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PubMed2005

Systematic reviews of health effects of social interventions: 2. Best available evidence: how low should you go?

STUDY OBJECTIVE: There is little guidance on how to select the best available evidence of health effects of social interventions. The aim of this paper was to assess the implications of setting particular inclusion criteria for evidence synthesis. DESIGN: Analysis of all relevant studies for one systematic review, followed by sensitivity analysis of the effects of selecting studies based on a two dimensional hierarchy of study design and study population. SETTING: Case study of a systematic review of the effectiveness of interventions in promoting a population shift from using cars towards walking and cycling. MAIN RESULTS: The distribution of available evidence was skewed. Population level interventions were less likely than individual level interventions to have been studied using the most rigorous study designs; nearly all of the population level evidence would have been missed if only randomised controlled trials had been included. Examining the studies that were excluded did not change the overall conclusions about effectiveness, but did identify additional categories of intervention such as health walks and parking charges that merit further research, and provided evidence to challenge assumptions about the actual effects of progressive urban transport policies. CONCLUSIONS: Unthinking adherence to a hierarchy of study design as a means of selecting studies may reduce the value of evidence synthesis and reinforce an "inverse evidence law" whereby the least is known about the effects of interventions most likely to influence whole populations. Producing generalisable estimates of effect sizes is only one possible objective of evidence synthesis. Mapping the available evidence and uncertainty about effects may also be important.

Automobile Driving↗

PubMed2006

Utility of indices of gun availability in the community.

OBJECTIVE: To estimate the degree to which the proportion of homicides and suicides committed with a gun is associated with reported availability of firearms across Chicago neighbourhoods. METHODS: Data were collected as part of the Project on Human Development in Chicago Neighborhoods (PHDCN), a combined neighbourhood and individual level study of the city of Chicago. The study used data from 837 PHDCN participants between the ages of 17 and 22, residing in 170 different neighbourhoods. Gun availability was measured via participant reports on whether they had carried a gun and whether they perceived gun access to be easy in their community. Data on suicides and homicides were obtained from the Chicago Department of Health. RESULTS: A 10% change in the proportion of homicides committed by a gun in a neighbourhood was associated with a 20% increase in both the odds of reported gun access and reported gun carrying (p=0.002 and 0.048, respectively). The proportion of firearm related suicides was not associated with either of those self reported measures. CONCLUSIONS: The proportion of firearm related homicides, but not the proportion of firearm related suicides, is a useful predictor of gun availability across small areas such as neighbourhoods.

Adolescent↗

PubMed2006

The irony of a rich country: issues of financial access to and availability of healthy food in the Republic of Ireland.

OBJECTIVE: To determine the weekly financial cost of a diet as recommended by national policy in two parents with two children, single parents with one child and single old people with low income, and begin to identify, in a rich country context, variation in food item availability, price and household purchasing capacity. DESIGN: Food baskets were developed based on national dietary recommendations and purchasing patterns of these household groups. National-level prices of each food were identified, as well as pricing across a representative selection of Irish retail outlet types. Basket costs were assessed relative to the financial capacity of household type. RESULTS: The types of retail outlets in which low-income groups tend to shop do not carry many own brand items and is less likely to stock healthy options, but when they do, they are more expensive than in other outlets. Single parents with one child, two adults with two children and single older people would have to spend 80%, 69% and 38%, respectively, of their weekly household income to purchase the food basket based on economy-line products. CONCLUSIONS: Financial access to and availability of healthy food options must be considered through a national policy cognisant of basic human needs for healthy living. This research provides evidence on the direct costs of healthy eating for policy and planning to ensure not only financial capacity but also to guarantee that affordable healthy food choices are physically available to all groups in society.

Budgets↗

PubMed1997

Use of paracetamol for suicide and non-fatal poisoning in the UK and France: are restrictions on availability justified?

