Tobacco use in first-episode psychosis, a multinational EU-GEI study.

BACKGROUND: Tobacco is a highly prevalent substance of abuse in patients with psychosis. Previous studies have reported an association between tobacco use and schizophrenia. The aim of this study was to analyze the relationship between tobacco use and first-episode psychosis (FEP), age at onset of psychosis, and specific diagnosis of psychosis. METHODS: The sample consisted of 1105 FEP patients and 1355 controls from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We assessed substance use with the Tobacco and Alcohol Questionnaire and performed a series of regression analyses using case-control status, age of onset of psychosis, and diagnosis as outcomes and tobacco use and frequency of tobacco use as predictors. Analyses were adjusted for sociodemographic characteristics, alcohol, and cannabis use. RESULTS: After controlling for cannabis use, FEP patients were 2.6 times more likely to use tobacco [p ⩽ 0.001; adjusted odds ratio (AOR) 2.6; 95% confidence interval (CI) [2.1-3.2]] and 1.7 times more likely to smoke 20 or more cigarettes a day (p = 0.003; AOR 1.7; 95% CI [1.2-2.4]) than controls. Tobacco use was associated with an earlier age at psychosis onset (ß = -2.3; p ⩽ 0.001; 95% CI [-3.7 to -0.9]) and was 1.3 times more frequent in FEP patients with a diagnosis of schizophrenia than in other diagnoses of psychosis (AOR 1.3; 95% CI [1.0-1.8]); however, these results were no longer significant after controlling for cannabis use. CONCLUSIONS: Tobacco and heavy-tobacco use are associated with increased odds of FEP. These findings further support the relevance of tobacco prevention in young populations.

Longitudinal associations between alcohol use, smoking, genetic risk scoring and symptoms of depression in the general population: a prospective 6-year cohort study.

BACKGROUND: Alcohol consumption, smoking and mood disorders are leading contributors to the global burden of disease and are highly comorbid. Yet, their interrelationships have remained elusive. The aim of this study was to examine the multi-cross-sectional and longitudinal associations between (change in) smoking and alcohol use and (change in) number of depressive symptoms. METHODS: In this prospective, longitudinal study, 6646 adults from the general population were included with follow-up measurements after 3 and 6 years. Linear mixed-effects models were used to test multi-cross-sectional and longitudinal associations, with smoking behaviour, alcohol use and genetic risk scores for smoking and alcohol use as independent variables and depressive symptoms as dependent variables. RESULTS: In the multi-cross-sectional analysis, smoking status and number of cigarettes per day were positively associated with depressive symptoms (p < 0.001). Moderate drinking was associated with less symptoms of depression compared to non-use (p = 0.011). Longitudinally, decreases in the numbers of cigarettes per day and alcoholic drinks per week as well as alcohol cessation were associated with a reduction of depressive symptoms (p = 0.001-0.028). Results of genetic risk score analyses aligned with these findings. CONCLUSIONS: While cross-sectionally smoking and moderate alcohol use show opposing associations with depressive symptoms, decreases in smoking behaviour as well as alcohol consumption are associated with improvements in depressive symptoms over time. Although we cannot infer causality, these results open avenues to further investigate interventions targeting smoking and alcohol behaviours in people suffering from depressive symptoms.

Assessing optimal frequency for image acquisition in computer vision systems developed to monitor feeding behavior of group-housed Holstein heifers.

