Regular Acetaminophen Use and Blood Pressure in People With Hypertension: The PATH-BP Trial.

BACKGROUND: Acetaminophen is widely used as first-line therapy for chronic pain because of its perceived safety and the assumption that, unlike nonsteroidal anti-inflammatory drugs, it has little or no effect on blood pressure (BP). Although observational studies suggest that acetaminophen may increase BP, clinical trials are lacking. We, therefore, studied the effects of regular acetaminophen dosing on BP in individuals with hypertension. METHODS: In this double-blind, placebo-controlled, crossover study, 110 individuals were randomized to receive 1 g acetaminophen 4× daily or matched placebo for 2 weeks followed by a 2-week washout period before crossing over to the alternate treatment. At the beginning and end of each treatment period, 24-hour ambulatory BPs were measured. The primary outcome was a comparison of the change in mean daytime systolic BP from baseline to end of treatment between the placebo and acetaminophen arms. RESULTS: One-hundred three patients completed both arms of the study. Regular acetaminophen, compared with placebo, resulted in a significant increase in mean daytime systolic BP (132.8±10.5 to 136.5±10.1 mm Hg [acetaminophen] vs 133.9±10.3 to 132.5±9.9 mm Hg [placebo]; P<0.0001) with a placebo-corrected increase of 4.7 mm Hg (95% CI, 2.9-6.6) and mean daytime diastolic BP (81.2±8.0 to 82.1±7.8 mm Hg [acetaminophen] vs 81.7±7.9 to 80.9±7.8 mm Hg [placebo]; P=0.005) with a placebo-corrected increase of 1.6 mm Hg (95% CI, 0.5-2.7). Similar findings were seen for 24-hour ambulatory and clinic BPs. CONCLUSIONS: Regular daily intake of 4 g acetaminophen increases systolic BP in individuals with hypertension by ≈5 mm Hg when compared with placebo; this increases cardiovascular risk and calls into question the safety of regular acetaminophen use in this situation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01997112. URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2013-003204-40.

Quantification of human urinary exosomes by nanoparticle tracking analysis.

Exosomes are vesicles that are released from the kidney into urine. They contain protein and RNA from the glomerulus and all sections of the nephron and represent a reservoir for biomarker discovery. Current methods for the identification and quantification of urinary exosomes are time consuming and only semi-quantitative. Nanoparticle tracking analysis (NTA) counts and sizes particles by measuring their Brownian motion in solution. In this study, we applied NTA to human urine and identified particles with a range of sizes. Using antibodies against the exosomal proteins CD24 and aquaporin 2 (AQP2), conjugated to a fluorophore, we could identify a subpopulation of CD24- and AQP2-positive particles of characteristic exosomal size. Extensive pre-NTA processing of urine was not necessary. However, the intra-assay variability in the measurement of exosome concentration was significantly reduced when an ultracentrifugation step preceded NTA. Without any sample processing, NTA tracked exosomal AQP2 upregulation induced by desmopressin stimulation of kidney collecting duct cells. Nanoparticle tracking analysis was also able to track changes in exosomal AQP2 concentration that followed desmopressin treatment of mice and a patient with central diabetes insipidus. When urine was stored at room temperature, 4°C or frozen, nanoparticle concentration was reduced; freezing at -80°C with the addition of protease inhibitors produced the least reduction. In conclusion, with appropriate sample storage, NTA has potential as a tool for the characterization and quantification of extracellular vesicles in human urine.

Assessing and addressing cardiovascular risk in adults with Turner syndrome.

UNLABELLED: Turner syndrome (TS), the result of a structurally abnormal or absent X chromosome, occurs in one in 2 000 live born females. The phenotype is highly variable, but short stature and gonadal dysgenesis are usually present. The main objective in adults with TS is health surveillance, but TS still causes a reduction in life expectancy of up to 13 years, with cardiovascular disease, congenital or acquired, as the major cause of an early death. While it has been established that all women with TS should undergo in-depth cardiovascular examination at diagnosis, advice on the cardiovascular management of women with TS is limited. Here, we provide a summary of our current practice within a multidisciplinary team, supported by our expertise in various aspects of cardiovascular risk management, and the evidence from research where it is available, with the aim of providing optimal support to our patients with TS. BACKGROUND: A dedicated Adult Turner Clinic was established in South East Scotland in 2002. This gynaecology-led clinic serves a population of roughly 1·2 million and, currently, reviews around 50 women with TS annually. Referrals for adult care come from paediatrics or general practice. Following a series of individual case discussions regarding the management of more complex cardiovascular problems, we have assembled a dedicated multidisciplinary group to determine a timely cardiovascular screening strategy, a basis for specialist referral, and appropriate hypertension management. This team now includes a paediatric endocrinologist, gynaecologist, cardiologist (with an interest in inherited disorders), vascular radiologist and hypertension specialist. Here, we review the literature on cardiovascular disease in women with TS and, make recommendations, based on relatively limited high-quality evidence, together with our experience, on the optimal timing of cardiovascular screening.

A systematic review of the effect of paracetamol on blood pressure in hypertensive and non-hypertensive subjects.

AIM: To review current evidence on the effect of paracetamol on blood pressure (BP), the quality of the previous studies and the validity of the results, and to summarize these findings. METHODS: A systematic literature review was performed by searching PubMed, the Cochrane library and EMBASE for publications between the years 1963 and 2012. RESULTS: We identified three case reports, seven prospective observational trials, six randomized controlled trials, one commentary and two reviews. Some, but not all, of the observational studies, which included over 147 000 patients, showed an increased risk of hypertension with paracetamol use. The randomized studies were generally small and the results were inconsistent. Three studies, which included 104 patients, showed an increase of systolic BP by ~4 mmHg, two studies, which included 27 patients, reported no change in BP and one study, which included 21 patients, reported a fall in BP although no placebo arm was included for comparison. CONCLUSIONS: The overall effect of paracetamol on BP is unclear. Given that paracetamol is often suggested as a safer alternative to non-steroidal anti-inflammatory drugs (NSAIDs), it would seem that further prospective evidence is now needed to address the effect of paracetamol on BP. This would be best done with larger studies in relevant cohorts using BP measured by ambulatory BP monitoring as the primary endpoint.

Development and evaluation of a regional diabetes service App for patient education, self-management and clinic engagement.

BACKGROUND: We created a free NHS App to deliver all patient information on type 1 diabetes to help promote self-management. This became an invaluable way of getting information to patients during the pandemic when all face-to-face clinics were suspended. The aim of this study is to investigate patient perceptions of the App. METHODS: A questionnaire-based cross-sectional study was designed by the diabetes team to obtain quantitative data. RESULTS: The mean score of patient accessibility to diabetes information and services before using the App was 5.1, and after using the App was 8.8 (p < 0.001). Among the patients, 91% would recommend the App, 57.2% agree the App helps them schedule and attend their screening appointments and 73.7% agree the App has improved their self-management of type 1 diabetes. CONCLUSION: Patients agree the App has improved accessibility to diabetes information and services and has helped with self-management of their condition. Patients are likely to recommend the App to friends and family who have diabetes.