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RATIONALE: A previous analysis found significantly higher lung function in the US paediatric cystic fibrosis (CF) population compared with the UK with this difference apparently decreasing in adolescence and adulthood. However, the cross-sectional nature of the study makes it hard to interpret these results. OBJECTIVES: To compare longitudinal trajectories of lung function in children with CF between the USA and UK and to explore reasons for any differences. METHODS: We used mixed effects regression analysis to model lung function trajectories in the study populations. Using descriptive statistics, we compared early growth and nutrition (height, weight, body mass index), infections (Pseudomonas aeruginosa, Staphylococcus aureus) and treatments (rhDnase, hypertonic saline, inhaled antibiotics). RESULTS: We included 9463 children from the USA and 3055 children from the UK with homozygous F508del genotype. Lung function was higher in the USA than in the UK when first measured at age six and remained higher throughout childhood. We did not find important differences in early growth and nutrition, or P.aeruginosa infection. Prescription of rhDNase and hypertonic saline was more common in the USA. Inhaled antibiotics were prescribed at similar levels in both countries, but Tobramycin was prescribed more in the USA and colistin in the UK. S. aureus infection was more common in the USA than the UK. CONCLUSIONS: Children with CF and homozygous F508del genotype in the USA had better lung function than UK children. These differences do not appear to be explained by early growth or nutrition, but differences in the use of early treatments need further investigation.
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Fibrosis Quística , Infecciones por Pseudomonas , Adolescente , Adulto , Niño , Estudios Transversales , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/epidemiología , Humanos , Pulmón , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/epidemiología , Pseudomonas aeruginosa , Sistema de Registros , Staphylococcus aureus , Reino Unido/epidemiologíaRESUMEN
OBJECTIVE: To determine the additional diagnostic value of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced imaging (DCE) in men requiring a repeat biopsy within the PICTURE study. PATIENTS AND METHODS: PICTURE was a paired-cohort confirmatory study in which 249 men who required further risk stratification after a previous non-magnetic resonance imaging (MRI)-guided transrectal ultrasonography-guided biopsy underwent a 3-Tesla (3T) multiparametic (mp)MRI consisting of T2-weighted imaging (T2W), DWI and DCE, followed by transperineal template prostate mapping biopsy. Each mpMRI was reported using a LIKERT score in a sequential blinded manner to generate scores for T2W, T2W+DWI and T2W+DWI+DCE. Area under the receiver-operating characteristic curve (AUROC) analysis was performed to compare the diagnostic accuracy of each combination. The threshold for a positive mpMRI was set at a LIKERT score ≥3. Clinically significant prostate cancer was analysed across a range of definitions including UCL/Ahmed definition 1 (primary definition), UCL/Ahmed definition 2, any Gleason ≥3 + 4 and any Gleason ≥4 + 3. RESULTS: Of 249 men, sequential MRI reporting was available for 246. There was a higher rate of equivocal lesions (44.6%) using T2W alone compared to the addition of DWI (23.9%) and DCE (19.8%). Using the primary definition of clinically significant disease, there was no significant difference in the overall accuracy between T2W, with an AUROC of 0.74 (95% confidence interval [CI] 0.68-0.80), T2W+DWI at 0.76 (95% CI 0.71-0.82), and T2W+DWI+DCE, with an AUROC of 0.77 (95% CI 0.71-0.82; P = 0.55). The AUROC values remained comparable using other definitions of clinically significant disease including UCL/Ahmed definition 2 (P = 0.79), Gleason ≥3 + 4 (P = 0.53) and Gleason ≥4 + 3 (P = 0.53). CONCLUSIONS: Using 3T MRI, a high level of diagnostic accuracy can be achieved using T2W as a single parameter in men with a prior biopsy; however, such a strategy can lead to a higher rate of equivocal lesions.
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Medios de Contraste , Imagen de Difusión por Resonancia Magnética/métodos , Imágenes de Resonancia Magnética Multiparamétrica/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Anciano , Estudios de Cohortes , Humanos , Biopsia Guiada por Imagen , Masculino , Persona de Mediana EdadRESUMEN
INTRODUCTION: Diagnosing prostate cancer routinely involves tissue biopsy and increasingly image guided biopsy using multiparametric MRI (mpMRI). Excess tissue after diagnosis can be used for research to improve the diagnostic pathway and the vertical assembly of prostate needle biopsy cores into tissue microarrays (TMAs) allows the parallel immunohistochemical (IHC) validation of cancer biomarkers in routine diagnostic specimens. However, tissue within a biopsy core is often heterogeneous and cancer is not uniformly present, resulting in needle biopsy TMAs that suffer from highly variable cancer detection rates that complicate parallel biomarker validation. MATERIALS AND METHODS: The prostate cores with the highest tumor burden (in terms of Gleason score and/or maximum cancer core length) were obtained from 249 patients in the PICTURE trial who underwent transperineal template prostate mapping (TPM) biopsy at 5 mm intervals preceded by mpMRI. From each core, 2 mm segments containing tumor or benign tissue (as assessed on H&E pathology) were selected, excised and embedded vertically into a new TMA block. TMA sections were then IHC-stained for the routinely used prostate cancer biomarkers PSA, PSMA, AMACR, p63, and MSMB and assessed using the h-score method. H-scores in patient matched malignant and benign tissue were correlated with the Gleason grade of the original core and the MRI Likert score for the sampled prostate area. RESULTS: A total of 2240 TMA cores were stained and IHC h-scores were assigned to 1790. There was a statistically significant difference in h-scores between patient matched malignant and adjacent benign tissue that is independent of Likert score. There was no association between the h-scores and Gleason grade or Likert score within each of the benign or malignant groups. CONCLUSION: The construction of highly selective TMAs from prostate needle biopsy cores is possible. IHC data obtained through this method are highly reliable and can be correlated with imaging. IHC expression patterns for PSA, PSMA, AMACR, p63, and MSMB are distinct in malignant and adjacent benign tissue but did not correlate with mpMRI Likert score.
