Epidemiology and economic burden of fragility fractures in Austria.

Fragility fractures are a frequent and costly event. In Austria, 92,835 fragility fractures occurred in patients aged ≥ 50 years in 2018, accruing direct costs of > 157 million €. Due to demographic aging, the number of fragility fractures and their associated costs are expected to increase even further. INTRODUCTION: Fragility fractures are frequently associated with long hospital stays, loss of independence, and increased need for care in the elderly, with consequences often leading to premature death. The aim of this study was to estimate the number of fragility fractures and associated healthcare costs in Austria in 2018. METHODS: The number of in-patient cases with relevant ICD-10 diagnoses in all Austrian public hospitals was derived from discharge documentation of diagnoses and procedures covering all public hospitals in Austria. Fractures resulting from falls from standing height in patients aged ≥ 50 years were used as a proxy for fragility fractures, and the number of in-patient and out-patient cases was estimated. The direct costs of these cases were calculated using the average cost of the corresponding in-patient hospital stay and the average cost for the out-patient stay. RESULTS: The present study estimated the number of fragility fractures (pelvis, thoracic and lumbar vertebra, hip, humerus, rib, forearm, and tibia) for 2018 at 92,835 or just over half of all fractures in patients aged ≥ 50 years, corresponding to a prevalence of 2,600 per 100,000 inhabitants of this age group. A constant increase in the proportion of fragility fractures among all fractures was observed with increasing age in both men and women. These fractures amounted to direct costs of > 157 million €. CONCLUSION: Fragility fractures are a frequent and costly event in Austria. Due to the aging of the population, the number of fragility fractures and their associated costs is expected to increase even further.

Familial sinistrality and handedness in patients with first episode schizophrenia: the EUFEST study.

The population with schizophrenia is characterised by a leftward shift in handedness-sinistrality. However, findings are inconsistent in chronic patients, and familial sinistrality (FS), defined as the presence of left-handed close relatives, might contribute to the discrepancies. Therefore the aim of this study was to investigate the strength of manual lateralisation in patients with first episode schizophrenia, taking into account familial sinistrality. The Edinburgh Inventory (EI) allowed us to categorise 179 patients from the EUFEST study and 189 controls presenting "strong handedness" (SH: EI absolute value between ∣81∣ and ∣100∣) or "weak-handedness" (WH: EI value between -80 and +80). The nominal logistic regression did not show an FS effect, but a nearly significant interaction between illness and FS (p =.07). There were fewer participants without FS presenting SH among patients (99/151: 65.6%) than among controls (134/164: 81.7%, p =.001). In contrast, the number of participants with FS presenting SH was similar between controls (68%) and patients (75%, p =.57). The presence of left-handed relatives (FS + ) tended to reduce manual lateralisation, but only in controls. This supports the notion that reduced manual lateralisation in schizophrenia is related to the illness rather than to familial left-handedness.

1-W antimonide-based vertical external cavity surface emitting laser operating at 2-microm.

We report a high-power optically pumped semiconductor vertical external cavity surface emitting laser operating at 2-mum wavelength. The gain material consisted of 15 GaInSb quantum-wells placed within a three-lambda GaSb cavity and grown on the top of an 18-pairs AlAsSb/GaSb Bragg reflector. For thermal management we have used a transparent diamond heat spreader bonded on the top of the structure. When cooled down to 5 degrees C, the laser emitted up to 1 W of optical power in a nearly diffraction-limited Gaussian beam demonstrating the high potential of antimonide material for VECSEL fabrication.

Localized proton and phosphorus magnetic resonance spectroscopy following electroconvulsive therapy.

Animal studies show that cerebral lactate increases after electrically induced seizures. We investigated three adult psychiatric patients by means of localized proton and phosphorous magnetic resonance spectroscopy in order to evaluate if such effects can be observed after electroconvulsive therapy (ECT). None of the patients had changes in cerebral energy metabolism following ECT. Within the limitations of in-vivo spectroscopy in a clinical setting, our results suggest that if lactate production increases after ECT, this effect is either very short or increased perfusion causes an efficient efflux of cerebral lactate.

