John Rathbone

Bio: John Rathbone is an academic researcher from Bond University. The author has contributed to research in topics: Number needed to treat & Randomized controlled trial. The author has an hindex of 29, co-authored 47 publications receiving 3392 citations. Previous affiliations of John Rathbone include University of Nottingham & University of Leeds.

Family intervention for schizophrenia

Abstract: Background People with schizophrenia from families that express high levels of criticism, hostility, or over involvement, have more frequent relapses than people with similar problems from families that tend to be less expressive of emotions. Forms of psychosocial intervention, designed to reduce these levels of expressed emotions within families, are now widely used. Objectives To estimate the effects of family psychosocial interventions in community settings for people with schizophrenia or schizophrenia-like conditions compared with standard care. Search methods We updated previous searches by searching the Cochrane Schizophrenia Group Trials Register (September 2008). Selection criteria We selected randomised or quasi-randomised studies focusing primarily on families of people with schizophrenia or schizoaffective disorder that compared community-orientated family-based psychosocial intervention with standard care. Data collection and analysis We independently extracted data and calculated fixed-effect relative risk (RR), the 95% confidence intervals (CI) for binary data, and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated mean differences (MD). Main results This 2009-10 update adds 21 additional studies, with a total of 53 randomised controlled trials included. Family intervention may decrease the frequency of relapse (n = 2981, 32 RCTs, RR 0.55 CI 0.5 to 0.6, NNT 7 CI 6 to 8), although some small but negative studies might not have been identified by the search. Family intervention may also reduce hospital admission (n = 481, 8 RCTs, RR 0.78 CI 0.6 to 1.0, NNT 8 CI 6 to 13) and encourage compliance with medication (n = 695, 10 RCTs, RR 0.60 CI 0.5 to 0.7, NNT 6 CI 5 to 9) but it does not obviously affect the tendency of individuals/families to leave care (n = 733, 10 RCTs, RR 0.74 CI 0.5 to 1.0). Family intervention also seems to improve general social impairment and the levels of expressed emotion within the family. We did not find data to suggest that family intervention either prevents or promotes suicide. Authors' conclusions Family intervention may reduce the number of relapse events and hospitalisations and would therefore be of interest to people with schizophrenia, clinicians and policy makers. However, the treatment effects of these trials may be overestimated due to the poor methodological quality. Further data from trials that describe the methods of randomisation, test the blindness of the study evaluators, and implement the CONSORT guidelines would enable greater confidence in these findings.

Early Intervention for Psychosis

Abstract: Background Proponents of early intervention have argued that outcome might be improved if more therapeutic effort were focused on the early stages of schizophrenia. Early intervention in schizophrenia has two elements that are distinct from standard care: early detection and phase-specific treatment. Both elements may be offered in addition to standard care, or may be provided by a specialised early intervention team. Early intervention is now well established as a therapeutic approach in America, Europe and Australasia, but it is unclear how far early detection, phase-specific treatments, and the use of early intervention teams are underpinned by evidence of effectiveness. Objectives This review aims to evaluate the effects of: i. early detection and treatment of people with prodromal symptoms; ii. the use of early intervention teams for people in their first episode of psychosis; and iii. phase-specific treatments for people in their first episode of psychosis. Search strategy We searched CINAHL (1982-2002), The Cochrane Controlled Trials Register (November 2001), The Cochrane Schizophrenia Group Register (July 2003), EMBASE (1980-2002), MEDLINE (1966-2002), PsycINFO (1967-2002), reference lists and contacted the European First Episode Network (2003). Selection criteria Randomised controlled trials designed to prevent progression to psychosis in people showing prodromal symptoms, or improve outcome for people with first episode psychosis. Eligible interventions, alone and in combination, included early detection, phase-specific treatments, and care from specialised early intervention teams. Non-randomised trials would only have been included if they had been studies of the effects of early detection strategies in reducing the duration of untreated psychosis (since this issue cannot be addressed by simple randomisation). Data collection and analysis Data were extracted independently by two reviewers and cross-checked. Relative risks (RR) and 95% confidence intervals (CI) were calculated for dichotomous data. Weighted mean differences (WMD) were calculated for continuous data. Main results In theory, seventeen different comparisons are possible, but the review only identified three studies that met inclusion criteria. One small trial (n=59) was concerned with a phase-specific intervention (low dose risperidone and cognitive behavioural therapy) for people with prodromal symptoms. This group were significantly less likely to develop psychosis at 6 month follow up than people who only received care from a specialised team which did not involve phase-specific treatment (n=59, 1 RCT, RR 0.27 CI 0.08 to 0.89, NNT 4 CI 2 to 20). This effect was not significant at 12 month follow up (n=59, 1 RCT, RR 0.54 CI 0.23 to 1.30). Another trial found that people in their first episode receiving a phase-specific intervention (family therapy) plus out patient care did have reduced admission rates care compared with those who received only outpatient care (n=83, 1 RCT, RR 0.28 CI 0.13 to 0.62, NNT 3 CI 2 to 6). The applicability of this finding was, however, questionable.Finally, one last study (n=76), comparing phase-specific intervention (family therapy) plus specialised team with specialised team for people in their first episode of schizophrenia found no difference between intervention and control groups at 12 months for the outcome of relapse but confidence intervals were wide (n=76, RR 1.06 CI 0.31 to 3.65). Reviewers' conclusions We identified insufficient trials to draw any definitive conclusions, although five ongoing trials should report shortly. The substantial international interest in early intervention offers an opportunity to make major positive changes in psychiatric practice, but this opportunity may be missed without a concerted international programme of research to address key unanswered questions.