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Biomarcadores de Tumor/metabolismo , Próstata/metabolismo , Neoplasias de la Próstata/diagnóstico , Humanos , Biopsia Guiada por Imagen , Inmunohistoquímica , Imagen por Resonancia Magnética , Masculino , Clasificación del Tumor , Próstata/diagnóstico por imagen , Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patologíaRESUMEN
BACKGROUND: Robot-assisted radical prostatectomy (RARP) has been rapidly adopted without robust evidence comparing its functional outcomes against laparoscopic radical prostatectomy (LRP) or open retropubic radical prostatectomy (ORP) approaches. This study compared patient-reported functional outcomes following RARP, LRP or ORP. METHODS: All men diagnosed with prostate cancer in England during April - October 2014 who underwent radical prostatectomy were identified from the National Prostate Cancer Audit and mailed a questionnaire 18 months after diagnosis. Group differences in patient-reported sexual, urinary, bowel and hormonal function (EPIC-26 domain scores) and generic health-related quality of life (HRQoL; EQ-5D-5L scores), with adjustment for patient and tumour characteristics, were estimated using linear regression. RESULTS: In all, 2219 men (77.0%) responded; 1310 (59.0%) had RARP, 487 (21.9%) LRP and 422 (19.0%) ORP. RARP was associated with slightly higher adjusted mean EPIC-26 sexual function scores compared with LRP (3·5 point difference; 95% CI: 1.1-5.9, P=0.004) or ORP (4.0 point difference; 95% CI: 1.5-6.5, P=0.002), which did not meet the threshold for a minimal clinically important difference (10-12 points). There were no significant differences in other EPIC-26 domain scores or HRQoL. CONCLUSIONS: It is unlikely that the rapid adoption of RARP in the English NHS has produced substantial improvements in functional outcomes for patients.
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Laparoscopía/métodos , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Calidad de Vida/psicología , Procedimientos Quirúrgicos Robotizados/métodos , Anciano , Estudios de Cohortes , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/psicología , Encuestas y CuestionariosRESUMEN
PURPOSE: We evaluated the detection of clinically significant prostate cancer using magnetic resonance imaging targeted biopsies and compared visual estimation to image fusion targeting in patients requiring repeat prostate biopsies. MATERIALS AND METHODS: The prospective, ethics committee approved PICTURE trial (ClinicalTrials.gov NCT01492270) enrolled 249 consecutive patients from January 11, 2012 to January 29, 2014. Men underwent multiparametric magnetic resonance imaging and were blinded to the results. All underwent transperineal template prostate mapping biopsies. In 200 men with a lesion this was preceded by visual estimation and image fusion targeted biopsies. As the primary study end point clinically significant prostate cancer was defined as Gleason 4 + 3 or greater and/or any grade of cancer with a length of 6 mm or greater. Other definitions of clinically significant prostate cancer were also evaluated. RESULTS: Mean ± SD patient age was 62.6 ± 7 years, median prostate specific antigen was 7.17 ng/ml (IQR 5.25-10.09), mean primary lesion size was 0.37 ± 1.52 cc with a mean of 4.3 ± 2.3 targeted cores per lesion on visual estimation and image fusion combined, and a mean of 48.7 ± 12.3 transperineal template prostate mapping biopsy cores. Transperineal template prostate mapping biopsies detected 97 clinically significant prostate cancers (48.5%) and 85 insignificant cancers (42.5%). Overall multiparametric magnetic resonance imaging targeted biopsies detected 81 clinically significant prostate cancers (40.5%) and 63 insignificant cancers (31.5%). In the 18 cases (9%) of clinically significant prostate cancer on magnetic resonance imaging targeted biopsies were benign or clinically insignificant on transperineal template prostate mapping biopsy. Clinically significant prostate cancer was detected in 34 cases (17%) on transperineal template prostate mapping biopsy but not on magnetic resonance imaging targeted biopsies and approximately half was present in nontargeted areas. Clinically significant prostate cancer was found on visual estimation and image fusion in 53 (31.3%) and 48 (28.4%) of the 169 patients (McNemar test p = 0.5322). Visual estimation missed 23 clinically significant prostate cancers (13.6%) detected by image fusion. Image fusion missed 18 clinically significant prostate cancers (10.8%) detected by visual estimation. CONCLUSIONS: Magnetic resonance imaging targeted biopsies are accurate for detecting clinically significant prostate cancer and reducing the over diagnosis of insignificant cancers. To maximize detection visual estimation as well as image fusion targeted biopsies are required.
