Behavioral Intervention Components Associated With Cost-effectiveness: A Comparison of Six Domains.

BACKGROUND: To help implement behavior change interventions (BCIs) it is important to be able to characterize their key components and determine their effectiveness. PURPOSE: This study assessed and compared the components of BCIs in terms of intervention functions identified using the Behaviour Change Wheel Framework (BCW) and in terms of their specific behavior change techniques (BCTs) identified using the BCT TaxonomyV1, across six behavioral domains and the association of these with cost-effectiveness. METHODS: BCIs in 251 studies targeting smoking, diet, exercise, sexual health, alcohol and multiple health behaviors, were specified in terms of their intervention functions and their BCTs, grouped into 16 categories. Associations with cost-effectiveness measured in terms of incremental cost-effectiveness ratio (ICER) upper and lower estimates were determined using regression analysis. RESULTS: The most prevalent functions were increasing knowledge through education (72.1%) and imparting skills through training (74.9%). The most prevalent BCT groupings were shaping knowledge (86.5%), changing behavioral antecedents (53.0%), supporting self-regulation (47.7%), and providing social support (44.6%). Intervention functions associated with better cost-effectiveness were those based on training (ßlow = -15044.3; p = .002), persuasion (ßlow = -19384.9; p = .001; ßupp = -25947.6; p < .001) and restriction (ßupp = -32286.1; p = .019), and with lower cost-effectiveness were those based on environmental restructuring (ß = 15023.9low; p = .033). BCT groupings associated with better cost-effectiveness were goals and planning (ßlow = -8537.3; p = .019 and ßupp = -12416.9; p = .037) and comparison of behavior (ßlow = -13561.9, p = .047 and ßupp = -30650.2; p = .006). Those associated with lower cost-effectiveness were natural consequences (ßlow = 7729.4; p = .033) and reward and threat (ßlow = 20106.7; p = .004). CONCLUSIONS: BCIs that focused on training, persuasion and restriction may be more cost-effective, as may those that encourage goal setting and comparison of behaviors with others.

Changes in prevalence of depression and anxiety following smoking cessation: results from an international cohort study (ATTEMPT).

BACKGROUND: Smoking cessation improves physical health but it has been suggested that in vulnerable individuals it may worsen mental health. This study aimed to identify the short- and longer-term effects of stopping smoking on depression and anxiety in the general population and in those with a history of these disorders. METHOD: Sociodemographic and smoking characteristics, and mental and physical health were assessed using established measures in the ATTEMPT cohort, an international longitudinal study of smokers (n = 3645). Smokers who had stopped for at least 3 months or less than 3 months at the 12-month follow-up were compared with current smokers (n = 1640). RESULTS: At follow-up, 9.7% [95% confidence interval (CI) 8.3-11.2] of smokers had stopped for less than 3 months and 7.5% (95% CI 6.3-8.9) for at least 3 months. Compared with current smokers, prevalence of depression prescriptions obtained in the last 2 weeks was lower for those who had stopped for less than 3 months [odds ratio (OR) 0.37, 95% CI 0.14-0.96] or at least 3 months (OR 0.25, 95% CI 0.06-0.94) after adjusting for baseline prescription levels and confounding variables. Adjusted prevalence of recent depression symptoms was also lower for ex-smokers who had stopped for less than 3 months (OR 0.34, 95% CI 0.15-0.78) or at least 3 months (OR 0.24, 95% CI 0.09-0.67) than among continuing smokers. There was no change in anxiety measures in the general population or any increase in anxiety or depression symptoms in ex-smokers with a past history of these conditions. CONCLUSIONS: Smoking cessation does not appear to be associated with an increase in anxiety or depression and may lead to a reduced incidence of depression.

The feasibility of measuring puffing behaviour in roll-your-own cigarette smokers.

