officials inappropriately obligated funds for work... Management Command officials did not support their estimate with a historical analysis of actual costs for anticipated future work, as required by

  17. [Diagnostics and new treatment methods of syndrome of inappropriate antidiuretic hormone secretion (SIADH)].

    PubMed

    Trolle, Christian; Rittig, Søren; Frøkjær, Jørgen; Jørgensen, Jens Otto Lunde

    2012-04-09

    New treatment methods of syndrome of inappropriate antidiuretic hormone secretion (SIADH) has emerged with the oral vasopressin V2-receptor antagonist (VV2RA) tolvaptan, but its therapeutic window remains to be defined. We present the scientific data and describe treatment possibilities of SIADH while raising the questions: "Does the present evidence enable us to identify who to treat with VV2RAs?" and "is VV2RAs justified as first-line treatment?".

  18. Aquaporin-4 antibody positive neuromyelitis optica with syndrome of inappropriate antidiuretic hormone secretion.

    PubMed

    You, Xiao-Fan; Qin, Wei; Hu, Wen-Li

    2011-01-01

    Neuromyelitis optica (NMO) has been reported to be associated with endocrinopathies, such as amenorrhea, galactorrhea, and diabetes mellitus. However, its association with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is extremely rare. We herein report an adult case of NMO with SIADH in a female Chinese patient. The patient was aquaporin-4 antibody positive, and her hypothalamic dysfunction may have been related to the development of SIADH.

  19. Culture-inappropriate antibiotic therapy decreases quality of life improvement after sinus surgery.

    PubMed

    Zhang, Zi; Palmer, James N; Morales, Knashawn H; Howland, Timothy J; Doghramji, Laurel J; Adappa, Nithin D; Chiu, Alexander G; Cohen, Noam A; Lautenbach, Ebbing

    2014-05-01

    Despite their widespread use, antibiotics have not been shown to improve chronic rhinosinusitis (CRS) outcomes. We aimed to determine whether culture-inappropriate postoperative antibiotic therapy was associated with less quality-of-life (QOL) improvement following functional endoscopic sinus surgery (FESS). This retrospective cohort study recruited 376 adult CRS patients undergoing FESS between October 1, 2007 to December 31, 2011. Patient demographics, comorbidities and medications were collected at baseline. Trimethoprim-sulfamethoxazole and clindamycin were administered for 2 weeks postoperatively. The antibiotic appropriateness was determined based on bacterial resistance profile of organisms identified during intraoperative culture. The QOL outcome was defined as change of 22-item Sinonasal Outcome Test scores from preoperative visit to 1-month, 3-month, and 6-month post-FESS. Clinically significant difference was defined as at least 0.5 standard deviations (SD) of baseline QOL score in the reference group. Mixed-effects regression models were performed. Seven percent of patients (n = 27) had culture-inappropriate antibiotic therapy, and additional 5% (n = 19) had culture-specific antibiotic adjustment. Compared to patients with culture-appropriate antibiotics, patients with culture-inappropriate antibiotics had significantly less improvement of QOL from baseline to postoperative 1-month and 3-month follow-up where the difference became clinically significant; patients with antibiotic adjustment had more QOL improvement from baseline to 1-month follow-up, but their QOL worsened at 3-month follow-up, and these changes were not clinically significant. However, all effects washed out at 6-month follow-up with no significant differences. Culture-inappropriate postoperative antibiotic therapy decreased short-term QOL improvement to a clinically meaningful level after FESS. Culture guided selection of antibiotics may improve short-term FESS outcome. © 2014 ARS

  20. Register-based indicators for potentially inappropriate medication in high-cost patients with excessive polypharmacy.

    PubMed

    Saastamoinen, Leena K; Verho, Jouko

    2015-06-01

    Excessive polypharmacy is often associated with inappropriate drug use. Because drug expenditures are heavily skewed and a considerable share of patients in the top 5% of the cost distribution have excessive polypharmacy, the appropriateness of their drug use should be reviewed. The aim of this study was to review the quality of drug use in patients with extremely high costs and excessive polypharmacy and to compare them with all drug users. This is a nationwide register study. The subjects of this study were all drug users in Finland over 15 years of age, n = 3,303,813. The measures used were annual total costs, average costs, and number of patients. The background characteristics used included gender, age, morbidity, number of prescribers, active substances, and indicators of potentially inappropriate drug use, for example, Beers criteria. The patients with high costs and excessive polypharmacy accounted for 22% of the total pharmaceutical expenditures but only 3% of drug users. One-third of them were elderly, compared with 11.3% of all drug users (p < 0.001). Almost all of them, 93.6%, had chronic disease compared with 34.0% of all the drug users (p < 0.001). The high-cost polypharmacy patients used more potentially inappropriate (28.0% vs 19.9%, p < 0.001) and anticholinergic drugs (26.7% vs. 9.6%, p < 0.001) and psychotropics more often simultaneously (20.4% vs. 3.8%, p < 0.001) than all drug users. Excessive polypharmacy with inappropriate medication use should be prevented using all the methods. The patients with excessive polypharmacy and high-drug costs provide a most interesting group for containing pharmaceutical costs via medication reviews. Copyright © 2015 John Wiley & Sons, Ltd.

  1. Predictors of inappropriate atrial sensing in long-term VDD-pacing systems.

    PubMed

    Huang, Chin-Chou; Tuan, Ta-Chuan; Fong, Man-Cai; Lee, Wen-Shin; Kong, Chi-Woon

    2010-09-01

    The efficacy and stability of the atrial electrode sensing function is essential for maintaining atrioventricular (AV) synchrony. This study aimed to explore the long-term reliability and causes of the long-term sensing failure of VDD systems. We enrolled all the patients with complete or high-degree AV block who received VDD pacemakers between August 1994 to January 2006 and who were followed up for more than 12 months. The interrogation parameters, including the atrial potentials (APs) and AV-synchrony ratio were acquired immediately post-implantation and at 3-6 month intervals thereafter. An inappropriate atrial sensing efficacy was defined as an AV-synchrony ratio of <90%. Totally 157 patients (70 +/- 12 years, 103 males) were enrolled into the study with a follow-up for 4.9 +/- 2.5 years. Twenty-six patients (16.6%) suffered from inappropriate atrial sensing. According to a Kaplan-Meier analysis, the incidence of inappropriate atrial sensing was higher in the patients with an age > or =72 years old (P = 0.047), mean AP during the implantation of <3.0 mV (P = 0.015), concomitant use of non-dihydropyridine calcium channel blockers (CCBs) (P = 0.003), and atrial fibrillation (AF) (P < 0.001). A Cox regression analysis showed that non-dihydropyridine CCBs (hazard ratio, 3.255; 95% confidence interval, 1.148-9.227, P = 0.026) and AF (hazard ratio, 6.507; 95% confidence interval, 2.478-17.104, P < 0.001) predicted inappropriate atrial sensing. VDD pacing is a reliable pacing modality. However, we should monitor the pacemaker sensing function in the patients with the concomitant use of non-dihydropyridine CCBs and AF.

