Specificity and sensibility of the Spanish version of the COMFORT Behaviour Scale for assessing pain, grade of sedation and withdrawal syndrome in the critically ill paediatric patient. Multicentre COSAIP study (Phase 1).

AIM: The main aim of this investigation was to analyse the specificity and sensibility of the COMFORT Behaviour Scale (CBS-S) in assessing grade of pain, sedation, and withdrawal syndrome in paediatric critical care patients. METHOD: An observational, analytical, cross-sectional and multicentre study conducted in Level III Intensive Care Areas of 5 children's university hospitals. Grade of sedation was assessed using the Spanish version of the CBS-S and the Bispectral Index on sedation, once per shift over one day. Grade of withdrawal was determined using the CBS-S and the Withdrawal Assessment Tool-1, once per shift over three days. RESULTS: A total of 261 critically ill paediatric patients with a median age of 5.07 years (P25:0.9-P75:11.7) were included in this study. In terms of the predictive capacity of the CBS-S, it obtained a Receiver Operation Curve of .84 (sensitivity of 81% and specificity of 76%) in relation to pain; .62 (sensitivity of 21% and specificity of 78%) in relation to sedation grade, and .73% (sensitivity of 40% and specificity of 74%) in determining withdrawal syndrome. CONCLUSIONS: The Spanish version of the COMFORT Behaviour Scale could be a useful, sensible and easy scale to assess the degree of pain, sedation and pharmacological withdrawal of critically ill paediatric patients.

Grade of sedation in the critically ill pediatric patient and its correlation with sociodemographic and clinical variables. Multicentre COSAIP study.

AIMS: To determine the grade of sedation in the critically ill paediatric patient using Biespectral Index Sensor (BIS) and to analyse its relationship with sociodemographic and clinical patient variables. METHODS: Observational, analytical, cross-sectional and multicentre study performed from May 2018 to January 2020 in 5 Spanish paediatric critical care units. Sex, age, reason for admission, presence of a chronic pathology, type and number of drugs and length of stay were the sociodemographic and clinical variables registered. Furthermore, the grade of sedation was assessed using BIS, once per shift over 24 h. RESULTS: A total of 261 paediatric patients, 53.64% of whom were male, with a median age of 1.61 years (0.35-6.55), were included in the study. Of the patients, 70.11% (n = 183) were under analgosedation and monitored using the BIS sensor. A median of BIS values of 51.24 ±â€¯14.96 during the morning and 50.75 ±â€¯15.55 during the night were observed. When comparing BIS values and sociodemographic and clinical paediatric variables no statistical significance was detected. CONCLUSIONS: Despite the limitations of the BIS, investigations and the present study show that BIS could be a useful instrument to assess grade of sedation in critically ill paediatric patients. However, further investigations which determine the sociodemographic and clinical variables involved in the grade of paediatric analgosedation, as well as studies that contrast the efficacy of clinical scales like the COMFORT Behaviour Scale-Spanish version, are required.

Specificity and sensibility of the Spanish version of the COMFORT Behaviour Scale for assessing pain, grade of sedation and withdrawal syndrome in the critically ill paediatric patient. Multicentre COSAIP study (Phase 1). / Especificidad y sensibilidad de la COMFORT Behavior Scale-Versión española para valorar el dolor, el grado de sedación y síndrome de abstinencia en el paciente crítico pediátrico. Estudio multicéntrico COSAIP (Fase 1).