Clozapine versus typical neuroleptic medication for schizophrenia.

Abstract: Summary of findings for the main comparison CLOZAPINE versus TYPICAL ANTIPSYCHOTICS -OVERALL for schizophrenia; Summary of findings 2 CLOZAPINEversusTYPICALANTIPSYCHOTICS forpeoplewithschizophreniawhose illnesshasprovedresistant totreatment1. COMPARISON 1. CLOZAPINE versus TYPICAL AN-TIPSYCHOTIC DRUGS - OVERALLAll data are derived from 50 studies.1.1 DeathFour deathsoccurredin614peopletreatedwithtypicalneurolep-tics compared with three deaths in 629 people treatedwith cloza-pine. There were no significant differences in mortality betweengroups (n=1243, 12 RCTs, RR 0.56 CI 0.1 to 2.3).1.2 Relapse rateWe included 19 short-term studies, and found incidences of re-lapse werelowerin theclozapine group (n=1303, RR 0.62 CI0.5to0.8,NNT21CI15to49)comparedwithtypicalantipsychoticdrugs. Long-term data (4 RCTs, n=578) also favoured clozapinebut data were heterogeneous (I-squared =76%) (RR 0.22 CI 0.1to 0.3).1.3 Global impression1.3.1 Clinical improvement as defined by study authorsWefound thatthenumber ofparticipants whohadnot improvedwere lower in the clozapine group (n=1119, 14 RCTs, RR 0.72CI 0.7 to 0.8, NNT 6 CI 5 to 8). Three long-term studies alsofavoured clozapine (n=719, RR 0.81 CI 0.7 to 0.9) but the dataare heterogeneous (I-squared statistic 81%).1.3.2 Readiness for hospital dischargeThere were no significant differences between treatment groupsfor the number of participants who were judged to be not readyfordischarge(short-term,n=447,5RCTs,RR0.88CI0.8to1.0).Long-termdataalsofailedtoshowasignificant difference(n=648,2 RCTs, RR 0.82 CI 0.6 to 1.1).1.4 Hospitalisation - Not discharged or readmitted within oneyear after dischargeData were available from two long-term studies (Essock 1996(H/CPZ/Flu),Rosenheck1993(H)),andwefoundnosignificantadvantageforclozapine(n=648,RR0.94CI0.9to1.0)comparedwith typical antipsychotic drugs.1.5 Unable to workWe found no significant difference in the number of participantswho were assessed as being unable to work (n=416, 4 RCTs, RR0.87CI0.8to1.0),althoughthedatasuggestedatrendfavouringclozapine (p=0.06).1.6 Participant dissatisfactionNosignificantdifferenceswerefoundfordissatisfactionwithtreat-mentintwoshort-termstudies(n=114,RR0.72CI0.4to1.3).Wefoundlonger-termdatain(Rosenheck1993(H)).Thesefavouredtheclozapinegroupwhowerelessdissatisfiedwiththeirtreatmentcomparedwithconventionalantipsychoticdrugs(n=423,RR0.45CI 0.3 to 0.8, NNT 13 CI 9 to 37).1.7 Leaving the study early - acceptability of treatmentWe used leaving the study early data as a proxy measure for theacceptability of treatment. Short-term data from 32 studies in-volving 2316 participants indicated that significantly more par-ticipantsgivenclozapinefoundtreatmentacceptable(RR0.81CI0.7 to 1.0, NNT 35 CI 20 to 217). Longer-term data from sixstudies showed a significant benefit in the clozapine group (n=982,RR0.60CI0.5to0.7,NNT15CI12to20).Thelong-termattrition rate fromclozapine treatment isapproximately 33% and56% when treated with typical antipsychotic drugs.1.8 Mental state1.8.1 BPRS and PANSSWe found BPRS mental state scores favoured clozapine duringshort-termassessmentin16studies(n=1205,WMD-3.79CI-4.9to -2.7), although the data were heterogeneous (I squared=69%).Longer-term BPRS data (Lee 1994 (mainly H)) were equivocal(n=52, WMD 0.80 CI -5.7 to 7.3). PANSS scores from threeChinesetrialsfavouredtheclozapinegroups(n=163,WMD-3.82CI -7.4 to -0.3) during short-term analysis. Also, PANSS scoresassessed over the long-term favoured clozapine (Rosenheck 1993(H), n=235, WMD -6.90 CI -10.7 to -3.1).1.8.2 Negative symptomsShort-termcontinuous data on negative symptom scores from sixshort-termtrialswith236participantsfavouredclozapine(SANS,WMD -7.12 CI -8.8 to -5.5) but these are heterogeneous data(Isquared=92%). Longer-termnegativesymptomsscoresassessedwiththePANSSnegativesubscorewerenotsignificantlydifferent(Rosenheck 1993 (H), n=235, WMD -0.90 CI -6.6 to 4.8).1.8.3 Positive symptomsWe found short-term SAPS scores were equivocal (Wang 2001(CPZ), n=60, WMD 4.39 CI -12.2 to 20.9). Longer-term datafrom the PANSS positive scores favoured clozapine (Rosenheck1993 (H), n=235, WMD -2.20 CI -3.3 to -1.1).1.9 Cognitive functionCognitive impairment from one small study (n=82) favoured theclozapine group who experienced less impairment (Klieser 1990(H),RR0.56CI0.3to0.9,NNT4CI3to21)whenassessedwiththe SKT scale compared with those given typical antipsychoticdrugs.Onesmallstudy(Lee1994(mainlyH),n=54)reporteddataon aseriesof cognitive functioning tests(verbal,memory or exec-utive functions etc.) and we found outcomes to be equivocal, ex-cept for ’psychomotor speedand attention’ scoreswhich favouredthe clozapine-treated participants over the three pre-stated cut-off points (short-term, WMD 1.40 CI 0.2 to 2.6, medium-term,WMD1.30CI0.01to3.0,long-term,WMD2.10CI0.8to3.4).Clozapine versus typical neuroleptic medication for schizophrenia (Review)

