anurajms/meta_analysis huggingface dataset:
primary outcome:
Growth hormone therapy for people with thalassaemia
Final heightheight (cm)height SDSheight SDS relative to expected height based on mid‐parental heightAdverse effects (such as but not limited to benign intracranial hypertension, slipped capital femoral epiphyses, effects on glucose metabolism in both non‐diabetic as well as diabetic patients and incidence of malignant disease, haemorrhagic stroke or cardiovascular events)Satisfaction (measured by validated questionnaires e.g. (Leiberman 1993; Rubin 2011))participantsparents or caregivers
primary outcome:
Vitamin D supplementation for sickle cell disease
Serum 25‐hydroxyvitamin D (25(OH)D) level (reported as absolute change from baseline)BMD measured by dual energy X‐ray absorptiometry (DEXA) and reported as per cent (%) change from baselineat lumbar spineat hipsat forearmtotal bodyAdverse events (e.g. nausea, drowsiness, vomiting, loss of appetite, constipation, confusion, cardiac arrhthymias, renal failure, coma)
primary outcome:
Gene therapy for haemophilia
Bleeding episode(s) (bleeding frequency, number of bleeding episodes per year, or as reported in the trial)Factor VIII or IX supplementation requirement (frequency as reported in the trials)Serious adverse events (resulting in death or life threatening complications, inpatient hospitalisation, significant or permanent disability, or one that requires additional intervention to prevent permanent damage or disability)Evidence of clotting factor antibody developmentEvidence of organ toxicityEvidence of tumour development
primary outcome:
Interventions for preventing silent cerebral infarcts in people with sickle cell disease
Proportion of participants developing new or progressive SCI lesions on MRIAll‐cause mortalitySerious adverse events (SAEs) associated with different therapies or SCD
primary outcome:
Transcutaneous electrical nerve stimulation (TENS) for pain management in sickle cell disease
Pain relief *Pain intensity (as assessed by visual analogue pain scale score (VAS) or other validated assessment tools for measuring pain intensity during the use of TENS)Frequency of pain episodes
primary outcome:
Early erythropoiesis‐stimulating agents in preterm or low birth weight infants
Proportion of infants exposed to one or more red blood cell (RBC) transfusionsNecrotising enterocolitis (NEC) (Bell's stage II or higher, or stage not reported)Any neurodevelopmental impairment at 18 to 22 months' corrected age (in children examined)Bayley‐II Mental Development Index (MDI) at 18 to 24 months' corrected age
primary outcome:
Late erythropoiesis‐stimulating agents to prevent red blood cell transfusion in preterm or low birth weight infants
Use of one or more red blood cell transfusions.
primary outcome:
Blood transfusions for treating acute chest syndrome in people with sickle cell disease
Chest painintensity (expressed as scores obtained through any validated patient‐reported outcomes instrument either generic or SCD specific)duration from time of start of symptomsFeverMortality
primary outcome:
Intravenous iron therapy for non‐anaemic, iron‐deficient adults
Haemoglobin concentration (g/L), measured at the end of follow‐upOverall quality of life, taken at the end of follow‐up, as measured by a quantitative quality‐of‐life measurement scale
primary outcome:
Treatment of dental complications in sickle cell disease
Resolution or reduction in the severity of the condition (as measured by)decayed, missing, filled teeth (DMFT) index, radiographic changes, salivary acid or streptococcus mutans levels for dental cariesgingival or plaque indices, probing depth, bone level for periodontal diseaseschange in teeth or jaw positions, cephalometric analysis, malocclusion indices (in case of malocclusions and craniofacial deformities)visual analogue scale, dichotomy scale or Likert scale for pain assessmentany other relevant measure reported
primary outcome:
Treatment for avascular necrosis of bone in people with sickle cell disease
Painpresence and level of painuse of analgesia during the first two weeks (doses of opioids will be converted into morphine equivalents to facilitate comparisons)weak opioids, e.g. codeine and tramadolstrong opioids, e.g. morphine and pethidineacetaminophen and non‐steroidal anti‐inflammatory drugs (NSAIDs) (open or selective Cox 2‐inhibitors)other analgesicsDeath and cause of deathAdverse events, the events will be classified as: immediate (less than 24 hours post‐intervention); early (one to eight days after intervention); and long‐term (more than eight days after intervention). Our definition of immediate, early, and long term is arbitrary.prevalence and timing of joint looseningbone fractureinfectionsintra‐operative bleedingcomplications of SCD during hospital admission (e.g. painful crises, acute chest syndrome and stroke)related to analgesia
primary outcome:
Prophylactic plasma transfusion for patients without inherited bleeding disorders or anticoagulant use undergoing non‐cardiac surgery or invasive procedures
All‐cause mortality (up to 24 hours, and up to 30 days)Major bleeding within 24 hours and within seven days as defined by the study, or by the following (based on Schulman 2010).Fatal bleeding.Intracranial/intraspinal/pericardial/intraocular/retroperitoneal, into a non‐operated joint, or intramuscular causing compartment syndrome.Surgical/invasive procedure site bleeding requiring a second intervention or reoperation.Surgical/invasive procedure site bleeding that causes a haematoma or haemarthrosis of sufficient size to delay mobilisation or wound healing.Surgical/invasive procedure site bleeding that is unexpected and prolonged or causes haemodynamic instability (as defined by the study) and is associated with a 20‐g/L drop in haemoglobin (Hb), or requiring two or more units of whole blood/red cells within 24 hours of bleeding.Extrasurgical/invasive procedure site bleeding associated with a 20‐g/L drop in Hb, or requiring two or more units of whole blood/red cells within 48 hours of bleeding.
