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1.
Med J Malaysia ; 79(3): 281-287, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38817060

RESUMEN

INTRODUCTION: Thalassaemia is one of the major health problems in Malaysia. With safe blood transfusion regime, the lifespan of patients with transfusion-dependent thalassaemia (TDT) has improved but at the cost of a higher risk of developing endocrine disorders. It is crucial for us to monitor the iron overload to prevent end organ damage. This study aims to evaluate the iron burden and prevalence of endocrinopathies in patients with TDT in Sarawak. MATERIALS AND METHODS: This retrospective cohort study was conducted between January 2020 to June 2020 in six government hospitals in Sarawak. A total of 89 patients with TDT, aged 10 years and above, were recruited. RESULTS: Out of the 89 patients, there were 54 males (60.7%) and 35 females (39.3%) with a median age of 21 years (range 10.0-65.0). Sixty-seven (75.3%) patients had betathalassaemia major and 15 (16.9%) patients had haemoglobin E beta-thalassaemia (HbE beta-thalassaemia), remaining seven patients had other genotypes. Thirty-one (34.8%) patients had mean serum ferritin 2500ng/ml and above, and 44 (66.6%) had liver iron concentration (LIC) ≥7mg/g. The prevalence of endocrine disorders in our cohort was 69.7%. The most common endocrinopathies were short stature (n=46, 51.7%), followed by hypogonadism (n=24, 26.9%), delayed puberty (n=23, 25.8%), hypothyroidism (n=10, 11.2%), diabetes mellitus (n=9, 10.1%), impaired glucose tolerance (n=6, 6.7%) and hypoparathyroidism (n=3, 3.3%). Endocrinopathies were significantly associated with age (p=0.01), age at initiating regular blood transfusion (p<0.01) and duration of regular blood transfusion (p<0.01). CONCLUSION: Our data shows that the development of endocrinopathies in TDT can be time dependent. Early detection of endocrine-related complications and prompt treatment with iron chelation therapy are important to improve morbidity and mortality. A multidisciplinary approach with good patient-doctor collaboration is the key to improving patient care in our settings.


Asunto(s)
Transfusión Sanguínea , Enfermedades del Sistema Endocrino , Sobrecarga de Hierro , Talasemia , Humanos , Masculino , Estudios Retrospectivos , Femenino , Malasia/epidemiología , Adulto , Niño , Adolescente , Enfermedades del Sistema Endocrino/epidemiología , Enfermedades del Sistema Endocrino/etiología , Adulto Joven , Talasemia/terapia , Talasemia/complicaciones , Talasemia/epidemiología , Transfusión Sanguínea/estadística & datos numéricos , Persona de Mediana Edad , Sobrecarga de Hierro/etiología , Sobrecarga de Hierro/epidemiología , Prevalencia , Anciano , Hierro/metabolismo
2.
Med J Malaysia ; 78(5): 594-601, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37775485

RESUMEN

INTRODUCTION: Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator is beneficial in acute ischaemic stroke (AIS). We aim to compare the realworld clinical outcomes and service efficiency of IVT in Malaysian primary stroke centres (PSCs) versus acute stroke ready hospitals (ASRHs). MATERIALS AND METHODS: We conducted a multi-centre cohort study involving 5 PSCs and 7 ASRHs in Malaysia. Through review of medical records of AIS patients who received IVT from 01 January 2014 to 30 June 2021, real-world data was extracted for analysis. Univariate and multivariate regression models were employed to evaluate the role of PSCs versus ASRHs in post-IVT outcomes and complications. Statistical significance was set at p<0.05. RESULTS: A total of 313 multi-ethnic Asians, namely 231 from PSCs and 82 from ASRHs, were included. Both groups were comparable in baseline demographic, clinical, and stroke characteristics. The efficiency of IVT delivery (door-toneedle time), functional outcomes (mRS at 3 months post- IVT), and rates of adverse events (intracranial haemorrhages and mortality) following IVT were comparable between the 2 groups. Notably, 46.8% and 48.8% of patients in PSCs and ASRHs group respectively (p=0.752) achieved favourable functional outcome (mRS≤1 at 3 months post-IVT). Regression analyses demonstrated that post-IVT functional outcomes and adverse events were independent of the role of PSCs or ASRHs. CONCLUSION: Our study provides real-world evidence which suggests that IVT can be equally safe, effective, and efficiently delivered in ASRHs. This may encourage the establishment of more ASRHs to extend the benefits of IVT to a greater proportion of stroke populations and enhance the regional stroke care.

