Who Guards the Guardians? Ian Kennedy, Bioethics and the ‘Ideology of Accountability’ in British Medicine

This article charts the history of bioethics in Britain through the work of the academic lawyer Ian Kennedy. From the late 1970s, Kennedy claimed that external oversight, which he termed ‘bioethics’, was needed to make medicine accountable to patients and the public. I believe these arguments provide a window onto the historical factors that generated the demand for bioethics, and help us determine why it became influential in recent decades. I detail how Kennedy's argument resonated with the Conservative enthusiasm for audit and consumer choice in the 1980s. Contrary to traditional portrayals of bioethics as a critique of medicine, I also show that Kennedy promised it would benefit doctors by improving decision making and maintaining public confidence. This analysis reframes bioethics as an important constituent of the ‘audit society’: fulfilling the neo-liberal demand for oversight and the medical demand for legitimacy

The Malaria-High Blood Pressure Hypothesis.

RATIONALE: Several studies have demonstrated links between infectious diseases and cardiovascular conditions. Malaria and hypertension are widespread in many low- and middle-income countries, but the possible link between them has not been considered. OBJECTIVE: In this article, we outline the basis for a possible link between malaria and hypertension and discuss how the hypothesis could be confirmed or refuted. METHODS AND RESULTS: We reviewed published literature on factors associated with hypertension and checked whether any of these were also associated with malaria. We then considered various study designs that could be used to test the hypothesis. Malaria causes low birth weight, malnutrition, and inflammation, all of which are associated with hypertension in high-income countries. The hypothetical link between malaria and hypertension can be tested through the use of ecological, cohort, or Mendelian randomization studies, each of which poses specific challenges. CONCLUSIONS: Confirmation of the existence of a causative link with malaria would be a paradigm shift in efforts to prevent and control hypertension and would stimulate wider research on the links between infectious and noncommunicable disease

Ethnic differences in and childhood influences on early adult pulse wave velocity: the determinants of adolescent, now young adult, social wellbeing, and health longitudinal study

Early determinants of aortic stiffness as pulse wave velocity are poorly understood. We tested how factors measured twice previously in childhood in a multiethnic cohort study, particularly body mass, blood pressure, and objectively assessed physical activity affected aortic stiffness in young adults. Of 6643 London children, aged 11 to 13 years, from 51 schools in samples stratified by 6 ethnic groups with different cardiovascular risk, 4785 (72%) were seen again at aged 14 to 16 years. In 2013, 666 (97% of invited) took part in a young adult (21–23 years) pilot follow-up. With psychosocial and anthropometric measures, aortic stiffness and blood pressure were recorded via an upper arm calibrated Arteriograph device. In a subsample (n=334), physical activity was measured >5 days via the ActivPal. Unadjusted pulse wave velocities in black Caribbean and white UK young men were similar (mean±SD 7.9±0.3 versus 7.6±0.4 m/s) and lower in other groups at similar systolic pressures (120 mm Hg) and body mass (24.6 kg/m2). In fully adjusted regression models, independent of pressure effects, black Caribbean (higher body mass/waists), black African, and Indian young women had lower stiffness (by 0.5–0.8; 95% confidence interval, 0.1–1.1 m/s) than did white British women (6.9±0.2 m/s). Values were separately increased by age, pressure, powerful impacts from waist/height, time spent sedentary, and a reported racism effect (+0.3 m/s). Time walking at >100 steps/min was associated with reduced stiffness (P<0.01). Effects of childhood waist/hip were detected. By young adulthood, increased waist/height ratios, lower physical activity, blood pressure, and psychosocial variables (eg, perceived racism) independently increase arterial stiffness, effects likely to increase with age

A structural comparison of salt forms of dopamine with the structures of other phenylethylamines

