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1.
Infect Dis Health ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38555194

RESUMO

BACKGROUND: Rates of antimicrobial resistance (AMR) for some pathogens in Australia are considerably higher in rural and remote compared to urban regions. The inaugural Hot North Antimicrobial Academy was a 9-month educational programme aimed to build workforce knowledge and capacity in antimicrobial use, audit, stewardship, surveillance and drug resistance in remote primary health care. METHODS: The Academy was advertised to Aboriginal and Torres Strait Islander, regional and remote healthcare workers. Participants were Aboriginal health practitioners, nurses, pharmacists and doctors from Queensland, Northern Territory, South Australia and Western Australia working in remote primary health care with a focus on Indigenous health. Due to COVID-19 restrictions, the Academy ran virtually from February-November 2021 using Microsoft Teams. The Academy was evaluated using surveys and yarning circles to assess impact and knowledge gain. RESULTS: Participants and faculty from across Australia attended 19 lectures and mentorship sessions. Eleven participants commenced and eight (73%) completed the Academy. The Academy raised participants awareness of AMR guidelines, governance and generating change; built confidence in advocacy; grew knowledge about drug resistant infections; and created a community of AMR champions in Indigenous health. CONCLUSION: The evaluation confirmed the Academy met the needs of participants, provided opportunities to move stewardship from tertiary hospitals into Indigenous and remote clinics and developed skills in research, audit, stewardship and advocacy for all involved. All sessions were recorded for future use, with facilitation by the National Aboriginal Community Controlled Health Organisation (NACCHO) in future years.

2.
Trials ; 24(1): 57, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36698201

RESUMO

BACKGROUND: Dysarthria after stroke is when speech intelligibility is impaired, and this occurs in half of all stroke survivors. Dysarthria often leads to social isolation, poor psychological well-being and can prevent return to work and social lives. Currently, a variety of outcome measures are used in clinical research and practice when monitoring recovery for people who have dysarthria. When research studies use different measures, it is impossible to compare results from trials and delays our understanding of effective clinical treatments. The aim of this study is to develop a core outcome set (COS) to agree what aspects of speech recovery should be measured for dysarthria after stroke (COS-Speech) in research and clinical practice. METHODS: The COS-Speech study will include five steps: (1) development of a long list of possible outcome domains of speech that should be measured to guide the survey; (2) recruitment to the COS-Speech study of three key stakeholder groups in the UK and Australia: stroke survivors, communication researchers and speech and language therapists/pathologists; (3) two rounds of the Delphi survey process; (4) a consensus meeting to agree the speech outcomes to be measured and a follow-up consensus meeting to match existing instruments/measures (from parallel systematic review) to the agreed COS-Speech; (5) dissemination of COS-Speech. DISCUSSION: There is currently no COS for dysarthria after stroke for research trials or clinical practice. The findings from this research study will be a minimum COS, for use in all dysarthria research studies and clinical practice looking at post-stroke recovery of speech. These findings will be widely disseminated using professional and patient networks, research and clinical forums as well as using a variety of academic papers, videos, accessible writing such as blogs and links on social media. TRIAL REGISTRATION: COS-Speech is registered with the Core Outcome Measures in Effectiveness Trials (COMET) database, October 2021 https://www.comet-initiative.org/Studies/Details/1959 . In addition, "A systematic review of the psychometric properties and clinical utility of instruments measuring dysarthria after stroke" will inform the consensus meeting to match measures to COS-Speech. The protocol for the systematic reviews registered with the International Prospective Register of Systematic Reviews. PROSPERO registration number: CRD42022302998 .


