Associations Between Aldosterone-Renin-Ratio and Bone Parameters Derived from Peripheral Quantitative Computed Tomography and Impact Microindentation in Men.

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.

Aldosterone and renin concentrations and blood pressure in young Indigenous and non-Indigenous adults in the Northern Territory: a cross-sectional study.

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.

Genicular artery embolization for early-stage knee osteoarthritis: results from a triple-blind single-centre randomized controlled trial.

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.

Willingness to be tested for a secondary cause of hypertension: a survey of the Australian general community.

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.

At Least Three Doses of Leading Vaccines Essential for Neutralisation of SARS-CoV-2 Omicron Variant.

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.

Detecting primary aldosteronism in Australian primary care: a prospective study.

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.

Indium-labelled autologous platelet sequestration studies predict response to splenectomy in immune thrombocytopenia: an Australian experience.

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.

Frailty associations with socioeconomic status, healthcare utilisation and quality of life among older women residing in regional Australia.

OBJECTIVES: The health and well-being of older women may be influenced by frailty and low socioeconomic status (SES). This study examined the association between frailty and SES, healthcare utilisation and quality of life (QOL) among older women in regional Australia. METHODS: Cross-sectional analysis of the Geelong Osteoporosis Study was conducted on 360 women (ages ≥60yr) in the 15-year follow up. Frailty was identified using modified Fried's phenotype. Individual SES measures and healthcare utilisation were documented by questionnaire. Area-based SES was determined by cross-referencing residential addresses with the Australian Bureau of Statistics Index of Relative Socio-economic Advantage and Disadvantage (IRSAD). QOL was measured using the Australian World Health Organisation Quality of Life Instrument (WHOQoL-Bref). Multinomial logistic regression was conducted with frailty groupings as outcome. RESULTS: Sixty-two (17.2%) participants were frail, 199 (55.3%) pre-frail and 99 (27.5%) robust. Frail participants were older with higher body mass index. Frailty was associated with lower education but not marital status, occupation or IRSAD. Strong associations with frailty were demonstrated for all WHOQoL-Bref domains. Frailty was associated with more primary care doctor visits (p<0.001). CONCLUSIONS: This population-based study highlights the significant impact of frailty on older women, indicating reduced QOL and increased primary care doctor visits.

The Added Burden of Personality Disorder on Subsidized Australian Health Service Utilization Among Women With Mental State Disorder.

This study aimed to investigate health service utilization among women with mental state disorder only (MSD-PD), mental state disorder plus personality disorder (MSD+PD), and controls in a population-based sample. Women (n = 635) from the Geelong Osteoporosis Study completed mental health assessments and were categorized into groups (MSD-PD, MSD+PD, controls). General practitioner (mental and non-mental health encounters) and specialized mental health service utilization was ascertained from data linkage to the Medicare Benefits Schedule, Australia (01/09/2008-31/12/2012). Negative binomial and binary logistic regression models were employed to assess health service utilization differences between groups. Results indicated that women with MSD+PD had more encounters of non-mental health service utilization than women with MSD-PD and controls. Age significantly modified these relationships: women with MSD+PD and MSD-PD had more encounters of health service utilization at midlife and in the seventh decade of life. No significant differences were found in the frequency of general practitioner mental health service utilization or specialized mental health service utilization between groups. These data suggest that the presence of co-occurring PD is associated with increased health service utilization among women with other common mental health problems. Healthcare providers should be vigilant to the presence of PD when establishing management plans with patients presenting with common mental health problems.

68Ga-PSMA-PET screening and transponder-guided salvage radiotherapy to the prostate bed alone for biochemical recurrence following prostatectomy: interim outcomes of a phase II trial.

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.

Prospective Screening for Primary Aldosteronism in Patients With Suspected Obstructive Sleep Apnea.

[Figure: see text].

Caustic Mist Exposure and Respiratory Outcomes in a Cohort Study of Alumina Refinery Workers.

A common chemical exposure in alumina refining is caustic mist. Although recognized as a strong airways irritant, little is known of the chronic respiratory effects of caustic mist in alumina refining. A suitable metric for caustic mist exposure assessment in alumina refining for epidemiological purposes has not been identified. Peak exposure is likely to be important, but is difficult to assess in epidemiological studies. In this study, we investigate the respiratory effects of caustic mist in an inception cohort (n = 416) of alumina refinery workers and describe the development and use of a peak exposure metric for caustic mist. We then compare the results with a metric based on duration of exposure. Participants were interviewed annually about respiratory symptoms and had a lung function test. Job history data were collected from each interview and levels of caustic mist were measured periodically by air monitoring. We found a weak association between the caustic mist peak exposure metric and reported cough (P for linear trend = 0.079) with the highest peak exposure group odds ratio = 2.32 (95% confidence interval: 1.27, 4.22). For lung function, we found declines in the forced expiratory volume in 1 second and forced vital capacity for changes in annual and absolute lung function for both metrics of exposure, but only the ratio of absolute lung function was statistically associated with an increasing duration of caustic exposure (P for linear trend = 0.011). In this cohort, we did not observe an association with respiratory symptoms or consistent decrements in lung function. There was little difference between the exposure metrics used for investigation of the chronic effects from caustic mist.

