Use of platelet transfusions prior to lumbar punctures or epidural anaesthesia for the prevention of complications in people with thrombocytopenia

Lise J Estcourt; Reem Malouf; Sally Hopewell; Carolyn Doree; Joost Van Veen

doi:10.1002/14651858.CD011980.pub3

腰穿刺或硬膜外麻醉前输注血小板预防血小板减少症患者并发症

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Referencias

References to studies included in this review

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References to studies excluded from this review

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otras versiones publicadas

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References to other published versions of this review

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estudios incluidos
estudios excluidos
otras referencias

Estcourt LJ, Ingram C, Hopewell S, Trivella M, Doree C, Stanworth SJ. Use of platelet transfusions prior to lumbar punctures or epidural anaesthesia for the prevention of complications in people with thrombocytopenia. Cochrane Database of Systematic Reviews 2015, Issue 12. [DOI: 10.1002/14651858.CD011980]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Ir a:

estudios excluidos

Howard 2000

Methods	Type of study: Retrospective cohort study Type of publication: Full Setting and country: USA Number of centres: 1 centre, St Jude Children’s Research Hospital, Memphis, TN Recruitment dates (start and end): February 1984 to July 1998 Study duration: 14 years Was a power calculation performed? No Platelet counts collected within 24 hours before lumbar puncture: Not from all children: 208 LPs were performed without platelet counts within 1 day of performing LPs
Participants	Inclusion criteria: Children with newly diagnosed ALL Exclusion criteria: Not reported Number of potentially eligible participants: 958 children undergoing 5442 LPs Number of participants analysed: 956 children. 1 child was excluded due to early death from sepsis before initiation of intrathecal therapy, and another was excluded because an intracranial haemorrhage at the time of diagnosis resulted in grossly bloody CSF at each of 11 LPs performed to relieve pressure. Number of participants with platelet counts < 50 x 10⁹/L: Not reported Age: Median 5.5 years (range 1 month to 18 years) Gender: 524 boys (55%) and 434 girls (45%) Ethnicity: 83% white, 13% black, 4% other races Coagulopathy: No information Platelet dysfunction: No information End‐stage renal disease: No information Diagnosis: ALL Number of lumbar punctures: 5223, 895 LPs performed at diagnosis. 41 LPs were excluded because no platelet count was performed within 1 day of LP, and 167 LPs were excluded because no platelet count was documented after transfusion of platelets. Number of lumbar punctures per participant: Median 5 LPs. Each child received 2 to 9 LPs during the study period for the administration of intrathecal chemotherapy in addition to 1 diagnostic LP. Platelet counts levels and number of lumber punctures: 1 to 5 x 10⁹/L (6 LPs), 6 to 10 x 10⁹/L (23 LPs), 11 to 20 x 10⁹/L (170 LPs), 21 to 30 x 10⁹/L (234 LPs), 31 to 40 x 10⁹/L (235 LPs), 41 to 50 x 10⁹/L (273 LPs) Treatment: Induction chemotherapy (prednisone, asparaginase, vincristine, daunorubicin, etoposide (or teniposide), and cytarabine with or without methotrexate) Co‐intervention (plasma transfusions, haemostatic agents): No information Were participants with active bleeding explicitly excluded? No information
Interventions	Platelet transfusion with all relevant information was missing; this included number of children who received the transfusion, number of children who did not receive the transfusion, platelet thresholds, dose, and frequency. All LPs were performed by paediatric oncologists, paediatric oncology fellows, paediatric residents, and nurse practitioners.
Outcomes	Primary outcomes: Serious complications including any neurological, infectious, or haemorrhagic problems apart from headache, nausea, irritability, or somnolence. Red blood cells per high‐powered microscopic field of 500 or more in the CSF was an indication of traumatic LP.
Notes	Trial register ID: Not reported Supported by: Cancer Center Support (CORE) Conflicts‐of‐interest statement: Not declared Ethical approval body: No information Contact email: [email protected] Address: Department of Hematology‐Oncology, ALSAC Bldg, Room C6005, St Jude Children's Research Hospital, Memphis, TN
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Confounding Major procedure‐related bleeding within 24 hours	Unclear risk	ROBINS‐I not performed, outcome not reported.
Confounding Serious adverse events: LP‐related or epidural anaesthetic‐related	Unclear risk	ROBINS‐I not performed, outcome not reported.
Selection of participants into the study Major procedure‐related bleeding within 24 hours	Unclear risk	ROBINS‐I not performed, outcome not reported.
Selection of participants into the study Serious adverse events: LP‐related or epidural anaesthetic‐related	Unclear risk	ROBINS‐I not performed, outcome not reported.
Classification of interventions Major procedure‐related bleeding within 24 hours	Unclear risk	ROBINS‐I not performed, outcome not reported.
Classification of interventions Serious adverse events: LP‐related or epidural anaesthetic‐related	Unclear risk	ROBINS‐I not performed, outcome not reported.
Deviations from intended interventions Major procedure‐related bleeding within 24 hours	Unclear risk	ROBINS‐I not performed, outcome not reported.
Deviations from intended interventions Serious adverse events: LP‐related or epidural anaesthetic‐related	Unclear risk	ROBINS‐I not performed, outcome not reported.
Incomplete outcome data (attrition bias) Major procedure‐related bleeding within 24 hours	Unclear risk	ROBINS‐I not performed, outcome not reported.
Incomplete outcome data (attrition bias) Serious adverse events: LP‐related or epidural anaesthetic‐related	Unclear risk	ROBINS‐I not performed, outcome not reported.
Measurement of outcomes Major procedure‐related bleeding within 24 hours	Unclear risk	ROBINS‐I not performed, outcome not reported.
Measurement of outcomes Serious adverse events: LP‐related or epidural anaesthetic‐related	Unclear risk	ROBINS‐I not performed, outcome not reported.
Selective reporting (reporting bias) Major procedure‐related bleeding within 24 hours	Unclear risk	ROBINS‐I not performed, outcome not reported.
Selective reporting (reporting bias) Serious adverse events: LP‐related or epidural anaesthetic‐related	Unclear risk	ROBINS‐I not performed, outcome not reported.
Overall bias Major procedure‐related bleeding within 24 hours	Unclear risk	ROBINS‐I not performed, outcome not reported.
Overall bias Serious adverse events: LP‐related or epidural anaesthetic‐related	Unclear risk	ROBINS‐I not performed, outcome not reported.