Assuntos
Disartria , Fala , Humanos , Disartria/diagnóstico , Disartria/etiologia , Disartria/terapia , Projetos de Pesquisa , Técnica Delphi , Revisões Sistemáticas como Assunto , Avaliação de Resultados em Cuidados de Saúde/métodos , Resultado do Tratamento
3.
Vaccine ; 40(32): 4531-4537, 2022 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-35718588

RESUMO

Children with cochlear implants are at increased risk of invasive pneumococcal disease, with national and international guidelines recommending additional pneumococcal vaccines for these children. This study aimed to examine the pneumococcal immunization status and rate of invasive pneumococcal disease in children with cochlear implants at a tertiary paediatric hospital over a 12-year period. Additionally, the impacts of vaccination reminders and a dedicated immunization clinic on pneumococcal vaccination rates were assessed. This quality improvement study included 200 children who had received a cochlear implant through the Children's Hearing Implant Program at a tertiary paediatric hospital servicing the state of Western Australia. The majority of children (88%) were not up to date with additionally recommended pneumococcal vaccinations. Over the 12-year study period, 2% of children developed invasive pneumococcal disease associated with cochlear implant infections. Generic and personalized electronic immunization reminders improved pneumococcal vaccine up-take in this paediatric cochlear implant setting from 12% (19/153) at baseline to 49% (75/153, p < 0.0001) post implementation. The value of a nurse-led dedicated immunization clinic was also demonstrated with all children (42/42, 100%) up to date with Prevenar13 and the majority (34/42, 81%) up to date with Pneumovax23 post initiation of this referral pathway. These data support the expansion of this model to other medically-at-risk paediatric groups that have been highlighted consistently to be under-vaccinated.


Assuntos
Implante Coclear , Implantes Cocleares , Infecções Pneumocócicas , Vacinas Pneumocócicas , Criança , Implante Coclear/efeitos adversos , Humanos , Infecções Pneumocócicas/etiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/efeitos adversos , Melhoria de Qualidade , Vacinação
4.
JAC Antimicrob Resist ; 4(1): dlac014, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35237755

RESUMO

BACKGROUND: Combination antibiotic therapy with an antitoxin agent, such as clindamycin, is included in some guidelines for severe, toxin-mediated Staphylococcus aureus infections. The evidence to support this practice is currently limited to in vitro, animal and observational human case-series data, with no previous randomized controlled trials (RCTs). OBJECTIVES: This pilot RCT aimed to determine the feasibility of conducting a clinical trial to examine if adjunctive clindamycin with standard therapy has greater efficacy than standard therapy alone for S. aureus infections. METHODS: We performed an investigator-initiated, open-label, multicentre, pilot RCT (ACTRN12617001416381p) in adults and children with severe S. aureus infections, randomized to standard antibiotic therapy with or without clindamycin for 7 days. RESULTS: Over 28 months, across nine sites, 127 individuals were screened and 34 randomized, including 11 children (32%). The primary outcome-number of days alive and free of systemic inflammatory response syndrome ≤14 days-was similar between groups: clindamycin (3 days [IQR 1-6]) versus standard therapy (4 days [IQR 0-8]). The 90 day mortality was 0% (0/17) in the clindamycin group versus 24% (4/17) in the standard therapy group. Secondary outcomes-microbiological relapse, treatment failure or diarrhoea-were similar between groups. CONCLUSIONS: As the first clinical trial assessing adjunctive clindamycin for S. aureus infections, this study indicates feasibility and that adults and children can be incorporated into one trial using harmonized endpoints, and there were no safety concerns. The CASSETTE trial will inform the definitive S. aureus Network Adaptive Platform (SNAP) trial, which includes an adjunctive clindamycin domain and participants with non-severe disease.

