Cannabis and schizophrenia

BACKGROUND Schizophrenia is a mental illness causing disordered beliefs, ideas and sensations. Many people with schizophrenia smoke cannabis, and it is unclear why a large proportion do so and if the effects are harmful or beneficial. It is also unclear what the best method is to allow people with schizophrenia to alter their cannabis intake. OBJECTIVES To assess the effects of specific psychological treatments for cannabis reduction in people with schizophrenia.To assess the effects of antipsychotics for cannabis reduction in people with schizophrenia.To assess the effects of cannabinoids (cannabis related chemical compounds derived from cannabis or manufactured) for symptom reduction in people with schizophrenia. SEARCH METHODS We searched the Cochrane Schizophrenia Group Trials Register, 12 August 2013, which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE, PUBMED and PsycINFO.We searched all references of articles selected for inclusion for further relevant trials. We contacted the first author of included studies for unpublished trials or data. SELECTION CRITERIA We included all randomised controlled trials involving cannabinoids and schizophrenia/schizophrenia-like illnesses, which assessed:1) treatments to reduce cannabis use in people with schizophrenia;2) the effects of cannabinoids on people with schizophrenia. DATA COLLECTION AND ANALYSIS We independently inspected citations, selected papers and then re-inspected the studies if there were discrepancies, and extracted data. For dichotomous data we calculated risk ratios (RR) and for continuous data, we calculated mean differences (MD), both with 95% confidence intervals (CI) on an intention-to-treat basis, based on a fixed-effect model. We excluded data if loss to follow-up was greater than 50%. We assessed risk of bias for included studies and used GRADE to rate the quality of the evidence. MAIN RESULTS We identified eight randomised trials, involving 530 participants, which met our selection criteria.For the cannabis reduction studies no one treatment showed superiority for reduction in cannabis use. Overall, data were poorly reported for many outcomes of interest. Our main outcomes of interest were medium-term data for cannabis use, global state, mental state, global functioning, adverse events, leaving the study early and satisfaction with treatment. 1. Reduction in cannabis use: adjunct psychological therapies (specifically about cannabis and psychosis) versus treatment as usualResults from one small study showed people receiving adjunct psychological therapies specifically about cannabis and psychosis were no more likely to reduce their intake than those receiving treatment as usual (n = 54, 1 RCT, MD -0.10, 95% CI -2.44 to 2.24, moderate quality evidence). Results for other main outcomes at medium term were also equivocal. No difference in mental state measured on the PANSS positive were observed between groups (n = 62, 1 RCT, MD -0.30 95% CI -2.55 to 1.95, moderate quality evidence). Nor for the outcome of general functioning measured using the World Health Organization Quality of Life BREF (n = 49, 1 RCT, MD 0.90 95% CI -1.15 to 2.95, moderate quality evidence). No data were reported for the other main outcomes of interest 2. Reduction in cannabis use: adjunct psychological therapy (specifically about cannabis and psychosis) versus adjunct non-specific psychoeducation One study compared specific psychological therapy aimed at cannabis reduction with general psychological therapy. At three-month follow-up, the use of cannabis in the previous four weeks was similar between treatment groups (n = 47, 1 RCT, RR 1.04 95% CI 0.62 to 1.74, moderate quality evidence). Again, at a medium-term follow-up, the average mental state scores from the Brief Pscychiatric Rating Scale-Expanded were similar between groups (n = 47, 1 RCT, MD 3.60 95% CI - 5.61 to 12.81, moderate quality evidence). No data were reported for the other main outcomes of interest: global state, general functioning, adverse events, leaving the study early and satisfaction with treatment. 3. Reduction in cannabis use: antipsychotic versus antipsychotic In a small trial comparing effectiveness of olanzapine versus risperidone for cannabis reduction, there was no difference between groups at medium-term follow-up (n = 16, 1 RCT, RR 1.80 95% CI 0.52 to 6.22, moderate quality evidence). The number of participants leaving the study early at medium term was also similar (n = 28, 1 RCT, RR 0.50 95% CI 0.19 to 1.29, moderate quality evidence). Mental state data were reported, however they were reported within the short term and no difference was observed. No data were reported for global state, general functioning, and satisfaction with treatment.With regards to adverse effects data, no study reported medium-term data. Short-term data were presented but overall, no real differences between treatment groups were observed for adverse effects. 4. Cannabinoid as treatment: cannabidiol versus amisulprideAgain, no data were reported for any of the main outcomes of interest at medium term. There were short-term data reported for mental state using the BPRS and PANSS, no overall differences in mental state were observed between treatment groups. AUTHORS' CONCLUSIONS Results are limited and inconclusive due to the small number and size of randomised controlled trials available and quality of data reporting within these trials. More research is needed to a) explore the effects of adjunct psychological therapy that is specifically about cannabis and psychosis as currently there is no evidence for any novel intervention being better than standard treatment,for those that use cannabis and have schizophrenia b) decide the most effective drug treatment in treating those that use cannabis and have schizophrenia, and c) assess the effectiveness of cannabidiol in treating schizophrenia. Currently evidence is insufficient to show cannabidiol has an antipsychotic effect

