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Sample records for inappropriate empiric antifungal

  1. Outcome of empirical or targeted antifungal therapy after antifungal prophylaxis in febrile neutropenia.

    PubMed

    Hahn-Ast, C; Felder, L; Mayer, K; Mückter, S; Ruhnke, M; Hein, R; Hellmich, M; Schwab, K; Rachow, T; Brossart, P; von Lilienfeld-Toal, M

    2016-05-01

    Azole prophylaxis has been shown to be effective in preventing invasive fungal infections (IFIs) and increasing survival in patients with prolonged neutropenia after myelosuppressive chemotherapy for haematological malignancies. Similarly, empirical antifungal therapy for persistent neutropenic fever has been shown to reduce IFI-related mortality. However, to date, there is little information with regard to the outcome of patients who receive both strategies. Here, we present our retrospective data on three cohorts of patients receiving empirical or targeted antifungal therapy after different antifungal prophylaxis regimens. All records from patients who received myelosuppressive induction chemotherapy for acute myelogenous leukemia (AML) in our centre from 2004-2010 were analysed. From 2004-2006, itraconazole was used as antifungal prophylaxis; for the first 6 months in 2007, local polyenes and from mid-2007 till 2010, posaconazole. Data of 315 courses of chemotherapy in 211 patients were analysed. Antifungal therapy (empirical or targeted, time point and antifungal agent at the physician's discretion) was initiated in 50/174 (29 %), 7/18 (39 %) and 34/123 courses (28 %, p = 0.615) in the itra cohort, the cohort without systemic prophylaxis and the posa cohort, respectively, and was effective in 24/50 (48 %), 5/7 (71 %) and 22/34 courses (65 %, p = 0.221), respectively. IFI occurred in 25/174 (14 %), 4/18 (22 %) and 16/123 (13 %) courses, respectively (p = 0.580). IFI-related survival was not different in the three cohorts. Antifungal treatment in patients with AML who received azole prophylaxis resulted in the expected efficacy-importantly, prior posaconazole prophylaxis did not render subsequent antifungal treatment less effective than prior itraconazole prophylaxis. PMID:27021301

  2. Impact of Inappropriate Empiric Antimicrobial Therapy on Mortality of Septic Patients with Bacteremia: A Retrospective Study

    PubMed Central

    Lueangarun, Saoraya; Leelarasamee, Amorn

    2012-01-01

    Background. Inappropriate empiric antimicrobials could be a major cause of unfavorable mortality rates in co-morbid patients. This study aimed to assess the prevalence and impact of first-dose and 24-hour inappropriate antimicrobials on mortality rates of bacteremic septic patients. Methods. A retrospective cohort study was employed. Case record forms of patients diagnosed as sepsis, severe sepsis, or septic shock with positive hemoculture during 2009 were retrieved from the medical wards, Siriraj Hospital. Demographic data, antimicrobial use, types of bacteria isolated from blood and susceptibilities, patients' comorbidities, 28-day and overall mortality rates were collected and analyzed. Results. There were 229 cases, mean age (SD) of 63.5 (17.2) years and mean (SD) APACHE II score of 24.7 (6.8). The prevalence of first-dose and 24-hour inappropriate antimicrobials was 29.7% and 25.3%, respectively. The 28-day and overall mortality rates between first-dose inappropriate and appropriate antimicrobial were 67.6% versus 60.2% (P = 0.301) and 75.0% versus 68.3% (P = 0.345), consequently. Patients with septic shock and inappropriate first-dose antimicrobials significantly had higher 28-day mortality rate (61.6% versus 41.9%; P = 0.017). Conclusion. Higher mortality rates in bacteremic septic patients were substantially associated with inappropriate first-dose antimicrobials and 3-hour delayed antimicrobial administration after sepsis diagnosis. PMID:22919379

  3. Empirical antifungal therapy with an echinocandin in critically-ill patients: prospective evaluation of a pragmatic Candida score-based strategy in one medical ICU

    PubMed Central

    2014-01-01

    Background Invasive candidiasis (IC) is a life-threatening ICU-acquired infection. A strong correlation between time to antifungal therapy (AFT) administration and outcome has been established. Empirical therapy benefit should be balanced with the risk of echinocandin overuse. We assessed therefore a decision rule that aimed at guiding empirical therapy. Methods A 45-month prospective cohort study in a teaching medical ICU. All of the patients with suspected IC (uncontrolled sepsis despite broad spectrum antibiotics without any bacterial proven infection in patients with Candida score ≥ 3 points including multifocal Candida sp. colonization) were eligible. The primary endpoint was proven IC diagnosis (i.e., candidemia) following treatment onset. Timing of AFT administration was also investigated in those latter patients. Antifungal therapy step-down and discontinuation was done according to international guidelines in patients with candidemia. Otherwise, echinocandin discontinuation was encouraged in patients without proven IC, excepting when a clinical improvement was achieved without any other explanation that antifungals initiation (i.e., probable IC). In addition, a survival multivariate analysis using a Cox model was conducted. Results Fifty-one patients were given an echinocandin with respect to our decision rule. Among them, candidemia was diagnosed thereafter in 9 patients. Over the same period, antifungal therapy was triggered by candidemia announcement (i.e., definite therapy) in 12 patients who did not fulfill criteria for empirical therapy before. Time elapsed from candidemia onset to echinocandin therapy initiation was shortened (0.4 [0.5] vs. 2.4 [2.8] hours; p = 0.04) when it was given empirically. In addition, 18 patients clinically improved under empirical antifungal therapy without any obvious other explanation, despite IC remained unproven. Moreover, echinocandin exposure duration was independently related to survival in those patients

  4. Meta-analysis of prophylactic or empirical antifungal treatment versus placebo or no treatment in patients with cancer complicated by neutropenia.

    PubMed Central

    Gøtzsche, P. C.; Johansen, H. K.

    1997-01-01

    OBJECTIVE: To determine whether antifungal agents given prophylactically or empirically decrease morbidity and mortality in patients with cancer complicated by neutropenia. DESIGN: Meta-analysis of randomised trials of amphotericin B, various lipid soluble formulations of amphotericin B (for example, AmBisome), fluconazole, ketoconazole, miconazole, or itraconazole compared with placebo or no treatment. SETTING: Trials conducted anywhere in the world. SUBJECTS: Patients with cancer complicated by neutropenia. MAIN OUTCOME MEASURES: Mortality, invasive fungal infection (defined as positive blood culture, oesophageal candidiasis, or lung or deep tissue infection), and colonisation. RESULTS: 24 trials with 2758 randomised patients were reviewed; the total number of deaths was 434. Prophylactic or empirical treatment with antifungals as a group bad no effect on mortality (odds ratio 0.92; 95% confidence interval 0.74 to 1.14). Amphotericin B decreased mortality significantly (0.58; 0.37 to 0.93) but the studies were small and the difference in number of deaths was only 15. Antifungal treatment decreased the incidence of invasive fungal infection (0.47; 0.35 to 0.64) and fungal colonisation (0.45; 0.30 to 0.69). For every 73 patients treated (95% confidence interval to 48 to 158) one case of fungal invasion was prevented in surviving patients. CONCLUSIONS: There seems to be no survival benefit of antifungal agents given prophylactically or empirically to patients with cancer complicated by neutropenia. These agents should be restricted to patients with proved infection and those in randomised trials. A large, definitive placebo controlled trial of amphotericin B is needed. PMID:9154027

  5. Antifungal polypeptides

    DOEpatents

    Altier, Daniel J.; Ellanskaya, Irina; Ellanskaya, legal representative, Natalia; Gilliam, Jacob T.; Hunter-Cevera, Jennie; Presnail, James K.; Schepers, Eric; Simmons, Carl R.; Torok, Tamas; Yalpani, Nasser

    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.

  6. 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. PMID:25707735

  7. Antifungal agents.

    PubMed

    Ryder, N S

    1999-12-01

    At this year's ICAAC Meeting, new data on approximately 20 different antifungal agents were presented, while no new agents were disclosed. Drugs in late development include the triazoles, voriconazole (Pfizer Ltd) and Sch-56592 (Schering-Plough Corp), and the echinocandins, caspofungin (Merck & Co Inc) and FK-463 (Fujisawa Pharmaceutical Co Ltd). In contrast to previous years, presentations on these and earlier developmental compounds were relatively modest in scope, with few significant new data. Little new information appeared on the most recent novel class of agents, the sordarins (Glaxo Wellcome plc). Early clinical results were presented for FK-463, showing acceptable tolerability and dose-dependent efficacy in AIDS-associated esophageal candidiasis. A new liposomal formulation of nystatin (Nyotran; Aronex Pharmaceuticals Inc) was shown to be equivalent to conventional amphotericin B in empiric therapy of presumed fungal infection in neutropenic patients, but with reduced toxicity. Intravenous itraconazole (Janssen Pharmaceutica NV) was an effective prophylactic therapy in invasive pulmonary aspergillosis, while oral itraconazole was discussed as a treatment for fungal infection in heart and liver transplant patients. The allylamine compound, terbinafine (Novartis AG), showed good clinical efficacy against fungal mycetoma, a serious tropical infection. A major highlight was the first presentation of inhibitors of fungal efflux pumps as a strategy for overcoming resistance. MC-510027 (milbemycin alpha-9; Microcide Pharmaceuticals Inc) and its derivatives, potentiated the antifungal activity of triazoles and terbinafine in a number of Candida spp. Another pump inhibitor, MC-005172 (Microcide Pharmaceuticals Inc) showed in vivo potentiation of fluconazole in a mouse kidney infection model. Microcide Pharmaceuticals Inc also presented inhibitors of bacterial efflux pumps. PMID:16113946

  8. Antifungal hydrogels

    PubMed Central

    Zumbuehl, Andreas; Ferreira, Lino; Kuhn, Duncan; Astashkina, Anna; Long, Lisa; Yeo, Yoon; Iaconis, Tiffany; Ghannoum, Mahmoud; Fink, Gerald R.; Langer, Robert; Kohane, Daniel S.

    2007-01-01

    Fungi are increasingly identified as major pathogens in bloodstream infections, often involving indwelling devices. Materials with antifungal properties may provide an important deterrent to these infections. Here we describe amphogel, a dextran-based hydrogel into which amphotericin B is adsorbed. Amphogel kills fungi within 2 h of contact and can be reused for at least 53 days without losing its effectiveness against Candida albicans. The antifungal material is biocompatible in vivo and does not cause hemolysis in human blood. Amphogel inoculated with C. albicans and implanted in mice prevents fungal infection. Amphogel also mitigates fungal biofilm formation. An antifungal matrix with these properties could be used to coat a variety of medical devices such as catheters as well as industrial surfaces. PMID:17664427

  9. The Rasch Model for Achievement Tests--Inappropriate in the Past, Inappropriate Today, Inappropriate Tomorrow.

    ERIC Educational Resources Information Center

    McLean, Leslie D.; Ragsdale, Ronald G.

    1983-01-01

    Robitaille and O'Shea used the Rasch model in developing a set of 40-item mathematics achievement tests. The Rasch model is inappropriate for such a purpose; their article presents the model in a too favorable light and continued application of the model encourages less desirable educational practice and misdirects scarce resources. (BRR)

  10. Conventional management of inappropriate sinus tachycardia.

    PubMed

    Olshansky, Brian; Sullivan, Renee M

    2016-06-01

    Inappropriate sinus tachycardia is a challenging problem to manage. There are limited data on the best method to evaluate and treat the problem. Here, we consider a conventional approach to inappropriate sinus tachycardia. PMID:26164138

  11. Pediatric Antifungal Agents

    PubMed Central

    Cohen-Wolkowiez, Michael; Moran, Cassandra; Benjamin, Daniel K.; Smith, P Brian

    2009-01-01

    Purpose of review In immunocompromised hosts, invasive fungal infections are common and fatal. In the past decade, the antifungal armamentarium against invasive mycoses has expanded greatly. The purpose of this report is to review the most recent literature addressing the use of antifungal agents in children. Recent findings Most studies evaluating the safety and efficacy of antifungal agents are limited to adults. However, important progress has been made in describing the pharmacokinetics and safety of newer antifungal agents in children, including the echinocandins. Summary Dosage guidelines for newer antifungal agents are currently based on adult and limited pediatric data. Because important developmental pharmacology changes occur throughout childhood impacting the pharmacokinetics of these agents, antifungal studies specifically designed for children are necessary. PMID:19741525

  12. 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. PMID:26798851

  13. Antifungal Treatment in Stem Cell Transplantation Centers in Turkey

    PubMed Central

    Akan, Hamdi; Atilla, Erden

    2016-01-01

    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. PMID:25913124

  14. 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…

  15. 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…

  16. Functional analysis of inappropriate mealtime behaviors.

    PubMed Central

    Piazza, Cathleen C; Fisher, Wayne W; Brown, Kimberly A; Shore, Bridget A; Patel, Meeta R; Katz, Richard M; Sevin, Bart M; Gulotta, Charles S; Blakely-Smith, Audrey

    2003-01-01

    The purpose of the current investigation was to apply the functional analysis described by Iwata, Dorsey, Slifer, Bauman, and Richman (1982/1994) to the inappropriate mealtime behaviors of 15 children who had been referred to an intensive program for the assessment and treatment of severe feeding disorders. During Study 1, we conducted descriptive assessments of children and parents during meals. The results of Study 1 showed that parents used the following consequences for inappropriate mealtime behaviors: coaxing and reprimanding, allowing the child to periodically take a break from or avoid eating, and giving the child preferred food or toys following inappropriate behavior. The effects of these consequences were tested systematically in Study 2 when we conducted analogue functional analyses with the children. During alternating meals, one of the consequences typically used by parents consistently followed inappropriate child behavior. Results indicated that these consequences actually worsened behavior for 10 of the 15 children (67%). These results suggested that the analogue functional analysis described by Iwata et al. may be useful in identifying the environmental events that play a role in feeding disorders. PMID:12858984

  17. Antifungal Compounds from Cyanobacteria

    PubMed Central

    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

    2015-01-01

    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. PMID:25871291

  18. New antifungal agents.

    PubMed

    Gupta, Aditya K; Tomas, Elizabeth

    2003-07-01

    Currently, use of standard antifungal therapies can be limited because of toxicity, low efficacy rates, and drug resistance. New formulations are being prepared to improve absorption and efficacy of some of these standard therapies. Various new antifungals have demonstrated therapeutic potential. These new agents may provide additional options for the treatment of superficial fungal infections and they may help to overcome the limitations of current treatments. Liposomal formulations of AmB have a broad spectrum of activity against invasive fungi, such as Candida spp., C. neoformans, and Aspergillus spp., but not dermatophyte fungi. The liposomal AmB is associated with significantly less toxicity and good rates of efficacy, which compare or exceed that of standard AmB. These factors may provide enough of an advantage to patients to overcome the increased costs of these formulations. Three new azole drugs have been developed, and may be of use in both systemic and superficial fungal infections. Voriconazole, ravuconazole, and posaconazole are triazoles, with broad-spectrum activity. Voriconazole has a high bioavailability, and has been used with success in immunocompromised patients with invasive fungal infections. Ravuconazole has shown efficacy in candidiasis in immunocompromised patients, and onychomycosis in healthy patients. Preliminary in vivo studies with posaconazole indicated potential use in a variety of invasive fungal infections including oropharyngeal candidiasis. Echinocandins and pneumocandins are a new class of antifungals, which act as fungal cell wall beta-(1,3)-D-glucan synthase enzyme complex inhibitors. Caspofungin (MK-0991) is the first of the echinocandins to receive Food and Drug Administration approval for patients with invasive aspergillosis not responding or intolerant to other antifungal therapies, and has been effective in patients with oropharyngeal and esophageal candidiasis. Standardization of MIC value determination has improved the

  19. Reducing inappropriate accident and emergency department attendances:

    PubMed Central

    Ismail, Sharif A; Gibbons, Daniel C; Gnani, Shamini

    2013-01-01

    Background Inappropriate attendances may account for up to 40% of presentations at accident and emergency (A&E) departments. There is considerable interest from health practitioners and policymakers in interventions to reduce this burden. Aim To review the evidence on primary care service interventions to reduce inappropriate A&E attendances. Design and setting Systematic review of UK and international primary care interventions. Method Studies published in English between 1 January 1986 and 23 August 2011 were identified from PubMed, the NHS Economic Evaluation Database, the Cochrane Collaboration, and Health Technology Assessment databases. The outcome measures were A&E attendances, patient satisfaction, clinical outcome, and intervention cost. Two authors reviewed titles and abstracts of retrieved results, with adjudication of disagreements conducted by the third. Studies were quality assessed using the Scottish Intercollegiate Guidelines Network checklist system where applicable. Results In total, 9916 manuscripts were identified, of which 34 were reviewed. Telephone triage was the single best-evaluated intervention. This resulted in negligible impact on A&E attendance, but exhibited acceptable patient satisfaction and clinical safety; cost effectiveness was uncertain. The limited available evidence suggests that emergency nurse practitioners in community settings and community health centres may reduce A&E attendance. For all other interventions considered in this review (walk-in centres, minor injuries units, and out-of-hours general practice), the effects on A&E attendance, patient outcomes, and cost were inconclusive. Conclusion Studies showed a negligible effect on A&E attendance for all interventions; data on patient outcomes and cost-effectiveness are limited. There is an urgent need to examine all aspects of primary care service interventions that aim to reduce inappropriate A&E attendance. PMID:24351497

  20. Epidemiology and definition of inappropriate sinus tachycardia.

    PubMed

    Pellegrini, Cara N; Scheinman, Melvin M

    2016-06-01

    Inappropriate sinus tachycardia (IST) is a clinical syndrome lacking formal diagnostic criteria. It is generally defined as an elevated resting heart rate (HR; >90-100 bpm) with an exaggerated response to physical or emotional stress and a clearly sinus mechanism. Clinical manifestations are broad from a complete lack of symptoms to incapacitating incessant tachycardia. Now understood to be relatively prevalent, it is observed to have a generally benign prognosis, though symptoms may persist for years. Whether IST is a single discrete entity or a heterogeneous condition with overlap to other syndromes such as postural orthostatic tachycardia syndrome remains a matter of debate. PMID:26310298

  1. 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. PMID:26310299

  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. 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

  4. Syndrome of inappropriate antidiuresis in doxylamine overdose.

    PubMed

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

    2012-01-01

    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. PMID:23166178

  5. [New antifungal agents: voriconazole and caspofungin].