primary outcome:
Multiple drug combinations of bortezomib, lenalidomide, and thalidomide for first‐line treatment in adults with transplant‐ineligible multiple myeloma: a network meta‐analysis
We included all trials fitting the inclusion criteria mentioned above, irrespective of reported outcomes. We estimated the relative ranking of the competing interventions according to each of the following outcomes.*The Grades are referring to the severity of AEs according to the Common Terminology Criteria for Adverse Events (CTCAE): Grade 1 refers to mild AEs; Grade 5 to death related to AEs
primary outcome:
Pharmacological interventions for painful sickle cell vaso‐occlusive crises in adults
Participant‐reported pain relief of 50% or greater at 6, 12, 24, 48 hours and at the end of treatment.Participant‐reported pain relief of 30% or greater at 6, 12, 24, 48 hours and at the end of treatment.Patient global impression of change (PGIC) very much improved.Patient global impression of change (PGIC) much or very much improved.
primary outcome:
Statins for children with familial hypercholesterolemia
Change in carotid intima‐media thicknessChange in serum LDL cholesterol levelChange in measures of growth and maturation, e.g. age of onset of puberty
primary outcome:
Regular long‐term red blood cell transfusions for managing chronic chest complications in sickle cell disease
Number of people with new diagnoses of chronic chest complicationschronic sickle lung diseasepulmonary hypertension (using a cut off of TRV 2.5 m/s to define pulmonary hypertension)Deathsfrom any causefrom chronic chest complications (chronic sickle lung disease and pulmonary hypertension)Transfusion‐related complications (up to 30 days post transfusion) including:alloimmunisationinfection from blood productsprocedural complications (such as device malfunction)iron overload (measured by serum ferritin, liver iron, or non‐invasive imaging)transfusion reactions
primary outcome:
Antibiotics for treating osteomyelitis in people with sickle cell disease
Time to resolution of signs and symptoms of active infection
primary outcome:
Splenectomy for people with thalassaemia major or intermedia
Frequency of transfusion (post splenectomy or discharge)Occurence of serious adverse events (resulting in death or life threatening complications, inpatient hospitalisation, significant or permanent disability, or one that necessitates an additional intervention to prevent further damage)Quality of life (as assessed by validated instruments or scales)
primary outcome:
Magnesium for treating sickle cell disease
Change in frequency of vaso‐occlusive painful crises as measured bypain diary of days with significant painnumber of painful days (where the pain is strong enough to require analgesics)Quality of life (measured using a validated scale)Length of hospital stay
primary outcome:
Antifibrinolytic therapy for preventing oral bleeding in patients with haemophilia or Von Willebrand disease undergoing minor oral surgery or dental extractions
Number of postoperative bleeding episodes requiring intervention*Side effects or other adverse events
primary outcome:
Hydroxyurea (hydroxycarbamide) for transfusion‐dependent β‐thalassaemia
Volume of blood required (red blood cell units)Frequency of blood transfusionMean Hb level
primary outcome:
Desmopressin acetate (DDAVP) for preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders
Maternal mortalityPost‐partum haemorrhage (PPH) (defined as excessive bleeding occurring within six weeks after delivery and also judged on the basis of any intervention required (e.g. transfusion, surgery))Infant mortality
primary outcome:
Aerobic physical exercise for adult patients with haematological malignancies
We predefined overall survival (OS) as the primary efficacy outcome. As this outcome was reported in one trial only, but mortality was reported in six trials, we also evaluated mortality.
primary outcome:
Mesenchymal stromal cells as treatment or prophylaxis for acute or chronic graft‐versus‐host disease in haematopoietic stem cell transplant (HSCT) recipients with a haematological condition
All‐cause mortalitySafety of MSC infusion – acute toxicity, ectopic tissue formation or oncogenesis
primary outcome:
Early discontinuation of antibiotics for febrile neutropenia versus continuation until neutropenia resolution in people with cancer
Thirty‐day mortality from any cause (all‐cause mortality). If all‐cause mortality was not available at 30 days, we used the time point reported by the study and documented it.
primary outcome:
Pro‐coagulant haemostatic factors for the prevention and treatment of bleeding in people without haemophilia
Mortality (all causes) (principal primary outcome for therapeutic intervention usage)The number of participants suffering arterial and/or venous thromboembolic events (principal primary outcome for prophylactic intervention usage)
primary outcome:
Vaccines for preventing invasive salmonella infections in people with sickle cell disease
Acute morbidity from salmonella infection (e.g. vaso‐occlusive, hyperhaemolytic, sequestration and aplastic crises; septicaemia; pneumonia; meningitis;osteomyelitis; acute chest syndrome)Mortality from salmonella infection
primary outcome:
Insecticide‐treated nets for preventing malaria
Child mortality from all causes.