OBJECTIVE: To investigate the relationship between the availability of paracetamol and its use for overdose and suicide. DESIGN: Analysis of routinely collected information on time trends for paracetamol suicides, non-fatal overdoses, and sales. SETTING: England and Wales and France. RESULTS: There were strong correlations between trends in paracetamol sales in the UK and trends in non-fatal paracetamol overdose in Oxford between 1976 and 1993 (Spearman's r = 0.86; 95% confidence interval (CI) 0.54, 0.96) and between paracetamol sales and non-fatal overdoses in France between 1974 and 1990 (r = 0.99; 95% CI 0.97, 1.00). Sales figures were also correlated with paracetamol related suicides in both England and Wales, 1983-91 (r = 0.72; 95% CI 0.11, 0.94) and France, 1974-90 (r = 0.79; 95% CI 0.50, 0.92). Similarly strong relationships were observed between trends in non-fatal overdoses and suicide by paracetamol poisoning in England and Wales (r = 0.85; 95% CI 0.61, 0.95) and France (r = 0.79; 95% CI 0.50, 0.92). It is estimated that approximately 32,000 overdoses involving paracetamol occur annually in England and Wales. Fatality rates from paracetamol overdose were four times as high in England and Wales (0.4%, 95% CI 0.38, 0.46) as in France (0.1%, 95% CI 0.06, 0.17). CONCLUSION: Trends towards greater availability of paracetamol are paralleled by increases in its use for both non-fatal overdose and suicide. Paracetamol related morbidity and mortality seem to be less frequent in France where the quantity of paracetamol in a single purchase is limited. Although not conclusive, these data add to a body of evidence which suggests that restrictions in the quantity of paracetamol available as a single purchase in the UK may reduce suicide and liver failure related to paracetamol.

Acetaminophen↗

PubMed1980

Inosine synthesis and phosphoribosylpyrophosphate availability in rat liver cells in the presence of allopurinol.

In the presence of allopurinol, apparent phosphoribosylpyrophosphate (PP-ribose-P) availability as measured by adenine incorporation into ribonucleotides was decreased in rat liver cells, hypoxanthine incorporation into ribonucleotides was increased, and there was a large synthesis of inosine from hypoxanthine. Inosine was formed directly by the reversal of the purine nucleoside phosphorylase reaction which was very rapid in liver cells. We tested the hypothesis that utilization of ribose 1-phosphate for inosine synthesis could decrease PP-ribose-P availability. Our results indicate that the apparent decrease of PP-ribose-P availability in the presence of allopurinol was due to competition between adenine and hypoxanthine salvage pathways into nucleotides, and not to the synthesis of inosine.

Adenine↗

PubMed1982

Effects of glycerol and fructose on purine synthesis de novo and on PP-ribose-P availability in rat liver cells.

Incubation of freshly isolated rat liver cells with glycerol resulted in an initial decrease, followed by an increase in purine synthesis de novo and in PP-ribose-P availability. The magnitude of these effects was dependent on the concentration of glycerol; as it increased, the initial period of latency or inhibition was prolonged, and the extent of the subsequent stimulation was greater. The intracellular Pi concentration and the [14C]ATP/[14C]ADP ratio were also initially decreased in these cells, and they too returned subsequently to normal values. All these changes were similar to those induced by fructose under the same conditions. The increase in PP-ribose-P availability always preceded that in purine synthesis de novo, indicating that, under most circumstances, PP-ribose-P availability is limiting for purine synthesis de novo. Finally, PP-ribose-P synthesis in these cells varied in parallel with the intracellular Pi concentration and with the ATP/ADP and ATP/AMP ratios.

Adenine↗

PubMed1985

Limitation of theophylline elimination by reduced oxygen availability in mouse hepatocytes and rat isolated livers.

The effect of oxygen availability on theophylline metabolism by mouse hepatocytes and rat isolated livers was examined. The elimination of theophylline by mouse hepatocytes and the metabolism of theophylline to dimethyluric acid by isolated, perfused rat livers was seriously impaired when the gas mixture supplied contained less than 28% oxygen. The correlation coefficients relating oxygen supply and the concentration of theophylline remaining in mouse hepatocyte suspensions were -0.74 to -0.84. In the isolated, perfused rat liver experiments, the correlation coefficient relating oxygen availability and dimethyluric acid production was 0.87. These observations are interpreted as supporting the hypothesis that oxygen availability per se is an important factor in determining the rate of theophylline metabolism.

Aerobiosis↗

PubMed1997

Deaths related to iodinated contrast media reported spontaneously to the U.S. Food and Drug Administration, 1978-1994: effect of the availability of low-osmolality contrast media.

