BIRMINGHAM CITY UNIVERSITY

FACULTY OF HEALTH

20 Credit Level 7 Research Module

SUMMATIVE ASSIGNMENT – PROTOCOL FOR A SYSTEMATIC REVIEW (3,000 WORDS).

The assignment for this module has been designed to give all students the opportunity to prepare a document demonstrating their ability to produce a coherent, theoretically based argument justifying secondary research within a specific field. The development of a protocol is a key requisite for systematic review work. The format for this assignment is informed mainly by Cochrane resources for preparing protocols and students are strongly encouraged to visit

www.cochrane-handbook.org

.

Remember this assignment is basically a statement of intent; the protocol outlines the plan for the review and should describe the rationale for the review; the objectives; and the methods that will be used to locate, select and critically appraise the studies, and to collect and analyze data from the included studies. Preparing a protocol for a review makes you stop and think about what you’re doing; it can act as a working document for the reviewer(s); it can prevent duplication; and very importantly it can minimise bias by being transparent about what you plan to do in advance. The following guidelines have been devised to help in the preparation of the assignment.

THE TITLE

The title has to provide enough information to help the reader decide if the review protocol is going to be relevant to them. The Cochrane Collaboration has decided on a standard format for titles which helps convey information as quickly as possible:

[Intervention] for [Problem] in [Category]

E.g. Topical negative pressure (TNP) for treating chronic wounds.

BACKGROUND/RATIONALE

You need to indicate the time span, languages and countries from which background information has been gained.

You need to present the background literature as a logical discussion, if necessary using sub-headings for clarification. It should include the size of the problem, uncertainty about dealing with it, why the intervention might work, and what it is supposed to achieve.

You need to critically analyse and appraise the background literature in two ways, consider firstly the data/theory proposed, secondly whether the methods used to gather the data were appropriate.

You need to conclude in a way that identifies the issues which arise from the background literature and leads into, or suggests the need for the proposed review. By the time the reader finishes your Background section they should be able to understand why you are asking the review question.

OBJECTIVES/REVIEW QUESTION(S)

In this section the main review question(s) to be addressed in your protocol needs to be stated. Getting the review question right is the most important step in doing your protocol. As well as telling others what the review is about, it will guide how you propose to search, select, appraise and analyse your studies. Make sure you spend time on this section. It is recommended that you structure your question using PICOD, PICO or PIO – this will depend on the type of question being asked.

P = Population i.e. the people affected by the intervention/exposure

I = Intervention/exposure under scrutiny

C = Counter intervention

O = Outcome(s) of interest

D = Design of the studies likely to yield the most valid data

E.g. To undertake a systematic review of all randomised controlled trials (RCTs) using TNP in the treatment of any patient with a chronic wound to determine:

a) If TNP is more effective than wound dressings in terms of improving healing rates, reducing cost, improving quality of life, minimising pain and providing comfort.

b) If there is an optimum TNP regimen in terms of foam type, degree of suction, continuous/intermittent suction, duration of suction.

METHODS OF THE REVIEW

This section is the formal description of what you plan to do once you have decided on your review question:

SEARCH STRATEGY

In your protocol the search strategy needs to be clearly described. PI(C)O(D) will help determine key words, Medical subject headings (MeSH), wildcards, acronyms, synonyms, transatlantic terms that will be used in your search strategy. You will need to describe how these will be linked with the appropriate Boolean operators (e.g. AND, OR, NOT) to develop a search strategy that will be used to search for primary studies from a variety of resources, which you need to state, such as electronic databases, journals, conference proceedings, reference lists, grey literature, research registers, researchers and manufacturers.

STUDY SELECTION CRITERIA AND PROCEDURES.

Following the search you need to clearly describe in your protocol the processes that will be used to decide if a primary study will be included or excluded from the review. This will initially depend on whether it fulfils the scope (PI(C)O(D))of the review protocol.

For types of participants you need to think about the health problem or population or setting.