Ning 2016

Methods	Type of study: Retrospective cohort study Type of publication: Full Setting and country: Sunnybrook Health Sciences Centre ‐ Canada Number of centres: 1 centre in Toronto Recruitment dates (start and end): January 2013 until December 2014 Study duration: 23 months Was a power calculation performed? No Platelet counts collected within 24 hours before lumbar puncture: Yes
Participants	Inclusion criteria: Adults (≥ 18 years) with malignancy undergoing LPs from January 2013 until December 2014 Exclusion criteria: People with coagulopathy INR ≥ 1.5, aPTT ≥ 40 s, fibrinogen ≤ 1.0 g/L Number of participants included: 135 Number of participants with platelet counts < 50 x 10⁹/L: 21; platelet transfusion group (n = 14) and no‐platelet transfusion group (n = 7) Number of participants analysed: 21 Age: Mean (range): platelet transfusion group: 50 (38 to 70) years; no‐platelet transfusion group: 57 (20 to 80) years Gender: Platelet transfusion group: female (n = 4) (22%); no‐platelet transfusion group: female (n = 5) (71.4%) Ethnicity: Not reported Coagulopathy: Platelet transfusion group (n = 0); no‐platelet transfusion group (n = 0) Platelet dysfunction: Platelet transfusion group (n = 0); no‐platelet transfusion group (n = 0) End‐stage renal disease: Platelet transfusion group (n = 0); no‐platelet transfusion group (n = 0) Diagnosis: Platelet transfusion group: lymphoma (n = 7), leukaemia (n = 7), other malignancies (n = 0); no‐platelet transfusion group: lymphoma (n = 4), leukaemia (n = 2), other malignancies (n = 1) Number of lumbar punctures: 28; platelet transfusion group (n = 18); no‐platelet transfusion group (n = 10) Number of lumbar punctures per participant: median 1 Number of lumber punctures and platelet counts: Pre‐LP platelet count ≤ 10 x 10⁹/L: platelet transfusion group (n = 1); no‐platelet transfusion group (n = 0) Pre‐LP platelet count 11 to 20 x 10⁹/L: platelet transfusion group (n = 5); no‐platelet transfusion group (n = 2) Pre‐LP platelet count 21 to 30 x 10⁹/L: platelet transfusion group (n = 3); no‐platelet transfusion group (n = 2) Pre‐LP platelet count 31 to 40 x 10⁹/L: platelet transfusion group (n = 6); no‐platelet transfusion group (n = 1) Pre‐LP platelet count 41 to 50 x 10⁹/L: platelet transfusion group (n = 3); no‐platelet transfusion group (n = 5) Co‐intervention (plasma transfusions, haemostatic agents): No information Were participants with active bleeding explicitly excluded? Yes, but participants with risk of bleeding were included: antiplatelet agents: platelet transfusion group (n = 2); no‐platelet transfusion group (n = 0) anticoagulants ‐ prophylactic: platelet transfusion group (n = 8); no‐platelet transfusion group (n = 1) anticoagulants ‐ therapeutic: platelet transfusion group (n = 1); no‐platelet transfusion group (n = 1)
Interventions	Platelet transfusion: single transfusion with either a pool of 4 units of buffy coat‐derived platelet or 1 unit of single‐donor apheresis platelet when platelet count ≤ 50 x 10⁹/L No platelet transfusion: no transfusion when platelet count ≤ 50 x 10⁹/L
Outcomes	Haemorrhagic complications (spinal, subdural, subarachnoid, and epidural haematomas) Traumatic tap: ≥ 500 x 10⁶/L red blood cells in the CSF
Notes	Trial register ID: Not reported Supported by: Not reported Conflicts‐of‐interest statement: Not reported Ethical approval body: Study was approved by the Institution's Research Ethics Board. Contact email: [email protected] Address: Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Rm B‐204, Toronto, ON M4N 3M5, Canada
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Confounding Major procedure‐related bleeding within 24 hours	Unclear risk	ROBINS‐I judgement (Serious) The following confounders were measured but not adjusted for: participants' diagnosis, age, gender, antiplatelet, anticoagulants, haemostasis.
