Objective and subjective vasomotor symptom outcomes in the CBT-Meno randomized controlled trial.

Objective: Vasomotor symptoms (hot flashes, night sweats) are common during the menopausal transition. Pharmacotherapy is effective but is associated with health risks for some women. There is an increasing demand for non-pharmacological interventions. The CBT-Meno protocol is a psychological intervention targeting a range of common menopausal symptoms. We compared the impact of CBT-Meno vs. waitlist on objective and subjective measures of vasomotor symptoms and on the relationship between vasomotor symptoms and sleep difficulties.Materials: The participants were 36 perimenopausal or postmenopausal women with co-occurring depressive symptoms who participated in the CBT-Meno trial (clinicaltrials.gov NCT02480192). Subjective measures included the Hot Flash Related Daily Interference Scale, the Greene Climacteric Scale, and the Pittsburgh Sleep Quality Inventory. Objective (physiological) and 'in-the-moment' measures of vasomotor symptoms were assessed with sternal skin conductance.Results: Greater improvements in vasomotor 'bothersomeness' and 'interference' were observed in the CBT-Meno condition compared to the waitlist condition. No between-group differences were observed in vasomotor frequency (subjectively or objectively recorded) or severity ratings. Sleep disturbance was unrelated to objectively measured vasomotor symptom frequency.Conclusion: The CBT-Meno trial improved subjective but not objective (physiological) measures of vasomotor symptoms. Self-reported sleep difficulties were unrelated to subjective or objective vasomotor symptoms.

Development of a standardized MRI scoring tool for CNS demyelination in children.

BACKGROUND AND PURPOSE: The degree to which MR imaging is useful in the diagnosis of MS is predicated on standardized and reliable evaluation of MR imaging parameters. We aimed to devise items for an MR imaging scoring tool that would have high inter-rater agreement and would be straightforward to apply. MATERIALS AND METHODS: On the basis of a literature search and consensus of an expert panel, we identified 48 parameters that describe acute CNS demyelination, predict MS diagnosis, or characterize demyelinating disorder mimics. MR images of children with clinically confirmed MS, monophasic ADEM, and angiography-negative biopsy-positive small-vessel primary angiitis of the CNS were scored by 2 neuroradiologists independently, using the preliminary 48-parameter tool. Parameters with Cohen κ ≥ 0.6 and deemed important in predicting diagnosis were retained. Parameters not visualized on routine clinical imaging or not important in differentiating MS, ADEM, and SV-cPACNS were discarded. RESULTS: Of 65 eligible patients, 55 children were enrolled (16 with monophasic ADEM, 27 with MS, 12 with SV-cPACNS); 10 were excluded (6 had hard-copy films, 4 did not meet MR imaging quality requirements). Of the 48 parameters, 16 were retained in the final scoring tool. The remaining 28 parameters were discarded: 4 had κ < 0.6 and were not deemed useful in predicting diagnosis; 9 were not visible on routinely acquired clinical images; and 15 had inter-rater agreement ≥0.6 but were not useful in differentiating monophasic ADEM, MS, and SV-cPACNS. CONCLUSIONS: We propose a 16-parameter MR imaging scoring tool that is straightforward to apply in the clinical setting and demonstrates high inter-rater agreement.

Validation of MRI predictors of multiple sclerosis diagnosis in children with acute CNS demyelination.

