Transesophageal echocardiography in children: New peephole to the heart

Markers of inflammation, including plasma C-reactive protein (CRP), are associated with an increased risk of cardiovascular disease, and it has been suggested that this association is causal. However, the relationship between inflammation and cardiovascular disease has not been extensively studied in patients with chronic kidney disease. To evaluate this, we used data from the Study of Heart and Renal Protection (SHARP) to assess associations between circulating CRP and LDL cholesterol levels and the risk of vascular and non-vascular outcomes. Major vascular events were defined as nonfatal myocardial infarction, cardiac death, stroke or arterial revascularization, with an expanded outcome of vascular events of any type. Higher baseline CRP was associated with an increased risk of major vascular events (hazard ratio per 3x increase 1.28; 95% confidence interval 1.19-1.38). Higher baseline LDL cholesterol was also associated with an increased risk of major vascular events (hazard ratio per 0.6 mmol/L higher LDL cholesterol; 1.14, 1.06-1.22). Higher baseline CRP was associated with an increased risk of a range of non-vascular events (1.16, 1.12-1.21), but there was a weak inverse association between baseline LDL cholesterol and non-vascular events (0.96, 0.92-0.99). The efficacy of lowering LDL cholesterol with simvastatin/ezetimibe on major vascular events, in the randomized comparison, was similar irrespective of CRP concentration at baseline. Thus, decisions to offer statin-based therapy to patients with chronic kidney disease should continue to be guided by their absolute risk of atherosclerotic events. Estimation of such risk may include plasma biomarkers of inflammation, but there is no evidence that the relative beneficial effects of reducing LDL cholesterol depends on plasma CRP concentration

Impact of CKD on Household Income

Introduction The impact of chronic kidney disease (CKD) on income is unclear. We sought to determine whether CKD severity, serious adverse events, and CKD progression affected household income. Methods Analyses were undertaken in a prospective cohort of adults with moderate-to-severe CKD in the Study of Heart and Renal Protection (SHARP), with household income information available at baseline screening and study end. Logistic regressions, adjusted for sociodemographic characteristics, smoking, and prior diseases at baseline, estimated associations during the 5-year follow-up, among (i) baseline CKD severity, (ii) incident nonfatal serious adverse events (vascular or cancer), and (iii) CKD treatment modality (predialysis, dialysis, or transplanted) at study end and the outcome “fall into relative poverty.” This was defined as household income <50% of country median income. Results A total of 2914 SHARP participants from 14 countries were included in the main analysis. Of these, 933 (32%) were in relative poverty at screening; of the remaining 1981, 436 (22%) fell into relative poverty by study end. Compared with participants with stage 3 CKD at baseline, the odds of falling into poverty were 51% higher for those with stage 4 (odds ratio [OR]: 1.51; 95% confidence interval [CI]: 1.09–2.10), 66% higher for those with stage 5 (OR: 1.66; 95% CI: 1.11–2.47), and 78% higher for those on dialysis at baseline (OR: 1.78, 95% CI: 1.22–2.60). Participants with kidney transplant at study end had approximately half the risk of those on dialysis or those with CKD stages 3 to 5. Conclusion More advanced CKD is associated with increased odds of falling into poverty. Kidney transplantation may have a role in reducing this risk

Lee Silverman voice treatment versus NHS speech and language therapy versus control for dysarthria in people with Parkinson's disease (PD COMM): pragmatic, UK based, multicentre, three arm, parallel group, unblinded, randomised controlled trial

