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1.
Nat Commun ; 14(1): 7072, 2023 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-37923737

RESUMO

Retrovirus integration into a host genome is essential for productive infections. The integration strand transfer reaction is catalyzed by a nucleoprotein complex (Intasome) containing the viral integrase (IN) and the reverse transcribed (RT) copy DNA (cDNA). Previous studies suggested that DNA target-site recognition limits intasome integration. Using single molecule Förster resonance energy transfer (smFRET), we show prototype foamy virus (PFV) intasomes specifically bind to DNA strand breaks and gaps. These break and gap DNA discontinuities mimic oxidative base excision repair (BER) lesion-processing intermediates that have been shown to affect retrovirus integration in vivo. The increased DNA binding events targeted strand transfer to the break/gap site without inducing substantial intasome conformational changes. The major oxidative BER substrate 8-oxo-guanine as well as a G/T mismatch or +T nucleotide insertion that typically introduce a bend or localized flexibility into the DNA, did not increase intasome binding or targeted integration. These results identify DNA breaks or gaps as modulators of dynamic intasome-target DNA interactions that encourage site-directed integration.


Assuntos
DNA Viral , Spumavirus , DNA Viral/metabolismo , Integrases/metabolismo , Retroviridae/genética , Retroviridae/metabolismo , Spumavirus/genética , Spumavirus/metabolismo , DNA Complementar , Integração Viral
2.
J Inorg Biochem ; 245: 112257, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37229820

RESUMO

Kinetic and structural investigations of the flavohemoglobin-type NO dioxygenase have suggested critical roles for transient Fe(III)O2 complex formation and O2-forced movements affecting hydride transfer to the FAD cofactor and electron-transfer to the Fe(III)O2 complex. Stark-effect theory together with structural models and dipole and internal electrostatic field determinations provided a semi-quantitative spectroscopic method for investigating the proposed Fe(III)O2 complex and O2-forced movements. Deoxygenation of the enzyme causes Stark effects on the ferric heme Soret and charge-transfer bands revealing the Fe(III)O2 complex. Deoxygenation also elicits Stark effects on the FAD that expose forces and motions that create a more restricted NADH access to FAD for hydride transfer and switch electron-transfer off. Glucose also forces the enzyme toward an off state. Amino acid substitutions at the B10, E7, E11, G8, D5, and F7 positions influence the Stark effects of O2 on resting heme spin states and FAD consistent with the proposed roles of the side chains in the enzyme mechanism. Deoxygenation of ferric myoglobin and hemoglobin A also induces Stark effects on the hemes suggesting a common 'oxy-met' state. The ferric myoglobin and hemoglobin heme spectra are also glucose-responsive. A conserved glucose or glucose-6-phosphate binding site is found bridging the BC-corner and G-helix in flavohemoglobin and myoglobin suggesting novel allosteric effector roles for glucose or glucose-6-phosphate in the NO dioxygenase and O2 storage functions. The results support the proposed roles of a ferric O2 intermediate and protein motions in regulating electron-transfer during NO dioxygenase turnover.


Assuntos
Ferro , Mioglobina , Ferro/química , Mioglobina/química , Oxigênio/química , Elétrons , Glucose-6-Fosfato , Heme/química , Óxido Nítrico/metabolismo
3.
Sci Rep ; 12(1): 4082, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35260723

RESUMO

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV), is a highly infectious RNA virus. A percentage of patients develop coronavirus disease 2019 (COVID-19) after infection, whose symptoms include fever, cough, shortness of breath and fatigue. Acute and life-threatening respiratory symptoms are experienced by 10-20% of symptomatic patients, particularly those with underlying medical conditions. One of the main challenges in the containment of COVID-19 is the identification and isolation of asymptomatic/pre-symptomatic individuals. A number of molecular assays are currently used to detect SARS-CoV-2. Many of them can accurately test hundreds or even thousands of patients every day. However, there are presently no testing platforms that enable more than 10,000 tests per day. Here, we describe the foundation for the REcombinase Mediated BaRcoding and AmplificatioN Diagnostic Tool (REMBRANDT), a high-throughput Next Generation Sequencing-based approach for the simultaneous screening of over 100,000 samples per day. The REMBRANDT protocol includes direct two-barcoded amplification of SARS-CoV-2 and control amplicons using an isothermal reaction, and the downstream library preparation for Illumina sequencing and bioinformatics analysis. This protocol represents a potentially powerful approach for community screening of COVID-19 that may be modified for application to any infectious or non-infectious genome.


