Checking the predictive accuracy of basic symptoms against ultra high-risk criteria and testing of a multivariable prediction model: Evidence from a prospective three-year observational study of persons at clinical high-risk for psychosis.

BACKGROUND: The aim of this study was to critically examine the prognostic validity of various clinical high-risk (CHR) criteria alone and in combination with additional clinical characteristics. METHODS: A total of 188 CHR positive persons from the region of Zurich, Switzerland (mean age 20.5 years; 60.2% male), meeting ultra high-risk (UHR) and/or basic symptoms (BS) criteria, were followed over three years. The test battery included the Structured Interview for Prodromal Syndromes (SIPS), verbal IQ and many other screening tools. Conversion to psychosis was defined according to ICD-10 criteria for schizophrenia (F20) or brief psychotic disorder (F23). RESULTS: Altogether n=24 persons developed manifest psychosis within three years and according to Kaplan-Meier survival analysis, the projected conversion rate was 17.5%. The predictive accuracy of UHR was statistically significant but poor (area under the curve [AUC]=0.65, P<.05), whereas BS did not predict psychosis beyond mere chance (AUC=0.52, P=.730). Sensitivity and specificity were 0.83 and 0.47 for UHR, and 0.96 and 0.09 for BS. UHR plus BS achieved an AUC=0.66, with sensitivity and specificity of 0.75 and 0.56. In comparison, baseline antipsychotic medication yielded a predictive accuracy of AUC=0.62 (sensitivity=0.42; specificity=0.82). A multivariable prediction model comprising continuous measures of positive symptoms and verbal IQ achieved a substantially improved prognostic accuracy (AUC=0.85; sensitivity=0.86; specificity=0.85; positive predictive value=0.54; negative predictive value=0.97). CONCLUSIONS: We showed that BS have no predictive accuracy beyond chance, while UHR criteria poorly predict conversion to psychosis. Combining BS with UHR criteria did not improve the predictive accuracy of UHR alone. In contrast, dimensional measures of both positive symptoms and verbal IQ showed excellent prognostic validity. A critical re-thinking of binary at-risk criteria is necessary in order to improve the prognosis of psychotic disorders.

Adolescents and adults at clinical high-risk for psychosis: age-related differences in attenuated positive symptoms syndrome prevalence and entanglement with basic symptoms.

BACKGROUND: The attenuated positive symptoms syndrome (APSS) is considered an at-risk indicator for psychosis. However, the characteristics and developmental aspects of the combined or enriched risk criteria of APSS and basic symptom (BS) criteria, including self-experienced cognitive disturbances (COGDIS) remain under-researched. METHOD: Based on the Structured Interview of Prodromal Syndromes (SIPS), the prevalence of APSS in 13- to 35-year-old individuals seeking help in an early recognition program for schizophrenia and bipolar-spectrum disorders was examined. BS criteria and COGDIS were rated using the Schizophrenia Proneness Instrument for Adults/Children and Youth. Participants meeting APSS criteria were compared with participants meeting only BS criteria across multiple characteristics. Co-occurrence (APSS+/BS+, APSS+/COGDIS+) was compared across 13-17, 18-22 and 23-35 years age groups. RESULTS: Of 175 individuals (age = 20.6 ± 5.8, female = 38.3%), 94 (53.7%) met APSS criteria. Compared to BS, APSS status was associated with suicidality, higher illness severity, lower functioning, higher SIPS positive, negative, disorganized and general symptoms scores, depression scores and younger age (18.3 ± 5.0 v. 23.2 ± 5.6 years, p < 0.0001) with age-related differences in the prevalence of APSS (ranging from 80.3% in 13- to 17-year-olds to 33.3% in 23- to 35-year-olds (odds ratio 0.21, 95% confidence interval 0.11-0.37). Within APSS+ individuals, fewer adolescents fulfilled combined risk criteria of APSS+/BS+ or APSS+/COGDIS+ compared to the older age groups. CONCLUSIONS: APSS status was associated with greater suicidality and illness/psychophathology severity in this help-seeking cohort, emphasizing the need for clinical care. The age-related differences in the prevalence of APSS and the increasing proportion of APSS+/COGDIS+ may point to a higher proportion of non-specific/transient, rather than risk-specific attenuated positive symptoms in adolescents.

