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1.
J Plast Reconstr Aesthet Surg ; 91: 258-267, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428234

RESUMO

INTRODUCTION: Advances in burns management have reduced mortality. Consequently, efficient resource management plays an increasingly important role in improving paediatric burns care. This study aims to assess the support requirements and outcomes of paediatric burns patients admitted to a burns centre intensive care unit in comparison to established benchmarks in burns care. METHOD: A retrospective review of burns patients under the age of 16 years old, admitted to a regional burns service intensive care unit between March 1998 and March 2016 was conducted. RESULTS: Our analysis included 234 patients, with the percentage of TBSA affected by burn injury ranging from 1.5% to 95.0%. The median (IQR) %TBSA was 20.0% (11.0-30.0), and the observed mortality rate was 2.6% (6/234). The median (IQR) length of stay was 0.7 days/%TBSA burn (0.4-1.2), 17.9% (41/229) required circulatory support and 2.6% (6/234) required renal replacement. Mortality correlated with smoke inhalation injury (P < 0.001), %TBSA burn (P = 0.049) and complications (P = 0.004) including infections (P = 0.013). CONCLUSIONS: Among children with burn injuries who require intensive care, the presence of inhalational injury and the diagnosis of infection are positively correlated with mortality. Understanding the requirements for organ support can facilitate a more effective allocation of resources within a burns service.


Assuntos
Queimaduras , Unidades de Terapia Intensiva , Humanos , Criança , Adolescente , Tempo de Internação , Cuidados Críticos , Hospitalização , Unidades de Queimados , Estudos Retrospectivos , Queimaduras/complicações
2.
J Plast Reconstr Aesthet Surg ; 83: 282-288, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37290369

RESUMO

Nitrous oxide is used as a recreational drug. Contact frostbite injury from compressed gas canisters has previously been described in the literature, but an increased number of such cases has been noted in our busy regional burns center in the UK. A single-center prospective case series of all patients referred and treated for frostbite injury secondary to misuse of nitrous oxide compressed gas canisters between January and December 2022 is presented. Data collection was performed through a referral database and patient case notes. Sixteen patients, of which 7 were male and 9 were female, satisfied the inclusion criteria. Mean patient age was 22.5 years. The median TBSA was 1%. In total, 50% of patients in the cohort had a delayed initial presentation to A&E of greater than 5 days. Eleven patients were reviewed at our burns center for further assessment and management. In total, 11 patients had bilateral inner thigh frostbite injuries, of which 8 had necrotic full-thickness injury, including subcutaneous fat. Seven patients were reviewed at our burns center and offered excision and split-thickness skin graft. Four patients presented with contact frostbite injury to the hand and one patient to the lower lip. This subgroup was managed successfully with conservative management alone. The reproducible pattern of frostbite injury secondary to the abuse of nitrous oxide compressed gas canisters is demonstrated in our case series. The distinct pattern of injury, patient cohort, and anatomical area affected presents an opportunity for targeted public health intervention in this group.


Assuntos
Queimaduras , Congelamento das Extremidades , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Óxido Nitroso/efeitos adversos , Queimaduras/terapia , Congelamento das Extremidades/induzido quimicamente , Congelamento das Extremidades/terapia , Transplante de Pele , Reino Unido
3.
J Neuroimmune Pharmacol ; 18(1-2): 100-111, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36380156

RESUMO

Trace amine-associated receptor 1 (TAAR1) is an established neuroregulatory G protein-coupled receptor with recent studies suggesting additional functions related to immunomodulation. Our lab has previously investigated TAAR1 expression within cells of the innate immune system and herein we aim to further elucidate TAAR1 function in both peripherally-derived and CNS-resident macrophages. The selective TAAR1 agonist RO5256390 was used in combination with common damage associated molecular patterns (ATP and ADP) to observe the effect of TAAR1 agonism on modulating cytokine secretion and metabolic profiles. In mouse bone-marrow derived macrophages, TAAR1 agonism inhibited TNF secretion following ATP stimulation, which appeared to be downstream of an associated pro-inflammatory shift in metabolic profile and transcriptional regulation of TNF synthesis. In contrast, TAAR1 agonism had no effect on ADP-induced TNF and IL-6 secretion in mouse microglia in either the presence or absence of astrocytes. In summary, we report a novel interaction between TAAR1 and purinergic signaling in peripherally-derived, but not CNS-resident, macrophages. These findings provide the first evidence of trace aminergic and purinergic crosstalk, and support the potential for TAAR1 as a novel therapeutic target in inflammatory disorders.


