Proportion of people with diabetic retinopathy and macular oedema varies by ethnicity in a tertiary retinal clinic in Australia: findings from the Liverpool Eye and Diabetes Study (LEADS).

OBJECTIVE: There are limited data on the influence of ethnicity on diabetic retinopathy (DR). We sought to determine the distribution of DR by ethnic group in Australia. DESIGN: Clinic-based cross-sectional study. SETTING: Participants with diabetes in a defined geographical region of Sydney, Australia, who attended a tertiary retina referral clinic. PARTICIPANTS: The study recruited 968 participants. INTERVENTION: Participants underwent a medical interview and retinal photography and scanning. PRIMARY OUTCOME MEASURES: DR was defined from two-field retinal photographs. Diabetic macular oedema (DMO) was defined from spectral domain optical coherence tomography (OCT-DMO). The main outcomes were any DR, proliferative DR (PDR), clinically significant macular oedema (CSME), OCT-DMO and sight-threatening DR (STDR). RESULTS: There was high proportion of any DR (52.3%), PDR (6.3%), CSME (19.7%), OCT-DMO (28.9%) and STDR (31.5%) in people attending a tertiary retinal clinic. Participants of Oceanian ethnicity had the highest proportion of any DR and STDR (70.4% and 48.1%, respectively), while the lowest proportion was in participants of East Asian ethnicity (38.3% and 15.8%, respectively). Proportion of any DR and STDR in Europeans was 54.5% and 30.3%, respectively. Independent predictive factors for diabetic eye disease were ethnicity, longer duration of diabetes, higher glycated haemoglobin and higher blood pressure. Even after adjusting for risk factors, Oceanian ethnicity remained associated with twofold higher odds of any DR (adjusted OR 2.10, 95% CI 1.10 to 4.00) and all other forms of DR including STDR (adjusted OR 2.22, 95% CI 1.19 to 4.15). CONCLUSION: In people attending a tertiary retinal clinic, the proportion of people with DR varies among ethnic groups. The high proportion in persons of Oceanian ethnicity suggests a need for targeted screening of this at-risk group. In addition to traditional risks factors, ethnicity may be an additional independent predictor of DR.

Stakeholder engagement variability across public, private and public-private partnership projects: A data-driven network-based analysis.

Stakeholder engagement is generally considered one of the most pertinent factors impacting project outcomes. However, there is lacking empirical evidence documenting patterns of stakeholder engagement and their potential differences between public, private and public-private partnership (PPP) projects. This study leverages social network research methods to capture and quantitively compare these engagement structures. Stakeholder network data were collected by an online questionnaire from 17 public, 30 private and 9 PPP projects. A series of network-based analyses were subsequently applied to the data at both the level of individual project stakeholders and entire project stakeholder ecologies. A statistically significant difference (p<0.05) exists among the network-level measures of network size, edge number, density and betweenness centralization across the three project types. Among these four network measures, the density varies significantly (p<0.05) between 'within budget' and cost overrun projects for the private and PPP projects. The top-5 stakeholder lists with respect to three node-level centrality values reveal distinctive differences across the three project types. To further interpret the data, exponential random graph models were also applied to determine the most statistically prevalent network motifs within each type of project. Again, statistically significant differences were found across these three project types. The findings consistently point to structural differences in patterns of stakeholder engagement across the public and private domain and illustrate the applicability of network data and analytical techniques to monitoring and managing complex webs of relationships among actors who affect and are affected by diverse types of projects.

A Randomized, Placebo-Controlled Study of Methotrexate to Increase Response Rates in Patients with Uncontrolled Gout Receiving Pegloticase: Primary Efficacy and Safety Findings.

