Inhalation versus intravenous technique for rapid emergence from anaesthesia in patients undergoing brain tumour surgery

  • Protocol
  • Intervention

Authors


Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

To compare the emergence from anaesthesia in patients receiving either inhalational (isoflurane, sevoflurane, desflurane) or intravenous (propofol) anaesthetic agents for maintenance of general anaesthesia during brain tumour surgery.

Background

Brain tumour surgery is usually carried out under general anaesthesia. Over the past years, both intravenous and inhalational anaesthetic agents have been used, however the superiority of one over the other remains debatable (Engelhard 2006; Lauta 2010; Magni 2005; Todd 1993). The anaesthetic goal during any neurosurgical procedure is to have a smooth induction of anaesthesia, stable intraoperative haemodynamics such as heart rate and blood pressure while maintaining appropriate cerebral oxygen supply, good operative conditions, and smooth and rapid emergence from anaesthesia. The latter also permits early neurological examination (Citerio 2009; Lauta 2010; Talke 2002).

Description of the condition

Early and rapid emergence from anaesthesia is desirable in most neurosurgical patients for early screening of potential complications such as haematoma, cerebrovascular ischaemia, cerebral herniation, neurological deficits, and tension pneumocephalus (Lauta 2010). Early awakening is important as the residual effect of anaesthesia may either give the false impression of a neurological deficit or prevent early diagnosis of an impending intracranial problem (Lauta 2010).

Description of the intervention

Several studies have shown that maintenance of anaesthesia with propofol, an intravenous anaesthetic agent, results in shorter emergence time following surgical procedures (Ozkose 2001; Visser 2001). Propofol has many of the properties of an ideal agent for neurosurgical patients, with beneficial cerebral haemodynamic effects reducing cerebral blood flow (CBF), favourable pharmacokinetics, and a high-quality recovery profile despite prolonged duration of infusion (Citerio 2009). Propofol produces a dose-dependent reduction of both brain oxygen requirements and CBF (Alkire1995). It maintains cerebrovascular reactivity to carbon dioxide (Craen 1992), preserves autoregulation of arterial blood pressure (Stephan 1987) and reduces intracranial pressure (Pinaud 1990). All of these are desirable effects during anaesthesia for neurosurgical procedures. However, the availability of newer and less soluble inhalational anaesthetic agents, such as sevoflurane and desflurane, has added a new dimension to recovery by allowing more rapid emergence and earlier discharge (Gupta 2004).

How the intervention might work

Propofol is highly lipophilic and rapidly crosses the blood-brain barrier resulting in a rapid onset of action. Emergence from sedation is also rapid because of fast redistribution into peripheral tissues and metabolic clearance (McKeage 2003). Anaesthesia for craniotomy must be conducted with emphasis on haemodynamic stability, a sufficient cerebral perfusion pressure (CPP), and avoidance of agents or procedures that increase the intracranial pressure (Petersen 2003). In brain tumour patients undergoing craniotomy, propofol anaesthesia is associated with lower intracranial pressure and cerebral swelling than volatile anaesthesia (Hans 2006). The potential neuroprotective effect of this drug could be mediated by its antioxidant properties, which can play a role in apoptosis, ischaemia-reperfusion injury and inflammatory-induced neuronal damage (Hans 2006).

Why it is important to do this review

In neurosurgical cases, it is always desirable to have rapid emergence from anaesthesia. This allows for early neurological assessment and recognition of potential postoperative complications such as haematoma formation and development of new neurologic deficits. Rapid diagnosis and treatment of the complications also has the advantage of reducing both morbidity and mortality in these patients, thereby reducing duration of intensive care unit and hospital stay. This may improve clinical outcomes and reduce the cost of care. The advantages of intravenous anaesthesia using propofol over inhaled anesthesia have been intensively discussed as the subject of numerous studies with opposing results (Gupta 2004). With the availability of newer intravenous and inhalational anaesthetic agents that have inherent advantages and disadvantages, we remain uncertain as to which technique may result in a more rapid early recovery from anaesthesia.