  2. Beers Criteria as a Proxy for Inappropriate Prescribing of Other Medications Among Older Adults

    PubMed Central

    Lund, Brian C; Steinman, Michael A; Chrischilles, Elizabeth A; Kaboli, Peter J

    2014-01-01

    BACKGROUND The Beers criteria are a compilation of medications deemed potentially inappropriate for older adults, and widely used a prescribing quality indicator. OBJECTIVE To determine whether Beers criteria serve as a proxy measure for other forms of inappropriate prescribing, as measured by comprehensive implicit review. METHODS Data for patients 65 years and older were obtained from the VA Enhanced Pharmacy Outpatient Clinic (EPOC) and the Iowa Medicaid Pharmaceutical Case Management (PCM) studies. Comprehensive measurement of prescribing quality was conducted using expert clinician review of medical records according to the Medication Appropriateness Index (MAI). MAI scores attributable to non-Beers medications (non-Beers MAI) were contrasted between patients who did and did not receive a Beers criteria medication. RESULTS Beers criteria medications accounted for 12.9% and 14.0% of total MAI scores in the two studies. Importantly, non-Beers MAI scores were significantly higher in patients receiving a Beers criteria medication in both studies (EPOC: 15.1 vs. 12.4, p = 0.02; PCM: 11.1 vs. 8.7, p = 0.04), after adjusting for important confounding factors. CONCLUSIONS Beers criteria utility extended beyond direct measurement of a limited set of inappropriate prescribing practices by serving as a clinically meaningful proxy for other inappropriate practices. Using prescribing quality indicators to guide interventions should thus identify patients for comprehensive medication review, rather than identifying specific targets for discontinuation. Future research should explore both the quality measurement and the intervention targeting applications of the Beers criteria, particularly when integrated with other indicators. PMID:21972251

  3. The syndrome of inappropriate secretion of antidiuretic hormone in the maxillofacial trauma patient.

    PubMed

    Lieblich, S E; Forman, D; Berger, J; Gold, B D

    1985-05-01

    The maxillofacial trauma patient whose neurologic status undergoes a rapid and serious deterioration may have a severe hyponatremia secondary to the inappropriate secretion of antidiuretic hormone (SIADH). Other causes of hyponatremia must be ruled out, especially posttraumatic cerebral salt wasting, which necessitates a different mode of therapy. A case of SIADH is reported, and the work-up and differential diagnosis of posttraumatic hyponatremia are discussed.

  4. Non-Empirical Confirmation

    NASA Astrophysics Data System (ADS)

    Dawid, Richard

    2016-06-01

    In fundamental physics today, some theories are taken to be probably viable despite a lack of strong (or any) empirical confirmation. This situation suggests, I argue, an extension of the concept of theory confirmation that allows for confirmation by observations that are not predicted by the theory in question. "Non-empirical confirmation", as I call the latter form of confirmation, plays a more conspicuous role today than in earlier periods of physics. It has always constituted a significant albeit implicit element of the assessment of physical theory, however, that has not been adequately accounted for in canonical reconstructions of the scientific method. The talk discusses the core argumentative structure of non-empirical confirmation, analyses the concept’s reliance on the empirical testability of the theories in question and addresses some worries that have been raised in its regard.

  5. Defining Empirically Based Practice.

    ERIC Educational Resources Information Center

    Siegel, Deborah H.

    1984-01-01

    Provides a definition of empirically based practice, both conceptually and operationally. Describes a study of how research and practice were integrated in the graduate social work program at the School of Social Service Administration, University of Chicago. (JAC)

  6. Defining Empirically Based Practice.

    ERIC Educational Resources Information Center

    Siegel, Deborah H.

    1984-01-01

    Provides a definition of empirically based practice, both conceptually and operationally. Describes a study of how research and practice were integrated in the graduate social work program at the School of Social Service Administration, University of Chicago. (JAC)

  7. Antifungal susceptibilities of Candida species isolated from urine culture.

    PubMed

    Toka Özer, Türkan; Durmaz, Süleyman; Yula, Erkan

    2016-09-01

    Candida spp. are the most common opportunistic mycosis worldwide. Although Candida albicans is the most common cause of urinary tract infections, the frequency of non-albicans Candida species is increasing with common use of antifungal in the prophylaxis and treatment. This may lead to difficulties in treatment. Antifungal tests should be applied with identification of species for effective treatment. In this study, identification of Candida species isolated from urine culture and investigation of susceptibility of these strains to amphotericin B, flucytosine, fluconazole, voriconazole was aimed. In this study, 58 Candida strains isolated from urine cultures at Osmaniye State Hospital between January 2012 and April 2013 were included. Urine culture and antifungal susceptibility tests were applied. Incidence rate of Candida spp. was determined as C. albicans (56.9%), Candida glabrata (20.6%), Candida tropicalis (10.3%), Candida parapsilosis (7%), Candida krusei (3.4%), Candida kefyr (1.8%). Most of the isolates were susceptible to amphotericin B, flucytosine, fluconazole, voriconazole. Twenty three (39.7%) Candida strains were isolated from internal medical branches and Intensive Care Unit and 12 (20.6%) from the Surgical Medical Branches. C. albicans and C. glabrata species were isolated most frequently as a candiduria factor in this hospital between January 2012 and April 2013. The analysis of antifungal susceptibility profile shows no significant resistance to antifungals. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  8. An antifungal defensin from Phaseolus vulgaris cv. 'Cloud Bean'.