OBJECTIVE: To assess efficacy, safety, pharmacokinetics, and immunogenicity of pegloticase plus methotrexate (MTX) versus pegloticase plus placebo cotreatment for uncontrolled gout in a randomized, placebo-controlled, double-blind trial. METHODS: This study included adults with uncontrolled gout, defined as serum urate ≥7 mg/dl, oral urate-lowering therapy failure or intolerance, and presence of ongoing gout symptoms including ≥1 tophus, ≥2 flares in the past 12 months, or gouty arthritis. Key exclusion criteria included MTX contraindication, current immunosuppressant use, G6PDH deficiency, and estimated glomerular filtration rate <40 ml/minute/1.73 m2 . Patients were randomized 2:1 to 52 weeks of pegloticase (8 mg biweekly) with either oral MTX (15 mg/week) or placebo. The primary end point was the proportion of treatment responders during month 6 (defined as serum urate <6 mg/dl for ≥80% of visits during weeks 20-24). Efficacy was evaluated in all randomized patients (intent-to-treat population), and safety was evaluated in all patients receiving ≥1 blinded MTX or placebo dose. RESULTS: A total of 152 patients were randomized, 100 to receive pegloticase plus MTX, 52 to receive pegloticase plus placebo. Significantly higher treatment response occurred during month 6 in the MTX group versus the placebo group (71.0% [71 of 100 patients] versus 38.5% [20 of 52 patients], respectively; between-group difference 32.3% [95% confidence interval 16.3%, 48.3%]) (P < 0.0001 for between-group difference). During the first 6 months of pegloticase plus MTX or pegloticase plus placebo treatment, 78 (81.3%) of 96 MTX patients versus 47 (95.9%) of 49 placebo patients experienced ≥1 adverse event (AE), most commonly gout flare (64 [66.7%] of 96 MTX patients and 34 [69.4%] of 49 placebo patients). Reports of AEs and serious AEs were comparable between groups, but the infusion reaction rate was considerably lower with MTX cotherapy (4.2% [4 of 96 MTX patients, including 1 patient who had anaphylaxis]) than with placebo cotherapy (30.6% [15 of 49 placebo patients, 0 who had anaphylaxis]) (P < 0.001). Antidrug antibody positivity was also lower in the MTX group. CONCLUSION: MTX cotherapy markedly increased pegloticase response rate over placebo (71.0% versus 38.5%) during month 6 with no new safety signals. These findings verify higher treatment response rate, lower infusion reaction incidence, and lower immunogenicity when pegloticase is coadministered with MTX.

Machine learning in project analytics: a data-driven framework and case study.

The analytic procedures incorporated to facilitate the delivery of projects are often referred to as project analytics. Existing techniques focus on retrospective reporting and understanding the underlying relationships to make informed decisions. Although machine learning algorithms have been widely used in addressing problems within various contexts (e.g., streamlining the design of construction projects), limited studies have evaluated pre-existing machine learning methods within the delivery of construction projects. Due to this, the current research aims to contribute further to this convergence between artificial intelligence and the execution construction project through the evaluation of a specific set of machine learning algorithms. This study proposes a machine learning-based data-driven research framework for addressing problems related to project analytics. It then illustrates an example of the application of this framework. In this illustration, existing data from an open-source data repository on construction projects and cost overrun frequencies was studied in which several machine learning models (Python's Scikit-learn package) were tested and evaluated. The data consisted of 44 independent variables (from materials to labour and contracting) and one dependent variable (project cost overrun frequency), which has been categorised for processing under several machine learning models. These models include support vector machine, logistic regression, k-nearest neighbour, random forest, stacking (ensemble) model and artificial neural network. Feature selection and evaluation methods, including the Univariate feature selection, Recursive feature elimination, SelectFromModel and confusion matrix, were applied to determine the most accurate prediction model. This study also discusses the generalisability of using the proposed research framework in other research contexts within the field of project management. The proposed framework, its illustration in the context of construction projects and its potential to be adopted in different contexts will significantly contribute to project practitioners, stakeholders and academics in addressing many project-related issues.

Axonal Transport Impairment and its Relationship with Diffusion Tensor Imaging Metrics of a Murine Model of p301L Tau Induced Tauopathy.

Diffusion Tensor Imaging (DTI) and Manganese Enhanced MRI (MEMRI) are noninvasive tools to characterize neural fiber microstructure and axonal transport. A combination of both may provide novel insights into the progress of neurodegeneration. To investigate the relationship of DTI and MEMRI in white matter of tauopathy, twelve optic nerves of 11-month-old p301L tau mice were imaged and finished with postmortem immunohistochemistry. MEMRI was used to quantify Mn2+ accumulation rates in the optic nerve (ON, termed ONAR) and the Superior Colliculus (SC, termed SCAR), the primary terminal site of ON in mice. We found that both ONAR and SCAR revealed a significant linear correlation with mean diffusion (mD) and radial diffusion (rD) but not with other DTI quantities. Immunohistochemistry findings showed that ONAR, mD, and rD are significantly correlated with the myelin content (Myelin Basic Protein, p < 0.05) but not with the axonal density (SMI-31), tubulin density, or tau aggregates (AT8 staining). In summary, slower axonal transport appeared to have less myelinated axons and thinner remaining axons, associated with reduced rD and mD of in vivo DTI. A combination of in vivo MEMRI and DTI can provide critical information to delineate the progress of white matter deficits in neurodegenerative diseases.

