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BACKGROUND: Pseudomonas aeruginosa (PA) is a common cause of healthcare-associated infection (PA-HAI) in the intensive care unit (ICU). AIM: To describe the epidemiology of PA-HAI in ICUs in Ontario, Canada, and to identify episodes of sink-to-patient PA transmission. METHODS: This was a prospective cohort study of patients in six ICUs from 2018 to 2019, with retrieval of PA clinical isolates, and PA-screening of antimicrobial-resistant organism surveillance rectal swabs, and of sink drain, air, and faucet samples. All PA isolates underwent whole-genome sequencing. PA-HAI was defined using US National Healthcare Safety Network criteria. ICU-acquired PA was defined as PA isolated from specimens obtained ≥48 h after ICU admission in those with prior negative rectal swabs. Sink-to-patient PA transmission was defined as ICU-acquired PA with close genomic relationship to isolate(s) previously recovered from sinks in a room/bedspace occupied 3-14 days prior to collection date of the relevant patient specimen. FINDINGS: Over ten months, 72 PA-HAIs occurred among 60/4263 admissions. The rate of PA-HAI was 2.40 per 1000 patient-ICU-days; higher in patients who were PA-colonized on admission. PA-HAI was associated with longer stay (median: 26 vs 3 days uninfected; P < 0.001) and contributed to death in 22/60 cases (36.7%). Fifty-eight admissions with ICU-acquired PA were identified, contributing 35/72 (48.6%) PA-HAIs. Four patients with five PA-HAIs (6.9%) had closely related isolates previously recovered from their room/bedspace sinks. CONCLUSION: Nearly half of PA causing HAI appeared to be acquired in ICUs, and 7% of PA-HAIs were associated with sink-to-patient transmission. Sinks may be an under-recognized reservoir for HAIs.
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Infecção Hospitalar , Unidades de Terapia Intensiva , Infecções por Pseudomonas , Pseudomonas aeruginosa , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/classificação , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/transmissão , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/transmissão , Infecções por Pseudomonas/microbiologia , Estudos Prospectivos , Ontário/epidemiologia , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Adulto , Idoso de 80 Anos ou mais , Sequenciamento Completo do GenomaRESUMO
A 41-year old woman was treated for cholera at one of the health centers in Blantyre. Two days after discharge from the treatment unit, she developed weakness of all 4 limbs and difficulties with speech. She was referred to the Queen Elizabeth Central Hospital. A CT scan of the brain showed hypodense lesions in the pons. A diagnosis of central pontine myelinolysis was made. She recovered slowly and was discharged from hospital 17 days after admission.
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Cólera , Mielinólise Central da Ponte , Feminino , Humanos , Adulto , Cólera/complicações , Cólera/diagnóstico , Cólera/patologia , Mielinólise Central da Ponte/diagnóstico , Mielinólise Central da Ponte/patologia , Ponte/patologia , Encéfalo , Tomografia Computadorizada por Raios X , Imageamento por Ressonância MagnéticaRESUMO
Male genital schistosomiasis (MGS) is hypothesized to increase seminal shedding of HIV-1. This prospective pilot study assessed seminal HIV-1 RNA shedding in men on long-term ART with and without a diagnosis of MGS. Study visits occurred at 0, 1, 3, 6 and 12 months. MGS was diagnosed by egg positivity on semen microscopy or PCR of seminal sediment. After optimization of the HIV-RNA assay, we examined 72 paired plasma and semen samples collected from 31 men (15 with and 16 without MGS) over 12 months. HIV-1 RNA was detected in 7/72 (9.7%) seminal samples and 25/72 (34.7%) plasma samples. When comparing sample pairs, 5/72 (6.9%) showed HIV-1 RNA detection only in the seminal sample. Overall, 3/31 (9.7%) participants, all with MGS, had detectable HIV-1 RNA in semen while plasma HIV-1 RNA was undetectable (< 22 copies/mL), with seminal levels ranging up to 400 copies/mL. Two participants showing HIV-1 RNA in seminal fluid from the MGS-negative group also had concomitant HIV-1 RNA detection in plasma. The findings suggest that MGS can be associated with low-level HIV-1 RNA shedding despite virologically suppressive ART. Further studies are warranted to confirm these observations and assess its implications.