    PubMed

    Wu, Xiangli; Sun, Jian; Zhang, Guoqing; Wang, Hexiang; Ng, Tzi Bun

    2011-01-15

    An antifungal peptide with a defensin-like sequence and exhibiting a molecular mass of 7.3kDa was purified from dried seeds of Phaseolus vulgaris 'Cloud Bean'. The isolation procedure entailed anion exchange chromatography on DEAE-cellulose, affinity chromatography an Affi-gel blue gel, cation exchange chromatography on SP-Sepharose, and gel filtration by fast protein liquid chromatography on Superdex 75. Although the antifungal peptide was unadsorbed on DEAE-cellulose, it was adsorbed on both Affi-gel blue gel and SP-Sepharose. The antifungal peptide exerted antifungal activity against Mycosphaerella arachidicola with an IC(50) value of 1.8 μM. It was also active against Fusarium oxysporum with an IC(50) value of 2.2 μM. It had no inhibitory effect on HIV-1 reverse transcriptase when tested up to 100 μM. Proliferation of L1210 mouse leukemia cells and MBL2 lymphoma cells was inhibited by the antifungal peptide with an IC(50) of 10 μM and 40 μM, respectively.

  9. In Search of the Holy Grail of Antifungal Therapy

    PubMed Central

    Chapman, Stanley W.; Sullivan, Donna C.; Cleary, John D.

    2008-01-01

    The ideal antifungal agent remains an elusive goal for treatment of life-threatening systemic fungal infections. Such an agent would have broad antifungal activity, low rates of resistance, flexible routes of administration, few associated adverse events, and limited drug-drug interactions. Only three of the seven classes of antifungal agents currently available are suitable for treatment of systemic infection: the polyenes, the azoles, and the echinocandins. None match all the characteristics of an ideal agent, the Holy Grail of antifungal therapy. Academia and industry need to collaborate in the search for new lead antifungal compounds using traditional screening methods as well as the new pharmacogenomics methods. Enhancing efficacy and reducing toxicity of the currently available therapeutic agents is also another important avenue of study. As an example, the Mycosis Research Center at the University of Mississippi Medical Center has identified pyogenic polyenes in commercial preparations of amphotericin B deoxycholate which correlate with infusion related toxicities. A highly purified formulation of amphotericin B appears promising, with a better therapeutic index compared to its parent compound as evidenced by results of in vitro and in vivo studies reviewed in this presentation. PMID:18596853

  10. Taxonomy and Antifungal Susceptibility of Clinically Important Rasamsonia Species

    PubMed Central

    Giraud, S.; Meijer, M.; Bertout, S.; Frisvad, J. C.; Meis, J. F.; Bouchara, J. P.; Samson, R. A.

    2013-01-01

    In recent years, Geosmithia argillacea has been increasingly reported in humans and animals and can be considered an emerging pathogen. The taxonomy of Geosmithia was recently studied, and Geosmithia argillacea and related species were transferred to the new genus Rasamsonia. The diversity among a set of Rasamsonia argillacea strains, including 28 clinical strains, was studied, and antifungal susceptibility profiles were generated. Data obtained from morphological studies and from phylogenetic analyses of internal transcribed spacer (ITS) and partial β-tubulin and calmodulin sequences revealed the presence of four species in the Rasamsonia argillacea complex, two of which are newly described here: R. piperina sp. nov. and R. aegroticola sp. nov. In contrast to other related genera, all Rasamsonia species can be identified with ITS sequences. A retrospective identification was performed on recently reported clinical isolates from animal or human patients. Susceptibility tests showed that the antifungal susceptibility profiles of the four members of the R. argillacea complex are similar, and caspofungin showed significant activity in vitro, followed by amphotericin B and posaconazole. Voriconazole was the least active of the antifungals tested. The phenotypically similar species R. brevistipitata and R. cylindrospora had different antifungal susceptibility profiles, and this indicates that correct species identification is important to help guide appropriate antifungal therapy. PMID:23077129

  11. Antifungal activity of essential oils against selected terverticillate penicillia.

    PubMed

    Felšöciová, Soňa; Kačániová, Miroslava; Horská, Elena; Vukovič, Nenad; Hleba, Lukáš; Petrová, Jana; Rovná, Katarina; Stričík, Michal; Hajduová, Zuzana

    2015-01-01

    The aim of this study was to screen 15 essential oils of selected plant species, viz. Lavandula angustifolia, Carum carvi, Pinus mungo var. pulmilio, Mentha piperita, Chamomilla recutita L., Pinus sylvestris, Satureia hortensis L., Origanum vulgare L., Pimpinella anisum, Rosmarinus officinalis L., Salvia officinalis L., Abietis albia etheroleum, Chamomilla recutita L. Rausch, Thymus vulgaris L., Origanum vulgare L. for antifungal activity against five Penicillium species: Penicillium brevicompactum, Penicillium citrinum, Penicillium crustosum, Penicillium expansum and Penicillium griseofulvum. The method used for screening included the disc diffusion method. The study points out the wide spectrum of antifungal activity of essential oils against Penicillium fungi. There were five essential oils of the 15 mentioned above which showed a hopeful antifungal activity: Pimpinella anisum, Chamomilla recutita L., Thymus vulgaris, Origanum vulgare L. The most hopeful antifungal activity and killing effect against all tested penicillia was found to be Origanum vulgare L. and Pimpinella anisum. The lowest level of antifungal activity was demonstrated by the oils Pinus mungo var. pulmilio, Salvia officinalis L., Abietis albia etheroleum, Chamomilla recutita L. Rausch, Rosmarinus officinalis.

  12. IPC synthase as a useful target for antifungal drugs.

    PubMed

    Sugimoto, Yuichi; Sakoh, Hiroki; Yamada, Koji

    2004-12-01

    Inositol phosphorylceramide (IPC) synthase is a common and essential enzyme in fungi and plants, which catalyzes the transfer of phosphoinositol to the C-1 hydroxy of ceramide to produce IPC. This reaction is a key step in fungal sphingolipid biosynthesis, therefore the enzyme is a potential target for the development of nontoxic therapeutic antifungal agents. Natural products with a desired biological activity, aureobasidin A (AbA), khafrefungin, and galbonolide A, have been reported. AbA, a cyclic depsipeptide containing 8 amino acids and a hydroxyl acid, is a broad spectrum antifungal with strong activity against many pathogenic fungi such as Candida spp., Cryptococcus neoformans, and some Aspergillus spp. Khafrefungin, an aldonic acid ester with a C22 long alkyl chain, has antifungal activity against C. albicans, Cr. Neoformans, and Saccharomyces cerevisiae. Galbonolide A is a 14-membered macrolide with fungicidal activity against clinically important strains, and is especially potent against Cr. neoformans. These classes of natural products are potent and specific antifungal agents. We review current progress in the development of IPC synthase inhibitors with antifungal activities, and present structure-activity relationships (SAR), physicochemical and structural properties, and synthetic methodology for chemical modification.