    PubMed

    Dupont, B

    2003-12-01

    Among new available antifungal agents voriconazole is a new triazole with an intravenous (i.v.) and oral formulation, and caspofungin is an echinocandin, new family with a new mode of action on the cell wall. It is available as an i.v. preparation. Both drugs have a broad spectrum targeting most of the usual pathogens: Candida and Aspergillus, even with low suceptibility or resistance to other antifungals. Voriconazole is also active on Scedosporium and Fusarium. The efficacy of these molecules was established in vitro and in experimental infections in animals either normal or immunosuppressed. Voriconazole is active in oropharyngeal and esophageal candidiasis, in refractory invasive candidiasis and as a first line treatment of invasive aspergillosis with better results than amphotéricine B. It was also effective in scedosporiosis and in fusariosis. Caspofungin is active in oropharyngeal and esophageal candidiasis, in invasive candidiasis ranking among the best drugs in non neutropenic patients. It was shown effective in refractory aspergillosis. As empirical treatment of febrile neutropenic patients, these molecules should probably be restricted to the highest risk-population. Safety is good, side effects are a rare cause of discontinuation of treatment, class specific drug-drug interactions occur with voriconazole. These molecules open an important field of investigations with combination of antifungal agents. PMID:15022787

  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. 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.

  8. 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. PMID:19543412

  9. [Porphyria and inappropriate antidiuretic hormone syndrome].

    PubMed

    López Montes, A; Lorenzo, I; Pérez Martínez, J

    2004-01-01

    We report the case of a 37-years-old woman with inappropriate antidiuretic hormone syndrome due to an attack of acute porphyria. The patient was admitted to our hospital for abdominal pain, sleepiness and pink urine. Family and personal history were normal. Seven days before the admission the patient had a laparoscopy operation for endometriosis in her left ovary. The patient had had two normal pregnancies. The physical examination was normal, the skin turgor was good and no edema was present, the blood pressure was 140/90 mmHg. Her serum sodium was 114 mEq/L, serum osmolality 243 mOsm/kg, urine sodium 146 mEq/L and urine osmolality 457 mOsm/kg. Values from laboratory examination revealed a normal peripheral haematogram, a normal kidney function, normal liver, adrenal and thyroid function. The urine tested for amino-levulinic acid, coproporphyrin and uroporphyrin was strongly positive. These findings are compatible with Porphyria Variegata or Coproporphyria Hereditary. A diagnosis of Porphyria acute with SIADH was made, and water fluid restriction, i.v. hypertonic saline infusion and furosemide to correct the hyponatremia was begun. In 1966, lesions of the median eminence of the hypothalamus and both hypothalamic -hypophyseal tracts were described in a patient with Porphyria acute intermittent and SIADH. It was suggested that SIADH occurred because of damage to these areas of the brain from excessive exposure to porphyrins. PMID:15219077

  10. 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. PMID:20369073

  11. 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. PMID:27241987

  12. 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,…

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 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...

  14. 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...

  15. 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...

  16. 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...

  17. Setting Limits: The Child Who Uses Inappropriate Language

    ERIC Educational Resources Information Center

    Greenberg, Polly

    2004-01-01

    This article discusses how to work with a child who uses inappropriate language. The words inappropriately used by young children are grouped into five categories: (1) names of body parts considered as private, and their nicknames; (2) bathroom words and body products; (3) religion-related words; (4) sexually charged words overheard when adults…

  18. 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…

  19. 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

  20. Candida Infections, Causes, Targets, and Resistance Mechanisms: Traditional and Alternative Antifungal Agents

    PubMed Central

    Spampinato, Claudia

    2013-01-01

    The genus Candida includes about 200 different species, but only a few species are human opportunistic pathogens and cause infections when the host becomes debilitated or immunocompromised. Candida infections can be superficial or invasive. Superficial infections often affect the skin or mucous membranes and can be treated successfully with topical antifungal drugs. However, invasive fungal infections are often life-threatening, probably due to inefficient diagnostic methods and inappropriate initial antifungal therapies. Here, we briefly review our current knowledge of pathogenic species of the genus Candida and yeast infection causes and then focus on current antifungal drugs and resistance mechanisms. An overview of new therapeutic alternatives for the treatment of Candida infections is also provided. PMID:23878798

  1. Chalcone derivatives as potential antifungal agents: Synthesis, and antifungal activity.

    PubMed

    Gupta, Deepa; Jain, D K

    2015-01-01

    Much research has been carried out with the aim to discover the therapeutic values of chalcone derivatives. Chalcones possess wide range of pharmacological activity such as antibacterial, antimalarial, antiprotozoal, antitubercular, anticancer, and antifungal agents etc. The presence of reactive α,β-unsaturated keto group in chalcones is found to be responsible for their biological activity. The rapid developments of resistance to antifungal agents, led to design, and synthesize the new antifungal agents. The derivatives of chalcones were prepared using Claisen-Schmidt condensation scheme with appropriate tetralone and aldehyde derivatives. Ten derivatives were synthesized and were biologically screened for antifungal activity. The newly synthesized derivatives of chalcone showed antifungal activity against fungal species, Microsporum gypseum. The results so obtained were superior or comparable to ketoconazole. It was observed that none of the compounds tested showed positive results for fungi Candida albicans nor against fungi Aspergillus niger. Chalcone derivatives showed inhibitory effect against M. gypseum species of fungus. It was found that among the chalcone derivatives so synthesized, two of them, that is, 4-chloro derivative, and unsubstituted derivative of chalcone showed antifungal activity superior to ketoconazole. Thus, these can be the potential new molecule as antifungal agent. PMID:26317075

  2. Update on azole antifungals.

    PubMed

    Zonios, Dimitrios I; Bennett, John E

    2008-04-01

    This is a comprehensive, clinically oriented review of the four commercially available triazoles: fluconazole, itraconazole, voriconazole, and posaconazole. Emphasis is placed in pharmacology, drug interactions, adverse events, antifungal activity, and the evolving perspective of their clinical use. Key clinical trials are briefly discussed, and specific drug indications summarized. Fluconazole remains a valuable low-cost choice for the treatment of various fungal infections, including candidiasis and cryptococcosis. It has relatively few drug interactions and is safe but lacks activity against filamentous fungi. The use of itraconazole is historically plagued by erratic bioavailability of the oral capsule, improved with the oral solution. Drug interactions are numerous. Itraconazole exhibits significant activity against Aspergillus and the endemic fungi. Voriconazole has revolutionized the treatment of aspergillosis in severely immunocompromised patients, but its use is compromised by complicated pharmacokinetics, notable drug interactions, and relatively significant adverse events. Finally, posaconazole is the last addition to the azole armamentarium with extended antifungal spectrum, significant activity against the zygomycetes, and, apparently, optimal safety profile. Posaconazole has a significant role for the prophylaxis of invasive fungal infections in severely immunocompromised patients. Multiple daily dosing, a need for fatty foods for absorption, and absence of an intravenous formulation restrict its use to selected populations. PMID:18366001

  3. Recent advances in antifungal chemotherapy.

    PubMed

    Petrikkos, George; Skiada, Anna

    2007-08-01

    For over 50 years, amphotericin B deoxycholate (AmBD) has been the 'gold standard' in antifungal chemotherapy, despite its frequent toxicities. However, improved treatment options for invasive fungal infections (IFIs) have been developed during the last 15 years. Newer antifungal agents, including less toxic lipid preparations of AmBD, triazoles and the echinocandins, have been added to our armamentarium against IFIs. Some of these newer drugs can now replace AmBD as primary therapy (e.g. caspofungin for candidiasis, voriconazole for aspergillosis), whilst others offer new therapeutic options for difficult-to-treat IFIs (e.g. posaconazole for zygomycosis, fusariosis and chromoblastomycosis). It is interesting that extended use of newer antifungals such as fluconazole, despite decreasing the mortality attributed to candidiasis, resulted in selection of species resistant to several antifungals (Candida krusei, Candida glabrata); whilst several publications suggest that prolonged use of voriconazole may expose severely immunocompromised patients to the risk of zygomycosis (breakthrough). On the other hand, the differences in the mode of action of newer antifungals such as echinocandins raise the question whether combination antifungal therapy is more effective than monotherapy. Finally, the availability of an oral formulation with excellent biosafety of several newer antifungals (e.g. posaconazole) makes them candidates for prophylactic or prolonged maintenance therapy. PMID:17524625

  4. 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

  5. Suppressive drug interactions between antifungals.

    PubMed

    de Vos, Marjon G J; Bollenbach, Tobias

    2014-04-24

    In this issue of Chemistry & Biology, Cokol and colleagues report a systematic study of drug interactions between antifungal compounds. Suppressive drug interactions occur more frequently than previously realized and come in different flavors with interesting implications. PMID:24766845

  6. Antifungal therapy with an emphasis on biofilms

    PubMed Central

    Pierce, Christopher G.; Srinivasan, Anand; Uppuluri, Priya; Ramasubramanian, Anand K.; López-Ribot, José Luis

    2013-01-01

    Fungal infections are on the rise as advances in modern medicine prolong the lives of severely ill patients. Fungi are eukaryotic organisms and there are a limited number of targets for antifungal drug development; as a result the antifungal arsenal is exceedingly limited. Azoles, polyenes and echinocandins, constitute the mainstay of antifungal therapy for patients with life-threatening mycoses. One of the main factors complicating antifungal therapy is the formation of fungal biofilms, microbial communities displaying resistance to most antifungal agents. A better understanding of fungal biofilms provides for new opportunities for the development of urgently needed novel antifungal agents and strategies. PMID:24011516

  7. 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

  8. Alternative approaches to antifungal therapies

    PubMed Central

    Mehra, T; Köberle, M; Braunsdorf, C; Mailänder-Sanchez, D; Borelli, C; Schaller, M

    2012-01-01

    The expansive use of immunosuppressive medications in fields such as transplantational medicine and oncology, the higher frequency of invasive procedures in an aging population and the HIV/AIDS pandemic have increased the frequency of systemic fungal infections. At the same time, increased resistance of pathogenic fungi to classical antifungal agents has led to sustained research efforts targeting alternative antifungal strategies. In this review, we focus on two promising approaches: cationic peptides and the targeting of fungal virulence factors. Cationic peptides are small, predominantly positively charged protein fragments which exert direct and indirect antifungal activities, one mechanism of action being the permeabilization of the fungal membrane. They include lysozyme, defensins, and cathelicidins, as well as novel synthetic peptides. Amongst fungal virulence factors, the targeting of candidal secreted aspartic proteinases seems to be a particularly promising approach. PMID:23078400

  9. Haloprogin: a Topical Antifungal Agent

    PubMed Central

    Harrison, E. F.; Zwadyk, P.; Bequette, R. J.; Hamlow, E. E.; Tavormina, P. A.; Zygmunt, W. A.

    1970-01-01

    Haloprogin was shown to be a highly effective agent for the treatment of experimentally induced topical mycotic infections in guinea pigs. Its in vitro spectrum of activity also includes yeasts, yeastlike fungi (Candida species), and certain gram-positive bacteria. The in vitro and in vivo antifungal activity of haloprogin against dermatophytes was equal to that observed with tolnaftate. The striking differences between the two agents were the marked antimonilial and selective antibacterial activities shown by haloprogin, contrasted with the negligible activities found with tolnaftate. Addition of serum decreased the in vitro antifungal activity of haloprogin to a greater extent than that of tolnaftate; however, diminished antifungal activity was not observed when haloprogin was applied topically to experimental dermatophytic infections. Based on its broad spectrum of antimicrobial activity, haloprogin may prove to be a superior topical agent in the treatment of dermatophytic and monilial infections in man. PMID:5422306

  10. Experimental Analysis of Response Covariation among Compliant and Inappropriate Behaviors.

    ERIC Educational Resources Information Center

    Parrish, John M.; And Others

    1986-01-01

    The study investigated the relationship between topographically different child behaviors (compliance and inappropriate activities) in four mentally retarded subjects (aged 3-5) by using a methodology that tests for response covariation. Regardless of the intervention used, the behavior targeted, or the direction manipulated, the nontargeted…

  11. 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…

  12. 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…

  13. 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…

  14. Altering the Inappropriate Comments of a Student with Multiple Disabilities

    ERIC Educational Resources Information Center

    Schoen, Sharon Faith; Thomas, Rachel

    2006-01-01

    This article offers an example of how teachers may successfully use a process for addressing problem behaviors in the classroom. The process includes (1) framing critical questions, (2) collecting relevant data, (3) taking well-researched actions, and (4) reflecting on the impact of these actions. Guided by these steps, the inappropriate comments…

  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. Inappropriate Student Behavior--A Problem for Student Teachers.

    ERIC Educational Resources Information Center

    Boyce, Ann

    1997-01-01

    Describes a strategy used in a preservice teacher education program to help student teachers and practicum students deal effectively with inappropriate pupil classroom behavior. The three-step strategy helps student teachers effectively identify and modify the behavior of children who misbehave. (SM)

  17. 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

  18. Antifungal activity of juniper extracts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  19. AB013. Inappropriate asthma therapy: a tale of two countries

    PubMed Central

    Nibber, Anjan; Belhassen, Manon; Van Ganse, Eric; Ryan, Dermot; Langlois, Carole; Appiagyei, Francis; Skinner, Derek; Laforest, Laurent; Soriano, Joan B.; Price, David

    2016-01-01

    Background Inappropriate prescribing and misuse of asthma medication, have been identified as potentially preventable factors linked to asthma exacerbations and deaths. A recent report by the National Review of Asthma Deaths drew attention to the excessive prescribing of reliever medication, and under-prescribing of controlled medication in the United-Kingdom (UK). The inappropriate prescribing of long-acting beta agonist (LABA) bronchodilator inhalers, as either a monotherapy or without inhaled corticosteroids (ICS) has been highlighted as a major preventable factor of asthma exacerbations and deaths. To determine whether the prevalence of inappropriate LABA therapy use in asthma in the UK and in France has changed over time. Methods Two interval, parallel, population-based cohorts (2007 and 2013), were developed in each country, utilising the UK Optimum Patient Care Research Database and the French Permanent Beneficiaries Sample database. Following inclusion, patients aged 6–40 years were studied over a 12-month period. The use of LABAs without ICS, and ≥2-fold higher use of LABA compared with ICS were investigated. Analyses were stratified by age groups: children (6–13 years) and adults (14–40 years). Results Overall, 39,743 UK and 4,910 French patients were included in 2007 and 14,036 and 5,657 in 2013. In 2013, LABA use without ICS occurred in 0.1% and 1.5% of UK and French adults respectively. This was a marked reduction from 2007 UK and French figures of 0.4% and 2.6% respectively (P<0.05 for both). Excessive use of LABA relative to ICS occurred in 0.2% of UK adults and in 0.7% of French adults in 2013. These percentages represented a decrease from the 2007 figures of 0.6% and 1.4% for UK (P=0.29) and France (P=0.003), respectively. In 2007, LABA inappropriate use was more frequent in French than UK asthmatic children (P<0.0001), but showed a downward trend by time in both countries (0.1% in 2013 in both countries). Conclusions Our study suggests

  20. 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. PMID:22185769

  1. Training should be the first step toward an antifungal stewardship program.

    PubMed

    Valerio, Maricela; Muñoz, Patricia; Rodríguez-González, Carmen; Sanjurjo, María; Guinea, Jesús; Bouza, Emilio

    2015-04-01

    The frequency of use of systemic antifungal agents has increased significantly in most tertiary centers. However, antifungal stewardship has received very little attention. The objective of this article was to assess the knowledge of prescribing physicians in our institution as a first step in the development of an antifungal stewardship program. Attending physicians from the departments that prescribe most antifungals were invited to complete a questionnaire based on current guidelines on diagnosis and therapy of invasive candidiasis and invasive aspergillosis (IA). The survey was completed by 60.8% (200/329) of the physicians who were invited to participate. The physicians belonged to the following departments: medical (60%), pediatric (19%), intensive care (15.5%), and surgical (5.5%). The mean (±SD) score of correct responses was 5.16±1.73. In the case of candidiasis, only 55% of the physicians clearly distinguished between colonization and infection, and 17.5% knew the local rate of fluconazole resistance. Thirty-three percent knew the accepted indications for antifungal prophylaxis, and 23% the indications for empirical therapy. However, most physicians knew which antifungals to choose when starting empirical therapy (73.5%). As for aspergillosis, most physicians (67%) could differentiate between colonization and infection, and 34.5% knew the diagnostic value of galactomannan. The radiological features of IA were well recognized by 64%, but only 31.5% were aware of the first line of treatment for IA, and 36% of the recommended duration of therapy. The usefulness of antifungal levels was known by 67%. This simple, easily completed questionnaire enabled us to identify which areas of our training strategy could be improved. PMID:25066382

  2. [Overtreatment: Initiatives to identify ineffective and inappropriate medical interventions].

