Heavy Drinkers and the Potential Impact of Minimum Unit Pricing-No Single or Simple Effect?

AIMS: To explore the potential impact of a minimum unit price (MUP: 50 pence per UK unit) on the alcohol consumption of ill Scottish heavy drinkers. METHODS: Participants were 639 patients attending alcohol treatment services or admitted to hospital with an alcohol-related condition. From their reported expenditure on alcohol in their index week, and assuming this remained unchanged, we estimated the impact of a MUP (50 ppu) on future consumption. (Around 15% purchased from both the more expensive on-sale outlets (hotels, pubs, bars) and from off-sales (shops and supermarkets). For them we estimated the change in consumption that might follow MUP if (i) they continued this proportion of 'on-sales' purchasing or (ii) their reported expenditure was moved entirely to off-sale purchasing (to maintain consumption levels)). RESULTS: Around 69% of drinkers purchased exclusively off-sale alcohol at <50 ppu. Their drinking, post MUP, may reduce by a mean of 33%. For this group, from a population of very heavy, ill consumers, we were unable to show a differential effect across multiple deprivation quintiles. For other drinkers there might be no reduction, especially if after MUP there were many products priced close to 50 ppu. Moving away from on-sales purchases could support, for some, an increase in consumption. CONCLUSIONS: While a proportion of our harmed, heavy drinkers might be able to mitigate the impact of MUP by changing purchasing habits, the majority are predicted to reduce purchasing. This analysis, focusing specifically on harmed drinkers, adds a unique dimension to the evidence base informing current pricing policy. SHORT SUMMARY: From drink purchasing data of heavy drinkers, we estimated the impact of legislating £0.50 minimum unit price. Over two thirds of drinkers, representing all multiple deprivation quintiles, were predicted to decrease alcohol purchasing; remainder, hypothetically, could maintain consumption. Our data address an important gap within the evidence base informing policy.

δ15N Values in Crassostrea virginica Shells Provides Early Direct Evidence for Nitrogen Loading to Chesapeake Bay.

Crassostrea virginica is one of the most common estuarine bivalves in the United States' east coast and is frequently found in archaeological sites and sub-fossil deposits. Although there have been several sclerochronological studies on stable carbon and oxygen isotopes in the shells of this species, less is known about δ15N values within their shells, which could be a useful paleoenvironmental proxy to assess estuarine nitrogen dynamics. Modern C. virginica samples were collected in Chesapeake Bay for comparison with archaeological shells from nearby sites ranging in age from ~100 to 3,200 years old. Left valves were sampled by milling the hinge area and the resulting powder was analyzed for %N and δ15N values. Comparison of δ15N values between C. virginica shells shows relatively constant values from ~1250 BC to ~1800 AD. After ~1800 AD, there are rapid increases in 15N enrichment in the shells, which continue to increase in value up to the modern shell values. The increase in δ15N values is evidence of early anthropogenic impact in Chesapeake Bay. These results corroborate the observation that coastal nitrogen pollution occurred earlier than the 19th century and support the use of oyster shell δ15N values as a useful environmental proxy.

Complementary Hydrogen Bonding Modulates Electronic Properties and Controls Self-Assembly of Donor/Acceptor Semiconductors.

A comprehensive investigation of the complementary H-bonding-mediated self-assembly between dipyrrolo[2,3-b:3',2'-e]pyridine (P2P) electron donors and naphthalenediimide/perylenediimide (NDI/PDI) acceptors is reported. The synthesis of parent P2P and several aryl-substituted derivatives is described, along with their optical, redox, and single-crystal packing characteristics. The dual functionality of heteroatoms in the P2P/NDI(PDI) assembly, which act as proton donors/acceptors and also contribute to π-conjugation, leads to H-bonding-induced perturbation of electronic levels. Concentration-dependent NMR and UV/Vis spectroscopic studies revealed a cooperative effect of H-bonding and π-π stacking interactions. This H-bonding-mediated co-assembly of donor (D) and acceptor (A) components leads to a new charge-transfer (CT) absorption that can be controlled throughout the visible range. The electronic interactions between D and A were further investigated by time-dependent DFT, which provided insights into the nature of the CT transition. Electropolymerization of difuryl-P2P afforded the first conjugated polymer incorporating H-bonding recognition units in its main chain.

