anurajms/meta_analysis huggingface dataset:
primary outcome:
Paracetamol (acetaminophen) or non‐steroidal anti‐inflammatory drugs, alone or combined, for pain relief in acute otitis media in children
Proportion of children with pain (yes/no) as rated by parents or carers or children themselves at various time points after study participation (24 hours, 48 to 72 hours, 4 to 7 days).Adverse events likely to be related to the use of paracetamol or NSAIDs (or both), such as kidney failure or dysfunction, liver failure or dysfunction, gastrointestinal complaints or bleeding, and hypersensitivity reactions such as erythema, urticaria (hives, skin itching), or anaphylactic shock.
primary outcome:
High flow nasal cannula for respiratory support in term infants
Death (before hospital discharge)Treatment failure (as defined by trial authors, but typically indicated by the need for intubation or reintubation within 72 hours of initial extubation)Chronic lung disease (defined as the need for supplemental oxygen at 28 days of life (Wilkinson 2016))
primary outcome:
Vocabulary interventions for second language (L2) learners up to six years of age
Receptive L2 vocabulary (both proximal and distal)Expressive L2 vocabulary (both proximal and distal)Mean length of utterance (MLU) (potential adverse effects)a
primary outcome:
Perioperative glycaemic control for people with diabetes undergoing surgery
All‐cause mortalitySevere hypoglycaemic episodesHypoglycaemic episodesInfectious complications
primary outcome:
Probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants
NEC before hospital discharge, confirmed at surgery or autopsy or using the following standardised clinical and radiological criteria (VON 2020):at least one of: bilious gastric aspirate or emesis, abdominal distention, or blood in stool; andat least one of: abdominal radiograph showing pneumatosis intestinalis, gas in the portal venous system, or free air in the abdomen.All‐cause mortality before hospital discharge
primary outcome:
Early nasal intermittent positive pressure ventilation (NIPPV) versus early nasal continuous positive airway pressure (NCPAP) for preterm infants
Respiratory failure: defined by respiratory acidosis, increased oxygen requirement, or apnea that was frequent or severe, leading to additional ventilatory support during the first week of life.Need for endotracheal tube (ETT) ventilation (intermittent positive pressure ventilation (IPPV) through an endotracheal tube)
primary outcome:
Continuous positive airway pressure (CPAP) for apnoea of prematurity
Failed CPAP: defined as any form of apnoea that is sufficiently frequent or severe as to require additional ventilator support, such as NIPPV or endotracheal intubation, or backup medical therapy such as a methylxanthine (for comparisons 1 and 2). The criteria used would be those defined by study authors (such as more than two apnoeic episodes within a four‐hour period requiring bag and mask ventilation)ApnoeaRates of apnoea and bradycardic events expressed as events per specified time period (apnoea with or without bradycardia or bradycardia alone)Differences in rates of apnoea (before and after treatment) expressed as events per hour (for all comparisons)
primary outcome:
Vedolizumab for induction and maintenance of remission in Crohn's disease
proportion of people who achieved clinical remissionproportion of people who maintained clinical remission
primary outcome:
Mobile phone‐based interventions for improving contraception use
Uptake of contraception (including postabortion and postpartum contraception)Uptake of a specific method of contraception (e.g. a long‐acting method)Adherence to contraception method (e.g. number of missed pills, attendance for repeat injection)Safe method switching (e.g. from one effective method to another with no gap during which time conception could occur)Discontinuation of contraceptionPregnancy or abortion (objectively measured or self‐reported)
primary outcome:
Oral contraceptives containing drospirenone for premenstrual syndrome
End scores, or change scores (or both) for psychological and somatic premenstrual symptoms, and functional impairment, measured via any validated prospective symptom rating tool. These tools may include:Daily Record of Severity of Problems (DRSP (Endicott 2006));Total of 24 items, with the first 21 items assessing psychological and physical symptoms, and last 3 items assessing functional impairment caused by the symptoms. The ratings are made daily through the menstrual cycle, with each item having a 6‐point severity scale (from 1 – not at all to 6 – extreme). Maximum total daily score is 144.Calendar of Premenstrual Experiences (COPE (Mortola 1990));Total of 22 items assessing behavioural and physical symptoms. The ratings are made daily through the menstrual cycle, with each item having a 4‐point severity scale (from 0 – not at all to 3 – a great deal). Maximum total daily score is 66.Moos’ Menstrual Distress Questionnaire (MDQ), which includes two forms, form C (cycle) and form T (today). Form C records the most recent cycle retrospectively and may overestimate symptoms (Ross 2003). Form T allows completion on a specific day. A profile based on repeated use of Form T is considered necessary to identify cyclical changes (Moos 2011). Studies that used solely form C will be excluded;Total of 47 items, each rated on a 6‐point severity scale (from 1‐ no experience of the symptoms to 6 – acute or partially disabling experience of the symptom). Form T is an assessment of current feelings. Form C is an assessment of each of the three phases (menstrual, intermenstrual, and premenstrual) of the most recent cycle. The maximum total daily score for Form T is 282.Premenstrual Tension Syndrome (PMTS) rating scales, which include the PMTS‐O (observer rating), and its revised version that includes the newer DSM diagnostic criteria of PMDD (PMTS‐OR), PMTS‐SR (self‐rating), and PMTS‐VAS (visual analogue scale (Steiner 2011)).The PMTS‐O has a total of 10 items, with eight items rated on a 5‐point severity scale (from 0 – no change to 4 – severe) and two items rated on a 3‐point severity scale (from 0 – no change to 2 – marked change). The PMTS‐SR has a total of 36 items, each answered as yes or no. The maximum total score for both PMTS‐O and PMTS‐SR is 36. The PMTS‐OR has a total of 11 items, and the maximum total score is increased to 40. The PMTS‐VAS has a total of 12 items, and each item is rated by marking on a line between not at all and very much, without any specific scores. The PMTS scales are to be completed during the follicular phase and the luteal phase of the same menstrual cycle.Withdrawals due to adverse events
primary outcome:
Opioids for procedural pain in neonates
Pain assessed with the following scales: ABC scale (Bellieni 2005); Bernese Pain Scale for Neonates (Cignacco 2004); Behavioral Indicators of Infant Pain (BIIP) (Holsti 2008); Douleur Aiguë du Nouveau‐né (DAN) (Acute Pain in Newborn infants, APN, English version) (Carbajal 1997); Neonatal Infant Pain Scale (NIPS) (Lawrence 1993); Neonatal Pain, Agitation, and Sedation Scale (N‐PASS) (Hummel 2008); Premature Infant Pain Profile (PIPP)/PIPP‐Revised (PIPP‐R) (Gibbins 2014; Stevens 1996). We planned to report the median and mean values of each pain scale assessed during the procedure; up to 30 minutes after the procedure; and at one to two hours after the procedure.Any harms.