Sexual disturbances during clozapine and haloperidol treatment for schizophrenia.

OBJECTIVE: The aim of this study was to evaluate the frequency and course of sexual disturbances associated with clozapine and haloperidol and their potential influence on compliance with medication regimens in patients with schizophrenia. METHOD: The authors prospectively investigated 153 patients with schizophrenia who received clozapine (N = 100) or haloperidol (N = 53) in a drug monitoring program. RESULTS: The frequency of sexual disturbances was lower in female patients than in male patients. There was no statistically significant difference between the patients taking haloperidol and those taking clozapine in the frequency of these disturbances. Clozapine plasma levels had a significant effect on diminished sexual desire and functional disturbances in male patients. Functional disturbances and diminished sexual desire did not have any influence on compliance in patients taking either haloperidol or clozapine. CONCLUSIONS: There was no statistically significant difference between haloperidol and clozapine in regard to their propensity to induce sexual side effects.

Association of olanzapine-induced weight gain with an increase in body fat.

OBJECTIVE: The goal of this study was to explore the pathophysiology of weight gain during treatment with olanzapine for schizophrenia. METHOD: The authors used a prospective, controlled, open study comparing body weight, body mass index, and related biological measures in mentally and physically healthy volunteers and olanzapine-treated patients with schizophrenia. Weight, eating behavior, leptin serum levels, body mass index, and body composition were assessed over an 8-week observation period. RESULTS: A significant increase in body weight, leptin serum levels, and percentage of body fat was seen in patients treated with olanzapine, but the drug-free comparison group did not show any significant changes. The weight gain during antipsychotic treatment with olanzapine was mainly attributable to an increase in body fat; patients' lean body mass did not change. CONCLUSIONS: In addition to the original finding that an increase in body fat is mainly responsible for olanzapine-induced weight gain, these findings confirm results obtained in other studies showing increases in body weight and serum leptin levels during treatment with second-generation antipsychotics.

Drug treatment of schizophrenia in the 1990s. Achievements and future possibilities in optimising outcomes.

The current state of the art of the pharmacological treatment of schizophrenia, and a review of the latest findings in antipsychotic drug development are presented. A first step in optimising treatment is an increase in the awareness and implementation of existing treatment standards. The introduction of clozapine challenges the view that all antipsychotics are of similar efficacy; the drug has an established superiority over some of the traditional antipsychotics in treatment-resistant patients. Newer agents such as zotepine, risperidone, quetiapine, olanzapine and sertindole, which have a lower risk of producing extrapyramidal motor symptoms, have been developed in the wake of clozapine. While it is still common to switch nonresponding patients to an antipsychotic of a different chemical class, clozapine treatment remains the only strategy based on sound scientific evidence in these patients, although the novel antipsychotics give rise to hope. Alternatively, combination treatment with benzodiazepines, lithium or an anticonvulsant has been employed. If treatment with a depot antipsychotic is planned, it is advisable to start a patient on the oral form of the same drug in order to obtain dose requirements and tolerability information of the drug in that patient. Long term maintenance therapy is crucial and continuous monitoring for the development of adverse effects essential.

Clozapine-induced transient white blood count disorders.

BACKGROUND: The aim of the study was to shed more light on the incidence and course of clozapine-induced transient white blood count (WBC) disorders. METHOD: In an analysis of our clozapine drug monitoring program, we evaluated the data of 68 patients receiving clozapine for the first time. Incidence rates were calculated by actuarial life table analysis. The potential influence of sex, age, dose, and plasma level was evaluated using discriminant analysis. RESULTS: Two patients developed progressive neutropenia, leading to agranulocytosis in one case. We also found the following transient hematologic dysfunctions: neutropenia (22.0%), eosinophilia (61.7%), and leukocytosis (40.9%). One patient showed chronic leukocytosis. Additionally, minor changes in the number of lymphocytes, monocytes, and basophilic granulocytes were detected in the study population. CONCLUSION: Hematologic side effects are frequently induced by the atypical antipsychotic clozapine. Next to agranulocytosis, a progressive and potentially lethal hematologic adverse effect, most of the WBC disorders are transient and appear to be harmless.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment of clozapine-induced agranulocytosis: a case report.