PURPOSE: To determine whether reports of iodinated contrast medium-related deaths have decreased since low-osmolality contrast media (LOCM) became widely available in the United States. MATERIALS AND METHODS: With use of reports to the U.S. Food and Drug Administration Spontaneous Reporting System, data on iodinated contrast medium-related deaths after LOCM became available (1987-1994) were compared with data on deaths in the period before (1978-1986) and with data on deaths in an even earlier period (1967-1977). RESULTS: In 1967-1994, more than 1,000 contrast medium-related deaths were reported, 850 occurring during 1978-1994. Excluding 22 myelography-related deaths, 37% [corrected] more deaths were reported each year in 1987-1994 than in 1978-1986. Most of this increase was associated with the use of nonionic contrast media. In 1966-1977, 228 deaths were reported; in 1978-1986, 376; and in 1987-1994, 474. In 1987-1994, 220 deaths were associated with use of high-osmolality contrast media alone, 32 with ionic LOCM alone, 214 with nonionic LOCM alone, and eight with combinations of contrast media. CONCLUSION: Despite the availability of LOCM in the United States, data for 1978-1994 do not show a marked decrease in contrast medium-related deaths. Since 1990, more deaths have been associated with LOCM than with conventional contrast media. Although these data have substantial limitations, they shed some light on contrast medium use and safety.

Adverse Drug Reaction Reporting Systems↗

PubMed2006

Effect of insulin on human skeletal muscle protein synthesis is modulated by insulin-induced changes in muscle blood flow and amino acid availability.

Insulin promotes muscle anabolism, but it is still unclear whether it stimulates muscle protein synthesis in humans. We hypothesized that insulin can increase muscle protein synthesis only if it increases muscle amino acid availability. We measured muscle protein and amino acid metabolism using stable-isotope methodologies in 19 young healthy subjects at baseline and during insulin infusion in one leg at low (LD, 0.05), intermediate (ID, 0.15), or high (HD, 0.30 mUxmin(-1)x100 ml(-1)) doses. Insulin was infused locally to induce muscle hyperinsulinemia within the physiological range while minimizing the systemic effects. Protein and amino acid kinetics across the leg were assessed using stable isotopes and muscle biopsies. The LD did not affect phenylalanine delivery to the muscle (-9 +/- 18% change over baseline), muscle protein synthesis (16 +/- 26%), breakdown, or net balance. The ID increased (P < 0.05) phenylalanine delivery (+63 +/- 38%), muscle protein synthesis (+157 +/- 54%), and net protein balance, with no change in breakdown. The HD did not change phenylalanine delivery (+12 +/- 11%) or muscle protein synthesis (+9 +/- 19%), and reduced muscle protein breakdown (-17 +/- 15%), thus improving net muscle protein balance but to a lesser degree than the ID. Changes in muscle protein synthesis were strongly associated with changes in muscle blood flow and phenylalanine delivery and availability. In conclusion, physiological hyperinsulinemia promotes muscle protein synthesis as long as it concomitantly increases muscle blood flow, amino acid delivery and availability.

Adult↗

PubMed2002

High carbohydrate availability increases LCFA uptake and decreases LCFA oxidation in perfused muscle.

To determine whether changes in long-chain fatty acid (LCFA) oxidative metabolism induced by elevated intracellular carbohydrate availability are due to changes in LCFA uptake or in mitochondrial transport capacity, rat hindquarters were perfused with 500 microM palmitate and [1-14C]palmitate or [1-14C]octanoate as well as with either low (LG) or high (HG) carbohydrate availability. Glucose uptake was higher in the HG vs. LG group (23.6 +/- 1.5 vs 4.7 +/- 0.9 micromol x g(-1) x h(-1), P < 0.05). Palmitate delivery was not significantly different between groups and averaged 97.1 +/- 4.6 nmol x min(-1) x g(-1) (P > 0.05). Fractional and total palmitate uptake values were 60% higher (P < 0.05) in the HG (0.125 +/- 0.012 and 7.4 +/- 1.2 nmol x min(-1) x g(-1)) vs. LG (0.079 +/- 0.009 and 11.8 +/- 1.5 nmol x min(-1) x g(-1)) group. Values of percent and total palmitate oxidized were significantly lower (P < 0.05) in the HG (9.1 +/- 1.1% and 1.31 +/- 0.16 nmol x min(-1) x g(-1)) vs. LG (23.4 +/- 5.2% and 0.76 +/- 0.08 nmol x min(-1) x g(-1)) group. Conversely, values of fractional uptake and percent oxidation of octanoate were not significantly different between groups (P > 0.05). Malonyl-CoA levels were inversely correlated with LCFA oxidation (P < 0.05). These results demonstrate that high carbohydrate availability in muscle is associated with a decrease in LCFA oxidation that is not due to a parallel decrease in LCFA uptake; rather, the decrease in LCFA oxidation could be due to malonyl-CoA inhibition of mitochondrial LCFA transport.