Confounding Serious adverse events: LP‐related or epidural anaesthetic‐related	High risk	ROBINS‐I judgement (Serious) The following confounders were measured but not adjusted for: participants' diagnosis, age, gender, antiplatelet, anticoagulants, haemostasis.
Selection of participants into the study Major procedure‐related bleeding within 24 hours	Low risk	ROBINS‐I judgement (Low) Selection of participants into the study was not based on participant characteristics observed after the start of the intervention. We were not aware of the exclusion of any participants from the analysis for this outcome.
Selection of participants into the study Serious adverse events: LP‐related or epidural anaesthetic‐related	Low risk	ROBINS‐I judgement (Low) Selection of participants into the study was not based on participant characteristics observed after the start of the intervention.
Classification of interventions Major procedure‐related bleeding within 24 hours	Low risk	ROBINS‐I judgement (Low) Both the group who received platelet transfusion and the group who did not receive platelet transfusion before LPs were clearly defined, and all the information used to define each group was equally reported.
Classification of interventions Serious adverse events: LP‐related or epidural anaesthetic‐related	Low risk	ROBINS‐I judgement (Low) Both the group who received platelet transfusion and the group who did not receive platelet transfusion before LPs were clearly defined, and all the information used to define each group was equally reported.
Deviations from intended interventions Major procedure‐related bleeding within 24 hours	Unclear risk	ROBINS‐I judgement (No information) No information reported.
Deviations from intended interventions Serious adverse events: LP‐related or epidural anaesthetic‐related	Unclear risk	ROBINS‐I judgement (No information) No information reported.
Incomplete outcome data (attrition bias) Major procedure‐related bleeding within 24 hours	Low risk	ROBINS‐I judgement (Low) Data for this outcome were available for all participants, and it is likely that no participants were excluded due to missing data.
Incomplete outcome data (attrition bias) Serious adverse events: LP‐related or epidural anaesthetic‐related	Low risk	ROBINS‐I judgement (Low) Data for this outcome were available for all participants, and it is likely that no participants were excluded due to missing data.
Measurement of outcomes Major procedure‐related bleeding within 24 hours	High risk	ROBINS‐I judgement (Serious) Outcome assessors were aware of the intervention received by each participant in the study, which could have influenced the assessment of this outcome. No information on whether the methods of assessing major bleeding were comparable across the platelet‐transfused and not‐transfused groups.
Measurement of outcomes Serious adverse events: LP‐related or epidural anaesthetic‐related	High risk	ROBINS‐I judgement (Serious) Outcome assessors were aware of the intervention status of the participants in the study, which could have influenced the assessment of this outcome. Information on outcome assessment methods was missing.
Selective reporting (reporting bias) Major procedure‐related bleeding within 24 hours	Unclear risk	ROBINS‐I judgement (No information) No information reported.
Selective reporting (reporting bias) Serious adverse events: LP‐related or epidural anaesthetic‐related	Unclear risk	ROBINS‐I judgement (No information) No information reported.
Overall bias Major procedure‐related bleeding within 24 hours	High risk	ROBINS‐I judgement (Serious)
Overall bias Serious adverse events: LP‐related or epidural anaesthetic‐related	High risk	ROBINS‐I judgement (Serious)