AIM: The main aim of this investigation was to analyse the specificity and sensibility of the COMFORT Behaviour Scale (CBS-S) in assessing grade of pain, sedation, and withdrawal syndrome in paediatric critical care patients. METHOD: An observational, analytical, cross-sectional and multicentre study conducted in Level III Intensive Care Areas of 5 children's university hospitals. Grade of sedation was assessed using the Spanish version of the CBS-S and the Bispectral Index on sedation, once per shift over one day. Grade of withdrawal was determined using the CBS-S and the Withdrawal Assessment Tool-1, once per shift over three days. RESULTS: A total of 261 critically ill paediatric patients with a median age of 5.07 years (P25:0.9-P75:11.7) were included in this study. In terms of the predictive capacity of the CBS-S, it obtained a Receiver Operation Curve of .84 (sensitivity of 81% and specificity of 76%) in relation to pain; .62 (sensitivity of 21% and specificity of 78%) in relation to sedation grade, and .73% (sensitivity of 40% and specificity of 74%) in determining withdrawal syndrome. CONCLUSIONS: The Spanish version of the COMFORT Behaviour Scale could be a useful, sensible and easy scale to assess the degree of pain, sedation and pharmacological withdrawal of critically ill paediatric patients.

Grade of sedation in the critically ill paediatric patient and its correlation with sociodemographic and clinical variables. Multicentre COSAIP study. / Grado de sedación del paciente crítico pediátrico y variables sociodemográficas y clínicas correlacionadas. Estudio multicéntrico COSAIP.

AIMS: To determine the grade of sedation in the critically ill paediatric patient using Biespectral Index Sensor (BIS) and to analyse its relationship with sociodemographic and clinical patient variables. METHODS: Observational, analytical, cross-sectional and multicentre study performed from May 2018 to January 2020 in 5 Spanish paediatric critical care units. Sex, age, reason for admission, presence of a chronic pathology, type and number of drugs and length of stay were the sociodemographic and clinical variables registered. Furthermore, the grade of sedation was assessed using BIS, 11per shift over 24hours. RESULTS: A total of 261 paediatric patients, 53.64% of whom were male, with a median age of 1.61 years (0.35-6.55), were included in the study. Of the patients, 70.11% (n=183) were under analgosedation and monitored using the BIS sensor. A median of BIS values of 51.24±14.96 during the morning and 50.75±15.55 during the night were observed. When comparing BIS values and sociodemographic and clinical paediatric variables no statistical significance was detected. CONCLUSIONS: Despite the limitations of the BIS, investigations and the present study show that BIS could be a useful instrument to assess grade of sedation in critically ill paediatric patients. However, further investigations which determine the sociodemographic and clinical variables involved in the grade of paediatric analgosedation, as well as studies that contrast the efficacy of clinical scales like the COMFORT Behaviour Scale-Spanish version, are required.

Comparative analysis of environmental noise levels in two paediatric intensive care units. / Niveles de ruido ambiental en dos unidades de cuidados intensivos pediátricos con diferente infraestructura.

AIMS: 1) To determine noise levels in two paediatric intensive care units (PICU) of a tertiary hospital and 2) to analyse whether these values comply with the current standards. METHOD: Observational, descriptive and cross-sectional study carried out in two PICU with different infrastructure: bays separated by curtains and individual bedrooms. A PCE-999 sound level meter was used to determine noise levels, which were registered in decibels (dB). At the same time, an ad hoc data recording document was designed in which we differentiated between each unit (open concept or closed), time of recording. RESULTS: A total of 330 tests, 72 from open PICUs and 258 from closed PICUs were collected. The noise in the open PICU was 56.74 ± 3.61 decibels versus 50.36 ± 4.71 in the closed PICU, obtaining the highest levels during the morning. DISCUSSION: As it occurs in other studies, noise levels exceed the allowed limits. At the same time, the main sources of noise in the PICU came from alarms, medical equipment, such as monitors or respirators, and conversations between health professional. CONCLUSIONS: This investigation has shown high levels of environmental noise in the two PICUs analysed. The data obtained indicate that the architectural concept of individual bedrooms may have an impact in decreasing this environmental input.

Comparative effectiveness and safety of antipsychotic drugs in schizophrenia treatment: a real-world observational study.