5.
Artigo em Inglês | MEDLINE | ID: mdl-35027061

RESUMO

BACKGROUND: The impacts of the COVID-19 pandemic have been vast and are not limited to physical health. Many adolescents have experienced disruptions to daily life, including changes in their school routine and family's financial or emotional security, potentially impacting their emotional wellbeing. In low COVID-19 prevalence settings, the impact of isolation has been mitigated for most young people through continued face-to-face schooling, yet there may still be significant impacts on their wellbeing that could be attributed to the pandemic. METHODS: We report on data from 32,849 surveys from Year 7-12 students in 40 schools over two 2020 survey cycles (June/July: 19,240; October: 13,609), drawn from a study of 79 primary and secondary schools across Western Australia, Australia. The Child Health Utility Index (CHU9D) was used to measure difficulties and distress in responding secondary school students only. Using comparable Australian data collected six years prior to the pandemic, the CHU9D was calibrated against the Kessler-10 to establish a reliable threshold for CHU9D-rated distress. RESULTS: Compared to 14% of responding 12-18-year-olds in 2013/2014, in both 2020 survey cycles almost 40% of secondary students returned a CHU9D score above a threshold indicative of elevated difficulties and distress. Student distress increased significantly between June and October 2020. Female students, those in older Grades, those with few friendships or perceived poor quality friendships, and those with poor connectedness to school were more likely to score above the threshold. CONCLUSIONS: In a large dataset collected during the first year of the COVID-19 pandemic, the proportion of secondary school students with scores indicative of difficulties and distress was substantially higher than a 2013/2014 benchmark, and distress increased as the pandemic progressed, despite the low local prevalence of COVID-19. This may indicate a general decline in social and emotional wellbeing exacerbated by the events of the pandemic. TRIAL REGISTRATION: ANZCTRN (ACTRN12620000922976). Retrospectively registered 17/08/2020. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380429&isReview=true .

6.
Int J Oral Maxillofac Surg ; 51(5): 621-624, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34481736

RESUMO

The multifactorial nature of head and neck squamous cell carcinoma (HNSCC) has led to increased efforts in establishing various risk factors. Well-known environmental risk factors for HNSCC include tobacco use, heavy alcohol consumption, immunosuppression, and more recently human papillomavirus infection. Familial clustering has been observed in cancers occurring at other sites, but not so much with oral squamous cell carcinoma (OSCC) without exposure to shared environmental risk factors. An unusual case of identical twins who presented with OSCC involving an identical site and exhibiting similar histological features is reported here. The two patients underwent identical surgery with curative intent, culminating in good outcomes. It appears that no other cases of identical twins with a similar presentation in time, anatomical site, and histopathology have been reported in the literature.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Infecções por Papillomavirus , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Humanos , Neoplasias Bucais/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Gêmeos Monozigóticos
7.
Br J Oral Maxillofac Surg ; 59(10): 1113-1119, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34772559

RESUMO

Temporomandibular joint (TMJ) ankylosis is a condition in which bony or fibrous adhesion of the anatomical joint components results in loss of function. This is particularly distressing and debilitating for patients who struggle to maintain good oral hygiene, which results in additional pain, oral disease, and ultimately, a poor aesthetic profile. A retrospective chart review was carried out to document the cases of three patients who attended a single centre for the management of ankylosis of the TMJ. Consent for chart review and use of photographs was gained from each one. Charts were obtained, records reviewed, and each of the cases written up for presentation in a case series. All three underwent arthroplasty of the TMJ and insertion of Matthews devices (two patients unilateral, one bilateral). All were followed up postoperatively. They experienced significant improvements in vertical mouth opening which have been maintained to the present. The Matthews device allows movement and physiotherapy postoperatively whilst maintaining the surgically created space. This prevents impingement on the tissues placed between the glenoid fossa and mandible, and appears to prevent relapse and further ankylosis. To our knowledge, few studies to date have documented the use of the Matthews device following interpositional arthroplasty of the TMJ.