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Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética Intervencional/métodos , Próstata/patología , Neoplasias de la Próstata/diagnóstico , Ultrasonografía Intervencional/métodos , Anciano , Biopsia con Aguja Gruesa/métodos , Estudios de Factibilidad , Humanos , Biopsia Guiada por Imagen/métodos , Masculino , Persona de Mediana Edad , Perineo/cirugía , Estudios Prospectivos , Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Resultado del TratamientoRESUMEN
OBJECTIVES: To evaluate the occurrence of severe urinary complications within 2 years of surgery in men undergoing either robot-assisted radical prostatectomy (RARP), laparoscopic radical prostatectomy (LRP) or retropubic open radical prostatectomy (ORP). PATIENTS AND METHODS: We conducted a population-based cohort study in men who underwent RARP (n = 4 947), LRP (n = 5 479) or ORP (n = 6 873) between 2008 and 2012 in the English National Health Service (NHS) using national cancer registry records linked to Hospital Episodes Statistics, an administrative database of admissions to NHS hospitals. We identified the occurrence of any severe urinary or severe stricture-related complication within 2 years of surgery using a validated tool. Multi-level regression modelling was used to determine the association between the type of surgery and occurrence of complications, with adjustment for patient and surgical factors. RESULTS: Men undergoing RARP were least likely to experience any urinary complication (10.5%) or a stricture-related complication (3.3%) compared with those who had LRP (15.8% any or 5.7% stricture-related) or ORP (19.1% any or 6.9% stricture-related). The impact of the type of surgery on the occurrence of any urinary or stricture-related complications remained statistically significant after adjustment for patient and surgical factors (P < 0.01). CONCLUSION: Men who underwent RARP had the lowest risk of developing severe urinary complications within 2 years of surgery.
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Laparoscopía/efectos adversos , Complicaciones Posoperatorias/etiología , Prostatectomía/efectos adversos , Prostatectomía/métodos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Estrechez Uretral/etiología , Anciano , Estudios de Cohortes , Inglaterra , Hematuria/etiología , Humanos , Laparoscopía/tendencias , Persona de Mediana Edad , Prostatectomía/tendencias , Procedimientos Quirúrgicos Robotizados/tendencias , Incontinencia Urinaria/etiologíaRESUMEN
BACKGROUND: The nipple-areola complex (NAC) is important aesthetically and functionally for both sexes. Methods for positioning the NAC in males are less well established in the literature compared to females but are just as important. OBJECTIVES: This study aims to determine the normal parameters for the male NAC, to review literature, and to present a reliable method for preoperative placement. METHODS: Normal male patients, with no prior chest wall conditions, were prospectively recruited to participate. General demographics and chest wall dimensions were recorded-sternal notch to nipple (SNND), internipple (IND), anterior axillary folds distances (AFD), NAC, and chest circumference were measured. Comparisons were made using t test and ANOVA. RESULTS: One hundred and fifty-eight patients were recruited (age range, 18-90 years); mostly (86.7%) with normal or overweight BMI. The IND averaged 249.4 mm, the SNND averaged 204.2 mm, and the AFD averaged 383.8 mm. Areola diameter averaged 26.6 mm and for the nipple, 6.9 mm. The IND:AFD ratio was 0.65. There was no statistical difference in the IND:AFD ratio, SNND, or NAC parameters comparing different ethnic groups. The SNND increased with greater BMI (P ≤ 0.001). Using these data, we suggest ideal NAC dimensions and devised a simple method for positioning of the NAC on the male chest wall. CONCLUSIONS: This is the largest study, with the widest range in age and BMI, to date on this topic. Although fewer men than women undergo surgery to the breast, there is a growing awareness for enhancing the appearance of the male chest wall.
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Antropometría , Pezones/anatomía & histología , Pared Torácica/anatomía & histología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Estética , Humanos , Masculino , Mamoplastia/métodos , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: Transrectal prostate biopsy has limited diagnostic accuracy. Prostate Imaging Compared to Transperineal Ultrasound-guided biopsy for significant prostate cancer Risk Evaluation (PICTURE) was a paired-cohort confirmatory study designed to assess diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) in men requiring a repeat biopsy. METHODS: All underwent 3 T mpMRI and transperineal template prostate mapping biopsies (TTPM biopsies). Multiparametric MRI was reported using Likert scores and radiologists were blinded to initial biopsies. Men were blinded to mpMRI results. Clinically significant prostate cancer was defined as Gleason ⩾4+3 and/or cancer core length ⩾6 mm. RESULTS: Two hundred and forty-nine had both tests with mean (s.d.) age was 62 (7) years, median (IQR) PSA 6.8 ng ml (4.98-9.50), median (IQR) number of previous biopsies 1 (1-2) and mean (s.d.) gland size 37 ml (15.5). On TTPM biopsies, 103 (41%) had clinically significant prostate cancer. Two hundred and fourteen (86%) had a positive prostate mpMRI using Likert score ⩾3; sensitivity was 97.1% (95% confidence interval (CI): 92-99), specificity 21.9% (15.5-29.5), negative predictive value (NPV) 91.4% (76.9-98.1) and positive predictive value (PPV) 46.7% (35.2-47.8). One hundred and twenty-nine (51.8%) had a positive mpMRI using Likert score ⩾4; sensitivity was 80.6% (71.6-87.7), specificity 68.5% (60.3-75.9), NPV 83.3% (75.4-89.5) and PPV 64.3% (55.4-72.6). CONCLUSIONS: In men advised to have a repeat prostate biopsy, prostate mpMRI could be used to safely avoid a repeat biopsy with high sensitivity for clinically significant cancers. However, such a strategy can miss some significant cancers and overdiagnose insignificant cancers depending on the mpMRI score threshold used to define which men should be biopsied.