primary outcome:
Drugs for preventing red blood cell dehydration in people with sickle cell disease
Number of deathsNumber of sickle pain crises (requirement for opiate treatment or self‐reported patient scales)Number of serious complications of sickle cell disease including stroke, acute chest syndrome and acute splenic sequestration
primary outcome:
Prophylactic platelet transfusions prior to surgery for people with a low platelet count
Mortality (all‐causes, secondary to bleeding, secondary to thromboembolism and secondary to infection) within 30 days and 90 days of surgery.Number of participants with major procedure‐related bleeding within seven days of surgery, defined as:surgical site bleeding requiring a second intervention or reoperation or surgical site bleeding that causes a haematoma or haemarthrosis of sufficient size to delay mobilisation or wound healing;bleeding of sufficient size to cause delayed wound healing, or wound infection or surgical site bleeding that was unexpected and prolonged or caused haemodynamic instability (as defined by the study) that was associated with a 20 g/L drop in haemoglobin (Hb);bleeding that required two or more units of whole blood/red cells within 24 hours of the bleeding;bleeding defined by the study with no further details.
primary outcome:
Conjugate Haemophilus influenzae type b vaccines for sickle cell disease
Mortality from Hib infectionsOverall mortalityAcute morbidity from Hib infections (e.g. vaso‐occlusive, hyperhaemolytic and sequestration crises, septicaemia, meningitis, pneumonia, acute chest syndrome, epiglottitis, cellulitis, arthritis, osteomyelitis, pericarditis).
primary outcome:
Effects of all‐trans retinoic acid (ATRA) in addition to chemotherapy for adults with acute myeloid leukaemia (AML) (non‐acute promyelocytic leukaemia (non‐APL))
Overall survival (OS) defined as time from random treatment assignment to death from any cause or to last follow‐up
primary outcome:
Comparison of a therapeutic‐only versus prophylactic platelet transfusion policy for people with congenital or acquired bone marrow failure disorders
The number of participants with at least one bleeding episode (WHO Grade 1 to 4, or WHO Grade 2 to 4)The total number of days on which bleeding occurred or the total number of bleeding episodes per participant (WHO Grade 1 to 4, or WHO Grade 2 to 4)The number of participants with at least one episode of severe or life‐threatening bleedingTime to first bleeding episode from the start of the study (WHO Grade 1 to 4, or WHO Grade 2 to 4)
primary outcome:
Folate supplementation in people with sickle cell disease
Folate concentration (using serum or plasma folate or erythrocyte folate)Hemoglobin concentration (grams per decilitre (g/dL))Adverse effects of the intervention, including but not limited to:increased incidence of priapism;the risk of masking cobalamin deficiency with consequent neuropsychiatric manifestations (nanogram per litre (ng/L));any other side effects (e.g. twin pregnancy, etc.), including SCD‐related morbidities (e.g. pain, acute splenic sequestration, strokes, priapism, recurrent infections).
primary outcome:
Mosquito repellents for malaria prevention
Clinical malaria: confirmed through blood smears or rapid diagnostic tests (P. falciparum or P. vivax);malaria parasitaemia (malaria infection incidence): confirmed through thick or thin blood smears, mRDTs, or polymerase chain reaction (PCR) (P. falciparum or P. vivax).
primary outcome:
Bisphosphonates in multiple myeloma: an updated network meta‐analysis
Overall survival (OS) (measured as mortality)Progression‐free survival (PFS)Skeletal‐related events (SRE): number of participants experiencing pathological fractures (vertebral and non‐vertebral), total skeletal‐related events (SREs) (as defined by individual authors; these included vertebral fractures, non‐vertebral fractures and osteolytic lesions)
primary outcome:
Thrombopoietin receptor agonists for prevention and treatment of chemotherapy‐induced thrombocytopenia in patients with solid tumours
Overall survival (OS), defined as the time interval from random treatment assignment to death from any cause, or to last follow‐up.Number and severity of bleeding episodes, including the number of patients with at least one: a) bleeding episode of any severity; and b) severe/life‐threatening bleeding episode (as defined in the individual trials).
primary outcome:
Splenectomy versus conservative management for acute sequestration crises in people with sickle cell disease
DeathEpisodes of ASS (in individuals who either had a partial splenectomy or conservative management)
primary outcome:
Hematopoietic stem cell transplantation for Gaucher disease
Hematological assessment ‐ hemoglobin concentration and platelet countsVisceral assessment ‐ liver and spleen volumes by volumetric computer tomography (CT) or magnetic resonance imaging (MRI) or ultrasoundMortality and morbidityoverall mortalitytransplant‐related mortalitytransplant‐related morbidity
primary outcome:
Prophylactic intravenous calcium therapy for exchange blood transfusion in the newborn
All‐cause death until discharge.Presence of cardiac dysrhythmias within one week of EBT.Number of infants with total serum calcium levels less than 8 mg/dL (2 mmol/L) or ionised calcium levels less than 4.4 mg/dL (1.1 mmol/L) within one week of EBT.
primary outcome:
Thrombopoietin mimetics for patients with myelodysplastic syndromes
Overall survival (OS), defined as the time interval from random treatment assignment/entry into the study to death from any cause or to last follow‐up.Mortality during study
primary outcome:
Plasma transfusions prior to lumbar punctures and epidural catheters for people with abnormal coagulation
Major procedure‐related bleeding within 24 hours of the procedure (as defined by 24 hours after removal of lumbar puncture needle or catheter in the case of epidural anaesthesia). For example: spinal haematoma; intraventricular, intracerebral or subarachnoid haemorrhage; or major bleeding (not further defined), as reported by individual studies.Serious adverse events:transfusion‐related complications within 24 hours of the procedure (including transfusion‐related acute lung injury (TRALI), transfusion‐transmitted infection, transfusion‐associated circulatory overload (TACO), transfusion‐associated dyspnoea (TAD), acute transfusion reactions);venous and arterial thromboembolism (including deep vein thrombosis; pulmonary embolism; stroke; myocardial infarction) (up to 30 days);lumbar puncture (LP)‐related or epidural anaesthetic‐related complications within seven days of the procedure (infection, headache, cerebral herniation, neurological symptoms such as radicular pain or numbness, back pain).