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Soropositividade para HIV , HIV-1 , Esquistossomose , Humanos , Masculino , HIV-1/genética , Projetos Piloto , Lagos , Malaui , Estudos Prospectivos , Genitália , RNARESUMO
Carbohydrates, proteins and lipids are essential nutrients to all animals; however, closely related species, populations, and individuals can display dramatic variation in diet. Here we explore the variation in macronutrient tolerance in Drosophila melanogaster using the Drosophila genetic reference panel, a collection of ~200 strains derived from a single natural population. Our study demonstrates that D. melanogaster, often considered a "dietary generalist", displays marked genetic variation in survival on different diets, notably on high-sugar diet. Our genetic analysis and functional validation identify several regulators of macronutrient tolerance, including CG10960/GLUT8, Pkn and Eip75B. We also demonstrate a role for the JNK pathway in sugar tolerance and de novo lipogenesis. Finally, we report a role for tailless, a conserved orphan nuclear hormone receptor, in regulating sugar metabolism via insulin-like peptide secretion and sugar-responsive CCHamide-2 expression. Our study provides support for the use of nutrigenomics in the development of personalized nutrition.
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Proteínas de Drosophila , Drosophila melanogaster , Animais , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Variação Genética , Nutrientes , Açúcares/metabolismo , Fatores de Transcrição/metabolismoRESUMO
OBJECTIVES: Exercise addiction can be secondary to eating disorders, or a primary condition in the absence of another disorder. Currently, to determine secondary exercise addiction, two screening tools must be administered. The aim of this study was to validate a novel screening tool able to stratify between primary and secondary exercise addiction, called the secondary exercise addiction scale (SEAS). METHODS: Phase 1 (n = 339) described the statistical reduction of an initial pool of scale items. Phase 2 (n = 382) used a confirmatory factor analysis (CFA) to examine the robustness of the latent structure. Phase 3 (n = 721) determined cut off scores for the eating disorder and exercise addiction sections of the SEAS and determine concurrent reliability with the exercise addiction inventory (EAI) and the SCOFF questionnaires. Phase 4 (n = 45) determined test-retest reliability. RESULTS: Phase 1 extracted two components: exercise addiction and eating disorder symptomology, with 11 items retained. The CFA in Phase 2 showed an acceptable fit to the proposed model (comparative fit index = 0.93, Tucker Lewis Index = 0.91). Phase 3 determined cut off scores of ≥ 28 (specificity = 91.97%), and ≥ 20 (specificity = 96.27%) in the respective exercise addiction and eating disorders sections of the SEAS. The respective sections also correlated well with the EAI (r = 0.70, p = < 0.001) and the SCOFF (r = 0.72, p = < 0.001). Phase 4 showed excellent test-retest reliability (exercise addiction r = 0.95, p = < 0.001, eating disorders r = 0.93, p = < 0.001). CONCLUSION: The SEAS appears to be a valid and reliable tool for measuring primary and secondary exercise addiction. Further studies are warranted to further validate this tool amongst clinical populations. LEVEL OF EVIDENCE: Level III: evidence obtained from cohort or case-control analytic studies.
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Comportamento Aditivo , Transtornos da Alimentação e da Ingestão de Alimentos , Comportamento Aditivo/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Humanos , Psicometria , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
COVID-19 vaccination has been globally accepted as a critical public health response measure to prevent severe disease and death, alleviate strain on healthcare systems, and prevent onward transmission of SARS-CoV-2. The South African Department of Health's plan to vaccinate 1.25 million healthcare workers through the Sisonke Early Access Vaccine Rollout for Healthcare Workers presented both opportunities and challenges in terms of designing and implementing a mass vaccination roll-out in the resource-limited state sector. We present our experiences and challenges from the largest hospital in Africa, and hope that this will assist other institutions with planning successful COVID-19 mass vaccination campaigns.