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Biopsia/métodos , Imagen por Resonancia Magnética/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Ultrasonido Enfocado Transrectal de Alta Intensidad/métodos , Anciano , Estudios de Cohortes , Humanos , Biopsia Guiada por Imagen , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Próstata/diagnóstico por imagen , Próstata/patología , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Ultrasonido Enfocado Transrectal de Alta Intensidad/efectos adversosRESUMEN
OBJECTIVES: To develop and validate a surgical performance indicator based on severe urinary complications that require an intervention within 2 years of radical prostatectomy (RP), identified in hospital administrative data. PATIENTS AND METHODS: Men who underwent RP between 2008 and 2012 in England were identified using hospital administrative data. A transparent coding framework based on procedure codes was developed to identify severe urinary complications which were grouped into 'stricture', 'incontinence' and 'other'. Their validity as a performance indicator was assessed by evaluating the consistency with diagnosis codes and association with patient and surgical characteristics. Kaplan-Meier methods were used to assess time to first occurrence and multivariable logistic regression was used to estimate adjusted odds ratios (ORs) for patient and surgical characteristics. RESULTS: A total of 17 299 men were included, of whom 2695 (15.6%) experienced at least one severe urinary complication within 2 years. High proportions of men with a complication had relevant diagnosis codes: 86% for strictures and 93% for incontinence. Urinary complications were more common in men from poorer socio-economic backgrounds (OR comparing lowest with highest quintile: 1.45; 95% confidence interval [CI] 1.26-1.67) and in those with prolonged length of hospital stay (OR 1.54, 95% CI 1.40-1.69), and were less common in men who underwent robot-assisted surgery (OR 0.65, 95% CI 0.58-0.74). CONCLUSION: These results show that severe urinary complications identified in administrative data provide a medium-term performance indicator after RP. They can be used for research assessing outcomes of treatment methods and for service evaluation comparing performance of prostate cancer surgery providers.
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Codificación Clínica , Evaluación de Resultado en la Atención de Salud , Complicaciones Posoperatorias , Prostatectomía/efectos adversos , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Trastornos Urinarios/diagnóstico , Anciano , Competencia Clínica , Constricción Patológica/diagnóstico , Constricción Patológica/etiología , Bases de Datos Factuales , Inglaterra , Humanos , Tiempo de Internación , Masculino , Servicio de Registros Médicos en Hospital/organización & administración , Persona de Mediana Edad , Reproducibilidad de los Resultados , Factores Socioeconómicos , Incontinencia Urinaria/diagnóstico , Incontinencia Urinaria/etiología , Trastornos Urinarios/etiologíaRESUMEN
OBJECTIVES: To determine whether modified transperineal template prostate-mapping (TTPM) biopsy protocols, altering the template or the biopsy density, have sensitivity and negative predictive value (NPV) equal to full 5-mm TTPM. PATIENTS AND METHODS: Retrospective analysis of an institutional registry including treatment-naïve men undergoing 5-mm TTPM biopsy analysed in a 20-zone fashion. The value of three modified strategies was assessed by comparing the information provided by selected zones against full 5-mm TTPM. Strategy 1, did not consider the findings of anterior areas; strategies 2 and 3 simulated a reduced biopsy density by excluding intervening zones. A bootstrapping technique was used to calculate reliable estimates of sensitivity and NPV of these three strategies for the detection of clinically significant disease (maximum cancer core length ≥4 mm and/or Gleason score ≥3 + 4). RESULTS: In all, 391 men with a median (interquartile range, IQR) age of 62 (58-67) years were included. The median (IQR) PSA level and PSA density were 6.9 (4.8-10) ng/mL and 0.17 (IQR 0.12-0.25) ng/mL/mL, respectively. A median (IQR) of 6 (2-9) cores out of 48 (33-63) taken per man were positive for prostate cancer. No cancer was detected in 67 men (17%), whilst low-, intermediate- and high-risk disease was identified in 78 (20%), 80 (21%), and 166 (42%), respectively. Strategy 1, 2 and 3 had sensitivities of 78% [95% confidence interval (CI) 73-84%], 85% (95% CI 80-90%) and 84% (95% CI 79-89%), respectively. The NPVs of the three strategies were 73% (95% CI 67-80%), 80% (95% CI 74-86%) and 79% (95% CI 72-84%), respectively. CONCLUSION: Altering the template or decreasing sampling density has a substantial negative impact on the ability of TTPM biopsy to exclude clinically significant disease. This should be considered when modified TTPM biopsy strategies are used to select men for tissue-preserving approaches, and when modified TTPM are used to validate new diagnostic tests.