Assuntos
Macrófagos , Receptores Acoplados a Proteínas G , Camundongos , Animais , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/metabolismo , Macrófagos/metabolismo , Transdução de Sinais , Trifosfato de Adenosina/metabolismo
4.
Genome Med ; 14(1): 99, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-36042521

RESUMO

BACKGROUND: Central conventional chondrosarcoma (CS) is the most common subtype of primary malignant bone tumour in adults. Treatment options are usually limited to surgery, and prognosis is challenging. These tumours are characterised by the presence and absence of IDH1 and IDH2 mutations, and recently, TERT promoter alterations have been reported in around 20% of cases. The effect of these mutations on clinical outcome remains unclear. The purpose of this study was to determine if prognostic accuracy can be improved by the addition of genomic data, and specifically by examination of IDH1, IDH2, and TERT mutations. METHODS: In this study, we combined both archival samples and data sourced from the Genomics England 100,000 Genomes Project (n = 356). Mutations in IDH1, IDH2, and TERT were profiled using digital droplet PCR (n = 346), whole genome sequencing (n=68), or both (n = 64). Complex events and other genetic features were also examined, along with methylation array data (n = 84). We correlated clinical features and patient outcomes with our genetic findings. RESULTS: IDH2-mutant tumours occur in older patients and commonly present with high-grade or dedifferentiated disease. Notably, TERT mutations occur most frequently in IDH2-mutant tumours, although have no effect on survival in this group. In contrast, TERT mutations are rarer in IDH1-mutant tumours, yet they are associated with a less favourable outcome in this group. We also found that methylation profiles distinguish IDH1- from IDH2-mutant tumours. IDH wild-type tumours rarely exhibit TERT mutations and tend to be diagnosed in a younger population than those with tumours harbouring IDH1 and IDH2 mutations. A major genetic feature of this group is haploidisation and subsequent genome doubling. These tumours evolve less frequently to dedifferentiated disease and therefore constitute a lower risk group. CONCLUSIONS: Tumours with IDH1 or IDH2 mutations or those that are IDHwt have significantly different genetic pathways and outcomes in relation to TERT mutation. Diagnostic testing for IDH1, IDH2, and TERT mutations could therefore help to guide clinical monitoring and prognostication.


Assuntos
Neoplasias Ósseas , Condrossarcoma , Adulto , Idoso , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Condrossarcoma/genética , Condrossarcoma/patologia , Humanos , Isocitrato Desidrogenase/genética , Modelos Genéticos , Mutação , Prognóstico
5.
Methods Mol Biol ; 2508: 225-234, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35737244

RESUMO

The propensity of cancer cells to preferentially undergo anaerobic metabolism despite oxygen being abundant is referred to as the Warburg effect. Measuring cellular metabolism is therefore central to understanding the cellular physiology of cancer cells. The Seahorse XFe Analyzer series allows real-time measurement of cellular metabolism. In the basic assay, two parameters, the oxygen consumption rate (OCR) and the extracellular acidification rate (ECAR), are used to determine real-time changes in the energy needs of live cells: OCR provides a measure of aerobic mitochondrial respiration; ECAR gives a measure of anaerobic glycolysis. Through the use of various respiration inhibitors, the Seahorse assay allows baseline respiration rate and total aerobic and anaerobic ATP production to be determined under a variety of experimental conditions. Here we describe the protocol for completing the Seahorse Real-Time ATP Rate Assay for adherent and suspension cancer cell lines. Depending on individual experimental results, more refined subsequent assays can then be performed to specifically determine, for example, the ability to utilize different substrates by the cell lines in the presence and absence of pharmacological and/or genetic interventions.


