Adverse effects associated with high-dose olanzapine therapy in patients admitted to inpatient psychiatric care.

CONTEXT: In 2012, Danish psychiatrist raised concerns regarding the use of high-dose olanzapine in the treatment of patients. The present study was part of an audit carried out by the Mental Health Services of the Capitol Region of Denmark regarding this topic. Objective. To assess the potential risks associated with high-dose olanzapine treatment (> 40 mg daily) in inpatient psychiatric units. METHODS: The study was an observational case series based on review of patient charts. The main inclusion criterion was treatment with at least one daily dose > 40 mg olanzapine during the index admission in the period between 1st of January and 15th of March 2012. Six additional criteria were applied in order to target the subgroup of patients most likely to have experienced an adverse event due to treatment with olanzapine. The physician order entry system and the central patient register containing patient specific information about diagnoses and treatments were used for identification of study population. RESULTS: The 91 patients included in the study received maximum daily doses of olanzapine ranging from 45 to 160 mg and in 25% of patients, the total antipsychotic load exceeded 2000 mg of chlorpromazine equivalents. Extrapyramidal symptoms and sedation were the most frequent adverse events with frequencies of 27% and 25%, respectively. Furthermore, other well-known adverse events such as weight gain (14%), hypotension (2%), neuroleptic malignant syndrome (2%) and corrected QT-interval (QTc) prolongation (1%) were also observed in some patients. Five patients died and in two of these cases, olanzapine was concluded to be a possible contributing cause of death. CONCLUSION: Increased frequency of extrapyramidal symptoms and sedation as well as severe toxicity was observed in patients treated with up to 160 mg olanzapine per day. In order to prevent harmful outcomes, the clinicians should be ready to act appropriately if toxic effects of olanzapine occur. Treatment cessation should be immediate if serious adverse events such as neuroleptic malignant syndrome arise.

Utility and adoption of CYP2D6 and CYP2C19 genotyping and its translation into psychiatric clinical practice.

OBJECTIVE: To describe clinical utility and adoption of routinely offered CYP2D6 and CYP2C19 genotyping (CYP test) in daily clinical practice of a psychiatric centre. METHOD: We described psychiatrists translations of CYP test results in patients with genotypes indicating poor or ultrarapid metabolizer status and treated with at least one CYP-dependent drug based on a retrospective review of medical records. Complementary, we used ethnographic participant observation and qualitative interviews to identify the barriers and incentives for the use of CYP test results. RESULTS: The cohort study included 101 of 1932 cases genotyped between 2003 and 2009. In 53 of 101 cases, test results were addressed in medical records. The most frequent response was to monitor drug concentrations (23 cases), observe for adverse events (18 cases) and adjust dosage (13 cases). In 33 of 101 cases, results were mentioned in the discharge letter. The ethnographic study indicated a poor adoption of the CYP test in clinical praxis. Test results were lost in workflows and knowledge transfer between laboratory and clinician and were absent from clinical routines, treatment conferences and educational fora. CONCLUSION: The CYP test has not gained foothold in clinical practice, and its potential clinical benefits are not utilized.

Decreasing candidaemia rate in abdominal surgery patients after introduction of fluconazole prophylaxis*.

Although abdominal surgery is an established risk factor for invasive candidiasis, the precise role of antifungal prophylaxis in these patients is not agreed upon. In 2007, fluconazole was added to the prophylactic antibiotic treatment for patients with gastrointestinal tract perforations or reoperation after colorectal surgery in two university hospitals in Copenhagen. Changes in candidaemia rates associated with this intervention were examined and potential interfering factors evaluated. Rates and clinical characteristics of candidaemias and other blood stream infections (BSIs) in abdominal surgery patients were compared before (1 January 2006 to 30 June 2007) and after the intervention (1 January 2008 to 30 June 2009). The departments' activity was assessed by number of bed-days, admissions and surgical procedures, and the consumption of antifungals was analysed. The candidaemia rate decreased from 1.5/1000 admissions in the pre-intervention to 0.3/1000 admissions in the post-intervention period (p 0.002). Numbers of BSIs and bed-days remained stable, and numbers of admissions and surgical procedures performed increased during the study period. Fluconazole consumption in the two abdominal surgery departments increased from 4.6 to 12.2 defined daily doses per 100 bed-days (p <0.001), and 3.2 to 5.0 (p 0.01), respectively, but remained unchanged in the intensive care units. We could not detect any increase in fluconazole-resistant strains (14/29 pre- and 2/7 post-intervention, p 0.43). The introduction of fluconazole prophylaxis was followed by a significantly decreased candidaemia rate. However, the observational study design does not allow conclusions regarding causality. No increase in resistance was detected, but follow-up was short and continuing surveillance is needed.

