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PubMed1983

Sensitivity to reinforcement in concurrent arithmetic and exponential schedules.

The generalized matching law states that the logarithm of the ratio of responses emitted or time spent responding in concurrent variable-interval schedules is a linear function of the logarithm of the ratio of reinforcements obtained. The slope of this relation, sensitivity to reinforcement, varies about 1.0 but has been shown to be different when obtained in different laboratories. The present paper analyzed the results from 18 experiments on concurrent variable-interval schedule performance and showed that response-allocation sensitivity to reinforcement was significantly smaller when arithmetic, rather than exponential, progressions were used to produce variable-interval schedules. There were no differences in time-allocation sensitivity between the two methods of constructing variable-interval schedules. Since the two laboratories have consistently used different methods for constructing variable-interval schedules, the differences in obtained sensitivities to reinforcement are explained. The reanalysis suggests that animals may be sensitive to differences in the distribution of reinforcements in time.

Journal Article↗
PubMed1985

Temporal proximity and reinforcement sensitivity in multiple schedules.

Distributions of reinforcers between two components of multiple variable-interval schedules were varied over a number of conditions. Sensitivity to reinforcement, measured by the exponent of the power function relating ratios of responses in the two components to ratios of reinforcers obtained in the components, did not differ between conditions with 15-s or 60-s component durations. The failure to demonstrate the "short-component effect," where sensitivity is high for short components, was consistent with reanalysis of previous data. With 60-s components, sensitivity to reinforcement decreased systematically with time since component alternation, and was higher in the first 15-s subinterval of the 60-s component than for the component whose total duration was 15 s. Varying component duration and sampling behavior at different times since component transition may not be equivalent ways of examining the effects of average temporal distance between components.

Journal Article↗
PubMed1995

Unit-price analysis of opioid consumption by monkeys responding under a progressive-ratio schedule of drug injection.

Several reports have indicated that drug consumption in self-administration procedures is a function of the ratio of the instrumental requirement to the dose of drug, a quantity termed unit price. We evaluated three predictions from this unit-price model in a reanalysis of data on opioid self-administration in rhesus monkeys responding under a progressive-ratio schedule (Hoffmeister, 1979). We evaluated whether consumption was inversely related to unit price, and compared the goodness of fit of an equation devised by Hursh, Raslear, Shurtleff, Bauman, and Simmons (1988) to that of a linear model predicting consumption as a function of dose. We also tested whether consumption was constant when the same unit price was comprised of different combinations of dose and instrumental requirement. Consumption declined overall as unit price increased. The equation devised by Hursh et al. and the linear model based on dose fit the data equally well. Drug consumption was not uniform at a given unit price. The analyses suggest limits on the unit-price model as a characterization of drug consumption.

Animals↗
PubMed2003

Evidence-based mucogingival therapy. Part 1: A critical review of the literature on root coverage procedures.

BACKGROUND: Systematic reviews of the literature are an increasingly important tool for providing evidence-based guidance to the practitioner. This review article and a companion paper deal with the surgical coverage of exposed root surfaces, but their aim is to promote a more up-to-date way of writing and publishing scientific articles in this field. This article presents the published data about surgical root coverage in table form and its aim is to identify updated minimum standards for data presentation. METHODS: Manual and computer-assisted searches were conducted to find the articles published on this topic during the 30-year period from 1970 to 2000. Articles that described the surgical procedure and reported at least the number of treated recessions and the duration of the follow-up, including case series, controlled studies, and randomized trials were selected and data were arranged in tables. RESULTS: Only 90 of the 290 articles that dealt with root coverage met the entry criteria; 25 of these were found only through manual searching. The overall clinical outcomes of different techniques appear to be satisfactory, but the published evidence is of little help in deciding which procedure is best suited for each clinical situation. Only a more homogeneous way of collecting and reporting clinical data and especially outcome measures will allow for an effective reanalysis which could help in everyday clinical decision making. Perhaps studies should be carried out and presented keeping in mind that the published results of sound clinical studies will, sooner or later, be reviewed and compared with other studies. CONCLUSION: A standard format with minimum requirements for data collection and presentation should be established and imposed by international journals in order to provide readers and researchers with more useful information.

