RESUMEN
Metastasis-directed therapy (MDT) for oligometastatic prostate cancer (PCa), including stereotactic body radiotherapy (SBRT), has shown promise but is still considered investigational. This is the 5-year analysis of the TRANSFORM trial, the largest prospective cohort of men with oligometastatic PCa treated with SBRT-based MDT. The primary endpoint was 5-year treatment escalation-free survival (TE-FS), defined as freedom from any new cancer therapy other than further SBRT. In total, 199 men received SBRT; 76.4% were hormone-naïve at baseline. The rate of 5-year TE-FS was 21.7% (95% confidence interval [CI]: 15.7%-28.7%) overall and 25.4% (95% CI: 18.1%-33.9%) in the hormone-naïve subgroup. The subgroups with International Society of Urological Pathology Grade Groups 4-5 disease (hazard ratio [HR] = 1.48, 95% CI: 1.05-2.01, p = .026), a higher baseline prostate-specific antigen (PSA) (HR = 1.06, 95% CI: 1.03-1.09, p < .001) and those who received prior androgen deprivation therapy (ADT) (HR = 2.13, 95% CI: 1.40-3.26, p < .001), were at greater risk of treatment escalation. Outcomes for participants with four or five initial lesions were comparable to those with one to three lesions. At last follow-up, 18.9% (95% CI: 13.2%-25.7%) of participants were free from treatment escalation (median follow-up of 67.9 months) and two participants had an undetectable PSA level. No treatment-related grade three or higher adverse events were reported. The findings of this study demonstrate that SBRT-based MDT is an effective option for delaying systemic treatment escalation in the context of oligometastatic PCa. Future randomised trials comparing SBRT-based MDT to standard-of-care ADT-based approaches are required to evaluate the impact of delaying ADT on survival.
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Neoplasias de la Próstata , Radiocirugia , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Radiocirugia/métodos , Anciano , Persona de Mediana Edad , Estudios Prospectivos , Metástasis de la Neoplasia , Anciano de 80 o más Años , Resultado del Tratamiento , Antígeno Prostático Específico/sangre , Fraccionamiento de la Dosis de RadiaciónRESUMEN
BACKGROUND AND OBJECTIVE: Chest x-ray (CXR) remains a core component of health monitoring guidelines for workers at risk of exposure to crystalline silica. There has however been a lack of evidence regarding the sensitivity of CXR to detect silicosis in artificial stone benchtop industry workers. METHODS: Paired CXR and high-resolution computed tomography (HRCT) images were acquired from 110 artificial stone benchtop industry workers. Blinded to the clinical diagnosis, each CXR and HRCT was independently read by two thoracic radiologists from a panel of seven, in accordance with International Labour Office (ILO) methodology for CXR and International Classification of HRCT for Occupational and Environmental Respiratory Diseases. Accuracy of screening positive (ILO major category 1, 2 or 3) and negative (ILO major category 0) CXRs were compared with identification of radiological features of silicosis on HRCT. RESULTS: CXR was positive for silicosis in 27/110 (24.5%) workers and HRCT in 40/110 (36.4%). Of the 83 with a negative CXR (ILO category 0), 15 (18.1%) had silicosis on HRCT. All 11 workers with ILO category 2 or 3 CXRs had silicosis on HRCT. In 99 workers ILO category 0 or 1 CXRs, the sensitivity of screening positive CXR compared to silicosis identified by HRCT was 48% (95%CI 29-68) and specificity 97% (90-100). CONCLUSION: Compared to HRCT, sensitivity of CXR was low but specificity was high. Reliance on CXR for health monitoring would provide false reassurance for many workers, delay management and underestimate the prevalence of silicosis in the artificial stone benchtop industry.
RESUMEN
Components of the renin-angiotensin-aldosterone system (RAAS) are present on bone cells. One measure of RAAS activity, the aldosterone-renin-ratio (ARR), is used to screen for primary aldosteronism. Associations between ARR and bone mineral density are conflicting. This study investigated associations between ARR and peripheral quantitative computed tomography (pQCT) and impact microindentation (IMI). Male participants (n = 431) were from the Geelong Osteoporosis Study. "Likely" primary aldosteronism was defined as ARR ≥ 70 pmol/mIU. Another group, "possible" primary aldosteronism, was defined as either ARR ≥ 70 pmol/mIU or taking a medication that affects the RAAS, but not a beta blocker, and renin < 15 mU/L. Using pQCT, images at 4% and 66% of radial (n = 365) and tibial (n = 356) length were obtained. Using IMI measurements, bone material strength index (BMSi; n = 332) was determined. Associations between ARR or likely/possible primary aldosteronism and IMI or pQCT-derived bone parameters were tested using median regression. ARR and aldosterone values were not associated with any of the pQCT-derived bone variables in either unadjusted or adjusted analyses. Men with likely primary aldosteronism (n = 16), had lower adjusted total bone area (radial 66% site, - 12.5%). No associations were observed for men with possible primary aldosteronism (unadjusted or adjusted). No associations with BMSi were observed (p > 0.05). There were no associations between ARR or aldosterone and pQCT-derived bone parameters. Men with likely primary aldosteronism had lower bone area, suggesting clinically high levels of ARR may have a negative impact on bone health.