primary outcome:
Bypassing agent prophylaxis in people with hemophilia A or B with inhibitors
Overall bleeding events (per month), as defined by study authors
primary outcome:
Optimisation of chemotherapy and radiotherapy for untreated Hodgkin lymphoma patients with respect to second malignant neoplasms, overall and progression‐free survival: individual participant data analysis
The primary endpoint is the time to occurrence of a secondary malignant neoplasm (secondary malignant neoplasm‐free survival). This is an adverse event.
primary outcome:
Deferasirox for managing iron overload in people with thalassaemia
Overall mortality measured at any point in time
primary outcome:
Fluid replacement therapy for acute episodes of pain in people with sickle cell disease
Duration of pain crisis
primary outcome:
Pathogen‐reduced platelets for the prevention of bleeding
Number, type, and severity of bleeding episodes. Bleeding was measured at up to 48 hours, 48 hours to 7 days, and more than 7 days.All‐cause mortality. Mortality was measured at up to 4 weeks, 4 to 12 weeks, and more than 12 weeks. Of particular interest were deaths from platelet transfusion‐related complications such as bleeding, infection, thromboembolism, or transfusion reactions.
primary outcome:
Comparison of first‐line chemotherapy including escalated BEACOPP versus chemotherapy including ABVD for people with early unfavourable or advanced stage Hodgkin lymphoma
As primary outcomes we chose overall survival (OS) and progression‐free survival (PFS). The definition of OS was time from randomisation until death as a result of any cause (Cheson 2007a).PFS was defined as the time from randomisation until disease progression, relapse or death as a result of any cause. PFS was provided by GHSG HD14, HD 2000 and EORTC 20012. However, we also accepted other definitions that addressed progression in the process of the disease such as freedom from treatment failure (FFTF) and event‐free survival (EFS). Freedom from treatment failure was defined as the time from randomisation until progression during treatment, lack of complete response at the end of treatment, relapse and death from any cause (GHSG HD9). The definition of EFS was time from randomisation to evidence of severe toxicity causing definite treatment discontinuation, progressive lymphoma, cardiorespiratory failure, secondary leukaemia, death due to any cause, whichever occurred first (GSM‐HD 2008). Within the review, data coming under these definitions were discussed as results of PFS.
primary outcome:
Unfractionated heparin versus low molecular weight heparins for avoiding heparin‐induced thrombocytopenia in postoperative patients
early‐onset is when HIT develops within 24 hours of heparin administration;delayed‐onset is when HIT is diagnosed after the discontinuation of heparin.
primary outcome:
Exercise for haemophilia
Bleed frequency (number of major bleeds reported per year, month, or week)Adverse events (e.g. bleed following exercise, worsening of symptoms)Quality of life (e.g. assessed through self‐administered questionnaires such as the 'Hemo‐QOL and SF‐36')
primary outcome:
Antibiotics for treating community‐acquired pneumonia in people with sickle cell disease
2. Number of days to become afebrile**This has been re‐classified from a secondary outcome.
primary outcome:
Hydroxyurea for reducing blood transfusion in non‐transfusion dependent beta thalassaemias
Frequency of blood transfusion measured by the volume transfused per kg per year (units transfused per kg per year (if sufficient data available) or other similar measures)Transfusion‐free interval (in months)Haemoglobin level (in g/dl or equivalent at intervals after commencing the intervention (e.g. every three to six months)
primary outcome:
Alternative agents to prophylactic platelet transfusion for preventing bleeding in people with thrombocytopenia due to chronic bone marrow failure: a meta‐analysis and systematic review
Number of participants with at least one bleeding episodeNumber of participants with at least one severe or life‐threatening bleeding episodeNumber of days bleeding occurred per participant
primary outcome:
Bisphosphonate therapy for osteogenesis imperfecta
Fracture reductionnumbers of breaksfrequency of breaks (rates)Change in BMD as assessed by DEXA
primary outcome:
Interventions for patients and caregivers to improve knowledge of sickle cell disease and recognition of its related complications
Patient and caregiver understanding of SCD and related complications (e.g. the 'Sickle Cell Disease Knowledge Questionnaire' (Armstrong 1993), the 'Illness Perception Questionnaire')Patient or caregiver (or both) ‐ reported signs and symptoms leading to self‐managementUtilization of health servicesnumber of acute hospitalizations (admission to hospital in‐patient services for an acute event)average length of hospital stayhospital appointments (scheduled, unscheduled and missed)primary care appointments (scheduled, unscheduled and missed)
primary outcome:
Bortezomib for the treatment of multiple myeloma
Overall survival (OS): time from date of randomisation to date of death (from any cause)Progression‐free survival (PFS): time from date of randomisation to date of progression or death (from any cause)
primary outcome:
Antifibrinolytics (lysine analogues) for the prevention of bleeding in people with haematological disorders
Number, site and severity of bleeding (i.e. any bleeding, clinically significant bleeding, life‐threatening bleeding)Thromboembolism (venous and arterial)
primary outcome:
Subsidising artemisinin‐based combination therapy in the private retail sector
ACT use (defined as the percentage of patients with fever/confirmed malaria who received an ACT on the day that the fever started or on the following day; Global Fund).Two studies reported data on ACT use (Kangwana 2011; Talisuna 2012; Table 3). In the first study (Kangwana 2011), ACT subsidy programmes increased ACT usage in children under five years of age by 25 percentage points (95% CI 14.1 to 35.9 percentage points; high certainty evidence). This suggests that in practice, among febrile children under five years of age with an ACT usage rate of 5% without a subsidy, subsidy programmes would increase usage by between 19% and 41%. In the second study (Talisuna 2012), ACT subsidy programmes resulted in a ten‐fold increase (95% CI 5.0 to 18.9) in ACT usage in children under five years of age and a six‐fold increase (95% CI 4.2 to 8.4) in ACT usage in all age groups (very low certainty evidence).
