RESUMEN
OBJECTIVES: Primary objectives: to determine whether local anaesthetic transperineal prostate (LATP) biopsy improves the detection of clinically significant prostate cancer (csPCa), defined as International Society of Urological Pathology (ISUP) Grade Group ≥2 disease (i.e., any Gleason pattern 4 disease), compared to transrectal ultrasound-guided (TRUS) prostate biopsy, in biopsy-naïve men undergoing biopsy based on suspicion of csPCa. SECONDARY OBJECTIVES: to compare (i) infection rates, (ii) health-related quality of life, (iii) patient-reported procedure tolerability, (iv) patient-reported biopsy-related complications (including bleeding, bruising, pain, loss of erectile function), (v) number of subsequent prostate biopsy procedures required, (vi) cost-effectiveness, (vii) other histological parameters, and (viii) burden and rate of detection of clinically insignificant PCa (ISUP Grade Group 1 disease) in men undergoing these two types of prostate biopsy. PATIENTS AND METHODS: The TRANSLATE trial is a UK-wide, multicentre, randomised clinical trial that meets the criteria for level-one evidence in diagnostic test evaluation. TRANSLATE is investigating whether LATP biopsy leads to a higher rate of detection of csPCa compared to TRUS prostate biopsy. Both biopsies are being performed with an average of 12 systematic cores in six sectors (depending on prostate size), plus three to five target cores per multiparametric/bi-parametric magnetic resonance imaging lesion. LATP biopsy is performed using an ultrasound probe-mounted needle-guidance device (either the 'Precision-Point' or BK UA1232 system). TRUS biopsy is performed according to each hospital's standard practice. The study is 90% powered to detect a 10% difference (LATP biopsy hypothesised at 55% detection rate for csPCa vs 45% for TRUS biopsy). A total of 1042 biopsy-naïve men referred with suspected PCa need to be recruited. CONCLUSIONS: This trial will provide robust prospective data to determine the diagnostic ability of LATP biopsy vs TRUS biopsy in the primary diagnostic setting.
Asunto(s)
Próstata , Neoplasias de la Próstata , Masculino , Humanos , Próstata/patología , Estudios Prospectivos , Calidad de Vida , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Biopsia/efectos adversos , Biopsia Guiada por Imagen/efectos adversos , Biopsia Guiada por Imagen/métodos , Imagen por Resonancia Magnética/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
BACKGROUND: Deceased donor kidneys are preserved in cold hypoxic conditions. Providing oxygen during preservation might improve post-transplant outcomes, particularly for kidneys subjected to greater degrees of preservation injury. This study aimed to investigate whether supplemental oxygen during hypothermic machine perfusion (HMP) could improve the outcome of kidneys donated after circulatory death. METHODS: This randomised, double-blind, paired, phase 3 trial was done in 19 European transplant centres. Kidney pairs from donors aged 50 years or older, donated after circulatory death, were eligible if both kidneys were transplanted into two different recipients. One kidney from each donor was randomly assigned using permuted blocks to oxygenated hypothermic machine perfusion (HMPO2), the other to HMP without oxygenation. Perfusion was maintained from organ retrieval to implantation. The primary outcome was 12-month estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation in pairs of donated kidneys in which both transplanted kidneys were functioning at the end of follow-up. Safety outcomes were reported for all transplanted kidneys. Intention-to-treat analyses were done. This trial is registered with the ISRCTN Registry, ISRCTN32967929, and is now closed. FINDINGS: Between March 15, 2015, and April 11, 2017, 197 kidney pairs were randomised with 106 pairs transplanted into eligible recipients. 23 kidney pairs were excluded from the primary analysis because of kidney failure or patient death. Mean eGFR at 12 months was 50·5 mL/min per 1·73 m2 (SD 19·3) in the HMPO2 group versus 46·7 mL/min per 1·73m2 (17·1) in HMP (mean difference 3·7 mL/min per 1·73m2, 95% CI -1·0 to 8·4; p=0·12). Fewer severe complications (Clavien-Dindo grade IIIb or more) were reported in the HMPO2 group (46 of 417, 11%, 95% CI 8% to 14%) than in the HMP group (76 of 474, 16%, 13% to 20%; p=0·032). Graft failure was lower with HMPO2 (three [3%] of 106) compared with HMP (11 [10%] of 106; hazard ratio 0·27, 95% CI 0·07 to 0·95; p=0·028). INTERPRETATION: HMPO2 of kidneys donated after circulatory death is safe and reduces post-transplant complications (grade IIIb or more). The 12-month difference in eGFR between the HMPO2 and HMP groups was not significant when both kidneys from the same donor were still functioning 1-year post-transplant, but potential beneficial effects of HMPO2 were suggested by analysis of secondary outcomes. FUNDING: European Commission 7th Framework Programme.