    PubMed

    Wild, Claudia; Mayer, Julia

    2016-04-01

    A growing number of international initiatives rise to the challenge of reduction of medical overuse. Increasingly, these activities are promoted by physicians and clinicians, and aim to identify and avoid inappropriate health interventions. This article places the Choosing Wisely initiative within the context of less well-known activities, 13 all together, and briefly describes their characteristics; in addition, similarities and differences regarding their methods are elaborated. PMID:26883771

  3. 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. PMID:17396439

  4. 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. PMID:24683293

  5. Reducing inappropriate ESR testing with computerized clinical decision support

    PubMed Central

    Gottheil, Stephanie; Khemani, Ekta; Copley, Katherine; Keeney, Michael; Kinney, Jeff; Chin-Yee, Ian; Gob, Alan

    2016-01-01

    Laboratory test overutilization increases health care costs, leads to unwarranted investigations, and may have a negative impact on health outcomes. The American Society of Clinical Pathology, in its Choosing Wisely Campaign, advocates that inflammation be investigated with C-reactive protein (CRP) instead of Erythrocyte Sedimentation Rate (ESR). London Health Sciences Centre (LHSC), a tertiary care hospital organization in Ontario, Canada, set a goal to reduce inappropriate ESR orders by 50%. After developing appropriateness criteria for ESR, we used a series of PDSA cycles to reduce inappropriate ESR ordering and analyzed our results with an interrupted time series design. Our intervention began with an educational bulletin and moved to city-wide implementation of computerized Clinical Decision Support (CDS). After implementation, ESR orders decreased by 40% from 386 orders per week to 241 orders per week. Our results are supported by previous literature on the effectiveness of CDS in reducing overutilization and suggest that provider habit is a significant contributor to inappropriate ordering. PMID:27096092

  6. 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

  7. 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. PMID:9220325

  8. Reducing inappropriate ESR testing with computerized clinical decision support.

    PubMed

    Gottheil, Stephanie; Khemani, Ekta; Copley, Katherine; Keeney, Michael; Kinney, Jeff; Chin-Yee, Ian; Gob, Alan

    2016-01-01

    Laboratory test overutilization increases health care costs, leads to unwarranted investigations, and may have a negative impact on health outcomes. The American Society of Clinical Pathology, in its Choosing Wisely Campaign, advocates that inflammation be investigated with C-reactive protein (CRP) instead of Erythrocyte Sedimentation Rate (ESR). London Health Sciences Centre (LHSC), a tertiary care hospital organization in Ontario, Canada, set a goal to reduce inappropriate ESR orders by 50%. After developing appropriateness criteria for ESR, we used a series of PDSA cycles to reduce inappropriate ESR ordering and analyzed our results with an interrupted time series design. Our intervention began with an educational bulletin and moved to city-wide implementation of computerized Clinical Decision Support (CDS). After implementation, ESR orders decreased by 40% from 386 orders per week to 241 orders per week. Our results are supported by previous literature on the effectiveness of CDS in reducing overutilization and suggest that provider habit is a significant contributor to inappropriate ordering. PMID:27096092

  9. A Prototype Antifungal Contact Lens

    PubMed Central

    Ciolino, Joseph B.; Hudson, Sarah P.; Mobbs, Ashley N.; Hoare, Todd R.; Iwata, Naomi G.; Fink, Gerald R.

    2011-01-01

    Purpose. To design a contact lens to treat and prevent fungal ocular infections. Methods. Curved contact lenses were created by encapsulating econazole-impregnated poly(lactic-co-glycolic) acid (PLGA) films in poly(hydroxyethyl methacrylate) (pHEMA) by ultraviolet photopolymerization. Release studies were conducted in phosphate-buffered saline at 37°C with continuous shaking. The contact lenses and their release media were tested in an antifungal assay against Candida albicans. Cross sections of the pre- and postrelease contact lenses were characterized by scanning electron microscopy and by Raman spectroscopy. Results. Econazole-eluting contact lenses provided extended antifungal activity against Candida albicans fungi. Fungicidal activity varied in duration and effectiveness depending on the mass of the econazole-PLGA film encapsulated in the contact lens. Conclusions. An econazole-eluting contact lens could be used as a treatment for fungal ocular infections. PMID:21527380

  10. Advancements in Topical Antifungal Vehicles.

    PubMed

    Kircik, Leon H

    2016-02-01

    The primary treatment for superficial fungal infections is antifungal topical formulations, and allylamines and azoles represent the two major classes of topical formulations that are used to treat these infections. The stratum corneum (SC) is composed of keratinocytes that are surrounded by a matrix of lipids. The efficacy of topically applied formulations depends on their ability to penetrate this lipid matrix, and the vehicle plays an integral role in the penetration of active molecule into skin. There are several challenges to formulating topical drugs, which include the biotransformation of the active molecules as they pass through the SC and the physical changes that occur to the vehicle itself when it is applied to the skin. This article will review current and emerging topical antifungal vehicles. PMID:26885798

  11. Antifungal stilbenoids from Stemona japonica.

    PubMed

    Zhang, Ya-Zhong; Xu, Guo-Bing; Zhang, Tong

    2008-01-01

    Three new dihydrostilbenes, stilbostemins P-R (1-3), and a new dihydrophenanthrene, stemanthrene G (4), were isolated from the roots of Stemona japonica together with three known bibenzyls, 3,5-dihydroxy-2'-methoxy bibenzyl (5), 3,3'-dihydroxy-2,5'-dimethoxy bibenzyl (6), and 3,5,2'-trihydroxy-4-methyl bibenzyl (7). Their structures were elucidated by spectroscopic analyses. Compounds 5 and 6 exhibited strong antifungal activities against Candida albicans. PMID:18636375

  12. 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

  13. Evaluation of vaginal antifungal formulations in vivo.

    PubMed Central

    McRipley, R. J.; Erhard, P. J.; Schwind, R. A.; Whitney, R. R.

    1979-01-01

    Relatively simple and rapid procedures have been developed for evaluating the local efficacy of vaginal antifungal agents in vivo in a vaginal candidiasis model in ovariectomized rats. The results of this investigation indicate that the model and methods described are quite suitable for screening potential antifungal substances and for assessing the chemotherapeutic effectiveness of new antifungal agents and formulations before carrying out clinical studies. PMID:392480

  14. 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

  15. 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

  16. Medically Inappropriate or Futile Treatment: Deliberation and Justification.

    PubMed

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

    2016-02-01

    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

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

    PubMed Central

    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. PMID:27034875

  18. Reduction of Inappropriate Behavior with Primary Mentally Handicapped Children Using Teacher Praise, Ignoring, and Parental Consequences.

    ERIC Educational Resources Information Center

    Sandeman, M. G.; McLaughlin, T. F.

    1982-01-01

    The effects of teacher praise, ignoring, time-out, and parental contingencies on the number of inappropriate behaviors of two mentally handicapped (IQ's 55 and 51) male students ages seven and nine were investigated in a one-year study. Both students reduced inappropriate noise and behavior, and the frequency of inappropriate behavior remained…

  19. 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.

  20. 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

  1. 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. PMID:25005365

  2. Antifungals: Mechanism of Action and Drug Resistance.

    PubMed

    Prasad, Rajendra; Shah, Abdul Haseeb; Rawal, Manpreet Kaur

    2016-01-01

    There are currently few antifungals in use which show efficacy against fungal diseases. These antifungals mostly target specific components of fungal plasma membrane or its biosynthetic pathways. However, more recent class of antifungals in use is echinocandins which target the fungal cell wall components. The availability of mostly fungistatic antifungals in clinical use, often led to the development of tolerance to these very drugs by the pathogenic fungal species. Thus, the development of clinical multidrug resistance (MDR) leads to higher tolerance to drugs and its emergence is helped by multiple mechanisms. MDR is indeed a multifactorial phenomenon wherein a resistant organism possesses several mechanisms which contribute to display reduced susceptibility to not only single drug in use but also show collateral resistance to several drugs. Considering the limited availability of antifungals in use and the emergence of MDR in fungal infections, there is a continuous need for the development of novel broad spectrum antifungal drugs with better efficacy. Here, we briefly present an overview of the current understanding of the antifungal drugs in use, their mechanism of action and the emerging possible novel antifungal drugs with great promise. PMID:26721281

  3. Natural and synthetic peptides with antifungal activity.

    PubMed

    Ciociola, Tecla; Giovati, Laura; Conti, Stefania; Magliani, Walter; Santinoli, Claudia; Polonelli, Luciano

    2016-08-01

    In recent years, the increase of invasive fungal infections and the emergence of antifungal resistance stressed the need for new antifungal drugs. Peptides have shown to be good candidates for the development of alternative antimicrobial agents through high-throughput screening, and subsequent optimization according to a rational approach. This review presents a brief overview on antifungal natural peptides of different sources (animals, plants, micro-organisms), peptide fragments derived by proteolytic cleavage of precursor physiological proteins (cryptides), synthetic unnatural peptides and peptide derivatives. Antifungal peptides are schematically reported based on their structure, antifungal spectrum and reported effects. Natural or synthetic peptides and their modified derivatives may represent the basis for new compounds active against fungal infections. PMID:27502155

  4. 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

  5. Inappropriate prescribing practices: the challenge and opportunity for patient safety.

    PubMed

    Taylor, Laurel K; Kawasumi, Yuko; Bartlett, Gillian; Tamblyn, Robyn

    2005-01-01

    Adverse clinical events related to inappropriate prescribing practices are an important threat to patient safety. Avoidance of inappropriate prescribing in community settings, where the majority of prescriptions are written, offers a major area of opportunity to improve quality of care and outcomes. Electronic medication order entry systems, with automated clinical risk screening and online alerting capabilities, appear as particularly promising enabling tools in such settings. The Medical Office of the Twenty First Century (MOXXI-III) research group is currently utilizing such a system that integrates identification of dosing errors, adverse drug interactions, drug-disease and allergy contraindications and potential toxicity or contraindications based on patient age. This paper characterizes the spectrum of alerts in an urban community of care involving 28 physicians and 32 pharmacies. Over a consecutive nine-month period, alerts were generated in 29% of 22,419 prescriptions, resulting in revised prescriptions in 14% of the alert cases. Drug-disease contraindications were the most common driver of alerts, accounting for 41% of the total and resulting in revised prescriptions in 14% of cases. In contrast, potential dosing errors generated only 8% of all alerts, but resulted in revised prescriptions 23% of the time. Overall, online evidence-based screening and alerting around prescription of medications in a community setting demands confirmation in prescribers' clinical decision making in almost one-third of prescriptions and leads to changed decisions in up to one-quarter of some prescribing categories. Its ultimate determination of clinical relevance to patient safety may, however, have to await more detailed examination of physician response to alerts and patient outcomes as a primary measure of utility. Patient safety is an increasingly recognized challenge and opportunity for stakeholders in improving health care delivery. It involves many issues, including

  6. Active packaging with antifungal activities.

    PubMed

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

    2016-03-01

    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. PMID:26803804

  7. Antifungal susceptibilities of Paecilomyces species.

    PubMed

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

    1998-07-01

    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

  8. 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

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

    PubMed

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

    1998-10-01

    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

  10. 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

  11. Inappropriate intracranial hemodynamics in the natural course of MELAS.

    PubMed

    Nishioka, Junko; Akita, Yukihiro; Yatsuga, Shuichi; Katayama, Koujyu; Matsuishi, Toyojiro; Ishibashi, Masatoshi; Koga, Yasutoshi

    2008-02-01

    The abnormalities of intracranial hemodynamics associated with strokelike episodes in MELAS are variable depend on the time phase from the onset of strokelike episodes and on the progression of the dementia state. To clarify the regional cerebral blood flows (rCBF) in the natural course of MELAS is very important to understand the pathogenic mechanism of this disorder, either cytopathy, angiopathy or both. We analyzed the serial studies of brain statistical parametric mapping (SPM) 99 single photon emission computed tomography (SPECT) in 5 MELAS patients in maximum 10 years interval, who fulfilled the clinical, pathological and genetic criteria of MELAS, and have an A3243G mutation in the mitochondrial tRNA(Leu(UUR)) gene. SPM is a proven and effective method for the voxel-by-voxel analysis of functional images which show the advantage in its promise of fully automated neurophysiological imaging analysis throughout the whole brain using various statistical analyses. SPECT acquisition was initiated and was reconstructed by iterative algorithm and were processed and analyzed with SPM 99 for Windows software. Statistics were displayed as Z scores (threshold: P < 0.01). The inappropriate intracranial hemodynamics was found not only at the acute but at the interictal phase, and was getting worse as the disease progress. Hypoperfusion in the posterior cingulate cortex was always observed (corrected P < 0.01) in MELAS patients, which is the typical finding reported in Alzheimer's disease. The inappropriate intracranial hemodynamics is a common feature and may be related with mitochondrial angiopathy in the natural course of MELAS. PMID:17664050

  12. Predictors of choice of initial antifungal treatment in intraabdominal candidiasis.

    PubMed

    Lagunes, L; Borgatta, B; Martín-Gomez, M T; Rey-Pérez, A; Antonelli, M; Righi, E; Merelli, M; Brugnaro, P; Dimopoulos, G; Garnacho-Montero, J; Colombo, A L; Luzzati, R; Menichetti, F; Muñoz, P; Nucci, M; Scotton, G; Viscoli, C; Tumbarello, M; Bassetti, M; Rello, J

    2016-08-01

    Intraabdominal candidiasis (IAC) is the second most frequent form of invasive candidiasis, and is associated with high mortality rates. This study aims to identify current practices in initial antifungal treatment (IAT) in a real-world scenario and to define the predictors of the choice of echinocandins or azoles in IAC episodes. Secondary analysis was performed of a multinational retrospective cohort at 13 teaching hospitals in four countries (Italy, Greece, Spain and Brazil), over a 3-year period (2011-2013). IAC was identified in 481 patients, 323 of whom received antifungal therapy (classified as the treatment group). After excluding 13 patients given amphotericin B, the treatment group was further divided into the echinocandin group (209 patients; 64.7%) and the azole group (101 patients; 32.3%). Median APACHE II scores were significantly higher in the echinocandin group (p 0.013), but IAT did not differ significantly with regard to the Candida species involved. Logistic multivariate stepwise regression analysis, adjusted for centre effect, identified septic shock (adjusted OR (aOR) 1.54), APACHE II >15 (aOR 1.16) and presence in surgical ward at diagnosis (aOR 1.16) as the top three independent variables associated with an empirical echinocandin regimen. No differences in 30-day mortality were observed between groups. Echinocandin regimen was the first choice for IAT in patients with IAC. No statistical differences in mortality were observed between regimens, but echinocandins were administered to patients with more severe disease. Some disagreements were identified between current clinical guidelines and prescription of antifungals for IAC at the bedside, so further educational measures are required to optimize therapies. PMID:27432766

  13. 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

  14. Antifungal isopimaranes from Hypoestes serpens.

    PubMed

    Rasoamiaranjanahary, L; Guilet, D; Marston, A; Randimbivololona, F; Hostettmann, K

    2003-09-01

    Five isopimarane diterpenes (7beta-hydroxyisopimara-8,15-dien-14-one, 14alpha-hydroxyisopimara-7,15-dien-1-one, 1beta,14alpha-dihydroxyisopimara-7,15-diene, 7beta-hydroxyisopimara-8(14),15-dien-1-one and 7beta-acetoxyisopimara-8(14),15-dien-1-one) have been isolated from the leaves of Hypoestes serpens (Acanthaceae). All compounds exhibited antifungal activity against both the plant pathogenic fungus Cladosporium cucumerinum and the yeast Candida albicans; two of them also displayed an acetylcholinesterase inhibition. The structures of the compounds were determined by means of spectrometric methods, including 1D and 2D NMR experiments and MS analysis. PMID:12943772

  15. 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

  16. 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.…

  17. 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

  18. The Prevalence of Antifungal Agents Administration in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Study

    PubMed Central

    Kargar, Mona; Ahmadvand, Alireza; Ahmadvand, Milad; Hadjibabaie, Molouk; Gholami, Kheirollah; Khoee, Seyed Hamid; Javadi, Mohammad Reza; Ghavamzadeh, Ardeshir

    2013-01-01

    Background Invasive fungal infections (IFIs) are chief infectious complications in patients undergoing hematopoietic stem cell transplantation (HSCT). However, the diagnosis of fungal infections is difficult, and often empiric treatment initiates. Since there is no data available on the prevalence of antifungal drugs administration in allogeneic HSCT recipients in Iran, we decided to conduct this study. Methods This study was a retrospective review of records of patients who received allogeneic HSCT in the Hematology-Oncology, Bone Marrow Transplantation center at Shariati Hospital in Tehran, between August 2009 and August 2010. Results Sixty (73.1%) patients consist of 41 men (68.3%) with mean age of 26.3 (± 1.2) years received allogeneic HSCT. Patients received prophylaxis with fulconazole however; in 28 patients (46.7%) it was switched to low dose amphotericin B. Fifteen patients (25%) received treatment with antifungal agents. Amphotericin B was the empiric agent administered. In 3 patients treatment was switched to voriconazole. Neither positive culture nor direct microscopic evidence was available from the obtained specimen. Only in one patient the result of serum galactomannan assay was positive. There were no significant differences in neutropenia duration (P value: 0.54), length of hospital stay (P value: 0.27) and number of patients developed graft versus host disease (P value: 0.07) between patients received antifungal agents with those who did not receive treatment. Conclusion In this study HSCT recipients received antifungal agents for prophylaxis. Twenty five percent of patients received treatment with antifungal agents empirically. Improvement in diagnosis of these infections can be helpful and lead to targeted therapy. We suggest larger prospective trials for better assessment of antifungal agent administration. PMID:24505528

  19. 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

    2014-01-01

    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. PMID:24609016

  20. Cefdinir-Induced Hepatotoxicity: Potential Hazards of Inappropriate Antibiotic Use

    PubMed Central

    Chen, Joy

    2008-01-01

    Drug-induced hepatotoxicity is well recognized but can cause some diagnostic problems, particularly if not previously reported. The present case involves a 22-year-old male who presented with jaundice and elevated liver enzymes after a course of cefdinir (Omnicef®) for streptococcal pharyngitis. A diagnosis of drug-induced liver injury was suspected but a liver biopsy was required after his jaundice worsened despite cessation of the presumed offending agent. A short course of steroids was initiated and eventually the jaundice resolved. This case highlights the need to suspect medication-induced liver injury in cases of jaundice, even if not previously reported. In addition, it illustrates the potential for adverse outcomes in situations where antibiotics are used inappropriately or where first line antibiotics are not used for routine infections. We report a case of a young male who developed jaundice associated with cefdinir use with pathological confirmation of moderate cholestasis with portal and lobular mixed inflammation and focal bile duct injury consistent with drug-induced liver injury. PMID:18752027

  1. 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. PMID:18480041

  2. 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. PMID:24122364

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. Clinical presentation of inappropriate sinus tachycardia and differential diagnosis.