primary outcome:
Oral iron supplements for children in malaria‐endemic areas
Clinical malaria: uncomplicated malaria, defined as a history of fever with parasitological confirmation (WHO 2010). We included cases of severe malaria if they were not reported separately.Severe malaria: cerebral malaria or acute Plasmodium falciparum malaria with signs of severity, or evidence of vital organ dysfunction, or both (WHO 2010). If it had been defined differently, we extracted the outcome as reported in the trial and used the trial authors' definitions.Death from any cause.
primary outcome:
Granulocyte and granulocyte‐macrophage colony stimulating factors for newly diagnosed patients with myelodysplastic syndromes
Overall survival (OS) was the primary outcome due to its relevance to patients with MDS and its importance as an indicator of the benefits of an intervention. OS was defined as the time interval from random treatment assignment or entry into a study to death from any cause or to last follow‐up.Five trials analysed overall survival (OS) (Greenberg 1993; Mantovani 1996; Ossenkoppele 1999; Verbeek 1999; Zwierzina 2005). Balleari 2006 and Taieb 1998 did not assess this outcome.Only one trial (Ossenkoppele 1999) reported of "longer median overall survival in the ﬁlgrastim arm" with no statistical significant difference (P = 0.22). Ossenkoppele included 33 patients in the G‐CSF arm, 31 in the control arm. (hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.44 to 1.47; P = 0.48) (see Analysis 1.1).Our meta‐analysis included both studies with 149 participants and showed no evidence for a difference between both arms (HR 0.88, 95% CI 0.62 to 1.26, P = 0.49) (see Analysis 2.1). Sensitivity analysis using the random‐effects model did not lead to differing results (HR 0.88, 95% CI 0.62 to 1.26, see Analysis 2.13).
primary outcome:
Piracetam for reducing the incidence of painful sickle cell disease crises
Number of painful sickle cell disease crisesPainintensity (expressed as scores obtained through any validated patient reported outcomes instrument either generic or sickle cell disease specific)durationThe requirement for opiate treatment during hospitalisation, Accident & Emergency Department visits or on discharge to home.dosetypefrequency
primary outcome:
Meditation for adults with haematological malignancies
We evaluated quality of life as the primary efficacy endpoint. It had to be measured with reliable and validated instruments.
primary outcome:
Washed versus unwashed red blood cells for transfusion for the prevention of morbidity and mortality in preterm infants
Mortality: before discharge from initial hospital or before a defined period of follow‐up (28 days, 12 months, or 18 months postnatal age, or a combination).ROP, grade 3 or more prior to discharge home (ICCRP 2005).Severe adverse findings at ultrasound (grades 3 to 4 IVH (Papile 1983), hydrocephalus, cortical atrophy, or periventricular leukomalacia) during first hospitalisation (Pinto‐Martin 1995).CLD requiring additional oxygen at 36 weeks' postmenstrual age or prior to discharge home (Shennan 1988).NEC, stage 2 or greater (Bell 1978).Cerebral palsy by physician assessment.Developmental delay (developmental quotient more than two standard deviations below the mean on validated assessment tool of cognitive function (e.g. Bayley Score of Infant Development).Blindness (visual acuity less than 20/200 in best eye).Deafness (hearing loss requiring amplification or cochlear implantation).
primary outcome:
Antibody therapies for lymphoma in children
Remission (partial, complete), relapse rate, event‐free and overall survival, and adverse effects for each lymphoma type and treatment option separately.Adverse effects of antibody therapy mentioned in the included studies, such as: immunosuppression (febrile neutropenia or use of antibiotics or infection), prolonged B‐cell depletion (longer than six months), progressive multi‐focal leukoencephalopathy, infusion reactions, skin changes, pulmonary toxicity, renal failure (due to acute cell lysis), hepatotoxicity, cardiac toxicity, seizures.
primary outcome:
Prophylactic antibiotics or G(M)‐CSF for the prevention of infections and improvement of survival in cancer patients receiving myelotoxic chemotherapy
Overall survivalAll cause mortality (including infection‐related, treatment‐related, or on‐trial mortality)Infection‐related mortality
primary outcome:
Low‐molecular‐weight heparins for managing vaso‐occlusive crises in people with sickle cell disease
PainIntensity (expressed as scores obtained through any validated patient‐reported outcomes instrument, either generic or SCD specific)DurationThe requirement for opiate treatmentDoseTypeFrequency
primary outcome:
Recombinant factor VIIa concentrate versus plasma‐derived concentrates for treating acute bleeding episodes in people with haemophilia and inhibitors
Early cessation of bleeding measured bychanges on any subjective or objective pain and mobility scale orby the volume of haematoma assessed radiologically at any point in the first 48 hours
primary outcome:
Comparison of different platelet transfusion thresholds prior to insertion of central lines in patients with thrombocytopenia
Major procedure‐related bleeding within 24 hours of the procedure.All‐cause mortality up to 30 days after the procedure.