Assuntos
COVID-19/diagnóstico , Proteínas de Ligação a DNA/metabolismo , Proteínas de Membrana/metabolismo , Técnicas de Amplificação de Ácido Nucleico/métodos , SARS-CoV-2/genética , Proteínas Virais/metabolismo , COVID-19/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Programas de Rastreamento , RNA Viral/análise , RNA Viral/metabolismo , SARS-CoV-2/isolamento & purificação
5.
J Biol Chem ; 296: 100550, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33744295

RESUMO

Retroviral integrases must navigate host DNA packaged as chromatin during integration of the viral genome. Prototype foamy virus (PFV) integrase (IN) forms a tetramer bound to two viral DNA (vDNA) ends in a complex termed an intasome. PFV IN consists of four domains: the amino terminal extension domain (NED), amino terminal domain (NTD), catalytic core domain (CCD), and carboxyl terminal domain (CTD). The domains of the two inner IN protomers have been visualized, as well as the CCDs of the two outer IN protomers. However, the roles of the amino and carboxyl terminal domains of the PFV intasome outer subunits during integration to a nucleosome target substrate are not clear. We used the well-characterized 601 nucleosome to assay integration activity as well as intasome binding. PFV intasome integration to 601 nucleosomes occurs in clusters at four independent sites. We find that the outer protomer NED and NTD domains have no significant effects on integration efficiency, site selection, or binding. The CTDs of the outer PFV intasome subunits dramatically affect nucleosome binding but have little effect on total integration efficiency. The outer PFV IN CTDs did significantly alter the integration efficiency at one site. Histone tails also significantly affect intasome binding, but have little impact on PFV integration efficiency or site selection. These results indicate that binding to nucleosomes does not correlate with integration efficiency and suggests most intasome-binding events are unproductive.


Assuntos
Histonas/metabolismo , Integrases/metabolismo , Nucleossomos/metabolismo , Spumavirus/metabolismo , Proteínas Virais/metabolismo , Integração Viral , Domínio Catalítico , Cromatina/genética , Cromatina/metabolismo , DNA Viral/genética , DNA Viral/metabolismo , Genoma Viral , Humanos , Integrases/genética , Multimerização Proteica , Spumavirus/genética , Spumavirus/crescimento & desenvolvimento , Proteínas Virais/química , Proteínas Virais/genética
6.
J Adv Nurs ; 77(3): 1453-1464, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33617021

RESUMO

AIM: To achieve profession-wide consensus on clinical practice standards for six broad Australian nurse practitioner specialty areas (termed metaspecialties). DESIGN: Sequential mixed methods with initial interpretive study (Interpretive Phase) followed by modified three-round Delphi study (Survey Phase). METHODS: Participants from all Australian jurisdictions were recruited. Main eligibility criterion was current endorsement as a nurse practitioner for 12 or more months. Interpretive Phase comprised in-depth interviews of purposeful sample of nurse practitioners to identify clinical care activities and practice processes. Six sets of draft clinical practice standards relevant to six previously identified metaspecialties were developed. Outcome informed Round 1 of Survey Phase (six nested web-based Delphi surveys), with draft standards reviewed profession-wide. Responses comprised scoring using Likert scales to calculate content validity indexes for individual standards with qualitative responses supporting decision-making. For Rounds 2 and 3, participants rated relevancy of original or revised standards after consideration of individual and group feedback. The study was conducted 2014-2017. RESULTS: Interpretive Phase: Analysis of interview data with 16 nurse practitioners provided 75 draft standards. Survey Phase: 221 nurse practitioners completed Round 1 (20% of then eligible Australian nurse practitioners). Weighted respondent retention was 92%. Seventy-three standards were validated, with final content validity indices of 92-100%. Scale-level indices were 98%, strongly validating metaspecialty taxonomy. CONCLUSION: A research-derived, professionally endorsed suite of nurse practitioner clinical practice standards was developed. This provides a broad clinical learning structure with metaspecialties guiding nurse practitioner student clinical education. IMPACT: The clinical practice standards and metaspecialty taxonomy strengthen nurse practitioner clinical education and professional development nationally and internationally. These novel study methods and findings are applicable to advanced specialty roles in other health professions.


