Fosfomycin trometamol: a review of its use as a single-dose oral treatment for patients with acute lower urinary tract infections and pregnant women with asymptomatic bacteriuria.

PubMed

Keating, Gillian M

2013-11-01

Fosfomycin trometamol (fosfomycin tromethamine) [Monuril(®), Monurol(®), Monural(®)] is approved in numerous countries worldwide, mainly for the treatment of uncomplicated urinary tract infections (UTIs). Fosfomycin has good in vitro activity against common uropathogens, such as Escherichia coli (including extended-spectrum β-lactamase-producing E. coli), Proteus mirabilis, Klebsiella pneumoniae and Staphylococcus saprophyticus, and the susceptibility of uropathogens to fosfomycin has remained relatively stable over time. A single oral dose of fosfomycin trometamol 3 g (the approved dosage) achieves high concentrations in urine. Results of recent randomized trials indicate that single-dose fosfomycin trometamol had similar clinical and/or bacteriological efficacy to 3- to 7-day regimens of ciprofloxacin, norfloxacin, cotrimoxazole or nitrofurantoin in women with uncomplicated lower UTIs. In addition, single-dose fosfomycin trometamol had similar bacteriological efficacy to a 5-day course of cefuroxime axetil or a 7-day course of amoxicillin/clavulanic acid in pregnant women with asymptomatic bacteriuria, and similar clinical and/or bacteriological efficacy to a 5-day course of cefuroxime axetil or amoxicillin/clavulanic acid or a 3-day course of ceftibuten in pregnant women with a lower UTI. Single-dose fosfomycin trometamol was generally well tolerated, with gastrointestinal adverse events (e.g. diarrhoea, nausea) reported most commonly. In conclusion, single-dose fosfomycin trometamol is an important option for the first-line empirical treatment of uncomplicated lower UTIs.

Fosfomycin Resistance in Escherichia coli, Pennsylvania, USA.

PubMed

Alrowais, Hind; McElheny, Christi L; Spychala, Caressa N; Sastry, Sangeeta; Guo, Qinglan; Butt, Adeel A; Doi, Yohei

2015-11-01

Fosfomycin resistance in Escherichia coli is rare in the United States. An extended-spectrum β-lactamase-producing E. coli clinical strain identified in Pennsylvania, USA, showed high-level fosfomycin resistance caused by the fosA3 gene. The IncFII plasmid carrying this gene had a structure similar to those found in China, where fosfomycin resistance is commonly described.

Inhibition of Fosfomycin Resistance Protein FosA by Phosphonoformate (Foscarnet) in Multidrug-Resistant Gram-Negative Pathogens

PubMed Central

Ito, Ryota; Tomich, Adam D.; McElheny, Christi L.; Mettus, Roberta T.; Sluis-Cremer, Nicolas

2017-01-01

ABSTRACT FosA proteins confer fosfomycin resistance to Gram-negative pathogens via glutathione-mediated modification of the antibiotic. In this study, we assessed whether inhibition of FosA by sodium phosphonoformate (PPF) (foscarnet), a clinically approved antiviral agent, would reverse fosfomycin resistance in representative Gram-negative pathogens. The inhibitory activity of PPF against purified recombinant FosA from Escherichia coli (FosA3), Klebsiella pneumoniae (FosAKP), Enterobacter cloacae (FosAEC), and Pseudomonas aeruginosa (FosAPA) was determined by steady-state kinetic measurements. The antibacterial activity of PPF against FosA in clinical strains of these species was evaluated by susceptibility testing and time-kill assays. PPF increased the Michaelis constant (Km) for fosfomycin in a dose-dependent manner, without affecting the maximum rate (Vmax) of the reaction, for all four FosA enzymes tested, indicating a competitive mechanism of inhibition. Inhibitory constant (Ki) values were 22.6, 35.8, 24.4, and 56.3 μM for FosAKP, FosAEC, FosAPA, and FosA3, respectively. Addition of clinically achievable concentrations of PPF (∼667 μM) reduced the fosfomycin MICs by ≥4-fold among 52% of the K. pneumoniae, E. cloacae, and P. aeruginosa clinical strains tested and led to a bacteriostatic or bactericidal effect in time-kill assays among representative strains. PPF inhibits FosA activity across Gram-negative species and can potentiate fosfomycin activity against the majority of strains with chromosomally encoded fosA. These data suggest that PPF may be repurposed as an adjuvant for fosfomycin to treat infections caused by some FosA-producing, multidrug-resistant, Gram-negative pathogens. PMID:28993329

Fosfomycin versus other antibiotics for the treatment of cystitis: a meta-analysis of randomized controlled trials.

PubMed

Falagas, Matthew E; Vouloumanou, Evridiki K; Togias, Antonios G; Karadima, Maria; Kapaskelis, Anastasios M; Rafailidis, Petros I; Athanasiou, Stavros

2010-09-01

Cystitis is a common infection. The alarmingly high resistance rates exhibited by contemporary uropathogens necessitate the re-evaluation of old antibiotics. To evaluate the effectiveness and safety of fosfomycin compared with other antibiotics for the treatment of patients with cystitis. We performed a meta-analysis of randomized controlled trials (RCTs), generated from searches performed in PubMed, Scopus and Cochrane CENTRAL, which involved patients with cystitis treated with fosfomycin versus other antibiotics. Twenty-seven trials (eight double-blind) were included. Sixteen of these 27 trials involved exclusively non-pregnant female patients, 3 involved adult mixed populations of older age, 5 involved pregnant patients and 3 involved paediatric patients. Regarding clinical success, no difference was found in the comprehensive analysis regarding all comparators combined [10 RCTs, 1657 patients, risk ratio (RR) = 1.00, 95% confidence interval (CI) = 0.98-1.03] in trials involving non-pregnant females and in trials involving mixed populations. Insufficient relevant data were provided from trials involving paediatric and pregnant patients. No difference between fosfomycin and comparators was also found in all comparisons regarding the remaining effectiveness outcomes (namely microbiological success/relapse/re-infection). Fosfomycin had a comparable safety profile with the evaluated comparators in non-pregnant women, mixed and paediatric populations, whereas it was associated with significantly fewer adverse events in pregnant women (4 RCTs, 507 patients, RR = 0.35, 95% CI = 0.12-0.97). In the era of high drug resistance rates, reported even among community-acquired uropathogens, fosfomycin may provide a valuable alternative option for the treatment of cystitis in non-pregnant and pregnant women and in elderly and paediatric patients.

Emergence of Plasmid-Mediated Fosfomycin-Resistance Genes among Escherichia coli Isolates, France.

PubMed

Benzerara, Yahia; Gallah, Salah; Hommeril, Baptiste; Genel, Nathalie; Decré, Dominique; Rottman, Martin; Arlet, Guillaume

2017-09-01

FosA, a glutathione S-transferase that inactivates fosfomycin, has been reported as the cause of enzymatic resistance to fosfomycin. We show that multiple lineages of FosA-producing extended spectrum β-lactamase Escherichia coli have circulated in France since 2012, potentially reducing the efficacy of fosfomycin in treating infections with antimicrobial drug-resistant gram-negative bacilli.

Fosfomycin in a single dose versus a 7-day course of amoxicillin-clavulanate for the treatment of asymptomatic bacteriuria during pregnancy.

PubMed

Estebanez, A; Pascual, R; Gil, V; Ortiz, F; Santibáñez, M; Pérez Barba, C

2009-12-01

The purpose of this paper was to compare the efficacy of a single dose of 3 g of fosfomycin to that of a 7-day regimen of amoxicillin-clavulanate in the treatment of asymptomatic bacteriuria during pregnancy. A randomised, prospective, interventional, analytical, longitudinal study was undertaken, in which the efficacy of two antibiotic regimens (one short and the other long) in the treatment of pregnant women with asymptomatic bacteriuria is compared. One hundred and nine patients were randomly assigned to two groups: 56 were treated with amoxicillin-clavulanate and 53 with fosfomycin. The two groups were similar in terms of co-morbidity, treatments received during pregnancy, obstetric, gynaecological and surgical history and laboratory data. The efficacy of the two regimens was similar and the eradication rate was over 80% in both groups (P = 0.720) (relative risk [RR] 1.195, 95% confidence interval [CI]: 0.451-3.165). The number of reinfections was greater in the amoxicillin-clavulanate group (P = 0.045). The secondary effects were lower in the fosfomycin group (P = 0.008). There were no significant differences in the number of persistences (P = 0.39), development of symptomatic urinary infections (P = 0.319) or recurrences (P = 0.96). Treatment with a single dose of fosfomycin is as effective as the standard course of treatment with amoxicillin-clavulanate and may be preferable due to its simpler administration and the smaller number of reinfections.

Activity of fosfomycin alone or combined with cefoxitin in vitro and in vivo in a murine model of urinary tract infection due to Escherichia coli harbouring CTX-M-15-type extended-spectrum β-lactamase.

PubMed

Lefort, Agnès; Chau, Françoise; Lepeule, Raphaël; Dubée, Vincent; Kitzis, Marie-Dominique; Dion, Sara; Fantin, Bruno

2014-04-01

The efficacy of fosfomycin alone or combined with cefoxitin was investigated in vitro and in a murine model of urinary tract infection due to susceptible Escherichia coli CFT073-RR and its transconjugant CFT073-RR Tc (pblaCTX-M-15) harbouring a plasmid carrying the blaCTX-M-15 gene. In vitro, the combination of cefoxitin and fosfomycin was synergistic and bactericidal and prevented the emergence of fosfomycin-resistant mutants of CFT073-RR and CFT073-RR Tc (pblaCTX-M-15) that were selected with fosfomycin alone. In vivo, the combination conferred an advantage in terms of kidney sterilisation of mice infected with either strain compared with fosfomycin monotherapy. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Fosfomycin residues in colostrum: Impact on morpho-physiology and microbiology of suckling piglets.

PubMed

Fernández Paggi, M B; Martínez, G; Diéguez, S N; Pérez Gaudio, D S; Decundo, J M; Riccio, M B; Amanto, F A; Tapia, M O; Soraci, A L

2018-06-01

Fosfomycin is a broad-spectrum bactericidal antibiotic widely used in pig farms for the treatment of a wide variety of bacterial infections. In this study, the elimination of disodium fosfomycin in colostrum/milk of the sow and the impact of this antibiotic on the microbiota and intestinal morpho-physiology of suckling piglets were analyzed. The average amount of fosfomycin eliminated in colostrum (after administration of 15 mg/kg IM) during the first 10 hr postpartum was 0.85 μg/ml, and the mean residual amount ingested by the piglets was 0.26 mg/kg. The elimination profile of fosfomycin concentrations in colostrum occurs at a time of profound changes in the morpho-physiology of the gastrointestinal tract of the piglet. However, the studied concentrations did not produce imbalances on the microbiota or on the morpho-physiology of the gastrointestinal tract of the piglet. Concentrations of fosfomycin were maintained in the mammary gland above the MIC for more than 8 hr for pathogenic bacteria of productive importance. This would indicate that fosfomycin may be considered safe for the specific treatment of bacterial infectious processes in sows during the peri- and postpartum period. This first study with disodium fosfomycin stimulates awareness in the proper use of antimicrobials at farrowing. © 2018 John Wiley & Sons Ltd.

Widespread Fosfomycin Resistance in Gram-Negative Bacteria Attributable to the Chromosomal fosA Gene

PubMed Central

Ito, Ryota; Tomich, Adam D.; Callaghan, Jake D.; McElheny, Christi L.; Mettus, Roberta T.; Sluis-Cremer, Nicolas

2017-01-01

ABSTRACT Fosfomycin is a decades-old antibiotic which is being revisited because of its perceived activity against many extensively drug-resistant Gram-negative pathogens. FosA proteins are Mn2+ and K+-dependent glutathione S-transferases which confer fosfomycin resistance in Gram-negative bacteria by conjugation of glutathione to the antibiotic. Plasmid-borne fosA variants have been reported in fosfomycin-resistant Escherichia coli strains. However, the prevalence and distribution of fosA in other Gram-negative bacteria are not known. We systematically surveyed the presence of fosA in Gram-negative bacteria in over 18,000 published genomes from 18 Gram-negative species and investigated their contribution to fosfomycin resistance. We show that FosA homologues are present in the majority of genomes in some species (e.g., Klebsiella spp., Enterobacter spp., Serratia marcescens, and Pseudomonas aeruginosa), whereas they are largely absent in others (e.g., E. coli, Acinetobacter baumannii, and Burkholderia cepacia). FosA proteins in different bacterial pathogens are highly divergent, but key amino acid residues in the active site are conserved. Chromosomal fosA genes conferred high-level fosfomycin resistance when expressed in E. coli, and deletion of chromosomal fosA in S. marcescens eliminated fosfomycin resistance. Our results indicate that FosA is encoded by clinically relevant Gram-negative species and contributes to intrinsic fosfomycin resistance. PMID:28851843

Fosfomycin Addition to Poly(D,L-Lactide) Coating Does Not Affect Prophylaxis Efficacy in Rat Implant-Related Infection Model, But That of Gentamicin Does

PubMed Central

Yorukoglu, Ali Cagdas; Kaleli, Ilknur; Bir, Ferda

2016-01-01

Gentamicin is the preferred antimicrobial agent used in implant coating for the prevention of implant-related infections (IRI). However, the present heavy local and systemic administration of gentamicin can lead to increased resistance, which has made its future use uncertain, together with related preventive technologies. Fosfomycin is an alternative antimicrobial agent that lacks the cross-resistance presented by other classes of antibiotics. We evaluated the efficacy of prophylaxis of 10% fosfomycin-containing poly(D,L-lactide) (PDL) coated K-wires in a rat IRI model and compared it with uncoated (Control 1), PDL-coated (Control 2), and 10% gentamicin-containing PDL-coated groups with a single layer of coating. Stainless steel K-wires were implanted and methicillin-resistant Staphylococcus aureus (ATCC 43300) suspensions (103 CFU/10 μl) were injected into a cavity in the left tibiae. Thereafter, K-wires were removed and cultured in tryptic soy broth and then 5% sheep blood agar mediums. Sliced sections were removed from the tibiae, stained with hematoxylin-eosin, and semi-quantitatively evaluated with X-rays. The addition of fosfomycin into PDL did not affect the X-ray and histopathological evaluation scores; however, the addition of gentamicin lowered them. The addition of gentamicin showed a protective effect after the 28th day of X-ray evaluations. PDL-only coating provided no protection, while adding fosfomycin to PDL offered a 20% level protection and adding gentamicin offered 80%. Furthermore, there were 103 CFU level growths in the gentamicin-added group, while the other groups had 105. Thus, the addition of fosfomycin to PDL does not affect the efficacy of prophylaxis, but the addition of gentamicin does. We therefore do not advise the use of fosfomycin as a single antimicrobial agent in coating for IRI prophylaxis. PMID:27806071

Evaluation of Activity and Emergence of Resistance of Polymyxin B and ZTI-01 (Fosfomycin for Injection) against KPC-Producing Klebsiella pneumoniae.

PubMed

Diep, John K; Sharma, Rajnikant; Ellis-Grosse, Evelyn J; Abboud, Cely S; Rao, Gauri G

2018-02-01

ZTI-01 (fosfomycin for injection) is a broad-spectrum antibiotic with a novel mechanism of action and is currently under development in the United States for treatment of complicated urinary tract infections. Globally, fosfomycin and polymyxin B are increasingly being used to treat multidrug-resistant Gram-negative infections. The objectives were to evaluate the pharmacodynamic activity of polymyxin B and fosfomycin alone and in combination against KPC-producing Klebsiella pneumoniae and to assess the rate and extent of emergence of resistance to different antibiotic regimens. Two clinical isolates, BRKP26 (MIC of polymyxin B[MIC PMB ], 0.5 mg/liter; MIC of fosfomycin [MIC FOF ], 32 mg/liter) and BRKP67 (MIC PMB , 8 mg/liter; MIC FOF , 32 mg/liter) at an initial inoculum of 10 7 CFU/ml, were evaluated over 168 h in a hollow-fiber infection model simulating clinically relevant polymyxin B (2.5-mg/kg loading dose as a 2 h-infusion followed by 1.5-mg/kg dose every 12 h [q12h] as a 1-h infusion) and fosfomycin (6 g q6h as a 1-h or 3-h infusion) regimens alone and in combination. Population analysis profiles (PAPs) and MIC testing were performed to assess emergence of resistance. Polymyxin B or fosfomycin monotherapy was ineffective and selected for resistance by 24 h. Polymyxin B plus a fosfomycin 1-h infusion demonstrated sustained bactericidal activity by 4 h, with undetectable colony counts beyond 144 h. Polymyxin B plus a fosfomycin 3-h infusion demonstrated bactericidal activity at 4 h, followed by regrowth similar to that of the control by 144 h. PAPs revealed resistant subpopulations by 120 h. The combination of polymyxin B and a fosfomycin 1-h infusion is a promising treatment option for KPC-producing K. pneumoniae and suppresses the emergence of resistance. Further evaluation of novel dosing strategies is warranted to optimize therapy. Copyright © 2018 Diep et al.

Evaluation of Activity and Emergence of Resistance of Polymyxin B and ZTI-01 (Fosfomycin for Injection) against KPC-Producing Klebsiella pneumoniae

PubMed Central

Diep, John K.; Sharma, Rajnikant; Ellis-Grosse, Evelyn J.; Abboud, Cely S.

2017-01-01

ABSTRACT ZTI-01 (fosfomycin for injection) is a broad-spectrum antibiotic with a novel mechanism of action and is currently under development in the United States for treatment of complicated urinary tract infections. Globally, fosfomycin and polymyxin B are increasingly being used to treat multidrug-resistant Gram-negative infections. The objectives were to evaluate the pharmacodynamic activity of polymyxin B and fosfomycin alone and in combination against KPC-producing Klebsiella pneumoniae and to assess the rate and extent of emergence of resistance to different antibiotic regimens. Two clinical isolates, BRKP26 (MIC of polymyxin B[MICPMB], 0.5 mg/liter; MIC of fosfomycin [MICFOF], 32 mg/liter) and BRKP67 (MICPMB, 8 mg/liter; MICFOF, 32 mg/liter) at an initial inoculum of 107 CFU/ml, were evaluated over 168 h in a hollow-fiber infection model simulating clinically relevant polymyxin B (2.5-mg/kg loading dose as a 2 h-infusion followed by 1.5-mg/kg dose every 12 h [q12h] as a 1-h infusion) and fosfomycin (6 g q6h as a 1-h or 3-h infusion) regimens alone and in combination. Population analysis profiles (PAPs) and MIC testing were performed to assess emergence of resistance. Polymyxin B or fosfomycin monotherapy was ineffective and selected for resistance by 24 h. Polymyxin B plus a fosfomycin 1-h infusion demonstrated sustained bactericidal activity by 4 h, with undetectable colony counts beyond 144 h. Polymyxin B plus a fosfomycin 3-h infusion demonstrated bactericidal activity at 4 h, followed by regrowth similar to that of the control by 144 h. PAPs revealed resistant subpopulations by 120 h. The combination of polymyxin B and a fosfomycin 1-h infusion is a promising treatment option for KPC-producing K. pneumoniae and suppresses the emergence of resistance. Further evaluation of novel dosing strategies is warranted to optimize therapy. PMID:29203494

Fosfomycin synergy in vitro with amoxicillin, daptomycin, and linezolid against vancomycin-resistant Enterococcus faecium from renal transplant patients with infected urinary stents.

PubMed

Descourouez, Jillian L; Jorgenson, Margaret R; Wergin, Justine E; Rose, Warren E

2013-03-01

Fosfomycin is a potential option for vancomycin-resistant enterococcus (VRE) infections despite limited in vitro and clinical data. In this study, 32 VRE isolates from renal transplant patients with urinary stent infections were susceptible to fosfomycin, daptomycin, and linezolid and resistant to amoxicillin, minocycline, and nitrofurantoin based on their MIC(50)s and MIC(90)s. Fosfomycin was bacteriostatic at 0.5 to 16× the MIC (32 to 2,048 μg/ml); synergy occurred when fosfomycin was combined with daptomycin (2.8 to 3.9 log(10) CFU/ml kill; P < 0.001) or amoxicillin (2.6 to 3.4; P < 0.05). These combinations may be potent options to treat VRE urinary infections pending investigation of clinical efficacy.

Phosphorus recovery from fosfomycin pharmaceutical wastewater by wet air oxidation and phosphate crystallization.

PubMed

Qiu, Guanglei; Song, Yonghui; Zeng, Ping; Xiao, Shuhu; Duan, Liang

2011-06-01

Fosfomycin pharmaceutical wastewater contains highly concentrated and refractory antibiotic organic phosphorus (OP) compounds. Wet air oxidation (WAO)-phosphate crystallization process was developed and applied to fosfomycin pharmaceutical wastewater pretreatment and phosphorus recovery. Firstly, WAO was used to transform concentrated and refractory OP substances into inorganic phosphate (IP). At 200°C, 1.0MPa and pH 11.2, 99% total OP (TOP) was transformed into IP and 58% COD was reduced. Subsequently, the WAO effluent was subjected to phosphate crystallization process for phosphorus recovery. At Ca/P molar ratio 2.0:1.0 or Mg/N/P molar ratio 1.1:1.0:1.0, 99.9% phosphate removal and recovery were obtained and the recovered products were proven to be hydroxyapatite and struvite, respectively. After WAO-phosphate crystallization, the BOD/COD ratio of the wastewater increased from 0 to more than 0.5, which was suitable for biological treatment. The WAO-phosphate crystallization process was proven to be an effective method for phosphorus recovery and for fosfomycin pharmaceutical wastewater pretreatment. Copyright © 2011 Elsevier Ltd. All rights reserved.

Fosfomycin

PubMed Central

Vouloumanou, Evridiki K.; Samonis, George; Vardakas, Konstantinos Z.

2016-01-01

SUMMARY The treatment of bacterial infections suffers from two major problems: spread of multidrug-resistant (MDR) or extensively drug-resistant (XDR) pathogens and lack of development of new antibiotics active against such MDR and XDR bacteria. As a result, physicians have turned to older antibiotics, such as polymyxins, tetracyclines, and aminoglycosides. Lately, due to development of resistance to these agents, fosfomycin has gained attention, as it has remained active against both Gram-positive and Gram-negative MDR and XDR bacteria. New data of higher quality have become available, and several issues were clarified further. In this review, we summarize the available fosfomycin data regarding pharmacokinetic and pharmacodynamic properties, the in vitro activity against susceptible and antibiotic-resistant bacteria, mechanisms of resistance and development of resistance during treatment, synergy and antagonism with other antibiotics, clinical effectiveness, and adverse events. Issues that need to be studied further are also discussed. PMID:26960938

[Epidemiological aspects relating to the determination of fosfomycin sensitivity: results of a study on 300 strains isolated in a hospital milieu in Turin].

PubMed

Vanini, G C; Moiraghi Ruggenini, A; Grassi, R; Maury, F; Giardini, F

1979-01-01

The AA. evaluated the sensitivity to Fosfomycin and to other commonly used antibiotics of 105 bacterial strains isolated from hospital environment and 195 from pathological materials. They also studied the problem of bacterial resistence to Fosfomycin considering the frequency of "inner colonies" and of bacterial cross-resistance to other antibiotics.

High-Level Fosfomycin Resistance in Vancomycin-Resistant Enterococcus faecium

PubMed Central

Guo, Yan; Tomich, Adam D.; McElheny, Christi L.; Cooper, Vaughn S.; Tait-Kamradt, Amelia; Wang, Minggui; Hu, Fupin; Rice, Louis B.; Sluis-Cremer, Nicolas

2017-01-01

Of 890 vancomycin-resistant Enterococcus faecium isolates obtained by rectal screening from patients in Pittsburgh, Pennsylvania, USA, 4 had MICs >1,024 μg/mL for fosfomycin. These isolates had a Cys119Asp substitution in the active site of UDP-N-acetylglucosamine enolpyruvyl transferase. This substitution increased the fosfomycin MIC >4-fold and rendered this drug inactive in biochemical assays. PMID:29048285

Optimal timing of oral fosfomycin administration for pre-prostate biopsy prophylaxis.

PubMed

Rhodes, Nathaniel J; Gardiner, Bradley J; Neely, Michael N; Grayson, M Lindsay; Ellis, Andrew G; Lawrentschuk, Nathan; Frauman, Albert G; Maxwell, Kelly M; Zembower, Teresa R; Scheetz, Marc H

2015-07-01

As the optimal administration time for fosfomycin peri-procedural prophylaxis is unclear, we sought to determine optimal administration times for fosfomycin peri-procedural prophylaxis. Plasma, peripheral zone and transition zone fosfomycin concentrations were obtained from 26 subjects undergoing transurethral resection of the prostate (TURP), following a single oral dose of 3 g of fosfomycin. Population pharmacokinetic modelling was completed with the Nonparametric Adaptive Grid (NPAG) algorithm (Pmetrics package for R), with a four-compartment model. Plasma and tissue concentrations were simulated during the first 24 h post-dose, comparing these with EUCAST susceptibility breakpoints for Escherichia coli, a common uropathogen. Non-compartmental-determined pharmacokinetic values in our population were similar to those reported in the package insert. Predicted plasma concentrations rapidly increased after the first hour, giving more than 90% population coverage for organisms with an MIC ≤4 mg/L over the first 12 h post-dose. Organisms with higher MICs fared much worse, with organisms at the EUCAST breakpoint being covered for <10% of the population at any time. Transitional zone prostate concentrations exceeded 4 mg/L for 90% of the population between hours 1 and 9. Peripheral zone prostate concentrations were much lower and only exceeded 4 mg/L for 70% of the population between hours 1 and 4. Until more precise plasma and tissue data are available, we recommend that fosfomycin prophylaxis be given 1-4 h prior to prostate biopsy. We do not recommend fosfomycin prophylaxis for subjects with known organisms with MICs >4 mg/L. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Relationship between Fosfomycin Exposure and Amplification of Escherichia coli Subpopulations with Reduced Susceptibility in a Hollow-Fiber Infection Model.

PubMed

VanScoy, Brian; McCauley, Jennifer; Bhavnani, Sujata M; Ellis-Grosse, Evelyn J; Ambrose, Paul G

2016-09-01

Understanding the relationship between antibiotic exposure and amplification of bacterial subpopulations with reduced drug susceptibility over time is important for evaluating the adequacy of dosing regimens. We utilized a hollow-fiber infection model to identify the fosfomycin intravenous dosing regimens that prevented the amplification of Escherichia coli bacterial subpopulations with reduced fosfomycin susceptibility. The challenge isolate was E. coli ATCC 25922 (agar MIC with glucose-6-phosphate, 1 mg/liter; agar MIC without glucose-6-phosphate, 32 mg/liter). The fosfomycin dosing regimens studied were 1 to 12 g every 8 h for 10 days to approximate that planned for clinical use. The studies included a no-treatment control regimen. Two bacterial subpopulations were identified, one with reduced susceptibility with agar MIC values ranging from 32 to 128 mg/liter and the other resistant with agar MIC values of 256 to >1,024 mg/liter on plates containing 5× and 256× the baseline MIC value, respectively. An inverted-U-shaped function best described the relationship between the amplification of the two bacterial subpopulations and drug exposure. The lowest fosfomycin dosing regimen that did not amplify a bacterial subpopulation with reduced susceptibility was 4 g administered every 8 h. Nearly immediate amplification of bacterial subpopulations with reduced susceptibility was observed with fosfomycin dosing regimens consisting of 1 to 2 g every 8 h. These data will be useful to support the selection of fosfomycin dosing regimens that minimize the potential for on-therapy amplification of bacterial subpopulations with reduced susceptibility. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Evaluation of fosfomycin activity against ESBL producing Enterobacteriaceae isolated from Iran.

PubMed

Kazemian, Hossein

2018-05-16

Rising rates of antimicrobial resistance among Enterobacteriaceae limit the use of reliably active forms of available drugs. The aim of this study was to investigate the prevalence of fosfomycin (US6794490B2) resistance gene among ESBL producing isolates in Iran. We tested 355 isolates of Enterobacteriacea collected from various clinical samples including urine, wounds, blood and other sources during June 2016 to July 2017. Antibiotic sensitivity and extended spectrum beta lactamase (ESBL) production were tested using agar dilution method according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. ESBL genes (blaTEM, bla SHV,bla CTX-M), plasmid-encoded fosfomycin resistance genes (fosA, fosB, fosA3 and fosC2) and chromosomal mutations (murA, glpT, uhpT) were detected by polymerase chain reaction (PCR). In this study, 151 of the 355 isolates were ESBL-positive. blaCTX-M (77%) was the most common gene followed by blaSHV (70%) and blaTEM (58%), either alone or in combination. Eighty nine percent (132/151) of the ESBL-positive isolates were MDR. Antimicrobial susceptibility rates were higher for fosfomycin (92.8%) and imipenem (35.5%) among ESBL-positive isolates. None of the ESBL- positive isolates harbored any mutations or plasmid-mediated fosfomycin resistance determinants. In conclusion, fosfomycin showed good antimicrobial activity against multidrug resistance ESBL- positive Enterobacteriaceae. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Elucidation of the pharmacokinetic/pharmacodynamic determinants of fosfomycin activity against Pseudomonas aeruginosa using a dynamic in vitro model.

PubMed

Bilal, Hajira; Peleg, Anton Y; McIntosh, Michelle P; Styles, Ian K; Hirsch, Elizabeth B; Landersdorfer, Cornelia B; Bergen, Phillip J

2018-06-01

To identify the fosfomycin pharmacokinetic (PK)/pharmacodynamic (PD) index (fT>MIC, fAUC/MIC or fCmax/MIC) most closely correlated with activity against Pseudomonas aeruginosa and determine the PK/PD target associated with various extents of bacterial killing and the prevention of emergence of resistance. Dose fractionation was conducted over 24 h in a dynamic one-compartment in vitro PK/PD model utilizing P. aeruginosa ATCC 27853 and two MDR clinical isolates (CR 1005 and CW 7). In total, 35 different dosing regimens were examined across the three strains. Microbiological response was examined by log changes and population analysis profiles. A Hill-type Emax model was fitted to the killing effect data (expressed as the log10 ratio of the area under the cfu/mL curve for treated regimens versus controls). Bacterial killing of no more than ∼3 log10 cfu/mL was achieved irrespective of regimen. The fAUC/MIC was the PK/PD index most closely correlated with efficacy (R2 = 0.80). The fAUC/MIC targets required to achieve 1 and 2 log10 reductions in the area under the cfu/mL curve relative to growth control were 489 and 1024, respectively. No regimen was able to suppress the emergence of resistance, and near-complete replacement of susceptible with resistant subpopulations occurred with virtually all regimens. Bacterial killing for fosfomycin against P. aeruginosa was most closely associated with the fAUC/MIC. Suppression of fosfomycin-resistant subpopulations could not be achieved even with fosfomycin exposures well above those that can be safely achieved clinically.

Vigilance on use of drugs, herbal products, and food supplements during pregnancy: focus on fosfomycin.

PubMed

Mannucci, C; Dante, G; Miroddi, M; Facchinetti, F; D'Anna, R; Santamaria, A; Lenti, M C; Vannacci, A; Calapai, F; Perone, M; Migliardi, G; Alibrandi, A; Navarra, M; Calapai, G

2017-09-17

Urinary tract infection (UTI) is defined as a common bacterial infection that can lead to significant morbidity such as stricture, fistula, abscess formation, bacteremia, sepsis, pyelonephritis, and kidney dysfunction with a mortality rates reported of 1% in men and 3% in women because of development of pyelonephritis. UTIs are more common in women and the 33% of them require antimicrobials treatment for at least one episode by the age of 24 years. UTIs are the most common infections observed during pregnancy and up to 30% of mothers with not treated asymptomatic bacteriuria may develop acute pyelonephritis which consequently can be associated to adverse maternal and fetal outcomes. All bacteriuria in pregnancy should be treated with antimicrobial treatments being safe for both the mother and the fetus. Approximately one every four women receives prescription of antibiotic treatment during pregnancy, nearly 80% of all the prescription medications during gestation. The use of fosfomycin to treat cystitis in pregnancy generally considered safe and effective. Even though use on antibiotics for urinary tract infections is considered generally safe for the fetus and mothers, this opinion is not based on specific studies monitoring the relationship of among urinary infections, consumption of antibiotics, and pregnancy outcomes. On this basis we decided to analyze data from the database of our multicenter study PHYTOVIGGEST, reporting data from 5362 pregnancies, focusing on use of fosfomycin. Principal outcomes of pregnancy in women treated with fosfomycin were taken into consideration. Women who have been treated with urinary antibiotics during the pregnancy were 183. With respect to the total number of pregnancies of our sample, these women represented the percentage of 3.49% (187/5362). Analysis of different outcomes of pregnancy such as gestational age, neonatal weight, and neonatal Apgar index did not show any significant difference. At the same time, analysis of data of pregnancy complicancies (such as urgent cesarean delivery, use of general anesthesia, need to induce labor) did not show any difference in women taking fosfomycin during pregnancy and those not taking it. Our data, based on a large number of pregnancies, confirm the safety use of fosfomycin use in pregnancy.

Frequency of colistin and fosfomycin resistance in carbapenem-resistant Enterobacteriaceae from a tertiary care hospital in Karachi.

PubMed

Qamar, Salima; Shaheen, Najma; Shakoor, Sadia; Farooqi, Joveria; Jabeen, Kauser; Hasan, Rumina

2017-01-01

Management of infections with carbapenem-resistant Enterobacteriaceae (CRE) is challenging. In recent times, agents such as colistin and fosfomycin have been used in combination with other antibiotics to treat such infections. In this study, we aim to seek frequency of colistin and fosfomycin resistance in CRE from Pakistan. This study was conducted at clinical laboratories, Aga Khan University Hospital. In total, 251 CRE were included in the study. Colistin minimum inhibitory concentrations (MICs) were performed using broth microdilution (BMD) method and VITEK ® 2 system, whereas fosfomycin susceptibility was performed using Kirby-Bauer method. MIC 50 and MIC 90 were calculated for colistin and agreement between VITEK and BMD was also calculated. Out of 251 strains colistin MIC of ≥4 µg/mL was seen in 40 (15.9%). Of these strains 20 (50%) were Klebsiella pneumoniae . Colistin MIC 50 and MIC 90 were found to be 0.5 and 16 µg/mL, respectively. BMD and VITEK 2 showed 100% categorical agreement. Essential agreement was 88.5% with kappa score 0.733 indicating strong agreement between VITEK and BMD. 31 out of 251 (12.3%) CREs were resistant to fosfomycin. Study shows frequency of colistin and fosfomycin resistance to be 15.9% and 12.3%, respectively. In countries where rate of CREs is high, emerging resistance against these last resort antibiotics is alarming as it leaves clinicians with almost no options to manage such multidrug resistant and extensively drug resistant infections.

Pharmacokinetics of Intraperitoneal and Intravenous Fosfomycin in Automated Peritoneal Dialysis Patients without Peritonitis

PubMed Central

Tobudic, Selma; Matzneller, Peter; Stoiser, Brigitte; Wenisch, Judith Maria; Vychytil, Andreas; Jaeger, Walter; Boehmdorfer, Michaela; Reznicek, Gottfried; Burgmann, Heinz

2012-01-01

Blood and dialysate concentrations of fosfomycin were determined after intravenous and intraperitoneal application of 4 mg/liter in patients undergoing automated peritoneal dialysis. Maximum serum concentrations after intravenous (287.75 ± 86.34 mg/liter) and intraperitoneal (205.78 ± 66.78 mg/liter) administration were comparable. Ratios of intraperitoneal to systemic exposure were 1.12 (intraperitoneal administration) and 0.22 (intravenous administration), indicating good systemic exposure after intraperitoneal application but limited penetration of fosfomycin into the peritoneal fluid after the intravenous dose. PMID:22564843

Pharmacokinetics of intraperitoneal and intravenous fosfomycin in automated peritoneal dialysis patients without peritonitis.

PubMed

Tobudic, Selma; Matzneller, Peter; Stoiser, Brigitte; Wenisch, Judith Maria; Zeitlinger, Markus; Vychytil, Andreas; Jaeger, Walter; Boehmdorfer, Michaela; Reznicek, Gottfried; Burgmann, Heinz

2012-07-01

Blood and dialysate concentrations of fosfomycin were determined after intravenous and intraperitoneal application of 4 mg/liter in patients undergoing automated peritoneal dialysis. Maximum serum concentrations after intravenous (287.75 ± 86.34 mg/liter) and intraperitoneal (205.78 ± 66.78 mg/liter) administration were comparable. Ratios of intraperitoneal to systemic exposure were 1.12 (intraperitoneal administration) and 0.22 (intravenous administration), indicating good systemic exposure after intraperitoneal application but limited penetration of fosfomycin into the peritoneal fluid after the intravenous dose.

Activity of Fosfomycin- and Daptomycin-Containing Bone Cement on Selected Bacterial Species Being Associated with Orthopedic Infections.

PubMed

Eick, Sigrun; Hofpeter, Kevin; Sculean, Anton; Ender, Claudia; Klimas, Susann; Vogt, Sebastian; Nietzsche, Sandor

2017-01-01

The purpose of this study was to determine activity of fosfomycin/gentamicin and daptomycin/gentamicin-containing PMMA bone-cement against Staphylococcus aureus (MRSA, MSSA), Staphylococcus epidermidis , Enterococcus faecium (VRE), and E. coli (ESBL; only fosfomycin). Test specimens of the bone cement were formed and bacteria in two concentrations were added one time or repeatedly up to 96 h. All fosfomycin-containing cement killed ultimately all MSSA, Staphylococcus epidermidis, and E. coli within 24 h; growth of MRSA was suppressed up to 48 h. Activity of daptomycin-containing cement depended on the concentration; the highest concentrated bone cement used (1.5 g daptomycin/40 g of powder) was active against all one-time added bacteria. When bacteria were added repeatedly to fosfomycin-containing cement, growth was suppressed up to 96 h and that of MRSA and VRE only up to 24 h. The highest concentration of daptomycin suppressed the growth of repeated added bacteria up to 48 h (VRE) until 96 h (MSSA, MRSA). In conclusion, PMMA bone cement with 1.5 g of daptomycin and 0.5 g of gentamicin may be an alternative in treatment of periprosthetic infections caused by Gram-positive bacteria.

Activity of Fosfomycin- and Daptomycin-Containing Bone Cement on Selected Bacterial Species Being Associated with Orthopedic Infections

PubMed Central

Hofpeter, Kevin; Sculean, Anton; Ender, Claudia; Klimas, Susann; Vogt, Sebastian; Nietzsche, Sandor

2017-01-01

The purpose of this study was to determine activity of fosfomycin/gentamicin and daptomycin/gentamicin-containing PMMA bone-cement against Staphylococcus aureus (MRSA, MSSA), Staphylococcus epidermidis, Enterococcus faecium (VRE), and E. coli (ESBL; only fosfomycin). Test specimens of the bone cement were formed and bacteria in two concentrations were added one time or repeatedly up to 96 h. All fosfomycin-containing cement killed ultimately all MSSA, Staphylococcus epidermidis, and E. coli within 24 h; growth of MRSA was suppressed up to 48 h. Activity of daptomycin-containing cement depended on the concentration; the highest concentrated bone cement used (1.5 g daptomycin/40 g of powder) was active against all one-time added bacteria. When bacteria were added repeatedly to fosfomycin-containing cement, growth was suppressed up to 96 h and that of MRSA and VRE only up to 24 h. The highest concentration of daptomycin suppressed the growth of repeated added bacteria up to 48 h (VRE) until 96 h (MSSA, MRSA). In conclusion, PMMA bone cement with 1.5 g of daptomycin and 0.5 g of gentamicin may be an alternative in treatment of periprosthetic infections caused by Gram-positive bacteria. PMID:28484708

Emerging Gram negative resistance to last-line antimicrobial agents fosfomycin, colistin and ceftazidime-avibactam - epidemiology, laboratory detection and treatment implications.

PubMed

Sherry, Norelle; Howden, Benjamin

2018-04-01

Multidrug-resistant (MDR) and extensively-drug-resistant (XDR) Gram-negative bacteria have emerged as a major threat to human health globally. This has resulted in the 're-discovery' of some older antimicrobials and development of new agents, however resistance has also rapidly emerged to these agents. Areas covered: Here we describe recent developments in resistance to three of the most important last-line antimicrobials for treatment of MDR and XDR Gram negatives: fosfomycin, colistin and ceftazidime-avibactam. Expert commentary: A key challenge for microbiologists and clinicians using these agents for treating patients with MDR and XDR Gram negative infections is the need to ensure appropriate reference methods are being used to test susceptibility to these agents, especially colistin and fosfomycin. These methods are not available in all laboratories meaning accurate results are either delayed, or potentially inaccurate as non-reference methods are employed. Combination therapy for MDR and XDR Gram negatives is likely to become more common, and future studies should focus on the clinical effects of monotherapy vs combination therapy, as well as validation of synergy testing methods. Effective national and international surveillance systems to detect and respond to resistance to these last line agents are also critical.

Plasmid-mediated fosfomycin resistance is due to enzymatic modification of the antibiotic.

PubMed Central

Llaneza, J; Villar, C J; Salas, J A; Suarez, J E; Mendoza, M C; Hardisson, C

1985-01-01

The molecular mechanism of plasmid-mediated resistance to fosfomycin is described. The antibiotic was inactivated intracellularly and remained inside the cells. Modification was also obtained from cell extracts and was not energy dependent. The modifying enzyme seems to have sulfhydryl groups in its active center. PMID:3899003

In vitro activity of potential old and new drugs against multidrug-resistant gram-negatives.

PubMed

Rizek, Camila; Ferraz, Juliana Rosa; van der Heijden, Inneke Marie; Giudice, Mauro; Mostachio, Anna Karina; Paez, Jorge; Carrilho, Claudia; Levin, Anna Sara; Costa, Silvia F

2015-02-01

The aim of this study was to evaluate the in vitro susceptibility of MDR gram-negatives bacteria to old drugs such as polymyxin B, minocycline and fosfomycin and new drugs such as tigecycline. One hundred and fifty-three isolates from 4 Brazilian hospitals were evaluated. Forty-seven Acinetobacter baumannii resistant to carbapenens harboring adeB, blaOxA23, blaOxA51, blaOxA143 and blaIMP genes, 48 Stenotrophomonas maltophilia including isolates resistant to levofloxacin and/or trimethoprim-sulfamethoxazole harboring sul-1, sul-2 and qnrMR and 8 Serratia marcescens and 50 Klebsiella pneumoniae resistant to carbapenens harboring blaKPC-2 were tested to determine their minimum inhibitory concentrations (MICs) by microdilution to the following drugs: minocycline, ampicillin-sulbactam, tigecycline, and polymyxin B and by agar dilution to fosfomycin according with breakpoint criteria of CLSI and EUCAST (fosfomycin). In addition, EUCAST fosfomycin breakpoint for Pseudomonas spp. was applied for Acinetobacter spp and S. maltophilia, the FDA criteria for tigecycline was used for Acinetobacter spp and S. maltophilia and the Pseudomonas spp polymyxin B CLSI criterion was used for S. maltophilia. Tigecycline showed the best in vitro activity against the MDR gram-negative evaluated, followed by polymyxin B and fosfomycin. Polymyxin B resistance among K. pneumoniae was detected in 6 isolates, using the breakpoint of MIC > 8 ug/mL. Two of these isolates were resistant to tigecycline. Minocycline was tested only against S. maltophilia and A. baumannii and showed excellent activity against both. Fosfomycin seems to not be an option to treat infections due to the A. baumannii and S. maltophilia isolates according with EUCAST breakpoint, on the other hand, showed excellent activity against S. marcescens and K. pneumoniae. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Evolution of sensitivity to fosfomycin in bacteria isolated in 1973, 1974 and 1975 in the Servicio de Microbiologia y Epidemiologia of the 'Clinica Puerta de Hierro', Madrid.

PubMed

Dámaso, D; Moreno-López, M; Martínez-Beltrán, J

1977-01-01

The bacteriostatic activity of fosfomycin was studied in vitro against 1,243 clinical isolations of gram-positive cocci and 4,086 isolations of gram-negative bacilli that were obtained in 1973, 1974 and in the period from January to May of 1975. MIC was determined by the agar diffusion method, quantifying it by means of the standard curve that was worked out with the strain of E. coli NCTC 10,418. A slight increase in resistance was observed in the gram-positive cocci: 64 mug/ml were inhibitory for 63% of the 249 isolations obtained in 1973, 59.1% of the 716 isolations obtained in 1974, and 57.5% of the 278 isolations from 1975. A slight loss of sensitivity was also observed in the gram-negative bacilli: the aforementioned concentration of fosfomycin inhibited 36% of the 742 isolations from 1973, 33.6% of the 2,387 isolations from 1974 and 32.6% of the 957 isolations from 1975. 933 g of this antibiotic were consumed in our hospital in 1973, 4,203 g in 1974 and 957 g in 1975. The consumption rate per patient per year was 0.15, 0.72 and 0.20 g, respectively. In conclusion, although no change was observed in the sensitivity of some bacterial strains to fosfomycin, the overall study indicates a slight decrease in the sensitivity, although it does not apparently have any relationship to the consumption of fosfomycin in our hospital.

Fosfomycin: An Alternative Therapy for the Treatment of UTI Amidst Escalating Antimicrobial Resistance.

PubMed

Sabharwal, Ekadashi Rajni; Sharma, Rajni

2015-12-01

Urinary tract infections (UTIs) are the most commonly encountered infectious diseases. The current study was undertaken with a dual purpose, to provide an insight into the current scenario of the microorganisms causing UTI, their antimicrobial sensitivity patterns and also try and evaluate the activity of fosfomycin against E. coli, both ESBL producers as well as non-producers. The study was conducted prospectively in the Department of Microbiology of a tertiary care hospital from January to June 2014. A total of 358 isolates from the urinary samples of the patients with a diagnosis of urinary tract infection were included in the study. Antibiotic sensitivity testing and extended spectrum beta lactamase (ESBL) production testing was done as per CLSI guidelines. These represented 297 (82.9%) gram-negative isolates and 61 (17%) gram-positive isolates. The 297 gram-negative isolates represented 265 (89.2%) members of the Enterobacteriaceae, 185 (69.8%) of which were Escherichia coli, 66 (24.9%) Klebsiella spp. and 14 (5.28%) Proteus spp. Non-fermentative Pseudomonas spp were isolated from 8.9% cases. Amongst the Gram negative isolates tested, 78 (21.8%) formed extended spectrum beta-lactamases. Of the total 358 isolates tested, 338 (94.4%) were found to be susceptible to fosfomycin. Fosfomycin showed good activity against both ESBL-producing and ESBL-negative E. coli isolates. The main finding of our study is that fosfomycin exhibits excellent antimicrobial activity even against the isolates with relatively high levels of antimicrobial resistance and hence can be a useful drug in our armamentarium.

Obtaining i.v. fosfomycin through an expanded-access protocol.

PubMed

Frederick, Corey M; Burnette, Jennifer; Aragon, Laura; Gauthier, Timothy P

2016-08-15

One hospital's experience with procuring i.v. fosfomycin via an expanded-access protocol to treat a panresistant infection is described. In mid-2014, a patient at a tertiary care institution had an infection caused by a gram-negative pathogen expressing notable drug resistance. Once it was determined by the infectious diseases (ID) attending physician that i.v. fosfomycin was a possible treatment for this patient, the ID pharmacist began the process of drug procurement. The research and ID pharmacists completed an investigational new drug (IND) application, which required patient-specific details and contributions from the ID physician. After obtaining approval of the IND, an Internet search identified a product vendor in the United Kingdom, who was then contacted to begin the drug purchasing and acquisition processes. Authorization of the transaction required signatures from key senior hospital administrators, including the chief financial officer and the chief operating officer. Approximately 6 days after beginning the acquisition process, the research pharmacist arranged for the wholesaler to expedite product delivery. The ID pharmacist contacted the wholesaler's shipping company at the U.S. Customs Office, providing relevant contact information to ensure that any unexpected circumstances could be quickly addressed. The product arrived at the U.S. Customs Office 8 days after beginning the acquisition process and was held in the U.S. Customs Office for 2 days. The patient received the first dose of i.v. fosfomycin 13 days after starting the expanded-access protocol process. I.V. fosfomycin was successfully procured through an FDA expanded-access protocol by coordinating efforts among ID physicians, pharmacists, and hospital executives. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Trend and seasonality of community-acquired Escherichia coli antimicrobial resistance and its dynamic relationship with antimicrobial use assessed by ARIMA models.

PubMed

Asencio Egea, María Ángeles; Huertas Vaquero, María; Carranza González, Rafael; Herráez Carrera, Óscar; Redondo González, Olga; Arias Arias, Ángel

2017-12-04

We studied the trend and seasonality of community-acquired Escherichia coli resistance and quantified its correlation with the previous use of certain antibiotics. A time series study of resistant community-acquired E. coli isolates and their association with antibiotic use was conducted in a Primary Health Care Area from 2008 to 2012. A Poisson regression model was constructed to estimate the trend and seasonality of E. coli resistance. A significant increasing trend in mean E. coli resistance to cephalosporins, aminoglycosides and nitrofurantoin was observed. Seasonal resistance to ciprofloxacin and amoxicillin-clavulanic acid was significantly higher in autumn-winter. There was a delay of 7, 10 and 12 months between the use of cotrimoxazole (P<0.038), fosfomycin (P<0.024) and amoxicillin-clavulanic acid (P<0.015), respectively, and the occurrence of E. coli resistance. An average delay of 10 months between the previous use of amoxicillin-clavulanic acid, cotrimoxazole and fosfomycin and the appearance of resistant community-acquired E. coli strains was detected. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

A Randomized Trial of the Amikacin Fosfomycin Inhalation System for the Adjunctive Therapy of Gram-Negative Ventilator-Associated Pneumonia: IASIS Trial.

PubMed

Kollef, Marin H; Ricard, Jean-Damien; Roux, Damien; Francois, Bruno; Ischaki, Eleni; Rozgonyi, Zsolt; Boulain, Thierry; Ivanyi, Zsolt; János, Gál; Garot, Denis; Koura, Firas; Zakynthinos, Epaminondas; Dimopoulos, George; Torres, Antonio; Danker, Wayne; Montgomery, A Bruce

2017-06-01

Clinical failures in ventilator-associated pneumonia (VAP) caused by gram-negative bacteria are common and associated with substantial morbidity, mortality, and resource utilization. We assessed the safety and efficacy of the amikacin fosfomycin inhalation system (AFIS) for the treatment of gram-negative bacterial VAP in a randomized double-blind, placebo-controlled, parallel group, phase 2 study between May 2013 and March 2016. We compared standard of care in each arm plus 300 mg amikacin/120 mg fosfomycin or placebo (saline), delivered by aerosol twice daily for 10 days (or to extubation if < 10 days) via the investigational eFlow Inline System (PARI GmbH). The primary efficacy end point was change from baseline in the Clinical Pulmonary Infection Score (CPIS) during the randomized course of AFIS/placebo, using the subset of patients with microbiologically proven baseline infections with gram-negative bacteria. There were 143 patients randomized: 71 to the AFIS group, and 72 to the placebo group. Comparison of CPIS change from baseline between treatment groups was not different (P = .70). The secondary hierarchical end point of no mortality and clinical cure at day 14 or earlier was also not significant (P = .68) nor was the hierarchical end point of no mortality and ventilator-free days (P = .06). The number of deaths in the AFIS group was 17 (24%) and 12 (17%) in the placebo group (P = .32). The AFIS group had significantly fewer positive tracheal cultures on days 3 and 7 than placebo. In this trial of adjunctive aerosol therapy compared with standard of care IV antibiotics in patients with gram-negative VAP, the AFIS was ineffective in improving clinical outcomes despite reducing bacterial burden. ClinicalTrials.gov; No.: NCT01969799; URL: www.clinicaltrials.gov. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Antimicrobial Resistance of Pseudomonas aeruginosa Isolated from Dogs and Cats in Primary Veterinary Hospitals in Japan.

PubMed

Yukawa, Shoichiro; Tsuyuki, Yuzo; Sato, Tomomi; Fukuda, Akira; Usui, Masaru; Tamura, Yutaka

2017-07-24

We collected 200 Pseudomonas aeruginosa isolates from dogs and cats in primary veterinary hospitals in Japan to investigate their antimicrobial resistance. Resistance rates against ciprofloxacin, cefotaxime, gentamicin, amikacin, and fosfomycin were 9%, 12.5%, 4.5%, 2.5%, and 35.5%, respectively. One strain displayed resistance (0.5%) to ceftazidime. We did not detect any imipenem-resistant or multidrug-resistant P. aeruginosa strains as defined by the Japanese Ministry of Health, Labour, and Welfare Law Concerning the Prevention of Infections and Medical Care for Patients with Infections. In addition, we did not find any P. aeruginosa isolates that produced metallo-β-lactamase, the aminoglycoside 6'-N-acetyltransferase AAC(6')-Iae, or the aminoglycoside acetyltransferase AAC(6')-Ib.

Treatment of recurrent complicated urinary tract infections in children with vesicoureteral reflux.

PubMed

Wu, Tsung-Hua; Huang, Fang-Liang; Fu, Lin-Shien; Chou, Chia-Man; Chien, Ya-Li; Huang, Chung-Ming; Lin, Chin-Fu; Chen, Po-Yen

2016-10-01

Urinary tract infections (UTIs) in children with vesicoureteral reflux (VUR) are often caused by uropathogens with a high rate of drug resistance and are associated with a high rate of recurrence with a single pathogen. In this study, we evaluated the incidence of recurrent UTI and the drug resistance pattern of Escherichia coli in children with VUR. We also evaluated whether combination therapy comprising fosomycin plus one other antimicrobial agent is effective for treatment of recurrent UTIs. We retrospectively reviewed the medical records of all children with VUR who developed at least one episode of UTI during the period January 1, 2003 to December 31, 2013 at a single medical center. The effectiveness of fosfomycin plus amikicin for Enterobacteriaceae or ceftazidime for Pseudomonas aeruginosa infections was prospectively studied in six children with recurrent relapsing UTIs. The study population comprised 129 children (age range, from 1month to 15 years; mean ± standard deviation, 2.37 ± 2.91 years) with VUR who developed at least one UTI during the 10-year study period; 68 (52.7%) had recurrent UTIs. The presence of an underlying urinary tract anomaly was predictive of recurrence (p = 0.028). The rates of susceptibility of E. coli to cefazolin (p < 0.001) and cefotaxime (p < 0.001) were significantly lower in patients with recurrent UTIs. Combination therapy with fosfomycin plus amikacin or ceftazidime was shown to be an effective therapeutic option for recurrent UTIs due to a single uropathogen. The rates of susceptibility of E. coli to commonly used antimicrobials were significantly lower in children who developed more than one episode of UTI. The empiric choice of cefazolin or cefotaxime was usually ineffective. Administration of fosfomycin plus amikacin or ceftazidime was an effective therapeutic and preventive strategy in children with VUR and recurrent relapsing UTI. Copyright © 2014. Published by Elsevier B.V.

[Evaluation of antibiotic resistance of Escherichia coli in urinary tract infections in Primary Care Barbastro Sector (Huesca)].

PubMed

Betrán, Ana; Cortés, Ana Ma; López, Concepción

2015-10-01

Evaluate the resistance of community-uropathogen, Escherichia coli to several antibiotics in our health sector and deduce empirical treatment options. E. coli strains isolated from urine cultures of patients from Primary Care Barbastro Sector, between January 2011 and December 2013, were studied. The resistances rates for nine common antibiotics were determined, and differences in sensitivity were analyzed, comparing confidence intervals for proportions by the method of Wilson. E. coli was the most frequently isolated bacteria (61.08% of positive urine cultures sent from Primary Care). Overall, there has been an increase in resistance of E. coli isolates in all antimicrobials studied. Still, resistance has remained below 4% compared to fosfomycin and nitrofurantoin and below 10% in cephalosporins second and third generation. Resistance to amoxicillin-clavulanate has increased progressively reaching 21.5% in 2013; only this antibiotic has presented a statistically significant increase. The maximum levels of resistance (over 30%) were found in the antibiotics administered orally and often indicated in uncomplicated urinary tract infections: trimethoprim-sulfamethoxazole, ciprofloxacin and ampicillin. Update knowledge susceptibility patterns of microorganisms most commonly isolated in urine samples in each health area allows to choose the most suitable and effective treatments trough empirical knowledge.

A simple LC-MS/MS method using HILIC chromatography for the determination of fosfomycin in plasma and urine: application to a pilot pharmacokinetic study in humans.

PubMed

Parker, Suzanne L; Lipman, Jeffrey; Roberts, Jason A; Wallis, Steven C

2015-02-01

A high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, using hydrophilic interaction liquid chromatography (HILIC) chromatography for the analysis of fosfomycin in human plasma and urine, has been developed and validated. The plasma method uses a simple protein precipitation using a low volume sample (10 μL) and is suitable for the concentration range of 1 to 2000 μg/mL. The urine method involves a simple dilution of 10 μL of sample and is suitable for a concentration range of 0.1 to 10 mg/mL. The plasma and urine results, reported, respectively, are for recovery (68, 72%), inter-assay precision (≤9.1%, ≤8.1%) and accuracy (range -7.2 to 3.3%, -1.9 to 1.6%), LLOQ precision (4.7%, 3.1%) and accuracy (1.7% and 1.2%), and includes investigations into the linearity, stability and matrix effects. The method was used in a pilot pharmacokinetic study of a critically ill patient receiving i.v. fosfomycin, which measured a maximum and minimum plasma concentration of 222 μg/mL and 172 μg/mL, respectively, after the initial dose, and a maximum and minimum plasma concentration of 868 μg/mL and 591μg/mL, respectively, after the fifth dose. The urine concentration was 2.03 mg/mL after the initial dose and 0.29 mg/mL after the fifth dose. Copyright © 2014 Elsevier B.V. All rights reserved.

Biocompatability of hydroxyapatite composite as a local drug delivery system.

PubMed

Krisanapiboon, A; Buranapanitkit, B; Oungbho, K

2006-12-01

To investigate the biocompatibility of hydroxyapatite composite (hydroxyapatite, plaster of Paris, and chitosan) impregnated with gentamicin, fosfomycin, imipenem, or amphotericin B. The interactions of the extract from each drug against osteoblast were tested using the methylthiotetrazole test. Extracts from all drugs showed good biocompatibility at concentrations varying from 10 microgram/ml to 1000 microgram/ml. Imipenem and amphotericin B at a concentration of 1000 microgram/ml had a significantly higher percentage of cell viability than the control group. No morphological change of osteoblast was observed in all drug tests at any concentrations. The hydroxyapatite composite had a good biocompatibility for carrying gentamicin, fosfomycin, imipenem, or amphotericin B.

Fosfomycin versus meropenem in bacteraemic urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli (FOREST): study protocol for an investigator-driven randomised controlled trial.

PubMed

Rosso-Fernández, Clara; Sojo-Dorado, Jesús; Barriga, Angel; Lavín-Alconero, Lucía; Palacios, Zaira; López-Hernández, Inmaculada; Merino, Vicente; Camean, Manuel; Pascual, Alvaro; Rodríguez-Baño, Jesús

2015-03-31

Finding therapeutic alternatives to carbapenems in infections caused by extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) is imperative. Although fosfomycin was discovered more than 40 years ago, it was not investigated in accordance with current standards and so is not used in clinical practice except in desperate situations. It is one of the so-called neglected antibiotics of high potential interest for the future. The main objective of this project is to demonstrate the clinical non-inferiority of intravenous fosfomycin with regard to meropenem for treating bacteraemic urinary tract infections (UTI) caused by ESBL-EC. This is a 'real practice' multicentre, open-label, phase III randomised controlled trial, designed to compare the clinical and microbiological efficacy, and safety of intravenous fosfomycin (4 g/6 h) and meropenem (1 g/8 h) as targeted therapy for this infection; a change to oral therapy is permitted after 5 days in both arms, in accordance with predetermined options. The study design follows the latest recommendations for designing trials investigating new options for multidrug-resistant bacteria. Secondary objectives include the study of fosfomycin concentrations in plasma and the impact of both drugs on intestinal colonisation by multidrug-resistant Gram-negative bacilli. Ethical approval was obtained from the Andalusian Coordinating Institutional Review Board (IRB) for Biomedical Research (Referral Ethics Committee), which obtained approval from the local ethics committees at all participating sites in Spain (22 sites). Data will be presented at international conferences and published in peer-reviewed journals. This project is proposed as an initial step in the investigation of an orphan antimicrobial of low cost with high potential as a therapeutic alternative in common infections such as UTI in selected patients. These results may have a major impact on the use of antibiotics and the development of new projects with this drug, whether as monotherapy or combination therapy. NCT02142751. EudraCT no: 2013-002922-21. Protocol V.1.1 dated 14 March 2014. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Fosfomycin enhances phagocyte-mediated killing of Staphylococcus aureus by extracellular traps and reactive oxygen species.

PubMed

Shen, Fengge; Tang, Xudong; Cheng, Wei; Wang, Yang; Wang, Chao; Shi, Xiaochen; An, Yanan; Zhang, Qiaoli; Liu, Mingyuan; Liu, Bo; Yu, Lu

2016-01-18

The successful treatment of bacterial infections is the achievement of a synergy between the host's immune defences and antibiotics. Here, we examined whether fosfomycin (FOM) could improve the bactericidal effect of phagocytes, and investigated the potential mechanisms. FOM enhanced the phagocytosis and extra- or intracellular killing of S. aureus by phagocytes. And FOM enhanced the extracellular killing of S. aureus in macrophage (MФ) and in neutrophils mediated by extracellular traps (ETs). ET production was related to NADPH oxidase-dependent reactive oxygen species (ROS). Additionally, FOM increased the intracellular killing of S. aureus in phagocytes, which was mediated by ROS through the oxidative burst process. Our results also showed that FOM alone induced S. aureus producing hydroxyl radicals in order to kill the bacterial cells in vitro. In a mouse peritonitis model, FOM treatment increased the bactericidal extra- and intracellular activity in vivo, and FOM strengthened ROS and ET production from peritoneal lavage fluid ex vivo. An IVIS imaging system assay further verified the observed in vivo bactericidal effect of the FOM treatment. This work may provide a deeper understanding of the role of the host's immune defences and antibiotic interactions in microbial infections.

Fosfomycin enhances phagocyte-mediated killing of Staphylococcus aureus by extracellular traps and reactive oxygen species

PubMed Central

Shen, Fengge; Tang, Xudong; Cheng, Wei; Wang, Yang; Wang, Chao; Shi, Xiaochen; An, Yanan; Zhang, Qiaoli; Liu, Mingyuan; Liu, Bo; Yu, Lu

2016-01-01

The successful treatment of bacterial infections is the achievement of a synergy between the host’s immune defences and antibiotics. Here, we examined whether fosfomycin (FOM) could improve the bactericidal effect of phagocytes, and investigated the potential mechanisms. FOM enhanced the phagocytosis and extra- or intracellular killing of S. aureus by phagocytes. And FOM enhanced the extracellular killing of S. aureus in macrophage (MФ) and in neutrophils mediated by extracellular traps (ETs). ET production was related to NADPH oxidase-dependent reactive oxygen species (ROS). Additionally, FOM increased the intracellular killing of S. aureus in phagocytes, which was mediated by ROS through the oxidative burst process. Our results also showed that FOM alone induced S. aureus producing hydroxyl radicals in order to kill the bacterial cells in vitro. In a mouse peritonitis model, FOM treatment increased the bactericidal extra- and intracellular activity in vivo, and FOM strengthened ROS and ET production from peritoneal lavage fluid ex vivo. An IVIS imaging system assay further verified the observed in vivo bactericidal effect of the FOM treatment. This work may provide a deeper understanding of the role of the host’s immune defences and antibiotic interactions in microbial infections. PMID:26778774

Fosfomycin and Tobramycin in Combination Downregulate Nitrate Reductase Genes narG and narH, Resulting in Increased Activity against Pseudomonas aeruginosa under Anaerobic Conditions

PubMed Central

McCaughey, Gerard; Gilpin, Deirdre F.; Schneiders, Thamarai; Hoffman, Lucas R.; McKevitt, Matt; Elborn, J. Stuart

2013-01-01

The activity of aminoglycosides, which are used to treat Pseudomonas aeruginosa respiratory infection in cystic fibrosis (CF) patients, is reduced under the anaerobic conditions that reflect the CF lung in vivo. In contrast, a 4:1 (wt/wt) combination of fosfomycin and tobramycin (F:T), which is under investigation for use in the treatment of CF lung infection, has increased activity against P. aeruginosa under anaerobic conditions. The aim of this study was to elucidate the mechanisms underlying the increased activity of F:T under anaerobic conditions. Microarray analysis was used to identify the transcriptional basis of increased F:T activity under anaerobic conditions, and key findings were confirmed by microbiological tests, including nitrate utilization assays, growth curves, and susceptibility testing. Notably, growth in subinhibitory concentrations of F:T, but not tobramycin or fosfomycin alone, significantly downregulated (P < 0.05) nitrate reductase genes narG and narH, which are essential for normal anaerobic growth of P. aeruginosa. Under anaerobic conditions, F:T significantly decreased (P < 0.001) nitrate utilization in P. aeruginosa strains PAO1, PA14, and PA14 lasR::Gm, a mutant known to exhibit increased nitrate utilization. A similar effect was observed with two clinical P. aeruginosa isolates. Growth curves indicate that nitrate reductase transposon mutants had reduced growth under anaerobic conditions, with these mutants also having increased susceptibility to F:T compared to the wild type under similar conditions. The results of this study suggest that downregulation of nitrate reductase genes resulting in reduced nitrate utilization is the mechanism underlying the increased activity of F:T under anaerobic conditions. PMID:23959314

Antibacterial efficacy and drug-induced tooth discolouration of antibiotic combinations for endodontic regenerative procedures.

PubMed

Mandras, N; Roana, J; Allizond, V; Pasqualini, D; Crosasso, P; Burlando, M; Banche, G; Denisova, T; Berutti, E; Cuffini, A M

2013-01-01

Elimination of microbial contamination from the root canal system is a precondition for successful root canal treatment. Teeth with immature root development, necrotic pulps and apical periodontitis present multiple challenges for successful treatment. Disinfection is achieved by irrigation followed by the placement of an intracanal medicament. A mixture of ciprofloxacin, metronidazole and minocycline (3-MIX S) has been shown to be very effective in eliminating endodontic pathogens in vitro and in vivo. Among the components of the mixture, minocycline can induce tooth discolouration after long-term oral use. Therefore, the elimination of minocycline from the above-mentioned combination has been suggested to prevent the occasion of this undesirable effect. The aim of this study was to investigate the potential antimicrobial efficacy of alternative antibiotic combinations [3-MIX C (clarithromycin); 3-MIX F (fosfomycin)] against bacteria from infected root canals. An additional objective was to evaluate their discolouration potential as possible alternatives to minocycline-based intracanal medicaments. Our in vitro results clearly demonstrated that 3-MIX C and 3-MIX F had a greater antimicrobial activity than 3-MIX S, underlying that clarithromycin still had a higher capacity to kill endodontic pathogens in vitro compared to fosfomycin. Both 3-MIX C and 3-MIX F were able to avoid the permanent staining effect of the crown.

Recurrent uncomplicated cystitis in women: allowing patients to self-initiate antibiotic therapy.

PubMed

2014-02-01

Acute uncomplicated cystitis is a lower urinary tract infection occurring in the absence of anatomic or functional abnormalities of the urinary tract or any other complicating factors.The organism responsible is often an enterobacterium, especially Escherichia coli. What is the role of antibiotic therapy for non-pregnant women with recurrent acute uncomplicated cystitis? We reviewed the available evidence using the standard Prescrire methodology. A single oral dose of fosfomycin trometamol is the antibiotic of choice for treating an episode of acute uncomplicated cystitis. Alternative antibiotics are certain fluoroquinolones or co-trimoxazole (a fixed-dose combination of sulfamethoxazole and trimethoprim). For recurrent acute uncomplicated cystitis, cranberry juice has modest efficacy in reducing the frequency of episodes. A number of non-drug measures are typically proposed, although their effects are unproven: drinking sufficient fluids and urinating regularly; urinating after sexual intercourse; and avoiding spermicides. The strategy that results in the lowest antibiotic exposure is a short course of antibiotics for each episode of urinary tract infection, initiated as soon as clinical symptoms appear. Long-term antibiotic therapy is sometimes offered. According to one systematic review, women taking long-term prophylactic antibiotic therapy had about 6 times fewer clinical recurrences than with placebo. According to one randomised trial, 3 g of fosfomycin trometamol taken as a single dose every ten days reduced the frequency of recurrence, resulting in 0.14 episodes of infection per year on average versus about 3 episodes with placebo (p < 0.001). The amount of antibiotic used when fosfomycin trometamol is taken every 10 days for 6 months is equivalent to treatment of 18 acute episodes of cystitis. When cystitis appears to be associated with sexual intercourse, two small randomised trials suggest that routine postcoital antibiotic treatment is more effective than placebo and as effective as long-term antibiotic therapy. Adverse effects, some of which can be serious, depend on the antibiotic used. The development of resistance among enterobacteria is one argument for limiting the use of antibiotics, in order to preserve their efficacy in serious infections. In practice, the strategy that uses the fewest antibiotics is to treat each episode as soon as the first clinical symptoms appear. Cases in which the frequency of recurrence warrants regular antibiotic prophylaxis are rare. The optimal antibiotic regimen in these cases has not been determined, either in clinical trials or by consensus.

TRIMETHOPRIM-SULFAMETHOXAZOLE RESISTANCE AND FOSFOMYCIN SUSCEPTIBILITY RATES IN UNCOMPLICATED URINARY TRACT INFECTIONS: TIME TO CHANGE THE ANTIMICROBIAL PREFERENCES.

PubMed

Guneysel, Ozlem; Suman, Enes; Ozturk, Tuba Cimilli

2016-03-01

Urinary tract infections (UTIs) are among the most common bacterial infections in adult population. They are prevalent in all age groups both in women and men. Also, UTIs are the most frequent indication for empirical antibiotic treatment in emergency department. The aim of this study was to determine the antibiotic resistance rates in the treatment of uncomplicated UTIs. Adult patients admitted to emergency department with uncomplicated UTIs were included in this cross-sectional study. Mid-stream urine samples were obtained under sterile conditions and cultured quantitatively. After 24 hours, the samples showing 10(5) colony forming unit per milliliter (CFU/mL) were tested for antibiotic susceptibility. Resistance to fosfomycin-trometamol (FT), amoxicillin-clavulanic acid (AC), ciprofloxacin (CIP), trimethoprim-sulfamethoxazole (TMP-SMX) and cefpodoxime (CEF) was tested by Kirby-Bauer disc diffusion system. Escherichia (E.) coli accounted for the vast majority (93.4%) of the organisms isolated in the study. Among the E. coli positive patients, resistance to TMP-SMX was the most common antibiotic resistance. The E. coli species detected in our study group were least resistant to FT (2.4%). The resistance rates, especially to CEF, AC and CIP, were significantly higher in patients over 50 years of age. In conclusion, in the treatment of uncomplicated UTIs, TMP-SMX should be excluded from empirical treatment, while fosfomycin could be a viable option in all age groups.

Resistance to oral antibiotics in 4569 Gram-negative rods isolated from urinary tract infection in children.

PubMed

Calzi, Anna; Grignolo, Sara; Caviglia, Ilaria; Calevo, Maria Grazia; Losurdo, Giuseppe; Piaggio, Giorgio; Bandettini, Roberto; Castagnola, Elio

2016-09-01

To investigate antibiotic resistance among pathogens isolated from urines in a tertiary care children's hospital in Italy. Retrospective analysis of prospectively collected data on antibiotic susceptibility of Gram-negatives isolated from urines at the Istituto Giannina Gaslini, Genoa - Italy from 2007 to 2014. Antibiotic susceptibility was evaluated. By means of CLSI criteria from 2007 to 2010, while from 2011 EUCAST criteria were adopted. Data on susceptibility to amoxicillin-clavulanate, co-trimoxazole, cefuroxime, nitrofurantoin, fosfomycin and ciprofloxacin were evaluated for Escherichia coli, while for other Enterobacteriaceae data were collected for amoxicillin-clavulanate, co-trimoxazole and ciprofloxacin and for ciprofloxacin against Pseudomonas aeruginosa. Univariate and multivariable analyses were performed for risk factors associated with resistance. A total of 4596 Gram-negative strains were observed in 3364 patients. A significant increase in the proportion of resistant strains was observed for E.coli against amoxicillin-clavulanate, cefuroxime and ciprofloxacin and for others Enterobacteriaceae against co-trimoxazole and ciprofloxacin. Resistance to nitrofurantoin and fosfomycin was very infrequent in E.coli. Logistic regression analysis showed that repeated episode of urinary tract infections was a risk factor for E.coli resistance to amoxicillin-clavulanate, co-trimoxazole and cefuroxime, while admission in one of the Units usually managing children with urinary tract malformations was significantly associated to resistance to amoxicillin-clavulanate and cefuroxime. In conclusion the present study shows an increase in antibiotic resistance in pediatric bacteria isolated from urines in children, especially in presence of repeated episodes and/or urinary tract malformations. This resistance is worrisome for beta-lactams and cotrimoxazole, and start to increase also for fluoroquinolones while nitrofurantoin and fosfomycin still could represent useful drugs for oral treatment of these infections. • Infections are frequent in patients with urinary tract malformations • Antibiotic prophylaxis can select for resistant pathogens What is New: • The increase in the resistance to β-lactams, co-trimoxazole or fluoroquinolones in pathogens causing urinary tract infections cause a reduction of drugs with oral formulations available for therapy • Old drugs like nitrofurantoin and fosfomycin can represent attractive compounds for oral treatment of urinary tract infections in children presence of resistance to other drug classes.

Effect of antibiotics on cellular stress generated in Shiga toxin-producing Escherichia coli O157:H7 and non-O157 biofilms.

PubMed

Angel Villegas, Natalia; Baronetti, José; Albesa, Inés; Etcheverría, Analía; Becerra, M Cecilia; Padola, Nora L; Paraje, M Gabriela

2015-10-01

Shiga toxin-producing Escherichia coli (STEC) are important food-borne pathogens, with the main virulence factor of this bacterium being its capacity to secrete Shiga toxins (Stxs). Therefore, the use of certain antibiotics for the treatment of this infection, which induces the liberation of Stxs, is controversial. Reactive oxygen and nitrogen species are also involved in the pathogenesis of different diseases. The purpose of this study was to analyze the effects of antibiotics on biofilms of STEC and the relationships between cellular stress and the release of Stx. To this end, biofilms of reference and clinical strains were treated with antibiotics (ciprofloxacin, fosfomycin and rifaximin) and the production of oxidants, the antioxidant defense system and toxin release were evaluated. Ciprofloxacin altered the prooxidant-antioxidant balance, with a decrease of oxidant metabolites and an increase of superoxide dismutase and catalase activity, being associated with high-levels of Stx production. Furthermore, inhibition of oxidative stress by exogenous antioxidants was correlated with a reduction in the liberation of Stx, indicating the participation of this phenomenon in the release of this toxin. In contrast, fosfomycin and rifaximin produced less alteration with a minimal production of Stx. Our data show that treatment of biofilm-STEC with these antibiotics induces oxidative stress-mediated release of Stx. Copyright © 2015 Elsevier Ltd. All rights reserved.

Identification of photoactivated adenylyl cyclases in Naegleria australiensis and BLUF-containing protein in Naegleria fowleri.

PubMed

Yasukawa, Hiro; Sato, Aya; Kita, Ayaka; Kodaira, Ken-Ichi; Iseki, Mineo; Takahashi, Tetsuo; Shibusawa, Mami; Watanabe, Masakatsu; Yagita, Kenji

2013-01-01

Complete genome sequencing of Naegleria gruberi has revealed that the organism encodes polypeptides similar to photoactivated adenylyl cyclases (PACs). Screening in the N. australiensis genome showed that the organism also encodes polypeptides similar to PACs. Each of the Naegleria proteins consists of a "sensors of blue-light using FAD" domain (BLUF domain) and an adenylyl cyclase domain (AC domain). PAC activity of the Naegleria proteins was assayed by comparing sensitivities of Escherichia coli cells heterologously expressing the proteins to antibiotics in a dark condition and a blue light-irradiated condition. Antibiotics used in the assays were fosfomycin and fosmidomycin. E. coli cells expressing the Naegleria proteins showed increased fosfomycin sensitivity and fosmidomycin sensitivity when incubated under blue light, indicating that the proteins functioned as PACs in the bacterial cells. Analysis of the N. fowleri genome revealed that the organism encodes a protein bearing an amino acid sequence similar to that of BLUF. A plasmid expressing a chimeric protein consisting of the BLUF-like sequence found in N. fowleri and the adenylyl cyclase domain of N. gruberi PAC was constructed to determine whether the BLUF-like sequence functioned as a sensor of blue light. E. coli cells expressing a chimeric protein showed increased fosfomycin sensitivity and fosmidomycin sensitivity when incubated under blue light. These experimental results indicated that the sequence similar to the BLUF domain found in N. fowleri functioned as a sensor of blue light.

Characterization of mutant histidine-containing proteins of the phosphoenolpyruvate:sugar phosphotransferase system of Escherichia coli and Salmonella typhimurium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Waygood, E.B.; Reiche, B.; Hengstenberg, W.