primary outcome:
Comparison of different platelet count thresholds to guide administration of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation
The number of participants with at least one bleeding episode.The total number of days on which bleeding occurred.Number of participants with at least one episode of severe or life‐threatening haemorrhage.Time to first bleeding episode from the start of study.
primary outcome:
Interleukin‐2 as maintenance therapy for children and adults with acute myeloid leukaemia in first complete remission
Disease‐free survival: defined as the time interval from the date of remission to leukaemic relapse or death from any cause.Overall survival: defined as the time interval from the date of randomisation or entry into study to death from any cause.
primary outcome:
Different doses of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation
The number of participants with at least one bleeding episode.The total number of days on which bleeding occurred per participant.The number of participants with at least one episode of severe or life‐threatening haemorrhage.Time to first bleeding episode from the start of the study.
primary outcome:
Additional plerixafor to granulocyte colony‐stimulating factors for haematopoietic stem cell mobilisation for autologous transplantation in people with malignant lymphoma or multiple myeloma
Overall survivalSuccessful stem cell collection
primary outcome:
Comparison of a restrictive versus liberal red cell transfusion policy for patients with myelodysplasia, aplastic anaemia, and other congenital bone marrow failure disorders
All‐cause mortalityMortality due to bleeding, infection, transfusion reactions, or iron overload, or both.
primary outcome:
A therapeutic‐only versus prophylactic platelet transfusion strategy for preventing bleeding in patients with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation
The number of participants with at least one bleeding episode.The total number of days on which bleeding occurred per participant.The number of participants with at least one episode of severe or life‐threatening bleeding.Time to first bleeding episode from the start of the study.
primary outcome:
The effects of idarubicin versus other anthracyclines for induction therapy of patients with newly diagnosed leukaemia
Overall survival (OS): defined as the time from randomisation or entry into study to death from any cause or last follow‐up.Disease‐free survival (DFS): defined as the time from complete remission (CR) to first relapse, or death from any cause or the last follow‐up.
primary outcome:
Interventions for prophylaxis of hepatic veno‐occlusive disease in people undergoing haematopoietic stem cell transplantation
Incidence of hepatic VOD (proportion of participants who developed hepatic VOD during the study period)Overall survival (reported as time‐to‐event data)
primary outcome:
Psychological therapies for sickle cell disease and pain
Pain status (frequency, duration, severity, location, precipitating factors, modulating factors)Mood (anxiety, depression)Coping strategies (behavioural responses, cognitive strategies)Health service utilisation (frequency of Accident & Emergency department visits and hospital admissions, duration of hospitalisations, consultations with doctors (including general practitioners))
primary outcome:
Janus kinase‐1 and Janus kinase‐2 inhibitors for treating myelofibrosis
Overall survival: the time from randomization until death from any cause (FDA 2007).Progression‐free survival: the time from randomization until objective tumor progression or death (FDA 2007).Safety:
primary outcome:
Sapropterin dihydrochloride for phenylketonuria
Change in blood phenylalanine concentration
primary outcome:
Enzyme replacement and substrate reduction therapy for Gaucher disease
Frequency of side effectsHaemoglobin and platelet countsHepatosplenomegalySpleen size (e.g. multiples of normal, tissue mL/kg body weight or mL)Liver size (e.g. multiples of normal, tissue mL/kg body weight or mL)
primary outcome:
Protein substitute for children and adults with phenylketonuria
Weight gain, body mass index, z scores, centiles, other indices of nutritional status or growthMeasures of neuropsychological performance
primary outcome:
Artemisinin‐naphthoquine for treating uncomplicated Plasmodium falciparum malaria
Treatment failure at Days 28, 42, and 63; PCR‐adjusted and PCR‐unadjusted.Our primary analysis drew on the WHO protocol for assessing and monitoring antimalarial drug efficacy (Bloland 2003). This protocol has been used to guide most efficacy trials since its publication in 2003, even though it was designed to assess the level of antimalarial resistance in the study area rather than for comparative trials. As a consequence, a high number of randomized participants are excluded from the final efficacy outcome as losses to follow‐up, or voluntary or involuntary withdrawals. For this reason we conducted a sensitivity analysis to restore the integrity of the randomization process and test the robustness of the results to this methodology. (For a summary of the methodology and sensitivity analysis see Table 1).
primary outcome:
Treatment for preventing bleeding in people with haemophilia or other congenital bleeding disorders undergoing surgery
MortalityBlood loss assessed objectivelyduring surgeryby variation of haemoglobin levelsby transfusion requirement (number of red blood cell (RBC) units infused)after surgeryby variation of haemoglobin levelsby transfusion requirement (number of RBC units infused)Need for re‐intervention
primary outcome:
Positron emission tomography‐adapted therapy for first‐line treatment in individuals with Hodgkin lymphoma
The specific aim of this systematic review was to meta‐analyse OS as the primary endpoint, as this is the outcome of greatest clinical relevance and utmost importance to patients.
