Classification of all pharmacological interventions tested in trials relevant to people with schizophrenia: A study-based analysis.

BACKGROUND: Systematic reviewing is a time-consuming and resource-intensive process. Information specialists are maintaining study-based registers to facilitate efficient conduct of systematic reviews. Classification of study-level meta-data -such as interventions -can result in much more accurate searches, saving time in the early steps of systematic reviewing. OBJECTIVE: To classify all pharmacological interventions from all schizophrenia trials. METHODS: We used Cochrane Schizophrenia's Study-based Register as the source of trials, Emtree and MeSH for synonyms, AdisInsight and CT.gov for research drugs and WHO ATC for marketed drugs. RESULTS: One third of tested interventions on patients with schizophrenia are pharmacological (816; belonging to 106 clinical classes) with antipsychotic drugs being the most researched (15.1%). Only 528 of these medications are listed in WHO ATC. Around one third of these drug interventions are seen only in research (236; from 21 pharmacological/biochemical classes). Within the pharmacological interventions, we identified 28 'qualifiers' including dose, route and timing of drug delivery. CONCLUSION: Identification and classification of pharmacological interventions from trials require use of many sources of information none of which are inclusive of all drugs. Limitations of each source are helpful to understand. Classification of non-pharmacological interventions is now a priority for clinical and information scientists and professionals.

Rapid tranquillisation in a psychiatric emergency hospital in Lebanon: TREC-Lebanon - a pragmatic randomised controlled trial of intramuscular haloperidol and promethazine v. intramuscular haloperidol, promethazine and chlorpromazine.

BACKGROUND: Agitated patients constitute 10% of all emergency psychiatric treatment. Management guidelines, the preferred treatment of clinicians differ in opinion and practice. In Lebanon, the use of the triple therapy haloperidol plus promethazine plus chlorpromazine (HPC) is frequently used but no studies involving this combination exists. METHOD: A pragmatic randomised open trial (September 2018-July 2019) in the Lebanese Psychiatric Hospital of the Cross in Beirut Lebanon involving 100 people requiring urgent intramuscular sedation due to aggressive behaviour were given intramuscular chlorpromazine 100 mg plus haloperidol 5 mg plus promethazine 25 mg (HPC) or intramuscular haloperidol 5 mg plus promethazine 25 mg. RESULTS: Primary outcome data were available for 94 (94%) people. People allocated to the haloperidol plus promethazine (HP) group showed no clear difference at 20 min compared with patients allocated to the HPC group [relative risk (RR) 0.84, 95% confidence interval (CI) 0.47-1.50]. CONCLUSIONS: Neither intervention consistently impacted the outcome of 'calm', or 'asleep' and had no discernible effect on the use of restraints, use of additional drugs or recurrence. If clinicians are faced with uncertainty on which of the two intervention combinations to use, the simpler HP is much more widely tested and the addition of chlorpromazine adds no clear benefit with a risk of additional adverse effects.

Classification of psychotherapy interventions for people with schizophrenia: development of the Nottingham Classification of Psychotherapies.

BACKGROUND: Currently, there is no accepted system for the classification of psychotherapies for application within systematic reviews. The creation of anuncomplicated, understandable and practical classification system is neccessary for conducting reliable systematic reviews. OBJECTIVE: To devise a system for classification of psychotherapy interventions-for use, initially, in systematic reviews. METHODS: Cochrane Schizophrenia's Register used as the source of randomised controlled trial. After being piloted and refined at least twice, finally we applied it to all relevant trials within the register. Basic statistical data already held within the register were extracted and used to calculate the distribution of schizophrenia research by form of psychotherapy. FINDINGS: The final classification system consisted of six definable broad 'boughs' two of which were further subdivided into 'branches'. The taxonomy accommodated all psychotherapy interventions described in the register. Of the initial 1645 intervention categories within the register, after careful recoding, 539 (33%) were psychotherapies (234 coded as 'Thought/Action' (cognitive & behavioural)-1495 studies; 135 'Cognitive Functioning'-652 studies; 113 'Social'-684 studies; 55 'Humanistic'-272 studies; 23 'Psychoanalytic/dynamic'-40 studies; and 63 'Other'-387 studies). For people with schizophrenia, across categories, the average size of psychotherapy trial is small (107) but there are notable and important exceptions. CONCLUSION: We reported a practical method for categorising psychotherapy interventions in evaluative studies with applications beyond schizophrenia. A move towards consensus on the classification and reporting of psychotherapies is needed. CLINICAL IMPLICATIONS: This classification can aid clinicians, clinical practice guideline developers, and evidence synthesis experts to recognise and compare the interventions from same or different classes.