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Hiperaldosteronismo , Hipertensión , Humanos , Masculino , Aldosterona/uso terapéutico , Renina/uso terapéutico , Hiperaldosteronismo/complicaciones , Sistema Renina-Angiotensina , Tomografía Computarizada por Rayos X , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológicoRESUMEN
OBJECTIVES: To evaluate aldosterone and renin levels and aldosterone-to-renin ratios (ARRs) in young Indigenous and non-Indigenous adults in the Northern Territory, and their association with blood pressure levels. DESIGN: Cross-sectional study; single time point sub-study of two prospective birth cohort studies. SETTING, PARTICIPANTS: Participants in the Aboriginal Birth Cohort (ABC) - born to Indigenous mothers at the Royal Darwin Hospital during 1987-1990 - and the Top End Cohort (TEC) - people born to non-Indigenous mothers in Darwin, recruited during 2007-2009 - aged 32-35 years at the time of this sub-study. MAIN OUTCOME MEASURES: Plasma aldosterone and direct renin concentrations; ARRs (positive screening test result for primary aldosteronism defined as > 70 pmol/mU); systolic and diastolic blood pressure. RESULTS: A total of 255 ABC (205 in remote, 50 in urban locations) and 76 TEC members participated. Median aldosterone concentration was similar for all three groups. The median renin concentration was 7.5 mU/L (interquartile range [IQR], 4.1-12.4 mU/L) in the TEC group, 12.4 mU/L (IQR, 5.1-19 mU/L) in the urban ABC group, and 29.3 mU/L (IQR, 15.0-52.9 mU/L) in the remote ABC group. The median ARR was 10 pmol/mU (IQR, 6-19 pmol/mU) in the remote ABC group, 28 pmol/mU (IQR, 16-70 pmol/mU) in the urban ABC group, and 43 pmol/mU (IQR, 26-74 pmol/mU) in the TEC group. Thirteen urban ABC participants (26%), 21 TEC participants (28%), and six people in the remote ABC group (3%) had ARR values above 70 pmol/mU. Adjusted for age and body mass index (BMI), mean systolic and diastolic blood pressure were lower for women than men in all participant groups; after adjusting for age, sex, and BMI, larger ARR was associated with higher systolic blood pressure in the TEC group but not the two ABC groups. CONCLUSION: Screening test results for primary aldosteronism were positive for about one-quarter of urban Indigenous and non-Indigenous participants. A prospective study that includes confirmatory testing would more accurately assess the prevalence of primary aldosteronism among Indigenous Australians in the Northern Territory.
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Hiperaldosteronismo , Hipertensión , Masculino , Adulto , Humanos , Femenino , Aldosterona , Presión Sanguínea , Estudios Prospectivos , Renina , Estudios Transversales , Northern Territory/epidemiología , Hiperaldosteronismo/diagnósticoRESUMEN
BACKGROUND: Primary aldosteronism (PA) represents the most common and potentially curable cause of secondary hypertension. However, PA is not commonly screened for, and up to 34% of patients who screen positive do not complete the full diagnostic process. This suggests that the diagnostic process may pose a barrier to patients and may contribute to the under-diagnosis of PA. AIMS: To evaluate the willingness of the Australian general public to undergo testing for secondary causes of hypertension and identify enablers or barriers to testing from the patients' perspective. METHODS: An online survey containing questions on knowledge and attitudes towards hypertension, willingness to be tested and enablers/barriers towards testing was distributed to the Australian community. RESULTS: Of 520 adult respondents (mean age 50.4 years, SD 27.3 years; 28.8% hypertensive; 56.0% female), the majority of non-hypertensive and hypertensive respondents (82.7% vs 70.0%; P = 0.03) were willing to undergo testing for a secondary cause of hypertension that involved blood and urine tests. Greater knowledge of hypertensive risk modification strategies and complications was predictive of willingness to be tested, whereas age, sex, education level, geographic location, socio-economic status and cardiovascular comorbidities were not. The top three barriers to testing included fear of a serious underlying condition, lack of belief in further testing and increased stress associated with further testing. CONCLUSION: A high proportion of patients are willing to engage in testing for a secondary cause of hypertension. Education about the risks associated with hypertension and the testing process may overcome several barriers to testing.
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Hiperaldosteronismo , Hipertensión , Adulto , Humanos , Femenino , Persona de Mediana Edad , Masculino , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/epidemiología , Australia/epidemiología , Hipertensión/diagnóstico , Hipertensión/epidemiología , Hipertensión/complicaciones , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To assess the identification of primary aldosteronism (PA) in newly diagnosed, treatment-naïve patients with hypertension by screening in primary care. DESIGN: Prospective study. SETTING: General practices in the South Eastern Melbourne Primary Health Network with at least three general practitioners and general practices elsewhere in Victoria that had referred patients to the Endocrine Hypertension Clinic at Monash Health, 2017-2020. PARTICIPANTS: Adults (18-80 years) with newly diagnosed hypertension (measurements of systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg on at least two occasions) and not taking antihypertensive medications were screened for PA by assessing their aldosterone-to-renin ratio (ARR). Participants with two ARR values exceeding 70 pmol/mU underwent saline suppression testing at the Endocrine Hypertension Service (Monash Health) to confirm the diagnosis of PA. MAIN OUTCOME MEASURES: Prevalence of PA (number of patients with confirmed PA divided by number screened). RESULTS: Sixty-two of 247 screened participants had elevated ARR values on screening (25%); for 35 people (14%; 95% CI, 10-19%), PA was confirmed by saline suppression testing. Baseline characteristics (mean age, sex distribution, median baseline blood pressure levels, and serum potassium concentration) were similar for people with or without PA. CONCLUSION: PA was diagnosed in 14% of patients with newly diagnosed hypertension screened by GPs, indicating a potential role for GPs in the early detection of an important form of secondary hypertension for which specific therapies are available.