Olanzapine for schizophrenia.

Abstract: Background Olanzapine is an atypical antipsychotic that is reported to be effective without producing the disabling extrapyramidal side effects associated with the older, typical antipsychotic drugs. Objectives To determine the clinical effects and safety of olanzapine as compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and schizophreniform psychoses. Search strategy The reviewers undertook electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 2, 1999), EMBASE (1980-1999), MEDLINE (1966-1999), PsycLIT (1974-1999) and The Cochrane Schizophrenia Group's Register (October 2000). References of all identified studies were searched for further trials, and the reviewers contacted relevant pharmaceutical companies and authors of trials. Selection criteria All randomised clinical trials comparing olanzapine to placebo or any antipsychotic treatment for those with schizophrenia or schizophreniform psychoses. Data collection and analysis Data were independently extracted. For homogeneous dichotomous data the random effects relative risk (RR), the 95% confidence intervals (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data the reviewers calculated weighted mean differences. Main results Twenty one trials are included. Attrition from olanzapine versus placebo studies was so great (olanzapine - 61%, placebo - 73% by six weeks, RR 0.85 CI 0.7-0.98, NNT 8 CI 5-40) that interpretation of results is problematic. Olanzapine appeared superior to placebo at six weeks for the outcome of 'no important clinical response' (RR 0.88 CI 0.8-0.98, NNT 8 CI 5-27) and global mental state scores. Although dizziness and dry mouth were reported more frequently in the olanzapine-treated group, this did not reach statistical significance. Tthe olanzapine group gained more weight. When compared to typical antipsychotic drugs, data from several small trials are incomplete; but, for the short term outcome of 'no important clinical response', olanzapine seem as effective as typical antipsychotics (n=2778, RR 0.9 CI 0.76-1.06). Brief Psychiatric Rating Scale (BPRS) data tended to be equivocal but Positive and Negative Syndrome Scale (PANSS) rating of total score and negative and positive symptom sub-scores favoured olanzapine. With high attrition in both groups (olanzapine - 36%, typical drug - 49% by 6 weeks, n=2738, RR 0.85 CI 0.66-1.1; olanzapine - 83%, typical drug - 90% by 1 year, n=2738, RR 0.9 CI 0.86-1.02), the assumptions included in all continuous data are considerable. Participants allocated olanzapine experienced fewer extrapyramidal side effects than people given haloperidol. Weight change data for the short term are not conclusive (n=2455, WMD 0.8kg CI -0.6-2.2) but the three to 12 month results suggest an average gain of four kilograms (n=233, WMD 4 CI 0.3-7.8). It is difficult to distinguish between olanzapine and other atypical drugs, although it may cause fewer extrapyramidal side effects than risperidone (n=339, RR 0.6 CI 0.4-0.9, NNH 8 CI 4-29). Olanzapine did cause more weight gain than its comparators but current data are not statistically significant (3-12 months, n=535, WMD 2.2kg CI -0.6-5). One study (n=180) found no clear differences between olanzapine and clozapine for people with treatment-resistant illness. Reviewer's conclusions The large proportions of participants leaving the studies early, in the large multi-centre trials makes it difficult to draw firm conclusions on clinical effects. For people with schizophrenia olanzapine may offer antipsychotic efficacy with fewer extrapyramidal side effects than typical drugs but more weight gain. Large, long-term randomised trials with participants, interventions and primary outcomes that are familiar to those wishing to help those with schizophrenia are long overdue.