Providing immediate neonatal care and resuscitation at birth beside the mother: clinicians' views, a qualitative study

Objectives: The aims of this study were to assess clinicians’ views and experiences of providing immediate neonatal care at birth beside the mother, and of using a mobile trolley designed to facilitate this bedside care. Design: Qualitative interview study with semistructured interviews. Results: The results were analysed using thematic analysis. Setting: A large UK maternity unit. Participants: Clinicians (n=20) from a range of disciplines who were present when the trolley was used to provide neonatal care at birth at the bedside. Five clinicians provided/observed advanced resuscitation by the bedside. Results: Five themes were identified: (1) Parents’ involvement, which included ‘Contact and involvement’, ‘Positive emotions for parents’ and ‘Staff communication’; (2) Reservations about neonatal care at birth beside the mother, which included ‘Impact on clinicians’ and ‘Impact on parents’; (3) Practical challenges in providing neonatal care at the bedside, which included ‘Cord length’ and ‘Caesarean section’; (4) Comparison of the trolley with usual resuscitation equipment and (5) Training and integration of bedside care into clinical routine, which included ‘Teething problems’ and ‘Training’. Conclusions: Overall, most clinicians were positive about providing immediate neonatal care at the maternal bedside, particularly in terms of the clinicians’ perceptions of the parents’ experience. Clinicians also perceived that their close proximity to parents improved communication. However, there was some concern about performing more intensive interventions in front of parents. Providing immediate neonatal care and resuscitation at the bedside requires staff training and support

Women's views and experiences of two alternative consent pathways for participation in a preterm intrapartum trial: a qualitative study

BACKGROUND: The Cord Pilot Trial compared alternative policies for timing of cord clamping at very preterm birth at eight UK hospitals. In addition to standard written consent, an oral assent pathway was developed for use when birth was imminent. The aim of this study was to explore women's views and experiences of two alternative consent pathways to participate in the Cord Pilot Trial. METHODS: We conducted a qualitative study using semi-structured interviews. A total of 179 participants in the Cord Pilot Trial were sent a postal invitation to take part in interviews. Women who agreed were interviewed in person or by telephone to explore their experiences of two consent pathways for a preterm intrapartum trial. Data were analysed using inductive systematic thematic analysis. RESULTS: Twenty-three women who gave either written consent (n = 18) or oral assent followed by written consent (n = 5) to participate in the trial were interviewed. Five themes were identified: (1) understanding of the implications of randomisation, (2) importance of staff offering participation, (3) information about the trial and time to consider participation, (4) trial secondary in women's minds and (5) reasons for agreeing to take part in the trial. Experiences were similar for the two consent pathways. Women recruited by the oral assent pathway reported being given less information about the trial but felt it was sufficient to make a decision regarding participation. There were gaps in women's understanding of the trial and intervention, regardless of the consent pathway. CONCLUSIONS: Overall, women were positive about their experiences of being invited to participate in the trial. The oral assent pathway seems an acceptable option for women if the intervention is low-risk and time is limited. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN21456601 . Registered on 28 February 2013

Randomised trial of cord clamping and initial stabilisation at very preterm birth