Computer vision systems have emerged as a potential tool to monitor the behavior of livestock animals. Such high-throughput systems can generate massive redundant data sets for training and inference, which can lead to higher computational and economic costs. The objectives of this study were (1) to develop a computer vision system to individually monitor detailed feeding behaviors of group-housed dairy heifers, and (2) to determine the optimal frequency of image acquisition to perform inference with minimal effect on feeding behavior prediction quality. Eight Holstein heifers (96 ± 6 d old) were housed in a group and a total of 25,214 images (1 image every second) were acquired using 1 RGB camera. A total of 2,209 images were selected and each animal in the image was labeled with its respective identification (1-8). The label was annotated only on animals that were at the feed bunk (head through the feed rail). From the labeled images, 1,392 were randomly selected to train a deep learning algorithm for object detection with YOLOv3 ("You Only Look Once" version 3) and 154 images were used for validation. An independent data set (testing set = 663 out of the 2,209 images) was used to test the algorithm. The average accuracy for identifying individual animals in the testing set was 96.0%, and for each individual heifer from 1 to 8 the accuracy was 99.2, 99.6, 99.2, 99.6, 99.6, 99.2, 99.4, and 99.6%, respectively. After identifying the animals at the feed bunk, we computed the following feeding behavior parameters: number of visits (NV), mean visit duration (MVD), mean interval between visits (MIBV), and feeding time (FT) for each heifer using a data set composed by 8,883 sequential images (1 image every second) from 4 time points. The coefficient of determination (R2) was 0.39, 0.78, 0.48, and 0.99, and the root mean square error (RMSE) were 12.3 (count), 0.78, 0.63, and 0.31 min for NV, MVD, MIBV, and FT, respectively, considering 1 image every second. When we moved from 1 image per second to 1 image every 5 (MIBV) or 10 (NV, MDV, and FT) s, the R2 observed were 0.55 (NV), 0.74 (MVD), 0.70 (MIBV), and 0.99 (FT); and the RMSE were 2.27 (NV, count), 0.38 min (MVD), 0.22 min (MIBV), and 0.44 min (FT). Our results indicate that computer vision systems can be used to individually identify group-housed Holstein heifers (overall accuracy = 99.4%). Based on individual identification, feeding behavior such as MVD, MIBV, and FT can be monitored with reasonable accuracy and precision. Regardless of the frequency for optimal image acquisition, our results suggested that longer time intervals of image acquisition would reduce data collecting and model inference while maintaining adequate predictive performance. However, we did not find an optimal time interval for all feeding behavior; instead, the optimal frequency of image acquisition is phenotype-specific. Overall, the best R2 and RMSE for NV, MDV, and FT were achieved using 1 image every 10 s, and for MIBV it was achieved using 1 image every 5 s, and in both cases model inference and data storage could be drastically reduced.

Application of network methods for understanding mental disorders: pitfalls and promise.

Galvanized with the availability of sophisticated statistical techniques and large datasets, network medicine has emerged as an active area of investigation. Following this trend, network methods have been utilized to understand the interplay between symptoms of mental disorders. This realistic approach that may provide an improved framework into understanding mental conditions and underlying mechanisms is certainly to be welcomed. However, we have noticed that symptom network studies tend to lose sight of the fundamentals, overlook major limitations embedded in study designs, and make inferences that are difficult to justify with current findings. There is concern that disregarding these flaws may halt the progress of the network approach in psychiatry. Therefore, in this paper, we first attempt to identify the pitfalls: (1) a reductionist understanding of medicine and psychiatry, thereby inadvertently reintroducing the dichotomy of medicine (lung cancer) and psychiatry (depression), (2) a shortsighted view of signs and symptoms, (3) overlooking the limitations of available datasets based on scales with embedded latent class structures, (4) overestimating the importance of the current findings beyond what is supported by the study design. By addressing current issues, the hope is to navigate this rapidly growing field to a more methodologically sound and reproducible path that will contribute to our understanding of mental disorders and its underlying mechanisms.

[A case-report on catatonia: a prevalent but under-recognised psychiatric illness]. / Katatonie: een veelvoorkomend, maar weinig herkend ziektebeeld.

We describe the case of a 63-year-old female patient with schizoaffective disorder who spent more than two months in two different psychiatric wards because of an unrecognised psychiatric illness. Ultimately, the patient was referred to the psychiatric ward of the university hospital where she was treated for catatonia with electroconvulsive therapy (ect). Three treatments with ect led to a full recovery of the patient.

Psychotic reactions to daily life stress and dopamine function in people with severe hearing impairment.