A systematic review of the public's knowledge and beliefs about antibiotic resistance

Abstract: Objectives The objective of this study was to systematically review quantitative and qualitative studies on the public's knowledge and beliefs about antibiotic resistance. Methods We searched four databases to July 2014, with no language or study design restrictions. Two reviewers independently extracted data. We calculated the median (IQR) of the proportion of participants who agreed with each statement and synthesized qualitative data by identifying emergent themes. Results Of 3537 articles screened, 54 studies (41 quantitative, 3 mixed methods and 10 qualitative) were included (55 225 participants). Most studied adults (50; 93% studies) and were conducted in Europe (23; 43%), Asia (14; 26%) or North America (12; 22%). Some participants [median 70% (IQR 50%-84%); n = 8 studies] had heard of antibiotic resistance, but most [median 88% (IQR 86%-89%); n = 2 studies] believed it referred to changes in the human body. Many believed excessive antibiotic use [median 70% (IQR 59%-77%); n = 11 studies] and not completing antibiotic courses [median 62% (IQR 47%-77%); n = 8 studies] caused resistance. Most participants nominated reducing antibiotic use [median 74% (IQR 72%-85%); n = 4 studies] and discussing antibiotic resistance with their clinician (84%, n = 1 study) as strategies to reduce resistance. Qualitative data supported these findings and additionally identified that: participants believed they were at low risk from antibiotic resistance participants; largely attributed its development to the actions of others; and strategies to minimize resistance should be primarily aimed at clinicians. Conclusions The public have an incomplete understanding of antibiotic resistance and misperceptions about it and its causes and do not believe they contribute to its development. These data can be used to inform interventions to change the public's beliefs about how they can contribute to tackling this global issue.

Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.

Abstract: Background and Purpose- The purpose of these guidelines is to provide an up-to-date comprehensive set of recommendations in a single document for clinicians caring for adult patients with acute arterial ischemic stroke. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators. These guidelines supersede the 2013 Acute Ischemic Stroke (AIS) Guidelines and are an update of the 2018 AIS Guidelines. Methods- Members of the writing group were appointed by the American Heart Association (AHA) Stroke Council's Scientific Statements Oversight Committee, representing various areas of medical expertise. Members were not allowed to participate in discussions or to vote on topics relevant to their relations with industry. An update of the 2013 AIS Guidelines was originally published in January 2018. This guideline was approved by the AHA Science Advisory and Coordinating Committee and the AHA Executive Committee. In April 2018, a revision to these guidelines, deleting some recommendations, was published online by the AHA. The writing group was asked review the original document and revise if appropriate. In June 2018, the writing group submitted a document with minor changes and with inclusion of important newly published randomized controlled trials with >100 participants and clinical outcomes at least 90 days after AIS. The document was sent to 14 peer reviewers. The writing group evaluated the peer reviewers' comments and revised when appropriate. The current final document was approved by all members of the writing group except when relationships with industry precluded members from voting and by the governing bodies of the AHA. These guidelines use the American College of Cardiology/AHA 2015 Class of Recommendations and Level of Evidence and the new AHA guidelines format. Results- These guidelines detail prehospital care, urgent and emergency evaluation and treatment with intravenous and intra-arterial therapies, and in-hospital management, including secondary prevention measures that are appropriately instituted within the first 2 weeks. The guidelines support the overarching concept of stroke systems of care in both the prehospital and hospital settings. Conclusions- These guidelines provide general recommendations based on the currently available evidence to guide clinicians caring for adult patients with acute arterial ischemic stroke. In many instances, however, only limited data exist demonstrating the urgent need for continued research on treatment of acute ischemic stroke.

