bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurotoxicity and dysfunction of dopaminergic systems associated with AIDS dementia
Authors: Nath Avindra , Anderson Carol , Jones Melina , Maragos William , Booze Rosemarie , Mactutus Charles , Bell Jeanne , Hauser Kurt F. , Mattson Mark
Published: April 2009

Infection with the human immunodefiency virus (HIV) selectively targets the basal ganglia resulting in loss of dopaminergic neurons. Although frequently asymptomatic, some patients may develop signs of dopamine deficiency de novo. Accordingly, they are highly susceptible to drugs that act on dopaminergic systems. Both neuroleptics and psychostimulants may exacerbate these symptoms. Experimental evidence suggests that viral proteins such as gp120 and Tat can cause toxicity to dopaminergic neurons, and this toxicity is synergistic with compounds such as methamphetamine and cocaine that also act on the dopaminergic system. In addition, other neurotransmitters that modulate dopaminergic function, such as glutamate and opioids, may also modify the susceptibility of the dopamine system to HIV. Therefore, a thorough understanding of the mechanisms that lead to this selective neurotoxicity of dopaminergic neurons would also likely lead to the development of therapeutic modalities for patients with HIV dementia.
Different effect of desipramine on locomotor activity in quinpiroletreated rats after repeated restraint and chronic mild stress
Authors: D'Aquila Paolo S. , Peana Alessandra T. , Carboni Vittorio , Serra Gino
Published: April 2009

We have studied the effect of chronic treatment with the tricyclic antidepressant drug desipramine on locomotor activity in rats challenged with the administration of the D2-like dopamine agonist quinpirole, after prolonged exposure to two different stress regimens, repeated restraint stress and chronic mild stress (different stressors randomly presented). These stress schedules have been previously reported to influence in opposite ways the sensitivity to the locomotor response mediated by the stimulation of mesolimbic dopamine receptors. In particular, repeated restraint has been reported to induce an increased response to the locomotor effect of amphetamine, while chronic mild stress has been reported to induce a decreased locomotor response to quinpirole. In the present study, repeated restraint stress failed to influence the locomotor activity after challenge with quinpirole, while chronic mild stress reduced this response. Chronic treatment with desipramine failed to influence this response in the control group, but exerted opposite effects in the two stressed groups. In particular, chronic desipramine reduced locomotor activity in quinpirole-treated rats in the restraint stress group, and increased it in the chronic mild stress group, thus preventing the subsensitivity induced by this stress regimen. The present results, taken together with results from earlier studies, are consistent with the hypothesis that the effect of antidepressants on the sensitivity of the mesolimbic dopamine receptors mediating the locomotor behavioural response tends to be opposite with respect to that exerted by stress, regardless of its direction. However, since we failed to show an increased locomotor activity after quinpirole challenge in the repeated restraint group, this hypothesis remains to be demonstrated. The two stress schedules reduced body weight gain in a similar way, therefore their different effects do not seem to be due to a difference in stress severity. Thus, the observation that both stress schedules reduced body weight gain in a similar way, but only chronic mild stress reduced the sensitivity to the locomotor response to quinpirole, shows that this effect is not an artefact of body weight decrease.
Effect of naloxone therapy on depersonalization: a pilot study
Authors: Nuller Yuri L. , Morozova Marina G. , Kushnir Olga N. , Hamper Nikita
Published: April 2009

To test the hypothesis of the role for the opioid system in the pathogenesis of depersonalization, the effect of naloxone (an opioid receptor blocker) on the symptoms and corticosteroids secretion was studied in patients with depersonalization syndrome. Fourteen depersonalization patients were treated with naloxone: 11 patients received single doses (1.6 or 4 mg i.v.) and three others received multiple infusions, with the maximal dosage being 10 mg, and the effect of naloxone on symptom severity was determined. In eight patients, the cortisol, cortisone and corticosterone content in the blood plasma was determined prior to and after the 4 mg naloxone infusion. A reversed-phase microcolumn high-performance liquid chromatography with ultraviolet detection was applied for assessment of glucocorticoids. In three of 14 patients, depersonalization symptoms disappeared entirely and seven patients showed a marked improvement. The therapeutic effect of naloxone provides evidence for the role of the endogenous opioid system in the pathogenesis of depersonalization.
The ‘Dalhousie Serotonin cocktail’ for treatment-resistant major depressive disorder
Authors: Dursun Serdar M. , Devarajan Sivakumaran , Kutcher Stanley
Published: April 2009