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Próstata/patología , Neoplasias de la Próstata/patología , Anciano , Biopsia/métodos , Protocolos Clínicos , Humanos , Masculino , Persona de Mediana Edad , Perineo , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
OBJECTIVES: To study muscle biopsy tissue from patients with juvenile dermatomyositis (JDM) in order to test the reliability of a score tool designed to quantify the severity of histological abnormalities when applied to biceps humeri in addition to quadriceps femoris. Additionally, to evaluate whether elements of the tool correlate with clinical measures of disease severity. METHODS: 55 patients with JDM with muscle biopsy tissue and clinical data available were included. Biopsy samples (33 quadriceps, 22 biceps) were prepared and stained using standardised protocols. A Latin square design was used by the International Juvenile Dermatomyositis Biopsy Consensus Group to score cases using our previously published score tool. Reliability was assessed by intraclass correlation coefficient (ICC) and scorer agreement (α) by assessing variation in scorers' ratings. Scores from the most reliable tool items correlated with clinical measures of disease activity at the time of biopsy. RESULTS: Inter- and intraobserver agreement was good or high for many tool items, including overall assessment of severity using a Visual Analogue Scale. The tool functioned equally well on biceps and quadriceps samples. A modified tool using the most reliable score items showed good correlation with measures of disease activity. CONCLUSIONS: The JDM biopsy score tool has high inter- and intraobserver agreement and can be used on both biceps and quadriceps muscle tissue. Importantly, the modified tool correlates well with clinical measures of disease activity. We propose that standardised assessment of muscle biopsy tissue should be considered in diagnostic investigation and clinical trials in JDM.
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Dermatomiositis/patología , Músculo Cuádriceps/patología , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Biopsia , Complejo CD3/metabolismo , Niño , Preescolar , Dermatomiositis/metabolismo , Femenino , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Inmunohistoquímica , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Miosinas/metabolismo , Músculo Cuádriceps/metabolismo , Reproducibilidad de los Resultados , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Factors associated with severe COVID-19 infection have been identified; however, the impact of infection on longer-term outcomes is unclear. The objective of this study was to examine the impact of COVID-19 infection on the trajectory of lung function and nutritional status in people with cystic fibrosis (pwCF). METHODS: This is a retrospective global cohort study of pwCF who had confirmed COVID-19 infection diagnosed between January 1, 2020 and December 31, 2021. Forced expiratory volume in one second percent predicted (ppFEV1) and body mass index (BMI) twelve months prior to and following a diagnosis of COVID-19 were recorded. Change in mean ppFEV1 and BMI were compared using a t-test. A linear mixed-effects model was used to estimate change over time and to compare the rate of change before and after infection. RESULTS: A total of 6,500 cases of COVID-19 in pwCF from 33 countries were included for analysis. The mean difference in ppFEV1 pre- and post-infection was 1.4 %, (95 % CI 1.1, 1.7). In those not on modulators, the difference in rate of change pre- and post-infection was 1.34 %, (95 % CI -0.88, 3.56) per year (p = 0.24) and -0.74 % (-1.89, 0.41) per year (p = 0.21) for those on elexacaftor/tezacaftor/ivacaftor. No clinically significant change was noted in BMI or BMI percentile before and after COVID-19 infection. CONCLUSIONS: No clinically meaningful impact on lung function and BMI trajectory in the year following infection with COVID-19 was identified. This work highlights the ability of the global CF community to unify and address critical issues facing pwCF.
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PURPOSE: Multiparametric magnetic resonance imaging can be used to guide prostate biopsy by targeting biopsies to areas in the prostate at high risk for cancer. We compared the detection of clinically significant and insignificant cancer by transperineal magnetic resonance imaging targeted biopsy and transperineal template guided prostate biopsy. MATERIALS AND METHODS: A total of 182 men with a lesion suspicious for cancer on multiparametric magnetic resonance imaging underwent transperineal magnetic resonance imaging targeted biopsy using a cognitive registration technique, followed by systematic transperineal template guided prostate biopsy. The primary outcome was the detection rate of clinically significant prostate cancer. Clinical significance was defined using maximum cancer core length 4 mm or greater and/or Gleason grade 3 + 4 or greater (University College London definition 2). We secondarily evaluated other commonly used thresholds of clinically significant disease, including maximum cancer core length 6 mm or greater and/or Gleason grade 4 + 3 or greater, maximum cancer core length 3 mm or greater and/or Gleason grade 3 + 4 or greater, and maximum cancer core length 2 or greater mm and/or Gleason grade 3 + 4 or greater. Strategies were statistically compared with the McNemar test. RESULTS: Mean ± SD patient age was 63.3 ± 7.2 years. Median prostate specific antigen was 6.7 ng/ml (IQR 4.7-10.0). Clinically significant cancer was detected by magnetic resonance imaging targeted biopsy and template guided prostate biopsy in 103 (57%) and 113 of the 182 men (62%) (p = 0.174), and clinically insignificant cancer was detected in 17 (9.3%) and 31 (17.0%), respectively (p = 0.024). CONCLUSIONS: Prostate biopsy targeted to suspicious lesions on multiparametric magnetic resonance imaging has encouraging rates of detection of clinically significant cancer while also decreasing the detection rate of clinically insignificant cancer. This is achieved with fewer biopsy cores than for systematic template guided biopsy. Further prospective, multicenter, comparative trials of the performance of targeting strategies are needed to consider magnetic resonance imaging targeted biopsy an alternative to conventional systematic biopsy.