Animals↗

PubMed1991

Glucose availability and sensitivity to anoxia of isolated rat peroneal nerve.

The contrast between resistance to ischemia and ischemic lesions in peripheral nerves of diabetic patients was explored by in vitro experiments. Isolated and desheathed rat peroneal nerves were incubated in the following solutions with different glucose availability: 1) 25 mM glucose, 2) 2.5 mM glucose, and 3) 2.5 mM glucose plus 10 mM 2-deoxy-D-glucose. Additionally, the buffering power of all of these solutions was modified. Compound nerve action potential (CNAP), extracellular pH, and extracellular potassium activity (aKe) were measured simultaneously before, during, and after a period of 30 min of anoxia. An increase in glucose availability led to a slower decline in CNAP and to a smaller rise in aKe during anoxia. This resistance to anoxia was accompanied by an enhanced extracellular acidosis. Postanoxic recovery of CNAP was always complete in 25 mM HCO3(-)-buffered solutions. In 5 mM HCO3- and in HCO3(-)-free solutions, however, nerves incubated in 25 mM glucose did not recover functionally after anoxia, whereas nerves bathed in solutions 2 or 3 showed a complete restitution of CNAP. We conclude that high glucose availability and low PO2 in the combination with decreased buffering power and/or inhibition of HCO3(-)-dependent pH regulation mechanisms may damage peripheral mammalian nerves due to a pronounced intracellular acidosis.

Action Potentials↗

PubMed1990

Effect of O2 availability on intrinsic vascular response to venous pressure elevation in postnatal swine intestine.

The goal of these experiments was to determine whether the intrinsic vascular response of postnatal intestine to acute venous pressure elevation was dependent on the preexisting level of oxygen availability. To this end, acute venous hypertension was applied to denervated loops of small intestine from 3- and 35-day-old swine anesthetized with pentobarbital during free-flow and controlled-flow perfusion. During controlled-flow perfusion, the base-line blood flow rate was set slightly above (+5%; high flow) or significantly below (-50%; low flow) the rate noted during free-flow perfusion so as to directly alter intestinal oxygen availability. The vascular response to venous hypertension noted under controlled high-flow perfusion was similar in both age groups and generally consistent with that noted under free-flow perfusion. In contrast, the response noted during low-flow perfusion was clearly age dependent. In the older group, vascular resistance decreased (27%), while arteriovenous oxygen content difference [(a-v)O2] and tissue oxygen uptake remained unchanged. In the younger group, vascular resistance remained unchanged, whereas (a-v)O2 and oxygen uptake decreased (14%). We conclude that the intrinsic vascular response to venous pressure elevation is dependent on the preexisting level of oxygen availability in intestine from 35- but not from 3-day-old swine. We speculate that the local metabolic vascular response to venous hypertension is more effective in intestine from older than from younger swine.

Aging↗

PubMed1997

Cytoskeleton modulates coupling between availability and activation of cardiac sodium channel.

The aim of this study was to investigate modulation of voltage-dependent steady-state activation and availability from inactivation of the cardiac Na+ channel by the cytoskeleton. As an experimental approach, we used long-lasting monitoring [63 +/- 5 (SE) min] of the half-point potentials of the steady-state availability curve (V(1/2A)) and normalized conductance curve (V(1/2G)) in 116 rat ventricular cardiomyocytes by whole cell patch clamp at 22-24 degrees C. Both half-point potentials shifted in the negative direction with time as an exponentially saturating change, with the shift of V(1/2G) being smaller and faster. An F-actin disrupter, cytochalasin D (Cyto-D, 20 microM), accelerated the rate of the V(1/2A) shift but decreased the range of the V(1/2G) shift. An F-actin stabilizer, phalloidin (100 microM), temporarily (for 28.2 +/- 2.2 min, n = 15) prevented the V(1/2A) shift but did not influence the V(1/2G) shift. The best fit for the V(1/2G)-V(1/2A) relationship in untreated cells (1,021 data points measured in 51 cells) was a second-degree (2.06) power function. Cytoskeleton-directed agents modified the relationship. In Cyto-D-treated cells, the V(1/2G)-V(1/2A) relationship was shifted (by 2.5 mV) toward positive V(1/2G). On the contrary, a microtubule stabilizer, taxol (100 microM), shifted the relationship toward negative V(1/2G) (by 12.2 mV). We conclude that coupling between availability and activation is modulated by F-actin-based and microtubular cytoskeleton.