1987-06-01

Histidine-containing phosphocarrier protein (HPr) is common to all of the phosphoenolpyruvate:sugar phosphotransferase systems (PTS) in Escherichia coli and Salmonella typhimurium, except the fructose-specific PTS. Strains which lack HPr activity (ptsH) have been characterized in the past, and it has proved difficult to delineate between tight and leaky mutants. In this study four different parameters of ptsH strains were measured: in vitro sugar phosphorylation activity of the mutant HPr; detection of /sup 32/P-labeled P-HPr; ability of monoclonal antibodies to bind mutant HPr; and sensitivity of ptsH strains to fosfomycin. Tight ptsH strains could be defined; they were fosfomycin resistant and producedmore » no HPr protein or completely inactive mutant HPr. All leaky ptsH strains were fosfomycin sensitive, Usually produced normal amounts of mutant HPr protein, and had low but measurable activity, and HPr was detectable as a phosphoprotein. This indicates that the regulatory functions of the PTS require a very low level of HPr activity (about 1%). The antibodies used to detect mutant HPr in crude extracts were two monoclonal immunoglobulin G antibodies Jel42 and Jel44. Both antibodies, which have different pIs, inhibited PTS sugar phosphorylation assays, but the antibody-JPr complex could still be phosphorylated by enzyme I. Preliminary evidence suggests that the antibodies bind to two different epitopes which are in part located in a ..beta..-sheet structure.« less

Fosfomycin i.v. for Treatment of Severely Infected Patients

ClinicalTrials.gov

2018-05-08

Bacterial Infections; Bone Diseases, Infectious; Osteomyelitis; Central Nervous System Bacterial Infections; Meningitis, Bacterial; Encephalitis; Brain Abscess; Urinary Tract Infections; Respiratory Tract Infections; Pneumonia, Bacterial; Skin Diseases, Bacterial; Soft Tissue Infections; Intraabdominal Infections; Sepsis; Bacteremia; Endocarditis, Bacterial

Analysis of the spectrum and antibiotic resistance of uropathogens in outpatients at a tertiary hospital.

PubMed

Yang, Bo; Yang, Fujia; Wang, Shanmei; Wang, Qian; Liu, Zhirui; Feng, Wei; Sun, Fengjun; Xia, Peiyuan

2018-05-01

The objective of this study was to analyse the distribution and antimicrobial resistance of bacterial uropathogens isolated from outpatients at Henan Provincial People's Hospital. A total of 1419 samples from 823 newly diagnosed and 596 recurrent UTI outpatients culture positive. Escherichia coli was the most common uropathogen. Compared with the recurrent group, the newly diagnosed group had a higher isolation rate of E. coli and Enterobacter cloacae but a lower isolation rate of Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp. Except for P. aeruginosa, the resistance of Gram-negative bacteria to most antibiotics was less than 30%. All Enterococcus and Staphylococcus spp. were sensitive to linezolid, vancomycin and teicoplanin. Both Gram-negative and -positive bacteria exhibited high susceptibility to fosfomycin. Uropathogens isolated from recurrent outpatients had higher resistance rates than did those isolated from newly diagnosed outpatients. Our study indicated that fosfomycin might be an excellent treatment option for outpatients with UTIs.

Daptomycin plus fosfomycin versus daptomycin monotherapy in treating MRSA: protocol of a multicentre, randomised, phase III trial.

PubMed

Shaw, E; Miró, J M; Puig-Asensio, M; Pigrau, C; Barcenilla, F; Murillas, J; Garcia-Pardo, G; Espejo, E; Padilla, B; Garcia-Reyne, A; Pasquau, J; Rodriguez-Baño, J; López-Contreras, J; Montero, M; de la Calle, C; Pintado, V; Calbo, E; Gasch, O; Montejo, M; Salavert, M; Garcia-Pais, M J; Carratalà, J; Pujol, M

2015-03-11

Despite the availability of new antibiotics such as daptomycin, methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies. The study aims to demonstrate that combination of daptomycin plus fosfomycin achieves higher clinical success rates in the treatment of MRSA bacteraemia than daptomycin alone. A multicentre open-label, randomised phase III study. Adult patients hospitalised with MRSA bacteraemia will be randomly assigned (1:1) to group 1: daptomycin 10 mg/kg/24 h intravenous; or group 2: daptomycin 10 mg/kg/24 h intravenous plus fosfomycin 2 gr/6 g intravenous. The main outcome will be treatment response at week 6 after stopping therapy (test-of-cure (TOC) visit). This is a composite variable with two values: Treatment success: resolution of clinical signs and symptoms (clinical success) and negative blood cultures (microbiological success) at the TOC visit. Treatment failure: if any of the following conditions apply: (1) lack of clinical improvement at 72 h or more after starting therapy; (2) persistent bacteraemia (positive blood cultures on day 7); (3) therapy is discontinued early due to adverse effects or for some other reason based on clinical judgement; (4) relapse of MRSA bacteraemia before the TOC visit; (5) death for any reason before the TOC visit. Assuming a 60% cure rate with daptomycin and a 20% difference in cure rates between the two groups, 103 patients will be needed for each group (α:0.05, ß: 0.2). Statistical analysis will be based on intention to treat, as well as per protocol and safety analysis. The protocol was approved by the Spanish Medicines and Healthcare Products Regulatory Agency (AEMPS). The sponsor commits itself to publishing the data in first quartile peer-review journals within 12 months of the completion of the study. NCT01898338. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

In Vitro Sensitivity and Resistance of 46 Leptospira Strains Isolated from Rats in the Philippines to 14 Antimicrobial Agents▿ †

PubMed Central

Chakraborty, Antara; Miyahara, Satoshi; Villanueva, Sharon Y. A. M.; Gloriani, Nina G.; Yoshida, Shin-ichi

2010-01-01

The in vitro susceptibilities of 46 Leptospira isolates from rats to 14 antimicrobial agents were tested. All of the strains were found to be sensitive to ampicillin, cefotaxime, ciprofloxacin, norfloxacin, doxycycline, erythromycin, and streptomycin. In contrast, the tested isolates showed resistance to amphotericin B, 5-fluorouracil, fosfomycin, trimethoprim, sulfamethoxazole, neomycin, and vancomycin. These findings will help in selecting effective and ineffective antimicrobials for treatment of leptospirosis and for the development of new selective media, respectively. PMID:20855741

In vitro antibacterial effect of fosfomycin combination therapy against colistin-resistant Klebsiella pneumoniae.

PubMed

Yu, Wei; Luo, Qixia; Shi, Qingyi; Huang, Chen; Yu, Xiao; Niu, Tianshui; Zhou, Kai; Zhang, Jiajie; Xiao, Yonghong

2018-01-01

Colistin is still a "last-resort" antibiotic used to manage human infections due to multidrug-resistant (MDR) Klebsiella pneumoniae . However, colistin-resistant K. pneumoniae (CR-Kp) isolates emerged a decade ago and had a worldwide distribution. The purpose of this study was to evaluate the genetic data of CR-Kp and identify the antibacterial activity of fosfomycin (FM) alone and in combination with amikacin (AMK) or colistin (COL) against CR-Kp in vitro. Three clinical CR-Kp isolates from three patients were collected. Whole-genome sequencing and bioinformatics analysis were performed. The Pharmacokinetics Auto Simulation System 400, by simulating human pharmacokinetics in vitro, was employed to simulate FM, AMK, and COL alone and in combination. Different pharmacodynamic parameters were calculated for determining the antimicrobial effect. Whole-genome sequencing revealed that none of the three isolates contain mcr gene and that no insertion was found in pmrAB , phoPQ , or mgrB genes. We found the antibacterial activity of AMK alone was more efficient than FM or COL against CR-Kp. The area between the control growth and antibacterial killing curves of FM (8 g every 8 hours) combined with AMK (15 mg/kg once daily) was higher than 170 LogCFU/mL·h -1 . In addition, the area between the control growth and antibacterial killing curves of FM (8 g every 8 hours) combined with COL (75,000 IU/kg every12 hours) was higher than that of monotherapies (>100 LogCFU/mL·h -1 vs <80 LogCFU/mL·h -1 ). FM (8 g every 8 hours) combined with AMK (15 mg/kg once daily) was effective at maximizing bacterial killing against CR-Kp.

Ibuprofen versus fosfomycin for uncomplicated urinary tract infection in women: randomised controlled trial

PubMed Central

Bleidorn, Jutta; Kochen, Michael M; Schmiemann, Guido; Wegscheider, Karl; Hummers-Pradier, Eva

2015-01-01

Study question Can treatment of the symptoms of uncomplicated urinary tract infection (UTI) with ibuprofen reduce the rate of antibiotic prescriptions without a significant increase in symptoms, recurrences, or complications? Methods Women aged 18-65 with typical symptoms of UTI and without risk factors or complications were recruited in 42 German general practices and randomly assigned to treatment with a single dose of fosfomycin 3 g (n=246; 243 analysed) or ibuprofen 3×400 mg (n=248; 241 analysed) for three days (and the respective placebo dummies in both groups). In both groups additional antibiotic treatment was subsequently prescribed as necessary for persistent, worsening, or recurrent symptoms. The primary endpoints were the number of all courses of antibiotic treatment on days 0-28 (for UTI or other conditions) and burden of symptoms on days 0-7. The symptom score included dysuria, frequency/urgency, and low abdominal pain. Study answer and limitations The 248 women in the ibuprofen group received significantly fewer course of antibiotics, had a significantly higher total burden of symptoms, and more had pyelonephritis. Four serious adverse events occurred that lead to hospital referrals; one of these was potentially related to the trial drug. Results have to be interpreted carefully as they might apply to women with mild to moderate symptoms rather than to all those with an uncomplicated UTI. What this paper adds Two thirds of women with uncomplicated UTI treated symptomatically with ibuprofen recovered without any antibiotics. Initial symptomatic treatment is a possible approach to be discussed with women willing to avoid immediate antibiotics and to accept a somewhat higher burden of symptoms. Funding, competing interests, data sharing German Federal Ministry of Education and Research (BMBF) No 01KG1105. Patient level data are available from the corresponding author. Patient consent was not obtained but the data are anonymised and risk of identification is low. Trial registration No ClinicalTrialGov Identifier NCT01488955. PMID:26698878

Antibiotic susceptibility-resistance profiles of super-shed Escherichia coli O157:H7

USDA-ARS?s Scientific Manuscript database

Introduction: Escherichia coli O157:H7 (O157) can cause diarrhea and serious secondary sequelae including kidney failure and death in humans. With antibiotics like fosfomycin, colistin and azithromycin, that do not stimulate toxin expression by O157, being considered for treatment of early gastroint...

Effect of hospitalization and antimicrobial therapy on antimicrobial resistance of colonizing Staphylococcus epidermidis.

PubMed

Knauer, Ariane; Fladerer, Petra; Strempfl, Christina; Krause, Robert; Wenisch, Christoph

2004-07-31

Endogenous infections with multi-resistant S. epidermidis are among the leading causes of nosocomial infections. The effect of hospitalization and antimicrobial therapy on antimicrobial resistance of colonizing staphylococci was determined from swabs of the nose, hand, axilla and groin from 157 patients on one day. Hospitalization for >72 hours, compared with <72 hours, was associated with a higher percentage of isolates resistant to oxacillin (56% versus 19%), gentamicin (40% versus 15%), trimethoprim (36% versus 17%), clindamycin (56% versus 17%), and fusidic acid (20% versus 4%; p < 0.01 for all), but not to rifampicin (6% versus 1%) or fosfomycin (43% versus 34%, p > 0.05 for both). Concurrent antimicrobial therapy resulted in increased resistance to oxacillin (61% versus 28%), gentamicin (43% versus 20%), and clindamycin (60% versus 26%; p < 0.01 for all), but not to trimethoprim (39% versus 23%), fusidic acid (19% versus 9%), rifampicin (6% versus 3%), or fosfomycin (46% versus 38%, p > 0.05 for all). The increase in resistant isolates was not independent, since hospitalization and antimicrobial therapy were correlated (p < 0.001). After adjustment for potential risk factors such as diabetes mellitus, central venous catheters, and hemodialysis, the odds ratio for oxacillin resistance was 2.8-3.6. None of the risk factors showed statistically significant results, except for the presence of neoplastic disease, which had a significant interaction (P=0.035). The within-subgroup odds ratios for patients with and without neoplasm were 4.2 (95% CI, 2.3-5.7) and 2.1 (95% CI, 0.78-3.12), respectively. These results show that hospitalization for more than three days, with or without antimicrobial therapy, and the presence of neoplastic disease are associated with increased antimicrobial resistance in colonizing S. epidermidis.

Antimicrobial Sensitivity of Avibacterium paragallinarum Isolates from Four Latin American Countries.

PubMed

Luna-Galaz, G A; Morales-Erasto, V; Peñuelas-Rivas, C G; Blackall, P J; Soriano-Vargas, E

2016-09-01

The antimicrobial sensitivity of 11 reference strains and 66 Avibacterium paragallinarum isolates from four Latin American countries was investigated. All 11 reference strains were sensitive to amoxicillin-clavulanic acid, ampicillin, fosfomycin, gentamicin, kanamycin, neomycin, penicillin, tetracycline, and trimethoprim-sulfamethoxazole. The 11 reference strains were all resistant to lincomycin. All isolates (100%) from Mexico, Panama, and Peru were sensitive to amoxicillin-clavulanic acid, ampicillin, and fosfomycin. The Ecuadorian isolates showed some level of resistance to all 16 agents tested. The Ecuadorian isolates were significantly more sensitive to erythromycin, lincomycin, and streptomycin, and significantly more resistant to gentamicin, kanamycin, penicillin, and tetracycline, than the Mexican isolates. A total of 57.5% (38/66) of tested isolates were multi-drug resistant (MDR), with 16 MDR patterns detected in 88.4% (23/26) of the antimicrobial-resistant isolates from Ecuador, and 8 MDR patterns detected in 42.8% (15/35) of the antimicrobial-resistant isolates from Mexico. In conclusion, the variation in antimicrobial sensitivity patterns between isolates from Ecuador and Mexico emphasizes the importance of active, ongoing monitoring of A. paragallinarum isolates.

[Clinical usefulness of the combined empirical therapy with flomoxef and fosfomycin for intractable respiratory tract infections. With a background of increasing MRSA incidence].

PubMed

Shimada, K; Kudoh, S; Hayashi, I; Shishido, H; Fukuchi, Y; Suzuki, H; Oritsu, M; Nakada, K; Sano, Y; Goto, H

1994-10-01

We conducted a multicenter trial to determine the clinical usefulness of the combined therapy with flomoxef (FMOX) and fosfomycin (FOM) (FF therapy) as an empirical therapy in the treatment of intractable respiratory tract infections, because FF therapy has clinically been proved to be very useful for the treatment of severe infections including MRSA infections. The overall efficacy rate of FF therapy was 69.2%. The efficacy rate for "pneumonia/lung abscess," which occupy the largest portions of respiratory tract infections, was 70.0%, showing a statistically significant difference from the efficacy rate for FMOX alone (56.7%) found in a previous study (P = 0.09 by chi-squared test). Although MRSA was eradicated in only 3 cases (37.5%) including superinfection cases, of 8 patients, from whom MRSA had been isolated as causative organisms, none of our patients were superinfected with MRSA. Thus it has been concluded that FF therapy is clinically very useful when used as an empirical therapy in the treatment of respiratory tract infections.

Cloning, Expression and Characterization of UDP-N-Acetylglucosamine Enolpyruvyl Transferase (MurA) from Wolbachia Endosymbiont of Human Lymphatic Filarial Parasite Brugia malayi

PubMed Central

Shahab, Mohd; Verma, Meenakshi; Pathak, Manisha; Mitra, Kalyan; Misra-Bhattacharya, Shailja

2014-01-01

Wolbachia, an endosymbiont of filarial nematode, is considered a promising target for treatment of lymphatic filariasis. Although functional characterization of the Wolbachia peptidoglycan assembly has not been fully explored, the Wolbachia genome provides evidence for coding all of the genes involved in lipid II biosynthesis, a part of peptidoglycan biosynthesis pathway. UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is one of the lipid II biosynthesis pathway enzymes and it has inevitably been recognized as an antibiotic target. In view of the vital role of MurA in bacterial viability and survival, MurA ortholog from Wolbachia endosymbiont of Brugia malayi (wBm-MurA) was cloned, expressed and purified for further molecular characterization. The enzyme kinetics and inhibition studies were undertaken using fosfomycin. wBm-MurA was found to be expressed in all the major life stages of B. malayi and was immunolocalized in Wolbachia within the microfilariae and female adults by the confocal microscopy. Sequence analysis suggests that the amino acids crucial for enzymatic activity are conserved. The purified wBm-MurA was shown to possess the EPSP synthase (3-phosphoshikimate 1-carboxyvinyltransferase) like activity at a broad pH range with optimal activity at pH 7.5 and 37°C temperature. The apparent affinity constant (K m) for the substrate UDP-N-acetylglucosamine was found to be 0.03149 mM and for phosphoenolpyruvate 0.009198 mM. The relative enzymatic activity was inhibited ∼2 fold in presence of fosfomycin. Superimposition of the wBm-MurA homology model with the structural model of Haemophilus influenzae (Hi-MurA) suggests binding of fosfomycin at the same active site. The findings suggest wBm-MurA to be a putative antifilarial drug target for screening of novel compounds. PMID:24941309

In Vivo Pharmacokinetics and Pharmacodynamics of ZTI-01 (Fosfomycin for Injection) in the Neutropenic Murine Thigh Infection Model against Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa.

PubMed

Lepak, Alexander J; Zhao, Miao; VanScoy, Brian; Taylor, Daniel S; Ellis-Grosse, Evelyn; Ambrose, Paul G; Andes, David R

2017-06-01

Fosfomycin is a broad-spectrum agent with activity against Gram-positive and Gram-negative bacteria, including drug-resistant strains, such as extended-spectrum-beta-lactamase (ESBL)-producing and carbapenem-resistant (CR) Gram-negative rods. In the present study, the pharmacokinetic/pharmacodynamic (PK/PD) activity of ZTI-01 (fosfomycin for injection) was evaluated in the neutropenic murine thigh infection model against 5 Escherichia coli , 3 Klebsiella pneumoniae , and 2 Pseudomonas aeruginosa strains, including a subset with ESBL and CR phenotypes. The pharmacokinetics of ZTI-01 were examined in mice after subcutaneous administration of 3.125, 12.5, 50, 200, 400, and 800 mg/kg of body weight. The half-life ranged from 0.51 to 1.1 h, area under the concentration-time curve (AUC 0-∞ ) ranged from 1.4 to 87 mg · h/liter, and maximum concentrations ranged from 0.6 to 42.4 mg/liter. Dose fractionation demonstrated the AUC/MIC ratio to be the PK/PD index most closely linked to efficacy ( R 2 = 0.70). Net stasis and bactericidal activity were observed against all strains. Net stasis was observed at 24-h AUC/MIC ratio values of 24, 21, and 15 for E. coli , K. , pneumoniae and P. aeruginosa , respectively. For the Enterobacteriaceae group, stasis was noted at mean 24-h AUC/MIC ratio targets of 23 and 1-log kill at 83. Survival in mice infected with E. coli 145 was maximal at 24-h AUC/MIC ratio exposures of 9 to 43, which is comparable to the stasis exposures identified in the PK/PD studies. These results should prove useful for the design of clinical dosing regimens for ZTI-01 in the treatment of serious infections due to Enterobacteriaceae and Pseudomonas . Copyright © 2017 American Society for Microbiology.

Mutations in the Primary Sigma Factor σA and Termination Factor Rho That Reduce Susceptibility to Cell Wall Antibiotics

PubMed Central

Lee, Yong Heon

2014-01-01

Combinations of glycopeptides and β-lactams exert synergistic antibacterial activity, but the evolutionary mechanisms driving resistance to both antibiotics remain largely unexplored. By repeated subculturing with increasing vancomycin (VAN) and cefuroxime (CEF) concentrations, we isolated an evolved strain of the model bacterium Bacillus subtilis with reduced susceptibility to both antibiotics. Whole-genome sequencing revealed point mutations in genes encoding the major σ factor of RNA polymerase (sigA), a cell shape-determining protein (mreB), and the ρ termination factor (rho). Genetic-reconstruction experiments demonstrated that the G-to-C substitution at position 336 encoded by sigA (sigAG336C), in the domain that recognizes the −35 promoter region, is sufficient to reduce susceptibility to VAN and works cooperatively with the rhoG56C substitution to increase CEF resistance. Transcriptome analyses revealed that the sigAG336C substitution has wide-ranging effects, including elevated expression of the general stress σ factor (σB) regulon, which is required for CEF resistance, and decreased expression of the glpTQ genes, which leads to fosfomycin (FOS) resistance. Our findings suggest that mutations in the core transcriptional machinery may facilitate the evolution of resistance to multiple cell wall antibiotics. PMID:25112476

Antibiotic Effects on Methicillin-Resistant Staphylococcus aureus Cytoplasmic Peptidoglycan Intermediate Levels and Evidence for Potential Metabolite Level Regulatory Loops.

PubMed

Vemula, Harika; Ayon, Navid J; Burton, Alloch; Gutheil, William G

2017-06-01

Cytoplasmic peptidoglycan (PG) precursor levels were determined in methicillin-resistant Staphylococcus aureus (MRSA) after exposure to several cell wall-targeting antibiotics. Three experiments were performed: (i) exposure to 4× MIC levels (acute); (ii) exposure to sub-MIC levels (subacute); (iii) a time course experiment of the effect of vancomycin. In acute exposure experiments, fosfomycin increased UDP-GlcNAc, as expected, and resulted in substantially lower levels of total UDP-linked metabolite accumulation relative to other pathway inhibitors, indicating reduced entry into this pathway. Upstream inhibitors (fosfomycin, d-cycloserine, or d-boroalanine) reduced UDP-MurNAc-pentapeptide levels by more than fourfold. Alanine branch inhibitors (d-cycloserine and d-boroalanine) reduced d-Ala-d-Ala levels only modestly (up to 4-fold) but increased UDP-MurNAc-tripeptide levels up to 3,000-fold. Downstream pathway inhibitors (vancomycin, bacitracin, moenomycin, and oxacillin) increased UDP-MurNAc-pentapeptide levels up to 350-fold and UDP-MurNAc-l-Ala levels up to 80-fold, suggesting reduced MurD activity by downstream inhibitor action. Sub-MIC exposures demonstrated effects even at 1/8× MIC which strongly paralleled acute exposure changes. Time course data demonstrated that UDP-linked intermediate levels respond rapidly to vancomycin exposure, with several intermediates increasing three- to sixfold within minutes. UDP-linked intermediate level changes were also multiphasic, with some increasing, some decreasing, and some increasing and then decreasing. The total (summed) UDP-linked intermediate pool increased by 1,475 μM/min during the first 10 min after vancomycin exposure, providing a revised estimate of flux in this pathway during logarithmic growth. These observations outline the complexity of PG precursor response to antibiotic exposure in MRSA and indicate likely sites of regulation (entry and MurD). Copyright © 2017 American Society for Microbiology.

[Application of Monural to treat pregnant women with asymptomatic bacteriuria and acute cystitis].

PubMed

Michova, M; Ivanov, St; Batashki, I

2009-01-01

Asymptomatic bacteriuria (AB) and cystitis affect 4-9% of pregnancies and are associated with pyelonephritis and preterm labor. Screening for AB and adequate antimicrobal therapy prevent most of these serious complications. Twenty- nine pregnant patients, suffering from AB and 9 cases with cystitis were treated with single dose Monura (Fosfomycin trometamol) in a prospective study.

Detection of acrA, acrB, aac(6')-Ib-cr, and qepA genes among clinical isolates of Escherichia coli and Klebsiella pneumoniae.

PubMed

Heidary, Mohsen; Bahramian, Aghil; Hashemi, Ali; Goudarzi, Mehdi; Omrani, Vahid Fallah; Eslami, Gita; Goudarzi, Hossein

2017-03-01

The distribution of drug resistance among clinical isolates of Escherichia coli and Klebsiella pneumoniae has limited the therapeutic options. The aim of this study was to report the prevalence of quinolone resistance genes among E. coli and K. pneumoniae clinical strains isolated from three educational hospitals of Tehran, Iran. A total of 100 strains of E. coli from Labbafinejad and Taleghani Hospitals and 100 strains of K. pneumoniae from Mofid Children and Taleghani Hospitals were collected between January 2013 and May 2014. Antimicrobial susceptibility tests were done by disk diffusion method based on Clinical and Laboratory Standards Institute guidelines. Detection of qepA, aac(6')-Ib-cr, acrA, and acrB genes was done by polymerase chain reaction (PCR). In this study, fosfomycin and imipenem against E. coli and fosfomycin and tigecycline against K. pneumoniae had the best effect in antimicrobial susceptibility tests. PCR assay using specific primers demonstrated that the prevalence of qepA, aac(6')-Ib-cr, acrA, and acrB genes among the 100 E. coli isolates was 0 (0%), 87 (87%), 92 (92%), and 84 (84%), respectively. The prevalence of qepA, aac(6')-Ib-cr, acrA, and acrB genes among the 100 K. pneumoniae isolates was 4 (4%), 85 (85%), 94 (94%), and 87 (87%), respectively. The distribution of qepA, aac(6')-Ib-cr, acrA, and acrB resistance determinants in E. coli and K. pneumoniae is a great concern. Therefore, infection control and prevention of spread of drug-resistant bacteria need careful management of medication and identification of resistant isolates.

[Primary and secondary prevention of urinary tract infections].

PubMed

Wagenlehner, F M E; Vahlensieck, W; Bauer, H W; Weidner, W; Naber, K G; Piechota, H J

2011-10-01

Urinary tract infections (UTI) are among the most frequent bacterial infections in the community and health care setting. Mostly young and, to some extent, postmenopausal women are affected by recurrent UTI (rUTI) defined as ≥3 UTI/year. On the other hand rUTI are frequently found in patients with complicating urological factors, e.g. urinary catheters. Modifiable predisposing factors in uncomplicated rUTI in women are rare. Continuous antibiotic prophylaxis or postcoital prophylaxis, if there is close correlation with sexual intercourse, are most effective to prevent rUTI. Nitrofurantoin, trimethoprim (or cotrimoxazole), and fosfomycin trometamol are available as first-line drugs. Oral cephalosporins and quinolones should be restricted to specific indications. Antibiotic prophylaxis reduces the number of uropathogens in the gut and/or vaginal flora and reduces bacterial"fitness". Given the correct indication, the recurrence rate of rUTI can be reduced by about 90%. In postmenopausal patients vaginal substitution of oestriol should be started first. Oral or parenteral immunoprophylaxis is another option in patients with rUTI. Other possibilities with varying scientific evidence are prophylaxis with cranberries or probiotics. The prophylaxis of catheter-associated UTI or asymptomatic bacteriuria should employ strategies which result in a reduction of frequency and duration of catheter drainage of the urinary tract. The currently available catheter materials have only little influence on reducing catheter-associated rUTI.

Targeted therapy against multi-resistant bacteria in leukemic and hematopoietic stem cell transplant recipients: guidelines of the 4th European Conference on Infections in Leukemia (ECIL-4, 2011)

PubMed Central

Averbuch, Diana; Cordonnier, Catherine; Livermore, David M.; Mikulska, Małgorzata; Orasch, Christina; Viscoli, Claudio; Gyssens, Inge C.; Kern, Winfried V.; Klyasova, Galina; Marchetti, Oscar; Engelhard, Dan; Akova, Murat

2013-01-01

The detection of multi-resistant bacterial pathogens, particularly those to carbapenemases, in leukemic and stem cell transplant patients forces the use of old or non-conventional agents as the only remaining treatment options. These include colistin/polymyxin B, tigecycline, fosfomycin and various anti-gram-positive agents. Data on the use of these agents in leukemic patients are scanty, with only linezolid subjected to formal trials. The Expert Group of the 4th European Conference on Infections in Leukemia has developed guidelines for their use in these patient populations. Targeted therapy should be based on (i) in vitro susceptibility data, (ii) knowledge of the best treatment option against the particular species or phenotype of bacteria, (iii) pharmacokinetic/pharmacodynamic data, and (iv) careful assessment of the risk-benefit balance. For infections due to resistant Gram-negative bacteria, these agents should be preferably used in combination with other agents that remain active in vitro, because of suboptimal efficacy (e.g., tigecycline) and the risk of emergent resistance (e.g., fosfomycin). The paucity of new antibacterial drugs in the near future should lead us to limit the use of these drugs to situations where no alternative exists. PMID:24323984

Antibiotic resistance of Clostridium perfringens isolates from broiler chickens in Egypt.

PubMed

Osman, K M; Elhariri, M

2013-12-01

The use of antibiotic feed additives in broiler chickens results in a high prevalence of resistance among their enteric bacteria, with a consequent emergence of antibiotic resistance in zoonotic enteropathogens. Despite growing concerns about the emergence of antibiotic-resistant strains, which show varying prevalences in different geographic regions, little work has been done to investigate this issue in the Middle East. This study provides insight into one of the world's most common and financially crippling poultry diseases, necrotic enteritis caused by Clostridium perfringens. The study was designed to determine the prevalence of antibiotic resistance in C. perfringens isolates from clinical cases of necrotic enteritis in broiler chickens in Egypt. A total of 125 isolates were obtained from broiler flocks in 35 chicken coops on 17 farms and were tested using the disc diffusion method. All 125 isolates were resistant to gentamicin, streptomycin, oxolinic acid, lincomycin, erythromycin and spiramycin. The prevalence of resistance to other antibiotics was also high: rifampicin (34%), chloramphenicol (46%), spectinomycin (50%), tylosin-fosfomycin (52%), ciprofloxacin (58%), norfloxacin (67%), oxytetracycline (71%), flumequine (78%), enrofloxacin (82%), neomycin (93%), colistin (94%), pefloxacin (94%), doxycycline (98%) and trimethoprim-sulfamethoxazole (98%). It is recommended that C. perfringens infections in Egypt should be treated with antibiotics for which resistant isolates are rare at present; namely, amoxicillin, ampicillin, cephradine, fosfomycin and florfenicol.

Urinary tract infection in pregnant population, which empirical antimicrobial agent should be specified in each of the three trimesters?

PubMed

Unlu, Bekir Serdar; Yildiz, Yunus; Keles, Ibrahim; Kaba, Metin; Kara, Halil; Tasin, Cuma; Erkilinc, Selcuk; Yildirim, Gulcin

2014-05-01

We aimed to investigate the bacterial profile and the adequacy of antimicrobial treatment in pregnant women with urinary tract infection. This retrospective observational study was conducted with 753 pregnant women who needed hospitalization because of UTI in each of the three trimesters. Midstream urine culture and antimicrobial susceptibility tests were evaluated. E. Coli was the most frequently isolated bacterial agent (82.2%), followed by Klebsiella spp. (11.2%). In each of the three trimesters, E. Coli remained the most frequently isolated bacterium (86%, 82.2%, 79.5%, respectively), followed by Klebsiella spp. (9%, 11.6%, 12.2%, respectively). Enterococcus spp. were isolated as a third microbial agent, with 43 patients (5.7%) in the three trimesters. The bacteria were found to be highly sensitive to fosfomycin, with 98-99% sensitivity for E.Coli and 88-89% for Klebsiella spp. and for Enterococcus spp. 93-100% nitrofurantoin sensitivity for each of the three trimesters. We demonstrated that E. Coli and Klebsiella spp. are the most common bacterial agents isolated from urine culture of pregnant women with UTI in each of the three trimesters. We consider fosfomycin to be the most adequate first-line treatment regimen due to high sensitivity to the drug, ease of use and safety for use in pregnancy

Studies on the biodegradation of fosfomycin: growth of Rhizobium huakuii PMY1 on possible intermediates synthesised chemically.

PubMed

McGrath, John W; Hammerschmidt, Friedrich; Preusser, Werner; Quinn, John P; Schweifer, Anna

2009-05-07

The first step of the mineralisation of fosfomycin by R. huakuii PMY1 is hydrolytic ring opening with the formation of (1R,2R)-1,2-dihydroxypropylphosphonic acid. This phosphonic acid and its three stereoisomers were synthesised by chemical means and tested as their ammonium salts for mineralisation as evidenced by release of P(i). Only the (1R,2R)-isomer was degraded. A number of salts of phosphonic acids such as (+/-)-1,2-epoxybutyl-, (+/-)-1,2-dihydroxyethyl-, 2-oxopropyl-, (S)-2-hydroxypropyl-, (+/-)-1-hydroxypropyl- and (+/-)-1-hydroxy-2-oxopropylphosphonic acid were synthesised chemically, but none supported growth. In vitro C-P bond cleavage activity was however detected with the last phosphonic acid. A mechanism involving phosphite had to be discarded as it could not be used as a phosphorus source. R. huakuii PMY1 grew well on (R)- and (S)-lactic acid and hydroxyacetone, but less well on propionic acid and not on acetone or (R)- and (+/-)-1,2-propanediol. The P(i) released from (1R,2R)-1,2-dihydroxypropylphosphonic acid labelled with one oxygen-18 in the PO3H2 group did not stay long enough in the cells to allow complete exchange of 18O for 16O by enzymic turnover.

[Urinary tract infection in pregnancy].

PubMed

Herráiz, Miguel Angel; Hernández, Antonio; Asenjo, Eloy; Herráiz, Ignacio

2005-12-01

Urinary tract infections, asymptomatic bacteriuria (AB), acute cystitis (AC) and acute pyelonephritis (AP), are favored by the morphological and functional changes involved in pregnancy. AB increases the risk of preterm labor, low birth weight and AP. AB should be detected by uroculture (other methods are not sufficiently effective) and treated early. Approximately 80% of cases are caused by Escherichia coli. The risks and effectiveness of the distinct antibiotic regimens should be evaluated: fosfomycin trometamol in monotherapy or as short course therapy is safe and effective for the treatment of AB and AC. AP is the most frequent cause of hospital admission for medical reasons in pregnant women and can lead to complications in 10% of cases, putting the lives of the mother and fetus at risk. Currently outpatient treatment of AP is recommended in selected cases. Adequate follow-up of pregnant women with urinary tract infections is required due to frequent recurrence.

[National S3 guideline on uncomplicated urinary tract infection: recommendations for treatment and management of uncomplicated community-acquired bacterial urinary tract infections in adult patients].

PubMed

Wagenlehner, F M E; Schmiemann, G; Hoyme, U; Fünfstück, R; Hummers-Pradier, E; Kaase, M; Kniehl, E; Selbach, I; Sester, U; Vahlensieck, W; Watermann, D; Naber, K G

2011-02-01

Urinary tract infections (UTI) belong to the most frequent bacterial infections in outpatients. Increasing antibiotic resistance rates and a new appreciation of the epidemiological side effects of antibiotics ("collateral damage") have warranted an update of the guidelines on uncomplicated UTI as an S3 clinical guideline. The guideline was developed by the Deutsche Gesellschaft für Urologie (DGU) in collaboration with the Deutsche Gesellschaft für Allgemein- und Familienmedizin (DEGAM), Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG), Deutsche Gesellschaft für Hygiene und Mikrobiologie (DGHM), Deutsche Gesellschaft für Infektiologie (DGI), Deutsche Gesellschaft für Nephrologie (DGfN), Paul-Ehrlich-Gesellschaft für Chemotherapie (PEG) and a patient representative. The systematic review of the literature on the topics of the guideline was performed for the time period of 1 January 1998 to 30 April 2008 in the databases of the Cochrane Library and MEDLINE. International guidelines of the years 1999-2007 were included. Uncomplicated UTI comprise uncomplicated cystitis and uncomplicated pyelonephritis. The leading uropathogen is Escherichia coli. The choice of the antibiotic substance follows the five primary aspects: (1) individual patient risk and antibiotic pretreatment; (2) bacterial spectrum and antibiotic susceptibility; (3) effectivity of the antimicrobial substance demonstrated in clinical studies; (4) epidemiological effects ("collateral damage"); and (5) adverse effects. If antibiotics such as trimethoprim/sulfamethoxazole or fluoroquinolones have previously been given, the risk for pathogens to become resistant against these substances is increased. Because of increasing resistance rates of E. coli against trimethoprim/sulfamethoxazole also in uncomplicated UTI, trimethoprim alone or in combination with sulfamethoxazole is no longer regarded as the first-line agent in the empiric treatment of uncomplicated cystitis, unless the regional resistance rate is below 20%. The antibiotic resistance rates of fluoroquinolones in uncomplicated UTI are still below 10% in Germany, but there is a significant emergence of resistance compared to earlier years. Moreover, fluoroquinolones and group 3 cephalosporins exhibit negative epidemiological effects resulting in selection of multi-resistant pathogens. Because these antibiotic classes are needed in therapy of life-threatening infections, such effects should be taken seriously. For substances like fosfomycin, nitrofurantoin or mecillinam"collateral damage" has not been documented or only to a lesser degree. Therefore, for empiric therapy of frequent uncomplicated cystitis fosfomycin-trometamol, nitrofurantoin or pivmecillinam (not listed in Germany) are recommended as first-line antibiotics. For oral first-line treatment of uncomplicated pyelonephritis, fluoroquinolones are still recommended in sufficiently high dosage due to the resistance rates of E. coli still being below 10% and the superior effectivity compared to other antibiotics. Asymptomatic bacteriuria (ASB) should only be treated in exceptional cases such as pregnant women or prior to expected mucocutaneous traumatising interventions of the urinary tract. The S3 guideline on uncomplicated urinary tract infections is a comprehensive set of evidence- and consensus-based recommendations dealing with epidemiology, diagnosis, therapy and management of uncomplicated bacterial UTI of adult outpatients. A broad implementation in all disciplines taking care of patients with UTI is necessary in order to ensure a prudent antibiotic policy in these frequent infections and thus improve patient care.

Antimicrobial susceptibilities of Stomatococcus mucilaginosus and of Micrococcus spp.

PubMed Central

von Eiff, C; Herrmann, M; Peters, G

1995-01-01

The in vitro susceptibilities of 63 isolates of Stomatococcus mucilaginosus and of 188 isolates of Micrococcus spp. to 18 antimicrobial agents were determined by the agar dilution method. Many beta-lactams, imipenem, rifampin, and the glycopeptides were shown to be active in vitro against Stomatococcus and Micrococcus isolates, whereas the activities of antibiotics such as some aminoglycosides, erythromycin, and fosfomycin against an important number of these microorganisms are limited. PMID:7695321

Etiological and Resistance Profile of Bacteria Involved in Urinary Tract Infections in Young Children

PubMed Central

Gómez-Luque, José María; Navarro-Marí, José María

2017-01-01

Background. The objective of this study was to identify the bacteria most frequently responsible for urinary tract infection (UTI) in the population of under-2-year-olds in our geographic area and to evaluate the activity of antibiotics widely used for UTI treatment during a 4-year study period. Materials and Methods. A retrospective analysis was conducted of data on the identification and susceptibility of microorganisms isolated in urine samples from children under 2 years of age. Results. A total of 1,045 uropathogens were isolated. Escherichia coli accounted for the majority (60.3%) of these, followed by Enterococcus faecalis (22.4%) and Klebsiella spp. (6.5%). The highest E. coli susceptibility rates (>90%) were to piperacillin-tazobactam, cefuroxime, cefotaxime, ceftazidime, imipenem, gentamicin, nitrofurantoin, and fosfomycin, and the lowest were to amoxicillin-clavulanic acid and cotrimoxazole. Among all bacteria isolated, we highlight the overall high activity of piperacillin-tazobactam, imipenem, nitrofurantoin, and fosfomycin against both community and hospital isolates and the reduced activity of amoxicillin-clavulanic acid, cephalosporins, gentamicin, and cotrimoxazole. There was no significant change in the total activity of any of the studied antibiotics over the 4-year study period. Conclusion. Empiric treatment with amoxicillin-clavulanic acid, cotrimoxazole, cephalosporins, and gentamicin may be inadequate due to their limited activity against uropathogens in our setting. PMID:28497052

The revival of old antibiotics for treatment of uncomplicated urinary tract infections in the era of antibiotic stewardship.

PubMed

Kranz, Jennifer; Helbig, Sina; Mandraka, Falitsa; Schmidt, Stefanie; Naber, Kurt G

2017-03-01

In the era of increasing antibiotic resistance worldwide, this review highlights the advantages of revival of old antibiotics for treatment of uncomplicated urinary tract infections (uUTIs). Recent studies have shown that these four oral old antibiotics, fosfomycin trometamol, nitrofurantoin, nitroxoline and pivmecillinam, show no increasing antibiotic resistance against uropathogens causing uUTI, are still effective for the treatment of uUTI and exhibit only minimal or no collateral damage as compared with fluoroquinolones or third-generation cephalosporines. According to the principles of antibiotic stewardship, the prudent use of antibiotics is needed. Therefore, recent international and national guidelines already favour these old oral antibiotics as first-choice treatment of uUTI. Unfortunately, implementation of these guidelines is still suboptimal.

Development and validation of a LC-MS/MS method for quantitation of fosfomycin - Application to in vitro antimicrobial resistance study using hollow-fiber infection model.

PubMed

Gandhi, Adarsh; Matta, Murali; Garimella, Narayana; Zere, Tesfalem; Weaver, James

2018-06-01

Extensive use and misuse of antibiotics over the past 50 years has contributed to the emergence and spread of antibiotic-resistant bacterial strains, rendering them as a global health concern. To address this issue, a dynamic in vitro hollow-fiber system, which mimics the in vivo environment more closely than the static model, was used to study the emergence of bacterial resistance of Escherichia coli against fosfomycin (FOS). To aid in this endeavor we developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for quantitative analysis of FOS in lysogeny broth. FOS was resolved on a Kinetex HILIC (2.1 × 50 mm, 2.6 μm) column with 2 mm ammonium acetate (pH 4.76) and acetonitrile as mobile phase within 3 min. Multiple reaction monitoring was used to acquire data on a triple quadrupole mass spectrometer. The assay was linear from 1 to 1000 μg/mL. Inter- and intra-assay precision and accuracy were <15% and between ±85 and 115% respectively. No significant matrix effect was observed when corrected with the internal standard. FOS was stable for up to 24 h at room temperature, up to three freeze-thaw cycles and up to 24 h when stored at 4°C in the autosampler. In vitro experimental data were similar to the simulated plasma pharmacokinetic data, further confirming the appropriateness of the experimental design to quantitate antibiotics and study occurrence of antimicrobial resistance in real time. The validated LC-MS/MS assays for quantitative determination of FOS in lysogeny broth will help antimicrobial drug resistance studies. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Comparative analysis on antibiotic resistance characteristics of Listeria spp. and Enterococcus spp. isolated from laying hens and eggs in conventional and organic keeping systems in Bavaria, Germany.

PubMed

Schwaiger, K; Schmied, E-M V; Bauer, J

2010-05-01

By investigating the prevalence and antimicrobial resistance characteristics of Gram-positive bacteria from organic and conventional keeping systems of laying hens, it was to be determined to what extent these properties are influenced by the different systems. For this purpose, a total of 799 cloacal swabs and 800 egg samples were examined. Prevalences for all selected bacteria from cloacal swabs were much the same for both organic and caged birds: Listeria spp.1.3%[org] versus 1.6%[con]; Enterococcus spp. 95.5%[org] versus 97.5%[con]. Egg contents and eggshells were generally contaminated to a lesser extent, primarily with Enterococcus spp. Listeria isolates were susceptible to almost all tested antibiotics, only three Listeria innocua from conventional keepings were resistant to clindamycin; one isolate additionally to imipenem. High percentages of Enterococcus faecalis were resistant to doxycycline and macrolides. Enterococcus faecium proved to have high resistance rates to clindamycin, fosfomycin and erythromycin; 9.1% were even resistant to the reserve antibiotic synercid. Further, Enterococcus spp. showed higher resistance rates to doxycycline, erythromycin, fosfomycin and rifampicin. No glycopeptide resistant enterococci were detected. A correlation between keeping system and resistance/susceptibility rates could be demonstrated. In detail, E. faecalis from organic laying hen husbandries showed significant lower resistance prevalences to tylosin, streptomycin and doxycycline; susceptibility rates were higher for enrofloxacin and ciprofloxacin. Rifampicin and imipenem were more effective in isolates from conventional keepings (P < 0.05). The amounts of resistant isolates of the Enterococcus raffinosus from organic farms were significantly lower, the amounts of sensitive isolates were significantly higher than from conventional farms concerning eight antibiotics (P < 0.05). When comparing the susceptibility/resistance rates, as well as the mean minimum inhibitory concentrations values, the consistent tendency is that bacteria from organic layer flocks are more susceptible to antimicrobials. These results show that organic livestock farming plays a part in contributing to reduced antibiotic resistance.

Diabetic foot infections: microbiological aspects, current and future antibiotic therapy focusing on methicillin-resistant Staphylococcus aureus.

PubMed

Ambrosch, Andreas; Haefner, Simone; Jude, Edward; Lobmann, Ralf

2011-12-01

Diabetic patients are at increased risk of complicated skin, skin structure and bone infections including infections of diabetic foot ulcerations (DFU). Analyses of epidemiology and microbial pathogenicity show that staphylococci seem to be predestined to induce such infections. In addition, multidrug resistance particularly due to an increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) seems to be the challenge for effective antibiotic therapy. With regard to infections with MRSA, classical agents like vancomycin, linezolid, fosfomycin or trimethroprim-sulphametoxazol might be agents of choice in DFU. New-generation drugs including broad-spectrum tetracyclines like tigecycline, first and second generation of cyclic lipopeptides, anti-MRSA β-lactams including ceftobiprole and anti-MRSA antibodies are developed or in progress and the hope for the future. © 2011 The Authors. © 2011 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

High anion gap metabolic acidosis induced by cumulation of ketones, L- and D-lactate, 5-oxoproline and acute renal failure.

PubMed

Heireman, Laura; Mahieu, Boris; Helbert, Mark; Uyttenbroeck, Wim; Stroobants, Jan; Piqueur, Marian

2017-07-27

Frequent causes of high anion gap metabolic acidosis (HAGMA) are lactic acidosis, ketoacidosis and impaired renal function. In this case report, a HAGMA caused by ketones, L- and D-lactate, acute renal failure as well as 5-oxoproline is discussed. A 69-year-old woman was admitted to the emergency department with lowered consciousness, hyperventilation, diarrhoea and vomiting. The patient had suffered uncontrolled type 2 diabetes mellitus, underwent gastric bypass surgery in the past and was chronically treated with high doses of paracetamol and fosfomycin. Urosepsis was diagnosed, whilst laboratory analysis of serum bicarbonate concentration and calculation of the anion gap indicated a  HAGMA. L-lactate, D-lactate, β-hydroxybutyric acid, acetone and 5-oxoproline serum levels were markedly elevated and renal function was impaired. We concluded that this case of HAGMA was induced by a variety of underlying conditions: sepsis, hyperglycaemia, prior gastric bypass surgery, decreased renal perfusion and paracetamol intake. Risk factors for 5-oxoproline intoxication present in this case are female gender, sepsis, impaired renal function and uncontrolled type 2 diabetes mellitus. Furthermore, chronic antibiotic treatment with fosfomycin might have played a role in the increased production of 5-oxoproline. Paracetamol-induced 5-oxoproline intoxication should be considered as a cause of HAGMA in patients with female gender, sepsis, impaired renal function or uncontrolled type 2 diabetes mellitus, even when other more obvious causes of HAGMA such as lactate, ketones or renal failure can be identified.

Evaluation of Antimicrobial Susceptibility of Enterobacteriaceae Causing Urinary Tract Infections in Africa

PubMed Central

Tansarli, Giannoula S.; Athanasiou, Stavros

2013-01-01

Our objective was to evaluate the antimicrobial susceptibility of Enterobacteriaceae causing urinary tract infections (UTIs) in adults in Africa. The PubMed database was systematically searched to identify relevant studies published after 2000. Google, World Health Organization, and African Field Epidemiology networks were also searched. Twenty-eight studies, accounting for 381,899 urine isolates from 14 African countries, met the inclusion criteria. Escherichia coli, Klebsiella spp., and Proteus spp. were the most commonly encountered uropathogens. Cefotaxime, imipenem, fosfomycin, and ciprofloxacin were the antibiotics with the highest activity against E. coli isolates from outpatients, with susceptibility being 92 to 99, 100, 100, and 68 to 91%, respectively. The susceptibility among Klebsiella spp. isolates from outpatients varied from 80 to 100% for amikacin and from 53 to 100% for ciprofloxacin, while susceptibility was 74 to 78, 97, and 77% for ciprofloxacin, amikacin, and fosfomycin, respectively, among Klebsiella species isolates from inpatients or patients with hospital-acquired UTIs. With regard to Proteus spp., the highest activity was observed among fluoroquinolones; 71 to 100% of the P. mirabilis isolates were susceptible to ciprofloxacin in four studies, and 74 to 100% of the P. vulgaris isolates were susceptible to ofloxacin in two studies. The currently available evidence suggests that the antimicrobial susceptibility patterns of Enterobacteriaceae uropathogens in African countries were similar to those in countries of southeast Europe. Further original studies are warranted from African countries for which there is limited published data. PMID:23689709

Therapeutic concentrations of antibiotics inhibit Shiga toxin release from enterohemorrhagic E. coli O104:H4 from the 2011 German outbreak

PubMed Central

2012-01-01

Background The shiga toxin-producing E. coli (STEC) O104:H4 caused a major outbreak in Germany in spring 2011. STEC are usually susceptible to common antibiotics. However, antibiotic treatment of STEC-infected patients is not recommended because STEC may enhance production and release of shiga toxins (STX) in response to antibiotics, which eventually enhances the frequency and severity of clinical symptoms, including haemolytic uraemic syndrome (HUS) and fatalities. Results We characterized the response to antibiotics of STEC O104:H4 isolates from two HUS patients during the German STEC outbreak in spring 2011 in comparison to the common STEC O157:H7. Liquid cultures of STEC O157:H7 and O104:H4 were incubated with graded dilutions of the antibiotics ciprofloxacin, meropenem, fosfomycin, gentamicin, rifampicin, and chloramphenicol. At defined times of antibiotic treatment, transcriptional activation of the STX2 gene, contents of STX and STX-activity in the culture supernatants were quantified. Unlike the common serotype O157:H7, STEC O104:H4 does not release STX in response to therapeutic concentrations of ciprofloxacin, meropenem, fosfomycin, and chloramphenicol. Conclusions In future outbreaks, the response of the respective epidemiologic STEC strain to antibiotics should be rapidly characterized in order to identify antibiotics that do not enhance the release of STX. This will eventually allow clinical studies tackling the question whether antibiotic treatment impacts on the eradication of STEC, clinical course of disease, and frequency of carriers. PMID:22853739

Local epidemiology and resistance profiles in acute uncomplicated cystitis (AUC) in women: a prospective cohort study in an urban urological ambulatory setting.

PubMed

Seitz, Michael; Stief, Christian; Waidelich, Raphaela

2017-10-16

Acute uncomplicated cystitis (AUC) is a common ailment in the urological setting. Guidelines for urinary tract infections are based on large-scale multi-centre, epidemiological and international studies. The objective of this observational study was to establish whether the results of a multi-centre study on the resistance profile of Escherichia coli (E. coli) in patients with AUC could be directly applied to an urological practice in a major European city or whether there are divergences in the resistance profile. An observational study was applied prospectively to 502 patients with AUC between January 2015 and January 2017). Personal data were anonymised. Exclusion criteria were the patient's age (<18) and treatment with an antibiotic in the week preceding examination. The average age was 32 (range 18-56). The most commonly detected bacteria was E. coli with 86%, followed by Enterococcus faecalis with 10% and Klebsiella pneumoniae with 4%. Resistance tests showed E. coli to be highly sensitive to fosfomycin (99.2%), nitrofurantoin (98.1%) and cefpodoxime (92.9%). E. coli exhibited resistance to ciprofloxacin (CIP) in 15.1%, to trimethoprim/sulfamethoxazole (TRS) in 25.2% and to amoxicillin/clavulanic acid (AMC) in 34% of cases. The comparison between data from this study and data from a multi-centre European (ECO-SENSI, ECO-SENSII and the 2014 update) showed relatively good sensitivity rates for fosfomycin and nitrofurantoin but significant differences in respect of resistance levels to TRS, CIP and AMC. AUC should therefore only be treated with TRS, CIP and AMC after a susceptibility test has been carried out.

Current and future therapies for Pseudomonas aeruginosa infection in patients with cystic fibrosis.

PubMed

Smith, Wynne D; Bardin, Emmanuelle; Cameron, Loren; Edmondson, Claire L; Farrant, Katie V; Martin, Isaac; Murphy, Ronan A; Soren, Odel; Turnbull, Andrew R; Wierre-Gore, Natasha; Alton, Eric W; Bundy, Jacob G; Bush, Andrew; Connett, Gary J; Faust, Saul N; Filloux, Alain; Freemont, Paul S; Jones, Andrew L; Takats, Zoltan; Webb, Jeremy S; Williams, Huw D; Davies, Jane C

2017-08-01

Pseudomonas aeruginosa opportunistically infects the airways of patients with cystic fibrosis and causes significant morbidity and mortality. Initial infection can often be eradicated though requires prompt detection and adequate treatment. Intermittent and then chronic infection occurs in the majority of patients. Better detection of P. aeruginosa infection using biomarkers may enable more successful eradication before chronic infection is established. In chronic infection P. aeruginosa adapts to avoid immune clearance and resist antibiotics via efflux pumps, β-lactamase expression, reduced porins and switching to a biofilm lifestyle. The optimal treatment strategies for P. aeruginosa infection are still being established, and new antibiotic formulations such as liposomal amikacin, fosfomycin in combination with tobramycin and inhaled levofloxacin are being explored. Novel agents such as the alginate oligosaccharide OligoG, cysteamine, bacteriophage, nitric oxide, garlic oil and gallium may be useful as anti-pseudomonal strategies, and immunotherapy to prevent infection may have a role in the future. New treatments that target the primary defect in cystic fibrosis, recently licensed for use, have been associated with a fall in P. aeruginosa infection prevalence. Understanding the mechanisms for this could add further strategies for treating P. aeruginosa in future. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Serotyping, Genotyping, and Antimicrobial Susceptibility of Ornithobacterium rhinotracheale Isolates from Mexico.

PubMed

Peña-Vargas, Edgar Rafael; Vega-Sánchez, Vicente; Morales-Erasto, Vladimir; Trujillo-Ruíz, Héctor Hugo; Talavera-Rojas, Martín; Soriano-Vargas, Edgardo

2016-09-01

The bacterium Ornithobacterium rhinotracheale is associated with respiratory disease and septicemia in poultry. In this study, 9 reference strains and a total of 23 isolates of O. rhinotracheale from respiratory diseased poultry from Mexico were serotyped and genotyped. Furthermore, the antimicrobial susceptibility of isolates and reference strains of O. rhinotracheale were determined. All isolates belong to serotype A and showed a clonal relationship. All reference strains and isolates were resistant to colistin, fosfomycin, gentamicin, kanamycin, streptomycin, and trimethoprim-sulfamethoxazole. These results should eventually be helpful in planning strategies for the control of O. rhinotracheale infections in poultry in Mexico.

Fosfomycin: Uses and potentialities in veterinary medicine

PubMed Central

Pérez, D.S.; Tapia, M.O.; Soraci, A.L.

2014-01-01

Fosfomycin (FOS) is a natural bactericidal broad-spectrum antibiotic which acts on proliferating bacteria by inhibiting cell wall and early murein/peptidoglycan synthesis. Bactericidal activity is evident against Gram positive and Gram negative bacteria and can also act synergistically with other antibiotics. Bacterial resistance to FOS may be natural or acquired. Other properties of this drug include inhibition of bacterial adhesion to epithelial cells, exopolysaccharide biofilm penetration, immunomodulatory effect, phagocytosis promotion and protection against the nephrotoxicity caused by other drugs. FOS has chemical characteristics not typically observed in organic phosphoric compounds and its molecular weight is almost the lowest of all the antimicrobials. It tends to form salts easily due to its acidic nature (disodium salt, for intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration; calcium and trometamol salt: for oral (PO) administration). FOS has a very low protein binding (<0.5%) which, along with its low molecular weight and water solubility, contributes to its good diffusion into fluids (cerebrospinal fluid, aqueous and vitreous humor, interstitial fluid) and tissues (placenta, bone, muscle, liver, kidney and skin/fat). In all species, important differences in the bioavailability have been found after administration in relation to the various derivatives of FOS salts. Pharmacokinetic profiles have been described in humans, chickens, rabbits, cows, dogs, horses and weaning piglets. The low toxicity and potential efficacy of FOS are the main factors that contribute to its use in humans and animals. Thus, it has been used to treat a broad variety of bacterial infections in humans, such as localized peritonitis, brain abscesses, severe soft tissue infections, cystitis and other conditions. In veterinary medicine, FOS is used to treat infectious diseases of broiler chickens and pigs. In broilers, it is administered for the treatment of E. coli and Salmonella spp. infections. In piglets, the drug is prescribed to treat a wide variety of bacterial infections. FOS penetration is demonstrated in phagocytic, respiratory (HEP-2) and intestinal (IPEC-J2) cells. Although not widely used in animals, the drug has shown good results in human medicine. The potentialities of FOS suggest that this drug is a promising candidate for the treatment of infections in veterinary medicine. For these reasons, the aim of this work is to provide animal health practitioners with information on a drug that is not extensively recognized. PMID:26623336

[Profile and susceptibility to antibiotics in urinary tract infections in children and newborns from 2012 to 2013: Data from 1879 urine cultures].

PubMed

Marzouk, M; Ferjani, A; Haj Ali, M; Boukadida, J

2015-05-01

We present recent data on the bacteriological profile and antibiotic susceptibility of uropathogenic bacteria isolated in children and newborns in our region over the past 2 years. A retrospective study on the positive urine cultures from pediatric and neonatal populations during 2012-2013. Bacteria were identified using conventional methods. Susceptibility testing was performed and interpreted as recommended by the committee of the susceptibility of the French Society of Microbiology (CA-SFM). We collected 1879 non-redundant bacteria with more than 73% Escherichia coli. Children and infants (mean age, 32 months [range, 1 month to 14 years]) accounted for 84% of the bacteria collected and newborns (mean age, 12 days [range, 1 day to 1 month]) 16%. A female predominance was observed in the pediatric population (M:F sex ratio, 3.2), whereas for the neonatal population, the proportions were almost identical in both sexes (M:F sex ratio, 1.1). Most of the positive urine cultures (n=1234) were from the community. Hospitalized patients (n=636) were divided into pediatric (60%) and neonatal units (40%). Five bacterial genera dominated the bacteriological profile: E. coli, Klebsiella sp., Proteus sp., Enterobacter sp., and Enterococcus. The susceptibility of the main BUP antibiotics used for treatment of frequent UTI showed the effectiveness of furadoine, imipenem, fosfomycin, and colistin. Amoxicillin kept constant activity against Enterococcus and Streptococcus agalactiae. The rates of resistance of Enterobacteriaceae to beta-lactam antibiotics were high, especially in the neonatal population. The production of extended-spectrum beta-lactamase (ESBL) was noted in 12.8% of pediatric Enterobacteria vs. 22.6% of the neonatal strains. For community Enterobacteriaceae, the activity of beta-lactam antibiotics was limited with 11.2% resistance to third-generation cephalosporins (C3G), including 8.6% ESBL production. The impact of widespread use of beta-lactam antibiotics in neonatal and pediatric environments is felt. Colistin, imipenem, and fosfomycin are the most frequently used antibiotics active against bacteria responsible for neonatal and pediatric UTI; however, they cannot be used as probabilistic treatment. Nitrofurans seem to be active antibiotics on UTI, but they present limits in their use in neonatal and pediatric populations. Their indication in case of pyelonephritis should be discussed. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Pseudomonas aeruginosa gshA Mutant Is Defective in Biofilm Formation, Swarming, and Pyocyanin Production

PubMed Central

Van Laar, Tricia A.; Esani, Saika; Birges, Tyler J.; Hazen, Bethany; Thomas, Jason M.

2018-01-01

ABSTRACT Pseudomonas aeruginosa is a ubiquitous Gram-negative bacterium that can cause severe opportunistic infections. The principal redox buffer employed by this organism is glutathione (GSH). To assess the role of GSH in the virulence of P. aeruginosa, a number of analyses were performed using a mutant strain deficient in gshA, which does not produce GSH. The mutant strain exhibited a growth delay in minimal medium compared to the wild-type strain. Furthermore, the gshA mutant was defective in biofilm and persister cell formation and in swimming and swarming motility and produced reduced levels of pyocyanin, a key virulence factor. Finally, the gshA mutant strain demonstrated increased sensitivity to methyl viologen (a redox cycling agent) as well as the thiol-reactive antibiotics fosfomycin and rifampin. Taken together, these data suggest a key role for GSH in the virulence of P. aeruginosa. IMPORTANCE Pseudomonas aeruginosa is a ubiquitous bacterium that can cause severe opportunistic infections, including many hospital-acquired infections. It is also a major cause of infections in patients with cystic fibrosis. P. aeruginosa is intrinsically resistant to a number of drugs and is capable of forming biofilms that are difficult to eradicate with antibiotics. The number of drug-resistant strains is also increasing, making treatment of P. aeruginosa infections very difficult. Thus, there is an urgent need to understand how P. aeruginosa causes disease in order to find novel ways to treat infections. We show that the principal redox buffer, glutathione (GSH), is involved in intrinsic resistance to the fosfomycin and rifampin antibiotics. We further demonstrate that GSH plays a role in P. aeruginosa disease and infection, since a mutant lacking GSH has less biofilm formation, is less able to swarm, and produces less pyocyanin, a pigment associated with infection. PMID:29669887

When sepsis persists: a review of MRSA bacteraemia salvage therapy.

PubMed

Kullar, Ravina; Sakoulas, George; Deresinski, Stan; van Hal, Sebastiaan J

2016-03-01

MRSA bacteraemia (MRSAB), including infective endocarditis, carries a high mortality rate, with up to 50% of patients failing initial therapy with vancomycin and requiring salvage therapy. Persistent MRSAB can be difficult to successfully eliminate, especially when source control is not possible due to an irremovable focus or the bacteraemia still persists despite surgical intervention. Although vancomycin and daptomycin are the only two antibiotics approved by the US FDA for the treatment of patients with MRSAB as monotherapy, the employment of novel strategies is required to effectively treat patients with persistent MRSAB and these may frequently involve combination drug therapy. Treatment strategies that are reviewed in this manuscript include vancomycin combined with a β-lactam, daptomycin-based therapy, ceftaroline-based therapy, linezolid-based therapy, quinupristin/dalfopristin, telavancin, trimethoprim/sulfamethoxazole-based therapy and fosfomycin-based therapy. We recommend that combination antibiotic therapy be considered for use in MRSAB salvage treatment. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The prevention and management of infections due to multidrug resistant organisms in haematology patients

PubMed Central

Trubiano, Jason A; Worth, Leon J; Thursky, Karin A; Slavin, Monica A

2015-01-01

Infections due to resistant and multidrug resistant (MDR) organisms in haematology patients and haematopoietic stem cell transplant recipients are an increasingly complex problem of global concern. We outline the burden of illness and epidemiology of resistant organisms such as gram-negative pathogens, vancomycin-resistant Enterococcus faecium (VRE), and Clostridium difficile in haematology cohorts. Intervention strategies aimed at reducing the impact of these organisms are reviewed: infection prevention programmes, screening and fluoroquinolone prophylaxis. The role of newer therapies (e.g. linezolid, daptomycin and tigecycline) for treatment of resistant and MDR organisms in haematology populations is evaluated, in addition to the mobilization of older agents (e.g. colistin, pristinamycin and fosfomycin) and the potential benefit of combination regimens. PMID:24341410

Potentiation activity of multiple antibacterial agents by Salvianolate from the Chinese medicine Danshen against methicillin-resistant Staphylococcus aureus (MRSA).

PubMed

Liu, Qing-Qing; Han, Jun; Zuo, Guo-Ying; Wang, Gen-Chun; Tang, Hua-Shu

2016-05-01

Salvianolate (SAL) is a prescribed medicine from the Chinese herb Danshen (Salvia miltiorrhiza Bunge). It has been widely used in treatment of coronary and other diseases with significant effects. The in vitro antimicrobial activities of SAL against infectious pathogens were assayed and its combined effects on 10 clinical isolates of SCCmec III type methicillin-resistant Staphylococcus aureus (MRSA) with ten antibiotics were evaluated. Susceptibility to each agent alone was tested using a broth microdilution method, and the chequerboard and time-kill experiments were used for the combined activities. The results showed MIC was 128-256 mg/L for SAL used alone against MRSA. Significant synergies were observed for SAL/Ampicillin (Fosfomycin, Erythromycin, Piperacillin-tazobactam or Clindamycin) combination against over half of the isolates, with their MICs reduced by times of dilution (TOD) to 4-32 (FICIs 0.375-0.5), respectively. SAL/AMP combination showed the best combined effect of synergy on bacteriostatic and bactericidal activities, while SAL/AMK combination reversed the resistance of MRSA to AMK. The results demonstrated that SAL enhanced widely the in vitro anti-MRSA efficacy of the ten antibacterial agents, which had potential for combinatory therapy of patients infected with MRSA and warrants further investigations. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

[Infections in orthopedics and traumatology. Pathogenesis and therapy].

PubMed

Scheffer, D; Hofmann, S; Pietsch, M; Wenisch, C

2008-07-01

Infections in orthopedics and traumatology are particularly challenging for the treating physician due to changing epidemiology and bacteriology, in particular immunosenescent patients and antimicrobial resistance. Numerous exogenous and endogenous factors contribute to the onset of bone/joint infection. Known clinical entities include osteitis/osteomyelitis, arthritis, prosthesis-associated infection and spondylitis/spondylodiscitis. Knowledge of epidemiology, bacteriology, and clinic and healing processes in infections leads to a better understanding of the various treatment strategies. Cephalosporin, fosfomycin, glycopeptide, lincosamide, oxazolidinones, ansamycins und fusidic acids represent the standard therapeutic agents in orthopedics and traumatology. Fluoroquinolones, glycylcyclines and lipopeptides are new and possibly promising alternatives. The most important indices of antibiotic agents used in everyday practice are discussed. In complicated cases, collaboration with a specialist for infectious diseases results in improved therapeutic results.

[Antimicrobial activity of fosfomycin under various conditions against standard strains, beta-lactam resistant strains, and multidrug efflux system mutants].

PubMed

Mikuniya, Takeshi; Hiraishi, Toru; Maebashi, Kazunori; Ida, Takashi; Takata, Toshihiko; Hikida, Muneo; Yamada, Sakuo; Gotoh, Naomasa; Nishino, Takeshi

2005-04-01

The purpose of this study was to evaluate the possible benefit of fosfomycin (FOM) as prophylactic antibiotic in terms of antimicrobial activity and the potential of inducibility of beta-lactamase, compared with cefazolin, cefotiam, cefmetazole, and piperacillin that are commonly used as perioperative agents. The in vitro activity of FOM against aerobic Gram-negative bacteria using Mueller-Hinton agar or nutrient agar supplemented with glucose-6-phosphate (G6P) as tested medium increased within a range from 2 to 256 times the activity in the medium without G6P. However, the susceptibility of Gram-positive bacteria to FOM remained largely unchanged with or without G6P. There was no aerobic- or anaerobic-bacteria which changed susceptibility against beta-lactam antibiotics under various tested medium conditions. FOM demonstrated strong bactericidal activity against Escherichia coli and Pseudomonas aeruginosa in a dose dependent manner, and decreased viable cell counts of Staphylococcus aureus. In the case of P. aeruginosa, transmission electron micrographs study revealed that numerous lysed cells were present 2 hours after treatment with FOM at four times the MIC. First and second generation cephalosporins induced AmpC-type beta-lactamase in a dose dependent manner among beta-lactamase inducible strains of P. aeruginosa and Enterobacter cloacae. On the other hand, inducible activity of FOM on beta-lactamase production was less than 1/25 to 1/65 compared with those of cephalosporins. In addition, FOM maintained strong antimicrobial activity for over then 20 years after marketing, because of the excellent stability against various types of beta-lactamase produced by plasmid-carrying bacteria and clinical isolates. FOM was not extruded by four types of efflux systems, such as MexAB-OprM, MexCD-OprJ, MexXY/ OprM and MexEF-OprN, however beta-lactam antibiotics were substrates of MexAB-OprM and MexCD-OprJ. In conclusion, FOM provides adequate coverage for both aerobic Gram-positive and Gram-negative bacteria causing postoperative infections. Further, FOM would not select/concentrate beta-lactamase producing bacteria in the clinical fields and would not be a substrate for multidrug efflux system of P. aeruginosa.

Antibacterial resistances in uncomplicated urinary tract infections in women: ECO·SENS II data from primary health care in Austria

PubMed Central

2012-01-01

Background Uncomplicated urinary tract infections (UTI) are a frequent reason for consultation of women in primary health care. To avoid therapy failure and development of resistances, the choice of an antibiotic should be based on the knowledge of recent local resistance data but these data are scarce for the Austrian primary health care sector. Within the context of the ECO·SENS II study it was the aim to obtain appropriate and relevant local resistance data and describe the changes in the resistance pattern in comparison to the ECO·SENS study. Methods 23 GPs from different parts of Austria participated in the study between July 2007 and November 2008. According to the defined inclusion- and exclusion criteria female patients with symptoms of an uncomplicated UTI were included and a midstream urine sample was collected. In case of significant bacteriuria susceptibility testing of E. coli against 14 antibiotics was performed. Descriptive statistical methods were used. Results In 313 patients included in the study, a total of 147 E. coli isolates (47%) were detected and tested. The resistance rates were in %: Mecillinam (0.0), nitrofurantoin (0.7), fosfomycin trometamol (0.7), gentamycin (1.4), cefotaxime (2.7), ceftazidime (2.7), Cephadroxil (4.1) and ciprofloxacin (4.1). Higher resistance rates were found in amoxicillin/clavulanic acid (8.9), nalidixic acid (9.6), trimethoprim/sulphamethoxazole (14.4), trimethoprim (15.8), sulphamethoxazole (21.2) and ampicillin (28.8). Additionally, the comparison of these results with the results of the ECO·SENS study demonstrated an increase in resistance rates of ampicillin, amoxicillin/clavulanic acid, nalidixic acid and ciprofloxacin. Conclusions The resistance data for E. coli in uncomplicated UTIs in women gained by this study are the most recent data for this disease in Austria at the moment. The increased resistance rates of amoxicillin/clavulanic acid, ciprofloxacin and nalidixic acid should be respected when choosing an appropriate antibiotic for uncomplicated UTIs. The use of ampicillin, sulphamethoxazole, trimethoprim and trimethoprim/sulphametoxazole in uncomplicated UTIs in women should be questioned at all. The findings of this study should result in a regular surveillance system of resistances emerging in the ambulatory sector designed after the model of the EARS-Net. PMID:22989349

The influence of glycyrrhiza and antibiotics on the purgative action of sennoside a from Daiokanzoto in mice.

PubMed

Matsui, Emi; Takayama, Kento; Sato, Eiji; Okamura, Nobuyuki

2011-01-01

Daiokanzoto (DKT), a Kampo medicine that includes the combination of two crude drugs (rhubarb and glycyrrhiza), is clinically effective for constipation. The aim of this study is to clarify the influence of glycyrrhiza, three glycyrrhiza constituents (glycyrrhizin, liquiritin, and liquiritin apioside), and eight antibiotics on the purgative action of DKT, rhubarb, or sennoside A, a constituent of rhubarb, in mice. The purgative actions of rhubarb and sennoside A were significantly intensified when glycyrrhiza was co-administered orally to mice. Liquiritin and liquiritin apioside but not glycyrrhizin showed significant amplification of the purgative action in a dose-dependent manner. The purgative actions of DKT and sennoside A were significantly reduced by the pre-administration of ampicillin, cefcapene pivoxil, faropenem, fosfomycin, or kanamycin, but were not affected by the pre-administration of clarithromycin or levofloxacin. On the other hand, the purgative action of sennoside A was significantly reduced by the pre-administration of minocycline, whereas that of DKT was not affected. The effect of minocycline on the purgative action of sennoside A was lost when glycyrrhiza was co-administered. These results suggest that liquiritin and liquiritin apioside contribute as active substances for the purgative action of DKT, and some antibiotics reduce the purgative action of DKT and sennoside A. Furthermore, glycyrrhiza has the ability to recover the purgative action of sennoside A suppressed by minocycline via an unknown mechanism.

Efficacy and safety of fosfomycin-trometamol in the prophylaxis for transrectal prostate biopsy. Prospective randomized comparison with ciprofloxacin.

PubMed

Lista, F; Redondo, C; Meilán, E; García-Tello, A; Ramón de Fata, F; Angulo, J C

2014-01-01

Prostate biopsy is the standardized diagnostic method for prostate cancer. However, although there is not a standardized protocol, there are recommendations in order to reduce the incidence of complications. The objective of the present work is to assess the efficacy and safety of antibiotic prophylaxis in the prostate biopsy by comparing two antibiotic regimes: two doses of fosfomycin-trometamol 3g (FMT) every 48 hours with 10 doses of oral ciprofloxacin 500 mg every 12 hours during 5 days. Randomized prospective study was performed with 671 patients who had undergone to walking transrectal ultrasound guided prostate biopsy. Patients of group A (n=312) were treated with ciprofloxacin, and patients of group B (n=359) with FMT. Efficacy and tolerability of two prophylactic regimes were compared. Urine culture was carried out at 2 weeks after biopsy. Initially, patients with asymptomatic bacteriuria were not treated with antibiotics; urine culture was repeated after 1 month, persistent bacteriuria was treated according to antibiogram. No differences between groups were found in age (P=.78), cancer presence (P=.9) or number of biopsy cylinders (P=.93). The mean number of cores obtained was 11.3 ± 3.25 (range 6-20). Digestive intolerance was observed for 9 patients (2.9%) of group A and 10 patients (2.8%) in group B. One patient (.3%) of group A showed severe allergic reaction. In total, 167 patients (24.6%) had complications: 16 (2.4%) fever, 47 (6.9%) hemospermia, 81 (11.9%) hematuria, 7 (1%) rectal bleeding and 16 (2.4%) urinary retention. No statistically differences between groups were observed (27.6% vs. 22.6%; P=.17). However, hemospermia was more frequent in group A (9.9% vs. 4.5%; P=.006). Bacteriuria after biopsy was detected in 44 patients (6.6%), being more frequent in group B patients (4.2% vs. 8.6%; P=.02) although a higher number of second treatment cycles were not needed (53.9% vs. 29%; P=.17). The likelihood of resistance to ciprofloxacin in patients with bacteriuria in A was greater than that of FMT in B (69.2% vs. 41.9%; P=.0004). Antibiotic prophylaxis with FMT (2 doses of 3g) in prostate biopsy is an alternative as effective and safe as ciprofloxacin (10 doses of 500 mg), which carries lower rate of resistance. According to our experience, this drug is a safe, well-tolerated, and easily manageable prophylactic option, facilitating patient compliance. More prospective multicenter studies are necessary to confirm these findings. Copyright © 2014 AEU. Published by Elsevier Espana. All rights reserved.

Resistance phenotypes and susceptibility of contemporary Serratia isolates in the university hospital of Crete, Greece.

PubMed

Samonis, George; Vardakas, Konstantinos Z; Maraki, Sofia; Stamouli, Petroula; Mavromanolaki, Viktoria-Eirini; Kofteridis, Diamantis P; Falagas, Matthew E

To study changes in the susceptibility of Serratia spp. in Crete, Greece (2010-2015). Non-duplicate isolates were examined using automated systems. Phenotypic confirmatory tests were applied. Three hundred and seventy-eight Serratia spp. were analyzed. Serratia marcescens (88.3%) was the predominant species. Fluoroquinolones (97.9%), carbapenems (97.4%) and fosfomycin (97.4%) were the most active followed by amikacin (95.5%), piperacillin/tazobactam (94.7%), and trimethoprim/sulfamethoxazole (94.4%). The activity of 3rd and 4th generation cephalosporins was 87-88.6%. The distribution of multi-drug resistant (MDR) strains varied, with a trend towards increasing frequency. ESBL (7.9%), carbapenemase (2.9%), AmpC (2.1%) and aminoglycoside modifying enzyme (10.6%) production were the commonest resistant phenotypes. The susceptibility of Serratia spp. varied during the study period a trend towards decreasing susceptibility, especially for non-carbapenem β-lactams and aminoglycosides.

In vitro susceptibility and resistance phenotypes in contemporary Enterobacter isolates in a university hospital in Crete, Greece.

PubMed

Maraki, Sofia; Vardakas, Konstantinos Z; Samonis, George; Perdikis, Dimitrios; Mavromanolaki, Viktoria Eirini; Kofteridis, Diamantis P; Falagas, Matthew E

2017-06-01

To study the evolution in the susceptibility of Enterobacter spp. in Crete, Greece from 2010 to 2015. Non-duplicate isolates were studied using automated systems. Phenotypic confirmatory tests were applied. A total of 939 Enterobacter isolates were included. Colistin was the most active antibiotic (97.9%) followed by imipenem (96.1%), gentamicin (95.7%), tigecycline (91.8%), cefepime (89.4%), chloramphenicol (85.8%), fosfomycin (85.5%), trimethoprim/sulfamethoxazole (83.3%) and piperacillin/tazobactam (73.3%). Antibiotic resistance did not increase during the study period for most antibiotics. Lower susceptibility was observed among multidrug-resistant strains and carbapenem-nonsusceptible isolates. AmpC was the most common resistant mechanism (21%); carbapenemases (3.7%) and aminoglycoside-modifying enzymes (6.5%) were also detected. A significant proportion of Enterobacter spp. was resistant to several antibiotics, most notably β-lactams.

Role of newer and re-emerging older agents in the treatment of infections caused by carbapenem-resistant Enterobacteriaceae.

PubMed

Thaden, Joshua T; Pogue, Jason M; Kaye, Keith S

2017-05-19

Antimicrobial resistance has been identified by the World Health Organization as "one of the three greatest threats to human health." Gram negative bacteria in particular drive this alarming trend. Carbapenem-resistant Enterobacteriaceae (CRE) such as Escherichia coli, Klebsiella pneumoniae, and Enterobacter species are of particular importance as they are associated with poor clinical outcomes and are common causes for a variety of infections including bacteremia, urinary tract infection, intra-abdominal infections and pneumonia. CRE are difficult to treat as carbapenem resistance is often accompanied by resistance to additional drug classes. For example, CRE may be extensively drug resistant or even pandrug resistant. Unfortunately, CRE infections have increased over the past 15 y while new and effective antibiotics have not kept pace. Recently, however, new agents have become available to help treat CRE infection, and several more are under development. This article reviews the efficacy, safety, and pharmacokinetic issues around 4 emerging agents to treat CRE - ceftazidime-avibactam, fosfomycin, tigecycline, and minocycline. In addition, an overview of agents in the antibiotic pipeline - meropenem-vaborbactam, imipenem-relebactam, plazomicin, and eravacycline is provided. More established agents, such as those in the polymyxin class and aminoglycoside class (other than the pipeline agent plazomicin), are not addressed here.