Changes in neurocognitive functioning during transition to manifest disease: comparison of individuals at risk for schizophrenic and bipolar affective psychoses.

BACKGROUND: Neurocognitive deficits are important aspects of schizophrenic disorder because they have a strong impact on social and vocational outcomes. Previously it was assumed that cognitive abilities progressively deteriorate with illness onset. However, recent research results have contradicted this with observations of continuous or even improved performance in individuals at risk for psychosis or manifest schizophrenia. The objective of our longitudinal study was to examine neurocognitive functioning in help-seeking individuals meeting basic symptoms or ultra-high-risk criteria for schizophrenic psychosis (HRSchiz) or risk criteria for affective psychosis (HRBip). The progression of cognitive functioning in individuals converting to psychosis was compared with that of at-risk individuals who did not convert during the follow-up period. METHOD: Data were available from 86 study participants who completed neurocognitive and clinical assessments at baseline and, on average, 12.8 (s.d. = 1.5) months later. Neurocognitive measures were grouped according to their load in factor analysis to five cognitive domains: speed, attention, fluency, learning and memory, and working memory. RESULTS: Neurocognitive functioning in HRSchiz and HRBip individuals generally improved over time. Subjects converting to manifest psychosis displayed a stable neurocognitive profile from baseline to follow-up. Compared with non-converters, they had already demonstrated a significantly lower level of performance during their baseline examinations. CONCLUSIONS: Our data provide no evidence for a progressive cognitive decline in individuals at risk of psychosis. In line with the neurodevelopmental model, our findings suggest that cognitive deficits are already present very early, before or during the prodromal stage of the illness.

Neurocognitive profiles in help-seeking individuals: comparison of risk for psychosis and bipolar disorder criteria.

BACKGROUND: Neurocognitive deficits are important aspects of the schizophrenic disorders because they have a strong impact on social and vocational outcomes. We expanded on previous research by focusing on the neurocognitive profiles of persons at high risk (HR) or ultra-high risk (UHR) for schizophrenic and affective psychoses. Our main aim was to determine whether neurocognitive measures are sufficiently sensitive to predict a group affiliation based on deficits in functional domains. METHOD: This study included 207 help-seeking individuals identified as HR (n = 75), UHR (n = 102) or at high risk for bipolar disorder (HRBip; n = 30), who were compared with persons comprising a matched, healthy control group (CG; n = 50). Neuropsychological variables were sorted according to their load in a factor analysis and were compared among groups. In addition, the likelihood of group membership was estimated using logistic regression analyses. RESULTS: The performance of HR and HRBip participants was comparable, and intermediate between the controls and UHR. The domain of processing speed was most sensitive in discriminating HR and UHR [odds ratio (OR) 0.48, 95% confidence interval (CI) 0.28-0.78, p = 0.004] whereas learning and memory deficits predicted a conversion to schizophrenic psychosis (OR 0.47, 95% CI 0.25-0.87, p = 0.01). CONCLUSIONS: Performances on neurocognitive tests differed among our three at-risk groups and may therefore be useful in predicting psychosis. Overall, cognition had a profound effect on the extent of general functioning and satisfaction with life for subjects at risk of psychosis. Thus, this factor should become a treatment target in itself.

The concurrent validity and sensitivity of change of the German version of the health of the nation outcome scales in a psychiatric inpatient setting.