Adding evidence of the effects of treatments into relevant Wikipedia pages: a randomised trial.

OBJECTIVES: To investigate the effects of adding high-grade quantitative evidence of outcomes of treatments into relevant Wikipedia pages on further information-seeking behaviour by the use of routinely collected data. SETTING: Wikipedia, Cochrane summary pages and the Cochrane Library. DESIGN: Randomised trial. PARTICIPANTS: Wikipedia pages which were highly relevant to up-to-date Cochrane Schizophrenia systematic reviews that contained a Summary of Findings table. INTERVENTIONS: Eligible Wikipedia pages in the intervention group were seeded with tables of best evidence of the effects of care and hyperlinks to the source Cochrane review. Eligible Wikipedia pages in the control group were left unchanged. MAIN OUTCOME MEASURES: Routinely collected data on access to the full text and summary web page (after 12 months). RESULTS: We randomised 70 Wikipedia pages (100% follow-up). Six of the 35 Wikipedia pages in the intervention group had the tabular format deleted during the study but all pages continued to report the same data within the text. There was no evidence of effect on either of the coprimary outcomes: full-text access adjusted ratio of geometric means 1.30, 95% CI: 0.71 to 2.38; page views 1.14, 95% CI: 0.6 to 2.13. Results were similar for all other outcomes, with exception of Altmetric score for which there was some evidence of clear effect (1.36, 95% CI: 1.05 to 1.78). CONCLUSIONS: The pursuit of fair balance within Wikipedia healthcare pages is impressive and its reach unsurpassed. For every person who sought and clicked the reference on the 'intervention' Wikipedia page to seek more information (the primary outcome), many more are likely to have been informed by the page alone. Enriching Wikipedia content is, potentially, a powerful way to improve health literacy and it is possible to test the effects of seeding pages with evidence. This trial should be replicated, expanded and developed. TRIAL REGISTRATION NUMBER: IRCT2017070330407N2.

Introducing RAPTOR: RevMan Parsing Tool for Reviewers.

BACKGROUND: Much effort is made to ensure Cochrane reviews are based on reliably extracted data. There is a commitment to wide access to these data-for novel processing and/or reuse-but delivering this access is problematic. AIM: To describe a proof-of-concept programme to extract, curate and structure data from Cochrane reviews. METHODS: One student of Applied Sciences (16 weeks full time), access to pre-publication review files and use of 'Eclipse' to create an open-access tool (RAPTOR) using the programming language Java. RESULTS: The final software batch processes hundreds of reviews in seconds, extracting all study data and automatically tidying and unifying presentation of data for return into the source review, reuse, or export for novel analyses. CONCLUSIONS: This software, despite being limited, illustrates how the efforts of reviewers meticulously extracting study data can be improved, disseminated and reused with little additional effort.

Study-based registers reduce waste in systematic reviewing: discussion and case report.

BACKGROUND: Maintained study-based registers (SBRs) have, at their core, study records linked to, potentially, multiple other records such as references, data sets, standard texts and full-text reports. Such registers can minimise and refine searching, de-duplicating, screening and acquisition of full texts. SBRs can facilitate new review titles/updates and, within seconds, inform the team about the potential workload of each task. METHODS: We discuss the advantages/disadvantages of SBRs and report a case of how such a register was used to develop a successful grant application and deliver results-reducing considerable redundancy of effort. RESULTS: SBRs saved time in question-setting and scoping and made rapid production of nine Cochrane systematic reviews possible. CONCLUSION: Whilst helping prioritise and conduct systematic reviews, SBRs improve quality. Those funding information specialists for literature reviewing could reasonably stipulate the resulting SBR to be delivered for dissemination and use beyond the life of the project.

A simple formula for enumerating comparisons in trials and network meta-analysis.