Efficacy of Topical Carbonic Anhydrase Inhibitors in Reducing Duration of Chronic Central Serous Chorioretinopathy.

Purpose: Topical carbonic anhydrase inhibitors (CAIs) can influence retinal fluid distribution, but their role in treating central serous chorioretinopathy (CSCR) has not been studied. We examined the efficacy of a topical CAI (dorzolamide) in treating chronic CSCR. Methods: Prospective, nonrandomized, controlled intervention study of patients with chronic CSCR of at least 3 months duration. Observed controls (n = 15) were recruited consecutively from 2016 to 2017; treated cases (n = 18) were recruited from 2018 to 2019. Controls were observed without active intervention, whereas treated cases were treated with topical dorzolamide for 3 months. The study end points were change in central macular thickness (CMT), change in best corrected visual acuity (BCVA), and proportion of eyes achieving complete resolution of subretinal fluid (SRF). All end points were at 3 months. Results: Treated patients who received topical CAI had greater reduction in CMT (-145.6 µm, 95% confidence interval [CI] -170.5 to -120.7) compared to observed controls (-45.1 µm, 95% CI -65.3 to -25.1) at the main study end point of 3 months (P = 0.015). A higher proportion of treated patients achieved complete resolution of SRF compared to observed controls (77.8% vs. 40.0%, P = 0.04) at 3 months. However, change in BCVA at 3 months was similar in both groups (P = 0.12). Conclusions: Topical CAI resulted in more rapid reduction of CMT compared to observation. These results, if confirmed in other studies, suggest topical CAI may be a viable treatment option for patients with chronic CSCR. Translational Relevance: Topical CAI is used to treat a number of retinal disorders, and may be a novel treatment option for chronic CSCR.

Systematic review of pleural-amniotic shunt insertion vs. conservative management in isolated bilateral fetal hydrothorax without hydrops.

OBJECTIVE: In the management of bilateral fetal hydrothorax where the fetus is non-hydropic and apparently otherwise normal, we wished to determine if pleural-amniotic shunt insertion was better than conservative management in terms of mortality. METHODS: A systematic review was conducted between 1992 and 2017. Data extracted was inspected for heterogeneity. Where there was comparative data available, the odds ratio (OR) and confidence interval (CI) were calculated. RESULTS: Seven studies were included in this systematic review. There was a paucity of comparative data where only 2 studies (28 cases) allowed for direct comparison. Within the limitations of the study, there was no difference between shunt insertion vs. conservative management in terms of stillbirth or miscarriage (OR = 1.00, 95% CI 0.12-8.34, heterogeneity I2 = 0%, p = 1.00). CONCLUSION: There is insufficient data available to determine whether the outcome is improved by pleural-amniotic shunt insertion compared with conservative management in cases of bilateral fetal hydrothorax where the fetus is non-hydropic and otherwise normal.

Profile of a population-based diabetic macular oedema study: the Liverpool Eye and Diabetes Study (Sydney).

PURPOSE: The population prevalence of diabetic macular oedema (DME) is unclear. Previous estimates have depended on photographic grading of clinically significant macular oedema, which is subjective and has resulted in widely varying estimates. With the advent of optical coherence tomography (OCT), the presence and severity of DME can now be assessed objectively and accurately. METHODS: The Liverpool Eye and Diabetes Study (LEADS) is a cross-sectional population-based study of patients with type 1 and type 2 diabetes in a multi-ethnic region of Sydney, Australia, to determine the population prevalence of OCT-defined DME, how this varies by ethnicity and association with systemic factors. This report describes the rationale, methodology and study aims. RESULTS: To date 646 patients out of an expected sample size of 2000 have been recruited. Baseline data are presented for patients with type 1 (n=75, 11.8%) and type 2 (n=562, 88.2%) diabetes recruited to date. Patients with type 1 diabetes were younger (39.5vs60.7 years), with longer duration of diabetes (18.1vs11.7 years), slightly worse glycaemic control (HbA1c 9.0vs8.3), and less likely to have hypertension (30.7vs71.4%), hypercholesterolaemia (33.3vs74.6%) and obesity (31.1vs51.5%, respectively, all p<0.05). CONCLUSIONS: The LEADS will provide objective estimates of the population prevalence of DME, how this varies with ethnicity and associations with systemic disease.