  13. Cadinene sesquiterpenes from Eupatorium adenophorum and their antifungal activity.

    PubMed

    Kundu, Aditi; Saha, Supradip; Walia, Suresh; Shakil, Najam A; Kumar, Jitendra; Annapurna, Kannepalli

    2013-01-01

    Bioactive constituents of Eupatorium adenophorum were investigated for antifungal activity. A structure-antifungal activity relationship of cadinene sesquiterpenes was predicted by evaluating individual derivatives. Cadinene derivatives were extracted from leaves of Eupatorium adenophorum using ethyl acetate. Five cadinene sesquiterpenes were isolated by column chromatography and Preparative Thin Layer Chromatography. Bioactivity of these cadinene sesquiterpenes were evaluated in vitro against four phytopathogenic fungi using poison food technique. Purified sesquiterpenes were spectroscopically elucidated as cadinan-3-ene-2,7-dione (1), 7-hydroxycadinan-3-ene-2-one (2), 5,6-dihydroxycadinan-3-ene-2,7-dione (3), cadinan-3,6-diene-2,7-dione (4) and 2-acetyl-cadinan-3,6-diene-7-one (5). Antifungal evaluation of these compounds against pathogenic fungi was found to be selective. Compound 1 was highly inhibitory towards S. rolfsii (ED50 181.60 ± 0.58 μgmL(-1)) and R. solani (ED50 189.74 ± 1.03 μgmL(-1)). Availability of plant material and significant antifungal activity makes the plant a potential source of antifungal agent and that can be exploited for the development of a natural fungicide.

  14. Chloroquine sensitizes biofilms of Candida albicans to antifungal azoles.

    PubMed

    Shinde, Ravikumar Bapurao; Raut, Jayant Shankar; Chauhan, Nitin Mahendra; Karuppayil, Sankunny Mohan

    2013-01-01

    Biofilms formed by Candida albicans, a human pathogen, are known to be resistant to different antifungal agents. Novel strategies to combat the biofilm associated Candida infections like multiple drug therapy are being explored. In this study, potential of chloroquine to be a partner drug in combination with four antifungal agents, namely fluconazole, voriconazole, amphotericin B, and caspofungin, was explored against biofilms of C. albicans. Activity of various concentrations of chloroquine in combination with a particular antifungal drug was analyzed in a checkerboard format. Growth of biofilm in presence of drugs was analyzed by XTT-assay, in terms of relative metabolic activity compared to that of drug free control. Results obtained by XTT-metabolic assay were confirmed by scanning electron microscopy. The interactions between chloroquine and four antifungal drugs were determined by calculating fractional inhibitory concentration indices. Azole resistance in biofilms was reverted significantly (p<0.05) in presence of 250μg/mL of chloroquine, which resulted in inhibition of biofilms at very low concentrations of antifungal drugs. No significant alteration in the sensitivity of biofilms to caspofungin and amphotericin B was evident in combination with chloroquine. This study for the first time indicates that chloroquine potentiates anti-biofilm activity of fluconazole and voriconazole.

  15. Antifungal-protein production in maize (Zea mays) suspension cultures.

    PubMed

    Perri, Fabio; Della Penna, Serena; Rufini, Francesca; Patamia, Maria; Bonito, Mariantonietta; Angiolella, Letizia; Vitali, Alberto

    2009-04-01

    The growing emergency due to the phenomenon of drug resistance to micro-organisms has pushed forward the search for new potential drug alternatives to those already in use. Plants represent a suitable source of new antifungal molecules, as they produce a series of defensive proteins. Among them are the PRPs (pathogenesis-related proteins), shown to be effective in vitro against human pathogens. An optimized and established cell-suspension culture of maize (Zea mays) was shown to constitutively secrete in the medium a series of PRPs comprising the antifungal protein zeamatin (P33679) with a final yield of approx. 3 mg/litre. The in-vitro-produced zeamatin possessed antifungal activity towards a clinical strain of the human pathogenic yeast Candida albicans, an activity comparable with the one reported for the same protein extracted from maize seeds. Along with zeamatin, other PRPs were expressed: a 9 kDa lipid-transfer protein, a 26 kDa xylanase inhibitor and a new antifungal protein, PR-5. A fast, two-step chromatographic procedure was set up allowing the complete purification of the proteins considered, making this cell line a valuable system for the production of potential antifungal agents in a reliable and easy way.

  16. Antifungal activity of multifunctional Fe 3O 4-Ag nanocolloids

    NASA Astrophysics Data System (ADS)

    Chudasama, Bhupendra; Vala, Anjana K.; Andhariya, Nidhi; Upadhyay, R. V.; Mehta, R. V.

    2011-05-01

    In recent years, rapid increase has been observed in the population of microbes that are resistant to conventionally used antibiotics. Antifungal drug therapy is no exception and now resistance to many of the antifungal agents in use has emerged. Therefore, there is an inevitable and urgent medical need for antibiotics with novel antimicrobial mechanisms. Aspergillus glaucus is the potential cause of fatal brain infections and hypersensitivity pneumonitis in immunocompromised patients and leads to death despite aggressive multidrug antifungal therapy. In the present article, we describe the antifungal activity of multifunctional core-shell Fe 3O 4-Ag nanocolloids against A. glaucus isolates. Controlled experiments are also carried out with Ag nanocolloids in order to understand the role of core (Fe 3O 4) in the antifungal action. The minimum inhibitory concentration (MIC) of nanocolloids is determined by the micro-dilution method. MIC of A. glaucus is 2000 μg/mL. The result is quite promising and requires further investigations in order to develop a treatment methodology against this death causing fungus in immunocompromised patients.

  17. New targets and delivery systems for antifungal therapy.

    PubMed

    Walsh, T J; Viviani, M A; Arathoon, E; Chiou, C; Ghannoum, M; Groll, A H; Odds, F C

    2000-01-01

    Development of new approaches for treatment of invasive fungal infections encompasses new delivery systems for approved and investigational compounds, as well as exploiting the cell membrane, cell wall and virulence factors as putative antifungal targets. Novel delivery systems consisting of cyclodextrins, cochleates, nanoparticles/nanospheres and long circulating ('stealth') liposomes, substantially modulate the pharmacokinetics of existing compounds, and may also be useful to enhance the delivery of antifungal agents to sites of infection. Further insights into the structure-activity relationship of the antifungal triazoles that target the biosynthesis of ergosterol in the fungal cell membrane have led to the development of highly potent broad spectrum agents, including posaconazole, ravuconazole and voriconazole. Similarly, a novel generation of cell-wall active semisynthetic echinocandin 1,3 beta-glucan inhibitors (caspofungin, FK463, and VER-002) has entered clinical development. These agents have potent and broad-spectrum activity against Candida spp, and potentially useful activity against Aspergillus spp. and Pneumocystis carinii. The ongoing convergence of the fields of molecular pathogenesis, antifungal pharmacology and vaccine development will afford the opportunity to develop novel targets to complement the existing antifungal armamentarium.

