THE IMPACT OF X-RAY UNIT TYPE USED FOR ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY PROCEDURES ON PATIENT DOSES.

To investigate whether the X-ray unit type used for interventional endoscopic retrograde cholangiopancreatography (ERCP) procedures may affect patient radiation doses. A total of 471 ERCP procedures performed in 4 hospitals with 4 types of X-ray units were studied. Kerma-area product (KAP), fluoroscopy time (T) and total number of radiographs acquired (F) were recorded. KAP, T and F values exhibited a great variation, ranging from 0.1 to 130.2 Gy cm2 (mean 16 Gy cm2), 0.13 to 33.7 min (mean 5.4 min) and 0 to 26 radiographs (mean 3.5), respectively. The respective mean values for the four types of X-ray units that were investigated were as follows: KAP: 17.4, 12.5, 5.6 and 36.3 Gy cm2, T: 4.7, 5.2, 3.8 and 11.5 min and F: 1.7, 7.4, 1.9 and 4.6 radiographs. The type of the X-ray unit seems to significantly affect patient radiation dose, with the C-arm delivering the lowest and the angiography unit the highest patient doses.

Medication discontinuation with depot and oral antipsychotics in outpatients with schizophrenia: comparison of matched cohorts from a 12-month observational study.

AIMS: This study compared all-cause medication discontinuation (any switch, augmentation or medication discontinuation) in matched cohorts of patients with schizophrenia who were initiated on depot or oral antipsychotics. Other objectives included between-group comparisons of resource use, and clinical and functional outcomes. METHODS: This post hoc analysis of a one-year, multicentre, prospective, observational study included outpatients with schizophrenia who required a change in their antipsychotic medication because of a physician-perceived risk of medication non-adherence. Patients were matched 1 : 1 using an optimal algorithm with rank-based Mahalanobis distances. All-cause medication discontinuation was compared using the Klein and Moeschberger test for survival and hazard ratios (HR) with 95% confidence intervals (CI) were calculated using a Cox proportional hazards model, stratifying on matched pairs. RESULTS: Forty patients who initiated a depot antipsychotic could be matched to patients who initiated an oral antipsychotic. Fewer depot-treated patients discontinued their antipsychotic medication at least once compared with oral-treated patients [20% (8/40) vs. 40% (16/40)]. Depot-treated patients discontinued their medication later (Klein and Moeschberger test p = 0.025) and were less likely to discontinue their initial antipsychotic medication [HR = 0.33 (95% CI, 0.12-0.92), p = 0.033] than oral-treated patients. There were few differences in resource use and no differences in clinical and functional outcomes between cohorts. CONCLUSION: In this matched-cohort analysis, patients with schizophrenia who were considered to be non-adherent with their prior oral antipsychotics were less likely to discontinue their medication for any cause if they were initiated on depot compared with oral antipsychotics.

An exploratory analysis of factors associated with weight change in a 16-week trial of oral vs. orally disintegrating olanzapine: the PLATYPUS study.

BACKGROUND: We conducted exploratory analyses of the data from a multinational, randomised study to identify factors associated with weight change after 16 weeks of treatment with standard olanzapine tablets (SOT) or sublingual orally disintegrating olanzapine (ODO). METHODS: One hundred and forty nine outpatients who gained weight during prior SOT therapy were enrolled into the study and treated with ODO (N = 84) or SOT (N = 65). Exploratory analyses were conducted with the subset of compliant patients (ODO: n = 60; SOT: n = 47). RESULTS: The decrease in the rate of weight gain at the end of study therapy (change from baseline) was greater in the ODO group than the SOT group (-0.59 kg/week vs. -0.38 kg/week, p = 0.0246). Age was negatively associated with weight change (p = 0.0203) in both treatment groups combined: patients gained 0.7 kg less for every 10 years of age. The least squares mean weight gain was lower with ODO than SOT in male patients (0.35 kg vs. 3.04 kg, p = 0.061), but not female patients and in American patients (0.55 kg vs. 6.21 kg, p < 0.0001), but not Canadian or Mexican patients. CONCLUSIONS: Although not conclusive, these data suggest that ODO may be a reasonable treatment option for some patients who gain weight with SOT. Further research is required to confirm these findings.

