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2.
J Pers Med ; 13(11)2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-38003848

RESUMO

Saliva is a largely unexplored liquid biopsy that can be readily obtained noninvasively. Not dissimilar to blood plasma or serum, it contains a vast array of bioconstituents that may be associated with the absence or presence of a disease condition. Given its ease of access, the use of saliva is potentially ideal in a point-of-care screening or diagnostic test. Herein, we developed a swab "dip" test in saliva obtained from consenting patients participating in a lung cancer-screening programme being undertaken in north-west England. A total of 998 saliva samples (31 designated as lung-cancer positive and 17 as prostate-cancer positive) were taken in the order in which they entered the clinic (i.e., there was no selection of participants) during the course of this prospective screening programme. Samples (sterile Copan blue rayon swabs dipped in saliva) were analysed using attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy. In addition to unsupervised classification on resultant infrared (IR) spectra using principal component analysis (PCA), a range of feature selection/extraction algorithms were tested. Following preprocessing, the data were split between training (70% of samples, 22 lung-cancer positive versus 664 other) and test (30% of samples, 9 lung-cancer positive versus 284 other) sets. The training set was used for model construction and the test set was used for validation. The best model was the PCA-quadratic discriminant analysis (QDA) algorithm. This PCA-QDA model was built using 8 PCs (90.4% of explained variance) and resulted in 93% accuracy for training and 91% for testing, with clinical sensitivity at 100% and specificity at 91%. Additionally, for prostate cancer patients amongst the male cohort (n = 585), following preprocessing, the data were split between training (70% of samples, 12 prostate-cancer positive versus 399 other) and test (30% of samples, 5 prostate-cancer positive versus 171 other) sets. A PCA-QDA model, again the best model, was built using 5 PCs (84.2% of explained variance) and resulted in 97% accuracy for training and 93% for testing, with clinical sensitivity at 100% and specificity at 92%. These results point to a powerful new approach towards the capability to screen large cohorts of individuals in primary care settings for underlying malignant disease.

3.
Am J Respir Crit Care Med ; 208(12): 1305-1315, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37820359

RESUMO

Rationale: Assessing the early use of video-assisted thoracoscopic surgery (VATS) or intrapleural enzyme therapy (IET) in pleural infection requires a phase III randomized controlled trial (RCT). Objectives: To establish the feasibility of randomization in a surgery-versus-nonsurgery trial as well as the key outcome measures that are important to identify relevant patient-centered outcomes in a subsequent RCT. Methods: The MIST-3 (third Multicenter Intrapleural Sepsis Trial) was a prospective multicenter RCT involving eight U.K. centers combining on-site and off-site surgical services. The study enrolled all patients with a confirmed diagnosis of pleural infection and randomized those with ongoing pleural sepsis after an initial period (as long as 24 h) of standard care to one of three treatment arms: continued standard care, early IET, or a surgical opinion with regard to early VATS. The primary outcome was feasibility based on >50% of eligible patients being successfully randomized, >95% of randomized participants retained to discharge, and >80% of randomized participants retained to 2 weeks of follow-up. The analysis was performed per intention to treat. Measurements and Main Results: Of 97 eligible patients, 60 (62%) were randomized, with 100% retained to discharge and 84% retained to 2 weeks. Baseline demographic, clinical, and microbiological characteristics of the patients were similar across groups. Median times to intervention were 1.0 and 3.5 days in the IET and surgery groups, respectively (P = 0.02). Despite the difference in time to intervention, length of stay (from randomization to discharge) was similar in both intervention arms (7 d) compared with standard care (10 d) (P = 0.70). There were no significant intergroup differences in 2-month readmission and further intervention, although the study was not adequately powered for this outcome. Compared with VATS, IET demonstrated a larger improvement in mean EuroQol five-dimension health utility index (five-level edition) from baseline (0.35) to 2 months (0.83) (P = 0.023). One serious adverse event was reported in the VATS arm. Conclusions: This is the first multicenter RCT of early IET versus early surgery in pleural infection. Despite the logistical challenges posed by the coronavirus disease (COVID-19) pandemic, the study met its predefined feasibility criteria, demonstrated potential shortening of length of stay with early surgery, and signals toward earlier resolution of pain and a shortened recovery with IET. The study findings suggest that a definitive phase III study is feasible but highlights important considerations and significant modifications to the design that would be required to adequately assess optimal initial management in pleural infection.The trial was registered on ISRCTN (number 18,192,121).