E.g. You would consider a study fulfilling the scope of the TNP review protocol if it defined chronic wounds as…

For types of interventions with a medication for example, you need to think about drug preparation, route of administration, dose, duration, frequency. For non-drug interventions such as an educational intervention, defining the intervention can be a bit more difficult – you need to consider exactly what was done, how often it was done, who did it, were they trained, etc.

E.g. You would consider a study fulfilling the scope of the TNP review protocol if it described the intervention of interest (in this example TNP) as…

For types of counter interventions you need to decide whether you will be comparing the intervention group with a placebo, nothing, sham treatment or some other treatment.

E.g. You would consider any RCTs as fulfilling the scope of the TNP review protocol where topical negative pressure was compared with no treatment/sham/standard (which needs to be defined)/other experimental interventions.

For types of outcome measures you need to think about the primary outcome of interest and how that can be determined in a valid and reliable way. There may be secondary outcomes of interest e.g. cost, quality of life, pain, comfort and adverse effects and how they too can be determined in a valid and reliable way.

E.g. As there is no consensus as to the most valid and reliable means of measuring healing rates of wounds, you would consider a study fulfilling the scope of the TNP review protocol if it measured healing by some objective method such as the time to complete healing.

For types of studies you need to consider the design that will best answer the question and whether you will restrict studies on the basis of language, date or publication status.

E.g. To evaluate topical negative pressure for the treatment of any patient with a chronic wound – you would consider a study fulfilling the scope of the TNP review protocol, in the first instance, if it was a randomized controlled trial – and in the absence of any RCTs, controlled clinical trials would be considered.

STUDY QUALITY ASSESSMENT CHECKLISTS AND PROCEDURES

If the study fulfils the scope PI(C)O(D) of the review you need to clearly describe in your protocol the processes used to determine the methodological quality of the primary study to decide if it will remain included, or be excluded, from the review. It is best to refer to www.cochrane-handbook.org. in order to determine the best way of assessing bias in a study. The CONSORT statement also provides useful guidance for what ought to be reported in RCTS at

www.consort-statement.org

.

DATA SYNTHESIS

If the study fulfils the scope of the review, and is of high methodological quality, the results of this study need to be extracted and considered for data synthesis. Data synthesis involves collating and summarising the results of included primary studies You need describe in your protocol your proposed method of extracting and synthesising the results of primary studies and how this will depend upon heterogeneity of the studies identified. You need to consider whether your synthesis would provide an estimate of overall effectiveness of an intervention; review effectiveness in different studies, populations and settings; investigate differences; answer the review question.

Within your protocol you need to consider how a data extraction form might be designed to collect all the information needed to address the review question(s) which includes the name of the review, date of data extraction, publication details, the scope (PI(C)O(D)), methodological quality (specific factors), and results of the primary studies.

REFERENCES

All references should be appended to the protocol using the Harvard system.

Guidelines for preparing a protocol for a systematic review approach/level 7/Dr Debra Evans/September 2010

PROTOCOL FOR A SYSTEMATIC REVIEW

THE TITLE

Effectiveness of Cognitive Behavioural Therapy (CBT) for Management of Schizophrenia and Substance Misuse in Adults

INTRODUTION

Schizophrenia is a mental illness that may affect male and female’s thinking, feeling, movement and behavior, this may happen between teenage years and early adulthood (Miller and Mason, 2011). Symptoms may include delusions, confusion, negative thoughts, and hallucination (Miller and Mason, 2011). Substance misuse, on the other hand, is using substances such as alcohol and other drugs in excess or in a way that may be damaging to health (World Health Organisation (WHO), 2017). Using these substances may lead to addiction which can affect the person’s cognitive and behavior (WHO, 2017; Hunt et al., 2013). Furthermore, using these substances by a person with a diagnosis of Schizophrenia could result in deterioration in their mental state (Kavanagh et al., 2002).