Objectives

To compare the emergence from anaesthesia in patients receiving either inhalational (isoflurane, sevoflurane, desflurane) or intravenous (propofol) anaesthetic agents for maintenance of general anaesthesia during brain tumour surgery.

Methods

Criteria for considering studies for this review

Types of studies

We will include randomized controlled trials (RCTs) that compare the use of intravenous anaesthetic agents such as propofol or etomidate with inhalational anaesthetic agents such as halothane, isoflurane, sevoflurane, enflurane or desflurane for maintenance of general anaesthesia during brain tumour surgery.

Types of participants

We will include patients of all age groups except neonates (infants less than 28 days old) who receive either inhalational or intravenous anaesthetic during craniotomy for brain tumours.

Types of interventions

Our experimental group will include patients receiving intravenous anaesthetic agent (propofol, etomidate), which will be compared to the control group. Our control group will include patients receiving inhalational anaesthetic agents such as halothane, isoflurane, sevoflurane, enflurane and desflurane. We will exclude studies where both inhalational anaesthetic agents and intravenous anaesthetic agents have been used for maintenance of anaesthesia in the same patient during surgery.

Types of outcome measures

Primary outcomes
  1. Emergence from anaesthesia (assessed by time to follow verbal commands), in minutes

  2. Adverse events during emergence, such as haemodynamic changes, agitation, desaturation, muscle weakness, nausea and vomiting, shivering and pain

Secondary outcomes
  1. Time to eye opening, in minutes

  2. Recovery from anaesthesia using the Aldrete or Modified Aldrete score (i.e. time to attain score of ≥ 9, in minutes)

  3. Opioid consumption, in micrograms

  4. Brain relaxation (as assessed by surgeon on 4 or 5-point scale)

  5. Complications of anaesthetic techniques, such as intraoperative haemodynamic instability in terms of hypotension or hypertension (mm Hg), increased or decreased heart rate (beats/minute) and brain swelling

Search methods for identification of studies

Electronic searches

We will search the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, latest issue), MEDLINE via OvidSP (1966 to date), and EMBASE via OvidSP (1980 to date).

Our MEDLINE search terms are found in Appendix 1. The MEDLINE search strategy is combined with the Cochrane highly sensitive search filter for identifying RCTs (Lefebvre 2011). The MEDLINE search strategy will be adapted for searching other databases.

We will not apply any language restriction.

Searching other resources

We will search for relevant ongoing trials on specific websites:

1. www.indmed.nic.in;

2. www.cochrane-sadcct.org;

3. www.Clinicaltrials.gov.

Data collection and analysis

Selection of studies

Using the results of the above searches, we will screen all titles and abstracts for eligibility. Two authors (HP and VA) will independently perform this screening. We will obtain and assess for relevance the full articles of all potentially eligible RCTs based on the preplanned checklist (Appendix 2). Each author will document the reason for exclusion of each trial. We will resolve any disagreement between the two authors by discussion with a third author (GPS), who will decide on the inclusion or exclusion of the study. We will compile a list of all eligible trials. In the case of additional information being required, GPS or HP will contact the first author of the relevant trial.

Data extraction and management

Two authors (HP and VA) will independently extract the data and assess the trial quality using a standardized form (Appendix 2). We will resolve any disagreement by discussion with the third author (GPS). We will perform the assessment as suggested in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Assessment of risk of bias in included studies

We will judge the quality of the studies on the basis of the quality domains:

1. random sequence generation;

2. allocation concealment;

3. blinding and outcome assessment;

4. Incomplete outcome data;

5. Selective reporting;

6. Any other bias.

We will consider a trial as having a low risk of bias if all domains are assessed as adequate. We will consider a trial as having a high risk of bias if one or more domain is assessed as inadequate or unclear.