Assuntos
Neoplasias , Smegmamorpha , Trifosfato de Adenosina/metabolismo , Animais , Linhagem Celular , Metabolismo Energético , Glicólise , Consumo de Oxigênio/fisiologia , Smegmamorpha/metabolismo
6.
BMC Cancer ; 22(1): 629, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35672690

RESUMO

The phase III clinical study of adjuvant liposomal muramyl tripeptide (MTP-PE) in resected high-grade osteosarcoma (OS) documented positive results that have been translated into regulatory approval, supporting initial promise for innate immune therapies in OS. There remains, however, no new approved treatment such as MTP-PE for either metastatic or recurrent OS. Whilst the addition of different agents, including liposomal MTP-PE, to surgery for metastatic or recurrent high-grade osteosarcoma has tried to improve response rates, a mechanistic hiatus exists in terms of a detailed understanding the therapeutic strategies required in advanced disease. Here we report a Bayesian designed multi-arm, multi-centre, open-label phase II study with randomisation in patients with metastatic and/or recurrent OS, designed to investigate how patients with OS might respond to liposomal MTP-PE, either given alone or in combination with ifosfamide. Despite the trial closing because of poor recruitment within the allocated funding period, with no objective responses in eight patients, we report the design and feasibility outcomes for patients registered into the trial. We demonstrate the feasibility of the Bayesian design, European collaboration, tissue collection with genomic analysis and serum cytokine characterisation. Further mechanistic investigation of liposomal MTP-PE alone and in combination with other agents remains warranted in metastatic OS.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Teorema de Bayes , Biomarcadores , Neoplasias Ósseas/patologia , Humanos , Lipossomos , Recidiva Local de Neoplasia/tratamento farmacológico , Osteossarcoma/patologia , Fosfatidiletanolaminas
7.
Healthcare (Basel) ; 10(4)2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35455781

RESUMO

BACKGROUND: Wide disparities in health status exist in the United States across race and ethnicity, broadly driven by social determinants of health-most notably race and ethnic group differences in income, education, and occupational status. However, disparities in disease frequency or severity remain underappreciated for many individual diseases whose distribution in the population varies. Such information is not readily accessible, nor emphasized in treatment guidelines or reviews used by practitioners. Specifically, a summary on disease-specific evidence of disparities from population-based studies is lacking. Our goal was to summarize the published evidence for specific disease disparities in the United States so that this knowledge becomes more widely available "at the bedside". We hope this summary stimulates health equity research at the disease level so that these disparities can be addressed effectively. METHODS: A targeted literature review of disorders in Pfizer's current pipeline was conducted. The 38 diseases included metabolic disorders, cancers, inflammatory conditions, dermatologic disorders, rare diseases, and infectious targets of vaccines under development. Online searches in Ovid and Google were performed to identify sources focused on differences in disease rates and severity between non-Hispanic Whites and Black/African Americans, and between non-Hispanic Whites and Hispanics. As a model for how this might be accomplished for all disorders, disparities in disease rates and disease severity were scored to make the results of our review most readily accessible. After primary review of each condition by one author, another undertook an independent review. Differences between reviewers were resolved through discussion. RESULTS: For Black/African Americans, 29 of the 38 disorders revealed a robust excess in incidence, prevalence, or severity. After sickle cell anemia, the largest excesses in frequency were identified for multiple myeloma and hidradenitis suppurativa. For Hispanics, there was evidence of disparity in 19 diseases. Most notable were metabolic disorders, including non-alcoholic steatohepatitis (NASH). CONCLUSIONS: This review summarized recent disease-specific evidence of disparities based on race and ethnicity across multiple diseases, to inform clinicians and health equity research. Our findings may be well known to researchers and specialists in their respective fields but may not be common knowledge to health care providers or public health and policy institutions. Our hope is that this effort spurs research into the causes of the many disease disparities that exist in the United States.

9.
Lung Cancer ; 165: 124-132, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35123155

RESUMO

Over the last 10 years, with the development of culture-free bacterial identification techniques, understanding of how the microbiome influences diseases has increased exponentially and has highlighted potential opportunities for its use as a diagnostic biomarker and interventional target in many diseases including malignancy. Initial research focused on the faecal microbiome since it contains the densest bacterial populations and many other mucosal sites, such as the lungs, were until recently thought to be sterile. However, in recent years, it has become clear that the lower airways are home to a dynamic bacterial population sustained by the migration and elimination of microbes from the gastrointestinal and upper airway tracts. As in the gut, the lung microbiome plays an important role in regulating mucosal immunity and maintaining the balance between immune tolerance and inflammation. Studies to date have all shown that the lung microbiome undergoes significant changes in the setting of pulmonary disease. In lung cancer, animal models and small patient cohort studies have suggested that microbiome dysbiosis may not only impact tumour progression and response to therapy, particularly immunotherapy, but also plays a key role in cancer pathogenesis by influencing early carcinogenic pathways. These early results have led to concerted efforts to identify microbiome signatures that represent diagnostic biomarkers of early-stage disease and to consider modulation of the lung microbiome as a potential therapeutic strategy. Lung microbiome research is in its infancy and studies to date have been small, single centre with significant methodological variation. Large, multicentre longitudinal studies are needed to establish the clinical potential of this exciting field.