OBJECTIVE: The objective was to compare, in a real-world setting, the risk of mental and physical health events associated with different antipsychotic drugs (clozapine, olanzapine, risperidone, quetiapine and first-generation antipsychotics) in patients with SZ. METHODS: This is a retrospective cohort study using administrative data. Outcome measures included any mental health event (suicide, hospitalization or emergency visit for mental disorders) and physical health event (death other than suicide, hospitalization or emergency visit for physical disorders). Cox proportional hazard models were used to estimate the hazard ratios of the events associated with the use of the different antipsychotic drugs. RESULTS: The cohort included 18 869 adult patients living in the province of Quebec (Canada) with SZ and starting antipsychotic drugs between January 1998 and December 2005. Results show that quetiapine and not using any antipsychotics were associated with an increased risk of mental and physical health events as compared to other drugs. The second finding is the confirmation of better performance of clozapine. The results were robust across sensitivity analyses. CONCLUSION: Both findings call for an international public health and drug agencies surveillance of 'real-world' antipsychotic medication to ensure the optimal choices in treatment guidelines for SZ.

[Perturbed consciousness in schizophrenia: an evaluation of C.D. Frith's model]. / Les perturbations de la conscience dans la schizophrénie: évaluation du modèle de C.D. Frith.

INTRODUCTION: While many neurocognitive models of schizophrenia coexist, a lot of attention has been centered on C.D. Frith's model over the past few years, especially in regard to its parsimony. BACKGROUND: The aim of this paper is to examine its validity. The model relies on the assumption that there are two main components: self-monitoring and monitoring. The first permits one to keep consciousness of personal goals and intentions with metarepresentations. Losing consciousness of personal goals would be the source of schizophrenics' avolition and losing consciousness of personal intentions would generate reference ideas. The second component refers to the so-called "theory of mind", which is the monitoring of others' mental content (knowledge and intentions). Disturbing monitoring would cause schizophrenics persecution disillusions, third order persecutions or speech content disorders. LITERATURE FINDINGS: After reviewing the empirical and theoretical bases of Frith's model, strengths and weaknesses are highlighted, in particular by contrasting Hardy-Baylé's and Abu-Akel's theoretical proposals. For explaining the monitoring impairments of schizophrenics, Hardy-Baylé's model emphasizes the executive functioning defect, while Abu-Akel's model proposes a "hyper theory of mind" where too many hypotheses would lead to misattributions. In addition, several criticisms of Frith's model are examined, particularly those voiced by phenomenologists who underline its reductionism presupposition and argue that the underlying cognitive conception of the "theory of mind" neglects the fundamental intersubjectivity issue. In addition, Gallagher points out that monitoring is a tautological concept and that intention is not like thinking inherent to behaviour. CONCLUSION: Frith's model validity is finally discussed at large in the light of these criticisms and competing models, and it is concluded that the self-monitoring part of the model needs to be redefined and that the measurement of the "theory of mind" has to be standardized.

Differential RNA expression between schizophrenic patients and controls of the dystrobrevin binding protein 1 and neuregulin 1 genes in immortalized lymphocytes.

The dystrobrevin binding protein 1 (DTNBP1) and neuregulin 1 (NRG1) genes have been related to schizophrenia (SZ) and bipolar disorder (BP) by several whole-genome linkage and associations studies. Few expression studies in post-mortem brains have also reported a lower or a higher expression of DTNBP1 and NRG1, respectively, in SZ. Since the difficulty to access post-mortem brains, we evaluated RNA expression of DTNBP1 and NRG1 in immortalized lymphocytes of SZ patients and unrelated-family controls. An antipsychotic stimulation was also used to challenge the genetic background of the subjects and enhance differential expression. Immortalized lymphocytes of twelve SZ and twelve controls were grown individually in the presence or not of the antipsychotic olanzapine (Zyprexa; EliLilly). RNA was extracted and pooled in four groups of three SZ and four groups of three controls, and used to probe Agilent 18K microchips. Mean gene expression values were contrasted between SZ and control groups using a T-test. For DTNBP1, RNA expression was lower in SZ than in controls before (-28%; p=0.02) and after (-30%; p=0.01) olanzapine stimulation. Similarly, NRG1 GGF2 isoform showed a lower expression in SZ before (-29%; p=0.04) and after (-33%; p=0.02) olanzapine stimulation. In contrast, NRG1 GGF isoform showed no significant difference between SZ and controls (-7%; p=0.61, +3%; p=0.86, respectively), but was slightly repressed by olanzapine in controls (-8%; p=0.008) but not in SZ (+1%; p=0.91). These results are in agreement with those observed in post-mortem brain when the isoforms involved are considered.