BACKGROUND: Granulocytopenia and agranulocytosis are severe side effects of clozapine therapy. Even if these side effects are detected early and if clozapine is discontinued, patients suffering from agranulocytosis are extremely endangered by infectious diseases for up to 3 to 4 weeks until hematologic recovery. Therefore, any treatment that reduces this critical time span would decrease the risks of clozapine treatment. METHOD: The case of a patient in whom severe agranulocytosis developed after 7 weeks of clozapine treatment is presented. RESULTS: After clozapine discontinuation, treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF), a glycoprotein that has been shown to stimulate the proliferation of precursor cells in the bone marrow and their differentiation into granulocytes and macrophages, was initiated. Under GM-CSF treatment, total granulocyte count rose from 63/cu mm to a value greater than 1500/cu mm within 5 days without complications or major side effects. CONCLUSION: This case report suggests that treatment with GM-CSF may lower the risks associated with clozapine-induced agranulocytosis and therefore may indirectly improve the safety of clozapine therapy.

Effect of cannabis use on cognitive functions and driving ability.

BACKGROUND: Neither experimental nor epidemiologic approaches have so far given definitive answers to the question of the potential effect of cannabis on driving ability. METHOD: To shed more light on this topic, we conducted a placebo-controlled double-blind study including 60 healthy volunteers (a negative urine drug screening test was prerequisite). On the first day, baseline data were obtained from a physical examination and a psychological test battery for the investigation of visual and verbal memory as well as cognitive perceptual performance. On the second day, subjects received a regular cigarette or one containing 290 microg/kg body weight of tetrahydrocannabinol. Physical and psychological assessments were performed immediately (15 minutes) after subjects smoked their cigarettes. Twenty-four hours later, physical and psychological examinations were repeated. RESULTS AND CONCLUSION: Our results suggest that perceptual motor speed and accuracy, 2 very important parameters of driving ability, seem to be impaired immediately after cannabis consumption.

Clozapine dose in the United States and Europe: implications for therapeutic and adverse effects.

The report (1) provides an overview of clozapine doses used in trials conducted in Europe and the United States, (2) compares data on efficacy, and (3) compares side effects of clozapine from recent European and U.S. investigations. The reviewed European trials used a mean dose of 283.7 mg/day, while the mean dose in the U.S. studies was 444 mg/day. Even though the mean doses used in the United States are considerably higher than those used in Europe, the response rates for the two continents are strikingly similar. The main differences in a comparison of two samples evaluated in New York and Innsbruck were found in the prevalence of seizures (Innsbruck, 0%; United States, 7.1%) and confusion (Innsbruck, 0%; United States, 14%). Excitement was less prevalent in the U.S. study. The data presented appear to suggest that a lower dose of clozapine may be as effective as a higher dose in the management of treatment-resistant schizophrenic patients and may cause fewer side effects.

Extrapyramidal side effects of clozapine and haloperidol.

Neuroleptic-induced extrapyramidal side effects (EPS) were evaluated in 92 patients treated with clozapine for the first time and 59 patients treated with haloperidol followed in a drug monitoring program. Side effects were measured by the Columbia University Rating Scale, the Simpson Dyskinesia Scale and the Hillside Akathisia Scale. The cumulative incidence rate for tremor was found to be 24.4% in the clozapine group and 39.3% in the haloperidol group. This did not amount to a statistically significant group difference. Bradykinesia was observed in 21.8% of the patients treated with clozapine and in 47.7% of the patients of haloperidol (P = 0.011). In the clozapine group the akathisia incidence rate was 5.6%, whereas haloperidol patients showed a higher rate of 31.7% (P = 0.005). Our results show higher incidence rates of tremor and bradykinesia during clozapine treatment than previous studies. We conclude that clozapine is not entirely free of EPS, but they are usually less severe and of a different quality than side effects induced by typical antipsychotics.