Assuntos
Doenças Transmissíveis , Doenças Pleurais , Sepse , Humanos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Estudos de Viabilidade , Doenças Transmissíveis/etiologia , Sepse/tratamento farmacológico , Sepse/cirurgia , Sepse/etiologia , Terapia Enzimática
4.
J Pers Med ; 13(7)2023 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-37511652

RESUMO

There is an increasing need for inexpensive and rapid screening tests in point-of-care clinical oncology settings. Herein, we develop a swab "dip" test in saliva obtained from consenting patients participating in a lung-cancer-screening programme being undertaken in North West England. In a pilot study, a total of 211 saliva samples (n = 170 benign, 41 designated cancer-positive) were randomly taken during the course of this prospective lung-cancer-screening programme. The samples (sterile Copan blue rayon swabs dipped in saliva) were analysed using attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy. An exploratory analysis using principal component analysis (PCA,) with or without linear discriminant analysis (LDA), was then undertaken. Three pairwise comparisons were undertaken including: (1) benign vs. cancer following swab analysis; (2) benign vs. cancer following swab analysis with the subtraction of dry swab spectra; and (3) benign vs. cancer following swab analysis with the subtraction of wet swab spectra. Consistent and remarkably similar patterns of clustering for the benign control vs. cancer categories, irrespective of whether the swab plus saliva sample was analysed or whether there was a subtraction of wet or dry swab spectra, was observed. In each case, MANOVA demonstrated that this segregation of categories is highly significant. A k-NN (using three nearest neighbours) machine-learning algorithm also showed that the specificity (90%) and sensitivity (75%) are consistent for each pairwise comparison. In detailed analyses, the swab as a substrate did not alter the level of spectral discrimination between benign control vs. cancer saliva samples. These results demonstrate a novel swab "dip" test using saliva as a biofluid that is highly applicable to be rolled out into a larger lung-cancer-screening programme.

5.
BMJ Open Respir Res ; 7(1)2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33184058

RESUMO

INTRODUCTION: The pulmonary passport (PP) is a secure web-based procedural logbook for specialist respiratory trainees with enhanced functionality that includes automated analysis to provide key performance metrics and in-platform interactions with supervisors. METHODS: This service evaluation study used preimplementation and postimplementation online surveys in both trainees and supervisors along with analysis of recorded data within the PP to evaluate the impact of this service on data capture, training, appraisal and quality assurance. RESULTS: From August 2017 to August 2019, 69/73 (95%) specialist respiratory trainees eligible to use the PP across two UK health education deaneries registered with the system and logged 7352 procedures. 3105 thoracic ultrasound procedures identified 2145 pleural effusions and resulted in 1253 pleural procedures of which 96% were successful. 4% of ultrasounds required referral to a more expert sonographer. Iatrogenic bleeding and pneumothorax both occurred in ≤1% of all pleural procedures. 1909 basic diagnostic bronchoscopies were recorded including 1236 bronchial washes, 328 brushes and 221 endobronchial biopsies where definite tumour was identified (biopsy sensitivity 74%). Preimplementation and postimplementation survey data confirmed the PP had increased the consistency of logging procedures by trainees, the depth of data captured, the review of procedural performance metrics in appraisal and the frequency of formal supervisor feedback. DISCUSSION: In this regional project, the implementation of a web-based procedural logbook has been feasible with excellent uptake and has enhanced procedural recording, supervision and appraisal. Furthermore, it provides unprecedented quality assurance at an individual trainee, trust and deanery level and has a number of potential wider applications in the future.