The structures of four salt forms of dopamine are reported. These are dopamine [2‐(3,4‐dihydroxyphenyl)ethan‐1‐aminium] benzoate, C8H12NO2+·C7H5O2−, I, dopamine 4‐nitrobenzoate, C8H12NO2+·C7H4NO4−, II, dopamine ethanedisulfonate, 2C8H12NO2+·C2H4O6S22−, III, and dopamine 4‐hydroxybenzenesulfonate monohydrate, C8H12NO2+·C6H5O4S−·H2O, IV. In all four structures, the dopamine cation adopts an extended conformation. Intermolecular interaction motifs that are common in the salt forms of tyramine can be found in related dopamine structures, but hydrogen bonding in the dopamine structures appear to be more variable and less predictable than for tyramine. Packing analysis discovered three dopamine‐containing groups of structures that can be described as isostructural with regards to the cation positions. Two of these groups contain both dopamine and tyramine species, and one of these is also highly variable in other ways too, containing anhydrous and hydrated forms, different anion types and ionized and neutral phenylethylamine species. As such, the group illustrates that packing behaviour can be robust and similar even where intermolecular interactions such as hydrogen bonds are very different

Cardiac effects of 6 months' dietary nitrate and spironolactone in patients with hypertension and with/at risk of type 2 diabetes, in the factorial design, double-blind, randomized controlled VaSera trial

Aims: The aims of the present study were to explore whether a long-term intervention with dietary nitrate [(NO 3 −), a potential tolerance-free source of beneficial vasoactive nitric oxide] and spironolactone (to oppose aldosterone's potential deleterious cardiovascular effects) improve cardiac structure/function, independently of blood pressure (BP), in patients with/at risk of type 2 diabetes (a population at risk of heart failure).Methods: A subsample of participants in our double-blind, randomized, factorial-design intervention (VaSera) trial of active beetroot juice as a nitrate source (≤11.2 mmol) or placebo (nitrate depleted) beetroot juice, and either ≤50 mg spironolactone or ≤16 mg doxazosin (control), had transthoracic cardiac ultrasounds at baseline (n = 105), and at 3 months and 6 months (n = 87) after the start of the intervention. Analysis was by modified intent-to-treat.Results: Nitrate-containing juice (n = 40) decreased left ventricular (LV) end-diastolic volume {−6.3 [95% confidence interval (CI) –11.1, –1.6] ml} and end-systolic volume [−3.2 (95% CI −5.9, –0.5) ml], and increased end-diastolic mass/volume ratio [+0.04 (95% CI 0.00, 0.07)], relative to placebo juice (n = 47). Spironolactone (n = 44) reduced relative wall thickness compared with doxazosin (n = 43) [−0.01 (95% CI −0.02, –0.00)]. Although spironolactone reduced LV mass index relative to baseline [−1.48 (95% CI −2.08, –0.88) g m –2.7], there was no difference vs. doxazosin [−0.85 (95% CI −1.76, 0.05) g m –2.7]. Spironolactone also decreased the E/A ratio [−0.12 (95% CI −0.19, –0.04)] and increased S′ (a tissue-Doppler systolic function index) by 0.52 (95% CI 0.05, 1.0) cm s –1. BP did not differ between the juices, or between the drugs.Conclusions: Six months' dietary nitrate decreased LV volumes ~5%, representing new, sustained, BP-independent benefits on cardiac structure, extending mechanisms characterized in preclinical models of heart failure. Spironolactone's effects on cardiac remodelling and systolic–diastolic function, although confirmatory, were independent of BP. </p

Clinical and Epidemiological Implications of 24-Hour Ambulatory Blood Pressure Monitoring for the Diagnosis of Hypertension in Kenyan Adults: A Population-Based Study.

BACKGROUND: The clinical and epidemiological implications of using ambulatory blood pressure monitoring (ABPM) for the diagnosis of hypertension have not been studied at a population level in sub-Saharan Africa. We examined the impact of ABPM use among Kenyan adults. METHODS AND RESULTS: We performed a nested case-control study of diagnostic accuracy. We selected an age-stratified random sample of 1248 adults from the list of residents of the Kilifi Health and Demographic Surveillance System in Kenya. All participants underwent a screening blood pressure (BP) measurement. All those with screening BP ≥140/90 mm Hg and a random subset of those with screening BP <140/90 mm Hg were invited to undergo ABPM. Based on the 2 tests, participants were categorized as sustained hypertensive, masked hypertensive, "white coat" hypertensive, or normotensive. Analyses were weighted by the probability of undergoing ABPM. Screening BP ≥140/90 mm Hg was present in 359 of 986 participants, translating to a crude population prevalence of 23.1% (95% CI 16.5-31.5%). Age standardized prevalence of screening BP ≥140/90 mm Hg was 26.5% (95% CI 19.3-35.6%). On ABPM, 186 of 415 participants were confirmed to be hypertensive, with crude prevalence of 15.6% (95% CI 9.4-23.1%) and age-standardized prevalence of 17.1% (95% CI 11.0-24.4%). Age-standardized prevalence of masked and white coat hypertension were 7.6% (95% CI 2.8-13.7%) and 3.8% (95% CI 1.7-6.1%), respectively. The sensitivity and specificity of screening BP measurements were 80% (95% CI 73-86%) and 84% (95% CI 79-88%), respectively. BP indices and validity measures showed strong age-related trends. CONCLUSIONS: Screening BP measurement significantly overestimated hypertension prevalence while failing to identify ≈50% of true hypertension diagnosed by ABPM. Our findings suggest significant clinical and epidemiological benefits of ABPM use for diagnosing hypertension in Kenyan adults