Does eosinophilia predict clozapine induced neutropenia?

The atypical antipsychotic clozapine carries a high risk of inducing agranulocytosis. We attempted to investigate whether eosinophilia during clozapine treatment has predictive value for subsequent neutropenia/agranulocytosis. One hundred and seventy-seven patients were studied in a prospective naturalistic design using haloperidol as the reference compound. Clozapine was found to differ from haloperidol in respect to their influence on neutrophil granulocytes. In the clozapine group patients with eosinophilia showed a decrease in neutrophil count (less than 2000/mm3 neutrophil granulocytes) significantly more often than patients without eosinophilia.

EEG alterations in patients treated with clozapine in relation to plasma levels.

It is well known that psychotropic drugs can induce EEG alterations. Dose dependence seems established; however, there are no data concerning the impact of plasma levels. The authors investigated the influence of clozapine plasma levels on the frequency of EEG alterations. Data from 29 inpatients (18 male, 11 female, 31.7 +/- 10.2 years) receiving clozapine in a dose range between 25 and 600 mg were collected prospectively. There was no psychotropic or anticholinergic comedication. All patients had normal EEGs before taking clozapine. Fifteen patients showed pathological changes (group 2) and 14 no changes (group 1). Discriminant analysis showed that EEG changes are dependent on plasma levels (P = 0.0009, plasma levels in group 1 mean 81.6 ng/ml, +/- SD 64.6, in group 2 235.7 ng/ml, +/- 169.8). A total of 72.4% of the patients were correctly classified as having either pathological EEG changes or none by this analysis. Variables such as dose, age, sex, weight and duration of treatment were not statistically relevant. It can therefore be suggested that clozapine plasma levels are a valid indicator for the appearance of electrophysiological reactions.

The effect of ritanserin on treatment-resistant neuroleptic induced akathisia: case reports.

1. The authors report three cases of neuroleptic induced akathisia resistant to treatment with anticholinergics, benzodiazepines and betablockers. 2. All three patients were treated with Ritanserin 10 mg bid and improved rapidly and substantially. 3. Discontinuation of Ritanserin led to a recurrence of akathisia.

Risk factors for the development of neuroleptic induced akathisia.

Neuroleptic induced akathisia (NIA) is a common and distressing side effect of antipsychotic treatment. Incidence rates are reported to be between 25% and 75%, depending on criteria used for diagnosis. The results of our four week prospective naturalistic study are based on the assessment of 73 inpatients, which were started on antipsychotic medication in one of the inpatient units of the Department of Psychiatry. NIA was rated with the Hillside Akathisia Scale. Assuming that both, objective as well subjective phenomena are necessary for a valid diagnosis of NIA, we calculated an incidence rate of 22.4%. 75% of all NIA cases occurred within the first three days of antipsychotic treatment. When attempting to determine risk factors for the development of NIA, we found a significant influence of dose increase in the first days of treatment.

Weight gain induced by clozapine.

Patients were investigated to gain more insight into the incidence and time course of clozapine induced weight gain (n = 81) and to compare weight gain in patients treated with clozapine (n = 31) with that of patients treated with standard antipsychotics (haloperidol, n = 11). 35.7% of the patients treated with clozapine gained weight according to our definition. If patients gained weight on clozapine this side effect was apparent within the first 12 weeks of treatment. Deviation from normal body weight at the beginning of treatment showed a significant influence on weight gain. Sex, severity of illness, comedication, mean clozapine dose and degree of improvement did not show an influence on this side effect. Weight increase was significantly higher in patients treated with clozapine than in patients treated with haloperidol.

Assessment of the alcohol withdrawal syndrome--validity and reliability of the translated and modified Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-A).