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Hiperaldosteronismo , Hipertensión , Adulto , Aldosterona , Australia , Humanos , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/diagnóstico , Hipertensión/complicaciones , Hipertensión/diagnóstico , Hipertensión/epidemiología , Atención Primaria de Salud , Estudios Prospectivos , ReninaRESUMEN
BACKGROUND: Splenectomy is an effective intervention in primary immune thrombocytopenia (ITP). Attempts to define pre-clinical predictors of platelet response to splenectomy are inconsistent. Based on international studies defining the likelihood of platelet response using platelet sequestration, patients with relapsed/refractory ITP being considered for splenectomy at a regional Australian hospital were assessed with 111 indium-labelled autologous platelet sequestration (ILAPS) studies. AIMS: To audit the use of ILAPS in an Australian setting and define its role in predicting response to splenectomy. METHODS: A retrospective review of all patients referred for an ILAPS study at a regional hospital was performed. Results for each patient were expressed as an 'R' value (spleen/ liver uptake ratio) to quantify the platelet sequestration pattern and outcome post-splenectomy, based on platelet counts. RESULTS: A total of 45 patients was identified: 13 underwent splenectomy and 32 were medically managed. Patients with favourable ILAPS scans (pure or predominant splenic sequestration) demonstrated a superior response post-splenectomy (100% overall response rate (ORR); 83.5% complete remission (CR)) compared with those with unfavourable ILAPS scans (mixed or pure hepatic sequestration) (71.4% ORR; 57.1% CR) over 12 months. CONCLUSIONS: The use of ILAPS in the Australian setting is feasible and this experience confirms larger international studies demonstrating its utility as a predictor of response to splenectomy in ITP. An unfavourable ILAPS scan could be considered a negative predictor of response prompting consideration for other emerging ITP treatments such as thrombopoietin-receptor agonists or B-cell depleting therapy such as Rituximab.
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Púrpura Trombocitopénica Idiopática , Trombocitopenia , Australia/epidemiología , Humanos , Indio , Púrpura Trombocitopénica Idiopática/cirugía , Estudios Retrospectivos , Esplenectomía , Trombocitopenia/cirugía , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate outcomes for men with biochemically recurrent prostate cancer who were selected for transponder-guided salvage radiotherapy (SRT) to the prostate bed alone by 68Ga-labelled prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-PET). METHODS: This is a single-arm, prospective study of men with a prostate-specific antigen (PSA) level rising to 0.1-2.5 ng/mL following radical prostatectomy. Patients were staged with 68Ga-PSMA-PET and those with a negative finding, or a positive finding localised to the prostate bed, continued to SRT only to the prostate bed alone with real-time target-tracking using electromagnetic transponders. The primary endpoint was freedom from biochemical relapse (FFBR, PSA > 0.2 ng/mL from the post-radiotherapy nadir). Secondary endpoints were time to biochemical relapse, toxicity and patient-reported quality of life (QoL). RESULTS: Ninety-two patients (median PSA of 0.18 ng/ml, IQR 0.12-0.36), were screened with 68Ga-PSMA-PET and metastatic disease was found in 20 (21.7%) patients. Sixty-nine of 72 non-metastatic patients elected to proceed with SRT. At the interim (3-year) analysis, 32 (46.4%) patients (95% CI 34.3-58.8%) were FFBR. The median time to biochemical relapse was 16.1 months. The rate of FFBR was 82.4% for ISUP grade-group 2 patients. Rates of grade 2 or higher gastrointestinal and genitourinary toxicity were 0% and 15.2%, respectively. General health and disease-specific QoL remained stable. CONCLUSION: Pre-SRT 68Ga-PSMA-PET scans detect metastatic disease in a proportion of patients at low PSA levels but fail to improve FFBR. Transponder-guided SRT to the prostate bed alone is associated with a favourable toxicity profile and preserved QoL. TRIAL REGISTRATION NUMBER: ACTRN12615001183572, 03/11/2015, retrospectively registered.
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Isótopos de Galio , Radioisótopos de Galio , Recurrencia Local de Neoplasia/radioterapia , Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata/radioterapia , Radiofármacos , Terapia Recuperativa/métodos , Anciano , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Estudios Prospectivos , Antígeno Prostático Específico/sangre , Prostatectomía , Neoplasias de la Próstata/cirugía , Resultado del TratamientoRESUMEN
Stereotactic body radiotherapy (SBRT) can delay escalation to systemic treatment in men with oligometastatic prostate cancer (PCa). However, large, prospective studies are still required to evaluate the efficacy of this approach in different patient groups. This is the interim analysis of a prospective, single institution study of men relapsing with up to five synchronous lesions following definitive local treatment for primary PCa. Our aim was to determine the proportion of patients not requiring treatment escalation following SBRT. In total, 199 patients were enrolled to receive fractionated SBRT (50 Gray in 10 fractions) to each visible lesion. Fourteen patients were castration resistant at enrolment. The proportion of patients not requiring treatment escalation 2 years following SBRT was 51.7% (95% CI: 44.1-59.3%). The median length of treatment escalation-free survival over the entire follow-up period was 27.1 months (95% CI; 21.8-29.4 months). Prior androgen deprivation therapy (ADT) predicted a significantly lower rate of freedom from treatment escalation at 2 years compared to no prior ADT (odds ratio = 0.21, 95% CI: 0.08-0.54, p = 0.001). There was no difference in the efficacy of SBRT when treating 4-5 vs. 1-3 initial lesions. A prostate-specific antigen (PSA) decline was induced in 75% of patients, with PSA readings falling to an undetectable level in six patients. No late grade three toxicities were observed. These interim results suggest that SBRT can be used to treat up to five synchronous PCa oligometastases to delay treatment escalation.