Do arterial stiffness and wave reflection underlie cardiovascular risk in ethnic minorities?

Increasing evidence indicates that remarkable differences in cardiovascular risk between ethnic groups cannot be fully explained by traditional risk factors such as hypertension, diabetes or dislipidemia measured in midlife. Therefore, the underlying pathophysiology leading to this “excess risk” in ethnic minority groups is still poorly understood, and one way to address this issue is to shift the focus from “risk” to examine target organs, particularly blood vessels and their arterial properties more directly. In fact, structural and functional changes of the vascular system may be identifiable at very early stages of life when traditional factors are not yet developed. Arterial stiffening, measured as aortic pulse wave velocity, and wave reflection parameters, especially augmentation index, seem to be an important pathophysiological mechanism for the development of cardiovascular disease and predict mortality independent of other risk factors. However, data regarding these arterial indices in ethnic minorities are relatively rare and the heterogeneity between populations, techniques and statistical methods make it difficult to fully understand their role

2016 European Society of Hypertension guidelines for the management of high blood pressure in children and adolescents

Increasing prevalence of hypertension (HTN) in children and adolescents has become a significant public health issue driving a considerable amount of research. Aspects discussed in this document include advances in the definition of HTN in 16 year or older, clinical significance of isolated systolic HTN in youth, the importance of out of office and central blood pressure measurement, new risk factors for HTN, methods to assess vascular phenotypes, clustering of cardiovascular risk factors and treatment strategies among others. The recommendations of the present document synthesize a considerable amount of scientific data and clinical experience and represent the best clinical wisdom upon which physicians, nurses and families should base their decisions. In addition, as they call attention to the burden of HTN in children and adolescents, and its contribution to the current epidemic of cardiovascular disease, these guidelines should encourage public policy makers to develop a global effort to improve identification and treatment of high blood pressure among children and adolescents

Selective in vitro replication of herpes simplex virus type 1 (HSV-1) ICP34.5 null mutants in primary human CNS tumours--evaluation of a potentially effective clinical therapy.

Primary tumours of the central nervous system (CNS) are an important cause of cancer-related deaths in adults and children. CNS tumours are mostly glial cell in origin and are predominantly astrocytomas. Conventional therapy of high-grade gliomas includes maximal resection followed by radiation treatment. The addition of adjuvant chemotherapy provides little improvement in survival time and hence assessment of novel therapies is imperative. We have evaluated the potential therapeutic use of the herpes simplex virus (HSV) mutant 1716 in the treatment of primary brain tumours. The mutant is deleted in the RL1 gene and fails to produce the virulence factor ICP34.5. 1716 replication was analysed in both established human glioma cell lines and in primary cell cultures derived from human tumour biopsy material. In the majority of cultures, virus replication occurred and consequential cell death resulted. In the minority of tumour cell lines which are non-permissive for mutant replication, premature shut-off of host cell protein synthesis was induced in response to lack of expression of ICP34.5. Hence RL1-negative mutants have the distinct advantage of providing a double hit phenomenon whereby cell death could occur by either pathway. Moreover, 1716, by virtue of its ability to replicate selectively within a tumour cell, has the potential to deliver a 'suicide' gene product to the required site immediately. It is our opinion that HSV which fails to express ICP34.5 could provide an effective tumour therapy