Case-Control Studies↗
PubMed1980

Los Angeles airport noise and mortality--faulty analysis and public policy.

A well-publicized investigation in Los Angeles showed a higher mortality rate in 1970-1971 among residents in a high-noise area near Los Angeles International Airport than in a low-noise control area. The authors of this report attributed the difference to the effects of jet aircraft noise. A reanalysis of the data did not confirm the original results. Once the confounding effects of age, race, and sex were taken into account by direct and indirect methods of standardization, there was little difference in the mortality experience of the airport and control areas. Adjusted mortality rates due to all causes, cardiovascular diseases, or cerebrovascular disease did not differ appreciably between the two areas and were nearly identical to those of Los Angeles County during 1970.

Adolescent↗
PubMed1983

Passenger car size and driver seat belt use.

The National Highway Traffic Safety Administration (NHTSA) claims, on the basis of survey results, that seat belt use in small cars is twice as high as in large cars. The agency interprets this as being due in part to perceptions of higher risk by small car occupants. In fact, little is known about the factors motivating belt use, including whether risk perception is important. A reanalysis of the NHTSA data indicates that most of the differences in belt use by car size can be explained by higher use in imported cars, and by geographical differences in belt use in domestic cars.

Automobiles↗
PubMed1993

The implications of an epidemiological mistake: a community's response to a perceived excess cancer risk.

OBJECTIVES: The response of community residents to a perceived cancer excess may include changes in attitude, health-related behavior, and property values. In 1986, a cancer agency conducted a study of cancer incidence (1979 to 1983) in two suburbs of Edmonton, Alberta, and reported elevations on the order of 25% over expected for most sites. Reanalysis of these data several months later revealed an error. Correction brought the rates into line with Alberta as a whole and with other communities surrounding Edmonton. METHODS: We used public opinion trends and property value trends (during the period of concern) to study the two communities affected by the allegation of increased cancer risk. RESULTS: A survey of residents found significant differences at the time in health-related behavior and beliefs suggesting increased perception of personal, family, and community risk and modest changes in behavior. Real estate values in one community temporarily lost an average of $4000, or about 5% of total value, compared with a similar, adjacent housing market. CONCLUSIONS: The perception of an elevated cancer risk, in the absence of a true risk, may have a substantial negative effect on the affected community, both psychologically and economically.

Adult↗
PubMed1997

Flawed gun policy research could endanger public safety.

A highly publicized recent study by Lott and Mustard concludes that laws easing restrictions on licenses for carrying concealed firearms in public substantially reduce violent crime. Several serious flaws in the study render the authors' conclusions insupportable. These flaws include misclassification of gun-carrying laws, endogeneity of predictor variables, omission of confounding variables, and failure to control for the cyclical nature of crime trends. Most of these problems should bias results toward overestimating the crime-reducing effects of laws making it easier to carry concealed firearms in public. Lott and Mustard's statistical models produce findings inconsistent with criminological theories and well-established facts about crime, and subsequent reanalysis of their data challenges their conclusions. Public health professionals should understand the methodological issues raised in this commentary, particularly when flawed research could influence the introduction of policies with potentially deleterious consequences.

Confounding Factors, Epidemiologic↗
PubMed1998

Social class, ethnicity, and mental illness: the importance of being more than earnest.

This paper revisits a landmark study of the prevalence of mental illness in the state of Massachusetts conducted by Edward Jarvis in the 19th century. Jarvis drew an improper conclusion about the relationship between social class, ethnicity, and insanity, asserting that the Irish foreign-born had a higher prevalence of insanity in each social stratum. A reanalysis of Jarvis' data shows that in both the pauper and independent social classes in Massachusetts, the prevalence of insanity was significantly lower among foreign-born persons than among native-born persons. On the basis of his misperception, Jarvis constructed elaborate etiological theories. These theories made a strong impact on the mental health service policies of his day. The effects of incomplete examination of data on etiological theories and mental health policy in current times are highlighted in this article.