  18. Natural products--antifungal agents derived from plants.

    PubMed

    Arif, Tasleem; Bhosale, J D; Kumar, Naresh; Mandal, T K; Bendre, R S; Lavekar, G S; Dabur, Rajesh

    2009-07-01

    A new spectrum of human fungal infections is increasing due to increased cancer, AIDS, and immunocompromised patients. The increased use of antifungal agents also resulted in the development of resistance to the present drugs. It makes necessary to discover new classes of antifungal compounds to cure fungal infections. Plants are rich source of bioactive secondary metabolites of wide variety such as tannins, terpenoids, saponins, alkaloids, flavonoids, and other compounds, reported to have in vitro antifungal properties. Since the plant kingdom provides a useful source of lead compounds of novel structure, a wide-scale investigation of species from the tropics has been considered. Therefore, the research on natural products and compounds derived from natural products has accelerated in recent years due to their importance in drug discovery. A series of molecules with antifungal activity against different strains of fungus have been found in plants, which are of great importance to humans. These molecules may be used directly or considered as a precursor for developing better molecules. This review attempts to summarize the current status of important antifungal compounds from plants.

  19. A Comparison of Descriptive and Functional Analyses of Inappropriate Mealtime Behavior.

    PubMed

    Borrero, Carrie S W; England, Jennie D; Sarcia, Ben; Woods, Julia N

    2016-12-01

    In recent years, rather than being used to assess the potential function of a response, descriptive assessment methods have been applied to evaluate potential consequences or contingencies for problem behavior (Borrero, Woods, Borrero, Masler, & Lesser in Journal of Applied Behavior Analysis, 43, 71-88. doi: 10.1901/jaba.2010.43-71, 2010) or to assist with designing baseline conditions to approximate caregiver behavior (Casey et al. in Behavior Modification, 33, 537-558. doi: 10.1177/0145445509341457, 2009). It has been shown that descriptive assessments of some forms of problem behavior (e.g., self-injury, aggression) are not good indicators of behavioral function and should not be used exclusively when conducting functional behavior assessments (Thompson & Iwata in Journal of Applied Behavior Analysis, 40, 333-338. doi: 10.1901/jaba.2007.56.06/epdf, 2007). However, the extent to which descriptive assessments of inappropriate mealtime behavior can predict behavioral function is not yet clear. We conducted descriptive assessments of inappropriate mealtime behavior and compared the results to functional analyses for ten children with severe food refusal. Results showed that, for 71 % of participants, the descriptive and functional analyses matched. These results suggest that the correspondence between descriptive and functional analyses, at least for inappropriate mealtime behavior, may be higher than that for other forms of problem behavior.

  20. Characteristics of the overflow pollution of storm drains with inappropriate sewage entry.

    PubMed

    Yin, Hailong; Lu, Yi; Xu, Zuxin; Li, Huaizheng; Schwegler, Benedict R

    2017-02-01

    To probe the overflow pollution of separate storm drains with inappropriate sewage entries, in terms of the relationship between sewage entries and the corresponding dry-weather and wet-weather overflow, the monitoring activities were conducted in a storm drainage system in the Shanghai downtown area (374 ha). In this study site, samples from inappropriately entered dry-weather sewage and the overflow due to storm pumps operation on dry-weather and wet-weather days were collected and then monitored for six water quality constituents. It was found that overflow concentrations of dry-weather period could be higher than those of wet-weather period; under wet-weather period, the overflow concentrations of storm drains were close to or even higher than that of combined sewers. Relatively strong first flush mostly occurred under heavy rain that satisfied critical rainfall amount, maximum rainfall intensity, and maximum pumping discharge, while almost no first flush effect or only weak first flush effect was found for the other rainfall events. Such phenomenon was attributed to lower in-line pipe storage as compared to that of the combined sewers, and serious sediment accumulation within the storm pipes due to sewage entry. For this kind of system, treating a continuous overflow rate is a better strategy than treating the maximum amount of early part of the overflow. Correcting the key inappropriate sewage entries into storm drains should also be focused.

  1. Misoperation of CT automatic tube current modulation systems with inappropriate patient centering: phantom studies.

    PubMed

    Matsubara, Kosuke; Koshida, Kichiro; Ichikawa, Katsuhiro; Suzuki, Masayuki; Takata, Tadanori; Yamamoto, Tomoyuki; Matsui, Osamu

    2009-04-01

    Inappropriate patient centering on the gantry changes the size of the localizer radiographs used for CT examinations, influencing the operation of CT automatic tube current modulation because tube current is controlled with information from localizer radiographs. The purpose of this study was to examine the influence of inappropriate patient centering on the gantry isocenter on automatic tube current modulation. An elliptical phantom was scanned with four automatic tube current modulation techniques after acquisition of localizer radiographs in the horizontal and vertical directions with the phantom center shifted from the gantry isocenter in the vertical direction. After scanning, the magnification rate of the frontal localizer radiographs, tube current-time product, and image noise were examined. On phantom studies, the magnification rate of localizer radiographs showed a linear relation to the vertical deviation of the phantom from the gantry isocenter. From 50 mm above to 50 mm below the gantry isocenter, tube current-time products ranged from 75% to 141% compared with those at the gantry isocenter. In addition, increases and decreases in the amount of image noise related to changes in tube current-time product were confirmed. Inappropriate patient centering causes misoperation of automatic tube current modulation systems, in which tube current is controlled with information from localizer radiographs, and thus causes increases in tube current or image noise.