Alcohol purchasing by ill heavy drinkers; cheap alcohol is no single commodity.

OBJECTIVES: Potential strategies to address alcohol misuse remain contentious. We aim to characterise the drink purchases of one population group: heavy drinkers in contact with Scottish health services. We contrast our findings with national sales data and explore the impact of socio-economic status on purchasing behaviour. STUDY DESIGN: Cross-sectional study comparing alcohol purchasing and consumption by heavy drinkers in Edinburgh and Glasgow during 2012. METHODS: 639 patients with serious health problems linked to alcohol (recruited within NHS hospital clinics (in- and out-patient settings) 345 in Glasgow, 294 in Edinburgh) responded to a questionnaire documenting demographic data and last week's or a 'typical' weekly consumption (type, brand, volume, price, place of purchase). Scottish Index of Multiple Deprivation quintile was derived as proxy of sociodemographic status. RESULTS: Median consumption was 184.8 (IQR = 162.2) UK units/week paying a mean of 39.7 pence per alcohol unit (£0.397). Off-sales accounted for 95% of purchases with 85% of those <50 pence (£0.5 UK) per alcohol unit. Corresponding figures for the Scottish population are 69% and 60%. The most popular low-priced drinks were white cider, beer and vodka with the most common off-sales outlet being the corner shop, despite supermarkets offering cheaper options. Consumption levels of the cheapest drink (white cider) were similar across all quintiles apart from the least deprived. CONCLUSIONS: Heavy drinkers from all quintiles purchase the majority of their drinks from off-sale settings seeking the cheapest drinks, often favouring local suppliers. While beer was popular, recent legislation impacting on the sale of multibuys may prevent the heaviest drinkers benefiting from the lower beer prices available in supermarkets. Non-etheless, drinkers were able to offset higher unit prices with cheaper drink types and maintain high levels of consumption. Whilst price is key, heavy drinkers are influenced by other factors and adapt their purchasing as necessary.

The RNA helicase p68 (DDX5) is selectively required for the induction of p53-dependent p21 expression and cell-cycle arrest after DNA damage.

The RNA helicase p68 (DDX5) is an established co-activator of the p53 tumour suppressor that itself has a pivotal role in orchestrating the cellular response to DNA damage. Although several factors influence the biological outcome of p53 activation, the mechanisms governing the choice between cell-cycle arrest and apoptosis remain to be elucidated. In the present study, we show that, while p68 is critical for p53-mediated transactivation of the cell-cycle arrest gene p21(WAF1/CIP1), it is dispensable for induction of several pro-apoptotic genes in response to DNA damage. Moreover, p68 depletion results in a striking inhibition of recruitment of p53 and RNA Pol II to the p21 promoter but not to the Bax or PUMA promoters, providing an explanation for the selective effect on p21 induction. Importantly, these findings are mirrored in a novel inducible p68 knockout mouse model in which p68 depletion results in a selective inhibition of p21 induction in several tissues. Moreover, in the bone marrow, p68 depletion results in an increased sensitivity to γ-irradiation, consistent with an increased level of apoptosis. These data highlight a novel function of p68 as a modulator of the decision between p53-mediated growth arrest and apoptosis in vitro and in vivo.

Carolina Foxtail (Alopecurus carolinianus): Susceptibility and Suitability as an Alternative Host to Rice Blast Disease (Magnaporthe oryzae [formerly M. grisea]).