10.
Int J Mol Sci ; 22(21)2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34769007

RESUMO

TAAR1 is a neuroregulator with emerging evidence suggesting a role in immunomodulation. Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. Here, we investigate TAAR1 expression in human primary monocytes, peripherally-derived macrophages, and MS brain tissue. RT-qPCR was used to assess TAAR1 levels in MS monocytes. Using a previously validated anti-human TAAR1 antibody and fluorescence microscopy, TAAR1 protein was visualized in lipopolysaccharide-stimulated or basal human macrophages, as well as macrophage/microglia populations surrounding, bordering, and within a mixed active/inactive MS lesion. In vivo, TAAR1 mRNA expression was significantly lower in MS monocytes compared to age- and sex-matched healthy controls. In vitro, TAAR1 protein showed a predominant nuclear localization in quiescent/control macrophages with a shift to a diffuse intracellular distribution following lipopolysaccharide-induced activation. In brain tissue, TAAR1 protein was predominantly expressed in macrophages/microglia within the border region of mixed active/inactive MS lesions. Considering that TAAR1-mediated anti-inflammatory effects have been previously reported, decreased mRNA in MS patients suggests possible pathophysiologic relevance. A shift in TAAR1 localization following pro-inflammatory activation suggests its function is altered in pro-inflammatory states, while TAAR1-expressing macrophages/microglia bordering an MS lesion supports TAAR1 as a novel pharmacological target in cells directly implicated in MS neuroinflammation.


Assuntos
Encéfalo/metabolismo , Inflamação/metabolismo , Macrófagos/metabolismo , Esclerose Múltipla/metabolismo , Doenças Neuroinflamatórias/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Adulto , Células Cultivadas , Feminino , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Microglia/metabolismo , RNA Mensageiro/metabolismo
11.
Eur J Cancer Care (Engl) ; 30(6): e13492, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34312918

RESUMO

OBJECTIVE: Lung cancer patients from ethnic minorities have poorer outcomes than their Caucasian counterparts. We compared lung cancer intervals between culturally and linguistically diverse (CALD) and Anglo-Australian patients to identify ethnic disparities. METHODS: This was a prospective, observational cohort study comprising a patient survey and reviews of patients' hospital and general practice records. Across three states, 577 (407 Anglo-Australian and 170 CALD) patients were recruited and their hospital records reviewed. The survey was returned by 189 (135 Anglo-Australian and 54 CALD) patients, and a review was completed by general practitioners (GPs) of 99 (76 Anglo-Australian and 23 CALD) patients. Survival and Cox regression analyses were conducted. RESULTS: CALD patients had longer hospital diagnostic interval [median 30 days, 95% confidence interval (CI) 26-34] than Anglo-Australian patients (median 17, 95% CI 14-20), p = 0.005, hazard ratio (HR) = 1.32 (95% CI 1.09-1.60). This difference persisted after relevant factors were taken into consideration, adjusted HR = 1.26 (95% CI 1.03-1.54, p = 0.022). CALD patients also reported longer prehospital intervals; however, these differences were not statistically significant. CONCLUSION: Target interventions need to be developed to address ethnic disparity in hospital diagnostic interval.


Assuntos
Etnicidade , Neoplasias Pulmonares , Austrália , Humanos , Estudos Prospectivos , População Branca
12.
J Trauma Acute Care Surg ; 90(6): e146-e154, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34016932

RESUMO

ABSTRACT: Abdominal compartment syndrome is a serious potential complication of burn injury, and carries high morbidity and mortality. Although there are generalised published guidelines on managing the condition, to date no management algorithm has yet been published tailored specifically to the burn injury patient. We set out to examine the literature on the subject in order to produce an evidence based management guideline, with the aim of improving outcomes for these patients. The guideline covers early detection and assessment of the condition as well as optimum medical, surgical and postoperative management. We believe that this guideline provides a much needed benchmark for managing burns patients with raised intra-abdominal pressure, as well as providing a template for further research and improvements in care.