BACKGROUND/OBJECTIVE: Despite the increase in roll-your-own (RYO) cigarette consumption in many countries, very little is known about RYO smokers. In order to estimate the health risks inherent in RYO use, it is important to assess exposure to tobacco toxins in this group. Exposure is determined by a number of factors, including puffing behaviour, but so far this issue has not been addressed among RYO smokers. This study sought both to determine the feasibility of measuring puffing behaviour in this group, its reliability and validity, and to characterise puffing behaviour among RYO smokers compared with smokers of factory-made (FM) cigarettes. METHODS: At two visits, 24 hours apart, 131 FM and 29 RYO cigarette smokers provided saliva samples that were assayed for cotinine, a measure of nicotine intake and thus smoke exposure. Self-reported puffing behaviour of participants, as well as their demographic and smoking characteristics were also assessed. At the end of the first visit, smokers were shown how to use a portable smoking topography machine that measures puffing behaviour, the CReSSmicro, and asked to smoke all cigarettes with this machine until the second visit, when participants were asked to provide feedback on using the device. RESULTS: Both RYO and FM cigarette smokers reported that the CReSSmicro was easy to use; however, RYO cigarette smokers were more likely to have missing data, to reduce cigarette consumption and to indicate a change in their puffing behaviour because of the device. Machine-determined puffing behaviour was equally stable over time in both groups with similar ability to predict exposure; cotinine levels were related to machine but not to self-reported puffing parameters. Overall, RYO smokers appeared to puff cigarettes less hard but for longer than FM cigarette smokers. CONCLUSION: The measurement of puffing behaviour using a topography device is feasible but less practicable for RYO than FM cigarette smokers. Puffing parameters show comparable reliability and validity for both groups of smokers and reveal some differences in smoking topography dependent on the type of cigarette smoked.

Mass isolation of cell surface membrane fragments from pigeon heart.

Cell surface membrane fragments were isolated and purified by successive rate zonal and isopycnic centrifugation of calcium oxalate-loaded pigeon heart microsomes in sucrose density gradients. The most highly purified cell membrane fraction sediments at a buoyant density of 1.105 g/ml. Some of the membrane pieces are present as open fragments and leaky vesicles, while others form tightly sealed vesicles of both inside-in and inside-out membrane orientation. The pigeon heart cell membrane preparation exhibits high (Na+ + K+ + Mg2+)-ATPase and adenylate cyclase activities. Additional activity of these enzymes is uncovered by sodium dodecyl sulfate and alamethicin, respectively. Electron microscopic inspection of the cell surface membrane preparation revealed (a) a predominance of thick-walled vesicles with smooth surfaces on negative staining and (b) binding of concanavalin A to the bulk of isolated membrane pieces following their incubation with the lectin.

Early presence of phospholamban in developing a chick heart.

Phosphorylation of phospholamban and development of reticular Ca2+ transport were studied in crude membrane preparations of embryonic, newborn and adult chick heart. Maximal phosphorylation of phospholamban by added catalytic subunit of cyclic AMP-dependent protein kinase increases from embryonic day 4-15. It decreases with further development. In the same membrane preparations active Ca2+-uptake into vesicles of sarcoplasmic reticulum rises from day 4-7 and decreases then slightly until day 20. A several-fold increase in Ca2+-transport activity occurs at the time of hatching. The data indicate separate genetic control for synthesis of phospholamban and sarcoplasmic reticulum Ca2+-ATPase.

Cytochemical localization of adenylate cyclase activity in heart tissue with cerium.

Adenylate cyclase (AC) activity showed a doses depending inactivation of the basal activity and of the sodium fluoride stimulation by cerium in homogenates of unfixed and fixed guinea pig hearts. The isoproterenol and guanine nucleotide stimulation was not more than two times of the basal activity in glutaraldehyde-prefixed heart homogenates in the presence of 2 mmol/l CeCl3. The inactivation of the AC (activity) by cerium was less than in the presence of lead. Test tube experiments showed no differences in the precipitation of imidodiphosphate in comparison with inorganic phosphate. The substrate AMP-PNP was not spontaneously hydrolysed by 2 mmol/l CeCl3. Ultrastructural analysis of cytochemical incubation of glutaraldehyde-fixed slices and small pieces of guinea pig heart tissue showed fine-amorphous precipitations of reaction products localized along the plasma membrane of the sarcolemma, the nexuses of the intercalated discs and the T-tubule membranes. No precipitates were found neither on the junctional nor on other SR membranes. Nonspecific coarse and clumped precipitates have been detected in the intercellular space on components of the basal membranes. It was not able to demonstrate cytochemically stimulation of AC by hormones or by sodium fluoride. The localization of the basal AC activity in heart tissue seems to be better with cerium as capture agent than with lead. However, differences in the localization of the AC activity in heart tissue were not observed.

Comparative immunocytochemical demonstration of G proteins in rat heart tissue.