Three-dimensional indices of renal perfusion in normal pregnancy and pre-eclampsia.

INTRODUCTION: We compared renal perfusion in normal pregnant women and women with pre-eclampsia using three-dimensional (3D) ultrasound. We measured the flow index (FI), vascular index (VI) and vascularisation flow index (VFI) which are believed to reflect vascularity and flow intensity. METHODS: Fourteen patients with normal pregnancy and 16 patients with pre-eclampsia were recruited. Imaging was conducted using a Voluson E8 machine and a 6-MHz trans-abdominal probe. The inferior border of the maternal left kidney was scanned. Volumes were acquired using 3D power Doppler angiography (3D-PDA). The FI, VI and VFI were generated using 'histogram' facility. RESULTS: Maternal characteristics between normal pregnant women and women with pre-eclampsia were not different in terms of maternal age, gestation or body mass index. Depth of insonnation was not different between groups. The FI, VI and the VFI were not different between groups. The mean (SD) for FI was 27.9 (7.4) vs. 27.1 (6.5) between women with normal pregnancy vs. women with pre-eclampsia. For VI, mean (SD) was 72.3(31.6) vs. 79.4 (28.7) respectively. For VFI, mean (SD) was 20.8 (10.8) vs. 20.8 (8.1) respectively. Using the Mann-Whitney U test, no statistical differences between groups were apparent. There was no correlation between FI measurements and maternal creatinine (Pearson's R square = 0.04; p = 0.45) or with maternal urea levels (Pearson's R square = 0.20; p = 0.10). CONCLUSION: Using 3D ultrasound, we failed to demonstrate a difference in maternal renal perfusion in normal pregnancy compared to pre-eclampsia. The lack of observed difference may be a reflection of the high variability in 3D measurements (i.e. poor investigative tool) rather than a true lack of difference in renal perfusion.

Isolated Ascites in a Monochorionic Twin after Fetoscopic Laser Ablation Is Not Necessarily Secondary to Recurrence or Anaemia: Bowel Complications in Twin-to-Twin Transfusion Syndrome after Fetoscopic Laser Ablation.

BACKGROUND/PURPOSE: We report a case study of jejunal atresia and the results of a systematic literature review of all reported cases of bowel complications occurring after fetoscopic laser ablation (FLA) for the treatment of twin-to-twin transfusion syndrome (TTTS). METHODS: A systematic literature review was performed of bowel complications after FLA for TTTS according to PRISMA guidelines. RESULTS: There are 11 published cases of small bowel atresia, 5 cases of necrotising enterocolitis (NEC), and 2 cases with foetal bowel perforations. Recipient twins were more likely to be affected by small bowel atresia (7 recipient and 4 donor cases) and NEC (3 recipient and 2 donor twins). Prenatal ultrasonographic abnormalities were demonstrated in 7 out of 9 cases with bowel atresia and in both cases of bowel perforation. The overall survival rate for neonates with bowel complications after FLA is 72%, but is much lower for co-twins at 22%. The survival rates for jejunoileal atresia and NEC are 91 and 40%, respectively. CONCLUSIONS: It is uncertain as to whether these bowel anomalies are due to bowel ischaemia associated with TTTS, the treatment with FLA, or a combination of both. Cases with prenatal abdominal ultrasonographic abnormalities after FLA should have close prenatal and postnatal assessment to detect bowel complications.

Prenatal surgery for spina bifida: a therapeutic dilemma. Proceedings of the SHINE conference, Belfast.

This is a transcript of a scientific conference on the subject of prenatal surgery for spina bifida. It represents the views of three patients, an obstetrician, a postnatal neurosurgeon, a neonatologist, a paediatric neurologist, two surgeons who practice open spina bifida foetal surgery, a fetoscopic surgeon and an obstetrician experienced in randomised trials and systematic reviews. Implications for current practice and recommendations for future research are also discussed in detail.

An Assessment of Fetal Cerebral and Hepatic Perfusion in Normal Pregnancy and Pre-Eclampsia Using Three-Dimensional Ultrasound.