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Fraccionamiento de la Dosis de Radiación , Metástasis de la Neoplasia/radioterapia , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Radiocirugia/métodos , Anciano , Antagonistas de Andrógenos/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/tratamiento farmacológicoRESUMEN
BACKGROUND: Inappropriate and excessive antimicrobial prescribing can lead to antimicrobial resistance. Antimicrobial Stewardship (AMS) principles are not well established in general practice in Australia despite the relatively high rate of community antimicrobial prescribing. Few interventions have been implemented that have resulted in a significant reduction or improvement in antimicrobial prescribing by General Practitioners (GPs). This study was therefore conducted to assess the impact of a novel GP educational intervention on the appropriateness of antimicrobial prescriptions as well as GP compliance with antimicrobial prescription guidelines. METHODS: In 2018, a simple GP educational intervention was rolled out in a large clinic with the aim of improving antimicrobial prescribing. It included face-to-face education sessions with GPs on AMS principles, antimicrobial resistance, current prescribing guidelines and microbiological testing. An antibiotic appropriateness audit on prescribing practice before and after the educational intervention was conducted. Data were summarised using percentages and compared across time points using Chi-squared tests and Poisson regression (results reported as risk ratios (RR) with 95% confidence intervals (CI)). RESULTS: Data from 376 and 369 prescriptions in July 2016 and July 2018, respectively, were extracted. There were significant improvements in appropriate antimicrobial selection (73.9% vs 92.8%, RR = 1.26; 95% CI = 1.18-1.34), appropriate duration (53.1% vs 87.7%, RR = 1.65; 95% CI = 1.49-1.83) and compliance with guidelines (42.2% vs 58.5%, RR = 1.39, 95% CI = 1.19-1.61) post- intervention. Documentation of antimicrobial duration directions, patient follow-up as well as patient weight significantly increased after the intervention (p < 0.001). There was significant reduction in; prescriptions without a listed indication for antimicrobial therapy, prescriptions without appropriate accompanying microbiological tests and the provision of unnecessary repeat prescriptions (p < 0.001). Inappropriate antimicrobial prescriptions observed pre-intervention for medical termination of pregnancy ceased post-intervention. CONCLUSIONS: Auditing GP antimicrobial prescriptions identified prescribing practices inconsistent with Australian guidelines. However, implementation of a simple education program led to significantly improved antimicrobial prescribing by GPs. These findings indicate the important role of AMS and continued antimicrobial education within general practice.
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Antiinfecciosos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos , Medicina General/educación , Médicos Generales/psicología , Australia , Humanos , Prescripción Inadecuada/prevención & control , Proyectos Piloto , Guías de Práctica Clínica como Asunto , PrescripcionesRESUMEN
BACKGROUND: Malnutrition is common in patients with chronic kidney disease (CKD) on dialysis. Oral protein-based nutritional supplements are often provided to patients whose oral intake is otherwise insufficient to meet their energy and protein needs. Evidence for the effectiveness of oral protein-based nutritional supplements in this population is limited. OBJECTIVES: The aims of this review were to determine the benefits and harms of using oral protein-based nutritional supplements to improve the nutritional state of patients with CKD requiring dialysis. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 12 December 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) of patients with CKD requiring dialysis that compared oral protein-based nutritional supplements to no oral protein-based nutritional supplements or placebo. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for eligibility, risk of bias, and extracted data from individual studies. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference and 95% CI for continuous outcomes. MAIN RESULTS: Twenty-two studies (1278 participants) were included in this review. All participants were adults on maintenance dialysis of whom 79% were on haemodialysis (HD) and 21% peritoneal dialysis. The follow-up period ranged from one to 12 months. The majority of studies were at unclear risk of selection, performance, and reporting bias. The detection bias was high for self-reported outcomes. Oral protein-based nutritional supplements probably lead to a higher mean change in serum albumin compared to the control group (16 studies, 790 participants: MD 0.19 g/dL, 95% CI 0.05 to 0.33; moderate certainty evidence), although there was considerable heterogeneity in the combined analysis (I2 = 84%). The increase was more evident in HD participants (10 studies, 526 participants: MD 0.28 g/dL, 95% CI 0.11 to 