primary outcome:
Eculizumab for treating patients with paroxysmal nocturnal hemoglobinuria
Overall survival defined as the time from randomisation until death from any cause, and measured in the intent‐to‐treat population (FDA 2007).
primary outcome:
Deferasirox for managing iron overload in people with myelodysplastic syndrome
Overall survival (measured at any point in time).
primary outcome:
Drugs for preventing malaria in pregnant women in endemic areas: any drug regimen versus placebo or no treatment
For the conceptual framework, see Figure 1.
primary outcome:
Interventions for treating acute bleeding episodes in people with acquired hemophilia A
Bleeding control (the response to therapy judged by a clinician as bleeding resolved with date or bleeding not resolved)
primary outcome:
Mycophenolate mofetil versus methotrexate for prevention of graft‐versus‐host disease in people receiving allogeneic hematopoietic stem cell transplantation
Incidence of acute GVHD.Overall survival.
primary outcome:
The role of additional radiotherapy for primary central nervous system lymphoma
OS, defined as the time from random treatment assignment into the study to death from any cause or to last available follow up.
primary outcome:
Deferasirox for managing transfusional iron overload in people with sickle cell disease
Time to death (any cause)
primary outcome:
Dihydroartemisinin‐piperaquine for treating uncomplicated Plasmodium falciparum malaria
Total failure at days 28, 42, and 63; PCR‐adjusted and PCR‐unadjusted.Our primary analyses drew on the WHO's protocol for assessing and monitoring antimalarial drug efficacy (Bloland 2003). This protocol has been used to guide most efficacy trials since its publication in 2003, even though it was designed to assess the level of antimalarial resistance in the study area rather than for comparative trials. As a consequence, a high number of randomized participants are excluded from the final efficacy outcome as losses to follow‐up or voluntary or involuntary withdrawals. For this reason we conducted a series of sensitivity analyses to restore the integrity of the randomization process and test the robustness of the results to this methodology (For a summary of the methodology and sensitivity analysis see Table 2).
primary outcome:
Primaquine for preventing relapse in people with Plasmodium vivax malaria treated with chloroquine
P. vivax parasitaemia detected more than 30 days after starting primaquine.Serious adverse events (fatal, life threatening, or requiring hospitalization).
primary outcome:
Artemisinin‐based combination therapy for treating uncomplicated Plasmodium vivax malaria
Recurrence of P. vivax parasitaemia by days 14 and 28.
primary outcome:
Interventions for the treatment of oral cavity and oropharyngeal cancers: surgical treatment
Overall survival (or total mortality; we also planned to evaluate disease‐related mortality, if possible)Disease‐free survival (i.e absence of new disease, progression, and mortality)Locoregional recurrenceRecurrence (including loco‐regional recurrence and distant metastasis)
primary outcome:
Hyperbaric oxygen therapy for late radiation tissue injury
Appropriate outcome measures depend on the nature of the LRTI and the anatomical location. Some outcome measures allow pooled analysis across different anatomical locations and reflect the generally similar effect of radiation on most tissues. However, given the high clinical heterogeneity present, for this update, we have largely eliminated the overall estimates of effect across different anatomical areas.Studies were eligible for inclusion in our quantitative analysis if they reported any of the outcomes listed under Primary outcomes and Secondary outcomes.
primary outcome:
Best first‐line therapy for people with advanced non‐small cell lung cancer, performance status 2 without a targetable mutation or with an unknown mutation status
Overall survival (OS), defined as time from start of treatment until death by any causeHealth‐related quality of life (HRQoL), measured via validated international scalesToxicity/adverse events (Common Terminology Criteria for Adverse Events [CTCAE] grade 3 to 5, and Patient Reported Outcomes [PRO]‐CTCAE if reported) (Kluetz 2016)
primary outcome:
Pegylated liposomal doxorubicin for relapsed epithelial ovarian cancer
Overall survival (OS): survival until death from all causesProgression‐free survival (PFS): survival until disease progression
primary outcome:
Local versus radical surgery for early rectal cancer with or without neoadjuvant or adjuvant therapy
We sought the following outcomes of interest.
primary outcome:
Prehabilitation versus no prehabilitation to improve functional capacity, reduce postoperative complications and improve quality of life in colorectal cancer surgery
Functional capacity determined with the 6‐minute walk test (6MWT) (maximum number of metres walked in six minutes in a corridor at least 20 metres long) postoperativelyPostoperative complication rate (Clavien‐Dindo scale (CD) or Comprehensive Complication Index (CCI) (Slankamenac 2013)) within 30 daysPatient‐reported HRQoL, measured using the following questionnaires: Short Form‐36 (SF‐36), Hospital Anxiety and Depression Scale (HADS), EuroQol‐5D (EQ‐5D), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires Core module and ColoRectal cancer module (EORTC QLQ‐C30/‐CR29))
primary outcome:
First‐line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta‐analysis
Overall survival (OS), defined as the time from random treatment assignment to death from any causeQuality of life (QoL), assessed with validated and reliable instrumentsSerious adverse events (SAEs)*, assessed as the number of participants with at least one eventIn one trial, QoL should have been assessed with FACT‐G, but we could not find results anywhere (NCT01392183).In another trial, QoL should have been assessed with FACIT‐F, but we could not find results anywhere (NCT01613846).Separate data for treatment‐naive participants were not reported in two trials (NCT00334282; NCT01030783).In one trial, 'time to definitive deterioration' analyses were reported, which were not a focus of this review (NCT00719264).In another trial, 'time to first deterioration' analyses were reported, which were not a focus of this review (NCT02811861).For one trial, we did not extract data because of a discrepancy between methods and reported results (NCT01064310).For one trial, it was not possible to estimate data from the provided graphs (NCT00631371).FKSI‐DRS in five trials (NCT00098657/NCT00083889; NCT00920816; NCT01108445; NCT03141177; NCT00903175).EQ‐5D‐VAS in three trials (NCT00098657/NCT00083889; NCT00920816; NCT02231749).FACT‐G in two trials NCT00098657/NCT00083889; NCT02231749).FACIT‐F in one trial (NCT00720941).