Asunto(s)
Frío , Trasplante de Riñón , Preservación de Órganos , Oxígeno , Perfusión , Método Doble Ciego , Europa (Continente) , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Oxígeno/fisiología , Supervivencia Tisular , Recolección de Tejidos y ÓrganosRESUMEN
PURPOSE: We hypothesized that 1) introducing prebiopsy multiparametric magnetic resonance imaging would increase the diagnostic yield of transrectal prostate biopsy and 2) this would inform recommendations regarding systematic transrectal prostate biopsy in the setting of negative prebiopsy multiparametric magnetic resonance imaging. MATERIALS AND METHODS: A total of 997 biopsy naïve patients underwent transrectal prostate biopsy alone to June 2016 (cohort 1) and thereafter 792 underwent transrectal prostate biopsy following prebiopsy multiparametric magnetic resonance imaging (cohort 2). Patients with lesions on prebiopsy multiparametric magnetic resonance imaging underwent cognitive targeted plus systematic transrectal prostate biopsy. Patients without lesions underwent systematic transrectal prostate biopsy. RESULTS: Cohort 2 comprised younger men (age 68 vs 69 years, p = 0.01) with lower prostate specific antigen (7.6 vs 7.9 ng/ml, p = 0.024) and smaller prostate volume (56.1 vs 62 cc, p = 0.006). In cohort 2 vs cohort 1 there was no increase in overall prostate cancer detection (57.6% vs 56.7%, p = 0.701), the Gleason Grade Group or the number of positive cores (each p >0.05). Increased multifocal prostatic intraepithelial neoplasia, maximum prostate cancer core length (5 mm or greater vs less than 5 mm) and radical surgery/high intensity focused ultrasound (each p <0.05) were observed in cohort 2. For Gleason Grade Group 2-5 prostate cancer negative prebiopsy multiparametric magnetic resonance imaging had 88.1% sensitivity, 59.8% specificity, 67.8% positive predictive value and 84% negative predictive value. For negative prebiopsy multiparametric magnetic resonance images a prostate specific antigen density cutoff of 0.15 ng/ml2 or greater increased clinically significant prostate cancer detection only if the latter was defined as Gleason Grade Group 3-5 disease and/or tumor length 6 mm or greater. CONCLUSIONS: Introducing prebiopsy multiparametric magnetic resonance imaging in our clinical setting increased the diagnostic yield of prostate cancer per biopsy core. Not performing a systematic transrectal prostate biopsy when prebiopsy multiparametric magnetic resonance imaging was negative would have led to under detection of 15.1% of Gleason Grade Group 2 or greater prostate cancer cases (approximately 1 in 6).
Asunto(s)
Imagen por Resonancia Magnética , Próstata/diagnóstico por imagen , Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Anciano , Biopsia , Estudios de Cohortes , Humanos , Masculino , Periodo PreoperatorioRESUMEN
INTRODUCTION: Prostatic capsular incision (CapI) is an iatrogenic breach of the prostatic capsule during radical prostatectomy (RP) that can cause positive surgical margins (PSMs) in organ-confined (pT2) prostate cancer, or the retention of benign prostatic tissue. We systematically interrogated the literature in order to clarify the definition of CapI, and the implications of this event for rates of PSM and biochemical recurrence (BCR). METHODS: A literature search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria using the search terms 'capsular incision' AND 'prostatectomy', and variations of each. In all, 18 studies were eligible for inclusion. RESULTS: A total of 51 057 RP specimens were included. The incidence of CapI ranged from 1.3% to 54.3%. CapI definitions varied and included a breach of the prostatic capsule 'exposing both benign or malignant prostate cancer cells', 'malignant tissue only', or 'benign tissue only'. The incidence of PSMs due to CapI ranged from 2.8% to 71.7%. Our meta-analysis results found that when CapI was defined as 'exposing malignant tissue only in organ-confined prostate cancer' there was an increased risk of BCR compared to patients with pT2 disease and no CapI (relative risk 3.53, 95% confidence interval 2.82-4.41; P < 0.001). CONCLUSIONS: The absolute impact of CapI on oncological outcomes is currently unclear due to inconsistent definitions. However, the data imply an association between CapI and PSMs and BCR. Reporting of possible areas of CapI on the operation note, or marking areas of concern on the specimen, are critical to assist CapI recognition by the pathologist.