Causality↗
PubMed2001

Automated constant denaturant capillary electrophoresis applied for detection of KRAS exon 1 mutations.

In this study, we have applied automated constant denaturant capillary electrophoresis (ACDCE) for the detection of KRAS exon 1 mutations. Samples from 191 sporadic colon carcinomas previously analyzed for KRAS mutations with allele-specific PCR (ASPCR), temporal temperature gradient electrophoresis (TTGE), and constant denaturant capillary electrophoresis (CDCE) were analyzed. In ACDCE, an unmodified ABI Prism 310 genetic analyzer with constant denaturant conditions separated fluorescein-labeled PCR products. Temperature in combination with a chemical denaturant was used for separation. The optimal separation conditions for PCR-amplified KRAS exon 1 fragments were determined by adjusting the temperature before electrophoresis. In the ACDCE analysis, the sequence of a mutant was determined by comparing the electropherogram of the fragment to that of known mutations followed by mixing the sample with control mutations before reanalysis. In a titration experiment mixing mutant and wild-type alleles, the sensitivity for mutation detection was shown to be 0.6% in this automated CDCE technique. The automation of CDCE allowed rapid analysis of a large number of test samples over as short period of time and with a commercially available apparatus.

Autoanalysis↗
PubMed1999

Cardiovascular pharmacology of hormone replacement therapy.

The incidence of cardiovascular disease in women is negligible before natural or surgically-induced menopause, and increases after menopause. Epidemiological data suggest that estrogen replacement therapy reduces the occurrence of coronary artery, and possibly cerebrovascular, disease by 25 to 50% in treated women compared with non-users. These findings are supported by the evidence that estrogens have a beneficial effect on cholesterol metabolism and deposition, contributing to the inhibition of atherosclerotic plaque formation in arterial walls. Early reports suggested that up to 60% of the protective effect of estrogens on coronary artery disease was attributable to favourable changes in plasma lipids. Reanalysis of the data indicated that the lipid changes probably account for approximately 25% of the cardioprotective effect of estrogens and that other effects are, therefore, likely to be important. The influence of estrogens on carbohydrate metabolism, atheroma formation and cardiovascular haemodynamics may also play an integral role in the overall beneficial effect of the hormones. Animal and human studies have shown that the administration of estrogens leads to a restoration of endothelial function, an increase in cardiac output, an increase in arterial flow velocity, a decrease in vascular resistance, and a decrease in systolic and diastolic blood pressure. Recent studies on hormone replacement regimens have shown that estrogens may favourably affect fibrinolysis and reduce plasma fibrinogen to premenopausal levels. Despite these effects of estrogens the recent Heart and Estrogen/Progestin Replacement Study (HERS) failed to show a cardioprotective effect of hormone replacement therapy (HRT) in elderly women with coronary artery disease. However, the HERS study has several limitations and stands alone against the large body of evidence that suggest that HRT may reduce cardiovascular mortality and morbidity.

Cardiovascular Diseases↗
PubMed2003

HMG-CoA reductase inhibitors in osteoporosis: do they reduce the risk of fracture?

Osteoporosis affects a large number of people in industrialised countries. It has clinical and public-health impacts, most importantly due to subsequent fractures. Osteoporotic fractures are one of the most common causes of disability and are associated with enormous healthcare expenditure. The majority of existing treatment options for osteoporosis only inhibit bone resorption and prevent excessive bone loss but are not capable of stimulating bone formation. However, several recent in vitro and in vivo studies in animals demonstrated that HMG-CoA reductase inhibitors stimulate the production of bone morphogenetic protein (BMP-2), which is a potent regulating protein in osteoblast differentiation and activity. This suggests that HMG-CoA reductase inhibitors may have an anabolic effect on bones, making them a potentially interesting treatment option for osteoporosis. Additionally, several studies in humans showed that some HMG-CoA reductase inhibitors may have a beneficial effect on bone turnover and may lead to an increase in bone mineral density. Consequently, several observational studies tried to evaluate whether use of HMG-CoA reductase inhibitors is associated with a decreased risk of fractures. Even though not all results of these epidemiological studies, using different designs in different study populations, were entirely consistent, they provided substantial evidence that HMG-CoA reductase inhibitor use may decrease the bone fracture risk by approximately 50%. On the other hand, reanalysis of two randomised controlled trials of HMG-CoA reductase inhibitor therapy, designed to assess cardiovascular outcomes, could not show that patients treated with HMG-CoA reductase inhibitors had a lower fracture risk in comparison with placebo-treated patients. Therefore, to conclusively assess the potential of HMG-CoA reductase inhibitors in the prevention and treatment of osteoporosis, randomised controlled trials need to be performed to address this conflicting issue. Until the results of such trials are available, practitioners should prescribe the drugs that have been proven to reduce the risk of osteoporotic fractures.

