[Revised S3 guidelines on schizophrenia : Developmental process and selected recommendations]. / Die aktualisierte S3-Leitlinie Schizophrenie : Entwicklungsprozess und ausgewählte Empfehlungen.

Schizophrenia is one of the most severe mental diseases and leads to significant personal and social impairments for affected persons. The illness is characterized by frequent relapses, results in increased mortality and is associated with the highest socioeconomic costs of all diseases. Moreover, patients with schizophrenia are often stigmatized in everyday life and also in most treatment settings. In 1998 the first German schizophrenia guidelines were published, followed by the first S3 guidelines for schizophrenia in 2006. The revision process started in 2012 coordinated by the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN) and the revised guidelines were published in 2019. The target group for the revised S3 guidelines includes all persons involved in the care of patients with schizophrenia in all sectors of the German healthcare system, including decision makers and insurance funds. Starting with an introduction of the biological, clinical and epidemiological basis of the disorder, recommendations for the diagnostics of schizophrenia, the detection of comorbidities, the use of antipsychotic medication and other somatic procedures, for psychotherapy, psychosocial interventions, handling of special treatment conditions and rehabilitation are made. Finally, recommendations for an evidence-based and optimal coordination within the healthcare system are made, followed by a discussion of the cost-effectiveness of treatment and presentation of strategies for improved quality management. The most important aspect of the revised S3 guidelines on schizophrenia is the multiprofessional cooperation in all phases of the disorder and an empathic and respectful therapeutic alliance.

Depressive symptoms, resilience, and personality traits in dry eye disease.

PURPOSE: Dry eye disease (DED) is a multifactorial disease of the ocular surface that leads to symptoms of discomfort and reduces quality of life. Several studies have shown an association with depression. We investigated the prevalence of depressive symptoms and their severity in DED patients and examined whether depressive symptoms correlate with signs, symptoms, or subtypes of DED or with psychological factors (resilience, premorbid personality, and subjective well-being). METHODS: This cross-sectional study (n = 64, mean age 56.72, 70% women) was conducted at the Dry Eye Clinic of the Department of Ophthalmology, University Hospital Düsseldorf. Psychological assessment included the Beck Depression Inventory, revised version (BDI-II); World Health Organization Well-Being Index (WHO-5); 13-item Resilience Scale (RS-13); and Munich Personality Test (MPT). DED parameters were assessed by the Ocular Surface Disease Index (OSDI), Schirmer test (ST), tear film break-up time (TBUT), and corneal fluorescein staining (CFS). As the reference for the BDI-II depression score, we used standard values from a German sample of healthy individuals (n = 582, 66% women). Multivariate logistic regression analysis was performed to investigate the effects of various parameters on depressive symptoms. Associations between variables were examined by Pearson or Spearman correlation tests. RESULTS: Among all participants, 61% had depressive symptoms (25% minimal, 14% mild, 17% moderate, and 5% severe). The mean BDI-II score (11.95, ± 8.46) was significantly higher than in the healthy reference group (p < .0001). It was not correlated with the severity of signs or symptoms of DED or with its subtypes, but it was significantly negatively correlated with resilience (p < .0001) and subjective well-being (p < .0001). Depressive symptoms were negatively correlated with the premorbid personality trait extraversion (p = .036) and frustration tolerance (p < .0001) and positively correlated with premorbid neuroticism (p = .001), isolation tendencies (p = .014), and esoteric tendencies (p = .001). CONCLUSIONS: Depressive symptoms of all degrees of severity are common in DED patients, but they are not associated with the severity of signs or symptoms of DED. Subjective well-being, resilience, and premorbid personality do not correlate with the signs or symptoms of DED, but they do correlate with depressive symptoms.

[Return-to-Work after depression - evaluation of a retrospective case-control study of an operational integrated care model]. / Rückkehr an den Arbeitsplatz nach depressiver Erkrankung - Evaluation einer retrospektiven Fall-Kontroll-Studie eines betriebsnahen integrierten Versorgungsmodells.