Assuntos
Broncoscopia , Competência Clínica , Internet , Humanos , Inquéritos e Questionários , Ultrassonografia
6.
Eur Respir J ; 56(5)2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32675200

RESUMO

BACKGROUND: Over 30% of adult patients with pleural infection either die and/or require surgery. There is no robust means of predicting at baseline presentation which patients will suffer a poor clinical outcome. A validated risk prediction score would allow early identification of high-risk patients, potentially directing more aggressive treatment thereafter. OBJECTIVES: To prospectively assess a previously described risk score (the RAPID (Renal (urea), Age, fluid Purulence, Infection source, Dietary (albumin)) score) in adults with pleural infection. METHODS: Prospective observational cohort study that recruited patients undergoing treatment for pleural infection. RAPID score and risk category were calculated at baseline presentation. The primary outcome was mortality at 3 months; secondary outcomes were mortality at 12 months, length of hospital stay, need for thoracic surgery, failure of medical treatment and lung function at 3 months. RESULTS: Mortality data were available in 542 out of 546 patients recruited (99.3%). Overall mortality was 10% at 3 months (54 out of 542) and 19% at 12 months (102 out of 542). The RAPID risk category predicted mortality at 3 months. Low-risk mortality (RAPID score 0-2): five out of 222 (2.3%, 95% CI 0.9 to 5.7%); medium-risk mortality (RAPID score 3-4): 21 out of 228 (9.2%, 95% CI 6.0 to 13.7%); and high-risk mortality (RAPID score 5-7): 27 out of 92 (29.3%, 95% CI 21.0 to 39.2%). C-statistics for the scores at 3 months and 12 months were 0.78 (95% CI 0.71-0.83) and 0.77 (95% CI 0.72-0.82), respectively. CONCLUSIONS: The RAPID score stratifies adults with pleural infection according to increasing risk of mortality and should inform future research directed at improving outcomes in this patient population.


Assuntos
Doenças Pleurais , Adulto , Humanos , Tempo de Internação , Projetos Piloto , Estudos Prospectivos , Fatores de Risco
7.
Respirology ; 25(7): 750-755, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31846131

RESUMO

BACKGROUND AND OBJECTIVE: Chemical pleurodesis is performed for patients with MPE with a published success rate of around 80%. It has been postulated that inflammation is key in achieving successful pleural symphysis, as evidenced by higher amounts of pain or detected inflammatory response. Patients with mesothelioma are postulated to have a lower rate of successful pleurodesis due to lack of normal pleural tissue enabling an inflammatory response. METHODS: The TIME1 trial data set, in which pleurodesis success and pain were co-primary outcome measures, was used to address a number of these assumptions. Pain score, systemic inflammatory parameters as a marker of pleural inflammation and cancer type were analysed in relation to pleurodesis success. RESULTS: In total, 285 patients were included with an overall success rate of 81.4%. There was a significantly higher rise in CRP in the Pleurodesis Success group compared with the Pleurodesis Failure group (mean difference: 19.2, 95% CI of the difference: 6.2-32.0, P = 0.004) but no significant change in WCC. There was no significant difference in pain scores or analgesia requirements between the groups. Patients with mesothelioma had a lower rate of pleurodesis success than non-mesothelioma patients (73.3% vs 84.9%, χ2 = 5.1, P = 0.023). CONCLUSION: Change in CRP during pleurodesis is associated with successful pleurodesis but higher levels of pain are not associated. Patients with mesothelioma appear less likely to undergo successful pleurodesis than patients with other malignancies, but there is still a significant rise in systemic inflammatory markers. The mechanisms of these findings are unclear but warrant further investigation.


Assuntos
Proteína C-Reativa/imunologia , Dor/imunologia , Derrame Pleural Maligno/terapia , Pleurodese/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Contagem de Leucócitos , Masculino , Mesotelioma/complicações , Pessoa de Meia-Idade , Derrame Pleural Maligno/etiologia , Neoplasias Pleurais/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Talco/administração & dosagem , Toracoscopia , Resultado do Tratamento
8.
N Engl J Med ; 378(14): 1313-1322, 2018 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-29617585