BACKGROUND: In a recent Canadian prospective study of children with acute demyelinating syndromes (ADS), we demonstrated that the presence of T2 periventricular and T1-hypointense lesions predicted MS diagnosis. We aimed to validate these predictors in a Dutch cohort of children with ADS. METHODS: Participants with ADS were identified from a prospective cohort or archived dataset. MS was diagnosed based on clinical or MRI evidence of relapsing disease. Baseline MRI scans were evaluated for the presence of the two predictive parameters. Sensitivity, specificity, positive (LR+) and negative likelihood ratios (LR-), and positive (PPV) and negative predictive value (NPV) were calculated to evaluate the performance of the MRI parameters at classifying children as having MS or monophasic demyelination. FINDINGS: Of 115 children identified with ADS between December 1993 and December 2009, MRI scans from 87 children (45 prospective; 47 archived) were evaluated; scans of 28 children were excluded due to incomplete or poor quality imaging. Mean duration of observation was longer in the archived group (7.1 years, SD 3.5) than the prospective cohort (3.3 years, SD 1.4). 30 children were diagnosed with MS. Performance of the parameters was not statistically different between the prospective cohort (sensitivity 93.3% [68.1-99.8]; specificity 86.7% [69.3-96.2]; LR+ 7.0 [2.8-17.6]; LR- 0.08 [0.01-0.5]; PPV 77.8% [52.4-93.6]; NPV 96.3% [81.0-99.9]) and archived group (sensitivity 66.7% [38.4-88.2]; specificity 85.2% [66.3-95.8]; LR+ 4.5 [1.7-11.9]; LR- 0.4 [0.2-0.8]; PPV 71.4% [41.9-91.6]; NPV 82.1% [63.1-93.9]). INTERPRETATION: In an independent Dutch cohort, we confirm that the presence of ≥1 T2 periventricular and ≥1 T1-hypointense lesions reliably identifies children with MS. FUNDING: Dutch MS Research Foundation.

The trajectory of recovery and the inter-relationships of symptoms, activity and participation in the first year following total hip and knee replacement.

OBJECTIVE: Primary total hip (THR) and knee (TKR) replacement outcomes typically include pain and function with a single time of follow-up post-surgery. This research evaluated the trajectory of recovery and inter-relationships within and across time of physical impairments (PI) (e.g., symptoms), activity limitations (AL), and social participation restrictions (PR) in the year following THR and TKR for osteoarthritis. DESIGN: Participants (hip: n=437; knee: 494) completed measures pre-surgery and at 2 weeks, 1, 3, 6 and 12 months post-surgery. These included PI (Hip Disability and Osteoarthritis Outcome Score (HOOS)/Knee Injury and Osteoarthritis Outcome Score (KOOS) symptoms and Chronic Pain Grade); AL (HOOS/KOOS activities of daily living and sports/leisure activities); and, PR (Late Life Disability and the Calderdale community mobility). Repeated measures analysis of variance (RANOVA) was used to evaluate the trajectory of recovery of outcomes and the inter-relationships of PI, AL and PR were evaluated using path analysis. All analyses were adjusted for age, sex, obesity, THR/TKR, low back pain and mood. RESULTS: THR: age 31-86 years with 55% female; TKR: age 35-88 years with 65% female. Significant improvements in outcomes were observed over time. However, improvements were lagged over time with earlier improvements in PI and AL and later improvements in PR. Within and across time, PI was associated with AL and AL was associated with PR. The magnitude of these inter-relationships varied over time. CONCLUSION: Given the lagged inter-relationship of PI, AL and PR, the provision and timing of interventions targeting all constructs are critical to maximizing outcome. Current care pathways focusing on short-term follow-up with limited attention to social and community participation should be re-evaluated.

Quality of life in childhood epilepsy: what is the level of agreement between youth and their parents?

Children and parents evaluate the child's quality of life (QOL) from their own perspectives; therefore, responses may differ, especially in abstract domains. We examined differences between self- and proxy-reported QOL of children with epilepsy. Children with active epilepsy (N=375) and their parents (N=378) separately completed the CHEQOL-25, a condition-specific QOL measure. The intraclass correlation coefficient was used to determine interrater agreement. Concordance on the Total CHEQOL-25 was 0.45 (P<0.01). Discrepancies were greatest for the subscales of Secrecy (0.24, P<0.01) and Present Concerns (0.32, P<0.01). School placement correlated with discrepancy in the Intrapersonal/Emotional subscale (r=0.19, P<0.05), and the child's age at testing correlated with discrepancy of the Total measure (r=0.15, P<0.01). This study demonstrates that parent perspectives alone are insufficient to measure their child's QOL. The CHEQOL-25 is a practical tool, with complementary parent and child versions, which can be used to determine health-related quality of life in children with epilepsy.