Assuntos
Medicina , Profissionais de Enfermagem , Austrália , Humanos , Inquéritos e Questionários
7.
J Biol Chem ; 296: 100186, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33310705

RESUMO

The substrates O2 and NO cooperatively activate the NO dioxygenase function of Escherichia coli flavohemoglobin. Steady-state and transient kinetic measurements support a structure-based mechanistic model in which O2 and NO movements and conserved amino acids at the E11, G8, E2, E7, B10, and F7 positions within the globin domain control activation. In the cooperative and allosteric mechanism, O2 migrates to the catalytic heme site via a long hydrophobic tunnel and displaces LeuE11 away from the ferric iron, which forces open a short tunnel to the catalytic site gated by the ValG8/IleE15 pair and LeuE11. NO permeates this tunnel and leverages upon the gating side chains triggering the CD loop to furl, which moves the E and F-helices and switches an electron transfer gate formed by LysF7, GlnE7, and water. This allows FADH2 to reduce the ferric iron, which forms the stable ferric-superoxide-TyrB10/GlnE7 complex. This complex reacts with internalized NO with a bimolecular rate constant of 1010 M-1 s-1 forming nitrate, which migrates to the CD loop and unfurls the spring-like structure. To restart the cycle, LeuE11 toggles back to the ferric iron. Actuating electron transfer with O2 and NO movements averts irreversible NO poisoning and reductive inactivation of the enzyme. Together, structure snapshots and kinetic constants provide glimpses of intermediate conformational states, time scales for motion, and associated energies.


Assuntos
Di-Hidropteridina Redutase/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , NADH NADPH Oxirredutases/metabolismo , Oxigenases/metabolismo , Regulação Alostérica , Di-Hidropteridina Redutase/química , Escherichia coli/química , Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/química , Humanos , Modelos Moleculares , NADH NADPH Oxirredutases/química , Óxido Nítrico/metabolismo , Oxigenases/química , Conformação Proteica
8.
Antimicrob Resist Infect Control ; 9(1): 35, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070419

RESUMO

BACKGROUND: Implementing sustainable practice change in hospital cleaning has proven to be an ongoing challenge in reducing healthcare associated infections. The purpose of this study was to develop a reliable framework-based approach to implement and quantitatively evaluate the implementation of evidence-based practice change in hospital cleaning. DESIGN/METHODS: The Researching Effective Approaches to Cleaning in Hospitals (REACH) trial was a pragmatic, stepped-wedge randomised trial of an environmental cleaning bundle implemented in 11 Australian hospitals from 2016 to 2017. Using a structured multi-step approach, we adapted the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework to support rigorous and tailored implementation of the cleaning bundle intervention in eleven diverse and complex settings. To evaluate the effectiveness of this strategy we examined post-intervention cleaning bundle alignment calculated as a score (an implementation measure) and cleaning performance audit data collected using ultraviolet (UV) gel markers (an outcome measure). RESULTS: We successfully implemented the bundle and observed improvements in cleaning practice and performance, regardless of hospital size, intervention duration and contextual issues such as staff and organisational readiness at baseline. There was a positive association between bundle alignment scores and cleaning performance at baseline. This diminished over the duration of the intervention, as hospitals with lower baseline scores were able to implement practice change successfully. CONCLUSION: Using a structured framework-based approach allows for pragmatic and successful implementation of clinical trials across diverse settings, and assists with quantitative evaluation of practice change. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12615000325505, registered on 4 September 2015.


Assuntos
Infecção Hospitalar/prevenção & controle , Zeladoria Hospitalar/métodos , Avaliação de Resultados em Cuidados de Saúde/métodos , Austrália , Prática Clínica Baseada em Evidências , Promoção da Saúde , Pesquisa sobre Serviços de Saúde , Número de Leitos em Hospital , Humanos , Filogenia
9.
Eur J Oncol Nurs ; 45: 101722, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32014709

RESUMO

PURPOSE: Alternatives to hospital follow-up (HFU) following treatment for cancer have been advocated. Telephone follow-up (TFU) and patient-initiated follow-up are being implemented but it is unclear if these approaches will meet the preferences and needs of patients. This study aimed to explore the preferences of endometrial cancer patients and their levels of satisfaction with HFU and nurse-led TFU. METHODS: A cross-sectional survey design was utilised and a questionnaire was administered to 236 patients who had participated in a randomised controlled trial comparing HFU with TFU for women diagnosed with Stage I endometrial cancer (ENDCAT trial). RESULTS: 211 (89.4%) patients returned the questionnaire; 105 in the TFU group and 106 in the HFU group. The TFU group were more likely to indicate that appointments were on time (p < 0.001) and were more likely to report that their appointments were thorough (p = 0.011). Participants tended to prefer what was familiar to them. Those in the HFU group tended to prefer hospital-based appointments while the TFU group tended to prefer appointments with a clinical nurse specialist, regardless of locality. CONCLUSIONS: To provide patient centred follow-up services we need to ensure that patient preferences are taken into account and understand that patients may come to prefer what they have experienced. Patient initiated approaches may become standard and preferred practice but TFU remains a high-quality alternative to HFU and may provide an effective transition between HFU and patient-initiated approaches.