BACKGROUND: Pre-eclampsia and placental causes of intrauterine growth restriction (IUGR) are part of the same spectrum of disorders. In IUGR, there is preferential shunting of blood to the fetal brain at the expense of other organs. We wanted to demonstrate that this also occurs in pre-eclampsia using three dimensional (3D) ultrasound. The 3D indices of perfusion are: flow index (FI), vascular index (VI) and vascularisation flow index (VFI) which reflect tissue vascularity and flow intensity. METHODS: Fourteen normal pregnant women and 14 with diagnosed pre-eclampsia were recruited. Scanning was conducted by 2 observers using a Voluson E8 machine. Perfusion was measured at a pre-defined position within the fetal brain and fetal liver. The power Doppler signals were quantified using the 'histogram facility' to generate 3 indices of vascularity: FI, VI and VFI. The unpaired t-test was used to compare differences between groups. The hypothesis was that fetal brain FI, VI and VFI would be similar between women with normal pregnancy and women with pre-eclampsia, but measurements would be reduced in the fetal liver in women with pre-eclampsia. RESULTS: Maternal characteristics of age, body mass index and gestation were not different between groups. The depth of insonnation did not differ between groups. Fetal cerebral perfusion was not different between women with a normal pregnancy compared to women with pre-eclampsia. The mean (SD) for FI was 22.4 (5.7) vs. 21.1 (4.3) respectively (p=0.49). For VI, the mean (SD) was as 64.7 (40.4) vs. 79.1 (27.4) respectively (p=0.28). For VFI, the mean (SD) was 14.8 (10.3) vs. 16.1 (5.5) respectively (p = 0.66). Fetal hepatic perfusion was not different between women with a normal pregnancy compared to women with pre-eclampsia. The mean (SD) for FI was 34.4 (19.9) vs. 27.8 (11.0) respectively (p = 0.28). For VI, mean (SD) was 67.6 (36.0) vs. 87.3 (25.8) respectively (p=0.11). For VFI, the mean (SD) was 19.6 (11.6) vs. 23.1 (10.6) respectively (p=0.42). CONCLUSION: Using 3D ultrasound, we were not able to demonstrate preferential shunting of blood to the fetal brain at the expense of the fetal liver. Due to the high variability of our data, no definite conclusions can be derived from this work. A larger study may be required.

Fetal umbilical artery Doppler pulsatility index and childhood neurocognitive outcome at 12†years.

OBJECTIVE: To determine whether an elevated fetal umbilical artery Doppler (UAD) pulsatility index (PI) at 28 weeks' gestation, in the absence of fetal growth restriction (FGR) and prematurity, is associated with adverse neurocognitive outcome in children aged 12 years. METHODS: Prospective cohort study, comparing children with a normal fetal UAD PI (<90th centile) (n=110) and those with an elevated PI (≥90th centile) (n=40). UAD was performed at 28, 32 and 34 weeks gestation. At 12 years of age, all children were assessed under standardised conditions at Queen's University, Belfast, UK to determine cognitive and behavioural outcomes using the British Ability Score-II and Achenbach Child Behavioural Checklist Parent Rated Version under standardised conditions. Regression analysis was performed, controlling for confounders such as gender, socioeconomic status and age at assessment. RESULTS: The mean age of follow-up was 12.4 years (±0.5 SD) with 44% of children male (n=63). When UAD was assessed at 28 weeks, the elevated fetal UAD group had lower scores in cognitive assessments of information processing and memory. Parameters included (1) recall of objects immediate verbal (p=0.002), (2) delayed verbal (p=0.008) and (3) recall of objects immediate spatial (p=0.0016). There were no significant differences between the Doppler groups at 32 or 34 weeks' gestation. CONCLUSIONS: An elevated UAD PI at 28 weeks' gestation in the absence of FGR or prematurity is associated with lower scores of declarative memory in children aged 12 years. A potential explanation for this is an element of placental insufficiency in the presence of the appropriately grown fetus, which affects the development of the fetal hippocampus and information processing and memory long-term. These findings, however, had no impact on overall academic ability, mental processing and reasoning or overall behavioural function.

Intervention versus a conservative approach in the management of TRAP sequence: a systematic review.

OBJECTIVE: In the management of twin reversed arterial perfusion (TRAP) sequence, we wished to (i) determine if intervention is better than a conservative approach and (ii) assess if any of the apparent adverse prognostic indicators could guide intervention. METHODS: A systematic review was conducted between 1994 and 2014. Data extracted were inspected for heterogeneity. Overall rates and confidence intervals (CIs) for each prognostic factor were calculated. Where there were comparative data, the odds ratio (OR) was calculated. RESULTS: Twenty-six studies were included in the review. When all cases were considered, intervention either by cord occlusion or by ablation conferred a better survival rate compared with conservative management (OR=2.22, 95% CI 1.23-4.01, heterogeneity I2=37%, P=0.008). This difference was greater in the presence of one or more poor prognostic features (OR=8.58, 95% CI 1.47-49.96, heterogeneity I2=0%, P=0.02). Survival was better using ablative techniques compared to cord occlusion (OR=9.84, 95% CI 1.56-62.00, heterogeneity I2=0%, P=0.01). CONCLUSION: Intervention either by cord occlusion or by ablation confers a better survival rate compared to conservative management. This appears more compelling if there are one or more poor prognostic features. Ablative techniques are superior to cord occlusion. There were insufficient data to determine which poor prognostic features should guide management.

Do Regular Ultrasound Scans Reduce the Incidence of Stillbirth in Women with Apparently Normal Pregnancies?

OBJECTIVE: To determine the incidence of stillbirth in women who have regular ante-natal ultrasound compared to those that have infrequent scans in a low risk population. STUDY DESIGN: A retrospective observational study was performed in a tertiary center with 5,700 deliveries per annum. Data on all deliveries was collected via the Northern Ireland Maternity System Database. Only women with an apparently low risk pregnancy were included. Women who had private antenatal care often had frequent scans in the third trimester. Women who did not have private antenatal care often had scans infrequently. The still birth rate was calculated for both groups of women from 2007 to 2011 and compared using a Chi-squared analysis. RESULTS: Our study included 23,519 'low-risk' deliveries spanning 2007-2011. This included 2,088 (9%) patients who had frequent ultrasound surveillance and delivery at term and 21,431 (91%) patients who did not. The overall stillbirth rate was 0.34% and 0.20% respectively which was not statistically different (p=0.31). CONCLUSION: There is no difference in the rate of stillbirth between patients who have more frequent ante-natal ultrasound surveillance compared with those who do not in a low risk population.

Clinical significance of incident hypokalemia and hyperkalemia in treated hypertensive patients in the antihypertensive and lipid-lowering treatment to prevent heart attack trial.

Concerns exist that diuretic-induced changes in serum potassium may have adverse effects in hypertensive patients. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, a large practice-based clinical trial, made it possible to examine consequences of observed changes in potassium during care in conventional practice settings. Normokalemic participants randomized to chlorthalidone (C) versus amlodipine or lisinopril as a first-step drug were stratified by year-1 potassium. Postyear-1 outcomes among hypokalemics (potassium, <3.5 mmol/L) and hyperkalemics (potassium, >5.4 mmol/L) were compared with normokalemics (potassium, 3.5-5.4 mmol/L). Year-1 hypokalemia incidence was 6.8%; incidence in C (12.9%) differed from amlodipine (2.1%; P<0.001) and lisinopril (1.0%; P<0.01). Hyperkalemia incidence (2.0%) was greater in lisinopril (3.6%) than in C (1.2%; P<0.01) or amlodipine (1.9%; P<0.01). Coronary heart disease occurred in 8.1% with hypokalemia, 8.0% with normokalemia, and 11.1% with hyperkalemia. Overall, mortality was higher in hypokalemics than in normokalemics (Cox hazard ratio, 1.21 [95% CI, 1.02-1.44]) with statistically significant (interaction, P<0.01) disparity in hazard ratios for the 3 treatment arms (hazard ratios, C=1.21, amlodipine=1.60, lisinopril=3.82). Hyperkalemia was associated with increased risk of combined cardiovascular disease (hazard ratio, 1.58 [95% CI, 1.15-2.18]) without significant treatment interactions. In conventional practice settings, the uncommon appearance of hyperkalemia was associated with increased cardiovascular disease risk. Hypokalemia was associated with increased mortality; however, the statistically significant heterogeneity in hazard ratios across treatment groups strongly suggests that the observed increase in mortality is unrelated to the specific effects of C. Thus, for most patients, concerns about potassium levels should not influence the clinician's decision about initiating hypertension treatment with low-moderate doses of thiazide diuretics (12.5-25.0 mg of C).

