Assessment and Treatment of Negative Symptoms in Schizophrenia-A Regional Perspective.

Clinicians and researchers consider that there are a variety of symptoms that constitute negative symptoms in schizophrenia, and they may use different definitions for the same symptoms. These differences are also reflected in a variety of negative symptom rating scales. Both research and clinical work are negatively affected by the lack of consensus regarding the symptoms that constitute negative symptoms in schizophrenia. Leading research groups have investigated ways to reduce heterogeneity in the domain of negative symptoms in schizophrenia; however, little attention has been paid to regional differences in the concepts of negative symptoms in schizophrenia. The objective of this review was to collect and summarize information about the assessment and treatment of negative symptoms of schizophrenia in Central and Eastern Europe (CEE). Nineteen experts from 17 countries in CEE participated in this project. The participants collected information about their countries, including the following: (1) the most important publications about negative symptoms in schizophrenia (irrespective of the time of their publication); (2) the most frequently used negative symptom of schizophrenia in clinical practice; (3) definitions of frequently used negative symptoms; and (4) treatment of negative symptoms in schizophrenia. The participating experts/countries most frequently reported the following five negative symptoms: avolition, blunted affect, alogia, asociality, and anhedonia. Several experts also considered other symptoms as belonging to the negative symptom domain, such as a decrease in energy level and changes in personality. The importance of evaluating the long-term course and the relationship between negative symptoms and other symptom domains was also noted. No noticeable differences were reported in the treatment of negative symptoms compared to currently published guidelines and algorithms. The most frequently reported negative symptoms included those defined by the NIMH-MATRICS consensus statement on negative symptoms and recently endorsed in a guidance paper of the European Psychiatric Association. The main differences in the concepts, names, and definitions of primary negative symptoms, especially those related to personality changes, and to the evaluation of the long-term course and relationship between different symptom domains in CEE compared to the current English language literature deserve the attention of psychiatrists and other professionals in this field.

Optimization of a Single Tube Practical Acoustic Thermometer.

When designing a single tube practical acoustic thermometer (PAT), certain considerations should be addressed for optimal performance. This paper is concerned with the main issues involved in building a reliable PAT. It has to be emphasised that a PAT measures the ratio of the time delay between the single temperature calibration point (ice point) and any other temperature. Here, we present different models of the speed of sound in tubes, including the effects of real gases and an error analysis of the most accurate model with a Monte Carlo simulation. Additionally, we introduce the problem of acoustic signal overlap and some possible solutions, one of which is acoustic signal cancellation, which aims to eliminate the unwanted parts of an acoustic signal, and another is to optimize the tube length for the parameters of the gas used and specific temperature range.

Prescribing patterns for inpatients with schizophrenia spectrum disorders in a psychiatric hospital in Slovenia: Results of 16-month prospective, non-interventional clinical research.

BACKGROUND: In Slovenia, there has been no evidence about the prescribing patterns for inpatients with psychotic disorders. The research aims to analyze drug utilization patterns for inpatients with psychotic disorder that are coded as F20-F29 according to International Classification of Diseases (ICD) 10th revision (schizophrenia spectrum disorders). SUBJECTS AND METHODS: Prospective research was conducted at the Psychiatric Hospital Idrija. The medical records of the inpatients admitted over a 12-month period were collected from the beginning to the end of their hospitalization. RESULTS: A total of 311 inpatients with 446 hospitalizations were included, producing a total of 3954 medication prescriptions. Medications prescribed pro re nata (the use of as needed) were also taken into account. Antipsychotics (N=1149, 43% of prescriptions) were the most often prescribed medications, followed by anxiolytics, antiparkinsonians, antidepressants, mood stabilizers and cardiovascular drugs. A total of 256 (82%) inpatients received at least one pro re nata medication. It was observed that the studied population was treated with one antipsychotic on 27 percent of prescriptions. CONCLUSIONS: Inpatients with schizophrenia spectrum disorders were exposed to a large number of different drugs. They were not received only psychotropic drugs but also other medications. With the knowledge about medications the implementation of clinical pharmacy services to the psychiatrists would significantly improve medication of inpatients with psychotic disorders and polypharmacotherapy.