We present use of a simple formula to calculate the number of pairwise comparisons of interventions within a single trial or network meta-analyses. We used the data from our previous network meta-analysis to build a study-based register and enumerated the direct pairwise comparisons from the trials therein. We then compared this with the number of comparisons predicted by use of the formula and finally with the reported number of comparisons (indirect or direct) within the network meta-analysis. A total of 133 trials of 8 interventions were selected which included 163 comparisons. The network of these showed 16 unique direct comparisons. The formula predicted an expected 28 indirect or direct comparisons and this is the number that were indeed reported. The formula produces an accurate enumeration of the potential comparisons within a single trial or network meta-analysis. Its use could help transparency of reporting should a shortfall occur between comparisons actually used and the potential total.

Day of the week to tweet: a randomised controlled trial.

OBJECTIVE: To assess the effects of using health social media on different days of the working week on web activity. DESIGN: Individually randomised controlled parallel group superiority trial. SETTING: Twitter and Weibo. PARTICIPANTS: 194 Cochrane Schizophrenia Group full reviews with an abstract and plain language summary web page. There were no human participants. INTERVENTIONS: Three randomly ordered slightly different messages (maximum of 140 characters), each containing a short URL to the freely accessible summary page, were sent on specific times on a single day. Each of these messages sent on Tuesday, Wednesday, Thursday and Friday was compared with the one sent on Monday. OUTCOME: The primary outcome was visits to the relevant Cochrane summary web page at 1 week. Secondary outcomes were other metrics of web activity at 1 week. RESULTS: There was no evidence that disseminating microblogs on different days of the working week resulted in any differences in target website activity as measured by Google Analytics (n=194, all page views, adjusted ratios of geometric means 0.86 (95% CI 0.63 to 1.18), 0.88 (95% CI 0.64 to 1.21), 0.88 (95% CI 0.65 to 1.21), 0.91 (95% CI 0.66 to 1.24) for Tuesday-Friday, respectively, overall p=0.89). There were consistent findings for all outcomes. However, activity on the review site substantially increased compared with weeks preceding the intervention. CONCLUSION: There are no clear differences in the effect when 1 weekday is compared with another, but our study suggests that using microblogging social media such as Twitter and Weibo do increase information-seeking behaviour on health. Tweet any day but do Tweet.

Electroconvulsive therapy for treatment-resistant schizophrenia.