primary outcome:
Angiogenesis inhibitors for the treatment of epithelial ovarian cancer
Overall survival (OS): survival until death from any cause
primary outcome:
Mammography in combination with breast ultrasonography versus mammography for breast cancer screening in women at average risk
Breast cancer mortality
primary outcome:
Interventions for weight reduction in obesity to improve survival in women with endometrial cancer
Overall survival; determined as the time from randomisation until death from any cause.Frequency of adverse events, of any nature. This was subdivided into mild–moderate adverse events (e.g. musculoskeletal or abdominal pain), and life‐threatening events (e.g. electrolyte imbalance requiring hospitalisation).
primary outcome:
Skin‐sparing mastectomy for the treatment of breast cancer
Overall survival: time to death during the follow‐up period, considered separately for ductal carcinoma in situ (DCIS) and early breast cancer
primary outcome:
Exercise interventions for adults with cancer receiving radiation therapy alone
Fatigue, measured by a validated questionnaire such as the Multidimensional Fatigue Inventory (MFI 20; Smets 1996), Functional Assessment of Cancer Therapy‐Fatigue (FACT‐F; Cella 2002), Brief Fatigue Inventory (BFI; Mendoza 1999), or Piper Fatigue Scale (PFS; Reeve 2012).
primary outcome:
Dose‐escalated radiotherapy for clinically localized and locally advanced prostate cancer
Time to death from prostate cancerSevere RT toxicity
primary outcome:
Preoperative combined mechanical and oral antibiotic bowel preparation for preventing complications in elective colorectal surgery
Number of participants with SSIs (infection of the incision site involving the skin and subcutaneous tissue (superficial), deep soft tissue (deep), or a part of the body deeper than the fascia/muscle layers that was opened or manipulated during the surgical procedure (organ/space) and occurs within 30 days after the surgical procedure);Number of participants with anastomotic leakage.
primary outcome:
Corticosteroids for the management of cancer‐related fatigue in adults with advanced cancer
Participant‐reported fatigue relief, assessed with validated scales, such as Functional Assessment of Chronic Illness Therapy‐Fatigue scale (FACIT‐F), European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ‐C30) fatigue subscale, Brief Fatigue Inventory, Profile of Mood States fatigue subscale, Visual Analog Fatigue Scale (VAFS), Multidimensional Fatigue Inventory (MFI), Edmonton Symptom Assessment System (ESAS) for reported relief of fatigue, or SF‐36 vitality subscale.
primary outcome:
Neoadjuvant treatment for stage III and IV cutaneous melanoma
Overall survival (OS), expressed as a hazard ratio (HR).Adverse events (AEs), expressed as the proportion of participants with Grade three or four AEs on the Common Terminology Criteria for Adverse Events (CTCAE) scale (CTCAE 2010).
primary outcome:
Coriolus (Trametes) versicolor mushroom to reduce adverse effects from chemotherapy or radiotherapy in people with colorectal cancer
Overall survival at one year, three years, and five years.Adverse event rates: the incidence of all reported adverse events or toxicities, including modification of treatment or withdrawal from the trial due to adverse events.
primary outcome:
Pre‐emptive antifungal therapy versus empirical antifungal therapy for febrile neutropenia in people with cancer
We considered all‐cause mortality as the primary outcome (survival period was defined as the time interval from random treatment assignment to either death from any cause or the last follow‐up).We did not separate the primary outcome data into short‐ (2 to 6 weeks), medium‐ (7 to 16 weeks), and long‐term (17 to 48 weeks) mortality (Higgins 2022). When possible, we also estimated mortality that occurred during hospitalisation.
primary outcome:
Interventions for preventing and ameliorating cognitive deficits in adults treated with cranial irradiation
The primary outcome for this review was cognitive performance as assessed by neuropsychological tests (and not self‐report); this could be a general or composite cognitive score or individual cognitive test scores using validated neuropsychological tests (e.g. Hopkins Verbal Learning Test‐Revised (HVLT‐R (HVLT‐R), Controlled Oral Word Association Test (COWA)). Cognitive functioning had to be measured at baseline and following intervention at any time point.In studies involving preventative interventions, we determined efficacy as a statistically significant improvement in cognitive functioning, or no change/decline from baseline. Studies could have objective cognitive functioning as a primary outcome or include cognitive performance as the secondary outcome to an alternative primary quality of life measure (e.g. fatigue, mood).In studies involving ameliorating interventions, we determined efficacy as a statistically significant improvement, or no change, in cognitive functioning from baseline. To increase the relevance of the review, we did not restrict eligible studies with respect to the time point at which cognitive functioning was measured at baseline or at follow‐up. We noted and discussed the time points at which cognitive functioning was measured.