Animals↗
PubMed2002

Bivalirudin: a review of its potential place in the management of acute coronary syndromes.

UNLABELLED: Bivalirudin, a synthetic analogue of hirudin, is a specific and reversible inhibitor of thrombin which binds directly with both fluid-phase and clot-bound thrombin. In patients with unstable angina undergoing percutaneous transluminal coronary angioplasty (PTCA), results from a large well designed study and its reanalysis (n = 4312) indicate that bivalirudin is more effective than heparin in the prevention of ischaemic complications for up to 90 days after the start of treatment. In addition, among patients undergoing PTCA for post myocardial infarction (MI) bivalirudin may be more effective than heparin in preventing ischaemic complications for up to 180 days after treatment was started. Data from dose-finding studies indicate bivalirudin has potential in the treatment of patients with unstable angina not undergoing percutaneous coronary intervention (PCI); however, well designed comparative studies are needed before firm conclusions can be made. Among patients with acute ST elevation MI, randomised trials have demonstrated bivalirudin to be significantly more effective than heparin in improving early patency in patients receiving thrombolytic therapy with streptokinase. Data from the Hirulog and Early Reperfusion/Occlusion (HERO)-1 trial (n = 412) indicate that bivalirudin recipients were significantly more likely to have Thrombin Inhibition in Myocardial Ischaemia (TIMI) grade 3 flow at 90 to 120 minutes than heparin recipients. In addition, data from the HERO-2 trial (n = 17 073) show bivalirudin was significantly more effective than heparin in reducing adjudicated 96-hour reinfarction and 30-day investigator-reported death/reinfarction than heparin. Bivalirudin was as effective as heparin in reducing 30-day mortality. Data from a meta-analysis of four randomised trials among patients undergoing PTCA or treatment for acute coronary syndromes indicate that, at after 30 to 50 days of follow-up, bivalirudin was significantly more effective than heparin in reducing the incidence of nonfatal MI and the combined endpoint of death or nonfatal MI. The most significant adverse events associated with bivalirudin are bleeding complications. In individual trials, bivalirudin was as well tolerated as heparin with, in general, a reduced incidence of bleeding complications. Additionally, bivalirudin provides a more consistent, predictable anticoagulant response. In 4312 patients with unstable angina undergoing PTCA the incidence of retroperitoneal bleeding, blood transfusion and major haemorrhage was significantly lower in bivalirudin than heparin recipients. Data from the HERO-2 trial in patients with acute MI indicate that although bivalirudin recipients had a significantly higher incidence of mild or moderate bleeding than heparin recipients, there was no difference in intracranial haemorrhage, severe bleeding or transfusions. Data from a meta-analysis among 5674 patients with ischaemic heart disease show bivalirudin recipients were at a significantly lower risk of haemorrhagic events than heparin recipients. CONCLUSIONS: Bivalirudin is an effective alternative to heparin in the prevention of ischaemic complications in patients with unstable angina undergoing PTCA. In addition, the drug has shown potential in the treatment of patients with unstable angina not undergoing PCI. For patients with MI, it is clear that bivalirudin can replace heparin in the management of MI where streptokinase is used as the thrombolytic agent. Further data are required on the efficacy of bivalirudin in patients undergoing thrombolysis with newer thrombolytics.