BACKGROUND: The Health of the Nation Outcome Scales (HoNOS) were developed to assess the severity of a mental illness. They are used as outcome measures in different countries, and are meanwhile translated from the original English version into many languages, among others into German (HoNOS-D). We conducted a study in order to estimate the concurrent validity and sensitivity to change using clinical parameters as ICD-10 diagnoses, as well as the Clinical Global Impression Scale (CGI), and the Association for Methodology and Documentation in Psychiatry (AMDP) psychopathology scale, a frequently used psychopathological rating system, in a representative clinical sample. SAMPLING AND METHODS: Data on the three instruments (CGI, AMDP, HoNOS-D) were collected at admission and discharge of 100 psychiatric inpatients using a representative clinical sample. Experienced clinicians completed the CGI, AMDP and HoNOS-D. Descriptive and comparative data analyses were performed. We estimated the concurrent validity by calculating correlations between the HoNOS and other scales. Secondly, we examined the differences between HoNOS scores related to diagnoses and demographic parameters. Thirdly we calculated change criteria and outcome effect size for the HoNOS. RESULTS: Even in a small clinical sample (n = 100), the HoNOS-D items are highly correlated with the corresponding AMDP syndromes (p < 0.003). The HoNOS-D score is associated with the CGI score (p < 0.01). Correlations of HoNOS symptoms, behavior and impairment items with AMDP syndromes as well as differences in diagnoses were appropriate and comprehensible as regards clinical content, and change on the HoNOS total score is statistically significant (t = 6.57, d.f. = 89, p < 0.0001). CONCLUSION: This study is the first to investigate the concurrent validity of HoNOS-D concerning psychopathology using the AMDP rating system in a clinical sample of patients with mental disorders in an inpatient setting. HoNOS-D can be recommended for routinely screening outcomes in inpatient psychiatric settings. Our analysis showed that HoNOS-D covers psychopathology corresponding to the AMDP rating system. A limitation of the study is that the study sample comprised only an inpatient population; there may well be differences compared to an outpatient sample.

Fabry's disease and psychosis: causality or coincidence?

A 21-year-old female with Fabry's disease (FD) presented acute psychotic symptoms such as delusions, auditory hallucinations and formal thought disorders. Since the age of 14, she had suffered from various psychiatric symptoms increasing in frequency and intensity. We considered the differential diagnoses of prodromal symptoms of schizophrenia and organic schizophrenia-like disorder. Routine examinations including cognitive testing, electroencephalography and structural magnetic resonance imaging revealed no pathological findings. Additional structural and functional imaging demonstrated a minor CNS involvement of FD, yet without functional limitations. In summary our examination results support the thesis that in the case of our patient a mere coincidence of FD and psychotic symptoms is more likely than a causal connection.

Sympathetic ophthalmia following postoperative endophthalmitis and evisceration.

PURPOSE: To report a case of sympathetic ophthalmia (SO) following purulent postoperative endophthalmitis and final evisceration of the affected eye. METHODS-RESULTS: A 64-year-old male underwent phacoemulsification complicated by endophthalmitis. Five months latter the eye was painful and had no light perception so an evisceration was performed. Two weeks latter granulomatous posterior uveitis developed in the fellow eye. SO was diagnosed and the patient was started on prednisone and cyclosporine. The inflammation subsided and visual acuity improved to 20/30. CONCLUSIONS: Bacterial endophthalmitis cannot prevent the development of SO. Prompt diagnosis and management is the most important factor for visual prognosis.

Demyelination in rheumatic diseases.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterised by multifocal areas of demyelination in the white matter of the brain and spinal cord. Autoantibodies, for example antinuclear antibodies, can also be present. MS and other demyelinating processes, such as transverse myelitis and optic neuritis (which may be clinically isolated cases or be part of the clinical spectrum of MS), are sometimes difficult to differentiate from CNS involvement in systemic autoimmune diseases like systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), Sjoegren's syndrome (SS), and Adamantiades-Behcet disease (BD). An acute isolated neurological syndrome presents the biggest diagnostic problem, since it is common in MS, but can also be the only feature or first manifestation in SLE, APS, SS, and BD. Indeed, the clinical presentation and lesions evidenced by magnetic resonance imaging may be similar.

Penetration of moxifloxacin and levofloxacin into cancellous and cortical bone in patients undergoing total hip arthroplasty.

Penetration of levofloxacin and moxifloxacin into cancellous and cortical bone was studied using high-performance liquid chromatography (HPLC) in 16 patients who underwent routine total hip arthroplasty. Our results demonstrate a good degree of penetration into bone for both quinolones. The mean cancellous penetration was 53.86% for moxifloxacin and 54.13% for levofloxacin. The penetration into cortical bone was 41.59% and 34.26% respectively. The concentrations for both quinolones were above the minimum inhibitory concentration (MIC(90s)) for the most common pathogens, so they can be used for the treatment of osteomyelitis.

[Innovative care models for treating psychosis]. / Neue Versorgungsmodelle in der Psychosebehandlung.