Actual vs. best practices for young children with cerebral palsy: a survey of paediatric occupational therapists and physical therapists in Quebec, Canada.

RATIONALE: Cerebral palsy (CP) constitutes a substantial portion of paediatric rehabilitation, yet little is known regarding actual occupational therapy (OT) and physical therapy (PT) practices. This study describes OT and PT practices for young children with CP in Quebec, Canada. METHODS: This was a cross-sectional survey. All eligible, consenting paediatric occupational therapists (OTs) and physical therapists (PTs) were interviewed using a structured telephone interview based on vignettes of two typical children with CP at two age points--18 months and 4 years. Reported practices were grouped according to the International Classification of Functioning, Disability and Health (ICF). RESULTS: 91.9% of PTs (n=62; 83.8% participation rate) and 67.1% of OTs (n=85; 91.4% participation rate) reported using at least one standardized paediatric assessment. OT and PT interventions focused primarily on impairments and primary function (such as gait function and activities of daily living). Both professions gave little attention to interventions related to play and recreation/leisure. Clinicians reported the need for more training and education specific to CP and to the use of research findings in clinical practice. CONCLUSION: Wide variations and gaps were identified in clinicians' responses suggesting the need for a basic standard of OT and PT management as well as strategies to encourage knowledge dissemination regarding current best practice.

Clinical diagnoses in young offspring from eastern Québec multigenerational families densely affected by schizophrenia or bipolar disorder.

OBJECTIVE: The follow-up since 1989 of a large sample of multigenerational families of eastern Québec that are densely affected by schizophrenia (SZ) or bipolar disorder (BP) has permitted to look at the rates of DSM diagnoses in the young offspring of a SZ parent (HRSZ) and of a BP parent (HRBP) who had an extremely loaded family history. METHOD: The sample (average age of 17.5, SD 4.5) consisted of 54 high-risk offspring (HR) having one parent affected by a DSM-IV SZ or BP. The parents descended from 21 multigenerational families that constitute a quasi-total sample of such kindred in eastern Québec. The HRs were administered a lifetime best estimate DSM-IV diagnosis. RESULTS: We observed that the rates, the diversity of diagnoses, the high comorbidity, the severity and the age of onset of the clinical diagnoses tended to be similar with those already reported in the offspring of affected parents with a low familial loading. Although the sample size was small, HRSZ and HRBP also tended to show similarities in their clinical status. CONCLUSION: Overall, taking into account methodological limitations, the observation early in life of some shared characteristics among HRSZ and HRBP in terms of non-psychotic diagnosis may be congruent with the accumulating evidence that several phenotypic features are shared in adulthood by the two major psychoses.

Knee height to predict stature in North American Caucasian frail free-living elderly receiving community services.

CONTEXT: Height is an important component of anthropometric assessment. Valid measures of height are difficult to obtain in the frail elderly. Equations to predict height, using knee height, were proposed for healthy but not for frail elderly. OBJECTIVE: The objectives of this study were to 1) develop and validate equations to predict height (measured and reported) in the frail elderly, 2) to verify the accuracy and reliability of equations, and 3) to compare predicted values with those predicted from existing equations for the healthy elderly. DESIGN AND SETTING: This is a secondary analysis of data from three cross-sectional studies and three randomized community trials in the Sherbrooke area, Quebec, Canada. PARTICIPANTS: Subjects (n=599) were Caucasian, aged 60 and over, and receiving community or Meals-on-Wheels services. ANALYSES: Variables associated with measured and reported heights were entered in multiple linear regression models (n = 409) to identify independent prediction factors. Reliability assessment and agreement analysis were performed with a sub-group of subjects (n=190). RESULTS: Knee height and age in men (R(2) = .718), and with the addition of weight and hip circumference in women (R(2) = .593), were identified as predictors of measured height. For reported height, knee height was a predictor in men (R(2) = .693), while weight was another predictor in women (R(2) = .540). These models predicted height just as well in the validation group (R(2) = .514 to .623). Errors of estimates ranged from +/- 3.31 cm to +/- 5.06 cm. Predicted values were closer to directly measured values in the frail elderly as compared to values obtained with equations in the healthy elderly which differed significantly. CONCLUSIONS: Equations were developed to predict measured and reported height in the frail elderly. These equations can be used when height cannot be measured directly or when postural problems (for measured height) or cognitive disorders (for reported height) can cause unreliable measurements.