Cholinesterase inhibitors slow decline in executive functions, rather than memory, in Alzheimer's disease: a 1-year observational study in the Sunnybrook dementia cohort.

To determine if there are differential treatment effects of second-generation cholinesterase inhibitors over one year, 130 patients (untreated=65, treated=65) meeting NINCDS-ADRDA criteria for mild or moderate probable AD underwent standardized cognitive testing at baseline and 12 months later at a university memory clinic. Patients were followed either prior to or after the availability of treatment and were matched on education and baseline Mini Mental State Examination (MMSE). A detailed medical history evaluation was conducted. In this well matched longitudinal observational cohort study, there were no differences in the prevalence of comorbid illnesses, concomitant medication use or vascular risk factors except for a greater number of treated patients with a previous history of smoking. Separate repeated measures MANCOVAs on the MMSE, Mattis Dementia Rating Scale (DRS), and its 5 subscores (attention, initiation/perseveration, conceptualization, construction and memory) (Bonferroni corrected), after covarying for the effects of smoking, and SSRI use, showed less decline over one year in the treated group in overall cognition and in all subscores of the DRS except for memory (effect sizes 0.5-0.7). Less decline was also seen in the treated group in function and in instrumental and basic activities of daily living as measured with the Disability Assessment for Dementia Scale (DAD) (effect sizes 0.4-0.8). Executive, language and visuospatial functions, rather than memory, appeared to be more amenable to stabilization over one year by cholinesterase inhibitors in AD.

Cross-cultural equivalence in depression assessment: Japan-Europe-North American study.

OBJECTIVE: Worldwide use of the Hamilton Rating Scale for Depression (HRSD) presupposes that depression symptomatology can be measured the same way across countries but no empirical study has yet examined this issue. We therefore examined cross-cultural consistency of factor structure of HRSD. METHOD: A 17-item HRSD data were sought for 5,185 individuals diagnosed with major depression in Japan, Europe and North America. Candidate factor structures were obtained with simultaneous component analysis (SCA) across the three cultures. They were then submitted to multiple-group confirmatory factor analysis (CFA). RESULTS: According to SCA, 3-, 4- or 5-factor solutions were found to optimally and adequately summarize the variables for all the three populations. When submitted to CFA, the 5-factor solution was the best fitting and the most parsimonious: they were 'anhedonia/retardation,''guilt/agitation,''bodily symptoms,''insomnia' and 'appetite.' CONCLUSION: Common underlying factors exist for HRSD among Japanese, European and American patients with major depression.

Predictors of outcome among high functioning children with autism and Asperger syndrome.

BACKGROUND: The objective of this paper is to assess the extent to which measures of cognitive abilities taken in an inception cohort of young high functioning children with autism and Asperger syndrome predict outcome roughly two and six years later. METHOD: Children who received a diagnosis of autism or Asperger syndrome (AS) and who had a nonverbal IQ score in the 'non-retarded' range were included in the inception cohort. Measures of language and nonverbal skills were taken when the children were 4-6 years of age and outcome assessments were completed when the children were 6-8 and 10-13 years of age. The three outcome measures consisted of scales of adaptive behaviours in socialisation and communication and a composite measure of autistic symptoms (abnormal language, abnormal body and object use, difficulties relating to others, sensory issues and social and self-help difficulties). RESULTS: The explanatory power of the predictor variables was greater for communication and social skills than for autistic symptoms. The power of prediction was stable over time but did differ by PDD subtype. In general, the association between language skills and outcome was stronger in the autism group than in the AS group. CONCLUSIONS: These results support the emphasis of early intervention programmes on language but more work needs to be done on understanding variables that influence outcome in social skills and autistic behaviours, particularly in those with AS.