It is generally accepted that modern mental health care gives community treatment priority over partial or full inpatient treatment. The requirements for community treatment of severely ill and chronic psychiatric patients are complex and, together with financing by the different social insurance providers, may lead to a rather problematic fragmentation of health service supply. Schizophrenia is considered the most expensive mental illness in Germany. It is estimated that indirect costs (expressed in financial terms) are five times higher than the direct costs of treatment and care. Innovative concepts of psychosocial intervention show that case management and assertive community treatment reduce the hospitalisation rate and duration of inpatient treatment, enhance social integration, and find the approval of most patients. However, there is no empirical evidence supporting this "psychiatry with no beds". Consideration should be given to psychosocial interventions as an alternative to inpatient hospital treatment such as day hospital care, crisis houses, or acute home treatment.

Demyelination in rheumatic diseases.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterised by multifocal areas of demyelination in the white matter of the brain and spinal cord. Autoantibodies, for example antinuclear antibodies, can also be present. MS and other demyelinating processes, such as transverse myelitis and optic neuritis (which may be clinically isolated cases or be part of the clinical spectrum of MS), are sometimes difficult to differentiate from CNS involvement in systemic autoimmune diseases like systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), Sjoegren's syndrome (SS), and Adamantiades-Behcet disease (BD). An acute isolated neurological syndrome presents the biggest diagnostic problem, since it is common in MS, but can also be the only feature or first manifestation in SLE, APS, SS, and BD. Indeed, the clinical presentation and lesions evidenced by magnetic resonance imaging may be similar.

Antiphospholipid antibody tests: spreading the net.

OBJECTIVE: To examine the hypothesis that testing for new antiphospholipid antibody specificities may help to identify the antiphospholipid syndrome (APS) in patients with systemic lupus erythematosus (SLE) with thrombosis who are repeatedly negative for anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA). METHODS: Three groups of patients with SLE were studied: (a) SLE/APS (n = 56): 51 female, mean (SD) age 46 (11) years, fulfilling 1999 Sapporo criteria for the APS; (b) SLE/thrombosis (n = 56): 53 female, age 42.6 (12) years, all with a history of thrombosis and persistently negative for aCL and/or LA; (c) SLE only (n = 56): 53 female, age 40 (11) years, without a history of thrombotic events. aCL and LA were retested in all samples. All patients were tested for anti-beta(2)-glycoprotein I (anti-beta(2)GPI) and antiprothrombin antibodies (aPT) by coating prothrombin on irradiated plates or using phosphatidylserine-prothrombin complex as the antigen (aPS-PT). RESULTS: Anti-beta(2)GPI were only present in patients from the SLE/APS group, all of whom were also positive for aCL. aPT and aPS-PT were also more commonly found in SLE/APS than in SLE/thrombosis or SLE only groups (54% v 5%, p<0.0001 or v 16%, p<0.0001 for aPT and 63% v 2%, p<0.0001 or v 11%, p<0.0001 for aPS-PT, respectively). No differences were found between SLE/thrombosis and SLE only groups (p = 1.5 for beta(2)GPI, p = 0.1 for aPT, and p = 0.1 for aPS-PT). CONCLUSION: Testing for aPT in patients with SLE with thrombosis, but persistently negative for aCL and LA, may be helpful in some selected cases. Anti-beta(2)GPI are not present in patients who are negative for aCL.

Prevalence and associations of an abnormal ankle-brachial index in systemic lupus erythematosus: a pilot study.

BACKGROUND: Accelerated atheroma is a well recognised complication of systemic lupus erythematosus (SLE). Its aetiology is multifactorial and several methods may be used to detect early signs of atheroma. METHODS: Patients aged

Light-dependent induction of strongly increased microalgal growth by methanol.

Low methanol concentrations (about 0.5% v/v) induce biomass production in cultures of the unicellular green alga Scenedesmus obliquus by more than 300%, compared to controls without this solvent. This effect on the microalgal growth was found to be dependent on the solvent concentration, the packed cell volume (PCV), light intensity and light quality. It could be shown that methanol addition leads to a decrease in size of the light harvesting complex (LHC) on the basis of chlorophylls and proteins, and thus to changes in structure and functioning of the photosynthetic apparatus. These alterations lead to enhanced photosynthesis and respiration rates. The action of methanol on the photosynthetic apparatus is thus comparable to the effect of enhanced CO(2) concentrations. These findings support the previously proposed pathway for methanol metabolization with CO(2) as the final product. We conclude that the subsequent assimilation of the increased CO(2) amounts by the Calvin-Benson cycle is a possible explanation for the methanol-mediated increase in biomass production in terms of PCV. The methanol effect is observed only in the light and in the presence of a functioning photosynthetic apparatus. Preliminary action spectra suggest that the primary photoreceptor is a chlorophyll-protein complex with two absorption maxima at 680 and 430 nm, which may possibly be attributed to the reaction center of photosystem II (PSII).