Mortality and morbidity during and after the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

A randomized, double-blind, active-controlled, multicenter trial assigned 32,804 participants aged 55 years and older with hypertension and ≥ 1 other coronary heart disease risk factors to receive chlorthalidone (n=15,002), amlodipine (n=8898), or lisinopril (n=8904) for 4 to 8 years, when double-blinded therapy was discontinued. Passive surveillance continued for a total follow-up of 8 to 13 years using national administrative databases to ascertain deaths and hospitalizations. During the post-trial period, fatal outcomes and nonfatal outcomes were available for 98% and 65% of participants, respectively, due to lack of access to administrative databases for the remainder. This paper assesses whether mortality and morbidity differences persisted or new differences developed during the extended follow-up. Primary outcome was cardiovascular mortality and secondary outcomes were mortality, stroke, coronary heart disease, heart failure, cardiovascular disease, and end-stage renal disease. For the post-trial period, data are not available on medications or blood pressure levels. No significant differences (P<.05) appeared in cardiovascular mortality for amlodipine (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.93-1.06) or lisinopril (HR, 0.97; CI, 0.90-1.03), each compared with chlorthalidone. The only significant differences in secondary outcomes were for heart failure, which was higher with amlodipine (HR, 1.12; CI, 1.02-1.22), and stroke mortality, which was higher with lisinopril (HR, 1.20; CI, 1.01-1.41), each compared with chlorthalidone. Similar to the previously reported in-trial result, there was a significant treatment-by-race interaction for cardiovascular disease for lisinopril vs chlorthalidone. Black participants had higher risk than non-black participants taking lisinopril compared with chlorthalidone. After accounting for multiple comparisons, none of these results were significant. These findings suggest that neither calcium channel blockers nor angiotensin-converting enzyme inhibitors are superior to diuretics for the long-term prevention of major cardiovascular complications of hypertension.

An assessment of vascularity and flow intensity of the placenta in normal pregnancy and pre-eclampsia using three-dimensional ultrasound.

OBJECTIVE: To test the hypothesis that parameters of vascularity and flow intensity of the placenta as determined by three-dimensional (3D) ultrasound, (1) are different in normal pregnancy compared to pre-eclampsia (2) decrease from the basal plate towards the chorionic plate. METHODS: Twenty women with normal pregnancy and 17 women with pre-eclampisa were studied. 3D power Doppler ultrasound was used to acquire individual placental volumes. Rotational measurements of placental volumes were acquired using virtual organ computer aided analysis (VOCAL). The power Doppler signals were then semi-quantified within 'histogram facility', which generates three vascularity and flow intensity parameters: flow index (FI), vascular index (VI) and vascularisation flow index (VFI). RESULTS: FI, VI and VFI were lower in pre-eclampsia compared to normal pregnancy in all regions of the placenta. This difference was statistically significant in most regions of the placenta after accounting for gestational age, body mass index and placental site. We were not able to demonstrate a decreasing gradient of these parameters from basal plate to chorionic plate. CONCLUSION: 3D ultrasound to assess placental vascularity and flow intensity appears to be an interesting research tool. However, other indices derived from Power Doppler may be more relevant to obstetric practice.

Prognosis of isolated mild to moderate fetal cerebral ventriculomegaly: a systematic review.

AIMS: To ascertain risk of aneuploidy, infection and neurological abnormality for the fetus diagnosed with isolated mild (10.1-12.0 mm) to moderate (12.1-15.0 mm) cerebral ventriculomegaly and to compare the neurological outcome between symmetrical vs. asymmetrical and stable vs. progressive ventriculomegaly. METHODS: A systematic review was conducted. Literature was identified by searching two bibliographical databases between 1980 and 2009 without language restrictions. The data extracted were inspected for heterogeneity. Overall rates and confidence intervals (CIs) for each prognostic factor were calculated. When comparative data existed, the odds ratio (OR) was calculated. RESULTS: The search strategy yielded 2150 relevant citations of which 28 studies were included in the review. The overall rate of infection and chromosomal abnormality was 1.5 and 5% (95% CI 3, 7), respectively. The risk of neurological abnormality regardless of karyotype or infection screen was 14% (95% CI 10, 18) and this reduced to 12% (95% CI 9, 15) when both chromosomes and infection screen were normal. The risk of neurological abnormality was significantly lower in stable compared to progressive ventriculomegaly [OR 0.29 (95% CI 0.15, 0.58)]. No significant differences were detected when symmetrical vs. asymmetrical ventriculomegaly were compared [OR 0.91 (95% CI 0.34, 2.41)]. CONCLUSION: This systematic review provides the physician with some estimates of prognosis in cases of isolated mild to moderate ventriculomegaly.