The alcohol withdrawal syndrome is a common phenomenon in psychiatric hospital care. Not only treatment strategies, but also the evaluation of the syndrome, are discussed controversially. The most widely used instrument is the Clinical Institute Withdrawal Assessment-Alcohol (CIWA-A) and the succeeding CIWA-Ar. We modified the CIWA-A and translated it into German. Validity and reliability of the modified and translated scale were analysed by several psychological tests as well as different somatic measures in 31 patients. The German version appears to be a valid and reliable instrument for the assessment of alcohol withdrawal syndrome useful for clinical routine as well as treatment trials.

Brain death and transcranial Doppler: experience in 130 cases of brain dead patients.

BACKGROUND AND PURPOSE: Diagnosis of brain death requires confirmation of the clinical diagnosis by appropriate tests, generally electroencephalography (EEG) and angiography. The diagnostic limitations or logistical problems inherent to these tests indicate the need to develop other more appropriate methods. The results obtained with transcranial Doppler (TCD) led us to conduct this prospective study of TCD recordings in brain dead patients. METHODS: 130 patients, aged 2-88 years were diagnosed as brain dead between July 1987 and June 1993. Clinical criteria were confirmed in all cases by EEG (n=88) and or angiography (n=64). Intracranial anterior circulation was insonated via temporal windows or, when impossible, via a transorbital approach. The posterior circulation was studied only in more recent patients. Examinations were made as soon as possible after brain death diagnosis and repeated for about 30 min. Vital parameters and treatments were taken into account. RESULTS: There was only one false negative result, in a patient with an extended skull defect, who retained TCD and angiographic intracranial circulation despite confirmed irreversible brain death. All other patients displayed typical ultrasonic patterns of cerebral circulation arrest: an oscillating signal (n= 190, 73%), a systolic spike (n=62, 24%) or a unilateral absence of signal (n=5). Despite a total correlation for positive diagnosis, TCD and angiography may differ as to the level of circulation arrest. TCD is useful for patients under sedative drugs. No false positive result was encountered but we were unable to insonate any intracranial artery in 5 patients. CONCLUSION: Data from previous studies and the results of this study indicate that TCD is a very sensitive and safe method for diagnosing cerebral circulatory arrest. TCD may be used as a confirmatory test alongside EEG and angiography. TCD is more widely applicable than EEG and may be earlier and safer than angiography.

[Anesthesia and intensive care of subarachnoid hemorrhage. A survey on practice in 32 centres]. / Anesthésie-réanimation de l'hémorragie sous-arachnoïdienne. Enquête sur les pratiques de 32 centres.

OBJECTIVE: To assess the current practices in anaesthesia and intensive care in patients experiencing subarachnoid haemorrhage (SAH). STUDY DESIGN: Analysis of questionnaire sent to the members of the French speaking Association of neuroanesthesia and intensive care. METHODS: The survey, performed in the summer of 1995, included questions on the composition of the neuroanesthesia team, anaesthesia, as well as medical and surgical treatments. RESULTS: Twenty-nine French and three non French centers answered the questionnaire. In 14 centers, more than 60 SAH had been treated in the previous year. Angiography was performed under sedation with a benzodiazepine associated with an opioid (54%). Criteria for choosing an endovascular approach were the site of the aneurysm (81%), its neck size (42%) and the underlying disease (42%). Anaesthesia was induced with either propofol (60%) or thiopentone (40%) associated with an opioid and a muscle relaxant. It was maintained with either isoflurane (59%) or propofol (41%). Nitrous oxide was often associated (62%). During anaesthesia, nimodipine (84%), mannitol (69%), anticonvulsants (47%), dopamine (31%) and lidocaine (9%) were also administered. Postoperatively, nimodipine was administered for prophylaxis of vasospasm (97%) and transcranial Doppler was employed to diagnose vasospasm (50%). Other techniques of care included hypervolaemia (89%), controlled arterial hypertension (36%) and haemodilution (36%).