3.
BJOG ; 126(12): 1437-1444, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31131503

RESUMEN

OBJECTIVE: To validate the NHSLA maternity claims taxonomy at the level of a single maternity service and assess its ability to direct quality improvement. DESIGN: Qualitative descriptive study. SETTING: Medico-legal claims between 1 January 2000 and 31 December 2016 from a maternity service in metropolitan Melbourne, Australia. POPULATION: All obstetric claims and incident notifications occurring within the date range were included for analysis. METHODS: De-identified claims and notifications data were derived from the files of the insurer of Victorian public health services. Data included claim date, incident date and summary, and claim cost. All reported issues were coded using the NHSLA taxonomy and the lead issue identified. MAIN OUTCOME MEASURES: Rate of claims and notifications, relative frequency of issues, a revised taxonomy. RESULTS: A combined total of 265 claims and incidents were reported during the 6 years. Of these 59 were excluded, leaving 198 medico-legal events for analysis (1.66 events/1000 births). The costs for all claims was $46.7 million. The most common claim issues were related to management of labour (n = 63, $17.7 million), cardiotocographic interpretation (n = 43, $24.4 million), and stillbirth (n = 35, $656,750). The original NHSLA classification was not sufficiently detailed to inform care improvement programmes. A revised taxonomy and coding flowchart is presented. CONCLUSIONS: Systematic analysis of obstetric medico-legal claims data can potentially be used to inform quality and safety improvement. TWEETABLE ABSTRACT: New taxonomy to target health improvement from maternity claims based on NHSLA Ten Years of Maternity Claims.


Asunto(s)
Benchmarking , Mala Praxis/legislación & jurisprudencia , Obstetricia/normas , Femenino , Humanos , Revisión de Utilización de Seguros , Servicios de Salud Materna/legislación & jurisprudencia , Servicios de Salud Materna/normas , Obstetricia/legislación & jurisprudencia , Embarazo , Mejoramiento de la Calidad , Medicina Estatal , Reino Unido
5.
Spinal Cord ; 56(12): 1116-1123, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-29955090

RESUMEN

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To determine the risk factors predictive of dysphagia after a spinal cord injury (SCI). SETTING: None. METHODS: A comprehensive literature search was performed in five scientific databases for English articles that identified risk factors for dysphagia after a SCI in adult (≥19 years) individuals. Data extracted included: author name, year and country of publication, participant demographics, sample size, study design, method of dysphagia diagnosis, and risk factor percentages. Methodological quality of studies was assessed using the Newcastle-Ottawa Scale. For identified risk factors, risk percentages were transformed into risk ratios (RR) with 95% confidence intervals. Quantitative synthesis was performed for risk factors reported in two or more studies using restricted maximum-likelihood estimator random effects models. RESULTS: Eleven studies met inclusion criteria of which ten studies were of moderate quality (n = 10). Significant risk factors included: age, injury severity, level of injury, presence of tracheostomy, coughing, voice quality, bronchoscopy need, pneumonia, mechanical ventilation, nasogastric tubes, comorbid injury, and a cervical surgery. Results of the quantitative synthesis indicated that the presence of a tracheostomy posed a threefold greater risk of the development of dysphagia (RR: 3.67); while, cervical surgery posed a 1.3 times greater risk of the development of dysphagia (RR: 1.30). CONCLUSIONS: Knowledge of these risk factors can be a resource for clinicians in the early diagnosis and appropriate medical management of dysphagia post SCI.


Asunto(s)
Trastornos de Deglución/epidemiología , Trastornos de Deglución/etiología , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/epidemiología , Humanos , Factores de Riesgo
6.
Spinal Cord ; 54 Suppl 1: S1-6, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27444714

RESUMEN

STUDY DESIGN: Clinical practice guidelines. OBJECTIVES: The objective was to develop the first Canadian clinical practice guidelines for the management of neuropathic pain in people with spinal cord injury (SCI). SETTING: The guidelines are relevant for inpatient and outpatient SCI rehabilitation settings in Canada. METHODS: The guidelines were developed in accordance with the Appraisal of Guidelines for Research and Evaluation II tool. A Steering Committee and Working Group reviewed the relevant evidence on neuropathic pain management (encompassing screening and diagnosis, treatment and models of care) after SCI. The quality of evidence was scored using Grading of Recommendations Assessment, Development and Evaluation (GRADE). A consensus process was followed to achieve agreement on recommendations and clinical considerations. RESULTS: The Working Group developed 12 recommendations for screening and diagnosis, 12 recommendations for treatment and 5 recommendations for models of care. Important clinical considerations accompany each recommendation. CONCLUSIONS: The Working Group recommendations for the management of neuropathic pain after SCI should be used to inform practice.