    PubMed

    Peyrol, Michael; Lévy, Samuel

    2016-06-01

    Inappropriate sinus tachycardia (IST) is a syndrome characterized by a sinus tachycardia not related to a medical condition, to a physiological response, or to medication or drugs and associated with symptoms, often invalidating and altering the quality of life of affected patients. It occurs predominantly in adolescents and young adults, and in the female sex. The diagnosis requires a complete work-up in order to exclude other causes of sinus tachycardia and one or several additional tests: 24-h ECG ambulatory recordings, echocardiogram, exercise testing, and autonomous nervous system assessment. It should be differentiated from the postural orthostatic tachycardia syndrome, with which it shares a number of symptoms, and other supraventricular tachycardias originating in the high right atrium. An electrophysiological study should be considered in selected cases in order to differentiate IST from other supraventricular tachycardias. The mechanism is still unclear, and possible etiologies may include intrinsic abnormality of the sinus node, autonomic dysfunction, hypersensitivity of the sinus node to catecholamines, blunted vagal system, or a combination of the above. The authors emphasize the wide spectrum of clinical presentations and the need to better define the IST and the criteria required to ascertain its diagnosis. PMID:26329720

  8. [MIKAMINOM ANTIFUNGAL THERAPY IN NEWBORNS AND INFANTS WITH SURGICAL PATHOLOGY].

    PubMed

    Melnikova, N I; Strogonov, I A; Kartseva, E V; Haritonova, G D; Gliznutsin, O E; Gabulaev, S V; Pulikova, E M

    2016-01-01

    Prolonged empiric and etiotropic therapy of multidrug-resistant or pan-resistant bacterial flora in different gestation age newborns has led to the growth of resistant fungalflora in intencive care units (ICU). According to risk factors and rating scales every child of ICU undergoing the abdominal cavity surgery is threatened the development of a fungal infection and requires antifungal therapy appointment or causal prophylactic. In recent years, before the advent of medications of the group of echinocandins, therapy of invasive fungal infections has been a challenge. Currently alternative drug to diflucane in neonates and infants is micafungine (mycamine) in the dose of 2-8 mg/kg/day, depending on the signs of infestation and severity of the condition. PMID:27192854

  9. Potentially inappropriate prescriptions in patients admitted to a psychiatric hospital.

    PubMed

    Soerensen, Ann Lykkegaard; Nielsen, Lars Peter; Poulsen, Birgitte Klindt; Lisby, Marianne; Mainz, Jan

    2016-07-01

    Background Very little is known about the general appropriateness of prescribing for psychiatric patients. Aims To identify prevalence and types of potentially inappropriate prescribing (PIP) of psychotropic and somatic medications, to assess the severity of potential clinical consequences and to identify possible predictive factors of PIP in a sample of adult psychiatric in-patients. Methods A descriptive, cross-sectional design using medication reviews by clinical pharmacologists to identify PIP during a 3-month period. The setting was in-patient units in a psychiatric department of a Danish university hospital during a 3-month period (September 2013-November 2013). Patients medication lists (n = 207) were reviewed at the time of admission and all identified PIPs were assessed for potential consequences by clinical pharmacologists. Results There were 349 PIP identified in 1291 prescriptions. The proportion of patients found to have at least one PIP was 123/207 (59%) and the proportions of patients with at least one PIP assessed to be potentially serious or fatal was 69/207 (33%) and 24/207 (12%), respectively. Interactions between drugs 125/207 (36%) and too high doses of drugs 56/207 (16%) were the most frequent PIP. Predictive factors for PIP were polypharmacy (>5 prescriptions) and having one or more somatic diagnoses. Conclusion PIP is common in psychiatric patients and potentially fatal. Particularly polypharmacy (>5 prescriptions) and concomitant somatic illness were associated with the probability of PIP. Improving the quality of prescribing might benefit from an interprofessional approach and thus better training of physicians and nurses is needed in order to minimize PIP. PMID:26824679

  10. 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

  11. 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.…

  12. Decreasing Inappropriate Behaviors for Adolescents with Autism Spectrum Disorders Using Modified Social Stories

    ERIC Educational Resources Information Center

    Graetz, Janet E.; Mastropieri, Margo A.; Scruggs, Thomas E.

    2009-01-01

    A multiple baseline design study was implemented to assess the effects of a modified social story intervention on inappropriate social behaviors of three adolescents with moderate autism. Baseline data were collected on inappropriate behaviors that included refusal to stand, use of a high-pitched voice, and placing hands/objects in mouth.…

  13. 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…

  14. Differential Effects of Classroom Lighting on Inappropriate Behaviors in a Severely Mentally Retarded Boy.

    ERIC Educational Resources Information Center

    Fletcher, Donna; Grey, Teresa

    1985-01-01

    A severely mentally retarded 9-year-old boy with a history of inappropriate classroom behaviors was videotaped in his classroom under normal cool white fluorescent and full spectrum florescent lighting. Inappropriate behaviors were considerably less frequent under full spectrum fluorescent lighting. (Author/CL)

  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. [Inappropriately ordered tests from hepatitis B vaccinated subjects].

    PubMed

    Ozbek, Ozgen Alpay; Oktem, Ibrahim Mehmet Ali

    2010-04-01

    Laboratory testing for viral hepatitis B constitutes a vast burden regarding the cost and the workload for health care system for many countries including ours. There are several reports stating that the cost in question is not always necessary. As a consequence of larger scale vaccination programmes, an increase in unnecessary hepatitis B testing is expected in vaccinated individuals. The present retrospective study aims to determine the rate of inappropriately ordered tests from vaccinated individuals and to discuss the causes and possible solutions of this problem. Laboratory records of 56.349 subjects admitted to Dokuz Eylul University Hospital, Izmir, during 2007 and 2009, were evaluated retrospectively for hepatitis B serological test results. Unnecessary testing was defined as the requests for HBsAg, anti-HBc, anti-HBc IgM, HBeAg and anti-HBe tests from those who had positive anti-HBs and negative anti-HBc results. The cost burden was calculated by taking account the prices recommended by the Department of Social Security. The appropriateness of anti-HBs test orders were not taken into evaluation since specific clinical conditions (immune response disorders, HIV infection, chronic hemodialysis, newborns of HBsAg positive mothers, contact with HBsAg carriers) were not clarified. It was found that among the 17.869 samples tested for both anti-HBs and anti-HBc, 4402 (24.6%) were ordered from subjects who were vaccinated against hepatitis B virus (anti-HBs positive, anti-HBc negative status). Thus, 11.405 (12.9%) tests out of a total of 88.174 hepatitis B tests (HBsAg, anti-HBc, anti-HBc IgM, HBeAg, anti-HBe) were unnecessarily ordered. Social security services and/or individuals paid approximately 59.000 USD for these unnecessary tests in three years, leading to an economic loss of approximately 20.000 USD yearly. Providing appropriate feedback to clinicians and reflex test application (to order a test according to the results of previous tests in accordance to

  17. Systemic antifungal prescribing in neonates and children: outcomes from the Antibiotic Resistance and Prescribing in European Children (ARPEC) Study.

    PubMed

    Lestner, J M; Versporten, A; Doerholt, K; Warris, A; Roilides, E; Sharland, M; Bielicki, J; Goossens, H

    2015-02-01

    The appropriate use of systemic antifungals is vital in the prevention and treatment of invasive fungal infection (IFI) in immunosuppressed children and neonates. This multicenter observational study describes the inpatient prescribing practice of antifungal drugs for children and neonates and identifies factors associated with prescribing variability. A single-day point prevalence study of antimicrobial use in hospitalized neonates and children was performed between October and December 2012. The data were entered through a study-specific Web-based portal using a standardized data entry protocol. Data were recorded from 17,693 patients from 226 centers. A total of 136 centers recorded data from 1,092 children and 380 neonates receiving at least one antifungal agent. The most frequently prescribed systemic antifungals were fluconazole (n=355) and amphotericin B deoxycholate (n=195). The most common indications for antifungal administration in children were medical prophylaxis (n=325), empirical treatment of febrile neutropenia (n=122), and treatment of confirmed or suspected IFI (n=100 [14%]). The treatment of suspected IFI in low-birthweight neonates accounted for the majority of prescriptions in the neonatal units (n=103). An analysis of variance (ANOVA) demonstrated no significant effect of clinical indication (prophylaxis or treatment of systemic or localized infection) on the total daily dose (TDD). Fewer than one-half of the patients (n=371) received a TDD within the dosing range recommended in the current guidelines. Subtherapeutic doses were prescribed in 416 cases (47%). The predominance of fluconazole and high incidence of subtherapeutic doses in participating hospitals may contribute to suboptimal clinical outcomes and an increased predominance of resistant pathogenic fungi. A global consensus on antifungal dosing and coordinated stewardship programs are needed to promote the consistent and appropriate use of antifungal drugs in neonates and children

  18. 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

  19. 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

  20. Antifungal drug discovery: the process and outcomes.

    PubMed

    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

  1. The Association between Inappropriate Weight Control Behaviors and Suicide Ideation and Attempt among Korean Adolescents.

    PubMed

    Lee, Sang Ah; Jang, Suk Yong; Shin, Jaeyong; Ju, Yeong Jun; Nam, Jin Young; Park, Eun Cheol

    2016-10-01

    Suicide is a leading cause of death among adolescents globally, and body weight is also a recognized reason for adolescent suicide. Therefore, we investigated the association between weight control behaviors (WCB) and suicide ideation and attempt, focusing on inappropriate weight control measures. We used data from the 2014 Korea Youth Risk Behavior Web-based Survey, representing a total of 35,224 boys and 34,361 girls aged 12 to 18 years. Adolescents were classified into groups based on WCB: appropriate WCB, inappropriate WCB, and no WCB. We performed logistic regression models to examine associations between WCB and suicide ideation and attempt, controlling for covariates. Both boys and girls with inappropriate WCB were more likely to report suicide ideation and attempt. Underweight and normal weight boys with inappropriate WCB were more likely to think or attempt suicide, and underweight girls with inappropriate WCB were also more likely to attempt suicide. Among five common WCB combinations, the combination of "regular exercise, fasting, eating less" was highly associated with suicide ideation and attempt. We confirmed that inappropriate WCB is associated with suicide ideation and attempt among Korean adolescents. Given the high incidence rate of suicide among adolescents and the adverse effect of inappropriate WCB, encouraging adolescents to control their weight in healthy ways is imperative. PMID:27550479

  2. Sex differences in the risk of receiving potentially inappropriate prescriptions among older adults

    PubMed Central

    Morgan, Steven G.; Weymann, Deirdre; Pratt, Brandy; Smolina, Kate; Gladstone, Emilie J.; Raymond, Colette; Mintzes, Barbara

    2016-01-01

    Objectives: to measure sex differences in the risk of receiving potentially inappropriate prescription drugs and to examine what are the factors that contribute to these differences. Design: a retrospective cohort study. Setting: community setting of British Columbia, Canada. Participants: residents of British Columbia aged 65 and older (n = 660,679). Measurements: we measured 2013 period prevalence of prescription dispensations satisfying the American Geriatrics Society's 2012 version of the Beers Criteria for potentially inappropriate medication use in older adults. We used logistic regressions to test for associations between this outcome and a number of clinical and socioeconomic factors. Results: a larger share of women (31%) than of men (26%) filled one or more potentially inappropriate prescription in the community. The odds of receiving potentially inappropriate prescriptions are associated with several clinical and socioeconomic factors. After controlling for those factors, community-dwelling women were at 16% higher odds of receiving a potentially inappropriate prescription than men (adjusted odds ratio = 1.16, 95% confidence interval = 1.12–1.21). Much of this sex difference stemmed from women's increased odds of receiving potentially inappropriate prescriptions for benzodiazepines and other hypnotics, for tertiary tricyclic antidepressants and for non-selective NSAIDs. Conclusion: there are significant sex differences in older adults' risk of receiving a potentially inappropriate prescription as a result of complex intersections between gender and other social constructs. Appropriate responses will therefore require changes in the information, norms and expectations of both prescribers and patients. PMID:27151390

  3. Synthesis, Antifungal Activities and Qualitative Structure Activity Relationship of Carabrone Hydrazone Derivatives as Potential Antifungal Agents

    PubMed Central

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

    2014-01-01

    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. PMID:24619221

  4. Antifungal activity of five species of Polygala

    PubMed Central

    Johann, Susana; Mendes, Beatriz G.; Missau, Fabiana C.; de Resende, Maria A.; Pizzolatti, Moacir G.

    2011-01-01

    Crude extracts and fractions of five species of Polygala – P. campestris, P. cyparissias, P. paniculata, P. pulchella and P. sabulosa – were investigated for their in vitro antifungal activity against opportunistic Candida species, Cryptococcus gattii and Sporothrix schenckii with bioautographic and microdilution assays. In the bioautographic assays, the major extracts were active against the fungi tested. In the minimal concentration inhibitory (MIC) assay, the hexane extract of P. paniculata and EtOAc fraction of P. sabulosa showed the best antifungal activity, with MIC values of 60 and 30 μg/mL, respectively, against C. tropicalis, C. gattii and S. schenckii. The compounds isolated from P. sabulosa prenyloxycoumarin and 1,2,3,4,5,6-hexanehexol displayed antifungal activity against S. schenckii (with MICs of 125 μg/mL and 250 μg/mL, respectively) and C. gattii (both with MICs of 250 μg/mL). Rutin and aurapten isolated from P. paniculata showed antifungal activity against C. gattii with MIC values of 60 and 250 μg/mL, respectively. In the antifungal screening, few of the isolated compounds showed good antifungal inhibition. The compound α-spinasterol showed broad activity against the species tested, while rutin had the best activity with the lowest MIC values for the microorganisms tested. These two compounds may be chemically modified by the introduction of a substitute group that would alter several physico-chemical properties of the molecule, such as hydrophobicity, electronic density and steric strain. PMID:24031724

  5. Inappropriateness of Medication Prescriptions to Elderly Patients in the Primary Care Setting: A Systematic Review

    PubMed Central

    Opondo, Dedan; Eslami, Saied; Visscher, Stefan; de Rooij, Sophia E.; Verheij, Robert; Korevaar, Joke C.; Abu-Hanna, Ameen

    2012-01-01

    Background Inappropriate medication prescription is a common cause of preventable adverse drug events among elderly persons in the primary care setting. Objective The aim of this systematic review is to quantify the extent of inappropriate prescription to elderly persons in the primary care setting. Methods We systematically searched Ovid-Medline and Ovid-EMBASE from 1950 and 1980 respectively to March 2012. Two independent reviewers screened and selected primary studies published in English that measured (in)appropriate medication prescription among elderly persons (>65 years) in the primary care setting. We extracted data sources, instruments for assessing medication prescription appropriateness, and the rate of inappropriate medication prescriptions. We grouped the reported individual medications according to the Anatomical Therapeutic and Chemical (ATC) classification and compared the median rate of inappropriate medication prescription and its range within each therapeutic class. Results We included 19 studies, 14 of which used the Beers criteria as the instrument for assessing appropriateness of prescriptions. The median rate of inappropriate medication prescriptions (IMP) was 20.5% [IQR 18.1 to 25.6%.]. Medications with largest median rate of inappropriate medication prescriptions were propoxyphene 4.52(0.10–23.30)%, doxazosin 3.96 (0.32 15.70)%, diphenhydramine 3.30(0.02–4.40)% and amitriptiline 3.20 (0.05–20.5)% in a decreasing order of IMP rate. Available studies described unequal sets of medications and different measurement tools to estimate the overall prevalence of inappropriate prescription. Conclusions Approximately one in five prescriptions to elderly persons in primary care is inappropropriate despite the attention that has been directed to quality of prescription. Diphenhydramine and amitriptiline are the most common inappropriately prescribed medications with high risk adverse events while propoxyphene and doxazoxin are the most commonly

  6. Screening antifungal activities of selected medicinal plants.

    PubMed

    Quiroga, E N; Sampietro, A R; Vattuone, M A

    2001-01-01

    Plants synthesise a vast array of secondary metabolites that are gaining importance for their biotechnological applications. The antifungal activity of the ethanolic extracts of ten Argentinean plants used in native medicine is reported. Antifungal assays included radial growth inhibition, disk and well diffusion assays and growth inhibition by broth dilution tests. The chosen test fungi were yeasts, microfungi and wood-rot causing Basidiomycetes. Extracts of Larrea divaricata, Zuccagnia punctata and Larrea cuneifolia displayed remarkable activity in the assays against the majority of the test fungi. In addition to the former plants, Prosopanche americana also inhibited yeast growth. PMID:11137353

  7. Inappropriate shocks delivered by implantable cardiac defibrillators during oversensing of activity of diaphagmatic muscle

    PubMed Central

    Babuty, D; Fauchier, L; Cosnay, P

    1999-01-01

    Two cases are reported (both men, one 72 and one 54 years old) of inappropriate shocks delivered by an implantable cardiac defibrillator (ICD) device, which oversensed the myopotentials induced by deep breathing and Valsalva manoeuvre. No damage to leads was associated with the oversensing of myopotentials. The mechanism of the inappropriate shocks was determined using real time electrograms. Modification of the duration of ventricular detection and decrease in sensitivity made it possible to avoid the oversensing of myopotentials and to deliver ICD treatment.