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Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Pessoal de Saúde , Vacinação em Massa/organização & administração , Humanos , Saúde Pública , África do SulRESUMO
BACKGROUND: Decades of studies document an association between Gammaproteobacteria in sink drains and hospital-acquired infections, but the evidence for causality is unclear. AIM: We aimed to develop a tool to assess the quality of evidence for causality in research studies that implicate sink drains as reservoirs for hospital-acquired Gammaproteobacterial infections. METHODS: We used a modified Delphi process with recruited experts in hospital epidemiology to develop this tool from a pre-existing causal assessment application. FINDINGS: Through four rounds of feedback and revision we developed the 'Modified CADDIS Tool for Causality Assessment of Sink Drains as a Reservoir for Hospital-Acquired Gammaproteobacterial Infection or Colonization'. In tests of tool application to published literature during development, mean percent agreement ranged from 46.7% to 87.5%, and the Gwet's AC1 statistic (adjusting for chance agreement) ranged from 0.13 to 1.0 (median 68.1). Areas of disagreement were felt to result from lack of a priori knowledge of causal pathways from sink drains to patients and uncertain influence of co-interventions to prevent organism acquisition. Modifications were made until consensus was achieved that further iterations would not improve the tool. When the tool was applied to 44 articles by two independent reviewers in an ongoing systematic review, percent agreement ranged from 93% to 98%, and the Gwet's AC1 statistic was 0.91-0.97. CONCLUSION: The modified causality tool was useful for evaluating studies that implicate sink drains as reservoirs for hospital-acquired infections and may help guide the conduct and reporting of future research.
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Infecção Hospitalar/prevenção & controle , Reservatórios de Doenças/microbiologia , Contaminação de Equipamentos/prevenção & controle , Equipamentos e Provisões Hospitalares/microbiologia , Infecções por Bactérias Gram-Negativas/prevenção & controle , Software , Causalidade , Infecção Hospitalar/microbiologia , Contaminação de Equipamentos/estatística & dados numéricos , Gammaproteobacteria , Infecções por Bactérias Gram-Negativas/transmissão , Hospitais/estatística & dados numéricos , Humanos , Controle de Infecções/métodosRESUMO
BACKGROUND: Hospital drains may be an important reservoir for carbapenemase-producing Enterobacterales (CPE). AIM: To determine prevalence of CPE in hospital drains exposed to inpatients with CPE, relatedness of drain and patient CPE, and risk factors for drain contamination. METHODS: Sink and shower drains in patient rooms and communal shower rooms exposed to 310 inpatients with CPE colonization/infection were cultured at 10 hospitals. Using short- and long-read whole-genome sequencing, inpatient and corresponding drain CPE were compared. Risk factors for drain contamination were assessed using multi-level modelling. FINDINGS: Of 1209 exposed patient room and communal shower room drains, 53 (4%) yielded 62 CPE isolates in seven (70%) hospitals. Of 49 CPE isolates in patient room drains, four (8%) were linked to prior room occupants. Linked drain/room occupant pairs included Citrobacter freundii ST18 isolates separated by eight single nucleotide variants (SNVs), related blaKPC-containing IncN3-type plasmids (different species), related blaKPC-3-containing IncN-type plasmids (different species), and related blaOXA-48-containing IncL/M-type plasmids (different species). In one hospital, drain isolates from eight rooms on two units were Enterobacter hormaechei separated by 0-6 SNVs. Shower drains were more likely to be CPE-contaminated than hand hygiene (odds ratio: 3.45; 95% confidence interval: 1.66-7.16) or patient-use (13.0; 4.29-39.1) sink drains. Hand hygiene sink drains were more likely to be CPE-contaminated than patient-use sink drains (3.75; 1.17-12.0). CONCLUSION: Drain contamination was uncommon but widely dispersed. Drain CPE unrelated to patient exposure suggests contamination by undetected colonized patients or retrograde (drain-to-drain) contamination. Drain types had different contamination risks.