Medication history on internal medicine wards: assessment of extra information collected from second drug interviews and GP lists.

PURPOSE: To assess the extra information about patients' pre-admission medication that second drug interviews and general practitioners' (GP) drug lists add to routine medication histories. METHODS: The medication histories of 81 patients from two medicine wards were compared with information collected from second interviews and GP drug lists. A panel of clinicians assessed the potential clinical impact of any discrepancies. RESULTS: In nine cases (11% CI: 6-20%) the medication history, the second interview and the GP lists were identical. The interviews revealed extra information about 54 prescription drugs and 72 over-the-counter drugs (OTCs) in 56 (69% CI: 58-78%) cases. The GP lists added 74 prescription drugs and 26 OTCs to the medication histories in 57 (70% CI: 60-79%) cases. Discrepancies were not associated with age, gender or number of drugs in medication history. In 18% (CI: 10-30%) of the cases, the specialist panel ascribed potential clinical problems to missing drug information. CONCLUSIONS: Second interviews and GP lists reveal extra information about pre-admission medication in two-thirds of cases. Both procedures should be routinely performed to compile a more comprehensive basis for drug prescribing. This approach may mend the course of roughly one in five patients.

Implementing a new drug record system: a qualitative study of difficulties perceived by physicians and nurses.

OBJECTIVES: To identify organisational difficulties faced by physicians and nurses when using drug prescribing sheets for recording both drug prescriptions and drug administration. DESIGN: Qualitative interview study. SETTING: Two general internal medicine wards. PARTICIPANTS: Seven physicians and eight nurses. MAIN OUTCOME MEASURES: Difficulties explicitly identified by the participants during the interviews. RESULTS: The implementation of procedures conflicted with existing structure, culture, and routines. Insufficient competence within the system to use the drug prescribing sheets created resistance and made people down the line create their own interpretations and solutions to the problems they faced. A total of nine problems were identified: (1) insufficient knowledge and uncertainty about procedures, (2) ignorance of sources of error, (3) unclear responsibilities, (4) low community spirit, (5) insufficient communication, (6) clinician autonomy and low acceptance of change, (7) strong professional identity, (8) low priority task, and (9) logistical problems. CONCLUSIONS: Unawareness of procedures, insufficient dissemination of knowledge, and insufficient cooperation and skepticism among those who put drug handling into practice is likely to have an impact on the quality of health care. The identification of these obstacles may help managers to improve the quality of the drug handling process on internal medicine wards and make it possible to select a framework for changing the clinical behaviour of doctors and nurses.

[Treatment of tinnitus with low-intensity laser]. / Behandling af tinnitus med lavenergi-laser.

UNLABELLED: This study evaluated the effect of low-power laser in the treatment of tinnitus in a randomized, prospective, double-blind, placebo-controlled trial. The active laser applied 50 mW (cw, 830 nm) over a period of 10 minutes per session. Forty-nine patients were included. The main outcome was measured using psychoacoustical match of tinnitus loudness, Visual Analog Scale (VAS) ratings of subjective loudness, annoyance and attention involved, scores on tinnitus-specific questionnaires, and a number of psychosocial questionnaires. Only few subjects (18%) experienced subjective improvement. There were no statistically significant differences between the effects of the active laser and placebo treatments. CONCLUSION: Low-power laser treatment is not indicated in the treatment of tinnitus. Reports of significant benefits of this treatment in previous studies may be explained by the placebo effect.

Reliability and validity of a Danish adaptation of the Tinnitus Handicap Inventory.