0.46; P = 0.001 for overall effect) and malnourished participants (8 studies, 405 participants: MD 0.31 g/dL, 95% CI 0.10 to 0.52, P = 0.003 for overall effect). Oral protein-based nutritional supplements also probably leads to a higher mean serum albumin at the end of the intervention (14 studies, 715 participants: MD 0.14 g/dL, 95% CI 0 to 0.27; moderate certainty evidence), however heterogeneity was again high (I2 = 80%). Again the increase was more evident in HD participants (9 studies, 498 participants: MD 0.21 g/dL, 95% CI 0.03 to 0.38; P = 0.02 for overall effect) and malnourished participants (7 studies, 377 participants: MD 0.25 g/dL, 95% CI 0.02 to 0.47; P = 0.03 for overall effect). Compared to placebo or no supplement, low certainty evidence showed oral protein-based nutritional supplements may result in a higher serum prealbumin (4 studies, 225 participants: MD 2.81 mg/dL, 95% CI 2.19 to 3.43), and mid-arm muscle circumference (4 studies, 216 participants: MD 1.33 cm, 95% CI 0.24 to 2.43) at the end of the intervention. Compared to placebo or no supplement, oral protein-based nutritional supplements may make little or no difference to weight (8 studies, 365 participants: MD 2.83 kg, 95% CI -0.43 to 6.09; low certainty evidence), body mass index (9 studies, 368 participants: MD -0.04 kg/m2, 95% CI -0.74 to 0.66; moderate certainty evidence) and lean mass (5 studies, 189 participants: MD 1.27 kg, 95% CI -1.61 to 4.51; low certainty evidence). Due to very low quality of evidence, it is uncertain whether oral protein-based nutritional supplements affect triceps skinfold thickness, mid-arm circumference, C-reactive protein, Interleukin 6, serum potassium, or serum phosphate. There may be little or no difference in the risk of developing gastrointestinal intolerance between participants who received oral protein-based nutritional supplements compared with placebo or no supplement (6 studies, 426 participants: RR 2.81, 95% CI 0.58 to 13.65, low certainty evidence). It was not possible to draw conclusions about cost or quality of life, and deaths were not reported as a study outcome in any of the included studies. AUTHORS' CONCLUSIONS: Overall, it is likely that oral protein-based nutritional supplements increase both mean change in serum albumin and serum albumin at end of intervention and may improve serum prealbumin and mid-arm muscle circumference. The improvement in serum albumin was more evident in haemodialysis and malnourished participants. However, it remains uncertain whether these results translate to improvement in nutritional status and clinically relevant outcomes such as death. Large well-designed RCTs in this population are required.
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Proteínas en la Dieta/administración & dosificación , Desnutrición/terapia , Diálisis Renal , Insuficiencia Renal Crónica/terapia , Albúmina Sérica/metabolismo , Administración Oral , Brazo/anatomía & histología , Sesgo , Biomarcadores/sangre , Proteínas en la Dieta/efectos adversos , Humanos , Desnutrición/sangre , Desnutrición/etiología , Diálisis Peritoneal/estadística & datos numéricos , Placebos/administración & dosificación , Prealbúmina/metabolismo , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Diálisis Renal/estadística & datos numéricos , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/complicaciones , Grosor de los Pliegues CutáneosRESUMEN
BACKGROUND: Information is scarce about the occupational health effects of exposure to alumina dust. This study examines the respiratory effects of inspirable alumina dust exposure in alumina refineries. METHODS: An inception cohort study at three alumina refineries in Western Australia recruited 416 participants (351 males, 65 females) between 1995 and 2000 who were followed up annually until 2008 or until exit from study. At each health interview a respiratory questionnaire and lung function test was undertaken, measuring forced expiratory volume in one second (FEV1 ) and forced vital capacity (FVC). Participants provided job histories which were combined with air monitoring data to calculate cumulative exposure to inspirable alumina dust (mg/m3 -years). Generalized estimating equations with Poisson distribution and mixed effects models were used to examine the effects of alumina exposure. RESULTS: The number of exposed participants was relatively small (n = 82, 19.7%). There was no association between alumina dust exposure and prevalence of cough, wheeze or rhinitis. No associations were found between measures of lung function and tertiles of alumina exposure in the first two follow-ups, or the whole follow-up period, though there was a suggestive dose-response trend across exposed groups for decline in absolute FEV1 (p for trend = .06). For mean annual change in FEV1 and FVC based on the first three follow-ups it was not possible to rule out an effect above a threshold level of exposure. CONCLUSION: There is no evidence of an association between exposure to alumina and the reporting of respiratory symptoms but some evidence for an effect on lung function.