van Veen 2004

Methods	Type of study: Retrospective cohort study Type of publication: Full Setting and country: Department of Haematology, Sheffield Children’s Hospital, UK Number of centres: 1 centre Recruitment dates (start and end): 1989 and 2003 Study duration: 14 years Was a power calculation performed? No Platelet counts collected within 24 hours before lumbar puncture: Unknown
Participants	Inclusion criteria: 226 children newly diagnosed acute lymphoblastic leukaemia (ALL) Exclusion criteria: Not reported Number of participants included: 226 children Number of participants with platelet counts < 50 x 10⁹/L: 135 children; 129 underwent LPs, 72 without a platelet transfusion Number of participants analysed: 129 Age: All were children, but not reported further. Gender: Not reported Ethnicity: Not reported Coagulopathy: Not reported Platelet dysfunction: Not reported End‐stage renal disease: Not reported Diagnosis: ALL Number of lumbar punctures: 129 Median of the number of lumbar punctures per participant: Not reported Number of lumber punctures and platelet counts: Platelet count < 10 x 10⁹/L: 22 LPs; 13 LPs platelet transfusion, 9 LPs no transfusion Platelet count 10 to 20 x 10⁹/L: 42 LPs; 20 LPs platelet transfusion, 22 LPs no transfusion Platelet count 21 to 50 x 10⁹/L: 65 LPs; 24 LPs platelet transfusion, 41 LPs no transfusion Treatment: Intrathecal chemotherapy Co‐intervention (plasma transfusions, haemostatic agents): No information Were participants with active bleeding explicitly excluded? No information
Interventions	Platelet transfusion: n = 57 children No platelet transfusion: n = 72 children
Outcomes	Traumatic tap Minor bleeding
Notes	Trial register ID: Not reported Supported by: Not reported Conflicts‐of‐interest statement: Not reported Ethical approval body: Not reported Contact email: [email protected] Address: Department of Haematology, Sheffield Children’s Hospital, Western Bank, Sheffield S10 2TH, UK
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Confounding Major procedure‐related bleeding within 24 hours	Unclear risk	ROBINS‐I judgement (Serious) No information was provided to suggest that potential confounding factors were considered and adjusted for in the analysis.
Confounding Serious adverse events: LP‐related or epidural anaesthetic‐related	High risk	ROBINS‐I judgement (Serious) No information was provided to suggest that potential confounding factors were considered and adjusted for in the analysis.
Selection of participants into the study Major procedure‐related bleeding within 24 hours	Low risk	ROBINS‐I judgement (Low) Selection of participants into the study was not based on their characteristics.
Selection of participants into the study Serious adverse events: LP‐related or epidural anaesthetic‐related	Low risk	ROBINS‐I judgement (Low) Selection of participants into the study was not based on their characteristics.
Classification of interventions Major procedure‐related bleeding within 24 hours	Low risk	ROBINS‐I judgement (Low) The assignment to the interventions (platelet transfusion or no platelet transfusion) was not based on characteristics.
Classification of interventions Serious adverse events: LP‐related or epidural anaesthetic‐related	Low risk	ROBINS‐I judgement (Low) The two groups were clearly defined with regard to the number of participants in each group, platelet counts, and the number of LP procedures.
Deviations from intended interventions Major procedure‐related bleeding within 24 hours	Unclear risk	ROBINS‐I judgement (No information) No information to suggest a cross‐contamination between platelet transfusion group and no‐platelet transfusion group occurred
Deviations from intended interventions Serious adverse events: LP‐related or epidural anaesthetic‐related	Unclear risk	ROBINS‐I judgement (No information) No information to suggest a cross‐contamination between platelet transfusion group and no‐platelet transfusion group occurred
Incomplete outcome data (attrition bias) Major procedure‐related bleeding within 24 hours	Low risk	ROBINS‐I judgement (Low) Data for this outcome were probably available for all participants.
Incomplete outcome data (attrition bias) Serious adverse events: LP‐related or epidural anaesthetic‐related	Low risk	ROBINS‐I judgement (Low) Data for this outcome were probably available for all participants.
Measurement of outcomes Major procedure‐related bleeding within 24 hours	High risk	ROBINS‐I judgement (Serious) The outcomes assessors were aware of participants' intervention status. However, the assessors knowledge of the intervention status would likely have had no influence on the reporting of this outcome.
Measurement of outcomes Serious adverse events: LP‐related or epidural anaesthetic‐related	High risk	ROBINS‐I judgement (Serious) The outcomes assessors were aware of participants' intervention status.
Selective reporting (reporting bias) Major procedure‐related bleeding within 24 hours	Unclear risk	ROBINS‐I judgement (No information)
Selective reporting (reporting bias) Serious adverse events: LP‐related or epidural anaesthetic‐related	Unclear risk	ROBINS‐I judgement (No information)
Overall bias Major procedure‐related bleeding within 24 hours	High risk	ROBINS‐I judgement (Serious)
Overall bias Serious adverse events: LP‐related or epidural anaesthetic‐related	High risk	ROBINS‐I judgement (Serious)