Localization of G proteins in the rat heart tissue was investigated using primary affinity-purified antibodies against synthetic peptides with amino acid sequences corresponding to alpha-subunits (alpha i common and alpha i 1, 2) of G proteins. Detection of immunoreactivity was performed with the peroxidase-anti-peroxidase complex (PAP), avidin-biotin complex (ABC) and fluorescein-labelled secondary antibodies for light microscopy and the protein A-gold technique for electron microscopy. In ventricles and atria, immunostaining for G proteins was detected in the sarcolemma and perinuclear space of cardiomyocytes. In endotheliocytes and fibroblasts, immunoreactivity was present also in the endoplasmic reticulum. All four immunocytochemical methods permit to demonstrate the same localization of G proteins in heart tissue. The ABC method and fluorescein labelled secondary antibodies technique showed the same sensitivity which is higher than that of the PAP method. Nomarski contrast microscopy enhanced the visualization of the final reaction product formed by the peroxidase reaction developed with diaminobenzidine in the ABC method. The results are discussed in terms of the role of G proteins in signal transduction via plasma membrane and membranes of the intracysternal space of the cell.

Prevalence, diagnosis and relation to tobacco dependence of chronic obstructive pulmonary disease in a nationally representative population sample.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the fourth most common cause of death worldwide. It is caused primarily by cigarette smoking. Given its importance, it is remarkable that reliable national prevalence data are lacking for most countries. This study provides estimates of the national prevalence of COPD in England, the extent of under-detection of the disorder, and patterns of cigarette smoking, dependence, and motivation to stop smoking in those with the disease. METHODS: Data from 8215 adults over the age of 35 who participated in the Health Survey for England were analysed. Information was obtained on self-reported and cotinine validated smoking status, cigarette dependence, motivation to stop smoking, COPD defined by spirometry using joint American Thoracic Society and European Respiratory Society criteria, and self-reports of diagnosis with respiratory disorders. RESULTS: Spirometry-defined COPD was present in 13.3% (95% CI 12.6 to 14.0) of participants, over 80% of whom reported no respiratory diagnosis. Even among people with severe or very severe COPD by spirometric assessment, only 46.8% (95% CI 39.1 to 54.6) reported any diagnosed respiratory disease. A total of 34.9% (95% CI 32.1 to 37.8) of people with spirometry-defined COPD were smokers compared with 22.4% (95% CI 21.4 to 23.4) of those without, and smoking prevalence increased with disease severity. Smokers with spirometry-defined COPD were more cigarette dependent but had no greater desire to quit than other smokers. CONCLUSION: COPD is common among adults in England and is predominantly undiagnosed. In smokers it is associated with higher degrees of cigarette dependence but not with a greater motivation to stop smoking.

[Action mechanism of the thyroid hormone in the heart cell--interaction of the thyroid hormone and catecholamines]. / Zum Wirkungsmechanismus des Schilddrüsenhormons an der Herzelle--Interaktion von Schilddrüsenhormon und Katecholaminen.

The thyroid hormones change the adrenergic reactivity of the myocardium. Since a series of cardiac functions, among others also ways of metabolism such as glycogenolysis and lipolysis underlie an adrenergic regulation, changes of the state of the thyroid gland manifest themselves on them. Investigations at the system of the beta-adrenergic receptor-adenylate-cyclase have shown that in hyperthyreosis and the beta-adrenergic number of receptors is increased by more than double. Moreover, references were got that the thyroid hormones have an influence on the coupling of the receptor to the catalytic subunit of the adenylate cyclase and a regulatory subunit of the enzyme which is regulated by guanine nucleotides. These findings help in the clarification of the causes for the changed reaction to the beta-adrenergic stimulation of the heart.

Decreased contractile response after exposure of the rat aorta to Db cAMP or IBMX.

Isometric tension developed by different receptor agonists was found to be decreased after pretreatment of rat aortic rings with IBMX or Db cAMP and only partially restored by CaCl2 and A 23187. The contraction produced by Bay k 8644 was converted into dose-dependent relaxation after pretreatment of the aorta rings with Db cAMP or IBMX. An alteration of the calcium channel is assumed to play a common role in the cAMP-dependent inhibition of the smooth muscle contraction.

Altered effect of BAY K 8644 after exposure of the rat aorta to IBMX or Db cAMP.

The development of isometric tension of aortic rings from rats was tested after cumulative administration of BAY K 8644 before and after exposure of the aortic preparations for 15 or 60 minutes to IBMX (10(-4) M) or Db cAMP (3.10(-4) M). BAY K 8644 exhibits dose-dependent contractions of those aortic rings which have not been exposed or have been exposed for only 15 minutes to IBMX or Db cAMP. BAY K 8644 application, after an exposure time of 60 minutes of the aortic rings to either IBMX or Db cAMP, resulted in a dose-dependent relaxation. This relaxing effect is counteracted by elevation of KCl (15 mM) in bath solution but was not changed by norepinephrine. The results indicate that long time exposure of the aortic rings to compounds capable of elevating intracellular cAMP level might induce changes of Ca channel gating.