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Biopsia con Aguja Gruesa/métodos , Imagen por Resonancia Magnética/métodos , Clasificación del Tumor/métodos , Próstata/patología , Neoplasias de la Próstata/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Perineo , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: The availability of mutation-specific cystic fibrosis modulator therapies has the potential to improve the lives of children and adults with cystic fibrosis. The frequency of mutations causing defects in the cystic fibrosis transmembrane conductance regulator (CFTR) function varies between sub-groups in multi-ethnic populations. The profile of patients eligible for CFTR modulator ivacaftor/tezacaftor/elexacaftor (Kaftrio™) therapy based on ethnicity has not been reported in the United Kingdom CF population. METHODS: We conducted a descriptive cross-sectional analysis of patients in the UK CF Registry who had annual review data submissions in 2019. Data analysed included demographic characteristics, spirometry, chronic Pseudomonas status, nutrition, and CF related diabetes status. The genotype data was stratified by whether there was at least one copy of F508del or no copy of F508del as current eligibility for ivacaftor/tezacaftor/elexacaftor, or projected future eligibility, is defined as having at least one copy of F508del mutation. RESULTS: Data from 9887 patients were reviewed, 46.7% female, mean age 22.5 years. 8.6% (n = 852) patients had no copy of F508del making them ineligible for ivacaftor/tezacaftor/elexacaftor. Overall, 93.4% of patients were of white ethnicity, with a similar proportion of those with at least one F508del being white (95.6%). This was reduced to 70.0% of those with no F508del. The proportion of people of Asian ethnicity was much higher in the no F508del group (19.2% vs 1.2%). Compared with one F508del patients, the no F508del group were older (25.2 years vs 22.2 years, p < 0.001), had higher prevalence of pancreatic sufficiency (39.0% vs 14.9% p < 0.001), lower prevalence of chronic Pseudomonas infection (21.1% vs. 26.6%, p < 0.001), and higher best FEV1 from the previous year (proportion with greater than 70% FEV1 predicted, 66.1% vs 63.0%, p = 0.005). CONCLUSION: Patients from black, Asian and minority ethnic backgrounds are significantly less likely to be eligible for ivacaftor/tezacaftor/elexacaftor based on the current prescribing policy in the UK. At present this is the most highly effective CF modulator therapy available to treat people with CF. The CF community should urgently address the unmet need for effective targeted therapies for patients without F508del.
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Regulador de Conductancia de Transmembrana de Fibrosis Quística , Fibrosis Quística , Adulto , Niño , Estudios Transversales , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Femenino , Humanos , Masculino , Mutación , Pruebas de Función Respiratoria , Adulto JovenRESUMEN
BACKGROUND: Airway clearance techniques (ACTs) are integral to cystic fibrosis (CF) management. However, there is no consensus as to which outcome measures (OMs) are best for assessing ACT efficacy. OBJECTIVES: To summarise OMs that have been assessed for their clinimetric properties (including validity, feasibility, reliability, and reproducibility) within the context of ACT research in CF. DESIGN AND METHODS: A systematic review was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) standards. Any parallel or cross-over randomised controlled trial (RCT) investigating outcome measures for ACT in the CF population were eligible for inclusion. The search was performed in five medical databases, clinicaltrials.gov, and abstracts from international CF conferences. The authors planned to independently assess study quality and risk of bias using the COnsensus-based Standards for the selection of health status Measurement InstrumeNts (COSMIN) risk of bias checklist with external validity assessment based upon study details (participants and study intervention). Two review authors (GS and MJ) independently screened search results against inclusion criteria, and further data extraction were planned but not required. RESULTS: No completed RCTs from the 187 studies identified met inclusion criteria for the primary or post hoc secondary objective. Two ongoing trials were identified. DISCUSSION AND CONCLUSION: This empty systematic review highlights that high-quality RCTs are urgently needed to investigate and validate the clinimetric properties of OMs used to assess ACT efficacy. With the changing demographics of CF combined with the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies, an accurate assessment of the current benefit of ACT or the effect of ACT withdrawal is a high priority for clinical practice and future research; OMs which have been validated for this purpose are essential. REGISTRATION: This systematic review was registered on the PROSPERO database (CRD42020206033).
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Fibrosis Quística , Fibrosis Quística/complicaciones , Fibrosis Quística/diagnóstico , Fibrosis Quística/terapia , Humanos , Evaluación de Resultado en la Atención de SaludRESUMEN
BACKGROUND: As part of the risk management plan in Europe, a long-term observational study was conducted to monitor the safety of colistimethate sodium dry powder for inhalation (CMS-DPI) compared to other inhaled antibiotics. METHODS: A cohort of CMS-DPI patients and a matched cohort were identified from the UK Cystic Fibrosis Registry (UKCFR) from 2014-2018. The primary outcome was a composite endpoint, defined as adverse events (AEs) or new cystic fibrosis (CF) complications. Other outcomes included pulmonary exacerbations and treatment discontinuations. RESULTS: Of 1466 and 3503 patients in the CMS-DPI and comparator cohorts, respectively, 82.7% and 79.4% had AEs. Among the most common new CF complications were osteopenia, CF-related diabetes, and increased liver enzymes. The adjusted event rate ratio (ERR) for the primary outcome was 1.25 (95% confidence interval [CI]: 1.18-1.33, p<0.001). After excluding new CF complications, there was no difference between cohorts (ERR=1.04, 95% CI: 0.79-1.38, p=0.785). Pulmonary exacerbations were common in CMS-DPI and comparator cohorts (78.0% and 79.9% of patients, respectively), with adjusted ERR of 1.02 (95% CI: 0.95-1.10, p=0.523). Rates of discontinuation were similar in the CMS-DPI and Tobramycin inhalation powder comparator cohorts (37.8% and 39.8% of patients, respectively). CONCLUSIONS: There was no difference in the rate of adverse events between CMS-DPI and comparator cohorts. The safety profile of CMS-DPI is similar to those of other inhaled antibiotics, supporting its long-term safety in people with CF. The UKCFR has developed a successful model for partnership with industry to conduct long-term studies aimed at assessing drug safety.