This protocol for a systematic review will focus on these two key papers:

1. Psychosocial Interventions for People with both Severe Mental Illness and Substance Misuse (Hunt et al., 2013) A Systematic Review of Randomised Controlled Trial (RCT).

2. Integrated Motivational Interviewing and Cognitive Behavioural Therapy (CBT) for People with Psychosis and Comorbid Substance Misuse: Randomised Controlled Trial (Barrowclough et al., 2010)

BACKGROUND/RATIONALE

People who have a diagnosis of mental illness and have problems with substance use or alcohol are classed as having ‘Dual diagnosis’ (Lieberman and Murray, 2012). Substance misuse is common among people with Schizophrenia, particularly in young men, living in the community or admitted in Mental Health Hospital (Kavanagh, et al., 2002; National Institute for Health and Care Excellence (NICE), 2011). Carra et al., (2015) reported 35% and 60% lifetime prevalence rates of substances misuse among people with Schizophrenia. In the USA, many people with a diagnosis of Schizophrenia also have alcohol or drug disorder (Regier, 1990). Similarly, in the

(
1
|
P a g e
)

United Kingdom, the rate of substance misuse among people with mental illness is estimated at about 25% (Barrowclough, 2010).

Although, there is still disputes as to whether there is a causal relationship between substance use and the development of Schizophrenia (Dickey, 2000; NICE, 2011). However, it is well-known that substance misuse affects psychosis and, may result in prolonged and serious condition (NICE, 2011). Substance misuse among people with Schizophrenia may be linked with an increased risk of illness and injury (Dickey, 2000). Substance misuse may also be associated with worse outcomes from Schizophrenia, as well as increased admission to inpatient and emergency services (Kavanagh et al., 2002).

Unfortunately, services for the treatment of substance misuse and Schizophrenia are often separated, with poor communication among inter-multidisciplinary (NICE, 2011). Also, people with dual diagnosis are often left out from services due to their comorbidity, which may have deprived them of getting treatment early. Furthermore, substance misuse may be omitted in assessments, unless routine screening is carried out. Yet, effective management of Schizophrenia and Substance misuse needs a wholly integrated approach due to the close inter- relationship of these illnesses (NICE, 2011).

Though, a wide range of interventions is currently available for the treatment of this population such as the use of antipsychotics medication (Kavanagh et al., 2002) and CBT, which targets primarily positive symptoms and motivational interventions targeting substance drug misuse (Lieberman and Murray, 2012). Cognitive Behavioural Therapy (CBT) interventions for Schizophrenia were first developed more than a decade ago, and a substantial body of evidence supports their effectiveness in improving psychotic symptoms (Jones et al., 2004). Hunt et al., (2013) identified Twelve Step recovery psychosocial interventions which may reduce substance use and misuse which intent to improve the patient’s motivation for change, also to increase the patient awareness and to develop coping strategies and self‐monitoring behavior. CBT has also been use to assist patients with schizophrenia and substance misuse to develop changes in lifestyles (Kavanagh et al., 2002). However, Lieberman and Murray, 2012 reported that CBT only targets the positive symptoms of Schizophrenia which are hallucinations, delusional beliefs, hearing voices and paranoid feelings, such as, a patient seeing things that are not real (Lieberman and Murray, 2012).

Hunt et al., (2013) reported that patients who have substance misuse diagnosis, without mental health problem may benefit from CBT, which may help them to adjust their behavior by improving

their managing skills. In contrast, the study reported that CBT for patients with dual diagnosis is more complex (Hunt et al., 2013). On the other hand, Barrowclough et. al, (2010) found that CBT for people with psychosis and substance misuse do not improve outcome in terms of hospitalisation, symptom outcomes, or functioning. However, the approach does reduce the amount of substance used for at least one year after completion of therapy. However, Hunt et al., (2013) identified that interventions that will reduce substance use are possible to improve, relapse rates, recovery, and bring about other positive outcomes. The systematic review (Hunt et al., 2013) found no indication to support the effectiveness of CBT and other psychosocial treatments for people with these disorders to remain in treatment or to decrease substance use or to improve mental state of people with Schizophrenia (Hunt et al., 2013). Overall, the evidence has low quality and study did not show any effectiveness of CBT for people with schizophrenia and substance misuse. For this reason, effective management for people with Schizophrenia and substance misuse need to be established.