[Behavior of adenylate cyclase in ischemic and necrotic myocardial tissue]. / Zum Verhalten der Adenylatzyklase im ischämischen und nekrotischen Herzgewebe.

The adenylate cyclase activity was determined in the left ventricles of rat hearts up to 60 min after severe ischemia and 24 hours after injection of a high dose of isoproterenol. The quantitative data show a progressive decline in the activity after 20 min of ischemia. Isoproterenol- and fluoride-stimulated activities were influenced in the same manner. The cytochemical localization showed no changes in the localization of the enzyme. But the number of cells with reaction products of the adenylate cyclase activity were decreased. The quantitative analysis of the adenylate cyclase activity in the myocardial necrosis produced by a single injection of 80 mg isoproterenol per kg body weight showed no changes in the basal activity of the enzyme however a significant reduction of the isoproterenol stimulation and a slight decrease of the fluoride-stimulated activity compared to the non-necrotic area of the same left ventricle. In cytochemical investigations no reaction of the adenylate cyclase activity was found in the centre of the necroses. But in the border zone of the basis the reaction product of the plasma membrane of the sarcolemma the main localization site of the enzyme activity was failed whereas the activity of the junctional SR was preserved. It was concluded that this activity is responsible for the unchanged basal activity in the necrotic and non-necrotic area.

Influence of thyroid state on the specific binding of noradrenaline to a cardiac particulate fraction and on catecholamine-sensitive cardiac adenylate cyclase activity.

Specific binding of [3H] noradrenaline, possibly to beta-adrenoreceptors, and adrenaline-sensitive adenylate cyclase activity were measured in particulate preparations from the myocardium of hypothyroid, euthyroid, and hyperthyroid rats. Noradrenaline affinity to the binding sites was decreased and the dose-response curve for the stimulation of adenylate cyclase activity by adrenaline was shifted to the right in hypothyroidism. The opposite changes (an increase in noradrenaline affinity and a shift in the adrenaline-adenylate cyclase dose-response curve to the left) were associated with the hyperthyroid state. These findings correlate well with the result of numerous studies according to which thyroid hormone increases and thyroid hormone deprivation decreases the sensitivity of the myocardium to cardiac sympathetic stimulation and circulating catecholamines.

G protein function in the ischaemic myocardium.

The activity of adenylyl cyclase (AC) is controlled by its interaction with receptor-regulated G proteins. The efficiency to form cyclic AMP is strongly influenced by the amount, the subspecies and function of these regulatory proteins. An impairment of AC function has been shown to occur in sarcolemmal preparations (SL) of hearts exposed to either local or global ischaemia. To examine the contribution of G protein function to this phenomenon, cholera toxin (CT)-catalysed ADP-ribosylation of Gs and pertussis toxin (PT)-catalysed ADP-ribosylation of G proteins have been investigated in SL of porcine hearts exposed to global ischaemia for 15-45 min. ADP-ribosylation by CT of an approximately 45 kDa polypeptide was 0.46 +/- 0.06 and ADP-ribosylation by PT of three 39-41 kDa polypeptides was 4.77 +/- 0.77 pmol mg-1 protein in SL of non-ischaemic myocardium. Whereas no change was observed in CT-catalyzed ribosylation after 30 min of ischaemia, there was a reduction in PT-catalyzed ADP-ribosylation to 3.7 +/- 0.35 pmol mg-1 protein after 30 min of ischaemia. Prolongation of ischaemia to 45 min did not reduce further ADP-ribosylation capacity. Quantitative immunoblotting of PT-sensitive G proteins suggests that the diminution of ADP-ribosylation occurred because of a loss of alpha-subunits of G0, Gi-1, and Gi-2 from sarcolemmal membranes.

Signal transfer in cardiac muscle. Alteration of the beta-adrenoceptor adenylate cyclase system in the hypertrophied myocardium.