Original research paper. Switching antipsychotics: Results of 16-month non-interventional, prospective, observational clinical research of inpatients with schizophrenia spectrum disorders.

The study aims to identify prescribing and switching patterns of antipsychotics in clinical practice. A 16-month, prospective study was conducted at the Psychiatric Hospital Idrija, Slovenia. Inpatients (N = 311) with schizophrenia spectrum disorders were observed. The causes for switching antipsychotics and switching strategies were analyzed. Analyzing a total of 3954 prescriptions, the collected data confirmed that treatment strategies in this psychiatric hospital are very complex. It was found that 37 percent of inpatients had at least one switch. Moreover, switches that included three or more antipsychotics were detected. The most common causes for switching antipsychotics were adverse reactions and inefficacy or lack of efficacy. Among switching options, abrupt switch was recorded several times. As some patients are receiving several antipsychotics at the same time, it is possible that unusual switching occurs in clinical practice. It seems that the choice of switching strategy is also affected by the cause and urgency for switching an antipsychotic.

Treatment patterns of schizophrenia based on the data from seven Central and Eastern European Countries.

OBJECTIVE: The aim is to analyze how schizophrenia is pharmacologically treated in seven CEE countries: Croatia, Estonia, Hungary, Poland, Serbia, Slovakia and Slovenia. METHODS: Psychiatrists from selected centers in each of participating countries were asked to complete a pre-defined questionnaire on their current clinical practice. Information on protocols and resource utilization in schizophrenia treatment was included and derived from randomly selected patient medical records. Expert opinions on country-wide treatment patterns were additionally sought. This sub-analysis focuses on pharmacological treatment patterns in the last six months and over the course of the disease. RESULTS: 961 patients' data show that during last six months the most commonly prescribed medications were oral atypical antipsychotics: olanzapine (n=268), clozapine (n=234) and risperidone (n=160). The most frequently prescribed atypical antipsychotics over course of disease were: risperidone (54.5%), olanzapine (52.4%) and clozapine (35.1%), along with haloperidol (39.3%). Experts reported risperidone (four countries) and olanzapine (three countries) as first-line treatment, with the same two medications prescribed as second-line treatment. Clozapine was the most reported medication for refractory patients. Approximately 22% of patients received polypharmacy with antipsychotics in at least one period over the disease course. Mean time since diagnosis was 13.1 years and on average 4.8 treatment courses received during that period. Anxiolytics (70%), antidepressants (42%), mood-stabilizers (27%) were also prescribed, with diazepam (35.4%), sertraline (10.5%), valproic acid (17.5%) the most commonly reported, respectively, in each group. The most frequently reported treatment change was switch from one oral atypical antipsychotic to another (51%). CONCLUSION: Oral atypical antipsychotics, mostly older drugs (risperidone, olanzapine, clozapine), were most commonly prescribed for schizophrenia treatment in participating countries. Given that results are from the first large-scale analysis of RWD, we believe these findings can be a benchmark for future real-world studies, which could contribute to the optimization of treatment for this debilitating disease.

Schizophrenia causes significant burden to patients' and caregivers' lives.

BACKGROUND: Schizophrenia is a serious public health problem and is ranked among the most disabling diseases in the world. The sub-study presented here was part of a larger project to characterize the burden of schizophrenia on healthcare systems and on individuals living with the disease in Central and Eastern Europe (CEE). AIMS: This sub-study aimed to assess and analyze the impact of schizophrenia on many aspects of the lives of patients and caregivers. METHODS: Psychiatrists from selected centers in seven Central and Eastern European countries were asked to complete a questionnaire in order to collect information about the disease history, characteristics, treatment protocols and resources used for each randomly selected patient. All data were statistically analyzed and compared between countries. RESULTS: Data from 961 patients with schizophrenia (mean age 40.7 years, 45.1% female) were included in the analysis. The mean number of days spent in hospital per patient per year across all seven countries was 25.3 days. Hospitalization occurred on average once per year, with psychiatrist visits 9.4 times per year. Of the patients in the study, 61% were single, 12% divorced and 22% married or cohabiting. Almost 84% were living with relatives or a partner; only 17% lived alone and, on average, 25% of patients received support from social workers. Relatives provided care for approximately 60% of patients and 4% of them had to stop working in order to do so. Twenty-nine percent of the patients were unemployed, and 56% received a disability pension or were retired, with only 19% in full-time employment or education. CONCLUSION: Schizophrenia has a significant effect on the lives of patients and caregivers and impacts their social integration.