 Keywords: implantable cardiac defibrillator;  inappropriate shocks;  myopotentials PMID:10220554

  8. 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)

  9. 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. PMID:27259370

  10. Efflux-Mediated Antifungal Drug Resistance†

    PubMed Central

    Cannon, Richard D.; Lamping, Erwin; Holmes, Ann R.; Niimi, Kyoko; Baret, Philippe V.; Keniya, Mikhail V.; Tanabe, Koichi; Niimi, Masakazu; Goffeau, Andre; Monk, Brian C.

    2009-01-01

    Summary: Fungi cause serious infections in the immunocompromised and debilitated, and the incidence of invasive mycoses has increased significantly over the last 3 decades. Slow diagnosis and the relatively few classes of antifungal drugs result in high attributable mortality for systemic fungal infections. Azole antifungals are commonly used for fungal infections, but azole resistance can be a problem for some patient groups. High-level, clinically significant azole resistance usually involves overexpression of plasma membrane efflux pumps belonging to the ATP-binding cassette (ABC) or the major facilitator superfamily class of transporters. The heterologous expression of efflux pumps in model systems, such Saccharomyces cerevisiae, has enabled the functional analysis of efflux pumps from a variety of fungi. Phylogenetic analysis of the ABC pleiotropic drug resistance family has provided a new view of the evolution of this important class of efflux pumps. There are several ways in which the clinical significance of efflux-mediated antifungal drug resistance can be mitigated. Alternative antifungal drugs, such as the echinocandins, that are not efflux pump substrates provide one option. Potential therapeutic approaches that could overcome azole resistance include targeting efflux pump transcriptional regulators and fungal stress response pathways, blockade of energy supply, and direct inhibition of efflux pumps. PMID:19366916

  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. Antifungal effect of some spice hydrosols.

    PubMed

    Boyraz, Nuh; Ozcan, Musa

    2005-12-01

    The antifungal effects of rosemary, cumin, sater (savory), basil and pickling herb hydrosols were investigated against Rhizoctonia solani, Fusarium oxysporum f. sp tulipae, Botrytis cinerea and Alternaria citri. Hydrosols of sater and pickling herb showed the most relevant fungicidal activity. PMID:16243447

  13. 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

  14. Inappropriate Postural Habits of High School Students from the Municipality of Ceres, Brazil.

    PubMed

    Noll, M; Noll, P Rs; Santos, E M; Silva Neto, A R; Candotti, C T

    2016-02-01

    This study aims to evaluate the prevalence of inappropriate postural habits in students. 827 Brazilian students aged 14 to 19 were evaluated with a self-administered questionnaire. A high prevalence of (>90%) inappropriate habits in sitting postures (on a chair, to write, and at a computer) and picking up an object off the floor was observed, suggesting the need to develop preventive programs. PMID:26897159

  15. Utilization of potentially inappropriate medications in elderly patients in a tertiary care teaching hospital in India

    PubMed Central

    Jhaveri, Binit N.; Patel, Tejas K.; Barvaliya, Manish J; Tripathi, Chandrabhanu

    2014-01-01

    Aim: To evaluate the use of potentially inappropriate medicines in elderly inpatients in a tertiary care teaching hospital. Materials and Methods: Retrospective analysis was performed for cases of elderly patients admitted between January 2010 and December 2010. Data on age, gender, diagnosis, duration of hospital stay, treatment, and outcome were collected. Prescriptions were assessed for the use of potentially inappropriate medications in geriatric patients by using American Geriatric Society Beer's criteria (2012) and PRISCUS list (2010). Results: A total of 676 geriatric patients (52.12% females) were admitted in the medicine ward. The average age of geriatric patients was 72.69 years. According to Beer's criteria, at least one inappropriate medicine was prescribed in 590 (87.3%) patients. Metoclopramide (54.3%), alprazolam (9%), diazepam (8%), digoxin > 0.125 mg/day (5%), and diclofenac (3.7%) were the commonly used inappropriate medications. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) in heart and renal failure patients was the commonly identified drug–disease interaction. According to PRISCUS list, at least one inappropriate medication was prescribed in 210 (31.06%) patients. Conclusion: Use of inappropriate medicines is highly prevalent in elderly patients. PMID:25276629

  16. 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. PMID:27417387

  17. 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

  18. Prescribing of psychotropics in the elderly: why is it so often inappropriate?

    PubMed

    Mort, Jane R; Aparasu, Rajender R

    2002-01-01

    Psychotropic medications are an important treatment approach to mental health disorders; such disorders are common in the elderly population. Elderly patients are more likely to experience adverse effects from these agents than their younger counterparts due to age-related changes in pharmacodynamic and pharmacokinetic parameters. Because of these factors, inappropriate use of psychotropic medications in elderly patients has become a focus of concern. In general an agent is considered inappropriate if the risk associated with its use exceeds its benefit. Implicit and explicit criteria for inappropriate use of medications in the elderly have been created and include psychotropic agents. These criteria vary in their make-up but the explicit criteria tend to agree that amitriptyline, doxepin, and benzodiazepines that have long half-lives are not appropriate. Although explicit inappropriate medication criteria have been in existence since 1991, elderly patients continue to receive inappropriate psychotropic medications. A wide array of factors may be responsible for this practice. Provider-related causes include deficits in knowledge, confusion due to the lack of a consensus on the inappropriate psychotropic criteria, difficulties in addressing an inappropriate medication started by a previous provider, multiple prescribers and pharmacies involved in the care of a patient, negative perceptions regarding aging, and cost issues. Patients may contribute to the problem by demanding an inappropriate medication. Finally, the healthcare setting may inadvertently contribute to inappropriate prescribing by such policies as restrictive formularies or lack of reimbursement for pharmacists' clinical services. Successful approaches to optimising prescribing have been either educational or administrative. Educational approaches (e.g. one-on-one sessions, academic detailing) seek to influence decision making, while administrative approaches attempt to enforce policies to curtail the

  19. Oral Antifungal Drugs in the Treatment of Dermatomycosis.

    PubMed

    Tsunemi, Yuichiro

    2016-01-01

    Oral antifungal drugs are used primarily to treat tinea unguium; however, they are also useful for other types of tinea. For example, a combination of topical and oral antifungal drugs is effective in hyperkeratotic tinea pedis that is unresponsive to topical monotherapy. In cases of tinea facialis adjacent to the eyes, ears, or mouth, or widespread tinea corporis, or tinea cruris involving the complex skin folds of the external genitalia, it is difficult to apply topical drugs to all the lesions; therefore, oral antifungal drugs are necessary. Oral antifungal drugs are also useful not only for tinea but for widespread pityriasis versicolor and Malassezia folliculitis, candidal onychomycosis, and candidal paronychia and onychia. Topical antifungal drugs are in fact unsuitable for some mycoses. In tinea capitis, for example, irritation by topical drugs is likely to enhance inflammation; therefore, oral antifungal drug monotherapy is preferable. In interdigital tinea pedis with erosion or contact dermatitis, topical drugs are difficult to use because they tend to cause irritant dermatitis, resulting in exacerbation of the condition. In such cases, treatment should begin with a combination of topical corticosteroid therapy and oral antifungal drugs active against dermatophytes. Topical antifungal drugs are used after the complications resolve. A combination of topical and oral antifungal drugs can shorten the treatment period, thus improving patient adherence to topical treatment. Oral antifungal drugs are useful because of their wide range of applications in the treatment of dermatomycosis. PMID:27251319

  20. From antidiabetic to antifungal: discovery of highly potent triazole-thiazolidinedione hybrids as novel antifungal agents.

    PubMed

    Wu, Shanchao; Zhang, Yongqiang; He, Xiaomeng; Che, Xiaoying; Wang, Shengzheng; Liu, Yang; Jiang, Yan; Liu, Na; Dong, Guoqiang; Yao, Jianzhong; Miao, Zhenyuan; Wang, Yan; Zhang, Wannian; Sheng, Chunquan

    2014-12-01

    In an attempt to discover a new generation of triazole antifungal agents, a series of triazole-thiazolidinedione hybrids were designed and synthesized by molecular hybridization of the antifungal agent fluconazole and rosiglitazone (an antidiabetic). Most of the target compounds showed good to excellent inhibitory activity against a variety of clinically important fungal pathogens. In particular, compounds (Z)-5-(2,4-dichlorobenzylidene)-3-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)thiazolidine-2,4-dione) (15 c), (Z)-3-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-5-(furan-3-ylmethylene)thiazolidine-2,4-dione (15 j), and (Z)-3-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-5-(furan-3-ylmethylene)thiazolidine-2,4-dione (15 r) were highly active against Candida albicans, with MIC80 values in the range of 0.03-0.15 μM. Moreover, compounds 15 j and 15 r were found to be effective against four fluconazole-resistant clinical isolates; these two compounds are particularly promising antifungal leads for further optimization. Molecular docking studies revealed that the hydrogen bonding interactions between thiazolidinedione and CYP51 from C. albicans are important for antifungal activity. This study also demonstrates the effectiveness of molecular hybridization in antifungal drug discovery. PMID:25196996

  1. 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. PMID:23496653

  2. A copeptin-based classification of the osmoregulatory defects in the syndrome of inappropriate antidiuresis.

    PubMed

    Fenske, W; Sandner, B; Christ-Crain, M

    2016-03-01

    The syndrome of inappropriate antidiuretic hormone secretion (SIADH), also referred to as syndrome of inappropriate antidiuresis (SIAD), is the most common cause of hyponatremia characterized by extracellular hypotonicity and impaired urine dilution in the absence of any recognizable nonosmotic stimuli for the antidiuretic hormone arginine vasopressin (AVP). Hyponatremia in SIADH is primarily the result of excessive water retention caused by a combination of inappropriate antidiuresis and persistent fluid intake in the presence of impaired osmoregulated inhibition of thirst. It is sometimes aggravated by a sodium deficiency caused by a decreased intake or a secondary natriuresis in response to elevated extracellular volume. Inappropriate antidiuresis usually results from endogenous production of AVP that can be either ectopic (from a malignancy) or eutopic (from the hypothalamus/neurohypophysis). Regardless of its origin, different types of osmotic dysregulation of AVP have been reported with possibly fundamental deviations in treatment need and efficacy. A recent quantitative analysis of 50 patients with SIADH, which underwent serial measurements of copeptin during hypertonic saline infusion, revealed five distinct types of osmoregulatory defect ("type A to E") without affiliation to specific underlying diseases. In addition to apparently impaired osmoregulated inhibition of AVP release in the majority of patients, 12% of patients showed an AVP-independent mechanism of inappropriate antidiuresis, whilst 20% of them presented a reverse relation between hormone release and serum osmolality, presumably related to interrupted nonosmotic inhibitory pathways. The interference of these different types of SIAD with clinical presentation and therapy response will be a relevant subject for future research. PMID:27156760

  3. Frequent Home Monitoring of ICD Is Effective to Prevent Inappropriate Defibrillator Shock Delivery.

    PubMed

    Bifulco, Paolo; Argenziano, Luigi; Romano, Maria; Cesarelli, Mario; Sansone, Mario; Casella, Stefano; Nardi, Stefano

    2014-01-01

    Recently, in the context of telemedicine, telemonitoring services are gaining attention. They are offered, for example, to patients with implantable cardioverter defibrillators (ICDs). A major problem associated with ICD therapy is the occurrence of inappropriate shocks which impair patients' quality of life and may also be arrhythmogenic. The telemonitoring can provide a valid support to intensify followup visits, in order to improve the prevention of inappropriate defibrillator shock, thus enhancing patient safety. Inappropriate shock generally depends on atrial fibrillation, supraventricular tachycardia, and abnormal sensing (such as those caused by electromagnetic interferences). As a practical example, an unusual case of an ICD patient who risked an inappropriate shock while taking a shower is reported. Continuous remote telemonitoring was able to timely warn cardiologist via GSM-SMS, who were able to detect improper sensing examining the intracardiac electrogram via Web. Patient was promptly contacted and warned to not further come in contact with the hydraulic system and any electrical appliance to prevent an inappropriate defibrillator shock. This demonstrates the effectiveness and usefulness of continuous remote telemonitoring in supporting ICD patients. PMID:24592279

  4. 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

  5. Natural Killer Cells and Antifungal Host Response

    PubMed Central

    Schmidt, Stanislaw; Zimmermann, Stefanie-Yvonne; Tramsen, Lars; Koehl, Ulrike

    2013-01-01

    As a result of improved experimental methodologies and a better understanding of the immune system, there is increasing insight into the antifungal activity of natural killer (NK) cells. Murine and human NK cells are able to damage fungi of different genera and species in vitro, and they exert both direct and indirect antifungal activity through cytotoxic molecules such as perforin and through cytokines and interferons, respectively. On the other hand, recent data suggest that fungi exhibit immunosuppressive effects on NK cells. Whereas clear in vivo data are lacking in humans, the importance of NK cells in the host response against fungi has been demonstrated in animal models. Further knowledge of the interaction of NK cells with fungi might help to better understand the pathogenesis of invasive fungal infections and to improve treatment strategies. PMID:23365210

  6. 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. PMID:23280633

  7. Antifungal stewardship in a tertiary-care institution: a bedside intervention.

    PubMed

    Valerio, M; Muñoz, P; Rodríguez, C G; Caliz, B; Padilla, B; Fernández-Cruz, A; Sánchez-Somolinos, M; Gijón, P; Peral, J; Gayoso, J; Frias, I; Salcedo, M; Sanjurjo, M; Bouza, E

    2015-05-01

    Antifungal stewardship (AFS) programmes are needed in tertiary-care hospitals. Our aim is to describe a bedside non-restrictive AFS programme, and to evaluate its economic impact. During the first year of the AFS a bundle of non-interventional measures were implemented. During the second year an infectious diseases specialist visited 453 patients receiving candins, liposomal amphotericin B, voriconazole or posaconazole. Monthly costs were studied with an interrupted time series (ITS) analysis. The main prescribing departments were haematology (35%), medical departments (23%), and intensive care units (20%). Reasons to start antifungal therapy were: targeted therapy (36%), prophylaxis (32%), empirical therapy (20%) and pre-emptive therapy (12%). At the initial visit, diagnostic advice was provided in 40% of cases. The most common therapeutic recommendations were to de-escalate the antifungal drug (17%) or to suspend it (7%). Annual total antifungal expenditure was reduced from US$3.8 million to US$2.9 million over the first 2 years, generating net savings of US$407,663 and US$824,458 per year after considering the cost of additional staff required. The ITS analyses showed a significant economic impact after the first 12 months of the intervention (p 0.042 at month 13), which was enhanced in the following 24 months (p 0.006 at month 35). The number of defined daily doses decreased from 66.4 to 54.8 per 1000 patient-days. Incidence of candidaemia was reduced from 1.49 to 1.14 (p 0.08) and related mortality was reduced from 28% to 16% (p 0.1). A collaborative and non-compulsory AFS program based on bedside intervention is an efficacious and cost-effective approach that optimizes the use of AF drugs. PMID:25748494

  8. 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

  9. 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

  10. 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. PMID:26883854

  11. Antifungal serum concentration monitoring: an update.

    PubMed

    Goodwin, Megan L; Drew, Richard H

    2008-01-01

    Invasive fungal infections (IFIs) are occurring with increasing incidence and are associated with significant morbidity and mortality. Understanding the relationship between the pharmacokinetic and pharmacodynamic properties of antifungals is essential to optimize the potential for favourable clinical and microbiological outcomes while minimizing risks of treatment-related toxicity. Antifungal serum concentrations may aid in the determination of appropriate dosing in select circumstances. The polyene and echinocandin classes of antifungals lack sufficient data to justify serum concentration monitoring in routine clinical practice. In contrast, serum concentration monitoring of flucytosine may help to reduce the risk of treatment-related haematological toxicity. Determination of itraconazole serum concentrations is advised in situations where the drug is used for prolonged periods to treat serious IFIs (such as invasive aspergillosis or histoplasmosis) because of variability in absorption following oral administration (most notable for the capsule formulation). The use of serum concentration monitoring during therapy with the extended-spectrum triazoles (i.e. voriconazole and posaconazole) is still evolving, due primarily to inter-patient variability in drug exposure combined with sparse data regarding relationships with efficacy (posaconazole) and both safety and efficacy (voriconazole). PMID:17999982

  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). PMID:19831024

  13. Antifungal Activity of Maytenin and Pristimerin

    PubMed Central

    Gullo, Fernanda P.; Sardi, Janaina C. O.; Santos, Vânia A. F. F. M.; Sangalli-Leite, Fernanda; Pitangui, Nayla S.; Rossi, Suélen A.; de Paula e Silva, Ana C. A.; Soares, Luciana A.; Silva, Julhiany F.; Oliveira, Haroldo C.; Furlan, Maysa; Silva, Dulce H. S.; Bolzani, Vanderlan S.; Mendes-Giannini, Maria José S.; Fusco-Almeida, Ana Marisa

    2012-01-01

    Fungal infections in humans have increased alarmingly in recent years, particularly in immunocompromised individuals. Among the infections systemic candidiasis, aspergillosis, cryptococcosis, paracoccidioidomycosis, and histoplasmosis mortality are more prevalent and more severe in humans. The current high incidence of dermatophytosis is in humans, especially as the main etiologic agents Trichophyton rubrum and Trichophyton mentagrophytes. Molecules pristimerin and maytenin obtained from the plant Maytenus ilicifolia (Celastraceae) are known to show various pharmacological activities. This study aimed to evaluate the spectrum of antifungal activity of maytenin and pristimerin and their cytotoxicity in human keratinocytes (NOK cells of the oral mucosa). It was concluded that the best spectrum of antifungal activity has been shown to maytenin with MIC varying from 0.12 to 125 mg/L, although it is also active with pristimerin MIC ranging between 0.12 and 250 mg/L. Regarding the toxicity, both showed to have high IC50. The SI showed high pristimerin against some species of fungi, but SI maytenin was above 1.0 for all fungi tested, showing a selective action of fungi. However, when comparing the two substances, maytenin also showed better results. The two molecules can be a possible prototype with a broad spectrum of action for the development of new antifungal agents. PMID:22675379

  14. 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. PMID:23721186

  15. 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. PMID:27216048

  16. [Synthesis and antifungal activity of butenafine hydrochloride (KP-363), a new benzylamine antifungal agent].