BACKGROUND: Minor stresses measured in daily life have repeatedly been associated with increased momentary psychotic experiences, both in individuals with psychotic disorders and in persons who are genetically at an increased risk for these disorders. Severe hearing impairment (SHI) is an environmental risk factor for psychotic disorder, possibly due to the experience of social exclusion. The aim of the current study is to investigate whether people with SHI exhibit higher levels of psychotic reactivity to social stressors in daily life than normal-hearing controls and whether this reactivity is associated with decreased baseline dopamine (DA) D2/3 receptor availability and/or elevated DA release following a dexamphetamine challenge. METHOD: We conducted an experience sampling study in 15 young adults with SHI and 19 matched normal-hearing controls who had previously participated in a single photon emission computed tomography study measuring DA D2/3 receptor availability and DA release in response to dexamphetamine. RESULTS: The association between social stress and momentary psychotic experiences in daily life was stronger among SHI participants than among normal-hearing controls. Interactions between social stress and baseline striatal DA D2/3 receptor availability or DA release were not significant in multilevel models of momentary psychotic experiences including age, sex and tobacco use. CONCLUSIONS: While both elevated striatal DA release and elevated psychotic stress reactivity have been found in the same population defined by an environmental risk factor, SHI, their inter-relationship cannot be established. Further research is warranted to clarify the association between biological and psychological endophenotypes and psychosis risk.

[The schizophrenia spectrum and other psychotic disorders in the DSM-5]. / Schizofreniespectrum en andere psychotische stoornissen in de DSM-5.

BACKGROUND: This article discusses changes made in the diagnostic criteria for psychotic disorders in the transition from DSM-IV to DSM-5. AIM: To review and evaluate the changes incorporated in the DSM-5 criteria for psychotic disorders. METHOD: Relevant documents and proceedings were reviewed on the basis of personal experience in the APA working group on psychotic disorders. RESULTS: The chapter on the 'schizophrenia spectrum and other psychotic disorders' in DSM-5 introduces a conceptual psychosis continuum, in which the level, number and duration of psychotic signs and symptoms are used to differentiate between various forms of psychotic disorders. The chapter includes only a few marginal adjustments, aimed at simplifying usage and measurement-based treatment. The DSM-5 Committee also aspired for harmonization with the ICD. The Committee was in favor of a new name for schizophrenia, but referred the matter to the WHO. The empirical basis for 'attentuated psychosis syndrome' was found to be insufficient for the syndrome to be included as a diagnosis. The most important changes in the criteria for schizophrenia are the elimination of the classic subtypes, the clarification of cross-sectional and longitudinal course specifiers, the elimination of special status of Schneiderian first-rank symptoms, and the clarification and better delineation of schizophrenia in terms of: a) the relationship between schizophrenia and schizoaffective disorders and b) the relationship between schizophrenia and catatonia. In schizoaffective disorder, the perspective shifts from an episode diagnosis in DSM-IV to a life course for the illness in DSM-5. Although the committee gave serious consideration to the inclusion of trans-diagnostic dimensions, these have not been included; a factor that precludes more personalised diagnoses, at least for the time being. CONCLUSION: The limitations of the classic system of categorical diagnosis are widely acknowledged and serious consideration has been given to the abolition of this type of diagnosis or at least to the possibility of enriching it with a transdiagnostic focus on dimensions of psychopathology. These steps have not been taken in DSM-5 - for the consensus committees this is evidently still a bridge too far.

Testing the estrogen hypothesis of schizophrenia: associations between cumulative estrogen exposure and cerebral structural measures.

BACKGROUND: Bone mineral density (BMD), as an indicator of cumulative estrogen exposure, may be reduced in female patients with psychotic disorder (van der Leeuw et al., 2013), possibly reflecting reduced cerebral exposure to estrogen and alterations in neuroprotective effects. To the degree that BMD is a marker of cumulative (endogenous) estrogen exposure, we hypothesized that BMD would be positively associated with cerebral gray and white matter indices. METHODS: Dual X-ray absorptiometry (DEXA) and magnetic resonance (MRI) scans were acquired in fourteen female patients diagnosed with a psychotic disorder. BMD was expressed in total BMD (g/cm(2)), Z- and T-scores. Cerebral cortical thickness (CT) (as indicator of gray matter status) and fractional anisotropy (FA) (as indicator of white matter integrity) were measured and served as the dependent variables in multilevel random regression models. BMD measures were the independent variables. RESULTS: Femoral BMD measures were positively associated with CT at trend significance (total BMD: B=0.266, 95% CI: -0.019-0.552, p=0.067; Z-score: B=0.034, 95% CI: 0.001-0.067, p=0.046; T-score: B=0.034, 95% CI: 0.000-0.068, p=0.052). There were no significant associations between femoral BMD measures and FA. CONCLUSIONS: The data suggest that in women with psychotic disorder, alterations in the neuroprotective effect of estrogen (as measured by BMD) impact cortical gray matter, but not white matter integrity. These findings merit further investigation and, if replicated, would lend support to the estrogen hypothesis of schizophrenia.