Animals↗

PubMed1994

Induction of low-T3 syndrome in exercising women occurs at a threshold of energy availability.

To investigate the relationship between energy availability (dietary energy intake minus energy expended during exercise) and thyroid metabolism, we studied 27 untrained, regularly menstruating women who performed approximately 30 kcal.kg lean body mass (LBM)-1.day-1 of supervised ergometer exercise at 70% of aerobic capacity for 4 days in the early follicular phase. A clinical dietary product was used to set energy availability in four groups (10.8, 19.0, 25.0, 40.4 kcal.kg LBM-1.day-1). For 9 days beginning 3 days before treatments, blood was sampled once daily at 8 A.M. Initially, thyroxine (T4) and free T4 (fT4), 3,5,3'-triiodothyronine (T3) and free T3 (fT3), and reverse T3 (rT3) were in the normal range for all subjects. Repeated-measures one-way analysis of variance followed by one-sided, two-sample post hoc Fischer's least significant difference tests of changes by treatment day 4 revealed that reductions in T3 (16%, P < 0.00001) and fT3 (9%, P < 0.01) occurred abruptly between 19.0 and 25.0 kcal.kg LBM-1.day-1 and that increases in fT4 (11%, P < 0.05) and rT3 (22%, P < 0.01) occurred abruptly between 10.8 and 19.0 kcal.kg LBM-1.day-1. Changes in T4 could not be distinguished. If energy deficiency suppresses reproductive as well as thyroid function, athletic amenorrhea might be prevented or reversed by increasing energy availability through dietary reform to 25 kcal.kg LBM-1.day-1, without moderating the exercise regimen.

Adult↗

PubMed1994

Initial fall in skeletal muscle force development during ischemia is related to oxygen availability.

We examined the hypothesis that the initial decline (first 1-2 min) in force development that occurs in working muscle when blood flow is halted is caused by O2 availability and not another factor related to blood flow. This was tested by reducing O2 delivery (muscle blood flow X arterial O2 content) to working muscle by either stopping blood flow [ischemia (I)] or maintaining blood flow with low arterial O2 content [hypoxemia (H)]. If initial decline in force development were similar between these two methods of reducing O2 delivery, it would suggest O2 availability as the common pathway. Isolated dog gastrocnemius muscle was stimulated at approximately 60-70% of maximal O2 uptake (1 isometric tetanic contraction every 2 s) until steady-state conditions of muscle blood flow and developed force were attained (approximately 3 min). Two conditions were then sequentially imposed on the working muscle: I, induced by shutting off pump controlling arterial perfusion of the muscle and clamping venous outflow, and H, induced by perfusing the muscle with deoxygenated blood (collected before testing while animal breathed N2) at steady-state blood flow level. Rates of the fall in force production in 17 matched conditions of H and I (approximately 40 s for each condition) were compared in 6 muscles tested. The blood perfusing the muscle during H had arterial PO2 = 8 +/- 1 (SE) Torr, arterial PCO2 = 37 +/- 1 Torr, and arterial pH = 7.39 +/- 0.03. The rate of decline in developed force was not significantly different (P = 0.46) between the 17 matched conditions of H (0.66 +/- 0.10 g force.g mass-1.s-1) and I (0.79 +/- 0.15 g force.g mass-1.s-1). These findings suggest that the initial fall in developed force in working skeletal muscle that occurs with ischemia is related to O2 availability.

Animals↗

PubMed2004

NAD(P)H fluorescence imaging of mitochondrial metabolism in contracting Xenopus skeletal muscle fibers: effect of oxygen availability.