Asunto(s)
Neuralgia/etiología , Neuralgia/rehabilitación , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/rehabilitación , Canadá , Humanos
7.
Spinal Cord ; 54 Suppl 1: S14-23, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27444715

RESUMEN

STUDY DESIGN: Clinical practice guidelines. OBJECTIVES: To develop the first Canadian clinical practice guidelines for treatment of neuropathic pain in people with spinal cord injury (SCI). SETTING: The guidelines are relevant for inpatient and outpatient SCI rehabilitation settings in Canada. METHODS: The CanPainSCI Working Group reviewed the evidence for different treatment options and achieved consensus. The Working Group then developed clinical considerations for each recommendation. Recommendations for research are also included. RESULTS: Twelve recommendations were developed for the management of neuropathic pain after SCI. The recommendations address both pharmacologic and nonpharmacologic treatment modalities. CONCLUSIONS: An expert Working Group developed recommendations for the treatment of neuropathic pain after SCI that should be used to inform practice.


Asunto(s)
Neuralgia/etiología , Neuralgia/rehabilitación , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/rehabilitación , Canadá , Humanos
8.
Spinal Cord ; 54 Suppl 1: S24-7, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27444716

RESUMEN

STUDY DESIGN: Clinical practice guidelines. OBJECTIVES: The project objectives were to develop the first Canadian recommendations on a model of care for the management of at- and below-level neuropathic pain in people with spinal cord injury (SCI). SETTING: The guidelines are relevant for inpatient and outpatient SCI rehabilitation settings in Canada. METHODS: On the basis of a review of the Accreditation Canada standards, the Steering Committee developed questions to guide the CanPainSCI Working Group when developing the recommendations. The Working Group agreed on recommendations through a consensus process. RESULTS: The Working Group developed five recommendations for the organization of neuropathic pain rehabilitation care in people with SCI. CONCLUSIONS: The Working Group recommendations for a model of care for at- and below-level neuropathic pain after SCI should be used to inform clinical practice.


Asunto(s)
Atención a la Salud/métodos , Neuralgia/etiología , Neuralgia/rehabilitación , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/rehabilitación , Humanos
9.
Spinal Cord ; 54 Suppl 1: S7-S13, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27444717

RESUMEN

STUDY DESIGN: Clinical practice guidelines. OBJECTIVES: To develop the first Canadian clinical practice guidelines for screening and diagnosis of neuropathic pain in people with spinal cord injury (SCI). SETTING: The guidelines are relevant for inpatient and outpatient SCI rehabilitation settings in Canada. METHODS: The CanPainSCI Working Group reviewed evidence to address clinical questions regarding screening and diagnosis of neuropathic pain after SCI. A consensus process was followed to achieve agreement on recommendations and clinical considerations. RESULTS: Twelve recommendations, based on expert consensus, were developed for the screening and diagnosis of neuropathic pain after SCI. The recommendations address methods for assessment, documentation tools, team member accountability, frequency of screening and considerations for diagnostic investigation. Important clinical considerations accompany each recommendation. CONCLUSIONS: The expert Working Group developed recommendations for the screening and diagnosis of neuropathic pain after SCI that should be used to inform practice.


Asunto(s)
Neuralgia/diagnóstico , Neuralgia/rehabilitación , Traumatismos de la Médula Espinal/diagnóstico , Traumatismos de la Médula Espinal/rehabilitación , Canadá , Humanos , Neuralgia/etiología , Traumatismos de la Médula Espinal/complicaciones
10.
Br J Cancer ; 112(3): 429-37, 2015 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-25584489