The number needed to treat for all-cause medication discontinuation in the treatment of schizophrenia: consistency across world geographies and study designs.

INTRODUCTION: The number needed to treat (NNT) for all-cause medication discontinuation in large, industry-sponsored, non-randomized, observational studies conducted across world geographies was compared with NNTs from CATIE, an 18-month, NIMH-sponsored, randomized study. METHODS: NNTs (with 95% confidence intervals) were calculated using data from 3 large Lilly-sponsored, non-randomized, observational studies (EU-SOHO, IC-SOHO, and US-SCAP, n=20 957). Group differences at medication initiation were adjusted by Cox regression modeling. These NNTs were compared with published NNTs for CATIE (phase 1). RESULTS: NNTs for olanzapine vs. risperidone and for olanzapine vs. quetiapine were similar across the observational studies and similar to those of CATIE. The NNTs for olanzapine vs. oral typical antipsychotics were similar across the observational studies but demonstrated a somewhat stronger effect size than the NNT reported for olanzapine vs. perphenazine in CATIE. DISCUSSION: NNTs for all-cause treatment discontinuation (a proxy measure of a medication's effectiveness from patients' and clinicians' perspectives) appear to be consistent across study designs (non-interventional, observational vs. RCT), study sponsorship (industry vs. independent), and across world geographies, suggesting that antipsychotics differ in this measure.

Changes in weight and metabolic parameters during treatment with antipsychotics and metformin: do the data inform as to potential guideline development? A systematic review of clinical studies.

BACKGROUND: Changes in weight and metabolic parameters have been commonly reported in patients with schizophrenia. Metformin has been evaluated in clinical studies to prevent or reduce weight gain and changes in metabolic parameters in non-diabetic subjects. We undertook a systematic review of the efficacy and safety of metformin in reducing weight gain and metabolic abnormalities in non-diabetic subjects with schizophrenia or bipolar disorder taking antipsychotic medication to establish if these data could potentially drive guideline development. METHODS: Medical databases were searched using terms including 'antipsychotic', 'atypical antipsychotic agent', 'antipsychotic agents', 'antipsychotic-drug' and 'metformin' and 'weight'. Studies reporting weight and/or metabolic outcomes in non-diabetic subjects with schizophrenia and bipolar disorder were included regardless of methodological type and subject age. RESULTS: Nine randomised double-blind studies and two open cohort studies evaluating metformin and changes in weight in trials up to 16 weeks were identified. In all, 495 participants received antipsychotics (mostly olanzapine), and three studies were in subjects aged < 18 years. The adult studies predominantly utilised non-Caucasian subjects with chronic schizophrenia. Weight and lifestyle intervention programmes were provided to all cohorts in eight studies, which confounded interpretation of the data. In ten studies, the addition of metformin to antipsychotic treatment was associated with either significantly attenuated weight gain or weight loss compared with control groups. Nine studies measured various glucose parameters. In four studies, subjects prescribed metformin had significantly improved glucose parameters relative to controls. The two studies of metformin in patients with first-episode schizophrenia demonstrated the largest improvement in weight and glucose parameters. CONCLUSIONS: Metformin may have some value in reducing or preventing weight gain and changes in metabolic parameters during treatment with antipsychotic medication particularly in first-episode psychosis; however, it has been predominantly studied short-term and in non-Caucasian populations. A number of new trials are due to report data 2009-2013 to aid definitive interpretation of the role of metformin. Further longer-term studies are warranted before definitive guidelines can be established.

Worldwide-Schizophrenia Outpatient Health Outcomes (W-SOHO): baseline characteristics of pan-regional observational data from more than 17,000 patients.