Assuntos
Anquilose , Artroplastia , Humanos , Estudos Retrospectivos , Articulação Temporomandibular , Transtornos da Articulação Temporomandibular
8.
Res Involv Engagem ; 6: 21, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32419954

RESUMO

BACKGROUND: Patient, Carer and Public Involvement (PCPI) should be embedded in health care research. Delivering PCPI can be challenging, but even when PCPI is carried out it is rarely reported resulting in lost opportunities for learning. This paper aims to describe PCPI in the OSCARSS study, a pragmatic-cluster randomised controlled trial with an embedded economic and process evaluation. METHODS: A carer research user group (RUG) co-developed OSCARSS to evaluate how to best deliver support to caregivers of stroke survivors. The PCPI activity involved regular meetings and preparatory work, from the initial conceptualisation of the study through to dissemination. Written reports, structured group discussions and individual interviews were carried out with the RUG and researchers to capture the added value and learning. This paper was co-authored by two of the RUG members with contributions from the wider RUG and researchers. RESULTS: The core six members of the caregiver RUG attended the majority of the meetings alongside three researchers, one of whom was the co-chief investigator. PCPI was instrumental in changing many aspects of the research protocol, design and delivery and contributed to dissemination and sharing of good practice. There were challenges due to the emotional toll when PCPI members shared their stories and the extensive time commitment. Positive experiences of learning and fulfilment were reported by the individual researchers and PCPI members. Wider organisational administrative and financial support facilitated the PCPI. The researchers' existing positive regard for PCPI and the clear focus of the group were key to the successful co-design of this research. CONCLUSIONS: The value and learning from the PCPI collaborative work with the researchers was of benefit to the study and the individuals involved. Specific PCPI influences were a challenge to pinpoint as successful co-design meant the researchers' and carers' contributions were intertwined and decision-making shared.

9.
Br J Dermatol ; 183(5): 808-820, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32034956

RESUMO

BACKGROUND: Scabies is a common parasitic skin condition that causes considerable morbidity globally. Clinical and epidemiological research for scabies has been limited by a lack of standardization of diagnostic methods. OBJECTIVES: To develop consensus criteria for the diagnosis of common scabies that could be implemented in a variety of settings. METHODS: Consensus diagnostic criteria were developed through a Delphi study with international experts. Detailed recommendations were collected from the expert panel to define the criteria features and guide their implementation. These comments were then combined with a comprehensive review of the available literature and the opinion of an expanded group of international experts to develop detailed, evidence-based definitions and diagnostic methods. RESULTS: The 2020 International Alliance for the Control of Scabies (IACS) Consensus Criteria for the Diagnosis of Scabies include three levels of diagnostic certainty and eight subcategories. Confirmed scabies (level A) requires direct visualization of the mite or its products. Clinical scabies (level B) and suspected scabies (level C) rely on clinical assessment of signs and symptoms. Evidence-based, consensus methods for microscopy, visualization and clinical symptoms and signs were developed, along with a media library. CONCLUSIONS: The 2020 IACS Criteria represent a pragmatic yet robust set of diagnostic features and methods. The criteria may be implemented in a range of research, public health and clinical settings by selecting the appropriate diagnostic levels and subcategories. These criteria may provide greater consistency and standardization for scabies diagnosis. Validation studies, development of training materials and development of survey methods are now required. What is already known about this topic? The diagnosis of scabies is limited by the lack of accurate, objective tests. Microscopy of skin scrapings can confirm the diagnosis, but it is insensitive, invasive and often impractical. Diagnosis usually relies on clinical assessment, although visualization using dermoscopy is becoming increasingly common. These diagnostic methods have not been standardized, hampering the interpretation of findings from clinical research and epidemiological surveys, and the development of scabies control strategies. What does this study add? International consensus diagnostic criteria for common scabies were developed through a Delphi study with global experts. The 2020 International Alliance for the Control of Scabies (IACS) Criteria categorize diagnosis at three levels of diagnostic certainty (confirmed, clinical and suspected scabies) and eight subcategories, and can be adapted to a range of research and public health settings. Detailed definitions and figures are included to aid training and implementation. The 2020 IACS Criteria may facilitate the standardization of scabies diagnosis.