RESUMEN
BACKGROUND: In the phase 3 SOLO2 trial (ENGOT Ov-21), maintenance therapy with olaparib tablets significantly prolonged progression-free survival (primary endpoint) compared with placebo in patients with a germline BRCA1 or BRCA2 (BRCA1/2) mutation and platinum-sensitive, relapsed ovarian cancer who had received two or more lines of previous chemotherapy. The most common subjective adverse effects included fatigue, nausea, and vomiting, which were typically low grade and self-limiting. Our a-priori hypothesis was that maintenance olaparib would not negatively affect health-related quality of life (HRQOL) and additionally that the prolongation of progression-free survival with olaparib would be underpinned by additional patient-centred benefits. METHODS: In SOLO2, 196 patients were randomly assigned to olaparib tablets (300 mg twice daily) and 99 to placebo. Randomisation was stratified by response to previous chemotherapy (complete vs partial) and length of platinum-free interval (>6-12 vs >12 months). The prespecified primary HRQOL analysis evaluated the change from baseline in the Trial Outcome Index (TOI) score during the first 12 months of the study. To be assessable, patients had to have an evaluable score at baseline and at least one evaluable follow-up form. Secondary planned quality-of-life (QOL) analyses included the duration of good quality of life (defined as time without significant symptoms of toxicity [TWiST] and quality-adjusted progression-free survival [QAPFS]). Efficacy and QOL outcomes were analysed in all randomly assigned patients (the full analysis set), and safety outcomes were analysed in all randomly assigned patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01874353, and is closed to new participants. FINDINGS: The adjusted average mean change from baseline over the first 12 months in TOI was -2·90 (95% CI -4·13 to -1·67) with olaparib and -2·87 (-4·64 to -1·10) with placebo (estimated difference -0·03; 95% CI -2·19 to 2·13; p=0·98). Mean QAPFS (13·96 [SD 10·96] vs 7·28 [5·22] months; difference 6·68, 95% CI 4·98-8·54) and mean duration of TWiST (15·03 [SD 12·79] vs 7·70 [6·42] months; difference 7·33, 95% CI 4·70-8·96) were significantly longer with olaparib than with placebo. INTERPRETATION: Olaparib maintenance therapy did not have a significant detrimental effect on HRQOL compared with placebo. There were clinically meaningful patient-centred benefits in both TWiST and QAPFS despite the adverse effects associated with olaparib. These patient-centred endpoints support the improvement in progression-free survival, the primary endpoint in SOLO2, and should be included in future trials of maintenance therapies. FUNDING: AstraZeneca.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Ftalazinas/uso terapéutico , Piperazinas/uso terapéutico , Calidad de Vida , Adulto , Anciano , Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma Epitelial de Ovario/genética , Carcinoma Epitelial de Ovario/mortalidad , Femenino , Humanos , Quimioterapia de Mantención/métodos , Persona de Mediana Edad , Mutación , Supervivencia sin Progresión , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To assess whether inhaled nitric oxide (iNO) improves survival without bronchopulmonary dysplasia (BPD) for preterm African American infants. STUDY DESIGN: An individual participant data meta-analysis was conducted, including 3 randomized, placebo-controlled trials that enrolled infants born at <34 weeks of gestation receiving respiratory support, had at least 15% (or a minimum of 10 infants in each trial arm) of African American race, and used a starting iNO of >5 parts per million with the intention to treat for 7 days minimum. The primary outcome was a composite of death or BPD. Secondary outcomes included death before discharge, postnatal steroid use, gross pulmonary air leak, pulmonary hemorrhage, measures of respiratory support, and duration of hospital stay. RESULTS: Compared with other races, African American infants had a significant reduction in the composite outcome of death or BPD with iNO treatment: 49% treated vs 63% controls (relative risk, 0.77; 95% CI, 0.65-0.91; P = .003; interaction P = .016). There were no differences between racial groups for death. There was also a significant difference between races (interaction P = .023) of iNO treatment for BPD in survivors, with the greatest effect in African American infants (P = .005). There was no difference between racial groups in the use of postnatal steroids, pulmonary air leak, pulmonary hemorrhage, or other measures of respiratory support. CONCLUSION: iNO therapy should be considered for preterm African American infants at high risk for BPD. iNO to prevent BPD in African Americans may represent an example of a racially customized therapy for infants.
Asunto(s)
Displasia Broncopulmonar/etnología , Mortalidad Infantil/etnología , Óxido Nítrico/administración & dosificación , Administración por Inhalación , Negro o Afroamericano/estadística & datos numéricos , Displasia Broncopulmonar/prevención & control , Glucocorticoides/administración & dosificación , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Tiempo de Internación/estadística & datos numéricos , Óxido Nítrico/efectos adversos , Factores Raciales , Terapia Respiratoria/efectos adversos , Terapia Respiratoria/estadística & datos numéricos , Tasa de SupervivenciaRESUMEN
Rather than maximizing intake of available macronutrients, insects increase intake of some nutrients and restrict intake of others. This selective consumption influences, and potentially optimizes, developmental time, reproduction and lifespan of the organism. Studies so far have focused on discriminating between protein and carbohydrate uptake and the consequences on fitness components at different life stages. However, it is largely unknown whether and how the developmental diets, which may entail habitat-specific nutrient restrictions, affect selective consumption in adults. We show that adult female D. melanogaster opt for the same protein to carbohydrate (P:C) ratio regardless of their developmental diet (P:C ratio of 1:1, 1:4 or 1:8). In contrast, males choose a diet that makes up for deficiencies; when protein is low during development, males increase protein consumption despite this being detrimental to starvation resistance. The sexual dimorphism in foraging choice could be due to the different energetic requirements of males and females. To investigate the effect of developmental diet on lifespan once an adult nutritional environment has been established, we also conducted a no-choice experiment. Here, adult lifespan increased as P:C ratio decreased, irrespective of developmental diet, thus demonstrating a 'cancelling out' effect of the nutritional environment experienced during early life stages. Our study provides novel insights into how developmental diet is linked to adult diet by presenting evidence for sexual dimorphism in foraging choice as well as life-stage dependency of diet on lifespan.