We will include a 'Risk of bias' table as part of the 'Table of characteristics of included studies' and a 'Risk of bias summary' figure, which will detail all of the judgements made for all included studies in the review.

Measures of treatment effect

We will undertake an analysis using RevMan 5.1 software. We will use relative risk (RR) to measure treatment effect for proportions (dichotomous outcomes) among the primary outcomes and adverse effects. We will convert continuous data to the mean difference (MD) using the inverse variance method and an overall MD will be calculated. We will use a fixed-effect model where there is no evidence of significant heterogeneity between studies, and a random-effects model if heterogeneity is likely (DerSimonian 1986). As an estimate of the statistical significance of a difference between the experimental and control interventions, we will calculate the RR and MD between groups and the 95% confidence intervals (CI). A statistically significant difference between the intervention and control groups will be assumed if the 95% CI does not include the value of no differential effect.

Unit of analysis issues

We will only include RCTs with a parallel group design in our review.

Dealing with missing data

We will perform quantitative analysis on an intention-to-treat (ITT) basis and contact the trial authors in order to obtain any missing data. We will analyse missing data, if any, by imputation using a best case and worst case scenario method. If we find insufficient data, the potential impact of the missing data will be considered in the interpretation of the results.

Assessment of heterogeneity

We will not perform meta-analysis if we suspect important clinical heterogeneity on examination of the included trials. We will use the Q statistic to test the statistical heterogeneity between trials and consider a P ≤ 0.05 as indicating significant heterogeneity; we will use the I2 statistic to assess the magnitude of heterogeneity (Higgins 2002). We will consider an I2 > 50% to indicate problematic heterogeneity between trials and will carefully consider the value of any pooled analysis. We will use a random-effects model analysis if the I2 is greater than 30%.

Assessment of reporting biases

We will assess publication bias and small study effect in a qualitative manner using a funnel plot. We will test for funnel plot asymmetry if there are more than 10 studies included in the meta-analysis.

Data synthesis

We will quantitatively review the included data and combine the data by intervention, outcome and population using the Cochrane Collaboration statistical software (RevMan 5.1). We will only synthesize the data in the absence of important clinical or statistical heterogeneity and we will express pooled estimates of the mean difference (MD) for continuous variables and relative risk (RR) for proportions, as described above.

Subgroup analysis and investigation of heterogeneity

Where appropriate, with obvious clinical or statistical (I2 > 50%) heterogeneity, we will consider subgroup analysis based on gender, location of tumour, size of tumour, types of opioids used, type of muscle relaxant, use of local anaesthetic, and use of nitrous oxide whenever the data indicates heterogeneity on that basis.

Sensitivity analysis

We will perform sensitivity analyses to explore the consistency of effect size measures in trials with low risk of bias versus those with high risk of bias and to investigate the impact of any missing data using the imputation method described above.

Summary of findings

We will use the principles of the GRADE system (Guyatt 2008) to assess the quality of the body of evidence associated with specific outcomes (mortality, emergence from anaesthesia, brain relaxation, intraoperative haemodynamic instability, hospital stay, three-months outcome) in our review and construct a 'Summary of findings' (SoF) table using the GRADE software. The GRADE approach appraises the quality of a body of evidence based on the extent to which one can be confident that an estimate of effect or association reflects the item being assessed. The quality of a body of evidence considers within study risk of bias (methodologic quality), the directness of the evidence, heterogeneity of the data, precision of effect estimates and risk of publication bias.

Acknowledgements

We would like to thank Mike Bennett (content editor), Cathal Walsh (statistical editor), Federico Bilotta and Rajesh Shetty (peer reviewers) for their help and editorial advice during the preparation of this protocol for the systematic review. We would also like to thank Jane Cracknell (Cochrane Anaesthesia Review Group (CARG)) for guiding us through this protocol and Karen Hovhannisyan (CARG) for preparing our search strategy.