Glutamate Dehydrogenase Affects Resistance to Cell Wall Antibiotics in Bacillus subtilis

PubMed Central

Lee, Yong Heon; Kingston, Anthony W.

2012-01-01

The glutamate dehydrogenase RocG of Bacillus subtilis is a bifunctional protein with both enzymatic and regulatory functions. Here we show that the rocG null mutant is sensitive to β-lactams, including cefuroxime (CEF), and to fosfomycin but that resistant mutants arise due to gain-of-function mutations in gudB, which encodes an otherwise inactive glutamate dehydrogenase. In the presence of CEF, ΔrocG ΔgudB mutant cells exhibit growth arrest when they reach mid-exponential phase. Using microarray-based transcriptional profiling, we found that the σW regulon was downregulated in the ΔrocG ΔgudB null mutant. A survey of σW-controlled genes for effects on CEF resistance identified both the NfeD protein YuaF and the flotillin homologue YuaG (FloT). Notably, overexpression of yuaFG in the rocG null mutant prevents the growth arrest induced by CEF. The YuaG flotillin has been shown previously to localize to defined lipid microdomains, and we show here that the yuaFGI operon contributes to a σW-dependent decrease in membrane fluidity. We conclude that glutamate dehydrogenase activity affects the expression of the σW regulon, by pathways that are yet unclear, and thereby influences resistance to CEF and other antibiotics. PMID:22178969

Glutamate dehydrogenase affects resistance to cell wall antibiotics in Bacillus subtilis.

PubMed

Lee, Yong Heon; Kingston, Anthony W; Helmann, John D

2012-03-01

The glutamate dehydrogenase RocG of Bacillus subtilis is a bifunctional protein with both enzymatic and regulatory functions. Here we show that the rocG null mutant is sensitive to β-lactams, including cefuroxime (CEF), and to fosfomycin but that resistant mutants arise due to gain-of-function mutations in gudB, which encodes an otherwise inactive glutamate dehydrogenase. In the presence of CEF, ΔrocG ΔgudB mutant cells exhibit growth arrest when they reach mid-exponential phase. Using microarray-based transcriptional profiling, we found that the σ(W) regulon was downregulated in the ΔrocG ΔgudB null mutant. A survey of σ(W)-controlled genes for effects on CEF resistance identified both the NfeD protein YuaF and the flotillin homologue YuaG (FloT). Notably, overexpression of yuaFG in the rocG null mutant prevents the growth arrest induced by CEF. The YuaG flotillin has been shown previously to localize to defined lipid microdomains, and we show here that the yuaFGI operon contributes to a σ(W)-dependent decrease in membrane fluidity. We conclude that glutamate dehydrogenase activity affects the expression of the σ(W) regulon, by pathways that are yet unclear, and thereby influences resistance to CEF and other antibiotics.

Beta-lactamases in Enterobacteriaceae infections in children.

PubMed

Moxon, Christopher Alan; Paulus, Stéphane

2016-07-05

Multi-drug resistance in Gram negative bacteria, particularly in Enterobacteriaceae, is a major clinical and public health challenge. The main mechanism of resistance in Enterobacteriaceae is linked to the production of beta-lactamase hydrolysing enzymes such as extended spectrum beta-lactamases (ESBL), AmpC beta-lactamases and carbapenemases (Carbapenemase Producing Enterobacteriaceae (CPE)). ESBL and CPE resistance genes are located on plasmids, which can be transmitted between Enterobacteriaceae, facilitating their spread in hospitals and communities. These plasmids usually harbour multiple additional co-resistance genes, including to trimethoprim-sulfamethoxazole, aminoglycosides, and fluoroquinolones, making these infections challenging to treat. Asymptomatic carriage in healthy children as well as community acquired infections are increasingly reported, particularly with ESBL. Therapeutic options are limited and previously little used antimicrobials such as fosfomycin and colistin have been re-introduced in clinical practice. Paediatric experience with these agents is limited hence there is a need to further examine their clinical efficacy, dosage and toxicity in children. Antimicrobial stewardship along with strict infection prevention and control practices need to be adopted widely in order to preserve currently available antimicrobials. The future development of novel agents effective against beta-lactamases producers and their applicability in children is urgently needed to address the challenge of multi-resistant Gram negative infections. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Diagnosis and treatment of urinary tract infections across age groups.

PubMed

Chu, Christine M; Lowder, Jerry L

2018-01-02

Urinary tract infections are the most common outpatient infections, but predicting the probability of urinary tract infections through symptoms and test results can be complex. The most diagnostic symptoms of urinary tract infections include change in frequency, dysuria, urgency, and presence or absence of vaginal discharge, but urinary tract infections may present differently in older women. Dipstick urinalysis is popular for its availability and usefulness, but results must be interpreted in context of the patient's pretest probability based on symptoms and characteristics. In patients with a high probability of urinary tract infection based on symptoms, negative dipstick urinalysis does not rule out urinary tract infection. Nitrites are likely more sensitive and specific than other dipstick components for urinary tract infection, particularly in the elderly. Positive dipstick testing is likely specific for asymptomatic bacteriuria in pregnancy, but urine culture is still the test of choice. Microscopic urinalysis is likely comparable to dipstick urinalysis as a screening test. Bacteriuria is more specific and sensitive than pyuria for detecting urinary tract infection, even in older women and during pregnancy. Pyuria is commonly found in the absence of infection, particularly in older adults with lower urinary tract symptoms such as incontinence. Positive testing may increase the probability of urinary tract infection, but initiation of treatment should take into account risk of urinary tract infection based on symptoms as well. In cases in which the probability of urinary tract infection is moderate or unclear, urine culture should be performed. Urine culture is the gold standard for detection of urinary tract infection. However, asymptomatic bacteriuria is common, particularly in older women, and should not be treated with antibiotics. Conversely, in symptomatic women, even growth as low as 10 2 colony-forming unit/mL could reflect infection. Resistance is increasing to fluoroquinolones, beta-lactams, and trimethoprim-sulfamethoxazole. Most uropathogens still display good sensitivity to nitrofurantoin. First-line treatments for urinary tract infection include nitrofurantoin, fosfomycin, and trimethoprim-sulfamethoxazole (when resistance levels are <20%). These antibiotics have minimal collateral damage and resistance. In pregnancy, beta-lactams, nitrofurantoin, fosfomycin, and trimethoprim-sulfamethoxazole can be appropriate treatments. Interpreting the probability of urinary tract infection based on symptoms and testing allows for greater accuracy in diagnosis of urinary tract infection, decreasing overtreatment and encouraging antimicrobial stewardship. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of Antibiotics on Shiga Toxin 2 Production and Bacteriophage Induction by Epidemic Escherichia coli O104:H4 Strain

PubMed Central

Bielaszewska, Martina; Idelevich, Evgeny A.; Zhang, Wenlan; Bauwens, Andreas; Schaumburg, Frieder; Mellmann, Alexander; Peters, Georg

2012-01-01

The role of antibiotics in treatment of enterohemorrhagic Escherichia coli (EHEC) infections is controversial because of concerns about triggering hemolytic-uremic syndrome (HUS) by increasing Shiga toxin (Stx) production. During the recent large EHEC O104:H4 outbreak, antibiotic therapy was indicated for some patients. We tested a diverse panel of antibiotics to which the outbreak strain is susceptible to interrogate the effects of subinhibitory antibiotic concentrations on induction of stx2-harboring bacteriophages, stx2 transcription, and Stx2 production in this emerging pathogen. Ciprofloxacin significantly increased stx2-harboring phage induction and Stx2 production in outbreak isolates (P values of <0.001 to <0.05), while fosfomycin, gentamicin, and kanamycin insignificantly influenced them (P > 0.1) and chloramphenicol, meropenem, azithromycin, rifaximin, and tigecycline significantly decreased them (P ≤ 0.05). Ciprofloxacin and chloramphenicol significantly upregulated and downregulated stx2 transcription, respectively (P < 0.01); the other antibiotics had insignificant effects (P > 0.1). Meropenem, azithromycin, and rifaximin, which were used for necessary therapeutic or prophylactic interventions during the EHEC O104:H4 outbreak, as well as tigecycline, neither induced stx2-harboring phages nor increased stx2 transcription or Stx2 production in the outbreak strain. These antibiotics might represent therapeutic options for patients with EHEC O104:H4 infection if antibiotic treatment is inevitable. We await further analysis of the epidemic to determine if usage of these agents was associated with an altered risk of developing HUS. PMID:22391549

Discovery of chlamydial peptidoglycan reveals bacteria with murein sacculi but without FtsZ

NASA Astrophysics Data System (ADS)

Pilhofer, Martin; Aistleitner, Karin; Biboy, Jacob; Gray, Joe; Kuru, Erkin; Hall, Edward; Brun, Yves V.; Vannieuwenhze, Michael S.; Vollmer, Waldemar; Horn, Matthias; Jensen, Grant J.

2013-12-01

Chlamydiae are important pathogens and symbionts with unique cell biological features. They lack the cell-division protein FtsZ, and the existence of peptidoglycan (PG) in their cell wall has been highly controversial. FtsZ and PG together function in orchestrating cell division and maintaining cell shape in almost all other bacteria. Using electron cryotomography, mass spectrometry and fluorescent labelling dyes, here we show that some environmental chlamydiae have cell wall sacculi consisting of a novel PG type. Treatment with fosfomycin (a PG synthesis inhibitor) leads to lower infection rates and aberrant cell shapes, suggesting that PG synthesis is crucial for the chlamydial life cycle. Our findings demonstrate for the first time the presence of PG in a member of the Chlamydiae. They also present a unique example of a bacterium with a PG sacculus but without FtsZ, challenging the current hypothesis that it is the absence of a cell wall that renders FtsZ non-essential.

Role of Combination Antimicrobial Therapy for Vancomycin-Resistant Enterococcus faecium Infections: Review of the Current Evidence.

PubMed

Yim, Juwon; Smith, Jordan R; Rybak, Michael J

2017-05-01

Enterococcus species are the second most common cause of nosocomial infections in the United States and are particularly concerning in critically ill patients with preexisting comorbid conditions. Rising resistance to antimicrobials that were historically used as front-line agents for treatment of enterococcal infections, such as ampicillin, vancomycin, and aminoglycosides, further complicates the treatment of these infections. Of particular concern are Enterococcus faecium strains that are associated with the highest rate of vancomycin resistance. The introduction of antimicrobial agents with specific activity against vancomycin-resistant Enterococcus (VRE) faecium including daptomycin, linezolid, quinupristin-dalfopristin, and tigecycline did not completely resolve this clinical dilemma. In this review, the mechanisms of action and resistance to currently available anti-VRE antimicrobial agents including newer agents such as oritavancin and dalbavancin will be presented. In addition, novel combination therapies including β-lactams and fosfomycin, and the promising results from in vitro, animal studies, and clinical experience in the treatment of VRE faecium will be discussed. © 2017 Pharmacotherapy Publications, Inc.

Bacterial prostatitis.

PubMed

Gill, Bradley C; Shoskes, Daniel A

2016-02-01

The review provides the infectious disease community with a urologic perspective on bacterial prostatitis. Specifically, the article briefly reviews the categorization of prostatitis by type and provides a distillation of new findings published on bacterial prostatitis over the past year. It also highlights key points from the established literature. Cross-sectional prostate imaging is becoming more common and may lead to more incidental diagnoses of acute bacterial prostatitis. As drug resistance remains problematic in this condition, the reemergence of older antibiotics such as fosfomycin, has proven beneficial. With regard to chronic bacterial prostatitis, no clear clinical risk factors emerged in a large epidemiological study. However, bacterial biofilm formation has been associated with more severe cases. Surgery has a limited role in bacterial prostatitis and should be reserved for draining of a prostatic abscess or the removal of infected prostatic stones. Prostatitis remains a common and bothersome clinical condition. Antibiotic therapy remains the basis of treatment for both acute and chronic bacterial prostatitis. Further research into improving prostatitis treatment is indicated.

[REASONS OF DELAYED DIAGNOSIS OF BLADDER TUBERCULOSIS].

PubMed

Kul'chavenja, E V; Holtobin, D P

2015-01-01

The fourth, terminal, stage of bladder tuberculosis (BT) manifests itself in irreversible changes and requires surgical treatment. To identify the reasons for delayed diagnosis of this urogenital tuberculosis complication. Medical history of 26 urogenital tuberculosis patients with a complicated form of stage 4 BT, referred to the Novosibirsk TB Research Institute for reconstructive surgery were analysed. In 22 patients, bladder volume ranged from 55 to 100 ml, 4 patients previously underwent cystostomy due to extremely small bladder volume. Average duration of BT hidden in the guise of "urogenital infection" was 6.2 years. Patients were treated with norfloxacin (a total of 104 courses), ciprofloxacin (86 courses), amikacin (43 courses), nitroxoline (27 courses), third generation cephalosporins (32 courses), lomefloxacin (17 courses), levofloxacin (11 courses), Amoxicillin clavulanate (4 courses), ampicillin (2 courses). It was demonstrated that all cases of BT stage 4 were iatrogenic. Irreversible debilitating complications occurred due to suboptimal therapy, primarily due to administration of amikacin and fluoroquinolones for urogenital infections, which was tuberculosis in disguise. Absence of M. tuberculosis growth does not exclude tuberculosis; pathological specimens must be further examined at least by PCR. Interventional material must be mandatory examined histologically and stained by Ziehl-Neelsen method to identify M. tuberculosis. Effective and not masking tuberculosis, optimal therapy for urogenital infections includes fosfomycin, furazidin (nitrofurantoin), gentamicin, III generation cephalosporins (in outpatient settings dispersible form of efixime should be preferable).

Antimicrobial susceptibility and emerging resistance determinants (blaCTX-M, rmtB, fosA3) in clinical isolates from urinary tract infections in the Bolivian Chaco.

PubMed

Bartoloni, Alessandro; Sennati, Samanta; Di Maggio, Tiziana; Mantella, Antonia; Riccobono, Eleonora; Strohmeyer, Marianne; Revollo, Carmen; Villagran, Ana Liz; Pallecchi, Lucia; Rossolini, Gian Maria

2016-02-01

Bolivia is among the lowest-resourced South American countries, with very few data available on antibiotic resistance in bacterial pathogens. The phenotypic and molecular characterization of bacterial isolates responsible for urinary tract infections (UTIs) in the Bolivian Chaco are reported here. All clinical isolates from UTIs collected in the Hospital Basico Villa Montes between June 2010 and January 2014 were analyzed (N=213). Characterization included susceptibility testing, extended-spectrum beta-lactamase (ESBL) detection, identification of relevant resistance determinants (e.g., CTX-M-type ESBLs, 16S rRNA methyltransferases, glutathione S-transferases), and genotyping of CTX-M producers. Very high resistance rates were observed. Overall, the lowest susceptibility was observed for trimethoprim-sulphamethoxazole, tetracycline, nalidixic acid, amoxicillin-clavulanic acid, ciprofloxacin, and gentamicin. Of E. coli and K. pneumoniae, 11.6% were ESBL producers. Resistance to nitrofurantoin, amikacin, and fosfomycin remained low, and susceptibility to carbapenems was fully preserved. CTX-M-15 was the dominant CTX-M variant. Four E. coli ST131 (two being H30-Rx) were identified. Of note, isolates harbouring rmtB and fosA3 were detected. Bolivia is not an exception to the very high resistance burden affecting many South American countries. Optimization of alternative approaches to monitor local antibiotic resistance trends in resource-limited settings is strongly encouraged to support the implementation of effective empiric treatment guidelines. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Treatment Options for Infections Caused by Carbapenem-resistant Enterobacteriaceae: Can We Apply “Precision Medicine” to Antimicrobial Chemotherapy?

PubMed Central

Perez, Federico; El Chakhtoura, Nadim G.; Papp-Wallace, Krisztina; Wilson, Brigid M; Bonomo, Robert A.

2016-01-01

Introduction For the past three decades, carbapenems played a central role in our antibiotic armamentarium, trusted to effectively treat infections caused by drug-resistant bacteria. The utility of this class of antibiotics has been compromised by the emergence of resistance especially among Enterobacteriaceae. Areas covered We review the current mainstays of pharmacotherapy against infections caused by carbapenem-resistant Enterobacteriaceae (CRE) including tigecycline, aminoglycosides, and rediscovered 'old' antibiotics such as fosfomycin and polymyxins, and discuss their efficacy and potential toxicity. We also summarize the clinical experience treating CRE infections with antibiotic combination therapy. Finally, we review ceftazidime/avibactam and imipenem/relebactam, a new generation of beta-lactamase inhibitors, which may offer alternatives to treat CRE infections. We critically evaluate the published literature, identify relevant clinical trials and review documents submitted to the United States Food and Drug Administration. Expert Opinion It is essential to define the molecular mechanisms of resistance and to apply insights about pharmacodynamic and pharmacokinetic properties of antibiotics, in order to maximize the impact of old and new therapeutic approaches against infections caused by CRE. A concerted effort is needed to carry out high-quality clinical trials that: i) establish the superiority of combination therapy vs. monotherapy; ii) confirm the role of novel beta-lactam/beta-lactamase inhibitor combinations as therapy against KPC- and OXA-48 producing Enterobacteriaceae; and, iii) evaluate new antibiotics active against CRE as they are introduced into the clinic. PMID:26799840

Emergence of KPC-producing Klebsiella pneumoniae in Uruguay: infection control and molecular characterization

PubMed Central

Marquez, C; Ingold, A; Echeverría, N; Acevedo, A; Vignoli, R; García-Fulgueiras, V; Viroga, J; Gonzalez, O; Odizzio, V; Etulain, K; Nuñez, E; Albornoz, H; Borthagaray, G; Galiana, A

2014-01-01

We describe the first outbreak of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP), the infection control measures adopted and the shift in resistance patterns of isolates during antibiotic treatment. The ST258 KPC-KP strain exhibited a multiresistant antibiotic phenotype including co-resistance to gentamycin, colistin and tigecycline intermediate susceptibility. Isolates before and after treatment had different behaviour concerning their antibiotic susceptibility and the population analysis profile study. A progressive increase in the aminoglycosides (acquiring amicacin resistance) and β-lactam MICs, and a decreased susceptibility to fosfomycin was observed throughout the administration of combined antimicrobial regimens including meropenem. A high meropenem resistance KPC-KP homogeneous population (MIC 256 Jg/mL), could arise from the meropenem heterogeneous low-level resistance KPC-KP population (MIC 8 Jg/mL), by the selective pressure of the prolonged meropenem therapy. The kpc gene was inserted in a Tn4401 isoform a, and no transconjugants were detected. The core measures adopted were successful to prevent evolution towards resistance dissemination. PMID:25356345

Draft genome sequence of Enterobacter cloacae HBY, a ST128 clinical strain co-producing KPC-2 and NDM-1 carbapenemases.

PubMed

Li, Xi; Zhu, Yongze; Shen, Mengyuan; Du, Jing; Zhang, Lei; Wang, Dairong

2018-03-01

Enterobacter cloacae is one of the major pathogens responsible for a variety of human infections. Here we report the draft genome sequence of multidrug-resistant E. cloacae strain HBY isolated from a female patient in China. Whole genomic DNA of E. cloacae strain HBY was extracted and was sequenced using an Illumina HiSeq™ 2000 platform. The generated sequence reads were assembled using CLC Genomics Workbench. The draft genome was annotated using Rapid Annotations using Subsystems Technology (RAST), and the presence of antimicrobial resistance genes was identified. The 5799439-bp genome contains various antimicrobial resistance genes conferring resistance to aminoglycosides, β-lactams, fosfomycin, macrolides, sulphonamides and fluoroquinolones. Notably, the strain was identified to carry two main carbapenemase genes (bla KPC-2 and bla NDM-1 ). The genome sequence reported in this study will provide valuable information to understand antibiotic resistance mechanisms in this strain. It is important to monitor the spread strains of Enterobacter sp. encoding both of these carbapenemase genes. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Effects of Low-Dose Amoxicillin on Staphylococcus aureus USA300 Biofilms.

PubMed

Mlynek, Kevin D; Callahan, Mary T; Shimkevitch, Anton V; Farmer, Jackson T; Endres, Jennifer L; Marchand, Mélodie; Bayles, Kenneth W; Horswill, Alexander R; Kaplan, Jeffrey B

2016-05-01

Previous studies showed that sub-MIC levels of β-lactam antibiotics stimulate biofilm formation in most methicillin-resistant Staphylococcus aureus (MRSA) strains. Here, we investigated this process by measuring the effects of sub-MIC amoxicillin on biofilm formation by the epidemic community-associated MRSA strain USA300. We found that sub-MIC amoxicillin increased the ability of USA300 cells to attach to surfaces and form biofilms under both static and flow conditions. We also found that USA300 biofilms cultured in sub-MIC amoxicillin were thicker, contained more pillar and channel structures, and were less porous than biofilms cultured without antibiotic. Biofilm formation in sub-MIC amoxicillin correlated with the production of extracellular DNA (eDNA). However, eDNA released by amoxicillin-induced cell lysis alone was evidently not sufficient to stimulate biofilm. Sub-MIC levels of two other cell wall-active agents with different mechanisms of action-d-cycloserine and fosfomycin-also stimulated eDNA-dependent biofilm, suggesting that biofilm formation may be a mechanistic adaptation to cell wall stress. Screening a USA300 mariner transposon library for mutants deficient in biofilm formation in sub-MIC amoxicillin identified numerous known mediators of S. aureus β-lactam resistance and biofilm formation, as well as novel genes not previously associated with these phenotypes. Our results link cell wall stress and biofilm formation in MRSA and suggest that eDNA-dependent biofilm formation by strain USA300 in low-dose amoxicillin is an inducible phenotype that can be used to identify novel genes impacting MRSA β-lactam resistance and biofilm formation. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

A meta-analysis of in vitro antibiotic synergy against Acinetobacter baumannii.

PubMed

March, Gabriel A; Bratos, Miguel A

2015-12-01

The aim of the work was to describe the different in vitro models for testing synergism of antibiotics and gather the results of antibiotic synergy against multidrug-resistant Acinetobacter baumannii (MDR-Ab). The different original articles were obtained from different web sites. In order to compare the results obtained by the different methods for synergy testing, the Pearson chi-square and the Fischer tests were used. Moreover, non-parametric chi-square test was used in order to compare the frequency distribution in each analysed manuscript. In the current meta-analysis 24 manuscripts, which encompassed 2016 tests of in vitro synergism of different antimicrobials against MDR-Ab, were revised. Checkerboard synergy testing was used in 11 studies, which encompasses 1086 tests (53.9%); time-kill assays were applied in 12 studies, which encompass 359 tests (17.8%); gradient diffusion methods were used in seven studies, encompassing 293 tests (14.5%). And, finally, time-kill plus checkerboard were applied in two studies, encompassing 278 tests (13.8%). By comparing these data, checkerboard and time-kill methods were significantly more used than gradient diffusion methods (p<0.005). Regarding synergy rates obtained on the basis of the applied method, checkerboard provided 227 tests (20.9%) with a synergistic effect; time-kill assays yielded 222 tests (61.8%) with a synergistic effect; gradient diffusion methods only provided 29 tests (9.9%) with a synergistic effect; and, finally, time-kill plus checkerboard yielded just 15 tests (5.4%) with a synergistic effect. When comparing these percentages, synergy rates reported by time-kill methods were significantly higher than that obtained by checkerboard and gradient diffusion methods (p<0.005). On the basis of the revised data, the combinations of a bactericidal antibiotic plus Tigecycline, Vancomycin or Teicoplanin are not recommended. The best combinations of antibiotics are those which include bactericidal antibiotics such as Carbapenems, Fosfomycin, Amikacin, Polymyxins, Rifampicin and Ampicillin/Sulbactam. Copyright © 2015. Published by Elsevier B.V.

Global Dissemination of Carbapenemase-Producing Klebsiella pneumoniae: Epidemiology, Genetic Context, Treatment Options, and Detection Methods

PubMed Central

Lee, Chang-Ro; Lee, Jung Hun; Park, Kwang Seung; Kim, Young Bae; Jeong, Byeong Chul; Lee, Sang Hee

2016-01-01

The emergence of carbapenem-resistant Gram-negative pathogens poses a serious threat to public health worldwide. In particular, the increasing prevalence of carbapenem-resistant Klebsiella pneumoniae is a major source of concern. K. pneumoniae carbapenemases (KPCs) and carbapenemases of the oxacillinase-48 (OXA-48) type have been reported worldwide. New Delhi metallo-β-lactamase (NDM) carbapenemases were originally identified in Sweden in 2008 and have spread worldwide rapidly. In this review, we summarize the epidemiology of K. pneumoniae producing three carbapenemases (KPCs, NDMs, and OXA-48-like). Although the prevalence of each resistant strain varies geographically, K. pneumoniae producing KPCs, NDMs, and OXA-48-like carbapenemases have become rapidly disseminated. In addition, we used recently published molecular and genetic studies to analyze the mechanisms by which these three carbapenemases, and major K. pneumoniae clones, such as ST258 and ST11, have become globally prevalent. Because carbapenemase-producing K. pneumoniae are often resistant to most β-lactam antibiotics and many other non-β-lactam molecules, the therapeutic options available to treat infection with these strains are limited to colistin, polymyxin B, fosfomycin, tigecycline, and selected aminoglycosides. Although, combination therapy has been recommended for the treatment of severe carbapenemase-producing K. pneumoniae infections, the clinical evidence for this strategy is currently limited, and more accurate randomized controlled trials will be required to establish the most effective treatment regimen. Moreover, because rapid and accurate identification of the carbapenemase type found in K. pneumoniae may be difficult to achieve through phenotypic antibiotic susceptibility tests, novel molecular detection techniques are currently being developed. PMID:27379038

Mononuclear non-heme iron enzymes with the 2-His-1-carboxylate facial triad: recent developments in enzymology and modeling studies.

PubMed

Bruijnincx, Pieter C A; van Koten, Gerard; Klein Gebbink, Robertus J M

2008-12-01

Iron-containing enzymes are one of Nature's main means of effecting key biological transformations. The mononuclear non-heme iron oxygenases and oxidases have received the most attention recently, primarily because of the recent availability of crystal structures of many different enzymes and the stunningly diverse oxidative transformations that these enzymes catalyze. The wealth of available structural data has furthermore established the so-called 2-His-1-carboxylate facial triad as a new common structural motif for the activation of dioxygen. This superfamily of mononuclear iron(ii) enzymes catalyzes a wide range of oxidative transformations, ranging from the cis-dihydroxylation of arenes to the biosynthesis of antibiotics such as isopenicillin and fosfomycin. The remarkable scope of oxidative transformations seems to be even broader than that associated with oxidative heme enzymes. Not only are many of these oxidative transformations of key biological importance, many of these selective oxidations are also unprecedented in synthetic organic chemistry. In this critical review, we wish to provide a concise background on the chemistry of the mononuclear non-heme iron enzymes characterized by the 2-His-1-carboxylate facial triad and to discuss the many recent developments in the field. New examples of enzymes with unique reactivities belonging to the superfamily have been reported. Furthermore, key insights into the intricate mechanistic details and reactive intermediates have been obtained from both enzyme and modeling studies. Sections of this review are devoted to each of these subjects, i.e. the enzymes, biomimetic models, and reactive intermediates (225 references).

Sewage sludge and liquid pig manure as possible sources of antibiotic resistant bacteria.

PubMed

Hölzel, Christina S; Schwaiger, Karin; Harms, Katrin; Küchenhoff, Helmut; Kunz, Anne; Meyer, Karsten; Müller, Christa; Bauer, Johann

2010-05-01

Within the last decades, the environmental spread of antibiotic resistant bacteria has become a topic of concern. In this study, liquid pig manure (n=305) and sewage sludge (n=111) - used as agricultural fertilizers between 2002 and 2005 - were investigated for the presence of Escherichia coli, Enterococcus faecalis and Enterococcus faecium. Bacteria were tested for their resistance against 40 chemotherapeutics including several "reserve drugs". E. coli (n=613) from pig manure were at a significantly higher degree resistant to streptomycin, doxycycline, spectinomycin, cotrimoxazole, and chloramphenicol than E. coli (n=116) from sewage sludge. Enterococci (Ent. faecalis, n=387, and Ent. faecium, n=183) from pig manure were significantly more often resistant to high levels of doxycycline, rifampicin, erythromycin, and streptomycin than Ent. faecalis (n=44) and Ent. faecium (n=125) from sewage sludge. Significant differences in enterococcal resistance were also seen for tylosin, chloramphenicol, gentamicin high level, fosfomycin, clindamicin, enrofloxacin, moxifloxacin, nitrofurantoin, and quinupristin/dalfopristin. By contrast, aminopenicillins were more effective in enterococci from pig manure, and mean MIC-values of piperacillin+tazobactam and third generation cefalosporines were significantly lower in E. coli from pig manure than in E. coli from sewage sludge. 13.4% (E. coli) to 25.3% (Ent. faecium) of pig manure isolates were high-level multiresistant to substances from more than three different classes of antimicrobial agents. In sewage sludge, high-level-multiresistance reached from 0% (Ent. faecalis) to 16% (Ent. faecium). High rates of (multi-) resistant bacteria in pig manure emphasize the need for a prudent - cautious - use of antibiotics in farm animals. Copyright 2010 Elsevier Inc. All rights reserved.

New pharmacological treatments for methicillin-resistant Staphylococcus aureus infections.

PubMed

Burke, Stuart L; Rose, Warren E

2014-03-01

Despite available treatment options for methicillin-resistant Staphylococcus aureus (MRSA), the morbidity and mortality attributed to the diverse infection manifestations of this pathogen remain high. More anti-MRSA agents are needed as options for treatment of these infections. Ideally, these new agents would be rapidly bactericidal for bloodstream clearance in septic patients, have few toxicities, be active against MRSA in biofilms, be easy to administer, and have oral bioavailability. This review focuses on MRSA agents in Phase III trials or antibiotics currently in the market, which are being studied for new indications. For each agent, the antimicrobial potency against MRSA, pharmacokinetic and pharmacodynamic considerations and approved and potential new indications are presented. The role of novel combination therapies is also introduced. The new lipoglycopeptides oritavancin, telavancin and dalbavancin have the potential to make a large impact on the treatment of MRSA due to unique pharmacokinetic/pharmacodynamic properties and proposed dosing regimens. Other new agents (omadacycline and tedizolid) as well as revisited older agents (fosfomycin and fusidic acid) appear promising but require further study for their potential role. Combination therapy may improve outcomes in patients with high MRSA infection burden or when patient or pathogen factors predict a worse outcome with monotherapy.

Protective effect of Lactobacillus casei strain Shirota against lethal infection with multi-drug resistant Salmonella enterica serovar Typhimurium DT104 in mice.

PubMed

Asahara, T; Shimizu, K; Takada, T; Kado, S; Yuki, N; Morotomi, M; Tanaka, R; Nomoto, K

2011-01-01

The anti-infectious activity of lactobacilli against multi-drug resistant Salmonella enterica serovar Typhimurium DT104 (DT104) was examined in a murine model of an opportunistic antibiotic-induced infection. Explosive intestinal growth and subsequent lethal extra-intestinal translocation after oral infection with DT104 during fosfomycin (FOM) administration was significantly inhibited by continuous oral administration of Lactobacillus casei strain Shirota (LcS), which is naturally resistant to FOM, at a dose of 10(8) colony-forming units per mouse daily to mice. Comparison of the anti-Salmonella activity of several Lactobacillus type strains with natural resistance to FOM revealed that Lactobacillus brevis ATCC 14869(T) , Lactobacillus plantarum ATCC 14917(T) , Lactobacillus reuteri JCM 1112(T) , Lactobacillus rhamnosus ATCC 7469(T) and Lactobacillus salivarius ATCC 11741(T) conferred no activity even when they obtained the high population levels almost similar to those of the effective strains such as LcS, Lact. casei ATCC 334(T) and Lactobacillus zeae ATCC 15820(T) . The increase in concentration of organic acids and maintenance of the lower pH in the intestine because of Lactobacillus colonization were correlated with the anti-infectious activity. Moreover, heat-killed LcS was not protective against the infection, suggesting that the metabolic activity of lactobacilli is important for the anti-infectious activity. These results suggest that certain lactobacilli in combination with antibiotics may be useful for prophylaxis against opportunistic intestinal infections by multi-drug resistant pathogens, such as DT104. Antibiotics such as FOM disrupt the metabolic activity of the intestinal microbiota that produce organic acids, and that only probiotic strains that are metabolically active in vivo should be selected to prevent intestinal infection when used clinically in combination with certain antibiotics. © 2010 The Authors. Journal of Applied Microbiology © 2010 The Society for Applied Microbiology.

Prevention of recurrent urinary tract infections.

PubMed

Wagenlehner, F M E; Vahlensieck, W; Bauer, H W; Weidner, W; Piechota, H J; Naber, K G

2013-03-01

Urinary tract infections (UTI) are among the most frequent bacterial infections in the community and health care setting. Mostly young and, to some extent, postmenopausal women are affected by recurrent UTI (rUTI) defined as ≥3 UTI/year or ≥2 UTI/half year. In contrast, rUTI is rare in healthy men. On the other hand, rUTI are frequently found in female and male patients with complicating urological factors, e.g. urinary catheters, infection stones. Remediable predisposing factors in uncomplicated rUTI in women are rare. In complicated rUTI the success depends mainly on the possibility to eliminate or at leastimprove the complicating risk factors. Continuous antibiotic prophylaxis or postcoital prophylaxis, if there is close correlation with sexual intercourse, are most effective to prevent rUTI. Nitrofurantoin, trimethoprim (or cotrimoxazole), and fosfomycin trometamol are available as first-line drugs. Oral cephalosporins and quinolones should be restricted to specific indications. Antibiotic prophylaxis reduces the number of uropathogens in the gut and/or vaginal flora and reduces bacterial "fitness". Given the correct indication, the recurrence rate of rUTI can be reduced by about 90%. Due to possible adverse events and the concern of selecting resistant pathogens, according to the guidelines of the European Association of Urology antimicrobial prophylaxis should be considered only after counselling, behavioural modification and non-antimicrobial measures have been attempted. In postmenopausal patients vaginal substitution of oestriol should be started first. Oral or parenteral immunoprophylaxis is another option in patients with rUTI. Other possibilities with varying scientific evidence are prophylaxis with cranberry products, specific plant combinations or probiotics. The prophylaxis of catheter-associated UTI should employ strategies which result in a reduction of frequency and duration of catheter drainage of the urinary tract. The currently available catheter materials have only little influence on reducing catheter-associated rUTI.

Comparison of reduced metagenome and 16S rRNA gene sequencing for determination of genetic diversity and mother-child overlap of the gut associated microbiota.

PubMed

Ravi, Anuradha; Avershina, Ekaterina; Angell, Inga Leena; Ludvigsen, Jane; Manohar, Prasanth; Padmanaban, Sumathi; Nachimuthu, Ramesh; Snipen, Lars; Rudi, Knut

2018-06-01

Use of the 16S rRNA gene in microbiota studies is limited by the lack of taxonomic and functional resolution. High resolution analyses are particularly important for understanding transmission and persistence of bacteria. The aim of our work was therefore to compare a novel reduced metagenome sequencing (RMS) approach with 16S rRNA gene sequencing to determine both the metagenome genetic diversity and the mother-to-child sharing of the microbiota in a cohort of 17 mother-child pairs. We found that although both approaches gave comparable results with respect to sample separation and taxonomy, RMS gave higher resolution and the potential for genomic-/functional assignment. Using RMS we estimated that the metagenome size increased from about 60 Mbp for 4-day-old children to about 225 Mbp for mothers. The 4-day-old children shared 7% of the metagenome sequences with the mothers, while the metagenome sequence sharing was >30% among the mothers. We found 15 genomes shared across >50% of the mothers, of which 10 belonged to Clostridia. Only Bacteroides showed a direct mother-child association, with B. vulgatus being abundant in both 4-day-old children and mothers. For the functional assignments, we identified a significant association between antibiotic usage during labor, and quantity of Fosfomycin resistance genes. In conclusion, our results show a higher functional and taxonomic resolution for RMS compared to 16S rRNA gene sequencing, where RMS enabled a detailed description of mother to child gut microbiota transmission - supporting a late recruitment of most gut bacteria and an effect of antibiotic treatment during labor on infant antibiotic resistance gene patterns. Copyright © 2018. Published by Elsevier B.V.

In-vitro activity of several antimicrobial agents against methicillin-resistant Staphylococcus aureus (MRSA) isolates expressing aminoglycoside-modifying enzymes: potency of plazomicin alone and in combination with other agents.

PubMed

López Díaz, María Carmen; Ríos, Esther; Rodríguez-Avial, Iciar; Simaluiza, Rosa Janneth; Picazo, Juan José; Culebras, Esther

2017-08-01

This study investigated the in-vitro activity of clinically relevant aminoglycosides and new antimicrobial agents-plazomicin, ceftobiprole and dalbavancin-against 55 methicillin-resistant Staphylococcus aureus (MRSA) isolates producing aminoglycoside-modifying enzymes (AMEs). The checkerboard method was used to assess synergism between plazomicin and four antibiotics (fosfomycin, ceftobiprole, cefoxitin and meropenem), and time-kill assays were performed for the most active combinations. Among the aminoglycosides tested, plazomicin was the most active agent against MRSA, with >90% of isolates being inhibited at a minimum inhibitory concentration (MIC) of ≤1 mg/L. MIC 50 and MIC 90 values for ceftobiprole and dalbavancin were 2 and 4 mg/L, and 0.125 and 0.125 mg/L, respectively. The most prevalent AME gene was aac(6')Ie-aph(2″)Ia (87.3%), followed by ant(4')Ia (52.7%) and aph(3')IIIa (52.7%). Plazomicin activity was not affected by the type or number of enzymes detected. In checkerboard and time-kill assays, indifference was the most common result achieved for the antibiotic combinations. Notably, no antagonism was observed with any combination tested. Overall, plazomicin in combination with meropenem had the highest synergistic effect, demonstrating synergy against seven isolates in the checkerboard assay and three isolates in time-kill curves. In conclusion, plazomicin showed potent activity against aminoglycoside-resistant MRSA isolates, regardless of the number and type of AMEs present. These findings indicate the potential utility of plazomicin in combination with meropenem for the treatment of MRSA infections. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Gut Microbiome of an 11th Century A.D. Pre-Columbian Andean Mummy

PubMed Central

Santiago-Rodriguez, Tasha M.; Fornaciari, Gino; Luciani, Stefania; Dowd, Scot E.; Toranzos, Gary A.; Marota, Isolina; Cano, Raul J.

2015-01-01

The process of natural mummification is a rare and unique process from which little is known about the resulting microbial community structure. In the present study, we characterized the microbiome of paleofeces, and ascending, transverse and descending colon of an 11th century A.D. pre-Columbian Andean mummy by 16S rRNA gene high-throughput sequencing and metagenomics. Firmicutes were the most abundant bacterial group, with Clostridium spp. comprising up to 96.2% of the mummified gut, while Turicibacter spp. represented 89.2% of the bacteria identified in the paleofeces. Microbiome profile of the paleofeces was unique when compared to previously characterized coprolites that did not undergo natural mummification. We identified DNA sequences homologous to Clostridium botulinum, Trypanosoma cruzi and human papillomaviruses (HPVs). Unexpectedly, putative antibiotic-resistance genes including beta-lactamases, penicillin-binding proteins, resistance to fosfomycin, chloramphenicol, aminoglycosides, macrolides, sulfa, quinolones, tetracycline and vancomycin, and multi-drug transporters, were also identified. The presence of putative antibiotic-resistance genes suggests that resistance may not necessarily be associated with a selective pressure of antibiotics or contact with European cultures. Identification of pathogens and antibiotic-resistance genes in ancient human specimens will aid in the understanding of the evolution of pathogens as a way to treat and prevent diseases caused by bacteria, microbial eukaryotes and viruses. PMID:26422376

Antimicrobial resistance of Listeria spp. recovered from processed bison.

PubMed

Li, Q; Sherwood, J S; Logue, C M

2007-01-01

The current study examined the antimicrobial susceptibility of 86 Listeria spp. isolated from processed bison carcasses. Susceptibility to 25 antimicrobial agents was determined using E-test and National Antimicrobial Resistance Monitoring System (NARMS) panels. Most Listeria isolates (88-98%) exhibited resistance to bacitracin, oxacillin, cefotaxime, and fosfomycin. Resistance to tetracycline (18.6%) was also common. Of the 16 tetracycline-resistant Listeria isolates, 15 carried tetM and 2 contained integrase of Tn1545 transposons. Rifampicin and trimethoprim-sulfamethoxazole were the most active antimicrobial agents against Listeria spp., with a MIC(90) of 0.38 microg ml(-1). Ampicillin, erythromycin, penicillin, gentamicin, and tobramycin also exhibited good activity against Listeria spp., with MIC(90) not exceeding 1 microg ml(-1). Differences in resistance among Listeria spp. was displayed, as Listeria innocua strains were more resistant than other Listeria species. The study showed that Listeria monocytogenes strains from bison were susceptible to the antibiotics most commonly used to treat human listeriosis. However, the presence of antimicrobial resistance in L. innocua indicates the potential for transfer of resistance and a conjugative transposon to L. monocytogenes. The findings of our study will provide useful information for the development of public health policy in the use of antimicrobials in food animal production.

Antibiotics-related adverse events in the infectious diseases department of a French teaching hospital: a prospective study.

PubMed

Courjon, J; Pulcini, C; Cua, E; Risso, K; Guillouet, F; Bernard, E; Roger, P-M

2013-12-01

Antibiotics are a significant cause of adverse events (AE), but few studies have focused on prescriptions in hospitalized patients. In infectious diseases departments, the high frequency and diversity of antibiotics prescribed makes AE post-marketing monitoring easier. The aim of our study was to assess the incidence and type of AE in the infectious diseases department of a French teaching tertiary-care hospital. The main characteristics of each hospitalization, including all antibiotics prescribed and any significant AE were recorded prospectively in the medical dashboard of the department. We included all patients having suffered an AE due to systemic antibiotics between January 2008 and March 2011. Among the 3963 hospitalized patients, 2682 (68%) received an antibiotic and 151/2682 (5.6%) suffered an AE. Fifty-two (34%) AE were gastrointestinal disorders, 32 (21%) dermatological, 20 (13%) hepatobiliary, 16 (11%) renal and urinary disorders, 13 (9%) neurological and 11 (7%) blood disorders. Rifampin, fosfomycin, cotrimoxazole and linezolid were the leading causes of AE. Sixty-two percent of the antibiotics causing an AE were stopped and 38% were continued (including 11% with a dose modification). Patients suffering from AE had an increased length of stay (18 vs 10 days, P < 0.001). Our data could help choosing the safest antibiotic when several options are possible.

Poultry hatcheries as potential reservoirs for antimicrobial-resistant Escherichia coli: A risk to public health and food safety.

PubMed

Osman, Kamelia M; Kappell, Anthony D; Elhadidy, Mohamed; ElMougy, Fatma; El-Ghany, Wafaa A Abd; Orabi, Ahmed; Mubarak, Aymen S; Dawoud, Turki M; Hemeg, Hassan A; Moussa, Ihab M I; Hessain, Ashgan M; Yousef, Hend M Y

2018-04-11

Hatcheries have the power to spread antimicrobial resistant (AMR) pathogens through the poultry value chain because of their central position in the poultry production chain. Currently, no information is available about the presence of AMR Escherichia coli strains and the antibiotic resistance genes (ARGs) they harbor within hatchezries. Therefore, this study aimed to investigate the possible involvement of hatcheries in harboring hemolytic AMR E. coli. Serotyping of the 65 isolated hemolytic E. coli revealed 15 serotypes with the ability to produce moderate biofilms, and shared susceptibility to cephradine and fosfomycin and resistance to spectinomycin. The most common β-lactam resistance gene was bla TEM , followed by bla OXA-1 , bla MOX -like , bla CIT -like , bla SHV and bla FOX . Hierarchical clustering of E. coli isolates based on their phenotypic and genotypic profiles revealed separation of the majority of isolates from hatchlings and the hatchery environments, suggesting that hatchling and environmental isolates may have different origins. The high frequency of β-lactam resistance genes in AMR E. coli from chick hatchlings indicates that hatcheries may be a reservoir of AMR E. coli and can be a major contributor to the increased environmental burden of ARGs posing an eminent threat to poultry and human health.

Comparative genomics analyses revealed two virulent Listeria monocytogenes strains isolated from ready-to-eat food.

PubMed

Lim, Shu Yong; Yap, Kien-Pong; Thong, Kwai Lin

2016-01-01

Listeria monocytogenes is an important foodborne pathogen that causes considerable morbidity in humans with high mortality rates. In this study, we have sequenced the genomes and performed comparative genomics analyses on two strains, LM115 and LM41, isolated from ready-to-eat food in Malaysia. The genome size of LM115 and LM41 was 2,959,041 and 2,963,111 bp, respectively. These two strains shared approximately 90% homologous genes. Comparative genomics and phylogenomic analyses revealed that LM115 and LM41 were more closely related to the reference strains F2365 and EGD-e, respectively. Our virulence profiling indicated a total of 31 virulence genes shared by both analysed strains. These shared genes included those that encode for internalins and L. monocytogenes pathogenicity island 1 (LIPI-1). Both the Malaysian L. monocytogenes strains also harboured several genes associated with stress tolerance to counter the adverse conditions. Seven antibiotic and efflux pump related genes which may confer resistance against lincomycin, erythromycin, fosfomycin, quinolone, tetracycline, and penicillin, and macrolides were identified in the genomes of both strains. Whole genome sequencing and comparative genomics analyses revealed two virulent L. monocytogenes strains isolated from ready-to-eat foods in Malaysia. The identification of strains with pathogenic, persistent, and antibiotic resistant potentials from minimally processed food warrant close attention from both healthcare and food industry.

Parallel Evolution of High-Level Aminoglycoside Resistance in Escherichia coli Under Low and High Mutation Supply Rates.

PubMed

Ibacache-Quiroga, Claudia; Oliveros, Juan C; Couce, Alejandro; Blázquez, Jesus

2018-01-01

Antibiotic resistance is a major concern in public health worldwide, thus there is much interest in characterizing the mutational pathways through which susceptible bacteria evolve resistance. Here we use experimental evolution to explore the mutational pathways toward aminoglycoside resistance, using gentamicin as a model, under low and high mutation supply rates. Our results show that both normo and hypermutable strains of Escherichia coli are able to develop resistance to drug dosages > 1,000-fold higher than the minimal inhibitory concentration for their ancestors. Interestingly, such level of resistance was often associated with changes in susceptibility to other antibiotics, most prominently with increased resistance to fosfomycin. Whole-genome sequencing revealed that all resistant derivatives presented diverse mutations in five common genetic elements: fhuA, fusA and the atpIBEFHAGDC, cyoABCDE , and potABCD operons. Despite the large number of mutations acquired, hypermutable strains did not pay, apparently, fitness cost. In contrast to recent studies, we found that the mutation supply rate mainly affected the speed (tempo) but not the pattern (mode) of evolution: both backgrounds acquired the mutations in the same order, although the hypermutator strain did it faster. This observation is compatible with the adaptive landscape for high-level gentamicin resistance being relatively smooth, with few local maxima; which might be a common feature among antibiotics for which resistance involves multiple loci.

Parallel Evolution of High-Level Aminoglycoside Resistance in Escherichia coli Under Low and High Mutation Supply Rates

PubMed Central

Ibacache-Quiroga, Claudia; Oliveros, Juan C.; Couce, Alejandro; Blázquez, Jesus

2018-01-01

Antibiotic resistance is a major concern in public health worldwide, thus there is much interest in characterizing the mutational pathways through which susceptible bacteria evolve resistance. Here we use experimental evolution to explore the mutational pathways toward aminoglycoside resistance, using gentamicin as a model, under low and high mutation supply rates. Our results show that both normo and hypermutable strains of Escherichia coli are able to develop resistance to drug dosages > 1,000-fold higher than the minimal inhibitory concentration for their ancestors. Interestingly, such level of resistance was often associated with changes in susceptibility to other antibiotics, most prominently with increased resistance to fosfomycin. Whole-genome sequencing revealed that all resistant derivatives presented diverse mutations in five common genetic elements: fhuA, fusA and the atpIBEFHAGDC, cyoABCDE, and potABCD operons. Despite the large number of mutations acquired, hypermutable strains did not pay, apparently, fitness cost. In contrast to recent studies, we found that the mutation supply rate mainly affected the speed (tempo) but not the pattern (mode) of evolution: both backgrounds acquired the mutations in the same order, although the hypermutator strain did it faster. This observation is compatible with the adaptive landscape for high-level gentamicin resistance being relatively smooth, with few local maxima; which might be a common feature among antibiotics for which resistance involves multiple loci. PMID:29615988

Dissemination of a Multidrug-Resistant VIM-1- and CMY-99-Producing Proteus mirabilis Clone in Bulgaria.

PubMed

Markovska, Rumyana; Schneider, Ines; Keuleyan, Emma; Ivanova, Dobrinka; Lesseva, Magdalena; Stoeva, Temenuga; Sredkova, Mariya; Bauernfeind, Adolf; Mitov, Ivan

2017-04-01

The aim of this study was to analyze the beta-lactamases and the molecular epidemiology of 19 clinically significant isolates of Proteus mirabilis with decreased susceptibility to imipenem, which have been collected from seven hospitals, located in different Bulgarian towns (Sofia, Varna, and Pleven). The isolates were obtained from blood, urine, tracheal and wound specimens. One additional isolate from hospital environment was included. Susceptibility testing, conjugation experiments, and plasmid replicon typing were carried out. Beta-lactamases were characterized by isoelectric focusing, PCR, and sequencing. Clonal relatedness was investigated by RAPD and PFGE. Integron mapping was performed by PCR and sequencing. All isolates showed a multidrug-resistance profile, but remained susceptible to piperacillin/tazobactam, cefepime, meropenem, and fosfomycin. They produced identical beta-lactamases, namely: TEM-1, VIM-1, and CMY-99. PCR mapping revealed that the bla VIM-1 gene was part of a class 1 integron that additionally included the aac(6')-I, dhfrA1, and ant(3″)-Ia genes. In addition, 17 of the isolates carried the armA gene. Conjugation experiments and plasmid replicon typing were unsuccessful. The isolates were clonally related according to RAPD and PFGE typing. This study reveals the nationwide distribution of a multidrug-resistant P. mirabilis clone producing VIM-1 and CMY-99 along with the presence of different aminoglycoside resistance mechanisms.

Isolation, identification and antimicrobial sensitivity of Ornithobacterium rhinotracheale in broilers chicken flocks of Khuzestan, Iran

PubMed Central

Mayahi, Mansour; Gharibi, Darioush; Ghadimipour, Rahim; Talazadeh, Forough

2016-01-01

Ornithobacterium rhinotracheale (ORT) is a bacterium associated with respiratory disease, growth retardation, decreased egg production and mortality in chickens and turkeys. The objective of this study was isolation, identification and evaluation of antimicrobial susceptibility of ORT bacterium in slaughtered broilers chicken flocks based on cultural and molecular tests in Khuzestan province, south-west of Iran. A total of 210 tracheal swab samples were collected from 21 broiler flocks slaughtered in abattoirs of the province. The results of cultural and biochemical tests showed that 23 (10.95%) isolates from tracheal swabs of 4 flocks (19.04%) were identified as ORT, but according to molecular characterization, 18 (8.57%) ORT isolates were positive in PCR assay and produced the predicted 784 bp amplification product. Finally, using the disk diffusion method, the drug resistance patterns of ORT isolates were determined against a panel of commonly used antimicrobial agents. Antimicrobial susceptibility test revealed that all isolates (100%) were sensitive to tetracycline, florfenicol and cephalexin. The highest antimicrobial resistance (89.00%) was seen for fosfomycin, sultrim and gentamicin. The results of present research showed that there was significant difference between the isolation rates of ORT from various areas of the province. As well, our findings indicated that the simultaneous use of both cultural and molecular techniques results in more comprehensive outcomes in the isolation and identification of the organismfrom understudy hosts. PMID:28144427

Bacillithiol, a New Player in Bacterial Redox Homeostasis

PubMed Central

2011-01-01

Abstract Bacillithiol (BSH), the α-anomeric glycoside of l-cysteinyl-d-glucosamine with l-malic acid, plays a dominant role in the cytosolic thiol redox chemistry of the low guanine and cytosine (GC) Gram-positive bacteria (phylum Firmicutes). BSH is functionally analogous to glutathione (GSH) but differs sufficiently in chemical structure that cells have evolved a distinct set of enzymes that use BSH as cofactor. BSH was discovered in Bacillus subtilis as a mixed disulfide with the redox-sensing repressor OhrR and in B. anthracis by biochemical analysis of pools of labeled thiols. The structure of BSH was determined after purification from Deinococcus radiodurans. Similarities in structure between BSH and mycothiol (MSH) facilitated the identification of biosynthetic genes for BSH in the model organism B. subtilis. Phylogenomic analyses have identified several candidate BSH-using or associated proteins, including a BSH reductase, glutaredoxin-like thiol-dependent oxidoreductases (bacilliredoxins), and a BSH-S-transferase (FosB) involved in resistance to the epoxide antibiotic fosfomycin. Preliminary results implicate BSH in cellular processes to maintain cytosolic redox balance and for adaptation to reactive oxygen, nitrogen, and electrophilic species. BSH also is predicted to chelate metals avidly, in part due to the appended malate moiety, although the implications of BSH for metal ion homeostasis have yet to be explored in detail. Antioxid. Redox Signal. 15, 123–133. PMID:20712413

Efficacy of non-carbapenem antibiotics for pediatric patients with first febrile urinary tract infection due to extended-spectrum beta-lactamase-producing Escherichia coli.

PubMed

Abe, Yoshifusa; Inan-Erdogan, Işil; Fukuchi, Kunihiko; Wakabayashi, Hitomi; Ogawa, Yasuha; Hibino, Satoshi; Sakurai, Shunsuke; Matsuhashi, Kazuhiko; Watanabe, Yoshitaka; Hashimoto, Kaori; Ugajin, Kazuhisa; Itabashi, Kazuo

2017-08-01

Although carbapenem is the recommended for urinary tract infection (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing organisms, non-carbapenems have been reported to be effective for adult patients with UTI caused by ESBL-producing organisms. The purpose of this study was to evaluate the efficacy of non-carbapenems for pediatric patients with UTI due to ESBL-producing Escherichia coli (E. coli) based on the microbiologic and clinical outcomes. Fifteen children, who were treated for first febrile UTI caused by ESBL-producing E. coli were enrolled in this study. Antimicrobial susceptibilities and ESBL production were determined according to the Clinical and Laboratory Standards Institute guidelines. To detect CTX-M genes, polymerase chain reaction was performed with specific primers for bla CTX-M detection. Of the 15 enrolled patients, 10 (66.7%) were boys and 5 (33.3%) were girls, with a median age of four months. VUR was detected in six patients (40%). For detection of bla CTX-M by PCR, CTX-M-3, CTX-M-8, CTX-M-14, and CTX-M-15 were detected in five, one, eight, and one patient, respectively. Overall, 14 of the 15 isolates (93.3%) were susceptible for fosfomycin (FOM), and all isolates were susceptible for cefmetazole (CMZ), flomoxef (FMOX), and imipenem/cilastatin (IPM/CS). Of the 15 patients, 12 (80%) clinically improved without the use of carbapenems. In conclusion, even if isolates of ESBL-producing E. coli are multidrug resistant based on MIC assessment, clinical susceptibility to non-carbapenems, such as CMZ, FMOX, and FOM, is possible. Accordingly, carbapenems may not be required all the time for treatment of pediatric UTI in clinical practice. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Diversity of Antibiotic Resistance Genes in Enterococcus Strains Isolated from Ready-to-Eat Meat Products.

PubMed

Chajęcka-Wierzchowska, Wioleta; Zadernowska, Anna; Łaniewska-Trokenheim, Łucja

2016-10-25

The objective of the study was to answer the question of whether the ready-to-eat meat products can pose indirect hazard for consumer health serving as reservoir of Enterococcus strains harboring tetracyclines, aminoglycosides, and macrolides resistance genes. A total of 390 samples of ready-to-eat meat products were investigated. Enterococcus strains were found in 74.1% of the samples. A total of 302 strains were classified as: Enterococcus faecalis (48.7%), Enterococcus faecium (39.7%), Enterococcus casseliflavus (4.3%), Enterococcus durans (3.0%), Enterococcus hirae (2.6%), and other Enterococcus spp. (1.7%). A high percentage of isolates were resistant to streptomycin high level (45%) followed by erythromycin (42.7%), fosfomycin (27.2%), rifampicin (19.2%), tetracycline (36.4%), tigecycline (19.9%). The ant(6')-Ia gene was the most frequently found gene (79.6%). Among the other genes that encode aminoglycosides-modifying enzymes, the highest portion of the strains had the aac(6')-Ie-aph(2'')-Ia (18.5%) and aph(3'')-IIIa (16.6%), but resistance of isolates from food is also an effect of the presence of aph(2'')-Ib, aph(2'')-Ic, aph(2'')-Id genes. Resistance to tetracyclines was associated with the presence of tetM (43.7%), tetL (32.1%), tetK (14.6%), tetW (0.7%), and tetO (0.3%) genes. The ermB and ermA genes were found in 33.8% and 18.9% of isolates, respectively. Nearly half of the isolates contained a conjugative transposon of the Tn916/Tn1545 family. Enterococci are widely present in retail ready-to-eat meat products. Many isolated strains (including such species as E. casseliflavus, E. durans, E. hirae, and Enterococcus gallinarum) are antibiotic resistant and carry transferable resistance genes. © 2016 Institute of Food Technologists®.

A Drug Combination Screen Identifies Drugs Active against Amoxicillin-Induced Round Bodies of In Vitro Borrelia burgdorferi Persisters from an FDA Drug Library

PubMed Central

Feng, Jie; Shi, Wanliang; Zhang, Shuo; Sullivan, David; Auwaerter, Paul G.; Zhang, Ying

2016-01-01

Although currently recommended antibiotics for Lyme disease such as doxycycline or amoxicillin cure the majority of the patients, about 10–20% of patients treated for Lyme disease may experience lingering symptoms including fatigue, pain, or joint and muscle aches. Under experimental stress conditions such as starvation or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which are a type of persister bacteria that appear resistant in vitro to customary first-line antibiotics for Lyme disease. To identify more effective drugs with activity against the round body form of B. burgdorferi, we established a round body persister model induced by exposure to amoxicillin (50 μg/ml) and then screened the Food and Drug Administration drug library consisting of 1581 drug compounds and also 22 drug combinations using the SYBR Green I/propidium iodide viability assay. We identified 23 drug candidates that have higher activity against the round bodies of B. burgdorferi than either amoxicillin or doxycycline. Eleven individual drugs scored better than metronidazole and tinidazole which have been previously described to be active against round bodies. In this amoxicillin-induced round body model, some drug candidates such as daptomycin and clofazimine also displayed enhanced activity which was similar to a previous screen against stationary phase B. burgdorferi persisters not exposure to amoxicillin. Additional candidate drugs active against round bodies identified include artemisinin, ciprofloxacin, nifuroxime, fosfomycin, chlortetracycline, sulfacetamide, sulfamethoxypyridazine and sulfathiozole. Two triple drug combinations had the highest activity against amoxicillin-induced round bodies and stationary phase B. burgdorferi persisters: artemisinin/cefoperazone/doxycycline and sulfachlorpyridazine/daptomycin/doxycycline. These findings confirm and extend previous findings that certain drug combinations have superior activity against B. burgdorferi persisters in vitro, even when pre-treated with amoxicillin. These findings may have implications for improved treatment of Lyme disease. PMID:27242757

A Drug Combination Screen Identifies Drugs Active against Amoxicillin-Induced Round Bodies of In Vitro Borrelia burgdorferi Persisters from an FDA Drug Library.

PubMed

Feng, Jie; Shi, Wanliang; Zhang, Shuo; Sullivan, David; Auwaerter, Paul G; Zhang, Ying

2016-01-01

Although currently recommended antibiotics for Lyme disease such as doxycycline or amoxicillin cure the majority of the patients, about 10-20% of patients treated for Lyme disease may experience lingering symptoms including fatigue, pain, or joint and muscle aches. Under experimental stress conditions such as starvation or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which are a type of persister bacteria that appear resistant in vitro to customary first-line antibiotics for Lyme disease. To identify more effective drugs with activity against the round body form of B. burgdorferi, we established a round body persister model induced by exposure to amoxicillin (50 μg/ml) and then screened the Food and Drug Administration drug library consisting of 1581 drug compounds and also 22 drug combinations using the SYBR Green I/propidium iodide viability assay. We identified 23 drug candidates that have higher activity against the round bodies of B. burgdorferi than either amoxicillin or doxycycline. Eleven individual drugs scored better than metronidazole and tinidazole which have been previously described to be active against round bodies. In this amoxicillin-induced round body model, some drug candidates such as daptomycin and clofazimine also displayed enhanced activity which was similar to a previous screen against stationary phase B. burgdorferi persisters not exposure to amoxicillin. Additional candidate drugs active against round bodies identified include artemisinin, ciprofloxacin, nifuroxime, fosfomycin, chlortetracycline, sulfacetamide, sulfamethoxypyridazine and sulfathiozole. Two triple drug combinations had the highest activity against amoxicillin-induced round bodies and stationary phase B. burgdorferi persisters: artemisinin/cefoperazone/doxycycline and sulfachlorpyridazine/daptomycin/doxycycline. These findings confirm and extend previous findings that certain drug combinations have superior activity against B. burgdorferi persisters in vitro, even when pre-treated with amoxicillin. These findings may have implications for improved treatment of Lyme disease.

In vitro activity of colistin mono- and combination therapy against colistin-resistant Acinetobacter baumannii, mechanism of resistance, and clinical outcomes of patients infected with colistin-resistant A. baumannii at a Thai university hospital.

PubMed

Lertsrisatit, Yongyut; Santimaleeworagun, Wichai; Thunyaharn, Sudaluck; Traipattanakul, Jantima

2017-01-01

Colistin is a drug of last resort for treating multidrug-resistant Acinetobacter baumannii infections. Unfortunately, colistin-resistant A. baumannii (CoR-AB) has been reported. Here, we examined the in vitro effect of mono- and combined antimicrobials against CoR-AB strains and their resistance mechanism, and evaluated the clinical outcomes of CoR-AB-infected patients. Seventeen clinical CoR-AB strains were isolated from patients at Phramongkutklao hospital, 2011-2015. The mono- and synergistic activities of colistin, tigecycline, sulbactam, imipenem, meropenem, amikacin, fosfomycin, and cotrimoxazole were examined by minimum inhibitory concentration (MIC) and fractional inhibitory concentration index. Clonal relationship and resistance genes were determined by repetitive extragenic palindromic polymerase chain reaction with specific primers. The effect of carbonyl cyanide 3-chlorophenylhydrazone combined with colistin was used to test efflux pump involvement. Patient treatment outcomes were also reported. The most prevalent infection in CoR-AB patients was pneumonia (35.3%), and all patients were administered colistin combined with another agent. The 30-day mortality was 70.6%, and the colistin MIC range and MIC50 was 16-512 μg/mL and 64 μg/mL, respectively. All CoR-AB strains were sensitive to tigecycline. Sporadic isolates were susceptible to sulbactam, imipenem, meropenem, and cotrimoxazole. A synergistic or additive effect was observed for colistin plus imipenem or meropenem (16.7%), sulbactam (66.7%), or tigecycline (66.7%). The CoR-AB isolates could be divided into four different clones (A-D) with a high prevalence of group B (47.1%). Eight isolates harbored blaOXA23, blaIMP , blaKPC , and blaNDM , and one contained blaOXA23 , blaIMP , and blaKPC , while the eight remaining isolates carried only blaOXA23 . The MIC values of all strains were greatly reduced for colistin plus carbonyl cyanide 3-chlorophenylhydrazone. CoR-AB clinical isolates exhibited very high colistin resistance and a high frequency of resistance genes. The mechanism of colistin resistance appears to be mediated via an efflux pump. Thus, certain antimicrobials could be used as salvage therapy for CoR-AB infection.

[Susceptibility and resistence of Pseudomonas aeruginosa to antimicrobial agents].

PubMed

Gamero Delgado, M C; García-Mayorgas, A D; Rodríguez, F; Ibarra, A; Casal, M

2007-06-01

Pseudomonas aeruginosa is an opportunistic microorganism that is frequently the cause of nosocomial infections. Multiple mechanisms are involved in its natural and acquired resistance to many of the antimicrobial agents commonly used in clinical practice. The objective of this study was to assess the susceptibility and resistance patterns of P. aeruginosa strains isolated in Hospital Reina Sofia between 2000 and 2005, as well as to analyze the differences between intrahospital and extrahospital isolates in 2005 and to compare the results with those obtained in other studies. A total of 3,019 strains of P. aeruginosa from different hospitals and nonhospital settings were evaluated, taking into consideration their degree of sensitivity to different antibiotics. The MICs were determined by means of the Wider I automated system (Soria Melguizo), taking into consideration the criteria of susceptibility and resistance recommended by MENSURA. Results of the analysis showed that P. aeruginosa maintained similar levels of antimicrobial susceptibility during the period 2000-2005, with increased susceptibility to amikacin, gentamicin and tobramycin. There were also important differences in the degree of susceptibility between intrahospital and extrahospital strains, except for imipenem and fosfomycin. The intrahospital difference in susceptibility was also evaluated, emphasizing the importance of periodically studying susceptibility and resistance patterns of P. aeruginosa in each setting in order to evaluate different therapeutic guidelines, as it is not always advisable to extrapolate data from different regions. These differences can be explained by the different use of antibiotics in each center and the geographic variations of the resistance mechanisms of P. aeruginosa.

Antibiotic susceptibility of methicillin-resistant staphylococci (MRS) of food origin: A comparison of agar disc diffusion method and a commercially available miniaturized test.

PubMed

Buzón-Durán, Laura; Capita, Rosa; Alonso-Calleja, Carlos

2018-06-01

Methicillin-resistant staphylococci (MRS) are a major concern to public and animal health. Thirty MRS (Staphylococcus aureus, S. cohnii, S. epidermidis, S. haemolyticus, S. hominis, S. lentus, S. lugdunensis, S. sciuri, and S. xylosus) isolates from meat and poultry preparations were tested for antimicrobial susceptibility to 11 antimicrobials (belonging to seven different categories) of clinical significance using both the standard agar disc diffusion method and a commercially available miniaturized system (Sensi Test Gram-positive). It is worth stressing that 16 isolates (53.33%) exhibited an extensively drug-resistant phenotype (XDR). The average number of resistances per strain was 4.67. These results suggest that retail meat and poultry preparations are a likely vehicle for the transmission of multi-drug resistant MRS. Resistance to erythromycin was the commonest finding (76.67% of strains), followed by tobramycin, ceftazidime (66.67%), ciprofloxacin (56.67%) and fosfomycin (53.33%). An agreement (kappa coefficient) of 0.64 was found between the two testing methods. Using the agar disc diffusion as the reference method, the sensitivity, specificity and accuracy of the miniaturized test were 98.44%, 69.44% and 83.33%, respectively. Most discrepancies between the two methods were due to isolates that were susceptible according to the disc diffusion method but resistant according to the miniaturized test (false positives). Copyright © 2017. Published by Elsevier Ltd.

Urinary tract infection by Acinetobacter baumannii and Pseudomonas aeruginosa: evolution of antimicrobial resistance and therapeutic alternatives.

PubMed

Jiménez-Guerra, Gemma; Heras-Cañas, Victor; Gutiérrez-Soto, Miguel; Del Pilar Aznarte-Padial, María; Expósito-Ruiz, Manuela; Navarro-Marí, José María; Gutiérrez-Fernández, José

2018-04-25

Acinetobacter baumannii and Pseudomonas aeruginosa are responsible for numerous nosocomial infections. The objective of this study was to determine the development of their susceptibility to ten antibiotics and the antibiotic consumption of patients with suspicion of urinary tract infection (UTI). A retrospective study was conducted on the susceptibility profiles of A. baumannii and P. aeruginosa isolates from 749 urine samples gathered between January 2013 and December 2016, and on the consumption of imipenem, meropenem and piperacillin-tazobactam between 2014 and 2016. Hospital patients were the source of 82 (91.1 %) of the 90 A. baumannii isolates detected and 555 (84.2 %) of the 659 P. aeruginosa isolates. Globally, the lowest percentage susceptibility values were found for fosfomycin, aztreonam and ciprofloxacin, while colistin continued to be the most active antibiotic in vitro. In 2016, the susceptibility of A. baumannii to carbapenem and piperacillin-tazobactam decreased to very low values, while the susceptibility of P. aeruginosa to carbapenem remained stable but its susceptibility to piperacillin-tazobactam decreased. There was a marked increase in the consumption of piperacillin-tazobactam. In our setting, it is no longer possible to use carbapenems and piperacillin-tazobactam for empirical treatment of UTI due to A. baumannii or to use piperacillin-tazobactam for empirical treatment of UTI due to P. aeruginosa. Colistin was found to be the most active antibiotic in vitro. There was a marked increase in the consumption of piperacillin-tazobactam.

Prospective evaluation of antibiotic treatment for urological procedure in patients presenting with neurogenic bladder.

PubMed

Weglinski, L; Rouzaud, C; Even, A; Bouchand, F; Davido, B; Duran, C; Salomon, J; Perronne, C; Denys, P; Chartier-Kastler, E; Dinh, A

2016-09-01

Patients presenting with neurogenic bladder often require urological procedures (urodynamic testing and botulinum toxin injections) and a preventive antibiotic therapy. We aimed to assess the efficacy of this little known strategy in a cohort of patients. All patients presenting with neurogenic bladder who underwent urological procedure were included in the study. They received an antibiotic therapy in accordance with the urine cytobacteriological examination results. The antibiotic therapy was initiated two days before the procedure and prolonged up until two days after the procedure if the culture was positive. Patients were treated with a single dose of fosfomycin-trometamol in case of a negative culture. The main study outcome was the occurrence of urinary tract infection (UTI), defined by a positive urine culture and symptoms, up until 14 days after the procedure. A total of 80 urological procedures were performed. Mean patient age was 47±13.1 years (sex ratio 1.22); 59 (73.8%) presented with asymptomatic bacteriuria before the procedure. Nine (11.1%) UTIs were recorded on Day 14, of which one (1.2%) was febrile. Two patients required an additional curative antibiotic therapy. No patient was hospitalized. Overall, 77.8% of UTIs were cured without antibiotic therapy. Screening and treating asymptomatic bacteriuria before urological procedures seems unnecessary and vainly exposes this population at high risk of infectious diseases to antibiotic therapies. This data should be confirmed by a randomized clinical trial. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

East and West African milk products are reservoirs for human and livestock-associated Staphylococcus aureus.

PubMed

Jans, Christoph; Merz, Axel; Johler, Sophia; Younan, Mario; Tanner, Sabine A; Kaindi, Dasel Wambua Mulwa; Wangoh, John; Bonfoh, Bassirou; Meile, Leo; Tasara, Taurai

2017-08-01

Staphylococcus aureus frequently isolated from milk products in sub-Saharan Africa (SSA) is a major pathogen responsible for food intoxication, human and animal diseases. SSA hospital-derived strains are well studied but data on the population structure of foodborne S. aureus required to identify possible staphylococcal food poisoning sources is lacking. Therefore, the aim was to assess the population genetic structure, virulence and antibiotic resistance genes associated with milk-derived S. aureus isolates from Côte d'Ivoire, Kenya and Somalia through spa-typing, MLST, and DNA microarray analysis. Seventy milk S. aureus isolates from the three countries were assigned to 27 spa (7 new) and 23 (12 new) MLST sequence types. Milk-associated S. aureus of the three countries is genetically diverse comprising human and livestock-associated clonal complexes (CCs) predominated by the CC5 (n = 10) and CC30 (n = 9) isolates. Panton-Valentine leukocidin, toxic shock syndrome toxin and enterotoxin encoding genes were predominantly observed among human-associated CCs. Penicillin, fosfomycin and tetracycline, but not methicillin resistance genes were frequently detected. Our findings indicate that milk-associated S. aureus in SSA originates from human and animal sources alike highlighting the need for an overarching One Health approach to reduce S. aureus disease burdens through improving production processes, animal care and hygienic measures. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synergism of coumarins from the Chinese drug Zanthoxylum nitidum with antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA).

PubMed

Zuo, Guo-Ying; Wang, Chun-Juan; Han, Jun; Li, Yu-Qing; Wang, Gen-Chun

2016-12-15

Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious therapeutic challenge in current clinic and new drug development. Natural coumarins have diverse bioactivities and the potential of resistance modifying effects. This study is to present in-depth evaluations of in vitro antimicrobial activities of four natural coumarins 5-geranyloxy-7-methoxycoumarin (Gm, 1), (5,7-dimethoxy-8-prenyloxycoumarin (artanin, Ar, 2)), isopimpinellin (Is, 3) and phellopterin (Ph, 4) from Zanthoxylum nitidum (Roxb.) DC. (Rutaceae) extracts, focusing on their potential restoration the activity of conventional antibacterial agents against clinical MRSA strains. Bioactivity-guided fractionation and spectral analyses were used to isolate the coumarins and identify the structures, respectively. The double broth microdilution method was used to assay the coumarins' alone activity. The classic checkerboard microdilution and dynamic time-killing methods were used to evaluate combinatory effects. The four plant coumarins Gm (1), Ar (2), Is (3) and Ph (4) were isolated and identified from Z. nitidum extracts. Coumarins 1-4 displayed promising inhibition against both MSSA and MRSA with minimal inhibitory concentrations (MICs) of 8-64µg/ml, but very weak against Gram-negative pathogen and yeast with MICs of 256 to ≥1024µg/ml. The geranyloxy and prenyloxy substitutions showed to be more active than the methoxy substitution on the coumarin skeletons. 1-4 also showing different extent of synergism with a total of eight conventional antibacterial agents, i.e. chloramphenicol (CL), gentamicin (CN), fosfomycin (FF), levofloxacin (LE), minocycline (MI), piperacillin/tazobactam (P/T), teicoplanin (TE) and vancomycin (VA) against ten clinical MRSA strains. Four to ten of the tested MRSA strains showed bacteriostatic synergy in the eleven combinations. The anti-MRSA modifying effects were related to different arrangement in the combinations with fractional inhibitory concentration indices (FICIs) from 0.187 to 1.125 and the three combinations CN (Is), CL (Ph) and MI (Gm) were the best ones. The enhancement of activity was also shown by 2-64 of dose reduction indices (DRIs) of the combined MICs, with VA (Ph) combination resulted the biggest DRI. The resistance of MRSA to antibacterial agents could be reversed in the combinations of CL (Gm or Ph), LE (Ph) and MI (Is) following the Clinical and Laboratory Standards Institute (CLSI) criteria. Six combinations P/T (Gm), TE (Ar), CN (Is), VA (Ph) and CL (Gm or Ph) also showed bactericidal synergy with Δlog 10 CFU/ml >2 at 24h incubation. The coumarins showed high potentiating effects of the antibacterial agents against multi-drug resistant SA. The resistance reversal effect of CL, LE and MI warrants further pharmacological investigation on combinatory therapy for the sake of fighting against MRSA infections. Copyright © 2016 Elsevier GmbH. All rights reserved.

Perceptions and Pedagogy: Exploring the Beliefs and Practices of an Effective Primary Science Teacher

ERIC Educational Resources Information Center

Fitzgerald, Angela; Dawson, Vaille; Hackling, Mark

2009-01-01

Effective science teaching is vital for improved student learning outcomes in primary school science. Therefore, there is a need to tease out the components of effective science teaching to better understand what effective primary teachers do in their classrooms and why they do it. Four primary teachers, each nominated as effective science…

In vitro susceptibility and resistance phenotypes in contemporary Citrobacter isolates in a University Hospital in Crete, Greece.

PubMed

Maraki, Sofia; Vardakas, Konstantinos Z; Mavromanolaki, Viktoria-Eirini; Kyriakidou, Margarita; Spais, George; Kofteridis, Diamantis P; Samonis, George; Falagas, Matthew E

2017-07-01

Data on Citrobacter spp. susceptibility are scarce. We sought to study the evolution in the susceptibility of 385 Citrobacter spp. at the University Hospital of Heraklion, Crete, Greece during a six-year period (2010-2015). Non-duplicate strains isolated from inpatients (intensive care unit, oncology, surgery, internal medicine, paediatrics) and outpatients were studied using Vitek 2. Phenotypic confirmatory tests were applied for detection of β-lactamases and aminoglycoside modifying enzymes. C. freundii (172, 44.7%) and C. koseri (166, 43.1%) were the most commonly isolated species. C. braakii (34), C. amalonaticus (6), C. youngae (6) and C. sedlakii (1) were the remaining isolates. Colistin and fosfomycin were the most active antibiotics (both 99.2%) followed by carbapenems (99%) aminoglycosides (96.6-98.4%), tigecycline (96.1%), cefepime (94.8%), ciprofloxacin (94.3%), tetracycline (92.7%), trimethoprim/sulphamethoxazole (91.4%), chloramphenicol (88.1%), piperacillin/tazobactam (86.5%) and 3rd generation cephalosporins (85.7%). C. freundii were more resistant than C. koseri. Antibiotic resistance did not increase during the study period for most antibiotics. Lower susceptibility to all antibiotics was observed among multi-drug resistant (MDR) strains. AmpC was the most common resistant mechanism (10.9%); carbapenemases (1.3%) and aminoglycoside modifying enzymes (2.9%) were also detected. All AmpC producers were resistant to cephalosporins but not to carbapenems. In all but one isolates aminoglycoside resistance was accompanied by acquired β-lactamases. Although Citrobacter species in general were susceptible, antibiotic susceptibility testing is required for the detection of resistant isolates.

