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1.
Artículo en Inglés | MEDLINE | ID: mdl-36971771

RESUMEN

BACKGROUND: Secukinumab has previously demonstrated sustained efficacy and favourable safety for up to 52 weeks in paediatric patients (children and adolescents aged 6 to <18 years) with severe chronic plaque psoriasis (NCT02471144). OBJECTIVE: To investigate the long-term (104 weeks) efficacy and safety of secukinumab. METHODS: After 52 weeks, patients continued to receive secukinumab low dose (LD [75/150 mg]) or high dose (HD [75/150/300 mg]). Patients on etanercept (0.8 mg/kg) until Week 52 entered follow-up. Data for patients receiving secukinumab LD from the beginning and those switching to secukinumab LD from placebo ('Any secukinumab' LD) and patients receiving secukinumab HD from the beginning and those switching to secukinumab HD from placebo ('Any secukinumab' HD) are presented. ASSESSMENTS: Psoriasis Area and Severity Index (PASI) score, PASI (75/90/100) responses, Investigator's Global Assessment modified 2011 (IGA mod 2011) 0/1 response, Children's Dermatology Life Quality Index (CDLQI) score and CDLQI 0/1 response up to Week 104, and, safety up to Week 104 for all patients and up to 4 years for some patients (~320 patient-years [PY] of treatment). RESULTS: Secukinumab-treated patients showed sustained PASI 75/90/100 and IGA mod 2011 0/1 responses up to Week 104. Throughout the second year of treatment, efficacy was similar for the 'Any secukinumab' LD and HD groups for PASI 75 and IGA mod 2011 0/1 responses. PASI 90/100 responses were mostly comparable between the dose groups up to Week 88, but higher in the 'Any secukinumab' HD than the 'Any secukinumab' LD group at Week 104. Patients achieved a sustained CDLQI 0/1 response that was similar between the 'Any secukinumab' LD (61.1%) and HD (65.0%) groups. Safety data were consistent with the established safety profile of secukinumab. CONCLUSION: Secukinumab demonstrated sustained long-term efficacy (up to 2 years) and a favourable safety profile (~320 PY of treatment) in paediatric patients with severe chronic plaque psoriasis.

2.
Harm Reduct J ; 20(1): 9, 2023 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-36691010

RESUMEN

BACKGROUND: Gay, bisexual and other men who have sex with men (GBMSM) are overrepresented in cohorts of people who inject drugs. GBMSM's substance use is usually explored in the context of its contribution to sexual risk. We examined drug use practices, connectedness to other people who inject drugs, peer-to-peer injecting, and access to care among men who inject drugs in Melbourne, Australia. We aim to describe similarities and differences in these parameters for GBMSM and other men. METHODS: Data were drawn from a prospective cohort study of people who inject drugs conducted in Melbourne, Australia, since 2009. This cross-sectional study used data collected between 2016 and 2021. Descriptive statistics were used to assess differences between GBMSM and other men. RESULTS: Of 525 men who injected drugs over the study period, 48 (9%) identified as gay or bisexual, or reported sex with other men in the past 12 months. GBMSM and other men reported similar socio-demographics, drug practices (age of injecting initiation, most injected drug, peer-to-peer injecting, receptive syringe sharing) and access to injecting-specific care (drug treatment, source of needle-syringes). A significantly greater percentage of GBMSM reported past 12-month hepatitis C testing (69% vs. 52%, p = 0.028) and preferring methamphetamine (31% vs. 16%, p = 0.022). A higher percentage of GBMSM reported knowing > 50 other people who inject drugs (46% vs. 37%), but this difference was not statistically significant. Both groups primarily obtained injecting equipment from needle-syringe programs; a minority had accessed injecting-specific primary care. CONCLUSION: Men who injected drugs in this cohort and those who identified as GBMSM reported similar drug and health-seeking practices. The higher prevalence of methamphetamine injecting among GBMSM may warrant different harm reduction support for this group. Health promotion should utilise opportunities to connect men who inject drugs in Melbourne to injecting-specific primary health care.