Bone mineral density as a marker of cumulative endogenous estrogen exposure: relationship to background genetic risk of psychotic disorder.

BACKGROUND: Alterations in bone mineral density (BMD) in patients with psychotic disorder may reflect the effect of treatment (disease effect observed in patients but not their siblings) or, as an intermediate marker of cumulative endogenous estrogen exposure, alterations in the neuroprotective effect of estrogen in the brain (vulnerability effect observed in patients and siblings). METHODS: Dual X-ray absorptiometry (DEXA) scans were acquired in 62 patients with a psychotic disorder, 67 non-psychotic siblings of patients with a psychotic disorder, and 48 controls. BMD (g/cm(2)), Z-scores and T-scores were measured in the lumbar spine and proximal femur. Associations between group and BMD were investigated with multilevel random regression analyses. Group×sex interactions and effects of antipsychotic medication (AP) on BMD were examined. RESULTS: Group was not associated with BMD outcome measures, although patients had consistently lower BMD measures compared to both siblings and controls. There were no significant group×sex interactions, but stratified analyses showed that BMD measures in female patients were significantly lower in comparison to female controls and siblings (e.g. total femoral BMD, P vs. C: B=-0.100, p=0.010; P vs. S: B=-0.104, p=0.008). After excluding female patients who used prolactin-raising AP, the effect was attenuated (e.g. total femoral BMD, P vs. C: B=-0.073, p=0.072; P vs. S: B=-0.085, p=0.051). In men, there were no significant BMD differences between patients and controls. CONCLUSION: Familial risk of psychotic disorder was not associated with BMD. Instead, decreased BMD in the femur may reflect treatment effects or non-familial risk associated with low cumulative endogenous estrogen levels in women.

[Anti-NMDA-receptor encephalitis: a new axis-III disorder in the differential diagnosis of childhood disintegrative disorder, early onset schizophrenia and late onset autism]. / Anti-NMDA-receptorencefalitis: een nieuwe as III-stoornis in de differentiaaldiagnose van desintegratiestoornis van de kinderleeftijd, vroeg optredende schizofrenie en laat optredend autisme.

Childhood disintegrative disorder (CDD), early onset schizophrenia (EOS), and late onset autism (LOA) often follow a similar course: initially, development is normal, then there is a sudden neuropsychiatric deterioration of social interaction and communication skills, which is combined with a decline in intelligence and reduction in daily activities. A 9-year-old boy was admitted to the paediatric ward with acute onset of secondary epileptic seizures. It was not long until the boy's symptoms resembled that of patients with cdd, eos and loa. Intensive tests led to the diagnosis of anti-NMDA-receptor encephalitis. Anti-NMDA-receptor encephalitis should be regarded as a possible organic cause underlying the syndromal presentation of CDD, EOS and LOA.

Age at onset of non-affective psychosis in relation to cannabis use, other drug use and gender.

BACKGROUND: Cannabis use is associated with an earlier age at onset of psychotic illness. The aim of the present study was to examine whether this association is confounded by gender or other substance use in a large cohort of patients with a non-affective psychotic disorder. METHOD: In 785 patients with a non-affective psychotic disorder, regression analysis was used to investigate the independent effects of gender, cannabis use and other drug use on age at onset of first psychosis. RESULTS: Age at onset was 1.8 years earlier in cannabis users compared to non-users, controlling for gender and other possible confounders. Use of other drugs did not have an additional effect on age at onset when cannabis use was taken into account. In 63.5% of cannabis-using patients, age at most intense cannabis use preceded the age at onset of first psychosis. In males, the mean age at onset was 1.3 years lower than in females, controlling for cannabis use and other confounders. CONCLUSIONS: Cannabis use and gender are independently associated with an earlier onset of psychotic illness. Our findings also suggest that cannabis use may precipitate psychosis. More research is needed to clarify the neurobiological factors that make people vulnerable to this precipitating effect of cannabis.