Possible association of the pro-melanin-concentrating hormone gene with a greater body mass index as a side effect of the antipsychotic olanzapine.

Following our report of a linkage at 12q24 with a phenotype of obesity under antipsychotics, we tested the pro-melanin-concentrating hormone (PMCH) candidate gene for a possible association in humans with the body mass index (BMI; kg/m2) in unrelated schizophrenic patients (SZ) receiving antipsychotics (N = 300) and in controls (CTL; N = 150). Subjects were classified in obese (OB) (BMI > or = 30 kg/m2), overweight (25 < or = BMI < 30 kg/m2), and normal weight (BMI < 25 kg/m2) groups. Single nucleotide polymorphisms (SNP) rs7973796 and rs11111201, located 5' at -4.5 kb and 3' at +1.8 kb, respectively, of PMCH were genotyped. Interaction effects of genotypes and antipsychotic treatment on BMI were tested in a covariance analysis with age and gender as covariates. Interaction effects on the prevalence of obesity were tested in a logistic regression analysis. For subjects under 50 years, the effect of the rs7973796 genotype on BMI differed between the SZ patients taking olanzapine and CTL group (interaction P = 0.025). Olanzapine-treated SZ patients carrying the ancestral homozygote genotype showed a higher BMI for rs7973796 (P = 0.016 with the LSMeans t-test) than the variant homozygotes. Accordingly, the ORs for obesity associated with rs7973796 genotypes differed in the SZ patients taking olanzapine compared to the CTL group (interaction P = 0.0094). The G allele was associated with an increase in the odds of obesity in SZ patients taking olanzapine. No association was observed for those over 50 years, or for rs11111201. These results suggest that the common allele of PMCH rs7973796 may be associated with a greater BMI in olanzapine-treated SZ patients.

Meals-on-wheels improves energy and nutrient intake in a frail free-living elderly population.

BACKGROUND: With the increasing life expectancy and associated health care cost in the elderly population, it is fundamental to study and improve interventions that help older persons to have a better and healthier life in their home for a longer period. OBJECTIVES: Evaluate the effect of Meals-on-Wheels (MOW) on dietary intakes of frail elderly. DESIGN: An untreated control group quasi-experimental design with pretest and post-test was used to compare users (n = 20) and non-users (n = 31) of MOW. Descriptive and dietary data were compared at pretest and 8 weeks later. Analysis of Covariance (ANCOVA) was used to control for initial differences between groups. RESULTS: Both groups were similar at pretest except for weight (p = 0.028) and weekly number of meals eaten outside the home (p = 0.008). In both groups, dietary intakes at pretest were below Estimated Average Requirements (EAR) for the same nutrients. At post-test, intake of most nutrients increased in the Experimental group in comparison with the Control group. After controlling with the ANCOVA model, increases were significant for energy (p = 0.050), protein (p = 0.030), lipid (p = 0.034) and thiamin (p = 0.035). Provision of MOW did not permit to achieve a low risk of nutrient inadequacy in the Experimental group. CONCLUSIONS: MOW programs improve dietary intakes of recipients. However, a more intensive intervention is needed to prevent nutrient deficiencies in this group.

Shared and specific susceptibility loci for schizophrenia and bipolar disorder: a dense genome scan in Eastern Quebec families.

