PHOENIX (Picking up Hidden Osteoporosis Effectively during Normal CT Imaging without additional X-rays): protocol for a randomised, multicentre feasibility study.

INTRODUCTION: Two million out of the UK's 5 million routine diagnostic CT scans performed each year incorporate the thoracolumbar spine or pelvic region. Up to one-third reveal undiagnosed osteoporosis or vertebral fractures. We developed an intervention, Picking up Hidden Osteoporosis Effectively during Normal CT Imaging without additional X-rays ('PHOENIX'), to facilitate early detection and management of osteoporosis in people attending hospitals for CT scans. METHODS AND ANALYSIS: A multicentre, randomised, pragmatic feasibility study. From the general CT-attending population, women aged ≥65 years and men aged ≥75 years attending for CT scans are invited to participate, via a novel consent form incorporating Fracture Risk Assessment (FRAX) questions. Those at increased 10-year risk (within the amber or red zones of the UK FRAX graphical outputs for further action) are block randomised (1:1:1) to (1) PHOENIX intervention, (2) active control or (3) usual care. The PHOENIX intervention comprises (i) retrieving the CT scans using the NHS Image Exchange Portal, (ii) Mindways QCT Pro software analysis of CT hip and spine none density with CT vertebral fracture assessment, (iii) sending the participants' general practitioner (GP) a clinical report including diagnosis, necessary investigations and recommended treatment. Baseline CT scans from groups 2 and 3 are assessed with the PHOENIX intervention only at study end. Assuming 25% attrition, the study is powered to find a predicted superior osteoporosis treatment rate with PHOENIX (20%) vs 16% among patients whose GPs were sent the FRAX questionnaire only (active control) and 5% in the usual care group. Five hospitals are participating to determine feasibility. The co-primary feasibility outcome measures are (a) ability to randomise 375 patients within 10 months and (b) retention of 75% of survivors, completing their 1-year bone health outcome questionnaire. Secondary 1-year outcomes include osteoporosis/vertebral fracture identification rates and osteoporosis treatment rates. Stakeholder acceptability and economic aspects are evaluated. ETHICS AND DISSEMINATION: Approved by committee (National Research Ethics Service) East of England (EE) as REF/19/EE/0176. Dissemination will be through the Royal Osteoporosis Society (to patients and public) as well as to clinician peers via national and international bone/rheumatology scientific and clinical meetings. TRIAL REGISTRATION NUMBER: ISRCTN14722819.

A Comparison of Dietary Intake Between Individuals Undergoing Maintenance Hemodialysis in the United Kingdom and China.

OBJECTIVE: Protein-energy wasting is highly prevalent in people with end-stage kidney disease receiving regular hemodialysis. Currently, it is unclear what the optimal nutritional recommendations are, which is further complicated by differences in dietary patterns between countries. The aim of the study was to understand and compare dietary intake between individuals receiving hemodialysis in Leicester, UK and Nantong, China. METHODS: The study assessed 40 UK and 44 Chinese participants' dietary intake over a period of 14 days using 24-hour diet recall interviews. Nutritional blood parameters were obtained from medical records. Food consumed by participants in the UK and China was analyzed using the Nutritics and Nutrition calculator to quantify nutritional intake. RESULTS: Energy and protein intake were comparable between UK and Chinese participants, but with both below the recommended daily intake. Potassium intake was higher in UK participants compared to Chinese participants (2,115 [888] versus 1,159 [861] mg/d; P < .001), as was calcium (618 [257] versus 360 [312] mg/d; P < .001) and phosphate intake (927 [485] versus 697 [434] mg/d; P = .007). Vitamin C intake was lower in UK participants compared to their Chinese counterparts (39 [51] versus 64 [42] mg/d; P = .024). Data are reported here as median (interquartile range). CONCLUSION: Both UK and Chinese hemodialysis participants have insufficient protein and energy in their diet. New strategies are required to increase protein and energy intakes. All participants had inadequate daily intake of vitamins C and D; there may well be a role in the oral supplementation of these vitamins, and further studies are urgently needed.

Obesity and central adiposity in Japanese immigrants: role of the Western dietary pattern.