Angina, Unstable↗
PubMed2004

Drotrecogin alfa (activated): a pharmacoeconomic review of its use in severe sepsis.

Drotrecogin alfa (activated) [Xigris] (DAA), the recombinant form of human activated protein C, is approved as an adjunctive therapy for patients with severe sepsis (sepsis associated with > or = 1 organ system failure [OSF]). In the international, randomised, double-blind, placebo-controlled PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) study, the absolute reduction in 28-day all-cause mortality with intravenous DAA 24 micro g/kg/h for 96 hours plus conventional care versus conventional care alone was 6.1%. Although lacking statistical power, a prospectively planned subgroup analysis of this study suggested that the absolute reduction in mortality increased in patients with a baseline APACHE (Acute Physiology and Chronic Health Evaluation) II score of > or = 25 or > or = 2 OSFs, with no clear treatment effect in patients with an APACHE II score of < or = 24 or 1 OSF. Three fully published cost-effectiveness/cost-utility models of DAA plus conventional care relative to conventional care alone adopted a national healthcare payer's and/or societal perspective in North America. The base-case (baseline) discounted incremental cost per life-year gained (LYG) with DAA for all patients with severe sepsis was $US15,801-33,300 (year of costing 2000-2002). The results were more favourable for patients with an APACHE II score of > or = 25 ($US10,833-19,723 per LYG), but considerably worse for patients with an APACHE II score of < or = 24 based on a post hoc reanalysis by the US FDA. Among several fully or partly published cost-effectiveness/cost-utility models that adopted a national healthcare payer's perspective in continental Western European countries, the base-case (baseline) undiscounted incremental cost per LYG was broadly similar and more favourable for patients with > or = 2 OSFs (9660-11,300 euros; year of costing/publication 1998/1999, 2000, 2002 or 2003) than for all patients with severe sepsis (13,436-15,071 euros) in those studies that reported both analyses. The DAA acquisition cost accounts for up to 95% of the additional cost of using the drug. In conclusion, DAA is a major advance in the treatment of severe sepsis, based on the significant mortality reduction observed in the PROWESS study. From a hospital/hospital pharmacy perspective, the drug is associated with a high acquisition cost and a small increase in other short-term costs. From a societal or national healthcare payer's perspective, however, its administration to patients who meet the PROWESS study inclusion criteria, especially individuals with more severe disease (e.g APACHE II score of > or =25 and/or > or = 2 OSFs), has a lifetime cost-effectiveness profile that compares well to that of many widely accepted therapies.

Anti-Infective Agents↗
PubMed2005

Do atypical antipsychotics cause stroke?

Post hoc analyses of pooled results from 11 randomised controlled trials of risperidone and olanzapine in elderly dementia subjects revealed an increased incidence of cerebrovascular adverse events compared with placebo. Reanalysis of the risperidone trials suggests that some of the increased incidence may be accounted for by nonspecific events that were not strokes. Large observational administrative health database studies appear to confirm that risperidone and olanzapine are not associated with an increased risk of stroke in elderly patients compared with typical antipsychotics or untreated dementia patients. A larger number of subjects with vascular and mixed dementias were included in the risperidone studies compared with the olanzapine studies, which likely accounts for the increased incidence of cerebrovascular adverse events in the risperidone trials compared with the olanzapine studies. Potential mechanisms proposed to explain an association between atypical antipsychotics and cerebrovascular adverse events include thromboembolic effects, cardiovascular effects (e.g. orthostatic hypotension, arrhythmias), excessive sedation resulting in dehydration and haemoconcentration, and hyperprolactinaemia. However, there is little evidence to support these hypothesised mechanisms at present. The association between atypical antipsychotics and cerebrovascular adverse events requires further clarification. At the present time, this association is another factor that clinicians should consider when weighing the risks and benefits of treating behavioural and psychological disturbances in elderly dementia patients.

Antipsychotic Agents↗
PubMed2006

Efficacy and safety of selective serotonin reuptake inhibitors in the treatment of depression in children and adolescents: practitioner review.