Asunto(s)
Dieta , Carbohidratos de la Dieta/metabolismo , Proteínas en la Dieta/metabolismo , Drosophila melanogaster/fisiología , Animales , Conducta de Elección , Drosophila melanogaster/crecimiento & desarrollo , Conducta Alimentaria , Femenino , Larva/crecimiento & desarrollo , Larva/fisiología , MasculinoRESUMEN
Importance: There are potential benefits and harms of hyperoxemia and hypoxemia for extremely preterm infants receiving more vs less supplemental oxygen. Objective: To compare the effects of different target ranges for oxygen saturation as measured by pulse oximetry (Spo2) on death or major morbidity. Design, Setting, and Participants: Prospectively planned meta-analysis of individual participant data from 5 randomized clinical trials (conducted from 2005-2014) enrolling infants born before 28 weeks' gestation. Exposures: Spo2 target range that was lower (85%-89%) vs higher (91%-95%). Main Outcomes and Measures: The primary outcome was a composite of death or major disability (bilateral blindness, deafness, cerebral palsy diagnosed as ≥2 level on the Gross Motor Function Classification System, or Bayley-III cognitive or language score <85) at a corrected age of 18 to 24 months. There were 16 secondary outcomes including the components of the primary outcome and other major morbidities. Results: A total of 4965 infants were randomized (2480 to the lower Spo2 target range and 2485 to the higher Spo2 range) and had a median gestational age of 26 weeks (interquartile range, 25-27 weeks) and a mean birth weight of 832 g (SD, 190 g). The primary outcome occurred in 1191 of 2228 infants (53.5%) in the lower Spo2 target group and 1150 of 2229 infants (51.6%) in the higher Spo2 target group (risk difference, 1.7% [95% CI, -1.3% to 4.6%]; relative risk [RR], 1.04 [95% CI, 0.98 to 1.09], P = .21). Of the 16 secondary outcomes, 11 were null, 2 significantly favored the lower Spo2 target group, and 3 significantly favored the higher Spo2 target group. Death occurred in 484 of 2433 infants (19.9%) in the lower Spo2 target group and 418 of 2440 infants (17.1%) in the higher Spo2 target group (risk difference, 2.8% [95% CI, 0.6% to 5.0%]; RR, 1.17 [95% CI, 1.04 to 1.31], P = .01). Treatment for retinopathy of prematurity was administered to 220 of 2020 infants (10.9%) in the lower Spo2 target group and 308 of 2065 infants (14.9%) in the higher Spo2 target group (risk difference, -4.0% [95% CI, -6.1% to -2.0%]; RR, 0.74 [95% CI, 0.63 to 0.86], P < .001). Severe necrotizing enterocolitis occurred in 227 of 2464 infants (9.2%) in the lower Spo2 target group and 170 of 2465 infants (6.9%) in the higher Spo2 target group (risk difference, 2.3% [95% CI, 0.8% to 3.8%]; RR, 1.33 [95% CI, 1.10 to 1.61], P = .003). Conclusions and Relevance: In this prospectively planned meta-analysis of individual participant data from extremely preterm infants, there was no significant difference between a lower Spo2 target range compared with a higher Spo2 target range on the primary composite outcome of death or major disability at a corrected age of 18 to 24 months. The lower Spo2 target range was associated with a higher risk of death and necrotizing enterocolitis, but a lower risk of retinopathy of prematurity treatment.
Asunto(s)
Discapacidades del Desarrollo/epidemiología , Enterocolitis Necrotizante/epidemiología , Recien Nacido Extremadamente Prematuro , Enfermedades del Prematuro/epidemiología , Oxígeno/sangre , Ceguera/epidemiología , Parálisis Cerebral/epidemiología , Sordera/epidemiología , Femenino , Humanos , Incidencia , Lactante , Mortalidad Infantil , Recién Nacido , Enfermedades del Prematuro/mortalidad , Estimación de Kaplan-Meier , Masculino , Oximetría , Oxígeno/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
RATIONALE: Higher pulse wave velocity (PWV) reflects increased arterial stiffness and is an established cardiovascular risk marker associated with lower long-chain n-3 polyunsaturated fatty acid intake in adults. Experimentally, maternal fatty acid intake in pregnancy has lasting effects on offspring arterial stiffness. OBJECTIVE: To examine the association between maternal consumption of oily fish, a source of long-chain n-3 polyunsaturated fatty acids, in pregnancy and child's aortic stiffness age 9 years. METHODS AND RESULTS: In a mother-offspring study (Southampton Women's Survey), the child's descending aorta PWV was measured at the age of 9 years using velocity-encoded phase-contrast MRI and related to maternal oily fish consumption assessed prospectively during pregnancy. Higher oily fish consumption in late pregnancy was associated with lower childhood aortic PWV (sex-adjusted ß=-0.084 m/s per portion per week; 95% confidence interval, -0.137 to -0.031; P=0.002; n=226). Mother's educational attainment was independently associated with child's PWV. PWV was not associated with the child's current oily fish consumption. CONCLUSIONS: Level of maternal oily fish consumption in pregnancy may influence child's large artery development, with potential long-term consequences for later cardiovascular risk.