Delirium with anticholinergic symptoms after a combination of paliperidone and olanzapine pamoate in a patient known to smoke cannabis: an unfortunate coincidence.

We report a case of delirium with anticholinergic symptoms in a 19-year-old female patient with schizophrenia. On the day the symptoms emerged, the patient received olanzapine long-acting injection and a higher dose of paliperidone. We observed symptoms ranging from confusion to delirium as well as some anticholinergic symptoms. The delirium lasted 24 hours and was managed by intravenous fluid substitution and oral benzodiazepines. Olanzapine pamoate, paliperidone and cannabis are central nervous system (CNS) depressants, and their combination can increase the risks of CNS depression. In this case report, we review the symptoms of delirium in a case of antipsychotic overdose and provide general guidelines for managing these symptoms. We also review possible complications in combined use of cannabis, olanzapine and paliperidone.

Epidemiology and Treatment Guidelines of Negative Symptoms in Schizo-phrenia in Central and Eastern Europe: A Literature Review.

AIM: To gather and review data describing the epidemiology of schizophrenia and clinical guidelines for schizophrenia therapy in seven Central and Eastern European countries, with a focus on negative symptoms. Methods : A literature search was conducted which included publications from 1995 to 2012 that were indexed in key databases. Results : Reports of mean annual incidence of schizophrenia varied greatly, from 0.04 to 0.58 per 1,000 population. Lifetime prevalence varied from 0.4% to 1.4%. One study reported that at least one negative symptom was present in 57.6% of patients with schizophrenia and in 50-90% of individuals experiencing their first episode of schizophrenia. Primary negative symptoms were observed in 10-30% of patients. Mortality in patients with schizophrenia was greater than in the general population, with a standardized mortality ratio of 2.58-4.30. Reasons for higher risk of mortality in the schizophrenia population included increased suicide risk, effect of schizophrenia on lifestyle and environment, and presence of comorbidities. Clinical guidelines overall supported the use of second-generation antipsychotics in managing negative symptoms of schizophrenia, although improved therapeutic approaches are needed. Conclusion : Schizophrenia is one of the most common mental illnesses and poses a considerable burden on patients and healthcare resources alike. Negative symptoms are present in many patients and there is an unmet need to improve treatment offerings for negative symptoms beyond the use of second-generation antipsychotics and overall patient outcomes.

Creative treatment of bipolar disorders.

Bipolar disorder is a mental disorder with chronic and remitting course. The disorder is related to high mortality and severely impairs everyday functioning. Therefore a scientifically sound and practical approach to treatment is needed. Making a long-term treatment plan usually also demands some creativity. The patient is interested in a number of issues, from the choice of therapy in acute phases to long-term treatment. Usual questions are how long shall I take the medications, do I really need all those pills or can we decrease the dosage of some drugs? This paper discussed the above mentioned questions in light of latest publications in this field.

Specific cognitive abilities are associated with diabetes self-management behavior among patients with type 2 diabetes.

AIM: Patients with diabetes differ in compliance to diabetes self-management which influences their long-term health. Psychological factors, namely depression and cognitive abilities, are associated with diabetes self-management behavior. The aim of the study was to identify independent association of particular cognitive functions with diabetes self-management. METHODS: In a cross sectional study 98 adults with type 2 diabetes attending Diabetes Outpatient Clinic were examined using the measures of diabetes self-management (Summary of Diabetes Self-Care Activities (SDSCA) measure), depression (Hamilton Depression Inventory (HDI)), diabetes distress (Problem Areas In Diabetes scale (PAID)), and the neuropsychological battery of tests for assessment of cognitive functions. Sociodemographic and diabetes-related data were collected. Univariate and multivariate regression analyses were used to identify and evaluate the predictors of diabetes self-management. RESULTS: Specific cognitive functions, namely immediate memory, visuospatial/constructional abilities, attention, and specific executive functions (planning and problem solving) were significantly associated with diabetes self-management. Among cognitive factors, planning and problem solving abilities were strongest predictors; furthermore, in a multivariate regression their association was independent from depression. CONCLUSIONS: Specific cognitive abilities, particularly planning and problem solving, play an independent role in diabetes self-management behaviors. Assessing patients' cognitive abilities may be of value for adjusting self-management education and treatment regimen.