We describe the successful treatment of five patients with treatment-resistant major depressive disorder (TR-MDD) with a combination pharmacotherapy of pindolol, tryptophan and nefazodone. Five TR-MDD outpatients who had previously not responded to at least four different antidepressant medication trials were initiated on 300 mg/day of nefazodone, 7.5 mg/day of pindolol and 1 g/day of tryptophan. Pindolol doses remained the same throughout the 20 weeks, while tryptophan and nefazodone dosages were gradually increased to 8 g/day and 450 mg/day, respectively. The Hamilton Depression Rating Scale (HAM-D) was used to evaluate outcome. By week 4, all cases demonstrated at least 50% decrease in HAM-D scores. At the end of the trial, the group mean HAM-D score had significantly decreased from 26.8 (± 1.9) to 1.8 (± 0.8) (p < 0.001). No significant adverse effects were reported. These results suggest that if serotonin availability and release is further enhanced by tryptophan in the presence of nefazodone and pindolol, an antidepressant effect may be produced in patients who are otherwise treatment-resistant. Due to limited sample size, an open design and an ‘unusually’ high successful efficacy rate of this preliminary study, controlled studies are required to confirm the efficacy of this treatment strategy.
Psychopathology and personality characteristics in relation to blood serotonin in Tourette's syndrome and obsessive–compulsive disorder
Authors: Cath Danielle C. , Spinhoven Philip , Landman Andrea D. , van Kempen Godfried M. J.
Published: April 2009

Family studies suggest an interrelationship between Gilles de la Tourette Syndrome (GTS) and some forms of obsessive–compulsive disorder (OCD). Some authors consider GTS to be part of a serotonergicallyrmediated cluster of OCD spectrum disorders. The present study was undertaken to compare measures of psychopathology, personality and blood serotonin between GTS and OCD (without tics), and to investigate whether an OCD spectrum hypothesis is supported for GTS. Fifteen GTS without OCD subjects, 21 tic with (+) OCD subjects, 15 OCD without tic subjects and 26 controls (all without serotonergic medication) were evaluated with self-rated and clinician-rated measures of psychopathology and personality. Whole blood serotonin (5-HT) and platelet monoamine oxidase activity (MAO) was measured, and Spearman's correlations were calculated between whole blood 5-HT, MAO and rating scale scores within the entire sample and within subgroups. There were main effects of OCD on anxiety, obsessive–compulsive, neuroticism and extraversion scores. There were main effects of tics on depression, obsessive–compulsive, trait anxiety and neuroticism scores, and on platelet MAO. There were interaction effects on platelet MAO, 5-HT, Yale–Brown Obsessive–Compulsive Rating Scale severity, trait anxiety and Eysenck Personality Questionnaire neuroticism scores. Platelet MAO activity was elevated in tic-free OCD subjects when compared to tic + OCD, GTS without OCD and controls. Whole blood 5-HT was lowered in tic + OCD patients in comparison to GTS without OCD and tic-free OCD subjects. Whole blood 5-HT and obsessive–compulsive severity were negatively correlated within OCD without tic patients and MAO and Leyton Obsessive Inventory scores were negatively related within GTS without OCD patients. The biochemical data of this study suggest that in tic + OCD and in tic-free OCD patients, 5-HT dysregulations play a role, but not necessarily in pure GTS. Serotonergic dysregulations within tic + OCD and tic-free OCD patients are distinct, suggesting differences in underlying pathophysiology. The finding that obsessions and compulsions can be associated with either 5-HT hypofunctionality or hyperfunctionality reveals a major weakness in the OCD spectrum theory, i.e. that the associations between obsessive–compulsive behaviours and 5-HT abnormalities are less specific than suggested by the original obsessive–compulsive spectrum model.
Comparative study of mortality rates and cardiac dysrhythmias in post-marketing surveillance studies of sertindole and two other atypical antipsychotic drugs, risperidone and olanzapine
Authors: Wilton Lynda V. , Heeley Emma L. , Pickering Ruth M. , Shakir Saad A.
Published: April 2009

Sertindole (Serdolect), an atypical antipsychotic, was voluntarily suspended in the European Union in 1998 following regulatory concerns over reports of serious cardiac dysrhythmias and sudden unexpected deaths. The reported causes of death, their frequency, prolongation of the rate corrected QT interval (QTc) and cardiac dysrhythmias in patients prescribed sertindole were compared with those for patients treated with two other atypical antipsychotics. All patients in England, prescribed atypical antipsychotics by general practitioners during each drug's immediate post-marketing period, were identified using an observational cohort technique, prescription-event monitoring. Mortality rates in the sertindole cohort were compared with those in a comparator cohort using standardized mortality ratios and incidence rate ratios. Cardiovascular events were reviewed and followed up to identify cases of prolongation of QTc interval. There was no statistically significant difference in mortality rates between sertindole and the comparator cohort, although confidence intervals (CI) were wide due to small numbers in the sertindole cohort. A much smaller number of patients were prescribed sertindole than the other antipsychotics. Six cases of prolongation of QTc interval were identified in 462 patients (1.3%, 95% CI 0.5–2.8) treated with sertindole and one with unspecified electrocardiogram changes in the comparator cohort of 16 542 patients. This study contributes to the understanding of the occurrence of prolongation of QTc interval during clinical use of sertindole, the incidence of which was similar to that in clinical trials. Although no statistically significant difference was shown in mortality rates between sertindole and comparator cohort, the sertindole cohort was too small to rule out an association between the use of this drug and cardiovascular deaths.
A case of depersonalization–derealization syndrome during treatment with quetiapine
Authors: Sarkar Jaydip , Jones Neil , Sullivan Gary
Published: April 2009