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Antibacterianos/uso terapéutico , Colistina/análogos & derivados , Fibrosis Quística/complicaciones , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Administración por Inhalación , Adolescente , Adulto , Anciano , Antibacterianos/administración & dosificación , Niño , Colistina/administración & dosificación , Colistina/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Infecciones del Sistema Respiratorio/microbiología , Brote de los Síntomas , Reino UnidoRESUMEN
PURPOSE: The aim of the current study was to determine patient-reported functional outcomes in men with prostate cancer (PCa) undergoing moderately hypofractionated (H-RT) or conventionally fractionated radiation therapy (C-RT) in a national cohort study. PATIENDS AND METHODS: All men diagnosed with PCa between April 2014 and September 2016 in the English National Health Service undergoing C-RT or H-RT were identified in the National Prostate Cancer Audit and mailed a questionnaire at least 18 months after diagnosis. We estimated differences in patient-reported urinary, bowel, sexual, and hormonal function-Expanded Prostate Cancer Index Composite short-form 26 domain scores on a 0 to 100 scale-and health-related quality of life-EQ-5D-5L on a 0 to 1 scale-using linear regression with adjustment for patient, tumor, and treatment-related factors in addition to GI and genitourinary baseline function, with higher scores representing better outcomes. RESULTS: Of the 17,058 men in the cohort, 77% responded: 8,432 men received C-RT (64.2%) and 4,699 H-RT (35.8%). Men in the H-RT group were older (age ≥ 70 years: 67.5% v 60.9%), fewer men had locally advanced disease (56.5% v 71.3%), were less likely to receive androgen-deprivation therapy (79.5% v 87.8%), and slightly more men had pretreatment genitourinary procedures (24.2% v 21.2%). H-RT was associated with small increases in adjusted mean Expanded Prostate Cancer Index Composite short-form 26 sexual (3.3 points; 95% CI, 2.1 to 4.5; P < .001) and hormonal function scores (3.2 points; 95% CI, 1.8 to 4.6; P < .001). These differences failed to meet established thresholds for a clinically meaningful change. There were no statistically significant differences in urinary or bowel function and quality of life. CONCLUSION: This is the first national cohort study comparing functional outcomes after H-RT and C-RT reported by patients. These real-world results further support the use of H-RT as the standard for radiation therapy in men with nonmetastatic PCa.
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Neoplasias de la Próstata/fisiopatología , Neoplasias de la Próstata/radioterapia , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Fraccionamiento de la Dosis de Radiación , Inglaterra/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Neoplasias de la Próstata/epidemiología , Calidad de Vida , Encuestas y Cuestionarios , Resultado del Tratamiento , Gales/epidemiologíaRESUMEN
BACKGROUND: Ivacaftor is the first in a class of drugs, CFTR modulators, that target the underlying defect in cystic fibrosis (CF). This long-term observational safety study evaluated CF disease progression in patients treated with ivacaftor in a real-world setting for up to 5â¯years. METHODS: Data from existing US and UK CF patient registries were used to assess longitudinal patterns in lung function, nutritional status, pulmonary exacerbations and hospitalizations, CF-related diabetes (CFRD), and Pseudomonas aeruginosa in ivacaftor-treated vs untreated comparator cohorts matched by age, sex, and disease severity. RESULTS: US analyses included 635 ivacaftor-treated patients and 1874 comparators followed for 5â¯years from year 1 of market availability (2012-2016). Evaluation of outcome patterns from pretreatment baseline (2011) through year 5 (2016), showed that relative to comparators, ivacaftor-treated patients had better preserved lung function (mean change in percent predicted FEV1, -0.7 percentage points with ivacaftor vs -8.3 percentage points in comparators) and improved nutritional status (mean body mass index change +2.4â¯kg/m2 with ivacaftor vs +1.6â¯kg/m2 in comparators). US patients treated with ivacaftor had significantly lower frequencies of exacerbations and hospitalizations in each of the 5â¯years of follow-up relative to pretreatment baseline and comparators. Favorable trends in CFRD and P. aeruginosa prevalence were also observed. Findings from the smaller UK registry were directionally similar to and consistent with US findings. CONCLUSIONS: This observational study represents the largest longitudinal analysis of patients treated with ivacaftor in a real-world setting. The findings support disease modification by CFTR modulation with ivacaftor.