The objective of this study was to determine the reliability and validity of a Danish translation of the Tinnitus Handicap Inventory (THI), a self-report measure of perceived tinnitus handicap. The Danish version of the THI was administered to 50 patients reporting tinnitus as their primary complaint or secondary to hearing loss. Construct validity was assessed using tinnitus symptom rating scales, the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI), the Tinnitus Coping Style Questionnaire (TCSQ), the Eysenck Personality Questionnaire (EPQ), and perceived tinnitus loudness and pitch. The Danish translation of the THI and its subscales showed good internal consistency reliabilities (c = 0.93 to alpha = 0.74) comparable to those of the original version. High to moderate correlations were observed between THI and psychological distress, tinnitus symptom ratings, neuroticism and maladaptive tinnitus coping. A confirmatory factor analysis failed to validate the three subscales of THI, and high intercorrelations found between the subscales question whether they represent three distinct factors. The results suggest that the Danish THI-Total scale may be a reliable and valid measure of general tinnitus related distress that can be used in a clinical setting to quantify the impact of tinnitus on daily living.

The low-power laser in the treatment of tinnitus.

The purpose of this study was to evaluate the low-power laser on the treatment of tinnitus. In a randomized, prospective, double-blind, placebo-controlled trial, either active or placebo low-power laser irradiation was given through the external acoustic meatus of the affected ear towards the cochlea. The active laser applied 50 mW (cw, 830 nm) over a period of 10 min per session. Forty-nine patients with severe, chronic uni- or bilateral tinnitus were studied. The main outcome was measured using psychoacoustical match of tinnitus loudness and pitch, Visual Analogue Scale (VAS) ratings of subjective loudness, annoyance and attention involved, scores on the Tinnitus Handicap Inventory (THI), the Tinnitus Coping Style Questionnaire (TCSQ), and a number of psychosocial questionnaires. The results showed only moderate (18%) subjective improvement with no statistically significant differences between the effects of the active laser and placebo treatments. Also, there were no statistically significant differences in prepost measurements of tinnitus loudness, VAS scores, THI scores, or TCSQ scores for patients treated with active laser compared with those treated with placebo. We conclude that low-power laser treatment is not indicated in the treatment of tinnitus. Reports of significant benefits of this treatment in previous, mostly uncontrolled or single-blinded studies may be explained by the placebo effect.

[Reliability of death certificates. The reproducibility of the recorded causes of death in patients admitted to departments of internal medicine]. / Pålideligheden af dødsattester. Reproducerbarheden ved udfyldelsen af dødsattestens diagnoser på patienter indlagt på medicinsk afdeling.

The aim of the study was to assess the reproducibility when different doctors fill in diagnoses on death certificates. Records from 40 patients who had died in 1994 during admission to a medical hospital department in Denmark were selected at random. Ten doctors filled in a death certificate for each patient (without knowledge of autopsy findings and results of examinations received after the patient's death). The agreement between the diagnoses was assessed using a rating scale with seven categories. Afterwards the 400 death certificates were mixed and coded by the Medicostatistical Section of the Danish National Board of Health. The diagnoses made by the ten doctors showed insignificant discrepancies in ten cases, larger discrepancies were found in eight cases and large discrepancies in 19 cases. In three cases the patient had died suddenly and little information was available. The coding was standardized at the Danish National Board of Health, but their diagnoses reflected the discrepancies between the doctors' diagnoses. In conclusion, the reproducibility of diagnoses on death certificates is so poor that information from the Registry of Causes of Death is of little use of administrative or scientific purposes.

[Written documentation of drug prescriptions. Accordance between medical records and dispensing records]. / Skriftlig dokumentation af medicinordinationer. Overensstemmelse imellem laegejournal og Medicinkardex.

UNLABELLED: A comparison of drug prescriptions entered on case records and nurses' drug lists is presented. Of 144 patients admitted to a general internal medicine ward, nine received no drugs. The remaining 135 had 606 (75.0%) items on both case record and drug list, 114 (14.1%) on the case record only, and 88 (10.9%) on the drug list only. For 48 patients (35.6%) drug lists were in accordance with their case record concerning the number and type of drug prescribed. Prescriptions on both documents were characterised by lack of accuracy. Of the 709 prescriptions on case records and 684 on drug lists, 428 (60.4%) and 411 (60.1%) respectively were unambiguous. CONCLUSION: Drug prescribing based on transcription from case records to nurses' drug lists implies a considerable risk of discrepancies. Thus, there is a significant risk of incorrect drug administration. A standardised card for drug prescriptions for common use by both physicians and nurses will therefore now be taken into use.