The blue autofluorescence (351 nm excitation, 450 nm emission) of single skeletal muscle fibers from Xenopus was characterized to be originating from mitochondrial NAD(P)H on the basis of morphological and functional correlations. This fluorescence signal was used to estimate the oxygen availability to isolated single Xenopus muscle fibers during work level transitions by confocal microscopy. Fibers were stimulated to generate two contractile periods that were only different in the PO2 of the solution perfusing the single fibers (PO2 of 30 or 0-2 Torr; pH = 7.2). During contractions, mean cellular NAD(P)H increased significantly from rest in the low PO2 condition with the core (inner 10%) increasing to a greater extent than the periphery (outer 10%). After the cessation of work, NAD(P)H decreased in a manner consistent with oxygen tensions sufficient to oxidize the surplus NAD(P)H. In contrast, NAD(P)H decreased significantly with work in 30 Torr PO2. However, the rate of NAD(P)H oxidation was slower and significantly increased with the cessation of work in the core of the fiber compared with the peripheral region, consistent with a remaining limitation in oxygen availability. These results suggest that the blue autofluorescence signal in Xenopus skeletal muscle fibers is from mitochondrial NAD(P)H and that the rate of NAD(P)H oxidation within the cell is influenced by extracellular PO2 even at high extracellular PO2 during the contraction cycle. These results also demonstrate that although oxygen availability influences the rate of NAD(P)H oxidation, it does not prevent NAD(P)H from being oxidized through the process of oxidative phosphorylation at the onset of contractions.

Animals↗

PubMed2003

Availability of low-threshold Ca2+ current in retinal ganglion cells.

Spiking in central neurons depends on the availability of inward and outward currents activated by depolarization and on the activation and priming of currents by hyperpolarization. Of these processes, priming by hyperpolarization is the least described. In the case of T-type Ca2+ current availability, the interplay of hyperpolarization and depolarization has been studied most completely in expression systems, in part because of the difficulty of pharmacologically separating the Ca2+ currents of native neurons. To facilitate understanding of this current under physiological conditions, we measured T-type current of isolated goldfish retinal ganglion cells with perforated-patch voltage-clamp methods in solutions containing a normal extracellular Ca2+ concentration. The voltage sensitivities and rates of current activation, inactivation, deactivation, and recovery from inactivation were similar to those of expressed alpha1G (CaV3.1) Ca2+ channel clones, except that the rate of deactivation was significantly faster. We reproduced the amplitude and kinetics of measured T currents with a numerical simulation based on a kinetic model developed for an alpha1G Ca2+ channel. Finally, we show that this model predicts the increase of T-type current made available between resting potential and spike threshold by repetitive hyperpolarizations presented at rates that are within the bandwidth of signals processed in situ by these neurons.

Algorithms↗

PubMed2002

Hungarian cancer mortality and food availability data in the last four decades of the 20th century.

OBJECTIVE: To identify the dietary risk factors present in the nutrition of the Hungarian population. METHOD: We evaluated Hungarian cancer mortality data, and carried out a comparative analysis of the Hungarian National Food Balance Sheets (food availability) and dietary surveys (energy and nutrient intake). RESULTS: The cancer mortality rate in Hungary is the highest in Europe and an analysis of the past 40 years has revealed a worsening trend. Assessment of the Hungarian dietary pattern suggests that the high fat intake could be a possible risk factor in the development of lung, colon, rectum, female breast and prostate cancer. The availability of fats in Hungary was found to be the highest in a European comparison in the second half of the 1990s, while the average fat energy percentage in the diet of the male and female population was 38.0% (SD 5.7) between 1992 and 1994. Apart from the high fat consumption, the insufficient intake of vegetables and fruits could be identified as a major, convincing risk factor present in the nutrition of Hungarians, and plays a role in the development of mouth and pharynx, esophagus, lung, stomach, colon and rectum cancers, and is a probable risk factor in the development of pancreatic tumors. The availability of vegetables and fruits in the Hungarian population is one of the lowest in Europe and, in addition, the intake of dietary fiber, carotenoids, and ascorbic acid is also inadequate. CONCLUSION: Hungary has the highest cancer mortality rate in Europe, and the death rate associated with this disease is increasing. Our analysis of food balance sheets and dietary survey data clearly demonstrate the presence of certain known dietary risk factors in the nutrition of the Hungarian population.

Adolescent↗