The objective of the study was to evaluate an operational integrated care model (IC) aiming at optimized treatment of depression. It consisted of cooperation between a company and an external clinic with respect to early recognition of the disorder, early access to treatment and support for return to work. METHOD: A retrospective group comparison of patients with depression receiving IC in a psychiatric outpatient clinic (N=64) and a control group with standard care in the same clinic (N=64) was performed. Primary outcome was return to work. RESULTS: Patients of the IC group returned to work significantly more often (Odds Ratio 11.9; p<0.001) and 91.2 days earlier (p=0.010) than those of the group that received standard care. CONCLUSION: Specific measures of an IC program might accelerate the process of return to work.

Development and implementation of quality indicators in a group of nine psychiatric hospitals.

Quality indicators (QI) are becoming increasingly important in mental healthcare in Germany. QI can be used for various purposes, such as for creating transparency as well as for benchmarking between hospitals. QI themselves are subject to high quality standards. The aim of this report is to describe the development and implementation of QI in a group of psychiatric hospitals. Since 2015, the LVR hospital group has developed and gradually implemented QI for the purposes of quality measurement, quality assurance and internal benchmarking in its nine psychiatric hospitals in a comprehensive, multidisciplinary, scientifically accompanied process. The full LVR-QI set, consisting of eight structure-, twelve process- and four outcome indicators as well as one patient satisfaction questionnaire, was implemented by 2019. In order to create high documentation quality and acceptance by clinicians, various implementation and dissemination strategies were used, such as written documentation manuals, staff training as well as regular face-to-face communication between the LVR hospitals, the LVR Institute for Health Services Research as the central coordinating body and the headquarters of the LVR hospital group. The QI led to a quality-oriented dialogue within and between the LVR hospitals.

Prevention of First-Episode Psychosis in People at Clinical High Risk: A Randomized Controlled, Multicentre Trial Comparing Cognitive-Behavioral Therapy and Clinical Management Plus Low-Dose Aripiprazole or Placebo (PREVENT).

BACKGROUND: There is limited knowledge of whether cognitive-behavioral therapy (CBT) or second-generation antipsychotics (SGAs) should be recommended as the first-line treatment in individuals at clinical high risk for psychosis (CHRp). HYPOTHESIS: To examine whether individual treatment arms are superior to placebo and whether CBT is non-inferior to SGAs in preventing psychosis over 12 months of treatment. STUDY DESIGN: PREVENT was a blinded, 3-armed, randomized controlled trial comparing CBT to clinical management plus aripiprazole (CM + ARI) or plus placebo (CM + PLC) at 11 CHRp services. The primary outcome was transition to psychosis at 12 months. Analyses were by intention-to-treat. STUDY RESULTS: Two hundred eighty CHRp individuals were randomized: 129 in CBT, 96 in CM + ARI, and 55 in CM + PLC. In week 52, 21 patients in CBT, 19 in CM + ARI, and 7 in CM + PLC had transitioned to psychosis, with no significant differences between treatment arms (P = .342). Psychopathology and psychosocial functioning levels improved in all treatment arms, with no significant differences. CONCLUSIONS: The analysis of the primary outcome transition to psychosis at 12 months and secondary outcomes symptoms and functioning did not demonstrate significant advantages of the active treatments over placebo. The conclusion is that within this trial, neither low-dose aripiprazole nor CBT offered additional benefits over clinical management and placebo.

Prevention of rehospitalization in schizophrenia: results of an integrated care project in Germany.

The goal of this study was to prevent rehospitalizations and thus to optimize satisfaction with treatment and quality of life in patients suffering by schizophrenia or schizoaffective disorder. A complex intervention with improved cooperation between in- and outpatient services was applied to 46 "high utilizing" patients after discharge from inpatient care during an intervention phase of 6 months. The study was controlled by a matched group of 47 patients receiving treatment as usual. The intervention was based on a computerized decision support module. Eight psychiatrists in private practices were supplied with this software to obtain guideline-based recommendations according to current psychopathology and clinical state. Suggested complex interventions by the software included psychoeducation, social competence group therapy, integrated psychological therapy, computer-based cognitive training, coping skills training, sociotherapy, nursing care, home visits, social-worker care, assistance to family members, and the use of an emergency call-in line. A local hospital project team arranged specifically suggested interventions. We intended to accomplish a reduction of rehospitalization rates by 50% in the intervention group within a 12-month follow-up phase. Satisfaction with treatment, subjective quality of life, and treatment costs in terms of daily inpatient costs were compared between both groups. Moderator variables such as socio-demographical aspects or influences of certain interventions to rehospitalization rate were analyzed. The sample included patients more seriously ill than originally expected. Subjects in the control group (CG) were older (46 years) than those subjects in the intervention group (IG) (40 years). Other sociodemographical aspects (sex, family status, level of education, and number of former hospitalizations) showed no differences between both groups. The rehospitalization rate and the mean length of inpatient treatment were reduced to nearly 50% in the intervention group. The rate of readmissions increased in the control group, leading to a difference of 23% between both groups. The most important factor to favorably influence rehospitalization rates was the participation in coping skills training. There was an increase in patient satisfaction with treatment, while the subjective quality of life remained constant. Since these improvements were accomplished with lower costs (in terms of inpatient care), cost effectiveness was higher in the IG than in the CG. The most important single factor to favorably influence rehospitalization rates was the participation in coping skills training. Only the guideline consistent complex therapies as common intervention caused the significant overall result. Thereby, satisfaction with treatment increased considerably during the 6 months of intervention and remained constant during 12 months of follow up. The model project described is an important step to gain evidence and experience with integrated care for patients with schizophrenia.