The goal of this study was to identify susceptibility loci shared by schizophrenia (SZ) and bipolar disorder (BP), or specific to each. To this end, we performed a dense genome scan in a first sample of 21 multigenerational families of Eastern Quebec affected by SZ, BP or both (N=480 family members). This probably constitutes the first genome scan of SZ and BP that used the same ascertainment, statistical and molecular methods for the concurrent study of the two disorders. We genotyped 607 microsatellite markers of which 350 were spaced by 10 cM and 257 others were follow-up markers in positive regions at the 10 cM scan. Lander and Kruglyak thresholds were conservatively adjusted for multiple testings. We maximized the lod scores (mod score) over eight combinations (2 phenotype severity levels x 2 models of transmission x 2 analyses, affected/unaffected vs affected-only). We observed five genomewide significant linkages with mod score >4.0: three for BP (15q11.1, 16p12.3, 18q12-q21) and two for the shared phenotype, that is, the common locus (CL) phenotype (15q26,18q12-q21). Nine mod scores exceeded the suggestive threshold of 2.6: three for BP (3q21, 10p13, 12q23), three for SZ (6p22, 13q13, 18q21) and three for the CL phenotype (2q12.3, 13q14, 16p13). Mod scores >1.9 might represent confirmatory linkages of formerly reported genomewide significant findings such as our finding in 6p22.3 for SZ. Several regions appeared to be shared by SZ and BP. One linkage signal (15q26) appeared novel, whereas others overlapped formerly reported susceptibility regions. Despite the methodological limitations we raised, our data support the following trends: (i) results from several genome scans of SZ and BP in different populations tend to converge in specific genomic regions and (ii) some of these susceptibility regions may be shared by SZ and BP, whereas others may be specific to each. The present results support the relevance of investigating concurrently SZ and BP within the same study and have implications for the modelling of genetic effects.

Non heart beating donors. Succesfully expanding the donor's pool.

OBJECTIVES: Expand the donors pool is one of the most hastening problems among transplant coordination teams all over the world. Our Hospital outlined thirteen years ago a specific policy to increase donors pool with non-heart-beating-donors program. METHODS: We have developed an specific program, called "code 9" to get donors from "previously healthy" people who die of sudden or unexpected death. Madrid has one of the best emergency medical services all over the world, with response time under eight minutes, and being able to perform all kind of advanced life support maneuvers in situ and during transfer to hospital. RESULTS: From 1989 we have reported the goodness of the program and the excellence of the organs transplanted. In Madrid, one of the most active communities in Spain in organ donors procurement, 33% of donors comes from this program. Organs and tissues obtained are of same or better quality than those obtained from encephalic death donors. CONCLUSIONS: Non-heart beating programs are a good option to increase donors pool.

A genome wide linkage study of obesity as secondary effect of antipsychotics in multigenerational families of eastern Quebec affected by psychoses.

Antipsychotics can induce in schizophrenic (SZ) and bipolar disorder (BP) patients serious body weight changes that increase risk for noncompliance to medication, and risk for cardiovascular diseases and diabetes. A genetic origin for this susceptibility to weight changes has been hypothesized because only a proportion of treated patients are affected, the degree of affection differing also in rates and magnitudes. In a first genome scan on obesity under antipsychotics in SZ and BP, we analyzed 21 multigenerational kindreds (508 family members) including several patients treated for a minimum of 3 years mainly with haloperidol or chlopromazine. Obesity was defined from medical files and was shown to be 2.5 times more frequent in patients treated with antipsychotics than in untreated family members (30 vs 12%). The nine pedigrees that showed at least two occurrences of obesity under antipsychotics were submitted to model-based linkage analyses. We observed a suggestive linkage with a multipoint Lod score (MLS) of 2.74 at 12q24. This linkage finding vanished when we used as phenotypes, obesity unrelated to antipsychotics, and when we used SZ or BP. This suggests that this positive linkage result with obesity is specific to the use of antipsychotics. A potential candidate gene for this linkage is the pro-melanin-concentrating hormone (PMCH) gene located at less then 1 cM of the linkage. PMCH encodes a neuropeptide involved in the control of food intake, energy expenditure, and in anxiety/depression. This first genome scan targeting the obesity side effect of antipsychotics identified 12q24 as a susceptibility region.