Treatment strategy for a multidrug-resistant Klebsiella UTI.

PubMed

Fleming, Erin; Heil, Emily L; Hynicka, Lauren M

2014-01-01

To describe the management strategy for a multidrug-resistant (MDR) Klebsiella urinary tract infection (UTI). A 69-year-old Caucasian woman with a past medical history of recurrent UTIs and a right-lung transplant presented with fever to 101.4°F, chills, malaise, and cloudy, foul-smelling urine for approximately 1 week. She was found to have a MDR Klebsiella UTI that was sensitive to tigecycline and cefepime. To further evaluate the degree of resistance Etest minimum inhibitory concentrations were requested for cefepime, amikacin, meropenem, and ertapenem. The patient received a 14-day course of amikacin, which resulted in resolution of her symptoms. One month later, the patient's UTI symptoms returned. The urine culture again grew MDR Klebsiella, sensitive only to tigecycline. Fosfomycin was initiated and resulted in limited resolution of her symptoms. Colistin was started, however, therapy was discontinued on day 5 secondary to the development of acute kidney injury. Despite the short course of therapy, the patient's symptoms resolved. The case presented lends itself well to numerous discussion items that are important to consider when determining optimal treatment for MDR Gram-negative bacilli (GNBs). Susceptibility testing is an important tool for optimizing antibiotic therapy, however, automated systems may overestimate the susceptibility profile for a MDR GNB. Treatment strategies evaluated to treat MDR GNB, include combination therapy with a carbepenem and synergy using polymyxin. We have described the management strategy for a MDR Klebsiella UTI, the consequences of the initial management strategy, and potential strategies to manage these types of infections in future patients.

Characterization of Enterobacteriaceae isolates obtained from a tertiary care hospital in Mexico, which produces extended-spectrum β-lactamase.

PubMed

Morfín-Otero, Rayo; Mendoza-Olazarán, Soraya; Silva-Sánchez, Jesús; Rodríguez-Noriega, Eduardo; Laca-Díaz, Jorge; Tinoco-Carrillo, Perla; Petersen, Luis; López, Perla; Reyna-Flores, Fernando; Alcantar-Curiel, Dolores; Garza-Ramos, Ulises; Garza-González, Elvira

2013-10-01

The prevalence and genetic characteristics of Escherichia coli and Klebsiella pneumoniae clinical isolates producing extended-spectrum β-lactamase (ESBL) were examined. Between October 2010 and March 2011, E. coli (n=460) and K. pneumoniae (n=78) isolates were collected at a tertiary care hospital in Guadalajara, Mexico. The minimum inhibitory concentration (MIC) for each isolate was determined using a broth microdilution method, and ESBL production was assayed. The presence of β-lactamase genes, blaSHV, blaCTX-M, and blaTLA-1, was detected by PCR and confirmed with sequencing. Only ESBL-producing isolates were further subjected to pulsed-field gel electrophoresis (PFGE) and plasmid profiling. All of the ESBL isolates were multidrug resistant and 75/460 (16.3%) E. coli isolates and 21/78 (26.9%) K. pneumoniae isolates were found to produce ESBL. For the E. coli isolates, >95% susceptibility to amikacin, meropenem, fosfomycin, imipenem, and nitrofurantoin was observed. For K. pneumoniae, similar results were obtained, with discrepancies observed for gentamicin and nitrofurantoin. PFGE further identified eleven pulsotypes for E. coli and three clusters of K. pneumoniae. CTX-M-15 was detected in 85% of ESBL-producing E. coli and in 76% of ESBL-producing K. pneumoniae. In contrast, SHV-5 ESBL was identified in 17% of E. coli isolates and in 86% of K. pneumoniae isolates. The bla-TLA-1 gene was not detected in any of the 96 isolates analyzed. Overall, CTX-M-15 and SHV-5 were found to have a high rate of spread throughout the hospital and were associated with strong multidrug resistance.

Anti-vRE and anti-MRSA activities of new quinolones and their synergism with commercial antibiotics. Part 2.

PubMed

Sakagami, Yoshikazu; Komemushi, Sadao; Tsukamoto, Goro; Kondo, Hirosato; Yoshikawa, Akiko; Muraoka, Osamu

2008-09-01

Anti-VRE and anti-MRSA activities of new quinolone derivatives [The two quinolone derivatives are 8- [3-[(ethylamino) methyl]-1-pyrrodinyl] -7-fluoro-9, 1-[(N-methylimino)methano]-5-oxo-5H-thiazolo[3,2-a]quinolone-4-carboxylic acid (compound A) and 7-fluoro-8-morpholino-9,1-[(N-methylimino) methanol-5-oxo-5H-thiazolo [3,2-a] quinolone-4-carboxylic acid (compound B)] and their synergism with commercial antibiotics were investigated. Compound A exhibited potent antibacterial activity against VRE and MRSA among the five new quinolone compounds tested, and showed superior activity to pefloxacin, ofloxacin and levofloxacin, which are clinically in use these days. With respect to the anti-VRE activity, compound A showed synergism with fosfomycin (FOM), and partial synergism with ampicillin (ABPC), gentaicin (GM), minocycline (MINO) and vancomycin hydrochloride (VCM). Partial synergism in anti-VRE activity was also observed between compound B and GM, MINO, FOM and VCM. Compound A also showed synergism with MINO and FOM in anti-MASA activity. Partial synergism was observed with ABPC, GM and VCM. Synergism with ABPC was not detected in anti-MRSA activity. On the other hand, the synergism of compound B with FOM, and the partial synergisms with ABPC, GM and MINO were also found against MRSA. No synergism with ABPC was found against MRSA. These results suggested that compound A and B could possibly reduce the daily administration dose of these antibiotics in the treatment of nosocomial infections, and also reduce the possibility of the occurrence of nosocomial infections caused by VRE and/or MRSA.

Draft genome sequence of an extensively drug-resistant Pseudomonas aeruginosa isolate belonging to ST644 isolated from a footpad infection in a Magellanic penguin (Spheniscus magellanicus).

PubMed

Sellera, Fábio P; Fernandes, Miriam R; Moura, Quézia; Souza, Tiago A; Nascimento, Cristiane L; Cerdeira, Louise; Lincopan, Nilton

2018-03-01

The incidence of multidrug-resistant bacteria in wildlife animals has been investigated to improve our knowledge of the spread of clinically relevant antimicrobial resistance genes. The aim of this study was to report the first draft genome sequence of an extensively drug-resistant (XDR) Pseudomonas aeruginosa ST644 isolate recovered from a Magellanic penguin with a footpad infection (bumblefoot) undergoing rehabilitation process. The genome was sequenced on an Illumina NextSeq ® platform using 150-bp paired-end reads. De novo genome assembly was performed using Velvet v.1.2.10, and the whole genome sequence was evaluated using bioinformatics approaches from the Center of Genomic Epidemiology, whereas an in-house method (mapping of raw whole genome sequence reads) was used to identify chromosomal point mutations. The genome size was calculated at 6436450bp, with 6357 protein-coding sequences and the presence of genes conferring resistance to aminoglycosides, β-lactams, phenicols, sulphonamides, tetracyclines, quinolones and fosfomycin; in addition, mutations in the genes gyrA (Thr83Ile), parC (Ser87Leu), phoQ (Arg61His) and pmrB (Tyr345His), conferring resistance to quinolones and polymyxins, respectively, were confirmed. This draft genome sequence can provide useful information for comparative genomic analysis regarding the dissemination of clinically significant antibiotic resistance genes and XDR bacterial species at the human-animal interface. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Detection and characterization of carbapenemase-producing Enterobacteriaceae in wounded Syrian patients admitted to hospitals in northern Israel.

PubMed

Lerner, A; Solter, E; Rachi, E; Adler, A; Rechnitzer, H; Miron, D; Krupnick, L; Sela, S; Aga, E; Ziv, Y; Peretz, A; Labay, K; Rahav, G; Geffen, Y; Hussein, K; Eluk, O; Carmeli, Y; Schwaber, M J

2016-01-01

Since 2013, four hospitals in northern Israel have been providing care for Syrian nationals, primarily those wounded in the ongoing civil war. We analyzed carbapenemase-producing Enterobacteriaceae (CPE) isolates obtained from these patients. Isolate identification was performed using the VITEK 2 system. Polymerase chain reaction (PCR) was performed for the presence of bla KPC, bla NDM, and bla OXA-48. Susceptibility testing and genotyping were performed on selected isolates. During the study period, 595 Syrian patients were hospitalized, most of them young men. Thirty-two confirmed CPE isolates were grown from cultures taken from 30 patients. All but five isolates were identified as Klebsiella pneumoniae and Escherichia coli. Nineteen isolates produced NDM and 13 produced OXA-48. Among a further 29 isolates tested, multilocus sequence typing (MLST) showed that ST278 and ST38 were the major sequence types among the NDM-producing K. pneumoniae and OXA-48-producing E. coli isolates, respectively. Most were resistant to all three carbapenems in use in Israel and to gentamicin, but susceptible to colistin and fosfomycin. The source for bacterial acquisition could not be determined; however, some patients admitted to different medical centers were found to carry the same sequence type. CPE containing bla NDM and bla OXA-48 were prevalent among Syrian wounded hospitalized patients in northern Israel. The finding of the same sequence type among patients at different medical centers implies a common, prehospital source for these patients. These findings have implications for public health throughout the region.

Uncomplicated Bacterial Communityacquired Urinary Tract Infection in Adults.

PubMed

Kranz, Jennifer; Schmidt, Stefanie; Lebert, Cordula; Schneidewind, Laila; Schmiemann, Guido; Wagenlehner, Florian

2017-12-15

Uncomplicated bacterial community-acquired urinary tract infection is among the more common infections in outpatient practice. The resistance level of pathogens has risen markedly. This S3 guideline contains recommendations based on current evidence for the rational use of anti - microbial agents and for the prevention of inappropriate use of certain classes of antibiotics and thus of the resulting drug resistance. The prevention of recurrent urinary tract infection is considered in this guideline for the first time. The guideline was updated under the aegis of the German Urological Society (Deutsche Gesellschaft für Urologie). A systematic literature search (period: 2008-2015) concerning the diagnosis, treatment, and prevention of uncomplicated urinary tract infections was carried out in the Cochrane Library, MEDLINE, and Embase databases. Randomized, controlled trials and systemic reviews were included. Relevant guidelines were identified in a guideline synopsis. Symptom-oriented diagnostic evaluation is highly valued. For the treatment of cystitis, fosfomycin-trometamol, nitrofurantoin, nitroxolin, pivmecillinam and trimethoprim are all equally recommended. Fluorquinolones and cephalosporins are not recommended. Uncomplicated pyelonephritis with a mild to moderate clinical course ought to be treated with oral cefpodoxime, ceftibuten, ciprofloxacin, or levofloxacin. For acute, uncomplicated cystitis, with mild to moderate symptoms, symptomatic treatment alone may be considered instead of antibiotics after discussion of the options with the patient. Mainly non-antibiotic measures are recommended for prophylaxis against recurrent urinary tract infection. Physicians who treat uncomplicated urinary tract infections should familiarize themselves with the newly revised guideline's recommendations on the selection and dosage of antibiotic treatment so that they can responsibly evaluate and plan antibiotic treatment for their affected patients.

Clonality, outer-membrane proteins profile and efflux pump in KPC- producing Enterobacter sp. in Brazil.

PubMed

Rosa, Juliana Ferraz; Rizek, Camila; Marchi, Ana Paula; Guimaraes, Thais; Miranda, Lourdes; Carrilho, Claudia; Levin, Anna S; Costa, Silvia F

2017-03-17

Carbapenems resistance in Enterobacter spp. has increased in the last decade, few studies, however, described the mechanisms of resistance in this bacterium. This study evaluated clonality and mechanisms of carbapenems resistance in clinical isolates of Enterobacter spp. identified in three hospitals in Brazil (Hospital A, B and C) over 7-year. Antibiotics sensitivity, pulsed-field gel electrophoresis (PFGE), PCR for carbapenemase and efflux pump genes were performed for all carbapenems-resistant isolates. Outer-membrane protein (OMP) was evaluated based on PFGE profile. A total of 130 isolates of Enterobacter spp were analyzed, 44/105 (41, 9%) E. aerogenes and 8/25 (32,0%) E. cloacae were resistant to carbapenems. All isolates were susceptible to fosfomycin, polymyxin B and tigecycline. KPC was present in 88.6% of E. aerogenes and in all E. cloacae resistant to carbapenems. The carbapenems-resistant E. aerogenes identified in hospital A belonged to six clones, however, a predominant clone was identified in this hospital over the study period. There is a predominant clone in Hospital B and Hospital C as well. The mechanisms of resistance to carbapenems differ among subtypes. Most of the isolates co-harbored blaKPC, blaTEM and /or blaCTX associated with decreased or lost of 35-36KDa and or 39 KDa OMP. The efflux pump AcrAB-TolC gene was only identified in carbapenems-resistant E. cloacae. There was a predominant clone in each hospital suggesting that cross-transmission of carbapenems-resistant Enterobacter spp. was frequent. The isolates presented multiple mechanisms of resistance to carbapenems including OMP alteration.

The management of multidrug-resistant Enterobacteriaceae.

PubMed

Bassetti, Matteo; Peghin, Maddalena; Pecori, Davide

2016-12-01

Multidrug-resistant (MDR) Enterobacteriaceae are often related to the production of extended-spectrum b-lactamases (ESBLs) and carbapenemase-producing Enterobacteriaceae (CRE), and represent an increasing global threat. Recommendations for the therapeutic management of MDR-related infections, however, are mainly derived from retrospective and nonrandomized prospective studies. The aim of this review is to discuss the challenges in the treatment of patients with infections because of MDR Enterobacteriaceae and provide an expert opinion while awaiting for more definitive data. To avoid the selection of carbapenemase-producing Enterobacteriaceae, carbapenem-sparing strategies should be considered. B-lactams/b-lactamase inhibitors, mainly piperacillin-tazobactam, minimum inhibitory concentration (MIC) 16/4mg/ml or less represents the best alternative to carbapenems for the treatment of ESBL-producing strains. Overall, combination therapy may be preferred over monotherapy for CRE. The combination of a carbapenem-containing regimen with colistin or high-dose tigecycline or aminoglycoside can be administered at high-dose prolonged infusion with therapeutic drug monitoring for the treatment of CRE with MIC for meropenem 8-16 mg/l or less. For MIC higher than 8-16 mg/l, the use of meropenem should be avoided and various combination therapies based on the in-vitro susceptibility of antimicrobials (e.g., colistin, high-dose tigecycline, fosfomycin, and aminoglycosides) should be selected. Carbapenem-sparing strategies should be used, when feasible, for ESBL infections. The majority of available nonrandomized studies highlight that combination for CRE seem to offer some therapeutic advantage over monotherapy. Strict infection control measures toward MDR Gram-negative pathogens remain necessary while awaiting for new treatment options.

Different antibiotic regimens for treating asymptomatic bacteriuria in pregnancy.

PubMed

Guinto, Valerie T; De Guia, Blanca; Festin, Mario R; Dowswell, Therese

2010-09-08

Asymptomatic bacteriuria occurs in 5% to 10% of pregnancies and, if left untreated, can lead to serious complications. To assess which antibiotic is most effective and least harmful as initial treatment for asymptomatic bacteriuria in pregnancy. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (March 2010) and reference lists of retrieved studies. Randomized controlled trials comparing two antibiotic regimens for treating asymptomatic bacteriuria. Review authors independently screened the studies for inclusion and extracted data. We included five studies involving 1140 women with asymptomatic bacteriuria. We did not perform meta-analysis; each trial examined different antibiotic regimens and so we were not able to pool results. In a study comparing a single dose of fosfomycin trometamol 3 g with a five-day course of cefuroxime, there was no significant difference in persistent infection (risk ratio (RR) 1.36, 95% confidence interval (CI) 0.24 to 7.75), shift to other antibiotics (RR 0.08, 95% CI 0.00 to 1.45), or in allergy or pruritus (RR 2.73, 95% CI 0.11 to 65.24). A comparison of seven-day courses of 400 mg pivmecillinam versus 500 mg ampicillin, both given four times daily, showed no significant difference in persistent infection at two weeks or recurrent infection, but there was an increase in vomiting (RR 4.57, 95% CI 1.40 to 14.90) and women were more likely to stop treatment early with pivmecillinam (RR 8.82, 95% CI 1.16 to 66.95). When cephalexin 1 g versus Miraxid(R) (pivmecillinam 200 mg and pivampicillin 250 mg) were given twice-daily for three days, there was no significant difference in persistent or recurrent infection. A one- versus seven-day course of nitrofurantoin resulted in more persistent infection with the shorter course (RR 1.76, 95% CI 1.29 to 2.40), but no significant difference in symptomatic infection at two weeks, nausea, or preterm birth. Comparing cycloserine with sulphadimidine, no significant differences in symptomatic, persistent, or recurrent infections were noted. We cannot draw any definite conclusion on the most effective and safest antibiotic regimen for the initial treatment of asymptomatic bacteriuria in pregnancy. One study showed advantages with a longer course of nitrofurantoin, and another showed better tolerability with ampicillin compared with pivmecillinam; otherwise, there was no significant difference demonstrated between groups treated with different antibiotics. Given this lack of conclusive evidence, it may be useful for clinicians to consider factors such as cost, local availability and side effects in the selection of the best treatment option.

In vitro synergism of magnolol and honokiol in combination with antibacterial agents against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA).

PubMed

Zuo, Guo-Ying; Zhang, Xin-Juan; Han, Jun; Li, Yu-Qing; Wang, Gen-Chun

2015-12-01

Methicillin-resistant Staphylococcus aureus (MRSA) is a problematic pathogen posing a serious therapeutic challenge in the clinic. It is often multidrug-resistant (MDR) to conventional classes of antibacterial agents and there is an urgent need to develop new agents or strategies for treatment. Magnolol (ML) and honokiol (HL) are two naturally occurring diallylbiphenols which have been reported to show inhibition of MRSA. In this study their synergistic effects with antibacterial agents were further evaluated via checkerboard and time-kill assays. The susceptibility spectrum of clinical MRSA strains was tested by the disk diffusion method. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of ML and HL were assayed by broth microdilution. The synergy was evaluated through checkerboard microdilution and time-killing experiments. ML and HL showed similar activity against both MSSA and MRSA with MIC/MBC at 16 ~ 64 mg/L, with potency similar to amikacin (AMK) and gentamicin (GEN). When they were used in combination with conventional antibacterial agents, they showed bacteriostatic synergy with FICIs between 0.25 ~ 0.5, leading to the combined MICs decreasing to as low as 1 ~ 2 and 1 ~ 16 mg/L for ML (HL) and the agents, respectively. MIC50 of the combinations decreased from 16 mg/L to 1 ~ 4 mg/L for ML (HL) and 8 ~ 128 mg/L to 2 ~ 64 mg/L for the antibacterial agents, which exhibited a broad spectrum of synergistic action with aminoglycosides (AMK, etilmicin (ETM) and GEN), floroquinolones (levofloxacin (LEV), ciprofloxacin and norfloxacin), fosfomycin (FOS) and piperacillin. The times of dilution (TOD, the extent of decreasing in MIC value) were determined up to 16 for the combined MIC. A more significant synergy after combining was determined as ML (HL) with AMK, ETM, GEN and FOS. ML (HL) combined with antibacterial agents did not show antagonistic effects on any of the ten MRSA strains. Reversal effects of MRSA resistance to AMK and GEN by ML and HL were also observed, respectively. All the combinations also showed better dynamic bactericidal activity against MRSA than any of single ML (HL) or the agents at 24 h incubation. The more significant synergy of combinations were determined as HL (ML) + ETM, HL + LEV and HL + AMK (GEN or FOS), with △LC24 of 2.02 ~ 2.25. ML and HL showed synergistic potentiation of antibacterial agents against clinical isolates of MRSA and warrant further pharmacological investigation.

Parental education, children's performance and the transition to higher secondary education: trends in primary and secondary effects over five Dutch school cohorts (1965-99).

PubMed

Kloosterman, Rianne; Ruiter, Stijn; de Graaf, Paul M; Kraaykamp, Gerbert

2009-06-01

According to Boudon, social background affects educational transitions as a result of differences in children's academic performance (primary effects) and differences in transition probabilities given children's level of academic performance (secondary effects). This study addresses historical changes in both primary and secondary effects on the educational transition from primary school to higher secondary education in The Netherlands. In addition, it considers changes over time in the relative importance of these effects. The study compares five cohorts of Dutch pupils, specifically those enrolling in secondary education in 1965, 1977, 1989, 1993 and 1999, and it employs counterfactual analyses. The main findings are that secondary effects have been stable and primary effects have fluctuated to some extent. As a result, the proportion of the total effect of social background accounted for by primary effects has increased somewhat, from 53 per cent to 58 per cent.

Examining the Effect of Automatic Promotion on Students' Learning Achievements in Uganda's Primary Education

ERIC Educational Resources Information Center

Okurut, Jeje Moses

2015-01-01

This study employed a difference-in-differences analysis technique to estimate the average treatment effect of automatic promotion on students' cognitive learning outcomes in Uganda's primary education. Regression results indicate a positive policy effect on learning achievements in literacy and numeracy at primary three (P3) and primary six (P6).…

Turkish Preservice Primary School Teachers' Science Teaching Efficacy Beliefs and Attitudes toward Science: The Effect of a Primary Teacher Education Program

ERIC Educational Resources Information Center

Bayraktar, Sule

2011-01-01

The main purpose of this study was to investigate the effectiveness of a primary teacher education program in improving science teaching efficacy beliefs (personal science teaching efficacy beliefs and outcome expectancy beliefs) of preservice primary school teachers. The study also investigated whether the program has an effect on student…

Using Meta-analyses for Comparative Effectiveness Research

PubMed Central

Ruppar, Todd M.; Phillips, Lorraine J.; Chase, Jo-Ana D.

2012-01-01

Comparative effectiveness research seeks to identify the most effective interventions for particular patient populations. Meta-analysis is an especially valuable form of comparative effectiveness research because it emphasizes the magnitude of intervention effects rather than relying on tests of statistical significance among primary studies. Overall effects can be calculated for diverse clinical and patient-centered variables to determine the outcome patterns. Moderator analyses compare intervention characteristics among primary studies by determining if effect sizes vary among studies with different intervention characteristics. Intervention effectiveness can be linked to patient characteristics to provide evidence for patient-centered care. Moderator analyses often answer questions never posed by primary studies because neither multiple intervention characteristics nor populations are compared in single primary studies. Thus meta-analyses provide unique contributions to knowledge. Although meta-analysis is a powerful comparative effectiveness strategy, methodological challenges and limitations in primary research must be acknowledged to interpret findings. PMID:22789450

Comparative analysis of metagenomes of Italian top soil improvers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gigliucci, Federica, E-mail: Federica.gigliucci@li

Biosolids originating from Municipal Waste Water Treatment Plants are proposed as top soil improvers (TSI) for their beneficial input of organic carbon on agriculture lands. Their use to amend soil is controversial, as it may lead to the presence of emerging hazards of anthropogenic or animal origin in the environment devoted to food production. In this study, we used a shotgun metagenomics sequencing as a tool to perform a characterization of the hazards related with the TSIs. The samples showed the presence of many virulence genes associated to different diarrheagenic E. coli pathotypes as well as of different antimicrobial resistance-associatedmore » genes. The genes conferring resistance to Fluoroquinolones was the most relevant class of antimicrobial resistance genes observed in all the samples tested. To a lesser extent traits associated with the resistance to Methicillin in Staphylococci and genes conferring resistance to Streptothricin, Fosfomycin and Vancomycin were also identified. The most represented metal resistance genes were cobalt-zinc-cadmium related, accounting for 15–50% of the sequence reads in the different metagenomes out of the total number of those mapping on the class of resistance to compounds determinants. Moreover the taxonomic analysis performed by comparing compost-based samples and biosolids derived from municipal sewage-sludges treatments divided the samples into separate populations, based on the microbiota composition. The results confirm that the metagenomics is efficient to detect genomic traits associated with pathogens and antimicrobial resistance in complex matrices and this approach can be efficiently used for the traceability of TSI samples using the microorganisms’ profiles as indicators of their origin. - Highlights: • Sludge- and green- based biosolids analysed by metagenomics. • Biosolids may introduce microbial hazards in the food chain. • Metagenomics enables tracking biosolids’ sources.« less

Cefoxitin-based antibiotic therapy for extended-spectrum β-lactamase-producing Enterobacteriaceae prostatitis: a prospective pilot study.

PubMed

Demonchy, Elisa; Courjon, Johan; Ughetto, Estelle; Durand, Matthieu; Risso, Karine; Garraffo, Rodolphe; Roger, Pierre-Marie

2018-06-01

The emergence of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) infections requires re-assessment of therapeutic choices. Here we report the efficacy of cefoxitin-based antibiotic therapy for ESBL-E prostatitis. A prospective study including patients with ESBL-E prostatitis resistant to trimethoprim/sulfamethoxazole and fluoroquinolones from January 2014 to March 2016 was conducted. Cefoxitin was administered by continuous infusion for 3 weeks in the case of acute bacterial prostatitis or 6 weeks in the case of chronic bacterial prostatitis (CBP), with intravenous fosfomycin for the first 5 days. Urological investigations were performed to diagnose underlying urinary tract pathology. Clinical and microbiological efficacy were evaluated 3 months (M3) and 6 months (M6) after the end of therapy. A total of 23 patients were included in the study. The median patient age was 74 years (range 48-88 years). Of the 23 infections, 14 (61%) were CBP and 12 (52%) were healthcare-associated infections. The bacteria involved were Escherichia coli in 11 cases, Klebsiella pneumoniae in 10 cases and Klebsiella oxytoca in 2 cases. Clinical cure was observed in 19/23 patients (83%) at M3 and in 17/22 patients (77%) at M6. Urocultures were sterile in 13/23 patients (57%) at M3 and in 9/19 patients (47%) and M6. Urinary colonisation was observed in 6/19 patients (32%) with clinical cure at M3 and 5/14 patients (36%) with clinical cure at M6. No resistance to cefoxitin was detected. Surgical treatment was required for 7/23 patients (30%). In conclusion, cefoxitin-based antibiotic therapy is suitable for difficult-to-treat ESBL-E infections such as prostatitis. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Lipid Requirements for the Enzymatic Activity of MraY Translocases and in Vitro Reconstitution of the Lipid II Synthesis Pathway*

PubMed Central

Henrich, Erik; Ma, Yi; Engels, Ina; Münch, Daniela; Otten, Christian; Schneider, Tanja; Henrichfreise, Beate; Sahl, Hans-Georg; Dötsch, Volker; Bernhard, Frank

2016-01-01

Screening of new compounds directed against key protein targets must continually keep pace with emerging antibiotic resistances. Although periplasmic enzymes of bacterial cell wall biosynthesis have been among the first drug targets, compounds directed against the membrane-integrated catalysts are hardly available. A promising future target is the integral membrane protein MraY catalyzing the first membrane associated step within the cytoplasmic pathway of bacterial peptidoglycan biosynthesis. However, the expression of most MraY homologues in cellular expression systems is challenging and limits biochemical analysis. We report the efficient production of MraY homologues from various human pathogens by synthetic cell-free expression approaches and their subsequent characterization. MraY homologues originating from Bordetella pertussis, Helicobacter pylori, Chlamydia pneumoniae, Borrelia burgdorferi, and Escherichia coli as well as Bacillus subtilis were co-translationally solubilized using either detergent micelles or preformed nanodiscs assembled with defined membranes. All MraY enzymes originating from Gram-negative bacteria were sensitive to detergents and required nanodiscs containing negatively charged lipids for obtaining a stable and functionally folded conformation. In contrast, the Gram-positive B. subtilis MraY not only tolerates detergent but is also less specific for its lipid environment. The MraY·nanodisc complexes were able to reconstitute a complete in vitro lipid I and lipid II forming pipeline in combination with the cell-free expressed soluble enzymes MurA-F and with the membrane-associated protein MurG. As a proof of principle for future screening platforms, we demonstrate the inhibition of the in vitro lipid II biosynthesis with the specific inhibitors fosfomycin, feglymycin, and tunicamycin. PMID:26620564

Occurrence of multi-antibiotic resistant Pseudomonas spp. in drinking water produced from karstic hydrosystems.

PubMed

Flores Ribeiro, Angela; Bodilis, Josselin; Alonso, Lise; Buquet, Sylvaine; Feuilloley, Marc; Dupont, Jean-Paul; Pawlak, Barbara

2014-08-15

Aquatic environments could play a role in the spread of antibiotic resistance genes by enabling antibiotic-resistant bacteria transferred through wastewater inputs to connect with autochthonous bacteria. Consequently, drinking water could be a potential pathway to humans and animals for antibiotic resistance genes. The aim of this study was to investigate occurrences of Escherichia coli and Pseudomonas spp. in drinking water produced from a karst, a vulnerable aquifer with frequent increases in water turbidity after rainfall events and run-offs. Water samples were collected throughout the system from the karstic springs to the drinking water tap during three non-turbid periods and two turbid events. E. coli densities in the springs were 10- to 1000-fold higher during the turbid events than during the non-turbid periods, indicating that, with increased turbidity, surface water had entered the karstic system and contaminated the spring water. However, no E. coli were isolated in the drinking water. In contrast, Pseudomonas spp. were isolated from the drinking water only during turbid events, while the densities in the springs were from 10- to 100-fold higher than in the non-turbid periods. All the 580 Pseudomonas spp. isolates obtained from the sampling periods were resistant (to between 1 and 10 antibiotics), with similar resistance patterns. Among all the Pseudomonas isolated throughout the drinking water production system, between 32% and 86% carried the major resistance pattern: ticarcillin, ticarcillin-clavulanic acid, cefsulodin, and/or aztreonam, and/or sulfamethoxazol-trimethoprim, and/or fosfomycin. Finally, 8 Pseudomonas spp. isolates, related to the Pseudomonas putida and Pseudomonas fluorescens species, were isolated from the drinking water. Thus, Pseudomonas could be involved in the dissemination of antibiotic resistance via drinking water during critical periods. Copyright © 2014 Elsevier B.V. All rights reserved.

Urinary tract infections in hospital pediatrics: many previous antibiotherapy and antibiotics resistance, including fluoroquinolones.

PubMed

Garraffo, A; Marguet, C; Checoury, A; Boyer, S; Gardrat, A; Houivet, E; Caron, F

2014-02-01

We studied antibiotic resistance in pediatric UTIs and we evaluated the impact of antibiotic exposure in the previous 12 months, very little French data being available for this population. We conducted a multicenter prospective study including children consulting for, or admitted in 2 hospitals. Prior antibiotic exposure was documented from their health record. One hundred and ten patients (73 girls), 11 days to 12 years of age, were included in 10 months. Ninety-six percent presented with pyelonephritis, associated to uropathy for 25%. Escherichia coli was predominant (78%), followed by Proteus spp. and Enterococcus spp. The antibiotic resistance rate of E. coli was high and close to that reported for adults with complicated UTIs: amoxicillin 60%, amoxicillin-clavulanate 35%, cefotaxim 5%, trimethoprim-sulfametoxazole 26%, nalidixic acid 9%, ciprofloxacin 7%, gentamycin 1%, nitrofurantoin and fosfomycin 0%. The antibiotic exposure in the previous 12 months involved 62 children (56%) most frequently with β-lactams (89%) for a respiratory tract infection (56%). A clear relationship between exposure and resistance was observed for amoxicillin (71% vs. 46%), first generation (65% vs. 46%) and third generation (9% vs. 3%) cephalosporins, or trimethoprim-sulfamethoxazole (36% vs. 15%). However, antibiotic exposure could not account alone for the results, as suggested by the 7% of ciprofloxacin resistance, observed without any identified previous treatment. Bacterial species and antibiotic resistance level in children are similar to those reported for adults. Antibiotic exposure in the previous 12 months increases the risk of resistance but other factors are involved (previous antibiotic therapies and fecal-oral or mother-to-child transmission). Copyright © 2013 Elsevier Masson SAS. All rights reserved.

The 2017 Update of the German Clinical Guideline on Epidemiology, Diagnostics, Therapy, Prevention, and Management of Uncomplicated Urinary Tract Infections in Adult Patients. Part II: Therapy and Prevention.

PubMed

Kranz, Jennifer; Schmidt, Stefanie; Lebert, Cordula; Schneidewind, Laila; Mandraka, Falitsa; Kunze, Mirjam; Helbig, Sina; Vahlensieck, Winfried; Naber, Kurt; Schmiemann, Guido; Wagenlehner, Florian M

2018-01-01

We aimed to update the 2010 evidence- and consensus-based national clinical guideline on the diagnosis and management of uncomplicated urinary tract infections (UTIs) in adult patients. Results are published in 2 parts. Part 1 covers methods, the definition of patient groups, and diagnostics. This second publication focuses on treatment of acute episodes of cystitis and pyelonephritis as well as on prophylaxis of recurrent UTIs. An interdisciplinary group consisting of 17 representatives of 12 medical societies and a patient representative was formed. Systematic literature searches were conducted in MEDLINE, EMBASE, and the Cochrane Library to identify literature published in 2010-2015. For the treatment of acute uncomplicated cystitis (AUC), fosfomycin-trometamol, nitrofurantoin, nitroxoline, pivmecillinam, and trimethoprim (depending on the local rate of resistance) are all equally recommended. Cotrimoxazole, fluoroquinolones, and cephalosporins are not recommended as antibiotics of first choice, for concern of an unfavorable impact on the microbiome. Mild to moderate uncomplicated pyelonephritis should be treated with oral cefpodoxime, ceftibuten, ciprofloxacin, or levofloxacin. For AUC with mild to moderate symptoms, instead of antibiotics symptomatic treatment alone may be considered depending on patient preference after discussing adverse events and outcomes. Primarily non-antibiotic options are recommended for prophylaxis of recurrent urinary tract infection. In accordance with the global antibiotic stewardship initiative and considering new insights in scientific research, we updated our German clinical UTI guideline to promote a responsible antibiotic use and to give clear hands-on recommendations for the diagnosis and management of UTIs in adults in Germany for healthcare providers and patients. © 2018 S. Karger AG, Basel.

Clustering of Staphylococcus aureus bovine mastitis strains from regions of Central-Eastern Poland based on their biochemical and genetic characteristics.

PubMed

Puacz, E; Ilczyszyn, W M; Kosecka, M; Buda, A; Dudziak, W; Polakowska, K; Panz, T; Białecka, A; Kasprowicz, A; Lisowski, A; Krukowski, H; Cuteri, V; Międzobrodzki, J

2015-01-01

Staphylococcus aureus strains were isolated from mastitic milk of cows with infected mammary glands. The animals were living in 12 different farms near Lublin, in Central-Eastern Poland. A biochemical identification method based on enzymatic assay was performed, followed by haemolytic and proteolytic tests. PCR-RFLP targeted on the gap gene allowed the genetic identification of strains at the species level and verified phenotypic identification results. A molecular typing method using triplex PCR was performed to recognize the genetic similarity of the analyzed strains. DNA microarray hybridization (StaphyType, Alere Technologies) was used for detection of antibiotic resistance and virulence associated markers. The results obtained indicate high genetic similarity in strains isolated from the same sites. High genetic similarities were also detected between strains isolated from cows from different farms of the same region. A slightly lower similarity was noted however, in strains from various regions indicating that the strains are herd specific and that the cow's infections caused by S. aureus were of a clonal character. In 21 representative isolates selected for DNA-microarray testing, only fosfomycin (fosB) and penicillin resistance markers (blaZ, blaI, blaR) were detected. The presence of genes coding for haemolysins (lukF, lukS, hlgA, hla, hld, hlb), proteases (aur, sspA, sspB, sspP), enterotoxins (entA, entD, entG, entI, entJ, entM, entN, entO, entR, entU, egc-cluster), adhesins (icaA, icaC, icaD, bbp, clfA, clfB, fib, fnbA, map, vwb) or immune evasion proteins (scn, chp, sak) was common and, with exceptions, matched triplex PCR-defined clusters.

Community-acquired febrile urinary tract infection caused by extended-spectrum beta-lactamase-producing bacteria in hospitalised infants.

PubMed

Hernández Marco, Roberto; Guillén Olmos, Elena; Bretón-Martínez, José Rafael; Giner Pérez, Lourdes; Casado Sánchez, Benedicta; Fujkova, Julia; Salamanca Campos, Marina; Nogueira Coito, José Miguel

2017-05-01

Extended-spectrum beta-lactamase (ESBL) producing bacteria are infrequent pathogens of urinary tract infections in children. The objective of our study was to investigate the presence, clinically associated characteristics and risk factors for acquisition of urinary tract infection/acute pyelonephritis (UTI/APN) in hospitalised children <2years old caused by community-acquired ESBL. A case-control study in a second level community hospital in Spain, in which 537 episodes of UTI/APN were investigated in a retrospective study between November 2005 and August 2014. Cases were patients with ESBL strains. For each case, four ESBL-negative controls were selected. A questionnaire with the variables of interest was completed for every patient, and the groups were compared. ESBL-positive strains were found in 19 (3,5%) cultures. Of these 16 (84%) were Escherichia coli. Vesicoureteral reflux (VUR) of any grade was more frequent in the ESBL group (60 vs. 29%), although without statistical significance. Relapses were more frequent in the ESBL group (42% vs. 18%) (P=.029; OR=3.2; 95%CI: 1.09-9.5). The prevalence of UTI/APN due to ESBL-positive strains increased slightly from 2.7% in the period 2005-2009 to 4.4% in the period 2010-2014. ESBL UTI/APN were associated with more frequent relapses. VUR of any grade was twice more frequent in the ESBL group. Piperacillin/tazobactam, fosfomycin and meropenem showed an excellent activity. Aminoglycosides may be a therapeutic option, and in our patients gentamicin was the antibiotic most used. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Temporal trends and risks factors for antimicrobial resistant Enterobacteriaceae urinary isolates from outpatients in Guadeloupe.

PubMed

Guyomard-Rabenirina, Stéphanie; Malespine, Joyce; Ducat, Célia; Sadikalay, Syndia; Falord, Mélanie; Harrois, Dorothée; Richard, Vincent; Dozois, Charles; Breurec, Sébastien; Talarmin, Antoine

2016-06-24

Urinary tract infections are bacterial infections most commonly encountered in the community. The resistance rate of uropathogens to commonly prescribed antibiotics has increased worldwide but there are no published data concerning the resistance of strains isolated from community-acquired UTI in Guadeloupe. To assess the susceptibility patterns of Enterobacteriaceae strains isolated from outpatients in Guadeloupe we conducted a prospective study from December 2012 to May 2014 among outpatients consulting at private and public laboratories for urine analysis. Risk factors for E. coli resistance to amoxicillin, third-generation cephalosporin, and ciprofloxacin were also determined. To study the trends of E. coli resistance rates over the past 10 years, data on the susceptibility patterns of E. coli from 2003 to 2014 were also collected from three major laboratories for a retrospective study. During the prospective study, we isolated 1293 bacterial strains from the urine of outpatients presenting for urine analysis. The most commonly isolated bacteria were E. coli (57 %) and Klebsiella pneumoniae (15.5 %). Thirty seven per cent of the E. coli strains were resistant to amoxicillin. Resistance rates to third generation cephalosporin were low for E. coli and other Enterobacteriaceae (3.1 and 12.2 % respectively) and mostly due to the presence of an Extended Spectrum Beta-lactamase. Resistance to cotrimoxazole and ciprofloxacin was moderate (17.8 and 15.6 % respectively). However, the resistance rate of E. coli to ciprofloxacin has significantly increased during the last 10 years. Risk factors were consistent with previously reported data, especially for the increasing ciprofloxacin resistance with age. General practitioners in Guadeloupe need to be better informed to favor the prescription of fosfomycin-trometamol to reduce the risk of resistance to fluoroquinolones.

[In-vitro activity of mecillinam against urine isolates of Escherichia coli from outpatient departments in Germany].

PubMed

Kresken, Michael; Körber-Irrgang, Barbara; Naber, Kurt G

2017-05-01

National and international guidelines recommend fosfomycin trometamol, nitrofurantoin, nitroxoline, and pivmecillinam as first-line agents for the treatment of acute uncomplicated cystitis. Escherichia coli is by far the leading cause of community-acquired urinary tract infections. Pivmecillinam (X-SYSTO ® ) is an oral prodrug of mecillinam, a penicillin derivative that was reintroduced to the German market in March 2016. This study aimed to investigate the proportion of mecillinam-resistant strains among E. coli isolates prior to the introduction of X-SYSTO ® in Germany.An in-vitro study was carried out to determine the minimal inhibitory concentrations (MICs) of mecillinam against 494 urine isolates of E. coli (including multidrug-resistant strains). Isolates were obtained from outpatients and collected in 25 laboratories between October and December 2013. MIC breakpoints defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) were applied for classifying the bacterial isolates as mecillinam-susceptible (MIC ≤ 8 mg/l) or resistant (MIC > 8 mg/l).The concentrations of mecillinam needed to inhibit 50 % and 90 % of the test isolates were 1 and 4 mg/l, respectively, for isolates displaying the extended spectrum β-lactamase phenotype, and 0.25 and 4 mg/l, respectively, for the remaining isolates. Overall, 98 % of the isolates were found to be mecillinam-susceptible (MIC ≤ 8 mg/l), and 2 % were found to be resistant (MIC > 8 mg/l).These findings support the recommendation to regard pivmecillinam as a first-line option for the treatment of acute uncomplicated cystitis. © Georg Thieme Verlag KG Stuttgart · New York.

Epidemic spread of OXA-48 beta-lactamase in Croatia.

PubMed

Bedenić, Branka; Slade, Mia; Starčević, Lidija Žele; Sardelić, Sanda; Vranić-Ladavac, Mirna; Benčić, Ana; Zujić Atalić, Vlasta; Bogdan, Maja; Bubonja-Šonje, Marina; Tomić-Paradžik, Maja; Tot, Tatjana; Lukić-Grlić, Amarela; Drenjančević, Domagoj; Varda-Brkić, Dijana; Bandić-Pavlović, Daniela; Mihaljević, Slobodan; Zarfel, Gernot; Gužvinec, Marija; Conzemius, Rick; Barišić, Ivan; Tambić-Andraševic, Arjana

2018-06-21

A dramatic increase in OXA-48 β-lactamase was observed recently not only in large hospital centres, but also in smaller suburban hospital centres in geographic areas bordering Croatia. The aim of the study was to analyse the epidemiology, the mechanisms of antibiotic resistance and the routes of spread of OXA-48 carbapenemase in Croatia. Carbapenemase and other β-lactamase and fluoroquinolone resistance genes were detected by PCR and sequencing. Whole-genome sequencing (WGS) was performed on five representative isolates. The isolates were genotyped by PFGE. Forty-eight isolates positive for OXA-48, collected from seven hospital centres in Croatia from May 2016 to May 2017, were analysed (40 Klebsiella pneumoniae, 5 Enterobacter cloacae, 2 Escherichia coli and one Citrobacter freundii). Thirty-three isolates were ESBL positive and harboured group 1 CTX-M 1 β-lactamases. In addition to the β-lactam resistance genes detected by PCR (blaSHV-1, blaOXA-48 and blaOXA-1), WGS of five representative isolates revealed the presence of genes encoding aminoglycoside resistance, aadA2 and aph3-Ia, fluoroquinolone resistance determinants aac(6)Ib-c, oqxA and oqxB, the sulfonamide resistance gene sul1, and fosA (fosfomycin resistance). IncL plasmid was found in all isolates. Two K. pneumoniae isolates belonged to ST16, two E. cloacae to ST66 and E. coli to ST354. K. pneumoniae isolates were allocated to five clusters by PFGE which occured in different hospitals, indicating epidemic spread. The OXA-48-positive organisms found in this study showed wide variability in antibiotic susceptibility, β-lactamase content and PFGE banding patterns. This study revealed a switch from the predominance of VIM-1 in 2012-2013 to that of OXA-48 in the 2015 to 2017.

Deciphering the Resistome of the Widespread Pseudomonas aeruginosa Sequence Type 175 International High-Risk Clone through Whole-Genome Sequencing

PubMed Central

López-Causapé, Carla; Ocampo-Sosa, Alain A.; Sommer, Lea M.; Domínguez, María Ángeles; Zamorano, Laura; Juan, Carlos; Tubau, Fe; Rodríguez, Cristina; Moyà, Bartolomé; Martínez-Martínez, Luis; Plesiat, Patrick

2016-01-01

Whole-genome sequencing (WGS) was used for the characterization of the frequently extensively drug resistant (XDR) Pseudomonas aeruginosa sequence type 175 (ST175) high-risk clone. A total of 18 ST175 isolates recovered from 8 different Spanish hospitals were analyzed; 4 isolates from 4 different French hospitals were included for comparison. The typical resistance profile of ST175 included penicillins, cephalosporins, monobactams, carbapenems, aminoglycosides, and fluoroquinolones. In the phylogenetic analysis, the four French isolates clustered together with two isolates from one of the Spanish regions. Sequence variation was analyzed for 146 chromosomal genes related to antimicrobial resistance, and horizontally acquired genes were explored using online databases. The resistome of ST175 was determined mainly by mutational events; resistance traits common to all or nearly all of the strains included specific ampR mutations leading to ampC overexpression, specific mutations in oprD conferring carbapenem resistance, or a mexZ mutation leading to MexXY overexpression. All isolates additionally harbored an aadB gene conferring gentamicin and tobramycin resistance. Several other resistance traits were specific to certain geographic areas, such as a streptomycin resistance gene, aadA13, detected in all four isolates from France and in the two isolates from the Cantabria region and a glpT mutation conferring fosfomycin resistance, detected in all but these six isolates. Finally, several unique resistance mutations were detected in single isolates; particularly interesting were those in genes encoding penicillin-binding proteins (PBP1A, PBP3, and PBP4). Thus, these results provide information valuable for understanding the genetic basis of resistance and the dynamics of the dissemination and evolution of high-risk clones. PMID:27736752

Deciphering the Resistome of the Widespread Pseudomonas aeruginosa Sequence Type 175 International High-Risk Clone through Whole-Genome Sequencing.

PubMed

Cabot, Gabriel; López-Causapé, Carla; Ocampo-Sosa, Alain A; Sommer, Lea M; Domínguez, María Ángeles; Zamorano, Laura; Juan, Carlos; Tubau, Fe; Rodríguez, Cristina; Moyà, Bartolomé; Peña, Carmen; Martínez-Martínez, Luis; Plesiat, Patrick; Oliver, Antonio

2016-12-01

Whole-genome sequencing (WGS) was used for the characterization of the frequently extensively drug resistant (XDR) Pseudomonas aeruginosa sequence type 175 (ST175) high-risk clone. A total of 18 ST175 isolates recovered from 8 different Spanish hospitals were analyzed; 4 isolates from 4 different French hospitals were included for comparison. The typical resistance profile of ST175 included penicillins, cephalosporins, monobactams, carbapenems, aminoglycosides, and fluoroquinolones. In the phylogenetic analysis, the four French isolates clustered together with two isolates from one of the Spanish regions. Sequence variation was analyzed for 146 chromosomal genes related to antimicrobial resistance, and horizontally acquired genes were explored using online databases. The resistome of ST175 was determined mainly by mutational events; resistance traits common to all or nearly all of the strains included specific ampR mutations leading to ampC overexpression, specific mutations in oprD conferring carbapenem resistance, or a mexZ mutation leading to MexXY overexpression. All isolates additionally harbored an aadB gene conferring gentamicin and tobramycin resistance. Several other resistance traits were specific to certain geographic areas, such as a streptomycin resistance gene, aadA13, detected in all four isolates from France and in the two isolates from the Cantabria region and a glpT mutation conferring fosfomycin resistance, detected in all but these six isolates. Finally, several unique resistance mutations were detected in single isolates; particularly interesting were those in genes encoding penicillin-binding proteins (PBP1A, PBP3, and PBP4). Thus, these results provide information valuable for understanding the genetic basis of resistance and the dynamics of the dissemination and evolution of high-risk clones. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Pyrrhocoricin, a proline-rich antimicrobial peptide derived from insect, inhibits the translation process in the cell-free Escherichia coli protein synthesis system.

PubMed

Taniguchi, Masayuki; Ochiai, Akihito; Kondo, Hiroshi; Fukuda, Shun; Ishiyama, Yohei; Saitoh, Eiichi; Kato, Tetsuo; Tanaka, Takaaki

2016-05-01

Previous studies have shown that pyrrhocoricin, a proline-rich antimicrobial peptide (PrAMP), killed sensitive species in a dose-dependent manner by specifically binding to DnaK. Here, on the basis of the finding that DnaK-deficient Escherichia coli strains are susceptible to PrAMPs, we used pyrrhocoricin to investigate internal targets other than DnaK. Using conventional antibiotics (bleomycin, streptomycin, and fosfomycin) that have known modes of action, first, we validated the availability of an assay using a cell-free rapid translation system (RTS), which is an in vitro protein synthesis system based on E. coli lysate, for evaluating inhibition of protein synthesis. We found that, similarly to bleomycin and streptomycin, pyrrhocoricin inhibited GFP synthesis in RTS in a concentration-dependent manner. In addition, blockage of transcription and translation steps in RTS was individually estimated using RT-PCR after gene expression to determine mRNA products and using sodium dodecyl sulfate-polyacrylamide gel electrophoresis to determine the amounts of GFP expressed from purified mRNA, respectively. The results demonstrated that this inhibition of GFP synthesis by pyrrhocoricin did not occur at the transcription step but rather at the translation step, in a manner similar to that of GFP synthesis by streptomycin, an inhibitor of the translation step by causing misreading of tRNA. These results suggest that RTS is a powerful assay system for determining if antimicrobial peptides inhibit protein synthesis and its transcription and/or translation steps. This is the first study to have shown that pyrrhocoricin inhibited protein synthesis by specifically repressing the translation step. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

In Vitro Activity of Oral Antimicrobial Agents against Pathogens Associated with Community-Acquired Upper Respiratory Tract and Urinary Tract Infections: A Five Country Surveillance Study.

PubMed

Biedenbach, Douglas J; Badal, Robert E; Huang, Ming-Yi; Motyl, Mary; Singhal, Puneet K; Kozlov, Roman S; Roman, Arthur Dessi; Marcella, Stephen

2016-06-01

Bacterial infections that cause community-acquired urinary tract infections (CA-UTI) and upper respiratory tract infections (CA-URTI) are most frequently treated empirically. However, an increase in antimicrobial resistance has become a problem when treating outpatients. This study determined the in vitro activities of oral antibiotics among 1501 pathogens from outpatients with CA-UTI and CA-URTI in medical centers during 2012 and 2013 from Argentina, Mexico, Venezuela, Russia, and the Philippines. Minimal inhibitory concentrations (MICs) were determined using broth microdilution and susceptibility defined by Clinical Laboratory Standards Institute (CLSI) and European Committee for Antimicrobial Susceptibility Testing (EUCAST) criteria. Ceftibuten (MIC50, ≤0.25 mg/L) was more potent in vitro compared to other β-lactams against Enterobacteriaceae from CA-UTI. Susceptibility to fluoroquinolones using CLSI criteria varied: Argentina and Mexico (50%), the Philippines (60%), Venezuela (70%), and Russia (80%). Fosfomycin susceptibility was >90% against Enterobacteriaceae in each country. Susceptibility among Enterobacteriaceae to trimethoprim-sulfamethoxazole was 30.6-75.6% and nitrofurantoin susceptibility also varied among the countries and was higher when EUCAST breakpoints were applied (65->90%) compared to CLSI (52-84%). All Haemophilus influenzae isolates from CA-URTI were susceptible to ceftibuten, cefixime, cefpodoxime, and cefuroxime using CLSI breakpoint criteria. EUCAST criteria produced intermediate and resistant MIC values for these oral cephalosporins. Country-specific susceptibility variation for fluoroquinolones, macrolides, and trimethoprim-sulfamethoxazole was observed among Streptococcus pneumoniae and Streptococcus pyogenes from CA-URTI. This study demonstrated that antimicrobial susceptibility patterns varied in the five countries investigated among pathogens from CA-UTI and CA-URTI. Merck & Co. Inc., Kenilworth, New Jersey, USA.

Free establishment of primary health care providers: effects on geographical equity.

PubMed

Isaksson, David; Blomqvist, Paula; Winblad, Ulrika

2016-01-23

A reform in 2010 in Swedish primary care made it possible for private primary care providers to establish themselves freely in the country. In the former, publicly planned system, location was strictly regulated by local authorities. The goal of the new reform was to increase access and quality of health care. Critical arguments were raised that the reform could have detrimental effects on equity if the new primary health care providers chose to establish foremost in socioeconomically prosperous areas. The aim of this study is to examine how the primary care choice reform has affected geographical equity by analysing patterns of establishment on the part of new private providers. The basis of the design was to analyse socio-economic data on individuals who reside in the same electoral areas in which the 1411 primary health care centres in Sweden are established. Since the primary health care centres are located within 21 different county councils with different reimbursement schemes, we controlled for possible cluster effects utilizing generalized estimating equations modelling. The empirical material used in the analysis is a cross-sectional data set containing socio-economic data of the geographical areas in which all primary health care centres are established. When controlling for the effects of the county council regulation, primary health care centres established after the primary care choice reform were found to be located in areas with significantly fewer older adults living alone as well as fewer single parents - groups which generally have lower socio-economic status and high health care needs. However, no significant effects were observed for other socio-economic variables such as mean income, percentage of immigrants, education, unemployment, and children <5 years. The primary care choice reform seems to have had some negative effects on geographical equity, even though these seem relatively minor.

Cost-effectiveness of filgrastim and pegfilgrastim as primary prophylaxis against febrile neutropenia in lymphoma patients.

PubMed

Lathia, Nina; Isogai, Pierre K; De Angelis, Carlo; Smith, Thomas J; Cheung, Matthew; Mittmann, Nicole; Hoch, Jeffrey S; Walker, Scott

2013-08-07

Febrile neutropenia is a serious toxicity of cancer chemotherapy that is usually treated in hospital. We assessed the cost-effectiveness of filgrastim and pegfilgrastim as primary prophylaxis against febrile neutropenia in diffuse large B-cell lymphoma (DLBCL) patients undergoing chemotherapy. We used a Markov model that followed patients through induction chemotherapy to compare the three prophylaxis strategies: 1) no primary prophylaxis against febrile neutropenia; 2) primary prophylaxis with 10 days of filgrastim therapy; and 3) primary prophylaxis with a single dose of pegfilgrastim. The target population was a hypothetical cohort of 64-year-old men and women with DLBCL. Data sources included published literature and current clinical practice. The analysis was conducted from a publicly funded health-care system perspective. The main outcome measures included costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). In the base-case analysis, costs associated with no primary prophylaxis, primary prophylaxis with 10 days of filgrastim, and primary prophylaxis with pegfilgrastim were CaD $7314, CaD $13947, and CaD $16290, respectively. The QALYs associated with the three strategies were 0.2004, 0.2015, and 0.2024, respectively. The ICER for the filgrastim vs no primary prophylaxis strategy was CaD $5796000 per QALY. The ICER for the pegfilgrastim vs filgrastim primary prophylaxis strategy was CaD $2611000 per QALY. All one-way sensitivity analyses yielded ICERs greater than CaD $400000 per QALY. Cost-effectiveness acceptability curves show that 20.0% of iterations are cost-effective at a willingness-to-pay threshold of CaD $1595000 for the filgrastim strategy and CaD $561000 for the pegfilgrastim strategy. Primary prophylaxis against febrile neutropenia with either filgrastim or pegfilgrastim is not cost-effective in DLBCL patients.

Long-Term Effects of Primary Schools on Mathematics Achievement of Students at Age 17

ERIC Educational Resources Information Center

Vanwynsberghe, Griet; Vanlaar, Gudrun; Van Damme, Jan; De Fraine, Bieke

2017-01-01

In the field of educational effectiveness research, school effects are generally studied in the short term (i.e. during the same phase of schooling). The aim of this study is to investigate long-term primary school effects on students' achievement in mathematics at the end of secondary education. We also investigate which primary school…

Different antibiotic regimens for treating asymptomatic bacteriuria in pregnancy

PubMed Central

Guinto, Valerie T; De Guia, Blanca; Festin, Mario R; Dowswell, Therese

2014-01-01

Background Asymptomatic bacteriuria occurs in 5% to 10% of pregnancies and, if left untreated, can lead to serious complications. Objectives To assess which antibiotic is most effective and least harmful as initial treatment for asymptomatic bacteriuria in pregnancy. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (March 2010) and reference lists of retrieved studies. Selection criteria Randomized controlled trials comparing two antibiotic regimens for treating asymptomatic bacteriuria. Data collection and analysis Review authors independently screened the studies for inclusion and extracted data. Main results We included five studies involving 1140 women with asymptomatic bacteriuria. We did not perform meta-analysis; each trial examined different antibiotic regimens and so we were not able to pool results. In a study comparing a single dose of fosfomycin trometamol 3 g with a five-day course of cefuroxime, there was no significant difference in persistent infection (risk ratio (RR) 1.36, 95% confidence interval (CI) 0.24 to 7.75), shift to other antibiotics (RR 0.08, 95% CI 0.00 to 1.45), or in allergy or pruritus (RR 2.73, 95% CI 0.11 to 65.24). A comparison of seven-day courses of 400 mg pivmecillinam versus 500 mg ampicillin, both given four times daily, showed no significant difference in persistent infection at two weeks or recurrent infection, but there was an increase in vomiting (RR 4.57, 95% CI 1.40 to 14.90) and women were more likely to stop treatment early with pivmecillinam (RR 8.82, 95% CI 1.16 to 66.95). When cephalexin 1 g versus Miraxid® (pivmecillinam 200 mg and pivampicillin 250 mg) were given twice-daily for three days, there was no significant difference in persistent or recurrent infection. A one- versus seven-day course of nitrofurantoin resulted in more persistent infection with the shorter course (RR 1.76, 95% CI 1.29 to 2.40), but no significant difference in symptomatic infection at two weeks, nausea, or preterm birth. Comparing cycloserine with sulphadimidine, no significant differences in symptomatic, persistent, or recurrent infections were noted. Authors’ conclusions We cannot draw any definite conclusion on the most effective and safest antibiotic regimen for the initial treatment of asymptomatic bacteriuria in pregnancy. One study showed advantages with a longer course of nitrofurantoin, and another showed better tolerability with ampicillin compared with pivmecillinam; otherwise, there was no significant difference demonstrated between groups treated with different antibiotics. Given this lack of conclusive evidence, it may be useful for clinicians to consider factors such as cost, local availability and side effects in the selection of the best treatment option. PMID:20824868

A Study on Primary and Secondary School Students' Misconceptions about Greenhouse Effect (Erzurum Sampling)

ERIC Educational Resources Information Center

Gul, Seyda; Yesilyurt, Selami

2011-01-01

The aim of this study is to determine what level of primary and secondary school students' misconceptions related to greenhouse effect is. Study group consists of totally 280 students attended to totally 8 primary and secondary schools (4 primary school, 4 secondary school) which were determined with convenient sampling method from center of…

Mathematics Performance and Principal Effectiveness: A Case Study of Some Coastal Primary Schools in Sri Lanka

ERIC Educational Resources Information Center

Egodawatte, Gunawardena

2012-01-01

This mixed method research study is situated in the school effectiveness research paradigm to examine the correlation between the effectiveness of urban, primary school principals and their students' performance in mathematics. Nine, urban, primary schools from Negombo, a coastal fishing area in Sri Lanka, were selected; their student achievements…

Long-Term Effects of Primary Schools on Educational Positions of Students 2 and 4 Years after the Start of Secondary Education

ERIC Educational Resources Information Center

Vanwynsberghe, Griet; Vanlaar, Gudrun; Van Damme, Jan; De Fraine, Bieke

2017-01-01

Although the importance of primary schools in the long term is of interest in educational effectiveness research, few studies have examined the long-term effects of schools over the past decades. In the present study, long-term effects of primary schools on the educational positions of students 2 and 4 years after starting secondary education are…

F14:A-:B- and IncX4 Inc group cfr-positive plasmids circulating in Escherichia coli of animal origin in Northeast China.

PubMed

Wang, Xiumei; Zhu, Yao; Hua, Xin; Chen, Fuguang; Wang, Changzhen; Zhang, Yanhe; Liu, Siguo; Zhang, Wanjiang

2018-04-01

The objective of this study was to investigate the prevalence of the cfr gene in Escherichia coli isolates from domestic animals in Northeast China and to characterize the cfr-containing plasmids. Between June 2015 and April 2016, 370 E. coli isolates were collected from pigs, chickens, and dairy cows in Northeast China. Among these, 111 were florfenicol resistant, including 109 isolates carrying the floR gene and 6 positives for cfr. The prevalence of cfr in E. coli isolates from the four northeast provinces in China was 1.6% (6/370), which was higher than that previously reported (0.08% and 0.5%). All six cfr-containing E. coli isolates were highly resistant to florfenicol (100%), cefotaxime (100%), and fosfomycin (100%). Complete sequence analysis of two cfr-carrying plasmids revealed high homology of the IncX4-type pEC14cfr plasmid with two other cfr-harboring plasmids, pSD11 and pGXEC6, found in swine E. coli isolates from southern China. pEC14cfr-like plasmids have been isolated in five provinces in southern and northern China. The isolation sites were up to 2700 kilometers apart, implying that pEC14cfr-like plasmids are likely to be national epidemic cfr-carrying plasmids that mediate the dissemination of cfr in China. Moreover, the genetic structure (IS26-IS26-cfr-rec-pre/mob-ramA-IS26) of the second cfr-carrying plasmid, IncF14:A-:B- pEC295cfr, represents a novel genetic environment for cfr identified for the first time in the present study. Sequence homology analysis indicated that the cfr-carrying element was most likely introduced into a cfr-negative pEC12 plasmid backbone, which evolved into the cfr-carrying vector, pEC295cfr. Moreover, isolation of the IncF14:A-:B- pEC295cfr plasmid harboring cfr suggests that IncFII plasmids maybe have become additional effective vehicles for cfr dissemination. These results highlight the importance of surveying the prevalence of IncX4 and IncFII plasmids in gram-negative bacteria, especially in swine E. coli isolates. Copyright © 2018 Elsevier B.V. All rights reserved.

Bacteriology and Antibiogram of Urinary Tract Infection Among Female Patients in a Tertiary Health Facility in South Eastern Nigeria.

PubMed

Oli, Angus N; Akabueze, Vivian B; Ezeudu, Chijioke E; Eleje, George U; Ejiofor, Obiora S; Ezebialu, Ifeanyichukwu U; Oguejiofor, Charlotte B; Ekejindu, Ifeoma M; Emechebe, George O; Okeke, Kenneth N

2017-01-01

Urinary Tract Infection (UTI) is a common contagion among men and women with the incidence relatively higher among women due to their differing anatomy. An understanding of the kind of pathogens implicated in urinary tract infections as well as antibiotic susceptibility profiling may help the clinician make rationally correct empirical choice in their treatment. This study is aimed at determining the type and antibiotic susceptibility pattern of bacterial uropathogens isolated from female patients attending Chukwuemeka Odumegwu Ojukwu University Teaching Hospital (COOUTH), Awka, Nigeria. Two hundred and forty patients with clinically diagnosed UTI and who were on at least 5 days' antibiotic holiday were recruited into the study. Their demographic characteristics were captured using pre-tested questionnaire. Their clean catch mid-stream urine samples were collected using sterile universal container and sent to the Microbiology Department for processing. Within 30 minutes of samples collection, the specimens were cultured and the isolates were identified, after 24 h of incubation, using standard microbiological techniques. Antibiotic susceptibility tests were done with standard antibiotic discs using the Kirby-bauer disc diffusion method. Out of the 240 urine samples, 89.17% yielded significant bacteriuria. The pathogens implicated were Escherichia coli (28.5%), Staphylococcus aureus (28.0%), Salmonella spp (22.8%) and Pseudomonas aeruginosa (20.5%). HIV status, patients age, pregnancy status and marital status all significantly affected bacteriuria rate (p value < 0.05), while patients' location (sub-urban/rural dwelling), and level of education did not (p value > 0.05). The pattern of microbial resistance to antibiotics suggests that ceftazidime, fosfomycin and cefoxitin may not be used as first-line agents in the empirical treatment of UTIs rather; levofloxacin, meropenem or aztreonam should be considered. Levofloxacin was significantly effective against all the isolates and may be administered empirically while waiting for the culture result (Mean % susceptibility was 79.85). E. coli and S. aureus were the predominant pathogens in the study and many were resistant to the commonly prescribed antibiotics and so leave the clinicians with only few alternative drugs for UTIs treatment. Routine surveillance and monitoring studies need to be constantly conducted to update clinicians on the prevalent pathogens and the rational and empirical treatment of UTIs. Aggressive and consistent health education using every possible media is also recommended to combat the menace of drug resistance occasioned by inappropriate antibiotic use.

Primary Student-Teachers' Conceptual Understanding of the Greenhouse Effect: A mixed method study

NASA Astrophysics Data System (ADS)

Ratinen, Ilkka Johannes

2013-04-01

The greenhouse effect is a reasonably complex scientific phenomenon which can be used as a model to examine students' conceptual understanding in science. Primary student-teachers' understanding of global environmental problems, such as climate change and ozone depletion, indicates that they have many misconceptions. The present mixed method study examines Finnish primary student-teachers' understanding of the greenhouse effect based on the results obtained via open-ended and closed-form questionnaires. The open-ended questionnaire considers primary student-teachers' spontaneous ideas about the greenhouse effect depicted by concept maps. The present study also uses statistical analysis to reveal respondents' conceptualization of the greenhouse effect. The concept maps and statistical analysis reveal that the primary student-teachers' factual knowledge and their conceptual understanding of the greenhouse effect are incomplete and even misleading. In the light of the results of the present study, proposals for modifying the instruction of climate change in science, especially in geography, are presented.

Influencing Intended Teaching Practice: Exploring pre-service teachers' perceptions of science teaching resources

NASA Astrophysics Data System (ADS)

Cooper, Grant; Kenny, John; Fraser, Sharon

2012-08-01

Many researchers have identified and expressed concern over the state of science education internationally, but primary teachers face particular obstacles when teaching science due to their poor science background and low confidence with science. Research has suggested that exemplary resources, or units that work, may be an effective way to support primary teachers. This study explores the effect of one such resource on the intentions of pre-service primary teachers to teach science. The resource in question is Primary Connections, a series of learning resources produced by the Australian Academy of Science specifically designed for primary science. Evaluative studies of Primary Connections have indicated its efficacy with practising primary teachers but there is little evidence of its impact upon pre-service teachers. The purpose of this study was to investigate how effective these quality teaching resources were in influencing the intentions of primary pre-service teachers to teach science after they graduated. The theory of planned behaviour highlighted the linkage between the intentions of the pre-service teachers to teach science, and their awareness of and experiences with using Primary Connections during their education studies. This enabled key factors to be identified which influenced the intentions of the pre-service teachers to use Primary Connections to teach science after they graduate. The study also provided evidence of how quality science teaching resources can be effectively embedded in a teacher education programme as a means of encouraging and supporting pre-service teachers to teach science.

Follow-up of cancer in primary care versus secondary care: systematic review

PubMed Central

Lewis, Ruth A; Neal, Richard D; Williams, Nefyn H; France, Barbara; Hendry, Maggie; Russell, Daphne; Hughes, Dyfrig A; Russell, Ian; Stuart, Nicholas SA; Weller, David; Wilkinson, Clare

2009-01-01

Background Cancer follow-up has traditionally been undertaken in secondary care, but there are increasing calls to deliver it in primary care. Aim To compare the effectiveness and cost-effectiveness of primary versus secondary care follow-up of cancer patients, determine the effectiveness of the integration of primary care in routine hospital follow-up, and evaluate the impact of patient-initiated follow-up on primary care. Design of study Systematic review. Setting Primary and secondary care settings. Method A search was carried out of 19 electronic databases, online trial registries, conference proceedings, and bibliographies of included studies. The review included comparative studies or economic evaluations of primary versus secondary care follow-up, hospital follow-up with formal primary care involvement versus conventional hospital follow-up, and hospital follow-up versus patient-initiated or minimal follow-up if the study reported the impact on primary care. Results There was no statistically significant difference for patient wellbeing, recurrence rate, survival, recurrence-related serious clinical events, diagnostic delay, or patient satisfaction. GP-led breast cancer follow-up was cheaper than hospital follow-up. Intensified primary health care resulted in increased home-care nurse contact, and improved discharge summary led to increased GP contact. Evaluation of patient-initiated or minimal follow-up found no statistically significant impact on the number of GP consultations or cancer-related referrals. Conclusion Weak evidence suggests that breast cancer follow-up in primary care is effective. Interventions improving communication between primary and secondary care could lead to greater GP involvement. Discontinuation of formal follow-up may not increase GP workload. However, the quality of the data in general was poor, and no firm conclusions can be reached. PMID:19566990

Effects of Aerobic Training on Primary Dysmenorrhea Symptomatology in College Females.

ERIC Educational Resources Information Center

Israel, Richard G.; And Others

1985-01-01

This study investigated the effects of a 12-week aerobic training program on menstrual distress symptoms in college females with clinically diagnosed primary dysmenorrhea. The findings suggest that aerobic training can significantly reduce the symptoms associated with primary dysmenorrhea. (Author/MT)

Effects of zinc oxide-eugenol and calcium hydroxide/ iodoform on delaying root resorption in primary molars without successors.

PubMed

Lin, Bichen; Zhao, Yuming; Yang, Jie; Wang, Wenjun; Ge, Li-hong

2014-01-01

The purpose of this study was to compare the effects of zinc oxide-eugenol (ZOE) and calcium hydroxide/iodoform paste (Vitapex), as root canal filling materials in pulpectomy, on delaying the root resorption of primary molars without permanent successors. Animal models without permanent successors were surgically established in beagle dogs. Root resorption was observed via periapical radiographs. The onset of root resorption of primary mandibular molars without successors occurred later (p<0.05) than physiologic resorption. ZOE pulpectomy clearly delayed the root resorption of primary molars without permanent successors (p<0.05), whereas resorption of primary molars with Vitapex pulpectomy started at almost the same time as physiologic resorption. Compared with Vitapex, ZOE was a more effective root canal filling material in delaying the root resorption of primary molars.

Dynamic sex roles among men who have sex with men and transmissions from primary HIV infection.

PubMed

Alam, Shah Jamal; Romero-Severson, Ethan; Kim, Jong-Hoon; Emond, Gilbert; Koopman, James S

2010-09-01

Previous studies estimating the fraction of transmissions from persons with primary HIV have not focused on the effects of switching sex role in male homosexual populations. Such behavioral fluctuations can increase the contribution of primary HIV in the overall population. We modeled HIV transmission with 8 compartments defined by 4 behavioral groups, with different anal-insertive and anal-receptive combinations, and 2 stages of infection. We explored the effects of fluctuating behavioral categories on endemic prevalence and the fraction of transmissions from primary HIV. We varied transition rates to develop the theory on how behavioral fluctuation affects infection patterns, and we used the transition rates in a Netherlands cohort to assess overall effects in a real setting. The dynamics of change in behavior-group status over time observed in the Netherlands cohort amplifies the prevalence of infection and the fraction of transmissions from primary HIV, resulting in the highest proportions of transmissions being from people with primary HIV. Fluctuation between dual- or receptive-role periods and no-anal-sex periods mainly determines this amplification. In terms of the total transmissions, the dual-role risk group is dominant. Fluctuation between insertive and receptive roles decreases the fraction of transmissions from primary HIV, but such fluctuation is infrequently observed. The fraction of transmissions from primary HIV is considerably raised by fluctuations in insertive and receptive anal sex behaviors. This increase occurs even when primary HIV or later infection status does not influence risk behavior. Thus, it is not simply biology but also behavior patterns and social contexts that determine the fraction of transmissions from primary HIV. Moreover, each primary HIV transmission has a larger population effect than each later infection transmission because the men to whom one transmits from primary HIV carry on more chains of transmissions than the men to whom one transmits later in infection. Reducing transmissions from primary HIV should be a primary focus of HIV control efforts.

Exploring the Mediating Effects of Trust on Principal Leadership and Teacher Professional Learning in Hong Kong Primary Schools

ERIC Educational Resources Information Center

Li, Lijuan; Hallinger, Philip; Walker, Allan

2016-01-01

This study attempted to identify effects of trust between principal leadership and teacher professional learning in Hong Kong primary schools. To verify the potential mediating effects of trust as a component of school capacity, survey data with a sample of 970 teachers from 32 local primary schools was used. Two questionnaires were combined to…

Effects of Watching Primary Debates in the 2000 U.S. Presidential Campaign.

ERIC Educational Resources Information Center

Benoit, William L.; McKinney, Mitchell S.; Stephenson, Michael T.

2002-01-01

Reports the results of two studies measuring the effects on undergraduate communication students of watching U.S. presidential primary debates. Concludes that primary debates are capable of influencing both policy and character impressions of the candidates, as well as changing voting intentions and increasing voter confidence. (SG)

Jordanian Preservice Primary Teachers' Perceptions of Mentoring in Science Teaching

NASA Astrophysics Data System (ADS)

Abed, Osama H.; Abd-El-Khalick, Fouad

2015-03-01

Quality mentoring is fundamental to preservice teacher education because of its potential to help student and novice teachers develop the academic and pedagogical knowledge and skills germane to successful induction into the profession. This study focused on Jordanian preservice primary teachers' perceptions of their mentoring experiences as these pertain to science teaching. The Mentoring for Effective Primary Science Teaching instrument was administered to 147 senior preservice primary teachers in a university in Jordan. The results indicated that the greater majority of participants did not experience effective mentoring toward creating a supportive and reflexive environment that would bolster their confidence in teaching science; further their understanding of primary science curriculum, and associated aims and school policies; help with developing their pedagogical knowledge; and/or furnish them with specific and targeted feedback and guidance to help improve their science teaching. Substantially more participants indicated that their mentors modeled what they perceived to be effective science teaching. The study argues for the need for science-specific mentoring for preservice primary teachers, and suggests a possible pathway for achieving such a model starting with those in-service primary teachers-much like those identified by participants in the present study-who are already effective in their science teaching.

Adjuvant treatment or primary topical monotherapy for ocular surface squamous neoplasia: a systematic review.

PubMed

Viani, Gustavo Arruda; Fendi, Ligia Issa de

2017-01-01

In this systematic review, we evaluated studies involving adjuvant and primary topical treatment for ocular surface squamous neoplasia (OSSN). The findings were: (i) adjuvant 5-fluorouracil (5-FU) reduces the risk of relapse after surgical excision with mild side effects [level Ib, grade of recommendation (GR) A]. (ii) Primary topical mitomycin (MMC) produces a high rate of complete response, low recurrence rate, and mild side effects (level Ib, GR A). (iii) Primary chemotherapy versus adjuvant chemotherapy produce similar rates of recurrence, with no significant difference (level IIb, GR B). (iv) Adjuvant 5-FU versus MMC showed no significant differences, with mild side effects in both groups and a better toxicity profile for MMC (level III, GR C). (v) Primary topical 5-FU versus MMC versus interferon (IFN) showed similar rates of tumor recurrence, mild side effects for all drugs, and more severe side effects in the 5-FU arm, followed successively by MMC and IFN (level III, GR C).

Effect of primary amines on magnetic properties of Fe-Ni films electroplated in a DES-based plating bath

NASA Astrophysics Data System (ADS)

Yanai, T.; Akiyoshi, T.; Yamaguchi, T.; Takashima, K.; Morimura, T.; Nakano, M.; Fukunaga, H.

2018-05-01

Fe-Ni alloy films were electroplated in DES-based plating baths with various primary amines, and we investigated the effect of the primary amines on the magnetic and the structural properties of the films. The primary amines of ammonium sulfamate, DL-α-alanine and L-glutamic acid reduced the coercivity and the surface roughness of the Fe-rich films (Fe > 70 at.%), and the reduction tendencies of the coercivity and the roughness show good agreement with the result of our previous study on another primary amine of glycine. From the results for the TEM observation, we found that the texture of the Fe-rich film is clearly different from that for the Fe-poor one (Fe < 30 at.%), and we concluded that the primary amines are effective additives for the Fe-rich films electroplated in the DES-based plating baths.

Preliminary investigation on the effects of primary airflow to coal particle distribution in coal-fired boilers

NASA Astrophysics Data System (ADS)

Noor, N. A. W. Mohd; Hassan, H.; Hashim, M. F.; Hasini, H.; Munisamy, K. M.

2017-04-01

This paper presents an investigation on the effects of primary airflow to coal fineness in coal-fired boilers. In coal fired power plant, coal is pulverized in a pulverizer, and it is then transferred to boiler for combustion. Coal need to be ground to its desired size to obtain maximum combustion efficiency. Coarse coal particle size may lead to many performance problems such as formation of clinker. In this study, the effects of primary airflow to coal particles size and coal flow distribution were investigated by using isokinetic coal sampling and computational fluid dynamic (CFD) modelling. Four different primary airflows were tested and the effects to resulting coal fineness were recorded. Results show that the optimum coal fineness distribution is obtained at design primary airflow. Any reduction or increase of air flow rate results in undesirable coal fineness distribution.

Health and Economic Implications of National Treatment Coverage for Cardiovascular Disease in India: Cost-Effectiveness Analysis.