Assuntos
Neoplasias do Endométrio/psicologia , Neoplasias do Endométrio/terapia , Serviços Hospitalares de Assistência Domiciliar/estatística & dados numéricos , Preferência do Paciente/psicologia , Satisfação do Paciente/estatística & dados numéricos , Telemedicina/estatística & dados numéricos , Telefone , Idoso , Estudos Transversais , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Preferência do Paciente/estatística & dados numéricos , Inquéritos e Questionários
10.
Clin Infect Dis ; 70(12): 2461-2468, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-31359053

RESUMO

BACKGROUND: Healthcare-associated infections (HAIs) remain a significant patient safety issue, with point prevalence estimates being ~5% in high-income countries. In 2016-2017, the Researching Effective Approaches to Cleaning in Hospitals (REACH) study implemented an environmental cleaning bundle targeting communication, staff training, improved cleaning technique, product use, and audit of frequent touch-point cleaning. This study evaluates the cost-effectiveness of the environmental cleaning bundle for reducing the incidence of HAIs. METHODS: A stepped-wedge, cluster-randomized trial was conducted in 11 hospitals recruited from 6 Australian states and territories. Bundle effectiveness was measured by the numbers of Staphylococcus aureus bacteremia, Clostridium difficile infection, and vancomycin-resistant enterococci infections prevented in the intervention phase based on estimated reductions in the relative risk of infection. Changes to costs were defined as the cost of implementing the bundle minus cost savings from fewer infections. Health benefits gained from fewer infections were measured in quality-adjusted life-years (QALYs). Cost-effectiveness was evaluated using the incremental cost-effectiveness ratio and net monetary benefit of adopting the cleaning bundle over existing hospital cleaning practices. RESULTS: Implementing the cleaning bundle cost $349 000 Australian dollars (AUD) and generated AUD$147 500 in cost savings. Infections prevented under the cleaning bundle returned a net monetary benefit of AUD$1.02 million and an incremental cost-effectiveness ratio of $4684 per QALY gained. There was an 86% chance that the bundle was cost-effective compared with existing hospital cleaning practices. CONCLUSIONS: A bundled, evidence-based approach to improving hospital cleaning is a cost-effective intervention for reducing the incidence of HAIs.


Assuntos
Infecções por Clostridium , Infecção Hospitalar , Austrália/epidemiologia , Análise Custo-Benefício , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Atenção à Saúde , Humanos
12.
Int J Nurs Stud ; 97: 1-6, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31129443

RESUMO

BACKGROUND: Catheter associated urinary tract infections are one of the most common infections acquired in hospital. A recent randomised control study demonstrated the benefit of using chlorhexidine (0.1%) for meatal cleaning prior to urinary catheter insertion, by reducing both catheter associated asymptomatic bacteriuria and infection. These findings raise the important question of whether a decision to switch from saline to chlorhexidine was likely to be cost-effective. The aim of this paper was to evaluate the cost-effectiveness of adopting routine use of chlorhexidine for meatal cleaning prior to urinary catheter insertion METHODS: The outcomes of this cost-effectiveness study are changes to health service costs in $AUD and changes to quality adjusted life years from a decision to adopt 0.1% chlorhexidine for meatal cleaning prior to urinary catheter insertion as compared to saline. Effectiveness outcomes for this study were taken from a 32 week stepped wedge randomised controlled study conducted in three Australian hospitals. RESULTS: The changes in health costs from switching from saline to 0.1% chlorhexidine per 100,000 catheterisations would save hospitals AUD$387,909 per 100,000 catherisations, prevent 70 cases of catheter associated urinary tract infections, release 282 bed days and provide a small improvement in health benefits of 1.43 quality adjusted life years. Using a maximum willingness to pay for a marginal quality adjusted life year threshold of AUD$28,000 per 100,000 catherisations, suggests that adopting chlorhexidine would be cost effective and potentially cost-saving. CONCLUSION: The findings from our work provide evidence to health system administrators and those responsible for drafting catheter associated urinary tract infections prevention guidelines that investing in switching from saline to chlorhexidine is not only clinically effective but also a sensible decision in the context of allocating finite healthcare resources.