A case is reported of a 65-year-old male patient with schizophrenia who developed depersonalization–derealization syndrome following treatment with quetiapine, an atypical antipsychotic. The literature is reviewed for possible biological mechanisms that may account for this phenomenon.
Effects of hydrocortisone administration on cognitive function in the elderly
Authors: Porter Richard J. , Barnett Nicola A. , Idey Ariane , McGuckin Elizabeth A. , O'Brien John T.
Published: April 2009

Previous studies have found adverse effects of both acute and chronic elevations of corticosteroids on cognitive function in humans and that cortisol levels may predict cognitive decline in elderly subjects. However, no previous studies have directly investigated the effects of hydrocortisone on cognitive functioning in the healthy elderly. Sixteen healthy elderly subjects took part in a placebo-controlled, double-blind, cross-over trial. Hydrocortisone 20 mg or placebo was administered twice, 12 h and 1 h before cognitive testing. On each occasion, a battery of neuropsychological tests was performed which included tests of attention, working memory, declarative memory and executive function. Salivary cortisol levels at the time of testing were elevated approximately 10-fold following hydrocortisone compared with placebo. No significant effects were found on memory or a range of other cognitive functions. The lack of effect of this regime of hydrocortisone is in contrast to studies in younger subjects. The elderly may be less sensitive to cognitive effects of short-term increases in cortisol levels, possibly due to an age-related downregulation of hippocampal glucocorticoid receptors.
Acute effects of low-dose interferon-α on serum cortisol and plasma interleukin-6
Authors: Cassidy Eugene M. , Manning Diarmuid , Byrne Sinead , Bolger Emer , Murray Frank , Sharifi Neda , Wallace Eleanor , Keogan Mary , O’Keane Veronica
Published: April 2009

Major depression is associated with both hypothalamic-pituitary-adrenal (HPA) axis overactivity and immune system activation. Depression is a common occurrence following interferon (IFN)-α treatment. While IFN-α is known to stimulate the HPA axis, little is known about the effects of exogenous IFN-α in humans on the proinflammatory cytokine interleukin (IL)-6, a marker of immune system activation. This study examined the acute effects of IFN-α on cortisol and IL-6 release, and the time course of any changes in these variables. Serum cortisol and plasma IL-6 were assessed in healthy volunteers over an 8-h period following 3 million units subcutaneous IFN-α or placebo using a double-blind, placebo-controlled crossover design. IFN-α resulted in a significant increase in both cortisol and IL-6. Regular sampling over 8 h did not delineate any sequential effect of the rise in these variables over time. We conclude that IFN-α acutely stimulates both the HPA axis and proinflammatory cytokine release. The hypothesis that the effect of IFN-α on the HPA axis is indirect and mediated by IL-6 was not supported by this study. Our findings are nonetheless of relevance to the aetiology of depression following IFN-α.
Corticosterone modulation of somatodendritic 5-HT1A receptor function in mice
Authors: Man Mei-See , Young Allan H. , McAllister-Williams R. Hamish
Published: April 2009

Corticosteroid modulation of serotonergic function may play a central role in mood disorders. 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) produces a hypothermia in mice that serves as an in-vivo model of somatodendritic 5-HT1A autoreceptor function. Daily injections (s.c.) of 50 mg/kg of corticosterone (CORT) for 3 days attenuates 8-OH-DPAT hypothermia tested 24 h later. This study sought to further clarify the nature of the CORT-mediated attenuation of somatodendritic 5-HT1A receptor function. Mice underwent various CORT manipulations prior to an 8-OH-DPAT challenge. Neither 14-day bilateral adrenalectomy (ADX), nor CORT 50 mg/kg/day, administered continuously by osmotic minipump over 72 h had any effect on the 8-OH-DPAT hypothermic response. In contrast, daily injections of CORT over three consecutive days caused a significant attenuation in 8-OH-DPAT hypothermia when tested 24 h later. However, administration of an additional dose of CORT 2 h prior to the 8-OH-DPAT challenge occluded this CORT-mediated attenuation in a dose-dependent fashion. The findings demonstrate that CORT modulates somatodendritic 5-HT1A receptor function in a complex manner. Attenuation is seen only after intermittent administration of CORT. In addition, the degree of attenuation depends on CORT concentrations at the time of testing. These findings may have implications regarding mechanisms of adaptation to stress.
Donepezil for memory dysfunction in schizophrenia
Authors: Howard Andrew K. , Thornton Allen E. , Altman Siemion , Honer William G.
Published: April 2009

A case is reported of a 54-year-old female patient with schizophrenia and cognitive impairment. Her memory dysfunction improved following the addition of donepezil to quetiapine. The possible implications for future studies are reviewed.
Venlafaxine: the relationship between dose, plasma concentration and clinical response in depressive patients.
Authors: Charlier C. , Pinto E. , Ansseau M. , Plomteux G.
Published: April 2009