The association between social phobia, social anxiety cognitions and paranoid symptoms.

OBJECTIVE: Previous research suggests high levels of comorbidity between social phobia and paranoid symptoms, although the nature of this association remains unclear. METHOD: Data were derived from the Early Developmental Stages of Psychopathology study, a 10-year longitudinal study in a representative German community sample of 3021 participants aged 14-24 years at baseline. The Munich-Composite International Diagnostic Interview was used to assess social phobia and paranoid symptoms, along with data on social phobia features. Cross-sectional and longitudinal analyses were conducted. Differential associations with environmental risk factors and temperamental traits were investigated. RESULTS: Lifetime social phobia and paranoid symptoms were associated with each other cross-sectionally (OR = 1.80, 95% CI = 1.31-2.47). Lifetime paranoid symptoms were associated specifically with social anxiety cognitions. Lifetime cognitions of negative evaluation predicted later onset of paranoid symptoms, whereas onset of social phobia was predicted by cognitions of loss of control and fear/avoidance of social situations. Lifetime social phobia and paranoid symptoms shared temperamental traits of behavioural inhibition, but differed in environmental risks. CONCLUSIONS: The present study showed that paranoid symptoms and social phobia share similarities in cognitive profile and inhibited temperament. Avoidance appears to be important in the development of social phobia, whereas cannabis use and traumatic experiences may drive paranoid thinking in vulnerable individuals.

Adversity and psychosis: a 10-year prospective study investigating synergism between early and recent adversity in psychosis.

OBJECTIVE: Recent studies have suggested that early adverse events, such as childhood trauma, may promote enduring liability for psychosis whereas more recent adverse events may act as precipitants. Examination of these environmental dynamics, however, requires prospective studies in large samples. This study examines whether the association between recent adverse events and psychosis is moderated by exposure to early adversity. METHOD: A random regional representative population sample of 3021 adolescents and young adults in Munich, Germany, was assessed three times over a period of up to 10 years, collecting information on sociodemographic factors, environmental exposures, and measures of psychopathology and associated clinical relevance. Evidence of statistical non-additivity between early adversity (two levels) and more recent adversity (four levels) was assessed in models of psychotic symptoms. Analyses were a priori corrected for age, gender, cannabis use, and urbanicity. RESULTS: Early and recent adversity were associated with each other (RR = 1.32, 95% CI 1.06-1.66; P = 0.014) and displayed statistical non-additivity at the highest level of exposure to recent adversity (χ(2) = 4.59; P = 0.032). CONCLUSION: The findings suggest that early adversity may impact on later expression of psychosis either by increasing exposure to later adversity and/or by rendering individuals more sensitive to later adversity if it is severe.

[The influence of cannabis on the course of bipolar disorder: a longitudinal analysis]. / De invloed van cannabis op het ziektebeloopvan de bipolaire stoornis; een longitudinale analyse.

BACKGROUND: Research shows that the use of cannabis has a negative impact on the onset and outcome of schizophrenia, but little is known about possible effects on mood disorders. AIM: To study the influence of cannabis use on clinical and social treatment outcomes in patients with bipolar disorders who had been treated for a period of 12 months. METHOD: 3459 bipolar patients were enrolled in an observational study. The influence of cannabis on various clinical and social treatment outcomes was examined over a period of one year. In addition, tests were applied in order to find out whether third, mediating variables had effects on possible associations between cannabis use and treatment outcomes. RESULTS: During 12 months of treatment cannabis users showed less compliance and higher levels of illness severity, mania and psychosis than did non-users. In addition, cannabis users were less satisfied with their lives and had less chance of forming relationships than non-users. There was little evidence that associations between cannabis use and treatment outcomes were mediated by third variables. CONCLUSION: Cannabis use clearly had an independent impact on clinical treatment outcomes in patients with bipolar disorder, but the impact on social outcomes was only modest.

[Serotonin-noradrenalin reuptake inhibitors in the treatment of non-malignant pain syndromes; a systematic review]. / Serotonine-noradrenalineheropnameremmers bij chronische niet-maligne pijnsyndromen; een systematisch overzicht.