We examined the association of nutritional factors with body fat deposition in a representative sample (n=530, aged 40-79 years) of first and second-generation Japanese-Brazilian population who was submitted to standardized questionnaires, including nutritional data, clinical examination and laboratory procedures. Dietary data were compared between groups of subjects defined by the presence of obesity or central adiposity. Associations of body mass index or waist circumference (dependent variables) with energy and nutrient intakes (main exposure of interest) were analyzed by multiple linear regression, with adjustment for gender, age, physical activity and generation. Groups of obese subjects and those with central adiposity consumed higher proportions of energy as fat and lower as carbohydrate than those without obesity and central adiposity (p<0.05). Stratifying by generation, second-generation was shown to take more energy as fat than the first-generation (p<0.05). In the regression models, protein intake was the only variable significantly associated with body mass index. Replacing body mass index by the waist circumference, male sex and protein intake were shown to be independent predictors of central adiposity. When second-generation was taken, total energy intake and all macronutrient intakes became significantly associated with body mass index (p<0.05) but only protein intake predicted waist circumference. We speculate that Japanese-Brazilians, genetically prone to insulin resistance, when exposed to unfavorable environment will express a number of metabolic disturbances. A deleterious dietary pattern may contribute to weight gain, was associated with abdominal fat deposition in particular a protein-rich diet, and reflected by their waist circumference. Intra-abdominal fat could be triggering insulin resistance, which would explain the increased prevalence rates of diabetes, dyslipidemia and hypertension seen in Japanese-Brazilians.

[Weight excess and abdominal fat in the metabolic syndrome among Japanese-Brazilians]. / Excesso de peso e gordura abdominal para a síndrome metabólica em nipo-brasileiros.

OBJECTIVE: Obesity, especially abdominal, has been associated with cardiovascular risk factors such as dyslipidemia, hypertension and diabetes mellitus (DM). The importance of these risk factors among Japanese-Brazilians was previously shown, although obesity is not a typical characteristic of Japanese migrants. In this study the prevalence of weight excess and central adiposity (CA) among Japanese-Brazilians and their association with metabolic disorders was evaluated. METHODS: A sample of 530 1st and 2nd generation Japanese-Brazilians (aged 40 - 79 years) went through anthropometric and blood pressure measurements, lipid profile and oral glucose tolerance tests. The prevalence rate (point and confidence interval) of overweight was calculated using a cut-off value of >26.4 kg/m2. CA diagnosis was based on waist-to-hip circumference ratio (WHR): greater-than-or-equal 0.85 and 0.95 in women and men, respectively. RESULTS: The prevalence of weight excess was 22.4% (CI 95% 20.6 - 28.1), and CA was 67.0% (95% CI 63.1 - 70.9). In addition to higher prevalence of DM, hypertension and dyslipidemia, stratifying by BMI and WHR, people with weight excess and CA revealed a poorer metabolic profile: blood pressure levels were significantly higher among those with weight excess with or without CA; CA individuals had higher glucose, triglycerides, total and LDL cholesterol, and lower HDL than those without weight excess or CA; fasting insulinemia was significantly higher among subjects with weight excess (with or without CA) than among those without weight excess or CA. CONCLUSION: Comparing subgroups with and without CA supports the hypothesis that abdominal fat accumulation represents a risk factor for insulin resistance-related diseases, even among Japanese descendants. The increased prevalence of metabolic syndrome among Japanese migrants could be attributed to visceral fat deposition, which has been implicated in the genesis of insulin resistance.

Excesso de peso e gordura abdominal para a síndrome metabólica em nipo-brasileiros / Weight excess and abdominal fat in the metabolic syndrome among Jananese-Brazilians

OBJETIVO: A obesidade, especialmente de distribuiçäo abdominal, associa-se a fatores de risco cardiovasculares como a dislipidemia, a hipertensäo arterial (HA) e o diabetes mellitus (DM). A importância desses fatores em nipo-brasileiros foi previamente demonstrada, apesar de a obesidade näo ser característica marcante dos migrantes japoneses. Realizou-se estudo com o objetivo de avaliar a prevalência de excesso de peso e a adiposidade central (AC) em nipo-brasileiros e suas relaçöes com distúrbios metabólicos.MÉTODOS: A amostra incluiu 530 nipo-brasileiros (40-79 anos) de primeira e segunda geraçöes, submetidos a medidas antropométricas de pressäo arterial, perfil lipídico e teste oral de tolerância à glicose. A prevalência (por ponto e intervalo de confiança) de excesso de peso foi calculada pelo valor de corte >26,4 kg/m2. O diagnóstico de AC foi baseado na razäo entre as circunferências da cintura e do quadril (RCQ), sendo que valores ü0,85 e ü0,95, para mulheres e homens, respectivamente, firmavam esse diagnóstico. RESULTADOS: A prevalência de excesso de peso foi de 22,4 por cento (IC95por centoó 20,6-28,1), e a de AC, de 67,0 por cento (IC95 por cento ó 63,1-70,9). Além de maiores prevalências de DM, HA e dislipidemia, estratificando-se pelo índice de massa corporal (IMC) e RCQ, indivíduos com excesso de peso e adiposidade central apresentaram pior perfil metabólico: a pressäo arterial foi significantemente maior naqueles com excesso de peso, sem e com AC; indivíduos com AC apresentaram maiores índices de glicemia, triglicerídeos, colesterol total e LDL e menor HDL quando comparados aos sem excesso de peso e sem AC; a insulinemia de jejum foi significantemente maior em indivíduos com excesso de peso (sem e com AC) do que naqueles sem excesso de peso e sem AC. CONCLUSAO: A comparaçäo de subgrupos com e sem adiposidade central foi compatível com a hipótese de que a deposiçäo abdominal de gordura representa fator de risco para doenças interligadas pela resistência à insulina, inclusive em populaçäo de origem oriental. A alta prevalência de síndrome metabólica nos migrantes japoneses pode ser decorrente da deposiçäo visceral de gordura, implicada na gênese da resistência à insulina