Antidepressant and benzodiazepine for major depression.

BACKGROUND: Anxiety frequently coexists with depression. Adding benzodiazepines to antidepressants is commonly used to treat people with depression, although there has been no convincing evidence to show that such a combination is more effective than antidepressants alone and that there are suggestions that benzodiazepines may lose their efficacy with long-term administration and that their chronic use carries risks of dependence. OBJECTIVES: To determine whether, among adult patients with major depression, adding benzodiazepines to antidepressants brings about any benefit in terms of symptomatic recovery or side-effects in the short term (less than 8 weeks) and long term (more than 2 months), in comparison with treatment by antidepressants alone. SEARCH STRATEGY: We searched MEDLINE (1972 to September 1997), EMBASE (1980 to September 1997), International Pharmaceutical Abstracts (1972 to September 1997), Biological Abstracts (1984 to September 1997), LILACS (1980 to September 1997), PsycLIT (1974 to September 1997), the Cochrane Library (issue 3, 1997) and the trial register of the Cochrane Depression, Anxiety and Neurosis Group (last searched March 1999), combined with hand searching, reference searching, SciSearch and personal contacts. SELECTION CRITERIA: All randomised controlled trials that compared combined antidepressant-benzodiazepine treatment with antidepressant alone for adult patients with major depression. Exclusion criteria are: antidepressant dosage lower than 100 mg of imipramine or its equivalent daily and duration of trial shorter than four weeks. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the eligibility and quality of the studies. Two reviewers independently extracted the data. Standardized weighted mean differences and relative risks were estimated with random effects model. The dropouts were assigned the least favourable outcome. Two sensitivity analyses examined the effect of this assumption as well as the effect of including medium quality studies. Three a priori subgroup analyses were performed with regard to the patients with or without comorbid anxiety and with regard to the type. MAIN RESULTS: Aggregating nine studies with a total of 679 patients, the combination therapy group was less likely to drop out than the antidepressant alone group (relative risk 0.63, 95% confidence interval 0.49 to 0.81). The intention-to-treat analysis (with people dropping out assigned the least favourable outcome) showed that the combination group was more likely to show improvement in their depression (defined as 50% or greater reduction in the depression scale from baseline) (relative risk 1.63, 95% confidence interval 1.18 to 2.27 at one week and relative risk 1.38, 95% confidence interval 1.15 to 1.66 at four weeks). The difference was no longer significant at six to eight weeks. None of the included RCTs lasted longer than eight weeks. The patients allocated to the combination therapy were less likely to drop out from the treatment due to side effects than those receiving antidepressants alone (relative risk 0.53, 95% confidence interval 0.32 to 0.86). However, these two groups of patients were equally likely to report at least one side effect (relative risk 0.99, 95% confidence interval 0.92 to 1.07). REVIEWER'S CONCLUSIONS: The potential benefits of adding a benzodiazepine to an antidepressant must be balanced judiciously against possible harms including development of dependence and accident proneness, on the one hand, and against continued suffering following no response and drop-out, on the other.

Childhood abuse and lifetime psychopathology in a community sample.