Although, the evidence is mixed on the effectiveness of CBT for management of people with Schizophrenia and substance misuse. Studies suggest CBT may not be better than pharmacological interventions for alcohol and opioid dependence (Hofmann et al., 2012; McMain, 2015). However, evidence shows the effectiveness of CBT for drug use and alcohol disorders (Dutra et al., 2008; Magill and Ray, 2009; McHugh et al., 2010) without comorbid with mental illness. Yet, research that will proof effectiveness of CBT for management of people with Schizophrenia and substance misuse is needed.

An electronic search was carried out the following databases: Cochrane Library, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Medline, PsycINFO, PsycARTICLES, The Birmingham City University library and Google Scholar including published and unpublished articles were searched for publications relating to the topic.

However, there are few studies that addressed the question. Few studies were found relating to the use of a variety of different psychosocial interventions such as Motivational interview, CBT, skills training, and integrated care models). There are rare studies that combined the effectiveness of CBT for both schizophrenia and substance misuse. However, the problem of comorbid of schizophrenia and substance misuse is now prevalence, therefore, there has been a gap in the provision of effective CBT and care for people with Schizophrenia and substance misuse. So, there is a need for research to strengthen future practice and policy. Therefore, systematically scrutinize of available literature is required to address this issue. To understand more about how and to what extent CBT is effective to manage people with schizophrenia and substance misuse and to evaluate the evidence-base of CBT for treating a patient with schizophrenia and substance misuse and patient outcomes.

Taking into consideration the high prevalence of people with schizophrenia and substance misuse, the important question this review pursues to answer is ‘’What is the Effectiveness of Cognitive Behavioural Therapy (CBT) for Management of Schizophrenia and Substance Misuse in adults?

AIMS

The aim of this systematic review is to review published primary literature to identify the effectiveness of Cognitive Behavioural Therapy (CBT) for Management of Schizophrenia and Substance Misuse in Adults and how CBT may have helped these people to improve in their recovery and to reduce the use of substances.

OBJECTIVES

The main objectives are:

1. To evaluate the effectiveness of CBT for a reduction in substance use by people with Schizophrenia

2. To review how often and if patients with schizophrenia and substance misuse willing to engage in CBT in planned sessions

3. To assess the extent to which patients with Schizophrenia and Substance Misuse are involved in CBT

4. To evaluate the impact of patient involvement in CBT and how it benefits their improvement and recovery and reduction in substance misuse

METHODS OF THE REVIEW

Following the Cochrane Handbook for Systematic Review the PICO acronym will be used to identify key elements of the question, the four PICO components include (P) Patients or problem or Population, (I) Interventions or treatment, (C) Comparison intervention or treatment and (O) Clinical Outcome(s) of interest (Higgins and Green, 2018)

TABLE 1. SHOWS PICO FRAMEWORKS

P

Adults with schizophrenia that also misuse substances

I

Cognitive Behaviour Therapy (CBT)

C

Patients managed by Antipsychotic Medication

O

Reduction in symptoms of Schizophrenia and reduction in the use of Substances

D

Randomised Controlled Trial (RCT) and Systematic review

The level of evidence that will meet the needs of the chosen question is RCT and Systematic review (SR). RCT and SR will eliminate variables which could potentially reduce the rigor of the conclusions (Moseley, et al, 2009).