Asunto(s)
Ácidos Grasos Omega-3/farmacología , Aceites de Pescado/farmacología , Tercer Trimestre del Embarazo , Efectos Tardíos de la Exposición Prenatal , Rigidez Vascular/efectos de los fármacos , Adulto , Animales , Peso al Nacer , Lactancia Materna , Niño , Escolaridad , Conducta Alimentaria , Femenino , Peces , Estudios de Seguimiento , Hemodinámica , Humanos , Imagen por Resonancia Magnética , Masculino , Embarazo , Primer Trimestre del Embarazo , Estudios Prospectivos , Análisis de la Onda del Pulso , Alimentos Marinos , Fumar/epidemiología , Factores SocioeconómicosRESUMEN
Importance: Standard treatment for endometrial cancer involves removal of the uterus, tubes, ovaries, and lymph nodes. Few randomized trials have compared disease-free survival outcomes for surgical approaches. Objective: To investigate whether total laparoscopic hysterectomy (TLH) is equivalent to total abdominal hysterectomy (TAH) in women with treatment-naive endometrial cancer. Design, Setting, and Participants: The Laparoscopic Approach to Cancer of the Endometrium (LACE) trial was a multinational, randomized equivalence trial conducted between October 7, 2005, and June 30, 2010, in which 27 surgeons from 20 tertiary gynecological cancer centers in Australia, New Zealand, and Hong Kong randomized 760 women with stage I endometrioid endometrial cancer to either TLH or TAH. Follow-up ended on March 3, 2016. Interventions: Patients were randomly assigned to undergo TAH (n = 353) or TLH (n = 407). Main Outcomes and Measures: The primary outcome was disease-free survival, which was measured as the interval between surgery and the date of first recurrence, including disease progression or the development of a new primary cancer or death assessed at 4.5 years after randomization. The prespecified equivalence margin was 7% or less. Secondary outcomes included recurrence of endometrial cancer and overall survival. Results: Patients were followed up for a median of 4.5 years. Of 760 patients who were randomized (mean age, 63 years), 679 (89%) completed the trial. At 4.5 years of follow-up, disease-free survival was 81.3% in the TAH group and 81.6% in the TLH group. The disease-free survival rate difference was 0.3% (favoring TLH; 95% CI, -5.5% to 6.1%; P = .007), meeting criteria for equivalence. There was no statistically significant between-group difference in recurrence of endometrial cancer (28/353 in TAH group [7.9%] vs 33/407 in TLH group [8.1%]; risk difference, 0.2% [95% CI, -3.7% to 4.0%]; P = .93) or in overall survival (24/353 in TAH group [6.8%] vs 30/407 in TLH group [7.4%]; risk difference, 0.6% [95% CI, -3.0% to 4.2%]; P = .76). Conclusions and Relevance: Among women with stage I endometrial cancer, the use of total abdominal hysterectomy compared with total laparoscopic hysterectomy resulted in equivalent disease-free survival at 4.5 years and no difference in overall survival. These findings support the use of laparoscopic hysterectomy for women with stage I endometrial cancer. Trial Registration: clinicaltrials.gov Identifier: NCT00096408; Australian New Zealand Clinical Trials Registry: CTRN12606000261516.
Asunto(s)
Neoplasias Endometriales/cirugía , Histerectomía/métodos , Laparoscopía , Anciano , Australia , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Femenino , Estudios de Seguimiento , Hong Kong , Humanos , Histerectomía/mortalidad , Análisis de Intención de Tratar , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Siembra Neoplásica , Neoplasias Primarias Secundarias , Nueva Zelanda , Factores de TiempoRESUMEN
BACKGROUND: Litter is known about the well-being of nursing home (NH) residents in Singapore. This study aimed to identify predictors of self-reported quality of life (QOL) of NH residents in Singapore. METHODS: In face-to-face interviews, trained medical students assessed each consenting resident recruited from 6 local NHs using a modified Minnesota QOL questionnaire, and rating scales and questions assessing independence, cognitive function, depression, and communication. Predictors of residents' QOL in five aspects (comfort, dignity, food enjoyment, autonomy, and security) were identified using the censored least absolute deviations (CLAD) models. RESULTS: A total of 375 residents completed the interviews. A higher score on comfort was negatively associated with major depression while a higher score on dignity was positively associated with no difficulty in communication with staff. Higher scores in food enjoyment were negatively associated with major depression and poorer cognitive function. Higher scores in autonomy were negatively associated with major depression, greater dependence, and difficulty in communication with staff. A higher score on security were negatively associated with major depression. CONCLUSION: It appears that depression and difficulty in communication with staff are the two main modifiable risk factors of poor quality of life of local NH residents.