BACKGROUND: Electroconvulsive therapy (ECT) involves the induction of a seizure by the administration of an electrical stimulus via electrodes usually placed bilaterally on the scalp and was introduced as a treatment for schizophrenia in 1938. However, ECT is a controversial treatment with concerns about long-term side effects such a memory loss. Therefore, it is important to determine its clinical efficacy and safety for people with schizophrenia who are not responding to their treatment. OBJECTIVES: Our primary objective was to assess the effects (benefits and harms) of ECT for people with treatment-resistant schizophrenia.Our secondary objectives were to determine whether ECT produces a differential response in people: who are treated with unilateral compared to bilateral ECT; who have had a long (more than 12 sessions) or a short course of ECT; who are given continuation or maintenance ECT; who are diagnosed with well-defined treatment-resistant schizophrenia as opposed to less rigorously defined treatment-resistant schizophrenia (who would be expected to have a greater affective component to their illness). SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials including clinical trial registries on 9 September 2015 and 4 August 2017. There were no limitations on language, date, document type, or publication status for the inclusion of records in the register. We also inspected references of all the included records to identify further relevant studies. SELECTION CRITERIA: Randomised controlled trials investigating the effects of ECT in people with treatment-resistant schizophrenia. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. For binary outcomes, we calculated the risk ratio (RR) and its 95% confidence intervals (CIs), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between the groups and its 95% CIs. We employed the fixed-effect model for all analyses. We assessed risk of bias for the included studies and created 'Summary of findings' tables using the GRADE framework. MAIN RESULTS: We included 15 studies involving 1285 participants (1264 completers with an average age of 18 to 46 years) with treatment-resistant schizophrenia. We rated most studies (14/15, 93.3%) as at high risk of bias due to issues related to the blinding of participants and personnel. Our main outcomes of interest were: (i) clinically important response to treatment; (ii) clinically important change in cognitive functioning; (iii) leaving the study early; (iv) clinically important change in general mental state; (v) clinically important change in general functioning; (vi) number hospitalised; and (vii) death. No trial reported data on death.The included trials reported useable data for four comparisons: ECT plus standard care compared with sham-ECT added to standard care; ECT plus standard care compared with antipsychotic added to standard care; ECT plus standard care compared with standard care; and ECT alone compared with antipsychotic alone.For the comparison ECT plus standard care versus sham-ECT plus standard care, only average endpoint BPRS (Brief Psychiatric Rating Scale) scores from one study were available for mental state; no clear difference between groups was observed (short term; MD 3.60, 95% CI -3.69 to 10.89; participants = 25; studies = 1; very low-quality evidence). One study reported data for service use, measured as number readmitted; there was a clear difference favouring the ECT group (short term; RR 0.29, 95% CI 0.10 to 0.85; participants = 25; studies = 1; low-quality evidence).When ECT plus standard care was compared with antipsychotics (clozapine) plus standard care, data from one study showed no clear difference for clinically important response to treatment (medium term; RR 1.23, 95% CI 0.95 to 1.58; participants = 162; studies = 1; low-quality evidence). Clinically important change in mental state data were not available, but average endpoint BPRS scores were reported. A positive effect for the ECT group was found (short-term BPRS; MD -5.20, 95% CI -7.93 to -2.47; participants = 162; studies = 1; very low-quality evidence).When ECT plus standard care was compared with standard care, more participants in the ECT group had a clinically important response (medium term; RR 2.06, 95% CI 1.75 to 2.42; participants = 819; studies = 9; moderate-quality evidence). Data on clinically important change in cognitive functioning were not available, but data for memory deterioration were reported. Results showed that adding ECT to standard care may increase the risk of memory deterioration (short term; RR 27.00, 95% CI 1.67 to 437.68; participants = 72; studies = 1; very low-quality evidence). There were no clear differences between groups in satisfaction and acceptability of treatment, measured as leaving the study early (medium term; RR 1.18, 95% CI 0.38 to 3.63; participants = 354; studies = 3; very low-quality evidence). Only average endpoint scale scores were available for mental state (BPRS) and general functioning (Global Assessment of Functioning). There were clear differences in scores, favouring ECT group for mental state (medium term; MD -11.18, 95% CI -12.61 to -9.76; participants = 345; studies = 2; low-quality evidence) and general functioning (medium term; MD 10.66, 95% CI 6.98 to 14.34; participants = 97; studies = 2; very low-quality evidence).For the comparison ECT alone versus antipsychotics (flupenthixol) alone, only average endpoint scale scores were available for mental state and general functioning. Mental state scores were similar between groups (medium-term BPRS; MD -0.93, 95% CI -6.95 to 5.09; participants = 30; studies = 1; very low-quality evidence); general functioning scores were also similar between groups (medium-term Global Assessment of Functioning; MD -0.66, 95% CI -3.60 to 2.28; participants = 30; studies = 1; very low-quality evidence). AUTHORS' CONCLUSIONS: Moderate-quality evidence indicates that relative to standard care, ECT has a positive effect on medium-term clinical response for people with treatment-resistant schizophrenia. However, there is no clear and convincing advantage or disadvantage for adding ECT to standard care for other outcomes. The available evidence was also too weak to indicate whether adding ECT to standard care is superior or inferior to adding sham-ECT or other antipsychotics to standard care, and there was insufficient evidence to support or refute the use of ECT alone. More good-quality evidence is needed before firm conclusions can be made.

Study protocol for a randomised controlled trial of haloperidol plus promethazine plus chlorpromazine versus haloperidol plus promethazine for rapid tranquilisation for agitated psychiatric patients in the emergency setting (TREC-Lebanon).