OBJECTIVE: To describe the Worldwide-Schizophrenia Outpatient Health Outcomes (W-SOHO) patient population at study entry, focusing on illness burden and prescribing practices across regions. METHODS: The SOHO study was a 3-year, prospective, observational study designed to assess costs and outcomes associated with antipsychotic use in outpatients initiating or changing antipsychotic (with an emphasis on olanzapine compared with other antipsychotics). SOHO was conducted in 10 European countries and 27 other countries as Intercontinental SOHO (IC-SOHO). Data from all countries have been pooled to produce the W-SOHO dataset. MAIN OUTCOMES MEASURES: Clinical Global Impression-Schizophrenia (CGI-SCH) severity scores, psychotropic medication use, adverse events, social interaction, housing and employment status, self-perceived health state (EuroQoL EQ-5D scale and Visual Analogue Scale, EQ-VAS), and reasons for initiation/change of antipsychotic. RESULTS: The W-SOHO database comprises 17,384 patients from six regions; East Asia (n = 1223), Central and Eastern Europe (n = 2175), Northern Europe (n = 4291), Southern Europe (n = 5788), Latin America (n = 2566), North Africa and the Middle East (n = 1341). Overall, patients were 38 +/- 13 years old (mean +/- SD), moderately ill (mean CGI-SCH overall score of 4.4 +/- 1.0) with a median duration of illness of 7 years (interquartile range 1-16 years); 43% were female, 10% were receiving antipsychotic medication for the first time. Adverse events were prevalent across all regions; on average, 50% (range 41-59%) of patients taking antipsychotics exhibited extrapyramidal symptoms at baseline, and 62% (34-67%) of patients reported sexual dysfunction in the previous month. On average, only 19% (16-23%) of patients were in paid employment and as many as 69% were living in dependent housing. CONCLUSIONS: Despite inherent diversity in these patients and the health care systems supporting them, there are striking cross-regional similarities in baseline characteristics for most measures. Not all countries are represented; regional comparisons may not be valid outside of the countries studied.

A randomized controlled trial of the effect of sublingual orally disintegrating olanzapine versus oral olanzapine on body mass index: the PLATYPUS Study.

BACKGROUND: Patients with schizophrenia and bipolar disorder have frequently reported weight gain during olanzapine treatment. Previous studies have observed a decrease in weight gain, or weight loss, in patients switching from standard olanzapine tablets (SOT) to orally disintegrating olanzapine (ODO) tablets. The primary objective of this study was to investigate the change in body mass index (BMI) in patients who had previously gained weight with SOT and continued with this therapy during the study period, compared with those patients who switched to ODO during the study period. METHODS: This was a 16-week, multicentre, randomized, double-blind, double-dummy, study of outpatients diagnosed with schizophrenia, schizoaffective disorder, related psychotic disorder or bipolar disorder, who were taking 5-20 mg SOT daily. Patients continued treatment with 5-20 mg olanzapine in a flexible single daily dose, and were randomized to either receive sublingual ODO plus an oral placebo, or sublingual placebo plus SOT. RESULTS: No statistically significant between group differences in mean change from baseline in BMI, weight or waist circumference were observed. Analysis of change in body weight from baseline, by pre-specified category (no change, loss of >or=1.5 kg, gain of >or=1.5 kg), revealed a significant difference between groups, favoring ODO patients, who also experienced a significant reduction in subjective appetite and better treatment compliance, compared to patients in the SOT group. CONCLUSIONS: In this study, patients treated with ODO experienced a similar mean change in BMI and weight from baseline, to those patients treated with SOT.

Intramuscular olanzapine vs. intramuscular short-acting antipsychotics: safety, tolerability and the switch to oral antipsychotic medication in patients with schizophrenia or acute mania.