Carolina foxtail (Alopecurus carolinianus) has not been reported to host Magnaporthe oryzae. A collection of Carolina foxtail obtained from several Arkansas locations over a 4-year period was inoculated with four races of the fungus under greenhouse conditions and, in all cases, inoculation resulted in the formation of irregular, yellow and brown lesions without obvious gray centers that are characteristic for blast on rice. Differences in these lesions were not observed among our collection. These lesions appeared to differ from typical blast lesions on inoculated rice leaves but were evident following artificial inoculation of Carolina foxtail in the greenhouse. M. oryzae races that differed in pathogenicity toward rice cultivars also displayed differences in lesion development on Carolina foxtail. The most virulent race on rice cultivars also produced lesions most rapidly on Carolina foxtail. These lesions developed more quickly on Carolina foxtail than on the most susceptible rice cultivars tested, including a susceptible California cultivar, M202. M. oryzae isolates cultured from these lesions in the infected Carolina foxtail caused typical disease symptoms of blast on inoculated rice cultivars. We suggest that Carolina foxtail is a new and previously unrecognized host for the blast pathogen.

Achieving blood pressure goals globally: five core actions for health-care professionals. A worldwide call to action.

The prevalence of hypertension continues to rise across the world, and most patients who receive medical intervention are not adequately treated to goal. A Working Group including representatives of nine international health-care organizations was convened to review the barriers to more effective blood pressure control and propose actions to address them. The group concluded that tackling the global challenge of hypertension will require partnerships among multiple constituencies, including patients, health-care professionals, industry, media, health-care educators, health planners and governments. Additionally, health-care professionals will need to act locally with renewed impetus to improve blood pressure goal rates. The Working Group identified five core actions, which should be rigorously implemented by practitioners and targeted by health systems throughout the world: (1) detect and prevent high blood pressure; (2) assess total cardiovascular risk; (3) form an active partnership with the patient; (4) treat hypertension to goal and (5) create a supportive environment. These actions should be pursued with vigour in accordance with current clinical guidelines, with the details of implementation adapted to the economic and cultural setting.

Antihypertensive therapy, the alpha-adducin polymorphism, and cardiovascular disease in high-risk hypertensive persons: the Genetics of Hypertension-Associated Treatment Study.

In a double-blind, outcome trial conducted in hypertensive patients randomized to chlorthalidone (C), amlodipine (A), lisinopril (L), or doxazosin (D), the alpha-adducin Gly460Trp polymorphism was typed (n=36 913). Mean follow-up was 4.9 years. Relative risks (RRs) of chlorthalidone versus other treatments were compared between genotypes (Gly/Gly+Gly/Trp versus Trp/Trp). Primary outcome was coronary heart disease (CHD). Coronary heart disease incidence did not differ among treatments or genotypes nor was there any interaction between treatment and genotype (P=0.660). Subgroup analyses indicated that Trp allele carriers had greater CHD risk with C versus A+L in women (RR=1.31) but not men (RR=0.91) with no RR gender differences for non-carriers (gender-gene-treatment interaction, P=0.002). The alpha-adducin gene is not an important modifier of antihypertensive treatment on cardiovascular risk, but women Trp allele carriers may have increased CHD risk if treated with C versus A or L. This must be confirmed to have implications for hypertension treatment.

Development of explicit criteria to measure adherence to hypertension guidelines.

Measures of adherence to hypertension guidelines have historically been based on prescription data or physician survey data regarding treatment practices. These methods have limitations that decrease their accuracy. As part of a randomized controlled study testing the effects of pharmacist/physician collaboration on adherence to hypertension guidelines, the investigators and an expert panel developed a JNC 7 measurement tool. The final guideline adherence measurement tool includes 22 explicit criteria in four domains of care. An exploratory factor analysis, conducted to assess the structure of the tool, suggests three underlying treatment dimensions in hypertension care. The adherence measurement tool will allow researchers to link specific elements of care to improved blood pressure control. In addition, use of the tool will provide clinicians with a taxonomy for evaluating practice and describing the effect of improved patient care on patient outcomes.

The paradigm has shifted to systolic blood pressure.