The relationship between plasma drug level of venlafaxine and daily intake was studied in 89 major depressive inpatients. In addition, changes over time in severity were assessed weekly in a subgroup of 22 depressed patients using the Montgomery and Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression improvement scale. The results indicate a moderate correlation between daily doses and plasma concentrations, together with a higher relationship between improvement on the MADRS scale and concentration. Moreover, plasma concentrations (for venlafaxine and its predominant metabolite, O-desmethylvenlafaxine) up to 400 µg/l can be considered as effective, as already suggested in a previous study. No case of venlafaxine discontinuation occurred during the longitudinal study, and the incidence of adverse event, as estimated by the Target Emergent Symptoms and Side-effects scale, was low, suggesting that the drug is well tolerated for such plasma concentrations.
Psychotropic drugs in mothers' milk: a comprehensive review of assay methods, pharmacokinetics and of safety of breast-feeding
Authors: Yoshida K. , Smith B. , Kumar R.
Published: April 2009

Many mentally ill women want to breast-feed their babies but, if theyare taking psychotropic drugs, there is very little systematic data upon which to base decisions about whether or not it is safe to do so.We therefore attempt to provide a comprehensive and critical summary of existing case reports and of studies of breast-feeding in relation to commonly used psychotropic drugs. The literature review focuses on the following drugs: antidepressants: tricyclics and serotonin selective reuptake inhibitors (SSRIs); antipsychotic drugs: chlorpromazine, perphenazine, haloperidol and clozapine; mood stabilizers: lithium and carbamazepine; and benzodiazepines. The research literature consists mainly of single case reports and there have been very few attempts at controlled, longitudinal investigations. Findings are often difficult to compare because of differences in methods or because of lack of key information. Most data are available about the tricyclic antidepressants but even here we have found that the reports cover only a grand total of 66 mother-infant pairs. Dilemmas about whether or not to contraindicate breast-feeding arise most commonly in relation to postnatal depression. The findings to date suggest that provided that infants are healthy at the outset it is likely that the benefits of breast-feeding will outweigh potential hazards if their mothers are taking established tricyclic drugs at recommended dose levels. Much less is known about risks associated with SSRI antidepressants or about antipsychotic drugs such as phenothiazines and butyrophenones or mood stabilizers such as carbamazepine, all of which enter breast-milk. Safeguards are suggested for future single case studies, which, as they accumulate, will provide a platform for mounting controlled prospective studies properly to test for any acute toxic effects and for possible long-term adverse effects of such drugs on infants' development. Appendix 1 is a review of assay methods. Appendix 2 examines pharmacokinetic factors in newborn preterm and sick infants with special reference to contraindications to breast-feeding. Appendix 3 is a review of methods for assessing infant health and development.
The effects of idazoxan on reaction times, eye movements and the mood of healthy volunteers and patients with upper respiratory tract illnesses
Authors: Smith Andrew , Sturgess Wendy , Richi Neil , Brice Carolyn , Collisonl Claire , Bailey Jayne , Wilson Sue , Nutt David J.
Published: April 2009

An experiment was carried out to determine whether idazoxan, a drug which increases the turnover of central noradrenaline, removes the malaise (reduced alertness, slower psychomotor performance) associated with upper respiratory tract illness (URTI). Eighty-one volunteers were tested when healthy and 17 returned to the laboratory when they developed URTIs. Those who remained healthy were then recalled as a control group. Volunteers were tested before and after receiving either idazoxan (40 mg) or a lactose placebo. Idazoxan removed the URTI-induced slowing in a simple reaction time task and this group performed at a comparable level to the healthy group. No significant stimulant effect of idazoxan was found in the healthy subjects. The results suggest that at least part of the malaise induced by URTIs may reflect reductions in central noradrenaline and that this can be reversed by compounds such as idazoxan.
Single dose pharmacodynamics of thioridazine and remoxipride in healthy younger and older volunteers
Authors: Swift C. G. , Lee D. R. , Maskrey V. L. , Yisak W. , Jackson S. H.D. , Tiplady B.
Published: April 2009

Phenothiazines are widely used in older patients, but little experimental work has been carried out in this age group. Two groups of healthy volunteers, a younger group (Y: six males and six females, aged 20-42 years) and an older group (0: six males and eight females, aged 65-77 years) took part in a randomized double-blind threeperiod crossover study in which they received by mouth single doses of thioridazine (Y: 50mg; 0: 25mg) remoxipride (Y: 100mg; 0: 50mg) or placebo. Measures of central nervous system (CNS) and haemodynamic function were carried out before drug administration and at 1.5-h intervals up to 9h post-dose, and blood samples were collected over a 24-h period. No significant differences in dose-corrected pharmacokinetic variables were found between the two groups. There was evidence of marked CNS depressant effects of thioridazine from both objective and subjective measures. The effects for remoxipride were similar, though generally less marked. After allowance was made for dose, there was little indication of any difference in degree of CNS depression between the two age groups. Haemodynamic measures showed orthostatic reductions in blood pressure with thioridazine which were particularly marked in the older group, who also showed lower compensatory increases in pulse rate. These results indicate potential problems with orthostatic hypotension with thioridazine in older patients. CNS depression may also be a problem, especially in patients with compromised cholinergic function.
An acute ischaemic event associated with the use of venlafaxine: a case report and proposed pathophysiological mechanisms
Authors: Reznik I. , Rosen Y. , Rosen B.
Published: April 2009

Venlafaxine, a structurally novel antidepressant, belongs to a new generation of antidepressants the serotonin/noradrenaline reuptake inhibitors. In clinical trials, venlafaxine was found safe and effective in most patients. However, significant changes in vital signs (hyperand hypotension) and cardiac conduction abnormalities were observed in a few patients, notably in elderly patients. We present a case of an elderly woman with a pre-existing history of ischaemic heart disease, who was treated with venlafaxine, and developed acute myocardial ischaemia within the first week of treatment. This is the first report of a possible association between an acute cardiovascular event and venlafaxine. The association of venlafaxine treatment with ischaemic events could be explained by its unique pharmacological and haemodynamic properties.
Does a four-week delay in the introduction of medication alter the course of functional psychosis?
Authors: Johnstone Eve C. , Owens David G. C. , Crow Timothy J. , Davis John M.
Published: April 2009

This study is an analysis of findings of a follow-up study of 105 patients with functional psychotic illness who had participated in a random and blind 4-week trial of pimozide, lithium, both and placebo. The intention was to examine the question of whether a 4-week delay in initiating antipsychotic treatment has a detrimental effect 2.5 years later. Detailed follow-up measures included need for care over the 2.5 years, treatments required, occupational decline, police contact, substance misuse, psychopathology and cognitive function. There was no evidence at all that those initially randomized to placebo had a poorer outcome in terms of any of these variables. It is concluded that a 4-week delay in initiating active treatment in patients with functional psychosis has no long-term adverse effects.
Dopamine as the wind of the psychotic fire: new evidence from brain imaging studies
Authors: Laruelle Marc , Abi-Dargham Anissa
Published: April 2009

Abnormalities of dopamine function in schizophrenia are suggested by the common antidopaminergic properties of antipsychotic medications. However, direct evidence of a hyperdopaminergic state in schizophrenia has been diffcult to demonstrate, given the diffculty of measuring dopamine transmission in the living human brain. This situation is rapidly changing. Recent developments in positron emission tomography and single-photon emission tomographic techniques enabled measurement of acute fluctuation of synaptic dopamine in the vicinity of D2receptors. Using this technique, we, and others, measured the increase in dopamine transmission following aute amphetamine challenge in untreated patients with schizophrenia and matched healthy subjects. Following a brief overview of these new brain imaging techniques, the main results derived with this method in patients with schizophrenia are described: (1) amphetamine-induced dopamine release is elevated in patients with schizophrenia, supporting the idea that schizophrenia is associated with dysregulation of dopamine transmission; (2) following amphetamine, hyperactivity of dopamine transmission is associated with activation of psychotic symptomatology; (3) this dysregulation of dopamine release is not a long-term consequence of previous neuroleptic treatment, and is detected in never-medicated patients experiencing a first episode of the illness; and (4) in contrast, this exaggerated response of the dopamine system to amphetamine exposure is not detected in patients studied during a period of illness stabilization, suggesting that the hyperdopaminergic state associated with schizophrenia fluctuates over time. In conclusion, a hyperdopaminergic state might be present in schizophrenia during the initial episode and subsequent relapses, but not during periods of remission. This finding has important consequences for the development of new treatment strategies for the remission phase.
A 12-week study comparing moclobemide and sertraline in the treatment of outpatients with atypical depression
Authors: SÖgaard Jesper , Lane Roger , Latimer Paul , Behnke Kirsten , Christiansen Poule E. , Nielsen Bjarne , Ravindran Arun V. , Reesal Robin T. , Goodwin Daryl P.
Published: April 2009

One hundred and ninety-seven outpatients with atypical depression [Atypical Depression Diagnostic Scale (ADDS) score=4] were randomized to 12 weeks of double-blind treatment with sertraline or moclobemide in a multicentre, parallel-group clinical trial. Patients were started on either 50 mg/day sertraline or 300 mg/day moclobemide. If the therapeutic response was not satisfactoryafter 4 weeks, the dose could be increased to either 100 mg/day sertraline or 450 mg/day moclobemide. Primary effcacy evaluations were the 29-item Hamilton Psychiatric Rating Scale for Depression (HAM-D) and the Clinical Global Impression of Improvement (CGI I) response rate (much or very much improved) at study endpoint. Secondary effcacy evaluations included the ADDS, the Hamilton Anxiety Scale (HAMA), the Leeds Sleep Scale, and the Battelle Quality of Life Battery (BQOLB). In the analysis of the 172 patient effcacy-evaluable population, there was significant baseline to endpoint improvement in all primary and secondary effcacy assessments after treatment with either sertraline or moclobemide. At the endpoint, the proportion of responders on CGI-I, was 77.5% in the sertraline group and 67.5% in the moclobemide group (p=0.052). The baseline to endpoint mean 29-item HAM-D score decreased from 35.9 to 14.5 in the sertraline group and from 36.3 to 16.1 in the moclobemide group. Sertraline also resulted in a significantly (p50.05) greater degree of improvement at the endpoint, compared with moclobemide, in the proportion of remitters on the HAMA (total score47), ADDS Category IID (Rejection Sensitivity), Leeds Sleep Factor 4 (Integrity of Behaviour Following Awakening), and on three dimensions of the BQOLB (Energy/Vitality, Social Interaction and Life Satisfaction). There were no other significant differences between treatment groups. Overall, both medications were well tolerated. In this study, both sertraline and moclobemide improved the symptoms of atypical depression.
Visual Analog Scales, Standard Gambles, and Relative Risk Aversion
Authors: Robinson Angela , Loomes Graham , Jones-Lee Michael
Published: April 2009

Background. It has been argued that visual analog scales (VASs) elicit an individual’s measurable value function. The theoretical link between an individual’s measurable value function v(.) and his or her von Neumann-Morgenstern utility function u(.) appears to provide a justification for transforming VAS scores into standard gamble (SG) utilities. However, VAS scores have been found to be subject to the effects of context, which casts doubt that the procedure is properly revealing v(.). Methods. The authors tested for the effects of context on VAS and SG scores. They also explored whether the range-frequency (R-F) model of Parducci offers a means of correcting VAS scores for the effects of context. Results and conclusions. The R-F model may provide a means of correcting VAS scores for the effects of context, but no stable relationship exists between these corrected scores and SG utilities. Hence, there remain no grounds for transforming VAS scores into SG utilities.
Factors Influencing Physicians’ Judgments of Adherence and Treatment Decisions for Patients with HIV Disease
Authors: Bogart Laura M. , Catz Sheryl L. , Kelly Jeffrey A. , Benotsch Eric G.
Published: April 2009

New medications for HIV reduce mortality and morbidity but require strict adherence. Thus, physicians treating HIV-positive patients must weigh both disease severity and likelihood of adherence when deciding whether to start patients on treatment. A national sample of 495 physicians surveyed via mail responded to clinical scenarios depicting HIV-positive patients and indicated whether they would start patients on medication (response rate = 53%). Scenarios varied on the patient characteristics of gender, disease severity, ethnicity, and risk group. Physicians predicted that patients with less severe disease, former injection drug users, and African American men would be less likely to adhere. Perceived adherence and disease severity influenced treatment decisions. Results are discussed in the context of attitudes about minority groups and injection drug users, which may influence adherence judgments in practice settings. Psychological research to identify better methods of predicting medication adherence may serve to inform medical decision making.
General Performance on a Numeracy Scale among Highly Educated Samples
Authors: Lipkus Isaac M. , Samsa Greg , Rimer Barbara K.
Published: April 2009

Background. Numeracy, how facile people are with basic probability and mathematical concepts, is associated with how people perceive health risks. Performance on simple numeracy problems has been poor among populations with little as well as more formal education. Here, we examine how highly educated participants performed on a general and an expanded numeracy scale. The latter was designed within the context of health risks. Method. A total of 463 men and women aged 40 and older completed a 3-item general and an expanded 7-item numeracy scale. The expanded scale assessed how well people 1) differentiate and perform simple mathematical operations on risk magnitudes using percentages and proportions, 2) convert percentages to proportions, 3) convert proportions to percentages, and 4) convert probabilities to proportions. Results. On average, 18% and 32% of participants correctly answered all of the general and expanded numeracy scale items. Approximately 16% to 20% incorrectly answered the most straightforward questions pertaining to risk magnitudes (e.g., Which represents the larger risk: 1%, 5%, or 10%?). A factor analysis revealed that the general and expanded risk numeracy items tapped the construct of global numeracy. Conclusions. These results suggest that even highly educated participants have difficulty with relatively simple numeracy questions, thus replicating in part earlier studies. The implication is that usual strategies for communicating numerical risk may be flawed. Methods and consequences of communicating health risk information tailored to a person’s level of numeracy should be explored further.
Prognostic Modeling with Logistic Regression Analysis
Authors: Steyerberg Ewout W. , Eijkemans Marinus J. C. , Harrell Frank E. , Habbema J. Dik F.
Published: April 2009

Clinical decision making often requires estimates of the likelihood of a dichotomous outcome in individual patients. When empirical data are available, these estimates may well be obtained from a logistic regression model. Several strategies may be followed in the development of such a model. In this study, the authors compare alternative strategies in 23 small subsamples from a large data set of patients with an acute myocardial infarction, where they developed predictive models for 30-day mortality. Evaluations were performed in an independent part of the data set. Specifically, the authors studied the effect of coding of covariables and stepwise selection on discriminative ability of the resulting model, and the effect of statistical “shrinkage” techniques on calibration. As expected, dichotomization of continuous covariables implied a loss of information. Remarkably, stepwise selection resulted in less discriminating models compared to full models including all available covariables, even when more than half of these were randomly associated with the outcome. Using qualitative information on the sign of the effect of predictors slightly improved the predictive ability. Calibration improved when shrinkage was applied on the standard maximum likelihood estimates of the regression coefficients. In conclusion, a sensible strategy in small data sets is to apply shrinkage methods in full models that include well-coded predictors that are selected based on external information.
Rationing versus Rationality
Authors: Jackson Terri
Published: April 2009

This commentary takes up A. David Paltiel’s invitation to reflect on how to promote the use of decision analysis and cost-effectiveness analysis in health. From the perspective of a health services researcher outside the U.S. system, I make 3 arguments. First, the unthinking use of the term rationing for all applications of cost-effectiveness analysis distorts research priorities and may jeopardize wider public support. Second, public skepticism about decision and cost-effectiveness analysis (and thus the skepticism of decision makers) is well founded when ethical dimensions of these methods are not considered. We must continue to refine our methods to take account of societal values. Third, the United States may have particular problems in adopting more rational decision making in health care. The dominance of for profit institutions in the U.S. health care system erodes the social legitimacy on which other systems depend to improve the rationality of health care decision making.
Optimal Investment in a Portfolio of HIV Prevention Programs
Authors: Zaric Gregory S. , Brandeau Margaret L.
Published: April 2009

Objectives. In this article, the authors determine the optimal allocation of HIV prevention funds and investigate the impact of different allocation methods on health outcomes. Methods. The authors present a resource allocation model that can be used to determine the allocation of HIV prevention funds that maximizes quality-adjusted life years (or life years) gained or HIV infections averted in a population over a specified time horizon. They apply the model to determine the allocation of a limited budget among 3 types of HIV prevention programs in a population of injection drug users and nonusers: needle exchange programs, methadone maintenance treatment, and condom availability programs. For each prevention program, the authors estimate a production function that relates the amount invested to the associated change in risky behavior. Results. The authors determine the optimal allocation of funds for both objective functions for a high-prevalence population and a low-prevalence population. They also consider the allocation of funds under several common rules of thumb that are used to allocate HIV prevention resources. It is shown that simpler allocation methods(e.g., allocation based on HIV incidence or notions of equity among population groups) may lead to allocations that do not yield the maximum health benefit. Conclusions. The optimal allocation of HIV prevention funds in a population depends on HIV prevalence and incidence, the objective function, the production functions for the prevention programs, and other factors. Consideration of cost, equity, and social and political norms may be important when allocating HIV prevention funds. The model presented in this article can help decision makers determine the health consequences of different allocations of funds.
Frequency or Probability? A Qualitative Study of Risk Communication Formats Used in Health Care
Authors: Schapira Marilyn M. , Nattinger Ann B. , McHorney Colleen A.
Published: April 2009

Background. The communication of probabilistic outcomes is an essential aspect of shared medical decision making. Methods. The authors conducted a qualitative study using focus groups to evaluate the response of women to various formats used in the communication of breast cancer risk. Findings. Graphic discrete frequency formats using highlighted human figures had greater salience than continuous probability formats using bar graphs. Potential biases in the estimation of risk magnitude were associated with the use of highlighted human figures versus bar graphs and the denominator size in graphics using highlighted human figures. The presentation of uncertainty associated with risk estimates caused some to loose trust in the information, whereas others were accepting of uncertainty in scientific data. Conclusion. The qualitative study identified new constructs with regard to how patients process probabilistic information. Further research in the clinical setting is needed to provide a theoretical justification for the format used when presenting risk information to patients.
Using Elicitation Techniques to Estimate the Value of Ambulatory Treatments for Major Depression
Authors: Normand Sharon-Lise T. , Frank Richard G. , McGuire Thomas G.
Published: April 2009

Estimating the value of spending on medical treatments in a health care system involves relating output, measured in terms of effectiveness, to cost, measured in terms of spending. Although information on spending at the system level often exists in administrative data, such as insurance claims, information on effectiveness is not always available. An inferential tool available to researchers in this context is elicitation. The authors develop an approach to elicit effectiveness parameters and apply it to a panel of 10 experts to estimate predictive Hamilton Depression Rating Scale scores representing postambulatory treatment outcomes. The elicited parameters are used to estimate outcomes associated with 120 acute phase treatments for major depression within a privately insured health insurance system. The outcome-adjusted price per full remission episode is estimated for each acute treatment, and corresponding 95% percentile bootstrap intervals are calculated. The average spending for all observed treatments was $473 (SE = 478), with a depression-free adjusted price per case of $5995 (95% confidence interval = $5959-$6031).
“You’re Perfect for the Procedure! Why Don’t You Want It?” Elderly Arthritis Patients’ Unwillingness to Consider Total Joint Arthroplasty Surgery: A Qualitative Study
Authors: Hudak Pamela L. , Clark Jocalyn P. , Hawker Gillian A. , Coyte Peter C. , Mahomed Nizar N. , Kreder Hans J. , Wright James G.
Published: April 2009

Objective. To explore the process by which elderly persons make decisions about a surgical treatment, total joint arthroplasty (TJA). Methods. In-depth interviews with 17 elderly individuals identified as potential candidates for TJA who were unwilling to undergo the procedure. Results. For the majority of participants, decision making involved ongoing deliberation of the surgical option, often resulting in a deferral of the treatment decision. Three assumptions may constrain elderly persons from making a decision about surgery. First, some participants viewed osteoarthritis not as a disease but as a normal part of aging. Second, despite being candidates for TJA according to medical criteria, many participants believed candidacy required a level of pain and disability higher than their current level. Third, some participants believed that if they either required or would benefit from TJA, their physicians would advise surgery. Conclusion. These assumptions may limit the possibility for shared decision making. Clinical Implications. Emphasis should be directed toward thinking about ways in which discussions about TJA might be initiated (and by whom) and considering how patients’ views on and knowledge of osteoarthritis in general might be addressed.
The Effects of Proficiency and Bias on Residents’ Interpretation of the Microscopic Urinalysis
Authors: Flach Stephen D. , Canaris Gay J. , Tape Thomas G. , Huntley Kathryn M. , Wigton Robert S.
Published: April 2009

Objective. This study aims to determine whether residents are influenced by clinical information when interpreting microscopic urinalysis (UA) and estimating the probability of a urinary tract infection (UTI), and to determine the accuracy and reliability of UA readings. Design. Residents estimated the UA white blood cell count and the probability of a UTI in vignettes using a fractional factorial design, varying symptoms, gender, and the white blood cell count on preprepared urine slides. Results. Individual-level results indicated a clinical information bias and poor accuracy. Seventeen of 38 residents increased the white blood cell count in response to female gender; 14 increased the white blood cell count in response to UTI symptoms. Forty-nine percent of the readings were inaccurate; agreement ranged from 50% to 67% for white and red blood cells and bacteria. Conclusion. Many residents gave inaccurate UA readings, and many readings varied with clinical information. A significant portion of residents needs assistance in objectively and accurately interpreting the UA.
Gone for a Soldier: The Anatomy of a Nineteenth-Century Army Family
Authors: Oddy Derek J.
Published: April 2009

This article discusses aspects of life in the British army in the nineteenth century. It explores the motivation of recruits and the conditions under which family life was possible for the rank-and-file soldier. Using a Scottish case study, the article shows how army life operated at the individual family level and how multigeneration army families were created. It also demonstrates ways in which the army contributed to population mobility in the United Kingdom before World War I.
“An Untiring Zest for Life”: Images and Self-Images of Old Women in England
Authors: Thane Pat
Published: April 2009

The prevailing view among historians and contemporaries is that old people were more highly regarded in the past and that old women were regarded more negatively than men. This article questions such simple changes over time and the uniformity and negativity of attitudes in the present. A variety of sources—diaries, letters, biographies, social investigation, and personal testimony—indicate how much can be retrieved about the images and self-images of old women. They suggest how varied these images have been. Older women, rich and poor, could belie and contest negative stereotypes and could be well respected.
Paternity and the Politics of Citizenship in Interwar France
Authors: Childers Kristen Stromberg
Published: April 2009

Fathers have been neglected in the historiography of gender, social reform, and citizenship in France. In the interwar years, fathers’ rights and responsibilities became key issues in the discourse surrounding the reduction of working hours and the politics of suffrage reform. Fathers figured largely in the aspirations of ideologically opposed groups and symbolized a competition for resources within the nascentwelfare state. Social reformers argued formore privileges or better living conditions for the père de famille, who represented the ideal citizen in the efforts at postwar reconstruction.
Home Ownership and Spacious Homes: Equity under Stress in Early-Twentieth-Century Canada
Authors: Baskerville Peter
Published: April 2009

This article attempts to contribute to a burgeoning literature on Canadian housing history. It approaches the nature of housing by linking two measurements often examined in isolation: ownership and interior space. Using data from the Canadian Families Project’s 5 percent random sample of the nominal census returns for Canada in 1901, this article presents the first national analysis comparing housing ownership and housing space in both rural and urban Canada. It attempts to determine, via a series of logistic regressions, the relative importance of several social and economic variables on a family’s chances of owning a home and of living in a crowded or relatively spacious environment. The article demonstrates that the social and economic influences on the chances of ownership differed in some significant ways from the influences on the chances of living in a spacious home.
Domestic Violence Prosecuted: Women Binding over Their Husbands for Assault at Westminster Quarter Sessions, 1685-1720
Authors: Hurl-Eamon Jennine
Published: April 2009

Recognizances have been studied very little as evidence of domestic violence, yet they can yield many insights for historians. Using more than one hundred recognizances for assaults by husbands upon wives in Westminster Quarter Sessions records, 1680-1720, this article argues that wives could prosecute even a relatively minor incident of violence. In contrast, servants and apprentices appear to have been able to prosecute assaults by employers only if they coincided with contractual violations. Adulterous lovers, neighbors, and extended family were present in domestic violence prosecutions at various times and, along with wives, appear to have played a role in limiting patriarchal power.
Family, Paisanaje, and Migration Among Madrid’s Merchants (1750-1800)
Authors: Sola-Corbacho Juan Carlos
Published: April 2009

During the second half of the eighteenth century, Madrid was the most important city and the largest market of the Spanish Bourbon empire. Its mercantile sector was the most powerful in Spain, even more than those of Cadiz or Barcelona. One of the most significant features of this socioeconomic sector is that most of its members were immigrants from other Spanish regions. In this article, the author will study the importance of the family and paisanaje links that these immigrants used to integrate into the mercantile sector of Madrid as well as the consequences of their strategies for the society and economy of the imperial capital. The most important of these consequences are that these strategies created a closed system of social relations and that the network of family ties created complex exchanges between Madrid and other regions of the Iberian peninsula.