***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more .  ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas 49 patients have been treated for 12 weeks with loxapine and thioridazine in a double-blind study . The evaluation was carried out with a covariance analysis with B.P.R.S. and NOSIE as bases and a variance analysis concerning the general clinical improvement . With 36 schizophrenics , the two treatments have shown significant and similar general improvement as early as the second week , and this in particular with all the factors and most of the items of the B.P.R.S. with 13 psychotic not schizophrenic patients , the covariance analysis showed that the results ( improvement of all the factors , with most of the items and in the total score of the B.P.R.S. ) , while comparable , were slightly in favour of loxapine for the item " disorientation " , for " disturbance of thought " , and " excitement-disorientation " , for the final score of B.P.R.S. , for the general and clinical improvement and for the alteration of the initial degree of severity . The analysis of the NOSIE showed a significant improvement which is similar for both treatments Newly admitted paranoid schizophrenic patients ( N = 68 ) were treated with either loxapine or chlorpromazine for up to 4 weeks . Mean maximum dosages were 84 mg/day of loxapine and 820 mg/day of chlorpromazine . Loxapine  showed efficacy superior to that of chlorpromazine , confirming earlier retrospective findings . Adverse reactions were also less troublesome with loxapine A double-blind , r and omized , multicentre trial was carried out in 47 psychotic patients to evaluate the efficacy of oral treatment with loxapine compared with perphenazine . In total , 22 patients were included in diagnostic Group I ( cases of acute schizophrenia and psychogenic ( reactive ) psychoses ) . The average maximum daily dose was 60.0 mg in the loxapine group and 36.8 mg in the perphenazine group . After 3-weeks ' treatment , no significant differences were found between the two treatment groups according to the Brief Psychiatric Rating Scale ( BPRS ) , Clinical Global Impression ( CGI ) Scale or side-effect records .  Twenty-five patients were included in diagnostic Group II ( cases of chronic schizophrenia ) . The average daily dosage was 81.1 mg in the loxapine group and 90.1 mg in the perphenazine group . After 10 to 12-weeks ' treatment , no significant differences between the two treatment groups could be found according to BPRS , CGI scale , Nurses ' Observation Scale for In-patient Evaluation ( NOSIE ) or side-effect records . The diastolic blood pressure ( lying and st and ing ) tended to increase slightly in both treatment groups . In conclusion , it was found that loxapine and perphenazine seemed to be equally effective and , based on experience with parenteral loxapine treatment , it is suggested that further investigation of oral loxapine should be carried out in psychotic patients in whom agitation is a feature The intramuscular and oral forms of loxapine succinate were compared in their clinical , side effect , and blood level characteristics in ten hospitalized chronic schizophrenic patients . The first phase of the study determined the single dose that produced moderate sedation ( i.e. , the sedation threshold ) , and this dose was essentially the same for the two forms . Continuous administration of the two forms using the individualized sedation threshold dosage also failed to indicate any clinical or side effect differences in the two forms . The blood level characteristics , however , did differ between the two forms . The kinetic studies indicated that there was a larger area under the loxapine curve with the intramuscular form than with the oral form , while the 8-OH loxapine area was larger with the oral form . The steady-state studies also showed that the i.m . form had higher loxapine levels than the oral form . The significance of these findings , both clinical ly and in terms of the relative activity of loxapine and its metabolites , is discussed Controlled clinical trials of the treatment of acute myocardial infa rct ion offer a unique opportunity for the study of the potential influence on outcome of bias in treatment assignment . A group of 145 papers was divided into those in which the r and omization process was blinded ( 57 papers ) , those in which it may have been unblinded ( 45 papers ) , and those in which the controls were selected by a nonr and om process ( 43 papers ) . At least one prognostic variable was maldistributed ( P less than 0.05 ) in 14.0 per cent of the blinded-r and omization studies , in 26.7 per cent of the unblinded-r and omization studies , and in 58.1 per cent of the nonr and omized studies . Differences in case-fatality rates between treatment and control groups ( P less than 0.05 ) were found in 8.8 per cent of the blinded-r and omization studies , 24.4 per cent of the unblinded-r and omization studies , and 58.1 per cent of the nonr and omized studies . These data emphasize the importance of keeping those who recruit patients for clinical trials from suspecting which treatment will be assigned to the patient under consideration A combined analysis of data from 11 controlled studies of loxapine versus either chlorpromazine or trifluoperazine in acute schizophrenia ( 5 studies ) and chronic schizophrenia ( 6 studies ) showed statistically significant superiority of loxapine on several items and factors of st and ardized psychiatric rating scales . Upon review of these findings , it was observed that the rating scale symptoms for which loxapine appeared superior to the reference compounds could , in the main , be considered a broad paranoid “ cluster ” . The data were then reanalyzed to detect possible differences in efficacy of loxapine versus the reference compounds in those patients with a clinical diagnosis of schizophrenia , paranoid type