Characterisation of genomic RNA of Coxsackievirus B3 in murine myocarditis: reliability of direct sequencing of reverse transcription-nested polymerase chain reaction products.

SWR mice develop viral myocarditis histologically similar to the human disease following inoculation with a cardiovirulent Coxsackievirus B3 (CVB3), reactivated from a sequenced cDNA clone of Nancy strain. A sequence of 215 nucleotides, or 628 nucleotides in representative cases, of the 5'non-translated region (5'NTR) of CVB3 genome was amplified from myocardial samples of the infected mice by reverse transcription-nested polymerase chain reaction (RT-NPCR). In order to verify the viral nucleotide sequence and detect the mutation frequency of the viral RNA, the nucleotide sequence of NPCR products were determined by direct sequencing in both orientations. The amplified products from mouse heart on day 1-13 post-inoculation were sequenced and, in each case, the consensus sequence was identical to the published sequence of CVB3 (Nancy strain). To evaluate further the reproducibility of these techniques, three tissue samples from the same infected mouse heart were processed independently. Sequences of their RT-NPCR products were identical to each other as well as to the published sequence. When two attenuated CVB3 mutants were amplified and sequenced, single mutations were detected. To evaluate the overall fidelity of these two combined techniques, genomic RNA of a different CVB3 Nancy strain stock, Coxsackievirus A9 or poliovirus sabin 1 was amplified and the NPCR products sequenced. Each product showed 100% homology with its published sequence. These results demonstrate that the coupled technique of the enterovirus RT-NPCR with direct sequencing of NPCR products generates accurate consensus sequence data and this technique proved to be useful in verification of enteroviral amplicons and in detection of nucleotide mutations. In addition, a low mutation frequency was found in the 5'NTR of CVB3 detected in myocardial samples of immunocompetent mice up to 13 days.

Similarity in genome organization between Molluscum contagiosum virus (MCV) and vaccinia virus (VV): identification of MCV homologues of the VV genes for protein kinase 2, structural protein VP8, RNA polymerase 35 kDa subunit and 3beta-hydroxysteroid dehydrogenase.

Molluscum contagiosum virus (MCV) and vaccinia virus (VV) are serologically unrelated poxviruses with a disparate genome composition (MCV, 66% G+C; VV, 33% G+C). Molecular studies of MCV have been hindered by the inability to propagate the virus in cells cultured in vitro. We sequenced 7765 bp of MCV DNA cloned from four widely spaced regions throughout the MCV genome and identified a total of 11 potential open reading frames (ORF), designated CX1-11. These include MCV homologues of the VV genes encoding protein kinase 2, structural protein VP8, RNA polymerase 35 kDa subunit and 3beta-hydroxysteroid dehydrogenase. The position and orientation of the MCV ORFs was collinear to the VV genome, with the exception of the region around ORF CX11 which is inverted in the MCV genome.

Elevated plasma levels of P-selectin (GMP-140/CD62P) in patients with Plasmodium falciparum malaria.

The plasma concentration of soluble P-selectin (GMP-140/CD62P/PADGEM), a selectin produced by activated platelets and endothelial cells, was quantitated in a group of adults and East African negro children presenting with either non-severe or severe (cerebral) malaria caused by Plasmodium falciparum. Sixty percent of adults with non-severe malaria had immunoreactive levels of P-selectin above 200 ng/ml (the maximum recorded for any normal healthy adult in the assay) and 86% of all African children with malaria had concentrations above normal irrespective of their clinical categorization, and most exceeded the maximum limits of the assay (> 640 ng/ml). There was no correlation between P-selectin levels and parasitemia. These results raise the possibility that elevated soluble P-selectin in malaria may have an important beneficial anti-inflammatory function.