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Contaminantes Ocupacionales del Aire/toxicidad , Óxido de Aluminio/toxicidad , Exposición por Inhalación/efectos adversos , Enfermedades Pulmonares/epidemiología , Enfermedades Profesionales/epidemiología , Exposición Profesional/efectos adversos , Adulto , Tos/epidemiología , Tos/etiología , Polvo , Industria Procesadora y de Extracción , Femenino , Humanos , Estudios Longitudinales , Enfermedades Pulmonares/etiología , Masculino , Enfermedades Profesionales/etiología , Prevalencia , Pruebas de Función Respiratoria , Ruidos Respiratorios/etiología , Rinitis/epidemiología , Rinitis/etiología , Pruebas Cutáneas , Australia Occidental/epidemiologíaRESUMEN
KEY POINTS: Approximately 5-10% pregnancies are affected by fetal growth restriction. Preterm infants affected by fetal growth restriction have a higher incidence of bronchopulmonary dysplasia. The present study is the first to measure pulmonary artery thickness and stiffness. The findings show that impaired vasculogenesis may be a contributory factor in the higher incidence of bronchopulmonary dysplasia in preterm growth restricted infants. The study addresses the mechanistic link between fetal programming and vascular architecture and mechanics. ABSTRACT: Bronchopulmonary dysplasia is the most common respiratory sequelae of prematurity and histopathologically features fewer, dysmorphic pulmonary arteries. The present study aimed to characterize pulmonary artery mechanics and cardiac function in preterm infants with fetal growth restriction (FGR) compared to those appropriate for gestational age (AGA) in the early neonatal period. This prospective study reviewed 40 preterm infants between 28 to 32 weeks gestational age (GA). Twenty infants had a birthweight <10th centile and were compared with 20 preterm AGA infants. A single high resolution echocardiogram was performed to measure right pulmonary arterial and right ventricular (RV) indices. The GA and birthweight of FGR and AGA infants were 29.8 ± 1.3 vs. 30 ± 0.9 weeks (P = 0.78) and 923.4 g ± 168 vs. 1403 g ± 237 (P < 0.001), respectively. Assessments were made at 10.5 ± 1.3 days after birth. The FGR infants had significantly thicker right pulmonary artery inferior wall (843.5 ± 68 vs. 761 ± 40 µm, P < 0.001) with reduced pulsatility (51.6 ± 7.6 µm vs. 59.7 ± 7.5 µm, P = 0.001). The RV contractility [fractional area change (28.7 ± 3.8% vs 32.5 ± 3.1%, P = 0.001), tricuspid annular peak systolic excursion (TAPSE) (5.2 ± 0.3% vs. 5.9 ± 0.7%, P = 0.0002) and myocardial performance index (0.35 ± 0.03 vs. 0.28 ± 0.02, P < 0.001)] was significantly impaired in FGR infants. Significant correlation between RV longitudinal contractility (TAPSE) and time to peak velocity/RV ejection time (measure of RV afterload) was noted (r2 = 0.5, P < 0.001). Altered pulmonary vascular mechanics and cardiac performance reflect maladaptive changes in response to utero-placental insufficiency. Whether managing pulmonary vascular disease will alter clinical outcomes remains to be studied prospectively.
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Displasia Broncopulmonar/fisiopatología , Retardo del Crecimiento Fetal/fisiopatología , Arteria Pulmonar/diagnóstico por imagen , Displasia Broncopulmonar/etiología , Gasto Cardíaco , Femenino , Frecuencia Cardíaca , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Recién Nacido , Recien Nacido Prematuro , Masculino , Contracción Miocárdica , Arteria Pulmonar/embriología , Arteria Pulmonar/patologíaRESUMEN
AIM: To evaluate the trend in presentation and postoperative outcomes of infants with hypertrophic pyloric stenosis (HPS) over the last decade. METHODS: This was a multicentre retrospective study in two tertiary paediatric centres between 2005 and 2015 inclusive. Participants included 626 infants who underwent a pyloromyotomy for HPS. We collected data on presentation features (age, weight, clinical signs, blood gas results, ultrasound findings) and postoperative outcomes (length of stay (LOS), complications, time to first postoperative feed). RESULTS: No trend was identified during the study period with regards to age, weight, biochemical findings (pH, chloride, base excess) or pre-operative ultrasound measurements. There was a downtrend in the number of palpated tumours over time, with a mean of 36% of tumours clinically palpated. Pyloric wall thickness had a moderate association with LOS in patients admitted for >8 days (correlation = 0.4752) but had a weak negative association with shorter lengths of stay (≤8 day, correlation = -0.094). Overall, median time to first feed was 7.80 h and improved yearly during the study period (hazard ratio = 1.07). CONCLUSIONS: Patients presenting with HPS are not being identified at an earlier age or with fewer biochemical derangements, in contrast to our initial perceptions. Subsequently, biochemical derangements can still play an important role in the diagnosis of HPS, and attention needs to be given to fluid management and electrolyte correction in all patients with HPS.