  2. Prevalence of inappropriate antibiotic prescriptions after the great east Japan earthquake, 2011.

    PubMed

    Iwata, Kentaro; Fukuchi, Takahiko; Hirai, Midori; Yoshimura, Kenichi; Kanatani, Yasuhiro

    2017-04-01

    Few studies have investigated the appropriateness of antibiotic use in postdisaster settings. We retrospectively evaluated clinical databases on health care delivered at clinics near shelters set up after the Great East Japan Earthquake, 2011. We defined appropriate, acceptable, and inappropriate antibiotic use for each diagnostic category, by applying and adopting precedent studies and clinical guidelines. From March to July, 2011, a total of 23,704 clinic visits occurred at 98 shelters with 7934 residents. Oral antibiotics were prescribed a total of 2253 times. The median age of the patients was 48.5 years old (range 0-97), and 43.7% were male. Of 2253 antibiotic prescriptions, 1944 were judged to be inappropriate (86.3% 95% CI 84.8%-87.7%). The most prescribed antibiotic was clarithromycin (646 times, 28.7%), followed by cefcapene pivoxil (644 times, 28.6%), levofloxacin (380, 16.9%), cefdinir (194, 8.6%), and cefditren pivoxil (98, 4.4%). The most frequent diagnosis for which antibiotics were prescribed was upper respiratory infection (URI, 1040 visits, 46.2%), followed by acute bronchitis (369, 16.4%), pharyngitis (298, 13.2%), traumatic injuries (194, 8.6%), acute gastroenteritis (136, 6.0%), urinary tract infections (UTIs, 123, 5.5%), and allergic rhinitis (5.1%). The majority of antibiotics prescribed at clinics after the Great East Japan Earthquake was inappropriate. Significant improvement of the use of antibiotics in postdisaster settings should be sought immediately in Japan.

  3. Medication regimen complexity and prevalence of potentially inappropriate medicines in older patients after hospitalisation.

    PubMed

    Chang, Wei Terk; Kowalski, Stefan R; Sorich, Wassana; Alderman, Christopher P

    2017-08-01

    Background There is a relative paucity of information to characterise potential changes in medication regimen complexity and prevalence of prescribing of potentially inappropriate medications after hospitalisation, both in Australia and elsewhere. Objective To evaluate medication regimen complexity and the prevalence of potentially inappropriate medications before and after admission to hospital. Setting General medical units of a tertiary care hospital in Australia. Methods Retrospective cohort study of patients aged 65 years and above. Medication complexity was measured by using the Medication Regimen Complexity Index (MRCI). Main outcome measure The primary outcome was the change in the Medication Regimen Complexity Index for all prescribed medications after hospitalization. Results A convenience sample of 100 patients was included in the study. There was a significant change in the mean medication complexity score (as measured using the MRCI), increasing from 29 at the time of admission to 32 at the time of discharge (p < 0.05). Factors such as baseline medication regimen complexity (pre-admission MRCI) and length of stay in the hospitals appear to influence the change in medication complexity. However, the proportion of patients prescribed at least one potentially inappropriate medicine (PIM) decreased significantly, from 52% pre-hospitalization to 42% at discharge (p = 0.04). Conclusions Relative to the time of admission, overall medication complexity increased and the proportion of patients who were prescribed PIMs decreased after hospitalisation.

  4. Secondary use of empirical research data in medical ethics papers on gamete donation: forms of use and pitfalls.

    PubMed

    Provoost, Veerle

    2015-03-01

    This paper aims to provide a description of how authors publishing in medical ethics journals have made use of empirical research data in papers on the topic of gamete or embryo donation by means of references to studies conducted by others (secondary use). Rather than making a direct contribution to the theoretical methodological literature about the role empirical research data could play or should play in ethics studies, the focus is on the particular uses of these data and the problems that can be encountered with this use. In the selection of papers examined, apart from being used to describe the context, empirical evidence was mainly used to recount problems that needed solving. Few of the authors looked critically at the quality of the studies they quoted, and several instances were found of empirical data being used poorly or inappropriately. This study provides some initial baseline evidence that shows empirical data, in the form of references to studies, are sometimes being used in inappropriate ways. This suggests that medical ethicists should be more concerned about the quality of the empirical data selected, the appropriateness of the choice for a particular type of data (from a particular type of study) and the correct integration of this evidence in sound argumentation. Given that empirical data can be misused also when merely cited instead of reported, it may be worthwhile to explore good practice requirements for this type of use of empirical data in medical ethics.

  5. [Recommendations in the empiric anti-infective agents of intra-abdominal infection].

    PubMed

    Guirao, X; Arias, J; Badía, J M; García-Rodríguez, J A; Mensa, J; Alvarez-Lerma, F; Borges, M; Barberán, J; Maseda, E; Salavert, M; Llinares, P; Gobernado, M; García Rey, C

    2009-09-01

    A significant number of patients with abdominal infection develop advanced stages of infection and mortality is still above 20%. Failure is multifactorial and is associated with an increase of bacterial resistance, inappropriate empirical treatment, a higher comorbidity of patients and poor source control of infection. These guidelines discuss each of these problems and propose measures to avoid the failure based on the best current scientific evidence.

  6. [Recommendations in the empiric anti-infective agents of intra-abdominal infection].

    PubMed

    Guirao, Xavier; Arias, Javier; Badía, Josep M A; García-Rodríguez, José A; Mensa, José; Alvarez-Lerma, Francisco; Borges, Marcio; Barberán, José; Maseda, Emilio; Salavert, Miguel; Llinares, Pedro; Gobernado, Miguel; García Rey, César

    2010-02-01

    A significant number of patients with abdominal infection develop advanced stages of infection and mortality is still above 20%. Failure is multifactorial and is associated with an increase of bacterial resitance, inappropriate empirical treatment, a higher comorbidity of patients and poor source control of infection. These guidelines discuss each of these problems and propose measures to avoid the failure based on the best current scientific evidence. Copyright 2009 AEC. Published by Elsevier Espana. All rights reserved.

  7. Exploring the molecular basis of antifungal synergies using genome-wide approaches

    USDA-ARS?s Scientific Manuscript database

    This is a review article summarizing genomic profiling strategies for determining the mechanism of action of antifungal synergies, and highlighting the potential applications of these technologies. Given the limitations of currently available antifungal agents and the development of drug resistance...

  8. Synthesis of natural acylphloroglucinol-based antifungal compounds against Cryptococcus species

    USDA-ARS?s Scientific Manuscript database

    Thirty-five analogs of naturally occurring acylphloroglucinols were designed and synthesized to identify antifungal compounds against Cryptococcus spp. that causes the life-threatening disseminated cryptococcosis. In vitro antifungal testing showed that 17 compounds were active against C. neoformans...