Assuntos
Escabiose , Administração Tópica , Consenso , Humanos , Escabiose/diagnóstico , Escabiose/epidemiologia , Pele
10.
Perspect Public Health ; 140(2): 102-107, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31334689

RESUMO

AIMS: Recovery approaches are identified as the overarching framework for improving mental health services for people with severe and enduring conditions. These approaches prioritise living well with long-term conditions, as evidenced by personal recovery outcomes. There is little research demonstrating how to support busy mental health teams, work in this way. This study assessed the impact of introducing a brief measure of recovery, the Hope, Agency and Opportunity (HAO), on the attitudes and behaviours of staff working in community mental health teams, to test whether routine use of such measures facilitates recovery-based practice. METHODS: Linguistic analysis assumes that language is indicative of wider attitudes and behaviours. Anonymised clinical notes recorded by community mental health team clinicians were analysed for recovery and non-recovery language, over 30 months. This covered periods before, during and after the introduction of the recovery measure. We used a single-case design (N = 1 community mental health team) and hypothesised that clinicians would use recovery-focused language more frequently, and non-recovery-focused language less frequently, following the introduction of the measure, and that these changes would be maintained at 18-month follow-up. RESULTS: Visual inspection of the data indicated that recovery-focused language increased following the introduction of the HAO, though this was not maintained at follow-up. This pattern was not supported by statistical analyses. No clear pattern of change was found for non-recovery-focused language. CONCLUSIONS: The introduction of a brief measure of recovery may have influenced staff attitudes and behaviours temporarily. Any longer term impact is likely to depend on ongoing commitment to the use of the measure, without which staff language, attitudes and behaviours return to previous levels.


Assuntos
Atitude do Pessoal de Saúde , Serviços Comunitários de Saúde Mental/organização & administração , Pessoal de Saúde/psicologia , Transtornos Mentais/terapia , Avaliação de Resultados em Cuidados de Saúde/organização & administração , Humanos , Equipe de Assistência ao Paciente/organização & administração , Terminologia como Assunto
11.
Eur Arch Paediatr Dent ; 20(2): 65-72, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30378001

RESUMO

AIM: To assess the knowledge, attitudes and behaviour of dentists nationwide in Ireland regarding the infant oral health visit, and also to elucidate whether dentists were aware of the recommendation for a first dental visit by age 1 year and of what care should be provided at this visit. METHODS: A validated 10-item questionnaire was distributed to a representative sample of non-paediatric dentists (non-PDs) and paediatric dentists (PDs) practicing in Ireland. The questionnaire focused on respondents' demographics in addition to their knowledge, attitudes and behaviour regarding the infant dental visit. RESULTS: Seventy-three percent of non-PDs reported seeing patients aged 0-36 months. Compared to all PD respondents, 58% of non-PDs believed that the first dental visit should occur by age 1 year. Furthermore, non-PDs provided the same care as PDs at the infant dental visit, with the exception of evaluating for fluoride needs and placing fluoride varnish. The main barrier to early oral healthcare was reported to be parents not requesting dental appointments for their infants. CONCLUSIONS: There remains a need to increase the proportion of non-PDs in Ireland seeing infants by their first birthday. It is recommended that Irish undergraduate and continuing education courses incorporate clinical training regarding the infant oral health visit and emphasise fluoride needs evaluation and fluoride varnish application. Additionally, a nationwide health promotion initiative is indicated to inform parents of the importance of a dental visit by age 1 year.


Assuntos
Assistência Odontológica para Crianças , Saúde Bucal , Atitude , Atitude do Pessoal de Saúde , Criança , Pré-Escolar , Odontólogos , Humanos , Lactente , Recém-Nascido , Irlanda , Padrões de Prática Odontológica
12.
J Antimicrob Chemother ; 74(1): 1-5, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30307507

RESUMO

Protein synthesis inhibitor antibiotics inhibit synthesis of new proteins, including exotoxins and other important virulence determinants in Staphylococcus aureus. A summary of the literature regarding the use of adjunctive protein synthesis inhibitors for toxin suppression in the setting of S. aureus infections is presented.