Asunto(s)
Metanfetamina , Minorías Sexuales y de Género , Abuso de Sustancias por Vía Intravenosa , Trastornos Relacionados con Sustancias , Masculino , Humanos , Abuso de Sustancias por Vía Intravenosa/epidemiología , Estudios Transversales , Homosexualidad Masculina , Estudios Prospectivos , Trastornos Relacionados con Sustancias/epidemiología , Australia/epidemiología
3.
J Eur Acad Dermatol Venereol ; 35(4): 938-947, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33068444

RESUMEN

BACKGROUND: Secukinumab has demonstrated sustained long-term efficacy with a favourable safety profile in various psoriatic disease manifestations in adults. OBJECTIVES: Here, the efficacy and safety of two secukinumab dosing regimens [low dose (LD) and high dose (HD)] in paediatric patients with severe chronic plaque psoriasis over one year are reported. METHODS: In this multicentre, double-blind study (NCT02471144), patients aged 6 to <18 years with severe chronic plaque psoriasis were stratified and randomized by weight (<25 kg, 25 to <50 kg, ≥50 kg) and age (6 to <12 years, 12 to <18 years) to receive low-dose (LD: 75/75/150 mg) or high-dose (HD: 75/150/300 mg) subcutaneous secukinumab or placebo or etanercept 0.8 mg/kg (up to a max of 50 mg). RESULTS: Overall, 162 patients were randomized to receive secukinumab LD (n = 40) or HD (n = 40), etanercept (n = 41) or placebo (n = 41). The co-primary objectives of the study were met with both secukinumab doses (LD and HD) showing superior efficacy compared to placebo (P < 0.0001) with respect to PASI 75 response (80.0%, 77.5% vs. 14.6%) and IGA mod 2011, 0 or 1 response (70%, 60% vs. 4.9%) at Week 12. Both secukinumab doses were superior to placebo (P < 0.0001) with respect to PASI 90 response at Week 12 (72.5%, 67.5% vs. 2.4%). The efficacy of both doses was sustained to Week 52 with secukinumab achieving higher responses vs. etanercept (PASI 75/90/100: LD, 87.5%/75.0%/40.0% and HD, 87.5%/80.0%/47.5.% vs. etanercept, 68.3%/51.2%/22.0% and IGA 0 or 1: LD, 72.5% and HD, 75.0% vs. etanercept, 56.1%). The safety profile of secukinumab was consistent with the adult Phase 3 studies, with no new safety signals identified. CONCLUSIONS: Both doses of secukinumab demonstrated high and sustained efficacy up to Week 52 with a favourable safety profile in paediatric patients with severe chronic plaque psoriasis.


Asunto(s)
Anticuerpos Monoclonales , Psoriasis , Adulto , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Niño , Método Doble Ciego , Humanos , Psoriasis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
5.
J Pediatr Urol ; 14(3): 243.e1-243.e6, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29580731

RESUMEN

INTRODUCTION: Historically, ureteroceles were surgically treated, as patients were diagnosed after developing symptoms. However, with the advance of fetal medicine, antenatal detection has provided an opportunity to look at the natural history of ureteroceles. OBJECTIVES: With data derived from a retrospective chart review of patients with ureteroceles that were detected antenatally, the current study aimed to determine which group of children would be at risk for failure on active surveillance. It was hypothesized that single system ureteroceles (SSU) and male patients with duplex system ureteroceles (DSU) would be ideal for observation. METHODS: Outcomes were assessed by descriptive statistics. Kaplan-Meier curves were utilized to estimate median duration on active surveillance in both single and duplex cohorts. Breakthrough febrile urinary tract infection (fUTI) and surgery were determined by Cox regression in the duplex system cohort. Surgery was considered surveillance failure. RESULTS: A total of 102 patients (64 females/38 males) met the criteria: 78 (76.5%) had DSU and 24 (23.5%) SSU. The overall median observation was 1.2 years (range 0.7-3.1). Follow-up ranged from 0.3 to 11.7 years for SSU, and from 0.02 to 17.3 years for DSU. The predictors of failure of active surveillance (AS) in DSU (surgical intervention) were male gender (HR 1.8, 1.0-3.3, P = 0.037), or fUTI (HR 3.1, 1.7-5.8, P = 0.002). Predictors of fUTI were contralateral hydroureter or ipsilateral hydronephrosis ± hydroureter (OR 9.5, 1.2-71.7, P = 0.028). Interestingly, vesicoureteral reflux (VUR) was not a predictor of fUTI. The SSU patients were ideal for AS, while in DSU, surveillance was successful in 30% of patients who were primarily females without contralateral hydroureter or ipsilateral hydronephrosis ± hydroureter. However, in contradiction to the hypothesis, males were at higher risk for surgical intervention in the DSU cohort. CONCLUSION: Active surveillance is an option for patients with antenatally detected ureteroceles, but careful long term follow up is mandatory. Parents should be advised that surgical intervention may still be necessary, particularly in males with DSU.