Assuntos
Clorexidina/uso terapêutico , Análise Custo-Benefício , Solução Salina/uso terapêutico , Cateterismo Urinário/efeitos adversos , Infecções Urinárias/etiologia , Infecções Urinárias/prevenção & controle , Humanos , Fatores de Risco
13.
Lancet Infect Dis ; 19(6): 611-619, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30987814

RESUMO

BACKGROUND: Evidence for the benefits of antiseptic meatal cleaning in reducing catheter-associated urinary tract infection (UTI) is inconclusive. We assessed the efficacy of 0·1% chlorhexidine solution compared with normal saline for meatal cleaning before urinary catheter insertion in reducing the incidence of catheter-associated asymptomatic bacteriuria and UTI. METHODS: A cross-sectional, stepped-wedge, open-label, randomised controlled trial was undertaken in Australian hospitals. Eligible hospitals were Australian public and private hospitals, with an intensive care unit and more than 30 000 hospital admissions per year. Hospitals were randomly assigned to an intervention crossover date using a computer-generated randomisation system. Crossover dates occurred every 8 weeks; during the first 8 weeks of the study, no hospitals were exposed to the intervention (control phase), after which each hospital sequentially crossed over from the control to the intervention every 8 weeks. Patients requiring a urinary cathetwer were potentially eligible for inclusion in this hospital-wide study. Participants were excluded if they were younger than 2 years, had a medical reason preventing the use of the chlorhexidine, had the catheter inserted in theatre, did not have the catheter insertion date documented, required in-and-out or suprapubic catheterisation, had symptoms and signs suggestive of UTI at the time of catheter insertion, or were currently undergoing treatment for UTI. The intervention was the use of 0·1% chlorhexidine solution for meatal cleaning before urinary catheterisation with 0·9% normal saline used in the control phase. Masking of hospitals was not possible because it was not feasible to mask staff administering the intervention. The co-primary outcomes were the number of cases of catheter-associated asymptomatic bacteriuria and UTI per 100 catheter-days and were assessed within 7 days of catheter insertion in the intention-to-treat population. This trial is registered with Australian New Zealand Clinical Trials Registry, number ACTRN12617000373370. FINDINGS: 21 hospitals were assessed for eligibility between Jan 5, 2017, and May 1, 2017; of these, three were successfully enrolled and randomised to one of three intervention crossover dates. 1642 participants in these hospitals were included in the study between Aug 1, 2017, and March 12, 2018, 697 (42%) in the control phase and 945 (58%) in the intervention period. In the control period, 13 catheter-associated UTI and 29 catheter-associated asymptomatic bacteriuria events in 2889 catheter-days (0·45 catheter-associated UTI cases and 1·00 catheter-associated asymptomatic bacteriuria cases per 100 catheter-days) were recorded compared with four catheter-associated UTI and 16 catheter-associated asymptomatic bacteriuria events in 2338 catheter-days (0·17 catheter-associated UTI cases and 0·68 catheter-associated asymptomatic bacteriuria cases per 100 catheter-days) during the intervention period. The intervention was associated with a 74% reduction in the incidence of catheter-associated asymptomatic bacteriuria (incident rate ratio 0·26, 95% CI 0·08-0·86, p=0·026), and a 94% decrease in the incidence of catheter-associated UTI (0·06, 95% CI 0·01-0·32, p=0·00080). There were no reported adverse events. INTERPRETATION: The use of chlorhexidine solution for meatal cleaning before catheter insertion decreased the incidence of catheter-associated asymptomatic bacteriuria and UTI and has the potential to improve patient safety. FUNDING: HCF Research Foundation.


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/prevenção & controle , Cateteres de Demora/efeitos adversos , Clorexidina/uso terapêutico , Cateterismo Urinário/efeitos adversos , Infecções Urinárias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
PLoS One ; 14(3): e0212764, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30865665

RESUMO

Eukaryotic DNA binding proteins must access genomic DNA that is packaged into chromatin in vivo. During a productive infection, retroviral integrases (IN) must similarly interact with chromatin to integrate the viral cDNA genome. Here we examine the role of nucleosome DNA unwrapping in the retroviral integrase search for a target site. These studies utilized PFV intasomes that are comprised of a tetramer of PFV IN with two oligomers mimicking the viral cDNA ends. Modified recombinant human histones were used to generate nucleosomes with increased unwrapping rates at different DNA regions. These modifications included the acetylmimetic H3(K56Q) and the chemically engineered H4(K77ac, K79ac). While transcription factors and DNA damage sensors may search nucleosome bound DNA during transient unwrapping, PFV intasome mediated integration appears to be unaffected by increased nucleosome unwrapping. These studies suggest PFV intasomes do not utilize nucleosome unwrapping to search nucleosome targets.