Objectives: For very preterm births, to compare alternatives policies for umbilical cord clamping and immediate neonatal care. Design: Parallel group randomised (1:1) trial, using sealed opaque numbered envelopes. Setting: Eight UK tertiary maternity units. Participants: 261 women expected to have a livebirth before 32 weeks, and their 276 babies. Interventions: Cord clamping after at least two minutes and immediate neonatal care with cord intact, or clamping within 20 seconds and immediate neonatal care after clamping. Main outcome measures: Intraventricular haemorrhage (IVH), death before discharge. Results: 132 women (137 babies) were allocated clamping ≥2 minutes and neonatal care cord intact, and 129 (139) clamping ≤20 and neonatal care after clamping; 6 mother infant dyads were excluded (2, 4) as birth was after 35+6 weeks, 1 withdrew (death data only available) (0, 1). Median gestation was 28.9 weeks for those allocated clamping ≥2 minutes, and 29.2 for those allocated clamping ≤20 seconds. Median time to clamping was 120 and 11 seconds respectively. 7 of 135 infants (5.2%) allocated clamping ≥2 minutes died and 15 of 135 (11.1%) allocated clamping ≤20 seconds; risk difference (RD) -5.9% (95% confidence interval -12.4% to 0.6%). Of livebirths, 43 of 134 (32%) had IVH versus 47 of 132 (36%) respectively; RD -3.5% (-14.9% to 7.8%). There were no clear differences in other outcomes for infants or mothers. Conclusions: This is promising evidence that clamping after at least 2 minutes and immediate neonatal care with cord intact at very preterm birth may improve outcome; a large trial is urgently needed

Women’s views and experiences of two alternative consent pathways for participation in a preterm intrapartum trial: a qualitative study

Background\ud The Cord Pilot Trial compared alternative policies for timing of cord clamping at very preterm birth at eight UK hospitals. In addition to standard written consent, an oral assent pathway was developed for use when birth was imminent. The aim of this study was to explore women’s views and experiences of two alternative consent pathways to participate in the Cord Pilot Trial.\ud \ud Methods\ud We conducted a qualitative study using semi-structured interviews. A total of 179 participants in the Cord Pilot Trial were sent a postal invitation to take part in interviews. Women who agreed were interviewed in person or by telephone to explore their experiences of two consent pathways for a preterm intrapartum trial. Data were analysed using inductive systematic thematic analysis\ud \ud Results\ud Twenty-three women who gave either written consent (n = 18) or oral assent followed by written consent (n = 5) to participate in the trial were interviewed. Five themes were identified: (1) understanding of the implications of randomisation, (2) importance of staff offering participation, (3) information about the trial and time to consider participation, (4) trial secondary in women’s minds and (5) reasons for agreeing to take part in the trial. Experiences were similar for the two consent pathways. Women recruited by the oral assent pathway reported being given less information about the trial but felt it was sufficient to make a decision regarding participation. There were gaps in women’s understanding of the trial and intervention, regardless of the consent pathway.\ud \ud Conclusions\ud Overall, women were positive about their experiences of being invited to participate in the trial. The oral assent pathway seems an acceptable option for women if the intervention is low-risk and time is limited.\ud \ud Trial registration\ud ISRCTN Registry, ISRCTN21456601. Registered on 28 February 2013

Clinicians' and womens' experiences of two consent pathways in a trial of timing of clamping at very preterm birth:a qualitative study

Background Recruitment to trials when birth is imminent requires offering consent at a difficult and stressful time, often with limited time. The Cord Pilot Trial assessed timing of cord clamping at very preterm birth. To ensure high risk women were not excluded we developed a two stage oral assent pathway, for use when birth was imminent. A third of women were recruited using this pathway. The aim of this study was to explore clinicians’ and women’s’ experiences of the two consent pathways. Methods A qualitative interview design with semi-structured interviews. Clinicians and women were recruited from the 8 trial sites. Results were analysed using systematic thematic analysis. Results 17 clinicians were interviewed, 11 had experience of both pathways and 6 of one stage written consent only. [DL1]Themes identified: consent as a continual process; consent as a record versus consent as a legal document; team approach; different consent pathways for different trials; balance between time and information. 23 women were interviewed, 5 had been offered oral assent and 18 one stage written consent. Themes identified: importance of staff; time and information; reasons for agreeing to consent; trial secondary in women’s minds; understanding randomisation. Conclusion Overall, clinicians thought that one stage written consent was optimal for offering consent but were positive about the use of oral assent when there is limited time for offering participation. Women were positive about their experiences, particularly about the staff who approached them. Nevertheless, there were gaps in understanding of the trial in some women’s accounts