Since the middle of the 20th century, most physicians and epidemiologists assessed the risks associated with hypertension based on the level of diastolic blood pressure (DBP). In a classic paper in 1971, the Framingham Heart Study clearly showed that systolic BP more accurately described the risk of all the complications we attribute to hypertension. It took 22 years until JNC V in 1993 also used systolic blood pressure (SBP) to define hypertension in US national guidelines. Since then, the paradigm has shifted dramatically. In JNC VI (1997) and JNC VII (2003), SBP has become the primary focus of risk stratification and treatment goals. This shift is a result of the Framingham results being confirmed by many others analyses, the most compelling of which is the recently published report of the Prospective Collaborative Study Group, which pooled 61 observational studies in more than 1 million volunteers with a collective experience of more than 12 million person-years. This group showed that the SBP level at baseline was a significantly more informative reading than DBP for predicting strokes and coronary heart disease (CHD). Furthermore, three trials of older individuals with isolated systolic hypertension, SHEP, SYST-Eur, and SYST-China, unambiguously demonstrated that effective antihypertensive therapy lowered the rate of strokes, heart failure, CHD, and even all-cause mortality. Finally, the World Health Organization (WHO)/International Society of Hypertension (ISH) Hypertension Trialists also showed that the level of SBP achieved in clinical trials comparing different antihypertensives with placebo and with each other was the strongest determinant of how effectively strokes and CHD events were reduced, although a similar relationship was not evident for heart failure. A recent metaregression analysis using new trials, many of which were used by the Trialists, and older studies not included in their analysis also showed that small differences in SBP can have a dramatic impact on cardiovascular outcomes. If there is one thing we have learned in the recent past, it is the need for us to focus on lowering SBP and getting it down to a reasonable goal. We have also learned that to do so, we will need to combine a variety of lifestyle and pharmacological approaches, always with combinations of drugs that will usually contain a low-dose thiazide-type diuretic with other antihypertensives.

Insulin resistance and weight gain in postmenopausal women of diverse ethnic groups.

OBJECTIVE: This study was conducted to examine the influence of insulin resistance on weight change in postmenopausal women of various ethnic groups. SUBJECTS: Data were obtained from 3389 women (60% White, 20% Black, 12% Hispanic, and 8% Asian/Pacific Islander), ages 50-79, enrolled in either the Women's Health Initiative Clinical trial or Observational Study, whose blood samples were selected randomly from the full cohort of 161 809 women for analyses. MEASUREMENTS: Glucose, insulin, and lipids were measured on fasting serum samples drawn at baseline and after 3 y of follow-up. Weight, height, waist circumference, and blood pressure were measured. Physical activity and energy intake were assessed via questionnaire. Insulin resistance was estimated using the HOMA (homeostasis model) calculation. RESULTS: Average age was 62 y, average BMI (body mass index) was 27.4 kg/m2, and average weight change was a gain of 0.4 kg in 3 y. In a multivariate analysis, insulin resistance and insulin concentrations were independent predictors of increases in weight in White women (P=0.002 and 0.004, respectively) and in the combined group (P=0.027 and 0.039). For the whole group, after adjustment for other covariates, those in the highest quartile of insulin resistance gained 0.4 kg in 3 y, whereas those in the lowest quartile lost 0.06 kg. Similar trends were found for insulin resistance and weight gain in Hispanic and Asian/Pacific Islander women, but they did not reach statistical significance. In Black women, no relation was seen between either insulin or insulin resistance and weight change. A significant interaction between obesity and insulin resistance was observed (P=0.002 for White women and 0.032 for the whole group), so that there is weight gain with increasing insulin resistance in the leaner women, but weight loss with increasing insulin resistance in the most obese. CONCLUSION: Insulin resistance appears to be a predictor of weight gain in postmenopausal women, except for the most obese women. The effect is more pronounced in women who have a lower BMI, and the effect was not seen in the Black women who as a group had a higher BMI.

Lip and gum lesions in sheep in two abattoirs in New Zealand.