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Aminofenoles/uso terapéutico , Fibrosis Quística , Progresión de la Enfermedad , Pseudomonas aeruginosa/aislamiento & purificación , Quinolonas/uso terapéutico , Pruebas de Función Respiratoria , Adulto , Agonistas de los Canales de Cloruro/uso terapéutico , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/epidemiología , Fibrosis Quística/microbiología , Fibrosis Quística/fisiopatología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Estudios Longitudinales , Masculino , Sistema de Registros/estadística & datos numéricos , Pruebas de Función Respiratoria/métodos , Pruebas de Función Respiratoria/estadística & datos numéricos , Reino Unido/epidemiología , Estados Unidos/epidemiologíaRESUMEN
Rationale: Ivacaftor can greatly improve clinical outcomes in people with cystic fibrosis (CF) and has been shown to have in vitro antibacterial properties, yet the long-term microbiological outcomes of treatment are unknown.Objectives: To investigate changes in respiratory microbiology associated with long-term ivacaftor use.Methods: This was a retrospective cohort study using data from the UK CF Registry 2011-2016. Primary outcome was the annual prevalence ratios for key CF pathogens between ivacaftor users and their contemporaneous comparators. Multivariable log-binomial regression models were designed to adjust for confounders. Changes in Pseudomonas aeruginosa status were compared between groups using nonparametric maximum likelihood estimate for the purposes of Kaplan-Meier approximation.Results: Ivacaftor use was associated with early and sustained reduction in P. aeruginosa rates (2016 adjusted prevalence ratio, 0.68; 95% confidence interval, 0.58-0.79; P < 0.001) via a combination of increased clearance in those with infection (ivacaftor: 33/87 [37.9%] vs. nonivacaftor: 432/1,872 [22.8%]; P < 0.001) and reduced acquisition in those without infection (49/134 [36.6%] vs. 1,157/2,382 [48.6%]; P = 0.01). The improved prevalence of P. aeruginosa infection was independent of reduced sampling in the ivacaftor cohort. Ivacaftor was also associated with reduced prevalence of Staphylococcus aureus and Aspergillus spp. but not Burkholderia cepacia complex.Conclusions: In this study, long-term ivacaftor use was associated with reduced infection with important CF pathogens including P. aeruginosa. These findings have implications for antibiotic stewardship and the need for ongoing chronic antimicrobial therapy in this cohort.
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Aminofenoles/uso terapéutico , Fibrosis Quística/complicaciones , Fibrosis Quística/tratamiento farmacológico , Activadores de Enzimas/uso terapéutico , Infecciones por Pseudomonas/epidemiología , Quinolonas/uso terapéutico , Adolescente , Adulto , Aspergillus/aislamiento & purificación , Burkholderia cepacia/aislamiento & purificación , Niño , Femenino , Humanos , Estimación de Kaplan-Meier , Funciones de Verosimilitud , Masculino , Análisis Multivariante , Pseudomonas aeruginosa/aislamiento & purificación , Sistema de Registros , Análisis de Regresión , Estudios Retrospectivos , Staphylococcus aureus/aislamiento & purificación , Resultado del Tratamiento , Reino Unido/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Men with negative prostate biopsies or those diagnosed with low-risk or low-volume intermediate-risk prostate cancers often require a second prostate biopsy prior to a treatment decision. Prostate HistoScanning (PHS) is an ultrasound imaging test that might inform prostate biopsy in such men. METHODS: PICTURE was a prospective, paired-cohort validating trial to assess the diagnostic accuracy of imaging in men requiring a further biopsy (clinicaltrials.gov, NCT01492270) (11 January 2012-29 January 2014). We enrolled 330 men who had undergone a prior TRUS biopsy but where diagnostic uncertainty remained. All eligible men underwent PHS and transperineal template prostate mapping (TTPM) biopsy (reference standard). Men were blinded to the imaging results until after undergoing TTPM biopsies. We primarily assessed the ability of PHS to rule out clinically significant prostate (negative predictive value [NPV] and sensitivity) for a target histological condition of Gleason ≥4+3 and/or a cancer core length (MCCL) ≥6 mm. We also assessed the role of visually estimated PHS-targeted biopsies. RESULTS: Of the 330 men enrolled, 249 underwent both PHS and TTPM biopsy. Mean (SD) age was 62 (7) years, median (IQR) PSA 6.8 (4.98-9.50) ng/ml, median (IQR) number of previous biopsies 1 (1-2) and mean (SD) gland size 37 (15.5) ml. One hundred and forty six (59%) had no clinically significant cancer. PHS classified 174 (70%) as suspicious. Sensitivity was 70.3% (95% CI 59.8-79.5) and NPV 41.3% (95% CI 27.0-56.8). Specificity and positive predictive value (PPV) were 14.7% (95% CI 9.1-22.0) and 36.8% (95% CI 29.6-44.4), respectively. In all, 213/220 had PHS suspicious areas targeted with targeting sensitivity 13.6% (95% CI 7.3-22.6), specificity 97.6% (95% CI 93.1-99.5), NPV 61.6% (95% CI 54.5-68.4) and PPV 80.0% (95% CI 51.9-95.7). CONCLUSIONS: PHS is not a useful test in men seeking risk stratification following initial prostate biopsy.