BACKGROUND: This study compared the safety, tolerability and switch to oral medication in patients with bipolar disorder or schizophrenia who received intramuscular (IM) olanzapine or other IM antipsychotics for the treatment of acute agitation. METHODS: Patients (N = 2011) from 15 countries participated in this prospective, observational, non-interventional study. Inpatients requiring treatment with at least one IM injection of a short-acting antipsychotic were assessed at baseline and within 7 days after the first IM injection. Treatment groups comprised: (i) patients prescribed IM olanzapine at baseline; and (ii) patients prescribed any other IM antipsychotic medication at baseline. Outcome measures included: treatment-emergent adverse events, concomitant psychotropic medication and the time taken to switch to oral medication. RESULTS: Fewer patients in the IM olanzapine group experienced an adverse event than patients in the other IM antipsychotic group (34.4% vs. 46.2%, p < 0.001). The most frequently reported adverse events in both groups were: sedation, Parkinsonism, disturbance in attention, akathisia, dystonia and orthostatic hypotension. Fewer patients in the IM olanzapine group used anticholinergics (13.9% vs. 42.5%, p < 0.001) or anxiolytics/hypnotics (47.6% vs. 51.6%, p = 0.023). Patients in the IM olanzapine group switched to oral medication earlier than patients in the other IM antipsychotic group (median time = 46.5 vs. 48.0 h, p = 0.009). CONCLUSIONS: These findings suggest that IM olanzapine may have a favourable impact on individual patients. However, the high rate of oral concomitant medication used throughout the study limits these findings from being associated with IM olanzapine alone.

Can increased food intake improve psychosis? A brief review and hypothesis.

Weight gain, diabetes, and changes in serum lipid profiles have been reported during treatment with typical and atypical antipsychotics. An association between diabetes and psychotic disorders was described long before the introduction of pharmacological agents for the treatment of schizophrenia. Several theories have been proposed to explain the baseline weight increase and metabolic disturbances in schizophrenia. Some studies suggest that increased food intake may improve psychotic symptoms in patients with schizophrenia but there have been conflicting results. Available clinical and basic research findings are discussed to evaluate the hypothesis that increased food intake may decrease sensitivity to dopamine signaling in the striatum. More research is needed to evaluate this potential link. However, basic animal research and evolutionary approaches can provide insights into metabolic disturbances associated with schizophrenia.

Rapid tranquilization with olanzapine in acute psychosis: a case series.

Acute, high-dose loading strategies (rapid neuroleptization) with the first-generation antipsychotics administered orally or parenterally, alone or combined with benzodiazepines, have been a commonly used treatment paradigm for controlling acutely agitated psychotic patients. The rationale was to achieve high plasma levels of drug within a shorter time period, resulting in rapid symptom mitigation. However, studies have shown that rapid neuroleptization with first-generation antipsychotics is associated with a greater incidence of side effects. To our knowledge, loading strategies with second-generation antipsychotics have not been investigated, primarily owing to a need for dose titration. Olanzapine, a second-generation antipsychotic, is well tolerated in doses ranging from 5 to 20 mg. The objective of this report was to determine experience with the use of up to 20 mg of an oral loading dose of olanzapine administered within 4 hours in the treatment of patients early in an acute psychotic phase of their illness. In the reported case series of 57 patients, olanzapine initiated at 15 to 20 mg/day was a safe and effective medication for rapidly calming the agitation of acutely agitated psychotic patients (rapid tranquilization). Furthermore, dose reduction over 2 to 3 weeks was achieved in a number of patients without appreciable loss of efficacy.

Replacement of the pyloric sphincter with the ileocecal valve: an experimental study.