Asunto(s)
Trastorno Depresivo Mayor/etiología , Casas de Salud , Calidad de Vida/psicología , Anciano , Anciano de 80 o más Años , Cognición , Trastorno Depresivo Mayor/psicología , Femenino , Humanos , Masculino , Autoinforme , SingapurRESUMEN
IMPORTANCE: Laparoscopic procedures are generally thought to have better outcomes than open procedures. Because of anatomical constraints, laparoscopic rectal resection may not be better because of limitations in performing an adequate cancer resection. OBJECTIVE: To determine whether laparoscopic resection is noninferior to open rectal cancer resection for adequacy of cancer clearance. DESIGN, SETTING, AND PARTICIPANTS: Randomized, noninferiority, phase 3 trial (Australasian Laparoscopic Cancer of the Rectum; ALaCaRT) conducted between March 2010 and November 2014. Twenty-six accredited surgeons from 24 sites in Australia and New Zealand randomized 475 patients with T1-T3 rectal adenocarcinoma less than 15 cm from the anal verge. INTERVENTIONS: Open laparotomy and rectal resection (n = 237) or laparoscopic rectal resection (n = 238). MAIN OUTCOMES AND MEASURES: The primary end point was a composite of oncological factors indicating an adequate surgical resection, with a noninferiority boundary of Δ = -8%. Successful resection was defined as meeting all the following criteria: (1) complete total mesorectal excision, (2) a clear circumferential margin (≥1 mm), and (3) a clear distal resection margin (≥1 mm). Pathologists used standardized reporting and were blinded to the method of surgery. RESULTS: A successful resection was achieved in 194 patients (82%) in the laparoscopic surgery group and 208 patients (89%) in the open surgery group (risk difference of -7.0% [95% CI, -12.4% to ∞]; P = .38 for noninferiority). The circumferential resection margin was clear in 222 patients (93%) in the laparoscopic surgery group and in 228 patients (97%) in the open surgery group (risk difference of -3.7% [95% CI, -7.6% to 0.1%]; P = .06), the distal margin was clear in 236 patients (99%) in the laparoscopic surgery group and in 234 patients (99%) in the open surgery group (risk difference of -0.4% [95% CI, -1.8% to 1.0%]; P = .67), and total mesorectal excision was complete in 206 patients (87%) in the laparoscopic surgery group and 216 patients (92%) in the open surgery group (risk difference of -5.4% [95% CI, -10.9% to 0.2%]; P = .06). The conversion rate from laparoscopic to open surgery was 9%. CONCLUSIONS AND RELEVANCE: Among patients with T1-T3 rectal tumors, noninferiority of laparoscopic surgery compared with open surgery for successful resection was not established. Although the overall quality of surgery was high, these findings do not provide sufficient evidence for the routine use of laparoscopic surgery. Longer follow-up of recurrence and survival is currently being acquired. TRIAL REGISTRATION: anzctr.org Identifier: ACTRN12609000663257.
Asunto(s)
Adenoma/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Laparoscopía/métodos , Laparotomía , Neoplasias del Recto/cirugía , Adenoma/patología , Adulto , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasia Residual , Calidad de Vida , Neoplasias del Recto/patología , Método Simple Ciego , Resultado del TratamientoRESUMEN
Sarcopenia is associated with adverse health outcomes. This study investigated whether skeletal muscle gene expression was associated with lean mass and grip strength in community-dwelling older men. Utilising a cross-sectional study design, lean muscle mass and grip strength were measured in 88 men aged 68-76 years. Expression profiles of 44 genes implicated in the cellular regulation of skeletal muscle were determined. Serum was analysed for circulating cytokines TNF (tumour necrosis factor), IL-6 (interleukin 6, IFNG (interferon gamma), IL1R1 (interleukin-1 receptor-1). Relationships between skeletal muscle gene expression, circulating cytokines, lean mass and grip strength were examined. Participant groups with higher and lower values of lean muscle mass (n = 18) and strength (n = 20) were used in the analysis of gene expression fold change. Expression of VDR (vitamin D receptor) [fold change (FC) 0.52, standard error for fold change (SE) ± 0.08, p = 0.01] and IFNG mRNA (FC 0.31; SE ± 0.19, p = 0.01) were lower in those with higher lean mass. Expression of IL-6 (FC 0.43; SE ± 0.13, p = 0.02), TNF (FC 0.52; SE ± 0.10, p = 0.02), IL1R1 (FC 0.63; SE ± 0.09, p = 0.04) and MSTN (myostatin) (FC 0.64; SE ± 0.11, p = 0.04) were lower in those with higher grip strength. No other significant changes were observed. Significant negative correlations between serum IL-6 (R = -0.29, p = 0.005), TNF (R = -0.24, p = 0.017) and grip strength were demonstrated. This novel skeletal muscle gene expression study carried out within a well-characterized epidemiological birth cohort has demonstrated that lower expression of VDR and IFNG is associated with higher lean mass, and lower expression of IL-6, TNF, IL1R1 and myostatin is associated with higher grip strength. These findings are consistent with a role of proinflammatory factors in mediating lower muscle strength in community-dwelling older men.