Effects of training program on recognition and management of depression and suicide risk evaluation for Slovenian primary-care physicians: follow-up study.

AIM: To implement and evaluate an educational program for primary care physicians on recognition and treatment of depression and suicide prevention. METHOD: The study was conducted in 3 Slovenian neighboring regions (Celje, Ravne na Koroskem, and Podravska) with similar suicide rates and other health indicators. All primary care physicians from Celje (N=155) and Ravne na Koroskem (N=35) were invited to participate in the educational program on depression treatment and suicide risk recognition. From January to March 2003, approximately half of them (82 out of 190; educational group) attended the program, whereas the other half (108 out of 190; control group 1) and physicians from the Podravska region (N=164; control group 2) did not attend the program. The prescription rates of antidepressants and anxiolytics before and after the intervention were compared between the studied regions. Also, suicide rates three-years before and after the intervention were compared. RESULTS: From 2002 to 2003, there was a 2.33-fold increase in the rate of antidepressant prescriptions in the educational group (P<0.05) and only 1.28-fold (P<0.05) and 1.34-fold (P<0.05) increase in control groups 1 and 2, respectively. However, the 12% decrease in suicide rate in the intervention regions was not significantly greater than the 4% decrease in the non-intervention region (P>0.05). CONCLUSION: Our training program was beneficial for primary care physicians' ability to recognize and manage depression. However, there was no significant decrease in local suicide rates.

Schizoaffective disorder: from Kraepelin to genes.

The original term schizoaffective disorder was invented 75 years ago by Kasanin as a response to diagnostic difficulty with patients who did not fit well in Kraepelin's dichotomy of dementia praecox and affective disorder. However, this was not the perfect solution since criteria for diagnosing schizoaffective disorder were not firmly set at that time. The broad category of schizoaffective disorders included not only patients with co-occurring schizophrenic and affective symptoms but also other "atypical" psychoses. Over time diagnostic criteria became more defined but the original question still remains the same: is there any such thing as schizoaffective disorder? This paper presents some historical and modern data which may help clarify this issue, but it is still premature to give a definitive answer on all pending questions related to this interesting topic.

Observation of treatment of depression in primary care setting in first week - what happens in first week of treatment with antidepressants?

Depression is frequently diagnosed and treated by general practicioners. In observational study we investigated the influence of the severity of depressive and anxiety symptoms on the frequency of patients' questions about mental disorder and their tendency to misinterpret the signs and symptoms of depression as side effects of medication. In 60 public health centers across Slovenia a total of 422 patients with depression treated with paroxetine were included. After one week of treatment one quarter of patients reported adverse effects and 15% of these patients misinterpreted signs of depression and anxiety for adverse effects. These patients tend to be more anxious and more depressed at the beginning of treatment. Half of them could not accept the explanation of their misinterpretation. A total of 55% patients had additional questions about illness at the second visit and these patients were also more anxious and more depressed at the beginning of treatment.

Light chain deposition disease restricted to the brain: The first case report.

A 35-year-old white male with symptoms of paranoid schizophrenia was treated by psychiatrists for 13 years. During the final year, he developed severe dysphagia, reduced strength of the upper extremity muscles, and cognitive dysfunction. The patient died in his sleep. The only pathology found in coronal brain sections was ill-defined periventricular foci with prominent, firm vessels. Microscopy revealed abundant, hematoxylin and eosin-eosinophilic, periodic acid-Schiff-positive, thioflavin T-positive, and Congo red-negative deposits in the vessel walls, with hypoxic encephalopathy in the affected regions. Immunohistochemistry showed lambda light chains as the main component of the deposits. Ultrastructural analysis showed amorphous electron dense material in the vessel walls. Perivascular B-cell proliferation was present in the vicinity of affected areas. Polymerase chain reaction was applied for the assessment of B-cell clonality, revealing monoclonal rearrangement of the heavy chain Ig gene. Neither in the kidney nor in any other organ were deposits detected. This is the first case report of light chain deposition disease restricted to the brain.