    PubMed

    Maeda, T; Takase, M; Ishibashi, A; Yamamoto, T; Sasaki, K; Arika, T; Yokoo, M; Amemiya, K

    1991-02-01

    In screening of new antifungal agents, bis(naphthalenemethyl)amines were found to have more potent antifungal activity than clotrimazole. Studies on their structure-activity relationships indicated that benzylamines had potent antifungal activity. Among them, butenafine hydrochloride (N-p-tert-butylbenzyl-N-methyl-1-naphthalenemethylamine hydrochloride, KP-363) has proved to show the strongest activity. It exhibits a wide spectrum activity in vitro against particularly dermatophytes (87 strains; minimal inhibitory concentration (MIC) range, 0.0015 to 0.05 microgram/ml), and also against Aspergillus (15 strains; MIC range, 0.025 to 0.78 microgram/ml), Cryptococcus neoformans (4 strains; MICs 0.78 and 1.56 micrograms/ml) and yeasts of genus Candida (67 strains; MIC range, 3.13 to greater than 100 micrograms/ml). PMID:2056447

  17. Make a lasting impression: the neural consequences of re-encountering people who emote inappropriately.

    PubMed

    Bayliss, Andrew P; Naughtin, Claire K; Lipp, Ottmar V; Kritikos, Ada; Dux, Paul E

    2012-12-01

    We can learn about the affective content of the environment by observing the behavior of others; their responses to stimuli tend to be appropriate to the context. To investigate the impact of observing such appropriate, compared with inappropriate, behaviors, we developed a novel behavioral task where participants observed different faces reacting to emotional scenes. We found that affective categorization of a scene was facilitated when it was presented alongside an appropriate facial expression (Experiment 1). Further, we observed that several brain areas in the right hemisphere-the putamen, insula, orbitofrontal cortex, and dorsal anterior cingulate cortex-were more activate when viewing faces that were previously observed emoting inappropriately (Experiment 2). We contend that these areas form a network that codes for the retrieval of affective conflict information generated by observing individuals producing inappropriate emotions. PMID:23095146

  18. [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. PMID:25272660

  19. Inappropriate shock for myopotential over-sensing in a patient with subcutaneous ICD.

    PubMed

    Corzani, Alessandro; Ziacchi, Matteo; Biffi, Mauro; Diemberger, Igor; Martignani, Cristian; Boriani, Giuseppe

    2015-01-01

    Inappropriate ICD shocks are common adverse events; they are mainly due to supraventricular arrhythmias and secondly are related to noise, undersensing, oversensing, device malfunctions. We present a case of inappropriate device therapy due to myopotential oversensing in a patient with a subcutaneous ICD (s-ICD). A 58 years old male with an s-ICD during the device interrogation showed a previous episode of suspected sustained ventricular tachycardia at 210 bpm, which was effectively treated with ICD shock. The patient experienced the electrical shock while holding a big gas-cylinder in his arms. The EGM analysis revealed many irregular ventricular signals of low amplitude lasting for 24 s and interrupted by the shock. The device showed no malfunctions. This is the first case report of inappropriate S-ICD shock related to myopotential over-sensing. By recording intracardiac EGM, we demonstrated that the noise was created by the activity of the pectorals muscles. PMID:25820052

  20. 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

  1. 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. PMID:22870060

  2. 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

  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. PMID:26924486

  4. Correlates of (inappropriate) benzodiazepine use: the Netherlands Study of Depression and Anxiety (NESDA)

    PubMed Central

    Manthey, Leonie; van Veen, Tineke; Giltay, Erik J; Stoop, José E; Neven, Arie Knuistingh; Penninx, Brenda W J H; Zitman, Frans G

    2011-01-01

    AIM Results on determinants of benzodiazepine (BZD) use in general and inappropriate use were inconsistent and mostly univariate. The relative importance of sociodemographic, psychological and physical determinants has never been investigated in a comprehensive, multivariate model. METHODS We included 429 BZD users and 2423 non-users from the Netherlands Study of Depression and Anxiety (NESDA) in order to investigate sociodemographic, psychological and physical determinants of BZD use and inappropriate use by logistic and linear regression analyses. RESULTS BZDs were used by a considerable proportion of the 2852 NESDA participants (15.0%). BZD use was independently associated with older age, singleness, unemployment, treatment in secondary care, higher medical consumption (more severe) anxiety, depression (OR [95% CI]= 1.95 [1.29, 2.93]), comorbidity, insomnia, SSRI (OR [95% CI]= 2.05 [1.55, 2.70]), TCA and other antidepressant (OR [95% CI]= 2.44 [1.64, 3.62]) use. Overall, BZD use was rarely in accordance with all guidelines, mainly because most users (82.5%) exceeded the recommended duration of safe use. Inappropriate use was independently associated with older age (β= 0.130) and chronic illnesses (β= 0.120). Higher scores on agreeableness were associated with less inappropriate use. CONCLUSIONS Mentally or physically vulnerable subjects were most likely to use BZDs. The most vulnerable (i.e. the old and physically ill) BZD users were at highest risk of inappropriate BZD use. Without further evidence of the effectiveness of BZDs in long-term use, caution in initiating BZD prescriptions is recommended, particularly when patients are chronically ill and old, as those are most likely to display inappropriate use. PMID:21219408

  5. 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.

  6. Inappropriate implantable cardioverter defibrillator shocks in fractured Sprint Fidelis leads associated with 'appropriate' interrogation.

    PubMed

    Farwell, David; Redpath, Calum; Birnie, David; Gollob, Michael; Lemery, Robert; Posan, Emoke; Green, Martin

    2008-06-01

    We present two patients with fractures within the pace-sense circuit of their Medtronic Sprint Fidelis leads who received inappropriate shocks from their Medtronic defibrillators during device interrogation. This was not simply a coincidence, but due to electromagnetic interference induced within the Sprint Fidelis lead by the device programmer during two-way communication with the defibrillator. Our subsequent investigations have uncovered at least two other similar incidents in Canada. We have also discovered that the Medtronic 'Auto-resume' feature may leave future patients uniquely vulnerable to such inappropriate shocks in the future. PMID:18456645

  7. Evaluation of the supply of antifungal medication for the treatment of vaginal thrush in the community pharmacy setting: a randomized controlled trial

    PubMed Central

    Schneider, Carl R.; Emery, Lyndal; Brostek, Raisa; Clifford, Rhonda M.

    Background The Pharmaceutical Society of Australia have developed "guidance" for the supply of several medicines available without prescription to the general public. Limited research has been published assessing the effect of these guidelines on the provision of medication within the practice of pharmacy. Objective To assess appropriate supply of non-prescription antifungal medications for the treatment of vaginal thrush in community pharmacies, with and without a guideline. A secondary aim was to describe the assessment and counseling provided to patients when requesting this medication. Methods A randomized controlled trial was undertaken whereby two simulated patients conducted visits to 100 randomly selected community pharmacies in a metropolitan region. A product-based request for fluconazole (an oral antifungal that has a guideline was compared to a product-based request for clotrimazole (a topical antifungal without a guideline). The same patient details were used for both requests. Outcome measures of the visits were the appropriateness of supply and referral to a medical practitioner. Results Overall 16% (n=16) of visits resulted in an appropriate outcome; 10% (n=5) of fluconozaole requests compared with 22% (n=11) of clotrimazole requests (chi-square=2.68, p=0.10). There was a difference in the type of assessment performed by pharmacy staff between visits for fluconazole and clotrimazole. A request for clotrimazole resulted in a significant increase in frequency in regards to assessment of the reason for the request (chi-square=8.57, p=0.003), symptom location (chi-square=8.27, p=0.004), and prior history (chi-square=5.09, p=0.02). Conclusions Overall practice was poor, with the majority of pharmacies inappropriately supplying antifungal medication. New strategies are required to improve current practice of community pharmacies for provision of non-prescription antifungals in the treatment of vaginal thrush. PMID:24223077

  8. 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

  9. 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. PMID:27069906

  10. 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. PMID:20702671

  11. 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. PMID:25796467

  12. 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…

  13. 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)

  14. 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…

  15. 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…

  16. 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.…

  17. Potentially inappropriate prescribing in an Irish elderly population in primary care

    PubMed Central

    Ryan, Cristín; O'Mahony, Denis; Kennedy, Julia; Weedle, Peter; Byrne, Stephen

    2009-01-01

    AIMS Screening tools have been formulated to identify potentially inappropriate prescribing (IP) in older people. Beers' criteria are the most widely used but have disadvantages when used in Europe. New IP screening tools called Screening Tool of Older Person's Prescriptions (STOPP) and Screening Tool to Alert doctors to Right Treatment (START) have been developed to identify potential IP and potential prescribing omissions (PPOs). The aim was to measure the prevalence rates of potential IP and PPOs in primary care using Beers' criteria, STOPP and START. METHODS Case records of 1329 patients ≥65 years old from three general practices in one region of southern Ireland were studied. The mean age ± SD of the patients was 74.9 ± 6.4 years, 60.9% were female. Patients' current diagnoses and prescription medicines were reviewed and the Beers' criteria, STOPP and START tools applied. RESULTS The total number of medicines prescribed was 6684; median number of medicines per patient was five (range 1–19). Overall, Beers' criteria identified 286 potentially inappropriate prescriptions in 18.3% (243) of patients, whilst the corresponding IP rate identified by STOPP was 21.4% (284), in respect of 346 potentially inappropriate prescriptions. A total of 333 PPOs were identified in 22.7% (302) of patients using the START tool. CONCLUSION Potentially inappropriate drug prescribing and errors of drug omission are highly prevalent among older people living in the community. Prevention strategies should involve primary care doctors and community pharmacists. PMID:20002089

  18. Inappropriate fixation of an endotracheal tube causing cuff malfunction resulting in difficult extubation.

    PubMed

    Nag, Deb Sanjay; Samaddar, Devi Prasad

    2016-01-01

    We discuss a case of difficult extubation, due to inadequate deflation of the tracheal tube cuff, despite collapse of the pilot balloon, on its aspiration. This was caused by inadvertent kinking of the pilot balloon tubing due to inappropriate tape fixation of the endotracheal tube. PMID:27591469

  19. Inappropriate and excessive guilt: instrument validation and developmental differences in relation to depression.

    PubMed

    Tilghman-Osborne, Carlos; Cole, David A; Felton, Julia W

    2012-05-01

    Inappropriate or excessive guilt is listed as a symptom of depression by the American Psychiatric Association (1994). Although many measures of guilt have been developed, definitional and operational problems exist, especially in the application of such measures in childhood and adolescence. To address these problems, the current study introduces the Inappropriate and Excessive Guilt Scale (IEGS), assesses its validity for use with children and adolescents, and tests its relation to depression across development. From a sample of 370 children between 7 and 16 years old, results provided (1) evidence that items designed to assess inappropriate and excessive guilt converged onto a single underlying factor, (2) support for the convergent, discriminant, and construct validity of the IEGS in a general youth population, and (3) evidence of incremental validity of the IEGS over-and-above other measures of guilt. Results also supported the hypothesis that inappropriate and excessive guilt as well as negative cognitive errors become less normative and more depressotypic with age. PMID:22086497

  20. Case of inappropriate ADH syndrome: hyponatremia due to polyethylene glycol bowel preparation.

    PubMed

    Ko, Sun-Hye; Lim, Chul-Hyun; Kim, Jae-Young; Kang, Seung Hun; Baeg, Myong Ki; Oh, Hyun Jin

    2014-09-14

    Colonoscopic screening has been reported to reduce deaths from colorectal cancer. Adequate bowel preparation is essential for this and safety is an important issue in choosing the methods. Polyethylene glycol (PEG) is regarded as a safe method for cleansing, especially compared with oral sodium phosphate. Here, we present a case of hyponatremia caused by the syndrome of inappropriate antidiuretic hormone (ADH) syndrome after PEG precolonoscopic cleansing resulting in generalized tonic-clonic seizures. A 62-year-old women had ingested PEG for precolonoscopic bowel cleansing. While waiting for the colonoscopy, she developed a stuporous mentality and generalized tonic-clonic seizures, which did not correlate with brain magnetic resonance imaging. Her serum sodium level was 113 mEq per liter and laboratory analyses were consistent with inappropriate ADH syndrome. Her thyroid and adrenal functions were normal. There were no malignancies, infections, respiratory disorders or central nervous disorders and she had no history of taking either diuretics or other medications, which might have caused inappropriate ADH syndrome. She was treated with 3% hypertonic saline and showed a complete neurological recovery as her sodium levels recovered. Follow-up visits showed the patient to have a normal sodium level without neurologic deficits. This case shows that inappropriate ADH syndrome can be caused by PEG preparation, which implies that physicians have to be aware of the possible side effects of this colonic cleansing approach and mindful of the possible ensuing symptoms. PMID:25232272

  1. Inappropriate and Excessive Guilt: Instrument Validation and Developmental Differences in Relation to Depression

    ERIC Educational Resources Information Center

    Tilghman-Osborne, Carlos; Cole, David A.; Felton, Julia W.

    2012-01-01

    Inappropriate or excessive guilt is listed as a symptom of depression by the American Psychiatric Association ("1994"). Although many measures of guilt have been developed, definitional and operational problems exist, especially in the application of such measures in childhood and adolescence. To address these problems, the current study…

  2. Deceleration Procedures for Inappropriate Social Behaviors with Severely Retarded Ss. Two Papers.

    ERIC Educational Resources Information Center

    Spangler, Robert S.; And Others

    Two papers describe studies to decrease inappropriate social behaviors of severely retarded students. R. Spangler and others in "The Effect of a Time-Out Procedure on the Duration of Tantrum Behavior in a 13-Year-Old Severely Retarded Male S" report on a three phase study in which a combination of verbal instructions and a timeout procedure…

  3. 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…

  4. Community Services, Issues, and Service Gaps for Individuals with Developmental Disabilities Who Exhibit Inappropriate Sexual Behaviors.

    ERIC Educational Resources Information Center

    Ward, Karen M.; Pfeiffer, Karl T.; Trigler, Jordan S.

    2001-01-01

    A national survey of 243 community agencies evaluated services provided for individuals with developmental disabilities who exhibit high-risk sexual behaviors and identified issues and service gaps. Common offenses were sexual behavior in public situations, inappropriate involvement of others, and involvement of minors. Major issues and problems…

  5. Dysgeusia in symptomatic syndrome of inappropriate antidiuretic hormone secretion: think of lung cancer

    PubMed Central

    Singh, Nishith K; Hayes, Shelbi; Hahs, Seth; Varney, Andrew

    2009-01-01

    The case of a 60-year-old woman who presented with marked dysgeusia to all food and symptomatic syndrome of inappropriate antidiuretic hormone secretion (SIADH) is described. She eventually turned out to have metastatic small cell lung cancer. The case study explores the interesting constellation of dysgeusia, SIADH and lung cancer. PMID:21686989

  6. 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…

  7. 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

  8. Inappropriate and Excessive Guilt: Instrument Validation and Developmental Differences in Relation to Depression

    PubMed Central

    Tilghman-Osborne, Carlos; Felton, Julia W.