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Evaluación de Resultado en la Atención de Salud , Estenosis Hipertrófica del Piloro/cirugía , Hospitales Pediátricos , Humanos , Lactante , Recién Nacido , Distribución de Poisson , Estenosis Hipertrófica del Piloro/epidemiología , Estenosis Hipertrófica del Piloro/fisiopatología , Estudios RetrospectivosRESUMEN
BACKGROUND: Delayed Sleep-Wake Phase Disorder (DSWPD) is characterised by sleep initiation insomnia when attempting sleep at conventional times and difficulty waking at the required time for daytime commitments. Although there are published therapeutic guidelines for the administration of melatonin for DSWPD, to our knowledge, randomised controlled trials are lacking. This trial tested the efficacy of 0.5 mg melatonin, combined with behavioural sleep-wake scheduling, for improving sleep initiation in clinically diagnosed DSWPD patients with a delayed endogenous melatonin rhythm relative to patient-desired (or -required) bedtime (DBT). METHODS: This randomised, placebo-controlled, double-blind clinical trial was conducted in an Australian outpatient DSWPD population. Following 1-wk baseline, clinically diagnosed DSWPD patients with delayed melatonin rhythm relative to DBT (salivary dim light melatonin onset [DLMO] after or within 30 min before DBT) were randomised to 4-wk treatment with 0.5 mg fast-release melatonin or placebo 1 h before DBT for at least 5 consecutive nights per week. All patients received behavioural sleep-wake scheduling, consisting of bedtime scheduled at DBT. The primary outcome was actigraphic sleep onset time. Secondary outcomes were sleep efficiency in the first third of time in bed (SE T1) on treatment nights, subjective sleep-related daytime impairment (Patient Reported Outcomes Measurement Information System [PROMIS]), PROMIS sleep disturbance, measures of daytime sleepiness, clinician-rated change in illness severity, and DLMO time. FINDINGS: Between September 13, 2012 and September 1, 2014, 307 participants were registered; 116 were randomised to treatment (intention-to-treat n = 116; n = 62 males; mean age, 29.0 y). Relative to baseline and compared to placebo, sleep onset occurred 34 min earlier (95% confidence interval [CI] -60 to -8) in the melatonin group. SE T1 increased; PROMIS sleep-related impairment, PROMIS sleep disturbance, insomnia severity, and functional disability decreased; and a greater proportion of patients showed more than minimal clinician-rated improvement following melatonin treatment (52.8%) compared to placebo (24.0%) (P < 0.05). The groups did not differ in the number of nights treatment was taken per protocol. Post-treatment DLMO assessed in a subset of patients (n = 43) was not significantly different between groups. Adverse events included light-headedness, daytime sleepiness, and decreased libido, although rates were similar between treatment groups. The clinical benefits or safety of melatonin with long-term treatment were not assessed, and it remains unknown whether the same treatment regime would benefit patients experiencing DSWPD sleep symptomology without a delay in the endogenous melatonin rhythm. CONCLUSIONS: In this study, melatonin treatment 1 h prior to DBT combined with behavioural sleep-wake scheduling was efficacious for improving objective and subjective measures of sleep disturbances and sleep-related impairments in DSWPD patients with delayed circadian phase relative to DBT. Improvements were achieved largely through the sleep-promoting effects of melatonin, combined with behavioural sleep-wake scheduling. TRIAL REGISTRATION: This trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12612000425897.
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Melatonina/uso terapéutico , Fármacos Inductores del Sueño/uso terapéutico , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Sueño/efectos de los fármacos , Actigrafía , Adolescente , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nueva Gales del Sur , Australia del Sur , Victoria , Adulto JovenRESUMEN
OBJECTIVES: To assess cardiac morphology and function in preterm infants with fetal growth restriction (FGR) compared with an appropriate for gestational age cohort, and to ascertain clinical correlation with neonatal sequelae. STUDY DESIGN: With informed consent, 20 infants born between 28 and 32 weeks of gestational age and birthweight (BW) <10th percentile were compared using conventional and tissue Doppler echocardiography with 20 preterm appropriate for gestational age infants. Total duration of respiratory support was recorded. RESULTS: The gestational age and BW of the infants with FGR and appropriate for gestational age infants were 29.8 ± 1.3 weeks vs 30 ± 0.9 weeks (P = .78) and 923.4 ± 168 g vs 1403 ± 237 g (P < .001), respectively. Preterm infants with FGR had significantly greater interventricular septal hypertrophy, greater free wall thickening, and lower sphericity indices (1.53 ± 0.15 vs 1.88 ± 0.2; P < .001), signifying globular and hypertrophied hearts. The transmitral E/A ratio and isovolumic relaxation time, markers of diastolic function, were significantly increased in the FGR cohort (0.84 ± 0.05 vs 0.78 ± 0.03 [P < .001] and 61.4 ± 4.1 ms vs 53.2 ± 3.2 ms [P < .001], respectively). Ejection fraction, as measured by the rate corrected mean velocity of circumferential fiber shortening was reduced (1.93 ± 0.4 circ/second vs 2.77 ± 0.5 circ/second; P < .001) in the FGR cohort. On follow-up, the total duration of respiratory support was significantly longer in the FGR cohort, and correlated with tissue Doppler E/E' (r = 0.65; P = .001), mean velocity of circumferential fiber shortening (r = -0.64; P = .001) and mitral annular peak systolic excursion (r = -0.57; P = .008). CONCLUSIONS: Preterm infants with FGR have altered cardiac function evident within days after birth, which is associated with respiratory sequelae.
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Ecocardiografía Doppler/métodos , Retardo del Crecimiento Fetal/fisiopatología , Corazón/fisiopatología , Peso al Nacer , Edad Gestacional , Humanos , Lactante , Recién Nacido , Recien Nacido PrematuroRESUMEN
OBJECTIVE: To compare health service utilization and disability claims among military personnel with multisymptom illness (MSI) (but no chronic diseases), those with chronic disease(s) and those without MSI or chronic diseases. MSI is also known as Gulf War illness. DESIGN: Cohort study. SETTING: Australia. PARTICIPANTS: In total, 1288 participants of a Gulf War veterans' study conducted in 2000-2003 (Wave-1) were followed up in 2011-2012 (Wave-2), aged on average 40 years. About 160 had MSI, 217 had chronic disease(s) and 911 had neither chronic disease(s) nor MSI. METHODS: At Wave-2, the cohort was linked to the national Medicare and Department of Veterans' Affairs (DVA) databases to obtain health service utilization and disability claims data recorded between 2001 and 2012. RESULTS: The likelihood of visiting a general practitioner (GP) (risk ratio [RR] = 1.04, 95% confidence interval [CI] = 0.92, 1.19) or visiting a specialist medical doctor (RR = 0.83; 95% CI = 0.54, 1.28) or hospitalizations (RR = 0.89; 95% CI = 0.61, 1.29) or) in the 12 months preceding Wave-2 or successfully claiming for DVA disability compensation (RR = 1.13; 95% CI = 0.86, 1.47) was similar for personnel with MSI and those with chronic disease(s). However, GP consultations, hospitalizations, specialist doctor consultations and disability claims were significantly higher among those with MSI than those without MSI/chronic diseases. CONCLUSIONS: Health service use and disability claims by personnel with MSI were comparable to those with chronic disease(s), but were in excess of those without MSI/chronic diseases. Hence recognition of the high health service use by personnel with MSI is important to ensure adequate provision of health services.