  9. Decreased delivery of inappropriate shocks achieved by remote monitoring of ICD: a substudy of the ECOST trial.

    PubMed

    Guédon-Moreau, Laurence; Kouakam, Claude; Klug, Didier; Marquié, Christelle; Brigadeau, François; Boulé, Stéphane; Blangy, Hugues; Lacroix, Dominique; Clémenty, Jacques; Sadoul, Nicolas; Kacet, Salem

    2014-07-01

    Inappropriate shocks remain a highly challenging complication of implantable cardioverter defibrillators (ICD). We examined whether automatic wireless remote monitoring (RM) of ICD, by providing early notifications of triggering events, lowers the incidence of inappropriate shocks. We studied 433 patients randomly assigned to RM (n = 221; active group) versus ambulatory follow-up (n = 212; control group). Patients in the active group were seen in the ambulatory department once a year, unless RM reported an event requiring an earlier ambulatory visit. Patients in the control group were seen in the ambulatory department every 6 months. The occurrence of first and further inappropriate shocks, and their causes in each group were compared. The characteristics of the study groups, including pharmaceutical regimens, were similar. Over a follow-up of 27 months, 5.0% of patients in the active group received ≥1 inappropriate shocks versus 10.4% in the control group (P = 0.03). A total of 28 inappropriate shocks were delivered in the active versus 283 in the control group. Shocks were triggered by supraventricular tachyarrhythmias (SVTA) in 48.5%, noise oversensing in 21.2%, T wave oversensing in 15.2%, and lead dysfunction in 15.2% of patients. The numbers of inappropriate shocks delivered per patient, triggered by SVTA and by lead dysfunction, were 74% and 98% lower, respectively, in the active than in the control group. RM was highly effective in the long-term prevention of inappropriate ICD shocks. © 2014 Wiley Periodicals, Inc.

  10. Antifungal Resistance, Metabolic Routes as Drug Targets, and New Antifungal Agents: An Overview about Endemic Dimorphic Fungi

    PubMed Central

    Parente-Rocha, Juliana Alves; Bailão, Alexandre Melo; Amaral, André Correa; Paccez, Juliano Domiraci; Borges, Clayton Luiz

    2017-01-01

    Diseases caused by fungi can occur in healthy people, but immunocompromised patients are the major risk group for invasive fungal infections. Cases of fungal resistance and the difficulty of treatment make fungal infections a public health problem. This review explores mechanisms used by fungi to promote fungal resistance, such as the mutation or overexpression of drug targets, efflux and degradation systems, and pleiotropic drug responses. Alternative novel drug targets have been investigated; these include metabolic routes used by fungi during infection, such as trehalose and amino acid metabolism and mitochondrial proteins. An overview of new antifungal agents, including nanostructured antifungals, as well as of repositioning approaches is discussed. Studies focusing on the development of vaccines against antifungal diseases have increased in recent years, as these strategies can be applied in combination with antifungal therapy to prevent posttreatment sequelae. Studies focused on the development of a pan-fungal vaccine and antifungal drugs can improve the treatment of immunocompromised patients and reduce treatment costs. PMID:28694566

  11. Antifungal prophylaxis following reduced-intensity stem cell transplantation.

    PubMed

    Kami, M; Murashige, N; Tanaka, Y; Narimatsu, H

    2006-12-01

    Reduced-intensity stem cell transplantation (RIST) has been developed to be a novel curative option for advanced hematologic diseases. Its minimal toxicity allows for transplantation in patients with advanced age or with organ dysfunction. Young patients without comorbidity can undergo RIST as outpatients. However, fungal infection remains an important complication in RIST. Given the poor prognosis of fungal infection, prophylaxis is critical in its management. The prophylactic strategy is recently changing with the development of RIST. Hospital equipment is important for fungal prophylaxis; however, the median day for the development of fungal infection is day 100, when most RIST patients are followed as outpatients. The focus of fungal management after RIST needs to shift from in-hospital equipment to oral antifungals. Various antifungals have recently been developed and introduced for clinical use. A major change in antifungal management will probably occur within several years.

  12. Design of amphotericin B oral formulation for antifungal therapy.

    PubMed

    Liu, Min; Chen, Meiwan; Yang, Zhiwen

    2017-11-01

    Amphotericin B (AmB) remains the "gold standard" for systemic antifungal therapy, even though new drugs are emerging as the attractive antifungal agents. Since AmB has negligible oral absorption as a consequence of its unfavorable physicochemical characterizations, its use is restricted to parenteral administration which is accompanied by severe side effects. As greater understanding of the gastrointestinal tract has developed, the advanced drug delivery systems are emerging with the potential to overcome the barriers of AmB oral delivery. Much research has demonstrated that oral AmB formulations such as lipid formulations may have beneficial therapeutic efficacy with reduced adverse effects and suitable for clinical application. Here we reviewed the different formulation strategies to enhance oral drug efficacy, and discussed the current trends and future perspectives for AmB oral administration in the treatment of antifungal infections.

  13. Targeting efflux pumps to overcome antifungal drug resistance.

    PubMed

    Holmes, Ann R; Cardno, Tony S; Strouse, J Jacob; Ivnitski-Steele, Irena; Keniya, Mikhail V; Lackovic, Kurt; Monk, Brian C; Sklar, Larry A; Cannon, Richard D

    2016-08-01

    Resistance to antifungal drugs is an increasingly significant clinical problem. The most common antifungal resistance encountered is efflux pump-mediated resistance of Candida species to azole drugs. One approach to overcome this resistance is to inhibit the pumps and chemosensitize resistant strains to azole drugs. Drug discovery targeting fungal efflux pumps could thus result in the development of azole-enhancing combination therapy. Heterologous expression of fungal efflux pumps in Saccharomyces cerevisiae provides a versatile system for screening for pump inhibitors. Fungal efflux pumps transport a range of xenobiotics including fluorescent compounds. This enables the use of fluorescence-based detection, as well as growth inhibition assays, in screens to discover compounds targeting efflux-mediated antifungal drug resistance. A variety of medium- and high-throughput screens have been used to identify a number of chemical entities that inhibit fungal efflux pumps.

  14. Antimicrobial and antifungal effects of tissue conditioners containing a photocatalyst.

    PubMed

    Uchimaru, Masayuki; Sakai, Takako; Moroi, Ryoji; Shiota, Susumu; Shibata, Yukie; Deguchi, Mikito; Sakai, Hidetaka; Yamashita, Yoshihisa; Terada, Yoshihiro

    2011-01-01

    This study examined the antimicrobial/antifungal ability of a tissue conditioner containing a photocatalyst for Escherichia coli, Streptococcus mutans, Staphylococcus aureus and Candida albicans. The photocatalyst was mixed with tissue conditioners powders at concentrations of 0, 10, 15, and 20 wt%. Tissue conditioners powders containing a photocatalyst were mixed with liquid to make test specimens. Test specimens inoculated by each microorganism were irradiated by ultraviolet light for 0-, 2- and 4 hours. The antimicrobial/antifungal effects were evaluated by the CFU technique. The CFU values of each microorganism for tissue conditioners containing a photocatalyst showed significant decrease following UV-irradiation. The improvement in antimicrobial/antifungal effects was concomitant with the increase of the mixing ratio and the irradiation time. Therefore, the results indicated that tissue conditioners containing a photocatalyst might have photocatalytic ability.