primary outcome:
Oral stimulation for promoting oral feeding in preterm infants
Time (days) taken to achieve exclusive oral feeding, defined as ingestion of all nutrient volumes in a 24‐hour period without gavage (McCain 2001)Time (days) spent in NICUTotal hospital stay (days)Duration (days) of parenteral nutrition
primary outcome:
Pentoxifylline for treatment of sepsis and necrotising enterocolitis in neonates
All‐cause mortality during hospital stay.
primary outcome:
Routine monitoring of gastric residual for prevention of necrotising enterocolitis in preterm infants
Risk of NEC stage ≥ 2 (modified Bell’s staging; Walsh 1986)Time to establish full enteral feeds ≥ 150 mL/kg/day(d)
primary outcome:
Nebulised hypertonic saline for cystic fibrosis
Lung function (absolute change and change in per cent (%) predicted)forced expiratory volume at one second (FEV1)forced vital capacity (FVC)lung volume (residual volume (RV) and total lung capacity (TLC))FEV0.5lung clearance index (LCI)Mortality
primary outcome:
Non‐pharmacological management of infant and young child procedural pain
Under the 24 different included interventions, we first separated studies into one of three age groups due to important developmental differences across these age groups impacting their responses to the painful stimulus.Preterm born neonate ‐ infants born at 36 weeks gestation between birth up to one month post‐natal age.Full‐term born neonate ‐ term‐born infants between birth up to one month post‐natal age.Full‐term born older infant ‐ term‐born infants between one month to 36 months postnatal age.Second, we further classified each study within an age group into one of two pain phases to reduce heterogeneity among included studies.Pain reactivity ‐ pain phase measured within the first 30 seconds after the acutely painful stimulus was discontinued.Immediate pain regulation ‐ pain phase measured after the first 30 seconds following the acutely painful stimulus. If multiple measurements were taken after the first 30 seconds elapsed, we utilised the measurement closest to the 30‐second time point. Our results are best understood as the immediate pain regulation response rather than regulation in a more prolonged sense.
primary outcome:
Antivirals for prevention of hepatitis B virus mother‐to‐child transmission in human immunodeficiency virus positive pregnant women co‐infected with hepatitis B virus
There are infant as well as maternal primary and secondary outcome measures. We planned to present outcome results at the longest follow‐up for each outcome in our main analysis.
primary outcome:
Hand hygiene for the prevention of infections in neonates
Incidence of suspected infection (author‐defined in study) within the first 28 days of life. We defined suspected infection “as defined by the individual provider OR evidenced by parent bringing child to medical care for chief complaint of infection, either parasitic, viral, or bacterial".Incidence of bacteriologically confirmed infection (types of infection as specified by study authors) within the first 28 days of life (bacteriologically confirmed infection defined as “bacteria isolated from the blood, urine, or cerebrospinal fluid (CSF), or any other infected site on the neonates")All‐cause mortality within the first seven days of life (early neonatal death)All‐cause mortality from the 8th to the 28th day of life (late neonatal death)
primary outcome:
Comparative effectiveness of psychological interventions for treating the psychological consequences of sexual abuse in children and adolescents: a network meta‐analysis
Psychological distress/mental health, including post‐traumatic stress disorder (PTSD; e.g. the Children's PTSD Inventory (Saigh 2000) or the Trauma Symptoms Checklist (Briere 1989)); depression (e.g. the Children's Depression Inventory (Kovacs 1992)); anxiety (e.g. State‐Trait Anxiety Inventory for Children (Spielberger 1973)); and self‐harm (e.g. item nine on the Child Depression Inventory (CDI) (Kovacs 1992)).Behaviour, including sexualised (e.g. the Child Sexual Behavior Inventory (CSBI) (Friedrich 1992a)), and internalising and externalising behaviours (e.g. the 'Externalising' subscale of the Child Behavior Checklist (CBCL) (Achenbach 1991)).Social functioning, including attachment (e.g. the Inventory of Parents and Peer Attachment (IPPA) (Armsden 1987)).Relationships with family and others, cognitive or academic attainment, and quality of life (e.g. the Warwick‐Edinburgh Mental Wellbeing Scale (WEMWBS) (NHS Health Scotland 2006).