Assuntos
Queimaduras/terapia , Síndromes Compartimentais/terapia , Medicina Baseada em Evidências/normas , Hipertensão Intra-Abdominal/terapia , Sociedades Médicas/normas , Queimaduras/complicações , Síndromes Compartimentais/diagnóstico , Síndromes Compartimentais/etiologia , Diagnóstico Precoce , Medicina Baseada em Evidências/métodos , Humanos , Hipertensão Intra-Abdominal/diagnóstico , Hipertensão Intra-Abdominal/etiologia , Resultado do Tratamento
13.
Ann Biomed Eng ; 49(11): 3128-3142, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33880631

RESUMO

Development of the Warrior Injury Assessment Manikin (WIAMan) capability has included the creation of injury assessment reference curves (IARCs) specific to under-body blast (UBB) loading mechanisms and injuries. The WIAMan IARCs were created from high-rate vertical loading tests of component post-mortem human surrogates (PMHS) and analogous components of the WIAMan anthropomorphic test device (ATD). Validation of the WIAMan IARCs is required prior to the WIAMan ATD being utilized for injury assessment in live-fire vehicle test events. A portion of the validation process involves evaluating the ability of the IARCs to predict injury at the system level (whole body). This study evaluates a methodology to assess the performance of the WIAMan IARCs using match-paired tests of whole body PMHS and the WIAMan ATD. The methodology includes a qualitative analysis designed to identify false-positive and false-negative ATD predictions, as well as a quantitative analysis that utilizes area under the receiver-operating characteristic curve (AROC) and Brier score indices to grade IARC performance. Three WIAMan IARCs were used to exemplify the proposed methodology and results are provided. Attributes of the false-prediction, AROC, and Brier score portions of the methodology are presented, with results indicating the new methodology is thorough and robust in evaluation of IARCs.


Assuntos
Traumatismos por Explosões , Manequins , Modelos Biológicos , Aceleração , Fenômenos Biomecânicos , Cadáver , Explosões , Humanos , Masculino , Militares
14.
J Plast Reconstr Aesthet Surg ; 74(6): 1402-1407, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33388270

RESUMO

BACKGROUND: The modern ethos of burn care requires a holistic approach that helps patients to not only survive but also maintain a good quality of life. Bromelain-based enzymatic debridement with Nexobrid™ (NXB) has been shown to selectively debride burnt tissue and allow dermal preservation, which has the potential to reduce surgical burden and improve scarring. In this study, early experience with the use of Nexobrid™ at a tertiary burns centre between July 2016 and December 2019 is presented. In particular, the study assessed whether NXB had changed the acute care delivered to this cohort. METHODS: A retrospective analysis of the patients' records was performed. Results were analysed and presented in the context of current literature. RESULTS: Twenty adult patients (17 male, 3 female) underwent enzymatic debridement with NXB. Median age was 42.5 years. Mean total burn surface area (TBSA) on admission was 20%. Twelve patients were admitted to the intensive care unit, and eight were admitted to the adult burns ward. Mean TBSA treated with NXB was 8.2%, usually within 24 h of admission (mean). All patients had anaesthetist-led analgesia. NXB debridement was successful in 55% of patients, obviating the need for escharotomy in some patients. Sixty percent of all patients required further surgery, and 80% of facial burns treated with NXB required further surgery. Inotrope support was associated with NXB failure (p = 0.015). Mean length of stay was 29 days. DISCUSSION: Current evidence, including our own findings, cannot justify replacing the current surgical standard of care with NXB, but it certainly solidifies enzymatic debridement as a useful adjunct that should form part of the modern burn surgeon's armamentarium.


Assuntos
Bromelaínas/uso terapêutico , Queimaduras , Desbridamento/métodos , Terapia Enzimática/métodos , Qualidade de Vida , Adulto , Queimaduras/psicologia , Queimaduras/terapia , Cicatriz/etiologia , Cicatriz/terapia , Terapia Combinada/métodos , Feminino , Humanos , Masculino , Manejo da Dor/métodos , Estudos Retrospectivos , Transplante de Pele/métodos , Resultado do Tratamento , Reino Unido/epidemiologia , Cicatrização/efeitos dos fármacos
15.
Transl Lung Cancer Res ; 9(4): 1667-1679, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32953540

RESUMO

Multidisciplinary care (MDC) is considered best practice in lung cancer care. Health care services have made significant investments in MDC through the establishment of multidisciplinary team (MDT) meetings. This investment is likely to be sustained in future. It is imperative that MDT meetings are efficient, effective, and sufficiently nimble to introduce new innovations to enable best practice. In this article, we consider the 'evidence-practice gaps' in the implementation of lung cancer MDC. These gaps were derived from the recurrent limitations outlined in existing studies and reviews. We address the contributions that implementation science and quality improvement can make to bridge these gaps by increasing translation and improving the uptake of innovations by teams.