PubMed

Basu, Sanjay; Bendavid, Eran; Sood, Neeraj

2015-11-01

Whether to cover cardiovascular disease costs is an increasingly pressing question for low- and middle-income countries. We sought to identify the impact of expanding national insurance to cover primary prevention, secondary prevention, and tertiary treatment for cardiovascular disease in India. We incorporated data from coverage experiments into a validated microsimulation model of myocardial infarction and stroke in India to evaluate the cost-effectiveness of alternate coverage strategies. Coverage of primary prevention alone saved 3.6 million disability-adjusted life-years (DALY) per annum at an incremental cost-effectiveness ratio of $469 per DALY averted when compared with the status quo of no coverage. Coverage of primary and secondary preventions was dominated by a strategy of covering primary prevention and tertiary treatment, which prevented 6.6 million DALYs at an incremental cost-effectiveness ratio of $2241 per DALY averted, when compared with that of primary prevention alone. The combination of all 3 categories yielded the greatest impact at an incremental cost per DALY averted of $5588 when compared with coverage of primary prevention plus tertiary treatment. When compared with the status quo of no coverage, coverage of all 3 categories of prevention/treatment yielded an incremental cost-effectiveness ratio of $1331 per DALY averted. In sensitivity analyses, coverage of primary preventive treatments remained cost-effective even if adherence and access to therapy were low, but tertiary coverage would require avoiding unnecessary procedures to remain cost-effective. Coverage of all 3 major types of cardiovascular treatment would be expected to have high impact and reasonable cost-effectiveness in India across a broad spectrum of access and adherence levels. © 2015 American Heart Association, Inc.

Web-based treatment for substance use disorders: differential effects by primary substance.

PubMed

Cochran, Gerald; Stitzer, Maxine; Campbell, Aimee N C; Hu, Mei-Chen; Vandrey, Ryan; Nunes, Edward V

2015-06-01

This secondary analysis of data from a large, multi-site effectiveness trial (NCT01104805) sought to determine whether effects of a web-based behavioral treatment (Therapeutic Education System [TES]) differed by participants' self-identified primary drug of abuse. The all-comers sample of individuals entering outpatient psychosocial counseling treatment for substance abuse (N=497) cited cannabis (22.9%; n=114), stimulants (34.4%, n=171), opioids (21.7%, n=108), or alcohol (20.9%, n=104) as their primary substance of abuse. Participants were randomly assigned to receive treatment-as-usual (TAU) with or without TES substituted for approximately 2h of usual counseling. Multivariate analyses of abstinence outcomes examined interactions of treatment effects with primary substance. Adjusted odds ratios (AORs) demonstrated that primary stimulant users receiving TES were more likely to be abstinent in the final four weeks of treatment compared to stimulant users receiving TAU (AOR=3.59, 95% CI=1.25-10.27). Adjusted odds ratios for alcohol (AOR=3.15, 95% CI=0.85-11.65) and cannabis (AOR=2.64, 95% CI=0.73-9.52) also were of similar magnitude to stimulants but did not reach significance. Abstinence among primary opioid users was not improved by the TES intervention (AOR=0.35, 95% CI=0.09-1.47). This study supports the TES web-delivered treatment as a viable intervention for the majority of substance users entering outpatient counseling treatment, with demonstrated effectiveness among stimulant users and promising effects in alcohol and cannabis users but little or no effect in primary opioid users. Web-delivered treatments hold promise for expanding the availability of effective behavioral interventions for the majority of substance use disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Moving effective treatment for posttraumatic stress disorder to primary care: A randomized controlled trial with active duty military.

PubMed

Cigrang, Jeffrey A; Rauch, Sheila A; Mintz, Jim; Brundige, Antoinette R; Mitchell, Jennifer A; Najera, Elizabeth; Litz, Brett T; Young-McCaughan, Stacey; Roache, John D; Hembree, Elizabeth A; Goodie, Jeffrey L; Sonnek, Scott M; Peterson, Alan L

2017-12-01

Many military service members with PTSD do not receive evidence-based specialty behavioral health treatment because of perceived barriers and stigma. Behavioral health providers in primary care can deliver brief, effective treatments expanding access and reducing barriers and stigma. The purpose of this randomized clinical trial was to determine if a brief cognitive-behavior therapy delivered in primary care using the Primary Care Behavioral Health model would be effective at reducing PTSD and co-occurring symptoms. A total of 67 service members (50 men, 17 women) were randomized to receive a brief, trauma-focused intervention developed for the primary care setting called Prolonged Exposure for Primary Care (PE-PC) or a delayed treatment minimal contact control condition. Inclusion criteria were significant PTSD symptoms following military deployment, medication stability, and interest in receiving treatment for PTSD symptoms in primary care. Exclusion criteria were moderate or greater risk of suicide, severe brain injury, or alcohol/substance use at a level that required immediate treatment. Assessments were completed at baseline, posttreatment/postminimal contact control, and at 8-week and 6-month posttreatment follow-up points. Primary measures were the PTSD Symptom Scale-Interview and the PTSD Checklist-Stressor-Specific. PE-PC resulted in larger reduction in PTSD severity and general distress than the minimal contact control. Delayed treatment evidenced medium to large effects comparable to the immediate intervention group. Treatment benefits persisted through the 6-month follow-up of the study. PE-PC delivered in integrated primary care is effective for the treatment of PTSD and co-occurring symptoms and may help reduce barriers and stigma found in specialty care settings. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

The FiCTION dental trial protocol – filling children’s teeth: indicated or not?

PubMed Central

2013-01-01

Background There is a lack of evidence for effective management of dental caries (decay) in children’s primary (baby) teeth and an apparent failure of conventional dental restorations (fillings) to prevent dental pain and infection for UK children in Primary Care. UK dental schools’ teaching has been based on British Society of Paediatric Dentistry guidance which recommends that caries in primary teeth should be removed and a restoration placed. However, the evidence base for this is limited in volume and quality, and comes from studies conducted in either secondary care or specialist practices. Restorations provided in specialist environments can be effective but the generalisability of this evidence to Primary Care has been questioned. The FiCTION trial addresses the Health Technology Assessment (HTA) Programme’s commissioning brief and research question “What is the clinical and cost effectiveness of restoration caries in primary teeth, compared to no treatment?” It compares conventional restorations with an intermediate treatment strategy based on the biological (sealing-in) management of caries and with no restorations. Methods/Design This is a Primary Care-based multi-centre, three-arm, parallel group, patient-randomised controlled trial. Practitioners are recruiting 1461 children, (3–7 years) with at least one primary molar tooth where caries extends into dentine. Children are randomized and treated according to one of three treatment approaches; conventional caries management with best practice prevention, biological management of caries with best practice prevention or best practice prevention alone. Baseline measures and outcome data (at review/treatment during three year follow-up) are assessed through direct reporting, clinical examination including blinded radiograph assessment, and child/parent questionnaires. The primary outcome measure is the incidence of either pain or infection related to dental caries. Secondary outcomes are; incidence of caries in primary and permanent teeth, patient quality of life, cost-effectiveness, acceptability of treatment strategies to patients and parents and their experiences, and dentists’ preferences. Discussion FiCTION will provide evidence for the most clinically-effective and cost-effective approach to managing caries in children’s primary teeth in Primary Care. This will support general dental practitioners in treatment decision making for child patients to minimize pain and infection in primary teeth. The trial is currently recruiting patients. Trial registration Protocol ID: NCTU: ISRCTN77044005 PMID:23725316

The FiCTION dental trial protocol - filling children's teeth: indicated or not?

PubMed

Innes, Nicola P T; Clarkson, Jan E; Speed, Chris; Douglas, Gail V A; Maguire, Anne

2013-06-01

There is a lack of evidence for effective management of dental caries (decay) in children's primary (baby) teeth and an apparent failure of conventional dental restorations (fillings) to prevent dental pain and infection for UK children in Primary Care. UK dental schools' teaching has been based on British Society of Paediatric Dentistry guidance which recommends that caries in primary teeth should be removed and a restoration placed. However, the evidence base for this is limited in volume and quality, and comes from studies conducted in either secondary care or specialist practices. Restorations provided in specialist environments can be effective but the generalisability of this evidence to Primary Care has been questioned. The FiCTION trial addresses the Health Technology Assessment (HTA) Programme’s commissioning brief and research question “What is the clinical and cost effectiveness of restoration caries in primary teeth, compared to no treatment?” It compares conventional restorations with an intermediate treatment strategy based on the biological (sealing-in) management of caries and with no restorations. This is a Primary Care-based multi-centre, three-arm, parallel group, patient-randomised controlled trial. Practitioners are recruiting 1461 children, (3-7 years) with at least one primary molar tooth where caries extends into dentine. Children are randomized and treated according to one of three treatment approaches; conventional caries management with best practice prevention, biological management of caries with best practice prevention or best practice prevention alone. Baseline measures and outcome data (at review/treatment during three year follow-up) are assessed through direct reporting, clinical examination including blinded radiograph assessment, and child/parent questionnaires. The primary outcome measure is the incidence of either pain or infection related to dental caries. Secondary outcomes are; incidence of caries in primary and permanent teeth, patient quality of life, cost-effectiveness, acceptability of treatment strategies to patients and parents and their experiences, and dentists’ preferences. FiCTION will provide evidence for the most clinically-effective and cost-effective approach to managing caries in children's primary teeth in Primary Care. This will support general dental practitioners in treatment decision making for child patients to minimize pain and infection in primary teeth. The trial is currently recruiting patients. Protocol ID: NCTU: ISRCTN77044005.

Binary asteroid orbit evolution due to primary shape deformation

NASA Astrophysics Data System (ADS)

Hirabayashi, Masatoshi; Jacobson, Seth A.; Davis, Alex

2017-10-01

About a sixth of all small asteroid systems are binary [Margot et al., Science, 2002]. Many binary asteroids consist of an elongated synchronous secondary body orbiting a fast-rotating spheroidal primary body with ridges on its equator. The primary in such systems has experienced a long-term spin-up due to the YORP effect [Vokrouhlick'y et al., Asteroid IV, 2015]. This spin-up process can make the primary reach its spin barrier inducing shape deformation processes that ease the structural condition for failure inside the primary [e.g., Holsapple, Icarus, 2010]. Earlier works have shown that structural heterogeneities in the primary such as the shape and density distribution induce asymmetric deformation [Sánchez and Scheeres, Icarus, 2016]. Here, we investigate how asymmetric shape deformation in the primary affects the mutual motion of a binary system. We use a dynamics model for an irregularly shaped binary system that accounts for possible deformation of the primary [Hirabayashi et al., LPSC, 2017]. In this model, we consider asymmetric deformation that occurs based on structural failure in the primary and thus it modifies the location of the center of mass of the system. Using 1999 KW4 as an example, we study a hypothetical case in which the primary is initially identical to the current shape [Ostro et al., Science, 2006] with an aspect ratio (AR) of 0.83 and then suddenly changes its shape to an AR of 0.76. The results show that the asymmetric deformation process and the shift of the center of mass excite the eccentricity of the mutual orbit. Considering that the original mutual orbit has an eccentricity of 0.0004, after the primary shape change the eccentricity reaches values up to 0.15. Also, since the gravity field is modified after deformation, the secondary’s spin is desynchronized from the mutual orbit. Since synchronicity is a requirement for the binary YORP (BYORP) effect, which modifies the semi-major axis of binary asteroids, a primary shape change temporarily pauses the BYORP effect, in effect lengthening the effective BYORP timescale.

Development of Effective Academic Affairs Administration System in Thai Primary Schools

ERIC Educational Resources Information Center

Thongnoi, Niratchakorn; Srisa-ard, Boonchom; Sri-ampai, Anan

2013-01-01

This research aimed to: 1) study current situations and problems of academic affairs administration system in Primary Schools. 2) develop an effective academic affairs administration system, and 3) evaluate the implementation of the developed system in the primary school, Thailand. Research and Development (R&D) was employed which consisted of…

The Effects of Servant Leadership on Teachers' Organizational Commitment in Primary Schools in Turkey

ERIC Educational Resources Information Center

Cerit, Yusuf

2010-01-01

This study examines the effects of servant leadership behaviours of primary school principals on teachers' school commitment. The research data were collected from 563 teachers working in primary schools in Duzce. Servant leadership behaviours of principals were measured with a servent organizational leadership assessment scale, and the teachers'…

Effect of a Science Diagram on Primary Students' Understanding about Magnets

ERIC Educational Resources Information Center

Preston, Christine

2016-01-01

The research investigated the effect of a science diagram on primary students' conceptual understanding about magnets. Lack of research involving students of primary age means that little is known about the potential of science diagrams to help them understand abstract concepts such as magnetism. Task-based interviews were conducted individually…

Louisiana SIP: LAC 33:III Ch 23 Subchap B, §2303--Aluminum Plants, §2303 Standards for Horizontal Stud Soderberg Primary Aluminum Plants and Prebake Primary Aluminum Plants; SIP effective 1989-05-08 (LAc49) to 2011-08-03 (LAad34 - Revised)

EPA Pesticide Factsheets

Louisiana SIP: LAC 33:III Ch 23 Subchap B, §2303--Aluminum Plants, §2303 Standards for Horizontal Stud Soderberg Primary Aluminum Plants and Prebake Primary Aluminum Plants; SIP effective 1989-05-08 (LAc49) to 2011-08-03 (LAad34 - Revised)

Group metacognitive therapy for repetitive negative thinking in primary and non-primary generalized anxiety disorder: an effectiveness trial.

PubMed

McEvoy, Peter M; Erceg-Hurn, David M; Anderson, Rebecca A; Campbell, Bruce N C; Swan, Amanda; Saulsman, Lisa M; Summers, Mark; Nathan, Paula R

2015-04-01

Generalized anxiety disorder (GAD) is a common and highly comorbid anxiety disorder characterized by repetitive negative thinking (RNT). Treatment trials tend to exclude individuals with non-primary GAD, despite this being a common presentation in real world clinics. RNT is also associated with multiple emotional disorders, suggesting that it should be targeted regardless of the primary disorder. This study evaluated the acceptability and effectiveness of brief group metacognitive therapy (MCT) for primary or non-primary GAD within a community clinic. Patients referred to a specialist community clinic attended six, two-hour weekly sessions plus a one-month follow-up (N=52). Measures of metacognitive beliefs, RNT, symptoms, positive and negative affect, and quality of life were completed at the first, last, and follow-up sessions. Attrition was low and large intent-to-treat effects were observed on most outcomes, particularly for negative metacognitive beliefs and RNT. Treatment gains increased further to follow-up. Benchmarking comparisons demonstrated that outcomes compared favorably to longer disorder-specific protocols for primary GAD. No control group or independent assessment of protocol adherence. Brief metacognitive therapy is an acceptable and powerful treatment for patients with primary or non-primary GAD. Copyright © 2014 Elsevier B.V. All rights reserved.

Exploring weight loss services in primary care and staff views on using a web-based programme.

PubMed

Ware, Lisa J; Williams, Sarah; Bradbury, Katherine; Brant, Catherine; Little, Paul; Hobbs, F D Richard; Yardley, Lucy

2012-01-01

Demand is increasing for primary care to deliver effective weight management services to patients, but research suggests that staff feel inadequately resourced for such a role. Supporting service delivery with a free and effective web-based weight management programme could maximise primary care resource and provide cost-effective support for patients. However, integration of e-health into primary care may face challenges. To explore primary care staff experiences of delivering weight management services and their perceptions of a web-based weight management programme to aid service delivery. Focus groups were conducted with primary care physicians, nurses and healthcare assistants (n = 36) involved in delivering weight loss services. Data were analysed using inductive thematic analysis. Participants thought that primary care should be involved in delivering weight management, especially when weight was aggravating health problems. However, they felt under-resourced to deliver these services and unsure as to the effectiveness of their input, as routine services were not evaluated. Beliefs that current services were ineffective resulted in staff reluctance to allocate more resources. Participants were hopeful that supplementing practice with a web-based weight management programme would enhance patient services and promote service evaluation. Although primary care staff felt they should deliver weight loss services, low levels of faith in the efficacy of current treatments resulted in provision of under-resourced and 'ad hoc' services. Integration of a web-based weight loss programme that promotes service evaluation and provides a cost-effective option for supporting patients may encourage practices to invest more in weight management services.

Future climate change driven sea-level rise: secondary consequences from human displacement for island biodiversity.

PubMed

Wetzel, Florian T; Kissling, W Daniel; Beissmann, Helmut; Penn, Dustin J

2012-09-01

Sea-level rise (SLR) due to global warming will result in the loss of many coastal areas. The direct or primary effects due to inundation and erosion from SLR are currently being assessed; however, the indirect or secondary ecological effects, such as changes caused by the displacement of human populations, have not been previously evaluated. We examined the potential ecological consequences of future SLR on >1,200 islands in the Southeast Asian and the Pacific region. Using three SLR scenarios (1, 3, and 6 m elevation, where 1 m approximates most predictions by the end of this century), we assessed the consequences of primary and secondary SLR effects from human displacement on habitat availability and distributions of selected mammal species. We estimate that between 3-32% of the coastal zone of these islands could be lost from primary effects, and consequently 8-52 million people would become SLR refugees. Assuming that inundated urban and intensive agricultural areas will be relocated with an equal area of habitat loss in the hinterland, we project that secondary SLR effects can lead to an equal or even higher percent range loss than primary effects for at least 10-18% of the sample mammals in a moderate range loss scenario and for 22-46% in a maximum range loss scenario. In addition, we found some species to be more vulnerable to secondary than primary effects. Finally, we found high spatial variation in vulnerability: species on islands in Oceania are more vulnerable to primary SLR effects, whereas species on islands in Indo-Malaysia, with potentially 7-48 million SLR refugees, are more vulnerable to secondary effects. Our findings show that primary and secondary SLR effects can have enormous consequences for human inhabitants and island biodiversity, and that both need to be incorporated into ecological risk assessment, conservation, and regional planning. © 2012 Blackwell Publishing Ltd.

Efficacy of self-help manuals for anxiety disorders in primary care: a systematic review.

PubMed

van Boeijen, Christine A; van Balkom, Anton J L M; van Oppen, Patricia; Blankenstein, Nettie; Cherpanath, Ammani; van Dyck, Richard

2005-04-01

The purpose of this study was to review effectiveness studies of self-help manuals for anxiety disorders in primary care. A systematic review of six identified randomized controlled trials was carried out. In addition to outcome, the articles were coded on quality variables. The studies included differed with respect to the methodological quality, measurements used and size of the study population. Despite these differences, global results suggest that a self-help manual is an effective treatment possibility for primary care patients with anxiety disorders. The more time that was spent on guidance on the use of the self-help manual the greater was its effectiveness. Treatment with a self-help manual for anxiety disorders may be effective in primary care. Data are lacking on the feasibility and cost-effectiveness of these manuals.

School Effectiveness at Primary Level of Education in Relation to Classroom Teaching

ERIC Educational Resources Information Center

Panigrahi, Manas Ranjan

2014-01-01

The study aims to investigate the relationship of School Effectiveness with regard to classroom teaching at primary level of education. The objectives of the study were to identify the more-effective and less-effective schools; to find out the differences between more-effective and less-effective schools in relation to physical facilities, Head…

40 CFR 141.60 - Effective dates.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS National Primary Drinking Water Regulations: Maximum Contaminant Levels and Maximum Residual Disinfectant Levels § 141.60 Effective dates. (a) The effective dates for § 141...

Effectiveness of School-Based Bullying Intervention Programs in Primary School

ERIC Educational Resources Information Center

Dogini, Eric U.

2012-01-01

Bullying behavior has reached pandemic proportions and is a growing concern in primary school. Most intervention programs in primary school are focused on bullying prevention or principally on the behavior of the bully. The purpose of this study was to explore whether a school-based bullying intervention program is an effective method for reducing…

Effectiveness of a Stress-Relief Initiative for Primary Caregivers of Adolescents with Intellectual Disability

ERIC Educational Resources Information Center

Hu, Jung; Lin, Jin-Ding; Yen, Chia-Feng; Loh, Ching-Hui; Hsu, Shang-Wei; Lin, Lan-Ping; Wu, Sheng-Ru

2010-01-01

Background: This study provides a perspective on the mental health status and analyses the effectiveness of a stress-relief program for primary caregivers of adolescents with intellectual disability (ID). Method: Seventy-seven primary caregivers of people with ID were recruited (intervention group, n = 31; non-intervention group, n = 46) to the…

Global Warming Responses at the Primary Secondary Interface: 2. Potential Effectiveness of Education

ERIC Educational Resources Information Center

Skamp, Keith; Boyes, Eddie; Stannistreet, Martin

2009-01-01

In an earlier paper (Skamp, Boyes, & Stanisstreet, 2009b), students' beliefs and willingness to act in relation to 16 specific actions related to global warming were compared across the primary secondary interface. More primary students believed in the effectiveness of most actions to reduce global warming and were willing to take those…

A Thought on Reviewing Ways in Primary School

ERIC Educational Resources Information Center

He, Xiaojun

2015-01-01

This paper will focus on the effective review of English in the third grade of primary school. In the first part, the author introduces the importance of improving the effective review of English in the third grade of primary school. Analyzing from the aspects of theories, teachers have to get a good knowledge of language theories and analyze it…

Effects of Continuing Professional Development on Group Work Practices in Scottish Primary Schools

ERIC Educational Resources Information Center

Thurston, A.; Christie, D.; Howe, C. J.; Tolmie, A.; Topping, K. J.

2008-01-01

The present study investigated the effects of a continuing professional development (CPD) initiative that provided collaborative group work skills training for primary school teachers. The study collected data from 24 primary school classrooms in different schools in a variety of urban and rural settings. The sample was composed of 332 pupils,…

Ethnic Favoritism in Primary Education in Kenya: Effects of Coethnicity with the President

ERIC Educational Resources Information Center

Li, Jia

2018-01-01

This study measures the effect of ethnic favoritism on primary education using data from the Kenya Demographic and Health Survey. In line with previous studies, this study confirms that having a coethnic president is expected to improve the likelihood of completing primary education. This study demonstrates that ethnic favoritism operates at the…

The Effect of Using Computer Edutainment on Developing 2nd Primary Graders' Writing Skills

ERIC Educational Resources Information Center

Mohammed Abdel Raheem, Azza Ashraf

2011-01-01

The present study attempted to examine the effect of using computer edutainment on developing 2nd graders' writing skills. The study comprised thirty-second year primary stage enrolled in Bani Hamad primary governmental school, Minia governorate. The study adopted the quasi-experimental design. Thirty participants were randomly assigned to one…

Mediating Effects of Trust, Communication, and Collaboration on Teacher Professional Learning in Hong Kong Primary Schools

ERIC Educational Resources Information Center

Li, Lijuan; Hallinger, Philip; Kennedy, Kerry John; Walker, Allan

2017-01-01

This study tests mediated principal leadership effects on teacher professional learning through collegial trust, communication and collaboration in Hong Kong primary schools. It is based on a series of single mediator studies, and uses the same convenience sample of 970 teachers from 32 local primary schools. It also adopts regression-based…

The Effect of Cooperative Writing Activities on Writing Anxieties of Prospective Primary School Teachers

ERIC Educational Resources Information Center

Erdogan, Ozge

2017-01-01

The purpose of this research is to determine the effect of cooperative writing activities on the writing anxieties of prospective primary school teachers. The study group of the research is composed of 30 prospective primary school teachers. A mixed method consisting of qualitative and quantitative research methods was used in the collection,…

The Effects of Servant Leadership Behaviours of School Principals on Teachers' Job Satisfaction

ERIC Educational Resources Information Center

Cerit, Yusuf

2009-01-01

This article examines the effects of servant leadership behaviours of primary school principals on teacher job satisfaction. The population of this study is 29 primary schools in Duzce, Turkey. Data were collected from 595 teachers working in primary schools in Duzce province of Turkey. Servant leadership behaviours of principals were determined…

Cost-effectiveness of cervical cancer screening with primary human papillomavirus testing in Norway.

PubMed

Burger, E A; Ortendahl, J D; Sy, S; Kristiansen, I S; Kim, J J

2012-04-24

New screening technologies and vaccination against human papillomavirus (HPV), the necessary cause of cervical cancer, may impact optimal approaches to prevent cervical cancer. We evaluated the cost-effectiveness of alternative screening strategies to inform cervical cancer prevention guidelines in Norway. We leveraged the primary epidemiologic and economic data from Norway to contextualise a simulation model of HPV-induced cervical cancer. The current cytology-only screening was compared with strategies involving cytology at younger ages and primary HPV-based screening at older ages (31/34+ years), an option being actively deliberated by the Norwegian government. We varied the switch-age, screening interval, and triage strategies for women with HPV-positive results. Uncertainty was evaluated in sensitivity analysis. Current cytology-only screening was less effective and more costly than strategies that involve switching to primary HPV testing in older ages. For unvaccinated women, switching at age 34 years to primary HPV testing every 4 years was optimal given the Norwegian cost-effectiveness threshold ($83,000 per year of life saved). For vaccinated women, a 6-year screening interval was cost-effective. When we considered a wider range of strategies, we found that an earlier switch to HPV testing (at age 31 years) may be preferred. Strategies involving a switch to HPV testing for primary screening in older women is expected to be cost-effective compared with current recommendations in Norway.

Secondary transfer effect among children: The role of social dominance orientation and outgroup attitudes.

PubMed

Vezzali, Loris; Di Bernardo, Gian Antonio; Stathi, Sofia; Cadamuro, Alessia; Lášticová, Barbara; Andraščiková, Simona

2018-02-24

Research has provided evidence that the effects of intergroup contact on prejudice reduction are not limited to the outgroup one has contact with (primary outgroup). Rather, they extend to secondary outgroups uninvolved in the contact situation (secondary transfer effect; Pettigrew, 2009, Social Psychology, 40, 55). We aimed to provide the first empirical evidence for the emergence of the secondary transfer effect among children. Majority (Italian) and minority (with an immigrant background) elementary schoolchildren were administered a questionnaire including measures of contact with the primary outgroup (minority children for the majority, majority children for the minority), prejudice towards the primary outgroup and towards a dissimilar secondary outgroup (disabled children), and social dominance orientation. Results revealed that among the majority group, contact with the primary outgroup had indirect associations with reduced prejudice towards the secondary outgroup. Specifically, we found evidence for sequential mediation by social dominance orientation and prejudice towards the primary outgroup. No secondary transfer effects emerged among minority group members. We discuss theoretical and practical implications of the findings, arguing for the importance of identifying the core processes driving the secondary transfer effect. © 2018 The British Psychological Society.

Systematic review of the effectiveness of primary care nursing.

PubMed

Keleher, Helen; Parker, Rhian; Abdulwadud, Omar; Francis, Karen

2009-02-01

This paper reports on a systematic review that sought to answer the research question: What is the impact of the primary and community care nurse on patient health outcomes compared with usual doctor-led care in primary care settings? A range of pertinent text-words with medical subject headings were combined and electronic databases were searched. Because of the volume of published articles, the search was restricted to studies with high-level evidence. Overall, 31 relevant studies were identified and included in the review. We found modest international evidence that nurses in primary care settings can provide effective care and achieve positive health outcomes for patients similar to that provided by doctors. Nurses are effective in care management and achieve good patient compliance. Nurses are also effective in a more diverse range of roles including chronic disease management, illness prevention and health promotion. Nevertheless, there is insufficient evidence about primary care nurses' roles and impact on patient health outcomes.

Advising people to take more exercise is ineffective: a randomized controlled trial of physical activity promotion in primary care.

PubMed

Hillsdon, Melvyn; Thorogood, Margaret; White, Ian; Foster, Charlie

2002-08-01

Over the last 10 years 'exercise referral schemes' have been popular even though the evidence for effectiveness of any one-to-one intervention in primary care is deficient. We report the results of a primary care based one-to-one intervention that compared the effect of two communication styles with a no-intervention control group on self-reported physical activity at 12 months. In all, 1658 middle-aged men and women were randomly assigned to 30 minutes of brief negotiation or direct advice in primary care or a no-intervention control group. The main outcome was self-reported physical activity at 12 months. Secondary outcome measures included change in blood pressure and body mass index. Intention-to-treat analysis revealed no significant differences in physical activity between groups. Brief negotiation group participants who completed the study increased their physical activity significantly more than controls. There was no change in body mass index in any group. The brief negotiation group produced a greater reduction in diastolic blood pressure than direct advice. If patients whose health may benefit from increased physical activity seek advice in primary care, 20-30 minutes of brief negotiation to increase physical activity is probably more effective than similar attempts to persuade or coerce. However, blanket physical activity promotion in primary care is not effective. The most effective way of increasing physical activity in primary care has yet to be determined.

Hepatoprotective effects of Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] on alcohol-damaged primary rat hepatocyte culture in vitro.

PubMed

Jiang, Wenhua; Bian, Yuzhu; Wang, Zhenghui; Chang, Thomas Ming Swi

2017-02-01

We have prepared a novel nanobiotherapeutic, Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase], which not only transports both oxygen and carbon dioxide but also a therapeutic antioxidant. Our previous study in a severe sustained 90 min hemorrhagic shock rat model shows that it has a hepatoprotective effect. We investigate its hepatoprotective effect further in this present report using an alcohol-damaged primary hepatocyte culture model. Results show that it significantly reduced ethanol-induced AST release, lipid peroxidation, and ROS production in rat primary hepatocytes culture. It also significantly enhanced the viability of ethanol-treated hepatocytes. Thus, the result shows that Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] also has some hepatoprotective effects against alcohol-induced injury in in vitro rat primary hepatocytes cell culture. This collaborate our previous observation of its hepatoprotective effect in a severe sustained 90-min hemorrhagic shock rat model.

Effect of Case Studies on Primary School Teaching Students' Attitudes toward Chemistry Lesson

ERIC Educational Resources Information Center

Ayyildiz, Yildizay; Tarhan, Leman

2012-01-01

The purpose of this study was to investigate the effect of case studies on Primary School Teaching students' attitudes toward chemistry lesson. The study was conducted on 63 freshmen from Department of Primary School Teaching at a university in Turkey. The students were taught using case studies about the subjects of Properties and States of…

Measuring Learning Quality in Ethiopia, India and Vietnam: From Primary to Secondary School Effectiveness

ERIC Educational Resources Information Center

Iyer, Padmini; Moore, Rhiannon

2017-01-01

This paper examines the way in which learning quality has been conceptualised and measured in school effectiveness surveys conducted by Young Lives, a longitudinal study of child poverty. Primary school surveys were conducted in Vietnam in 2010-11 and Ethiopia in 2012-13, and surveys at upper-primary and secondary level were conducted in Ethiopia,…

Investigating the Effects of Asthma Medication on the Cognitive and Psychosocial Functioning of Primary School Children with Asthma

ERIC Educational Resources Information Center

Naude, H.; Pretorius, E.

2003-01-01

The effects of asthma medication on the cognitive and psychosocial functioning of primary school children with asthma are investigated. A questionnaire survey was conducted in a primary school in Stellenbosch (South Africa) with a population of six hundred and thirty-five students. Among these students, fifty-nine asthmatic children were…

Exploring the Effects of Classroom Culture on Primary Pre-Service Teachers' Professional Development

ERIC Educational Resources Information Center

Altun, Taner

2013-01-01

This study aims to examine primary student teachers' (PSTs) perceptions about the effects of pre-formed classroom culture on their professional development. In the study, a mixed method approach was used. The study group consisted of 4th year student teachers who attend a primary teacher education program leading to a B.Ed. degree at the Fatih…

Assessment of HIV/AIDS and Life Skills Delivery in Primary Schools in Tanzania

ERIC Educational Resources Information Center

Rushahu, Bernadetha Gabriel

2015-01-01

This study was conducted to assess the effectiveness of HIV/AIDS and the Life Skills Education delivery in primary schools in Tanzania. Specifically the study investigated pupils' views about the effect of HIV/AIDS and Life Skills teaching in primary schools in Tanzania; assessed pupils' knowledge related to HIV/AIDS and Life Skills education, and…

The Effect of Organizational Trust on the Culture of Teacher Leadership in Primary Schools

ERIC Educational Resources Information Center

Demir, Kamile

2015-01-01

The purpose of this research is to examine the effect of the level of trust of primary school teachers towards their organization in relation to their perceptions of the school having a culture of teacher leadership. Participants of the study consisted of 378 teachers working in Burdur public primary schools. The data collection tool used two…

Institutional Placement: Phases of the Transition.

ERIC Educational Resources Information Center

Zarit, Steven H.; Whitlatch, Carol J.

1992-01-01

Examined consequences of institutionalization for 555 caregivers of dementia patients. Consistent with stress process model, institutionalization was hypothesized to have large impact on primary effects of caregiving and lesser influence on secondary effects and well-being. Following placement, caregivers experienced relief from primary effects of…

Effect of an acid mine drainage effluent on phytoplankton biomass and primary production at Britannia Beach, Howe Sound, British Columbia.

PubMed

Levings, C D; Varela, D E; Mehlenbacher, N M; Barry, K L; Piercey, G E; Guo, M; Harrison, P J

2005-12-01

We investigated the effect of acid mine drainage (AMD) from an abandoned copper mine at Britannia Beach (Howe Sound, BC, Canada) on primary productivity and chlorophyll a levels in the receiving waters of Howe Sound before, during, and after freshet from the Squamish River. Elevated concentrations of copper (integrated average through the water column >0.050 mgl(-1)) in nearshore waters indicated that under some conditions a small gyre near the mouth of Britannia Creek may have retained the AMD from Britannia Creek and from a 30-m deep water outfall close to shore. Regression and correlation analyses indicated that copper negatively affected primary productivity during April (pre-freshet) and November (post-freshet). Negative effects of copper on primary productivity were not supported statistically for July (freshet), possibly because of additional effects such as turbidity from the Squamish River. Depth-integrated average and surface chlorophyll a were correlated to copper concentrations in April. During this short study we demonstrated that copper concentrations from the AMD discharge can negatively affect both primary productivity and the standing stock of primary producers in Howe Sound.

The role of the premotor cortex and the primary motor cortex in action verb comprehension: evidence from Granger causality analysis.

PubMed

Yang, Jie; Shu, Hua

2012-08-01

Although numerous studies find the premotor cortex and the primary motor cortex are involved in action language comprehension, so far the nature of these motor effects is still in controversy. Some researchers suggest that the motor effects reflect that the premotor cortex and the primary motor cortex make functional contributions to the semantic access of action verbs, while other authors argue that the motor effects are caused by comprehension. In the current study, we used Granger causality analysis to investigate the roles of the premotor cortex and the primary motor cortex in processing of manual-action verbs. Regions of interest were selected in the primary motor cortex (M1) and the premotor cortex based on a hand motion task, and in the left posterior middle temporal gyrus (lexical semantic area) based on the reading task effect. We found that (1) the left posterior middle temporal gyrus had a causal influence on the left M1; and (2) the left posterior middle temporal gyrus and the left premotor cortex had bidirectional causal relations. These results suggest that the premotor cortex and the primary motor cortex play different roles in manual verb comprehension. The premotor cortex may be involved in motor simulation that contributes to action language processing, while the primary motor cortex may be engaged in a processing stage influenced by the meaning access of manual-action verbs. Further investigation combining effective connectivity analysis and technique with high temporal resolution is necessary for better clarification of the roles of the premotor cortex and the primary motor cortex in action language comprehension. Copyright © 2012 Elsevier Inc. All rights reserved.

Cost-effectiveness of primary offer of IVF vs. primary offer of IUI followed by IVF (for IUI failures) in couples with unexplained or mild male factor subfertility.

PubMed

Pashayan, Nora; Lyratzopoulos, Georgios; Mathur, Raj

2006-06-23

In unexplained and mild male factor subfertility, both intrauterine insemination (IUI) and in-vitro fertilisation (IVF) are indicated as first line treatments. Because the success rate of IUI is low, many couples failing IUI subsequently require IVF treatment. In practice, it is therefore important to examine the comparative outcomes (live birth-producing pregnancy), costs, and cost-effectiveness of primary offer of IVF, compared with primary offer of IUI followed by IVF for couples failing IUI. Mathematical modelling was used to estimate comparative clinical and cost effectiveness of either primary offer of one full IVF cycle (including frozen cycles when applicable) or "IUI + IVF" (defined as primary IUI followed by IVF for IUI failures) to a hypothetical cohort of subfertile couples who are eligible for both treatment strategies. Data used in calculations were derived from the published peer-reviewed literature as well as activity data of local infertility units. Cost-effectiveness ratios for IVF, "unstimulated-IUI (U-IUI) + IVF", and "stimulated IUI (S-IUI) + IVF" were 12,600 pounds sterling, 13,100 pound sterling and 15,100 pound sterling per live birth-producing pregnancy respectively. For a hypothetical cohort of 100 couples with unexplained or mild male factor subfertility, compared with primary offer of IVF, 6 cycles of "U-IUI + IVF" or of "S-IUI + IVF" would cost an additional 174,200 pounds sterling and 438,000 pounds sterling, representing an opportunity cost of 54 and 136 additional IVF cycles and 14 to 35 live birth-producing pregnancies respectively. For couples with unexplained and mild male factor subfertility, primary offer of a full IVF cycle is less costly and more cost-effective than providing IUI (of any modality) followed by IVF.

Cost-effectiveness of primary offer of IVF vs. primary offer of IUI followed by IVF (for IUI failures) in couples with unexplained or mild male factor subfertility

PubMed Central

Pashayan, Nora; Lyratzopoulos, Georgios; Mathur, Raj

2006-01-01

Background In unexplained and mild male factor subfertility, both intrauterine insemination (IUI) and in-vitro fertilisation (IVF) are indicated as first line treatments. Because the success rate of IUI is low, many couples failing IUI subsequently require IVF treatment. In practice, it is therefore important to examine the comparative outcomes (live birth-producing pregnancy), costs, and cost-effectiveness of primary offer of IVF, compared with primary offer of IUI followed by IVF for couples failing IUI. Methods Mathematical modelling was used to estimate comparative clinical and cost effectiveness of either primary offer of one full IVF cycle (including frozen cycles when applicable) or "IUI + IVF" (defined as primary IUI followed by IVF for IUI failures) to a hypothetical cohort of subfertile couples who are eligible for both treatment strategies. Data used in calculations were derived from the published peer-reviewed literature as well as activity data of local infertility units. Results Cost-effectiveness ratios for IVF, "unstimulated-IUI (U-IUI) + IVF", and "stimulated IUI (S-IUI) + IVF" were £12,600, £13,100 and £15,100 per live birth-producing pregnancy respectively. For a hypothetical cohort of 100 couples with unexplained or mild male factor subfertility, compared with primary offer of IVF, 6 cycles of "U-IUI + IVF" or of "S-IUI + IVF" would cost an additional £174,200 and £438,000, representing an opportunity cost of 54 and 136 additional IVF cycles and 14 to 35 live birth-producing pregnancies respectively. Conclusion For couples with unexplained and mild male factor subfertility, primary offer of a full IVF cycle is less costly and more cost-effective than providing IUI (of any modality) followed by IVF. PMID:16796733

Extended spectrum β-lactamase and plasmid mediated quinolone resistance in Escherichia coli fecal isolates from healthy companion animals in Algeria.

PubMed

Yousfi, Massilia; Mairi, Assia; Touati, Abdelaziz; Hassissene, Lila; Brasme, Lucien; Guillard, Thomas; De Champs, Christophe

2016-07-01

The aim of this study was to evaluate the rate of fecal carriage of Escherichia coli strains producing Extended-spectrum β-lactamases (ESBLs) and plasmid-mediated quinolone resistance (PMQR) isolated from healthy pets (dogs and cats) in Algeria. Fecal samples from 171 healthy pets (102 dogs and 69 cats) in one veterinary practice and private owners were included. After isolates identification, antibiotic susceptibility was determined by disk diffusion procedure. ESBL were detected by combination disk tests. PCR and sequencing were used to characterize genes encoding ESBLs and PMQR. Transfer of ESBL and PMQR genes was assessed by conjugation experiments. Phylogenetic groups of E. coli were determined by PCR. Of the 171 animals, 20 carried an ESBL producing E. coli giving a prevalence of ESBL fecal carriage of 11.7%. All isolates were susceptible to carbapenems, cefoxitin, piperacillin-tazobactam, amikacin and fosfomycine. For the rest of the tested β-lactams, susceptibility rates ranged from 35% to 70% for cefepime and amoxicillin-clavulanic acid respectively. Concerning the non-beta-lactams antibiotics, the rates of susceptibility ranged between 5% to trimethoprim and 95% for chloramphenicol. The beta-lactamase genes identified in E. coli isolates were blaCTX-M-15, blaCTX-M-1, blaSHV-12 and blaTEM-1. The PMQR determinants aac(6')-Ib-cr, qnrS1 and qnrB5 genes were identified in 15 isolates. Transconjugants were obtained for two isolates. Phylogenetic analysis showed that E. coli isolates belong to commensal phylogroups of A and B1. We reported here for the first time in Algeria ESBL and PMQR-producing E. coli in healthy cats and dogs. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Susceptibility of bacteria isolated from acute gastrointestinal infections to rifaximin and other antimicrobial agents in Mexico.

PubMed

Novoa-Farías, O; Frati-Munari, A C; Peredo, M A; Flores-Juárez, S; Novoa-García, O; Galicia-Tapia, J; Romero-Carpio, C E

2016-01-01

Bacterial resistance may hamper the antimicrobial management of acute gastroenteritis. Bacterial susceptibility to rifaximin, an antibiotic that achieves high fecal concentrations (up to 8,000μg/g), has not been evaluated in Mexico. To determine the susceptibility to rifaximin and other antimicrobial agents of enteropathogenic bacteria isolated from patients with acute gastroenteritis in Mexico. Bacterial strains were analyzed in stool samples from 1,000 patients with diagnosis of acute gastroenteritis. The susceptibility to rifaximin (RIF) was tested by microdilution (<100, <200, <400 and <800μg/ml) and susceptibility to chloramphenicol (CHL), trimethoprim-sulfamethoxazole (T-S), neomycin (NEO), furazolidone (FUR), fosfomycin (FOS), ampicillin (AMP) and ciprofloxacin (CIP) was tested by agar diffusion at the concentrations recommended by the Clinical & Laboratory Standards Institute and the American Society for Microbiology. Isolated bacteria were: enteropathogenic Escherichia coli (E. coli) (EPEC) 531, Shigella 120, non-Typhi Salmonella 117, Aeromonas spp. 80, enterotoxigenic E. coli (ETEC) 54, Yersinia enterocolitica 20, Campylobacter jejuni 20, Vibrio spp. 20, Plesiomonas shigelloides 20, and enterohemorrhagic E. coli (EHEC 0:157) 18. The overall cumulative susceptibility to RIF at <100, <200, <400, and <800μg/ml was 70.6, 90.8, 99.3, and 100%, respectively. The overall susceptibility to each antibiotic was: AMP 32.2%, T-S 53.6%, NEO 54.1%, FUR 64.7%, CIP 67.3%, CLO 73%, and FOS 81.3%. The susceptibility to RIF <400 and RIF <800μg/ml was significantly greater than with the other antibiotics (p<0.001). Resistance of enteropathogenic bacteria to various antibiotics used in gastrointestinal infections is high. Rifaximin was active against 99-100% of these enteropathogens at reachable concentrations in the intestine with the recommended dose. Copyright © 2015 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

Emergence of Klebsiella variicola positive for NDM-9, a variant of New Delhi metallo-β-lactamase, in an urban river in South Korea.

PubMed

Di, Doris Y W; Jang, Jeonghwan; Unno, Tatsuya; Hur, Hor-Gil

2017-04-01

To examine the presence of pathogenic bacteria carrying New Delhi metallo-β-lactamase in the environment and to characterize the genome structures of these strains. Phenotypic screening of antimicrobial susceptibility and WGS were conducted on three Klebsiella variicola strains possessing NDM-9 isolated from an urban river. Three carbapenem-resistant K. variicola isolated from Gwangju tributary were found to possess bla NDM-9 genes. Antimicrobial susceptibility testing indicated resistance of these strains to aminoglycosides, carbapenems, cephems, folate pathway inhibitors, fosfomycin and penicillins, but susceptibility to fluoroquinolones, phenicols, tetracyclines and miscellaneous agents. WGS revealed that the 108 kb IncFII(Y)-like plasmids carry bla NDM-9 sandwiched between IS 15 for the GJ1 strain, IS 26 for the GJ2 strain, IS 15D1 for the GJ3 strain and IS Vsa3 , and further bracketed by IS 26 and Tn AS3 along with the mercury resistance operon upstream and the class 1 integron composed of gene cassettes of aadA2 , dfrA12 and sul1 downstream. An aph(3')-Ia gene conferring resistance to aminoglycosides is located after the integrons. Chromosomally encoded bla LEN-13 , fosA , aqxA and oqxB genes, as well as plasmid-mediated bla TEM-1B and bla CTX-M-65 encoding ESBL, ant(3')-Ia and mph (A) genes, were also identified. The findings of the present study provide us with the information that NDM-9 has been spreading into the environment. Dissemination of NDM-9 in the environment has raised a health risk alarm as this variant of NDM carries MDR genes with highly transferable mobile genetic elements, increasing the possibility of resistance gene transfer among microorganisms in the environment. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Major globally disseminated clonal complexes of antimicrobial resistant enterococci associated with infections in cancer patients in Brazil.

PubMed

Santos, Barbara A; Oliveira, Jéssica S; Cardoso, Nayara T; Barbosa, André V; Superti, Silvana V; Teixeira, Lúcia M; Neves, Felipe P G

2017-11-01

Cancer and hematological malignancies constitute major comorbidities in enterococcal infections, but little is known about the characteristics of enterococci affecting cancer patients. The aim of this study was to characterize 132 enterococcal clinical isolates obtained from cancer patients attending a Cancer Reference Center in Brazil between April 2013 and March 2014. Susceptibility to 17 antimicrobial agents was assessed by disk diffusion method. Resistance and virulence genes were investigated by PCR. Multilocus sequence typing (MLST) was performed for selected Enterococcus faecalis and Enterococcus faecium isolates. The predominant species was E. faecalis (108 isolates), followed by E. faecium (18), Enterococcus gallinarum (3), Enterococcus avium (2) and Enterococcus durans (1). Multidrug-resistant (MDR) isolates made up 44.7%, but all isolates were susceptible to fosfomycin, linezolid and glycopeptides. The most prevalent genes associated with erythromycin- and tetracycline-non susceptible isolates were erm(B) (47/71; 66.2%) and tet(M) (24/68; 35.3%), respectively. High-level resistance (HLR) to gentamicin was found in 22 (16.7%) isolates and 13 (59.1%) of them carried the aac(6')-Ie-aph(2″)-Ia gene. HLR to streptomycin was detected in 34 (25.8%) isolates, of which 15 (44.1%) isolates had the ant(6')-Ia gene. The most common virulence genes were gelE (48.9%), esp (30.5%) and asa1 (29.8%). MLST performed for 26 E. faecalis isolates revealed 18 different sequence-types (STs), with seven corresponding to novel STs (625, 626, 627, 628, 629, 630, and 635). On the other hand, nine of 10 E. faecium isolates analyzed by MLST belonged to a single clonal complex, comprised of mostly ST412, which emerged worldwide after mid-2000s, but also two novel STs (963 and 964). We detected major globally disseminated E. faecalis and E. faecium clonal complexes along with novel closely related STs, indicating the fitness and continuous evolution of these hospital-adapted lineages. Copyright © 2017 Elsevier B.V. All rights reserved.

Susceptibility to rifaximin and other antimicrobials of bacteria isolated in patients with acute gastrointestinal infections in Southeast Mexico.

PubMed

Novoa-Farias, O; Frati-Munari, A C; Peredo, M A; Flores-Juárez, S; Novoa-García, O; Galicia-Tapia, J; Romero-Carpio, C E

Enteropathogenic bacteria isolated in Mexico City have shown a high rate of resistance to different antibiotics, with the exception of rifaximin (RIF). RIF is a nonabsorbable antibiotic that reaches high fecal concentrations (≈ 8,000μg/g). Susceptibility to antimicrobials can vary in different geographic regions. To study the susceptibility to rifaximin and other antimicrobials of enteropathogenic bacteria isolated in patients with acute diarrhea in the southeastern region of Mexico. A total of 614 strains of bacteria isolated from patients with acute diarrhea from 4 cities in Southeast Mexico were analyzed. An antibiogram with the following antibiotics was created: ampicillin (AMP), trimethoprim/sulfamethoxazole (T-S), neomycin (NEO), furazolidone (FUR), ciprofloxacin (CIP), chloramphenicol (CHL), and fosfomycin (FOS), assessed through the agar diffusion method at the standard concentrations recommended by the Clinical and Laboratory Standards Institute (CLSI) and the American Society for Microbiology (ASM), and RIF, assessed through microdilution at 4 concentrations. The bacteria were Escherichia coli (55%), as the majority, in all its pathogenic variants, Shigella (16.8%), Salmonella (15.3%), Aeromonas (7.8%), and less than 5% Campylobacter, Yersinia, Vibrio, and Plesiomonas. The accumulated overall susceptibility to RIF was 69.1, 90.8, 98.9, and 100% at concentrations of 100, 200, 400, and 800μg/ml, respectively. Overall susceptibility to other antibiotics was FOS 82.8%, CHL 76.8%, CIP 73.9%, FUR 64%, T-S 58.7%, NEO 55.8%, and AMP 23.8%. Susceptibility to RIF at 400 and 800μg was significantly greater than with the other antimicrobials (P<.001). The data of the present study were similar to those of a previous study carried out in Mexico City: susceptibility to RIF in > 98% of the bacterial strains and a high frequency of resistance to several common antimicrobials. Copyright © 2017 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

The Effect of Chilling and Ce Addition on the Microstructure and Mechanical Properties of Al-23Si Alloy

NASA Astrophysics Data System (ADS)

Vijeesh, V.; Narayan Prabhu, K.

2017-01-01

The present work involves the study of the effect of varying concentration of Ce addition on microstructure and mechanical properties of Al-23%Si alloys. Melt-treated alloys were solidified in copper, brass, stainless steel molds to assess the effect of cooling rate. The effect on microstructure was assessed by measuring the fineness of primary silicon and eutectic silicon particle characteristics. The Ce melt treatment transformed the coarse and irregular primary silicon into refined polyhedral silicon crystals, and the effect was more significant at higher cooling rates. Although the melt treatment had refined the eutectic silicon at lower cooling rates, it did not show any considerable effect on the eutectic silicon at higher cooling rates. The mechanical properties of the alloy increased significantly with increase in cooling rates and cerium concentration. Analysis of the results and literature reveals that the refined primary silicon was formed as a result of an invariant reaction between Ce compounds and primary silicon at higher temperatures.

Effect of Ga Addition on Morphology and Recovery of Primary Si During Al-Si Alloy Solidification Refining

NASA Astrophysics Data System (ADS)

Li, Jingwei; Bai, Xiaolong; Li, Yanlei; Ban, Boyuan; Chen, Jian

2015-12-01

The effect of Ga addition on alloy macrostructure, morphology and recovery rate of primary Si during the Al-Si-Ga alloy solvent refining process of silicon was studied in this work. The addition of Ga to Al-Si alloy could change the morphology of the primary Si. The average plate thickness of the primary Si increases with increase of Ga content. With the increase of Ga content, the average plate length of the primary Si crystals becomes larger when the Ga content is less than 5% in the Al-30%Si-xGa alloy, but becomes smaller when the Ga content exceeds 5%. Al-Si-Ga alloys consist of three types, primary Si, GaxAl1-x, (α-Al+Si+β-Ga) eutectic. (111) is the preferred growth surface of the plate-like primary Si. The recovery rate of the primary Si increases with the increase of Ga content. When the Ga content increased to 20% in Al-30%Si-xGa alloy, the relative recovery rate of the primary Si increased to 50.41% than that in Al-30%Si alloy.

The Efficacy of Mindfulness-Based Interventions in Primary Care: A Meta-Analytic Review.

PubMed

Demarzo, Marcelo M P; Montero-Marin, Jesús; Cuijpers, Pim; Zabaleta-del-Olmo, Edurne; Mahtani, Kamal R; Vellinga, Akke; Vicens, Caterina; López-del-Hoyo, Yolanda; García-Campayo, Javier

2015-11-01

Positive effects have been reported after mindfulness-based interventions (MBIs) in diverse clinical and nonclinical populations. Primary care is a key health care setting for addressing common chronic conditions, and an effective MBI designed for this setting could benefit countless people worldwide. Meta-analyses of MBIs have become popular, but little is known about their efficacy in primary care. Our aim was to investigate the application and efficacy of MBIs that address primary care patients. We performed a meta-analytic review of randomized controlled trials addressing the effect of MBIs in adult patients recruited from primary care settings. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane guidelines were followed. Effect sizes were calculated with the Hedges g in random effects models. The meta-analyses were based on 6 trials having a total of 553 patients. The overall effect size of MBI compared with a control condition for improving general health was moderate (g = 0.48; P = .002), with moderate heterogeneity (I(2) = 59; P <.05). We found no indication of publication bias in the overall estimates. MBIs were efficacious for improving mental health (g = 0.56; P = .007), with a high heterogeneity (I(2) = 78; P <.01), and for improving quality of life (g = 0.29; P = .002), with a low heterogeneity (I(2) = 0; P >.05). Although the number of randomized controlled trials applying MBIs in primary care is still limited, our results suggest that these interventions are promising for the mental health and quality of life of primary care patients. We discuss innovative approaches for implementing MBIs, such as complex intervention and stepped care. © 2015 Annals of Family Medicine, Inc.

The Efficacy of Mindfulness-Based Interventions in Primary Care: A Meta-Analytic Review

PubMed Central

Demarzo, Marcelo M.P.; Montero-Marin, Jesús; Cuijpers, Pim; Zabaleta-del-Olmo, Edurne; Mahtani, Kamal R.; Vellinga, Akke; Vicens, Caterina; López-del-Hoyo, Yolanda; García-Campayo, Javier

2015-01-01

PURPOSE Positive effects have been reported after mindfulness-based interventions (MBIs) in diverse clinical and nonclinical populations. Primary care is a key health care setting for addressing common chronic conditions, and an effective MBI designed for this setting could benefit countless people worldwide. Meta-analyses of MBIs have become popular, but little is known about their efficacy in primary care. Our aim was to investigate the application and efficacy of MBIs that address primary care patients. METHODS We performed a meta-analytic review of randomized controlled trials addressing the effect of MBIs in adult patients recruited from primary care settings. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane guidelines were followed. Effect sizes were calculated with the Hedges g in random effects models. RESULTS The meta-analyses were based on 6 trials having a total of 553 patients. The overall effect size of MBI compared with a control condition for improving general health was moderate (g = 0.48; P = .002), with moderate heterogeneity (I2 = 59; P <.05). We found no indication of publication bias in the overall estimates. MBIs were efficacious for improving mental health (g = 0.56; P = .007), with a high heterogeneity (I2 = 78; P <.01), and for improving quality of life (g = 0.29; P = .002), with a low heterogeneity (I2 = 0; P >.05). CONCLUSIONS Although the number of randomized controlled trials applying MBIs in primary care is still limited, our results suggest that these interventions are promising for the mental health and quality of life of primary care patients. We discuss innovative approaches for implementing MBIs, such as complex intervention and stepped care. PMID:26553897

Effect of aromatherapy massage on pain in primary dysmenorrhea: A meta-analysis.

PubMed

Sut, Necdet; Kahyaoglu-Sut, Hatice

2017-05-01

This meta-analysis investigates the effect of aromatherapy massage on pain in primary dysmenorrhea. Randomized controlled trials were searched by keywords in several databases (Pubmed, ISI Web of Sciences, and Google Scholar). Six randomized controlled trials that included 362 participants with primary dysmenorrhea, comparing abdominal aromatherapy massage (n = 184) with massage with placebo oils (n = 178), were analyzed in the meta-analysis. The change in the visual analogue scale (VAS) pain score from the first menstruation cycle to the second cycle at the first menstruation day was used as the primary outcome. Aromatherapy massage with essential oils was superior to massage with placebo oils (standardized mean difference = -1.06 [95% CI: -1.55 to -0.55]). Abdominal aromatherapy massage with essential oils is an effective complementary method to relieve pain in primary dysmenorrhea. Copyright © 2017 Elsevier Ltd. All rights reserved.

Variability in primary productivity determines metapopulation dynamics

PubMed Central

2016-01-01

Temporal variability in primary productivity can change habitat quality for consumer species by affecting the energy levels available as food resources. However, it remains unclear how habitat-quality fluctuations may determine the dynamics of spatially structured populations, where the effects of habitat size, quality and isolation have been customarily assessed assuming static habitats. We present the first empirical evaluation on the effects of stochastic fluctuations in primary productivity—a major outcome of ecosystem functions—on the metapopulation dynamics of a primary consumer. A unique 13-year dataset from an herbivore rodent was used to test the hypothesis that inter-annual variations in primary productivity determine spatiotemporal habitat occupancy patterns and colonization and extinction processes. Inter-annual variability in productivity and in the growing season phenology significantly influenced habitat colonization patterns and occupancy dynamics. These effects lead to changes in connectivity to other potentially occupied habitat patches, which then feed back into occupancy dynamics. According to the results, the dynamics of primary productivity accounted for more than 50% of the variation in occupancy probability, depending on patch size and landscape configuration. Evidence connecting primary productivity dynamics and spatiotemporal population processes has broad implications for metapopulation persistence in fluctuating and changing environments. PMID:27053739

Variability in primary productivity determines metapopulation dynamics.

PubMed

Fernández, Néstor; Román, Jacinto; Delibes, Miguel

2016-04-13

Temporal variability in primary productivity can change habitat quality for consumer species by affecting the energy levels available as food resources. However, it remains unclear how habitat-quality fluctuations may determine the dynamics of spatially structured populations, where the effects of habitat size, quality and isolation have been customarily assessed assuming static habitats. We present the first empirical evaluation on the effects of stochastic fluctuations in primary productivity--a major outcome of ecosystem functions--on the metapopulation dynamics of a primary consumer. A unique 13-year dataset from an herbivore rodent was used to test the hypothesis that inter-annual variations in primary productivity determine spatiotemporal habitat occupancy patterns and colonization and extinction processes. Inter-annual variability in productivity and in the growing season phenology significantly influenced habitat colonization patterns and occupancy dynamics. These effects lead to changes in connectivity to other potentially occupied habitat patches, which then feed back into occupancy dynamics. According to the results, the dynamics of primary productivity accounted for more than 50% of the variation in occupancy probability, depending on patch size and landscape configuration. Evidence connecting primary productivity dynamics and spatiotemporal population processes has broad implications for metapopulation persistence in fluctuating and changing environments. © 2016 The Authors.

Reducing overweight and obesity: closing the gap between primary care and public health.

PubMed

Anderson, Peter

2008-12-01

Although overweight and obesity are major risk factors for ill health and premature death, leading to significant increases in workload and prescribing costs, primary health care providers continue to find managing overweight and obesity a difficult business. Six questions are addressed in an attempt to close the gap between primary care activities and public health goals to reduce overweight and obesity: what is overweight and obesity; what is the health impact of overweight and obesity; is individually directed advice effective in reducing overweight and obesity; can we increase the involvement of primary care in reducing overweight and obesity; how can public health actions complement the role of primary care; and how do we chose cost-effective interventions? Systematic reviews and key texts were identified from literature searches to provide a narrative summary to answer the six questions. Overweight is defined as a body mass index (BMI) of > or = 25 and obesity as a BMI of > or = 30 where BMI = weight (kg)/height (m(2)). There is a positive relationship between the level of BMI and a wide range of conditions, including cancers and cardiovascular diseases. There is evidence that individually directed advice can reduce overweight and obesity or its risk. There is mixed evidence for the effectiveness of strategies in increasing the involvement of primary care in reducing overweight and obesity. There are many examples of public health actions that complement the role of primary care in reducing overweight and obesity. Overall cost-effective policy analyses have not been done per se for overweight and obesity but have shown that a combination of personal and non-personal interventions can be effective and cost-effective in reducing cardiovascular events. The gap between primary care and public health in reducing overweight and obesity can be closed, but it requires sustained political support and investment.

Cost-effectiveness of cervical cancer screening with primary human papillomavirus testing in Norway

PubMed Central

Burger, E A; Ortendahl, J D; Sy, S; Kristiansen, I S; Kim, J J

2012-01-01

Background: New screening technologies and vaccination against human papillomavirus (HPV), the necessary cause of cervical cancer, may impact optimal approaches to prevent cervical cancer. We evaluated the cost-effectiveness of alternative screening strategies to inform cervical cancer prevention guidelines in Norway. Methods: We leveraged the primary epidemiologic and economic data from Norway to contextualise a simulation model of HPV-induced cervical cancer. The current cytology-only screening was compared with strategies involving cytology at younger ages and primary HPV-based screening at older ages (31/34+ years), an option being actively deliberated by the Norwegian government. We varied the switch-age, screening interval, and triage strategies for women with HPV-positive results. Uncertainty was evaluated in sensitivity analysis. Results: Current cytology-only screening was less effective and more costly than strategies that involve switching to primary HPV testing in older ages. For unvaccinated women, switching at age 34 years to primary HPV testing every 4 years was optimal given the Norwegian cost-effectiveness threshold ($83 000 per year of life saved). For vaccinated women, a 6-year screening interval was cost-effective. When we considered a wider range of strategies, we found that an earlier switch to HPV testing (at age 31 years) may be preferred. Conclusions: Strategies involving a switch to HPV testing for primary screening in older women is expected to be cost-effective compared with current recommendations in Norway. PMID:22441643

Investigating Primary Source Literacy

ERIC Educational Resources Information Center

Archer, Joanne; Hanlon, Ann M.; Levine, Jennie A.

2009-01-01

Primary source research requires students to acquire specialized research skills. This paper presents results from a user study testing the effectiveness of a Web guide designed to convey the concepts behind "primary source literacy". The study also evaluated students' strengths and weaknesses when conducting primary source research. (Contains 3…

Primary aberrations in focused radially polarized vortex beams

NASA Astrophysics Data System (ADS)

Biss, David P.; Brown, T. G.

2004-02-01

We study the effect of primary aberrations on the 3-D polarization of the electric field in a focused lowest order radially polarized beam. A full vector diffraction treatment of the focused beams is used. Attention is given to the effects of primary spherical, astigmatic, and comatic aberrations on the local polarization, Strehl ratio, and aberration induced degradation of the longitudinal field at focus

An Evaluation of the Effectiveness of the New Primary School Mathematics Curriculum in Practice

ERIC Educational Resources Information Center

Gomleksiz, Mehmet Nuri; Bulut, Ilhami

2007-01-01

The aim of this study is to determine and compare the views of primary school teachers on the implementation and effectiveness of the new primary school mathematics curriculum. For that aim, a 32-item Likert-type Mathematics Curriculum Scale was developed. The reliability of the scale was tested through Cronbach Alpha (0.98), Spearman-Brown (0.93)…

Effect of Emotional Intelligence and Gender on Job Satisfaction of Primary School Teachers

ERIC Educational Resources Information Center

Singh, Bhagat; Kumar, Arun

2016-01-01

The objective of the study was to find out the effect of EI and gender on job satisfaction of primary school teachers. A total of 300 (150 male and 150 female) primary school teachers were selected randomly for the study. Emotional Intelligence Scale (EIS) and Teachers' Job Satisfaction Scale (TJSS) were used to collect the data. The study found a…

Using the Instructional Core to Implement a Professional Learning Programme for Primary Science Teachers in Australia: Teacher Learning and Student Skill Outcomes

ERIC Educational Resources Information Center

Loughland, Tony; Nguyen, Hoa Thi Mai

2016-01-01

There has been a call for effective professional learning to improve the quality of the science teaching of primary teachers in Australia. It seems from the literature that teaching science effectively is a challenging endeavour for primary teachers. Professional learning based on the instructional core framework is an emerging approach that has…

Effects of Storylines Embedded within the Context-Based Approach on Pre-Service Primary School Teachers' Conceptions of Matter and Its States

ERIC Educational Resources Information Center

Demircioglu, Hülya; Ayas, Alipasa; Demircioglu, Gökhan; Özmen, Haluk

2015-01-01

In this study, the effect of the context-based approach on pre-service primary school teachers' understanding of matter and its states and their attitude towards chemistry was investigated. Using a simple experimental design, the study was conducted with 35 pre-service primary school teachers who were exposed to context-based material with…

Do primary care professionals agree about progress with implementation of primary care teams: results from a cross sectional study.

PubMed

Tierney, E; O'Sullivan, M; Hickey, L; Hannigan, A; May, C; Cullen, W; Kennedy, N; Kineen, L; MacFarlane, A

2016-11-22

Primary care is the cornerstone of healthcare reform with policies across jurisdictions promoting interdisciplinary team working. The effective implementation of such health policies requires understanding the perspectives of all actors. However, there is a lack of research about health professionals' views of this process. This study compares Primary Healthcare Professionals' perceptions of the effectiveness of the Primary Care Strategy and Primary Care Team (PCT) implementation in Ireland. Design and Setting: e-survey of (1) General Practitioners (GPs) associated with a Graduate Medical School (N = 100) and (2) Primary Care Professionals in 3 of 4 Health Service Executive (HSE) regions (N = 2309). After piloting, snowball sampling was used to administer the survey. Descriptive analysis was carried out using SPSS. Ratings across groups were compared using non-parametric tests. There were 569 responses. Response rates varied across disciplines (71 % for GPs, 22 % for other Primary Healthcare Professionals (PCPs). Respondents across all disciplines viewed interdisciplinary working as important. Respondents agreed on lack of progress of implementation of formal PCTs (median rating of 2, where 1 is no progress at all and 5 is complete implementation). GPs were more negative about the effectiveness of the Strategy to promote different disciplines to work together (median rating of 2 compared to 3 for clinical therapists and 3.5 for nurses, P = 0.001). Respondents identified resources and GP participation as most important for effective team working. Protected time for meetings and capacity to manage workload for meetings were rated as very important factors for effective team working by GPs, clinical therapists and nurses. A building for co-location of teams was rated as an important factor by nurses and clinical therapists though GPs rated it as less important. Payment to attend meetings and contractual arrangements were considered important factors by GPs but not by nurses or clinical therapists. PCPs and GPs agree there is limited PCT implementation. GPs are most negative about this implementation. There is some disagreement about which resources are most important for effective PCT working. These findings provide valuable data for clinicians and policy makers about implementation of interdisciplinary teams in primary care.

77 FR 24959 - Scientific Information Request on Local Therapies for Unresectable Primary Hepatocellular Carcinoma

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-26

... solicited to inform our Comparative Effectiveness Review of Local Therapies for Unresectable Primary... device will improve the quality of this comparative effectiveness review. AHRQ is requesting this scientific information and conducting this comparative effectiveness review pursuant to Section 1013 of the...

The impact of surgical resection of the primary tumor on the development of synchronous colorectal liver metastasis: a systematic review.

PubMed

Pinson, H; Cosyns, S; Ceelen, Wim P

2018-05-22

In recent years different therapeutic strategies for synchronously liver metastasized colorectal cancer were described. Apart from the classical staged surgical approach, simultaneous and liver-first strategies are now commonly used. One theoretical drawback of the classical approach is, however, the stimulatory effect on liver metastases growth that may result from resection of the primary tumour. This systematic review, therefore, aims to investigate the current insights on the stimulatory effects of colorectal surgery on the growth of synchronous colorectal liver metastases in humans. The systematic review was conducted according to the PRISMA statement. A literature search was performed using PubMed and Embase. Articles investigating the effects of colorectal surgery on synchronous colorectal liver metastases were included. Primary endpoints were metastatic tumor volume, metabolic and proliferative activity and tumour vascularization. Four articles meeting the selection criteria were found involving 200 patients. These studies investigate the effects of resection of the primary tumour on synchronous liver metastases using histological and radiological techniques. These papers support a possible stimulatory effect of resection of the primary tumor. Some limited evidence supports the hypothesis that colorectal surgery might stimulate the growth and development of synchronous colorectal liver metastases.

"Free Primary Education" in Lesotho and the Disadvantages of the Highlands

ERIC Educational Resources Information Center

Urwick, James

2011-01-01

This article explores the effects of national policies associated with "Education for All" on a disadvantaged region, the highlands of Lesotho. Since 2000 a programme of "Free Primary Education" has improved the position of the highlands in access to primary schooling; nevertheless, highland primary schools compare poorly with…

[Effects nutrients on the seedlings root hair development and root growth of Poncirus trifoliata under hydroponics condition].

PubMed

Cao, Xiu; Xia, Ren-Xue; Zhang, De-Jian; Shu, Bo

2013-06-01

Ahydroponics experiment was conducted to study the effects of nutrients (N, P, K, Ca, Mg, Fe, and Mn) deficiency on the length of primary root, the number of lateral roots, and the root hair density, length, and diameter on the primary root and lateral roots of Poncirus trifoliata seedlings. Under the deficiency of each test nutrient, root hair could generate, but was mainly concentrated on the root base and fewer on the root tip. The root hair density on lateral roots was significantly larger than that on primary root, but the root hair length was in adverse. The deficiency of each test nutrient had greater effects on the growth and development of root hairs, with the root hair density on primary root varied from 55.0 to 174.3 mm(-2). As compared with the control, Ca deficiency induced the significant increase of root hair density and length on primary root, P deficiency promoted the root hair density and length on the base and middle part of primary root and on the lateral roots significantly, Fe deficiency increased the root hair density but decreased the root hair length on the tip of primary root significantly, K deficiency significantly decreased the root hair density, length, and diameter on primary root and lateral roots, whereas Mg deficiency increased the root hair length of primary root significantly. In all treatments of nutrient deficiency, the primary root had the similar growth rate, but, with the exceptions of N and Mg deficiency, the lateral roots exhibited shedding and regeneration.

Enantioselective Effects of Chiral Pesticides on their Primary Targets and Secondary Targets.

PubMed

Yang, Ye; Zhang, Jianyun; Yao, Yijun

2017-01-01

Enantioselectivity has been well recognized in the environmental fate and effects of chiral pesticides. Enantiospecific action of the optical enantiomers on the biological molecules establishes the mechanistic basis for the enantioselective toxicity of chiral pesticides to both target and non-target organisms. We undertook a structured search of bibliographic databases for research literature concerning the enantioselective effects of chiral pesticides, including insecticides, herbicides and fungicides, on biomolecules in various species by using some key words. The results of the relevant literatures were reviewed in the text and summarized in tables. Pesticides generally exert their activity on the target organisms via disrupting the primary target biomolecules. In non-target species, effects of pesticides on the secondary targets distinguished from the primary ones make great contribution to their toxicity. Recent investigations have provided convincing evidence of enantioselective toxicity of chiral pesticides to both target and non-target species which is recognized to result from their enantiospecific action on the primary or secondary targets in organisms. This review confirms that chiral pesticides have enantiospecific effects on both primary and secondary target biomolecules in organisms. Future studies regarding toxicological effects of chiral pesticides should focus on the relationship between the enantiomeric difference in the compound-biomolecules interaction and the enantioselectivity in their toxicity.

Effect of micro-aeration on anaerobic digestion of primary sludge under septic tank conditions.

PubMed

Diak, James; Örmeci, Banu; Kennedy, Kevin J

2013-04-01

Micro-aeration, which refers to the addition of very small amounts of air, is a simple technology that can potentially be incorporated in septic tanks to improve the digestion performance. The purpose of this study was to investigate and compare the effects of micro-aeration on anaerobic digestion of primary sludge under septic tank conditions. 1.6 L batch reactor experiments were carried out in duplicate using raw primary sludge, with 4.1 % total solids, and diluted primary sludge, with 2.1 % total solids. Reactors were operated for 5 weeks at room temperature to simulate septic tank conditions. Micro-aeration rate of 0.00156 vvm effectively solubilised chemical oxygen demand (COD) and improved the subsequent degradation of COD. Micro-aeration also increased the generation of ammonia and soluble proteins, but did not improve the reduction in total and volatile solids, or the reduction in carbohydrates. Experiments using diluted sludge samples showed similar trends as the experiments with raw sludge, which suggest that initial solids concentration did not have a significant effect on the degradation of primary sludge under septic tank conditions.

From Efficacy to Effectiveness and Beyond: What Next for Brief Interventions in Primary Care?

PubMed Central

O’Donnell, Amy; Wallace, Paul; Kaner, Eileen

2014-01-01

Background: Robust evidence supports the effectiveness of screening and brief alcohol interventions in primary healthcare. However, lack of understanding about their “active ingredients” and concerns over the extent to which current approaches remain faithful to their original theoretical roots has led some to demand a cautious approach to future roll-out pending further research. Against this background, this paper provides a timely overview of the development of the brief alcohol intervention evidence base to assess the extent to which it has achieved the four key levels of intervention research: efficacy, effectiveness, implementation, and demonstration. Methods: Narrative overview based on (1) the results of a review of systematic reviews and meta-analyses of the effectiveness of brief alcohol intervention in primary healthcare and (2) synthesis of the findings of key additional primary studies on the improvement and evaluation of brief alcohol intervention implementation in routine primary healthcare. Results: The brief intervention field seems to constitute an almost perfect example of the evaluation of a complex intervention. Early evaluations of screening and brief intervention approaches included more tightly controlled efficacy trials and have been followed by more pragmatic trials of effectiveness in routine clinical practice. Most recently, attention has shifted to dissemination, implementation, and wider-scale roll-out. However, delivery in routine primary health remains inconsistent, with an identified knowledge gap around how to successfully embed brief alcohol intervention approaches in mainstream care, and as yet unanswered questions concerning what specific intervention component prompt the positive changes in alcohol consumption. Conclusion: Both the efficacy and effectiveness of brief alcohol interventions have been comprehensively demonstrated, and intervention effects seem replicable and stable over time, and across different study contexts. Thus, while unanswered questions remain, given the positive evidence amassed to date, research efforts should maintain a continued focus on promoting sustained implementation of screening and brief alcohol intervention approaches in primary care to ensure that those who might benefit from screening and brief alcohol interventions actually receive such support. PMID:25221524

Effectiveness of Case Management for 'At Risk' Patients in Primary Care: A Systematic Review and Meta-Analysis.

PubMed

Stokes, Jonathan; Panagioti, Maria; Alam, Rahul; Checkland, Kath; Cheraghi-Sohi, Sudeh; Bower, Peter

2015-01-01

An ageing population with multimorbidity is putting pressure on health systems. A popular method of managing this pressure is identification of patients in primary care 'at-risk' of hospitalisation, and delivering case management to improve outcomes and avoid admissions. However, the effectiveness of this model has not been subjected to rigorous quantitative synthesis. We carried out a systematic review and meta-analysis of the effectiveness of case management for 'at-risk' patients in primary care. Six bibliographic databases were searched using terms for 'case management', 'primary care', and a methodology filter (Cochrane EPOC group). Effectiveness compared to usual care was measured across a number of relevant outcomes: Health--self-assessed health status, mortality; Cost--total cost of care, healthcare utilisation (primary and non-specialist care and secondary care separately), and; Satisfaction--patient satisfaction. We conducted secondary subgroup analyses to assess whether effectiveness was moderated by the particular model of case management, context, and study design. A total of 15,327 titles and abstracts were screened, 36 unique studies were included. Meta-analyses showed no significant differences in total cost, mortality, utilisation of primary or secondary care. A very small significant effect favouring case management was found for self-reported health status in the short-term (0.07, 95% CI 0.00 to 0.14). A small significant effect favouring case management was found for patient satisfaction in the short- (0.26, 0.16 to 0.36) and long-term (0.35, 0.04 to 0.66). Secondary subgroup analyses suggested the effectiveness of case management may be increased when delivered by a multidisciplinary team, when a social worker was involved, and when delivered in a setting rated as low in initial 'strength' of primary care. This was the first meta-analytic review which examined the effects of case management on a wide range of outcomes and considered also the effects of key moderators. Current results do not support case management as an effective model, especially concerning reduction of secondary care use or total costs. We consider reasons for lack of effect and highlight key research questions for the future. The review protocol is available as part of the PROSPERO database (registration number: CRD42014010824).

Effectiveness of Case Management for 'At Risk' Patients in Primary Care: A Systematic Review and Meta-Analysis

PubMed Central

Stokes, Jonathan; Panagioti, Maria; Alam, Rahul; Checkland, Kath; Cheraghi-Sohi, Sudeh; Bower, Peter

2015-01-01

Background An ageing population with multimorbidity is putting pressure on health systems. A popular method of managing this pressure is identification of patients in primary care ‘at-risk’ of hospitalisation, and delivering case management to improve outcomes and avoid admissions. However, the effectiveness of this model has not been subjected to rigorous quantitative synthesis. Methods and Findings We carried out a systematic review and meta-analysis of the effectiveness of case management for ‘at-risk’ patients in primary care. Six bibliographic databases were searched using terms for ‘case management’, ‘primary care’, and a methodology filter (Cochrane EPOC group). Effectiveness compared to usual care was measured across a number of relevant outcomes: Health – self-assessed health status, mortality; Cost – total cost of care, healthcare utilisation (primary and non-specialist care and secondary care separately), and; Satisfaction – patient satisfaction. We conducted secondary subgroup analyses to assess whether effectiveness was moderated by the particular model of case management, context, and study design. A total of 15,327 titles and abstracts were screened, 36 unique studies were included. Meta-analyses showed no significant differences in total cost, mortality, utilisation of primary or secondary care. A very small significant effect favouring case management was found for self-reported health status in the short-term (0.07, 95% CI 0.00 to 0.14). A small significant effect favouring case management was found for patient satisfaction in the short- (0.26, 0.16 to 0.36) and long-term (0.35, 0.04 to 0.66). Secondary subgroup analyses suggested the effectiveness of case management may be increased when delivered by a multidisciplinary team, when a social worker was involved, and when delivered in a setting rated as low in initial ‘strength’ of primary care. Conclusions This was the first meta-analytic review which examined the effects of case management on a wide range of outcomes and considered also the effects of key moderators. Current results do not support case management as an effective model, especially concerning reduction of secondary care use or total costs. We consider reasons for lack of effect and highlight key research questions for the future. Review Protocol The review protocol is available as part of the PROSPERO database (registration number: CRD42014010824). PMID:26186598

Face-seal lubrication: 1: Proposed and published models

NASA Technical Reports Server (NTRS)

Ludwig, L. P.