To assess the clinical effectiveness of two speech and language therapy approaches versus no speech and language therapy for dysarthria in people with Parkinson's disease. Pragmatic, UK based, multicentre, three arm, parallel group, unblinded, randomised controlled trial. The speech and language therapy interventions were delivered in outpatient or home settings between 26 September 2016 and 16 March 2020. 388 people with Parkinson's disease and dysarthria. Participants were randomly assigned to one of three groups (1:1:1): 130 to Lee Silverman voice treatment (LSVT LOUD), 129 to NHS speech and language therapy, and 129 to no speech and language therapy. LSVT LOUD consisted of four, face-to-face or remote, 50 min sessions each week delivered over four weeks. Home based practice activities were set for up to 5-10 mins daily on treatment days and 15 mins twice daily on non-treatment days. Dosage for the NHS speech and language therapy was determined by the local therapist in response to the participants' needs (estimated from prior research that NHS speech and language therapy participants would receive an average of one session per week over six to eight weeks). Local practices for NHS speech and language therapy were accepted, except for those within the LSVT LOUD protocol. Analyses were based on the intention to treat principle. The primary outcome was total score at three months of self-reported voice handicap index. People who received LSVT LOUD reported lower voice handicap index scores at three months after randomisation than those who did not receive speech and language therapy (-8.0 points (99% confidence interval -13.3 to -2.6); P<0.001). No evidence suggests a difference in voice handicap index scores between NHS speech and language therapy and no speech and language therapy (1.7 points (-3.8 to 7.1); P=0.43). Patients in the LSVT LOUD group also reported lower voice handicap index scores than did those randomised to NHS speech and language therapy (-9.6 points (-14.9 to -4.4); P<0.001). 93 adverse events (predominately vocal strain) were reported in the LSVT LOUD group, 46 in the NHS speech and language therapy group, and none in the no speech and language therapy group. No serious adverse events were recorded. LSVT LOUD was more effective at reducing the participant reported impact of voice problems than was no speech and language therapy and NHS speech and language therapy. NHS speech and language therapy showed no evidence of benefit compared with no speech and language therapy. ISRCTN registry ISRCTN12421382. [Abstract copyright: © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Lee Silverman Voice Treatment versus NHS Speech and Language Therapy versus control for dysarthria in Parkinson’s disease (PD COMM):a UK, multicentre, pragmatic, randomised controlled trial

Objectives: We aimed to assess the clinical effectiveness of two speech and language therapy (SLT) approaches versus no speech and language therapy for dysarthria in people with Parkinson’s disease. Design: This was a pragmatic, UK-wide, multicentre, three-arm, parallel group, unblinded, randomised controlled trial. Participants were randomly assigned using minimisation in a 1:1:1 ratio to Lee Silverman Voice Treatment (LSVT LOUD®), NHS SLT, or no SLT. Analyses were based on the intention to treat principle.Setting: The speech and language therapy interventions were delivered in outpatient or home settings.Participants: Between September 2016 and March 2020, 388 people with Parkinson’s disease and dysarthria were randomised into the trial: 130 to LSVT LOUD®, 129 to NHS SLT, and 129 to no SLT.Interventions: Lee Silverman Voice Treatment (LSVT LOUD®) consisted of four, face-to-face or remote, 50-minute sessions each week delivered over 4 weeks. Home-based practice activities were set for up to 5 to 10 minutes daily on treatment days and 15 minutes twice daily on non-treatment days. NHS Speech and language therapy (NHS SLT) dosage was determined by the local therapist in response to individual participants’ needs. Prior research suggested that NHS SLT participants would receive an average of one session per week over 6 to 8 weeks. Local practices for NHS SLT were accepted, except for those within the LSVT LOUD® protocol. Main outcome measures: The primary outcome was the self-reported Voice Handicap Index (VHI) total score at 3 months.Results: People randomised to LSVT LOUD® reported lower VHI scores at 3 months post-randomisation than those who were randomised to no SLT (-8·0 points (99%CI: -13·3 to -2·6); p = 0·0001). There was no evidence of a difference in VHI scores between NHS SLT and no SLT (1·7 points; (99%Cl: -3·8 to 7·1); p = 0·43). Patients randomised to LSVT LOUD® also reported lower VHI scores than those randomised to NHS SLT (-9·6 points; (99%CI: -14·9 to -4·4); p &lt; 0.0001). There were 93 adverse events (predominately vocal strain) in the LSVT LOUD® group, 46 in the NHS SLT group, and none in the no SLT group. There were no serious adverse events. Conclusions: LSVT LOUD® was more effective at reducing the participant reported impact of voice problems than no SLT and NHS SLT. NHS SLT showed no evidence of benefit compared to no SLT. Trial registration: The completed trial registration is ISRCTN12421382. Funding: NIHR HTA Programme, project number HTA 10/135/02. <br/

Prognostic utility of estimated albumin excretion rate in chronic kidney disease: results from the Study of Heart and Renal Protection

