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.

GaSb-based lasers with two-dimensional photonic crystal mirrors.

We present the realization of two-dimensional (2D) photonic crystals (PhCs) on the GaSb material system. An electron cyclotron resonance reactive ion etch process using Cl(2)/Ar allows the fabrication of PhCs covering air fill factors of f = 20%-50%, lattice periods of a = 400-500 nm and aspect ratios of 5:1. Quality and reflectivity of these structures are evaluated by incorporating the PhCs as high reflective back mirrors in GaSb-based ridge waveguide lasers with cavity lengths between 200 and 1100 µm with the front facet as cleaved. The shortest devices show remarkable threshold currents below 12 mA and efficiencies of 0.23 W A(-1), yielding a maximum output power of almost 19 mW, proving the applicability of the chosen approach to numerous further concepts based on 2D PhCs on the GaSb material system.

Discretely tunable single-mode lasers on GaSb using two-dimensional photonic crystal intracavity mirrors.

We report on single-mode emitting coupled cavity ridge waveguide lasers on the GaSb material system in the 2 µm spectral range using two-dimensional (2D) photonic crystals (PhCs). Eight rows of 2D PhCs lateral to the ridge waveguides act as intermediate mirrors and are used to create two coupled cavities. This leads to preferential emission at one single longitudinal mode in the emission spectrum with side mode suppression ratios of 30-35 dB. Monolithic integration of high reflectivity 2D PhC back mirrors allows the realization of cavity lengths as short as 300 µm with threshold currents as low as 18.5 mA while reaching output powers well above 18 mW. Under variation of driving current the lasers exhibit both discrete and continuous tuning behavior over a wide current range very well explicable by simulation of the sub-threshold spectra, rendering the devices especially interesting for multi-gas sensing by absorption spectroscopy.

High performance short period superlattice digital alloy InSb/Ga(x)In(1-x)Sb laser emitting at 1.9 µm.

For the first time, lasers with short period superlattice based quantum wells have successfully been fabricated and characterized on the (AlGaIn)(AsSb) material system. These new quantum wells are composed of alternating InSb/Ga(x)In(1-x)Sb layers with submonolayer thickness. Distributed-feedback lasers fabricated from the epitaxial layers emit in the wavelength range around 1.9 µm. Side mode suppression ratios over 35 dB and very low threshold currents of 23 mA were realized. The laser emission wavelength can be varied from 1.844 to 1.902 µm using grating periods between 255.0 and 263.8 nm.

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.

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.

Off-label use of antipsychotic drugs.

Despite the fact that most antipsychotics have only been formally evaluated for the treatment of schizophreniform disorder, schizophrenia, mania, and schizoaffective disorder (defined as "classical indications"), antipsychotics are widely used for the treatment of a broad range of symptoms and disorders. In this study, 173 patients who were having their prescriptions for antipsychotics filled at local pharmacies were interviewed. In 115 patients (66.5%), an antipsychotic was prescribed for off-label indications. Patients most often stated that they took antipsychotics as a tranquilizer or an anxiolytic. Neither gender, education, duration of treatment, nor efficacy of treatment showed an influence on the prescription practices for antipsychotics. In contrast, family status and side effects showed a significant influence. A classical indication was more often found in married and widowed patients than in unmarried or divorced ones. Patients in whom antipsychotics were prescribed for the treatment of schizophrenia, schizophreniform disorder, mania, or schizoaffective disorder experienced side effects more often than others. Age was also important for the indication of antipsychotics. Classical indications of antipsychotics were most often found in patients aged 30 to 49 years. In older patients (49-70 years), antipsychotics were almost exclusively used for off-label indications. In classical indications, clozapine was used more frequently (50%) than other antipsychotics. Melperone was primarily prescribed for off-label use.

Selection bias in clinical trials with antipsychotics.

Although the selection of patients is known to be a powerful factor affecting the results of clinical trials, little is known about recruitment issues. Many patients with schizophrenia who are screened for a clinical trial of an investigational antipsychotic are ultimately not included in the study. Therefore, the question arises of whether the results obtained by studying a selected group of patients are really representative of the general population of patients with schizophrenia. The authors studied possible reasons for selective sampling in 200 patients who were consecutively admitted to inpatient units of Innsbruck's Department of Psychiatry with a diagnosis of schizophreniform or schizophrenic disorder over a time period of 33 months. Apart from demographic data and a psychopathologic rating (using the Brief Psychiatric Rating Scale), the authors recorded whether or not a patient was included in a phase III study and whether or not those were not included would have theoretically been eligible for such a study. Twenty-seven patients were finally recruited for a clinical trial. These patients were younger, on average, had a more recent onset of illness, and had experienced fewer psychotic episodes in the past. A history of noncompliance with previous treatment and the refusal of consent were the most common reasons for not including theoretically eligible patients in a clinical trial.

Compliance with antipsychotic treatment.

OBJECTIVE: Despite the demonstrated efficacy of antipsychotics the relapse rate among patients with schizophrenia remains high. One major reason for this is non-compliance. In this article we review different factors influencing compliance and discuss possibilities to enhance compliance among schizophrenic patients. METHOD: This review is based on a systematic literature search in Medline. RESULTS: We summarize the four main factors (patient-, environment-, physician- and treatment-related) that influence compliance and discuss possible measures to enhance compliance. Next to many other variables discussed in more detail, it is crucial to ensure a positive doctor-patient relationship and to provide sufficient information about the benefit/risk ratio of the medication as well as about the illness itself to build up and sustain compliance. Significant others should be included into the therapeutic alliance whenever possible. CONCLUSION: Despite many published reports on compliance, it remains to be a problem of eminent clinical relevance. Clinicians must not underestimate it in order to optimize the treatment of patients with schizophrenia.

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.

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.

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.

[Compliance problems in treatment of schizophrenic patients]. / Compliance-Probleme bei der Behandlung schizophrener Patienten.

Compliance is the degree of adherence to an appropriate medical advise. Especially in longterm treatment, therapeutic success depends largely on patient compliance. In the treatment of schizophrenia with antipsychotic agents a non-compliance rate up to 80% is the reason for the difference between the relatively good outcome of controlled treatment studies and the bad results in clinical reality. 4 groups of variables can be identified, which influence compliant behaviour: patient-related factors, factors related to the patients environment, physician-related factors, and medication-related factors. Possibilities to ameliorate the compliance of schizophrenic patients during long-term therapy are discussed.

Long-term pharmacokinetics of clozapine.

BACKGROUND: Previous studies of clozapine pharmacokinetics have shown a wide intra- and inter-individual variability of plasma levels in patients on stable clozapine doses. We investigated dose-plasma level relationships and intra-individual variability of plasma levels during maintenance treatment with clozapine. METHOD: Forty-one patients on clozapine were followed for 26 weeks with repeated plasma level measurements and assessments of co-medication and clinical symptoms. In a second step, 15 patients on stable clozapine doses between treatment Weeks 12 and 52 were followed in the same way. Coefficient of variation was used as a parameter of plasma level deviation. RESULTS: Dose-plasma level correlations stayed significant from Week 6 to Week 26 (n = 41). The group of patients followed up to Week 52 showed a mean intra-individual coefficient of variation of 52.8% (s.d. = 20.6), and remained stable psychopathologically. CONCLUSIONS: Even though clozapine plasma levels may show a significant degree of variation, this is not necessarily reflected in a change in psychopathology.

Hepatotoxicity of clozapine.

Two hundred thirty-eight patients treated with either haloperidol or clozapine were investigated to shed more light on the incidence and severity of antipsychotic-induced liver enzyme increase. Serum glutamic-pyruvic transaminase (SGPT) increase was most frequently seen in both treatment groups. When analyzing the incidence rates for patients with increased liver enzyme values (serum glutamic-oxaloacetic transaminase, SGPT, gamma-glutamyl transpeptidase) that were higher than twice the upper limit of the normal range, clozapine-treated patients showed an SGPT increase (37.3%) significantly more frequently than patients treated with haloperidol (16.6%). Both patients with higher clozapine plasma levels and male patients were at a higher risk for an SGPT increase. At least 60% of the increase of the different enzymes remitted within the first 13 weeks of treatment. In general, the authors conclude that clozapine-induced liver enzyme elevation seems to be a common and mostly transient phenomenon.

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.

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.