Assuntos
DNA Viral/metabolismo , Genoma Viral , Nucleossomos/metabolismo , Spumavirus/metabolismo , Integração Viral/fisiologia , Sistema Livre de Células/química , Sistema Livre de Células/metabolismo , DNA Viral/química , Histonas/química , Histonas/metabolismo , Humanos , Nucleossomos/química , Spumavirus/química
15.
Lancet Infect Dis ; 19(4): 410-418, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30858014

RESUMO

BACKGROUND: The hospital environment is a reservoir for the transmission of microorganisms. The effect of improved cleaning on patient-centred outcomes remains unclear. We aimed to evaluate the effectiveness of an environmental cleaning bundle to reduce health care-associated infections in hospitals. METHODS: The REACH study was a pragmatic, multicentre, randomised trial done in 11 acute care hospitals in Australia. Eligible hospitals had an intensive care unit, were classified by the National Health Performance Authority as a major hospital (public hospitals) or having more than 200 inpatient beds (private hospitals), and had a health-care-associated infection surveillance programme. The stepped-wedge design meant intervention periods varied from 20 weeks to 50 weeks. We introduced the REACH cleaning bundle, a multimodal intervention, focusing on optimising product use, technique, staff training, auditing with feedback, and communication, for routine cleaning. The primary outcomes were incidences of health-care-associated Staphylococcus aureus bacteraemia, Clostridium difficile infection, and vancomycin-resistant enterococci infection. The secondary outcome was the thoroughness of cleaning of frequent touch points, assessed by a fluorescent marking gel. This study is registered with the Australian and New Zealand Clinical Trial Registry, number ACTRN12615000325505. FINDINGS: Between May 9, 2016, and July 30, 2017, we implemented the cleaning bundle in 11 hospitals. In the pre-intervention phase, there were 230 cases of vancomycin-resistant enterococci infection, 362 of S aureus bacteraemia, and 968 C difficile infections, for 3 534 439 occupied bed-days. During intervention, there were 50 cases of vancomycin-resistant enterococci infection, 109 of S aureus bacteraemia, and 278 C difficile infections, for 1 267 134 occupied bed-days. After the intervention, vancomycin-resistant enterococci infections reduced from 0·35 to 0·22 per 10 000 occupied bed-days (relative risk 0·63, 95% CI 0·41-0·97, p=0·0340). The incidences of S aureus bacteraemia (0·97 to 0·80 per 10 000 occupied bed-days; 0·82, 0·60-1·12, p=0·2180) and C difficile infections (2·34 to 2·52 per 10 000 occupied bed-days; 1·07, 0·88-1·30, p=0·4655) did not change significantly. The intervention increased the percentage of frequent touch points cleaned in bathrooms from 55% to 76% (odds ratio 2·07, 1·83-2·34, p<0·0001) and bedrooms from 64% to 86% (1·87, 1·68-2·09, p<0·0001). INTERPRETATION: The REACH cleaning bundle was successful at improving cleaning thoroughness and showed great promise in reducing vancomycin-resistant enterococci infections. Our work will inform hospital cleaning policy and practice, highlighting the value of investment in both routine and discharge cleaning practice. FUNDING: National Health and Medical Research Council (Australia).


Assuntos
Bacteriemia/epidemiologia , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/prevenção & controle , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Desinfecção/métodos , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/prevenção & controle , Austrália/epidemiologia , Bacteriemia/microbiologia , Bacteriemia/prevenção & controle , Clostridioides difficile , Infecções por Clostridium/microbiologia , Infecções por Clostridium/transmissão , Infecção Hospitalar/transmissão , Hospitais , Humanos , Higiene , Incidência , Unidades de Terapia Intensiva , Prevalência , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/transmissão , Staphylococcus aureus , Raios Ultravioleta , Enterococos Resistentes à Vancomicina
16.
HERD ; 12(2): 44-54, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29925276