Primary outcomes: reduction in substance use, reduce relapse rates, improve mental state

Secondary outcomes: improve quality of life, social functioning

SEARCH STRATEGY

An electronic search was carried out the following databases: Cochrane Library, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Medline, PsycINFO, PsycARTICLES, The Birmingham City University library and Google Scholar including published and unpublished articles were searched for publications relating to the topic.

Search terms are summarised in Table 2, using synonyms terms, this will be used in various combinations to search for relevant articles. The search will look for articles in English Language only. The articles published from 2008 to 2018 were selected. A copy of the search strategy as developed and executed on Cochrane and PsycINFO are included as Appendices.

While searching on CINAHL the asterisk (*) truncation symbol was used to substitute one of the characters in the word, to search for the root of the term. This will retrieve all forms of the terms in one search and increasing the accuracy of the search (Vanvuuren, 2011). For illustration, Schizophrenia was typed as Schizophreni* in the search.

This review protocol utilised Medical Subject Heading (MeSH) to search for the most suitable words that are associated with the review question. Then the words are combined to MeSH to search for articles on PsycINFO in order to make the search procedure more accurate. Wildcards may also be used to search for root words of a term by replacing one or two letters of the word with the symbol (Vanvuuren, 2011). But, wildcards are not utilised in this review.

Boolean operators were used to search concurrently for each word and to combine the search by using AND and OR (Bramer et al. 2016). Population words are typed on the database as first (‘’Schizophrenia’’, ‘’Adult*’’, “Psychosis” and ‘’Substance misuse’’), followed by Intervention (CBT), then, Comparison (Antipsychotics) lastly Outcomes terms were typed on the database (‘Substance misuse’’ and ‘’drug misuse’’). Then, Boolean Operator tool OR was used to expands the search and to retrieve more results. Moreover, “AND” Operator was used to narrow the search and retrieved the fewer result. These are included in Appendices 1 and 2. This significantly reduces the search results to 1 PsycINFO article and 4 Cochrane articles.

TABLE 2: Search Terms

POPULATION

INTERVENTION

COMPARISON

OUTCOME

INDEX TERMS (MAIN TERMS)

Adults with
schizophrenia that also misuse substances

Cognitive Behavioural Therapy (CBT)

Antipsychotic medication

Reduction in symptoms of Schizophrenia and reduction in the use of Substances

FREE TEXT TERMS (SYNONYMS)

Adults

CBT

Antipsychotic

Substance misuse

Grown-ups
Schizophrenia

Behavioural Therapy

Antipsychotic agent
Antipsychotic drug

Alcohol misuse
Drug misuse

Mental disorder

Talking Therapy

Neuroleptic

Mental illness

Neuroleptic drug

Psychosis

Neuroleptic agent

Delusions

STUDY SELECTION CRITERIA AND PROCEDURES

Inclusion and exclusion criteria were applied to give more clear information about the review question. The inclusion criteria are adult people between 19 – 44 years old of age as (Population), Schizophrenia and substance misuse. Relevant articles published in the English language between 2008 to 2018 were used., to ensure the review examines the current practice. The exclusion criteria are older adult and adults more than 44 years of age, and articles not published in the English language excluded because of limited translation resources

Inclusion and exclusion criteria have been developed based on a scoping review and are presented in Table 3. Randomised Controlled Trial (RCT) and Systematic review papers will be included. However, Observational studies, Cohort studies and Survey papers not relevant to CBT for people with schizophrenia and substance misuse will be excluded.