BACKGROUND: Several surgical methods have been devised and applied to overcome the complications associated with the loss of the pyloric sphincter after distal gastrectomy. However, none of these methods creates an efficient sphincteric mechanism at the anastomotic site. The purpose of this experimental study in dogs was to replace the pylorus with the ileocecal valve and determine whether its sphincteric function would be preserved in its new location without affecting gastrointestinal motility and the health of the animals. METHODS: Thirteen dogs underwent surgical removal of the pyloric sphincter and a partial distal gastrectomy. The ileocecal valve, with a short segment of ileum, was then relocated so that the ileal segment was anastomosed to the stomach while the cecal segment was anastomosed to the duodenum. Intestinal continuity was reestablished by anastomosing the distal ileum with the ascending colon. Intraileal and intracolic pressures were measured in all animals prior to and following transposition of the ileocecal valve. In 3 of these animals, pre-pyloric (intragastric) and post-pyloric (intraduodenal) pressures were also measured before the pylorus was removed. Pressure measurements on both sides of the transposed ileocecal valve were performed again 4-6 months later. All pressure measurements were made directly with a water manometer. Radiographic and fluoroscopic studies were carried out on all animals to assess gastrointestinal motility, gastric emptying times, and the sphincteric competence of the transposed ileocecal valve. Hematological and biochemical studies intended to assess the nutritional status of all animals were carried out. Also, postoperative measurements were made of gastric basic acid output. RESULTS: All animals were alive and well 4-6 months after the initial operative procedure. Hematological studies and biochemical tests and studies of liver function remained normal. There was a slight reduction in serum B12 levels and, as expected, a significant postoperative reduction in gastric basic acid output. The intraluminal pressure measurements and the radiographic and fluoroscopic studies all showed that the sphincteric mechanism of the ileocecal valve was preserved in its new location, that gastrointestinal motility was not impaired, and that the healthy condition of the animals was maintained. Gross and histological examination of the transposed segments of the intestinal tract did not reveal any abnormalities. CONCLUSION: Because the anatomy and physiology of the human alimentary tract are similar to those of the dog, this technique may be applicable clinically, when indicated, to avoid and/or relieve complications resulting from gastrectomy, when those complications do not respond or have not responded to conservative management.

Clozapine-associated neuroleptic malignant syndrome: two new cases and a review of the literature.

BACKGROUND: Clozapine has recently been found to be associated with neuroleptic malignant syndrome (NMS). Our objective is to determine if clozapine causes NMS, if the presentation of clozapine-induced NMS differs from that of traditional agents, and which set of diagnostic criteria will most readily allow diagnosis of NMS associated with clozapine. METHODS: Two new cases of clozapine-associated NMS are presented, along with previously reported cases from the literature, identified by using a MEDLINE search (1966-August 1998). From all cases, concomitant medications and washout periods were examined (if available) to assess clozapine as the likely cause of NMS. Characteristics of clozapine and traditional antipsychotic-induced NMS were compared. Different diagnostic criteria for NMS were applied to the cases to determine which were more likely to diagnose the syndrome. RESULTS: Clozapine was deemed a highly probable cause of NMS in 14 cases, a medium probability cause in five cases, and a low probability cause in eight cases. The most commonly reported clinical features were tachycardia, mental status changes, and diaphoresis. Fever, rigidity, and elevated creatine kinase were less prominent than in NMS associated with classical neuroleptics. CONCLUSIONS: Clozapine appears to cause NMS, although the presentation may be different than that of traditional antipsychotics. Levenson's original and Addonizio's modified criteria were more likely to diagnose NMS than were other criteria. Clozapine-associated NMS may present with fewer clinical features. Limitations are the lack of detailed information provided by many of the case reports and the use of "modified" diagnostic criteria for retrospective diagnosis.

Frequency of electroconvulsive therapy use at a provincial mental hospital: a retrospective study.

In this retrospective study the frequency of electroconvulsive therapy use in the Waterford Hospital, a provincial mental hospital over a period of 14 years is examined. The results indicate that the use of electroconvulsive therapy has declined significantly. The three local general hospitals, St. Claire's Mercy Hospital, The Grace Hospital and the General Hospital have also experienced a decline in the use of electroconvulsive therapy. The potential reasons for this decline are explored and the findings are discussed particularly in the context of a 1986 study that found high rates of electroconvulsive therapy use at the Waterford Hospital.