OBJECTIVE: The authors assessed lifetime psychopathology in a general population sample and compared the rates of five psychiatric disorder categories between those who reported a childhood history of either physical or sexual abuse and those who did not. METHOD: A modified version of the Composite International Diagnostic Interview and a self-completed questionnaire on child abuse were administered to a probability sample (N=7,016) of Ontario residents 15 to 64 years of age. RESULTS: Those reporting a history of childhood physical abuse had significantly higher lifetime rates of anxiety disorders, alcohol abuse/dependence, and antisocial behavior and were more likely to have one or more disorders than were those without such a history. Women, but not men, with a history of physical abuse had significantly higher lifetime rates of major depression and illicit drug abuse/dependence than did women with no such history. A history of childhood sexual abuse was also associated with higher rates of all disorders considered in women. In men, the prevalence of disorders tended to be higher among those who reported exposure to sexual abuse, but only the associations with alcohol abuse/dependence and the category of one or more disorders reached statistical significance. The relationship between a childhood history of physical abuse and lifetime psychopathology varied significantly by gender for all categories except for anxiety disorders. Although not statistically significant, a similar relationship was seen between childhood history of sexual abuse and lifetime psychopathology. CONCLUSIONS: A history of abuse in childhood increases the likelihood of lifetime psychopathology; this association appears stronger for women than men.

Health-related quality of life in childhood disorders: a modified focus group technique to involve children.

OBJECTIVES: Qualitative methodology has been under-utilized in child health research due to lack of a specific set of instruments. The objective of this study was to develop a child-centred qualitative research methodology to facilitate direct exploration of health-related quality of life (HRQL) issues and to identify the quality of life elements in pre-adolescent children with a chronic medical condition. STUDY DESIGN: Purposeful stratified sampling of children, ages 6-12, who function in a regular school class, with active epilepsy who were assembled in small focus groups. The groups met in four phases and were led by moderators who probed preset open questions and activities. RESULTS: The study demonstrated that our modified focus groups process was a powerful exploratory experience eliciting meaningful and important issues in quality of life beyond what parents and health professionals expected, and helped identify HRQL elements in childhood epilepsy. CONCLUSION: Modified focus groups are appropriate and suitable to explore quality of life issues in pre-adolescent children with a chronic medical condition. The process is feasible and trustworthy.

Applying Bradford Hill's criteria for causation to neuropsychiatry: challenges and opportunities.

Establishing an argument of causation is an important research activity with major clinical and scientific implications. Sir Austin Bradford Hill proposed criteria to establish such an argument. These criteria include the strength of the association, consistency, specificity, temporal sequence, biological gradient, biologic rationale, coherence, experimental evidence, and analogous evidence. These criteria are reviewed with the goal of facilitating an increase in rigor for establishing arguments of causation in neuropsychiatry. The challenges and opportunities related to these criteria in neuropsychiatry are reviewed, as are two important arguments for causation: one for poststroke depression and one for brain injury as a cause of psychiatric disorders.

Physical growth and current health status of infants who were of extremely low birth weight and controls at adolescence.

OBJECTIVES: To compare the physical growth, current health status, and utilization of health care resources by extremely low birth weight (ELBW) and control (C) adolescents and to look at changes over time. METHODS: A longitudinal regional cohort study was conducted. Growth measures were converted to z scores on the National Center for Health Statistics growth curves. Information regarding current health status/health care utilization was obtained by parental interviews. RESULTS: A total of 154 (91%) of 169 ELBW survivors between 12 and 16 years and 125 (86%) of 145 controls participated. Neurosensory impairments were present in 28% of ELBW survivors and 2% of control participants. Mean z scores for both height and weight were below 0 for ELBW survivors (weight: -0.35; height: -0.55) compared with control participants (weight: 0.40; height: 0.28). However, among ELBW survivors, significant catch-up growth occurred in both parameters between age 8 and adolescence but remained stable among control participants. ELBW survivors had a higher prevalence of visual problems (57% vs 21%), seizures (7% vs 1%), developmental delay (26% vs 1%), learning disabilities (34% vs 10%), and hyperactivity (9% vs 2%) and used more specialists and community resources than did control participants. CONCLUSIONS: Although physical growth continues to be compromised and substantial morbidity remains among ELBW survivors at adolescence, there seems to be some catch-up growth, a reduction in the prevalence of acute health problems, and a decrease in the utilization of medical resources.

Attitudes of parents and health care professionals toward active treatment of extremely premature infants.