A prospective, randomized comparison of semitendinosus and gracilis tendon versus patellar tendon autografts for anterior cruciate ligament reconstruction: five-year follow-up.

BACKGROUND: There are still controversies about graft selection for primary anterior cruciate ligament reconstruction. Prospective randomized long-term studies are needed to determine the differences between the materials. HYPOTHESIS: Five years after anterior cruciate ligament reconstruction, there is a difference between hamstring and patellar tendon grafts in development of degenerative knee joint disease. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: From June 1999 to March 2000, 64 patients were included in this prospective study. A single surgeon performed primary arthroscopically assisted anterior cruciate ligament reconstruction in an alternating sequence. In 32 patients, anterior cruciate ligament reconstruction was performed with hamstring tendon autograft, whereas in the other 32 patients, anterior cruciate ligament reconstruction was performed with patellar tendon autograft. RESULTS: At the 5-year follow-up, no statistically significant differences were seen with respect to the Lysholm score, clinical and KT-2000 arthrometer laxity testing, anterior knee pain, single-legged hop test, or International Knee Documentation Committee classification results; 23 patients (82%) in the hamstring tendon group and 23 patients (88%) in the patellar tendon group returned to their preinjury activity levels. Graft rupture occurred in 2 patients from the hamstring tendon group (7%) and in 2 patients from the patellar tendon group (8%). Grade B abnormal radiographic findings were seen in 50% (13/26) of patients in the patellar tendon group and in 17% (5/28) of patients in the hamstring tendon group (P = .012). CONCLUSION: Both hamstring and patellar tendon grafts provided good subjective outcomes and objective stability at 5 years. No significant differences in the rate of graft failure were identified. Patients with patellar tendon grafts had a greater prevalence of osteoarthritis at 5 years after surgery.

Increased Th1 and Th2 immune reactivity with relative Th2 dominance in patients with acute exacerbation of schizophrenia.

AIM: To determine concentration of T helper (Th(1)) cytokines and Th(2) cytokines in patients with acute exacerbation of schizophrenia and compare the cytokine profiles between subtypes of schizophrenia. METHOD: One hundred inpatients with acute exacerbation of schizophrenia and 34 matched healthy subjects from the same population without psychiatric history were included in the study. According to predominant symptom complexes the patients were divided into three subgroups: hallucinations and delusions (n=36); disorganized behavior (n=33), and primary, enduring negative or deficit symptoms (n=31). In vitro IFN-gamma and IL-4 secretion by peripheral blood mononuclear cells after stimulation with ionomycin and phorbol 12 myristate 13 acetate was measured by enzyme-linked immunosorbent assay (ELISA) tests. RESULTS: Significant increase in in vitro secretion of IFN-gamma (21,505 vs 14,915 pg/mL; P=0.037; independent samples t test) and IL-4 (32 vs 15 pg/mL; P<0.001) with a shift to the Th(2) (1,022 vs 1,432 pg/mL; P=0.005) immune response was observed in patients with schizophrenia compared to healthy controls. We found pronounced effects of age and age at first hospitalisation on the Th(1)/Th(2) immune balance (R(2)=0.068; P=0.037). There were no significant differences in in vitro secretion of IFN-gamma (P=0.734; one-way analysis of variance), IL-4 (P=0.485) and IFN-gamma/IL-4 ratio (P=0.293) between the subgroups of patients with schizophrenia. CONCLUSION: Our findings indicate a simultaneous increase of in vitro reactivity of both Th(1) and Th(2) arm of cell mediated immunity, with a relative predominance of Th(2) immunity in patients with acute exacerbation of schizophrenia.