primary outcome:
Alemtuzumab for multiple sclerosis
Relapse‐free survival. Relapse was defined as newly developed or recently worsened symptoms of neurological dysfunction, lasting longer than 24 hours and objectively confirmed. However, we considered less stringent criteria and assessed these separately.Sustained disease progression‐free survival, defined as at least 1.0‐point increase in the Expanded Disability Status Scale (EDSS) score (Kurtzke 1983) for participants with a baseline score of 5.0 or less or at least 0.5‐point increase for participants with a baseline score of 5.5 points or greater confirmed at six months. We considered a 1‐point increase in EDSS score confirmed at three months' follow‐up as a surrogate outcome measure of progression.Adverse events: number of participants with at least one adverse event, including serious adverse events.
primary outcome:
Interventions for the symptoms and signs resulting from jellyfish stings
At least a clinically significant reduction in pain within six hours. In this composite outcome, we included participants who reported cessation of pain and data that were also described by study authors as a clinically important or clinically significant reduction in pain according to their own definitions; we accepted measurements on a validated pain scale, such as the visual analogue scale (VAS). If study authors did not interpret a reduction of pain as clinically important, we used a cut‐off of 50% of the maximum possible pain relief or a 50% reduction in pain intensity. For studies in which more than one time point was reported, we included the final time point up to six hours from injury.Adverse events due to treatment. We included:the number of participants with any serious adverse event (defined as death or any life‐threatening event, requiring inpatient hospitalisation or prolongation of existing hospitalisation, resulting in persistent or significant disability/incapacity, or requiring intervention to prevent permanent impairment or damage);adverse event withdrawals; andthe number of participants with a minor adverse event (defined as an adverse event that does not qualify as serious) at one day and one week.
primary outcome:
Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis
Eradication of P aeruginosa from the respiratory tract as defined byclearance of P aeruginosa from BAL, sputum or oropharyngeal cultures at 1, 2, 3, 6, 12 and 24 months after commencement of therapytime to next isolation of P aeruginosa from BAL, sputum or oropharyngeal cultures
primary outcome:
Acetylcholinesterase inhibitors for autistic spectrum disorders
Core features of autism spectrum disorder, that is, social communication and stereotypy or restricted, repetitive patterns of behaviour, interests or activities. Outcomes needed to be measured by standardised diagnostic assessment instruments, including, but not limited to, the Childhood Autism Rating Scale (CARS), the Autism Diagnostic Interview‐Revised (ADI‐R; Lord 1994), the Autism Diagnostic Observation Schedule (ADOS), or the Diagnostic Interview for Social and Communication Disorders (DISCO). Assessment tools for social communication and repetitive and restricted behaviours, included the Social Communication Questionnaire (Rutter 2003b), and the Repetitive Behavior Scale‐Revised (RBS‐R (Bodfish 2000)).Adverse events, including risk or presence of side effects directly attributed to the use of AChEIs including:gastrointestinal (e.g. nausea, vomiting, diarrhoea);urinary incontinence;fatigue;sedation; andsleep disruption.
primary outcome:
Interleukin‐6 blocking agents for treating COVID‐19: a living systematic review
Our outcome selection was based on the CORE outcome sets developed by the WHO (WHO Working Group 2020), and advice from content experts.We predefined the following critical and important outcome measures.
primary outcome:
Prebiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants
NEC before discharge from hospital, confirmed at surgery or autopsy or using standardised clinical and radiological criteria (VON 2020):at least one of: bilious gastric aspirate or emesis; or abdominal distention; or blood in stool; andat least one of: abdominal radiograph showing pneumatosis intestinalis; or gas in the portal venous system; or free air in the abdomenAll‐cause mortality before discharge from hospital
primary outcome:
Lactoferrin for the postoperative management of term neonates after gastrointestinal surgery
Incidence of culture‐proven invasive infection (positive bacterial culture in cerebrospinal fluid or blood)All‐cause neonatal mortality (28 days)
primary outcome:
Videolaryngoscopy versus direct laryngoscopy for tracheal intubation in neonates
Time required for successful intubation, defined as total time in seconds from the first insertion of the laryngoscope blade into the mouth until final confirmation of endotracheal tube (ETT) placement by any or a combination of the following: clinical exam (auscultation, visible vapor in the ETT, adequate chest rise); increase in saturation of peripheral oxygen (SpO₂); presence of end‐tidal carbon dioxide (ET‐CO₂); or chest radiographNumber of intubation attempts: insertion and removal of the laryngoscope blade was defined as an attempt, irrespective of the success of the intubationSuccess rate at first attempt
primary outcome:
Nasal high flow therapy for primary respiratory support in preterm infants
Death (before hospital discharge) or BPD (as defined below).Death (before hospital discharge).BPD, defined as receiving supplemental oxygen or respiratory support (or both) at 36 weeks' postmenstrual age (PMA) for infants born at less than 32 weeks' gestation, or at 28 days of age for infants born at 32 weeks' gestation or greater. Note: data from studies that reported an outcome of 'BPD', 'chronic lung disease' or 'CLD' without a clear accompanying definition were still included in this outcome.Treatment failure (as defined in the included studies) within 72 hours of trial entrya.Mechanical ventilation via an endotracheal tube within 72 hours of trial entrya.