BACKGROUND: Chronic pain and depressive symptoms are often comorbid. Antidepressants seem to influence not only the symptoms of depression but also the perception of pain. AIM: To give a systematic overview of the efficacy and safety of serotonin-noradrenalin reuptake inhibitors (SNRI) in the treatment of chronic non-malignant pain syndromes. METHODS: We reviewed the literature by means of PubMed and PsycInfo using combinations of the words 'pain' 'venlafaxine' and 'duloxetine'. We selected clinical studies that investigated the influence of SNRIs on pain perception. RESULTS: Fourteen articles met our selection criteria. Medical conditions involved were fibromyalgia, diabetic neuropathy and post mastectomy pain. Twelve studies demonstrated the efficacy and safety of venlafaxine and duloxetine in the treatment of non-malignant pain. CONCLUSION: The results revealed that SNRIs are effective in reducing pain particularly in the treatment of diabetic neuropathy. Results with regard to the other medical conditions are less clear. More research is needed to find out in which medical conditions SNRIs have a significant pain reducing effect and why this effect does not hold in the case of other medical conditions.

Pre-operative injections of epoetin-alpha versus post-operative retransfusion of autologous shed blood in total hip and knee replacement: a prospective randomised clinical trial.

This prospective randomised clinical trial evaluated the effect of alternatives for allogeneic blood transfusions after total hip replacement and total knee replacement in patients with pre-operative haemoglobin levels between 10.0 g/dl and 13.0 g/dl. A total of 100 patients were randomly allocated to the Eprex (pre-operative injections of epoetin) or Bellovac groups (post-operative retransfusion of shed blood). Allogeneic blood transfusions were administered according to hospital policy. In the Eprex group, 4% of the patients (two patients) received at least one allogeneic blood transfusion. In the Bellovac group, where a mean 216 ml (0 to 700) shed blood was retransfused, 28% (14 patients) required the allogeneic transfusion (p = 0.002). When comparing Eprex with Bellovac in total hip replacement, the percentages were 7% (two of 30 patients) and 30% (nine of 30 patients) (p = 0.047) respectively, whereas in total knee replacement, the percentages were 0% (0 of 20 patients) and 25% (five of 20 patients) respectively (p = 0.042). Pre-operative epoetin injections are more effective but more costly in reducing the need for allogeneic blood transfusions in mildly anaemic patients than post-operative retransfusion of autologous blood.

Early exposure to cannabis and risk for psychosis in young adolescents in Trinidad.

OBJECTIVE: Cannabis use increases the risk for psychosis, but psychotogenic effects of cannabis may be restricted to exposure during early adolescence. METHOD: Four hundred and seventy-two participants (aged 12-23 years), randomly selected from the general population in Trinidad, completed questionnaires on past and current cannabis use and psychotic symptoms (using the Community Assessment of Psychic Experiences). RESULTS: Cannabis use increased the risk of experiencing psychotic symptoms and this effect was conditional on early exposure, defined around the mean age of onset of cannabis use. Thus, exposure before but not after the age of 14 years predicted psychotic symptoms (respectively beta: 0.71, 95% CI 0.22; 1.19, P = 0.004 and beta: -0.11, 95% CI -0.57; 0.36, P = 0.66). The developmental effect of cannabis use was independent of use of other drugs or current use of cannabis. CONCLUSION: Early adolescence may be a critical period with regard to the psychotogenic effect of cannabis across geographical settings and ethnic groups.

Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2 and MnSOD genes: a meta-analysis of pharmacogenetic interactions.