OBJECTIVES: To compare the attitudes of neonatologists, neonatal nurses, the parents of extremely low birth weight (ELBW) children, and the parents of normal birth weight children toward saving infants of borderline viability and who should be involved in the decision-making process and to compare physicians' and nurses' estimates of the proportion of infants who are born at various gestational ages with regard to survival, morbidity, and treatment. METHODS: A questionnaire was given to 169 parents of ELBW children and 123 parents of term children, who were part of a longitudinal study of the outcome of ELBW infants. A similar questionnaire was completed by 98 Canadian neonatologists and 99 neonatal nurses. RESULTS: Physicians tended to be more optimistic than nurses regarding the probability of survival and freedom from serious disabilities and would recommend to parents life-saving interventions for their child at earlier gestational ages. A significant majority of parents believed that attempts should be made to save all infants, irrespective of condition or weight at birth, compared with only 6% of health professionals who endorsed this. In contrast to parents, health professionals believed that economic costs to society should be a factor in deciding whether to save an ELBW infant. However, health professionals did not believe that the economic status of the parents should be a factor, although the stress of raising an infant with disabilities should be. Most respondents believed that the parents and physicians should make the final decision but that other bodies, such as ethics committees or the courts, should not. CONCLUSION: Health care professionals must recognize that their attitudes toward saving ELBW infants differ from those of parents. Parents, whether of term or extremely premature children, are more in favor of intervening to save the infant irrespective of its weight or condition at birth than are professionals. It therefore is imperative that there be joint decision making, combining the knowledge of the physician with the wishes of the parents.

Antidepressant plus benzodiazepine for major depression.

BACKGROUND: Anxiety frequently coexists with depression. Adding benzodiazepines to antidepressants is commonly used to treat people with depression, although there has been no convincing evidence to show that such a combination is more effective than antidepressants alone and that there are suggestions that benzodiazepines may lose their efficacy with long-term administration and that their chronic use carries risks of dependence. OBJECTIVES: To determine whether, among adult patients with major depression, adding benzodiazepines to antidepressants brings about any benefit in terms of symptomatic recovery or side-effects in the short term (less than 8 weeks) and long term (more than 2 months), in comparison with treatment by antidepressants alone. SEARCH STRATEGY: We searched MEDLINE (1972 to September 1997), EMBASE (1980 to September 1997), International Pharmaceutical Abstracts (1972 to September 1997), Biological Abstracts (1984 to September 1997), LILACS (1980 to September 1997), PsycLIT (1974 to September 1997), the Cochrane Library (issue 3, 1997) and the trial register of the Cochrane Depression, Anxiety and Neurosis Group (last searched March 1999), combined with hand searching, reference searching, SciSearch and personal contacts. SELECTION CRITERIA: All randomised controlled trials that compared combined antidepressant-benzodiazepine treatment with antidepressant alone for adult patients with major depression. Exclusion criteria are: antidepressant dosage lower than 100 mg of imipramine or its equivalent daily and duration of trial shorter than four weeks. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the eligibility and quality of the studies. Two reviewers independently extracted the data. Standardized weighted mean differences and relative risks were estimated with random effects model. The dropouts were assigned the least favourable outcome. Two sensitivity analyses examined the effect of this assumption as well as the effect of including medium quality studies. Three a priori subgroup analyses were performed with regard to the patients with or without comorbid anxiety and with regard to the type. MAIN RESULTS: Aggregating nine studies with a total of 679 patients, the combination therapy group was less likely to drop out than the antidepressant alone group (relative risk 0.63, 95% confidence interval 0.49 to 0.81). The intention-to-treat analysis (with people dropping out assigned the least favourable outcome) showed that the combination group was more likely to show improvement in their depression (defined as 50% or greater reduction in the depression scale from baseline) (relative risk 1.63, 95% confidence interval 1.18 to 2.27 at one week and relative risk 1.38, 95% confidence interval 1.15 to 1.66 at four weeks). The difference was no longer significant at six to eight weeks. None of the included RCTs lasted longer than eight weeks. The patients allocated to the combination therapy were less likely to drop out from the treatment due to side effects than those receiving antidepressants alone (relative risk 0.53, 95% confidence interval 0.32 to 0.86). However, these two groups of patients were equally likely to report at least one side effect (relative risk 0.99, 95% confidence interval 0.92 to 1.07). REVIEWER'S CONCLUSIONS: The potential benefits of adding a benzodiazepine to an antidepressant must be balanced judiciously against possible harms including development of dependence and accident proneness, on the one hand, and against continued suffering following no response and drop-out, on the other.