primary outcome:
Conventional chest physiotherapy compared to other airway clearance techniques for cystic fibrosis
Pulmonary function tests (measured as z scores or percent (%) predicted (age and height corrected) because of the potential for wide variations in participant age groups)forced expiratory volume in one second (FEV1)forced vital capacity (FVC);average forced expiratory flow between 25% and 75% of FVC (FEF25–75)Number of respiratory exacerbations per year defined by any of the following:number of days in hospital per year for respiratory exacerbationsnumber of admissions to hospital per year for respiratory exacerbationsnumber of intravenous (IV) antibiotics courses per year for respiratory exacerbationsnumber of IV antibiotics days per year for respiratory exacerbationstime to first respiratory exacerbation
primary outcome:
Personalised interventions for subgroups of children with conduct problems
Improvement in child conduct problems or disruptive behaviour, measured by, for example, the Eyberg Child Behavior Inventory (ECBI) (Eyberg 1978).Any adverse events (such as emotional or psychological trauma of any type, perhaps if a parent was to experience an increase in anxiety or depression throughout the course of a parent‐focused treatment; or an increase in negative parenting practices, such as shouting or criticism). These could be measured through validated tools such as the Family Life Interview (Llewellyn 2010), or through practitioner reports.
primary outcome:
Fecal transplantation for treatment of inflammatory bowel disease
Induction of clinical remission in UC or CD at longest follow‐upMaintenance of clinical remission in UC or CD at longest follow‐upSerious adverse events in UC or CD as defined by study authors
primary outcome:
Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents
Severity or improvement of ADHD symptoms measured by validated scales such as the Child Behavior Checklist, Achenbach 1983, or Conners Rating Scales, Conners 1998. Severity was a continuous measure based on endpoint or change scores, while improvement was a dichotomous outcome based on author‐defined improvements in scores.
primary outcome:
Airway clearance techniques compared to no airway clearance techniques for cystic fibrosis
Pulmonary function tests (change from baseline)Forced expiratory volume in one second (FEV1)Forced vital capacity (FVC)Lung clearance index (LCI)Respiratory exacerbationsNumber of respiratory exacerbations per yearNumber of days in hospital per yearNumber of days of intravenous antibiotics per year
primary outcome:
Systemic opioid regimens for postoperative pain in neonates
Pain assessed with validated methods during the administration of selected drugs. The following scales, developed to assess pain, fulfill validity and reliability criteria for newborn infants (term and preterm on mechanical ventilation for any respiratory disease) when critically reviewed (Giordano 2019) were, as follows: Neonatal Infant Pain Scale (NIPS) (Lawrence 1983); Premature Infant Pain Profile (PIPP) (Stevens 1996); COMFORTneo (Van Dijk 2009); Neonatal Pain, Agitation and Sedation Scale (N‐PASS) (Hummel 2008), as well as Visual Analogue Scale (VAS).All‐cause mortality during initial hospitalizationMajor neurodevelopmental disability: cerebral palsy, developmental delay (Bayley Scales of Infant Development ‐ Mental Development Index Edition II (BSID‐MDI‐II; Bayley 1993), Bayley Scales of Infant and Toddler Development ‐ Edition III Cognitive Scale (BSITD‐III) (Bayley 2005)), or Griffiths Mental Development Scale ‐ General Cognitive Index (GCI) (Griffiths 1954; Griffiths 1970), assessment greater than two standard deviations (SDs) below the mean), intellectual impairment (intelligence quotient (IQ) greater than two SDs below the mean), blindness (vision less than 6/60 in both eyes), or sensorineural deafness requiring amplification (Jacobs 2013). We planned to separately assess data on children aged 18 to 24 months and aged three to five years.Cognitive and educational outcomes in children older than five years old
primary outcome:
Nebulised hypertonic saline solution for acute bronchiolitis in infants
Length of hospital stay or time taken to be ready for discharge (inpatients).Rate of hospitalisation (outpatients or emergency department patients).
primary outcome:
Non‐opioid analgesics for procedural pain in neonates
Pain assessed with the following scales: ABC scale (Bellieni 2005); Bernese Pain Scale for Neonates (Cignacco 2004); Behavioral Indicators of Infant Pain (BIIP) (Holsti 2008); Douleur Aiguë du Nouveau‐né (DAN) (Acute Pain in Newborn infants, APN, English version) (Carbajal 1997); Neonatal Infant Pain Scale (NIPS) (Lawrence 1993); Neonatal Pain, Agitation, and Sedation Scale (N‐PASS) (Hummel 2008); Premature Infant Pain Profile (PIPP)/PIPP‐Revised (PIPP‐R) (Gibbins 2014; Stevens 1996). If a study reported more than one pain scale among those specified above, we reported them separately. We planned to report the mean values of each pain scale assessed:during the procedure;up to 10 minutes after the procedure;between 11 and 59 minutes after the procedure; andat one to two hours after the procedure.
primary outcome:
Chest physiotherapy for acute bronchiolitis in paediatric patients between 0 and 24 months old
Time to recovery.Change in the severity status of bronchiolitis.
primary outcome:
Bubble devices versus other pressure sources for nasal continuous positive airway pressure in preterm infants
Treatment failure indicated by recurrent apnoea, hypoxia, hypercarbia, increasing oxygen requirement, or the receipt of mechanical ventilation within 72 hours after initiation of nasal CPAPAll‐cause mortality prior to hospital dischargeNeurodevelopmental impairment assessed by a validated test after 12 months' post‐term: neurological evaluations, developmental scores, and classifications of disability, including cerebral palsy and auditory and visual impairment
primary outcome:
Zinc supplementation for preventing mortality, morbidity, and growth failure in children aged 6 months to 12 years
1. All‐cause mortality2. Cause‐specific mortality2.1 Mortality due to all‐cause diarrhea2.2 Mortality due to lower respiratory tract infection (LRTI, including pneumonia)2.3 Mortality due to malaria
primary outcome:
Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD)
ADHD symptoms (attention, hyperactivity and impulsivity), measured over the short term (within six months) and over the long term (longer than six months) by psychometric instruments or by observations of behaviour, using, for example, Conners' Teacher Rating Scales (Conners 1998a; Conners 2008). Raters could be teachers, independent assessors, or parents. We chose to report the results of teacher‐rated outcomes as the primary outcome (see Results).Number of serious adverse events. We defined a serious adverse event as any event that led to death, was life‐threatening, required inpatient hospitalisation or prolongation of existing hospitalisation, resulted in persistent or significant disability, or as any important medical event that may have jeopardised the patient's life or that required intervention for prevention. We considered all other adverse events to be considered non‐serious (ICH 1996).