AIM: To build a profile of the oral lesions that occur in sheep in New Zealand that need to be considered within the differential diagnosis of foot-and-mouth disease. METHODS: Lesions of the anterior lips and gums of sheep were surveyed in two abattoirs, photographed, and described grossly and histopathologically. RESULTS: A sequence of lesions in order of age and stage of healing are described and illustrated, and their pathogenesis discussed. Lesions of the midline of the lips and gums of traumatic or irritant aetiology were common, and the prevalence was higher in adult sheep than in lambs. CONCLUSIONS: The majority of lesions observed appeared to be primarily of traumatic aetiology. They probably arose from the fright/flight response behaviour of sheep, resulting in the mouth impacting against wire fences or yard railings while being handled. A smaller percentage of lesions may have been due to abrasive or irritant feed or soil. The presence of plant material and bacteria in lesions delayed healing and contributed to the formation of ulcers.

Assessing soil biodiversity across Great Britain: national trends in the occurrence of heterotrophic bacteria and invertebrates in soil.

An assessment of the biodiversity of soils was a component of the Countryside Survey 2000 (CS2000). This was the first integrated survey of soil biota and chemical properties at a national scale. A total of 1052 soil samples were collected across Great Britain during CS2000 and analysed for a range of soil microbial and invertebrate characteristics resulting in the production of a series of robust datasets. A principal objective was to use these datasets to investigate relationships between soil biota and environmental factors such as geographical location, vegetation, land use, land cover, soil type and pollutant levels as first stages in characterising the inherent biodiversity of British soils and investigating the potential of soil biodiversity as indicators of soil health at a regional or national scale. Preliminary results for culturable heterotrophic, invertebrate taxa, Acari, Collembola and Oribatid mites are presented here to illustrate the nature of the data collected and the patterns of soil biodiversity in relation to large-scale regional, vegetation and soil characteristics across the British countryside.

Pharmacogenetic approaches to hypertension therapy: design and rationale for the Genetics of Hypertension Associated Treatment (GenHAT) study.

The Genetics of Hypertension Associated Treatment (GenHAT) study will determine whether variants in hypertension susceptibility genes interact with antihypertensive medication to modify coronary heart disease (CHD) risk in hypertensives. GenHAT is an ancillary study of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial, ALLHAT, a double-blind, randomized trial of 42 418 hypertensives, 55 years of age or older, with systolic or diastolic hypertension and one or more risk factors for cardiovascular disease. About 50% are non-white, and about half are female. ALLHAT completes follow-up in March 2002. GenHAT is typing variants in hypertension genes; completion of genotyping is scheduled for 2003. Analysis of gene-treatment interactions in relation to outcomes include CHD, stroke, heart failure, and blood pressure lowering. To our knowledge, GenHAT is the largest pharmacogenetic study ever conducted. An added strength is its ability to link gene-treatment interactions with important clinical outcomes across diverse ethnic and gender groups.

Impacts of soil faunal community composition on model grassland ecosystems.

Human impacts, including global change, may alter the composition of soil faunal communities, but consequences for ecosystem functioning are poorly understood. We constructed model grassland systems in the Ecotron controlled environment facility and manipulated soil community composition through assemblages of different animal body sizes. Plant community composition, microbial and root biomass, decomposition rate, and mycorrhizal colonization were all markedly affected. However, two key ecosystem processes, aboveground net primary productivity and net ecosystem productivity, were surprisingly resistant to these changes. We hypothesize that positive and negative faunal-mediated effects in soil communities cancel each other out, causing no net ecosystem effects.

Pulse pressure and risk of cardiovascular events in the systolic hypertension in the elderly program.

Pulse pressure has been related to higher risk of cardiovascular events in older persons. Isolated systolic hypertension is common among the elderly and is accompanied by elevated pulse pressure. Treatment of isolated systolic hypertension may further increase pulse pressure if diastolic pressure is lowered to a greater extent than systolic pressure. Little is known regarding pulse pressure as a predictor of cardiovascular outcomes in elderly persons with isolated systolic hypertension, and the influence of treatment on the pulse pressure effect. We assessed the relation between pulse pressure, measured throughout the follow-up period, and the incidence of coronary heart disease (CHD), heart failure (HF), and stroke in 4,632 participants in the Systolic Hypertension in the Elderly Program, a 5-year randomized, placebo-controlled clinical trial of treatment of isolated systolic hypertension in older adults. In the treatment group, a 10-mm Hg increase in pulse pressure was associated with a statistically significant 32% increase in risk of HF and a 24% increase in risk of stroke after controlling for systolic blood pressure and other known risk factors, as well as with a 23% increase in risk of HF and a 19% increase in risk of stroke after controlling for diastolic blood pressure and other risk factors. Pulse pressure was not significantly associated with HF or stroke in the placebo group, nor with incidence of CHD in either the placebo or treatment group. These results suggest that pulse pressure is a useful marker of risk for HF and stroke among older adults being treated for isolated systolic hypertension.