Mental illness stigma and disclosure: consequences of coming out of the closet.

The present study investigated disclosure patterns among mental health consumers (N = 500) and examined the relationships among disclosure, perceived stigmatization, perceived social support, and self-esteem. Results suggest that selective disclosure optimizes social support and limits stigmatization. Perceived stigmatization has a detrimental impact on self-esteem, especially for those who are relatively open about their mental disorder.

Predictors of treatment response to psychological interventions in people at clinical high risk of first-episode psychosis.

AIM: Psychological interventions, such as cognitive behavioural therapy (CBT) and supportive counselling (SC), are used to treat people with schizophrenia and people at clinical high risk (CHR) of psychosis. However, little information is available on predictors of treatment response. This study aims to identify such predictors of psychological interventions in CHR. METHODS: A total of 128 help-seeking CHR outpatients were randomized into two groups-integrated psychological intervention (IPI), including CBT, and SC-for 12 months. Multiple regression analysis was used to identify demographic, symptomatic and functional variables that predict improvement in positive (PANSS Positive), negative (PANSS Negative) and basic symptoms (Basic symptom total score) and improvement in functioning (GAF) at 1-year follow up. RESULTS: In the merged group (IPI + SC), people who lived independently, were younger and presented with higher baseline functioning showed more improvement in symptomatic outcomes at follow up. Negative symptoms at baseline predicted less improvement in positive and basic symptoms. Being married or cohabiting and living in the primary family were found to correlate with good functioning at 1-year follow up. CONCLUSIONS: Younger CHR individuals and those who are functioning well may particularly benefit from early intervention. Treatment might need to be modified for low-functioning CHR and those who already display higher scores of negative symptoms. Registration number: NCT00204087.

Negative schemata about the self and others and paranoid ideation in at-risk states and those with persisting positive symptoms.

BACKGROUND: The objective of this study is to test the conflicting theories concerning the association of negative self and other schemata and paranoid ideation. METHODS: A risk-based approach, including risk stratification, is used to gain insight into the association of the negative self and other schemata that may be shared by individuals or differentiate between individuals at clinical high risk (CHR) for a first-episode psychosis and those with full-blown psychosis. The dataset includes a sample of individuals at CHR (n = 137) and a sample of individuals with persisting positive symptoms (PPS, n = 211). The CHR sample was subdivided according to a prognostic index yielding 4 CHR sub-classes with increasing risk for transition to psychosis. RESULTS: Negative beliefs about the self were associated with paranoid ideation in CHR and a lower risk state. In the highest risk state and full-blown psychosis, there is an association with negative beliefs about others. CONCLUSION: These findings are in line with theories suggesting a switch from a predominantly activated negative self-schema to a malevolent others-schema in association with paranoid ideation along the risk-continuum. However, due to methodological limitations these results should be replicated by future studies.

Clinical high risk for psychosis: gender differences in symptoms and social functioning.