RESUMO

In 2012, a tertiary neonatal intensive care unit (NICU) transitioned from an open plan (OP) to a dual occupancy (DO) NICU. The DO design aimed to provide a developmental appropriate, family-centered environment for neonates and their families. During planning, staff questioned the impact DO would have on staff workflow and activity. To explore the impact of changing from an OP to a DO NICU, a prospective longitudinal study was undertaken from 2011 to 2014, using observational, time and motion, and surveys methods. Main outcome measures included distance walked by staff, minutes of staff activity, and staff perceptions of the DO design. Results highlighted no significant difference in the distances clinical nurses walked nor time spent providing direct clinical care, whereas technical support staff walked further than other staff in both designs. Staff perceived the DO design created a developmentally appropriate, family-centered environment that facilitated communication and collaboration between staff and families. Staff described the main challenges of the DO design such as effective staff communication, gaining educational opportunities, and the isolation of staff and families compared to the OP design. Our study provides new evidence that DO provides an improved developmentally environment and has similar positive benefits to single-family room for neonates and families. Such design may reduce the larger floor plan's impact on staff walking distance and work practices. Challenges of staff transition can be minimized by planning and leadership throughout the development and move to a new design.


Assuntos
Arquitetura Hospitalar/estatística & dados numéricos , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Terapia Intensiva Neonatal/métodos , Terapia Intensiva Neonatal/estatística & dados numéricos , Enfermeiros Neonatologistas/psicologia , Enfermeiros Neonatologistas/estatística & dados numéricos , Fluxo de Trabalho , Adulto , Atitude do Pessoal de Saúde , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
17.
J Glob Antimicrob Resist ; 16: 254-259, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30412781

RESUMO

OBJECTIVES: The aim of this study was to evaluate the incidence of single-drug resistant, multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR) Escherichia coli urinary tract infections (UTIs) in a sample of Australian Capital Territory (ACT) residents. METHODS: Laboratory-based retrospective data from all ACT residents whose urine samples were processed from January 2009 to December 2013 at ACT Pathology were utilised. Multivariate logistic regression models were constructed to determine the associations of age, sex, urine sample source and socioeconomic status with risk of resistant infections. RESULTS: A total of 146 915 urine samples from 57 837 ACT residents were identified over 5 years. The mean±standard deviation age of residents at first sample submitted was 48±26years, and 64.4% were female. The 5-year incidence of single-drug resistant E. coli UTI was high for ampicillin, trimethoprim and cefazolin (6.8%, 3.5% and 1.9%, respectively). No PDR E. coli UTI was detected. Five-year incidences of MDR and XDR E. coli UTIs were 1.9% and 0.2%, respectively, which is low in comparison with international rates. Female sex and age ≥38 years were significantly associated with single-drug and multidrug resistance. The risk of single-drug resistance was significantly higher in samples from after-hours general practice (GP) clinics compared with hospitals, office-hours GP clinics, and community and specialist health services (adjusted odds ratio=2.6, 95% confidence interval 2.2-3.1). CONCLUSIONS: These findings have significant implications for antimicrobial prescribing given the identified risk factors for the detection of resistance, especially in patients attending after-hours GP clinics.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Farmacorresistência Bacteriana Múltipla , Infecções por Escherichia coli/epidemiologia , Escherichia coli/efeitos dos fármacos , Infecções Urinárias/microbiologia , Adulto , Idoso , Austrália , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/urina , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções Urinárias/epidemiologia , Adulto Jovem
18.
Jt Comm J Qual Patient Saf ; 44(10): 613-622, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30064955

RESUMO

BACKGROUND: Previous literature has linked the level and types of staffing of health facilities to the risk of acquiring a health care-associated infection (HAI). Investigating this relationship is challenging because of the lack of rigorous study designs and the use of varying definitions and measures of both staffing and HAIs. METHODS: The objective of this study was to understand and synthesize the most recent research on the relationship of hospital staffing and HAI risk. A systematic review was undertaken. Electronic databases MEDLINE, PubMed, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched for studies published between January 1, 2000, and November 30, 2015. RESULTS: Fifty-four articles were included in the review. The majority of studies examined the relationship between nurse staffing and HAIs (n = 50, 92.6%) and found nurse staffing variables to be associated with an increase in HAI rates (n = 40, 74.1%). Only 5 studies addressed non-nurse staffing, and those had mixed results. Physician staffing was associated with an increased HAI risk in 1 of 3 studies. Studies varied in design and methodology, as well as in their use of operational definitions and measures of staffing and HAIs. CONCLUSION: Despite the lack of consistency of the included studies, overall, the results of this systematic review demonstrate that increased staffing is related to decreased risk of acquiring HAIs. More rigorous and consistent research designs, definitions, and risk-adjusted HAI data are needed in future studies exploring this area.