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Enterobacter/isolamento & purificação , Contaminação de Equipamentos , Hospitais , Quartos de Pacientes , Abastecimento de Água , Proteínas de Bactérias , Farmacorresistência Bacteriana , Infecções por Enterobacteriaceae/prevenção & controle , Humanos , Ontário , beta-LactamasesRESUMO
The majority of variation in six traits critical to the growth, survival and reproduction of plant species is thought to be organised along just two dimensions, corresponding to strategies of plant size and resource acquisition. However, it is unknown whether global plant trait relationships extend to climatic extremes, and if these interspecific relationships are confounded by trait variation within species. We test whether trait relationships extend to the cold extremes of life on Earth using the largest database of tundra plant traits yet compiled. We show that tundra plants demonstrate remarkably similar resource economic traits, but not size traits, compared to global distributions, and exhibit the same two dimensions of trait variation. Three quarters of trait variation occurs among species, mirroring global estimates of interspecific trait variation. Plant trait relationships are thus generalizable to the edge of global trait-space, informing prediction of plant community change in a warming world.
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Desenvolvimento Vegetal , Tundra , Clima , Ecossistema , Plantas/classificação , Plantas/genéticaRESUMO
Preventing vancomycin-resistant enterococci (VRE) infection is a healthcare priority. However, the cost-effectiveness of VRE control interventions is unclear. The aim of this study was to synthesize evidence on economic evaluation of VRE control practices such as screening, contact precautions, patient cohorting, and others. The literature was searched from January 1985 to June 2018, and included economic evaluations of VRE control practices in hospital settings, published in English. A total of 4711 articles were screened; nine primary studies met our criteria. All studies evaluated some form of VRE screening and contact precautions, in populations ranging from single hospital wards (or select patient groups) to multiple healthcare facilities. There was significant variability in the interventions and comparisons used. Most studies (N = 7) conducted a cost-effectiveness analysis; two studies were cost-consequence studies. All economic evaluations were from the hospital perspective. Four studies found implementing enhanced VRE-specific control practices to be cost-effective/cost-saving and two studies found that discontinuing VRE-specific control practices was not cost-effective. Three studies found decreasing VRE-specific control practices to be cost-effective/cost-saving. The quality of the included studies was generally low according to the Joanna Briggs Institute (JBI) checklist for economic evaluations; major limitations included risks of bias in intervention effect estimates, and a lack of sensitivity analyses. Most studies show that some form of VRE screening and use of Contact Precautions is cost-effective. The low study quality and heterogeneity of interventions and comparators precludes definitive conclusions about the cost effectiveness of specific VRE control interventions. Additional high-quality economic evaluations are needed to strengthen the available evidence.
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Análise Custo-Benefício , Infecção Hospitalar/economia , Infecção Hospitalar/prevenção & controle , Infecções por Bactérias Gram-Positivas/economia , Infecções por Bactérias Gram-Positivas/prevenção & controle , Controle de Infecções/economia , Hospitais/estatística & dados numéricos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Enterococos Resistentes à Vancomicina/patogenicidadeRESUMO
Background. The Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN SOS) has been performing active influenza surveillance since 2009 (ClinicalTrials.gov identifier: NCT01517191). Influenza A and B viruses are identified and characterized using real-time reverse-transcriptase polymerase chain reaction (RT-PCR), and multiplex testing has been performed on a subset of patients to identify other respiratory virus aetiologies. Since both methods can identify influenza A and B, a direct comparison was performed.Methods. Validated real-time RT-PCRs from the World Health Organization (WHO) to identify influenza A and B viruses, characterize influenza A viruses into the H1N1 or H3N2 subtypes and describe influenza B viruses belonging to the Yamagata or Victoria lineages. In a subset of patients, the Seeplex RV15 One-Step ACE Detection assay (RV15) kit was also used for the detection of other respiratory viruses.Results. In total, 1111 nasopharyngeal swabs were tested by RV15 and real-time RT-PCRs for influenza A and B identification and characterization. For influenza A, RV15 showed 98.0â% sensitivity, 100â% specificity and 99.7â% accuracy. The performance characteristics of RV15 were similar for influenza A subtypes H1N1 and H3N2. For influenza B, RV15 had 99.2â% sensitivity, 100â% specificity and 99.8â% accuracy, with similar assay performance being shown for both the Yamagata and Victoria lineages.Conclusions. Overall, the detection of circulating subtypes of influenza A and lineages of influenza B by RV15 was similar to detection by real-time RT-PCR. Multiplex testing with RV15 allows for a more comprehensive respiratory virus surveillance in hospitalized adults, without significantly compromising the reliability of influenza A or B virus detection.