1976-01-01

The numerous published theories on the mechanism of hydrodynamic lubrication of face seals were reviewed. These theories employ either an inclined-slider-bearing macrogeometry or an inclined-slider-bearing microgeometry to produce hydrodynamic pressure that separates the surfaces of the primary seal. Secondary seal friction and primary ring inertia effects are not considered. Hypothetical seal operating models were devised to include secondary seal friction and primary ring inertia effects. It was hypothesized that these effects induce relative angular misalinement of the primary seal faces and that this misalinement is, in effect, an inclined slider macrogeometry. Stable running was postulated for some of these hypothetical operating models. In others, periodic loss of hydrodynamic lubrication was postulated to be possible with certain combinations of waviness and angular misalinement. Application of restrictions that apply to seal operation led to a hydrodynamic governing equation for the new model that is a two-dimensional, time-dependent Reynolds equation with the short-bearing approximation.

Effectiveness of and Dropout from Outpatient Cognitive Behavioral Therapy for Adult Unipolar Depression: A Meta-Analysis of Nonrandomized Effectiveness Studies

ERIC Educational Resources Information Center

Hans, Eva; Hiller, Wolfgang

2013-01-01

Objective: The primary aim of this study was to assess the overall effectiveness of and dropout from individual and group outpatient cognitive behavioral therapy (CBT) for adults with a primary diagnosis of unipolar depressive disorder in routine clinical practice. Method: We conducted a random effects meta-analysis of 34 nonrandomized…

Primary Prevention of Sexual Violence in Aotearoa New Zealand.

PubMed

Dickson, Sandra; Willis, Gwenda M

2017-03-01

The extensive and sometimes profoundly damaging effects of sexual violence and large numbers of victims necessitate dedicated attention to primary prevention efforts. Few studies have examined the scope of current prevention activities or their fit with empirical research into effective prevention strategies. The current article presents findings from a survey of primary prevention activities in non-Māori and bicultural communities within Aotearoa New Zealand. Forty-four respondents representing 42 agencies responded to a comprehensive survey that canvased types of sexual violence primary prevention activities undertaken, sexual violence primary prevention programs, and barriers and supports to sexual violence prevention work. Consistent with findings from previous international surveys, the focus of primary prevention work in New Zealand was on sexual violence education and increasing awareness. Findings are discussed in the context of the sexual violence prevention literature and what works in prevention more broadly to help identify promising initiatives as well as gaps in current practices. Recommendations for advancing sexual violence primary prevention research are also provided.

Cost-effectiveness of granulocyte colony-stimulating factor prophylaxis in chemotherapy-induced febrile neutropenia among breast cancer and Non-Hodgkin's lymphoma patients under Taiwan's national health insurance system.

PubMed

Wen, Tsun-Jen; Wen, Yu-Wen; Chien, Chun-Ru; Chiang, Shao-Chin; Hsu, William Wei-Yuan; Shen, Li-Jiuan; Hsiao, Fei-Yuan

2017-04-01

The beneficial effects of granulocyte colony-stimulating factor (G-CSF) prophylaxis on reducing the risk of chemotherapy-induced febrile neutropenia (CIFN) were well documented throughout the literature. However, existing data regarding its cost-effectiveness were conflicting. We estimated the cost-effectiveness of G-CSF prophylaxis in CIFN under Taiwan's National Health Insurance (NHI) system. Data on clinical outcomes and direct medical costs were derived for 5179 newly diagnosed breast cancer and 629 non-Hodgkin's lymphoma (NHL) patients from the NHI claims database. Patients were further categorized into three subgroups as "primary-", "secondary-" and "no -" prophylaxis based on their patterns of G-CSF use. Generalized estimating equations were applied to estimate the impact of G-CSF use on the incidence of CIFN. The incremental cost-effectiveness ratios of primary and secondary prophylactic G-CSF use were calculated and sensitivity analyses were performed. Primary prophylaxis of G-CSF decreased the incidence of CIFN by 27% and 83%, while secondary prophylaxis by 34% and 22% in breast cancer and NHL patients, respectively. Compared with those with no prophylaxis, the incremental cost per CIFN reduced in primary prophylaxis is $931 and $52 among patients with breast cancer and NHL, respectively. In contrast, secondary prophylaxis is dominated by no prophylaxis and primary prophylaxis in both cancer patients. Primary but not secondary prophylactic use of G-CSF was cost-effective in CIFN in breast cancer and NHL patients under Taiwan's NHI system. © 2016 John Wiley & Sons, Ltd.

One size fits some: the impact of patient treatment attitudes on the cost-effectiveness of a depression primary-care intervention.

PubMed

Pyne, Jeffrey M; Rost, Kathryn M; Farahati, Farah; Tripathi, Shanti P; Smith, Jeffrey; Williams, D Keith; Fortney, John; Coyne, James C

2005-06-01

Despite their impact on outcomes, the effect of patient treatment attitudes on the cost-effectiveness of health-care interventions is not widely studied. This study estimated the impact of patient receptivity to antidepressant medication on the cost-effectiveness of an evidence-based primary-care depression intervention. Twelve community primary-care practices were stratified and then randomized to enhanced (intervention) or usual care. Subjects included 211 patients beginning a new treatment episode for major depression. At baseline, 111 (52.6%) and 145 (68.7%) reported receptivity to antidepressant medication and counseling respectively. The intervention trained the primary-care teams to assess, educate, and monitor depressed patients. Twelve-month incremental (enhanced minus usual care) total costs and quality-adjusted life years (QALYs) were calculated. Among patients receptive to antidepressants, the mean incremental cost-effectiveness ratio was dollar 5,864 per QALY (sensitivity analyses up to dollar 14,689 per QALY). For patients not receptive to antidepressants, the mean incremental QALY score was negative (for both main and sensitivity analyses), or the intervention was at least no more effective than usual care. These findings suggest a re-thinking of the 'one size fits all' depression intervention, given that half of depressed primary-care patients may be non-receptive to antidepressant medication treatment. A brief assessment of treatment receptivity should occur early in the treatment process to identify patients most likely to benefit from primary-care quality improvement efforts for depression treatment. Patient treatment preferences are also important for the development, design, and analysis of depression interventions.

The effect of increased primary schooling on adult women's HIV status in Malawi and Uganda: Universal Primary Education as a natural experiment.

PubMed

Behrman, Julia Andrea

2015-02-01

This paper explores the causal relationship between primary schooling and adult HIV status in Malawi and Uganda, two East African countries with some of the highest HIV infection rates in the world. Using data from the 2010 Malawi Demographic Health Survey and the 2011 Uganda AIDS Indicator Survey, the paper takes advantage of a natural experiment, the implementation of Universal Primary Education policies in the mid 1990s. An instrumented regression discontinuity approach is used to model the relationship between increased primary schooling and adult women's HIV status. Results indicate that a one-year increase in schooling decreases the probability of an adult woman testing positive for HIV by 0.06 (p < 0.01) in Malawi and by 0.03 (p < 0.05) in Uganda. These results are robust to a variety of model specifications. In a series of supplementary analyses a number of potential pathways through which such effects may occur are explored. Findings indicate increased primary schooling positively affects women's literacy and spousal schooling attainment in Malawi and age of marriage and current household wealth in Uganda. However primary schooling has no effect on recent (adult) sexual behavior. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

Do Offshore Wind Farms Influence Marine Primary Production?

NASA Astrophysics Data System (ADS)

Tweddle, J. F.; Murray, R. B. O.; Gubbins, M.; Scott, B. E.

2016-02-01

Primary producers (phytoplankton) form the basis of marine food-webs, supporting production of higher trophic levels, and act as a sink of CO2. We considered the impact of proposed large scale offshore wind farms in moderately deep waters (> 45 m) off the east coast of Scotland on rates of primary production. A 2 stage modelling process was used, employing state-of-the-art 3-D hydrographic models with the ability to capture flow at the spatial resolution of 10 m combined with 1-D vertical modelling using 7 years of local forcing data. Through influencing the strength of stratification via changes in current flow, large (100 m) modelled wind turbine foundations had a significant effect on primary producers, consistently reducing total annual primary production, although within the range of natural interannual variability. The percentage reduction was largest over submarine banks less than 54 m in depth, and was outside the range of natural interannual variability. Smaller (10 m) turbine foundations had no discernible effect on total annual primary production. The results indicate that smaller foundations should be favored as a mitigation measure, in terms of effects on primary production, and this type of analysis should be considered within sectoral planning and licensing processes for future renewable energy developments.

How to Guide Effective Student Questioning: A Review of Teacher Guidance in Primary Education

ERIC Educational Resources Information Center

Stokhof, Harry J. M.; De Vries, Bregje; Martens, Rob L.; Bastiaens, Theo J.

2017-01-01

Although the educational potential of student questions is widely acknowledged, primary school teachers need support to guide them to become effective for learning the curriculum. The aim of this review is to identify which teacher guidance supports effective student questioning. Thirty-six empirical studies on guiding student questioning in…

Effective Practical Work in Primary Science: The Role of Empathy

ERIC Educational Resources Information Center

Abrahams, Ian; Reiss, Michael

2010-01-01

"Getting Practical-Improving practical work in science" is a government-funded programme intended to improve the effectiveness and affective value of practical work in school science in England. In order to evaluate the effectiveness of the programme in terms of achieving its aims, ten primary and twenty secondary schools have been…

Effectiveness of a weight loss program in community-cased primary care offices: High-intensity intervention versus low-intensity intervention

USDA-ARS?s Scientific Manuscript database

Despite the call for primary care providers (PCPs) to offer obese patients intense behavioral therapy for weight loss, few studies have examined the effectiveness of such interventions in real-world, community-based medical practices. This study evaluated the effectiveness of a physician-guided weig...

Effective School Evaluation in Primary Schools from the Dimension of Parents

ERIC Educational Resources Information Center

Akan, Durdagi

2017-01-01

The aim of this study is to analyze the effectiveness of the primary schools depending on "parents" dimension according to the perceptions of administrator and teacher in terms of different variables. It employed descriptive survey model. Data was collected through effective school questionnaire with the aim of determining the…

Cost-Effectiveness of Primary HPV Testing, Cytology and Co-testing as Cervical Cancer Screening for Women Above Age 30 Years.

PubMed

Jin, Xian Wen; Lipold, Laura; Foucher, Julie; Sikon, Andrea; Brainard, Jennifer; Belinson, Jerome; Schramm, Sarah; Nottingham, Kelly; Hu, Bo; Rothberg, Michael B

2016-11-01

Cervical cancer screening guidelines for women aged ≥30 years allow for co-testing or primary cytology testing. Our objective was to determine the test characteristics and costs associated with Cytology, HPV and Co-testing screening strategies. Retrospective cohort study of women undergoing cervical cancer screening with both cytology and HPV (Hybrid Capture 2) testing from 2004 to 2010 in an integrated health system. The electronic health record was used to identify women aged ≥30 years who had co-testing. Unsatisfactory or unavailable test results and incorrectly ordered tests were excluded. The main outcome was biopsy-proven cervical intraepithelial neoplasia grade 3 or higher (CIN3+). The final cohort consisted of 99,549 women. Subjects were mostly white (78.4 %), married (70.7 %), never smokers (61.3 %) and with private insurance (86.1 %). Overall, 5121 (5.1 %) tested positive for HPV and 6115 (6.1 %) had cytology ≥ ASCUS; 1681 had both and underwent colposcopy and 310 (0.3 %) had CIN3+. Sensitivity for CIN3+ was 91.9 % for Primary Cytology, 99.4 % for Co-testing, and 94.8 % for Primary HPV; specificity was 97.3 % for Co-testing and Primary Cytology and 97.9 % for Primary HPV. Over a 3-year screening interval, Primary HPV detected more cases of CIN3+ and was less expensive than Primary Cytology. Co-testing detected 14 more cases of CIN3+ than Primary HPV, but required an additional 100,277 cytology tests and 566 colposcopies at an added cost of $2.38 million, or $170,096 per additional case detected. Primary HPV was more effective and less expensive than Primary Cytology. Primary HPV screening appears to represent a cost-effective alternative to Co-testing.

Metabolic and structural integrity of magnetic nanoparticle-loaded primary endothelial cells for targeted cell therapy.

PubMed

Orynbayeva, Zulfiya; Sensenig, Richard; Polyak, Boris

2015-05-01

To successfully translate magnetically mediated cell targeting from bench to bedside, there is a need to systematically assess the potential adverse effects of magnetic nanoparticles (MNPs) interacting with 'therapeutic' cells. Here, we examined in detail the effects of internalized polymeric MNPs on primary rat endothelial cells' structural intactness, metabolic integrity and proliferation potential. The intactness of cytoskeleton and organelles was studied by fluorescent confocal microscopy, flow cytometry and high-resolution respirometry. MNP-loaded primary endothelial cells preserve intact cytoskeleton and organelles, maintain normal rate of proliferation, calcium signaling and mitochondria energy metabolism. This study provides supportive evidence that MNPs at doses necessary for targeting did not induce significant adverse effects on structural integrity and functionality of primary endothelial cells - potential cell therapy vectors.

Primary amenorrhea in anorexia nervosa: impact on characteristic masculine and feminine traits.

PubMed

Baker, Jessica H; Sisk, Cheryl L; Thornton, Laura M; Brandt, Harry; Crawford, Steven; Fichter, Manfred M; Halmi, Katherine A; Johnson, Craig; Jones, Ian; Kaplan, Allan S; Mitchell, James E; Strober, Michael; Treasure, Janet; Woodside, D Blake; Berrettini, Wade H; Kaye, Walter H; Bulik, Cynthia M; Klump, Kelly L

2014-01-01

Animal studies indicate that gonadal hormones at puberty have an effect on the development of masculine and feminine traits. However, it is unknown whether similar processes occur in humans. We examined whether women with anorexia nervosa (AN), who often experience primary amenorrhea, exhibit attenuated feminization in their psychological characteristics in adulthood due to the decrease/absence of gonadal hormones at puberty. Women with AN were compared on a number of psychological characteristics using general linear models on the basis of the presence/absence of primary amenorrhea. Although women with primary amenorrhea exhibited lower anxiety scores than those without primary amenorrhea, in general, results did not provide evidence of attenuated feminization in women with AN with primary amenorrhea. Future research should utilize novel techniques and direct hormone measurement to explore the effects of pubertal gonadal hormones on masculine and feminine traits. Copyright © 2013 John Wiley & Sons, Ltd and Eating Disorders Association.

Pre-Service Primary Science Teachers' Understandings of the Effect of Temperature and Pressure on Solid-Liquid Phase Transition of Water

ERIC Educational Resources Information Center

Yalcin, Fatma Aggul

2012-01-01

The aim of this study was to explore pre-service primary teachers' understandings of the effect of temperature and pressure on the solid-liquid phase transition of water. In the study a survey approach was used, and the sample consisted of one-hundred and three, third year pre-service primary science teachers. As a tool for data collection, a test…

Effectiveness of a virtual intervention for primary healthcare professionals aimed at improving attitudes towards the empowerment of patients with chronic diseases: study protocol for a cluster randomized controlled trial (e-MPODERA project).

PubMed

González-González, Ana Isabel; Orrego, Carola; Perestelo-Perez, Lilisbeth; Bermejo-Caja, Carlos Jesús; Mora, Nuria; Koatz, Débora; Ballester, Marta; Del Pino, Tasmania; Pérez-Ramos, Jeannet; Toledo-Chavarri, Ana; Robles, Noemí; Pérez-Rivas, Francisco Javier; Ramírez-Puerta, Ana Belén; Canellas-Criado, Yolanda; Del Rey-Granado, Yolanda; Muñoz-Balsa, Marcos José; Becerril-Rojas, Beatriz; Rodríguez-Morales, David; Sánchez-Perruca, Luis; Vázquez, José Ramón; Aguirre, Armando

2017-10-30

Communities of practice are based on the idea that learning involves a group of people exchanging experiences and knowledge. The e-MPODERA project aims to assess the effectiveness of a virtual community of practice aimed at improving primary healthcare professional attitudes to the empowerment of patients with chronic diseases. This paper describes the protocol for a cluster randomized controlled trial. We will randomly assign 18 primary-care practices per participating region of Spain (Catalonia, Madrid and Canary Islands) to a virtual community of practice or to usual training. The primary-care practice will be the randomization unit and the primary healthcare professional will be the unit of analysis. We will need a sample of 270 primary healthcare professionals (general practitioners and nurses) and 1382 patients. We will perform randomization after professionals and patients are selected. We will ask the intervention group to participate for 12 months in a virtual community of practice based on a web 2.0 platform. We will measure the primary outcome using the Patient-Provider Orientation Scale questionnaire administered at baseline and after 12 months. Secondary outcomes will be the sociodemographic characteristics of health professionals, sociodemographic and clinical characteristics of patients, the Patient Activation Measure questionnaire for patient activation and outcomes regarding use of the virtual community of practice. We will calculate a linear mixed-effects regression to estimate the effect of participating in the virtual community of practice. This cluster randomized controlled trial will show whether a virtual intervention for primary healthcare professionals improves attitudes to the empowerment of patients with chronic diseases. ClicalTrials.gov, NCT02757781 . Registered on 25 April 2016. Protocol Version. PI15.01 22 January 2016.

HDAC6 inhibition suppresses chondrosarcoma by restoring the expression of primary cilia.

PubMed

Xiang, Wei; Guo, Fengjing; Cheng, Weiting; Zhang, Jiaming; Huang, Junming; Wang, Rui; Ma, Zhongxi; Xu, Kai

2017-07-01

Chondrosarcoma is a bone tumor characterized by the secretion of a cartilage-like extracellular matrix. It has been proved to lack extracellular sensor primary cilia. This study aimed to illustrate a feasible therapeutic method for chondrosarcoma by regulating primary cilia assembly through inhibiting histone deacetylases 6 (HDAC6) activation. In order to detect the interaction between primary cilia and HDAC6 in human chondrosarcoma, Tubastatin A and small interfering RNA (siRNA) were used to inhibit the endogenous expression of HDAC6. Cell viability test and Transwell assay were applied to evaluate the effects of malignant biological properties. Primary cilia staining and related proteins were detected. The abnormal expression of HDAC6 and cilia intraflagellar transport protein 88 (IFT88) was found in chondrosarcoma tissues. The inhibition of HDAC6 could downregulate the proliferation of chondrosarcoma cells in a concentration- and time-dependent manner and suppress the invasion capacity of tumor cells. Besides, the downregulation of HDAC6 exhibited a negative effect on the proliferation of relevant proteins but a positive effect on the primary cilia-related expression of IFT88 and acetylated α-tubulin. Primary cilia restoration could be observed after HDAC6 siRNA transfection. The Aurora A-HDAC6 cascade was involved in regulating primary cilia resorption by affecting α-tubulin deacetylation and Tubastatin A could inhibit chondrosarcoma cell growth in vivo. These results indicate that restricting HDAC6 can restore primary cilia assembly accompanied with suppressed chondrosarcoma cell proliferation and invasion capacities. Thus, promoting primary cilia restoration by targeting HDAC6 may be a feasible potential therapeutic method for chondro-sarcoma treatment.

Cell-type-specific and differentiation-status-dependent variations in cytotoxicity of tributyltin in cultured rat cerebral neurons and astrocytes.

PubMed

Oyanagi, Koshi; Tashiro, Tomoko; Negishi, Takayuki

2015-08-01

Tributyltin (TBT) is an organotin used as an anti-fouling agent for fishing nets and ships and it is a widespread environmental contaminant at present. There is an increasing concern about imperceptible but serious adverse effect(s) of exposure to chemicals existing in the environment on various organs and their physiological functions, e.g. brain and mental function. Here, so as to contribute to improvement of and/or advances in in vitro cell-based assay systems for evaluating brain-targeted adverse effect of chemicals, we tried to evaluate cell-type-specific and differentiation-status-dependent variations in the cytotoxicity of TBT towards neurons and astrocytes using the four culture systems differing in the relative abundance of these two types of cells; primary neuron culture (> 95% neurons), primary neuron-astrocyte (2 : 1) mix culture, primary astrocyte culture (> 95% astrocytes), and passaged astrocyte culture (100% proliferative astrocytes). Cell viability was measured at 48 hr after exposure to TBT in serum-free medium. IC50's of TBT were 198 nM in primary neuron culture, 288 nM in primary neuron-astrocyte mix culture, 2001 nM in primary astrocyte culture, and 1989 nM in passaged astrocyte culture. Furthermore, in primary neuron-astrocyte mix culture, vulnerability of neurons cultured along with astrocytes to TBT toxicity was lower than that of neurons cultured purely in primary neuron culture. On the other hand, astrocytes in primary neuron-astrocyte mix culture were considered to be more vulnerable to TBT than those in primary or passaged astrocyte culture. The present study demonstrated variable cytotoxicity of TBT in neural cells depending on the culture condition.

A randomized controlled trial of single point acupuncture in primary dysmenorrhea.

PubMed

Liu, Cun-Zhi; Xie, Jie-Ping; Wang, Lin-Peng; Liu, Yu-Qi; Song, Jia-Shan; Chen, Yin-Ying; Shi, Guang-Xia; Zhou, Wei; Gao, Shu-Zhong; Li, Shi-Liang; Xing, Jian-Min; Ma, Liang-Xiao; Wang, Yan-Xia; Zhu, Jiang; Liu, Jian-Ping

2014-06-01

Acupuncture is often used for primary dysmenorrhea. But there is no convincing evidence due to low methodological quality. We aim to assess immediate effect of acupuncture at specific acupoint compared with unrelated acupoint and nonacupoint on primary dysmenorrhea. The Acupuncture Analgesia Effect in Primary Dysmenorrhoea-II is a multicenter controlled trial conducted in six large hospitals of China. Patients who met inclusion criteria were randomly assigned to classic acupoint (N = 167), unrelated acupoint (N = 167), or non-acupoint (N = 167) group on a 1:1:1 basis. They received three sessions with electro-acupuncture at a classic acupoint (Sanyinjiao, SP6), or an unrelated acupoint (Xuanzhong, GB39), or nonacupoint location, respectively. The primary outcome was subjective pain as measured by a 100-mm visual analog scale (VAS). Measurements were obtained at 0, 5, 10, 30, and 60 minutes following the first intervention. In addition, patients scored changes of general complaints using Cox retrospective symptom scales (RSS-Cox) and 7-point verbal rating scale (VRS) during three menstrual cycles. Secondary outcomes included VAS score for average pain, pain total time, additional in-bed time, and proportion of participants using analgesics during three menstrual cycles. Five hundred and one people underwent random assignment. The primary comparison of VAS scores following the first intervention demonstrated that classic acupoint group was more effective both than unrelated acupoint (-4.0 mm, 95% CI -7.1 to -0.9, P = 0.010) and nonacupoint (-4.0 mm, 95% CI -7.0 to -0.9, P = 0.012) groups. However, no significant differences were detected among the three acupuncture groups for RSS-Cox or VRS outcomes. The per-protocol analysis showed similar pattern. No serious adverse events were noted. Specific acupoint acupuncture produced a statistically, but not clinically, significant effect compared with unrelated acupoint and nonacupoint acupuncture in primary dysmenorrhea patients. Future studies should focus on effects of multiple points acupuncture on primary dysmenorrhea. Wiley Periodicals, Inc.

Health psychology in primary care: recent research and future directions.

PubMed

Thielke, Stephen; Thompson, Alexander; Stuart, Richard

2011-01-01

Over the last decade, research about health psychology in primary care has reiterated its contributions to mental and physical health promotion, and its role in addressing gaps in mental health service delivery. Recent meta-analyses have generated mixed results about the effectiveness and cost-effectiveness of health psychology interventions. There have been few studies of health psychology interventions in real-world treatment settings. Several key challenges exist: determining the degree of penetration of health psychology into primary care settings; clarifying the specific roles of health psychologists in integrated care; resolving reimbursement issues; and adapting to the increased prescription of psychotropic medications. Identifying and exploring these issues can help health psychologists and primary care providers to develop the most effective ways of applying psychological principles in primary care settings. In a changing health care landscape, health psychologists must continue to articulate the theories and techniques of health psychology and integrated care, to put their beliefs into practice, and to measure the outcomes of their work.

Evaluating the potential for primary care to serve as a mental health home for people with schizophrenia.

PubMed

Grove, Lexie R; Olesiuk, William J; Ellis, Alan R; Lichstein, Jesse C; DuBard, C Annette; Farley, Joel F; Jackson, Carlos T; Beadles, Christopher A; Morrissey, Joseph P; Domino, Marisa Elena

2017-07-01

Primary care-based medical homes could improve the coordination of mental health care for individuals with schizophrenia and comorbid chronic conditions. The objective of this paper is to examine whether persons with schizophrenia and comorbid chronic conditions engage in primary care regularly, such that primary care settings have the potential to serve as a mental health home. We examined the annual primary care and specialty mental health service utilization of adult North Carolina Medicaid enrollees with schizophrenia and at least one comorbid chronic condition who were in a medical home during 2007-2010. Using a fixed-effects regression approach, we also assessed the effect of medical home enrollment on utilization of primary care and specialty mental health care and medication adherence. A substantial majority (78.5%) of person-years had at least one primary care visit, and 17.9% had at least one primary care visit but no specialty mental health services use. Medical home enrollment was associated with increased use of primary care and specialty mental health care, as well as increased medication adherence. Medical home enrollees with schizophrenia and comorbid chronic conditions exhibited significant engagement in primary care, suggesting that primary-care-based medical homes could serve a care coordination function for persons with schizophrenia. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of HER-2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease

PubMed Central

Zidan, J; Dashkovsky, I; Stayerman, C; Basher, W; Cozacov, C; Hadary, A

2005-01-01

HER-2 overexpression, a predictive marker of tumour aggressiveness and responsiveness to therapy, occurs in 20–30% of breast cancer. Although breast cancer is a heterogeneous disease, HER-2 measurement is carried out in primary tumour. This study aims to evaluate HER-2 overexpression in primary and metastases and its effect on treatment decisions. Biopsies from primary breast cancer and corresponding metastases from 58 patients were studied. HER-2 overexpression was evaluated immunohistochemically in all primary and metastatic sites. Positive overexpression in primary and/or metastases was confirmed by fluorescence in situ hybridisation (FISH). Discordance in HER-2 overexpression between primary and metastatic sites was 14% (eight of 58 patients). Concordance was found in 50 (86%) of patients (95% CI: 77–95). In one patient (2%), HER-2 was negative in metastasis but positive in primary. In seven (12%) patients, HER-2 was positive in metastases and negative in primary (95% CI: 3.7–20), and three of them responded to trastuzumab. Gene amplification by FISH was found in all cases with HER-2 positive (+2 and +3) by immunohistochemistry. Our data suggest that a possible discordance of HER-2 overexpression between primary and metastases should be considered when making treatment decisions in patients with primary HER-2-negative tumours. PMID:16106267

40 CFR 141.60 - Effective dates.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Effective dates. 141.60 Section 141.60 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS National Primary Drinking Water Regulations: Maximum Contaminant Levels...

Effectiveness of transdiagnostic Internet cognitive behavioural treatment for mixed anxiety and depression in primary care.

PubMed

Newby, Jill M; Mewton, Louise; Williams, Alishia D; Andrews, Gavin

2014-08-01

Internet-delivered cognitive behavioural treatment (iCBT) has been shown to be effective for the combined treatment of depression and anxiety in randomised controlled trials. The degree to which these findings generalise to patients in primary care awaits further investigation. Using an open-trial design, we investigated adherence to, and effectiveness of a 6-lesson therapist-assisted iCBT program for mixed anxiety and depression for patients (n = 707) who completed the program under the supervision of primary care clinicians (general practitioners, psychologists and other allied health professionals). Primary outcome measures were the PHQ-9 (depression), GAD-7 (generalised anxiety), K-10 (distress), WHODAS-II (disability), mini-SPIN (social anxiety) and panic disorder severity scale self-report version (PDSS). Adherence to the iCBT program was modest (47.3%), but within-subjects effect sizes ranged from medium (0.51 for PDSS) to large (1.20 for PHQ-9). The lack of control group, limited post-treatment data due to drop-out, and short follow-up period. iCBT is an effective treatment for mixed depression and anxiety when delivered in primary care settings. Methods to increase adherence are needed to optimise the benefits to patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Better health outcomes at lower costs: the benefits of primary care utilisation for chronic disease management in remote Indigenous communities in Australia's Northern Territory.

PubMed

Zhao, Yuejen; Thomas, Susan L; Guthridge, Steven L; Wakerman, John

2014-10-04

Indigenous residents living in remote communities in Australia's Northern Territory experience higher rates of preventable chronic disease and have poorer access to appropriate health services compared to other Australians. This study compared health outcomes and costs at different levels of primary care utilisation to determine if primary care represents an efficient use of resources for Indigenous patients with common chronic diseases namely hypertension, diabetes, ischaemic heart disease, chronic obstructive pulmonary disease and renal disease. This was an historical cohort study involving a total of 14,184 Indigenous residents, aged 15 years and over, who lived in remote communities and used a remote clinic or public hospital from 2002 to 2011. Individual level demographic and clinical data were drawn from primary care and hospital care information systems using a unique patient identifier. A propensity score was used to improve comparability between high, medium and low primary care utilisation groups. Incremental cost-effectiveness ratios and acceptability curves were used to analyse four health outcome measures: total and, avoidable hospital admissions, deaths and years of life lost. Compared to the low utilisation group, medium and high levels of primary care utilisation were associated with decreases in total and avoidable hospitalisations, deaths and years of life lost. Higher levels of primary care utilisation for renal disease reduced avoidable hospitalisations by 82-85%, deaths 72-75%, and years of life lost 78-81%. For patients with ischaemic heart disease, the reduction in avoidable hospitalisations was 63-78%, deaths 63-66% and years of life lost 69-73%. In terms of cost-effectiveness, primary care for renal disease and diabetes ranked as more cost-effective, followed by hypertension and ischaemic heart disease. Primary care for chronic obstructive pulmonary disease was the least cost-effective of the five conditions. Primary care in remote Indigenous communities was shown to be associated with cost-savings to public hospitals and health benefits to individual patients. Investing $1 in primary care in remote Indigenous communities could save $3.95-$11.75 in hospital costs, in addition to health benefits for individual patients. These findings may have wider applicability in strengthening primary care in the face of high chronic disease prevalence globally.

An eye movement analysis of the effect of interruption modality on primary task resumption.

PubMed

Ratwani, Raj; Trafton, J Gregory

2010-06-01

We examined the effect of interruption modality (visual or auditory) on primary task (visual) resumption to determine which modality was the least disruptive. Theories examining interruption modality have focused on specific periods of the interruption timeline. Preemption theory has focused on the switch from the primary task to the interrupting task. Multiple resource theory has focused on interrupting tasks that are to be performed concurrently with the primary task. Our focus was on examining how interruption modality influences task resumption.We leverage the memory-for-goals theory, which suggests that maintaining an associative link between environmental cues and the suspended primary task goal is important for resumption. Three interruption modality conditions were examined: auditory interruption with the primary task visible, auditory interruption with a blank screen occluding the primary task, and a visual interruption occluding the primary task. Reaction time and eye movement data were collected. The auditory condition with the primary task visible was the least disruptive. Eye movement data suggest that participants in this condition were actively maintaining an associative link between relevant environmental cues on the primary task interface and the suspended primary task goal during the interruption. These data suggest that maintaining cue association is the important factor for reducing the disruptiveness of interruptions, not interruption modality. Interruption-prone computing environments should be designed to allow for the user to have access to relevant primary task cues during an interruption to minimize disruptiveness.

The effects of thermal gradients on the Mars Observer Camera primary mirror

NASA Technical Reports Server (NTRS)

Applewhite, Roger W.; Telkamp, Arthur R.

1992-01-01

The paper discusses the effect of thermal gradients on the optical performance of the primary mirror of Mars Observer Camera (MOC), which will be launched on the Mars Observer spacecraft in September 1992. It was found that mild temperature gradients can have a large effect on the mirror surface figure, even for relatively low coefficient-of-thermal-expansion materials. However, in the case of the MOC primary mirror, it was found that the radius of curvature (ROC) of the reflective surface of the mirror changed in a nearly linear fashion with the radial temperature gradient, with little additional aberration. A solid-state ROC controller using the thermal gradient effect was implemented and verified.

Interaction effects of metals and salinity on biodegradation of a complex hydrocarbon waste.

PubMed

Amatya, Prasanna L; Hettiaratchi, Joseph Patrick A; Joshi, Ramesh C

2006-02-01

The presence of high levels of salts because of produced brine water disposal at flare pits and the presence of metals at sufficient concentrations to impact microbial activity are of concern to bioremediation of flare pit waste in the upstream oil and gas industry. Two slurry-phase biotreatment experiments based on three-level factorial statistical experimental design were conducted with a flare pit waste. The experiments separately studied the primary effect of cadmium [Cd(II)] and interaction effect between Cd(II) and salinity and the primary effect of zinc [Zn(II)] and interaction effect between Zn(II) and salinity on hydrocarbon biodegradation. The results showed 42-52.5% hydrocarbon removal in slurries spiked with Cd and 47-62.5% in the slurries spiked with Zn. The analysis of variance showed that the primary effects of Cd and Cd-salinity interaction were statistically significant on hydrocarbon degradation. The primary effects of Zn and the Zn-salinity interaction were statistically insignificant, whereas the quadratic effect of Zn was highly significant on hydrocarbon degradation. The study on effects of metallic chloro-complexes showed that the total aqueous concentration of Cd or Zn does not give a reliable indication of overall toxicity to the microbial activity in the presence of high salinity levels.

Effect of Mass Flow on Stack Eductor Performance.

DTIC Science & Technology

1984-06-01

absolute viscosity, lbf-sec/ft2 - density, Ibm/ft 3 "function of" ENGLISH LETTER SYMBOLS 2 A - area, in , ft B - atmospheric pressure, in Hg c - sonic... absolute temperature ratio T* - tertiary flow to primary flow absolute temperature t ratio - secondary -o primary mass flow rate ratio W* - tertiary to...secondary to primary absolute Tp temperature ratio TiL tertiary to primary absolute -TE temperature ratio secondary to primary flow density ratio

Using electronic medical records analysis to investigate the effectiveness of lifestyle programs in real-world primary care is challenging: a case study in diabetes mellitus.

PubMed

Linmans, Joris J; Viechtbauer, Wolfgang; Koppenaal, Tjarco; Spigt, Mark; Knottnerus, J André

2012-07-01

The increasing prevalence of diabetes suggests a gap between real world and controlled trial effectiveness of lifestyle interventions, but real-world investigations are rare. Electronic medical registration facilitates research on real-world effectiveness, although such investigations may require specific methodology and statistics. We investigated the effects of real-world primary care for patients with type 2 diabetes mellitus (T2DM). We used medical records of patients (n=2,549) with T2DM from 10 primary health care centers. A mixed-effects regression model for repeated measurements was used to evaluate the changes in weight and Hemoglobin A1c (HbA1c) over time. There was no statistically significant change in weight (+0.07 kg, P=0.832) and HbA1c (+0.03%, P=0.657) during the observation period of 972 days. Most patients maintained their physical activity level (70%), and 54 % had an insufficient activity level. The variability in the course of weight and HbA1c was because of differences between patients and not between health care providers. Despite effective lifestyle interventions in controlled trial settings, we found that real-world primary care is only able to stabilize weight and HbA1c in patients with T2DM over time. Medical registration can be used to monitor the actual effectiveness of interventions in primary care. Copyright © 2012 Elsevier Inc. All rights reserved.

Cost-Effectiveness of Primary Care Management With or Without Early Physical Therapy for Acute Low Back Pain: Economic Evaluation of a Randomized Clinical Trial.

PubMed

Fritz, Julie M; Kim, Minchul; Magel, John S; Asche, Carl V

2017-03-01

Economic evaluation of a randomized clinical trial. Compare costs and cost-effectiveness of usual primary care management for patients with acute low back pain (LBP) with or without the addition of early physical therapy. Low back pain is among the most common and costly conditions encountered in primary care. Early physical therapy after a new primary care consultation for acute LBP results in small clinical improvement but cost-effectiveness of a strategy of early physical therapy is unknown. Economic evaluation was conducted alongside a randomized clinical trial of patients with acute, nonspecific LBP consulting a primary care provider. All patients received usual primary care management and education, and were randomly assigned to receive four sessions of physical therapy or usual care of delaying referral consideration to permit spontaneous recovery. Data were collected in a randomized trial involving 220 participants age 18 to 60 with LBP <16 days duration without red flags or signs of nerve root compression. The EuroQoL EQ-5D health states were collected at baseline and after 1-year and used to compute the quality adjusted life year (QALY) gained. Direct (health care utilization) and indirect (work absence or reduced productivity) costs related to LBP were collected monthly and valued using standard costs. The incremental cost-effectiveness ratio was computed as incremental total costs divided by incremental QALYs. Early physical therapy resulted in higher total 1-year costs (mean difference in adjusted total costs = $580, 95% CI: $175, $984, P = 0.005) and better quality of life (mean difference in QALYs = 0.02, 95% CI: 0.005, 0.35, P = 0.008) after 1-year. The incremental cost-effectiveness ratio was $32,058 (95% CI: $10,629, $151,161) per QALY. Our results support early physical therapy as cost-effective relative to usual primary care after 1 year for patients with acute, nonspecific LBP. 2.

Interventions to promote or improve the mental health of primary care nurses: a systematic review.

PubMed

Duhoux, Arnaud; Menear, Matthew; Charron, Maude; Lavoie-Tremblay, Mélanie; Alderson, Marie

2017-11-01

To synthesize the evidence on the effectiveness of interventions aiming to promote or improve the mental health of primary care nurses. Primary care nurses have been found to have high levels of emotional exhaustion and to be at increased risk of suffering from burnout, anxiety and depression. Given the increasingly critical role of nurses in high-performing primary care, there is a need to identify interventions that can effectively reduce these professionals' mental health problems and promote their well-being. We conducted a systematic review on the effectiveness of interventions at the individual, group, work environment or organizational level. Eight articles reporting on seven unique studies met all eligibility criteria. They were non-randomized pre-post intervention studies and reported positive impacts of interventions on at least some outcomes, though caution is warranted in interpreting these results given the moderate-weak methodological quality of studies. This systematic review found moderate-weak evidence that primary, secondary and combined interventions can reduce burnout and stress in nurses practising in community-based health care settings. The results highlight a need for the implementation and evaluation of new strategies tailored for community-based nurses practising in primary care. © 2017 John Wiley & Sons Ltd.

The Effect of Mathematical Worksheets Based on Multiple Intelligences Theory on the Academic Achievement of the Students in the 4th Grade Primary School

ERIC Educational Resources Information Center

Inan, Cemil; Erkus, Serdar

2017-01-01

The aim of this research is to examine the effect of Math worksheets based on the Multiple Intelligences Theory on the academic achievement of students in the 4th grade primary school. The sample of the research consists of 64 (32 experimental and 32 control) students who are studying in the 4th grade in a primary school affiliated to the Ministry…

Patients with primary insomnia in the sleep laboratory: do they present with typical nights of sleep?

PubMed

Hirscher, Verena; Unbehaun, Thomas; Feige, Bernd; Nissen, Christoph; Riemann, Dieter; Spiegelhalder, Kai

2015-08-01

The validity of sleep laboratory investigations in patients with insomnia is important for researchers and clinicians. The objective of this study was to examine the first-night effect and the reverse first-night effect in patients with chronic primary insomnia compared with good sleeper controls. A retrospective comparison of a well-characterised sample of 50 patients with primary insomnia and 50 good sleeper controls was conducted with respect to 2 nights of polysomnography, and subjective sleep parameters in the sleep laboratory and the home setting. When comparing the first and second sleep laboratory night, a significant first-night effect was observed across both groups in the great majority of the investigated polysomnographic and subjective variables. However, patients with primary insomnia and good sleeper controls did not differ with respect to this effect. Regarding the comparison between the sleep laboratory nights and the home setting, unlike good sleeper controls, patients with primary insomnia reported an increased subjective sleep efficiency on both nights (in part due to a reduced bed time) and an increased subjective total sleep time on the second night. These results suggest that even the second sleep laboratory night does not necessarily provide clinicians and researchers with a representative insight into the sleep perception of patients with primary insomnia. Future studies should investigate whether these findings also hold for other patient populations. © 2015 European Sleep Research Society.

The effects of organization on medical utilization: an analysis of service line organization.

PubMed

Byrne, Margaret M; Charns, Martin P; Parker, Victoria A; Meterko, Mark M; Wray, Nelda P

2004-01-01

To determine whether clinical service lines in primary care and mental health reduces inpatient and urgent care utilization. All VHA medical centers were surveyed to determine whether service lines had been established in primary care or mental health care prior to the beginning of fiscal year 1997 (FY97). Facility-level data on medical utilization from Veterans Health Affairs (VHA) administrative databases were used for descriptive and multivariate regression analyses of utilization and of changes in measures between FY97 and FY98. Nine primary care-related and 5 mental health-related variables were analyzed. Primary care and mental health service lines had been established in approximately half of all facilities. Service lines varied in duration and extent of restructuring. Mere presence of a service line had no positive and several negative effects on measured outcome variables. More detailed analyses showed that some types of service lines have statistically significant and mostly negative effects on both mental health and primary care-related measures. Newly implemented service lines had significantly less improvement in measures over time than facilities with no service line. Health care organizations are implementing innovative organizational structures in hopes of improving quality of care and reducing resource utilization. We found that service lines in primary care and mental health may lead to an initial period of disruption, with little evidence of a beneficial effect on performance for longer duration service lines.

Systematic review of integrated models of health care delivered at the primary-secondary interface: how effective is it and what determines effectiveness?

PubMed

Mitchell, Geoffrey K; Burridge, Letitia; Zhang, Jianzhen; Donald, Maria; Scott, Ian A; Dart, Jared; Jackson, Claire L

2015-01-01

Integrated multidisciplinary care is difficult to achieve between specialist clinical services and primary care practitioners, but should improve outcomes for patients with chronic and/or complex chronic physical diseases. This systematic review identifies outcomes of different models that integrate specialist and primary care practitioners, and characteristics of models that delivered favourable clinical outcomes. For quality appraisal, the Cochrane Risk of Bias tool was used. Data are presented as a narrative synthesis due to marked heterogeneity in study outcomes. Ten studies were included. Publication bias cannot be ruled out. Despite few improvements in clinical outcomes, significant improvements were reported in process outcomes regarding disease control and service delivery. No study reported negative effects compared with usual care. Economic outcomes showed modest increases in costs of integrated primary-secondary care. Six elements were identified that were common to these models of integrated primary-secondary care: (1) interdisciplinary teamwork; (2) communication/information exchange; (3) shared care guidelines or pathways; (4) training and education; (5) access and acceptability for patients; and (6) a viable funding model. Compared with usual care, integrated primary-secondary care can improve elements of disease control and service delivery at a modestly increased cost, although the impact on clinical outcomes is limited. Future trials of integrated care should incorporate design elements likely to maximise effectiveness.

Effects of Classroom-Based Energizers on Primary Grade Students' Physical Activity Levels

ERIC Educational Resources Information Center

Bailey, Catherine Goffreda; DiPerna, James Clyde

2015-01-01

The primary aim of this study was to determine the effects of classroom-based exercise breaks (Energizers; Mahar, Kenny, Shields, Scales, & Collins, 2006) on students' physical activity levels during the school day. A multiple baseline design across first grade (N = 3) and second grade (N = 3) classrooms was used to examine the effects of the…

Effects of a 2-Year School-Based Intervention of Enhanced Physical Education in the Primary School

ERIC Educational Resources Information Center

Sacchetti, Rossella; Ceciliani, Andrea; Garulli, Andrea; Dallolio, Laura; Beltrami, Patrizia; Leoni, Erica

2013-01-01

Background: This study aimed to assess whether a school-based physical education intervention was effective in improving physical abilities and influencing daily physical activity habits in primary school children. The possible effect on body mass index (BMI) was also considered. Methods: Twenty-six 3rd-grade classes were randomly selected…

Primary care training and the evolving healthcare system.

PubMed

Peccoralo, Lauren A; Callahan, Kathryn; Stark, Rachel; DeCherrie, Linda V

2012-01-01

With growing numbers of patient-centered medical homes and accountable care organizations, and the potential implementation of the Patient Protection and Affordable Care Act, the provision of primary care in the United States is expanding and changing. Therefore, there is an urgent need to create more primary-care physicians and to train physicians to practice in this environment. In this article, we review the impact that the changing US healthcare system has on trainees, strategies to recruit and retain medical students and residents into primary-care internal medicine, and the preparation of trainees to work in the changing healthcare system. Recruitment methods for medical students include early preclinical exposure to patients in the primary-care setting, enhanced longitudinal patient experiences in clinical clerkships, and primary-care tracks. Recruitment methods for residents include enhanced ambulatory-care training and primary-care programs. Financial-incentive programs such as loan forgiveness may encourage trainees to enter primary care. Retaining residents in primary-care careers may be encouraged via focused postgraduate fellowships or continuing medical education to prepare primary-care physicians as both teachers and practitioners in the changing environment. Finally, to prepare primary-care trainees to effectively and efficiently practice within the changing system, educators should consider shifting ambulatory training to community-based practices, encouraging resident participation in team-based care, providing interprofessional educational experiences, and involving trainees in quality-improvement initiatives. Medical educators in primary care must think innovatively and collaboratively to effectively recruit and train the future generation of primary-care physicians. © 2012 Mount Sinai School of Medicine.

Robust estimation of the proportion of treatment effect explained by surrogate marker information.

PubMed

Parast, Layla; McDermott, Mary M; Tian, Lu

2016-05-10

In randomized treatment studies where the primary outcome requires long follow-up of patients and/or expensive or invasive obtainment procedures, the availability of a surrogate marker that could be used to estimate the treatment effect and could potentially be observed earlier than the primary outcome would allow researchers to make conclusions regarding the treatment effect with less required follow-up time and resources. The Prentice criterion for a valid surrogate marker requires that a test for treatment effect on the surrogate marker also be a valid test for treatment effect on the primary outcome of interest. Based on this criterion, methods have been developed to define and estimate the proportion of treatment effect on the primary outcome that is explained by the treatment effect on the surrogate marker. These methods aim to identify useful statistical surrogates that capture a large proportion of the treatment effect. However, current methods to estimate this proportion usually require restrictive model assumptions that may not hold in practice and thus may lead to biased estimates of this quantity. In this paper, we propose a nonparametric procedure to estimate the proportion of treatment effect on the primary outcome that is explained by the treatment effect on a potential surrogate marker and extend this procedure to a setting with multiple surrogate markers. We compare our approach with previously proposed model-based approaches and propose a variance estimation procedure based on a perturbation-resampling method. Simulation studies demonstrate that the procedure performs well in finite samples and outperforms model-based procedures when the specified models are not correct. We illustrate our proposed procedure using a data set from a randomized study investigating a group-mediated cognitive behavioral intervention for peripheral artery disease participants. Copyright © 2015 John Wiley & Sons, Ltd.

Adult community health-promoting interventions in primary health care: A systematic review.

PubMed

March, Sebastià; Torres, Elena; Ramos, María; Ripoll, Joana; García, Atanasio; Bulilete, Oana; Medina, David; Vidal, Clara; Cabeza, Elena; Llull, Micaela; Zabaleta-del-Olmo, Edurne; Aranda, José Manuel; Sastre, Silvia; Llobera, Joan

2015-07-01

To examine evidence on the effectiveness of health-promoting community interventions carried out in primary health care. Systematic review of originals and systematic reviews of health-promoting community interventions with the participation of primary health care. A working definition of community activities was used in the inclusion criteria. Databases searched up to 2013: PUBMED, EMBASE, CINHAL, Web of SCIENCE, IBECS, IME, and PSICODOC. No restrictions on year of publication or design. Articles were reviewed by separate researchers to identify risks of bias. Fifty-one articles published between 1966 and 2013 were included: 11 systematic reviews and 40 originals that described 39 community interventions. There is evidence on the effectiveness of community interventions in reducing cardiovascular risk factors, encouraging physical exercise, preventing falls and improving self-care among chronic patients compared with usual individual care. The effectiveness of some interventions increases when the community is involved in their development. Most assessments show positive results despite design limitations. The community approach may be more effective than the individual in usual preventive interventions in primary care. There is a lack of evidence on many community interventions in primary care and further research is needed. Copyright © 2015 Elsevier Inc. All rights reserved.

20 CFR 404.282 - Effective date of recomputations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Section 404.282 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Computing Primary Insurance Amounts Recomputing Your Primary Insurance Amount... Social Security benefit amount is effective for the first month you are entitled to the pension. Finally...

Automated outreach to increase primary adherence to cholesterol-lowering medications.

PubMed

Derose, Stephen F; Green, Kelley; Marrett, Elizabeth; Tunceli, Kaan; Cheetham, T Craig; Chiu, Vicki Y; Harrison, Teresa N; Reynolds, Kristi; Vansomphone, Southida S; Scott, Ronald D

2013-01-14

Primary nonadherence occurs when new prescriptions are not dispensed. Little is known about how to reduce primary nonadherence. We performed a randomized controlled trial to evaluate an automated system to decrease primary nonadherence to statins for lowering cholesterol. Adult members of Kaiser Permanente Southern California with no history of statin use within the past year who did not fill a statin prescription after 1 to 2 weeks were passively enrolled. The intervention group received automated telephone calls followed 1 week later by letters for continued nonadherence; the control group received no outreach. The primary outcome was a statin dispensed up to 2 weeks after delivery of the letter. Secondary outcomes included refills at intervals up to 1 year. Intervention effectiveness was determined by intent-to-treat analysis and Fisher exact test. Subgroups were examined using logistic regression. There were 2606 participants in the intervention group and 2610 in the control group. Statins were dispensed to 42.3% of intervention participants and 26.0% of control participants (absolute difference, 16.3%; P < .001). The relative risk for the intervention vs control group was 1.63 (95% CI, 1.50-1.76). Intervention effectiveness varied slightly by age (P = .045) but was effective across all age strata. Differences in the frequency of statin dispensations persisted up to 1 year (P < .001). The intervention was effective in reducing primary nonadherence to statin medications. Because of low marginal costs for outreach, this strategy appears feasible for reducing primary nonadherence. This approach may generalize well to other medications and chronic conditions.

Practical Approaches for Achieving Integrated Behavioral Health Care in Primary Care Settings

PubMed Central

Ratzliff, Anna; Phillips, Kathryn E.; Sugarman, Jonathan R.; Unützer, Jürgen; Wagner, Edward H.

2016-01-01

Behavioral health problems are common, yet most patients do not receive effective treatment in primary care settings. Despite availability of effective models for integrating behavioral health care in primary care settings, uptake has been slow. The Behavioral Health Integration Implementation Guide provides practical guidance for adapting and implementing effective integrated behavioral health care into patient-centered medical homes. The authors gathered input from stakeholders involved in behavioral health integration efforts: safety net providers, subject matter experts in primary care and behavioral health, a behavioral health patient and peer specialist, and state and national policy makers. Stakeholder input informed development of the Behavioral Health Integration Implementation Guide and the GROW Pathway Planning Worksheet. The Behavioral Health Integration Implementation Guide is model neutral and allows organizations to take meaningful steps toward providing integrated care that achieves access and accountability. PMID:26698163

Practical Approaches for Achieving Integrated Behavioral Health Care in Primary Care Settings.

PubMed

Ratzliff, Anna; Phillips, Kathryn E; Sugarman, Jonathan R; Unützer, Jürgen; Wagner, Edward H

Behavioral health problems are common, yet most patients do not receive effective treatment in primary care settings. Despite availability of effective models for integrating behavioral health care in primary care settings, uptake has been slow. The Behavioral Health Integration Implementation Guide provides practical guidance for adapting and implementing effective integrated behavioral health care into patient-centered medical homes. The authors gathered input from stakeholders involved in behavioral health integration efforts: safety net providers, subject matter experts in primary care and behavioral health, a behavioral health patient and peer specialist, and state and national policy makers. Stakeholder input informed development of the Behavioral Health Integration Implementation Guide and the GROW Pathway Planning Worksheet. The Behavioral Health Integration Implementation Guide is model neutral and allows organizations to take meaningful steps toward providing integrated care that achieves access and accountability.

Effectiveness of Psychological and Educational Interventions to Prevent Depression in Primary Care: A Systematic Review and Meta-Analysis.

PubMed

Conejo-Cerón, Sonia; Moreno-Peral, Patricia; Rodríguez-Morejón, Alberto; Motrico, Emma; Navas-Campaña, Desirée; Rigabert, Alina; Martín-Pérez, Carlos; Rodríguez-Bayón, Antonina; Ballesta-Rodríguez, María Isabel; Luna, Juan de Dios; García-Campayo, Javier; Roca, Miquel; Bellón, Juan Ángel

2017-05-01

Although evidence exists for the efficacy of psychosocial interventions to prevent the onset of depression, little is known about its prevention in primary care. We aimed to evaluate the effectiveness of psychological and educational interventions to prevent depression in primary care. We conducted a systematic review and meta-analysis of relevant randomized controlled trials (RCTs) examining the effect of psychological and educational interventions to prevent depression in nondepressed primary care attendees. We searched MEDLINE, PsycINFO, Web of Science, OpenGrey Repository, Cochrane Central Register of Controlled Trials, and other sources up to May 2016. At least 2 reviewers independently evaluated the eligibility criteria, extracted data, and assessed the risk of bias. We calculated standardized mean differences (SMD) using random-effects models. We selected 14 studies (7,365 patients) that met the inclusion criteria, 13 of which were valid to perform a meta-analysis. Most of the interventions had a cognitive-behavioral orientation, and in only 4 RCTs were the intervention clinicians primary care staff. The pooled SMD was -0.163 (95%CI, -0.256 to -0.070; P = .001). The risk of bias and the heterogeneity (I 2 = 20.6%) were low, and there was no evidence of publication bias. Meta-regression detected no association between SMD and follow-up times or SMD and risk of bias. Subgroup analysis suggested greater effectiveness when the RCTs used care as usual as the comparator compared with those using placebo. Psychological and educational interventions to prevent depression had a modest though statistically significant preventive effect in primary care. Further RCTs using placebo or active comparators are needed. © 2017 Annals of Family Medicine, Inc.

Effectiveness of Psychological and Educational Interventions to Prevent Depression in Primary Care: A Systematic Review and Meta-Analysis

PubMed Central

Conejo-Cerón, Sonia; Moreno-Peral, Patricia; Rodríguez-Morejón, Alberto; Motrico, Emma; Navas-Campaña, Desirée; Rigabert, Alina; Martín-Pérez, Carlos; Rodríguez-Bayón, Antonina; Ballesta-Rodríguez, María Isabel; Luna, Juan de Dios; García-Campayo, Javier; Roca, Miquel; Bellón, Juan Ángel

2017-01-01

PURPOSE Although evidence exists for the efficacy of psychosocial interventions to prevent the onset of depression, little is known about its prevention in primary care. We aimed to evaluate the effectiveness of psychological and educational interventions to prevent depression in primary care. METHODS We conducted a systematic review and meta-analysis of relevant randomized controlled trials (RCTs) examining the effect of psychological and educational interventions to prevent depression in nondepressed primary care attendees. We searched MEDLINE, PsycINFO, Web of Science, OpenGrey Repository, Cochrane Central Register of Controlled Trials, and other sources up to May 2016. At least 2 reviewers independently evaluated the eligibility criteria, extracted data, and assessed the risk of bias. We calculated standardized mean differences (SMD) using random-effects models. RESULTS We selected 14 studies (7,365 patients) that met the inclusion criteria, 13 of which were valid to perform a meta-analysis. Most of the interventions had a cognitive-behavioral orientation, and in only 4 RCTs were the intervention clinicians primary care staff. The pooled SMD was −0.163 (95%CI, −0.256 to −0.070; P = .001). The risk of bias and the heterogeneity (I2 = 20.6%) were low, and there was no evidence of publication bias. Meta-regression detected no association between SMD and follow-up times or SMD and risk of bias. Subgroup analysis suggested greater effectiveness when the RCTs used care as usual as the comparator compared with those using placebo. CONCLUSIONS Psychological and educational interventions to prevent depression had a modest though statistically significant preventive effect in primary care. Further RCTs using placebo or active comparators are needed. PMID:28483893

Why does primary angioplasty not work in registries? Quantifying the susceptibility of real-world comparative effectiveness data to allocation bias.

PubMed

Sen, Sayan; Davies, Justin E; Malik, Iqbal S; Foale, Rodney A; Mikhail, Ghada W; Hadjiloizou, Nearchos; Hughes, Alun; Mayet, Jamil; Francis, Darrel P

2012-11-01

Meta-analysis of registries (comparative effectiveness research) shows that primary angioplasty and fibrinolysis have equivalent real-world survival. Yet, randomized, controlled trials consistently find primary angioplasty superior. Can unequal allocation of higher-risk patients in registries have masked primary angioplasty benefit? First, we constructed a model to demonstrate the potential effect of allocation bias. We then analyzed published registries (55022 patients) for allocation of higher-risk patients (Killip class ≥1) to determine whether the choice of reperfusion therapy was affected by the risk level of the patient. Meta-regression was used to examine the relationship between differences in allocation of high-risk patient to primary angioplasty or fibrinolysis and mortality. Initial modeling suggested that registry outcomes are sensitive to allocation bias of high-risk patients. Across the registries, the therapy receiving excess high-risk patients had worse mortality. Unequal distribution of high-risk status accounted for most of the between-registry variance (adjusted R(2)(meta)=83.1%). Accounting for differential allocation of higher-risk patients, primary angioplasty gave 22% lower mortality (odds ratio, 0.78; 95% confidence interval, 0.64-0.97; P=0.029). We derive a formula, called the number needed to abolish, highlighting situations in which comparative effectiveness studies are particularly vulnerable to this bias. In ST-segment elevation myocardial infarction, clinicians' preference for management of a few high-risk patients can shift mortality substantially. Comparative effectiveness research in any disease is vulnerable to this, especially diseases with an immediately identifiable high-risk subgroup that clinicians prefer to allocate to 1 therapy. For this reason, preliminary indications from registry-based comparative effectiveness research should be definitively tested by randomized, controlled trials.

Cost-utility analysis of searching electronic health records and cascade testing to identify and diagnose familial hypercholesterolaemia in England and Wales.

PubMed

Crosland, Paul; Maconachie, Ross; Buckner, Sara; McGuire, Hugh; Humphries, Steve E; Qureshi, Nadeem

2018-05-17

The cost effectiveness of cascade testing for familial hypercholesterolaemia (FH) is well recognised. Less clear is the cost effectiveness of FH screening when it includes case identification strategies that incorporate routinely available data from primary and secondary care electronic health records. Nine strategies were compared, all using cascade testing in combination with different index case approaches (primary care identification, secondary care identification, and clinical assessment using the Simon Broome (SB) or Dutch Lipid Clinic Network (DLCN) criteria). A decision analytic model was informed by three systematic literature reviews and expert advice provided by a NICE Guideline Committee. The model found that the addition of primary care case identification by database search for patients with recorded total cholesterol >9.3 mmol/L was more cost effective than cascade testing alone. The incremental cost-effectiveness ratio (ICER) of clinical assessment using the DLCN criteria was £3254 per quality-adjusted life year (QALY) compared with case-finding with no genetic testing. The ICER of clinical assessment using the SB criteria was £13,365 per QALY (compared with primary care identification using the DLCN criteria), indicating that the SB criteria was preferred because it achieved additional health benefits at an acceptable cost. Secondary care identification, with either the SB or DLCN criteria, was not cost effective, alone (dominated and dominated respectively) or combined with primary care identification (£63, 514 per QALY, and £82,388 per QALY respectively). Searching primary care databases for people at high risk of FH followed by cascade testing is likely to be cost-effective. Copyright © 2018 Elsevier B.V. All rights reserved.

Sex steroid hormone determination of the maternal brain: effects beyond reproduction.

PubMed

Kinsley, C H; Meyer, E; Rafferty, K A

2012-10-01

Herein we discuss the effects of hormones on reproduction, but with a focus on the ripples that emanate from the main effects. That is, the role of hormones in reproductive events is both well-known and well accepted; less studied and understood are effects that appear to be ancillary to the primary objectives of the hormonal effects, which support, complement and extend their primary effects. We present evidence for how the hormonal stimulation of pregnancy constructs the maternal brain; makes it more efficient; enhances cognition; regulates stress responsiveness; modifies sensory systems (we discuss mainly olfaction); neurogenesis; and learning. Thus, steroid and other hormones and neuropeptides restructure the nervous system, particularly of females, to produce and regulate maternal behavior as well as behaviors and physiological systems that contribute to and support what is arguably the primary function of the hormones: survival and effective nurturance of the female's metabolic and genetic investment.

The Effectiveness of a Brief Asthma Education Intervention for Child Care Providers and Primary School Teachers

ERIC Educational Resources Information Center

Neuharth-Pritchett, Stacey; Getch, Yvette Q.

2016-01-01

Limited information exists about management of asthma in child care settings and primary school classrooms. The goal of this study was to evaluate a brief asthma management intervention for child care providers and primary school teachers. Child care providers and primary school teachers were recruited to participate in two 3-h workshops on asthma…

Preparing Kindergarten Two Children for Primary One in Singapore: Perceptions and Practices of Parents, Kindergarten Teachers and Primary Schoolteachers

ERIC Educational Resources Information Center

Choy, Mian Yee; Karuppiah, Nirmala

2016-01-01

Successful transition from preschool to primary school is believed to have long-term positive effects on a child's academic performance and social competence. In this study, data were gathered from preschool teachers, primary schoolteachers and parents through the use of questionnaires and semi-structured interviews, on their perceptions and…

Learning about What Constitutes Effective Training from a Pilot Programme to Improve Music Education in Primary Schools

ERIC Educational Resources Information Center

Rogers, Lynne; Hallam, Susan; Creech, Andrea; Preti, Costanza

2008-01-01

The new primary strategy in England has raised the profile of foundation subjects, including music, yet many primary school teachers lack skills and confidence in their ability to teach music. This research explores a year-long programme of training across 16 primary schools in England that sought to improve music education. The programme involved…

Impact of fine mesh sieve primary treatment on nitrogen removal in moving bed biofilm reactors.

PubMed

Rusten, B; Razafimanantsoa, V A; Andriamiarinjaka, M A; Otis, C L; Sahu, A K; Bilstad, T

2016-01-01

The purpose of this project was to investigate the effect of selective particle removal during primary treatment on nitrogen removal in moving bed biofilm reactors (MBBRs). Two small MBBR pilot plants were operated in parallel, where one train treated 2 mm screened municipal wastewater and the other train treated wastewater that had passed through a Salsnes Filter SF1000 rotating belt sieve (RBS) with a 33 µs sieve cloth. The SF1000 was operated without a filter mat on the belt. The tests confirmed that, for the wastewater characteristics at the test plant, Salsnes Filter primary treatment with a 33 µs RBS and no filter mat produced a primary effluent that was close to optimum. Removal of organic matter with the 33 µs sieve had no negative effect on the denitrification process. Nitrification rates improved by 10-15% in the train with 33 µs RBS primary treatment. Mass balance calculations showed that without RBS primary treatment, the oxygen demand in the biological system was 36% higher. Other studies have shown that the sludge produced by RBS primary treatment is beneficial for biogas production and will also significantly improve sludge dewatering of the combined primary and biological sludge.

Examining the Effect of Class Size on Classroom Engagement and Teacher-Pupil Interaction: Differences in Relation to Pupil Prior Attainment and Primary vs. Secondary Schools

ERIC Educational Resources Information Center

Blatchford, Peter; Bassett, Paul; Brown, Penelope

2011-01-01

It is widely recognized that we need to know more about effects of class size on classroom interactions and pupil behavior. This paper extends research by comparing effects on pupil classroom engagement and teacher-pupil interaction, and examining if effects vary by pupil attainment level and between primary and secondary schools. Systematic…

Posttraumatic stress disorder symptom severity and control beliefs as the predictors of academic burnout amongst adolescents following the Wenchuan Earthquake.

PubMed

Zhou, Xiao; Zhen, Rui; Wu, Xinchun

2017-01-01

Background : Previous studies indicate that posttraumatic stress disorder (PTSD) and control beliefs can affect burnout and their unique role in this situation has been examined, but fewer studies have examined their combined role in adolescent's academic burnout following traumatic events. Objective : This study examined the combined effect of PTSD symptom severity and control beliefs on academic burnout among adolescents, and assessed the moderating role of primary and secondary control beliefs in the relation between PTSD symptom severity and academic burnout. Methods : Seven hundred and forty-five adolescents were investigated using self-report questionnaires, and a series of regression equations examined the impact of PTSD severity and control beliefs on academic burnout. Results : PTSD symptom severity is associated positively with academic burnout, while primary and secondary control beliefs have a negative relation with academic burnout. In addition, primary control beliefs buffer the positive effects of PTSD symptom severity on academic burnout. We found that the positive relation between PTSD symptom severity and academic burnout in the low primary control beliefs group is more intense than that found in the high primary control beliefs group. Conclusions : PTSD symptom severity is a risk factor, whereas primary and secondary control beliefs are protective factors in academic burnout. In addition, PTSD symptom severity and primary control beliefs have a combined effect on academic burnout in adolescents following natural disasters.

Efficacy of Ginger for Alleviating the Symptoms of Primary Dysmenorrhea: A Systematic Review and Meta-analysis of Randomized Clinical Trials.

PubMed

Daily, James W; Zhang, Xin; Kim, Da Sol; Park, Sunmin

2015-12-01

There has been no attempt to date to synthesize the available evidence for the efficacy of ginger for treating primary dysmenorrhea. This systematic review evaluates the current evidence for the effectiveness of ginger for treating primary dysmenorrhea. Literature searches were conducted using 12 electronic databases including PubMed, EMBASE, Cochrane Library, Korean databases, Chinese medical databases, and Indian scientific database. Search terms used were: "ginger" or "Zingiber officinale" and "dysmenorrhea" and "pain." Studies using ginger as a treatment of primary dysmenorrhea were considered for inclusion. The major outcome of primary dysmenorrhea was assessed using a pain visual analogue score (PVAS). Initial searches yielded 29 articles. Of these original results, seven met specific selection criteria. Four of the RCTs compared the therapeutic efficacy of ginger with a placebo during the first 3-4 days of the menstrual cycle and were included in the meta analysis. The meta-analysis of these data showed a significant effect of ginger in reducing PVAS in subjects having primary dysmenorrhea (risk ratio, -1.85; 95% CI of -2.87, -0.84, P = 0.0003). Six RCTs out of 7 exhibited low to moderate of risk of bias. Collectively these RCTs provide suggestive evidence for the effectiveness of 750-2000 mg ginger powder during the first 3-4 days of menstrual cycle for primary dysmenorrhea. Wiley Periodicals, Inc.

Collateral benefits of the family check-up in early childhood: primary caregivers' social support and relationship satisfaction.

PubMed

McEachern, Amber D; Fosco, Gregory M; Dishion, Thomas J; Shaw, Daniel S; Wilson, Melvin N; Gardner, Frances

2013-04-01

This research investigated potential collateral benefits of the Family Check-Up (FCU) intervention, namely, primary caregivers' perceived social support and couple relationship satisfaction. A subsample of 435 low-income families with a 2-year-old child was recruited to participate in a randomized controlled trial assessing preventative effects of the FCU. Longitudinal growth models were used to evaluate intention-to-treat effects of the FCU on increases in primary caregivers' ratings of social support satisfaction with perceived social support and significant-other relationships, and indirect effects on primary caregivers through improvements in children's behavior problems. Support was found for a model in which reductions in child problem behavior from ages 2 to 4 predicted positive change in caregiver-rated social support and relationship satisfaction over a 3-year period. This indirect effects model is discussed with respect to implications for early childhood prevention research focused on improving family functioning. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

Collateral Benefits of the Family Check-Up in Early Childhood: Primary Caregivers’ Social Support and Relationship Satisfaction

PubMed Central

McEachern, Amber D.; Dishion, Thomas J.; Wilson, Melvin N.; Fosco, Gregory M.; Shaw, Daniel S.; Gardner, Frances

2013-01-01

This research investigated potential collateral benefits of the Family Check-Up (FCU) intervention, namely, primary caregivers’ perceived social support and couple relationship satisfaction. A subsample of 435 low-income families with a 2-year-old child was recruited to participate in a randomized controlled trial assessing preventative effects of the FCU. Longitudinal growth models were used to evaluate intention-to-treat effects of the FCU on increases in primary caregivers’ ratings of social support satisfaction with perceived social support and significant-other relationships, and indirect effects on primary caregivers through improvements in children's behavior problems. Support was found for a model in which reductions in child problem behavior from ages 2 to 4 predicted positive change in caregiver-rated social support and relationship satisfaction over a 3-year period. This indirect effects model is discussed with respect to implications for early childhood prevention research focused on improving family functioning. PMID:23458695

40 CFR 142.22 - Review of State variances, exemptions and schedules.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS IMPLEMENTATION Review of...) Not later than 18 months after the effective date of the interim national primary drinking water... (and schedules prescribed pursuant thereto) by the States with primary enforcement responsibility...

Hippocampus and Basal Forebrain Volumetry for Dementia and Mild Cognitive Impairment Diagnosis: Could It Be Useful in Primary Care?

PubMed

Teipel, Stefan J; Keller, Felix; Thyrian, Jochen R; Strohmaier, Urs; Altiner, Attila; Hoffmann, Wolfgang; Kilimann, Ingo

2017-01-01

Once a patient or a knowledgeable informant has noticed decline in memory or other cognitive functions, initiation of early dementia assessment is recommended. Hippocampus and cholinergic basal forebrain (BF) volumetry supports the detection of prodromal and early stages of Alzheimer's disease (AD) dementia in highly selected patient populations. To compare effect size and diagnostic accuracy of hippocampus and BF volumetry between patients recruited in highly specialized versus primary care and to assess the effect of white matter lesions as a proxy for cerebrovascular comorbidity on diagnostic accuracy. We determined hippocampus and BF volumes and white matter lesion load from MRI scans of 71 participants included in a primary care intervention trial (clinicaltrials.gov identifier: NCT01401582) and matched 71 participants stemming from a memory clinic. Samples included healthy controls and people with mild cognitive impairment (MCI), AD dementia, mixed dementia, and non-AD related dementias. Volumetric measures reached similar effect sizes and cross-validated levels of accuracy in the primary care and the memory clinic samples for the discrimination of AD and mixed dementia cases from healthy controls. In the primary care MCI cases, volumetric measures reached only random guessing levels of accuracy. White matter lesions had only a modest effect on effect size and diagnostic accuracy. Hippocampus and BF volumetry may usefully be employed for the identification of AD and mixed dementia, but the detection of MCI does not benefit from the use of these volumetric markers in a primary care setting.

The clinical significance of occult gynecologic primary tumours in metastatic cancer.

PubMed

Hannouf, M B; Winquist, E; Mahmud, S M; Brackstone, M; Sarma, S; Rodrigues, G; Rogan, P K; Hoch, J S; Zaric, G S

2017-10-01

We estimated the frequency of occult gynecologic primary tumours (gpts) in patients with metastatic cancer from an uncertain primary and evaluated the effect on disease management and overall survival (os). We used Manitoba administrative health databases to identify all patients initially diagnosed with metastatic cancer during 2002-2011. We defined patients as having an "occult" primary tumour if the primary was classified at least 6 months after the initial diagnosis. Otherwise, we considered patients to have "obvious" primaries. We then compared clinicopathologic and treatment characteristics and 2-year os for women with occult and with obvious gpts. We used Cox regression adjustment and propensity score methods to assess the effect on os of having an occult gpt. Among the 5953 patients diagnosed with metastatic cancer, occult primary tumours were more common in women ( n = 285 of 2552, 11.2%) than in men ( n = 244 of 3401, 7.2%). In women, gpts were the most frequent occult primary tumours ( n = 55 of 285, 19.3%). Compared with their counterparts having obvious gpts, women with occult gpts ( n = 55) presented with similar histologic and metastatic patterns but received fewer gynecologic diagnostic examinations during diagnostic work-up. Women with occult gpts were less likely to undergo surgery, waited longer for radiotherapy, and received a lesser variety of chemotherapeutic agents. Having an occult compared with an obvious gpt was associated with decreased os (hazard ratio: 1.62; 95% confidence interval: 1.2 to 2.35). Similar results were observed in adjusted analyses. In women with metastatic cancer from an uncertain primary, gpts constitute the largest clinical entity. Accurate diagnosis of occult gpts early in the course of metastatic cancer might lead to more effective treatment decisions and improved survival outcomes.

The clinical significance of occult gynecologic primary tumours in metastatic cancer

PubMed Central

Hannouf, M.B.; Winquist, E.; Mahmud, S.M.; Brackstone, M.; Sarma, S.; Rodrigues, G.; Rogan, P.K.; Hoch, J.S.; Zaric, G.S.

2017-01-01

Objective We estimated the frequency of occult gynecologic primary tumours (gpts) in patients with metastatic cancer from an uncertain primary and evaluated the effect on disease management and overall survival (os). Methods We used Manitoba administrative health databases to identify all patients initially diagnosed with metastatic cancer during 2002–2011. We defined patients as having an “occult” primary tumour if the primary was classified at least 6 months after the initial diagnosis. Otherwise, we considered patients to have “obvious” primaries. We then compared clinicopathologic and treatment characteristics and 2-year os for women with occult and with obvious gpts. We used Cox regression adjustment and propensity score methods to assess the effect on os of having an occult gpt. Results Among the 5953 patients diagnosed with metastatic cancer, occult primary tumours were more common in women (n = 285 of 2552, 11.2%) than in men (n = 244 of 3401, 7.2%). In women, gpts were the most frequent occult primary tumours (n = 55 of 285, 19.3%). Compared with their counterparts having obvious gpts, women with occult gpts (n = 55) presented with similar histologic and metastatic patterns but received fewer gynecologic diagnostic examinations during diagnostic work-up. Women with occult gpts were less likely to undergo surgery, waited longer for radiotherapy, and received a lesser variety of chemotherapeutic agents. Having an occult compared with an obvious gpt was associated with decreased os (hazard ratio: 1.62; 95% confidence interval: 1.2 to 2.35). Similar results were observed in adjusted analyses. Conclusions In women with metastatic cancer from an uncertain primary, gpts constitute the largest clinical entity. Accurate diagnosis of occult gpts early in the course of metastatic cancer might lead to more effective treatment decisions and improved survival outcomes. PMID:29089807

Effective recruitment strategies in primary care research: a systematic review.

PubMed

Ngune, Irene; Jiwa, Moyez; Dadich, Ann; Lotriet, Jaco; Sriram, Deepa

2012-01-01

Patient recruitment in primary care research is often a protracted and frustrating process, affecting project timeframes, budget and the dissemination of research findings. Yet, clear guidance on patient recruitment strategies in primary care research is limited. This paper addresses this issue through a systematic review. Articles were sourced from five academic databases - AustHealth, CINAHL, the Cochrane Methodology Group, EMBASE and PubMed/Medline; grey literature was also sourced from an academic library and the Primary Healthcare Research & Information Service (PHCRIS) website. Two reviewers independently screened the articles using the following criteria: (1) published in English, (2) reported empirical research, (3) focused on interventions designed to increase patient recruitment in primary care settings, and (4) reported patient recruitment in primary care settings. Sixty-six articles met the inclusion criteria. Of these, 23 specifically focused on recruitment strategies and included randomised trials (n = 7), systematic reviews (n = 8) and qualitative studies (n = 8). Of the remaining articles, 30 evaluated recruitment strategies, while 13 addressed the value of recruitment strategies using descriptive statistics and/or qualitative data. Among the 66 articles, primary care chiefly included general practice (n = 30); nursing and allied health services, multiple settings, as well as other community settings (n = 30); and pharmacy (n = 6). Effective recruitment strategies included the involvement of a discipline champion, simple patient eligibility criteria, patient incentives and organisational strategies that reduce practitioner workload. The most effective recruitment in primary care research requires practitioner involvement. The active participation of primary care practitioners in both the design and conduct of research helps to identify strategies that are congruent with the context in which patient care is delivered. This is reported to be the optimal recruitment strategy.

Assessment of the Effectiveness of the Educational Environment Supported by Computer Aided Presentations at Primary School Level

ERIC Educational Resources Information Center

Kose, Erdogan

2009-01-01

The objective of this study is to assess the effectiveness of the educational environment supported by computer aided presentations at primary school. The effectiveness of the environment has been evaluated in terms of students' learning and remembering what they have learnt. In the study, we have compared experimental group and control group in…

Effect of oxalic acid and steam pretreatment on the primary properties of UF-bonded rice straw particleboards

Treesearch

Xianjun Li; Zhiyong Cai; Jerrold E. Winandy; Altaf H. Basta

2011-01-01

The objective is to evaluate the effect of oxalic acid (OA) and steam-pretreatment on the primary performance of rice straw particleboards. In addition, the effect of various treatment conditions on carbohydrates released from rice straw particles was investigated. The results show that steam- and short durations of OA-treatment significantly improved the mechanical...

Effectiveness of Game and Poem Enhanced Instructional Strategies and Verbal Ability on Students' Interest in Mathematics Learning

ERIC Educational Resources Information Center

Frederick-Jonah, Toinpere Mercy; Igbojinwaekwu, Patrick Chukwuemeka

2015-01-01

This study investigated the effects of game and poem-enhanced instructional strategies on students' interest in mathematics. The moderating effects of verbal ability were also examined on the dependent variable. A quasi-experimental design was adopted. Three hundred and forty four students in the sixth year of their primary education (primary 6…

Across the divide: "Primary care departments working together to redesign care to achieve the Triple Aim".