Assuntos
Infecção Hospitalar/epidemiologia , Corpo Clínico Hospitalar/estatística & dados numéricos , Recursos Humanos de Enfermagem Hospitalar/estatística & dados numéricos , Admissão e Escalonamento de Pessoal/estatística & dados numéricos , Humanos , Estudos Observacionais como Assunto , Medição de Risco , Fatores de Risco , Carga de Trabalho
19.
Am J Infect Control ; 46(9): 980-985, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29550084

RESUMO

BACKGROUND: The Researching Effective Approaches to Cleaning in Hospitals (REACH) study tested a multimodal cleaning intervention in Australian hospitals. This article reports findings from a pre/post questionnaire, embedded into the REACH study, that was administered prior to the implementation of the intervention and at the conclusion of the study. METHODS: A cross-sectional questionnaire, nested within a stepped-wedge trial, was administered. The REACH intervention was a cleaning bundle comprising 5 interdependent components. The questionnaire explored the knowledge, reported practice, attitudes, roles, and perceived organizational support of environmental services staff members in the hospitals participating in the REACH study. RESULTS: Environmental services staff members in 11 participating hospitals completed 616 pre- and 307 post-test questionnaires (n = 923). Increases in knowledge and practice were seen between the pre-and post-test questionnaires. Minimal changes were observed in attitudes regarding the role of cleaning and in perceived organizational support. CONCLUSION: To our knowledge, this is the first study to report changes in knowledge, attitudes, and perceived organizational support in environmental services staff members, in the context of a large multicenter clinical trial. In this underexplored group of hospital workers, findings suggest that environmental services staff members have a high level of knowledge related to cleaning practices and understand the importance of their role.


Assuntos
Infecção Hospitalar/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Zeladoria Hospitalar/métodos , Recursos Humanos em Hospital/psicologia , Adulto , Austrália , Estudos Transversais , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
20.
Aust Health Rev ; 42(3): 340-347, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28514641

RESUMO

Objective Hospital emergency departments (ED) in Australia and internationally have been experiencing increased demand, resulting in reduced hospital quality, impaired access and adverse health outcomes. Effective evaluation of new ED service models and their effect on outcomes is reliant on baseline measures of the staffing configuration and organisational characteristics of the EDs being studied. The aim of the present study was to comprehensively measure these variables in Australian EDs. Methods Australian hospital EDs with 24-h medical and nursing cover were identified and invited to participate in the study. Telephone interviews were conducted with nursing or medical department managers to collect data related to hospital characteristics, ED workforce and training and ED service and operational models. Results Surveys were completed in 87% of the population sample (n=135). Metropolitan EDs were significantly more likely to retain higher full-time equivalents (FTEs) in several medical (staff specialist, registrar, resident and intern) and nursing (nurse practitioner (NP), nurse educator, nurse unit manager and registered nurse) positions. NPs were employed by 52% of Australian EDs overall, but this ranged from 40% to 75% depending on jurisdiction. The most commonly used operational models were FastTrack teams (72% of EDs), short-stay/observational unit (59%) and patient liaison models for aged care (84%) and mental health (61%). EDs that employed NPs were significantly more likely to use FastTrack (P=0.002). Allied health services most frequently available within these EDs were radiology (60%), social work (69%), physiotherapy (70%) and pharmacy (65%). Conclusions The present study has established a baseline measure of the staffing configuration and organisational characteristics of Australian EDs. What is known about the topic? EDs are overcrowded due, in part, to the combined effect of increased service demand and access block. Innovative service and workforce models have been implemented by health departments aiming to improve service and performance. National uptake of these service and workforce innovations is unknown. What does this paper add? The present study is the most comprehensive to date profiling Australian EDs covering hospital characteristics, workforce configuration, operational models and NP service patterns and practice. What are the implications for practitioners? Information from the present study will assist health service planners to evaluate workforce and service reform models, and to monitor trends in emergency service development.


Assuntos
Serviço Hospitalar de Emergência/organização & administração , Serviço Hospitalar de Emergência/estatística & dados numéricos , Pessoal de Saúde/estatística & dados numéricos , Admissão e Escalonamento de Pessoal/organização & administração , Austrália , Pesquisas sobre Atenção à Saúde , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Necessidades e Demandas de Serviços de Saúde , Humanos , Entrevistas como Assunto , Modelos Organizacionais , Profissionais de Enfermagem/estatística & dados numéricos , Recursos Humanos de Enfermagem Hospitalar , Recursos Humanos
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