Improving quality of care and outcome at very preterm birth: the Preterm Birth research programme, including the Cord pilot RCT

BACKGROUND:Being born very premature (i.e. before 32 weeks’ gestation) has an impact on survival and quality of life. Improving care at birth may improve outcomes and parents’ experiences. OBJECTIVES:To improve the quality of care and outcomes following very preterm birth. DESIGN:We used mixed methods, including a James Lind Alliance prioritisation, a systematic review, a framework synthesis, a comparative review, qualitative studies, development of a questionnaire tool and a medical device (a neonatal resuscitation trolley), a survey of practice, a randomised trial and a protocol for a prospective meta-analysis using individual participant data. SETTING:For the prioritisation, this included people affected by preterm birth and health-care practitioners in the UK relevant to preterm birth. The qualitative work on preterm birth and the development of the questionnaire involved parents of infants born at three maternity hospitals in southern England. The medical device was developed at Liverpool Women’s Hospital. The survey of practice involved UK neonatal units. The randomised trial was conducted at eight UK tertiary maternity hospitals. PARTICIPANTS:For prioritisation, 26 organisations and 386 individuals; for the interviews and questionnaire tool, 32 mothers and seven fathers who had a baby born before 32 weeks’ gestation for interviews evaluating the trolley, 30 people who had experienced it being used at the birth of their baby (19 mothers, 10 partners and 1 grandmother) and 20 clinicians who were present when it was being used; for the trial, 261 women expected to have a live birth before 32 weeks’ gestation, and their 276 babies. INTERVENTIONS:Providing neonatal care at very preterm birth beside the mother, and with the umbilical cord intact; timing of cord clamping at very preterm birth. MAIN OUTCOME MEASURES:Research priorities for preterm birth; feasibility and acceptability of the trolley; feasibility of a randomised trial, death and intraventricular haemorrhage. REVIEW METHODS:Systematic review of Cochrane reviews (umbrella review); framework synthesis of ethics aspects of consent, with conceptual framework to inform selection criteria for empirical and analytical studies. The comparative review included studies using a questionnaire to assess satisfaction with care during childbirth, and provided psychometric information. RESULTS:Our prioritisation identified 104 research topics for preterm birth, with the top 30 ranked. An ethnographic analysis of decision-making during this process suggested ways that it might be improved. Qualitative interviews with parents about their experiences of very preterm birth identified two differences with term births: the importance of the staff appearing calm and of staff taking control. Following a comparative review, this led to the development of a questionnaire to assess parents’ views of care during very preterm birth. A systematic overview summarised evidence for delivery room neonatal care and revealed significant evidence gaps. The framework synthesis explored ethics issues in consent for trials involving sick or preterm infants, concluding that no existing process is ideal and identifying three important gaps. This led to the development of a two-stage consent pathway (oral assent followed by written consent), subsequently evaluated in our randomised trial. Our survey of practice for care at the time of birth showed variation in approaches to cord clamping, and that no hospitals were providing neonatal care with the cord intact. We showed that neonatal care could be provided beside the mother using either the mobile neonatal resuscitation trolley we developed or existing equipment. Qualitative interviews suggested that neonatal care beside the mother is valued by parents and acceptable to clinicians. Our pilot randomised trial compared cord clamping after 2 minutes and initial neonatal care, if needed, with the cord intact, with clamping within 20 seconds and initial neonatal care after clamping. This study demonstrated feasibility of a large UK randomised trial. Of 135 infants allocated to cord clamping ≥ 2 minutes, 7 (5.2%) died and, of 135 allocated to cord clamping ≤ 20 seconds, 15 (11.1%) died (risk difference –5.9%, 95% confidence interval –12.4% to 0.6%). Of live births, 43 out of 134 (32%) allocated to cord clamping ≥ 2 minutes had intraventricular haemorrhage compared with 47 out of 132 (36%) allocated to cord clamping ≤ 20 seconds (risk difference –3.5%, 95% CI –14.9% to 7.8%). LIMITATIONS:Small sample for the qualitative interviews about preterm birth, single-centre evaluation of neonatal care beside the mother, and a pilot trial. CONCLUSIONS:Our programme of research has improved understanding of parent experiences of very preterm birth, and informed clinical guidelines and the research agenda. Our two-stage consent pathway is recommended for intrapartum clinical research trials. Our pilot trial will contribute to the individual participant data meta-analysis, results of which will guide design of future trials. FUTURE WORK:Research in preterm birth should take account of the top priorities. Further evaluation of neonatal care beside the mother is merited, and future trial of alternative policies for management of cord clamping should take account of the meta-analysis. STUDY REGISTRATION:This study is registered as PROSPERO CRD42012003038 and CRD42013004405. In addition, Current Controlled Trials ISRCTN21456601. FUNDING:This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 7, No. 8. See the NIHR Journals Library website for further project information