Assuntos
Antibacterianos/administração & dosagem , Toxinas Bacterianas/biossíntese , Inibidores da Síntese de Proteínas/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Toxinas Bacterianas/antagonistas & inibidores , Humanos , Inibidores da Síntese de Proteínas/farmacologia
13.
J Pediatr ; 207: 103-108.e1, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30545562

RESUMO

OBJECTIVE: To develop a parent-reported Pediatric Rhinosinusitis Symptom Scale (PRSS) that could be used to monitor symptoms of young children with acute sinusitis in response to therapy. STUDY DESIGN: We developed an 8-item symptom severity scale and evaluated its internal reliability, construct validity, and responsiveness in children 2-12 years of age with acute sinusitis. Parents of 258 children with acute sinusitis completed the PRSS at the time of diagnosis, as a diary at home, and at the follow-up visit at days 10-12. Based on psychometric results and additional parent feedback, we revised the scale. We evaluated the revised version in 185 children with acute sinusitis. RESULTS: Correlations between the scale and reference measures on the day of enrollment were in the expected direction and of the expected magnitude. PRSS scores at the time of presentation correlated with radiographic findings (P < .001), functional status (P < .001), and parental assessment of overall symptom severity (P < .001). Responsiveness (standardized response mean) and test-retest reliability of the revised scale were good (2.17 and 0.75, respectively). CONCLUSIONS: We have developed an outcome measure to track the symptoms of acute sinusitis. Data presented here support the use of the PRSS as a measure of change in symptom burden in clinical trials of children with acute sinusitis.


Assuntos
Avaliação de Resultados em Cuidados de Saúde/métodos , Sinusite/fisiopatologia , Doença Aguda , Criança , Pré-Escolar , Análise Fatorial , Feminino , Humanos , Avaliação de Resultados em Cuidados de Saúde/normas , Pais , Estudos Prospectivos , Reprodutibilidade dos Testes
14.
Epidemiol Infect ; 147: e4, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30109840

RESUMO

Streptococcus pyogenes (or Group A Streptococcus, GAS) is a Gram-positive human pathogen responsible for a diverse array of superficial, invasive and immune-related diseases. GAS infections have historically been diseases of poverty and overcrowding, and remain a significant problem in the developing world and in disadvantaged populations within developed countries. With improved living conditions and access to antibiotics, the rates of GAS diseases in developed societies have gradually declined during the 20th century. However, genetic changes in circulating GAS strains and/or changes in host susceptibility to infection can lead to dramatic increases in the rates of specific diseases. No situations exemplify this more than the global upsurge of invasive GAS disease that originated in the 1980s and the regional increases in scarlet fever in north-east Asia and the UK. In each case, increased disease rates have been associated with the emergence of new GAS strains with increased disease-causing capability. Global surveillance for new GAS strains with increased virulence is important and determining why certain populations suddenly become susceptible to circulating strains remains a research priority. Here, we overview the changing epidemiology of GAS infections and the genetic alterations that accompany the emergence of GAS strains with increased capacity to cause disease.