primary outcome:
Postnatal phenobarbital for the prevention of intraventricular haemorrhage in preterm infants
All grades of IVH (Papile 1978)Severe IVH (i.e. grade III and IV IVH)
primary outcome:
Botulinum toxin for the treatment of strabismus
We included trials when study design, participants, interventions and comparators met the inclusion criteria, irrespective of whether our prespecified outcome data were reported.
primary outcome:
Systemic corticosteroid regimens for prevention of bronchopulmonary dysplasia in preterm infants
Combined outcome of death or BPD at 36 weeks' PMA (BPD defined as the need for respiratory support or oxygen dependency at 36 weeks' PMA).
primary outcome:
Medical interventions for traumatic hyphema
Proportion of participants with best‐corrected visual acuity (BCVA) of 20/40 or better assessed at short‐, medium‐, and long‐term follow‐up, defined respectively as two weeks or less; more than two weeks but within two months; and more than two months from the traumatic event. We also assessed VA at resolution of hyphema.Time to resolution of primary hemorrhage (hyphema) defined as the length of time from onset to disappearance of hyphema.
primary outcome:
Ultrasound‐guided arterial cannulation in the paediatric population
First‐attempt success rateIncidence of complicationsHaematomaIschaemic damage
primary outcome:
Ataluren and similar compounds (specific therapies for premature termination codon class I mutations) for cystic fibrosis
Quality of life (QoL; measured using validated quantitative scales or scores (e.g. Cystic Fibrosis Questionnaire ‐ Revised (CFQ‐R) (Quittner 2009))Total QoL scoreDifferent subdomainsMeasures of respiratory function (litres or per cent (%) predicted for age, sex and height)Forced expiratory flow rate in one second (FEV1; relative change from baseline)FEV1 (absolute values)Forced vital capacity (FVC; absolute values and relative change from baseline)Adverse eventsGraded by review authors as mild (therapy does not need to be discontinued)Graded by review authors as moderate (therapy is discontinued and the adverse effect ceases)Graded by review authors as severe (life‐threatening or debilitating effects or those that persist even after treatment is discontinued)
primary outcome:
Systemic opioids versus other analgesics and sedatives for postoperative pain in neonates
Pain assessed with validated methods during the administration of selected drugs. The following scales were developed to assess pain, fulfill validity and reliability criteria for newborn infants (term and preterm on mechanical ventilation for any respiratory disease) when critically reviewed (Giordano 2019): NIPS (Lawrence 1983); Premature Infant Pain Profile (PIPP) (Stevens 1996); COMFORTneo (Van Dijk 2009); and Neonatal Pain, Agitation and Sedation Scale (N‐PASS) (Hummel 2008).Major neurodevelopmental disability: cerebral palsy; developmental delay (Bayley Scales of Infant Development ‐ Mental Development Index Edition II (BSID‐MDI‐II; Bayley 1993), Bayley Scales of Infant and Toddler Development ‐ Edition III Cognitive Scale (BSITD‐III) (Bayley 2005), or Griffiths Mental Development Scale ‐ General Cognitive Index (GCI) (Griffiths 1954; Griffiths 1970), assessment greater than two standard deviations (SDs) below the mean); intellectual impairment (intelligence quotient (IQ) greater than two SDs below the mean); blindness (vision less than 6/60 in both eyes); or sensorineural deafness requiring amplification (Jacobs 2013). We assessed data on children aged 18 to 24 months and aged three to five years separately.Cognitive and educational outcomes in children more than five years old.All‐cause mortality during initial hospitalization.
primary outcome:
Interventions for preventing and treating kidney disease in IgA vasculitis
Reduction in kidney function including ESKD, acute kidney insufficiency or significant increase in SCr, significant reduction in GFR or both as defined by the investigatorsDevelopment, persistence or worsening of proteinuria, development of nephrotic syndrome or acute nephritic syndrome as defined by the investigatorsComplications of therapy e.g. infection, bleeding, leucopenia, hypertension.