16.
AME Case Rep ; 3: 21, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31463426

RESUMO

Acute colonic pseudo-obstruction (ACPO) as a result of anterior lumbar spinal surgery can result in colonic perforation. ACPO is often treated successfully with conservative measures, reserving surgical intervention for severe cases. The most severe cases can result in colonic perforation with a concomitant high mortality rate. Herein we outline a case of a 72-year-old male with multiple medical comorbidities and history of intermittent constipation who underwent anterior lumbar interbody fusion (ALIF) of L5-S1. The patient's multiple medical comorbidities placed him at risk for ACPO. His postoperative course was complicated by an ileus. The patient initially underwent conservative management that failed, resulting in colonic perforation. He underwent urgent exploratory laparotomy and repair of colonic perforation by the general surgery service. The patient had spontaneous return of bowel function on postoperative day 5, and at 6 months, he was doing well. The main purpose of this case report is to present a unique case of colonic perforation after ALIF. Understanding patient risk factors can help in early identification and treatment of potentially life-threatening complications. Surgeons should discuss the possibility of this complication with the patient during surgical counseling for anterior lumbar surgery.

17.
J Org Chem ; 84(8): 4837-4845, 2019 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-30716275

RESUMO

( R)-Boc-2-methylproline (3a) was synthesized in good yield with excellent stereochemical control from alanine benzyl ester hydrochloride 11. The process, which is based on a modification of one described by Kawabata, proceeds in four steps and requires no chromatography. The product ( R)-Boc-2-methylproline (3a) was then carried forward in three steps to produce veliparib 1, a poly(ADP-ribose) polymerase inhibitor.


Assuntos
Antineoplásicos/farmacologia , Benzimidazóis/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Poli(ADP-Ribose) Polimerases/metabolismo , Prolina/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Benzimidazóis/síntese química , Benzimidazóis/química , Ciclização , Humanos , Estrutura Molecular , Inibidores de Poli(ADP-Ribose) Polimerases/síntese química , Inibidores de Poli(ADP-Ribose) Polimerases/química , Prolina/análogos & derivados , Prolina/síntese química , Prolina/química
18.
Thorax ; 74(4): 362-370, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30630891

RESUMO

BACKGROUND: International research has focused on screening and mass media campaigns to promote earlier patient presentation and detect lung cancer earlier. This trial tested the effect of a behavioural intervention in people at increased risk of lung cancer on help-seeking for respiratory symptoms. METHODS: Parallel, individually randomised controlled trial. Eligible participants were long-term smokers with at least 20 pack-years, aged 55 and above. The CHEST intervention entailed a consultation to discuss and implement a self-help manual, followed by self-monitoring reminders to encourage help-seeking for respiratory symptoms. The control group received a brief discussion about lung health. Both groups had baseline spirometry. Telephone randomisation was conducted, 1:1, stratified Medical Research Council (MRC) dyspnoea score and general practice. Participants could not be blinded; data extraction and statistical analyses were performed blinded to group assignment. The primary outcome was respiratory consultation rates. RESULTS: We randomised 551 participants (274 intervention, 277 control) from whom the primary outcome was determined for 542 (269 intervention, 273 control). There was a 40% relative increase in respiratory consultations in the intervention group: (adjusted rates (95% CI) intervention 0.57 (0.47 to 0.70), control 0.41 (0.32 to 0.52), relative rate 1.40 (1.08 to 1.82); p=0.0123). There were no significant differences in time to first respiratory consultation, total consultation rates or measures of psychological harm. The incremental cost-effectiveness ratio was $A1289 per additional respiratory consultation. CONCLUSIONS: A behavioural intervention can significantly increase consulting for respiratory symptoms in patients at increased risk of lung cancer. This intervention could have an important role in primary care as part of a broader approach to improve respiratory health in patients at higher risk. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry (1261300039 3752). This was registered pre-results.