    2014-01-01

    Inappropriate or excessive guilt is listed as a symptom of depression by the American Psychiatric Association (1994). Although many measures of guilt have been developed, definitional and operational problems exist, especially in the application of such measures in childhood and adolescence. To address these problems, the current study introduces the Inappropriate and Excessive Guilt Scale (IEGS), assesses its validity for use with children and adolescents, and tests its relation to depression across development. From a sample of 370 children between 7 and 16 years old, results provided (1) evidence that items designed to assess inappropriate and excessive guilt converged onto a single underlying factor, (2) support for the convergent, discriminant, and construct validity of the IEGS in a general youth population, and (3) evidence of incremental validity of the IEGS over-and-above other measures of guilt. Results also supported the hypothesis that inappropriate and excessive guilt as well as negative cognitive errors become less normative and more depressotypic with age. PMID:22086497

  9. 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…

  10. 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…

  11. 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…

  12. 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…

  13. 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…

  14. Inappropriate speech in a severely retarded child: a case study in language conditioning and generalization

    PubMed Central

    Barton, Elizabeth Spindler

    1970-01-01

    The modification of inappropriate speech, a class of behaviors rather than a limited number of specific examples, is little known in the severely retarded. In this study, operant techniques were used to modify the strikingly bizarre and inappropriate speech of a severely retarded boy. The boy's appropriate verbal responses to questions about magazine pictures were reinforced with candy. When he responded inappropriately, the magazine was withdrawn, and social interaction was discontinued for a 10-sec timeout period. Negative responses were ignored, the next picture displayed, and the next question asked immediately. In 10 sessions, appropriate responses increased from 26% to 86% of all responses. A reversal of reinforcement was then introduced, in which inappropriate responses were reinforced, appropriate responses resulted in timeout, and negative responses were treated as before. This reduced the percentage of appropriate responses to 24%. Subsequent sessions of reinforcement for appropriate responses increased appropriate responses to 96% of all responses. At significant stages in the experiment, a measure of possible generalization was attempted. Although some generalization was recorded, it was minimal: some explanations are discussed. PMID:16795272

  15. Inappropriate overuse of inhaled corticosteroids for COPD patients: impact on health costs and health status.

    PubMed

    de Miguel-Díez, Javier; Carrasco-Garrido, Pilar; Rejas-Gutierrez, Javier; Martín-Centeno, Antonio; Gobartt-Vázquez, Elena; Hernandez-Barrera, Valentín; Gil de, Miguel Angel; Jimenez-Garcia, Rodrigo

    2011-06-01

    The aim of this study was to evaluate the relationship between inappropriate overuse of inhaled corticosteroids and self-reported health status and the annual cost of patients with stable chronic obstructive pulmonary disease (COPD) recruited in the primary-care setting. An observational, crossover, descriptive study was conducted. Patients with stable COPD and aged ≥40 years, evaluated in primary care, were included. Data collected were demographic variables, clinical characteristics, self-reported health status (SF-12), the severity of the illness, treatment, and health-care resource utilization in the past year. The patients were recruited during a period of 3 months (from January 1 to March 31, 2003). Use was considered inappropriate when corticosteroids were prescribed by physicians for patients not meeting criteria for its use as recommended in guidelines. A total of 10,711 patients [75.6% males; mean age = 67.1 (SD = 9.66) years] were evaluated. Disease severity was mild in 35.5% of the cases, moderate in 53.4%, and severe in 11.2%. Among them, 3,697 (34.5%) subjects were prescribed inhaled corticosteroids or drug combinations containing such therapies, with a rate of inappropriate use of 18.2%. Physical health status was significantly lower among patients showing inappropriate corticosteroids use: 37.35 (SD = 9.53) vs. 40.7 (SD = 9.80) (p < 0.05). The annual cost per patient of COPD management was significantly higher in the group with inappropriate inhaled corticosteroids use: 1,590 (SD = 1,834) vs. 1,157 (SD = 1,536) (p < 0.05). Factors statistically associated with inappropriate use of corticosteroids were educational attainment [OR: 2.77 (95% CI: 1.36-5.63) for nonuniversity training], a history of heart disease [OR: 1.42 (95% CI: 1.02-1.97)], depression [OR: 1.47 (95% CI: 1.05-2.05)], any allergy [OR 1.69 (95% CI: 1.13-2.54)], and physical health status [OR 0.97 (95% CI: 0.96-0.98)]. Lack of adherence to the

  16. 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

  17. Antifungal cyclic peptides from the marine sponge Microscleroderma herdmani

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  18. Antifungal and antiviral products of marine organisms.

    PubMed

    Cheung, Randy Chi Fai; Wong, Jack Ho; 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; Ye, Xiu Juan; Xia, Jiang; Ng, Tzi Bun

    2014-04-01

    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 aforementioned 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 prospects of

  19. The Impact of WHO Essential Medicines Policies on Inappropriate Use of Antibiotics

    PubMed Central

    Holloway, Kathleen Anne; Rosella, Laura; Henry, David

    2016-01-01

    Background 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. Aims To determine whether public sector inappropriate antibiotic use is lower in countries reporting implementation of selected essential medicines policies. Materials and Methods 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. Results 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

  20. 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.

  1. 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

  2. Combination Antifungal Therapy for Invasive Aspergillosis Revisited

    PubMed Central

    Panackal, Anil A.

    2016-01-01

    Invasive aspergillosis (IA) causes significant morbidity and mortality among immunocompromised hosts. Combination therapy with mold-active triazoles and echinocandins has been used with the hope of improving outcomes over monotherapy, especially in the setting of refractory disease. Herein, I update our prior systematic review and meta-analysis on combination therapy for salvage IA in the context of the recently published randomized clinical trial of combination therapy for primary IA. Clinicians should consider combination antifungals for IA in refractory disease despite immune reconstitution when there are concerns for resistance or pharmacokinetic variability. PMID:27441304

  3. 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

  4. Synthesis and investigation of novel benzimidazole derivatives as antifungal agents.

    PubMed

    Chandrika, Nishad Thamban; Shrestha, Sanjib K; Ngo, Huy X; Garneau-Tsodikova, Sylvie

    2016-08-15

    The rise and emergence of resistance to antifungal drugs by diverse pathogenic fungal strains have resulted in an increase in demand for new antifungal agents. Various heterocyclic scaffolds with different mechanisms of action against fungi have been investigated in the past. Herein, we report the synthesis and antifungal activities of 18 alkylated mono-, bis-, and trisbenzimidazole derivatives, their toxicities against mammalian cells, as well as their ability to induce reactive oxygen species (ROS) in yeast cells. Many of our bisbenzimidazole compounds exhibited moderate to excellent antifungal activities against all tested fungal strains, with MIC values ranging from 15.6 to 0.975μg/mL. The fungal activity profiles of our bisbenzimidazoles were found to be dependent on alkyl chain length. Our most potent compounds were found to display equal or superior antifungal activity when compared to the currently used agents amphotericin B, fluconazole, itraconazole, posaconazole, and voriconazole against many of the strains tested. PMID:27301676

  5. 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

  6. Resistance to antifungals that target CYP51.

    PubMed

    Parker, Josie E; Warrilow, Andrew G S; Price, Claire L; Mullins, Jonathan G L; Kelly, Diane E; Kelly, Steven L

    2014-10-01

    Fungal diseases are an increasing global burden. Fungi are now recognised to kill more people annually than malaria, whilst in agriculture, fungi threaten crop yields and food security. Azole resistance, mediated by several mechanisms including point mutations in the target enzyme (CYP51), is increasing through selection pressure as a result of widespread use of triazole fungicides in agriculture and triazole antifungal drugs in the clinic. Mutations similar to those seen in clinical isolates as long ago as the 1990s in Candida albicans and later in Aspergillus fumigatus have been identified in agriculturally important fungal species and also wider combinations of point mutations. Recently, evidence that mutations originate in the field and now appear in clinical infections has been suggested. This situation is likely to increase in prevalence as triazole fungicide use continues to rise. Here, we review the progress made in understanding azole resistance found amongst clinically and agriculturally important fungal species focussing on resistance mechanisms associated with CYP51. Biochemical characterisation of wild-type and mutant CYP51 enzymes through ligand binding studies and azole IC50 determinations is an important tool for understanding azole susceptibility and can be used in conjunction with microbiological methods (MIC50 values), molecular biological studies (site-directed mutagenesis) and protein modelling studies to inform future antifungal development with increased specificity for the target enzyme over the host homologue. PMID:25320648

  7. Novel antifungal peptides from Ceylon spinach seeds.

    PubMed

    Wang, H; Ng, T B

    2001-11-01

    Two novel antifungal peptides, designated alpha- and beta-basrubrins, respectively, were isolated from seeds of the Ceylon spinach Basella rubra. The purification procedure involved saline extraction, (NH(4))(2)SO(4) precipitation, ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on CM-cellulose and FPLC-gel filtration on Superdex peptide column. alpha- and beta-basrubrins exhibited a molecular weight of 4.3 and 5 kDa, respectively. They inhibited translation in a rabbit reticulocyte system with an IC(50) value of 400 and 100 nM, respectively. alpha- and beta-basrubrin inhibited HIV-1 reverse transcriptase by (79.4 +/- 7.8)% and (54.6 +/- 3.6)%, respectively, at a concentration of 400 microM, and (10.56 +/- 0.92)% and (2.12 +/- 0.81)%, respectively, at a concentration of 40 microM. Both alpha- and beta-basrubrins exerted potent antifungal activity toward Botrytis cinerea, Mycosphaerella arachidicola, and Fusarium oxysporum. PMID:11688973

  8. 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

  9. [An update on antifungal susceptibility testing].

    PubMed

    Tapia P, Cecilia V

    2009-04-01

    Due to increasing of invasive fungal infections and emergeney of antifungal drugs resistant fungi, standardized methods of antifungal susceptibility testing (AST) have been developed. The Clinical Laboratory Standards Instutute (CLSI) and the European for Committee Antimicrobial Susceptibility Testing (EUCAST) have guidelines for susceptibility of yeasts by broth microdilution (M27-A2 and E. Dis. 7.1 documents, respectively). Both are equivalent, although they present methodological and interpretative breakpoints differences. In addition, the CLSI have the M38-A (for filamentous fungi) and M44-A (disk diffusion) documents, whereas EUCAST is developing a document for Aspergillus spp. Furthermore, commercial methods are available that display good correlation with the methods of reference such as E-test, Sensititre and Vitek2. The interpretation of the results must be careful because the determination of the minimum inhibitory concentration (CIM) is difficult for fungi, there are host factors involved and not always there is a correlation between MIC and clinical outcome. Due to these methods are laborious and require trained personnel, to ask for AST to a reference laboratory is recommendable. PMID:19621145

  10. Synergistic Antifungal Effect of Glabridin and Fluconazole

    PubMed Central

    Liu, Wei; Li, Li Ping; Zhang, Jun Dong; Li, Qun; Shen, Hui; Chen, Si Min; He, Li Juan; Yan, Lan; Xu, Guo Tong; An, Mao Mao; Jiang, Yuan Ying

    2014-01-01

    The incidence of invasive fungal infections is increasing in recent years. The present study mainly investigated glabridin (Gla) alone and especially in combination with fluconazole (FLC) against Cryptococcus neoformans and Candida species (Candida albicans, Candida tropicalis, Candida krusei, Candida parapsilosis and Candida Glabratas) by different methods. The minimal inhibitory concentration (MIC) and the minimal fungicidal concentration (MFC) indicated that Gla possessed a broad-spectrum antifungal activity at relatively high concentrations. After combining with FLC, Gla exerted a potent synergistic effect against drug-resistant C. albicans and C. tropicalis at lower concentrations when interpreted by fractional inhibitory concentration index (FICI). Disk diffusion test and time-killing test confirming the synergistic fungicidal effect. Cell growth tests suggested that the synergistic effect of the two drugs depended more on the concentration of Gla. The cell envelop damage including a significant decrease of cell size and membrane permeability increasing were found after Gla treatment. Together, our results suggested that Gla possessed a synergistic effect with FLC and the cell envelope damage maybe contributed to the synergistic effect, which providing new information for developing novel antifungal agents. PMID:25058485

  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. Potentiation of Azole Antifungals by 2-Adamantanamine

    PubMed Central

    Sun, Lingmei; Lister, Ida; Keating, John; Nantel, Andre; Long, Lisa; Ghannoum, Mahmoud; North, Jeffrey; Lee, Richard E.; Coleman, Ken; Dahl, Thomas; Lewis, Kim

    2013-01-01

    Azoles are among the most successful classes of antifungals. They act by inhibiting α-14 lanosterol demethylase in the ergosterol biosynthesis pathway. Oropharyngeal candidiasis (OPC) occurs in about 90% of HIV-infected individuals, and 4 to 5% are refractory to current therapies, including azoles, due to the formation of resistant biofilms produced in the course of OPC. We reasoned that compounds affecting a different target may potentiate azoles to produce increased killing and an antibiofilm therapeutic. 2-Adamantanamine (AC17) was identified in a screen for compounds potentiating the action of miconazole against biofilms of Candida albicans. AC17, a close structural analog to the antiviral amantadine, did not affect the viability of C. albicans but caused the normally fungistatic azoles to become fungicidal. Transcriptome analysis of cells treated with AC17 revealed that the ergosterol and filamentation pathways were affected. Indeed, cells exposed to AC17 had decreased ergosterol contents and were unable to invade agar. In vivo, the combination of AC17 and fluconazole produced a significant reduction in fungal tissue burden in a guinea pig model of cutaneous candidiasis, while each treatment alone did not have a significant effect. The combination of fluconazole and AC17 also showed improved efficacy (P value of 0.018) compared to fluconazole alone when fungal lesions were evaluated. AC17 is a promising lead in the search for more effective antifungal therapeutics. PMID:23689724

  13. Antifungal Quinoline Alkaloids from Waltheria indica.

    PubMed

    Cretton, Sylvian; Dorsaz, Stéphane; Azzollini, Antonio; Favre-Godal, Quentin; Marcourt, Laurence; Ebrahimi, Samad Nejad; Voinesco, Francine; Michellod, Emilie; Sanglard, Dominique; Gindro, Katia; Wolfender, Jean-Luc; Cuendet, Muriel; Christen, Philippe

    2016-02-26

    Chemical investigation of a dichloromethane extract of the aerial parts of Waltheria indica led to the isolation and characterization of five polyhydroxymethoxyflavonoids, namely, oxyanin A (1), vitexicarpin (3), chrysosplenol E (4), flindulatin (5), 5-hydroxy-3,7,4'-trimethoxyflavone (6), and six quinolone alkaloids, waltheriones M-Q (2, 7, 8, 10, 11) and 5(R)-vanessine (9). Among these, compounds 2, 7, 8, 10, and 11 have not yet been described in the literature. Their chemical structures were established by means of spectroscopic data interpretation including (1)H and (13)C, HSQC, HMBC, COSY, and NOESY NMR experiments and UV, IR, and HRESIMS. The absolute configurations of the compounds were established by ECD. The isolated constituents and 10 additional quinoline alkaloids previously isolated from the roots of the plant were evaluated for their in vitro antifungal activity against the human fungal pathogen Candida albicans, and 10 compounds (7, 9, 11-16, 18, 21) showed growth inhibitory activity on both planktonic cells and biofilms (MIC ≤ 32 μg/mL). Their spectrum of activity against other pathogenic Candida species and their cytotoxicity against human HeLa cells were also determined. In addition, the cytological effect of the antifungal isolated compounds on the ultrastructure of C. albicans was evaluated by transmission electron microscopy. PMID:26848627

  14. Antifungal drug resistance of oral fungi.

    PubMed

    Niimi, Masakazu; Firth, Norman A; Cannon, Richard D

    2010-02-01

    Fungi comprise a minor component of the oral microbiota but give rise to oral disease in a significant proportion of the population. The most common form of oral fungal disease is oral candidiasis, which has a number of presentations. The mainstay for the treatment of oral candidiasis is the use of polyenes, such as nystatin and amphotericin B, and azoles including miconazole, fluconazole, and itraconazole. Resistance of fungi to polyenes is rare, but some Candida species, such as Candida glabrata and C. krusei, are innately less susceptible to azoles, and C. albicans can acquire azole resistance. The main mechanism of high-level fungal azole resistance, measured in vitro, is energy-dependent drug efflux. Most fungi in the oral cavity, however, are present in multispecies biofilms that typically demonstrate an antifungal resistance phenotype. This resistance is the result of multiple factors including the expression of efflux pumps in the fungal cell membrane, biofilm matrix permeability, and a stress response in the fungal cell. Removal of dental biofilms, or treatments to prevent biofilm development in combination with antifungal drugs, may enable better treatment and prevention of oral fungal disease. PMID:20155503

  15. Microbial Biotransformation to Obtain New Antifungals.

    PubMed

    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

  16. Potentially inappropriate drug prescribing in elderly hospitalized patients: an analysis and comparison of explicit criteria.