Background: Agitated and aggressive behaviours are common in the psychiatric setting and rapid tranquilisation is sometimes unavoidable. A survey of Lebanese practice has shown that an intramuscular haloperidol, promethazine and chlorpromazine combination is a preferred form of treatment but there are no randomised trials of this triple therapy. Methods: This is a pragmatic randomised trial. Setting - the psychiatric wards of the Psychiatric Hospital of the Cross, Jal Eddib, Lebanon. Participants - any adult patient in the hospital who displays an aggressive episode for whom rapid tranquilisation is unavoidable, who has not been randomised before, for whom there are no known contraindications. Randomisation - stratified (by ward) randomisation and concealed in closed opaque envelope by independent parties. Procedure - if the clinical situation arises requiring rapid tranquilisation, medical residents overseeing the patient will open a TREC-Lebanon envelope in which will be notification of which group of treatments should be preferred [Haloperidol + Promethazine + Chlorpromazine (HPC) or Haloperidol + Promethazine (HP)], along with forms for primary, secondary and serious adverse effects. Treatment is not given blindly. Outcome - primary outcome is calm or tranquil at 20 minutes post intervention. Secondary outcomes are calm/tranquil at 40, 60 and 120 minutes post intervention, asleep, adverse effects, use of straitjacket and leaving the ward. Follow-up will be up to two weeks post randomisation. Discussion: Findings from this study will compare the HPC versus HP combination used in Lebanon's psychiatry emergency routine practice. Trial registration: ClinicalTrials.gov NCT03639558. Registration date, August 21, 2018.

The pharmacological management of acute behavioural disturbance: Data from a clinical audit conducted in UK mental health services.

BACKGROUND: A quality improvement programme addressing prescribing practice for acutely disturbed behaviour was initiated by the Prescribing Observatory for Mental Health. METHOD: This study analysed data from a baseline clinical audit conducted in inpatient mental health services in member trusts. RESULTS: Fifty-eight mental health services submitted data on 2172 episodes of acutely disturbed behaviour. A benzodiazepine alone was administered in 60% of the 1091 episodes where oral medication only was used and in 39% of the 1081 episodes where parenteral medication (rapid tranquillisation) was used. Haloperidol was combined with lorazepam in 22% of rapid tranquillisation episodes and with promethazine in 3%. Physical violence towards others was strongly associated with receiving rapid tranquillisation in men (odds ratio 1.74, 1.25-2.44; p<0.001) as was actual or attempted self-harm in women (odds ratio 1.87, 1.19-2.94; p=0.007). Where physical violence towards others was exhibited, a benzodiazepine and antipsychotic was more likely to be prescribed than a benzodiazepine alone (odds ratio 1.39, 1.00-1.92; p=0.05). The data suggested that 25% of patients were at least 'extremely or continuously active' in the hour after rapid tranquillisation was administered. CONCLUSION: The current management of acutely disturbed behaviour with parenteral medication may fail to achieve a calming effect in up to a quarter of episodes. The most common rapid tranquillisation combination used was lorazepam and haloperidol, for which the randomised controlled trial evidence is very limited. Rapid tranquillisation prescribing practice was not wholly consistent with the relevant National Institute for Health and Care Excellence guideline, which recommends intramuscular lorazepam on its own or intramuscular haloperidol combined with intramuscular promethazine. Clinical factors prompting the use of rapid tranquillisation rather than oral medication may differ between the genders.

Physical health monitoring after rapid tranquillisation: clinical practice in UK mental health services.

BACKGROUND: We aimed to assess the quality of physical health monitoring following rapid tranquillisation (RT) for acute behavioural disturbance in UK mental health services. METHODS: The Prescribing Observatory for Mental Health (POMH-UK) initiated an audit-based quality improvement programme addressing the pharmacological treatment of acute behavioural disturbance in mental health services in the UK. RESULTS: Data relating to a total of 2454 episodes of RT were submitted by 66 mental health services. Post-RT physical health monitoring did not reach the minimum recommended level in 1933 (79%) episodes. Patients were more likely to be monitored (OR 1.78, 95% CI 1.39-2.29, p < 0.001) if there was actual or threatened self-harm, and less likely to be monitored if the episode occurred in the evening (OR 0.79, 95% CI 0.62-1.0, p < 0.001) or overnight (OR 0.57, 95% CI 0.44-0.75, p < 0.001). Risk factors such as recent substance use, RT resulting in the patient falling asleep, or receiving high-dose antipsychotic medication on the day of the episode, did not predict whether or not the minimum recommended level of post-RT monitoring was documented. CONCLUSIONS: The minimum recommended level of physical health monitoring was reported for only one in five RT episodes. The findings also suggest a lack of targeting of at-risk patients for post-RT monitoring. Possible explanations are that clinicians consider such monitoring too demanding to implement in routine clinical practice or not appropriate in every clinical situation. For example, physical health measures requiring direct contact with a patient may be difficult to undertake, or counter-productive, if RT has failed. These findings prompt speculation that post-RT monitoring practice would be improved by the implementation of guidance that integrated and refined the currently separate systems for undertaking and recording physical health observations post-RT, determining nursing observation schedules and detecting acute deterioration in physical health. The effectiveness and clinical utility of such an approach would be worth testing.