Intramuscular (IM) ziprasidone 20 mg is effective in reducing acute agitation associated with psychosis: a double-blind, randomized trial.

RATIONALE: Intramuscular (IM) conventional antipsychotics and/or benzodiazepines are effective in the short-term treatment of acutely agitated psychotic patients but may be associated with adverse effects. A short-acting IM formulation of the novel antipsychotic, ziprasidone, which may offer advantages over conventional agents, has been developed. OBJECTIVE: To compare ziprasidone IM 2 mg (n=38) and 20 mg (n=41) in the acute control and short-term management of agitated psychotic patients. METHODS: A prospective, randomized, double-blind, 24-h study assessed efficacy using the Behavioral Activity Rating Scale (BARS) and the PANSS. The BARS is a validated rating scale for the assessment of treatment response in acute agitation associated with psychosis. Following the initial dose, three more doses could be given 4 h apart if needed during the 24-h period. RESULTS: The mean BARS score had decreased 15 min after the first 20 mg IM dose and was statistically significantly lower than the 2 mg group at 30 min post-dose. The improvement with the 20 mg dose increased until 2 h, and was maintained until at least 4 h post-dose (P<0.001). Two hours after the first injection, almost all of the patients receiving ziprasidone 20 mg were BARS responders compared with just one-third of those receiving 2 mg ziprasidone (P<0.001). The calming effect of ziprasidone was also evident by the significant reduction in PANSS agitation items (P<0.05) and CGI-severity at 4 h (P=0.008). Both ziprasidone doses were very well tolerated. Ziprasidone IM 20 mg was not associated with EPS, dystonia, akathisia, respiratory depression or with excessive sedation. CONCLUSIONS: Ziprasidone IM 20 mg substantially and significantly reduced the symptoms of acute agitation in patients with psychotic disorders. Ziprasidone 20 mg IM was very well tolerated and produced no dystonia or akathisia.

Ziprasidone: comprehensive overview and clinical use of a novel antipsychotic.

Ziprasidone (5-[2-(4-(1,2,-benzisothiazol-3-yl) piperazin-l-yl] ethyl]-6 -chloro indolin-2-one hydrochloride hydrate) is a novel antipsychotic with a pattern of receptor occupancy and preclinical attributes predictive of broad therapeutic efficacy and a favourable tolerability profile in the treatment of psychotic illness. Clinical trials indicate that ziprasidone is effective against positive, negative and affective symptoms in schizophrenia and schizoaffective disorder with minimal motor, cognitive, weight gain, prolactin related, or anticholinergic side effects. In addition, an im. formulation appears to be rapidly effective with significantly less motor side effect liability than haloperidol.

Obesidade, hipertensäo arterial e suas influências sobre a massa e funçäo do ventrículo esquerdo / Obesity, hypertension and your influence about the left ventricular function and mass