The beta-adrenoceptor adenylate cyclase complex (beta ACR), located in the sarcolemmal membrane, is one of the most effective signal transduction systems regulating function and metabolism of heart muscle primarily via cyclic AMP. It is thought to play an important role in adaptive mechanisms of the heart as to pressure load and stressful stimuli. Present knowledge about composition and function of beta ARC enable us to clear up which of the single components of this system contributes to pathophysiological alterations of heart function. Cardiac beta ARC was investigated in three experimental groups: I) adult rats of WKY strain (WKY), II) adult rats of WKY strain cardiac hypertrophy in which was induced by aortic constriction (WKYAC), and III) adult spontaneously hypertensive rats (SHR). Quantitative assessment of beta-adrenoceptor number (beta AR) as revealed by [3H]dihydroalprenolol binding studies showed a significant reduction to 30% and 35% of control beta AR in membrane preparations of WKYAC and SHR, respectively. The diminished density of myocardial beta AR was accompanied by a reduction of the maximum stimulatory effect of 1(-)adrenaline on adenylate cyclase (AC). Evidence was obtained for a close correlation between the diminished response of beta ARC to beta AR-mediated stimuli and the heart index as measure of cardiac hypertrophy. No correlation between graduated states of hypertrophy and activation of AC has been observed by NaF and Gpp(NH)p. The results indicate that in rat hearts severe hypertrophy of which was induced by pressure-load, mainly the beta AR component of the beta ARC complex contributes to the reduction of beta ARC-mediated responsiveness of the hypertrophied myocardium.

Diltiazem prevents the depression of adenylyl cyclase activity induced by the calcium paradox in rat.

In isolated rat hearts the calcium paradox, induced by perfusion for 3 minutes in the absence of calcium followed by perfusion for 10 minutes in the presence of calcium, depressed the activation of adenylyl cyclase by l-isoproterenol, NaF and forskolin. The characteristics of the beta-adrenoceptors and the activation of adenylyl cyclase by guanylyl imidodiphosphate were not changed. The findings suggest an uncoupling of beta-adrenoceptors from the catalytic site of the adenylate cyclase complex. Diltiazem, at 0.4 microM in the perfusion medium, greatly reduced the diminution of the activation of adenylate cyclase by isoproterenol and forskolin, and completely prevented the depression of the activation of adenylate cyclase by NaF. These effects may be due to interference by diltiazem with the mechanisms that promote an excessive influx of calcium into the heart during the calcium paradox.

Responsiveness of cardiac adenylate cyclase in the normal and ischemic myocardium. Role of oxygen free radicals.

Cyclic AMP has been shown to play a significant regulatory role in a number of myocardial cell functions. The cAMP-forming adenylate cyclase complex is localized in the sarcolemmal membrane which is the major site of lipid peroxidation by oxygen-derived free radicals known to be increased in the ischemic myocardium. Adenylate cyclase function was found to be depressed in the ischemic myocardium but the specific biochemical mechanism responsible for this effect is still unknown. Therefore, the effect of free radical formation on adenylate cyclase was studied. Highly purified sarcolemmal membranes, exhibiting an NaF-stimulated activity of 3.46 +/- 0.65 nmol cAMP formed min-1 mg-1 of protein, were exposed to free radicals formation of which was induced by Fe++/ascorbate. A rapid loss of adenylate cyclase activation by 1-isoproterenol, NaF, and Gpp(NH)p has been observed. Concentration of malondialdehyde (MAD), a key intermediate in the formation of peroxides, was positively correlated to the rapid loss of adenylate cyclase activity. As result, adenylate cyclase was found to be highly susceptible to free radical-induced damage. It is thought that this effect might be one of the causes of the biochemical dearrangements contributing to the alteration of sarcolemmal membrane function in myocardial ischemia resulting in the reduction or loss of metabolic and contractile regulation of the heart.

[Determination of triiodothyronine intake in the retrograde perfused Langendorff rabbit heart. A study of the binding capacity and distribution in subcellular fractions]. / Bestimmung der Trijodthyroninaufnahme im retrograd perfundierten Langendorff-Kaninchenherzen--Eine studie über die Bindungskapazität und Verteilung in den subzellulären Fraktionen.

In an experimental set after Langendorff hearts of rabbits are retrogradely perfused and the myocardial intake of 125J T3 depending on the T3-concentration under oxygenation, hypoxia and cardioplegy is estimated. With the help of a discontinuing saccharose gradient after electron microscopic differentiation of the stratifications the identification of the subcellular bindings of the 125J-T3 taken was performed. It was shown that under our experimental conditions the heart possesses a large intake capacity for free T3, in which case the value established of 115.42 ng T3/g of heart tissue could be achieved under unphysiologically high offer of T3. An influence of the hypoxia and cardioplegy on the intake of T3 was proved and the possibilities of the increased T3-binding were discussed. The clinical phenomenon of a decrease of T3 in myocardial infarction could experimentally be proved by an increased T3-extraction under hypoxia.