Managing acutely aggressive or agitated people in a psychiatric setting: a survey in Lebanon.

Background: Violent patients constitute 10% of all psychiatric admissions. Treatment options and clinical practice interventions vary across the globe and no survey of practice in a Middle Eastern setting exists. Surveying treatments in Lebanon will show treatment interventions used in this part of the world and, most importantly, provide the treatment options that could potentially be used for clinical trials pertaining to emergency psychiatry. Methods: A survey of clinicians' opinions and practice was conducted between July and August 2017 at the largest psychiatric hospital in Lebanon. Results: Five of seven experienced psychiatrists provided opinions when interviewed of their preferred intervention when dealing with an emergency psychiatric episode. Whilst this varied in detail, there was a consistent view that there should first be verbal control, then use of medications, and finally physical restrain of the patient. A total of 39 emergency episodes (28 people) occurred in the one month (64% men in their 30s). Bipolar disorder was the most frequent single diagnosis behind the aggression (n=16, 41%; 12 people 43%) but the combined schizophrenia-like illnesses underlay 18 of the 39 episodes (46%; 13/28 people 46%). In clinical life, we found evidence of high family involvement, but little attempts made at initial verbal control in the hospital. All 39 episodes involved administration of pharmacological interventions. Medications were used in 29 of cases (74%) and non-medication interventions used in the remaining 10/39 (26%). Conclusion: This survey provides some evidence that clinicians' preferences may not fully reflect clinical practice but also that experienced clinicians are using several clearly effective techniques to manage these very difficult situations. However, as for other parts of the world, treatment in Lebanon has limited or no underpinning by evidence from well-designed, conducted and reported evaluative studies.

Risperidone for psychosis-induced aggression or agitation (rapid tranquillisation).