Para avaliar as influências da obesidade e da hipertensão sobre a massa de ventrículo esquerdo (MVE), estudamos 121 mulheres divididas em 4 grupos: não-obesas normotensas (n = 25), não-obesas hipertensas (n = 30), obesas normotensas (n = 24) e obesas hipertensas (n = 42) quanto a parâmetros antropométricos, ecocardiográficos e de monitorização ambulatorial da pressão arterial (MAPA). As pacientes obesas hiperten- sas apresentaram maior MVE que os outros grupos - não-obesas normotensas, não-obesas hipertensas e obesas normotensas (167 +/- 38,8 vs. 113 +/- 26,4; vs. 133 +/- 26,5; vs. 132 +/- 29,2g; p < 0,05, respectivamente) e maior diâmetro de átrio esquerdo (AE) quando comparadas aos grupos de não-obesas, tanto normotensas como hipertensas (36 +/- 4,3 vs. 33 +/- 5,1; vs. 35 +/- 3,9mm; p < 0,05, respectivamente). Obesas normotensas apresentaram MVE similar à do grupo não-obesas hipertensas (133 +/- 26,5 vs. 132 +/- 29,5g; NS) e aumento de AE quando comparadas às não-obesas normotensas (35 +/- 3,9 vs. 31 +/- 4,6mm; p < 0,05). Detectou-se correlação entre a circunferência da cintura e a razão cintura-quadril com os níveis pressóricos à MAPA, assim como entre estas medidas e parâmetros ecocardiográficos que avaliam a massa cardíaca; o índice de massa corporal só se correlacionou ao diâmetro do AE. A correção da MVE pela altura ao invés da superfície corpórea aumentou a prevalência de hipertrofia de VE nas obesas (10,6 vs. 36,7 por cento, p < 0,01), mas não nas não-obesas. Ausência de descenso noturno da pressão arterial sistólica à MAPA (non-dipper) foi mais prevalente nas pacientes obesas, hipertensas ou não; entretanto, as obesas hipertensas non-dippers não diferiram das dippers quanto à MVE. Nossos dados demonstram que a obesidade associada à hipertensão aumenta a MVE de modo mais importante do que as condições isoladamente. Concluímos, ainda, que pacientes obesas também apresentam alta freqüência de alterações do ritmo da pressão arterial de 24 horas, caracterizada por menor queda pressórica durante o sono.

Antipsychotic treatment of psychosis and agitation in the elderly.

Agitated, aggressive behavior and psychosis are common manifestations of Alzheimer's disease that frequently lead to institutionalization. The usefulness of conventional neuroleptic treatment in this population is limited by narrow therapeutic windows because of limited efficacy and high sensitivity to side effects. More recently, investigational clinical trials have suggested potential utility for atypical antipsychotics such as risperidone, olanzapine, and quetiapine in treatment of behaviorally disturbed individuals and for the psychotic manifestations of dementia.

Olanzapine versus placebo in the treatment of acute mania. Olanzapine HGEH Study Group.

OBJECTIVE: The primary intent of this study was to compare the efficacy and safety of olanzapine and placebo in the treatment of acute mania. METHOD: The design involved a random-assignment, double-blind, placebo-controlled parallel group study of 3 weeks' duration. After a 2- to 4-day screening period, qualified patients were assigned to either olanzapine (N = 70) or placebo (N = 69). Patients began double-blind therapy with either olanzapine, 10 mg, or placebo given once per day. After the first day of treatment, the daily dose could be adjusted upward or downward, as clinically indicated, by one capsule (olanzapine, 5 mg/day) within the allowed range of one to four capsules. The primary efficacy measure in the protocol was defined as a change from baseline to endpoint in total score on the Young Mania Rating Scale. Clinical response was defined a priori as a decrease of 50% or more from baseline in Young Mania Rating Scale total score. RESULTS: The olanzapine group experienced significantly greater mean improvement in Young Mania Rating Scale total score than the placebo group. On the basis of the clinical response criteria, significantly more olanzapine-treated patients (48.6%) responded than those assigned to placebo (24.2%). Somnolence, dizziness, dry mouth, and weight gain occurred significantly more often with olanzapine. There were no statistically significant differences between the olanzapine-treated and placebo-treated patients with respect to measures of parkinsonism, akathisia, and dyskinesias. No discontinuations of treatment due to adverse events occurred in the olanzapine treatment group. CONCLUSIONS: The results from this study suggest that compared with placebo, olanzapine has superior efficacy for the symptoms of acute mania.

Ziprasidone 80 mg/day and 160 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 6-week placebo-controlled trial. Ziprasidone Study Group.

In this double-blind study, patients with an acute exacerbation of schizophrenia or schizoaffective disorder were randomized to receive either ziprasidone 80 mg/day (n = 106) or 160 mg/day (n = 104) or placebo (n = 92), for 6 weeks. Both doses of ziprasidone were statistically significantly more effective than placebo in improving the PANSS total, BPRS total, BPRS core items, CGI-S, and PANSS negative subscale scores (p < .05). Ziprasidone 160 mg/day significantly improved depressive symptoms in patients with clinically significant depression at baseline (MADRS > or = 14, over-all mean 23.5) (p < .05) as compared with placebo. The percentage of patients experiencing adverse events was similar in each treatment group, and resultant discontinuation was rare. The most frequent adverse events associated with ziprasidone were generally mild dyspepsia, nausea, dizziness, and transient somnolence. Ziprasidone was shown to have a very low liability for inducing movement disorders and weight gain. The results indicate that ziprasidone is effective and well tolerated in the treatment of the positive, negative, and depressive symptoms of an acute exacerbation of schizophrenia or schizoaffective disorder.