RESUMO

BACKGROUND: Malignant pleural effusion affects more than 750,000 persons each year across Europe and the United States. Pleurodesis with the administration of talc in hospitalized patients is the most common treatment, but indwelling pleural catheters placed for drainage offer an ambulatory alternative. We examined whether talc administered through an indwelling pleural catheter was more effective at inducing pleurodesis than the use of an indwelling pleural catheter alone. METHODS: Over a period of 4 years, we recruited patients with malignant pleural effusion at 18 centers in the United Kingdom. After the insertion of an indwelling pleural catheter, patients underwent drainage regularly on an outpatient basis. If there was no evidence of substantial lung entrapment (nonexpandable lung, in which lung expansion and pleural apposition are not possible because of visceral fibrosis or bronchial obstruction) at 10 days, patients were randomly assigned to receive either 4 g of talc slurry or placebo through the indwelling pleural catheter on an outpatient basis. Talc or placebo was administered on a single-blind basis. Follow-up lasted for 70 days. The primary outcome was successful pleurodesis at day 35 after randomization. RESULTS: The target of 154 patients undergoing randomization was reached after 584 patients were approached. At day 35, a total of 30 of 69 patients (43%) in the talc group had successful pleurodesis, as compared with 16 of 70 (23%) in the placebo group (hazard ratio, 2.20; 95% confidence interval, 1.23 to 3.92; P=0.008). No significant between-group differences in effusion size and complexity, number of inpatient days, mortality, or number of adverse events were identified. No significant excess of blockages of the indwelling pleural catheter was noted in the talc group. CONCLUSIONS: Among patients without substantial lung entrapment, the outpatient administration of talc through an indwelling pleural catheter for the treatment of malignant pleural effusion resulted in a significantly higher chance of pleurodesis at 35 days than an indwelling catheter alone, with no deleterious effects. (Funded by Becton Dickinson; EudraCT number, 2012-000599-40 .).


Assuntos
Derrame Pleural Maligno/terapia , Pleurodese/métodos , Talco/administração & dosagem , Idoso , Assistência Ambulatorial , Cateteres de Demora , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pleural Maligno/mortalidade , Pleurodese/efeitos adversos , Qualidade de Vida , Método Simples-Cego , Análise de Sobrevida
9.
Am J Respir Crit Care Med ; 197(4): 502-508, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-28926296

RESUMO

RATIONALE: Patients with malignant pleural effusion experience breathlessness, which is treated by drainage and pleurodesis. Incomplete drainage results in residual dyspnea and pleurodesis failure. Intrapleural fibrinolytics lyse septations within pleural fluid, improving drainage. OBJECTIVES: To assess the effects of intrapleural urokinase on dyspnea and pleurodesis success in patients with nondraining malignant effusion. METHODS: We conducted a prospective, double-blind, randomized trial. Patients with nondraining effusion were randomly allocated in a 1:1 ratio to intrapleural urokinase (100,000 IU, three doses, 12-hourly) or matched placebo. MEASUREMENTS AND MAIN RESULTS: Co-primary outcome measures were dyspnea (average daily 100-mm visual analog scale scores over 28 d) and time to pleurodesis failure to 12 months. Secondary outcomes were survival, hospital length of stay, and radiographic change. A total of 71 subjects were randomized (36 received urokinase, 35 placebo) from 12 U.K. centers. The baseline characteristics were similar between the groups. There was no difference in mean dyspnea between groups (mean difference, 3.8 mm; 95% confidence interval [CI], -12 to 4.4 mm; P = 0.36). Pleurodesis failure rates were similar (urokinase, 13 of 35 [37%]; placebo, 11 of 34 [32%]; adjusted hazard ratio, 1.2; P = 0.65). Urokinase was associated with decreased effusion size visualized by chest radiography (adjusted relative improvement, -19%; 95% CI, -28 to -11%; P < 0.001), reduced hospital stay (1.6 d; 95% CI, 1.0 to 2.6; P = 0.049), and improved survival (69 vs. 48 d; P = 0.026). CONCLUSIONS: Use of intrapleural urokinase does not reduce dyspnea or improve pleurodesis success compared with placebo and cannot be recommended as an adjunct to pleurodesis. Other palliative treatments should be used. Improvements in hospital stay, radiographic appearance, and survival associated with urokinase require further evaluation. Clinical trial registered with ISRCTN (12852177) and EudraCT (2008-000586-26).