RESUMEN

BACKGROUND: Rilotumumab, an investigational, monoclonal antibody, inhibits MET-mediated signalling. In a randomized phase 2 trial of rilotumumab±epirubicin/cisplatin/capecitabine in gastric or oesophagogastric junction cancer, patients receiving rilotumumab showed a trend towards improved survival, especially in MET-positive patients, but no clear dose-response relationship was observed. Exposure-response and biomarker analyses were used for dose selection and to differentiate patient subpopulations that may benefit most from treatment. Here, we analyse rilotumumab exposure-survival and exposure-safety and the impact of MET expression on these relationships. METHODS: Individual rilotumumab exposure parameters were generated using population pharmacokinetic modelling. Relationships among rilotumumab dose (7.5 and 15 mg kg(-1)), exposure, and clinical outcomes (progression-free survival (PFS) and overall survival (OS)) were evaluated with Cox regression models and Kaplan-Meier plots. MET status and other baseline covariates were evaluated in subgroup and multivariate analyses. Treatment-emergent adverse events were summarised by exposure. RESULTS: Among MET-positive patients, higher rilotumumab exposure, vs placebo and low exposure, was associated with improved median PFS (80% CI: 7.0 (5.7-9.7) vs 4.4 (2.9-4.9) and 5.5 (4.2-6.8) months) and OS (13.4 (10.6-18.6) vs 5.7 (4.7-10.2) and 8.1 (6.9-11.1) months) without increased toxicity. No rilotumumab benefit was seen among MET-negative patients. CONCLUSIONS: Rilotumumab had an exposure-dependent treatment effect in patients with MET-positive gastric or oesophagogastric junction cancer.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/farmacocinética , Proteínas Proto-Oncogénicas c-met/genética , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adulto , Anciano , Anticuerpos Monoclonales Humanizados , Relación Dosis-Respuesta a Droga , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Resultado del Tratamiento
11.
Spinal Cord ; 53(11): 780-5, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26193817

RESUMEN

OBJECTIVES: To conduct a systematic review and meta-analysis to examine the effect of transcranial direct current stimulation (tDCS) on reducing neuropathic pain intensity in individuals with spinal cord injury (SCI). METHODS: Medline, CINAHL, EMBASE and PsycINFO databases were searched for all relevant articles published from 1980 to November 2014. Trials were included if (i) tDCS intervention group and a placebo control group were present; (ii) at least 50% of participants in the study had an SCI and there were at least three participants; (iii) participants were aged 18 years or older; and (iv) persistent pain for at least 3 months. Studies were excluded if: (i) the tDCS intervention group was compared with an active treatment group; (ii) there was insufficient reporting detail to enable pooling of data; and (iii) it was a nonclinical trial (that is, reviews, epidemiology, basic sciences). A standardized mean difference (SMD) ± s.e. and 95% confidence interval (CI) was calculated for each outcome of interest and the results were pooled using a fixed or random effects model, as appropriate. Effect sizes were interpreted as: small > 0.2, moderate > 0.5, large > 0.8. RESULTS: Five studies met inclusion criteria of which four were randomized controlled trials and one was a prospective controlled trial. The pooled analysis found a significant effect of tDCS on reducing neuropathic pain after SCI post treatment (SMD = 0.510 ± 0.202; 95% CI, 0.114-0.906; P < 0.012); however, this effect was not maintained at follow-up (SMD = 0.353 ± 0.272; 95% CI, -0.179 to 0.886; P < 0.194). A reduction of 1.33 units on a 10-item scale was observed post treatment. No significant adverse events were reported. CONCLUSION: Meta-analytic results indicate a moderate effect of tDCS in reducing neuropathic pain among individuals with SCI; however, the effect was not maintained at follow-up. A mean pooled decrease of 1.33 units on a 10-item scale was found post treatment. Several factors were implicated in the effectiveness of tDCS in reducing pain. Due to the limited number of studies and lack of follow-up, more evidence is required before treatment recommendations can be made.


Asunto(s)
Neuralgia/etiología , Neuralgia/terapia , Traumatismos de la Médula Espinal/complicaciones , Estimulación Transcraneal de Corriente Directa/métodos , Animales , Manejo de la Enfermedad , Humanos
12.
Spinal Cord ; 52(1): 34-8, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24216615