AIM: Schizophrenia is a heterogeneous disorder that presents differently in men and women: men show a higher propensity to negative symptoms, lower social functioning, earlier age at onset and co-morbid substance abuse, whereas women display more affective symptoms. It is unknown whether these differences extend to subjects at high risk (HR) of psychosis. Thus, the aim of the present study was to address this question. METHODS: Clinical symptoms and functioning were assessed using structured interviews in 239 HR subjects (female, n = 80). The definition of being at HR was based on the criteria used in the European Prediction of Psychosis Study (EPOS). RESULTS: Men displayed more pronounced negative symptoms, higher rates of past substance abuse disorders and higher deficits in social functioning. No gender difference was found for depression, which affected almost 50% of the cohort, or age at onset for the fulfilment of HR criteria. CONCLUSION: The higher impairment in specific symptoms observed in male schizophrenia patients was also present in subjects at HR for psychosis. Further studies are required to determine whether these symptoms are gender-specific predictors of transition to psychosis and whether they warrant gender-specific interventions. The high propensity to depression in the present cohort, which was particularly pronounced in the male cohort compared with the general population, in conjunction with the observed increase in negative symptoms and functional impairment, should alert clinicians to the necessity for the identification and treatment of HR subjects, irrespective of the degree to which these features are associated with transition risk.

Prevalence of metabolic syndrome in female and male patients at risk of psychosis.

Metabolic Syndrome (MetS) is one of the most common factors underlying the high rate of mortality observed in patients with schizophrenia. Recent research on this topic revealed that many of the patients studied were, in fact, in a medicated state. As such, it is unclear whether MetS is causally associated with the disorder itself or the medication used to treat it. In this study, patients with a clinically high risk of expressing first episode psychosis (CHR) were examined regarding the prevalence of MetS. N=144 unmedicated and antipsychotic-naïve CHR patients, aged between 18 and 42years and suffering from unmanifested prodromal symptoms, were compared with a cohort of N=3995 individuals from the "German Metabolic and Cardiovascular Risk Study" (GEMCAS). A slightly higher prevalence of individual MetS criteria was observed in the CHR group compared to the GEMCAS sample; specifically, the following were noted: a higher blood pressure (35.0% vs. 28.0%), increased waist circumference (17.6% vs. 15.1%), and increased fasting blood glucose (9.4% vs. 4.0%) in CHR patients. Additionally, the rate of reduced HDL cholesterol concentrations was lower in the control group (20.2% vs. 13.3%).

Evaluation of factors influencing medication compliance in inpatient treatment of psychotic disorders.

RATIONALE: Short- and long-term compliance to prescribed antipsychotic drugs is of particular concern in regard to medication choice and treatment outcome in the care of psychotic disorders. OBJECTIVE: We evaluated patient-related and treatment-related factors associated with medication compliance in inpatients with a diagnosis of schizophrenia, schizoaffective disorder, or other psychotic disorder. METHODS: Within a naturalistic study in seven psychiatric hospitals, individuals with a psychotic disorder were assessed weekly on mental state, social functioning, side effects, and medication compliance. Logistic regression analyses were computed to assess patient and clinical predictors of medication compliance. RESULTS: We found a significant association between medication compliance and substance abuse (OR 0.52, CI 0.32-0.85), involuntary admission (OR 0.60, CI 0.41-0.89), history of aggressive behavior (OR 0.57, CI 0.38-0.85), and no school graduation (OR 0.59, CI 0.41-0.86). Individuals with pronounced paranoid or negative symptoms were also less compliant in taking their prescribed medication. There was no association between the initial inpatient antipsychotic medication regime and patients' compliance. Individuals who switched from a typical to an atypical antipsychotic drug were more compliant than those with their typical antipsychotic drug maintained. Those with higher medication compliance showed significantly greater improvement of their psychiatric symptoms during the inpatient stay. CONCLUSION: Patient-related in addition to disease-related factors may strongly influence medication compliance. Besides more compliance with atypicals supposed by the literature, there may be a higher propensity for atypical drugs to be prescribed to those assumed to be more compliant.

The German Research Network on Schizophrenia--impact on the management of schizophrenia.

The German Research Network On Schizophrenia (GRNS) is a nationwide network currently comprising 16 psychiatric university departments and 14 state and district hospitals, as well as six local networks of psychiatric practices and general practitioners collaborating on about 25 interrelated, multicenter projects on schizophrenia research. The GRNS aims to intensify collaboration and knowledge exchange between leading research institutions and qualified routine care facilities, both within (horizontal network) and between (vertical network) the two levels of research and care, in order to create the scientific preconditions for optimization of the management of schizophrenia. The concept and the first results of studies aiming at the investigation of (i) strategies for early detection and early intervention in the prodromal stage of psychosis; (ii) treatment in first-episode schizophrenia; (iii) quality management; and (iv) destigmatization, are described as examples of this effort.