    PubMed

    Di Giorgio, Concetta; Provenzani, Alessio; Polidori, Piera

    2016-04-01

    Background The management of therapy in elderly is a critical aspect of primary care. The physio-pathological complexity of the elderly involves the prescription of multiple drugs, exposing them to a higher risk of adverse reactions. Objective Aim of this study was to assess the medication use and (potential) inappropriate medications and prescribing omissions in the elderly before and during hospitalization, according to the main tools in literature described, and their relation to the number of comorbidities. Setting The study was carried out by the Clinical Pharmacists at ISMETT, an Italian Research Institute. Methods The prescriptions of elderly, admitted in ISMETT between January and December 2012, were analyzed. The information about clinical profile of elderly and prescriptions was obtained from the electronic medical records. 2012 Beers criteria, Screening Tool of Older Person's Prescriptions/Screening Tool to Alert doctors to Right Treatment criteria, and Improving Prescribing in the Elderly criteria were used to evaluate the appropriateness of prescriptions. The correlation between the number of comorbidities and the different tools was analyzed with the Spearman correlation coefficient. The frequency analysis was done with the Pearson Chi square test. Main outcome measure Percentage of potentially inappropriate medications and prescribing omissions before/during hospitalization in elderly. Results 1027 elderly were admitted between January and December 2012. At admission and during hospitalization, according to Beers criteria 24 and 49 % of elderly had at least one potentially inappropriate medication, respectively; according to the Screening Tool of Older Person's Prescriptions criteria 21 and 27 %, respectively; according to the Improving Prescribing in the Elderly criteria 28 and 25 %, respectively; and then, according to Screening Tool to Alert doctors to Right Treatment criteria 28 and 33 % had at least one potentially prescribing omission

  17. A prospective determination of the incidence of perceived inappropriate care in critically ill patients

    PubMed Central

    Singal, Rohit K; Sibbald, Robert; Morgan, Brenda; Quinlan, Mel; Parry, Neil; Radford, Michael; Martin, Claudio M

    2014-01-01

    BACKGROUND: Health care providers’ perceptions regarding appropriateness in end-of-life treatments have been widely studied. While nurses and physicians believe that rationing and other cost-related practices sometimes occur in the intensive care unit (ICU), they allege that treatment is often excessive. OBJECTIVE: To prospectively determine the incidence and causes of health care providers’ perceptions regarding appropriateness of end-of-life treatments. METHODS: The present prospective study collected data from patients admitted to the medical-surgical trauma ICU of a 30-bed, Canadian teaching hospital over a three-month period. Daily surveys were completed independently by bedside nurses, charge nurses and attending physician. RESULTS: In total, 5224 of 6558 expected surveys (representing 294 patients) were analyzed, yielding a response rate of 79.7%. The incidence of perceived inappropriate care in the present study was 6.5% (19 of 294 patients), with ongoing treatment for >2 days after this determination occurring in 1% (three of 294 patients). However, at least one caregiver perceived inappropriate care at some point in 110 of 294 (37.5%) patients. In these cases, in which processes to address care were not already underway, respondents believed that important issues resulting in provision of inappropriate treatments included patient-family issues and communication before or in the ICU. Caregivers did not know their patients’ wishes 22% (1129 of 5224) of the time. CONCLUSIONS: Although ongoing inappropriate care appeared to be a rare occurrence, the issue was a concern to at least one caregiver in one-third of cases. Public awareness for end-of-life issues, adequate communication, and up-to-date knowledge and practice in determining the wishes of critically ill patients are potential target areas to improve end-of-life care and reduce inappropriate care in the ICU. A daily, prospective survey of multidisciplinary caregivers, such as the survey used in

  18. 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…

  19. 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…

  20. Identification of antifungal compounds produced by Lactobacillus casei AST18.

    PubMed

    Li, Hongjuan; Liu, Lu; Zhang, Shuwen; Cui, Wenming; Lv, Jiaping

    2012-08-01

    Lactobacillus casei AST18 was screened as an antifungal lactic acid bacteria which we have reported before. In this research, the antifungal properties of cell-free culture filtrate (CCF) from L. casei AST18 were detected, and the antifungal compounds of CCF were prepared by ultrafiltration, and semi-preparative HPLC, and then determined by GC-MS. CCF was sensitive to pH and heat treatment but it was not affected by the treatment of trypsin and pepsin. Through the treatment of ultrafiltration and semi-preparative HPLC there were two parts of CCF which showed antifungal activities: part 1 and part 4. Lactic acid was identified as the main antifungal compound in part 1. In part 4, three small molecular substances were detected with GC-MS. The three potential antifungal substances were cyclo-(Leu-Pro), 2,6-diphenyl-piperidine, and 5,10-diethoxy-2,3,7,8-tetrahydro-1H,6H-dipyrrolo[1,2-a;1',2'-d]pyrazine. The antifungal activity of L. casei AST18 was a synergistic effect of lactic acid and cyclopeptides. PMID:22580887

  1. Inappropriate gene activation in FSHD: a repressor complex binds a chromosomal repeat deleted in dystrophic muscle.

    PubMed

    Gabellini, Davide; Green, Michael R; Tupler, Rossella

    2002-08-01

    Facioscapulohumeral muscular dystrophy (FSHD), a common myopathy, is an autosomal dominant disease of unknown molecular mechanism. Almost all FSHD patients carry deletions of an integral number of tandem 3.3 kilobase repeats, termed D4Z4, located on chromosome 4q35. Here, we find that in FSHD muscle, 4q35 genes located upstream of D4Z4 are inappropriately overexpressed. We show that an element within D4Z4 specifically binds a multiprotein complex consisting of YY1, a known transcriptional repressor, HMGB2, an architectural protein, and nucleolin. We demonstrate that this multiprotein complex binds D4Z4 in vitro and in vivo and mediates transcriptional repression of 4q35 genes. Based upon these results, we propose that deletion of D4Z4 leads to the inappropriate transcriptional derepression of 4q35 genes resulting in disease. PMID:12176321

  2. A Review of Potentially Inappropriate Prescribing in Over 65's in Livinghealth Clinic.

    PubMed

    Sweeney, J; Laoire, F O; Linehan, G; Herlihy, D

    2015-06-01

    Polypharmacy and potentially inappropriate prescribing (PIP) are areas of growing importance and concern. Optimising drug prescribing in older people is challenging and complex at,the individual GP level. At a national level it is an important public health issue for the care and management of the ageing Irish population. The aim of this study was to estimate the prevalence of PIP in Livinghealth Clinic using the STOPP (Screening Tool for Older Persons' Prescribing) criteria and to identify areas of PIP. LHC audits demonstrated PIP levels of between 16% and 29%. Our findings were similar to other studies in that proton pump inhibitors (PPIs) at maximum therapeutic dosage for >8 weeks, and long acting benzodiazepines prescribed for > 1 month, continue to be significant areas of PIP. However, not all identified PIP maybe inappropriate. The STOPP criteria are a useful screening tool for older persons' prescribing, but are best used together with clinical assessment and discretion. PMID:26182803

  3. 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.

  4. Pharmacokinetics and Pharmacodynamics of Antifungals in Children: Clinical Implications

    PubMed Central

    Autmizguine, Julie; Guptill, Jeffrey T.; Cohen-Wolkowiez, Michael; Benjamin, Daniel K.; Capparelli, Edmund V.

    2014-01-01

    Invasive fungal disease (IFD) remains life-threatening in premature infants and immunocompromised children despite the recent development of new antifungal agents. Optimal dosing of antifungals is one of the few factors clinicians can control to improve outcomes of IFD. However, dosing in children cannot be extrapolated from adult data because IFD pathophysiology, immune response, and drug disposition differ from adults. We critically examined the literature on pharmacokinetics (PK) and pharmacodynamics (PD) of antifungal agents and highlight recent developments in treating pediatric IFD. To match adult exposure in pediatric patients, dosing adjustment is necessary for almost all antifungals. In young infants, the maturation of renal and metabolic functions occurs rapidly and can significantly influence drug exposure. Fluconazole clearance doubles from birth to 28 days of life and, beyond the neonatal period, agents like fluconazole, voriconazole, and micafungin require higher dosing than in adults due to faster clearance in children. As a result, dosing recommendations are specific to bracketed ranges of age. Pharmacodynamics principles of antifungals mostly rely on in vitro and in vivo models but very few pharmacodynamics studies specifically address IFD in children. Exposure-response relationship may differ in younger children compared with adults, especially in infants with invasive candidiasis who are at higher risk of disseminated disease and meningoencephalitis, and by extension severe neurodevelopmental impairment. Micafungin is the only antifungal agent for which a specific target of exposure was proposed based on a neonatal hematogenous Candida meningoencephalitis animal model. In this review, we found that pediatric data on drug disposition of newer triazoles and echinocandins are lacking, dosing of older antifungals such as fluconazole and amphotericin B products still need optimization in young infants, and that target PK/PD indices need to be

  5. 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. PMID:26089312

  6. Treatment of a patient with dementia and inappropriate sexual behaviors with citalopram.

    PubMed

    Chen, Stephen T

    2010-01-01

    Inappropriate sexual behaviors (ISBs) associated with dementias and their treatment have not been commonly reported in the medical literature. This report presents an elderly male patient with moderately severe dementia and incident onset of ISBs who was treated with citalopram (20-mg daily) and subsequently displayed a reduction in ISBs. A review of the literature suggests that ISBs may be underrecognized and undertreated, and therefore should be actively monitored and treated. PMID:20693867

  7. 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

  8. Modelling verbal aggression, physical aggression and inappropriate sexual behaviour after acquired brain injury

    PubMed Central

    James, Andrew I. W.; Böhnke, Jan R.; Young, Andrew W.; Lewis, Gary J.

    2015-01-01

    Understanding the underpinnings of behavioural disturbances following brain injury is of considerable importance, but little at present is known about the relationships between different types of behavioural disturbances. Here, we take a novel approach to this issue by using confirmatory factor analysis to elucidate the architecture of verbal aggression, physical aggression and inappropriate sexual behaviour using systematic records made across an eight-week observation period for a large sample (n = 301) of individuals with a range of brain injuries. This approach offers a powerful test of the architecture of these behavioural disturbances by testing the fit between observed behaviours and different theoretical models. We chose models that reflected alternative theoretical perspectives based on generalized disinhibition (Model 1), a difference between aggression and inappropriate sexual behaviour (Model 2), or on the idea that verbal aggression, physical aggression and inappropriate sexual behaviour reflect broadly distinct but correlated clinical phenomena (Model 3). Model 3 provided the best fit to the data indicating that these behaviours can be viewed as distinct, but with substantial overlap. These data are important both for developing models concerning the architecture of behaviour as well as for clinical management in individuals with brain injury. PMID:26136449

  9. Optimal Programming of ICDs for Prevention of Appropriate and Inappropriate Shocks.

    PubMed

    Lo, Ronald; Al-Ahmad, Amin; Hsia, Henry; Zei, Paul C; Wang, Paul J

    2008-09-01

    Expansion of indications for implantable cardioverter-defibrillators (ICDs) has led to a significant increase in the number of patients receiving ICDs and the number of lives saved because of ICD therapy. However, appropriate or inappropriate shocks are frequent and may result in a significant decrease in quality of life in patients with ICDs. Atrial fibrillation with rapid ventricular response, sinus tachycardia, atrial tachycardia or atrial flutter with rapid conduction, and other supraventricular tachycardias are the most common arrhythmias causing inappropriate therapy. Other causes include oversensing of diaphragmatic potentials or myopotentials, T-wave oversensing, double or triple counting of intracardiac signals, lead fractures or header connection problems, lead chatter or noise, and electromagnetic interference. Strategies to reduce inappropriate therapy using device programming rely on the ability to distinguish supraventricular and atrial arrhythmias from ventricular tachycardia. Avoiding therapy for nonsustained ventricular arrhythmias and increasing the role of antitachycardia pacing to terminate ventricular tachycardia are key approaches to reducing shocks for ventricular arrhythmias. Optimal programming holds great promise for decreasing the overall incidence of shock therapy and increasing ICD acceptance. PMID:18814830

  10. Threatening and otherwise inappropriate letters to members of the United States Congress.

    PubMed

    Dietz, P E; Matthews, D B; Martell, D A; Stewart, T M; Hrouda, D R; Warren, J

    1991-09-01

    The authors examine the characteristics of threatening and otherwise inappropriate communications sent to members of the U.S. Congress by a sample of 86 subjects, 20 of whom threatened assassination. We quote excerpts from these letters and provide quantitative data on such variables as the volume, duration, form, and appearance of such communications; the enclosures; the subjects' perceived relationships to the recipients; the thematic content of the communications; and the messages and threats communicated. Comparisons between 43 subjects who pursued encounters with members of Congress and 43 who did not revealed 17 factors associated with such pursuit. In this population, threateners were significantly less likely to pursue an encounter than inappropriate letter writers who did not threaten, regardless of the type of threat or the harm threatened. Inappropriate letters to members of Congress are compared with those directed to Hollywood celebrities. Mentally disordered persons writing to public figures often mention and sometimes threaten public figures other than those to whom the letters are addressed, which raises important issues regarding notification of endangered third parties and the sharing of information among protective agencies. PMID:1955833

  11. Novel drug delivery strategies for improving econazole antifungal action.

    PubMed

    Firooz, Alireza; Nafisi, Shohreh; Maibach, Howard I

    2015-11-10

    Econazole is a commonly used azole antifungal in clinical treatment of superficial fungal infections. It is generally used as conventional cream and gel preparations under the brand names of Spectazole (United States), Ecostatin (Canada), Pevaryl (Western Europe). Treatment efficiency of antifungal drugs depends on their penetration through target layers of skin at effective concentrations. Econazole's poor water solubility limits its bioavailability and antifungal effects. Therefore, formulation strategies have been examined for delivering econazole through targeted skin sites. The present overview focuses on novel nano-based formulation approaches used to improve econazole penetration through skin for treatment of superficial fungal infections. PMID:26383840

  12. 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. PMID:26586600

  13. Neutral red assay in minimum fungicidal concentrations of antifungal agents.

    PubMed

    Fukuda, T; Naka, W; Tajima, S; Nishikawa, T

    1996-01-01

    We assayed the fungicidal effects of antifungal agents using neutral red staining. Fungal elements of Trichophyton mentagrophytes and T. rubrum were treated with various concentrations of antifungal agents in 96-well filtration plates and then stained with neutral red. The amount of neutral red incorporated by the surviving viable cells was determined from the automated spectrophotometric readings at 550 nm. The minimum fungicidal concentrations (MFCs) of antifungal agents determined by this assay correlated well with those determined by conventional assay. This newly developed procedure should provide a rapid, reproducible, quantitative, qualitative and semi-automated susceptibility test for determination of the MFCs of the fungicidal agents. PMID:8912170

  14. 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. PMID:26265360

  15. Antifungal Susceptibilities of Bloodstream Isolates of Candida Species from Nine Hospitals in Korea: Application of New Antifungal Breakpoints and Relationship to Antifungal Usage

    PubMed Central

    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. PMID:25706866

  16. Antifungal steroid saponins from Dioscorea cayenensis.

    PubMed

    Sautour, M; Mitaine-Offer, A-C; Miyamoto, T; Dongmo, A; Lacaille-Dubois, M-A

    2004-01-01

    From the rhizomes of Dioscorea cayenensis Lam.-Holl (Dioscoreaceae), the new 26- O- beta- D-glucopyranosyl-22-methoxy-3 beta,26-dihydroxy-25( R)-furost-5-en-3- O- alpha- L-rhamnopyranosyl-(1-->4)- alpha- L-rhamnopyranosyl-(1-->4)-[ alpha- L-rhamnopyranosyl-(1-->2)]- beta- D-glucopyranoside ( 1) was isolated together with the known dioscin ( 2) and diosgenin 3- O- alpha- L-rhamnopyranosyl-(1-->4)- alpha- L-rhamnopyranosyl-(1-->4)-[ alpha- L-rhamnopyranosyl-(1-->2)]- beta- D-glucopyranoside ( 3). Their structures were established on the basis of spectral data. Compound 2 exhibited antifungal activity against the human pathogenic yeasts Candida albicans, C. glabrata and C. tropicalis (MICs of 12.5, 12.5 and 25 micro g/mL, respectively) whereas 3 showed weak activity and 1 was inactive. PMID:14765305

  17. Voriconazole: a new triazole antifungal agent.

    PubMed

    Johnson, Leonard B; Kauffman, Carol A

    2003-03-01

    Voriconazole is a second-generation azole antifungal agent that shows excellent in vitro activity against a wide variety of yeasts and molds. It can be given by either the intravenous or the oral route; the oral formulation has excellent bioavailability. The side effect profile of voriconazole is unique in that non-sight-threatening, transient visual disturbances occur in approximately 30% of patients given the drug. Rash (which can manifest as photosensitivity) and hepatitis also occur. The potential for drug-drug interactions is high and requires that careful attention be given to dosage regimens and monitoring of serum levels and effects of interacting drugs. Voriconazole has been approved for the treatment of invasive aspergillosis and refractory infections with Pseudallescheria/Scedosporium and Fusarium species, and it will likely become the drug of choice for treatment of serious infections with those filamentous fungi. PMID:12594645

  18. 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

  19. 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. PMID:26826375

  20. 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. PMID:12165338

  1. 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.

  2. 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.

  3. 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...

  4. 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

  5. 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 Roman Law, which helped hold…

  6. 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. PMID:12946723

  7. 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

  8. Antioxidant and antifungal activity of Verbena officinalis L. leaves.

    PubMed

    Casanova, E; García-Mina, J M; Calvo, M I

    2008-09-01

    The scavenging activity against DPPH (1,1-diphenil-2-picrylhydrazyl) radical and the antifungal effect against chloroform, ethyl acetate and 50% methanolic extracts of Verbena officinalis leaves were investigated. The activity of different fractions of 50% methanolic extract and some isolated compounds were also investigated. The results suggest that 50% methanolic extract and caffeoyl derivatives could potentially be considered as excellent and readily available sources of natural antifungal and antioxidant compounds. PMID:18498054

  9. Antifungal activity of polymer-based copper nanocomposite coatings

    NASA Astrophysics Data System (ADS)

    Cioffi, Nicola; Torsi, Luisa; Ditaranto, Nicoletta; Sabbatini, Luigia; Zambonin, Pier Giorgio; Tantillo, Giuseppina; Ghibelli, Lina; D'Alessio, Maria; Bleve-Zacheo, Teresa; Traversa, Enrico

    2004-09-01

    Eukaryotes, such as fungi, can be harmful pathogen agents, and the control of their bioactivity is critical as humans are eukaryote organisms, too. Here, copper/polymer nanocomposites are proposed as antifungal spinnable coatings with controlled copper-releasing properties. The tests of the bioactivity show that fungal growth is inhibited on the nanocomposite-coated plates, and the antifungal activity can be modulated by controlling the Cu nanoparticle loading.

  10. 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