RESUMEN

OBJECTIVE: To assess the validity of different administrative data sources available for the identification of traumatic spinal cord injured (TSCI) patients. STUDY DESIGN: Retrospective validation study. SETTING: Ontario, Canada. PARTICIPANTS: Adult patients seen in tertiary outpatient spinal cord rehabilitation clinics after 1 April 2002. OUTCOME MEASURES: Sensitivity, specificity, positive and negative predicative values of diagnostic ICD10 codes from Canadian Institutes of Health Discharge Abstracts (CIHI-DAD), Rehabilitation Coding Groups (RCG) from that National Rehabilitation System (NRS), and spinal cord injury fee codes from the Ontario Healthcare Insurance Plan (OHIP). Secondary outcome was the agreement between actual lesion level and RCG/ICD10 coded lesion level. RESULTS: The RCG codes in the NRS have high sensitivity (92%, 95% confidence interval (CI): 87-95%) and specificity (97%, 95% CI: 94-99%) for the identification of true TSCI patients, whereas CIHI-DAD ICD10 codes are highly specific (99%, 95% CI: 95-100) and moderately sensitive (76%, 95% CI: 79-87%). OHIP fee codes had poor sensitivity (64%, 95% CI: 57-71%). Agreement between true lesion level and the NRS and CIHI-DAD coding is good (Kappa of 0.65-0.88 and 0.56-0.70, respectively). CONCLUSION: This study demonstrated that the NRS is able to accurately discriminate between patients with and without a TSCI. A large population of incident and prevalent TSCI patients are identifiable using administrative data. SPONSORSHIP: This study was funded by a grant from the Division of Urology, Western University.


Asunto(s)
Algoritmos , Codificación Clínica/normas , Traumatismos de la Médula Espinal/clasificación , Adulto , Codificación Clínica/métodos , Femenino , Humanos , Clasificación Internacional de Enfermedades , Masculino , Persona de Mediana Edad , Ontario
13.
Spinal Cord ; 52(2): 89-96, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24296804

RESUMEN

STUDY DESIGN: Systematic review and effectiveness analysis. OBJECTIVES: Assess the effectiveness of anticonvulsants for the management of post spinal cord injury (SCI) neuropathic pain. SETTING: Studies from multiple countries were included. METHODS: CINAHL, Cochrane, EMBASE and MEDLINE were searched up to April 2013. Quality assessment was conducted using the Jadad and the Downs and Black tools. Effect sizes and odds ratios were calculated for primary and secondary outcome in the included studies. RESULTS: Gabapentinoids, valproate, lamotrigine, levetiracetam and carbamazepine were examined in the 13 included studies, ten of which are randomized controlled trials. Large effect size (0.873-3.362) for improvement of pain relief was found in 4 of the 6 studies examining the effectiveness of gabapentin. Pregabalin was shown to have a moderate to large effect (0.695-3.805) on improving neuropathic pain post SCI in 3 studies. Valproate and levetiracetam were not effective in improving neuropathic pain post SCI, while lamotrigine was effective in reducing neuropathic pain amongst persons with incomplete lesions and carbamazepine was found effective for relief of moderate to intense pain. CONCLUSION: Gabapentin and pregabalin are the two anticonvulsants which have been shown to have some benefit in reducing neuropathic pain.


Asunto(s)
Analgésicos/uso terapéutico , Anticonvulsivantes/uso terapéutico , Neuralgia/tratamiento farmacológico , Manejo del Dolor/métodos , Traumatismos de la Médula Espinal/fisiopatología , Aminas/efectos adversos , Aminas/uso terapéutico , Analgésicos/efectos adversos , Anticonvulsivantes/efectos adversos , Ácidos Ciclohexanocarboxílicos/efectos adversos , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Gabapentina , Humanos , Neuralgia/etiología , Pregabalina , Ensayos Clínicos Controlados Aleatorios como Asunto , Ácido gamma-Aminobutírico/efectos adversos , Ácido gamma-Aminobutírico/análogos & derivados , Ácido gamma-Aminobutírico/uso terapéutico
14.
Spinal Cord ; 51(7): 516-21, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23608811

RESUMEN

STUDY DESIGN: Prospective scoping review. OBJECTIVES: To conduct a scoping review of all the literature related to bladder cancer in individuals with spinal cord injuries (SCI). METHODS: Literature search of the databases Pubmed, CINAHL, ProQuest, PsychINFO and Scopus up to and including August 2012. Articles related to bladder cancer among SCI patients were identified, and data pertaining to epidemiology, risk factors, screening, prevention and management was reviewed and summarized. RESULTS: An association between bladder cancer and SCI was first reported in the 1960s, with some case reports suggesting an alarmingly high rate among SCI patients. More recent epidemiological studies have reported this risk to be substantially lower. However, bladder cancer in SCI patients tends to present at an earlier age and at a more advanced pathological stage than bladder cancer in the general population. Presenting symptoms may be atypical, and early recognition is important to improve prognosis with surgical resection. Several risk factors have been identified, including indwelling catheters, urinary tract infections and bladder calculi. Screening of SCI patients for bladder cancer is routinely recommended in many SCI management guidelines and by expert consensus; however, evidence for screening tools and protocols is lacking. CONCLUSION: Bladder cancer is a rare, and potentially lethal occurrence in SCI patients. Physicians need to have a high index of suspicion for bladder cancer, particularly among SCI patients managed with long-term indwelling catheters.