BACKGROUND: Aggressive, agitated or violent behaviour due to psychosis constitutes an emergency psychiatric treatment where fast-acting interventions are required. Risperidone is a widely accessible antipsychotic that can be used to manage psychosis-induced aggression or agitation. OBJECTIVES: To examine whether oral risperidone alone is an effective treatment for psychosis-induced aggression or agitation. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (up to April 2017); this register is compiled by systematic searches of major resources (including AMED, BIOSIS CINAHL, Embase, MEDLINE, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings. There are no language, date, document type, or publication status limitations for inclusion of records into the register. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing rapid use of risperidone and other drugs, combinations of drugs or placebo for people exhibiting aggression or agitation (or both) thought to be due to psychosis. DATA COLLECTION AND ANALYSIS: We independently inspected all citations from searches, identified relevant abstracts, and independently extracted data from all included studies. For binary data we calculated risk ratio (RR) and for continuous data we calculated mean difference (MD), all with 95% confidence intervals (CI) and used a fixed-effect model. We assessed risk of bias for the included studies and used the GRADE approach to produce a 'Summary of findings' tables. MAIN RESULTS: The review now contains data from nine trials (total n = 582) reporting on five comparisons. Due to risk of bias, small size of trials, indirectness of outcome measures and a paucity of investigated and reported 'pragmatic' outcomes, evidence was graded as very-low quality. None of the included studies provided useable data on our primary outcome 'tranquillisation or asleep' by 30 minutes, repeated need for tranquillisation or any economic outcomes. Data were available for our other main outcomes of agitation or aggression, needing restraint, and incidence of adverse effects.Risperidone versus haloperidol (up to 24 hours follow-up)For the outcome, specific behaviour - agitation, no clear difference was found between risperidone and haloperidol in terms of efficacy, measured as at least 50% reduction in the Positive and Negative Syndrome Scale - Psychotic Agitation Sub-score (PANSS-PAS) (RR 1.04, 95% CI 0.86 to 1.26; participants = 124; studies = 1; very low-quality evidence) and no effect was observed for need to use restraints (RR 2.00, 95% CI 0.43 to 9.21; participants = 28; studies = 1; very low-quality evidence). Incidence of adverse effects was similar between treatment groups (RR 0.94, 95% CI 0.54 to 1.66; participants = 124; studies = 1; very low-quality evidence).Risperidone versus olanzapineOne small trial (n = 29) reported useable data for the comparison risperidone versus olanzapine. No effect was observed for agitation measured as PANSS-PAS endpoint score at two hours (MD 2.50, 95% CI -2.46 to 7.46; very low-quality evidence); need to use restraints at four days (RR 1.43, 95% CI 0.39 to 5.28; very-low quality evidence); specific movement disorders measured as Behavioural Activity Rating Scale (BARS) endpoint score at four days (MD 0.20, 95% CI -0.43 to 0.83; very low-quality evidence).Risperidone versus quetiapineOne trial reported (n = 40) useable data for the comparison risperidone versus quetiapine. Aggression was measured using the Modified Overt Aggression Scale (MOAS) endpoint score at two weeks. A clear difference, favouring quetiapine was observed (MD 1.80, 95% CI 0.20 to 3.40; very-low quality evidence). No evidence of a difference between treatment groups could be observed for incidence of akathisia after 24 hours (RR 1.67, 95% CI 0.46 to 6.06; very low-quality evidence). Two participants allocated to risperidone and one allocated to quetiapine experienced myocardial ischaemia during the trial.Risperidone versus risperidone + oxcarbazepineOne trial (n = 68) measured agitation using the Positive and Negative Syndrome Scale - Excited Component.(PANSS-EC) endpoint score and found a clear difference, favouring the combination treatment at one week (MD 2.70, 95% CI 0.42 to 4.98; very low-quality evidence), but no effect was observed for global state using Clinical Global Impression - Improvement (CGI-I) endpoint score at one week (MD -0.20, 95% CI -0.61 to 0.21; very-low quality evidence). Incidence of extrapyramidal symptoms after 24 hours was similar between treatment groups (RR 1.59, 95% CI 0.49 to 5.14; very-low quality evidence).Risperidone versus risperidone + valproic acidTwo trials compared risperidone with a combination of risperidone plus valproic acid. No clear differences between the treatment groups were observed for aggression (MOAS endpoint score at three days: MD 1.07, 95% CI -0.20 to 2.34; participants = 54; studies = 1; very low-quality evidence) or incidence of akathisia after 24 hours: RR 0.75, 95% CI 0.28 to 2.03; participants = 122; studies = 2; very low-quality evidence). AUTHORS' CONCLUSIONS: Overall, results for the main outcomes show no real effect for risperidone. The only data available for use in this review are from nine under-sampled trials and the evidence available is of very low quality. This casts uncertainty on the role of risperidone in rapid tranquillisation for people with psychosis-induced aggression. High-quality pragmatic RCTs are feasible and are needed before clear recommendations can be drawn on the use of risperidone for psychosis-induced aggression or agitation.

Calcium channel blockers for antipsychotic-induced tardive dyskinesia.