ALL: acute lymphoblastic leukaemia

aPPT: activated partial thromboplastin time
CSF: cerebral spinal fluid

INR: International normalised ratio
LP: lumbar puncture

Characteristics of excluded studies [ordered by study ID]

Ir a:

estudios incluidos

Study	Reason for exclusion
Beilin 1997	No platelet transfusions
Bernstein 2016	No platelet transfusions
Breuer 1982	Wrong study design: case report and review of vascular sources of needle‐induced bleeding in lumbar puncture
Choi 2009	Review
Dresner 2010	Wrong study design: commentary
Eriksson 2007	Wrong population: a case report on a woman with pre‐eclampsia and normal platelet counts
Feusner 2004	Review
Foerster 2015	No platelet transfusions
Frenk 2005	No comparator: all parturients with platelets count less than 50 x 10⁹/L received platelet transfusion before regional anaesthesia
Hasegawa 2012	Wrong intervention
Hua 2014	Review
Kandemir 2016	Wrong study design: case report
Kasama 1997	Wrong study design: case report
Kimura 2001	Wrong study design: case report (2 people with essential thrombocythaemia)
Kotelko 1989	Wrong study design: case report (a 31‐year‐old primigravida with previously diagnosed May‐Hegglin anomaly)
Kotera 2010	Wrong study design: case report (a 31‐year‐old woman with aplastic anaemia was admitted for the management of delivery at 33 weeks of gestation)
Kuczkowski 2006	Wrong study design: case report (a parturient with immune thrombocytopenic purpura)
Lecompte 2003	Wrong population: Von Willebrand disease
Lee 2007	Wrong study design: case series (4 patients); 2 cases of spinal epidural haematoma and 2 cases of intracranial subdural haematoma after lumbar puncture in children receiving chemotherapy for acute lymphoblastic leukaemia and non‐Hodgkin lymphoma
Liu 2014	Wrong study design: case report
Mayumi 1983	Wrong study design: case report
McLendon 2011	Wrong indication
McLure 2003	No platelet transfusions
Meneses 2009	Wrong indication: assessment of safety of general anaesthesia for lumbar puncture
Mitchell 2012	Review
Moeschler 2016	Wrong population: cancer patients and intrathecal drug delivery systems
Moller 2015	Wrong study design: online survey
NCT01972529	Wrong intervention: avatrombopag vs placebo
NCT01976104	Wrong intervention: avatrombobag vs placebo
Noris 2014	No platelet transfusions
Osmanagaoglu 2006	No comparator
Palit 2008	No platelet transfusions
Pivalizza 2005	Wrong study design: commentary
Ramanathan 1988	No platelet transfusions
Rolbin 1988	No platelet transfusions
Ruell 2006	No platelet transfusions
Self 2007	Wrong population: people on antiplatelet therapy
Steer 1993	Wrong study design: case report (a 26‐year‐old woman with idiopathic thrombocytopenia was admitted for induction of labour)
Totadri 2014	No platelet transfusions
Valent 2011	Review
Vavricka 2003	No comparator
Waldman 1987	No platelet transfusions
Webert 2003	No comparator
Welter 2008	No platelet transfusions
Wirtz 2000	Wrong study design: case report (a 12‐year‐old male with acute lymphoblastic leukaemia)
Wolfe 2016	Review
Wong 1989	Wrong population: children with meningococcal infection

Figure 1

Study flow diagram.