primary outcome:
Catheter insertion techniques for improving catheter function and clinical outcomes in peritoneal dialysis patients
Early PD catheter function: catheter function at the time of PD catheter insertion (primary catheter function) and up to 30 days following PD catheter insertion. If the observation period commenced from the start of PD, then this was collected. Early catheter failure was indicated by an event which meant the catheter could not be used to perform a PD exchange/effective PD treatment (which may or may not have required transfer to HD). This is measured as a binary outcome (functioning or non‐functioning).Long‐term PD catheter function: this was defined as a functioning PD catheter that was sufficient to permit successful PD/PD exchanges following catheter insertion. PD catheter failure rate at one year was collected if reported. Catheter failure may or may not have resulted in the transfer to HD. This was also measured as a binary outcome (functioning or non‐functioning)Technique failure (i.e. the inability to perform successful PD resulting in transfer to HD): technique failure was defined as the patient requiring having been off PD and established on HD for a minimum of 30 days, as described by Lan 2016. In that study percentage returning to PD within 12 months was 24% if the duration on HD was 30 days or less but significantly lower when examining patients with a longer duration on HD (e.g. return after 180 days on HD was 3%). Mechanical causes for technique failure were highest in the 30‐day duration of the HD cohort, making it a useful definition in this situation for early technique failure with predominantly mechanical aetiology. Thirty‐day transfer to HD and 180‐day transfer to HD data were to be collected if reported.Death: included in technique failure however death censored technique failure was planned to be reported separately as this has been found to be more sensitive to centre practice. Kidney recovery and transplantation were not classified as technique failure.Complications of PD catheter insertion were examined as primary outcome measures. These included:Exit‐site infection (early as defined within studies)Early peritonitis episode within 30 days of PD catheter insertionBowel perforationHaemorrhage/haemoperitoneumCatheter tip migrationPD catheter drainage painExit‐site leakageCatheter use: whether the PD catheter was ever used for PD.
primary outcome:
Probiotics for management of functional abdominal pain disorders in children
Global improvement or treatment success as defined by the primary studies.Complete resolution of pain.Severity of pain or change in the severity of pain.Frequency of pain or change in the frequency of pain.
primary outcome:
Stem cell‐based interventions for the prevention and treatment of intraventricular haemorrhage and encephalopathy of prematurity in preterm infants
All‐cause neonatal mortality (mortality less than 28 days of age)Major neurodevelopmental disability: cerebral palsy, developmental delay (Bayley Mental Developmental Index (Bayley 1993; Bayley 2006) or Griffiths Mental Development Scale (Griffiths 1954) assessment greater than two standard deviations (SDs) below the mean), intellectual impairment (intelligence quotient (IQ) greater than two SDs below the mean), blindness (vision less than 6/60 in both eyes), or sensorineural deafness requiring amplification (Jacobs 2013). We planned to separately assess data on children aged 18 to 24 months and those aged three to five yearsFor prevention trials: GM‐IVH: any grade; severe IVH grade 3 to 4 (for prevention studies only) (Papile 1978)For prevention trials: EoP (Volpe 2005)For GM‐IVH treatment trials: extension of pre‐existing non‐severe GM‐IVH (e.g. grade 1 to 2) to severe IVH (e.g. grade 3 to 4) (yes/no) (Papile 1978). Although the timing for neuroimaging might differ between trials, within each trial the intervals schedule must be identical in the intervention and control groups. If both ultrasound and MRI are available for the same infants, we plan to refer to the modality with the highest IVH grade
primary outcome:
Antibiotics for chronic pulmonary infection in children with a neurodisability (neurodevelopmental disorder)
Cumulative number of days of hospital admission secondary to respiratory causes per child or young person within one yearQuality‐of‐life measures as validated patient‐reported or parent/carer‐reported outcomes (such as DISABKIDS‐CP (Baars 2005), CP QOL Child (Waters 2006)) or CP QOL Teen (Davis 2013)Average time to next pulmonary exacerbation (defined according to the trialist or by the provision of additional antibiotics) within one year
primary outcome:
Behavioural and cognitive‐behavioural interventions for outwardly directed aggressive behaviour in people with intellectual disabilities
Change in aggressive behaviour (frequency/severity of incidents), for example measured using the Aberrant Behavior Checklist (Aman 1985), or number of incidents (Singh 2013; Singh 2016; Singh 2020a)Change in ability to control anger, for example measured using the Provocation Inventory (PI) (Novaco 2003)Change in adaptive functioning, for example using the Matson Evaluation of Social Skills for Individuals with Severe Mental Retardation (MESSIER; Matson 1998)Adverse effects, such as death, or adverse effects from treatment
primary outcome:
Vitamin D for the management of asthma
Incidence of severe asthma exacerbations, defined as those requiring treatment with systemic corticosteroids
primary outcome:
Active cycle of breathing technique for cystic fibrosis
Quality of life ‐ all instruments that measure the ability of participants to perform activities of daily living (including but not limited to the Cystic Fibrosis Questionnaire (CFQ), Health Assessment Questionnaire (HAQ), Quality of Well Being (QWB) scale, and Nottingham Health Profile (NHP))Personal preference ‐ the nominated technique of choice by the participant at the conclusion of the study, or by comparison of technique acceptabilityMortality
primary outcome:
Physical interventions to interrupt or reduce the spread of respiratory viruses
Numbers of cases of viral respiratory illness (including acute respiratory infections (ARI), influenza‐like illness (ILI), COVID‐like illness and laboratory‐confirmed influenza, SARS‐CoV‐2 or other viral pathogens).Adverse events related to the intervention.
primary outcome:
Surgical versus non‐surgical interventions for treating patellar dislocation
Recurrent patellar dislocation.Validated patient‐rated knee and physical function scores for patellar dislocation outcomes (Paxton 2003), e.g. the Lysholm score (Lysholm 1982), the Tegner activity score (Tegner 1985), the Hughston visual analogue score (VAS) (Flandry 1991), the Norwich Patellar Instability score (Smith 2014), the Banff‐II Patellar Instability Instrument (Hiemstra 2013) and the Kujala Patellofemoral Disorders score (Kujala 1993).
primary outcome:
Vitamin D as an adjunct to antibiotics for the treatment of acute childhood pneumonia
Time to resolution of acute illnessDuration of hospitalisation
primary outcome:
Bisphosphonates for osteoporosis in people with cystic fibrosis
Fractures: number of participants with any fracture; number of participants with fractures by site:non‐vertebral;vertebral.