Systematic review and meta-analysis of the role of personality disorder in randomised controlled trials of pharmacological interventions for adults with mood disorders.

BACKGROUND: Personality disorder (PD) may affect the efficacy of pharmacological interventions for mood disorders, but the extent to which this occurs is uncertain. We aimed to examine the available published evidence concerning the role of PD in pharmacological treatment outcomes of randomised controlled trials (RCTs) for adults with mood disorders (i.e. depressive and bipolar spectrum disorders). METHODS: A systematic search of Cochrane Central Register of Controlled Clinical Trials, PubMed, EMBASE, PsycINFO, CINAHL Complete, and Google Scholar databases was undertaken to identify studies of interest. Data were independently extracted by two reviewers. The Cochrane Risk of Bias tool was used to assess methodological quality and risk of bias. A random effects model was utilised and statistical heterogeneity was assessed using the I2 statistic. This systematic review was registered with PROSPERO (CRD42018089279) and the protocol is published. RESULTS: The search yielded 11,640 studies. Subsequent to removing duplicates, 9657 studies were screened at title and abstract stage and 1456 were assessed at full-text stage. Eighteen studies met criteria for inclusion in this review. Meta-analysis did not reveal a significant difference between groups for treatment outcome (standardised mean difference 0.22 [-0.09, 0.54]; I2: 69%, p=0.17) and remission (risk ratio 0.84 [0.64, 1.11]; I2: 51%, p=0.22). LIMITATIONS: This review was limited by lack of studies on bipolar disorder. CONCLUSION: PD comorbidity does not appear to affect treatment efficacy of pharmacological interventions for adults with mood disorders.

Respiratory outcomes among refinery workers exposed to inspirable alumina dust: A longitudinal study in Western Australia.

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.

The effectiveness of a simple antimicrobial stewardship intervention in general practice in Australia: a pilot study.

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.

Oral protein-based supplements versus placebo or no treatment for people with chronic kidney disease requiring dialysis.

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.

Fractionated stereotactic body radiotherapy for up to five prostate cancer oligometastases: Interim outcomes of a prospective clinical trial.

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.

Presentation and outcomes in hypertrophic pyloric stenosis: An 11-year review.

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.

Preterm growth restriction and bronchopulmonary dysplasia: the vascular hypothesis and related physiology.

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.

Effect of a clinical flowchart incorporating Wells score, PERC rule and age-adjusted D-dimer on pulmonary embolism diagnosis, scan rates and diagnostic yield.

OBJECTIVE: To assess the association between the use of a flowchart incorporating Wells score, PERC rule and age-adjusted D-dimer and subsequent imaging and yield rates of computed tomography pulmonary angiogram and nuclear medicine ventilation perfusion scans being ordered in the ED for the assessment of pulmonary embolism. METHODS: A flowchart governing ED pulmonary embolism investigation was introduced across three EDs in Melbourne, Australia for a 12 month period. Comparison of pulmonary embolism imaging rates and yield with the preceding 12 months was performed. RESULTS: A total of 1815 pre-implementation scans were performed compared with 1116 scans post-implementation. Because of growth in patient attendances over this time, this equated to an imaging rate of 14.5 per 1000 presentations pre-implementation and 8.6 per 1000 presentations post-implementation (P < 0.001). Overall pulmonary embolism imaging yield rates rose from 9.9% to 16.5% (P < 0.001). A total of 179 pre-implementation pulmonary embolisms were identified, with an incidence of 1.4 per 1000 presentations. This compared to 184 pulmonary embolisms post-implementation, with an incidence of 1.4 per 1000 presentations (P = 0.994). CONCLUSION: The introduction of a clinical flowchart incorporating Wells score, PERC rule and age-adjusted D-dimer was associated with an increase in ED computed tomography pulmonary angiogram and nuclear medicine ventilation perfusion yield rate from 9.9% to 16.5% across the three enrolment hospitals when investigating possible pulmonary embolism. This corresponded to a 40% relative reduction in pulmonary embolism imaging. Diagnosis rates remained unchanged and no cases of missed pulmonary embolism attributable to the flowchart were identified.