Appendices

Appendix 1. Search strategy for MEDLINE (OvidSP)

1.     exp Brain Neoplasms/
2.     Neurosurgery/ or Neurosurgical Procedures/
3.     (((brain or neuro*) adj3 (tumor* or neoplasm* or cancer or carcinoma or sarcoma)) and (operat* or surg*)).mp.
4.     1 or 2 or 3
5.     Anesthetics, Inhalation/ or Anesthesia, Inhalation/ or Anesthesia, Intravenous/
6.     ((Inhalat* and intraven*) adj3 an?esth*).mp.
7.     5 or 6
8.     4 and 7

Appendix 2. Data extraction forms

 

Review title or ID
     

 

Study ID (surname of first author and year first full report of study was published e.g. Smith 2001)
     

 

Report IDs of other reports of this study (e.g. duplicate publications, follow-up studies)
     

 

Notes:        

 

 

 

1.     General Information

 

Date form completed (dd/mm/yyyy)     
Name/ID of person extracting data

     

 

Report title

(title of paper/ abstract/ report that data are extracted from)

     

 

Report ID

(ID for this paper/ abstract/ report)

     

 

Reference details

 

     

 

 

Report author contact details

     

 

Publication type

(e.g. full report, abstract, letter)

     

 

Study funding sources

(including role of funders)

     

 

Possible conflicts of interest

(for study authors)

     

 

Notes:      

 

 

 

2.     Study Eligibility

 

Study Characteristics

Eligibility criteria

(Insert eligibility criteria for each characteristic as defined in the Protocol)

YesNoUnclear

Location in text

(pg & ¶/fig/table)

Type of studyRandomized Controlled Trial        

Controlled Clinical Trial

(quasi-randomized trial)

        

Participants

 

     

 

 

        
Types of intervention

     

 

 

        
Types of outcome measures

     

 

 

        
INCLUDE EXCLUDE 

Reason for exclusion

 

     

Notes:        

 

 

       

 

DO NOT PROCEED IF STUDY EXCLUDED FROM REVIEW

3.     Population and setting

 

 

Description

Include comparative information for each group (i.e. intervention and controls) if available

Location in text

(pg & ¶/fig/table)

Population description

(from which study participants are drawn)

          

Setting

(including location and social context)

          
Inclusion criteria          
Exclusion criteria          
Method/s of recruitment of participants          

Informed consent obtained

 

          

Yes     No    Unclear

          

Notes:        

 

 

    

 

4.     Methods

 

 

Descriptions as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Aim of study

 

 

          
Design (e.g. parallel, crossover, cluster)          

Unit of allocation

(by individuals, cluster/ groups or body parts)

          

Start date

 

     

 

     

End date

 

     

 

     

Total study duration

 

          
Ethical approval needed/ obtained for study

          

Yes     No    Unclear

          

Notes:        

 

 

    

 

5.     Risk of Bias assessment

See Chapter 8 of the Cochrane Handbook

 

Domain

Risk of bias

 

Support for judgement

 

Location in text

(pg & ¶/fig/table)

Low riskHigh riskUnclear

Random sequence generation

(selection bias)

             

Allocation concealment

(selection bias)

 

             

Blinding of participants and personnel

(performance bias)

   

Outcome group: All/     

     

     
(if required)   

Outcome group:      

     

     

Blinding of outcome assessment

(detection bias)

   

Outcome group: All/     

     

     
(if required)   

Outcome group:      

     

     

Incomplete outcome data

(attrition bias)

 

             

Selective outcome reporting?

(reporting bias)

             

Other bias

 

 

             

Notes:        

 

 

 

6.     Participants

Provide overall data and, if available, comparative data for each intervention or comparison group.