An EST and STS-based YAC contig map of human chromosome 9q22.3.

We have isolated 48 yeast artificial chromosome (YAC) clones from a 4 cM/27 cR region of human chromosome 9q22.3 encompassed by the markers cen-D9S196-D9S173-tel. Within this region, we have assembled a 4.3-Mb YAC contig across the interval cen-FACC-D9S173-tel containing 42 clones. As a first step toward completing the detailed transcription map of the region, we have mapped 9 gene sequences and 10 expressed sequence tags. Fifteen polymorphic microsatellite repeat markers and 17 novel sequence-tagged sites from the region are also described. The mapping of polymorphic simple tandem repeat markers has permitted the integration of existing genetic and physical maps of the region. Together these maps provide a valuable resource for fine structure mapping and DNA sequencing across the region as well as for the identification of disease gene loci and the isolation of novel coding sequences.

Effects on renal sodium and potassium excretion of vasopressin and oxytocin in conscious dogs.

Renal effects of arginine vasopressin and oxytocin were studied in conscious dogs, made water-diuretic by a waterload equivalent to 2% of body weight. Body water and content of sodium were maintained by separate servo-controlled infusions. Peptides were infused for 60 min at rates of 50 pg kg-1 min-1 (arginine vasopressin) or 1 ng kg-1 min-1 (oxytocin), either separately or combined. Infusions increased plasma arginine vasopressin to 1.9 +/- 0.2 (arginine vasopressin alone) and 1.8 +/- 0.3 pg kg-1 (arginine vasopressin plus oxytocin and plasma oxytocin to 72 +/- 5 (oxytocin alone) and 77 +/- 8 pg ml-1 (oxytocin plus arginine vasopressin). Arginine vasopressin or arginine vasopressin plus oxytocin increased urine osmolality similarly by a factor of 13, decreased urine flow to between 5 and 7% of control and decreased free water clearance. Oxytocin reduced urine flow and free water clearance and increased urine osmolality by a factor of 2. Oxytocin and arginine vasopressin separately increased excretion of sodium from 4 +/- 2 to 15 +/- 6 mumol min-1 and from 7 +/- 4 to 25 +/- 13 mumol min-1, respectively. Arginine vasopressin plus oxytocin led to a pronounced natriuresis (13 +/- 4 to 101 +/- 27 mumol min-1). Arginine vasopressin and arginine vasopressin plus oxytocin increased the excretion of potassium by a factor of 2.5. Oxytocin and arginine vasopressin plus oxytocin increased urinary Na+/K+ ratio by a factor of 3.7.(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous servo-controlled replacement of urinary sodium loss in conscious dogs.

A method for continuous servo-controlled infusion of sodium chloride to dogs is reported. The servo system consists of a sodium-sensitive electrode, a modified commercial flowmeter, a thermistor, a control unit, and a pump. Based on analog inputs from electrode, flowmeter, and thermistor, the control unit generates appropriate numbers of voltage steps, which drive the pump infusing a concentrated solution of sodium chloride. Inputs from the thermistor are necessary to correct for the influence of fluctuations in urine temperature. The sodium servo system has been tested together with a weight servo mechanism in conscious water-diuretic dogs. Furosemide (1 microgram.kg-1.min-1) was infused to change the rate of sodium excretion by a factor of 17 from 3 +/- 1 to 50 +/- 15 mumols/min. Within this range, the apparatus replaced the sodium losses with great accuracy. From seven experiments the average system response in micromoles per minute (NaIn) measured in 10-min periods against mean renal excretion of sodium (NaEx) was NaIn = 0.98.NaEx - 1.37. The servo system provides a tool for accurate maintenance of body sodium irrespective of large changes in the rate of sodium excretion.

Dipylidiasis in a 57-year-old woman.

An interesting case of tapeworm infection in a human caused by Dipylidium caninum was recently diagnosed in the Illawarra area of N.S.W. Since it involved and adult (a 57-year-old woman) and recorded human infections are rare in the Australian literature, it was decided to describe this case of dipylidiasis.