TABLE 3: INCLUSION AND EXCLUSION

Inclusion

Exclusion

Population

Schizophrenia

Depression

Substance Misuse

Anxiety

Adult 18 – 44

More than 44

Intervention

Cognitive Therapy

Behavioural

Emotional Freedom
Technique (EFT), Psychoanalysis, and Group Therapy

Comparison

Antipsychotic medications

Antidepressants medications

Outcomes

Reduction in symptoms of schizophrenia and reduction in Substance Misuse

Designs

Randomised Controlled Trial (RCT) and Systematic review

Observational studies
Cohort studies Survey studies

Between 2008 – 2018

Before 2008

Studies in English Language

Studies Language

not

in

English

STUDY QUALITY ASSESSMENT CHECKLISTS AND PROCEDURES

After searching the databases, the results are processed to categorise suitable articles to remove the risks of bias. Systematic Review (SR) study (secondary research) and Randomised Control Trial (RCT) study (primary research) were chosen to answer the review question because only one RCT article was found relating to the review question after searching all the databases. Though, primary research articles are best to carry out a Protocol. However, SR is considered to provide the best evidence of all question types, because they are based on the findings of multiple studies that were identified in systematic literature search (Burns et al., 2011). Furthermore, the position of systematic reviews is at the top of evidence of hierarchy. However, the process of a rigorous systematic review can take years to complete and findings can, therefore, be superseded by more recent evidence. RCT research was chosen to answer the question because RCT is the best to research design to answer a question related to Therapy (Davidson and Illes, 2013). Systematic review is on level 1 and RCT is on level 2 on the hierarchy of evidence (Burns et al., 2011). For intervention question the hierarchy of evidence ranks quantitative research design (systematic review and RCT) as providing higher levels of confidence and the studies will have reliable answers to the question compared with other design with lower levels of confidence (Melnyk, and Fineout-Overholt, 2011).

In the systematic review article (Hunt et al., 2013), the review addressed a clearly focused question which clearly identified the population, intervention, and outcome in the review question (Critical Appraisal Skills Program, (CASP, 2018a). The author used the RCTs articles which appropriate study design are to address the review question (CASP, 2018a). The author assesses the quality of the included studies and rated the evidence as low or very low due to high or unclear risks of bias because of poor trial methods, methodological difficulties occurred which hinder pooling and interpreting results (CASP, 2018a; Hunt et al., 2013). Overall, the study followed Cochrane guidelines (Higgins and Green, 2018) for systematic review, to clearly specify its objectives, methods, results, and conclusion to show the reliability of the review to minimise biases. However, it was challenging to identify the key aspects of each intervention given that these are mostly complex, multi‐faceted interventions. Little attention was paid to reporting the fidelity of the delivery of each intervention. There are some problems in the study including small heterogeneous samples, flawed experimental designs, high attrition rates, and short follow-up periods which is not in accordance with Cochrane Handbook guidance (Higgins and Green, 2018) and Consort-statement (2018).

(
17
|
P a g e
)

The RCT article (Barrowclough et al., 2010), clearly addressed the focused issue in terms of the population studied, intervention, comparator, and outcomes were considered (CASP, 2018b). This small study was conducted in 6 sites but only 2 sites were randomised, the assignment of patients to treatments were randomised in these sites, the risk of selection bias was unclear as random generation and allocation concealment was not reported and performance and detection bias were unclear as blinding was not reported (Barrowclough, 2010; CASP, 2018b). There is a high risk of selective reporting bias as many results were reported per site rather than by randomised arms (Barrowclough, 2010), this is not in line with the Consort-statement guidance (2018). However, important clinical outcomes were considered, and it is relevant to this review protocol (CASP, 2018b).

DATA SYNTHESIS

Data synthesis is used to assess the collective findings into a meaning statement (Munn et al., 2014) with the literature included in this review, data synthesis will be carried out.

The systematic article (Hunt et al., 2013) included 32 RCTs and it found no indication to support any one of the psychosocial treatment, including CBT. None of the psychosocial treatment is effective for people with Schizophrenia to remain in treatment or to reduce substance use or to improve their mental state (Hunt et al., 2013). The systematic article found out that CBT alone compared with usual treatment showed no significant difference for losses from treatment at 3 months which the authors identifies the confidence interval (CI) of the result as low quality (Hunt et al., 2013). For this reason, high-quality research is required to address these in order to improve the evidence.