BACKGROUND: Given the widespread reports involving the use of selective serotonin reuptake inhibitors (SSRIs) in children, the present paper reviews and discusses published double-blind, placebo-controlled studies assessing the safety and efficacy of SSRIs in children and adolescents with major depressive disorder. METHODS: Published and unpublished double-blind, placebo-controlled studies of SSRIs in children and adolescents with depression during the years 1990-2004 were reviewed. A MEDLINE search was performed using the words 'depression', 'randomised controlled trial', 'SSRIs', 'children' and 'adolescents'. The GlaxoSmithKline website was also searched for relevant studies on paroxetine. Outcome measures were the Clinical Global Impressions scale, the Children's Depression Rating Scale-Revised, the Hamilton Rating Scale for Depression, the depression subscales of the Kiddie Schedule for Affective Disorders and Schizophrenia for Adolescents-Lifetime version, and the Montgomery and Asberg Depression Rating Scale. Adverse effects and withdrawal rates are reported. RESULTS: There were seven randomised, placebo-controlled trials involving 1619 children and adolescents aged 6-18 years in total. The SSRIs fluoxetine, paroxetine, sertraline and citalopram were reported to exhibit safety and efficacy for treatment of depression in children and adolescents. Reanalysis of published and unpublished studies by the US FDA and the UK's Medicines and Healthcare products Regulatory Agency (MHRA) raised alerts regarding higher suicidal ideation rates from SSRIs in this population. Present guidelines are discussed. CONCLUSIONS: SSRIs remain a first-line pharmacological treatment for depression in children and adolescents for whom psychotherapy has failed or is unavailable. Suicidal ideation and behaviours merit close monitoring. More studies are needed.

Adolescent↗
PubMed2006

A meta-analysis of randomized, placebo-controlled clinical trials of Efamol evening primrose oil in atopic eczema. Where do we go from here in light of more recent discoveries?

UNLABELLED: The global incidence of atopic eczema is escalating. While new treatment options are becoming available, previous treatments with certain confirmed benefits are still worth investigating as safe and effective therapies. One such treatment, Efamol evening primrose oil (EPO), was proven efficacious in a 1989 meta-analysis of randomized, double-blind, placebo-controlled clinical trials. A decade of further testing and subsequent independent reanalysis of 26 clinical studies including 1207 patients presented here, establishes that Efamol EPO has a simultaneous, beneficial effect on itch/pruritus, crusting, oedema and redness (erythema) that becomes apparent between 4 and 8 weeks after treatment is initiated. However, the magnitude of this effect is reduced in association with increasing frequency of potent steroid use. This and other confounding variables that are now being reported in the literature may account for historically reported inconsistent patient response. Recent research has uncovered unique complexities in fatty acid metabolism and immune response in the atopic condition beyond those previously reported and may well have identified a subcategory of non-responders and has helped established those that can consistently derive significant benefit. Further research is needed to provide a better understanding of the physiology behind this complex disorder and the beneficial role that fatty acids can play in its development and management. CONCLUSION: Efamol EPO has a simultaneous, beneficial effect on itch/pruritus, crusting, oedema and redness (erythema) that becomes apparent between 4 and 8 weeks after treatment is initiated. However, the magnitude of this effect is reduced in association with increasing frequency of potent steroid use.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

Comments on "Breast cancer: evidence for a relation to fission products in the diet".

For over 30 years, Ernest Sternglass (recently joined by Jay Gould) has claimed that large occurrences of health effects result from small exposures to ionizing radiation. A recent study published in the Journal claimed to show a "supralinear" dose-effect relationship versus curies per million persons. The authors of this article show that Sternglass and Gould did not follow accepted scientific methods, never calculated the dose equivalent to the population studied, misinterpreted the raw data, and did not evaluate any possible confounding factors that could influence the observed breast cancer mortality. The reanalysis of the raw data shows that, while there may have been changes in the mortality patterns from breast cancer in the four geographical regions reported, Sternglass and Gould failed to demonstrate a relationship between the operational histories of the Haddam Neck, Millstone, and Indian Point reactors and breast cancer mortality.

Air Pollutants, Radioactive↗