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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Summary of findings for the main comparison. Platelet transfusion compared with no platelet transfusion for lumbar puncture procedures

Platelet transfusion compared with no platelet transfusion for lumbar puncture procedures
Patient or population: People with thrombocytopenia Intervention: Platelet transfusion Comparison: No platelet transfusion
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	No platelet transfusions	Platelet transfusion
Major procedure‐related bleeding within 24 hours of the procedure	No cases of major bleeding		Not estimated	150 (2 studies)	⊕⊝⊝⊝ Very low ^{1, 2}
All‐cause mortality up to 30 days after the procedure	‐	‐	‐	‐	‐	Not reported
Transfusion‐related complications within 24 hours of the procedure	‐	‐	‐	‐	‐	Not reported
Procedure‐related (lumbar puncture or epidural anaesthetic) complications within 7 days of the procedure	No serious adverse events		Not estimated	21 (1 study)	⊕⊝⊝⊝ Very low^{1, 2}
Quality of life (as defined by the individual studies)	‐	‐	‐	‐	‐	Not reported
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. The initial rating was 'low' as all included studies were non‐randomised studies. Very low quality: We are very uncertain about the estimate.
¹Downgraded one level due to imprecision (low event rate). No events occurred. ²We would also have downgraded due to risk of performance and detection bias, but could not because the quality of the evidence was already very low.

Summary of findings for the main comparison. Platelet transfusion compared with no platelet transfusion for lumbar puncture procedures

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Referencias

References to studies included in this review

Howard 2000 {published data only}

Ning 2016 {published data only}

van Veen 2004 {published data only}

References to studies excluded from this review

Beilin 1997 {published data only}

Bernstein 2016 {published data only}

Breuer 1982 {published data only}

Choi 2009 {published data only}

Dresner 2010 {published data only}

Eriksson 2007 {published data only}

Feusner 2004 {published data only}

Foerster 2015 {published data only}

Frenk 2005 {published data only}

Hasegawa 2012 {published data only}

Hua 2014 {published data only}

Kandemir 2016 {published data only}

Kasama 1997 {published data only}

Kimura 2001 {published data only}

Kotelko 1989 {published data only}

Kotera 2010 {published data only}

Kuczkowski 2006 {published data only}

Lecompte 2003 {published data only}

Lee 2007 {published data only}

Liu 2014 {published data only}

Mayumi 1983 {published data only}

McLendon 2011 {published data only}

McLure 2003 {published data only}

Meneses 2009 {published data only}

Mitchell 2012 {published data only}

Moeschler 2016 {published data only}

Moller 2015 {published data only}

NCT01972529 {published data only}

NCT01976104 {published data only}

Noris 2014 {published data only}

Osmanagaoglu 2006 {published data only}

Palit 2008 {published data only}

Pivalizza 2005 {published data only}

Ramanathan 1988 {published data only}

Rolbin 1988 {published data only}

Ruell 2006 {published data only}

Self 2007 {published data only}

Steer 1993 {published data only}

Totadri 2014 {published data only}

Valent 2011 {published data only}

Vavricka 2003 {published data only}

Waldman 1987 {published data only}

Webert 2003 {published data only}

Welter 2008 {published data only}

Wirtz 2000 {published data only}

Wolfe 2016 {published data only}

Wong 1989 {published data only}

Additional references

Afdhal 2008

BCSH 2003

BCSH 2004

Birchall 2015

Blumberg 2010

Burrows 1990

Chapman 2015

Covidence [Computer program]

Deeks 2011

Doherty 2014

EPOC 2017

Erbay 2014

Estcourt 2012

Estcourt 2016

GMA 2009

Higgins 2011a

Higgins 2011b

Higgins 2011c

Hui 2011

Kaufman 2015

Kumar 2015

Lefebvre 2011

Leguit 2010

Levi 2009