The RCT article (Barrowclough et al., 2010), found Therapy is not effective for substance misuse, but have a statistically significant effect on amount used per substance using day (adjusted ORs for main substance 1.50, 95% CI 1.08 to 2.09; P=0.016; and all substances 1.48, 95% CI 1.07 to 2.05; P=0.017) (Barrowclough et al., 2010). Treatment had a statistically significant effect on readiness to change use at 12 months (adjusted OR 2.05, 95% CI 1.26 to 3.31; P=0.004) however, it was not maintained at 24 months (0.78, 95% CI 0.48 to 1.28; P=0.320). There were no effects of treatment on clinical outcomes such as relapses, psychotic symptoms, functioning, and self-harm (Barrowclough et al., 2010).

Data extraction table will use to analyse and synthesise key elements selected papers and meta- analysis will be used to analyse the findings from selected articles using standardised statistical procedures to draw a relationship between the papers to address the review question (Polit and Becks, 2010). The table will identify the authors of the article, year, and time, aim, type of source,

data collection method, strengths and weaknesses analysis, main result and Theme will be included in the extraction table if the related papers are being grouped. CASP tool will be used to assess the potential studies for rigour, and ensure they are free from significant methodological issues which may impact on the quality of the review findings (Betany, 2012).

Appropriate critical appraisal tools will be used to scrutinise the articles to critic its relevance and trust-worthiness (Gerrish and Lathlean, 2015). For example, Randomised Controlled Trial CASP tool will be using to appraise RCT articles (CASP, 2018b).

Word count – 3116 including in-cite references in brackets

REFERENCES

Barrowclough, C., Haddock, G., Wykes, T., Beardmore, R., Conrod, P., Craig, T., Davies, L., Dunn, G., Eisner, E., Lewis, S., Moring, J., Steel, C. and Tarrier, N. (2010). Integrated motivational interviewing and cognitive behavioural therapy for people with psychosis and comorbid substance misuse: randomised controlled trial. BMJ, 341. pp.6325-6325.

Bettany-Saltikov, J. (2012) How to do Systematic Literature Review in Nursing. A-step-by-step guide. Berkshire, England. Mc-Graw-Hill Education.

Bramer, W. M., Giustini, D. & Kramer, B.M.R. (2016) Comprising the Coverage, recall, and precision of searches for 120 Systematic reviews in Embase, MEDLINE, and Google Search: A prospective study. Systematic Reviews, 5(39). Available at: Doi:10.1186/s13643-016-0215-9

Burns, P., Rohrich, R.J., and Chung, K. (2011) The Levels of Evidence and their role in Evidence- Based Medicine. Plastic and Reconstructive Surgery. 128(1):305-310

Carra, G., Bartoli, F., Clerici, M. and el-Guebaly, N. (2015) Psychopathology of Trumpets and Old Uncertainties. Journal of Psychopathology. 21 :390-399.

Consort Transparent Reporting Trial (2018) The CONSORT Flow Diagram. Available at:

http://www.consort-statement.org/

[Accessed 12 January 2019].

Critical Appraisal Skills Program (2018a) Systematic Review Checklist. Available at: https://casp- uk.net/wp-content/uploads/2018/01/CASP-Systematic-Review-Checklist_2018 [Accessed 13

December 2018]

Critical Appraisal Skills Program. (2018b) Randomised control trial Checklist. Available at: https://casp-uk.net/wp-content/uploads/2018/03/CASP-Randomised-Controlled-Trial-Checklist- 2018_fillable_form [Accessed 13 December 2018]

Davidson, M., and Iles, R. (2013). Evidence-based practice in therapeutic health care. In, Liamputtong, P. (ed.). Research Methods in Health: Foundations for Evidence-Based Practice (2nd ed.). South Melbourne: Oxford University Press.

Dickey B, Azeni H, Weiss R, et al. (2000) Schizoprhenia, substance use disorders and medical co-morbidity. J Ment Health Policy Econ. 3(1). 27–33

Dutra, L., Stathopoulou, G., Basden, S. L., et al. (2008) A meta-analytic review of psychosocial interventions for substance use disorders. Am J Psychiatry. 165. 179–87.

