Is statin-modified reduction in lipids the most important preventive therapy for cardiovascular disease? A pro/con debate.

The most prescribed medications in the world are statins, lipid modifiers that have been available for over 25 years and amongst the most investigated of all drug classes. With over a million patient years of trial data and publications in the most prestigious medical journals, it is remarkable that quite so much debate remains as to their place in healthcare. They have had a bittersweet passage, with vocal concerns over their possible risks, from suicide to cancer, and allegations that they do not work in women or the elderly, to statements that the whole published dataset, on over 200,000 patients consenting to enter trials, was fatally compromised by being industry-funded by and large. On the other side, there have been billions of dollars spent on generating their evidence base followed by promotion which has returned that investment many times over in profits, and a powerful scientific lobby that argue they are wonder drugs and that continued nihilism on their value risks patient lives. So who is right

Detection of Lyman-alpha Emitting Galaxies at Redshift z=4.55

Studies of the formation and early history of galaxies have been hampered by the difficulties inherent in detecting faint galaxy populations at high redshift. As a consequence, observations at the highest redshifts (3.5 < z < 5) have been restricted to objects that are intrinsically bright. These include quasars, radio galaxies, and some Ly alpha-emitting objects that are very close to (within ~10 kpc) -- and appear to be physically associated with -- quasars. But the extremely energetic processes which make these objects easy to detect also make them unrepresentative of normal (field) galaxies. Here we report the discovery using Keck spectroscopic observations of two Ly alpha-emitting galaxies at redshift z = 4.55, which are sufficiently far from the nearest quasar (~700 kpc) that radiation from the quasar is unlikely to provide the excitation source of the Ly alpha emission. Instead, these galaxies appear to be undergoing their first burst of star formation, at a time when the Universe was less than one billion years old.Comment: 8 pages, 1 landscape table, and 3 PostScript figures. Uses aaspp4.sty, flushrt.sty, aj_pt4.sty, overcite.sty (style macros available from xxx.lanl.gov) Figure 1 is bitmapped to 100 dpi. The original PostScript version of Fig. 1 is available via anonymous ftp to ftp://hubble.ifa.hawaii.edu/pub/preprints To appear in Natur

Prenatal Vitamin D Supplementation and Child Respiratory Health: A Randomised Controlled Trial

PMCID: PMC3691177This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Lessons from the English primary care sentinel network's response to the COVID-19 pandemic

This Comment reflects our experience of deploying the Oxford-Royal College of General Practitioner's Research and Surveillance Centre (RSC), England's primary care sentinel network, in response to the COVID-19 pandemic

Long term changes in health-related quality of life for people with heart failure: the ECHOES study

Aims Heart failure (HF) impairs all aspects of health-related quality of life (HRQoL), but little is known about the effect of developing HF on HRQoL over time. We aimed to report changes in HRQoL over a 13-year period. Methods and results HRQoL was measured in the Echocardiographic Heart of England Screening (ECHOES) study and the ECHOES-X follow-up study (N = 1618) using the SF-36 questionnaire (Version 1). Mixed modelling compared changes in HRQoL across diagnostic groups, adjusting for potential predictors and design variables. Patients who had developed HF with reduced ejection fraction (HFrEF) or HF with preserved ejection fraction (HFpEF) at rescreening had significantly greater reduction in physical functioning (PF) and role physical (RP) scores compared with those without HF; adjusted mean difference in PF: HFrEF −16.1, [95% confidence interval (CI) −22.2 to −10.1]; HFpEF −14.6, (95% CI −21.2 to −8.1); in RP: HFrEF −20.7, (95% CI −31.8 to −9.7); HFpEF −19.3, (95% CI −31.0 to −7.6). Changes in HRQoL of those with a HF diagnosis at baseline and rescreen, with exception of role emotion, were similar to those without HF but started from a much lower baseline score. Conclusions People with a new diagnosis of HF at rescreening had a significant reduction in HRQoL. Conversely, for those with HF detected on initial screening, little change was observed in HRQoL scores on rescreening. Further research is required to understand the development of HF over time and to test interventions designed to prevent decline in HRQoL, potentially through earlier diagnosis and treatment optimization

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

Patients with Endoscopically Visible Polypoid Adenomatous Lesions Within the Extent of Ulcerative Colitis Have an Increased Risk of Colorectal Cancer Despite Endoscopic Resection.

OBJECTIVES: Ulcerative colitis (UC) is associated with an increased risk of colorectal cancer (CRC). Few studies have looked at long-term outcomes of endoscopically visible adenomatous lesions removed by endoscopic resection in these patients. We aimed to assess the risk of developing CRC in UC patients with adenomatous lesions that develop within the segment of colitis compared to the remainder of an ulcerative colitis cohort. METHODS: We identified patients with a confirmed histological diagnosis of UC from 1991 to 2004 and noted outcomes till June 2011. The Kaplan-Meier method was used to estimate cumulative probability of subsequent CRC. Factors associated with risk of CRC were assessed in a Cox proportional hazards model. RESULTS: Twenty-nine of 301 patients with UC had adenomatous lesions noted within the segment of colitis. The crude incidence rate of developing colon cancer in patients with UC was 2.45 (95 % CI 1.06-4.83) per 1000 PYD and in those with UC and polypoid adenomas within the extent of inflammation was 11.07 (95 % CI 3.59-25.83) per 1000 PYD. Adjusted hazards ratio of developing CRC on follow-up in UC patients with polypoid dysplastic adenomatous lesions within the extent of inflammation was 4.0 (95 % CI 1.3-12.4). CONCLUSIONS: The risk of developing CRC is significantly higher in UC patients with polypoid adenomatous lesions, within the extent of inflammation, despite endoscopic resection. Patients and physicians should take the increased risk into consideration during follow-up of these patients

Solonamide B Inhibits Quorum Sensing and Reduces Staphylococcus aureus Mediated Killing of Human Neutrophils

Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a serious human pathogen, and particularly the spread of community associated (CA)-MRSA strains such as USA300 is a concern, as these strains can cause severe infections in otherwise healthy adults. Recently, we reported that a cyclodepsipeptide termed Solonamide B isolated from the marine bacterium, Photobacterium halotolerans strongly reduces expression of RNAIII, the effector molecule of the agr quorum sensing system. Here we show that Solonamide B interferes with the binding of S. aureus autoinducing peptides (AIPs) to sensor histidine kinase, AgrC, of the agr two-component system. The hypervirulence of USA300 has been linked to increased expression of central virulence factors like α-hemolysin and the phenol soluble modulins (PSMs). Importantly, in strain USA300 Solonamide B dramatically reduced the activity of α-hemolysin and the transcription of psma encoding PSMs with an 80% reduction in toxicity of supernatants towards human neutrophils and rabbit erythrocytes. To our knowledge this is the first report of a compound produced naturally by a Gram-negative marine bacterium that interferes with agr and affects both RNAIII and AgrA controlled virulence gene expression in S. aureus

Association of guideline and policy changes with incidence of lifestyle advice and treatment for uncomplicated mild hypertension in Primary Care: a longitudinal cohort study in the Clinical Practice Research Datalink

Objectives Evidence to support initiation of pharmacological treatment in patients with uncomplicated (low risk) mild hypertension is inconclusive. As such, clinical guidelines are contradictory and healthcare policy has changed regularly. The aim of this study was to determine the incidence of lifestyle advice and drug therapy in this population and whether secular trends were associated with policy changes. Design Longitudinal cohort study. Setting Primary care practices contributing to the Clinical Practice Research Datalink in England. Participants Data were extracted from the linked electronic health records of patients aged 18–74 years, with stage 1 hypertension (blood pressure between 140/90 and 159/99 mm Hg), no cardiovascular disease (CVD) risk factors and no treatment, from 1998 to 2015. Patients exited if follow-up records became unavailable, they progressed to stage 2 hypertension, developed a CVD risk factor or received lifestyle advice/treatment. Primary outcome measures The association between policy changes and incidence of lifestyle advice or treatment, examined using an interrupted time-series analysis. Results A total of 108 843 patients were defined as having uncomplicated mild hypertension (mean age 51.9±12.9 years, 60.0% female). Patientsspent a median 2.6 years (IQR 0.9–5.5) in the study, after which 12.2% (95% CI 12.0% to 12.4%) were given lifestyle advice, 29.9% (95% CI 29.7% to 30.2%) were prescribed medication and 19.4% (95% CI 19.2% to 19.6%) were given both. The introduction of the quality outcomes framework (QOF) and subsequent changes to QOF indicators were followed by significant increases in the incidence of lifestyle advice. Treatment prescriptions decreased slightly over time, but were not associated with policy changes. Conclusions Despite secular trends that accord with UK guidance, many patients are still prescribed treatment for mild hypertension. Adequately powered studies are needed to determine if this is appropriate

Accuracy of monitors used for blood pressure checks in English retail pharmacies::a cross-sectional observational study

BACKGROUND: Free blood pressure (BP) checks offered by community pharmacies provide a potentially useful opportunity to diagnose and/or manage hypertension, but the accuracy of the sphygmomanometers in use is currently unknown. AIM: To assess the accuracy of validated automatic BP monitors used for BP checks in a UK retail pharmacy chain. DESIGN AND SETTING: Cross-sectional, observational study in 52 pharmacies from one chain in a range of locations (inner city, suburban, and rural) in central England. METHOD: Monitor accuracy was compared with a calibrated reference device (Omron PA-350), at 50 mmHg intervals across the range 0–300 mmHg (static pressure test), with a difference from the reference monitor of +/− 3 mmHg at any interval considered a failure. The results were analysed by usage rates and length of time in service. RESULTS: Of 61 BP monitors tested, eight (13%) monitors failed (that is, were >3 mmHg from reference), all of which underestimated BP. Monitor failure rate from the reference monitor of +/− 3 mmHg at any testing interval varied by length of time in use (2/38, 5% <18 months; 4/14, 29% >18 months, P = 0.038) and to some extent, but non-significantly, by usage rates (4/22, 18% in monitors used more than once daily; 2/33, 6% in those used less frequently, P = 0.204). CONCLUSION: BP monitors within a pharmacy setting fail at similar rates to those in general practice. Annual calibration checks for blood pressure monitors are needed, even for new monitors, as these data indicate declining performance from 18 months onwards