Asunto(s)
Regulación de la Expresión Génica , Sarcopenia/patología , Anciano , Antropometría , Biopsia , Composición Corporal , Estudios de Cohortes , Estudios Transversales , Inglaterra , Perfilación de la Expresión Génica , Humanos , Interferón gamma/metabolismo , Interleucina-6/metabolismo , Masculino , Persona de Mediana Edad , Fuerza Muscular , Músculo Esquelético/metabolismo , Miostatina/metabolismo , Reacción en Cadena de la Polimerasa , Receptores Tipo I de Interleucina-1/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The prevalence of obesity continues to increase in the developing world. The effects of obesity on the cardiovascular system include changes in systolic and diastolic function. More recently obesity has been linked with impairment of longitudinal myocardial deformation properties in children. We sought to determine the effect of increased body mass index (BMI) on cardiac deformation in a group of children taking part in the population-based Southampton Women's Survey to detect early cardiovascular changes associated with increasing BMI before established obesity. Sixty-eight children at a mean age of 9.4 years old underwent assessment of longitudinal myocardial deformation in the basal septal segment of the left ventricle (LV) using two-dimensional speckle tracking echocardiography. Parameters of afterload and preload, which may influence deformation, were determined from cardiac magnetic resonance imaging. BMI was determined from the child's height and weight at the time of echocardiogram. Greater pediatric BMI was associated with greater longitudinal myocardial deformation or strain in the basal septal segment of the LV (ß = 1.6, p < 0.001); however, this was not related to contractility or strain rate in this part of the heart (ß = 0.001, p = 0.92). The end-diastolic volume of the LV increased with increasing BMI (ß = 3.93, p < 0.01). In young children, regional deformation in the LV increases with increasing BMI, whilst normal contractility is maintained. This effect may be explained by the increased preload of the LV associated with increased somatic growth. The long-term implications of this altered physiology need to be followed-up.
Asunto(s)
Índice de Masa Corporal , Enfermedades Cardiovasculares/epidemiología , Ventrículos Cardíacos/diagnóstico por imagen , Obesidad/epidemiología , Función Ventricular/fisiología , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/patología , Aorta Torácica/fisiopatología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etiología , Niño , Ecocardiografía , Femenino , Estudios de Seguimiento , Ventrículos Cardíacos/patología , Humanos , Incidencia , Imagen por Resonancia Cinemagnética , Masculino , Obesidad/complicaciones , Obesidad/fisiopatología , Valores de Referencia , Reproducibilidad de los Resultados , Factores de Riesgo , Reino Unido/epidemiologíaRESUMEN
While many studies have assessed the efficacy of similarity-based cues for auditory stream segregation, much less is known about whether and how the larger-scale structure of sound sequences support stream formation and the choice of sound organization. Two experiments investigated the effects of musical melody and rhythm on the segregation of two interleaved tone sequences. The two sets of tones fully overlapped in pitch range but differed from each other in interaural time and intensity. Unbeknownst to the listener, separately, each of the interleaved sequences was created from the notes of a different song. In different experimental conditions, the notes and/or their timing could either follow those of the songs or they could be scrambled or, in case of timing, set to be isochronous. Listeners were asked to continuously report whether they heard a single coherent sequence (integrated) or two concurrent streams (segregated). Although temporal overlap between tones from the two streams proved to be the strongest cue for stream segregation, significant effects of tonality and familiarity with the songs were also observed. These results suggest that the regular temporal patterns are utilized as cues in auditory stream segregation and that long-term memory is involved in this process.
Asunto(s)
Señales (Psicología) , Música , Periodicidad , Percepción de la Altura Tonal , Percepción del Tiempo , Estimulación Acústica , Adolescente , Adulto , Análisis de Varianza , Audiometría , Femenino , Humanos , Masculino , Discriminación de la Altura Tonal , Psicoacústica , Factores de Tiempo , Adulto JovenRESUMEN
Despite infectious pandemics proving particularly detrimental to those with Obsessive-Compulsive Disorder (OCD), the investigation of analogous experimental paradigms is lacking. To address this gap, we conducted two studies employing vignettes that depicted contamination-related situations commonly experienced during a pandemic (e.g., Coughing into hands and failing to use hand sanitizer). We manipulated the salience of these vignettes across three levels: high contamination, low contamination, and a neutral control condition. Our examination of state anxiety and disgust responses in all participants revealed the successful manipulation of the vignettes' impact. Specifically, individuals with more severe OCD symptoms reported significantly higher levels of state disgust and anxiety for both high and low contamination vignettes, in contrast to the group with lower symptom severity. No significant differences were observed in the neutral vignette condition between the high- and low-scoring groups. Interestingly, for those with higher OCD symptoms, high salience contamination-focused vignettes resulted in similarly elevated state disgust and anxiety, regardless of whether the vignettes were situated in public (Study 1) or domestic (Study 2) settings. This suggests that the heightened sensitivity to contamination-related scenarios observed in individuals with OCD symptoms in the present study is not confined to a specific context. These findings support the use of contamination-focused vignettes as analogues for studying infectious pandemics and provide valuable insights into OCD models, interventions, and future research.