A search for specific and common susceptibility loci for schizophrenia and bipolar disorder: a linkage study in 13 target chromosomes.

We report the first stage of a genome scan of schizophrenia (SZ) and bipolar disorder (BP) covering 18 candidate chromosomal areas. In addition to testing susceptibility loci that are specific to each disorder, we tested the hypothesis that some susceptibility loci might be common to both disorders. A total of 480 individuals from 21 multigenerational pedigrees of Eastern Québec were evaluated by means of a consensus best-estimate diagnosis made blind to diagnoses in relatives and were genotyped with 220 microsatellite markers. Two-point and multipoint model-based linkage analyses were performed and mod scores (Z, for max Z(max)) are reported. The strongest linkage signals were detected at D18S1145 (in 18q12; Z = 4.03) for BP, and at D6S334 (in 6p 22-24; Z(het) = 3.47; alpha = 0.66) for SZ. Three other chromosomal areas (3q, 10p, and 21q) yielded linkage signals. Chromosomes 3p, 4p, 5p, 5q, 6q, 8p, 9q, 11q, 11p, 12q, 13q, 18p and 22q showed no evidence of linkage. The 18q12 results met the Lander and Kruglyak (1995) criterion for a genome-wide significant linkage and suggested that this susceptibility region may be shared by SZ and BP. The 6p finding provided confirmatory evidence of linkage for SZ. Our results suggest that both specific and common susceptibility loci must be searched for SZ and BP.

Male gender is associated with deficit schizophrenia: a meta-analysis.

An association between deficit schizophrenia and male gender could be expected, since male schizophrenic subjects have been repeatedly found more severe than females on several dimensions of severity. Surprisingly, very few studies have confirmed such an association. We performed a more definitive test of this association using a meta-analysis. A pooled odds ratio was computed based on the 23 studies that reported the gender ratio in deficit vs. non-deficit schizophrenia. We tested for the heterogeneity of the association and examined the potential impact of the sampling method, the method used to assess the deficit syndrome, the breadth of diagnoses included and the mean duration of illness. A highly significant association between male gender and deficit schizophrenia was observed (pooled odds ratio=1.75). There was no definitive evidence that differences across studies in sampling methods, breadth of diagnoses included, mean duration of illness and methods to assess the deficit syndrome affected the strength of the association. However, the studies using the "Proxy Deficit Syndrome" method to assess the deficit syndrome yielded qualitatively weaker evidence. This significant association between male gender and deficit schizophrenia may reflect the influence of a gender related factor (e.g. sexual hormones) or gender differences in the liability to different etiologies of schizophrenia. The role of gender as a potential confounder must be closely examined in studies comparing deficit and non-deficit SZ.

Subtyping schizophrenia according to outcome or severity: a search for homogeneous subgroups.

There is a growing consensus that current definitions of schizophrenia (SZ) include different disorders, or else different dimensions underlain by different pathophysiologies. This article reviews the evidence for the validity of three novel strategies to subtype SZ according to outcome or severity (deficit vs. nondeficit, Kraepelinian vs. non-Kraepelinian, congenital vs. adult-onset). Medline and bibliographies were used to locate articles. The methodology of the studies was reviewed, and their results were grouped according to seven validating criteria. Several differences were found between subtypes, particularly for the deficit/nondeficit subtypes. However, for most of these differences, replications have yet to be undertaken. Important indicators of etiology from the environmental risk factors and genetic domains have received very little attention. These three subtyping strategies represent promising attempts to address the etiologic heterogeneity of SZ. However, one cannot conclude whether these strategies identify etiologically distinct SZ subgroups. We propose ten methodological and conceptual recommendations for future studies aimed at the identification of valid SZ subtypes according to outcome or severity.