Despite accumulating evidence pointing to a genetic basis for tardive dyskinesia, results to date have been inconsistent owing to limited statistical power and limitations in molecular genetic methodology. A Medline, EMBASE and PsychINFO search for literature published between 1976 and June 2007 was performed, yielding 20 studies from which data were extracted for calculation of pooled estimates using meta-analytic techniques. Evidence from pooled data for genetic association with tardive dyskinesia (TD) showed (1) in COMT(val158met), using Val-Val homozygotes as reference category, a protective effect for Val-Met heterozygotes (OR=0.63, 95% CI: 0.46-0.86, P=0.004) and Met carriers (OR=0.66, 95% CI: 0.49-0.88, P=0.005); (2) in Taq1A in DRD2, using the A1 variant as reference category, a risk-increasing effect for the A2 variant (OR=1.30, 95% CI: 1.03-1.65, P=0.026), and A2-A2 homozygotes using A1-A1 as reference category (OR=1.80, 95% CI: 1.03-3.15, P=0.037); (3) in MnSOD Ala-9Val, using Ala-Ala homozygotes as reference category, a protective effect for Ala-Val (OR=0.37, 95% CI: 0.17-0.79, P=0.009) and for Val carriers (OR=0.49, 95% CI: 0.24-1.00, P=0.047). These analyses suggest multiple genetic influences on TD, indicative of pharmacogenetic interactions. Although associations are small, the effects underlying them may be subject to interactions with other loci that, when identified, may have acceptable predictive power. Future genetic research will take advantage of new genomic knowledge. Molecular Psychiatry (2008) 13, 544-556; doi:10.1038/sj.mp.4002142; published online 8 January 2008.

Experience in the first four years of rapid recovery; is it safe?

The average length of hospital stay after Total Hip Replacement (THR) has been decreasing over time. Recently, many hospitals have commenced rapid recovery programs such as Joint Care. In Joint Care the patients are usually discharged on the fifth post-operative day with relatively fresh surgical wounds. The aim of this study is to evaluate the Joint Care program after THR. Between February 2000 and February 2004, the Joint Care program was used in 611 patients after THR. The average age of the patients was 66.3 yrs (SD 9.3; range 24-86 yrs) and 68% (n= 415) of them were female. All clinical and outpatient charts as well as nursery records were evaluated. The follow up was from 6 months to 4 years (average: 2.5 years). At the planned fifth post-operative day, 92% (n = 562) of patients were discharged from hospital (SD 1.7 days; range 6-25 days). 3.8% (n= 23) of the remaining cases faced wound problems--prolonged wound drainage in 2.3% (n = 14) and potential superficial infection in 1.5% (n = 9) - causing a delay in their discharge. The readmission rate was 6.4% (n = 39) due to hip dislocation (3.4%; n = 21), re-evaluation of wound (1.5%; n= 9), deep infection (1.2%; n = 7)) and cardiac events (0.3%; n = 2). All the infection cases were treated effectively with debridement and antibiotics and no revision for any reason was reported. The Joint Care program seems to be effective after THR. Post-operative hip dislocation was the main reason for post-operative readmission. However, no clear signs that the intensive rehabilitation program caused more complications compared to previous regimens were evident. The above results encourage the application of rapid recovery programs in Orthopaedic surgery and joint replacement.

Effects of epoetin alfa on blood transfusions and postoperative recovery in orthopaedic surgery: the European Epoetin Alfa Surgery Trial (EEST).

BACKGROUND AND OBJECTIVE: Preoperative epoetin alfa administration decreases transfusion requirements and may reduce transfusion complications, such as postoperative infection due to immune suppression and thus hospitalization time. This study examined the impact of preoperative epoetin alfa administration on postoperative recovery and infection rate. METHODS: In an open randomized controlled multicentre trial in patients undergoing orthopaedic surgery, the effects of preoperative administration of epoetin alfa vs. routine care were compared in six countries. Haemoglobin (Hb) values, transfusions, time to ambulation, time to discharge, infections and safety were evaluated in patients with preoperative Hb concentrations 10-13g dL(-1) (on-treatment population: epoetin n = 460; control n = 235), from study entry until 4-6 weeks after surgery. Outcome was also compared in patients with and without transfusion. RESULTS: Epoetin-treated patients had higher Hb values from the day of surgery until discharge (P < 0.001) and lower transfusion rates (12% vs. 46%; P < 0.001). Epoetin treatment delivered no significant effect on postoperative recovery (time to ambulation, time to discharge and infection rate). However, the time to ambulation (3.8+/-4.0 vs. 3.1+/-2.2days; P < 0.001)and the time to discharge (12.9+/-6.4 vs. 10.2+/-5.0 days; P < 0.001) was longer in the transfused than in the non-transfused patients. Side-effects in both groups were comparable. CONCLUSIONS: Epoetin alfa increases perioperative Hb concentration in mild-to-moderately anaemic patients and thus reduces transfusion requirements. Patients receiving blood transfusions require a longer hospitalization than non-transfused patients.