BACKGROUND: Schizophrenia and related disorders affect a sizable proportion of any population. Antipsychotic medications are the primary treatment for these disorders. Antipsychotic medications are associated with a variety of adverse effects including tardive dyskinesia. Dyskinesia is a disfiguring movement disorder of the orofacial region that can be tardive (having a slow or belated onset). Tardive dyskinesia is difficult to treat, despite experimentation with several treatments. Calcium channel blockers (diltiazem, nifedipine, nimodipine, verapamil, flunarizine) have been among these experimental treatments. OBJECTIVES: To determine the effects of calcium channel blocker drugs (diltiazem, nifedipine, nimodipine, verapamil) for treatment of neuroleptic-induced tardive dyskinesia in people with schizophrenia, schizoaffective disorder or other chronic mental illnesses. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (July 2015 and April 2017), inspected references of all identified studies for further trials and contacted authors of trials for additional information. SELECTION CRITERIA: We selected randomised controlled trials comparing calcium channel blockers with placebo, no intervention or any other intervention for people with both tardive dyskinesia and schizophrenia or serious mental illness who remained on their antipsychotic medication. DATA COLLECTION AND ANALYSIS: We independently extracted data and estimated risk ratios of dichotomous data or mean differences (MD) of continuous data, with 95% confidence intervals (CI). We assumed that people who left the trials early had no improvement. We also created a 'Summary of findings' table using GRADE. MAIN RESULTS: Previous versions of this review included no trials. From the 2015 search, we identified three cross-over trials that could be included. The 2017 search found no new studies relevant to this review. The included trials randomised 47 inpatients with chronic mental illnesses in the USA and China. Trials were published in the 1990s and were of short duration (six to 10 weeks). Overall, the risk of bias was unclear, mainly due to poor reporting; allocation concealment was not described, generation of the sequence was not explicit, studies were not clearly blinded, and attrition and outcome data were not fully reported. Findings were sparse, no study reported on the primary outcome 'no clinically important improvement in tardive dyskinesia symptoms,' but two small studies (37 participants) found no difference on the tardive dyskinesia symptoms scale Abnormal Involuntary Movement Scale (AIMS) scores between diltiazem or flunarizine and placebo after three to four weeks' treatment (MD -0.71, 95% CI -2.68 to 1.26, very low quality evidence). Only one study randomising 20 participants reported on adverse events, and reported that there were no adverse events with flunarizine or with placebo (very low quality evidence). One study with 18 participants reported no events of deterioration in mental state with diltiazem or with placebo (very low quality evidence). No studies reported on acceptability of treatment or on social confidence, social inclusion, social networks or personalised quality of life outcomes designated important to patients. AUTHORS' CONCLUSIONS: Available evidence from randomised controlled trials is extremely limited and very low quality, conclusions cannot be drawn. The effects of calcium channel blockers for antipsychotic-induced tardive dyskinesia are unknown. Their use is experimental and should only be given in the context of well-designed randomised trials.

Monitoring oral health of people in Early Intervention for Psychosis (EIP) teams: The extended Three Shires randomised trial.

BACKGROUND: The British Society for Disability and Oral Health guidelines made recommendations for oral health care for people with mental health problems, including providing oral health advice, support, promotion and education. The effectiveness of interventions based on these guidelines on oral health-related outcomes in mental health service users is untested. OBJECTIVE: To acquire basic data on the oral health of people with or at risk of serious mental illness. To determine the effects of an oral health checklist in routine clinical practice. DESIGN: Clinician and service user-designed cluster randomised trial. SETTINGS AND PARTICIPANTS: The trial compared a simple form for monitoring oral health care with standard care (no form) for outcomes relevant to service use and dental health behaviour for people with suspected psychosis in Mid and North England. Thirty-five teams were divided into two groups and recruited across 2012-3 with one year follow up. RESULTS: 18 intervention teams returned 882 baseline intervention forms and 274 outcome sheets one year later (31%). Control teams (n=17) returned 366 baseline forms. For the proportion for which data were available at one year we found no significant differences for any outcomes between those allocated to the initial monitoring checklist and people in the control group (Registered with dentist (p=0.44), routine check-up within last year (p=0.18), owning a toothbrush (p=0.99), cleaning teeth twice a day (p=0.68), requiring urgent dental treatment (p=0.11). CONCLUSION: This trial provides no clear evidence that Care Co-ordinators (largely nursing staff) using an oral health checklist improves oral health behaviour or oral health state in those thought to be at risk of psychosis or with early psychosis.

SEED: a tool for disseminating systematic review data into Wikipedia.

Wikipedia, the free-content online encyclopaedia, contains many heavily accessed pages relating to healthcare. Cochrane systematic reviews contain much high-grade evidence but dissemination into Wikipedia has been slow. New skills are needed to both translate and relocate data from Cochrane reviews to implant into Wikipedia pages. This letter introduces a programme to greatly simplify the process of disseminating the summary of findings of Cochrane reviews into Wikipedia pages.