BACKGROUND: Estimated albumin excretion rate (eAER) provides a better estimate of 24-h albuminuria than albumin:creatinine ratio (ACR). However, whether eAER is superior to ACR in predicting end-stage renal disease (ESRD), vascular events (VEs) or death is uncertain. METHODS: The prognostic utility of ACR and eAER (estimated from ACR, sex, age and race) to predict mortality, ESRD and VEs was compared using Cox proportional hazards regression among 5552 participants with chronic kidney disease in the Study of Heart and Renal Protection, who were not on dialysis at baseline. RESULTS: During a median follow-up of 4.8 years, 1959 participants developed ESRD, 1204 had a VE and 1130 died (641 from a non-vascular, 369 from a vascular and 120 from an unknown cause). After adjustment for age, sex and eGFR, both ACR and eAER were strongly and similarly associated with ESRD risk. The average relative risk (RR) per 10-fold higher level was 2.70 (95% confidence interval 2.45-2.98) for ACR and 2.67 (2.43-2.94) for eAER. Neither ACR nor eAER provided any additional prognostic information for ESRD risk over and above the other. For VEs, there were modest positive associations between both ACR and eAER and risk [adjusted RR per 10-fold higher level 1.37 (1.22-1.53) for ACR and 1.36 (1.22-1.52) for eAER]. Again, neither measure added prognostic information over and above the other. Similar results were observed when ACR and eAER were related to vascular mortality [RR per 10-fold higher level: 1.64 (1.33-2.03) and 1.62 (1.32-2.00), respectively] or to non-vascular mortality [1.53 (1.31-1.79) and 1.50 (1.29-1.76), respectively]. CONCLUSIONS: In this study, eAER did not improve risk prediction of ESRD, VEs or mortality

Strategies to improve retention in randomised trials.

Loss to follow-up from randomised trials can introduce bias and reduce study power, affecting the generalisability, validity and reliability of results. Many strategies are used to reduce loss to follow-up and improve retention but few have been formally evaluated

Laparoscopic resection of a residual retroperitoneal tumor mass of nonseminomatous testicular germ cell tumors

Resection of a residual retroperitoneal tumor mass (RRRTM) is standard procedure after combination chemotherapy for metastatic nonseminomatous testicular germ cell tumors (NSTGCT). At the University Medical Center Groningen, 79 consecutive patients with disseminated NSTGCT were treated with cisplatin combination chemotherapy between 2005 and 2007. Laparoscopic RRRTM was performed for patients with RRTM located less than 5 cm ventrally or laterally from the aorta or the vena cava. The 29 patients who fulfilled the criteria had a median age of 25 years (range, 16-59 years). The stages of disease before chemotherapy treatment according to the Royal Marsden classification were 2A (n = 6, 21%), 2B (n = 14, 48%), 2C (n = 3, 10%), and 4 with a lymph node status of N2 (n = 6, 21%). The median duration of laparoscopy was 198 min (range, 122-325 min). The median diameter of the RRTM was 21 mm (range, 11-47 mm). Laparoscopic resection was successful for 25 patients (86%). Conversion was necessary for three patients (10%): two due to bleeding and one because of obesity. One nonplanned hand-assisted procedure (3%) also had to be performed. Histologic examination of the specimens showed fibrosis or necrosis in 12 patients (41%), mature teratoma in 16 patients (55%), and viable tumor in 1 patient (3%). The median hospital stay was 1 day (range, 1-6 days). During a median follow-up period of 47 months (29-70 months), one patient experienced an early relapse (1 month after the end of treatment) (4%). For properly selected patients, laparoscopic resection of RRTM is an improvement in the combined treatment of disseminated NSTGCT and associated with a short hospital stay, minimal morbidity, rapid recovery, and a neat cosmetic result. Long-term data to prove oncologic efficacy are awaited

Brain age predicts mortality

Age-associated disease and disability are placing a growing burden on society. However, ageing does not affect people uniformly. Hence, markers of the underlying biological ageing process are needed to help identify people at increased risk of age-associated physical and cognitive impairments and ultimately, death. Here, we present such a biomarker, ‘brain-predicted age’, derived using structural neuroimaging. Brain-predicted age was calculated using machine-learning analysis, trained on neuroimaging data from a large healthy reference sample (N = 2001), then tested in the Lothian Birth Cohort 1936 (N = 669), to determine relationships with age-associated functional measures and mortality. Having a brain-predicted age indicative of an older-appearing brain was associated with: weaker grip strength, poorer lung function, slower walking speed, lower fluid intelligence, higher allostatic load and increased mortality risk. Furthermore, while combining brain-predicted age with grey matter and cerebrospinal fluid volumes (themselves strong predictors) not did improve mortality risk prediction, the combination of brain-predicted age and DNA-methylation-predicted age did. This indicates that neuroimaging and epigenetics measures of ageing can provide complementary data regarding health outcomes. Our study introduces a clinically-relevant neuroimaging ageing biomarker and demonstrates that combining distinct measurements of biological ageing further helps to determine risk of age-related deterioration and death

Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease

Background: Researchers have suggested that omega-3 polyunsaturated fatty acids from oily fish (long-chain omega-3 (LCn3), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), as well as from plants (alpha-linolenic acid (ALA)) benefit cardiovascular health. Guidelines recommend increasing omega-3-rich foods, and sometimes supplementation, but recent trials have not confirmed this. Objectives: To assess effects of increased intake of fish- and plant-based omega-3 for all-cause mortality, cardiovascular (CVD) events, adiposity and lipids. Search methods: We searched CENTRAL, MEDLINE and Embase to April 2017, plus ClinicalTrials.gov and World Health Organization International Clinical Trials Registry to September 2016, with no language restrictions. We handsearched systematic review references and bibliographies and contacted authors. Selection criteria: We included randomised controlled trials (RCTs) that lasted at least 12 months and compared supplementation and/or advice to increase LCn3 or ALA intake versus usual or lower intake. Data collection and analysis: Two review authors independently assessed studies for inclusion, extracted data and assessed validity. We performed separate random-effects meta-analysis for ALA and LCn3 interventions, and assessed dose-response relationships through meta-regression. Main results: We included 79 RCTs (112,059 participants) in this review update and found that 25 were at low summary risk of bias. Trials were of 12 to 72 months' duration and included adults at varying cardiovascular risk, mainly in high-income countries. Most studies assessed LCn3 supplementation with capsules, but some used LCn3- or ALA-rich or enriched foods or dietary advice compared to placebo or usual diet. Meta-analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all-cause mortality (RR 0.98, 95% CI 0.90 to 1.03, 92,653 participants; 8189 deaths in 39 trials, high-quality evidence), cardiovascular mortality (RR 0.95, 95% CI 0.87 to 1.03, 67,772 participants; 4544 CVD deaths in 25 RCTs), cardiovascular events (RR 0.99, 95% CI 0.94 to 1.04, 90,378 participants; 14,737 people experienced events in 38 trials, high-quality evidence), coronary heart disease (CHD) mortality (RR 0.93, 95% CI 0.79 to 1.09, 73,491 participants; 1596 CHD deaths in 21 RCTs), stroke (RR 1.06, 95% CI 0.96 to 1.16, 89,358 participants; 1822 strokes in 28 trials) or arrhythmia (RR 0.97, 95% CI 0.90 to 1.05, 53,796 participants; 3788 people experienced arrhythmia in 28 RCTs). There was a suggestion that LCn3 reduced CHD events (RR 0.93, 95% CI 0.88 to 0.97, 84,301 participants; 5469 people experienced CHD events in 28 RCTs); however, this was not maintained in sensitivity analyses - LCn3 probably makes little or no difference to CHD event risk. All evidence was of moderate GRADE quality, except as noted. Increasing ALA intake probably makes little or no difference to all-cause mortality (RR 1.01, 95% CI 0.84 to 1.20, 19,327 participants; 459 deaths, 5 RCTs),cardiovascular mortality (RR 0.96, 95% CI 0.74 to 1.25, 18,619 participants; 219 cardiovascular deaths, 4 RCTs), and it may make little or no difference to CHD events (RR 1.00, 95% CI 0.80 to 1.22, 19,061 participants, 397 CHD events, 4 RCTs, low-quality evidence). However, increased ALA may slightly reduce risk of cardiovascular events (from 4.8% to 4.7%, RR 0.95, 95% CI 0.83 to 1.07, 19,327 participants; 884 CVD events, 5 RCTs, low-quality evidence), and probably reduces risk of CHD mortality (1.1% to 1.0%, RR 0.95, 95% CI 0.72 to 1.26, 18,353 participants; 193 CHD deaths, 3 RCTs), and arrhythmia (3.3% to 2.6%, RR 0.79, 95% CI 0.57 to 1.10, 4,837 participants; 141 events, 1 RCT). Effects on stroke are unclear. Sensitivity analysis retaining only trials at low summary risk of bias moved effect sizes towards the null (RR 1.0) for all LCn3 primary outcomes except arrhythmias, but for most ALA outcomes, effect sizes moved to suggest protection. LCn3 funnel plots suggested that adding in missing studies/results would move effect sizes towards null for most primary outcomes. There were no dose or duration effects in subgrouping or meta-regression. There was no evidence that increasing LCn3 or ALA altered serious adverse events, adiposity or lipids, although LCn3 slightly reduced triglycerides and increased HDL. ALA probably reduces HDL (high- or moderate-quality evidence). Authors' conclusions: This is the most extensive systematic assessment of effects of omega-3 fats on cardiovascular health to date. Moderate- and high-quality evidence suggests that increasing EPA and DHA has little or no effect on mortality or cardiovascular health (evidence mainly from supplement trials). Previous suggestions of benefits from EPA and DHA supplements appear to spring from trials with higher risk of bias. Low-quality evidence suggests ALA may slightly reduce CVD event risk, CHD mortality and arrhythmia