Asunto(s)
Medicina Basada en la Evidencia , Traumatismos de la Médula Espinal/mortalidad , Neoplasias de la Vejiga Urinaria/mortalidad , Cálculos Urinarios/mortalidad , Cateterismo Urinario/mortalidad , Infecciones Urinarias/mortalidad , Causalidad , Comorbilidad , Humanos , Factores de Riesgo , Tasa de Supervivencia
15.
Ann Oncol ; 23(11): 2834-2842, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22700995

RESUMEN

BACKGROUND: We evaluated the efficacy and safety of ganitumab (a mAb antagonist of insulin-like growth factor 1 receptor) or conatumumab (a mAb agonist of human death receptor 5) combined with gemcitabine in a randomized phase 2 trial in patients with metastatic pancreatic cancer. PATIENTS AND METHODS: Patients with a previously untreated metastatic pancreatic adenocarcinoma and an Eastern Cooperative Oncology Group (ECOG) performance status ≤1 were randomized 1 : 1 : 1 to i.v. gemcitabine 1000 mg/m(2) (days 1, 8, and 15 of each 28-day cycle) combined with open-label ganitumab (12 mg/kg every 2 weeks [Q2W]), double-blind conatumumab (10 mg/kg Q2W), or double-blind placebo Q2W. The primary end point was 6-month survival rate. Results In total, 125 patients were randomized. The 6-month survival rates were 57% (95% CI 41-70) in the ganitumab arm, 59% (42-73) in the conatumumab arm, and 50% (33-64) in the placebo arm. The grade ≥3 adverse events in the ganitumab, conatumumab, and placebo arms, respectively, included neutropenia (18/22/13%), thrombocytopenia (15/17/8%), fatigue (13/12/5%), alanine aminotransferase increase (15/5/8%), and hyperglycemia (18/2/3%). CONCLUSIONS: Ganitumab combined with gemcitabine had tolerable toxicity and showed trends toward an improved 6-month survival rate and overall survival. Additional investigation into this combination is warranted. Conatumumab combined with gemcitabine showed some evidence of activity as assessed by the 6-month survival rate.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/secundario , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/tratamiento farmacológico , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Placebos , Receptor IGF Tipo 1/antagonistas & inhibidores , Receptor IGF Tipo 1/inmunología , Tasa de Supervivencia , Resultado del Tratamiento , Gemcitabina
16.
Intern Med J ; 46(5): 638-9, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-27170248

Asunto(s)
Liderazgo , Humanos
17.
Water Sci Technol ; 64(6): 1374-82, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22214094

RESUMEN

The work presented herein was completed in an effort to characterize the forces influencing ventilation in gravity sewers and to develop a mathematical model, based on conservation of momentum, capable of accounting for friction at the headspace/pipe interface, drag at the air/water interface, and buoyancy caused by air density differences between a sewer headspace and ambient. Experiments were completed on two full scale sewer reaches in Australia. A carbon monoxide-based tracer technique was used to measure the ventilation rate within the sewer headspaces. Additionally, measurements of pressure, relative humidity, and temperature were measured in the ambient air and sewer headspace. The first location was a five kilometre long sewer outfall beginning at a wastewater treatment plant and terminating at the ocean. The second location was a large gravity sewer reach fitted with ventilation fans. At the first location the headspace was entirely sealed except for openings that were controlled during the experiments. In this situation forces acting on the headspace air manifested mostly as a pressure distribution within the reach, effectively eliminating friction at the pipe wall. At the second location, air was forced to move near the same velocity as the wastewater, effectively eliminating drag at the air/water interface. These experiments allowed individual terms of the momentum equation to be evaluated. Experimental results were compared to the proposed mathematical model. Conclusions regarding model accuracy are provided along with model application guidance and assumptions.