RESUMEN
Emergence delirium remains a clinically significant issue, which often leads to distress among pediatric patients, parents, and staff in the short term; and may also result in postoperative maladaptive behaviors persisting for weeks to months. Although several diagnostic tools are available, the Pediatric Anesthesia Emergence Delirium Scale is most often utilized. Many risk factors contributing to the likelihood of a pediatric patient developing emergence delirium have been identified; however, its accurate prediction remains challenging. Recently, intraoperative electroencephalographic monitoring has been used to improve the prediction of emergence delirium. Similarly, it may also prevent emergence delirium if the anesthesiologist ensures that the at-risk patient rouses only after the onset of appropriate electroencephalogram patterns, thus indicating a change to natural sleep. Prediction of at-risk patients is crucial; preventing emergence delirium may begin early during patient preparation by using non-pharmacological methods (i.e., the ADVANCE program). Intraoperative electroencephalographic monitoring can predict emergence delirium. This review also discusses a range of pharmacological treatment options which may assist the anesthesiologist in preventing emergence delirium among at-risk patients.
RESUMEN
BACKGROUND: Israel's pronatalist cultures result in a social expectation to have children and drive Israel's fertility rate of 2.9. Israeli policy reflects this through funding unlimited fertility treatment up to two children. Societal pressure to have children exacerbates challenges of fertility treatment. Furthermore, the lack of financial burden creates a culture of perseverance following treatment failures. Whilst the experiences of Israeli women using fertility treatment have been studied, the experiences of women who migrated to Israel and were therefore raised in a different society have not. This study aimed to address this gap in knowledge. METHODS: A qualitative study using semi-structured interviews to investigate the experiences of 13 English-speaking women who utilised Israeli state funded fertility treatment. Participants were located across Israel and were recruited using purposive sampling through social media. Data was analysed using framework analysis. RESULTS: Despite not being aimed at specific ethnic or religious groups, all respondents were Jewish. Three themes were identified: 1. Systemic factors: The lack of financial burden was positive, however, participants struggled to navigate the bureaucratic healthcare system, especially when experiencing a language barrier. 2. Influence of others: Encountering a cold bedside manner alongside contending with the expectations of a pronatalist society was challenging. Participants utilised support from other migrants who appreciated the same culture shock. Understanding of healthcare professionals regarding shared religious values further improved treatment experiences. 3. Impact of journey: Participants often withdrew socially and the treatment process implicated upon their lives, jobs and relationships. CONCLUSION: Navigating a bureaucratic system and pronatalist society are difficulties associated with fertility treatment in Israel. The lack of financial burden and an understanding of religious and cultural beliefs by healthcare providers improved treatment experience. Better provision of resources in English and further research into supporting women who are navigating Israel's pronatalist society is required.
Asunto(s)
Investigación Cualitativa , Humanos , Femenino , Israel , Adulto , LenguajeRESUMEN
INTRODUCTION: This work reports on an unusual finding observed during image quality assessment in the preparation for the clinical implementation of breast magnetic resonance image-guided radiotherapy (MRIgRT) on a 1.5 Tesla (T) magnetic resonance linear accelerator (MR-Linac) (Elekta AB, Stockholm, Sweden). CASE AND OUTCOMES: A patient with T2 N0 M0 right breast invasive ductal carcinoma, receiving adjuvant radiotherapy, underwent two imaging sessions on the MR-Linac. The imaging protocol included T1- and T2-weighted (W) turbo spin echo (TSE) sequences, a T1W mDixon, and a T2W TSE navigated sequence acquired on end-expiration. All images were reconstructed in the axial plane. Images were assessed for image quality and appropriateness for use within the treatment pathway using visual grading analysis (VGA). An artefact in the right breast was noted independently by all observers. The patient's skin and medical notes were reviewed for possible explanation. The findings were discussed with the patient's responsible clinician, and subsequent referral to the local multi-disciplinary team (MDT) for radiologist review was made. On further investigation, the patient's images demonstrated a signal void in the subareolar region of the right breast coinciding with the surgical site. This was distal from the tumour bed and deemed unlikely to be related to a Magseed marker or intraoperative clips. The patient reported no history of nipple tattoo or piercing. There was nothing on clothing that this could be attributed to. DISCUSSION: Following MDT review, where all potential sources of signal void were considered, it was concluded that the cause was Magtrace, a superparamagnetic iron oxide tracer, recommended for sentinel lymph node localisation in patients with breast cancer in the United Kingdom. The artefact was characteristic of a magnetic susceptibility artefact. These can arise from local magnetic field inhomogeneities caused by the presence of the metal compounds in MagTrace. For breast MRIgRT on the MR-Linac, treatment verification and the possibility of real-time replanning is a critical aspect. The magnetic susceptibility artefact significantly inhibited plan adaption and confidence in the online image registration process making the patient ineligible for treatment on the MR-Linac. CONCLUSION: As part of ongoing work-up for breast MRIgRT, the screening of patients for Magtrace is now included. Optimisation of MR imaging sequences for radiotherapy planning and image review to minimise distortion are being developed.