[Assessment-Based Home Treatment for People with Severe Psychotic Disorders]. / Assessmentgesteuertes Home Treatment für Patienten mit schweren psychotischen Störungen.

OBJECTIVE: Although there is growing evidence for clinical effectiveness of crisis resolution teams (also called Home Treatment Teams) for patients with severe psychotic disorders, a lot of studies suffer from poor model fidelity, which leads to an ignorance of specific effective factors. METHODS: Here we present the implementation of an assessment-based Home Treatment in Germany. Assessment-derived therapeutic tasks are shared between team members by a manualized process. RESULTS: We visited 32 patients almost 600 times in 15 months. The median was 15.5 visits per patient. Adherence to Home Treatment intervention was significantly stronger (unplanned discharge 16 %) compared to prior hospitalization (unplanned discharge 50 %) (Chi-square test, p = 0.003). CONCLUSION: Applying this model, a detailed definition of specific tasks for team members leads to a high model fidelity and increases patients' compliance to therapy.

Coping as a predictor of treatment outcome in people at clinical high risk of psychosis.

AIM: The concept of coping is relevant to recent models of psychosis, and people with established psychotic disorders have been found to predominately use maladaptive coping strategies. This study aimed to examine the general coping patterns of people at clinical high risk of psychosis (CHR) and to investigate whether pre-therapy coping behaviour plays a role in predicting responsiveness to early interventions. METHODS: One hundred twenty-eight help-seeking CHR outpatients were randomized into two treatment groups: either receiving integrated psychological intervention (IPI), including cognitive behaviour therapy, or supportive counselling (SC) for 12 months. Of those, 91 persons completed a Stress Coping Questionnaire (SCQ) at intake: 45 in the IPI group and 46 in the SC group. General coping behaviour in this sample was analysed and several regressions were conducted separately for each treatment group to examine coping as a predictor of outcome after 12 months of different forms of treatment. RESULTS: Participants relied significantly more on negative than on positive coping strategies, t(90) = -7.185, P < 0.001, and within the positive strategies, stress control was the most preferred one, t(90) = 10.979, P < 0.001. Several pre-therapy coping strategies significantly predicted improvement in symptomatic outcome in both treatment groups, explaining between 16% and 25% of variance. The predictive value of coping was higher in the SC group. CONCLUSIONS: Maladaptive coping behaviours were found to emerge in the early stages of psychosis and coping behaviour contributed significantly to the prediction of post-treatment symptom improvement. These findings indicate a need for psychosocial support and coping strategy enhancement in people at risk of psychosis.

Cognitive-behavioral therapy in the pre-psychotic phase: an exploratory study.

Although the efficacy of cognitive-behavioral therapy (CBT) in schizophrenia has been established for persistent psychotic symptoms, little information is available on the effects of CBT in the pre-psychotic phase. We developed a comprehensive CBT program for clients in the early initial prodromal state that showed good feasibility and promising treatment effects in an uncontrolled prospective study. The specificity of these effects needs to be explored in a controlled trial.

Interventions in the initial prodromal states of psychosis in Germany: concept and recruitment.

BACKGROUND: The Early Detection and Intervention Programme of the German Research Network on Schizophrenia (GRNS) investigates the initial prodromal phase of psychosis in a multidimensional approach. Two intervention strategies are being studied by two large-scale multicentre projects. AIMS: To present the concept of the intervention studies, and to provide an interim report of the recruitment procedure. METHOD: Comprehensive cognitive-behavioural therapy has been developed for patients in the "early initial prodromal state". For patients in the "late initial prodromal state" the atypical neuroleptic amisulpride is explored. Both interventions are evaluated in randomised controlled trials using clinical management as the control condition. RESULTS: Between January 2001 and March 2003, 1212 individuals seeking help for mental health problems were screened for putative prodromal symptoms at four university centres. More than 388 individuals fulfilled criteria for both interventions and 188 (48.5%) gave informed consent to participate in the trials. CONCLUSIONS: The screening procedure appears to be feasible and trial participation seems to be acceptable to a relevant proportion of people at increased risk of developing psychosis.