Is antidepressant-benzodiazepine combination therapy clinically more useful? A meta-analytic study.

BACKGROUND: Anxiety frequently coexists with depression, and benzodiazepines are often prescribed together with antidepressants. However, benzodiazepines themselves have little or no antidepressive effects and we lack firm evidence for or against this combination therapy. We therefore conducted a meta-analysis of relevant randomized controlled trials to date. METHODS: All randomized controlled trials that compared antidepressant-benzodiazepine treatment with antidepressant alone for adult patients with major depression were sought by electronic searches of Medline and several other databases (January 1972 to December 1998), combined with hand searching, reference searching and SciSearch. Two reviewers independently assessed the eligibility and quality of the studies. Relative risks were estimated with random effects model. RESULTS: Aggregating nine studies with a total of 679 patients, the combination therapy group was 37% (95%CI: 19-51%) less likely to drop out than the antidepressant alone group. The intention-to-treat analysis showed that the former were 63% (18-127%) to 38% (15-66%) more likely to show response (defined as 50% or greater reduction in the depression scale from baseline) up to 4 weeks. LIMITATIONS: None of the included RCTs followed the patients beyond 8 weeks. CONCLUSIONS: The potential benefits of adding a benzodiazepine to an antidepressant must be balanced judiciously against possible harm, including development of dependence and accident proneness, on the one hand, and against continued suffering following no response and drop-out, on the other.

Guidelines as rationing tools: a qualitative analysis of psychosocial patient selection criteria for cardiac procedures.

BACKGROUND: Cardiac procedure guidelines often include psychosocial criteria for selecting patients that potentially introduce social value judgements into clinical decisions and decisions about the rationing of care. The aim of this study was to investigate the terms and justifications for and the meanings of psychosocial patient characteristics used in cardiac procedure guidelines. METHODS: We selected English-language guidelines published since 1990 and chapters in textbooks published since 1989. These guidelines amalgamated multiple sources of evidence and expertise and made recommendations regarding patient selection for specific procedures. A multidisciplinary team of physicians and social scientists extracted passages regarding psychosocial criteria and developed categories and conceptual relationships to describe and interpret their content. RESULTS: Sixty-five papers met the criteria for inclusion in the study. Forty-five (69%) mentioned psychosocial criteria as procedure indications or contraindications. The latter fell into several categories, including behavioural and psychological issues, relationships with significant others, financial resources, social roles and environmental circumstances. INTERPRETATION: Psychosocial characteristics are portrayed as having 2 roles in patient selection: as risk factors intrinsic to the candidate or as indicators of need for special intervention. Guidelines typically simply list psychosocial contraindications without clarifying their specific nature or providing any justification for their use. Psychosocial considerations can help in the evaluation of patients for cardiac procedures, but they become ethically controversial when used to restrict access. The use of psychosocial indications and contraindications could be improved by more precise descriptions of the psychosocial problem at issue, explanations regarding why the criterion matters and justification of the characteristic using a biological rationale or research evidence.

Regression toward the mean: its etiology, diagnosis, and treatment.