PubMed

Koslov, Steven; Trowbridge, Elizabeth; Kamnetz, Sandra; Kraft, Sally; Grossman, Jeffrey; Pandhi, Nancy

2016-09-01

Primary care is considered the foundation of an effective health care system. However, primary care departments at academic health centers have numerous challenges to overcome when trying to achieve the Triple Aim. As part of an organizational initiative to redesign primary care at a large academic health center, departments of internal medicine, general pediatrics and adolescent medicine, and family medicine worked together to comprehensively redesign primary care. This article describes the process of aligning these three primary care departments: defining panel size, developing a common primary care job description, redesigning the primary care compensation plan, redesigning the care model, and developing standardized staffing. Prior to the initiative, the rate of patient satisfaction was 85%, anticoagulation measurement 65%, pneumococcal vaccination 85%, breast cancer screening 79%, and colorectal cancer screening 69%. These rates all improved to 87%, 75%, 88%, 80%, and 80% respectively. Themes around key challenges to departmental integration are identified: (1) implementing effective communication strategies; (2) addressing specialty differences in primary care delivery; (3) working within resource limitations; and (4) developing long-term sustainability. Primary care in this large academic health center was transformed through developing a united primary care leadership team that bridged individual departments to create and adopt a common vision and solutions to shared problems. Our collaboration has achieved improvements across patient satisfaction, clinical safety metrics, and publicly-reported preventive care outcomes. The description of this experience may be useful for other academic health centers or other non-integrated delivery systems undertaking primary care practice transformation. Copyright © 2015 Elsevier Inc. All rights reserved.

Across the Divide: “Primary Care Departments Working Together to Redesign Care to Achieve the Triple Aim”

PubMed Central

Koslov, Steven; Trowbridge, Elizabeth; Kamnetz, Sandra; Kraft, Sally; Grossman, Jeffrey; Pandhi, Nancy

2016-01-01

Background Primary care is considered the foundation of an effective health care system. However, primary care departments at academic health centers have numerous challenges to overcome when trying to achieve the Triple Aim. Methods As part of an organizational initiative to redesign primary care at a large academic health center, departments of internal medicine, general pediatrics and adolescent medicine, and family medicine worked together to comprehensively redesign primary care. This article describes the process of aligning these three primary care departments: defining panel size, developing a common primary care job description, redesigning the primary care compensation plan, redesigning the care model, and developing standardized staffing. Results Prior to the initiative, the rate of patient satisfaction was 85%, anticoagulation measurement 65%, pneumococcal vaccination 85%, breast cancer screening 79%, and colorectal cancer screening 69%. These rates all improved to 87%, 75%, 88%, 80%, and 80% respectively. Themes around key challenges to departmental integration are identified: (1) implementing effective communication strategies; (2) addressing specialty differences in primary care delivery; (3) working within resource limitations; and (4) developing long-term sustainability. Conclusions Primary care in this large academic health center was transformed through developing a united primary care leadership team that bridged individual departments to create and adopt a common vision and solutions to shared problems. Our collaboration has achieved improvements across patient satisfaction, clinical safety metrics, and publicly-reported preventive care outcomes. Implications The description of this experience may be useful for other academic health centers or other non-integrated delivery systems undertaking primary care practice transformation. PMID:27637827

Brief cognitive behavioral therapy in primary care: a hybrid type 2 patient-randomized effectiveness-implementation design.

PubMed

Cully, Jeffrey A; Armento, Maria E A; Mott, Juliette; Nadorff, Michael R; Naik, Aanand D; Stanley, Melinda A; Sorocco, Kristen H; Kunik, Mark E; Petersen, Nancy J; Kauth, Michael R

2012-07-11

Despite the availability of evidence-based psychotherapies for depression and anxiety, they are underused in non-mental health specialty settings such as primary care. Hybrid effectiveness-implementation designs have the potential to evaluate clinical and implementation outcomes of evidence-based psychotherapies to improve their translation into routine clinical care practices. This protocol article discusses the study methodology and implementation strategies employed in an ongoing, hybrid, type 2 randomized controlled trial with two primary aims: (1) to determine whether a brief, manualized cognitive behavioral therapy administered by Veterans Affairs Primary Care Mental Health Integration program clinicians is effective in treating depression and anxiety in a sample of medically ill (chronic cardiopulmonary diseases) primary care patients and (2) to examine the acceptability, feasibility, and preliminary outcomes of a focused implementation strategy on improving adoption and fidelity of brief cognitive behavioral therapy at two Primary Care-Mental Health Integration clinics. The study uses a hybrid type 2 effectiveness/implementation design to simultaneously test clinical effectiveness and to collect pilot data on a multifaceted implementation strategy that includes an online training program, audit and feedback of session content, and internal and external facilitation. Additionally, the study engages the participation of an advisory council consisting of stakeholders from Primary Care-Mental Health Integration, as well as regional and national mental health leaders within the Veterans Administration. It targets recruitment of 320 participants randomized to brief cognitive behavioral therapy (n = 200) or usual care (n = 120). Both effectiveness and implementation outcomes are being assessed using mixed methods, including quantitative evaluation (e.g., intent-to-treat analyses across multiple time points) and qualitative methods (e.g., focus interviews and surveys from patients and providers). Patient-effectiveness outcomes include measures of depression, anxiety, and physical health functioning using blinded independent evaluators. Implementation outcomes include patient engagement and adherence and clinician brief cognitive behavioral therapy adoption and fidelity. Hybrid designs are needed to advance clinical effectiveness and implementation knowledge to improve healthcare practices. The current article describes the rationale and challenges associated with the use of a hybrid design for the study of brief cognitive behavioral therapy in primary care. Although trade-offs exist between scientific control and external validity, hybrid designs are part of an emerging approach that has the potential to rapidly advance both science and practice. NCT01149772 at http://www.clinicaltrials.gov/ct2/show/NCT01149772.

Pulse-train Stimulation of Primary Somatosensory Cortex Blocks Pain Perception in Tail Clip Test

PubMed Central

Lee, Soohyun; Hwang, Eunjin; Lee, Dongmyeong

2017-01-01

Human studies of brain stimulation have demonstrated modulatory effects on the perception of pain. However, whether the primary somatosensory cortical activity is associated with antinociceptive responses remains unknown. Therefore, we examined the antinociceptive effects of neuronal activity evoked by optogenetic stimulation of primary somatosensory cortex. Optogenetic transgenic mice were subjected to continuous or pulse-train optogenetic stimulation of the primary somatosensory cortex at frequencies of 15, 30, and 40 Hz, during a tail clip test. Reaction time was measured using a digital high-speed video camera. Pulse-train optogenetic stimulation of primary somatosensory cortex showed a delayed pain response with respect to a tail clip, whereas no significant change in reaction time was observed with continuous stimulation. In response to the pulse-train stimulation, video monitoring and local field potential recording revealed associated paw movement and sensorimotor rhythms, respectively. Our results show that optogenetic stimulation of primary somatosensory cortex at beta and gamma frequencies blocks transmission of pain signals in tail clip test. PMID:28442945

[Influence of an exercise therapy on primary chronic constipation].

PubMed

Beradze, G; Sherozia, M; Shankulashvili, G

2011-09-01

During the primary chronic constipation increase of exercise stress is a commonly recognized recommendation, but not existence of specific schemes and forms of tension, restricts wide usage of this method. Subject of the research was the evaluation of exercise therapy effectiveness in patients with primary chronic constipation. The research was carried out on 15 patients, who were undergone exercise therapy sessions for their stoutness and spinal pathologies. Research group consisted of 8 patients with irritable intestine syndrome, who were provided by standard treatment. All researched patients kept a diary, with numeral evaluation of defecation type. Analysis of the findings displayed satisfactory effectiveness of the exercise therapy during the primary chronic constipation.

Managing depression in primary care.

PubMed

Ng, Chung Wai Mark; How, Choon How; Ng, Yin Ping

2017-08-01

Major depression is common in the primary care setting. In the final article of this series, we illustrate the approach to the management of depression in primary care. Psychotherapy has been shown to be as effective as antidepressants for mild to moderate major depression. The common myth that antidepressants are addictive should be addressed. Antidepressants should be started at a subtherapeutic dose to assess tolerability, then gradually increased until a minimally effective dose is achieved. Apart from pharmacotherapy and psychotherapy, management of depression should include managing stressors, engaging social and community support, dealing with stigma and discrimination, and managing concomitant comorbidities. A strong therapeutic relationship and empathic listening are important between the primary care physician and patient. Copyright: © Singapore Medical Association.

Managing depression in primary care

PubMed Central

Ng, Chung Wai Mark; How, Choon How; Ng, Yin Ping

2017-01-01

Major depression is common in the primary care setting. In the final article of this series, we illustrate the approach to the management of depression in primary care. Psychotherapy has been shown to be as effective as antidepressants for mild to moderate major depression. The common myth that antidepressants are addictive should be addressed. Antidepressants should be started at a subtherapeutic dose to assess tolerability, then gradually increased until a minimally effective dose is achieved. Apart from pharmacotherapy and psychotherapy, management of depression should include managing stressors, engaging social and community support, dealing with stigma and discrimination, and managing concomitant comorbidities. A strong therapeutic relationship and empathic listening are important between the primary care physician and patient. PMID:28848991

Comparison of the effect of honey and mefenamic acid on the severity of pain in women with primary dysmenorrhea.

PubMed

Amiri Farahani, Ë Leila; Hasanpoor-Azghdy, Seyedeh Batool; Kasraei, Hengameh; Heidari, Tooba

2017-08-01

Primary dysmenorrhea starts simultaneously with menstruation or before it and usually continues for 48-72 h. As a prevalence disorder, it affects about 80-97% of women in the reproductive age. The conventional treatment modalities of primary dysmenorrhea are associated with complications and side effects. In addition, there is a lack of knowledge of the effect of honey on the treatment of primary dysmenorrhea. The objective of this study is to investigate the effect of honey on the severity of pain in women with dysmenorrhea. A randomized crossover clinical trial was conducted on 56 female students. Subjects were randomly assigned to two groups. Groups I and II received honey and mefenamic acid in the 'first treatment period', respectively. In the 'second treatment period', the intervention methods were reversed between the groups. Samples recorded the severity of pain during the first 3 days of menstruation. There were no significant differences in the most severe level of pain in the first and second months of the first treatment period, and the first and second months of the second treatment period between the groups. Honey and the mefenamic acid capsules led to the same amount of pain relief in women with primary dysmenorrhea. Honey is suggested to be used for pain relief due to its lower side effects and pharmacological complications.

Influence of income, hours worked, and loan repayment on medical students' decision to pursue a primary care career.

PubMed

Rosenthal, M P; Diamond, J J; Rabinowitz, H K; Bauer, L C; Jones, R L; Kearl, G W; Kelly, R B; Sheets, K J; Jaffe, A; Jonas, A P

To assess the specialty plans of current fourth-year medical students and, for those not choosing primary care specialties, to investigate the potential effect that changes in key economic or lifestyle factors could have in attracting such students to primary care. A survey study was sent to 901 fourth-year medical students in the 1993 graduating classes of six US medical schools. Comparisons were made between students choosing and not choosing primary care specialties. For the non-primary care students, we also evaluated whether alteration of income, hours worked, or loan repayment could attract them to primary care careers. Of the 688 responses (76% response rate), primary care specialties were chosen by 27% of the students and non-primary care specialties by 73%. One quarter (25%) of the non-primary care students indicated they would change to primary care for one of the following factors: income (10%), hours worked (11%), or loan repayment (4%). For students whose debt was $50,000 or greater, the loan repayment option became much more important than for students with lesser debt. In all, a total of 45% (n = 313) of the students indicated either they were planning to enter primary care (n = 188) or they would change to a primary care specialty (n = 125) with appropriate adjustments in income, hours worked, or loan repayment. Significant changes in economic and lifestyle factors could have a direct effect on the ability to attract students to primary care. Including such changes as part of health system reform, especially within the context of a supportive medical school environment, could enable the United States to approach a goal of graduating 50% generalist physicians.

Platelet-released growth factors inhibit proliferation of primary keratinocytes in vitro.

PubMed

Bayer, Andreas; Tohidnezhad, Mersedeh; Berndt, Rouven; Lippross, Sebastian; Behrendt, Peter; Klüter, Tim; Pufe, Thomas; Jahr, Holger; Cremer, Jochen; Rademacher, Franziska; Simanski, Maren; Gläser, Regine; Harder, Jürgen

2018-01-01

Autologous thrombocyte concentrate lysates as platelet-released growth factors (PRGF) or Vivostat Platelet Rich Fibrin (PRF ® ) represent important tools in modern wound therapy, especially in the treatment of chronic, hard-to-heal or infected wounds. Nevertheless, underlying cellular and molecular mechanisms of the beneficial clinical effects of a local wound therapy with autologous thrombocyte concentrate lysates are poorly understood. Recently, we have demonstrated that PRGF induces antimicrobial peptides in primary keratinocytes and accelerates keratinocytes' differentiation. In the present study we analyzed the influence of PRGF on primary human keratinocytes' proliferation. Using the molecular proliferation marker Ki-67 we observed a concentration- and time dependent inhibition of Ki-67 gene expression in PRGF treated primary keratinocytes. These effects were independent from the EGFR- and the IL-6-R pathway. Inhibition of primary keratinocytes' proliferation by PRGF treatment was confirmed in colorimetric cell proliferation assays. Together, these data indicate that the clinically observed positive effects of autologous thrombocytes concentrates in the treatment of chronic, hard-to-heal wounds are not based on an increased keratinocytes proliferation. Copyright © 2017 Elsevier GmbH. All rights reserved.

Mitigating the Effects of Family Poverty on Early Child Development through Parenting Interventions in Primary Care.

PubMed

Cates, Carolyn Brockmeyer; Weisleder, Adriana; Mendelsohn, Alan L

2016-04-01

Poverty related disparities in early child development and school readiness are a major public health crisis, the prevention of which has emerged in recent years as a national priority. Interventions targeting parenting and the quality of the early home language environment are at the forefront of efforts to address these disparities. In this article we discuss the innovative use of the pediatric primary care platform as part of a comprehensive public health strategy to prevent adverse child development outcomes through the promotion of parenting. Models of interventions in the pediatric primary care setting are discussed with evidence of effectiveness reviewed. Taken together, a review of this significant body of work shows the tremendous potential to deliver evidence-based preventive interventions to families at risk for poverty related disparities in child development and school readiness at the time of pediatric primary care visits. We also addresss considerations related to scaling and maximizing the effect of pediatric primary care parenting interventions and provide key policy recommendations. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Effectiveness of Problem-Solving Therapy for Older, Primary Care Patients with Depression: Results from the IMPACT Project

ERIC Educational Resources Information Center

Arean, Patricia; Hegel, Mark; Vannoy, Steven; Fan, Ming-Yu; Unuzter, Jurgen

2008-01-01

Purpose: We compared a primary-care-based psychotherapy, that is, problem-solving therapy for primary care (PST-PC), to community-based psychotherapy in treating late-life major depression and dysthymia. Design and Methods: The data here are from the IMPACT study, which compared collaborative care within a primary care clinic to care as usual in…

39 CFR 254.2 - Definition of primary function area and criteria used to determine whether an alteration has an...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 39 Postal Service 1 2010-07-01 2010-07-01 false Definition of primary function area and criteria used to determine whether an alteration has an effect on an area containing a primary function that is... ARCHITECTURAL BARRIERS ACT § 254.2 Definition of primary function area and criteria used to determine whether an...

39 CFR 254.2 - Definition of primary function area and criteria used to determine whether an alteration has an...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 39 Postal Service 1 2011-07-01 2011-07-01 false Definition of primary function area and criteria used to determine whether an alteration has an effect on an area containing a primary function that is... ARCHITECTURAL BARRIERS ACT § 254.2 Definition of primary function area and criteria used to determine whether an...

39 CFR 254.2 - Definition of primary function area and criteria used to determine whether an alteration has an...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 39 Postal Service 1 2014-07-01 2014-07-01 false Definition of primary function area and criteria used to determine whether an alteration has an effect on an area containing a primary function that is... ARCHITECTURAL BARRIERS ACT § 254.2 Definition of primary function area and criteria used to determine whether an...

39 CFR 254.2 - Definition of primary function area and criteria used to determine whether an alteration has an...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 39 Postal Service 1 2012-07-01 2012-07-01 false Definition of primary function area and criteria used to determine whether an alteration has an effect on an area containing a primary function that is... ARCHITECTURAL BARRIERS ACT § 254.2 Definition of primary function area and criteria used to determine whether an...

39 CFR 254.2 - Definition of primary function area and criteria used to determine whether an alteration has an...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 39 Postal Service 1 2013-07-01 2013-07-01 false Definition of primary function area and criteria used to determine whether an alteration has an effect on an area containing a primary function that is... ARCHITECTURAL BARRIERS ACT § 254.2 Definition of primary function area and criteria used to determine whether an...

Protocol for the Hall Technique study: A trial to measure clinical effectiveness and cost-effectiveness of stainless steel crowns for dental caries restoration in primary molars in young children.

PubMed

Tonmukayakul, Utsana; Martin, Rachel; Clark, Richard; Brownbill, John; Manton, David; Hall, Martin; Armfield, Jason; Smith, Michael; Shankumar, Ramini; Sivasithamparam, Kavitha; Martin-Kerry, Jacqueline; Calache, Hanny

2015-09-01

The Hall Technique (HT) is a carious primary molar treatment that does not require local analgesia, carious tissue removal or tooth preparation. The carious lesions in carefully selected teeth are sealed with a stainless steel crown (preformed metal crown). The study aims are to determine the clinical effectiveness, acceptability and cost-effectiveness of the HT for management of carious lesions in young dental patients. Children, aged 3-7years, with a primary molar tooth with a carious lesion extending no further than the middle third of dentine, with no signs or symptoms of pulp inflammation or infection, and attending one of three community agencies are recruited. Target sample size is 220. A control tooth with an intra-coronal restoration is sourced from the same mouth. The primary outcome is the period of time free from further treatment. The assessments are scheduled at 6, 12 and 24months. In addition to the clinical assessment, acceptability of the HT will be assessed via questionnaires among patients and their primary carers at baseline, 6, 12 and 24months. Cost-outcome description and cost-effectiveness analysis from healthcare provider and societal perspective will be conducted. The clinical effectiveness, acceptability and cost-effectiveness of the HT in the community dental setting will be evaluated. The results of this study will determine the implementation of HT in the management of dental caries in young children. Copyright © 2015 Elsevier Inc. All rights reserved.

Adenovirus vector covalently conjugated to polyethylene glycol with a cancer-specific promoter suppresses the tumor growth through systemic administration.

PubMed

Yao, Xinglei; Yoshioka, Yasuo; Morishige, Tomohiro; Eto, Yusuke; Narimatsu, Shogo; Mizuguchi, Hiroyuki; Mukai, Yohei; Okada, Naoki; Nakagawa, Shinsaku

2010-01-01

Cancer gene therapy with adenovirus vectors (Adv) is limited to local administration because systemic administration of Adv produces a weak therapeutic effect and severe side effects. Previously, we generated a dual cancer-specific Adv system by using Adv covalently conjugated to polyethylene glycol (PEG) for transductional targeting and the telomere reverse transcriptase (TERT) promoter as a cancer-specific promoter for transcriptional targeting (PEG-Ad-TERT). We demonstrated that systemic administration of PEG-Ad-TERT showed superior antitumor effects against lung metastatic cancer with negligible side effects. Here, we investigated the therapeutic efficacy of systemic administration of PEG-Ad-TERT for the treatment of primary tumors. We first evaluated the transgene expression of PEG-Ad-TERT containing the luciferase gene (PEG-Ad-TERT/Luc) in primary tumors. Systemic administration of PEG-Ad-TERT/Luc resulted high transgene expression, similar to that observed in tumors for the conventional cytomegalovirus (CMV) promoter-driven Adv containing the luciferase gene (Ad-CMV/Luc). By comparison, transgene expression was 2500-fold lower than that of Ad-CMV/Luc in liver. We then examined the therapeutic effect of systemic administration of PEG-Ad-TERT containing the herpes simplex virus thymidine kinase (HSVtk) gene (PEG-Ad-TERT/HSVtk) for the treatment of primary tumors. We showed that PEG-Ad-TERT/HSVtk produced a notable antitumor effect against primary tumors with negligible side effects. These results demonstrated that PEG-Ad-TERT can be regarded as a prototype Adv with suitable efficacy and safety for systemic cancer gene therapy against both metastatic and primary tumors.

Numerical calculation of primary slot leakage inductance of a Single-sided HTS linear induction motor used for linear metro

NASA Astrophysics Data System (ADS)

Li, Dong; Wen, Yinghong; Li, Weili; Fang, Jin; Cao, Junci; Zhang, Xiaochen; Lv, Gang

2017-03-01

In the paper, the numerical method calculating asymmetric primary slot leakage inductances of Single-sided High-Temperature Superconducting (HTS) Linear Induction Motor (HTS LIM) is presented. The mathematical and geometric models of three-dimensional nonlinear transient electromagnetic field are established and the boundary conditions are also given. The established model is solved by time-stepping Finite Element Method (FEM). Then, the three-phase asymmetric primary slot leakage inductances under different operation conditions are calculated by using the obtained electromagnetic field distribution. The influences of the special effects such as longitudinal end effects, transversal edge effects, etc. on the primary slot leakage inductance are investigated. The presented numerical method is validated by experiments carried out on a 3.5 kW prototype with copper wires which has the same structures with the HTS LIM.

Sulforaphane suppressed LPS-induced inflammation in mouse peritoneal macrophages through Nrf2 dependent pathway.

PubMed

Lin, Wen; Wu, Rachel T; Wu, Tienyuan; Khor, Tin-Oo; Wang, Hu; Kong, Ah-Ng

2008-10-15

Sulforaphane (SFN) is a natural isothiocyanate that is present in cruciferous vegetables such as broccoli and cabbage. Previous studies have shown that SFN is effective in preventing carcinogenesis induced by carcinogens in rodents, which is related in part to its potent anti-inflammation properties. In the present study, we compared the anti-inflammatory effect of SFN on LPS-stimulated inflammation in primary peritoneal macrophages derived from Nrf2 (+/+) and Nrf2 (-/-) mice. Pretreatment of SFN in Nrf2 (+/+) primary peritoneal macrophages potently inhibited LPS-stimulated mRNA expression, protein expression and production of TNF-alpha, IL-1beta, COX-2 and iNOS. HO-1 expression was significantly augmented in LPS-stimulated Nrf2 (+/+) primary peritoneal macrophages by SFN. Interestingly, the anti-inflammatory effect was attenuated in Nrf2 (-/-) primary peritoneal macrophages. We concluded that SFN exerts its anti-inflammatory activity mainly via activation of Nrf2 in mouse peritoneal macrophages.

Acute physical exercise affected processing efficiency in an auditory attention task more than processing effectiveness.

PubMed

Dutke, Stephan; Jaitner, Thomas; Berse, Timo; Barenberg, Jonathan

2014-02-01

Research on effects of acute physical exercise on performance in a concurrent cognitive task has generated equivocal evidence. Processing efficiency theory predicts that concurrent physical exercise can increase resource requirements for sustaining cognitive performance even when the level of performance is unaffected. This hypothesis was tested in a dual-task experiment. Sixty young adults worked on a primary auditory attention task and a secondary interval production task while cycling on a bicycle ergometer. Physical load (cycling) and cognitive load of the primary task were manipulated. Neither physical nor cognitive load affected primary task performance, but both factors interacted on secondary task performance. Sustaining primary task performance under increased physical and/or cognitive load increased resource consumption as indicated by decreased secondary task performance. Results demonstrated that physical exercise effects on cognition might be underestimated when only single task performance is the focus.

Randomized trial of the effectiveness of combined behavioral/pharmacological smoking cessation treatment in Syrian primary care clinics.

PubMed

Ward, Kenneth D; Asfar, Taghrid; Al Ali, Radwan; Rastam, Samer; Weg, Mark W Vander; Eissenberg, Thomas; Maziak, Wasim

2013-02-01

Effectiveness of nicotine replacement therapy (NRT) for smoking cessation has not been evaluated in low income countries, such as Syria, where it is expensive and not widely available. We evaluated whether nicotine patch boosts smoking cessation rates when used in conjunction with behavioral support in primary care clinics in Aleppo, Syria. Two arm, parallel group, randomized, placebo controlled, double-blinded multi-site trial. Four primary care clinics in Aleppo, Syria.  Two hundred and sixty-nine adult primary care patients received behavioral cessation counseling from a trained primary care physician and were randomized to receive six weeks of treatment with nicotine versus placebo patch. Primary end-points were prolonged abstinence (no smoking after a 2-week grace period) at end of treatment, and 6 and 12 months post-quit day, assessed by self-report and exhaled carbon monoxide levels of <10 p.p.m. Treatment adherence was excellent and nicotine patch produced expected reductions in urges to smoke and withdrawal symptoms, but no treatment effect was observed. The proportion of patients in the nicotine and placebo groups with prolonged abstinence was 21.6% and 20.0%, respectively, at end of treatment, 13.4% and 14.1% at 6 months, and 12.7% and 11.9% at 12 months.  Nicotine patches may not be effective in helping smokers in low-income countries to stop when given as an adjunct to behavioural support. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

Effectiveness of leukocyte immunotherapy in primary recurrent spontaneous abortion (RSA).

PubMed

Gharesi-Fard, Behrouz; Zolghadri, Jaleh; Foroughinia, Leila; Tavazoo, Fahimeh; Samsami Dehaghani, Alamtaj

2007-09-01

Recurrent spontaneous abortion (RSA) is defined as three or more sequential abortions before the twentieth week of gestation. There are evidences to support an allo-immunologic mechanism for RSA. One of the methods for treatment of RSA is leukocyte therapy; however there is still controversy about effectiveness of this method. To evaluate the effectiveness of leukocyte therapy for treatment of RSA. Ninety two non-pregnant women with at least three sequential abortions (60 primary & 32 secondary aborters) recognized as RSA were referred to our Laboratory for immunotherapy. All the cases were immunized by isolated lymphocytes from their husbands. Fifty to 100 million washed and resuspended mononuclear cells were injected by I.V., S.C., and I.D. route. The result of each injection was checked by WBC cross matching between couples after four weeks of injections. Immunization was repeated in fifth week to a maximum of 3 times if needed. Eighty one age-matched non-pregnant RSA women (52 primary and 29 secondary aborters) with at least three sequential abortions were also included in this study as controls. The control group was not immunized. 67 out of 92 (72.8%) immunized cases and 44 out of 81 controls (54.3%) showed a successful outcome of pregnancy (p<0.02). Comparison of primary and secondary aborters indicated a significantly better outcome only in primary (75% vs. 42.3%. p<0.001) but not in secondary aborters (68.8% vs. 75.9%, p = 0.7). The present investigation showed the effectiveness of leukocyte therapy in primary but not in secondary RSA patients. Despite the current controversy and limitation of leukocyte therapy in RSA, the results of our investigation provide evidence supporting the use of allo-immunization in improving the outcome of pregnancy in primary RSA patients.

Modeling of second-harmonic generation of circumferential guided wave propagation in a composite circular tube

NASA Astrophysics Data System (ADS)

Li, Mingliang; Deng, Mingxi; Gao, Guangjian; Xiang, Yanxun

2018-05-01

This paper investigated modeling of second-harmonic generation (SHG) of circumferential guided wave (CGW) propagation in a composite circular tube, and then analyzed the influences of interfacial properties on the SHG effect of primary CGW. Here the effect of SHG of primary CGW propagation is treated as a second-order perturbation to its linear wave response. Due to the convective nonlinearity and the inherent elastic nonlinearity of material, there are second-order bulk driving forces and surface/interface driving stresses in the interior and at the surface/interface of a composite circular tube, when a primary CGW mode propagates along its circumference. Based on the approach of modal expansion analysis for waveguide excitation, the said second-order driving forces/stresses are regarded as the excitation sources to generate a series of double-frequency CGW modes that constitute the second-harmonic field of the primary CGW propagation. It is found that the modal expansion coefficient of each double-frequency CGW mode is closely related to the interfacial stiffness constants that are used to describe the interfacial properties between the inner and outer circular parts of the composite tube. Furthermore, changes in the interfacial stiffness constants essentially influence the dispersion relation of CGW propagation. This will remarkably affect the efficiency of cumulative SHG of primary CGW propagation. Some finite element simulations have been implemented of response characteristics of cumulative SHG to the interfacial properties. Both the theoretical analyses and numerical simulations indicate that the effect of cumulative SHG is found to be much more sensitive to changes in the interfacial properties than primary CGW propagation. The potential of using the effect of cumulative SHG by primary CGW propagation to characterize a minor change in the interfacial properties is considered.

Effectiveness of a Geriatric Care Model for frail older adults in primary care: Results from a stepped wedge cluster randomized trial.

PubMed

Hoogendijk, Emiel O; van der Horst, Henriëtte E; van de Ven, Peter M; Twisk, Jos W R; Deeg, Dorly J H; Frijters, Dinnus H M; van Leeuwen, Karen M; van Campen, Jos P C M; Nijpels, Giel; Jansen, Aaltje P D; van Hout, Hein P J

2016-03-01

Primary care-based comprehensive care programs have the potential to improve outcomes in frail older adults. We evaluated the impact of the Geriatric Care Model (GCM) on the quality of life of community-dwelling frail older adults. A 24-month stepped wedge cluster randomized controlled trial was conducted between May 2010 and March 2013 in 35 primary care practices in the Netherlands, and included 1147 frail older adults. The intervention consisted of a geriatric in-home assessment by a practice nurse, followed by a tailored care plan. Reassessment occurred every six months. Nurses worked together with primary care physicians and were supervised and trained by geriatric expert teams. Complex patients were reviewed in multidisciplinary consultations. The primary outcome was quality of life (SF-12). Secondary outcomes were health-related quality of life, functional limitations, self-rated health, psychological wellbeing, social functioning and hospitalizations. Intention-to-treat analyses based on multilevel modeling showed no significant differences between the intervention group and usual care regarding SF-12 and most secondary outcomes. Only for IADL limitations we found a small intervention effect in patients who received the intervention for 18months (B=-0.25, 95%CI=-0.43 to -0.06, p=0.007), but this effect was not statistically significant after correction for multiple comparisons. The GCM did not show beneficial effects on quality of life in frail older adults in primary care, compared to usual care. This study strengthens the idea that comprehensive care programs add very little to usual primary care for this population. The Netherlands National Trial Register NTR2160. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Carcinogens induce loss of the primary cilium in human renal proximal tubular epithelial cells independently of effects on the cell cycle

PubMed Central

Radford, Robert; Slattery, Craig; Jennings, Paul; Blacque, Oliver; Pfaller, Walter; Gmuender, Hans; Van Delft, Joost; Ryan, Michael P.

2012-01-01

The primary cilium is an immotile sensory and signaling organelle found on the majority of mammalian cell types. Of the multitude of roles that the primary cilium performs, perhaps some of the most important include maintenance of differentiation, quiescence, and cellular polarity. Given that the progression of cancer requires disruption of all of these processes, we have investigated the effects of several carcinogens on the primary cilium of the RPTEC/TERT1 human proximal tubular epithelial cell line. Using both scanning electron microscopy and immunofluorescent labeling of the ciliary markers acetylated tubulin and Arl13b, we confirmed that RPTEC/TERT1 cells express primary cilium upon reaching confluence. Treatment with the carcinogens ochratoxin A (OTA) and potassium bromate (KBrO3) caused a significant reduction in the number of ciliated cells, while exposure to nifedipine, a noncarcinogenic renal toxin, had no effect on primary cilium expression. Flow cytometric analysis of the effects of all three compounds on the cell cycle revealed that only KBrO3 resulted in an increase in the proportion of cells entering the cell cycle. Microarray analysis revealed dysregulation of multiple pathways affecting ciliogenesis and ciliary maintenance following OTA and KBrO3 exposure, which were unaffected by nifedipine exposure. The primary cilium represents a unique physical checkpoint with relevance to carcinogenesis. We have shown that the renal carcinogens OTA and KBrO3 cause significant deciliation in a model of the proximal tubule. With KBrO3, this was followed by reentry into the cell cycle; however, deciliation was not found to be associated with reentry into the cell cycle following OTA exposure. Transcriptomic analysis identified dysregulation of Wnt signaling and ciliary trafficking in response to OTA and KBrO3 exposure. PMID:22262483

Effective strategies for prevention, control, and treatment of obesity in primary health care setting for adolescents, adults, and elderly people: A protocol for systematic review and meta-analysis.

PubMed

Marques, Emanuele Souza; Leite, Tatiana Henriques; Azeredo, Catarina Machado; Cunha, Diana Barbosa; Verly Júnior, Eliseu

2018-06-01

It is unquestionable that obesity is a global epidemic and one of the main public health problems in the world. The management of obesity in Primary Health Care has an important role if being considered the magnitude and serious consequence of this problem. Despite this, there is no effective standard protocol for the treatment of this disease. Studies that synthesize and assess the effectiveness of strategies for prevention, control, and treatment of obesity in Primary Health Care setting are still scarce. The objective of this study is review and synthesize study evidence for obesity management strategies among adolescents, adults and elderly developed at the Primary Health Care worldwide. Seven electronic databases (Medline, Lilacs, Embase, Psycinfo, Cochrane, WHOLIS and Open Gray) will be searched with no date limit for identification of clinical trials examining the effectiveness of prevention, control and treatment of obesity in Primary Health Care. As primary outcome will be changes in body weight. As secondary outcomes will be body mass index, body adiposity, waist circumference, and waist-hip ratio. Two independent authors will perform the selection of studies, data extraction, and the assessment of risk of bias. The results will be published in a peer-reviewed journal. This systematic review will be first to synthesize scientific evidence for obesity management strategies at Primary Health Care among adolescents, adults, and elderly. The review will benefit healthcare professionals and policymakers. Ethical approval is not required in this study because the data used include peer-reviewed publications, which do not comprise any information that could identify subjects. PROSPERO (CRD42018092416).

Fluoroscopic removal of retrievable self-expandable metal stents in patients with malignant oesophageal strictures: Experience with a non-endoscopic removal system.

PubMed

Kim, Pyeong Hwa; Song, Ho-Young; Park, Jung-Hoon; Zhou, Wei-Zhong; Na, Han Kyu; Cho, Young Chul; Jun, Eun Jung; Kim, Jun Ki; Kim, Guk Bae

2017-03-01

To evaluate clinical outcomes of fluoroscopic removal of retrievable self-expandable metal stents (SEMSs) for malignant oesophageal strictures, to compare clinical outcomes of three different removal techniques, and to identify predictive factors of successful removal by the standard technique (primary technical success). A total of 137 stents were removed from 128 patients with malignant oesophageal strictures. Primary overall technical success and removal-related complications were evaluated. Logistic regression models were constructed to identify predictive factors of primary technical success. Primary technical success rate was 78.8 % (108/137). Complications occurred in six (4.4 %) cases. Stent location in the upper oesophagus (P=0.004), stricture length over 8 cm (P=0.030), and proximal granulation tissue (P<0.001) were negative predictive factors of primary technical success. If granulation tissue was present at the proximal end, eversion technique was more frequently required (P=0.002). Fluoroscopic removal of retrievable SEMSs for malignant oesophageal strictures using three different removal techniques appeared to be safe and easy. The standard technique is safe and effective in the majority of patients. The presence of proximal granulation tissue, stent location in the upper oesophagus, and stricture length over 8 cm were negative predictive factors for primary technical success by standard extraction and may require a modified removal technique. • Fluoroscopic retrievable SEMS removal is safe and effective. • Standard removal technique by traction is effective in the majority of patients. • Three negative predictive factors of primary technical success were identified. • Caution should be exercised during the removal in those situations. • Eversion technique is effective in cases of proximal granulation tissue.

COST-UTILITY ANALYSIS OF PRIMARY PROPHYLAXIS, COMPARED WITH ON-DEMAND TREATMENT, FOR PATIENTS WITH SEVERE HEMOPHILIA TYPE A IN COLOMBIA.

PubMed

Castro Jaramillo, Héctor Eduardo; Moreno Viscaya, Mabel; Mejia, Aurelio E

2016-01-01

This article presents a cost-utility analysis from the Colombian health system perspective comparing primary prophylaxis to on-demand treatment using exogenous clotting factor VIII (FVIII) for patients with severe hemophilia type A. We developed a Markov model to estimate expected costs and outcomes (measured as quality-adjusted life-years, QALYs) for each strategy. Transition probabilities were estimated using published studies; utility weights were obtained from a sample of Colombian patients with hemophilia and costs were gathered using local data. Both deterministic and probabilistic sensitivity analysis were performed to assess the robustness of results. The additional cost per QALY gained of primary prophylaxis compared with on-demand treatment was 105,081,022 Colombian pesos (COP) (55,204 USD), and thus not considered cost-effective according to a threshold of up to three times the current Colombian gross domestic product (GDP) per-capita. When primary prophylaxis was provided throughout life using recombinant FVIII (rFVIII), which is much costlier than FVIII, the additional cost per QALY gained reached 174,159,553 COP (91,494 USD). using a decision rule of up to three times the Colombian GDP per capita, primary prophylaxis (with either FVIII or rFVIII) would not be considered as cost-effective in this country. However, a final decision on providing or preventing patients from primary prophylaxis as a gold standard of care for severe hemophilia type A should also consider broader criteria than the incremental cost-effectiveness ratio results itself. Only a price reduction of exogenous FVIII of 50 percent or more would make primary prophylaxis cost-effective in this context.

Treatment of brain metastases: chemotherapy.

PubMed

Grimm, Sean A

2012-02-01

Although systemic therapy is the primary therapeutic modality for disseminated cancer, it plays a limited role in the treatment of brain metastases (BM). This review discusses the blood-brain barrier (BBB), interactions of systemic therapy with supportive care agents used in BM patients, the role of primary tumor sensitivity in the treatment of BM, and unique issues related to the specific primary tumor histologies. The specialized physiology of the brain vasculature that forms the BBB may preclude large and/or water-soluble systemic agents from reaching BM. Once metastases grow larger than 1-2 mm, there is preclinical and clinical evidence that the BBB is at least partially disrupted. Thus, the best treatment strategy in established BM may be to use an agent that is effective against the primary tumor regardless of its apparent BBB permeability. The use of anticonvulsants and corticosteroids must be carefully considered as they can decrease the effectiveness of systemic anti-tumor therapy. Despite the absence of level I data to routinely recommend the use of systemic therapy for solid tumor BM, these treatments should be considered in patients with good performance status and multiple, small metastases, especially if the primary tumor is chemosensitive. The systemic treatment of BM will continue to evolve as effective small-molecule inhibitors are developed and treatment regimens for each specific primary tumor are optimized.

Plastic scintillator with effective pulse shape discrimination for neutron and gamma detection

DOEpatents

Zaitseva, Natalia P.; Carman, M Leslie; Cherepy, Nerine; Glenn, Andrew M.; Hamel, Sebastien; Payne, Stephen A.; Rupert, Benjamin L.

2016-04-12

In one embodiment, a scintillator material includes a polymer matrix; and a primary dye in the polymer matrix, the primary dye being a fluorescent dye, the primary dye being present in an amount of 5 wt % or more; wherein the scintillator material exhibits an optical response signature for neutrons that is different than an optical response signature for gamma rays. In another embodiment, a scintillator material includes a polymer matrix; and a primary dye in the polymer matrix, the primary dye being a fluorescent dye, the primary dye being present in an amount greater than 10 wt %.

40 CFR 142.10 - Requirements for a determination of primary enforcement responsibility.

Code of Federal Regulations, 2011 CFR

2011-07-01

... drinking water regulations (NPDWRs) in effect under part 141 of this chapter; (b) Has adopted and is... PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS... enforcement responsibility. A State has primary enforcement responsibility for public water systems in the...

40 CFR 142.10 - Requirements for a determination of primary enforcement responsibility.

Code of Federal Regulations, 2012 CFR

2012-07-01

... drinking water regulations (NPDWRs) in effect under part 141 of this chapter; (b) Has adopted and is... PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS... enforcement responsibility. A State has primary enforcement responsibility for public water systems in the...

Continuing Professional Development and Learning in Primary Science Classrooms

ERIC Educational Resources Information Center

Fraser, Christine A.

2010-01-01

This article explores the effects of continuing professional development (CPD) on teachers' and pupils' experiences of learning and teaching science in primary classrooms. During 2006-2007, quantitative and qualitative data were elicited from two primary teachers in Scotland using questionnaires, semi-structured interviews and video-stimulated…

Effective Intervention in Primary Schools: Nurture Groups.

ERIC Educational Resources Information Center

Bennathan, Marion; Boxall, Marjorie

This book summarizes the experiences of nurture groups (small special education classes started in 1970 in London schools), where young children from disadvantaged environments are prepared to access the full primary school curriculum. Chapter 1, "Children at Risk of Failure in Primary Schools" (Marion Bennathan), discusses the incidence…

Effective Primary Schools in Geographically Isolated Areas of Vietnam

ERIC Educational Resources Information Center

Ikeda, Miyako

2010-01-01

This study identifies the major characteristics of "effective" primary schools in isolated areas in Vietnam. It suggests areas in which the implementation of beneficial changes can occur. Pupils in isolated areas of Vietnam are, in many respects, educationally disadvantaged. Usually, these pupils are in schools that have fewer…

THE EFFECTS OF ELEVATED METALS ON BENTHIC COMMUNITY METABOLISM IN A ROCKY MOUNTAIN STREAM

EPA Science Inventory

The effects of elevated metals (dissolved Zn, Mn and/or Fe) in a Rocky Mountain stream were assessed using measures of primary productivity, community respiration and water-column toxicity. Primary productivity was measured as rates of O2 evolution from natural substrates incubat...

SEASONAL EFFECTS OF ULTRAFINE, FINE, AND COARSE PARTICULATE MATTER (PM) ON HUMAN PRIMARY AIRWAY EPITHELIAL CELLS

EPA Science Inventory

SEASONAL EFFECTS OF ULTRAFINE, FINE, AND COARSE PARTICULATE MATTER (PM) ON HUMAN PRIMARY AIRWAY EPITHELIAL CELLS

Exposure of humans to PM results in increased mortality and morbidity. Recent toxicology studies have shown a number of pathophysiological pulmonary and car...

Bilingual Children with Primary Language Impairment: 3 Months after Treatment

ERIC Educational Resources Information Center

Pham, Giang; Ebert, Kerry Danahy; Kohnert, Kathryn

2015-01-01

Background: Evidence on the treatment effectiveness for bilingual children with primary language impairment (PLI) is needed to advance both theory and clinical practice. Of key interest is whether treatment effects are maintained following the completion of short-term intense treatments. Aims: To investigate change in select language and cognitive…

Behavioural activation by mental health nurses for late-life depression in primary care: a randomized controlled trial.

PubMed

Janssen, Noortje; Huibers, Marcus J H; Lucassen, Peter; Voshaar, Richard Oude; van Marwijk, Harm; Bosmans, Judith; Pijnappels, Mirjam; Spijker, Jan; Hendriks, Gert-Jan

2017-06-26

Depressive symptoms are common in older adults. The effectiveness of pharmacological treatments and the availability of psychological treatments in primary care are limited. A behavioural approach to depression treatment might be beneficial to many older adults but such care is still largely unavailable. Behavioural Activation (BA) protocols are less complicated and more easy to train than other psychological therapies, making them very suitable for delivery by less specialised therapists. The recent introduction of the mental health nurse in primary care centres in the Netherlands has created major opportunities for improving the accessibility of psychological treatments for late-life depression in primary care. BA may thus address the needs of older patients while improving treatment outcome and lowering costs.The primary objective of this study is to compare the effectiveness and cost-effectiveness of BA in comparison with treatment as usual (TAU) for late-life depression in Dutch primary care. A secondary goal is to explore several potential mechanisms of change, as well as predictors and moderators of treatment outcome of BA for late-life depression. Cluster-randomised controlled multicentre trial with two parallel groups: a) behavioural activation, and b) treatment as usual, conducted in primary care centres with a follow-up of 52 weeks. The main inclusion criterion is a PHQ-9 score > 9. Patients are excluded from the trial in case of severe mental illness that requires specialized treatment, high suicide risk, drug and/or alcohol abuse, prior psychotherapy, change in dosage or type of prescribed antidepressants in the previous 12 weeks, or moderate to severe cognitive impairment. The intervention consists of 8 weekly 30-min BA sessions delivered by a trained mental health nurse. We expect BA to be an effective and cost-effective treatment for late-life depression compared to TAU. BA delivered by mental health nurses could increase the availability and accessibility of non-pharmacological treatments for late-life depression in primary care. This study is retrospectively registered in the Dutch Clinical Trial Register NTR6013 on August 25th 2016.

Pathways to research impact in primary healthcare: What do Australian primary healthcare researchers believe works best to facilitate the use of their research findings?

PubMed

Reed, Richard L; McIntyre, Ellen; Jackson-Bowers, Eleanor; Kalucy, Libby

2017-03-02

Primary healthcare researchers are under increasing pressure to demonstrate measurable and lasting improvement in clinical practice and healthcare policy as a result of their work. It is therefore important to understand the effectiveness of the research dissemination strategies used. The aim of this paper is to describe the pathways for research impact that have been achieved across several government-funded primary healthcare projects, and the effectiveness of these methods as perceived by their Chief Investigators. The project used an online survey to collect information about government-funded primary healthcare research projects. Chief Investigators were asked how they disseminated their findings and how this achieved impact in policy and practice. They were also asked to express their beliefs regarding the most effective means of achieving research impact and describe how this occurred. Chief Investigators of 17 projects indicated that a number of dissemination strategies were used but that professional networks were the most effective means of promoting uptake of their research findings. Utilisation of research findings for clinical practice was most likely to occur in organisations or among individual practitioners who were most closely associated with the research team, or when research findings were included in educational programmes involving clinical practice. Uptake of both policy- and practice-related research was deemed most successful if intermediary organisations such as formal professional networks were engaged in the research. Successful primary healthcare researchers had developed critical relationships with intermediary organisations within primary healthcare before the initiation of the research and had also involved them in the design. The scale of research impact was influenced by the current policy environment, the type and significance of the results, and the endorsement (or lack thereof) of professional bodies. Chief Investigators believed that networks were the most effective means of research dissemination. Researchers who were embedded in professional, clinical or policy-focussed intermediary organisations, or had developed partnerships with clinical services, which had a vested interest in the research findings, were more able to describe a direct impact of their research. This suggests that development of these relationships and engagement of these stakeholders by primary healthcare researchers is a vital step for optimal research utilisation in the primary healthcare setting.

Primary intestinal lymphangiectasia in children: is octreotide an effective and safe option in the treatment?

PubMed

Sari, Sinan; Baris, Zeren; Dalgic, Buket

2010-10-01

Octreotide has been suggested as a medical treatment option in refractory cases of primary intestinal lymphangiectasia (IL). There are few data about the long-term effect and safety of octreotide for IL in the literature. In the present article we analyzed pediatric cases of primary IL with long-term octreotide treatment and discussed its safety profile. Between 1999 and 2008, 13 children were diagnosed in our clinic as having IL. Six patients with primary IL were followed up, receiving octreotide therapy. The clinical data of the patients and duration of therapy, dose, and side effects of octreotide were evaluated. Octreotide, 15 to 20 μg per body weight 2 times daily subcutaneously, was given to all of the patients. Duration of the octreotide treatment changed between 3 and 37 months. Stool frequency decreased in all of the patients after starting octreotide treatment. Serum albumin could be maintained at normal levels in 3 patients. The requirement of albumin infusions decreased in all of the patients. Acute pancreatitis was observed as a side effect of octreotide in 1 patient. Octreotide may help to maintain serum albumin levels, improve clinical findings, and decrease the requirement of albumin infusions in refractory cases of primary IL.

Primary Care Physicians' Experience with Disease Management Programs

PubMed Central

Fernandez, Alicia; Grumbach, Kevin; Vranizan, Karen; Osmond, Dennis H; Bindman, Andrew B

2001-01-01

OBJECTIVE To examine primary care physicians' perceptions of how disease management programs affect their practices, their relationships with their patients, and overall patient care. DESIGN Cross-sectional mailed survey. SETTING The 13 largest urban counties in California. PARTICIPANTS General internists, general pediatricians, and family physicians. MEASUREMENTS AND MAIN RESULTS Physicians' self-report of the effects of disease management programs on quality of patient care and their own practices. Respondents included 538 (76%) of 708 physicians: 183 (34%) internists, 199 (38%) family practitioners, and 156 (29%) pediatricians. Disease management programs were available 285 to (53%) physicians; 178 had direct experience with the programs. Three quarters of the 178 physicians believed that disease management programs increased the overall quality of patient care and the quality of care for the targeted disease. Eighty-seven percent continued to provide primary care for their patients in these programs, and 70% reported participating in major patient care decisions. Ninety-one percent reported that the programs had no effect on their income, decreased (38%) or had no effect (48%) on their workload, and increased (48%)) their practice satisfaction. CONCLUSIONS Practicing primary care physicians have generally favorable perceptions of the effect of voluntary, primary care-inclusive, disease management programs on their patients and on their own practice satisfaction. PMID:11318911

Representation of Sound Objects within Early-Stage Auditory Areas: A Repetition Effect Study Using 7T fMRI

PubMed Central

Da Costa, Sandra; Bourquin, Nathalie M.-P.; Knebel, Jean-François; Saenz, Melissa; van der Zwaag, Wietske; Clarke, Stephanie

2015-01-01

Environmental sounds are highly complex stimuli whose recognition depends on the interaction of top-down and bottom-up processes in the brain. Their semantic representations were shown to yield repetition suppression effects, i. e. a decrease in activity during exposure to a sound that is perceived as belonging to the same source as a preceding sound. Making use of the high spatial resolution of 7T fMRI we have investigated the representations of sound objects within early-stage auditory areas on the supratemporal plane. The primary auditory cortex was identified by means of tonotopic mapping and the non-primary areas by comparison with previous histological studies. Repeated presentations of different exemplars of the same sound source, as compared to the presentation of different sound sources, yielded significant repetition suppression effects within a subset of early-stage areas. This effect was found within the right hemisphere in primary areas A1 and R as well as two non-primary areas on the antero-medial part of the planum temporale, and within the left hemisphere in A1 and a non-primary area on the medial part of Heschl’s gyrus. Thus, several, but not all early-stage auditory areas encode the meaning of environmental sounds. PMID:25938430

The pivotal role of primary care in meeting the health needs of people recently released from prison.

PubMed

Kinner, Stuart A; Young, Jesse T; Carroll, Megan

2015-12-01

Australia's prison population is growing at a rate well in excess of population growth. Indigenous Australians are over-represented by a factor of 13. Prisoners are a profoundly marginalised group characterised by complex health and social needs. Despite improvements in health during incarceration, poor health outcomes after release are common, and the net effect of incarceration is usually health depleting. Given the need for effective care coordination, primary care plays a pivotal role in meeting the health needs of this population. In this paper we review what is known about patterns of primary care utilisation in ex-prisoners, identify evidence-based strategies for increasing access to primary care in ex-prisoners, and consider how such contact may shape subsequent health service outcomes. Primary care is a necessary but not sufficient condition for effective post-release support. Positive outcomes may depend more on the quality than the quantity of care received. Given massive over-representation of Indigenous people in Australia's prisons, and compelling evidence of preventable morbidity and mortality after release from prison, effective models of care for this population are an important component of closing the gap in Indigenous life expectancy. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Leptin Receptor Metabolism Disorder in Primary Chondrocytes from Adolescent Idiopathic Scoliosis Girls.

PubMed

Wang, Yun-Jia; Yu, Hong-Gui; Zhou, Zhen-Hai; Guo, Qiang; Wang, Long-Jie; Zhang, Hong-Qi

2016-07-20

To investigate the underlying mechanisms of low metabolic activity of primary chondrocytes obtained from girls with adolescent idiopathic scoliosis (AIS); AIS is a spine-deforming disease that often occurs in girls. AIS is associated with a lower bone mass than that of healthy individuals and osteopenia. Leptin was shown to play an important role in bone growth. It can also regulate the function of chondrocytes. Changes in leptin and Ob-R levels in AIS patients have been reported in several studies. The underlying mechanisms between the dysfunction of peripheral leptin signaling and abnormal chondrocytes remain unclear; The following parameters were evaluated in AIS patients and the control groups: total serum leptin levels; Ob-R expression in the plasma membrane of primary chondrocytes; JAK2 and STAT3 phosphorylation status. Then, we inhibited the lysosome and proteasome and knocked down clathrin heavy chain (CHC) expression in primary chondrocytes isolated from girls with AIS and evaluated Ob-R expression. We investigated the effects of leptin combined with a lysosome inhibitor or CHC knockdown in primary chondrocytes obtained from AIS patients; Compared with the controls, AIS patients showed similar total serum leptin levels, reduced JAK2 and STAT3 phosphorylation, and decreased cartilage matrix synthesis in the facet joint. Lower metabolic activity and lower membrane expression of Ob-R were observed in primary chondrocytes from the AIS group than in the controls. Lysosome inhibition increased the total Ob-R content but had no effect on the membrane expression of Ob-R or leptin's effects on AIS primary chondrocytes. CHC knockdown upregulated the membrane Ob-R levels and enhanced leptin's effects on AIS primary chondrocytes; The underlying mechanism of chondrocytes that are hyposensitive to leptin in some girls with AIS is low plasma membrane Ob-R expression that results from an imbalance between the rate of receptor endocytosis and the insertion of newly synthesized receptors into the membrane.

[Effects of nootropic agents on visual functions and lacrimal antioxidative activity in patients with primary open-angle glaucoma].

PubMed

Davydova, N G; Kuznetsova, T P; Borisova, S A; Abdulkadyrova, M Zh

2006-01-01

The paper presents the results of an investigation of the effect of the nootropic agents pantogam and nooclerine on visual functions in patients with primary open-angle glaucoma. These agents have been found to have a beneficial effect on the functional activity of the retina and optic nerve, light sensitivity, hemo- and hydrodynamics of the eye.

Dropout Prevention and Intervention Programs: Effects on School Completion and Dropout among School-Aged Children and Youth. Campbell Systematic Reviews. 2011:8

ERIC Educational Resources Information Center

Wilson, Sandra Jo; Tanner-Smith, Emily E.; Lipsey, Mark W.; Steinka-Fry, Katarzyna; Morrison, Jan

2011-01-01

The objectives of this systematic review were to summarize the available evidence on the effects of prevention and intervention programs aimed at primary and secondary students for increasing school completion or reducing school dropout. The primary focus of the meta-analysis was to examine the comparative effectiveness of different programs and…

Effects of School Quality, School Citizenship Policy, and Student Body Composition on the Acquisition of Citizenship Competences in the Final Year of Primary Education

ERIC Educational Resources Information Center

Dijkstra, Anne Bert; Geijsel, Femke; Ledoux, Guuske; van der Veen, Ineke; ten Dam, Geert

2015-01-01

This study examines the effects of general educational quality of schools, school citizenship policy, and ethnic homogeneity of the student body on the acquisition of citizenship competences in the final year of primary education. The theoretical framework is based on developmental, psychological, and sociological studies into effects of social…

Effects of Explicit Instruction on the Acquisition of Students' Science Inquiry Skills in Grades 5 and 6 of Primary Education

ERIC Educational Resources Information Center

Kruit, P. M.; Oostdam, R. J.; van den Berg, E.; Schuitema, J. A.

2018-01-01

In most primary science classes, students are taught science inquiry skills by way of learning by doing. Research shows that explicit instruction may be more effective. The aim of this study was to investigate the effects of explicit instruction on the acquisition of inquiry skills. Participants included 705 Dutch fifth and sixth graders. Students…

The effectiveness and cost-effectiveness of lay counsellor-delivered psychological treatments for harmful and dependent drinking and moderate to severe depression in primary care in India: PREMIUM study protocol for randomized controlled trials.

PubMed

Patel, Vikram; Weobong, Benedict; Nadkarni, Abhijit; Weiss, Helen A; Anand, Arpita; Naik, Smita; Bhat, Bhargav; Pereira, Jesina; Araya, Ricardo; Dimidjian, Sona; Hollon, Steven D; King, Michael; McCambridge, Jim; McDaid, David; Murthy, Pratima; Velleman, Richard; Fairburn, Christopher G; Kirkwood, Betty

2014-04-02

The leading mental health causes of the global burden of disease are depression in women and alcohol use disorders in men. A major hurdle to the implementation of evidence-based psychological treatments in primary care in developing countries is the non-availability of skilled human resources. The aim of these trials is to evaluate the effectiveness and cost-effectiveness of two psychological treatments developed for the treatment of depression and alcohol use disorders in primary care in India. This study protocol is for parallel group, randomized controlled trials (Healthy Activity Program for moderate to severe depression, Counselling for Alcohol Problems for harmful and dependent drinking) in eight primary health centres in Goa, India. Adult primary care attendees will be screened with the Patient Health Questionnaire for depression and, in men only, the Alcohol Use Disorders Identification Test for drinking problems. Screen-positive attendees will be invited to participate; men who screen positive for both disorders will be invited to participate in the Counselling for Alcohol Problems trial. Those who consent will be allocated in a 1:1 ratio to receive either the respective psychological treatment plus enhanced usual care or enhanced usual care only using a computer generated allocation sequence, stratified by primary health centre and, for depression, by sex. The enhanced usual care comprises providing primary health centre doctors with contextualized World Health Organization guidelines and screening results. Psychological treatments will be delivered by lay counsellors, over a maximum period of three months. Primary outcomes are severity of disorder and remission rates at three months post-enrolment and, for the Counselling for Alcohol Problems trial, drinking and the impact of drinking on daily lives. Secondary outcomes include severity of disorder and remission rates at 12 months, disability scores, suicidal behaviour and economic impact, and cost-effectiveness at three and 12 months. 500 participants with depression and 400 participants with harmful drinking will be recruited. Primary analyses will be intention-to-treat. These trials may offer a new approach for the treatment of moderate-severe depression and drinking problems in primary care that is potentially scalable as it relies on delivery by a single pool of lay counsellors. Both trials are registered with the International Society for the Registration of Clinical Trials (Healthy Activity Programme registration number ISRCTN95149997; Counselling for Alcohol Problems registration number ISRCTN76465238).

The effectiveness and cost-effectiveness of lay counsellor-delivered psychological treatments for harmful and dependent drinking and moderate to severe depression in primary care in India: PREMIUM study protocol for randomized controlled trials

PubMed Central

2014-01-01

Background The leading mental health causes of the global burden of disease are depression in women and alcohol use disorders in men. A major hurdle to the implementation of evidence-based psychological treatments in primary care in developing countries is the non-availability of skilled human resources. The aim of these trials is to evaluate the effectiveness and cost-effectiveness of two psychological treatments developed for the treatment of depression and alcohol use disorders in primary care in India. Methods/design This study protocol is for parallel group, randomized controlled trials (Healthy Activity Program for moderate to severe depression, Counselling for Alcohol Problems for harmful and dependent drinking) in eight primary health centres in Goa, India. Adult primary care attendees will be screened with the Patient Health Questionnaire for depression and, in men only, the Alcohol Use Disorders Identification Test for drinking problems. Screen-positive attendees will be invited to participate; men who screen positive for both disorders will be invited to participate in the Counselling for Alcohol Problems trial. Those who consent will be allocated in a 1:1 ratio to receive either the respective psychological treatment plus enhanced usual care or enhanced usual care only using a computer generated allocation sequence, stratified by primary health centre and, for depression, by sex. The enhanced usual care comprises providing primary health centre doctors with contextualized World Health Organization guidelines and screening results. Psychological treatments will be delivered by lay counsellors, over a maximum period of three months. Primary outcomes are severity of disorder and remission rates at three months post-enrolment and, for the Counselling for Alcohol Problems trial, drinking and the impact of drinking on daily lives. Secondary outcomes include severity of disorder and remission rates at 12 months, disability scores, suicidal behaviour and economic impact, and cost-effectiveness at three and 12 months. 500 participants with depression and 400 participants with harmful drinking will be recruited. Primary analyses will be intention-to-treat. Discussion These trials may offer a new approach for the treatment of moderate-severe depression and drinking problems in primary care that is potentially scalable as it relies on delivery by a single pool of lay counsellors. Trial registration Both trials are registered with the International Society for the Registration of Clinical Trials (Healthy Activity Programme registration number ISRCTN95149997; Counselling for Alcohol Problems registration number ISRCTN76465238). PMID:24690184

Implementing collaborative care for depression treatment in primary care: A cluster randomized evaluation of a quality improvement practice redesign

PubMed Central

2011-01-01

Background Meta-analyses show collaborative care models (CCMs) with nurse care management are effective for improving primary care for depression. This study aimed to develop CCM approaches that could be sustained and spread within Veterans Affairs (VA). Evidence-based quality improvement (EBQI) uses QI approaches within a research/clinical partnership to redesign care. The study used EBQI methods for CCM redesign, tested the effectiveness of the locally adapted model as implemented, and assessed the contextual factors shaping intervention effectiveness. Methods The study intervention is EBQI as applied to CCM implementation. The study uses a cluster randomized design as a formative evaluation tool to test and improve the effectiveness of the redesign process, with seven intervention and three non-intervention VA primary care practices in five different states. The primary study outcome is patient antidepressant use. The context evaluation is descriptive and uses subgroup analysis. The primary context evaluation measure is naturalistic primary care clinician (PCC) predilection to adopt CCM. For the randomized evaluation, trained telephone research interviewers enrolled consecutive primary care patients with major depression in the evaluation, referred enrolled patients in intervention practices to the implemented CCM, and re-surveyed at seven months. Results Interviewers enrolled 288 CCM site and 258 non-CCM site patients. Enrolled intervention site patients were more likely to receive appropriate antidepressant care (66% versus 43%, p = 0.01), but showed no significant difference in symptom improvement compared to usual care. In terms of context, only 40% of enrolled patients received complete care management per protocol. PCC predilection to adopt CCM had substantial effects on patient participation, with patients belonging to early adopter clinicians completing adequate care manager follow-up significantly more often than patients of clinicians with low predilection to adopt CCM (74% versus 48%%, p = 0.003). Conclusions Depression CCM designed and implemented by primary care practices using EBQI improved antidepressant initiation. Combining QI methods with a randomized evaluation proved challenging, but enabled new insights into the process of translating research-based CCM into practice. Future research on the effects of PCC attitudes and skills on CCM results, as well as on enhancing the link between improved antidepressant use and symptom outcomes, is needed. Trial Registration ClinicalTrials.gov: NCT00105820 PMID:22032247

Study protocol of EMPOWER participatory action research (EMPOWER-PAR): a pragmatic cluster randomised controlled trial of multifaceted chronic disease management strategies to improve diabetes and hypertension outcomes in primary care.

PubMed

Ramli, Anis S; Lakshmanan, Sharmila; Haniff, Jamaiyah; Selvarajah, Sharmini; Tong, Seng F; Bujang, Mohamad-Adam; Abdul-Razak, Suraya; Shafie, Asrul A; Lee, Verna K M; Abdul-Rahman, Thuhairah H; Daud, Maryam H; Ng, Kien K; Ariffin, Farnaza; Abdul-Hamid, Hasidah; Mazapuspavina, Md-Yasin; Mat-Nasir, Nafiza; Miskan, Maizatullifah; Stanley-Ponniah, Jaya P; Ismail, Mastura; Chan, Chun W; Abdul-Rahman, Yong R; Chew, Boon-How; Low, Wilson H H

2014-09-13

Chronic disease management presents enormous challenges to the primary care workforce because of the rising epidemic of cardiovascular risk factors. The chronic care model was proven effective in improving chronic disease outcomes in developed countries, but there is little evidence of its effectiveness in developing countries. The aim of this study was to evaluate the effectiveness of the EMPOWER-PAR intervention (multifaceted chronic disease management strategies based on the chronic care model) in improving outcomes for type 2 diabetes mellitus and hypertension using readily available resources in the Malaysian public primary care setting. This paper presents the study protocol. A pragmatic cluster randomised controlled trial using participatory action research is underway in 10 public primary care clinics in Selangor and Kuala Lumpur, Malaysia. Five clinics were randomly selected to provide the EMPOWER-PAR intervention for 1 year and another five clinics continued with usual care. Each clinic consecutively recruits type 2 diabetes mellitus and hypertension patients fulfilling the inclusion and exclusion criteria over a 2-week period. The EMPOWER-PAR intervention consists of creating/strengthening a multidisciplinary chronic disease management team, training the team to use the Global Cardiovascular Risks Self-Management Booklet to support patient care and reinforcing the use of relevant clinical practice guidelines for management and prescribing. For type 2 diabetes mellitus, the primary outcome is the change in the proportion of patients achieving HbA1c < 6.5%. For hypertension without type 2 diabetes mellitus, the primary outcome is the change in the proportion of patients achieving blood pressure < 140/90 mmHg. Secondary outcomes include the proportion of patients achieving targets for serum lipid profile, body mass index and waist circumference. Other outcome measures include medication adherence levels, process of care and prescribing patterns. Patients' assessment of their chronic disease care and providers' perceptions, attitudes and perceived barriers in care delivery and cost-effectiveness of the intervention are also evaluated. Results from this study will provide objective evidence of the effectiveness and cost-effectiveness of a multifaceted intervention based on the chronic care model in resource-constrained public primary care settings. The evidence should instigate crucial primary care system change in Malaysia. ClinicalTrials.gov NCT01545401.

Hormonal treatment and flight feather molt in immature Sandhill Cranes

USGS Publications Warehouse

Gee, G.F.; Lewis, J.C.

1982-01-01

Molt, the production of a new generation of feathers, is a poorly understood physiological phenomenon in nondomestic birds. Often in large birds like geese, flight is restricted by clipping the primary remiges on 1 wing and flight is restored after the molt when the primaries are replaced. A similar technique would be desirable for use with cranes conditioned for release to the native habitat. However, immature sandhill cranes (Grus canadensis) did not appear to replace their primaries annually; therefore, we studied their flight feather molt (from 4 months to 3.5 years of age) and attempted to influence molting. Under natural conditions tail feathers (rectrices) were replaced annually and all secondaries replaced in 2.5-year-old birds. However, replacement of primaries in immature sandhill cranes appears to be a gradual process beginning the 2nd year; about 33% of the original primaries (present at 10 months of age) persisted in the 3.5-year-oId birds. Pulling out the primaries of immature sandhill cranes induces the growth of new primaries, as is true of many other birds. However, the new primaries were incapable of supporting flight, fell out repeatedly, and those that remained were often deformed. Pulling the primaries, under the influence of tranquilizers and anesthetics to relax the feather papillae, also did not induce normal growth of the replacement primaries. Progesterone (including excessively high doses), thyroxine, and follicle stimulating hormone, although effective in inducing feather replacement in domestic poultry, had no effect on crane molt.

Paying for Primary Care: The Factors Associated with Physician Self-selection into Payment Models.

PubMed

Rudoler, David; Deber, Raisa; Barnsley, Janet; Glazier, Richard H; Dass, Adrian Rohit; Laporte, Audrey

2015-09-01

To determine the factors associated with primary care physician self-selection into different payment models, we used a panel of eight waves of administrative data for all primary care physicians who practiced in Ontario between 2003/2004 and 2010/2011. We used a mixed effects logistic regression model to estimate physicians' choice of three alternative payment models: fee for service, enhanced fee for service, and blended capitation. We found that primary care physicians self-selected into payment models based on existing practice characteristics. Physicians with more complex patient populations were less likely to switch into capitation-based payment models where higher levels of effort were not financially rewarded. These findings suggested that investigations aimed at assessing the impact of different primary care reimbursement models on outcomes, including costs and access, should first account for potential selection effects. Copyright © 2015 John Wiley & Sons, Ltd.

Analysis of neutron spectrum effects on primary damage in tritium breeding blankets

NASA Astrophysics Data System (ADS)

Choi, Yong Hee; Joo, Han Gyu

2012-07-01

The effect of neutron spectrum on primary damages in a structural material of a tritium breeding blanket is investigated with a newly established recoil spectrum estimation system. First, a recoil spectrum generation code is developed to obtain the energy spectrum of primary knock-on atoms (PKAs) for a given neutron spectrum utilizing the latest ENDF/B data. Secondly, a method for approximating the high energy tail of the recoil spectrum is introduced to avoid expensive molecular dynamics calculations for high energy PKAs using the concept of recoil energy of the secondary knock-on atoms originated by the INtegration of CAScades (INCAS) model. Thirdly, the modified spectrum is combined with a set of molecular dynamics calculation results to estimate the primary damage parameters such as the number of surviving point defects. Finally, the neutron spectrum is varied by changing the material of the spectral shifter and the result in primary damage parameters is examined.

Enhanced Primary Care Treatment of Behavioral Disorders With ECHO Case-Based Learning.

PubMed

Komaromy, Miriam; Bartlett, Judy; Manis, Kathryn; Arora, Sanjeev

2017-09-01

The Extension for Community Healthcare Outcomes (ECHO) model offers a way for primary care providers to develop expertise in addressing behavioral health issues of primary care patients. It provides an alternative to traditional continuing medical education (CME) for ongoing training and support for health care providers. ECHO uses videoconferencing to connect multiple primary care teams simultaneously with academic specialists and builds capacity via mentorship and case-based learning. ECHO aims to expand access to care by developing capacity to treat common, complex conditions in underserved areas. Participants in an integrated addictions and psychiatry teleECHO program reported that when they presented a patient case, the feedback they received was highly valuable and led them to change their care plans more than 75% of the time. ECHO is an effective model for teaching primary care teams about behavioral health and may be more effective than traditional CME approaches.

Ginsenoside compound K promotes β-amyloid peptide clearance in primary astrocytes via autophagy enhancement.

PubMed

Guo, Jinhui; Chang, Li; Zhang, Xin; Pei, Sujuan; Yu, Meishuang; Gao, Jianlian

2014-10-01

The aim of the present study was to investigate the effect of ginsenoside compound K on β-amyloid (Aβ) peptide clearance in primary astrocytes. Aβ degradation in primary astrocytes was determined using an intracellular Aβ clearance assay. Aggregated LC3 in astrocyte cells, which is a marker for the level of autophagy, was detected using laser scanning confocal microscope. The effect of compound K on the mammalian target of rapamycin (mTOR)/autophagy pathway was determined using western blot analysis, and an enzyme-linked immunosorbent assay was used for Aβ detection. The results demonstrated that compound K promoted the clearance of Aβ and enhanced autophagy in primary astrocytes. In addition, it was found that phosphorylation of mTOR was inhibited by compound K, which may have contributed to the enhanced autophagy. In conclusion, compound K promotes Aβ clearance by enhancing autophagy via the mTOR signaling pathway in primary astrocytes.

Contribution of Benson's Relaxation Technique and Brief Psycho-Educational Intervention on Quality of Life of Primary Caregivers of Iranian Children with Chronic Diseases.

PubMed

Mowla, Forough; Khanjari, Sedigheh; Inanlou, Mehrnoush

Chronic diseases leave a significant effect on not only the afflicted children but also their parents. Chronic diseases in children may also influence their parents' or primary caregivers' quality of life (QoL). To determine the effectiveness of a Brief Psycho-educational Intervention (BPI) and Benson's Relaxation Technique (BRT) on the QoL of primary caregivers of children with chronic diseases. The present quasi-experimental pre-test post-test design was conducted on 100 parents with children who had one chronic disease (50 in each of the control and intervention groups) and were admitted to two state-run pediatric hospitals in Tehran, Iran in 2014. The primary caregivers' QoL was assessed using the SF-36 questionnaire before (T1) and four weeks after the intervention (T2). The training was done in four 60-70minute sessions over one week with a 4-week follow-up. Paired t-test, independent t-test, chi-square and Fisher's exact tests were used to analyze the data. On average, large effect sizes (ES≥0.80) were observed after interventions in SF-36 subscales that measured the effect of emotional roles. Small (0.20-0.49) to moderate (0.50-0.79) ESs were found in subscales measuring physical functioning, physical-role, bodily pain, vitality, social functioning and mental health. General health scores remained relatively unchanged at T2. These results suggested that BPI and BRT were effective strategies to improve the QoL of primary caregivers. Furthermore, interventions with low cost, and good safety and outcome could improve the QoL of primary caregivers of children with chronic diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Palliative chemotherapy among people living in poverty with metastasised colon cancer: facilitation by primary care and health insurance.

PubMed

Gorey, Kevin M; Bartfay, Emma; Kanjeekal, Sindu M; Wright, Frances C; Hamm, Caroline; Luginaah, Isaac N; Zou, Guangyong; Holowaty, Eric J; Richter, Nancy L; Balagurusamy, Madhan K

2016-08-23

Many Americans with metastasised colon cancer do not receive indicated palliative chemotherapy. We examined the effects of health insurance and physician supplies on such chemotherapy in California. We analysed registry data for 1199 people with metastasised colon cancer diagnosed between 1996 and 2000 and followed for 1 year. We obtained data on health insurance, census tract-based socioeconomic status and county-level physician supplies. Poor neighbourhoods were oversampled and the criterion was receipt of chemotherapy. Effects were described with rate ratios (RR) and tested with logistic regression models. Palliative chemotherapy was received by less than half of the participants (45%). Facilitating effects of primary care (RR=1.23) and health insurance (RR=1.14) as well as an impeding effect of specialised care (RR=0.86) were observed. Primary care physician (PCP) supply took precedence. Adjusting for poverty, PCP supply was the only significant and strong predictor of chemotherapy (OR=1.62, 95% CI 1.02 to 2.56). The threshold for this primary care advantage was realised in communities with 8.5 or more PCPs per 10 000 inhabitants. Only 10% of participants lived in such well-supplied communities. This study's observations of facilitating effects of primary care and health insurance on palliative chemotherapy for metastasised colon cancer clearly suggested a way to maximise Affordable Care Act (ACA) protections. Strengthening America's system of primary care will probably be the best way to ensure that the ACA's full benefits are realised. Such would go a long way towards facilitating access to palliative care. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Internet cognitive behavioural therapy for mixed anxiety and depression: a randomized controlled trial and evidence of effectiveness in primary care.

PubMed

Newby, J M; Mackenzie, A; Williams, A D; McIntyre, K; Watts, S; Wong, N; Andrews, G

2013-12-01

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) have the highest co-morbidity rates within the internalizing disorders cluster, yet no Internet-based cognitive behavioural therapy (iCBT) programme exists for their combined treatment. We designed a six-lesson therapist-assisted iCBT programme for mixed anxiety and depression. Study 1 was a randomized controlled trial (RCT) comparing the iCBT programme (n = 46) versus wait-list control (WLC; n = 53) for patients diagnosed by structured clinical interview with MDD, GAD or co-morbid GAD/MDD. Primary outcome measures were the Patient Health Questionnaire nine-item scale (depression), Generalized Anxiety Disorder seven-item scale (generalized anxiety), Kessler 10-item Psychological Distress scale (distress) and 12-item World Health Organization Disability Assessment Schedule II (disability). The iCBT group was followed up at 3 months post-treatment. In study 2, we investigated the adherence to, and efficacy of the same programme in a primary care setting, where patients (n = 136) completed the programme under the supervision of primary care clinicians. The RCT showed that the iCBT programme was more effective than WLC, with large within- and between-groups effect sizes found (>0.8). Adherence was also high (89%), and gains were maintained at 3-month follow-up. In study 2 in primary care, adherence to the iCBT programme was low (41%), yet effect sizes were large (>0.8). Of the non-completers, 30% experienced benefit. Together, the results show that iCBT is effective and adherence is high in research settings, but there is a problem of adherence when translated into the 'real world'. Future efforts need to be placed on developing improved adherence to iCBT in primary care settings.

Changes in Patterns of Teacher Interaction in Primary Classrooms: 1976-96.

ERIC Educational Resources Information Center

Galton, Maurice; Hargreaves, Linda; Comber, Chris; Wall, Debbie; Pell, Tony

1999-01-01

Addresses the effectiveness of teaching methods in English primary school classrooms. Evaluates the interventions designed to change primary educators' teaching methods by replicating the Observational Research and Classroom Learning Evaluation (ORACLE) study that was originally conducted in 1976. Compares the results from the original study to…

Investigation of Teachers' Attitudes towards Computer Use in Primary Education in Kurdistan

ERIC Educational Resources Information Center

Balisane, Hewa

2015-01-01

Technological advances have pervasively changed our behaviours, beliefs and approaches in working, socialising and entertaining. Educators, including those in primary education, have acknowledged the positive effects of computer use in the classroom in various ways. With regard to pedagogical consideration, primary school teachers have adopted…

77 FR 59932 - Single Source Award; Exception to Competition

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-01

... Primary Care Integration Project. In fiscal year (FY) 2012, $486,394 will be available to fully fund this..., effectively, and efficiently implement the CHW Behavioral Health Primary Care Integration Project within their... qualified to carry out the CHW Behavioral Health Primary Care Integration Project because of their...

Genetics Home Reference: early-onset primary dystonia

MedlinePlus

... such as seizures or a loss of intellectual function (dementia). Early-onset primary dystonia does not affect a person's intelligence. On ... of torsinA. The altered protein's effect on the function of nerve cells in the brain ... with early-onset primary dystonia do not have a loss of nerve ...

Posttraumatic stress disorder symptom severity and control beliefs as the predictors of academic burnout amongst adolescents following the Wenchuan Earthquake

PubMed Central

Zhou, Xiao; Zhen, Rui; Wu, Xinchun

2017-01-01

ABSTRACT Background: Previous studies indicate that posttraumatic stress disorder (PTSD) and control beliefs can affect burnout and their unique role in this situation has been examined, but fewer studies have examined their combined role in adolescent’s academic burnout following traumatic events. Objective: This study examined the combined effect of PTSD symptom severity and control beliefs on academic burnout among adolescents, and assessed the moderating role of primary and secondary control beliefs in the relation between PTSD symptom severity and academic burnout. Methods: Seven hundred and forty-five adolescents were investigated using self-report questionnaires, and a series of regression equations examined the impact of PTSD severity and control beliefs on academic burnout. Results: PTSD symptom severity is associated positively with academic burnout, while primary and secondary control beliefs have a negative relation with academic burnout. In addition, primary control beliefs buffer the positive effects of PTSD symptom severity on academic burnout. We found that the positive relation between PTSD symptom severity and academic burnout in the low primary control beliefs group is more intense than that found in the high primary control beliefs group. Conclusions: PTSD symptom severity is a risk factor, whereas primary and secondary control beliefs are protective factors in academic burnout. In addition, PTSD symptom severity and primary control beliefs have a combined effect on academic burnout in adolescents following natural disasters. PMID:29296242

The contribution of dietitians to the primary health care workforce.