Cord pilot trial - immediate versus deferred cord clamping for very preterm birth (before 32 weeks gestation): study protocol for a randomized controlled trial

Background: Preterm birth is the most important single determinant of adverse outcome in the United Kingdom; one in every 70 babies (1.4%) is born before 32 weeks (very preterm), yet these births account for over half of infant deaths. Deferring cord clamping allows blood flow between baby and placenta to continue for a short time. This often leads to increased neonatal blood volume at birth and may allow longer for transition to the neonatal circulation. Optimal timing for clamping the cord remains uncertain, however. The Cochrane Review suggests that deferring umbilical cord clamping for preterm births may improve outcome, but larger studies reporting substantive outcomes and with long-term follow-up are needed. Studies of the physiology of placental transfusion suggest that flow in the umbilical cord at very preterm birth may continue for several minutes. This pilot trial aims to assess the feasibility of conducting a large randomised trial comparing immediate and deferred cord clamping in the UK. Methods/Design: Women are eligible for the trial if they are expected to have a live birth before 32 weeks gestation. Exclusion criteria are known monochorionic twins or clinical evidence of twin-twin transfusion syndrome, triplet or higher order multiple pregnancy, and known major congenital malformation. The interventions will be cord clamping within 20 seconds compared with cord clamping after at least two minutes. For births with cord clamping after at least two minutes, initial neonatal care is at the bedside. For the pilot trial, outcomes include measures of recruitment, compliance with the intervention, retention of participants and data quality for the clinical outcomes. Information about the trial is available to women during their antenatal care. Women considered likely to have a very preterm birth are approached for informed consent. Randomisation is close to the time of birth. Follow-up for the women is for one year, and for the children to two years of age (corrected for gestation at birth). The target sample size is 100 to 110 mother-infant pairs recruited over 12 months at eight sites. Trial registration: ISRCTN21456601, registered on 28 February 2013

Implementing core nice guidelines for osteoarthritis in primary care with a model consultation (MOSAICS): A cluster randomised controlled trial

Objective To determine the effectiveness of a model osteoarthritis consultation, compared with usual care, on physical function and uptake of NICE osteoarthritis recommendations, in adults ≥45 years consulting with peripheral joint pain in UK general practice. Method Two-arm cluster-randomised controlled trial with baseline health survey. Eight general practices in England. Participants: 525 adults ≥45 years consulting for peripheral joint pain, amongst 28,443 population survey recipients. Four intervention practices delivered the model osteoarthritis consultation to patients consulting with peripheral joint pain; four control practices continued usual care. The primary clinical outcome of the trial was the SF-12 physical component score (PCS) at six months; the main secondary outcome was uptake of NICE core recommendations by six months, measured by osteoarthritis quality indicators. A Linear Mixed Model was used to analyse clinical outcome data (SF-12 PCS). Differences in quality indicator outcomes were assessed using logistic regression. Results 525 eligible participants were enrolled (mean age 67.3 years, SD 10.5; 59.6% female): 288 from intervention and 237 from control practices. There were no statistically significant differences in SF-12 PCS: mean difference at the 6-month primary endpoint was -0.37 (95% CI -2.32, 1.57). Uptake of core NICE recommendations by six months was statistically significantly higher in the intervention arm compared with control: e.g. increased written exercise information, 20.5% (7.9, 28.3). Conclusion Whilst uptake of core NICE recommendations was increased, there was no evidence of benefit of this intervention, as delivered in this pragmatic randomised trial, on the primary outcome of physical functioning at six months. Trial registration ISRCTN06984617