Asunto(s)
Tratamiento Conservador/métodos , Predicción , Diagnóstico Prenatal/métodos , Ureterocele/diagnóstico , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Embarazo , Estudios Retrospectivos , Ureterocele/terapia
6.
J Assist Reprod Genet ; 35(5): 735-751, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29497954

RESUMEN

An equilibrium needs to be established by the cellular and acellular components of the ovarian follicle if developmental competence is to be acquired by the oocyte. Both cumulus cells (CCs) and follicular fluid (FF) are critical determinants for oocyte quality. Understanding how CCs and FF influence oocyte quality in the presence of deleterious systemic or pelvic conditions may impact clinical decisions in the course of managing infertility. Given that the functional integrities of FF and CCs are susceptible to concurrent pathological conditions, it is important to understand how pathophysiological factors influence natural fertility and the outcomes of pregnancy arising from the use of assisted reproduction technologies (ARTs). Accordingly, this review discusses the roles of CCs and FF in ensuring oocyte competence and present new insights on pathological conditions that may interfere with oocyte quality by altering the intrafollicular environment.


Asunto(s)
Células del Cúmulo , Líquido Folicular/fisiología , Oocitos/fisiología , Animales , Células del Cúmulo/citología , Células del Cúmulo/fisiología , Diabetes Mellitus/patología , Endometriosis/patología , Femenino , Líquido Folicular/citología , Humanos , Infertilidad Femenina/etiología , Infertilidad Femenina/patología , Obesidad/complicaciones , Obesidad/patología , Oocitos/citología , Infección Pélvica/complicaciones , Infección Pélvica/patología , Síndrome del Ovario Poliquístico , Embarazo
7.
Artículo en Inglés | MEDLINE | ID: mdl-28929537

RESUMEN

Registry data on invasive cervical cancers (n = 1,274) from four major hospitals (1984-2012) were analysed to determine their value for informing local service delivery in Australia. The methodology comprised disease-specific survival analyses using Kaplan-Meier product-limit estimates and Cox proportional hazards models and treatment analyses using logistic regression. Five- and 10-year survivals were 72% and 68%, respectively, equating with relative survival estimates for Australia and the USA. Most common treatments were surgery and radiotherapy. Systemic therapies increased in recent years, generally with radiotherapy, but were less common for residents from less accessible areas. Surgery was more common for younger women and early-stage disease, and radiotherapy for older women and regional and more advanced disease. The proportion of glandular cancers increased in-step with national trends. Little evidence of variation in risk-adjusted survival presented over time or by Local Health District. The study illustrates the value of local registry data for describing local treatment and outcomes. They show the lower use of systemic therapies among residents of less accessible areas which warrants further investigation. Risk-adjusted treatment and outcomes did not vary by socio-economic status, suggesting equity in service delivery. These data are important for local evaluation and were not available from other sources.


Asunto(s)
Adenocarcinoma/terapia , Carcinoma de Células Escamosas/terapia , Accesibilidad a los Servicios de Salud , Histerectomía , Radioterapia , Sistema de Registros , Neoplasias del Cuello Uterino/terapia , Adenocarcinoma/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Australia , Carcinoma de Células Escamosas/mortalidad , Bases de Datos Factuales , Atención a la Salud , Manejo de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Modelos de Riesgos Proporcionales , Análisis de Supervivencia , Tasa de Supervivencia , Neoplasias del Cuello Uterino/mortalidad
8.
Ann Oncol ; 29(1): 36-43, 2018 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-29253069

RESUMEN

Oncology has come a long way in addressing patients' quality of life, together with developing surgical, radio-oncological and medical anticancer therapies. However, the multiple and varying needs of patients are still not being met adequately as part of routine cancer care. Supportive and palliative care interventions should be integrated, dynamic, personalised and based on best evidence. They should start at the time of diagnosis and continue through to end-of-life or survivorship. ESMO is committed to excellence in all aspects of oncological care during the continuum of the cancer experience. Following the 2003 ESMO stand on supportive and palliative care (Cherny N, Catane R, Kosmidis P. ESMO takes a stand on supportive and palliative care. Ann Oncol 2003; 14(9): 1335-1337), this position paper highlights the evolving and growing gap between the needs of cancer patients and the actual provision of care. The concept of patient-centred cancer care is presented along with key requisites and areas for further work.


Asunto(s)
Neoplasias/terapia , Cuidados Paliativos/métodos , Cuidados Paliativos/normas , Atención Dirigida al Paciente/métodos , Atención Dirigida al Paciente/normas , Humanos , Guías de Práctica Clínica como Asunto , Calidad de Vida , Cuidado Terminal/métodos , Cuidado Terminal/normas
9.
J Public Health (Oxf) ; 40(3): e336-e342, 2018 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-29281039

RESUMEN

Background: To assess the structure of individual-level needle and syringe coverage measurement formula, and to estimate the impact of coverage-related behaviours/parameters (instances of syringe acquisition, total syringes acquired, peer-to-peer syringe distribution, injecting frequency) on overall coverage. Methods: Data are drawn from the Melbourne (Australia) injecting drug user cohort study, 2010-16. Data from 518 participants were analysed. We used correlations to explore the relationships between coverage parameters; pooled multiple-linear regression to estimate the effect of each parameter on coverage over time; and exploratory factor analysis to assess the relevance of each parameter within the coverage formula. Results: A 1-unit increase in injecting frequency over time reduced coverage by 10.93 percentage points, almost twice as much as other coverage parameters. Factor analysis results indicated potential improvements to coverage formula structure. Conclusions: Our results suggest that reducing injecting frequency amongst people who inject drugs has the largest improvement in coverage levels, indicating harm reduction services should prioritize it. We also demonstrate that coverage measurement has been inconsistent to date. We sought to refine the method to assist in generating comparable research.


Asunto(s)
Jeringas/estadística & datos numéricos , Adulto , Femenino , Humanos , Masculino , Programas de Intercambio de Agujas/estadística & datos numéricos , Factores de Riesgo , Abuso de Sustancias por Vía Intravenosa/epidemiología , Victoria
10.
J Viral Hepat ; 24(9): 714-724, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28632952

RESUMEN

Inadequate response to injecting drug use (IDU) is a significant problem the world over. Low levels of funding, political inaction, poor levels of health service coverage, high prevalence and incidence of IDU-related blood-borne viruses (BBVs) and ongoing stigmatization/marginalization affect people who inject drugs (PWID) regardless of the income status of the country they reside in. These barriers and system failings are, however, exacerbated in low and middle-income countries (LMICs), meaning that the potential consequences of inaction are more pressing. In this narrative review, we describe the levels of IDU and IDU-specific BBV prevalence in LMICs; levels of harm reduction implementation; the consequences of late or insufficient response, the shortcomings of data collection and dissemination; and the barriers to effective LMIC harm reduction implementation. We also exemplify cases where IDU-related harms and BBV epidemics have been successfully curtailed in LMICs, showing that effective response, despite the barriers, is possible. In conclusion, we suggest four key priorities on the basis of the review: confirming the presence or absence of IDU in LMICs, improving the collection and dissemination of national IDU-specific data, increasing the level of harm reduction programme implementation in LMICs, and increasing both national and international advocacy for PWID and attendant public health interventions.


Asunto(s)
Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/epidemiología , Virosis/epidemiología , Virosis/transmisión , Países en Desarrollo , Humanos , Prevalencia
11.
Artículo en Inglés | MEDLINE | ID: mdl-28271574

RESUMEN

Monitoring screening mammography effects in small areas is often limited by small numbers of deaths and delayed effects. We developed a risk score for breast cancer death to circumvent these limitations. Screening, if effective, would increase post-diagnostic survivals through lead-time and related effects, as well as mortality reductions. Linked cancer and BreastScreen data at four hospitals (n = 2,039) were used to investigate whether screened cases had higher recorded survivals in 13 small areas, using breast cancer deaths as the outcome (M1), and a risk of death score derived from TNM stage, grade, histology type, hormone receptor status, and related variables (M2). M1 indicated lower risk of death in screened cases in 12 of the 13 areas, achieving statistical significance (p < .05) in 5. M2 indicated lower risk scores in screened cases in all 13 areas, achieving statistical significance in 12. For cases recently screened at diagnosis (<6 months), statistically significant reductions applied in 8 areas (M1) and all 13 areas (M2). Screening effects are more detectable in small areas using these risk scores than death itself as the outcome variable. An added advantage is the application of risk scores for providing a marker of screening effect soon after diagnosis.


Asunto(s)
Neoplasias de la Mama/prevención & control , Detección Precoz del Cáncer/estadística & datos numéricos , Distribución por Edad , Anciano , Neoplasias de la Mama/mortalidad , Femenino , Humanos , Mamografía/estadística & datos numéricos , Tamizaje Masivo/estadística & datos numéricos , Persona de Mediana Edad , Sistema de Registros , Medición de Riesgo , Análisis de Área Pequeña , Factores Socioeconómicos , Australia del Sur/epidemiología
12.
Pharmacogenomics J ; 17(1): 21-28, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27503581

RESUMEN

Irinotecan chemotherapy toxicities can be severe, and may result in treatment delay, morbidity and in some rare cases death. This systematic review of systematic reviews synthesises all meta-analyses on biomarkers for irinotecan toxicity across all genetic models for Asians, Caucasians, low dose, medium/high dose and regimens with and without fluorouracil. False-positive findings are a problem in pharmacogenetics, increasing the importance of systematic reviews. Four systematic reviews that investigated the effect of the polymorphisms UGT1A1*6 and/or*28 on neutropenia or diarrhoea toxicity were included. Both UGT1A1*6 and *28 were reliably demonstrated to be risk factors for irinotecan-induced neutropenia, with tests for both polymorphisms potentially being particularly useful in Asian cancer patients. UGT1A1*6 and *28 were also related to diarrhoea toxicity; however, at low doses of irinotecan there was evidence that UGT1A1*28 was not. In synthesising the best available evidence, this umbrella systematic review provides a novel reference for clinicians applying personalised medicine and identifies important research gaps.


Asunto(s)
Antineoplásicos Fitogénicos/efectos adversos , Camptotecina/análogos & derivados , Diarrea/genética , Glucuronosiltransferasa/genética , Metaanálisis como Asunto , Neutropenia/genética , Farmacogenética , Variantes Farmacogenómicas , Polimorfismo de Nucleótido Simple , Revisiones Sistemáticas como Asunto , Camptotecina/efectos adversos , Diarrea/inducido químicamente , Diarrea/enzimología , Predisposición Genética a la Enfermedad , Heterocigoto , Homocigoto , Humanos , Irinotecán , Neutropenia/inducido químicamente , Neutropenia/enzimología , Oportunidad Relativa , Pruebas de Farmacogenómica , Fenotipo , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de Riesgo , Resultado del Tratamiento
13.
Eur J Cancer Care (Engl) ; 25(5): 753-63, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27255681

RESUMEN

Data from registries at four major public hospitals in South Australia indicate increased 5-year disease-specific survivals for colorectal cancer from 48% to 63% between 1980-1986 and 2005-2010. For 80+ year olds, the increase was smaller, from 47% to 52%. Risk of case fatality halved overall, adjusting for age, gender, stage, differentiation and sub-site. Patients aged 80+ years had a lower risk reduction of about a third (hazards ratio: 0.69; 95% confidence limits, 0.52-0.92). Percentages having surgery and other specified treatments were lower for 80+ year olds than younger cases, although increases in treatment intensity occurred in this age range during 1980-2010, as seen in younger ages, in accordance with guidelines. The study illustrates the important feedback clinical registries can provide to clinicians on care patterns and outcomes in their hospital settings. Feedback can be the subject of local deliberations on how to achieve the best outcomes, including in the elderly by considering the best trade-offs between optimal cancer care and accommodations for co-morbidity and frailty. Clinical registry data can be used in comparative effectiveness research in local settings where there are sufficient case numbers.


Asunto(s)
Neoplasias del Colon/terapia , Neoplasias del Recto/terapia , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Neoplasias del Colon/mortalidad , Femenino , Hospitales Públicos/estadística & datos numéricos , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias del Recto/mortalidad , Australia del Sur
14.
Ann Oncol ; 27(9): 1712-8, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27287210

RESUMEN

BACKGROUND: ARCHER 1042, a randomized phase II trial, explored the impact of prophylactic treatment on select dermatologic adverse events of interest (SDAEI), diarrhea, and mucositis associated with dacomitinib, an oral irreversible pan-human epidermal growth factor receptor (HER) inhibitor, in development for advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced NSCLC treated with dacomitinib were enrolled in two cohorts. Cohort I patients were randomized 1:1 to receive oral doxycycline or placebo (4 weeks). Cohort II patients received oral VSL#3 probiotic plus topical alclometasone. Primary end points for Cohorts I and II were incidence of all grade and grade ≥2 SDAEI in the first 8 weeks of treatment and quality of life (QoL) assessed by the Skindex-16 survey. Additional primary end points for Cohort II were incidence of all grade and grade ≥2 diarrhea and mucositis in the first 8 weeks of treatment; QoL regarding diarrhea and mucositis incidence was assessed by the modified-Oral Mucositis Daily Questionnaire. RESULTS: Cohort I randomized 114 evaluable patients: 56 in the doxycycline arm, 58 in the placebo arm. Cohort II enrolled 59 evaluable patients. Doxycycline significantly reduced the incidence of grade ≥2 SDAEI by 50% (P = 0.016) compared with placebo. The incidence of all grade SDAEI was lower with doxycycline than with placebo but did not reach statistical significance. Doxycycline was associated with less deterioration in QoL compared with placebo. Alclometasone was associated with less deterioration in QoL compared with placebo but did not statistically significantly reduce the incidence of all grade or grade ≥2 SDAEI. VSL#3 did not reduce the incidence of all grade or grade ≥2 diarrhea and did not impact mucositis scores. CONCLUSIONS: Doxycycline was effective as a prophylactic treatment for dacomitinib-induced grade ≥2 SDAEI. Both doxycycline and alclometasone reduced the negative impact in patient-reported dermatologic AEs. The probiotic was not effective for preventing diarrhea or mucositis.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Enfermedades Gastrointestinales/patología , Quinazolinonas/administración & dosificación , Enfermedades de la Piel/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Mutación , Calidad de Vida , Quinazolinonas/efectos adversos , Enfermedades de la Piel/inducido químicamente , Resultado del Tratamiento
15.
J Fish Biol ; 89(2): 1378-92, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27350593

RESUMEN

Two hundred and eighty-seven longnose sucker Catostomus catostomus were collected from 14 lakes in Labrador, 52 from three lakes in Ontario, 43 from two lakes in British Columbia and 32 from a lake in Yukon; a total of 414 in all. The resulting 34 haplotypes (20 in Labrador) contained moderate haplotypic diversity (h = 0·657) and relatively low nucleotide diversity (π = 3·730 × 10(-3) . Mean ϕST (0·453, P < 0·05) over all populations revealed distinct genetic structuring among C. catostomus populations across Canada, based on province, which was validated by the analysis and spatial analysis of molecular variance (c. 80% variation between provinces). These results probably reflect the historical imprint of recolonization from different refugia and possibly indicate limited ongoing gene flow within provinces. A haplotype network revealed one major and two minor clades within Labrador that were assigned to the Atlantic, Beringian and Mississippian refugia, respectively, with tests of neutrality and mismatch distribution indicative of a recent population expansion in Labrador, dated between c. 3500 and 8300 years ago.


Asunto(s)
Cipriniformes/genética , ADN Mitocondrial/genética , Flujo Génico , Animales , Colombia Británica , Canadá , Variación Genética , Genética de Población , Haplotipos , Lagos , Terranova y Labrador , Ontario , Filogenia , Filogeografía , Análisis de Secuencia de ADN
16.
Ir Med J ; 109(9): 466, 2016 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-28125180

RESUMEN

In Ireland, Warfarin is the primary anticoagulant prescribed in the secondary prevention of provoked DVT. We completed a comprehensive cost analysis of a trial group of 24 patients treated with Rivaroxaban (between November 2013 and December 2014), versus a control group treated with Warfarin (between January 2008 and November 2013). The groups were matched for gender (3/7 M/F ratio), DVT type (5 proximal, 19 distal DVTs), provoking factor (20 traumatic, 4 atraumatc), and age. We calculated the cost for each group based on drug administration and clinic costs (labour, sample analysis, and additional costs). Warfarin patients attended clinic 14.58 times; Rivaroxaban patients attended 2.92 times. Overall, the cost per patient on Rivaroxaban is €273.30 versus €260.68 with warfarin. This excludes patient costs which would further increase cost of Warfarin therapy.


Asunto(s)
Anticoagulantes/economía , Inhibidores del Factor Xa/economía , Rivaroxabán/economía , Trombosis de la Vena/tratamiento farmacológico , Warfarina/economía , Anticoagulantes/administración & dosificación , Costos y Análisis de Costo , Costos de los Medicamentos , Inhibidores del Factor Xa/administración & dosificación , Femenino , Humanos , Irlanda , Masculino , Rivaroxabán/administración & dosificación , Prevención Secundaria/economía , Trombosis de la Vena/etiología , Warfarina/administración & dosificación
17.
Support Care Cancer ; 23(11): 3307-15, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26018599

RESUMEN

PURPOSE: Chemotherapy-induced diarrhoea (CID) has a significant impact. A medicinal food product (ReCharge) containing iron-saturated lactoferrin and anhydrous milk fat reduces the detrimental effects of chemotherapy on the gut in animals. We report results of a randomised blinded placebo-controlled phase IIb trial investigating the efficacy and safety of ReCharge in preventing CID. METHODS: Eligible patients were adults due to start the first cycle of a 2- or 3-week-cycle chemotherapy regimen, had an Eastern Cooperative Oncology Group (ECOG) status of 3 or less, had adequate haematological, liver and renal function and provided written informed consent. Patients (197) were randomised to ReCharge or placebo. They consumed 100-g study product for 2 weeks before and 6 weeks after starting chemotherapy, completed daily diaries for 8 weeks and attended clinic visits until 12 weeks (2-week cycles) or 14 weeks (3-week cycles). The primary outcome was days with CID. RESULTS: The mean number of days with diary-recorded CID was marginally but not statistically significantly lower on ReCharge than placebo (-2.0, 95 % CI (-4.7 to 0.7), p = 0.2). The proportion reporting diarrhoea in the previous cycle at the clinic visit was 30 % lower (p = 0.012) on ReCharge. Missing diary data may have contributed to the discrepancy. No significant differences were found in quality of life or other adverse events. CONCLUSIONS: We found no clear evidence that ReCharge reduced CID as measured by patient self-report diary. The converse finding of benefit as recorded at clinic visits and incomplete adherence to diary completion indicates that further research is required into methods for measuring CID.


Asunto(s)
Antidiarreicos/uso terapéutico , Antineoplásicos/efectos adversos , Diarrea/inducido químicamente , Diarrea/prevención & control , Helados , Adulto , Anciano , Antineoplásicos/uso terapéutico , Diarrea/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Placebos , Calidad de Vida , Autoinforme
18.
Support Care Cancer ; 23(11): 3165-72, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25814442

RESUMEN

PURPOSE: Esophageal cancer has a high mortality rate, and its multimodality treatment is often associated with significant rates of severe toxicity. Effort is needed to uncover ways to maximize effectiveness of therapy through identification of predictive markers of response and toxicity. As such, the aim of this study was to identify genes predictive of chemoradiotherapy-induced gastrointestinal toxicity using an immune pathway-targeted approach. METHODS: Adults with esophageal cancer treated with chemotherapy consisting of 5-fluorouracil and cisplatin and 45-50 Gy radiation were recruited to the study. Pre-therapy-collected whole blood was analyzed for relative expression of immune genes using real-time polymerase chain reaction (RT-PCR). Gene expression was compared between patients who experienced severe regimen-related gastrointestinal toxicity vs. those experiencing mild to moderate toxicity. RESULTS: Blood from 31 patients were analyzed by RT-PCR. Out of 84 immune genes investigated, TNF was significantly elevated (2.05-fold, p = 0.025) in the toxic group (n = 12) compared to the non-toxic group (n = 19). Nausea and vomiting was the most commonly documented severe toxicity. No associations between toxicity and response, age, sex, histology, or treatment were evident. CONCLUSIONS: This study supports evidence of TNF as a predictive biomarker in regimen-related gastrointestinal toxicity. Confirming these findings in a larger cohort is warranted.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Biomarcadores de Tumor/biosíntesis , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias Esofágicas/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/biosíntesis , Adenocarcinoma/genética , Adenocarcinoma/radioterapia , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/radioterapia , Cisplatino/efectos adversos , Cisplatino/uso terapéutico , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/radioterapia , Femenino , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Rayos gamma , Humanos , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Náusea/tratamiento farmacológico , Proyectos Piloto , ARN Mensajero/biosíntesis , Reacción en Cadena en Tiempo Real de la Polimerasa , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/genética , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológico
19.
Oral Dis ; 21(1): 17-30, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24456144

RESUMEN

Oral mucositis in patients undergoing cancer therapy is a significant problem. Its prevalence ranges between 20 and 100%, depending on treatment type and protocols and patient-based variables. Mucositis is self-limiting when uncomplicated by infection. Unfortunately, the incidence of developing a local or systemic infection during the course of the treatment is very high. At this stage, it is unclear which role oral microbiota play in the onset, duration, and severity of oral mucositis. Nevertheless, there is growing interest in this underexplored topic, and new studies are being undertaken to unravel their impact on the pathogenesis of mucositis.


Asunto(s)
Microbiota/fisiología , Boca/microbiología , Estomatitis/etiología , Humanos , Mucosa Bucal/microbiología , Factores de Riesgo , Estomatitis/microbiología
20.
Reprod Sci ; 21(12): 1465-71, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24675987

RESUMEN

UNLABELLED: The etiology of endometriosis remains poorly understood but circulating stem cells may contribute. Telomeres shorten with cell divisions and age. Stem cells attempt to compensate for telomere attrition through the action of telomerase. Since circulating stem cells may contribute to endometriosis, we compared telomere content in lymphocytes of patients with and without endometriosis. METHODS: Observational study comparing peripheral lymphocytes telomere content, measured by quantitative polymerase chain reaction, in patients with (n = 86) and without endometriosis (n = 21). FINDINGS: Patients with endometriosis had longer telomeres than that of matched, endometriosis-free controls (telomere to single copy gene ratio [T/S ratio] of 1.62 vs 1.34, respectively, P = .00002). Patients with endometriosis were 8.1-fold more likely to have long telomeres. (odds ratio = 8.1, 95% confidence interval: 1.28-51.57, P = .0264). INTERPRETATION: Longer telomeres could be consistent with a stem cell origin of endometriosis.


Asunto(s)
Endometriosis/genética , Linfocitos/metabolismo , Homeostasis del Telómero , Telómero/genética , Adulto , Estudios de Casos y Controles , Endometriosis/sangre , Endometriosis/diagnóstico , Femenino , Marcadores Genéticos , Humanos , Reacción en Cadena de la Polimerasa , Telómero/metabolismo
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