primary outcome:
Glucocorticoids for croup in children
Change in clinical croup score from baseline to 2, 6, 12, and/or 24 hours.Return visits or (re)admissions to the hospital, or both.
primary outcome:
Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low birth weight infants
Failure of PDA closure after the first course of paracetamol treatment (closure and failure of closure confirmed by echocardiographic criteria)Neurodevelopmental impairment (neurodevelopmental outcome assessed by a standardized and validated assessment tool or a child developmental specialist, or both) at any age reported (outcome data grouped at 12, 18, 24, 36, and 60 months, if available)Death or disability (outcome data grouped at 12, 18, 24, 36, and 60 months, if available)
primary outcome:
Late (≥ 7 days) inhaled corticosteroids to reduce bronchopulmonary dysplasia in preterm infants
Combined outcome of mortality or BPD at 36 weeks' PMA (BPD defined as oxygen dependency, respiratory support dependency, or both, at 36 weeks' PMA)Mortality at 36 weeks' PMABPD at 36 weeks' PMA
primary outcome:
Vaccines for the common cold
Incidence of the common cold after vaccination, regardless of the causal agent determined by laboratory or clinical examination. In future updates, we will consider the incidence of the common cold as one of the primary outcomes, measured 60 days after the last dose of the vaccine.Vaccine safety, i.e. adverse events ("any untoward medical occurrence that may present during treatment with a pharmaceutical product but which does not necessarily have a causal relationship with this treatment") and adverse drug reactions ("a response to a drug which is noxious, uninitiated and which occurs at doses normally used in men for prophylaxis, diagnosis, or therapy of disease, or for the modification of physiologic functions") (Nebeker 2004).Mortality: vaccine related and all cause.
primary outcome:
Homeopathic medicinal products for preventing and treating acute respiratory tract infections in children
Cure: defined as the reduction or resolution of symptoms of ARTIs (fever/body temperature, cough, pain, malaise/feeling of illness, rhinorrhoea, etc.) in the short term (up to 14 days) and long term (up to 3 months), as a treatment outcome.Disease severity, as measured by mean symptom scores.Recurrence of ARTIs (time to recurrence included).
primary outcome:
Interventions for the eradication of meticillin‐resistant Staphylococcus aureus (MRSA) in people with cystic fibrosis
Eradication of MRSA (as defined by negative respiratory culture after completion of the eradication protocol)Time until next positive MRSA isolate from clinically relevant respiratory culture
primary outcome:
Family‐centred interventions for Indigenous early childhood well‐being by primary healthcare services
Overall health and well‐beingIf available, the inclusion of one primary outcome (listed below) from each included study.Psychological health and emotional behaviour of children including:level of stress, upset, crying, infant separation distress, child anxiety, insomnia, mood, fears and behavioural regression, well‐being;self‐esteem, levels of confidence, self‐expression; andcoping, adjustment, compliance.Physical health and developmental health outcomes of children including:Clinical assessments (e.g. injury resolution);Physiological measures (e.g. anaemia levels); andDevelopmental milestones.Family health‐enhancing lifestyle or behaviour outcomes including:weight control, control over child's food intake, birth weight;breastfeeding;reduced substance misuse, reduced smoking, reduced alcohol consumption, reduced addictions, and other risk taking;home safety, safe sleeping.Psychological health of parent/carer including:level of stress, anxiety, depression, mood, well‐being;self‐esteem, levels of confidence in parenting; andperceptions of coping, sense of control.Adverse events or harms, including:health behaviours (e.g. violence);clinical adverse effects;poor utilisation or access;low quality of care; andincreased inequities.
primary outcome:
Ultrasound guidance versus landmark method for peripheral venous cannulation in adults
First‐pass success of cannulationOverall success of cannulationPain
primary outcome:
Bioengineered nerve conduits and wraps for peripheral nerve repair of the upper limb
British Medical Research Council (BMRC) grading at 24 months or more for:muscle strength, using manual muscle testing (MMT);sensory recovery.