Gerrish, K. and Lathlean, J. (2015) The Research Process in Nursing. 7th edn. UK: John Wiley and Sons Ltd.

Higgins, J.and Green, S. (2018) Cochrane Handbook for Systematic Reviews of Interventions.

Wiley: United Kingdom.

Hofmann, S., Asnaani, A., Vonk, I., & Sawyer, A. (2012). The efficacy of cognitive behavioural therapy: A review of meta-analyses. Cognit Ther Res. 36(5). Pp 427–440.

Hunt, G.E., Siegfried, N., Morley,K., Sitharthan, T and Cleary, M. (2013) Psychosocial interventions for people with both severe mental illness and substance misuse. Available at: https://

www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001088.pub3/full?highlightAbst

ract=withdrawn%7Ccbt%7Cmisus%7Cmisuse%7Cdrug [Accessed 03 January 2019]

Jones, C., Cormac, I., Silveira da Mota Neto, J. and Campbell, C. (2004) Cognitive Behaviour Therapy for Schizophrenia: Cochrane Systematic Review-Intervention. Available at: https://www.cochranelibrary. [Accessed 03 January 2019]

Kavanagh, D., McGrath, J., Saunders, J., Dore, G. and Clark, D. (2002). Substance Misuse in Patients with Schizophrenia. Drugs. 62(5). pp.743-755.

Lieberman, J.A. and Murray, R.M. (2012) Comprehensive Care of Schizophrenia: A Textbook of Clinical Management. 2nd ed. Oxford University Press: Oxford.

Magill M, and Ray L. A (2009) Cognitive-behavioral treatment with adult alcohol and illicit

drug users: a meta-analysis of randomized controlled trials. J Stud Alcohol Drugs. (7). Pp. 516– 27.

McHugh, R.K., Hearon, B.A., and Otto, M. W (2010) Cognitive Behavioral Therapy for Substance Use Disorders. Psychiatr Clin N Am 33. 511–525.

McMain, S., Newman, M., Segal, Z., & DeRubeis, R. (2015). Cognitive behavioral therapy: Current status and future research directions. Psychother Res, 25(3). pp 321–329.

Melnyk, B.M and Fineout-Overholt, E (2011) Evidence-based Practice in Nursing & Healthcare: A Guide to Best Practice. Lippincott Williams & Wilkins

Miller, R and Mason, S. (2011) Diagnosis Schizophrenia’’ An Excellent Guide for Patient S and their Families. 2nd ed. Columbia University Press: U.S.A.

Munn, Z., Tufanaru,C., and Aromataris, E. (2014) Data Extraction and Synthesis: The steps following study selection in a systematic review. American Journal of Nursing, 114 (7). pp 49 -54

National Institute for Health and Care Excellence (2011) Psychosis with Coexisting Substance Misuse: Assessment and Management in Adults and Young People. British Library: UK

Polit, D.F. Beck, C.T. (2010) Essentials of Nursing Research: Methods, Appraisal and Utilisation. 7th edn. Philadelphia: Lippincott Williams & Wilkins

Regier, D.A., Farmer, M.E., Rae, D.S., Locke, B.Z., Keith, S.J., Judd, L.L., et al. (1990) Comorbidity of mental disorders with alcohol and other drug abuse: results from the Epidemiologic Catchment Area (ECA) Study. JAMA. (264) pp 2511-2518.

Vanvuuren, M.S. (2011) Literacy Research and the Victorian and Edwardian Ages 1830 -1910. Strategies and Sources. Literacy Research.

World Health Organisation (2017) Schizophrenia. Available at: https://

www.who.int/news-

nom/factsheets/detail/schizophrenia [Accessed 10 December 2018]

APPENDIX 1

APPENDIX 2