This paper explores the phenomenon of "regression toward the mean." The primary effect of this is to affect scores on retesting so that they are closer to the population mean. Thus, people who are selected for inclusion in a study because their scores on some measure are above (or below) some criterion have values on retesting that are less extreme. This may make it appear that the study participants have improved; this will occur even in the absence of an effective intervention. We explore the reasons for regression toward the mean and how it can be detected and discuss some methods that may minimize its effects.

Two-year outcome of preschool children with autism or Asperger's syndrome.

OBJECTIVE: DSM-IV specifies that Asperger's disorder is a type of pervasive developmental disorder without clinically significant cognitive or language delay. There are no data, however, on the outcome of children with Asperger's disorder or on whether their outcome differs from that of children with autism. The objectives of this study were to compare the outcome of groups of children with these disorders over a period of 2 years on variables independent of the defining criteria and to identify variables that might account for these differences. METHOD: All children 4-6 years of age who came for assessment or were currently in treatment at a pervasive developmental disorder service of one of several centers in a large geographic region were identified. Children who received a diagnosis of autism (N=46) or Asperger's syndrome (N=20) on the basis of a diagnostic interview and had an IQ in the nonretarded range were given a battery of cognitive, language, and behavioral tests. Families were contacted roughly 2 years after the date of their enrollment in the study, and many of the tests were readministered. RESULTS: Children with Asperger's syndrome had better social skills and fewer autistic symptoms 2 years after study enrollment than the children with autism. The differences in outcome could not be explained by initial differences in IQ and language abilities. Children with autism who had developed verbal fluency at follow-up were very similar to the children with Asperger's syndrome at study enrollment. CONCLUSIONS: Although the exact mechanism for the differences in outcome remain to be determined, it appears that Asperger's disorder and autism represent parallel but potentially overlapping developmental trajectories.

Antidepressant plus benzodiazepine for major depression.

BACKGROUND: Anxiety frequently coexists with depression. There is no systematic review to show if adding benzodiazepines to antidepressants can bring about any advantage over antidepressants alone in the treatment of depression, although such a combination prescription appears to be widely practiced worldwide OBJECTIVES: To determine whether, among adult patients with major depression, adding benzodiazepines to antidepressants brings about any benefit in terms of symptomatic recovery or side-effects in the short term (less than 8 weeks) and long term (more than 2 months), in comparison with treatment by antidepressants alone. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE, International Pharmaceutical Abstracts, Biological Abstracts, LILACS, PsycLit, the Cochrane Library and the trial register of the Cochrane Depression, Anxiety and Neurosis Group (January 1972 to December 1998), combined with hand searching, reference searching, SciSearch and personal contacts. SELECTION CRITERIA: All randomized controlled trials that compared combined antidepressant-benzodiazepine treatment with antidepressant alone for adult patients with major depression (Feighner criteria, RDC, DSM-III, DSM-III-R, DSM-IV or ICD-10). Exclusion criteria are: antidepressant dosage lower than 100 mg of imipramine or its equivalent daily and duration of trial shorter than 4 weeks. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the eligibility and quality of the studies. Two reviewers independently extracted the data. Standardized weighted mean differences and relative risks were estimated with random effects model. The dropouts were assigned the least favorable outcome. Two sensitivity analyses examined the effect of this assumption as well as the effect of including medium quality studies. Three a priori subgroup analyses were performed with regard to the patients with or without comorbid anxiety and with regard to the types of benzodiazepines tested. MAIN RESULTS: Aggregating nine studies with a total of 679 patients, the combination therapy group was 37% (95%CI: 19 to 51%) less likely to drop out than the antidepressant alone group. The intention-to-treat analysis showed that the former were 63% (18 to 127%) to 38% (15 to 66%) more likely to show response (defined as 50% or greater reduction in the depression scale from baseline) up to 4 weeks. REVIEWER'S CONCLUSIONS: The potential benefits of adding a benzodiazepine to an antidepressant must be balanced judiciously against possible harms including development of dependence and accident proneness, on the one hand, and against continued suffering following no response and drop-out, on the other.