Safety of controlled-onset extended-release verapamil in middle-aged and older patients with hypertension and coronary artery disease.

BACKGROUND: Our purpose was to study the safety of controlled-onset, extended-release (COER) verapamil in patients with hypertension or coronary artery disease, with a focus on elderly patients. METHODS: Adverse event data were pooled from 7 double-blind, multicenter, randomized trials including 1999 patients with hypertension or chronic stable angina pectoris. There were 1042 patients who received COER verapamil 180 to 540 mg once daily in the evening for up to 10 weeks, 373 patients who received placebo, and 584 who received an active comparator agent. Data were analyzed according to the following groups: all patients, patients with hypertension, patients with angina, older patients (>/=65 years old), and younger patients (<65 years old). Adverse event rates were compared across the treatment groups by the Fisher exact test. RESULTS: In all patients combined, the incidence of constipation (13% vs 2%), dizziness (6% vs 2%), and back pain (3% vs 1%) was higher in patients treated with COER verapamil than with placebo. Patients with hypertension had more back pain (4% vs 1%) and constipation (12% vs 1%) with COER verapamil than with placebo, whereas patients with angina had more bradycardia (2.6% vs 0%), dizziness (8% vs 2%), and constipation (15% vs 3%). Older patients treated with COER verapamil had more bradycardia, constipation, dizziness, and fatigue and had fewer headaches compared with younger patients treated with COER verapamil. Second- or third-degree atrioventricular block was not observed after administration of COER verapamil in any subgroup. CONCLUSION: These data demonstrate that COER verapamil has an acceptable safety profile that is largely unrelated to age in patients with hypertension or coronary artery disease.

One-year study of felodipine or placebo for stage 1 isolated systolic hypertension.

Asubstantial number of older hypertensive patients have stage 1 isolated systolic hypertension (systolic blood pressure between 140 and 159 mm Hg and diastolic blood pressure <90 mm Hg), but there are currently no data showing that drug treatment is effective, safe, and/or beneficial. To compare the effects of active treatment compared with placebo on blood pressure, left ventricular hypertrophy, and quality of life among older stage 1 isolated systolic hypertensive patients, a randomized, double-blind, parallel-group, multicenter clinical trial comparing felodipine (2.5, 5, or 10 mg once daily) and matching placebo was performed in 171 patients (49% male, average age 66+/-7 years, with 49% white and 30% Hispanic) with a baseline blood pressure of 149+/-7/83+/-6 mm Hg. During 52 weeks of treatment, patients randomized to active treatment achieved significantly lower blood pressures (137.0+/-11.7/80.2+/-7.6 mm Hg for extended-release felodipine versus 147.5+/-16.0/83.5+/-9.7 mm Hg for placebo, P<0.01 for each), a reduced incidence of left ventricular hypertrophy (7% for extended release felodipine versus 24% for placebo, P<0.04), and improved quality of life (change in Psychological General Well-Being index, 3.0+/-6.8 for extended-release felodipine versus -0.8+/-10.3 for placebo, P<0.01) versus baseline. There were no clinically significant differences between treatments in tolerability or adverse effects. Stage 1 isolated systolic hypertension can be effectively and safely treated pharmacologically. Treatment reduced progression to the higher stages of hypertension, reduced the incidence of left ventricular hypertrophy, and improved an overall measure of the quality of life. Larger and longer studies will be needed to document any long-term reduction in cardiovascular event rates associated with treating stage 1 systolic hypertension.