PubMed

Howatson, Alexandra; Wall, Clare R; Turner-Benny, Petrina

2015-12-01

Dietetic intervention is effective in the management of nutrition-related conditions and their comorbidities. New Zealand has an increasing need for primary and preventive health care to reduce the burden of non-communicable disease. To review the recent evidence of effectiveness of dietetic intervention in primary health care on health and wider economic outcomes. Health benefits and cost benefits of employing dietitians to perform nutrition intervention in the primary health care setting are evaluated in the areas of obesity in conjunction with diabetes and cardiovascular disease, and malnutrition in older adults. An electronic literature search of four scientific databases, websites of major dietetic associations and high-impact nutrition and dietetic journals was conducted. Randomised controlled trials and non-randomised studies conducted from 2000 to 2014 were included. Dietetic intervention demonstrates statistically and clinically significant impacts on health outcomes in the areas of obesity, cardiovascular disease, diabetes, and malnutrition in older adults, when compared to usual care. Dietitians working in primary health care can also have significant economic benefits, potentially saving the health care system NZ$5.50-$99 for every NZ$1 spent on dietetic intervention. New Zealand must look to new models of health care provision that are not only patient-centred but are also cost-effective. This review demonstrates that dietitians in primary health care can improve patients' health and quality of life. Increasing the number of dietitians working in primary health care has the potential to make quality nutrition care accessible and affordable for more New Zealanders.

Organizational culture predicts job satisfaction and perceived clinical effectiveness in pediatric primary care practices.

PubMed

Brazil, Kevin; Wakefield, Dorothy B; Cloutier, Michelle M; Tennen, Howard; Hall, Charles B

2010-01-01

In recent years, there has been a growing understanding that organizational culture is related to an organization's performance. However, few studies have examined organizational culture in medical group practices. The purpose of this study was to examine the relationship of organizational culture on provider job satisfaction and perceived clinical effectiveness in primary care pediatric practices. This cross-sectional study included 36 primary care pediatric practices located in Connecticut. There were 374 participants in this study, which included 127 clinicians and 247 nonclinicians. Office managers completed a questionnaire that recorded staff and practice characteristics; all participants completed the Organizational Culture Scale, a questionnaire that assessed the practice on four cultural domains (i.e., group, developmental, rational, and hierarchical), and the Primary Care Organizational Questionnaire that evaluated perceived effectiveness and job satisfaction. Hierarchical linear models using a restricted maximum likelihood estimation method were used to evaluate whether the practice culture types predicted job satisfaction and perceived effectiveness. Group culture was positively associated with both satisfaction and perceived effectiveness. In contrast, hierarchical and rational culture were negatively associated with both job satisfaction and perceived effectiveness. These relationships were true for clinicians, nonclinicians, and the practice as a whole. Our study demonstrates that practice culture is associated with job satisfaction and perceived clinical effectiveness and that a group culture was associated with high job satisfaction and perceived effectiveness.

RECODE: design and baseline results of a cluster randomized trial on cost-effectiveness of integrated COPD management in primary care.

PubMed

Kruis, Annemarije L; Boland, Melinde R S; Schoonvelde, Catharina H; Assendelft, Willem J J; Rutten-van Mölken, Maureen P M H; Gussekloo, Jacobijn; Tsiachristas, Apostolos; Chavannes, Niels H

2013-03-23

Favorable effects of formal pulmonary rehabilitation in selected moderate to severe COPD patients are well established. Few data are available on the effects and costs of integrated disease management (IDM) programs on quality of care and health status of COPD patients in primary care, representing a much larger group of COPD patients. Therefore, the RECODE trial assesses the long-term clinical and cost-effectiveness of IDM in primary care. RECODE is a cluster randomized trial with two years of follow-up, during which 40 clusters of primary care teams (including 1086 COPD patients) are randomized to IDM or usual care. The intervention started with a 2-day multidisciplinary course in which healthcare providers are trained as a team in essential components of effective COPD IDM in primary care. During the course, the team redesigns the care process and defines responsibilities of different caregivers. They are trained in how to use feedback on process and outcome data to guide implement guideline-driven integrated healthcare. Practice-tailored feedback reports are provided at baseline, and at 6 and 12 months. The team learns the details of an ICT program that supports recording of process and outcome measures. Afterwards, the team designs a time-contingent individual practice plan, agreeing on steps to be taken in order to integrate a COPD IDM program into daily practice. After 6 and 12 months, there is a refresher course for all teams simultaneously to enable them to learn from each other's experience. Health status of patients at 12 months is the primary outcome, measured by the Clinical COPD Questionnaire (CCQ). Secondary outcomes include effects on quality of care, disease-specific and generic health-related quality of life, COPD exacerbations, dyspnea, costs of healthcare utilization, and productivity loss. This article presents the protocol and baseline results of the RECODE trial. This study will allow to evaluate whether IDM implemented in primary care can positively influence quality of life and quality of care in mild to moderate COPD patients, thereby making the benefits of multidisciplinary rehabilitation applicable to a substantial part of the COPD population. Netherlands Trial Register (NTR): NTR2268.

Reducing heart disease through the vegetarian diet using primary prevention.

PubMed

Sticher, Megan A; Smith, Christine B; Davidson, Susan

2010-03-01

To evaluate research on the vegetarian diet for its safety, effectiveness in reducing heart disease, special considerations, contraindications, and its association with decreased cardiovascular disease risk. Selected research and evidence-based dietary guidelines found by searching CINAHL, PubMed, Ovid databases, and the World Wide Web. A carefully planned vegetarian diet with adequate supplementation may be effective for primary prevention of heart disease. The vegetarian diet is cost effective, safe, and relatively easy to implement. Improved dietary choices can help improve many chronic conditions. Guidelines for proper nutrition within a vegetarian lifestyle are readily accessible to patients and professionals alike. Referral to a dietitian is an appropriate option in primary care settings.

Cooperative Learning in Science: Follow-up from primary to high school

NASA Astrophysics Data System (ADS)

Thurston, Allen; Topping, Keith J.; Tolmie, Andrew; Christie, Donald; Karagiannidou, Eleni; Murray, Pauline

2010-03-01

This paper reports a two-year longitudinal study of the effects of cooperative learning on science attainment, attitudes towards science, and social connectedness during transition from primary to high school. A previous project on cooperative learning in primary schools observed gains in science understanding and in social aspects of school life. This project followed 204 children involved in the previous project and 440 comparison children who were not as they undertook transition from 24 primary schools to 16 high schools. Cognitive, affective, and social gains observed in the original project survived transition. The implications improving the effectiveness of school transition by using cooperative learning initiatives are explored. Possibilities for future research and the implications for practice and policy are discussed.

Factors shaping intersectoral action in primary health care services.

PubMed

Anaf, Julia; Baum, Fran; Freeman, Toby; Labonte, Ron; Javanparast, Sara; Jolley, Gwyn; Lawless, Angela; Bentley, Michael

2014-12-01

To examine case studies of good practice in intersectoral action for health as one part of evaluating comprehensive primary health care in six sites in South Australia and the Northern Territory. Interviews with primary health care workers, collaborating agency staff and service users (Total N=33); augmented by relevant documents from the services and collaborating partners. The value of intersectoral action for health and the importance of partner relationships to primary health care services were both strongly endorsed. Factors facilitating intersectoral action included sufficient human and financial resources, diverse backgrounds and skills and the personal rewards that sustain commitment. Key constraining factors were financial and time limitations, and a political and policy context which has become less supportive of intersectoral action; including changes to primary health care. While intersectoral action is an effective way for primary health care services to address social determinants of health, commitment to social justice and to adopting a social view of health are constrained by a broader health service now largely reinforcing a biomedical model. Effective organisational practices and policies are needed to address social determinants of health in primary health care and to provide a supportive context for workers engaging in intersectoral action. © 2014 Public Health Association of Australia.

The effectiveness of motivational interviewing for health behaviour change in primary care settings: a systematic review.

PubMed

Morton, Katie; Beauchamp, Mark; Prothero, Anna; Joyce, Lauren; Saunders, Laura; Spencer-Bowdage, Sarah; Dancy, Bernadette; Pedlar, Charles

2015-01-01

Motivational interviewing (MI) is a patient-centred approach to behaviour change that was originally developed in the addiction field but has increasingly been applied to public health settings with a focus on health promotion. The purpose of this review was to examine the evidence base for MI interventions in primary care settings with non-clinical populations to achieve behaviour change for physical activity, dietary behaviours and/or alcohol intake. We also sought to explore the specific behaviour change techniques included in MI interventions within primary care. Electronic databases were searched for relevant articles and 33 papers met inclusion criteria and were included. Approximately 50% of the included studies (n = 18) demonstrated positive effects in relation to health behaviour change. The efficacy of MI approaches is unclear given the inconsistency of MI descriptions and intervention components. Furthermore, research designs that do not isolate the effects of MI make it difficult to determine the effectiveness of such approaches. We offer a number of recommendations for researchers and practitioners seeking to include MI within behaviour change interventions to help improve the quality of the research and the effectiveness of MI-based interventions within primary care settings.

Primary Health Care as a Foundation for Strengthening Health Systems in Low- and Middle-Income Countries.

PubMed

Bitton, Asaf; Ratcliffe, Hannah L; Veillard, Jeremy H; Kress, Daniel H; Barkley, Shannon; Kimball, Meredith; Secci, Federica; Wong, Ethan; Basu, Lopa; Taylor, Chelsea; Bayona, Jaime; Wang, Hong; Lagomarsino, Gina; Hirschhorn, Lisa R

2017-05-01

Primary health care (PHC) has been recognized as a core component of effective health systems since the early part of the twentieth century. However, despite notable progress, there remains a large gap between what individuals and communities need, and the quality and effectiveness of care delivered. The Primary Health Care Performance Initiative (PHCPI) was established by an international consortium to catalyze improvements in PHC delivery and outcomes in low- and middle-income countries through better measurement and sharing of effective models and practices. PHCPI has developed a framework to illustrate the relationship between key financing, workforce, and supply inputs, and core primary health care functions of first-contact accessibility, comprehensiveness, coordination, continuity, and person-centeredness. The framework provides guidance for more effective assessment of current strengths and gaps in PHC delivery through a core set of 25 key indicators ("Vital Signs"). Emerging best practices that foster high-performing PHC system development are being codified and shared around low- and high-income countries. These measurement and improvement approaches provide countries and implementers with tools to assess the current state of their PHC delivery system and to identify where cross-country learning can accelerate improvements in PHC quality and effectiveness.

The Anthropogenic "Greenhouse Effect": Greek Prospective Primary Teachers' Ideas about Causes, Consequences and Cures

ERIC Educational Resources Information Center

Ikonomidis, Simos; Papanastasiou, Dimitris; Melas, Dimitris; Avgoloupis, Stavros

2012-01-01

This study explores the ideas of Greek prospective primary teachers about the anthropogenic greenhouse effect, particularly about its causes, consequences and cures. For this purpose, a survey was conducted: 265 prospective teachers completed a closed-form questionnaire. The results showed serious misconceptions in all areas (causes, consequences…

Effects of Kindergarten Retention for At-Risk Children's Mathematics Development

ERIC Educational Resources Information Center

Vandecandelaere, Machteld; Schmitt, Eric; Vanlaar, Gudrun; De Fraine, Bieke; Van Damme, Jan

2015-01-01

When a child does not seem to be ready for primary school, a popular practice is to grant the child more time by letting it repeat kindergarten. However, previous quasi-experimental research demonstrated negative, though diminishing, effects of kindergarten retention on academic learning during the first years of primary school. The present study…

Project-Based Learning in Primary Schools: Effects on Pupils' Learning and Attitudes

ERIC Educational Resources Information Center

Kaldi, Stavroula; Filippatou, Diamanto; Govaris, Christos

2011-01-01

This study focuses upon the effectiveness of project-based learning on primary school pupils regarding their content knowledge and attitudes towards self-efficacy, task value, group work, teaching methods applied and peers from diverse ethnic backgrounds. A cross-curricular project was implemented within the curriculum area of environmental…

Principals' Role and Public Primary Schools' Effectiveness in Four Latin American Cities

ERIC Educational Resources Information Center

Anderson, Joan B.

2008-01-01

This article examines the effectiveness of observable and quantifiable traits in and approaches of school principals in enhancing student achievement. Data were gathered on 2,048 fourth-grade students in 96 public primary schools in Leon, Mexico; Belo Horizonte, Brazil; Buenos Aires, Argentina; and Santiago, Chile. The UNESCO/ORELAC (United…

Effective Strategies for Teaching Evolution: The Primary Evolution Project

ERIC Educational Resources Information Center

Hatcher, Chris

2015-01-01

When Chris Hatcher joined the Primary Evolution Project team at the University of Reading, his goal was to find effective strategies to teach evolution in a way that keeps children engaged and enthused. Hatcher has collaborated with colleagues at the University's Institute of Education to break the evolution unit down into distinct topics and…

Effect of Training in Math Metacognitive Strategy on Fractional Achievement of Nigerian Schoolchildren

ERIC Educational Resources Information Center

Onu, V. C.; Eskay, M.; Igbo, J. N.; Obiyo, N.; Agbo, O.

2012-01-01

This study examined the effect of training in math metacognition on fractional mathematics among primary school pupils, with a quasi-experimental design, specifically a post-test only control group design. Two intact classes were randomly selected and assigned to treatment and control conditions. Sixty primary six pupils constituted the sample…

Longitudinal Data on the Effectiveness of Mathematics Mini-Games in Primary Education

ERIC Educational Resources Information Center

Bakker, Marjoke; Van den Heuvel-Panhuizen, Marja; Robitzsch, Alexander

2015-01-01

This paper describes a dataset consisting of longitudinal data gathered in the BRXXX project. The aim of the project was to investigate the effectiveness of online mathematics mini-games in enhancing primary school students' multiplicative reasoning ability (multiplication and division). The dataset includes data of 719 students from 35 primary…

Effects of phytoestrogens on protein turnover in rainbow trout primary myocytes

USDA-ARS?s Scientific Manuscript database

Soybean-derived ingredients used in aquaculture feeds may contain phytoestrogens, but it is unknown if these compounds can mimic the catabolic effects of estradiol in fish muscle. Six day-old rainbow trout primary myocytes were exposed to increasing concentrations (10 nM – 100 µM) of either geniste...

The Differential Effects of Labelling: How Do "Dyslexia" and "Reading Difficulties" Affect Teachers' Beliefs

ERIC Educational Resources Information Center

Gibbs, Simon; Elliott, Julian

2015-01-01

This paper reports a survey of primary school teachers' beliefs about working with poor readers. The primary research question was "does the way difficulties with reading are labelled affect the teachers' beliefs about their ability to intervene effectively?" An opportunity sample of teachers was surveyed using 2 questionnaires. One…

Place of Instructional Supervision in Enhancing Public Primary School Teachers' Effectiveness

ERIC Educational Resources Information Center

Nwambam, Aja Sunday; Eze, Prisca Ijeoma

2017-01-01

The study examined the place of instructional supervision in enhancing teachers' effectiveness in public primary schools in Ebonyi State. Four research questions were formulated to guide the study. Descriptive survey research design was adopted for the study. The population of the study consists of all the 462,186 teachers including the…

Experienced Primary School Teachers' Thoughts on Effective Teachers of Literacy and Numeracy

ERIC Educational Resources Information Center

Md-Ali, Ruzlan; Karim, Hamida Bee Bi Abdul; Yusof, Fahainis Mohd

2016-01-01

Purpose: This paper presents the characteristics of effective literacy and numeracy teachers within the current context of teaching in Malaysia from the viewpoints of a sample of trained and experienced primary school teachers of literacy and numeracy. The characteristics were established based on what the teachers perceived as important in…

Improving Learning in Primary Schools of Developing Countries: A Meta-Analysis of Randomized Experiments

ERIC Educational Resources Information Center

McEwan, Patrick J.

2015-01-01

I gathered 77 randomized experiments (with 111 treatment arms) that evaluated the effects of school-based interventions on learning in developing-country primary schools. On average, monetary grants and deworming treatments had mean effect sizes that were close to zero and not statistically significant. Nutritional treatments, treatments that…

EFFECT OF ARSENICALS ON THE EXPRESSION OF CELL CYCLE PROTEINS AND EARLY SIGNALING EVENTS IN PRIMARY HUMAN KERATINOCYTES.

EPA Science Inventory

Effect of Arsenicals on the Expression of Cell Cycle Proteins and Early Signaling Events in Primary Human Keratinocytes.

Mudipalli, A, Owen R. D. and R. J. Preston, Environmental Carcinogenesis Division, USEPA, RTP, NC 27711.

Environmental exposure to arsenic is a m...

Effectiveness of Rotary Endodontic Instruments on Smear Layer Removal in Root Canals of Primary Teeth: A Scanning Electron Microscopy Study.

PubMed

Subramaniam, Priya; Girish Babu, K L; Tabrez, T A

2016-01-01

The present SEM study was undertaken to evaluate the effect of root canal instrumentation using both manual and rotary files in the root canals of primary anterior teeth. Thirty freshly extracted primary maxillary incisors were divided into 3 groups of 10 teeth each. In Group I, root canals were instrumented with rotary NiTi files; in Group II, the root canals were instrumented using manual NiTi K files and; in Group III, manual instrumentation was done with stainless steel K files. Longitudinal sections were prepared and processed for observation under SEM at the coronal, middle and apical thirds. Scoring of smear layer was done according to Hulsmann and the data obtained was subjected to statistical analysis. Rotary files cleaned the coronal and middle thirds of root canals more effectively. Statistically there was no significant difference between the groups. Lowest score of 2.6 in the apical third of root canals was seen with hand NiTi files. Rotary instrumentation was as effective as manual instrumentation in removal of smear layer in the root canals of primary anterior teeth.

Effectiveness of Group Cognitive Behavioral Therapy for Insomnia (CBT-I) in a Primary Care Setting.

PubMed

Davidson, Judith R; Dawson, Samantha; Krsmanovic, Adrijana

2017-05-02

Primary care is where many patients with insomnia first ask for professional help. Cognitive-behavioral therapy for insomnia (CBT-I) is the recommended treatment for chronic insomnia. Although CBT-I's efficacy is well established, its effectiveness in real-life primary care has seldom been investigated. We examined the effectiveness of CBT-I as routinely delivered in a Canadian primary care setting. The patients were 70 women and 11 men (mean age = 57.0 years, SD = 12.3); 83% had medical comorbidity. For the first 81 patients who took the six-session group program we compared initial and postprogram sleep diaries, sleep medication use, Insomnia Severity Index (ISI), the Hospital Anxiety and Depression Scale (HADS), and visits to the family physician. Sleep onset latency, wake after sleep onset, total sleep time, sleep efficiency, and ISI scores improved significantly (p < .001). Mood ratings also improved (p < .001). Use of sleep medication decreased (p < .001). Effect sizes were medium to large. Eighty-eight percent of patients no longer had clinically significant insomnia (ISI score ≤ 14) by the last session; 61% showed at least "moderate" improvement (ISI score reduction > 7). Wait-list data from 42 patients showed minimal sleep and mood improvements with the passage of time. Number of visits to the family physician six months postprogram decreased, although not significantly (p = .108). The CBT-I program was associated with improvement on all sleep and mood measures. Effect sizes were similar to, or larger than, those found in randomized controlled trials, demonstrating the real-world effectiveness of CBT-I in an interdisciplinary primary care setting.

The long-term effects of the micrometeoroid and orbital debris environments on materials used in space

NASA Technical Reports Server (NTRS)

Cour-Palais, Burton G.

1989-01-01

The long-term effects of the orbital debris and micrometeoroid environments on materials that are current candidates for use on space vehicles are discussed. In addition, the limits of laboratory testing to determine these effects are defined and the need for space-based data is delineated. The impact effects discussed are divided into primary and secondary surfaces. Primary surfaces are those that are subject to erosion, pitting, the degradation and delamination of optical coatings, perforation of atomic oxygen erosion barriers, vapor coating of optics and the production of secondary ejecta particles. Secondary surfaces are those that are affected by the result of the perforation of primary surfaces, for example, vapor deposition on electronic components and other sensitive equipment, and the production of fragments with damage potential to internal pressurized elements. The material properties and applications that are required to prevent or lessen the effects described, are defined.

Primary focal hyperhidrosis: diagnosis and management. .

PubMed

Wang, Rena; Solish, Nowell; Murray, Christian A

2008-12-01

Primary focal hyperhidrosis is a common and serious medical condition that causes considerable psychosocial morbidity. Diagnostic and effective management strategies can improve patients' quality of living dramatically.

Effects of Auricular Acupressure Therapy on Primary Dysmenorrhea for Female High School Students in South Korea.

PubMed

Cha, Nam Hyun; Sok, Sohyune R

2016-09-01

To examine the effect of auricular acupressure therapy on primary dysmenorrhea among female high school students in South Korea. A randomized controlled trial was employed. The study sample consisted of 91 female high school students, with 45 participants in the experimental group and 46 in the control group in two regions of South Korea. The average age of the participants was 16.7 years, and the average age of menarche was 12.2 years. Auricular acupressure therapy including an auricular acupressure needle on skin paper tape was applied on an ear for 3 days during periods of extreme primary dysmenorrhea. The acupoint names were Jagung, Sinmun, Gyogam, and Naebunbi. For the placebo control group, only the skin paper tape without an auricular acupressure needle was applied on the same acupoints. Measures used were the Menstrual Distress Questionnaire to assess primary dysmenorrhea, and the visual analog scale to assess abdominal and back pain of participants. There were significant differences on abdominal pain (t = 24.594, p < .001), back pain (t = 22.661, p < .001), and primary dysmenorrhea (t = 32.187, p < .001) between the two groups. Auricular acupressure therapy decreased abdominal pain, back pain, and primary dysmenorrhea of female high school students in South Korea. Auricular acupressure therapy was an effective intervention for alleviating abdominal pain, back pain, and primary dysmenorrhea of female high school students in South Korea. For feasibility of the auricular acupressure therapy in practice, it is needed to train and learn the exact positions of acupoints in ear. Health providers should consider providing auricular acupressure therapy as an alternative method for reducing abdominal and back pain, and primary dysmenorrhea in female high school students in South Korea. © 2016 Sigma Theta Tau International.

Protocol for the Rural Engagement in Primary Care for Optimizing Weight Reduction (RE-POWER) Trial: Comparing three obesity treatment models in rural primary care.

PubMed

Befort, Christie A; VanWormer, Jeffrey J; DeSouza, Cyrus; Ellerbeck, Edward F; Kimminau, Kim S; Greiner, Allen; Gajewski, Byron; Huang, Terry; Perri, Michael G; Fazzino, Tera L; Christifano, Danielle; Eiland, Leslie; Drincic, Andjela

2016-03-01

Obesity disproportionately affects rural residents in the United States, and primary care has the potential to fill a major gap in the provision of weight management services for rural communities. The objective of this cluster-randomized pragmatic trial is to evaluate the comparative effectiveness of three obesity treatment models in rural primary care: the Intensive Behavior Therapy fee-for-service (FFS) model reimbursed by Medicare, a team-based model that recognizes the patient-centered medical home (PCMH) as a preferred delivery approach, and the centralized disease management (DM) model, in which phone-based counseling is provided outside of the primary care practice. We hypothesize that the PCMH and DM treatments will be more effective than FFS in reducing weight at 24 months. Thirty-six practices from the rural Midwestern U.S. are randomized to deliver one of the three interventions to 40 patients (N=1440) age 20 to 75 with a BMI 30-45 kg/m(2). In the FFS arm, primary care providers and their personnel counsel patients to follow evidence-based weight loss guidelines using the Medicare-designated treatment schedule. In the PCMH arm, patients receive a comprehensive weight management intervention delivered locally by practice personnel using a combination of in-person and phone-based group sessions. In the DM arm, the same intervention is delivered remotely by obesity treatment specialists via group conference calls. The primary outcome is weight loss at 24 months. Additional measures include fasting glucose, lipids, quality of life indicators, and implementation process measures. Findings will illuminate effective obesity treatment intervention(s) in rural primary care. Copyright © 2016. Published by Elsevier Inc.

Cost-effectiveness of a Primary Care Intervention to Treat Obesity

PubMed Central

Tsai, Adam G.; Wadden, Thomas A.; Volger, Sheri; Sarwer, David B.; Vetter, Marion; Kumanyika, Shiriki; Berkowitz, Robert I.; Diewald, Lisa; Perez, Joanna; Lavenberg, Jeffrey; Panigrahi, Eva R.; Glick, Henry A.

2013-01-01

Background Data on the cost-effectiveness of the behavioral treatment of obesity are not conclusive. The cost-effectiveness of treatment in primary care settings is particularly relevant. Methods We conducted a within-trial cost-effectiveness analysis of a primary care-based obesity intervention. Study participants were randomized to: Usual Care (quarterly visits with their primary care provider); Brief Lifestyle Counseling (Brief LC; quarterly provider visits plus monthly weight loss counseling visits; or Enhanced Brief Lifestyle Counseling (Enhanced Brief LC; all above interventions, plus choice of meal replacements or weight loss medication). A health care payer perspective was used. Intervention costs were estimated from tracking data obtained prospectively. Quality adjusted life years (QALYs) were estimated with the EuroQol-5D. We estimated cost per kilogram-year of weight loss and cost per QALY. Results Weight losses after 2 years were 1.7, 2.9, and 4.6 kg for Usual Care, Brief LC, and Enhanced Brief LC, respectively (p = 0.003 for comparison of Enhanced Brief LC vs. Usual Care). The incremental cost per kilogram-year lost was $292 for Enhanced Brief LC compared to Usual Care (95% CI $38 to $394). The incremental cost per QALY was $115,397, but the 95% CI were undefined. Comparison of short term cost per kg with published estimates of longer term cost per QALYs suggested that the intervention could be cost-effective over the long term (≥ 10 years). Conclusions A primary care intervention that included monthly counseling visits and a choice of meal replacements or weight loss medication could be a cost-effective treatment for obesity over the long term. However, additional studies are needed on the cost-effectiveness of behavioral treatment of obesity. PMID:23921780

Reflections from organization science on the development of primary health care research networks.

PubMed

Fenton, E; Harvey, J; Griffiths, F; Wild, A; Sturt, J

2001-10-01

In the UK, policy changes in primary health care research and development have led to the establishment of primary care research networks. These organizations aim to increase research culture, capacity and evidence base in primary care. As publicly funded bodies, these networks need to be accountable. Organizational science has studied network organizations including why and how they develop and how they function most effectively. This paper draws on organizational science to reflect on why primary care research networks appear to be appropriate for primary care research and how their structures and processes can best enable the achievement of their aims.

[Modifiable risk factors for primary headache. A systematic review].

PubMed

Albers, L; Ziebarth, S; von Kries, R

2014-08-01

Strategies to prevent primary headaches could be very beneficial, especially given that primary headaches can lead to the development of chronic headache. In order to establish headache prevention strategies, the modifiable risk factors for primary headaches need to be identified. A systematic literature search on the risk factors for primary headaches was conducted independently by two persons using the databases MEDLINE and Embase. Further inclusion criteria were observational studies in adult general populations or case-control studies, where the effect sizes were reported as odds ratios or where the odds ratios could be calculated from the given data. In all, 24 studies were included in the analysis. There was a large amount of heterogeneity among the studies concerning headache acquisition, headache classification, and risk factors for headache development. Independent of headache trigger and definition of headache, the association between headache and the risk factor "stress" was very high: The meta-analysis shows an overall effect of 2.26 (odds ratio; 95 %-CI = [1.79; 2.85]). Studies evaluating neck and shoulder pain also report a strong association with headache; however, these results could not be summarized in a meta-analysis. Equally, the overall effects of smoking and coffee consumption on headaches could not be verified because the effect sizes were rather small and predominantly noticeable only at higher doses. A strong association between headache and the risk factors stress and neck and shoulder pain was confirmed. The effect sizes of smoking and coffee consumption on headaches were rather small.

Clonidine is effective for the treatment of primary idiopathic hyperhidrosis and hot flushes: a case report.

PubMed

Albadrani, Ahmed

2017-01-17

While primary hyperhidrosis can be seen in men, accompanying hot flushes is rarely seen in men. Primary hyperhidrosis is thought to be related to overactivity of the sympathetic nervous system while hot flushes are believed to be related to altered peripheral vascular reactivity and a narrowed thermoregulatory zone. I report the case of a 29-year-old man of Arab origin who presented to a dermatology clinic with a complaint of generalized sweating, with heavier involvement of his inguinal region, axilla, and lower back. His complaint was associated with a transient hot sensation and erythema over the affected areas. He did not respond to topical antiperspirants containing aluminum chloride, topical aluminum chloride, or to botulinum toxin A injected in both inguinal areas. He was then referred to an endocrinology clinic to rule out secondary causes of hyperhidrosis and hot flushes; a primary diagnosis was confirmed. He did not respond to oral glycopyrrolate and additionally was complaining of its anticholinergic side effects. The glycopyrrolate was then replaced with oral clonidine 0.15 mg twice a day. Clonidine was well tolerated without remarkable side effects and he quickly started to feel marked improvement which was maintained for 2 years. I report an atypical presentation of primary hyperhidrosis and hot flushes that was effectively controlled by clonidine without remarkable side effects. Further research on a large number of patients may be required before recommending clonidine in similar conditions.

Effects of ozone, ultraviolet and peracetic acid disinfection of a primary-treated municipal effluent on the immune system of rainbow trout (Oncorhynchus mykiss).

PubMed

Hébert, N; Gagné, F; Cejka, P; Bouchard, B; Hausler, R; Cyr, D G; Blaise, C; Fournier, M

2008-08-01

Municipal sewage effluents are complex mixtures that are known to compromise the health condition of aquatic organisms. The aim of this study was to evaluate the impacts of various wastewater disinfection processes on the immune system of juvenile rainbow trout (Oncorhynchus mykiss). The trout were exposed to a primary-treated effluent for 28 days before and after one of each of the following treatments: ultraviolet (UV) radiation, ozonation and peracetic acid. Immune function was characterized in leucocytes from the anterior head kidney by the following three parameters: phagocytosis activity, natural cytotoxic cells (NCC) function and lymphocyte (B and T) proliferation assays. The results show that the fish mass to length ratio was significantly decreased for the primary-treated and all three disinfection processes. Exposure to the primary-treated effluent led to a significant increase in macrophage-related phagocytosis; the addition of a disinfection step was effective in removing this effect. Both unstimulated and mitogen-stimulated T lymphocyte proliferation in fish decreased dramatically in fish exposed to the ozonated effluent compared to fish exposed to either the primary-treated effluent or to aquarium water. Stimulation of T lymphocytes proliferation was observed with the peracetic acid treatment group. In conclusion, the disinfection strategy used can modify the immune system in fish at the level of T lymphocyte proliferation but was effective to remove the effects on phagocytosis activity.

Improving Patient Safety Culture in Primary Care: A Systematic Review.

PubMed

Verbakel, Natasha J; Langelaan, Maaike; Verheij, Theo J M; Wagner, Cordula; Zwart, Dorien L M

2016-09-01

Patient safety culture, described as shared values, attitudes and behavior of staff in a health-care organization, gained attention as a subject of study as it is believed to be related to the impact of patient safety improvements. However, in primary care, it is yet unknown, which effect interventions have on the safety culture. To review literature on the use of interventions that effect patient safety culture in primary care. Searches were performed in PubMed, EMBASE, CINAHL, and PsychINFO on March 4, 2013. Terms defining safety culture were combined with terms identifying intervention and terms indicating primary care. Inclusion followed if the intervention effected patient safety culture, and effect measures were reported. The search yielded 214 articles from which two were eligible for inclusion. Both studies were heterogeneous in their interventions and outcome; we present a qualitative summary. One study described the implementation of an electronic medical record system in general practices as part of patient safety improvements. The other study facilitated 2 workshops for general practices, one on risk management and another on significant event audit. Results showed signs of improvement, but the level of evidence was low because of the design and methodological problems. These studies in general practice provide a first understanding of improvement strategies and their effect in primary care. As the level of evidence was low, no clear preference can be determined. Further research is needed to help practices make an informed choice for an intervention.

A comparison of latanoprost monotherapy with a combination therapy of timolol/dorzolamide in patients with primary open-angle glaucoma.

PubMed

Caça, Ihsan; Simsek, Hüseyin; Unlü, Kaan; Ari, Seyhmus; Keklikçi, Ugur

2006-01-01

We compared latanoprost monotherapy therapy with timolol/ dorzolamide in patients with primary open-angle glaucoma to evaluate the effects on intraocular pressure (IOP) and occurrence of adverse events. IOP and topical side effects were evaluated at the beginning, first, and third months. Mean IOP was decreased at the third month. The most common side effect was hyperemia (43.6%). We concluded that latanoprost reduces IOP better than fixed combination and its topical side effects are tolerable.

Group Investigation Teaching Technique in Turkish Primary Science Courses

ERIC Educational Resources Information Center

Aksoy, Gokhan; Gurbuz, Fatih

2013-01-01

This study examined the effectiveness of group investigation teaching technique in teaching "Light" unit 7th grade primary science education level. This study was carried out in two different classes in the Primary school during the 2011-2012 academic year in Erzurum, Turkey. One of the classes was the Experimental Group (group…

Assessing Learning in the Primary Classroom. Understanding Primary Education Series

ERIC Educational Resources Information Center

Johnson, Sandra

2011-01-01

"Assessing Learning in the Primary Classroom" is an accessible introduction to the concepts critical to a professional understanding of this vital aspect of a teacher's role. It comprehensively considers the principles underpinning effective assessment, the different forms it can take and the different purposes it serves, both within and beyond…

Influence of Examinations Oriented Approaches on Quality Education in Primary Schools in Kenya

ERIC Educational Resources Information Center

Mackatiani, Caleb Imbova

2017-01-01

This paper provides a critical appraisal of the influence of examinations oriented approaches on quality education in primary schools in Kenya. The purpose of the study was to determine effects of examination oriented teaching approaches on learning achievement among primary school pupils in Kakamega County, Kenya. It explored the assumptions…

Seasonal distribution of net primary production by functional groups in Chihuahuan Desert, and the role of seasonal precipitation

USDA-ARS?s Scientific Manuscript database

In hot deserts, precipitation is the principal driver for net primary production.  This study tested two hypotheses regarding aboveground net primary production (ANPP) and the effects of precipitation on ANPP in the Chihuahuan Desert, with emphasis on differences among seasons and among functional g...

Making More Effective Use of Moderation

ERIC Educational Resources Information Center

Rodger, Pauline

2018-01-01

Holt Primary School is a village school in which teachers work as a team within a climate of respect and trust. The teachers were fortunate to take part in the Bath Spa TAPS (Teacher Assessment in Primary Science) research project, which also overlapped with undertaking Gold PSQM (Primary Science Quality Mark). As a result, teacher confidence in…

The Opinions of Primary School Teachers' Candidates towards Material Preparation and Usage

ERIC Educational Resources Information Center

Genc, Zeynep

2016-01-01

Instruction materials help students to acquire more memorable information. Instruction materials have an important effect on providing more permanent and simple way of learning in every step of education. Instruction materials are the most frequently used by primary school teachers. Primary school teachers should support their lectures with…

Classroom Observation Data and Instruction in Primary Mathematics Education: Improving Design and Rigour

ERIC Educational Resources Information Center

Thompson, Carla J.; Davis, Sandra B.

2014-01-01

The use of formal observation in primary mathematics classrooms is supported in the literature as a viable method of determining effective teaching strategies and appropriate tasks for inclusion in the early years of mathematics learning. The twofold aim of this study was to (a) investigate predictive relationships between primary mathematics…

Understanding Teacher Expertise in Primary Science: A Sociocultural Approach

ERIC Educational Resources Information Center

Traianou, Anna

2006-01-01

In recent years much emphasis has been placed, both by researchers and by policy-makers, on the role that subject knowledge plays in the classroom practice of primary teachers. Within UK research on primary science education, this emphasis is often linked with constructivist ideas about effective teaching. In this article, I explore the…

Development of Program to Enhance Team Building Leadership Skills of Primary School Administrators

ERIC Educational Resources Information Center

Sairam, Boonchauy; Sirisuthi, Chaiyuth; Wisetrinthong, Kanjana

2017-01-01

Team building leadership skills are important to understandings of how the primary school administrators might work towards creating more effective teamwork in the school. This research aimed 1) to study the components of team building leadership skills needed for primary school administrators, 2) to examine the current states and desirable…

Distributed Leadership: Key to Improving Primary Students' Mathematical Knowledge

ERIC Educational Resources Information Center

Larson, Matthew R.; Smith, Wendy M.

2013-01-01

The purpose of this article is to present the findings of a quantitative study focused on primary mathematics teachers who participated in an intensive professional development program and then had leadership responsibility for the implementation of a new primary mathematics curriculum in their district. The study examines the effect of the…

Evaluation of Turkish Grammar Instruction Based on Primary School Teachers' Opinions

ERIC Educational Resources Information Center

Anilan, Hüseyin

2014-01-01

This study aims to evaluate the effectiveness of the holistic approach to Turkish grammar instruction in the first stage of primary education from the opinions and experiences of Turkish primary school teachers. This study is a qualitative research designed as a phenomenological study. The study participants were selected using maximum variation…

The Effects of a Professional Development Programme on Primary School Teachers' Perceptions of Physical Education

ERIC Educational Resources Information Center

Harris, Jo; Cale, Lorraine; Musson, Hayley

2011-01-01

The impact of a professional development programme on primary school teachers' perceptions of physical education was investigated. Primary school teachers from five local education authorities in England provided data for the study via pre-course audits, course evaluations immediately following the programme, and focus groups and individual…

Clinical and cost-effectiveness of computerised cognitive behavioural therapy for depression in primary care: Design of a randomised trial

PubMed Central

de Graaf, L Esther; Gerhards, Sylvia AH; Evers, Silvia MAA; Arntz, Arnoud; Riper, Heleen; Severens, Johan L; Widdershoven, Guy; Metsemakers, Job FM; Huibers, Marcus JH

2008-01-01

Background Major depression is a common mental health problem in the general population, associated with a substantial impact on quality of life and societal costs. However, many depressed patients in primary care do not receive the care they need. Reason for this is that pharmacotherapy is only effective in severely depressed patients and psychological treatments in primary care are scarce and costly. A more feasible treatment in primary care might be computerised cognitive behavioural therapy. This can be a self-help computer program based on the principles of cognitive behavioural therapy. Although previous studies suggest that computerised cognitive behavioural therapy is effective, more research is necessary. Therefore, the objective of the current study is to evaluate the (cost-) effectiveness of online computerised cognitive behavioural therapy for depression in primary care. Methods/Design In a randomised trial we will compare (a) computerised cognitive behavioural therapy with (b) treatment as usual by a GP, and (c) computerised cognitive behavioural therapy in combination with usual GP care. Three hundred mild to moderately depressed patients (aged 18–65) will be recruited in the general population by means of a large-scale Internet-based screening (N = 200,000). Patients will be randomly allocated to one of the three treatment groups. Primary outcome measure of the clinical evaluation is the severity of depression. Other outcomes include psychological distress, social functioning, and dysfunctional beliefs. The economic evaluation will be performed from a societal perspective, in which all costs will be related to clinical effectiveness and health-related quality of life. All outcome assessments will take place on the Internet at baseline, two, three, six, nine, and twelve months. Costs are measured on a monthly basis. A time horizon of one year will be used without long-term extrapolation of either costs or quality of life. Discussion Although computerised cognitive behavioural therapy is a promising treatment for depression in primary care, more research is needed. The effectiveness of online computerised cognitive behavioural therapy without support remains to be evaluated as well as the effects of computerised cognitive behavioural therapy in combination with usual GP care. Economic evaluation is also needed. Methodological strengths and weaknesses are discussed. Trial registration The study has been registered at the Netherlands Trial Register, part of the Dutch Cochrane Centre (ISRCTN47481236). PMID:18590518

a System Dynamics Model to Study the Importance of Infrastructure Facilities on Quality of Primary Education System in Developing Countries

NASA Astrophysics Data System (ADS)

Pedamallu, Chandra Sekhar; Ozdamar, Linet; Weber, Gerhard-Wilhelm; Kropat, Erik

2010-06-01

The system dynamics approach is a holistic way of solving problems in real-time scenarios. This is a powerful methodology and computer simulation modeling technique for framing, analyzing, and discussing complex issues and problems. System dynamics modeling and simulation is often the background of a systemic thinking approach and has become a management and organizational development paradigm. This paper proposes a system dynamics approach for study the importance of infrastructure facilities on quality of primary education system in developing nations. The model is proposed to be built using the Cross Impact Analysis (CIA) method of relating entities and attributes relevant to the primary education system in any given community. We offer a survey to build the cross-impact correlation matrix and, hence, to better understand the primary education system and importance of infrastructural facilities on quality of primary education. The resulting model enables us to predict the effects of infrastructural facilities on the access of primary education by the community. This may support policy makers to take more effective actions in campaigns.

[Levers in Primary Health Care - Identifying Strategic Success Factors for Improved Primary Care in Upper Austria].

PubMed

Kriegel, J; Rebhandl, E; Reckwitz, N; Hockl, W

2016-12-01

Current and projected general practitioner (GP) and primary care in Austria shows structural and process inadequacies in the quality as well as assurance of healthcare supply. The aim is therefore to develop solution- and patient-oriented measures that take patient-related requirements and medical perspectives into account. Using an effect matrix, subjective expert and user priorities were ascertained, cause and effect relationships were examined, and an expanded circle of success for the optimization of GP and primary care in Upper Austria was developed. Through this, the relevant levers for target-oriented development and optimization of the complex system of GP and primary care in Upper Austria were identified; these are training to become general practitioners, entrepreneurs as well as management and coordination. It is necessary to further adapt the identified levers conceptually and operationally in a targeted approach. This is to be achieved by means of the primary health care (PHC) concept as well as management tools and information and communication technologies (ICT) associated with it. © Georg Thieme Verlag KG Stuttgart · New York.

Mineral trioxide aggregate versus calcium hydroxide for pulpotomy in primary molars.

PubMed

Liu, He; Zhou, Qiong; Qin, Man

2011-01-01

To compare the effects of mineral trioxide aggregate (MTA) and calcium hydroxide (CH) for pulpotomy in primary molars. A randomised, bilateral self-controlled clinical trial was designed to compare the clinical effect of MTA and CH in pulpotomies in primary molars in 4- to 9-year-old children. Children with two similar-sized cavities on bilateral primary molar counterparts requiring pulpotomies were included. The two contralateral molars in each patient were randomly assigned to MTA or CH treatment. Clinical and radiographic examinations were performed to evaluate the treatment results at post-treatment recall. Seventeen pairs of self-controlled contralateral teeth were available for follow-up evaluations. The success rate of MTA was 94.1% (16/17), while the success rate of CH was 64.7% (11/17). Internal root resorption was the most frequent reason for failure in the CH group. Crown discolouration was common in the MTA-treated group. MTA was more successful than CH for pulpotomies in primary molar teeth, and may be a suitable replacement for CH in primary molar pulpotomies.

Effectiveness of a Psychoeducational Parenting Group on Child, Parent and Family Behavior: A Pilot Study in a Family Practice Clinic with an Underserved Population

PubMed Central

Berge, Jerica M.; Law, David D.; Johnson, Jennifer; Wells, M. Gawain

2013-01-01

Background Although integrated care for adults in primary care has steadily increased over the last several decades, there remains a paucity of research regarding integrated care for children in primary care. Purpose To report results of a pilot study testing initial feasibility of a parenting psychoeducational group targeting child behavioral problems within a primary care clinic. Method The participants (n = 35) were parents representing an underserved population from an inner-city primary care clinic. Participants attended a 12-week psychoeducational parenting group and reported pre- and post-measures of family functioning, child misbehavior and dyadic functioning. Paired t-tests and effects sizes are reported. Results Participants reported statistically significant improvement in family functioning, child misbehavior and couple functioning after participating in the parenting psychoeducational group. Conclusions Results suggest initial feasibility of a parenting psychoeducational group within a primary care clinic with an underserved population. This intervention may be useful for other primary care clinics seeking to offer more integrative care options for children and their families. PMID:20939627

Primary teachers conducting inquiry projects: effects on attitudes towards teaching science and conducting inquiry

NASA Astrophysics Data System (ADS)

van Aalderen-Smeets, Sandra I.; Walma van der Molen, Juliette H.; van Hest, Erna G. W. C. M.; Poortman, Cindy

2017-01-01

This study used an experimental, pretest-posttest control group design to investigate whether participation in a large-scale inquiry project would improve primary teachers' attitudes towards teaching science and towards conducting inquiry. The inquiry project positively affected several elements of teachers' attitudes. Teachers felt less anxious about teaching science and felt less dependent on contextual factors compared to the control group. With regard to attitude towards conducting inquiry, teachers felt less anxious and more able to conduct an inquiry project. There were no effects on other attitude components, such as self-efficacy beliefs or relevance beliefs, or on self-reported science teaching behaviour. These results indicate that practitioner research may have a partially positive effect on teachers' attitudes, but that it may not be sufficient to fully change primary teachers' attitudes and their actual science teaching behaviour. In comparison, a previous study showed that attitude-focused professional development in science education has a more profound impact on primary teachers' attitudes and science teaching behaviour. In our view, future interventions aiming to stimulate science teaching should combine both approaches, an explicit focus on attitude change together with familiarisation with inquiry, in order to improve primary teachers' attitudes and classroom practices.

Role Clarification Processes for Better Integration of Nurse Practitioners into Primary Healthcare Teams: A Multiple-Case Study

PubMed Central

D'Amour, Danielle; Contandriopoulos, Damien; Chouinard, Véronique; Dubois, Carl-Ardy

2014-01-01

Role clarity is a crucial issue for effective interprofessional collaboration. Poorly defined roles can become a source of conflict in clinical teams and reduce the effectiveness of care and services delivered to the population. Our objective in this paper is to outline processes for clarifying professional roles when a new role is introduced into clinical teams, that of the primary healthcare nurse practitioner (PHCNP). To support our empirical analysis we used the Canadian National Interprofessional Competency Framework, which defines the essential components for role clarification among professionals. A qualitative multiple-case study was conducted on six cases in which the PHCNP role was introduced into primary care teams. Data collection included 34 semistructured interviews with key informants involved in the implementation of the PHCNP role. Our results revealed that the best performing primary care teams were those that used a variety of organizational and individual strategies to carry out role clarification processes. From this study, we conclude that role clarification is both an organizational process to be developed and a competency that each member of the primary care team must mobilize to ensure effective interprofessional collaboration. PMID:25692039

Role clarification processes for better integration of nurse practitioners into primary healthcare teams: a multiple-case study.

PubMed

Brault, Isabelle; Kilpatrick, Kelley; D'Amour, Danielle; Contandriopoulos, Damien; Chouinard, Véronique; Dubois, Carl-Ardy; Perroux, Mélanie; Beaulieu, Marie-Dominique

2014-01-01

Role clarity is a crucial issue for effective interprofessional collaboration. Poorly defined roles can become a source of conflict in clinical teams and reduce the effectiveness of care and services delivered to the population. Our objective in this paper is to outline processes for clarifying professional roles when a new role is introduced into clinical teams, that of the primary healthcare nurse practitioner (PHCNP). To support our empirical analysis we used the Canadian National Interprofessional Competency Framework, which defines the essential components for role clarification among professionals. A qualitative multiple-case study was conducted on six cases in which the PHCNP role was introduced into primary care teams. Data collection included 34 semistructured interviews with key informants involved in the implementation of the PHCNP role. Our results revealed that the best performing primary care teams were those that used a variety of organizational and individual strategies to carry out role clarification processes. From this study, we conclude that role clarification is both an organizational process to be developed and a competency that each member of the primary care team must mobilize to ensure effective interprofessional collaboration.

Combined effect of oblateness, radiation and a circular cluster of material points on the stability of triangular liberation points in the R3BP

NASA Astrophysics Data System (ADS)

Singh, Jagadish; Taura, Joel John

2014-06-01

This paper studies the motion of an infinitesimal mass in the framework of the restricted three-body problem (R3BP) under the assumption that the primaries of the system are radiating-oblate spheroids, enclosed by a circular cluster of material points. It examines the effects of radiation and oblateness up to J 4 of the primaries and the potential created by the circular cluster, on the linear stability of the liberation locations of the infinitesimal mass. The liberation points are found to be stable for 0< μ< μ c and unstable for , where μ c is the critical mass value depending on terms which involve parameters that characterize the oblateness, radiation forces and the circular cluster of material points. The oblateness up to J 4 of the primaries and the gravitational potential from the circular cluster of material points have stabilizing propensities, while the radiation of the primaries and the oblateness up to J 2 of the primaries have destabilizing tendencies. The combined effect of these perturbations on the stability of the triangular liberation points is that, it has stabilizing propensity.

Seatbelt usage: is there an association with obesity?

PubMed

Behzad, B; King, D M; Jacobson, S H

2014-09-01

Wearing a seatbelt can prevent motor vehicle crash deaths. While primary seatbelt laws are designed to encourage vehicle passengers to wear seatbelts by allowing law enforcement officers to issue tickets when passengers do not wear seatbelts, discomfort may discourage obese individuals from wearing a seatbelt. The objective of this study is to assess the association between state-level obesity and seatbelt usage rates in the US, and to examine the possible role played by seatbelt laws in these associations. The strength of the association between obesity rates, seatbelt usage, and primary seatbelt laws at the state level is investigated using data from 2006 to 2011. Linear regression analysis is employed. This model estimates that increasing the obesity rate by 1% in a state where a primary seatbelt law (by which law enforcement officers can issue a ticket when seatbelts are not worn) is in effect is associated with a 0.06% decrease in seatbelt usage. However the same percentage of increase in the obesity rate in a state where no primary seatbelt law is in effect is associated with a 0.55% decrease in seatbelt usage. The magnitude of the statistical association between state obesity rates and state-level seatbelt usage is related to the existence of a primary seatbelt law, such that obesity has less impact on seatbelt usage in states where primary seatbelt laws are in effect. Published by Elsevier Ltd.

Schistosoma japonicum infection in the pig: the effect of a patent primary infection on a challenge infection.

PubMed

Willingham, A L; Bøgh, H O; Johansen, M V; Christensen, N O; Nansen, P

1997-06-24

The response of pigs to a challenge infection of Schistosoma japonicum following a primary infection was assessed using parasitological parameters and eosinophil counts. Twenty-five Danish Landrace/Yorkshire/Duroc crossbred pigs were divided into four groups. Group A (n = 10) received a primary infection, group B (n = 5) received both a primary and challenge infection, group C (n = 5) received a challenge control infection and group D (n = 5) received no infection serving as helminth-free controls. A dose of 850 cercariae was administered by intramuscular injection at the primary infection (week 0) and challenge infection (week 12). The pigs were perfused at week 21, except for half of the group A pigs which were slaughtered at week 12. Challenge infection did not result in higher worm burdens or tissue egg counts in group B than group A at week 21 and mature/immature worm ratios were similar for the two groups. In addition, no increases in faecal egg counts or eosinophil counts were observed in group B after challenge infection. The results indicate that pigs are able to mount a very rapid and effective response to reinfection with S. japonicum following a patent primary infection resulting in prevention of establishment of challenge infection schistosomes. An anti-worm effect appears to be the main feature of this regulatory host response.

Genotoxic and clastogenic effects of monohaloacetic acid drinking water disinfection by-products in primary human lymphocytes.

PubMed

Escobar-Hoyos, Luisa F; Hoyos-Giraldo, Luz Stella; Londoño-Velasco, Elizabeth; Reyes-Carvajal, Ingrid; Saavedra-Trujillo, Diana; Carvajal-Varona, Silvio; Sánchez-Gómez, Adalberto; Wagner, Elizabeth D; Plewa, Michael J

2013-06-15

The haloacetic acids (HAAs) are the second-most prevalent class of drinking water disinfection by-products formed by chemical disinfectants. Previous studies have determined DNA damage and repair of HAA-induced lesions in mammalian and human cell lines; however, little is known of the genomic DNA and chromosome damage induced by these compounds in primary human cells. The aim of this study was to evaluate the genotoxic and clastogenic effects of the monoHAA disinfection by-products in primary human lymphocytes. All monoHAAs were genotoxic in primary human lymphocytes, the rank order of genotoxicity and cytotoxicity was IAA > BAA > CAA. After 6 h of repair time, only 50% of the DNA damage (maximum decrease in DNA damage) was repaired compared to the control. This demonstrates that primary human lymphocytes are less efficient in repairing the induced damage by monoHAAs than previous studies with mammalian cell lines. In addition, the monoHAAs induced an increase in the chromosome aberration frequency as a measurement of the clastogenic effect of these compounds. These results coupled with genomic technologies in primary human cells and other mammalian non-cancerous cell lines may lead to the identification of biomarkers that may be employed in feedback loops to aid water chemists and engineers in the overall goal of producing safer drinking water. Copyright © 2013 Elsevier Ltd. All rights reserved.

Integrated economic and experimental framework for screening of primary recovery technologies for high cell density CHO cultures

PubMed Central

Popova, Daria; Stonier, Adam; Pain, David; Titchener‐Hooker, Nigel J.

2016-01-01

Abstract Increases in mammalian cell culture titres and densities have placed significant demands on primary recovery operation performance. This article presents a methodology which aims to screen rapidly and evaluate primary recovery technologies for their scope for technically feasible and cost‐effective operation in the context of high cell density mammalian cell cultures. It was applied to assess the performance of current (centrifugation and depth filtration options) and alternative (tangential flow filtration (TFF)) primary recovery strategies. Cell culture test materials (CCTM) were generated to simulate the most demanding cell culture conditions selected as a screening challenge for the technologies. The performance of these technology options was assessed using lab scale and ultra scale‐down (USD) mimics requiring 25–110mL volumes for centrifugation and depth filtration and TFF screening experiments respectively. A centrifugation and depth filtration combination as well as both of the alternative technologies met the performance selection criteria. A detailed process economics evaluation was carried out at three scales of manufacturing (2,000L, 10,000L, 20,000L), where alternative primary recovery options were shown to potentially provide a more cost‐effective primary recovery process in the future. This assessment process and the study results can aid technology selection to identify the most effective option for a specific scenario. PMID:27067803

Internal performance characteristics of vectored axisymmetric ejector nozzles

NASA Technical Reports Server (NTRS)

Lamb, Milton

1993-01-01

A series of vectoring axisymmetric ejector nozzles were designed and experimentally tested for internal performance and pumping characteristics at NASA-Langley Research Center. These ejector nozzles used convergent-divergent nozzles as the primary nozzles. The model geometric variables investigated were primary nozzle throat area, primary nozzle expansion ratio, effective ejector expansion ratio (ratio of shroud exit area to primary nozzle throat area), ratio of minimum ejector area to primary nozzle throat area, ratio of ejector upper slot height to lower slot height (measured on the vertical centerline), and thrust vector angle. The primary nozzle pressure ratio was varied from 2.0 to 10.0 depending upon primary nozzle throat area. The corrected ejector-to-primary nozzle weight-flow ratio was varied from 0 (no secondary flow) to approximately 0.21 (21 percent of primary weight-flow rate) depending on ejector nozzle configuration. In addition to the internal performance and pumping characteristics, static pressures were obtained on the shroud walls.

Optimal Treatment Decision for Brain Metastases of Unknown Primary Origin: The Role and Timing of Radiosurgery

PubMed Central

Han, Hyun Jin; Chang, Won Seok; Jung, Hyun Ho; Park, Yong Gou

2016-01-01

Background Up to 15% of all patients with brain metastases have no clearly detected primary site despite intensive evaluation, and this incidence has decreased with the use of improved imaging technology. Radiosurgery has been evaluated as one of the treatment modality for patients with limited brain metastases. In this study, we evaluated the effectiveness of radiosurgery for brain metastases from unknown primary tumors. Methods We retrospectively evaluated 540 patients who underwent gamma knife radiosurgery (GKRS) for brain metastases radiologically diagnosed between August 1992 and September 2007 in our institution. First, the brain metastases were grouped into metachronous, synchronous, and precocious presentations according to the timing of diagnosis of the brain metastases. Then, synchronous and precocious brain metastases were further grouped into 1) unknown primary; 2) delayed known primary; and 3) synchronous metastases according to the timing of diagnosis of the primary origin. We analyzed the survival time and time to new brain metastasis in each group. Results Of the 540 patients, 29 (5.4%) presented precocious or synchronous metastases (34 GKRS procedures for 174 lesions). The primary tumor was not found even after intensive and repeated systemic evaluation in 10 patients (unknown primary, 34.5%); found after 8 months in 3 patients (delayed known primary, 1.2%); and diagnosed at the same time as the brain metastases in 16 patients (synchronous metastasis, 55.2%). No statistically significant differences in survival time and time to new brain metastasis were found among the three groups. Conclusion Identification of a primary tumor before GKRS did not affect the patient outcomes. If other possible differential diagnoses were completely excluded, early GKRS can be an effective treatment option for brain metastases from unknown primary tumor. PMID:27867920

A simple, cost-effective method for generating murine colonic 3D enteroids and 2D monolayers for studies of primary epithelial cell function.

PubMed

Fernando, Elizabeth H; Dicay, Michael; Stahl, Martin; Gordon, Marilyn H; Vegso, Andrew; Baggio, Cristiane; Alston, Laurie; Lopes, Fernando; Baker, Kristi; Hirota, Simon; McKay, Derek M; Vallance, Bruce; MacNaughton, Wallace K

2017-11-01

Cancer cell lines have been the mainstay of intestinal epithelial experimentation for decades, due primarily to their immortality and ease of culture. However, because of the inherent biological abnormalities of cancer cell lines, many cellular biologists are currently transitioning away from these models and toward more representative primary cells. This has been particularly challenging, but recent advances in the generation of intestinal organoids have brought the routine use of primary cells within reach of most epithelial biologists. Nevertheless, even with the proliferation of publications that use primary intestinal epithelial cells, there is still a considerable amount of trial and error required for laboratories to establish a consistent and reliable method to culture three-dimensional (3D) intestinal organoids and primary epithelial monolayers. We aim to minimize the time other laboratories spend troubleshooting the technique and present a standard method for culturing primary epithelial cells. Therefore, we have described our optimized, high-yield, cost-effective protocol to grow 3D murine colonoids for more than 20 passages and our detailed methods to culture these cells as confluent monolayers for at least 14 days, enabling a wide variety of potential future experiments. By supporting and expanding on the current literature of primary epithelial culture optimization and detailed use in experiments, we hope to help enable the widespread adoption of these innovative methods and allow consistency of results obtained across laboratories and institutions. NEW & NOTEWORTHY Primary intestinal epithelial monolayers are notoriously difficult to maintain culture, even with the recent advances in the field. We describe, in detail, the protocols required to maintain three-dimensional cultures of murine colonoids and passage these primary epithelial cells to confluent monolayers in a standardized, high-yield and cost-effective manner. Copyright © 2017 the American Physiological Society.

The causal effect of increased primary schooling on child mortality in Malawi: Universal primary education as a natural experiment.

PubMed

Makate, Marshall; Makate, Clifton

2016-11-01

The primary objective of this analysis is to investigate the causal effect of mother's schooling on under-five health - and the passageways through which schooling propagates - by exploiting the exogenous variability in schooling prompted by the 1994 universal primary schooling program in Malawi. This education policy, which saw the elimination of tuition fees across all primary schooling grades, creates an ideal setting for observing the causal influence of improved primary school enrollment on the under-five fatality rates of the subsequent generation. Our analysis uses data from three waves of the nationally representative Malawi Demographic and Health Surveys conducted in 2000, 2004/05, and 2010. To address the potential endogeneity of schooling, we employ the mother's age at implementation of the tuition-free primary school policy in 1994 as an instrumental variable for the prospect of finishing primary level instruction. The results suggest that spending one year in school translated to a 3.22 percentage point reduction in mortality for infants and a 6.48 percent reduction for children under age five years. For mothers younger than 19 years, mortality was reduced by 5.95 percentage points. These figures remained approximately the same even after adjusting for potential confounders. However, we failed to find any statistically meaningful effect of the mother's education on neonatal survival. The juvenile fatality estimates we find are weakly robust to several robustness checks. We also explored the potential mechanisms by which increased maternal schooling might help enhance child survival. The findings indicated that an added year of motherly learning considerably improves the prospect of prenatal care use, literacy levels, father's educational level, and alters fertility behavior. Our results suggest that increasing the primary schooling prospects for young women might help reduce under-five mortality in less-industrialized regions experiencing high under-five fatalities such as in sub-Saharan Africa. Copyright © 2016 Elsevier Ltd. All rights reserved.

A retrospective analysis of the relationship between medical student debt and primary care practice in the United States.

PubMed

Phillips, Julie P; Petterson, Stephen M; Bazemore, Andrew W; Phillips, Robert L

2014-01-01

We undertook a study to reexamine the relationship between educational debt and primary care practice, accounting for the potentially confounding effect of medical student socioeconomic status. We performed retrospective multivariate analyses of data from 136,232 physicians who graduated from allopathic US medical schools between 1988 and 2000, obtained from the American Association of Medical Colleges Graduate Questionnaire, the American Medical Association Physician Masterfile, and other sources. Need-based loans were used as markers for socioeconomic status of physicians' families of origin. We examined 2 outcomes: primary care practice and family medicine practice in 2010. Physicians who graduated from public schools were most likely to practice primary care and family medicine at graduating educational debt levels of $50,000 to $100,000 (2010 dollars; P <.01). This relationship between debt and primary care practice persisted when physicians from different socioeconomic status groups, as approximated by loan type, were examined separately. At higher debt, graduates' odds of practicing primary care or family medicine declined. In contrast, private school graduates were not less likely to practice primary care or family medicine as debt levels increased. High educational debt deters graduates of public medical schools from choosing primary care, but does not appear to influence private school graduates in the same way. Students from relatively lower income families are more strongly influenced by debt. Reducing debt of selected medical students may be effective in promoting a larger primary care physician workforce. © 2014 Annals of Family Medicine, Inc.

A Retrospective Analysis of the Relationship Between Medical Student Debt and Primary Care Practice in the United States

PubMed Central

Phillips, Julie P.; Petterson, Stephen M.; Bazemore, Andrew W.; Phillips, Robert L.

2014-01-01

PURPOSE We undertook a study to reexamine the relationship between educational debt and primary care practice, accounting for the potentially confounding effect of medical student socioeconomic status. METHODS We performed retrospective multivariate analyses of data from 136,232 physicians who graduated from allopathic US medical schools between 1988 and 2000, obtained from the American Association of Medical Colleges Graduate Questionnaire, the American Medical Association Physician Masterfile, and other sources. Need-based loans were used as markers for socioeconomic status of physicians’ families of origin. We examined 2 outcomes: primary care practice and family medicine practice in 2010. RESULTS Physicians who graduated from public schools were most likely to practice primary care and family medicine at graduating educational debt levels of $50,000 to $100,000 (2010 dollars; P <.01). This relationship between debt and primary care practice persisted when physicians from different socioeconomic status groups, as approximated by loan type, were examined separately. At higher debt, graduates’ odds of practicing primary care or family medicine declined. In contrast, private school graduates were not less likely to practice primary care or family medicine as debt levels increased. CONCLUSIONS High educational debt deters graduates of public medical schools from choosing primary care, but does not appear to influence private school graduates in the same way. Students from relatively lower income families are more strongly influenced by debt. Reducing debt of selected medical students may be effective in promoting a larger primary care physician workforce. PMID:25384816

A comparative evaluation of antibacterial effectiveness of sodium hypochlorite, Curcuma longa, and Camellia sinensis as irrigating solutions on isolated anaerobic bacteria from infected primary teeth.

PubMed

Dhariwal, Neha Shashikant; Hugar, Shivayogi M; Harakuni, Sheetal; Sogi, Suma; Assudani, Harsha G; Mistry, Laresh Naresh

2016-01-01

In endodontics, most of the commercial intra-canal medicaments have cytotoxic reactions and because of their inability to eliminate bacteria from dentinal tubules, recent medicine has turned its attention to the usage of biologic medication prepared from natural plants. The literature to testify the efficacy of natural alternatives in primary teeth is meagre and its effects as irrigating solutions need to be evaluated. To evaluate the antibacterial effectiveness of sodium hypochlorite, ethanolic extracts of Curcuma longa (turmeric) and Camellia sinensis (green tea) as irrigating solutions against the anaerobic bacteria isolated from the root canals of infected primary teeth. Thirty patients were selected based on the selected inclusion and exclusion criteria. Preoperative radiographs were taken. Rubber dam isolation and working length estimation were done, following which thirty samples were taken from the root canals of infected primary teeth using sterile absorbent paper points and transferred to tubes containing thioglycolate transport medium. The bacteria were then isolated using standard microbiological protocols and were subjected to antibiotic sensitivity testing using the three test irrigants. SPSS 18 software using Chi-square test was used for statistical analysis. The most commonly isolated bacteria included Porphyromonas sp., Bacteroides fragilis, Peptostreptococcus, and Staphylococcus aureus. Sodium hypochlorite and C. longa (turmeric) showed good antibacterial effect and were effective against most of the isolated bacteria. There was statistically significant difference in the antibacterial effect among the three tested groups (P < 0.001). The least effective was C. sinensis (green tea). The infected primary teeth almost always present with a polymicrobial structure with a wide variety of anaerobic bacteria. The chemo-mechanical preparation plays an important role in eradicating the population of predominant micro-organisms in treating these teeth with promising effects with the use of newer test irrigants while avoiding the side effects of sodium hypochlorite.

Oral fennel (Foeniculum vulgare) drop effect on primary dysmenorrhea: Effectiveness of herbal drug.

PubMed

Bokaie, Mahshid; Farajkhoda, Tahmineh; Enjezab, Behnaz; Khoshbin, Azam; Karimi-Zarchi, Mojgan; Zarchi Mojgan, Karimi

2013-03-01

Primary dysmenorrhea refers to the occurrence of painful menstrual cramps of uterus and is considered as a gynecological complaint. The common treatment for this problem is medical therapy such as mefenamic acid [non-steroidal anti-inflammatory drugs (NSAIDs)] and oral contraceptive pills, both of which work by reducing myometrial activity. Fennel contains an antispasmodic and anethol agents and may be helpful for management of primary dysmenorrhea. The aim of this study was to evaluate the effects of oral fennel drop for treating primary dysmenorrhea. Sixty college students suffering from primary dysmenorrhea were randomly assigned to two groups and followed up for two cycles. Statistical analysis was performed using SPSS version 16. P < 0.05 was considered to be statistically significant. Parametric and non-parametric tests were adopted. Comparison of pain intensity in the two groups showed that there was no significant difference in pain relief between the two groups. Comparison of bleeding severity in the study group before and after intervention was demonstrated from the first day to the fifth day (PV on first day, second day, third day, fourth day, and fifth day 0.948, 0.330, 0.508, 0.583, 0.890, respectively). It seems that fennel can be effective in reducing the severity of dysmenorrhea, but it has an unpleasant taste in view of most of the volunteers.

Comparative effects on rat primary astrocytes and C6 rat glioma cells cultures after 24-h exposure to silver nanoparticles (AgNPs)

NASA Astrophysics Data System (ADS)

Salazar-García, Samuel; Silva-Ramírez, Ana Sonia; Ramirez-Lee, Manuel A.; Rosas-Hernandez, Hector; Rangel-López, Edgar; Castillo, Claudia G.; Santamaría, Abel; Martinez-Castañon, Gabriel A.; Gonzalez, Carmen

2015-11-01

The aim of this work was to compare the effects of 24-h exposure of rat primary astrocytes and C6 rat glioma cells to 7.8 nm AgNPs. Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and current treatments lead to diverse side-effects; for this reason, it is imperative to investigate new approaches, including those alternatives provided by nanotechnology, like nanomaterials (NMs) such as silver nanoparticles. Herein, we found that C6 rat glioma cells, but no primary astrocytes, decreased cell viability after AgNPs treatment; however, both cell types diminished their proliferation. The decrease of glioma C6 cells proliferation was related with necrosis, while in primary astrocytes, the decreased proliferation was associated with the induction of apoptosis. The ionic control (AgNO3) exerted a different profile than AgNPs; the bulk form did not modify the basal effect in each determination, whereas cisplatin, a well-known antitumoral drug used as a comparative control, promoted cytotoxicity in both cell types at specific concentrations. Our findings prompt the need to determine the fine molecular and cellular mechanisms involved in the differential biological responses to AgNPs in order to develop new tools or alternatives based on nanotechnology that may contribute to the understanding, impact and use of NMs in specific targets, like glioblastoma cells.

Sulforaphane suppressed LPS-induced inflammation in mouse peritoneal macrophages through Nrf2 dependent pathway

PubMed Central

Lin, Wen; Wu, Rachel T; Wu, Tienyuan; Khor, Tin-Oo; Wang, Hu; Kong, Ah-Ng

2008-01-01

Sulforaphane (SFN) is a natural isothiocyanate that is present in cruciferous vegetables such as broccoli and cabbage. Previous studies have shown that SFN is effective in preventing carcinogenesis induced by carcinogens in rodents, which is related in part to its potent anti-inflammation properties. In the present study, we compared the anti-inflammatory effect of SFN on LPS-stimulated inflammation in primary peritoneal macrophages derived from Nrf2 (+/+) and Nrf2 mice. Pretreatment of SFN in Nrf2 (+/+) primary peritoneal macrophages potently inhibited LPS-stimulated mRNA expression, protein expression and production of TNFα, IL-1β, Cox-2 and iNOS. HO-1 expression, which is significantly augmented in LPS-stimulated Nrf2 (+/+) primary peritoneal macrophages by SFN. Interestingly, the anti-inflammatory effect was attenuated in Nrf2 (−/−) primary peritoneal macrophages. We concluded that SFN exerts its anti-inflammatory activity mainly via activation of Nrf2 in mouse peritoneal macrophages. PMID:18755157

Effects of morphology and wavelength on the measurement accuracy of soot volume fraction by laser extinction

NASA Astrophysics Data System (ADS)

Wang, Ya-fei; Huang, Qun-xing; Wang, Fei; Chi, Yong; Yan, Jian-hua

2018-01-01

A novel method to evaluate the quantitative effects of soot morphology and incident wavelength on the measurement accuracy of soot volume fraction, by the laser extinction (LE) technique is proposed in this paper. The results indicate that the traditional LE technique would overestimate soot volume fraction if the effects of morphology and wavelength are not considered. Before the agglomeration of isolated soot primary particles, the overestimation of the LE technique is in the range of 2-20%, and rises with increasing primary particle diameter and with decreasing incident wavelength. When isolated primary particles are agglomerated into fractal soot aggregates, the overestimation would exceed 30%, and rise with increasing primary particle number per soot aggregate, fractal dimension and fractal prefactor and with decreasing incident wavelength to a maximum value of 55%. Finally, based on these results above, the existing formula of the LE technique gets modified, and the modification factor is 0.65-0.77.

The Effects of School-Based Maum Meditation Program on the Self-Esteem and School Adjustment in Primary School Students

PubMed Central

Yoo, Yang Gyeong; Lee, In Soo

2013-01-01

Self-esteem and school adjustment of children in the lower grades of primary school, the beginning stage of school life, have a close relationship with development of personality, mental health and characters of children. Therefore, the present study aimed to verify the effect of school-based Maum Meditation program on children in the lower grades of primary school, as a personality education program. The result showed that the experimental group with application of Maum Meditation program had significant improvements in self-esteem and school adjustment, compared to the control group without the application. In conclusion, since the study provides significant evidence that the intervention of Maum Meditation program had positive effects on self-esteem and school adjustment of children in the early stage of primary school, it is suggested to actively employ Maum Meditation as a school-based meditation program for mental health promotion of children in the early school ages, the stage of formation of personalities and habits. PMID:23777717

Aspirin and the Primary Prevention of Cardiovascular Diseases: An Approach Based on Individualized, Integrated Estimation of Risk.

PubMed

Volpe, Massimo; Battistoni, Allegra; Gallo, Giovanna; Coluccia, Roberta; De Caterina, Raffaele

2017-09-01

While the use of aspirin in the secondary prevention of cardiovascular (CVD) is well established, aspirin in primary prevention is not systematically recommended because the absolute CV event reduction is similar to the absolute excess in major bleedings. Recently, emerging evidence suggests the possibility that the assumption of aspirin, may also be effective in the prevention of cancer. By adding to the CV prevention benefits the potential beneficial effect of aspirin in reducing the incidence of mortality and cancer could tip the balance between risks and benefits of aspirin therapy in the primary prevention in favour of the latter and broaden the indication for treatment with in populations at average risk. While prospective and randomized study are currently investigating the effect of aspirin in prevention of both cancer and CVD, clinical efforts at the individual level to promote the use of aspirin in global (or total) primary prevention could be already based on a balanced evaluation of the benefit/risk ratio.

Basal insulin initiation in primary vs. specialist care: similar glycaemic control in two different patient populations.

PubMed

Orozco-Beltran, D; Pan, C; Svendsen, A L; Faerch, L; Caputo, S

2016-03-01

To investigate the effect of healthcare provider (HCP) type (primary vs. specialist) on glycaemic control and other treatment parameters. Study of Once-Daily Levemir (SOLVE(™) ) is an international, 24-week, observational study of insulin initiation in people with type 2 diabetes. A total of 17,374 subjects were included, comprising 4144 (23.9%) primary care subjects. Glycaemic control improved in both HCP groups from baseline to final visit [glycated haemoglobin (HbA1c) -1.2 ± 1.4% (-13.1 ± 15.3 mmol/mol) and -1.3 ± 1.6% (-14.2 ± 17.5 mmol/mol), respectively]. After adjustment for known confounders, there was no statistically significant effect of HCP group on final HbA1c [-0.04%, 95% confidence interval (CI) -0.09 to -0.01 (-0.4 mmol/mol, 95% CI -1.0-0.1 mmol/mol), p = 0.1590]. However, insulin doses at the final visit were higher in primary care patients (+0.06, 95% CI 0.06-0.07 U/kg, p < 0.0001). Logistic regression demonstrated a significant effect of HCP type (primary vs. specialist care) on hypoglycaemia risk [odds ratio (OR) 0.75, 95% CI 0.64-0.87, p = 0.0002]. Primary care physicians took more time to train patients and had more frequent contact with patients than specialists (both p < 0.0001). Primary care physicians and specialists achieved comparable improvements in glycaemic control following insulin initiation. © 2016 The Authors. International Journal of Clinical Practice Published by John Wiley & Sons Ltd.

Primary Enforcement of Mandatory Seat Belt Laws and Motor Vehicle Crash Deaths.

PubMed

Harper, Sam; Strumpf, Erin C

2017-08-01

Policies that allow directly citing motorists for seat belt non-use (primary enforcement) have been shown to reduce motor vehicle crash deaths relative to secondary enforcement, but the evidence base is dated and does not account for recent improvements in vehicle designs and road safety. The purpose of this study was to test whether recent upgrades to primary enforcement still reduce motor vehicle crash deaths. In 2016, researchers used motor vehicle crash death data from the Fatal Analysis Reporting System for 2000-2014 and calculated rates using both person- and exposure-based denominators. Researchers used a difference-in-differences design to estimate the effect of primary enforcement on death rates, and estimated negative binomial regression models, controlling for age, substance use involvement, fixed state characteristics, secular trends, state median household income, and other state-level traffic safety policies. Models adjusted only for crash characteristics and state-level covariates models showed a protective effect of primary enforcement (rate ratio, 0.88, 95% CI=0.77, 0.98; rate difference, -1.47 deaths per 100,000 population, 95% CI= -2.75, -0.19). After adjustment for fixed state characteristics and secular trends, there was no evidence of an effect of upgrading from secondary to primary enforcement in the whole population (rate ratio, 0.98, 95% CI=0.92, 1.04; rate difference, -0.22, 95% CI= -0.90, 0.46) or for any age group. Upgrading to primary enforcement no longer appears protective for motor vehicle crash death rates. Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

A study protocol testing the implementation, efficacy, and cost effectiveness of the ezParent program in pediatric primary care

PubMed Central

Schoeny, Michael; Risser, Heather; Johnson, Tricia

2016-01-01

Introduction Up to 20% of children demonstrate behavior problems that interfere with relationship development and academic achievement. Parent participation in behavioral parent training programs has been shown to decrease child problem behaviors and promote positive parent-child relationships. However, attendance and parent involvement in face-to-face parent training remain low. Testing the implementation, efficacy, and cost of alternative delivery models is needed to (a) increase the reach and sustainability of parent training interventions and (b) address the barriers to parent participation and implementation of such programs, specifically in primary health care settings. The purpose of this paper is to describe the study protocol evaluating the implementation, efficacy, and cost-effectiveness of delivering the tablet-based ezParent program in pediatric primary care sites. Methods The implementation of the ezParent in four pediatric primary care sites will be evaluated using a descriptive design and cost-effectiveness analysis. The efficacy of the ezParent will be tested using a randomized controlled trial design with 312 parents of 2 to 5 year old children from pediatric primary care settings. Data on parenting and child behavior outcomes will be obtained from all participants at baseline, and 3, 6, and 12 months post baseline. Discussion Integrating and evaluating the implementation of the ezParent in pediatric primary care is an innovative opportunity to promote positive parenting with potential for universal access to the preschool population and for low cost by building on existing infrastructure in pediatric primary care. PMID:27592122

The Effect of Text Types on Reading Comprehension

ERIC Educational Resources Information Center

Sahin, Ayfer

2013-01-01

Aim of this study is to determine the effect of narrative and informative text types on Reading Comprehension levels of Primary Education 4th and 5th grade students. Application was fulfilled in 2011-2012 academic year with 134 students in a primary education school in Province Kirsehir. Reading comprehension tests prepared according to text types…

Implementing Self-Assessment in Singapore Primary Schools: Effects on Students' Perceptions of Self-Assessment

ERIC Educational Resources Information Center

Wong, Hwei Ming

2017-01-01

Student academic self-assessment engages the students in deliberate reflection about what they are learning and how they are learning it. This intervention study investigated the effects of self-assessment training on students' perceptions towards self-assessment in two Singaporean primary schools. The study, which used a pretest-posttest design,…