Assuntos
Derrame Pleural Maligno/terapia , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Idoso , Método Duplo-Cego , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Cuidados Paliativos/métodos , Derrame Pleural Maligno/enzimologia , Pleurodese/métodos , Estudos Prospectivos
10.
JAMA ; 314(24): 2641-53, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26720026

RESUMO

IMPORTANCE: For treatment of malignant pleural effusion, nonsteroidal anti-inflammatory drugs (NSAIDs) are avoided because they may reduce pleurodesis efficacy. Smaller chest tubes may be less painful than larger tubes, but efficacy in pleurodesis has not been proven. OBJECTIVE: To assess the effect of chest tube size and analgesia (NSAIDs vs opiates) on pain and clinical efficacy related to pleurodesis in patients with malignant pleural effusion. DESIGN, SETTING, AND PARTICIPANTS: A 2×2 factorial phase 3 randomized clinical trial among 320 patients requiring pleurodesis in 16 UK hospitals from 2007 to 2013. INTERVENTIONS: Patients undergoing thoracoscopy (n = 206; clinical decision if biopsy was required) received a 24F chest tube and were randomized to receive opiates (n = 103) vs NSAIDs (n = 103), and those not undergoing thoracoscopy (n = 114) were randomized to 1 of 4 groups (24F chest tube and opioids [n = 28]; 24F chest tube and NSAIDs [n = 29]; 12F chest tube and opioids [n = 29]; or 12F chest tube and NSAIDs [n = 28]). MAIN OUTCOMES AND MEASURES: Pain while chest tube was in place (0- to 100-mm visual analog scale [VAS] 4 times/d; superiority comparison) and pleurodesis efficacy at 3 months (failure defined as need for further pleural intervention; noninferiority comparison; margin, 15%). RESULTS: Pain scores in the opiate group (n = 150) vs the NSAID group (n = 144) were not significantly different (mean VAS score, 23.8 mm vs 22.1 mm; adjusted difference, -1.5 mm; 95% CI, -5.0 to 2.0 mm; P = .40), but the NSAID group required more rescue analgesia (26.3% vs 38.1%; rate ratio, 2.1; 95% CI, 1.3-3.4; P = .003). Pleurodesis failure occurred in 30 patients (20%) in the opiate group and 33 (23%) in the NSAID group, meeting criteria for noninferiority (difference, -3%; 1-sided 95% CI, -10% to ∞; P = .004 for noninferiority). Pain scores were lower among patients in the 12F chest tube group (n = 54) vs the 24F group (n = 56) (mean VAS score, 22.0 mm vs 26.8 mm; adjusted difference, -6.0 mm; 95% CI, -11.7 to -0.2 mm; P = .04) and 12F chest tubes vs 24F chest tubes were associated with higher pleurodesis failure (30% vs 24%), failing to meet noninferiority criteria (difference, -6%; 1-sided 95% CI, -20% to ∞; P = .14 for noninferiority). Complications during chest tube insertion occurred more commonly with 12F tubes (14% vs 24%; odds ratio, 1.91; P = .20). CONCLUSIONS AND RELEVANCE: Use of NSAIDs vs opiates resulted in no significant difference in pain scores but was associated with more rescue medication. NSAID use resulted in noninferior rates of pleurodesis efficacy at 3 months. Placement of 12F chest tubes vs 24F chest tubes was associated with a statistically significant but clinically modest reduction in pain but failed to meet noninferiority criteria for pleurodesis efficacy. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN33288337.


Assuntos
Analgésicos Opioides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Tubos Torácicos/efeitos adversos , Manejo da Dor/métodos , Derrame Pleural Maligno/terapia , Pleurodese/métodos , Idoso , Algoritmos , Analgesia/métodos , Analgésicos Opioides/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Intervalos de Confiança , Desenho de Equipamento , Feminino , Humanos , Masculino , Medição da Dor/métodos , Derrame Pleural Maligno/complicações , Terapia de Salvação/métodos , Terapia de Salvação/estatística & dados numéricos , Toracoscopia/instrumentação , Falha de Tratamento
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