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Enfermedad Crónica , Servicios de Salud/estadística & datos numéricos , Síndrome del Golfo Pérsico , Ayuda a Lisiados de Guerra/estadística & datos numéricos , Veteranos , Adulto , Australia , Estudios de Cohortes , Guerra del Golfo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Following the 1990-1991 Gulf War, Gulf War veterans (veterans) reported health symptoms more commonly than non-deployed groups. This article examines symptom persistence, incidence and prevalence 20 years on. METHODS: In 2000-2003 and 2011-2012, a 63-item symptom checklist was administered to 697 veterans and 659 comparison group. Symptomatology was compared using log-binomial regression. RESULTS: Both veterans and comparison group reported significantly increased prevalence (3-52%) over time in more than half the symptoms, with a similar overall rate of increase. Half the symptoms had higher incidence (risk-ratios ranged 1.43-1.50) and a quarter were more persistent (risk-ratios ranged 1.12-1.20) in veterans than the comparison group. CONCLUSIONS: Symptomatology increased in both groups over time, but persisted to a similar extent and had higher incidence among veterans than the comparison group. The gap in symptom prevalence between the two groups remained unchanged. These findings suggest enduring health consequences of Gulf War service.
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Guerra del Golfo , Síndrome del Golfo Pérsico/epidemiología , Veteranos/estadística & datos numéricos , Adulto , Lista de Verificación , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Síndrome del Golfo Pérsico/etiología , Prevalencia , Análisis de Regresión , Evaluación de Síntomas/métodos , Estados Unidos/epidemiologíaRESUMEN
This study investigated the effects of transcatheter arterial embolization (TAE) on pain, function, and quality of life in people with early-stage symptomatic knee osteoarthritis (OA) compared to a sham procedure. A total of 59 participants with symptomatic Kellgren-Lawrence grade 2 knee OA were randomly allocated to TAE or a sham procedure. The intervention group underwent TAE of one or more genicular arteries. The control group received a blinded sham procedure. The primary outcome was knee pain at 12 months according to the Knee injury and Osteoarthritis Outcome Score (KOOS) pain scale. Secondary outcomes included self-reported function and quality of life (KOOS, EuroQol five-dimension five-level questionnaire (EQ-5D-5L)), self-reported Global Change, six-minute walk test, 30-second chair stand test, and adverse events. Subgroup analyses compared participants who received complete embolization of all genicular arteries (as distinct from embolization of some arteries) (n = 17) with the control group (n = 29) for KOOS and Global Change scores at 12 months. Continuous variables were analyzed with quantile regression, adjusting for baseline scores. Dichotomized variables were analyzed with chi-squared tests. Overall, 58 participants provided questionnaire data at 12 months. No significant differences were found for the primary and secondary outcomes, with both groups improving following the procedure. At 12 months, KOOS pain scores improved by 41.3% and 29.4% in the intervention and control groups, respectively. No adverse events occurred. Subgroup analysis indicated that the complete embolization group had significantly better KOOS Sports and Recreation, KOOS Quality of Life, and Global Change scores than the control group; 76.5% of participants who received complete embolization reporting being moderately or much better compared to 37.9% of the control group. TAE might produce benefits above placebo, but only when complete embolization of all genicular arteries is performed. Further comparative studies are required before definitive conclusions regarding the effectiveness of TAE can be made. Level of evidence: I.
RESUMEN
Plasma samples taken at different time points from donors who received either AstraZeneca (Vaxzevria) or Pfizer (Comirnaty) or Moderna (Spikevax) coronavirus disease-19 (COVID-19) vaccine were assessed in virus neutralization assays against Delta and Omicron variants of concern and a reference isolate (VIC31). With the Pfizer vaccine there was 6-8-fold reduction in 50% neutralizing antibody titres (NT50) against Delta and VIC31 at 6 months compared to 2 weeks after the second dose; followed by 25-fold increase at 2 weeks after the third dose. Neutralisation of Omicron was only consistently observed 2 weeks after the third dose, with most samples having titres below the limit of detection at earlier timepoints. Moderna results were similar to Pfizer at 2 weeks after the second dose, while the titres for AstraZeneca samples derived from older donors were 7-fold lower against VIC31 and below the limit of detection against Delta and Omicron. Age and gender were not found to significantly impact our results. These findings indicate that vaccine matching may be needed, and that at least a third dose of these vaccines is necessary to generate sufficient neutralising antibodies against emerging variants of concern, especially Omicron, amidst the challenges of ensuring vaccine equity worldwide.