Assuntos
Neoplasias Pulmonares/diagnóstico , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Fumantes/psicologia , Idoso , Austrália , Autoavaliação Diagnóstica , Detecção Precoce de Câncer/métodos , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde , Transtornos Respiratórios/etiologia , Autocuidado , Fumar/efeitos adversos
19.
Support Care Cancer ; 27(2): 485-493, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29980906

RESUMO

PURPOSE: Improving the coordination of care for people with lung cancer is a health priority. This study aimed to tailor an existing care coordination survey for a lung cancer population, investigate coordination experiences for patients who had received hospital-based treatment and identify any factors that may be associated with poor care coordination. METHODS: We conducted a cross-sectional survey of lung patients within two tertiary hospitals in Sydney, Australia. The Cancer Care Coordination Questionnaire for Patients (CCCQ-P) is a psychometrically valid and reliable survey originally developed for colorectal cancer. We pilot tested a survey adaptation with lung cancer patients, support group members and medical specialists (n = 49). A revised survey was mailed to eligible patients via their medical specialist. RESULTS: Fifty-three of 118 eligible participants (45%) completed the CCCQ-P; most had early-stage disease and were about 70 years old. Overall, participants reported positive experiences of care coordination (mean total score 78.1), with high scores on communication and navigation subscales. The most problematic areas related to administrative aspects of care coordination and communication and information provision. Two patient groups (those residing in regional and rural areas, or no experience with the health system prior to diagnosis) reported significantly lower scores on the navigation subscale. CONCLUSIONS: This study found that lung cancer patients' experience of care coordination was positive, but highlighted the need for strategies to assist patients living in rural areas, and those with no experience of the health care system. The CCCQ-P survey instrument can be used in future lung cancer studies.


Assuntos
Atenção à Saúde/tendências , Neoplasias Pulmonares/diagnóstico , Idoso , Comunicação , Estudos Transversais , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Inquéritos e Questionários
20.
BMC Cancer ; 18(1): 754, 2018 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-30031382

RESUMO

BACKGROUND: Lung cancer is the leading cause of cancer mortality worldwide. Early diagnosis and treatment is a key factor in reducing mortality and improving patient outcomes. To achieve this, it is important to understand the diagnostic pathways of cancer patients. Patients from Culturally and Linguistically Diverse (CALD) are a vulnerable group for lung cancer with higher mortality rates than Caucasian patients. The aim of this study is to explore differences in the lung cancer diagnostic pathways between CALD and Anglo-Australian patients and factors underlying these differences. METHODS: This is a prospective, observational cohort study using a mixed-method approach. Quantitative data regarding time intervals in the lung cancer diagnostic pathways will be gathered via patient surveys, General practitioner (GP) review of general practice records, and case-note analysis of hospital records. Qualitative data will be gathered via structured interviews with lung cancer patients, GPs, and hospital specialists. The study will be conducted in five study sites across three states in Australia. Anglo-Australian patients and patients from five CALD groups (i.e., Arabic, Chinese, Greek, Italian and Vietnamese communities) will mainly be identified through the list of new cases presented at lung multidisciplinary team meetings. For the quantitative component, it is anticipated that 724 patients (362 Anglo-Australian and 362 CALD patients) will be recruited to obtain a final sample of 290 (145 per group) assuming a 50% patient survey completion rate and a 80% GP record review completion rate. For the qualitative component, 60 interviews with lung cancer patients (10 Anglo-Australian and 10 patients per CALD group), 20 interviews with GPs, and 20 interviews with specialists will be conducted. DISCUSSION: This is the first Australian study to compare the time intervals along the lung cancer diagnostic pathway between CALD and Anglo-Australian patients. The study will also explore the underlying patient, healthcare provider, and health system factors that influence the time intervals in the two groups. This information will improve our understanding of the effect of ethnicity on health outcomes among lung cancer patients and will inform future interventions aimed at early diagnosis and treatment for lung cancer, particularly patients from CALD backgrounds. TRIAL REGISTRATION: The project was retrospectively registered with Australian New Zealand Clinical Trials Registry (registration number: ACTRN12617000957392 , date registered: 4th July 2017).


Assuntos
Diversidade Cultural , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etnologia , Austrália , Protocolos Clínicos , Cultura , Clínicos Gerais , Humanos , Neoplasias Pulmonares/terapia , Estudos Prospectivos , Fatores de Tempo
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