Long-term efficacy and safety comparison of sertindole and haloperidol in the treatment of schizophrenia. The Sertindole Study Group.

Sertindole is an atypical antipsychotic that is efficacious in schizophrenia and is associated infrequently with extrapyramidal symptoms (EPS). This study assessed time to treatment failure with 24 mg/day sertindole or 10 mg/day haloperidol in 282 clinically stable neuroleptic-responsive outpatients with schizophrenia. During a 5-week transition period, patients were randomized to treatment with sertindole or haloperidol; other treatments were gradually discontinued. Patients then received treatment through Day 365. Time to treatment failure was numerically superior in sertindole-treated patients compared with haloperidol-treated patients, although this difference was not statistically significant. Sertindole-treated patients, however, remained free of hospitalization for exacerbation of schizophrenia and remained medically compliant significantly longer than did haloperidol-treated patients. In addition, there were significantly fewer reports of EPS in sertindole-treated patients and sertindole therapy was generally well tolerated. Patients transitioned well from other antipsychotic agents to sertindole. Sertindole appears to be an effective long-term treatment for schizophrenia.

Treatment of the refractory schizophrenic patient.

As antipsychotic treatment evolves toward a broader range of efficacy and more benign side effect profiles, our criteria for treatment-refractory schizophrenia may become more subtle. Unidimensional concepts of treatment resistance may be replaced by multiaxial descriptions of the target symptoms, side effects, and compliance issues that limit the ultimate goals of enhanced psychosocial function and quality of life. Augmentation strategies, increasing insight into dose response relationships, and atypical agents may benefit patients who failed to respond to or tolerate previous therapies. The advantages of newer agents in treatment-resistant schizophrenia may arise in part from their preferential targeting of newer agents in treatment-resistant schizophrenia may arise in part from their preferential targeting of mesolimbic compared with motor and tuberoinfundibular dopaminergic pathways.

Controlled, dose-response study of sertindole and haloperidol in the treatment of schizophrenia. Sertindole Study Group.

OBJECTIVE: This multicenter, double-blind, placebo-controlled study evaluated the efficacy and safety of three doses of sertindole (12, 20, and 24 mg/day) and haloperidol (4, 8, and 16 mg/day) in the treatment of psychotic symptoms for 497 hospitalized patients with schizophrenia. METHOD: The patients were randomly assigned to one of the medication groups and received treatment for 8 weeks. Changes in Positive and Negative Syndrome Scale, Scale for the Assessment of Negative Symptoms, Brief Psychiatric Rating Scale, and Clinical Global Impression scores were used as evaluations of treatment efficacy. Three rating scales were used to assess extrapyramidal symptoms as well as the occurrence of adverse events and the use of medications related to extrapyramidal symptoms. RESULTS: Both sertindole and haloperidol were comparably effective in the treatment of psychosis, and all dose levels were significantly more effective than placebo. For the treatment of negative symptoms, only sertindole, 20 mg/day, was significantly more effective than placebo. For all extrapyramidal symptom measures, sertindole was clinically and statistically indistinguishable from placebo, and rates of extrapyramidal symptoms were not dose related. All dose levels of haloperidol produced significantly more extrapyramidal symptoms than placebo or sertindole. Adverse events associated with sertindole treatment were mild in severity. CONCLUSIONS: Sertindole is a new antipsychotic agent effective for the treatment of both the positive and negative symptoms of schizophrenia, with motor side effects that are indistinguishable from those associated with placebo.

Different side effect profiles of risperidone and clozapine in 20 outpatients with schizophrenia or schizoaffective disorder: a pilot study.

OBJECTIVE: The purpose of this study was to compare the side effect +profiles of clozapine and risperidone. METHOD: The subjects were 20 outpatients with schizophrenia or schizoaffective disorder who were clinically stable on a regimen of clozapine at the time of screening. They underwent a randomized-order crossover comparison of 6 weeks of risperidone treatment and 6 weeks of clozapine treatment. Clinical and neurocognitive variables were assessed by raters blind to medication status, and severity of side effects was determined from patients' self-reports. RESULTS: Side effect measures, but not clinical ratings, were significantly different after 6 weeks of treatment with the two drugs. Patients required more benztropine for motor effects and complained of more insomnia with risperidone and more sedation with clozapine. Body weight was higher at the end of clozapine treatment than at the end of risperidone treatment. CONCLUSIONS: In this exploratory study, the side effect profiles of clozapine and risperidone were consistent with the different pharmacodynamic profiles of the two drugs.