Realist review - a new method of systematic review designed for complex policy interventions

Abstract: Evidence-based policy is a dominant theme in contemporary public services but the practical realities and challenges involved in using evidence in policy-making are formidable. Part of the problem is one of complexity. In health services and other public services, we are dealing with complex social interventions which act on complex social systems--things like league tables, performance measures, regulation and inspection, or funding reforms. These are not 'magic bullets' which will always hit their target, but programmes whose effects are crucially dependent on context and implementation. Traditional methods of review focus on measuring and reporting on programme effectiveness, often find that the evidence is mixed or conflicting, and provide little or no clue as to why the intervention worked or did not work when applied in different contexts or circumstances, deployed by different stakeholders, or used for different purposes. This paper offers a model of research synthesis which is designed to work with complex social interventions or programmes, and which is based on the emerging 'realist' approach to evaluation. It provides an explanatory analysis aimed at discerning what works for whom, in what circumstances, in what respects and how. The first step is to make explicit the programme theory (or theories)--the underlying assumptions about how an intervention is meant to work and what impacts it is expected to have. We then look for empirical evidence to populate this theoretical framework, supporting, contradicting or modifying the programme theories as it goes. The results of the review combine theoretical understanding and empirical evidence, and focus on explaining the relationship between the context in which the intervention is applied, the mechanisms by which it works and the outcomes which are produced. The aim is to enable decision-makers to reach a deeper understanding of the intervention and how it can be made to work most effectively. Realist review does not provide simple answers to complex questions. It will not tell policy-makers or managers whether something works or not, but will provide the policy and practice community with the kind of rich, detailed and highly practical understanding of complex social interventions which is likely to be of much more use to them when planning and implementing programmes at a national, regional or local level.

A rating scale for drug-induced akathisia

Abstract: A rating scale for drug-induced akathisia has been derived that incorporates diagnostic criteria for pseudoakathisia, and mild, moderate, and severe akathisia. It comprises items for rating the observable, restless movements which characterise the condition, the subjective awareness of restlessness, and any distress associated with the akathisia. In addition, there is an item for rating global severity. A standard examination procedure is recommended. The inter-rater reliability for the scale items (Cohen's kappa) ranged from 0.738 to 0.955. Akathisia was found in eight of 42 schizophrenic in-patients, and nine had pseudoakathisia, where the typical sense of inner restlessness was not reported.

Cannabinoids for Medical Use: A Systematic Review and Meta-analysis.

Abstract: Importance Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear. Objective To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids. Data Sources Twenty-eight databases from inception to April 2015. Study Selection Randomized clinical trials of cannabinoids for the following indications: nausea and vomiting due to chemotherapy, appetite stimulation in HIV/AIDS, chronic pain, spasticity due to multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, or Tourette syndrome. Data Extraction and Synthesis Study quality was assessed using the Cochrane risk of bias tool. All review stages were conducted independently by 2 reviewers. Where possible, data were pooled using random-effects meta-analysis. Main Outcomes and Measures Patient-relevant/disease-specific outcomes, activities of daily living, quality of life, global impression of change, and AEs. Results A total of 79 trials (6462 participants) were included; 4 were judged at low risk of bias. Most trials showed improvement in symptoms associated with cannabinoids but these associations did not reach statistical significance in all trials. Compared with placebo, cannabinoids were associated with a greater average number of patients showing a complete nausea and vomiting response (47% vs 20%; odds ratio [OR], 3.82 [95% CI, 1.55-9.42]; 3 trials), reduction in pain (37% vs 31%; OR, 1.41 [95% CI, 0.99-2.00]; 8 trials), a greater average reduction in numerical rating scale pain assessment (on a 0-10-point scale; weighted mean difference [WMD], −0.46 [95% CI, −0.80 to −0.11]; 6 trials), and average reduction in the Ashworth spasticity scale (WMD, −0.12 [95% CI, −0.24 to 0.01]; 5 trials). There was an increased risk of short-term AEs with cannabinoids, including serious AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination. Conclusions and Relevance There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs.