Opioid maintenance therapy in Switzerland: an overview of the Swiss IMPROVE study.

BACKGROUND/AIMS: Switzerland's drug policy model has always been unique and progressive, but there is a need to reassess this system in a rapidly changing world. The IMPROVE study was conducted to gain understanding of the attitudes and beliefs towards opioid maintenance therapy (OMT) in Switzerland with regards to quality and access to treatment. To obtain a "real-world" view on OMT, the study approached its goals from two different angles: from the perspectives of the OMT patients and of the physicians who treat patients with maintenance therapy. The IMPROVE study collected a large body of data on OMT in Switzerland. This paper presents a small subset of the dataset, focusing on the research design and methodology, the profile of the participants and the responses to several key questions addressed by the questionnaires. METHODS: IMPROVE was an observational, questionnaire-based cross-sectional study on OMT conducted in Switzerland. Respondents consisted of OMT patients and treating physicians from various regions of the country. Data were collected using questionnaires in German and French. Physicians were interviewed by phone with a computer-based questionnaire. Patients self-completed a paper-based questionnaire at the physicians' offices or OMT treatment centres. RESULTS: A total of 200 physicians and 207 patients participated in the study. Liquid methadone and methadone tablets or capsules were the medications most commonly prescribed by physicians (60% and 20% of patient load, respectively) whereas buprenorphine use was less frequent. Patients (88%) and physicians (83%) were generally satisfied with the OMT currently offered. The current political framework and lack of training or information were cited as determining factors that deter physicians from engaging in OMT. About 31% of OMT physicians interviewed were ≥60 years old, indicating an ageing population. Diversion and misuse were considered a significant problem in Switzerland by 45% of the physicians. CONCLUSION: The subset of IMPROVE data presented gives a present-day, real-life overview of the OMT landscape in Switzerland. It represents a valuable resource for policy makers, key opinion leaders and drug addiction researchers and will be a useful basis for improving the current Swiss OMT model.

[Multicentric evaluation of a self-screening questionnaire for occupational bladder cancer]. / Évaluation multicentrique d'un auto-questionnaire de dépistage des cancers de vessie d'origine professionnelle.

OBJECTIVE: Evaluate a self-screening questionnaire for bladder cancer of occupational origin and analyse an influence of exposure to a carcinogen bladder tumor on prognosis. PATIENTS AND METHODS: Five hundred and thirty-one patients followed, between 2005 and 2010, for bladder cancer in two university centers have received a self-screening questionnaire derived from questionnaire KVP 08. Patients who responded positively to at least one of the items were considered to have a self-screening questionnaire "positive". Patients were finally invited to take an appointment for consultation in occupational pathology. RESULTS: The response rate to self-screening questionnaire was 39.9% (212/531). It was "positive" in 82 cases (38.7%). Among the 82 patients with a self-screening questionnaire "positive", 46 patients consulted in occupational pathology (56%). Occupational exposure to a bladder carcinogen was documented in 91.3% of cases. Among the 22 patients who consulted in occupational pathology with a self-screening questionnaire "negative", an occupational exposure to a bladder carcinogen was documented in 13.6% of cases. The sensibility of the self-screening questionnaire was 91.3%, the specificity 86.4% and the accuracy 89.7%. The relative risk to have an occupational exposure if the self-screening questionnaire was "positive" was 6.69. The analysis of groups "positive" versus "negative" does not reveal any statistically significant difference in terms of tumor aggressiveness and disease-free survival. CONCLUSION: The self-screening questionnaire was considered relevant with good reliability for detection of occupational exposure to a bladder carcinogen.

Effects of secretin on extracellular amino acid concentrations in rat hippocampus.

In 1998, Horvath et al. (1998) observed a marked improvement in speech, eye contact, and attention in autistic children five weeks after treatment with secretin, which ocurred in the course of an endoscopic investigation. Since autism is hypothesized to be a hypoglutamatergic disorder we investigated the in vivo effects of secretin on extracellular amino acids in the rat brain. Studies were carried out on freely moving rats with microdialysis probes in the hippocampus. Amino acids were examined using tandem mass spectroscopy and HPLC/fluorometric detection. Following secretin injection (8.7 microg/kg i.p.), considerable increases in microdialysate glutamate and gamma-aminobutyric acid (GABA) levels were observed; other amino acids were not affected. The observed increased microdialysate concentrations of glutamate and GABA following secretin application may explain the results of the Horvath study.

Practice-based research: lessons from community pharmacist participants.

We designed this project to determine community pharmacists' opinions regarding the challenges and motivations of their recent participation in a pharmacy practice-based research study At the conclusion of a randomized, multicenter study, 87 community pharmacist-investigators were sent a questionnaire that explored four areas: motivating factors to participate, barriers to participation, communication tools used by study coordinators, and design issues for future studies. Fifty-eight (67%) completed questionnaires were returned. Key factors motivating participation in the study were desire to improve the profession and opportunity to learn. Time was the greatest barrier to participation. Pharmacy practice-based research has two distinct advantages. First, it translates clinical knowledge into direct application in the community. Second, it provides needed data to demonstrate the value of enhanced pharmacy practice. Thorough understanding of pharmacists' opinions is necessary to optimize the design of future studies.

Quality of life in head and neck cancer.

Because treatments for patients with cancer of the head and neck can have major impact on physical, social, and psychological function, the collection of quality of life (QOL) data in this group of patients is critical for our specialty. The University of Washington Quality of Life data have been collected and analyzed on three subsets of cancer patients. Information learned from these patients is summarized and strategies for future projects are outlined.

Quality of life in patients with head and neck cancer: lessons learned from 549 prospectively evaluated patients.

OBJECTIVES: To summarize our quality-of-life (QOL) research findings for patients with head and neck cancer, to suggest areas for future productive QOL research, and to discuss how to undertake QOL studies in a cost-effective manner. DESIGN: Review of previously published analyses of advanced larynx cancer, advanced oropharynx cancer, and neck-dissection cases and current data from the complete set of patients. PATIENTS: From January 1, 1993, through December 31, 1998, data on 549 patients were entered in our head and neck database. Of these patients, 364 met additional criteria for histologic findings (squamous cell carcinoma) and the restriction of their cancer to 4 major anatomical sites (oral, oropharynx, hypopharynx, or larynx). Of these, 339 patients were more than 1 year beyond initial treatment. Complete baseline TNM staging and QOL data were obtained for 260 of these patients, of whom 210 presented with an untreated first primary tumor (index cases) to the University of Washington, Seattle. INTERVENTION: Pretreatment QOL was assessed with an interviewer-supervised self-administered questionnaire. Subsequent self-administered tests were completed at 3, 6, 12, 24, and 36 months. Other data collected on each patient included cancer site, stage, treatment, histologic findings, type of surgical reconstruction, and current disease and vital status. RESULTS/CONCLUSIONS: It is difficult to achieve "statistically significant" results in a single-institution setting. The "composite" QOL score may not be a sufficiently sensitive tool. Analysis of separate domains may be more effective.

Genetic fingerprinting of grape plant (Vitis vinifera) using random amplified polymorphic DNA (RAPD) analysis and dynamic size-sieving capillary electrophoresis.

Dynamic size-sieving capillary electrophoresis with laser-induced fluorescence detection (DSCE-LIF) was combined with random amplified polymorphic DNA (RAPD) analysis to demonstrate the feasibility of the genetic analysis of grape plant varieties and clones within a variety. Parameters of the genomic DNA extraction process, as well as those of the RAPD analysis, were optimized specifically for this application. Polymorphic DNA fragments were generated for four different grape plant varieties including Cabernet Franc, Cabernet Sauvignon, Merlot, and Chardonnay. Relative to slab gel electrophoresis (SGE) with ethidium bromide staining, DSCE-LIF provided superior separation efficiency and detection limits in the analysis of DNA polymorphic bands. Optimal DSCE-LIF analyses were achieved using a 10-fold RAPD sample dilution, hydrodynamic sample injection, and 100 ng/mL of YO-PRO-1 DNA intercalator in the dynamic size-sieving buffer solution. In addition, the reproducibility of both the DSCE-LIF and RAPD analyses were demonstrated.

Impact of neck dissection on quality of life.

OBJECTIVES: For decades, the gold standard for treatment of cervical metastasis was radical neck dissection (RND). Current oncologic philosophy allows for treatment of appropriately staged neck disease with modified radical neck dissection (MRND) or selective neck dissection (SND). The purposes of this study were to determine the impact of various forms of neck dissection on patients' quality of life (QOL) and to evaluate the responsiveness of the University of Washington (UW) QOL shoulder domain. STUDY DESIGN: Prospective accumulation of QOL data from patients treated for head and neck cancer at UW. METHODS: Eighty-four patients were identified from the UW QOL registry who had undergone neck dissection and had completed pretreatment and posttreatment QOL questionnaires at 6 and 12 months. RESULTS: Compared with pretreatment scores, the MRND and RND groups reported worse shoulder function at 6 and 12 months (P<.0005). The MRND group reported greater shoulder disability at 6 months compared with the SND group (P = .002), but by 12 months, there was no difference between the two groups. Shoulder function for the RND group was worse than the SND group at 6 and 12 months (P = .004). There was a trend toward decreased pain after treatment in the SND and MRND groups. There were no significant differences in subjective appearance, activity, recreation, chewing, swallowing, or speech in the three groups after treatment. CONCLUSIONS: Consistent with findings of published functional studies, this study confirmed that the three forms of neck dissection affect patients' QOL differently. This study demonstrates that the UW QOL shoulder domain is a responsive instrument in assessing the effect of neck dissection on shoulder function.

Review of recent clinical studies with olanzapine.

Olanzapine is a novel antipsychotic agent displaying a unique and pleotrophic pharmacology, which distinguishes it from other existing treatments. Clinical investigations employing olanzapine have demonstrated a number of potential therapeutic advantages in reference not only to placebo but also to contemporary drug standards in the management of psychosis. This paper reviews data on the pharmacokinetics, efficacy and safety of olanzapine, its benefits for quality of life, and economic aspects to assist clinicians in determining where they can usefully employ it.

Vertebral development and amphibian evolution.

Amphibians provide an unparalleled opportunity to integrate studies of development and evolution through the investigation of the fossil record of larval stages. The pattern of vertebral development in modern frogs strongly resembles that of Paleozoic labyrinthodonts in the great delay in the ossification of the vertebrae, with the centra forming much later than the neural arches. Slow ossification of the trunk vertebrae in frogs and the absence of ossification in the tail facilitate the rapid loss of the tail during metamorphosis, and may reflect retention of the pattern in their specific Paleozoic ancestors. Salamanders and caecilians ossify their centra at a much earlier stage than frogs, which resembles the condition in Paleozoic lepospondyls. The clearly distinct patterns and rates of vertebral development may indicate phylogenetic separation between the ultimate ancestors of frogs and those of salamanders and caecilians within the early radiation of ancestral tetrapods. This divergence may date from the Lower Carboniferous. Comparison with the molecular regulation of vertebral development described in modern mammals and birds suggests that the rapid chondrification of the centra in salamanders relative to that of frogs may result from the earlier migration of sclerotomal cells expressing Pax1 to the area surrounding the notochord.

Transforming growth factor alpha with insulin stimulates cell proliferation in vivo in adult rat vestibular sensory epithelium.

Hair cells, the sensory receptors of the mammalian inner ear, have long been thought to be produced only during embryogenesis, and postnatal hair cell loss is considered to be irreversible and is associated with permanent hearing and balance deficits. Little is known about the factors that regulate hair cell genesis and differentiation. The mitogenic effects of insulin and transforming growth factor alpha (TGFalpha) were assayed in vivo in normal and drug-damaged rat inner ear. Tritiated thymidine and autoradiographic techniques were used to identify cells synthesizing DNA. Simultaneous infusion of TGFalpha and insulin directly into the inner ear of adult rats stimulated DNA synthesis in the vestibular sensory receptor epithelium. New supporting cells and putative new hair cells were produced. Infusion of insulin alone or TGFalpha alone failed to stimulate significant DNA synthesis. These results suggest that exogenous growth factors may have utility for therapeutic treatment of hearing and balance disorders in vivo.

Transforming growth factor-alpha with insulin induces proliferation in rat utricular extrasensory epithelia.

Hair cell loss in the human inner ear leads to sensorineural hearing loss and vestibular dysfunction. Recent studies suggest that exogenous addition of growth factors, for example, transforming growth factor-alpha with insulin, may stimulate the production of new supporting cells and hair cells in the mature mammalian vestibular sensory epithelium. Before any growth factor can be seriously considered for the treatment of clinical problems related to hair cell loss, its effects on the extrasensory epithelia must also be fully explored. The aim of this study was to determine whether transforming growth factor-alpha and insulin stimulate cell proliferation in rodent vestibular extrasensory epithelia. The cell proliferation marker, tritiated thymidine, was infused along with transforming growth factor-alpha, insulin, or transforming growth factor-alpha plus insulin into the inner ears of adult rats via osmotic pumps. Effects of the test agents were assessed on normal and drug-damaged utricles. Drug damage was produced by delivering gentamicin directly into the inner ear before the infusion of test agent. Animals were killed 4 or 10 days after pump placement. Utricles were sectioned, processed for autoradiography, and examined for labeled cells within the extrasensory epithelia. In normal animals, transforming growth factor-alpha plus insulin stimulated DNA synthesis in all regions of the extrasensory epithelia, suggesting that these agents are mitogenic for these tissues.

Cochlear pathology induced by aminoglycoside ototoxicity during postnatal maturation in cats.

Cochlear pathology resulting from neonatal administration of the aminoglycoside antibiotic, neomycin sulfate, was studied in young kittens at 15-24 days postnatal. Hearing thresholds showed severe to profound hearing loss in all but one animal. Scanning electron microscopy demonstrated that initial hair cell degeneration occurred in the extreme base (hook region) of the cochlea and sequentially progressed to the basal, middle, then the apical coil of the cochlea. The first row of outer hair cells degenerated first, followed by row 2, then row 3; the last cells to degenerate in a given region were the inner hair cells. This pattern of hair cell degeneration is similar to that seen in adults with neomycin ototoxicity. In contrast, the spiral ganglion exhibited a different pattern of degeneration with initial cell loss occurring in the middle of the cochlea, about 40-60% from the base (approximately 2.8-8 kHz). Thus, neuronal degeneration apparently is not secondary to sensory cell loss, but rather comprises an independent process in these neonatal animals. Taken together, the findings suggest that the spiral ganglion cell loss in the middle cochlear turn results from increased aminoglycoside sensitivity associated with an earlier initial onset of function in these neurons as compared to other cochlear regions.

Double-blind comparison of olanzapine versus risperidone in the treatment of schizophrenia and other psychotic disorders.

Olanzapine and risperidone, both second-generation antipsychotic agents, represent two different pharmacologic strategies. Although they share some in vitro properties, they differ by virtue of their chemical structure, spectrum of receptor binding affinities, animal neuropharmacology, pharmacokinetics, and in vivo neuroimaging profile. Based on such differences, it was hypothesized that the two compounds would show distinct safety and/or efficacy characteristics. To test this hypothesis, an international, multicenter, double-blind, parallel-group, 28-week prospective study was conducted with 339 patients who met DSM-IV criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. Results of the study indicated that both olanzapine and risperidone were safe and effective in the management of psychotic symptoms. However, olanzapine demonstrated significantly greater efficacy in negative symptoms (Scale for Assessment of Negative Symptoms summary score), as well as overall response rate (> or = 40% decrease in the Positive and Negative Syndrome Scale total score). Furthermore, a statistically significantly greater proportion of the olanzapine-treated than risperidone-treated patients maintained their response at 28 weeks based on Kaplan-Meier survival curves. The incidence of extrapyramidal side effects, hyperprolactinemia, and sexual dysfunction was statistically significantly lower in olanzapine-treated than risperidone-treated patients. In addition, statistically significantly fewer adverse events were reported by olanzapine-treated patients than by their risperidone-treated counterparts. Thus, the differential preclinical profiles of these two drugs were also evident in a controlled, clinical investigation. Olanzapine seemed to have a risk-versus-benefit advantage.

Epidemic oro-facial Kaposi's sarcoma (eKS)--report on 124 cases.

Oro-facial epidemic Kaposi's sarcoma (eKS) was observed in 124 patients (123 homo-/bisexual men, average age 37.9 years, and one 35-year-old transsexual patient). Average survival time was 1 year 9 months (range: 3 months 4 years 6 months). 57.3% of the patients had died. The hard and/or soft palate, gingiva and tongue were most frequently affected, with falling frequency within these locations. Oral manifestations of eKS appear to be common; treatment modalities must be optimised.

Impairment of cranio-facial nerves due to AIDS. Report of 2 cases.

2 cases of disorders of craniofacial nerves resulting from progressive multifocal leucoencephalopathy are described. Clinical symptoms occurred as facial paralysis, hypaesthesia, hemianopsia and deafness. In both patients, the impairment of the central nervous system (CNS) preceded indicative AIDS symptoms. Both patients died about 3 months after the first CNS symptoms had been diagnosed. Clinical and neurohistopathological findings as well as differential diagnoses are discussed.