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Vírus da Influenza A/isolamento & purificação , Vírus da Influenza B/isolamento & purificação , Influenza Humana/virologia , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase Multiplex/métodos , Adulto , Canadá/epidemiologia , Feminino , Hospitalização , Humanos , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Vírus da Influenza B/classificação , Vírus da Influenza B/genética , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Influenza Humana/terapia , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
AIM: Plant functional groups are widely used in community ecology and earth system modelling to describe trait variation within and across plant communities. However, this approach rests on the assumption that functional groups explain a large proportion of trait variation among species. We test whether four commonly used plant functional groups represent variation in six ecologically important plant traits. LOCATION: Tundra biome. TIME PERIOD: Data collected between 1964 and 2016. MAJOR TAXA STUDIED: 295 tundra vascular plant species. METHODS: We compiled a database of six plant traits (plant height, leaf area, specific leaf area, leaf dry matter content, leaf nitrogen, seed mass) for tundra species. We examined the variation in species-level trait expression explained by four traditional functional groups (evergreen shrubs, deciduous shrubs, graminoids, forbs), and whether variation explained was dependent upon the traits included in analysis. We further compared the explanatory power and species composition of functional groups to alternative classifications generated using post hoc clustering of species-level traits. RESULTS: Traditional functional groups explained significant differences in trait expression, particularly amongst traits associated with resource economics, which were consistent across sites and at the biome scale. However, functional groups explained 19% of overall trait variation and poorly represented differences in traits associated with plant size. Post hoc classification of species did not correspond well with traditional functional groups, and explained twice as much variation in species-level trait expression. MAIN CONCLUSIONS: Traditional functional groups only coarsely represent variation in well-measured traits within tundra plant communities, and better explain resource economic traits than size-related traits. We recommend caution when using functional group approaches to predict tundra vegetation change, or ecosystem functions relating to plant size, such as albedo or carbon storage. We argue that alternative classifications or direct use of specific plant traits could provide new insights for ecological prediction and modelling.
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BACKGROUND: Influenza outbreaks in hospital settings affect vulnerable patient populations and pose considerable risk of morbidity and mortality; however, key information regarding these outbreaks is limited. OBJECTIVE: To describe surveillance data on influenza outbreaks in Ontario hospitals between 2012-13 and 2015-16 and compare H3N2- and H1N1-dominant influenza seasons. METHODS: Hospital laboratory-confirmed influenza outbreaks occurring between September 1, 2012 and August 31, 2016 were analysed for indicators of outbreak duration and severity (case attack rate, pneumonia rate and fatality rate). Frequency, duration and severity of influenza A outbreaks were compared between H3N2- (2012-13, 2014-15) and H1N1-dominant seasons (2013-14, 2015-16). RESULTS: Over the four years, there were 256 hospital outbreaks involving 1,586 patients that included 91 cases of pneumonia and 40 deaths. The total number of outbreaks was lowest in the 2015-16 (n=36) and highest in the 2014-15 (n=117) influenza seasons. The 2014-15 season also had the highest number of influenza cases (n=753), pneumonia cases (n=46), fatalities (n=18) and hospital sites reporting ≥1 outbreak (n=72). Median outbreak duration ranged from 4.5 days in 2013-14 to 6.0 days in 2015-16. Comparisons of H3N2 and H1N1 seasons did not identify statistically significant differences in outbreak duration or severity; however, significantly more influenza A outbreaks than influenza B outbreaks were reported in H3N2 seasons compared with H1N1 seasons (p<0.05). CONCLUSION: While H3N2-dominant years contribute to influenza morbidity and mortality through an increased number of hospital outbreaks, the duration and severity of influenza A outbreaks are not significantly different in H3N2 and H1N1 seasons.