 

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Total no. randomized

(or total pop. at start of study for NRCTs)

          

Clusters

(if applicable, no., type, no. people per cluster)

          
Baseline imbalances          

Withdrawals and exclusions

(if not provided below by outcome)

          
Age          
Sex          
Race/Ethnicity          
Severity of illness          

Co-morbidities

 

          
Other treatment received (additional to study intervention)          

Other relevant sociodemographics

 

          

Subgroups measured

 

          

Subgroups reported

 

          

Notes:        

 

 

 

7.     Intervention groups

Copy and paste table for each intervention and comparison group

 

Intervention Group 1

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Group name

 

          

No. randomized to group

(specify whether no. people or clusters)

          

Theoretical basis (include key references)

 

          
Description (include sufficient detail for replication, e.g. content, dose, components)          
Duration of treatment period          
Timing (e.g. frequency, duration of each episode)          
Delivery (e.g. mechanism, medium, intensity, fidelity)          

Providers

(e.g. no., profession, training, ethnicity etc. if relevant)

          

Co-interventions

 

          
Economic variables
(i.e. intervention cost, changes in other costs as result of intervention)
          

Resource requirements to replicate intervention

(e.g. staff numbers, cold chain, equipment)

          

Notes:        

 

 

 

8.     Outcomes

Copy and paste table for each outcome.

 

Outcome 1

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Outcome name

 

     Mortality     
Time points measured          
Time points reported          
Outcome definition (with diagnostic criteria if relevant)          
Person measuring/reporting          

Unit of measurement

(if relevant)

 

          
Scales: upper and lower limits (indicate whether high  or low score is good)          
Is outcome/tool validated?

          

Yes     No    Unclear

          
Imputation of missing data
(e.g. assumptions made for ITT analysis)
          

Assumed risk estimate

(e.g. baseline or population risk noted  in Background)

          
Power          

Notes:        

 

    

 

Outcome 2

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Outcome name

 

Emergence from anaesthesia     
Time points measured          
Time points reported          
Outcome definition (with diagnostic criteria if relevant)          
Person measuring/reporting          

Unit of measurement

(if relevant)

 

          
Scales: upper and lower limits (indicate whether high  or low score is good)          
Is outcome/tool validated?

          

Yes     No    Unclear

          
Imputation of missing data
(e.g. assumptions made for ITT analysis)
          

Assumed risk estimate

(e.g. baseline or population risk noted  in Background)

          
Power          

Notes:        

 

    

 

Outcome 3

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Outcome name

 

      Brain relaxation     
Time points measured          
Time points reported          
Outcome definition (with diagnostic criteria if relevant)          
Person measuring/reporting          

Unit of measurement

(if relevant)

 

          
Scales: upper and lower limits (indicate whether high  or low score is good)          
Is outcome/tool validated?

          

Yes     No    Unclear

          
Imputation of missing data
(e.g. assumptions made for ITT analysis)
          

Assumed risk estimate

(e.g. baseline or population risk noted  in Background)

          
Power          

Notes:        

 

    

 

Outcome 4

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Outcome name

 

Intraoperative haemodynamic instability     
Time points measured          
Time points reported          
Outcome definition (with diagnostic criteria if relevant)          
Person measuring/reporting          

Unit of measurement

(if relevant)

 

          
Scales: upper and lower limits (indicate whether high  or low score is good)          
Is outcome/tool validated?

          

Yes     No    Unclear

          
Imputation of missing data
(e.g. assumptions made for ITT analysis)
          

Assumed risk estimate

(e.g. baseline or population risk noted  in Background)

          
Power          

Notes:        

 

    

 

Outcome 5

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Outcome name

 

Hospital stay     
Time points measured          
Time points reported          
Outcome definition (with diagnostic criteria if relevant)          
Person measuring/reporting          

Unit of measurement

(if relevant)

 

          
Scales: upper and lower limits (indicate whether high  or low score is good)          
Is outcome/tool validated?