primary outcome:
Statins for Smith‐Lemli‐Opitz syndrome
Survival including:overall survival, encompassing SLOS‐related (see below) and SLOS‐unrelated deaths (e.g. death due to accidents, prematurity, sudden infant death syndrome (SIDS), other genetic or metabolic conditions, etc.); andSLOS‐related deaths specifically, which include all deaths deemed by the investigators of the individual studies to have been most likely a direct result of the individual having SLOS (e.g. due to overwhelming infections without an underlying immunodeficiency, severe feeding problems and malnutrition due to gastrointestinal abnormalities related to SLOS, or death from severe visceral or brain malformations associated with SLOS).Changes in severity or frequency (or both) of the neurobehavioral manifestations associated with SLOS, assessed by comparison with each individual's corresponding baseline, i.e. at the time of initial enrolment in the study:anxiety (evaluated using, e.g. the Pediatric Anxiety Rating Scale (PARS)) (PARS 2002);ADHD (evaluated using, e.g. the Conner's Continuous Performance Test (CCPT) or the Test of Variables of Attention (TOVA)) (Edwards 2007);pro‐active aggression against others or self (i.e. self‐mutilation) (assessed using, e.g. the Buss‐Perry Aggression Questionnaire (BPAQ) and the Functional Assessment of Self‐Mutilation (FASM) tools) (Buss 1992; Lloyd 1997);emotional lability (e.g. tantrums or aggressive outbursts to obtain tangible objects, i.e. reactive aggression), or agitation, or irritability (assessed using, e.g. the Emotion Regulation Checklist (ERC) or the irritability subscale of the Aberrant Behavior Checklist‐Community (ABC‐C) tools) (Aman 1995; Shields 1997);sleep disturbances (evaluated using, e.g. the Pediatric Sleep Questionnaire (PSQ) or the Children's Sleep Habits Questionnaire tools) (Chervin 2000; Owens 2000); andASD (evaluated using, e.g. the Autism Diagnostic Observational Schedule (ADOS)) (Lord 2001).Statin‐related adverse reactions:liver‐related: hepatotoxicity assessed by hepatic injury biomarkers and defined as having serum glutamic‐oxaloacetatic transaminase (SGOT; also known as aspartate aminotransferase (AST)) or serum glutamic‐pyruvic transaminase (SGPT; also known as alanine aminotransferase (ALT)) levels reaching or exceeding three times the upper limit of normal (ULN) (Rosenson 2019a);muscle‐related: myalgias (self‐reported by participants or their caregivers or both), myopathy (defined as elevations in the levels of creatine phosphokinase (CPK) often to 10 times the upper limit of normal (ULN) (Starck 2002a), or aldolase, or lactate dehydrogenase (LDH), or any combination of these parameters), or rhabdomyolysis (Rosenson 2019b);skin‐related: increased or worsening photosensitivity following statin initiation (measured quantitatively as UV‐A tolerance in joules/cm²) (Starck 2002a); andothers: depletion of or reduction in CoQ10 levels (Qu 2018; Rundek 2004), or developing one of the rare statin‐related adverse reactions such as cognitive dysfunction, sleep disturbances, abdominal pain, diarrhea or neuropathy (Haas 2007; Rosenson 2019a).
primary outcome:
Inhaled anti‐pseudomonal antibiotics for long‐term therapy in cystic fibrosis
Lung function (measured in litres (L) or per cent (%) predicted)forced expiratory volume in one second (FEV1)forced vital capacity (FVC)Exacerbation of respiratory infection (defined as any deterioration in clinical condition resulting in treatment with oral or intravenous antibiotics, either at home or in hospital)hospital admissionsdays in hospitalcourses of intravenous antibioticspulmonary exacerbationsfrequencytime to first exacerbation
primary outcome:
Pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia
Analgesia and sedation assessed with validated scales in the neonatal population: the Echelle Douleur Inconfort Nouveau‐ne (EDIN) scale (Debillon 2001), COMFORTneo (COMFORTNeo 2016; van Dijk 2009), Neonatal Pain, Agitation and Sedation Scale (N‐PASS) (Hummel 2008), pain assessment tool, the Astrid Lindgren and Lund Children's Hospital's Pain and Stress Assessment Scale for Preterm and Sick Newborn Infants (ALPS‐neo) (Lundqvist 2014), Neonatal Facial Coding System (NFCS) (Grunau 1986; Peters 2003), and CRIES (Crying, Requires oxygen, Increased vital signs, Expression, Sleepless) scale (Krechel 1995). However, none of these scales are validated for assessing pain during therapeutic hypothermia. We planned to report the mean values of each scale assessed at 30 minutes, three hours, and 12 hours after the administration of the intervention. We planned to report analgesia and sedation scores separately.All‐cause mortality to discharge.
primary outcome:
Support for healthy breastfeeding mothers with healthy term babies
Stopping any breastfeeding at six months postpartum.Stopping exclusive breastfeeding at six months postpartum.Stopping any breastfeeding at four to six weeks postpartum.Stopping exclusive breastfeeding at four to six weeks postpartum.
primary outcome:
Biomarkers as point‐of‐care tests to guide prescription of antibiotics in people with acute respiratory infections in primary care
Number of participants given an antibiotic prescription at the index consultation and within 28 days follow‐up.Number of participants with substantial improvement (including full recovery) within seven days follow‐up.Total mortality within 28 days follow‐up.
primary outcome:
Tumor necrosis factor (TNF) inhibitors for juvenile idiopathic arthritis‐associated uveitis
Standardization of Uveitis Nomenclature (SUN) criteria score for anterior chamber (AC) cell grading (SUN 2005)Success defined as 0 to trace cells on SUN‐grading; or two‐step decrease in activity based on SUN‐gradingFailure defined as two‐step increase in activity SUN‐grading
primary outcome:
Splinting for the non‐operative management of developmental dysplasia of the hip (DDH) in children under six months of age
Measurement of acetabular index at years one, two, and five, as determined by radiographs (angle).Need for operative intervention (dichotomous):to achieve reduction; andto address dysplasia.Complications (dichotomous):avascular necrosis (AVN; there are several grading systems, most commonly "total" AVN (Salter 1969), and "partial" AVN (Gage 1972));femoral nerve palsy;other nerve palsies; andpressure areas on skin.
primary outcome:
Increased versus stable doses of inhaled corticosteroids for exacerbations of chronic asthma in adults and children
Treatment failure: need for rescue systemic corticosteroids* in all randomised participants (i.e. intention‐to‐treat (ITT) analysis).
primary outcome:
Laser therapy for treating hypertrophic and keloid scars
Severity of keloid or hypertrophic scars (or both) measured by health professional and/or participant using a specific scale (as defined by the authors).Incidence and severity of treatment‐related adverse effects.
primary outcome:
Appetite stimulants for people with cystic fibrosis
Change in body weight (kg)Change in body compositionlean body mass (LBM)fat massbody mass index (BMI)Change in pulmonary functionforced expiratory volume in one second (FEV1) (L)FEV1 % predicted