  15. Comparison of antifungal activities of Vietnamese citrus essential oils.

    PubMed

    Van Hung, Pham; Chi, Pham Thi Lan; Phi, Nguyen Thi Lan

    2013-03-01

    Citrus essential oils (EOs) are volatile compounds from citrus peels and widely used in perfumes, cosmetics, soaps and aromatherapy. In this study, inhibition of citrus EOs extracted from Vietnamese orange (Citrus sinensis), mandarin (Citrus reticulata Blanco), pomelo (Citrus grandis Osbeck) and lime (Citrus aurantifolia Swingle) on the growth of plant pathogenic fungi, Mucor hiemalis, Penicillium expansum and Fusarium proliferatum was investigated. The EOs of the citrus peels were obtained by cold-pressing method and the antifungal activity of EOs was evaluated using the agar dilution method. The results show that the EOs had significant antifungal activity. Lime EO was the best inhibitor of M. hiemalis and F. proliferatum while pomelo EO was the most effective against P. expansum. These results indicate that citrus EOs can be used as antifungal natural products in the food, pharmaceutical and cosmetic industries.

  16. Antifungal drug resistance among Candida species: mechanisms and clinical impact.

    PubMed

    Sanguinetti, Maurizio; Posteraro, Brunella; Lass-Flörl, Cornelia

    2015-06-01

    The epidemiology of Candida infections has changed in recent years. Although Candida albicans is still the main cause of invasive candidiasis in most clinical settings, a substantial proportion of patients is now infected with non-albicans Candida species. The various Candida species vary in their susceptibility to the most commonly used antifungal agents, and the intrinsic resistance to antifungal therapy seen in some species, along with the development of acquired resistance during treatment in others, is becoming a major problem in the management of Candida infection. A better understanding of the mechanisms and clinical impact of antifungal drug resistance is essential for the efficient treatment of patients with Candida infection and for improving treatment outcomes. Herein, we report resistance to the azoles and echinocandins among Candida species.

  17. Antifungal susceptibility against yeasts isolated from pediatric oncology patients.

    PubMed

    Kersun, L S; Reilly, A F; Ingram, M E; Nicholaou, M J; McGowan, K L

    2008-06-01

    Yeast infections cause morbidity in children with cancer and we evaluated species distribution and antifungal susceptibilities of the etiologic agents in this group. Specimens from 58 children yielded 64 cultures positive for yeasts. Central venous catheters were present in 56 (97%) of the children and neutrophil counts were <500 cells/ml3 in 34% of the patients. Twenty-two (38%) had received recent antifungal treatment, with 15 (25%) receiving fluconazole (FLU) prophylaxis. The Candida isolates recovered from four (27%) of the children on FLU prophylaxis, were resistant to this drug. Candida albicans isolates were susceptible to 100% of antifungals tested, whereas non-C. albicans Candida spp. were variable in their susceptibility patterns. FLU prophylaxis minimally affected susceptibility.

  18. Mechanisms of antifungal drug resistance in Candida dubliniensis.

    PubMed

    Coleman, David C; Moran, Gary P; McManus, Brenda A; Sullivan, Derek J

    2010-06-01

    Candida dubliniensis was first described in 1995 and is the most closely related species to the predominant human fungal pathogen Candida albicans. C. dubliniensis is significantly less prevalent and less pathogenic than C. albicans and is primarily associated with infections in HIV-infected individuals and other immunocompromised cohorts. The population structure of C. dubliniensis consists of three well-defined major clades and is significantly less diverse than C. albicans. The majority of C. dubliniensis isolates are susceptible to antifungal drugs commonly used to treat Candida infections. To date only two major patterns of antifungal drug resistance have been identified and the molecular mechanisms of these are very similar to the resistance mechanisms that have been described previously in C. albicans. However, significant differences are evident in the predominant antifungal drug mechanisms employed by C. dubliniensis, differences that reflect its more clonal nature, its lower prevalence and characteristics of its genome, the complete sequence of which has only recently been determined.

  19. Antifungal Effect of Chitosan as Ca2+ Channel Blocker

    PubMed Central

    Lee, Choon Geun; Koo, Ja Choon; Park, Jae Kweon

    2016-01-01

    The aim of this study was to investigate antifungal activity of a range of different molecular weight (MW) chitosan against Penicillium italicum. Our results demonstrate that the antifungal activity was dependent both the MW and concentration of the chitosan. Among a series of chitosan derived from the hydrolysis of high MW chitosan, the fractions containing various sizes of chitosan ranging from 3 to 15 glucosamine units named as chitooligomers-F2 (CO-F2) was found to show the highest antifungal activity against P. italicum. Furthermore, the effect of CO-F2 toward this fungus was significantly reduced in the presence of Ca2+, whereas its effect was recovered by ethylenediaminetetraacetic acid, suggesting that the CO-F2 acts via disruption of Ca2+ gradient required for survival of the fungus. Our results suggest that CO-F2 may serve as potential compounds to develop alternatives to synthetic fungicides for the control of the postharvest diseases. PMID:27298599

  20. Hsp21 Potentiates Antifungal Drug Tolerance in Candida albicans

    PubMed Central

    Mayer, François L.; Wilson, Duncan; Hube, Bernhard

    2013-01-01

    Systemic infections of humans with the fungal pathogen Candida albicans are associated with a high mortality rate. Currently, efficient treatment of these infections is hampered by the relatively low number of available antifungal drugs. We recently identified the small heat shock protein Hsp21 in C. albicans and demonstrated its fundamental role for environmental stress adaptation and fungal virulence. Hsp21 was found in several pathogenic Candida species but not in humans. This prompted us to investigate the effects of a broad range of different antifungal drugs on an Hsp21-null C. albicans mutant strain. Our results indicate that combinatorial therapy targeting Hsp21, together with specific antifungal drug targets, has strong synergistic potential. In addition, we demonstrate that Hsp21 is required for tolerance to ethanol-induced stress and induction of filamentation in response to pharmacological inhibition of Hsp90. These findings might pave the way for the development of new treatment strategies against Candida infections. PMID:23533680