and in those patients of any diagnostic subtype other than paranoid . Results of these analyses demonstrated clear superiority of loxapine in paranoid schizophrenic patients ; nonparanoid patients  responded at least equally as well to loxapine as to the reference compounds . Findings could not be attributed to inadequate dosages of the reference compounds or ine quality of treatment groups at baseline A comparison of loxapine and haloperidol parenterally in acute psychotic , agitated patients was carried out as a r and omized double‐blind trial . The trial covered 15 patients in each group , and the diagnoses were psychogenic psychosis ( 18 cases ) and acute schizophrenia ( 12 cases ) . The patients received 25–50 mg loxapine or 2.5–5 mg haloperidol combined with biperiden 2.5–5 mg every 6–12 hours over a 72‐hour period . The average daily dose was 130 mg loxapine or 12 mg haloperidol The st and ard drug Stelazine ( STEL ) , at a dose of 50 mg/day , exhibited therapeutic activity significantly different from placebo ( PL ) activity on several variables , most notably BPRS , attesting to the sensitivity of the experiment . On the other h and , the investigational drug , loxapine ( LOX ) , in doses of 100 mg/day for four weeks , could be differentiated from PL as treatment in the described population on only one variable ( NGI-Imp . ) and one item of the BPRS . On several variables , positive trends were noted , but the differences from PL did not attain the critical values necessary for statistical significance at P smaller than 0.05 . One might speculate that the relatively short duration of treatment in this study might account for the difference between these disappointing results and the more gratifying results of a previous loxapine study in chronic long-term institutionalized schizophrenics with the same oral dose The authors compared loxapine with chlorpromazine in in patients with paranoid schizophrenia and found no difference in clinical efficacy . Thus a previous finding , based on retrospective analyses , that loxapine was superior to other neuroleptics in the treatment of paranoid schizophrenia was not verified in this prospect i ve study In a parallel groups , double-blind study , 54 acutely psychotic schizophrenics were given loxapine or haloperidol parenterally for 24 to 72 hours , then orally for a total study period of up to 10 days . Dosage ratios of loxapine to haloperidol ranged from a minimum of 2.7:1 to a maximum of 4.4:1 . Both groups showed significant and rapid improvement from baseline . Forty-eight percent of the loxapine patients and 33 % of the haloperidol patients achieved and maintained a global severity of illness rating of mild or better . By the end of the study , 84 % of the loxapine patients and 63 % of the haloperidol patients had achieved an improvement rating of moderate or marked . This difference approached significance ( p less than .10 ) . The most frequently reported adverse experiences were dystonic reactions and akathisia . The number and severity of adverse experiences did not differ significantly between drug groups . Intramuscular loxapine was at least as effective as haloperidol in the initial management of hostile and aggressive schizophrenic patients . The maintenance of therapeutic response after conversion to oral concentrate was comparable with the two drugs BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales  were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials A double-blind comparative trial of loxapine and trifluoperazine was carried out in 57 acute and chronic schizophrenic patients . In both groups of patients loxapine proved to be equivalent in its effects to trifluoperazine and there were suggestions it might be rather more effective in chronic patients . Side-effects were simitar with the two drugs but anticholinergic effects , excitement , dizziness and faintness occurred rather more commonly with loxapine . Laboratory tests , urine analysis , cardiovascular and ophthalmological investigations showed no significant abnormalities Two double-blind trials comparing loxapine and thioridazine were conducted in hospitalized adult males diagnosed as having symptoms of chronic psychosis associated with organic brain syndrome or mental retardation . The drugs were administered orally in the ranges of loxapine 10–150 mg/day and thioridazine 150–750 mg/day for 13 weeks . In the first trial loxapine was found to be generally superior to thioridazine on the Brief Psychiatric Rating Scale , Nurses Observation Scale for Inpatient Evaluation and Clinical Global Impression . The second trial failed to confirm this superiority . The heterogeneity of diagnostic categories included may explain the discrepancy . Extra-pyramidal symptoms and sedative effects were common to both groups and consistent with the pharmacologic profiles of the study drugs A study was conducted evaluating the efficacy of loxapine succinate in newly admitted schizophrenic patients through a four-week double-blind comparison with trifluoperazine .  Twenty-four patients received between 40 and 80 mg loxapine succinate daily and 19 patients received between 20 and 50 mg trifluoperazine daily . The two groups showed comparable significant improvement on the BPRS and CGI . The discharge and termination rates of the two groups were not significantly different and the incidence and severity of side effects , most frequently extrapyramidal signs , were similar in both groups . Loxapine succinate was judged to be an effective treatment for newly admitted schizophrenic patients 
    Output:
    
Very limited heterogeneous data suggest that , given intramuscularly ( IM ) , loxapine may be at least as sedating as IM haloperidol and thiothixene .
REVIEW ER 'S CONCLUSIONS Loxapine is antipsychotic but its effects are under research ed .
It is not clearly different from typical drugs in either its positive or adverse effects