16.
Sci Rep ; 8(1): 5466, 2018 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-29615812

RESUMO

Metastatic melanoma remains difficult to treat despite recent approvals of several new drugs. Recently we reported encouraging results of Phase I clinical trial of radiolabeled with 188Re murine monoclonal IgM 6D2 to melanin in patients with Stage III/IV melanoma. Subsequently we generated a novel murine IgG 8C3 to melanin. IgGs are more amenable to humanization and cGMP (current Good Manufacturing Practice) manufacturing than IgMs. We performed comparative structural analysis of melanin-binding IgM 6D2 and IgG 8C3. The therapeutic efficacy of 213Bi- and 188Re-labeled 8C3 and its comparison with anti-CTLA4 immunotherapy was performed in B16-F10 murine melanoma model. The primary structures of these antibodies revealed significant homology, with the CDRs containing a high percentage of positively charged amino acids. The 8C3 model has a negatively charged binding surface and significant number of aromatic residues in its H3 domain, suggesting that hydrophobic interactions contribute to the antibody-melanin interaction. Radiolabeled IgG 8C3 showed significant therapeutic efficacy in murine melanoma, safety towards healthy melanin-containing tissues and favorable comparison with the anti-CTLA4 antibody. We have demonstrated that antibody binding to melanin relies on both charge and hydrophobic interactions while the in vivo data supports further development of 8C3 IgG as radioimmunotherapy reagent for metastatic melanoma.


Assuntos
Anticorpos/química , Anticorpos/imunologia , Melaninas/imunologia , Melanoma/imunologia , Melanoma/terapia , Radioimunoterapia/métodos , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/terapia , Sequência de Aminoácidos , Animais , Linhagem Celular Tumoral , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Melanoma/patologia , Camundongos , Neoplasias Cutâneas/patologia , Relação Estrutura-Atividade , Melanoma Maligno Cutâneo
17.
Biochem Biophys Res Commun ; 479(4): 793-799, 2016 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-27687546

RESUMO

The Wnt signalling pathway in beta-cells has been linked to the development of type 2 diabetes. Investigating the impact of a non-canonical Wnt ligand, Wnt4, on beta-cell function we found that in INS-1 cells, Wnt4 was able to completely block Wnt3a stimulated cell growth and insulin secretion. However, despite high levels of Wnt4 protein being detected in INS-1 cells, reducing the expression of Wnt4 had no impact on cell growth or Wnt3a signalling. As such, the role of the endogenously expressed Wnt4 in beta-cells is unclear, but the data showing that Wnt4 can act as a negative regulator of canonical Wnt signalling in beta-cells suggests that this pathway could be a potential target for modulating beta-cell function.


Assuntos
Células Secretoras de Insulina/metabolismo , Proteína Wnt3A/metabolismo , Proteína Wnt4/metabolismo , Animais , Linhagem Celular , Proliferação de Células , Glucose/metabolismo , Glucose/farmacologia , Humanos , Imuno-Histoquímica , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/efeitos dos fármacos , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Ratos , Via de Sinalização Wnt , Proteína Wnt3A/antagonistas & inibidores , Proteína Wnt3A/farmacologia , Proteína Wnt4/genética , Proteína Wnt4/farmacologia , beta Catenina/genética , beta Catenina/metabolismo
18.
Epidemiol Infect ; 144(9): 1991-8, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26833141

RESUMO

Impetigo is common in remote Indigenous children of northern Australia, with the primary driver in this context being Streptococcus pyogenes [or group A Streptococcus (GAS)]. To reduce the high burden of impetigo, the transmission dynamics of GAS must be more clearly elucidated. We performed whole genome sequencing on 31 GAS isolates collected in a single community from children in 11 households with ⩾2 GAS-infected children. We aimed to determine whether transmission was occurring principally within households or across the community. The 31 isolates were represented by nine multilocus sequence types and isolates within each sequence type differed from one another by only 0-3 single nucleotide polymorphisms. There was evidence of extensive transmission both within households and across the community. Our findings suggest that strategies to reduce the burden of impetigo in this setting will need to extend beyond individual households, and incorporate multi-faceted, community-wide approaches.


Assuntos
Transmissão de Doença Infecciosa , Genoma Bacteriano , Genótipo , Impetigo/epidemiologia , Impetigo/transmissão , Análise de Sequência de DNA , Streptococcus pyogenes/classificação , Streptococcus pyogenes/isolamento & purificação , Austrália/epidemiologia , Criança , Pré-Escolar , Características da Família , Feminino , Variação Genética , Humanos , Masculino , Epidemiologia Molecular , Tipagem de Sequências Multilocus , Polimorfismo de Nucleotídeo Único
19.
J Laryngol Otol ; 129(5): 478-83, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25994382

RESUMO

BACKGROUND: Surgery is currently the only curative treatment for medullary thyroid cancer. Unfortunately, the surgical strategy that will offer patients at each disease stage the best chance of a biochemical cure remains unclear. The American Thyroid Association and British Thyroid Association guidelines offer different strategies. METHODS: A retrospective analysis of the surgical management of 47 patients with medullary thyroid cancer diagnosed between 1994 and 2013 was performed. Surgical management was compared with current American Thyroid Association and British Thyroid Association guidelines. Outcome was defined as the first post-operative calcitonin measurement. RESULTS: All patients with stage I-III disease achieved a post-operative biochemical cure regardless of the guidelines followed. The overall biochemical cure rate for patients with stage IVa disease was significantly reduced to 10 per cent (p < 0.01), but the biochemical cure rate for stage IVa disease patients who underwent bilateral lateral lymph node dissection was 33.3 per cent. CONCLUSION: The conservative, surveillance-driven approach recommended by the American Thyroid Association is appropriate for stage I-III disease. However, the more aggressive approach advocated by the British Thyroid Association might provide stage IVa disease patients a greater chance of achieving a biochemical cure.


Assuntos
Carcinoma Neuroendócrino/cirurgia , Guias de Prática Clínica como Assunto/normas , Neoplasias da Glândula Tireoide/cirurgia , Adulto , Idoso , Carcinoma Neuroendócrino/patologia , Intervalo Livre de Doença , Feminino , Fidelidade a Diretrizes , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Sociedades Médicas , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia , Reino Unido , Estados Unidos
20.
Rural Remote Health ; 14(2): 2759, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24924831

RESUMO

INTRODUCTION: Australian Indigenous children suffer a high burden of diarrhoeal disease. Nitazoxanide is an antimicrobial that has been shown to be effective against a broad range of enteropathogens. To date, its use has not been reported in the tropical Top End (northernmost part) of the Northern Territory, Australia. The objective was to describe the use of nitazoxanide at the Royal Darwin Hospital, Northern Territory, and to assess any association with the time to resolution of diarrhoea. METHODS: Eligible children (≤13 years) were identified from dispensary records as having been prescribed nitazoxanide during the audit period, 1 July 2007 to 31 March 2012. Patient demographics, symptoms, diarrheal aetiology, treatment details and clinical outcomes were obtained by chart review. RESULTS: Twenty-eight children were treated with nitazoxanide, mostly for Cryptosporidium infection associated with prolonged diarrhoea. Dehydration was evident in 27 (96%) children on admission, and 11 (41%) were underweight. Diarrhoeal duration prior to treatment was 11.5 days (6.5 days pre- and 5 days post-admission). For children ≥12 months, nitazoxanide was prescribed according to guidelines stipulated by the Centers for Disease Control and Prevention (CDC). Resolution of diarrhoea occurred a median of 2.4 days (IQR: 1.4-7.3) after starting treatment. An increase in weight for length at discharge was found for all children. CONCLUSIONS: Prompt resolution of diarrhoea without adverse outcomes suggests nitazoxanide may be an effective treatment for Cryptosporidium infection in this setting. Its role in the treatment of other causes of infectious diarrhoea needs further investigation. Randomised trials will further direct its use and determine optimal dosing regimens.


Assuntos
Anti-Infecciosos/uso terapêutico , Disenteria/tratamento farmacológico , Tiazóis/uso terapêutico , Adolescente , Criança , Desidratação/epidemiologia , Disenteria/epidemiologia , Disenteria/etnologia , Feminino , Humanos , Masculino , Havaiano Nativo ou Outro Ilhéu do Pacífico , Nitrocompostos , Northern Territory/epidemiologia , Fatores Socioeconômicos , Magreza/epidemiologia
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