[Neuropsychological Functioning as a Predictor of Treatment Response to Psychoeducational, Cognitive Behavioral Therapy in People at Clinical High Risk of First Episode Psychosis]. / Neuropsychologische Funktionen als Prädiktoren des Therapieerfolgs von psychoedukativer, kognitiv verhaltenstherapeutischer Therapie bei Personen mit erhöhtem Psychoserisiko.

OBJECTIVE: Investigate whether treatment response in people at clinical high risk of psychosis (CHR) is predicted by their cognitive performance. METHOD: 128 CHR outpatients were randomized into two treatment groups, one receiving integrated psychological intervention (IPI), including psychoeducation, the other receiving supportive counselling (SC) for 12 months. Multiple regression analysis was used to identify neurocognitive predictors of treatment response in a subgroup of n = 105, measured by symptomatic and functional improvement at 1-year follow-up. RESULTS: In the IPI, treatment response was associated with performance of executive control and processing speed (R²â€Š= 0.27, p = 0.002). In both treatment groups, performance of working memory/attention was a significant predictor (IPI: R²â€Š= 0.15, p = 0.039, SC: R²â€Š= 0.19, p = 0.012). CONCLUSION: Cognitive performance is associated with treatment response in CHR people. The enhancement of cognitive performance is a useful target of early intervention.

Switching antipsychotics in inpatient schizophrenia care: predictors and outcomes.

BACKGROUND: Within a pharmacoepidemiologic study, characteristics of patients with schizophrenia switched from first- to second-generation antipsychotics (FGAs and SGAs, respectively) or to antipsychotic polypharmacy were compared with those of patients maintained on treatment with FGAs. The primary aim was to assess factors associated with antipsychotic switching and to compare disease course with regard to mental state and social functioning. METHOD: Adult inpatients with an ICD-10 diagnosis of schizophrenia or schizoaffective disorder were assessed in 7 psychiatric hospitals. Data were collected between 2001 and 2002. For those patients (N = 847) with an antipsychotic prescription at discharge, t tests and covariance and logistic regression analyses were used to evaluate the relationship between demographic and clinical characteristics and antipsychotic switching. RESULTS: Patients switched from FGAs to SGAs had fewer previous psychiatric admissions, a shorter illness duration, fewer substance disorders, and a higher probability of working in a competitive setting but more pronounced symptoms than those maintained on treatment with FGAs. Mental state and social functioning after case-mix adjustment were more favorable in the group switched to SGA monotherapy but not in those patients administered FGAs and SGAs concurrently at discharge. Logistic regression controlling for demographic and clinical variables revealed that a short disease duration (p <.05), fewer previous psychiatric hospitalizations (p <.01), voluntary admission (p <.05), and pronounced thought disorder (p <.05) were significantly associated with switching from FGAs to SGAs. Hospital differences were also observed. CONCLUSION: Remaining on FGAs or switching to SGAs in schizophrenia care depends strongly on institutional practices in addition to the previous disease course and health care utilization.

Validation of polypharmacy process measures in inpatient schizophrenia care.

The influence of combining antipsychotics and different classes of psychotropic drugs on treatment outcome in schizophrenia remains unclear. As part of a comprehensive quality management program, we prospectively evaluated two schizophrenia polypharmacy performance measures in a cohort of 1,075 consecutively recruited individuals with schizophrenia in seven psychiatric hospitals. Multiple concurrent antipsychotic and overall psychotropic polypharmacy rates were noticeably high. In case-mix-adjustment models controlling for a variety of confounding baseline parameters, patients discharged with more than one antipsychotic had significantly poorer outcomes with respect to both mental state and social functioning. Prescription of more than three psychotropic agents did not adversely affect social functioning when patients taking more than three were compared to patients given fewer medications. Case-mix models suggest that antipsychotic polypharmacy, while used more often for individuals with chronic disease and more thought disturbance, is only partly a reaction to disease severity. The antipsychotic polypharmacy process measure may be used to identify treatment problems in order to find alternatives to polypharmacy. The measure can be easily assessed in a variety of settings and does not depend on the availability of case-mix data. The rising trend toward polypharmacy in schizophrenia care, which is not supported by current guideline recommendations, warrants critical appraisal.