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A multi-country outbreak of Mycobacterium chimaera infection associated with contaminated heater-cooler devices (HCDs) has been reported, with more than 70 cases in Europe and the United States and two cases in Canada to date. The epidemiological and microbiological characteristics of this outbreak provide evidence for common-source transmission of M. chimaera from the exhaust air of intrinsically contaminated HCDs to patients during cardiac surgery. To date, all reported cases have been associated with Stöckert 3T HCDs manufactured at one plant by LivaNova prior to September 2014. Implantation of prosthetic material increases the risk of infection. Infections usually present as prosthetic valve endocarditis, vascular graft infection or disseminated infection. Reported mortality rates have varied, but were often over 40%. Several measures are recommended to facilitate case-finding and mitigate risk of exposure. The feasibility of some risk mitigation measures and their effectiveness in reducing the risk of exposure are yet to be determined. Until HCDs are redesigned in a manner that prevents water contamination and aerosolization, separating the HCD exhaust air from the operating room air during surgery may be the most effective risk mitigation strategy. However, possible unintended consequences of this approach should be considered. This overview summarizes findings from peer-reviewed and other relevant national documents on key features of the outbreak, including the source, identified risk factors for infection, signs and symptoms of infection, burden of disease, risk mitigation measures, management challenges and knowledge gaps.
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The objective of this study was to determine the impact of selective susceptibility reporting on ciprofloxacin utilization and Gram-negative susceptibility to ciprofloxacin in a hospital setting. Historically at our institution, the microbiology laboratory practice was to report ciprofloxacin susceptibility for all Enterobacteriaceae regardless of susceptibility to other agents. A selective reporting policy was implemented which involved the suppression of ciprofloxacin susceptibility to Enterobacteriaceae when there was lack of resistance to the antibiotics on the Gram-negative panel. Ciprofloxacin utilization (measured in defined daily doses [DDD] per 1,000 patient days) was collected before and after the intervention and compared to moxifloxacin, trimethoprim-sulfamethoxazole, nitrofurantoin, and amoxicillin-clavulanate. Monthly susceptibility of Pseudomonas aeruginosa and Escherichia coli to ciprofloxacin was tabulated. An interrupted time series analysis using segmented regression was performed. The mean monthly ciprofloxacin utilization decreased from 87 (95% CI, 83.7 to 91.2) to 39 (95% CI, 35.0 to 44.0) DDD per 1,000 patient days before and after the implementation of selective reporting, respectively. There was an immediate and sustained reduction in ciprofloxacin usage at 1, 3, 6, 12, and 24 months postintervention (P < 0.001). A compensatory increase in amoxicillin-clavulanate use was noted starting at 6 months postintervention and persisted for the study period (P < 0.027). Susceptibility of E. coli, but not that of P. aeruginosa, to ciprofloxacin was higher than predicted starting 12 months after the intervention (P < 0.05). In conclusion, selective reporting of ciprofloxacin susceptibly may be a useful intervention to reduce targeted antimicrobial utilization and improve Gram-negative susceptibility to ciprofloxacin. This approach should be considered as part of a broader multimodal antimicrobial stewardship program.
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Antibacterianos/uso terapêutico , Ciprofloxacina/uso terapêutico , Farmacorresistência Bacteriana , Uso de Medicamentos/normas , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Testes de Sensibilidade Microbiana/métodos , Antibacterianos/farmacologia , Ciprofloxacina/farmacologia , Hospitais , Humanos , Análise de Séries Temporais InterrompidaRESUMO
Huperzine A (HupA) is an acetylcholinesterase (AChE) inhibitor extracted from Huperzia Serrata, a firmoss, which has been used for various diseases in traditional Chinese medicine for fever and inflammation. More recently, it has been used in Alzheimer's disease and other forms of dementia with a presumed mechanism of action via central nicotinic and muscarinic receptors. HupA is marketed as a dietary supplement in the U.S. This article reviews newly proposed neuroprotective and anticonvulsant HupA properties based on animal studies. HupA exerts its effects mainly via α7nAChRs and α4ß2nAChRs, thereby producing a potent anti-inflammatory response by decreasing IL-1ß, TNF-α protein expression, and suppressing transcriptional activation of NF-κB signaling. Thus, it provides protection from excitotoxicity and neuronal death as well as increase in GABAergic transmission associated with anticonvulsant activity.