Asunto(s)
Modelos Teóricos , Ventilación , Eliminación de Residuos Líquidos , Aguas del Alcantarillado
18.
Pharmacogenomics J ; 10(1): 30-9, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19918262

RESUMEN

Noradrenaline and adrenaline are neurotransmitters of the sympathetic nervous system that interact with various adrenergic receptor (ADR) subtypes, and this regulates the basal metabolic rate, thermogenesis and efficiency of energy utilization. We examined a possible role of the gene coding for ADRA1A receptor in weight gain in schizophrenia subjects exposed to antipsychotics. A total of 401 schizophrenia in-patients treated with antipsychotics for >2 years were recruited and a final 394 DNA samples were genotyped. Their body mass indexes (BMIs) were recorded for 12 months and parameterized to be correlated in regression. Among the 58 single-nucleotide polymorphisms (SNPs) genotyped, 44 valid SNPs, which had minor allele frequency > or =0.03, were analyzed in statistics. Linear regression model with age, gender, diabetes, use of typical antipsychotics and use of atypical antipsychotics as covariates, with or without gender interaction, showed evidence of associations between the ADRA1A gene and BMI. Most of the SNPs associated with BMI are located in the promoter and intron regions, and being female appeared to enhance the gene effect. Our study suggests that the ADRA1A gene is involved in weight gain among schizophrenia patients treated with antipsychotics. Further molecular dissection of the ADRA1A gene warrants better understanding on weight gain mechanisms in schizophrenia.


Asunto(s)
Antipsicóticos/uso terapéutico , Índice de Masa Corporal , Receptores Adrenérgicos alfa 1/genética , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/genética , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Femenino , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Obesidad/etiología , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Esquizofrenia/complicaciones , Aumento de Peso/genética
19.
Phys Rev Lett ; 104(16): 161101, 2010 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-20482038

RESUMEN

We report studies of ultrahigh-energy cosmic-ray composition via analysis of depth of air shower maximum (X(max)), for air shower events collected by the High-Resolution Fly's Eye (HiRes) observatory. The HiRes data are consistent with a constant elongation rate d/d[log(E)] of 47.9+/-6.0(stat)+/-3.2(syst) g/cm2/decade for energies between 1.6 and 63 EeV, and are consistent with a predominantly protonic composition of cosmic rays when interpreted via the QGSJET01 and QGSJET-II high-energy hadronic interaction models. These measurements constrain models in which the galactic-to-extragalactic transition is the cause of the energy spectrum ankle at 4x10(18) eV.

20.
Mol Psychiatry ; 13(12): 1129-37, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18180752

RESUMEN

Artificial intelligence has become a possible solution to resolve the problem of loss of information when complexity of a disease increases. Obesity phenotypes are observable clinical features of drug-naive schizophrenic patients. In addition, atypical antipsychotic medications may cause these unwanted effects. Here we examined the performance of neuro-fuzzy modeling (NFM) in predicting weight changes in chronic schizophrenic patients exposed to antipsychotics. Two hundred and twenty inpatients meeting DSMIV diagnosis of schizophrenia, treated with antipsychotics, either typical or atypical, for more than 2 years, were recruited. All subjects were assessed in the same study period between mid-November 2003 and mid-April 2004. The baseline and first visit's physical data including weight, height and circumference were used in this study. Clinical information (Clinical Global Impression and Life Style Survey) and genotype data of five single nucleotide polymorphisms were also included as predictors. The subjects were randomly assigned into the first group (105 subjects) and second group (115 subjects), and NFM was performed by using the FuzzyTECH 5.54 software package, with a network-type structure constructed in the rule block. A complete learned model trained from merged data of the first and second groups demonstrates that, at a prediction error of 5, 93% subjects with weight gain were identified. Our study suggests that NFM is a feasible prediction tool for obesity in schizophrenic patients exposed to antipsychotics, with further improvements required.


Asunto(s)
Antipsicóticos/farmacología , Peso Corporal/efectos de los fármacos , Pesos y Medidas Corporales/métodos , Lógica Difusa , Modelos Biológicos , Esquizofrenia/fisiopatología , Adulto , Antipsicóticos/uso terapéutico , Peso Corporal/fisiología , Escalas de Valoración Psiquiátrica Breve , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Esquizofrenia/tratamiento farmacológico , Adulto Joven
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