          

Yes     No    Unclear

          
Imputation of missing data
(e.g. assumptions made for ITT analysis)
          

Assumed risk estimate

(e.g. baseline or population risk noted  in Background)

          
Power          

Notes:        

 

    

 

Outcome 6

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Outcome name

 

3 months outcome

 

     
Time points measured          
Time points reported          
Outcome definition (with diagnostic criteria if relevant)          
Person measuring/reporting          

Unit of measurement

(if relevant)

 

          
Scales: upper and lower limits (indicate whether high  or low score is good)          
Is outcome/tool validated?

          

Yes     No    Unclear

          
Imputation of missing data
(e.g. assumptions made for ITT analysis)
          

Assumed risk estimate

(e.g. baseline or population risk noted  in Background)

          
Power          

Notes:        

 

    

 

9.     Results

Copy and paste the appropriate table for each outcome, including additional tables for each time point and subgroup as required.

 

Dichotomous outcome (Mortality)

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Comparison          
Outcome          
Subgroup          
Timepoint
(specify whether from start or end of intervention)
          
ResultsInterventionComparison     
No. eventsNo. participantsNo. eventsNo. participants
                    
No. missing participants and reasons               
No. participants moved from other group and reasons               
Any other results reported          

Unit of analysis (by individuals, cluster/groups or body parts)

 

          
Statistical methods used and appropriateness of these methods (e.g. adjustment for correlation)          
Reanalysis required? (specify)

          

Yes     No    Unclear

          
Reanalysis possible?

          

Yes     No    Unclear

          
Reanalysed results          

Notes:        

 

 

       

 

Dichotomous outcome (Brain relaxation))

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Comparison          
Outcome          
Subgroup          
Timepoint
(specify whether from start or end of intervention)
          
ResultsInterventionComparison     
No. eventsNo. participantsNo. eventsNo. participants
                    
No. missing participants and reasons               
No. participants moved from other group and reasons               
Any other results reported          

Unit of analysis (by individuals, cluster/groups or body parts)

 

          
Statistical methods used and appropriateness of these methods (e.g. adjustment for correlation)          
Reanalysis required? (specify)

          

Yes     No    Unclear

          
Reanalysis possible?

          

Yes     No    Unclear

          
Reanalysed results          

Notes:        

 

 

       

 

Dichotomous outcome (Three months outcome)

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Comparison          
Outcome          
Subgroup          
Timepoint
(specify whether from start or end of intervention)
          
ResultsInterventionComparison     
No. eventsNo. participantsNo. eventsNo. participants
                    
No. missing participants and reasons               
No. participants moved from other group and reasons               
Any other results reported          

Unit of analysis (by individuals, cluster/groups or body parts)

 

          
Statistical methods used and appropriateness of these methods (e.g. adjustment for correlation)          
Reanalysis required? (specify)

          

Yes     No    Unclear

          
Reanalysis possible?

          

Yes     No    Unclear

          
Reanalysed results          

Notes:        

 

 

       

 

 

Continuous outcome (Emergence from anaesthesia)

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Comparison          
Outcome          
Subgroup          
Timepoint
(specify whether from start or end of intervention)
          
Post-intervention or change from baseline?          
ResultsInterventionComparison 
MeanSD (or other variance)No. participantsMeanSD (or other variance)No. participants     
                              
No. missing participants and reasons               
No. participants moved from other group and reasons               

Any other results reported

 

          

Unit of analysis

(individuals, cluster/ groups or body parts)

          
Statistical methods used and appropriateness of these methods (e.g. adjustment for correlation)          
Reanalysis required? (specify)

          

Yes     No    Unclear

          
Reanalysis possible?

          

Yes     No    Unclear

          
Reanalysed results          

Notes:        

 

 

 
           

 

Continuous outcome (Intraoperative haemodynamic instability)

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Comparison          
Outcome          
Subgroup          
Timepoint
(specify whether from start or end of intervention)
          
Post-intervention or change from baseline?          
ResultsInterventionComparison 
MeanSD (or other variance)No. participantsMeanSD (or other variance)No. participants     
                              
No. missing participants and reasons               
No. participants moved from other group and reasons               

Any other results reported

 

          

Unit of analysis

(individuals, cluster/ groups or body parts)

          
Statistical methods used and appropriateness of these methods (e.g. adjustment for correlation)          
Reanalysis required? (specify)

          

Yes     No    Unclear

          
Reanalysis possible?

          

Yes     No    Unclear

          
Reanalysed results          

Notes:        

 

 

 
           

 

Continuous outcome (Hospital stay)

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Comparison          
Outcome          
Subgroup          
Timepoint
(specify whether from start or end of intervention)
          
Post-intervention or change from baseline?          
ResultsInterventionComparison 
MeanSD (or other variance)No. participantsMeanSD (or other variance)No. participants     
                              
No. missing participants and reasons               
No. participants moved from other group and reasons               

Any other results reported

 

          

Unit of analysis

(individuals, cluster/ groups or body parts)

          
Statistical methods used and appropriateness of these methods (e.g. adjustment for correlation)          
Reanalysis required? (specify)

          

Yes     No    Unclear

          
Reanalysis possible?

          

Yes     No    Unclear

          
Reanalysed results          

Notes:        

 

 

 
           

 

 

Other outcome

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Comparison          
Outcome          
Subgroup          
Timepoint
(specify whether from start or end of intervention)
          
ResultsIntervention resultSD (or other variance)Control resultSD (or other variance)     
                    
Overall resultsSE (or other variance)
          
No. participantsInterventionControl 
          
No. missing participants and reasons               
No. participants moved from other group and reasons               
Any other results reported          
Unit of analysis (by individuals, cluster/groups or body parts)          
Statistical methods used and appropriateness of these methods          
Reanalysis required? (specify)

          

Yes     No    Unclear

          
Reanalysis possible?

          

Yes     No    Unclear

          
Reanalysed results          

Notes:        

 

 

       

 

10. Applicability

 

Have important populations been excluded from the study? (consider disadvantaged populations, and possible differences in the intervention effect)

          

Yes     No    Unclear

     
Is the intervention likely to be aimed at disadvantaged groups? (e.g. lower socioeconomic groups)

          

Yes     No    Unclear

     

Does the study directly address the review question?

(any issues of partial or indirect applicability)

          

Yes     No    Unclear

     

Notes:        

 

 

 

11. Other information

 

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Key conclusions of study authors

 

          

References to other relevant studies

 

          
Correspondence required for further study information (from whom, what and when)     

Notes:        

 

 

Contributions of authors

Conceiving the review: Gyaninder Pal Singh (GPS)

Co-ordinating the review: GPS, Hemanshu Prabhakar (HP)

Undertaking manual searches: GPS, Vidhu Anand (VA)

Screening search results: HP, VA

Organizing retrieval of papers: GP, HP

Screening retrieved papers against inclusion criteria: HP, VA

Appraising quality of papers: HP, VA

Abstracting data from papers: HP, VA

Writing to authors of papers for additional information: GPS, HP

Providing additional data about papers: GPS, HP

Obtaining and screening data on unpublished studies: HP, VA

Data management for the review: GPS, HP

Entering data into Review Manager (RevMan 5.1): GPS, HP

RevMan statistical data: Mani Kalaivani (MK), HP

Other statistical analysis not using RevMan: MK

Interpretation of data: MK, GPS, HP

Statistical inferences: MK, GPS

Writing the review: GPS

Securing funding for the review:

Performing previous work that was the foundation of the present study:

Guarantor for the review (one author): GPS

Person responsible for reading and checking review before submission: GPS, HP

Declarations of interest

Gyaninder Pal Singh: none known

Hemanshu Prabhakar: none known

Mani Kalaivani: none known

Vidhu Anand: none known

Sources of support

Internal sources

  • All India Institute of Medical Sciences, New Delhi, India.

External sources

  • No sources of support supplied

Ancillary