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Alcaloides , Anticonvulsivantes , Epilepsia/tratamento farmacológico , Sesquiterpenos , Alcaloides/uso terapêutico , Animais , Anticonvulsivantes/uso terapêutico , Inibidores da Colinesterase/farmacologia , Humanos , Fármacos Neuroprotetores/uso terapêutico , Sesquiterpenos/uso terapêuticoRESUMO
We wanted to examine tolerability and efficacy of NSI-189, a benzylpiperizine-aminiopyridine neurogenic compound for treating major depressive disorder (MDD). This was a Phase 1B, double blind, randomized, placebo controlled, multiple-dose study with three cohorts. The first cohort received 40 mg q.d. (n=6) or placebo (n=2), the second cohort 40 mg b.i.d. (n=6) or placebo (n=2), and the third cohort 40 mg t.i.d. (n=6) or placebo (n=2). Twenty-four patients with MDD were recruited, with the diagnosis and severity confirmed through remote interviews. Eligible patients received NSI-189 or placebo for 28 days in an inpatient setting with assessments for safety, pharmacokinetics (PK) and efficacy. Outpatient follow-up visits were conducted until day 84 (±3). NSI-189 was relatively well tolerated at all doses, with no serious adverse effects. NSI-189 area under the curve increased in a dose-related and nearly proportional manner across the three cohorts, with a half-life of 17.4-20.5 h. The exploratory efficacy measurements, including Symptoms Of Depression Questionnaire (SDQ), Montgomery-Asberg Depression Scale (MADRS), Clinical Global Impressions-Improvement (CGI-I), and The Massachusetts General Hospital (MGH) Cognitive and Physical Functioning Questionnaire (CPFQ) showed a promising reduction in depressive and cognitive symptoms across all measures for NSI-189, with significant improvement in the SDQ and CPFQ, and a medium to large effect size for all measures. These improvements persisted during the follow-up phase. In summary, NSI-189 shows potential as a treatment for MDD in an early phase study. The main limitation of this preliminary study was the small sample size of each cohort.
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Aminopiridinas/administração & dosagem , Transtorno Depressivo Maior/tratamento farmacológico , Piperazinas/administração & dosagem , Adulto , Aminopiridinas/farmacocinética , Biomarcadores Farmacológicos/sangue , Depressão/sangue , Depressão/tratamento farmacológico , Depressão/metabolismo , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/metabolismo , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piperazinas/farmacocinética , Escalas de Graduação Psiquiátrica , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/farmacocinética , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Resultado do TratamentoRESUMO
Vancomycin-variable enterococcus (VVE) is an emerging pathogen. VVE isolates initially appear phenotypically susceptible to vancomycin but possesses the vanA gene and can develop in vitro and in vivo resistance to vancomycin. We report a case of VVE bacteremia and describe how VVE poses diagnostic and therapeutic dilemmas.
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Antibacterianos/farmacologia , Bacteriemia/microbiologia , Enterococcus/efeitos dos fármacos , Enterococcus/isolamento & purificação , Infecções por Bactérias Gram-Positivas/microbiologia , Resistência a Vancomicina , Vancomicina/farmacologia , Idoso , Proteínas de Bactérias/genética , Carbono-Oxigênio Ligases/genética , Eletroforese em Gel de Campo Pulsado , Enterococcus/classificação , Enterococcus/genética , Feminino , Humanos , Testes de Sensibilidade Microbiana , Tipagem MolecularRESUMO
Intramuscular adrenaline is the gold standard treatment for anaphylaxis. Intramuscular injection provides more rapid and higher plasma concentrations than subcutaneous routes. Given the increasing epidemic of obesity patients are at increased risk of subcutaneous delivery, we therefore assessed the depth of subcutaneous tissue in a population of patients with anaphylaxis. Patients already prescribed adrenaline autoinjectors (AAIs) for anaphylaxis were examined with ultrasound, and measurements of skin-to-muscle depth (STMD) at anterolateral thigh and anterior thigh were performed. Twenty-eight patients (23 female, 5 male) with an age range of 18-75 took part in the study, and in 68%, the STMD was greater than AAI needle length (15.02 mm), using the anterolateral thigh as the recommended administration site. The key predictors for increased STMD were female gender (P=0.0003) and a BMI > 30 (P=0.04). AAIs require longer needles to ensure intramuscular administration, and ultrasound at point of prescription would aid needle length selection.